Attachment

ANATOMY
HEAD
AND
NECK
8/26/22, 5:01 PM Anterior Scalene Muscle - MRCEM Success
Anterior Scalene Muscle LAST UPDATED: 19TH

FEBRUARY 2019
ANATOMY / HEAD AND NECK / NECK
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The anterior scalene muscle is a synergistic stabiliser of the neck and acts together
with the other scalene muscles to elevate rib I.
It originates from the anterior tubercles of the transverse processes of vertebrae C3
- C6 and inserts onto the scalene tubercle and upper surface of rib I.
It is innervated by the anterior rami of C5 - C6.
ANTERIOR SCALENE MUSCLE. (IMAGE BY USER:MIKAEL HÄGGSTRÖM (IMAGE:GRAY387.PNG)

[PUBLIC DOMAIN], VIA WIKIMEDIA COMMONS)
https://mrcemsuccess.com/explanation/scalenus-anterior/?_sft_qc=neck 2/3
8/26/22, 5:03 PM Neck Spaces and Fascia - MRCEM Success
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Neck Spaces and Fascia LAST UPDATED: 20TH

APRIL 2020
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Neck Fascia
The neck fascia is divided into the superficial and deep fascia.
The superficial cervical fascia lies between the dermis and the deep cervical
fascia. It contains numerous structures:
Neurovascular supply to the skin
Superficial veins (e.g. the external jugular vein)
Superficial lymph nodes
Fat
Platysma muscle
The deep cervical fascia lies, as its name suggests, ‘deep’ to the superficial fascia
and platysma muscle. This fascia is organised into several layers:
1) an investing layer (blue) which lies deep to the superficial fascia and
surrounds all structures in the neck
2) the prevertebral layer (green) which surrounds the vertebral column and
the deep muscles associated with the back
3) the pretracheal layer (yellow) which encloses the viscera of the neck (the
trachea, oesophagus and thyroid)
4) the carotid sheaths (red) which receive a contribution from the other
three fascial layers and surround the two major neurovascular bundles on
either side of the neck (containing the common carotid artery, the internal
carotid artery, the internal jugular vein and the vagus nerve)
The trapezius and sternocleidomastoid muscles lie within the investing layer of the
deep cervical fascia.
https://mrcemsuccess.com/explanation/neck/?_sft_qc=neck 2/4
The viscera of the neck lie anterior to the prevertebral fascia, within the
pretracheal layer.
The prevertebral muscles lie within the prevertebral fascial layer and act as weak
neck flexors.
LAYERS OF THE DEEP CERVICAL FASCIA: INVESTING LAYER (BLUE), PREVERTEBRAL

LAYER (GREEN), PRETRACHEAL LAYER (YELLOW), CAROTID SHEATHS (RED). (IMAGE
MODIFIED BY FRCEM SUCCESS. ORIGINAL BY HENRY VANDYKE CARTER [PUBLIC DOMAIN],
VIA WIKIMEDIA COMMONS)
Neck Spaces
Between the fascial layers in the neck are spaces that may provide a conduit for
the spread of infections from the neck to the mediastinum:
The pretracheal space lies between the investing layer of cervical fascia and
the pretracheal fascia and passes between the neck and the anterior part of
the superior mediastinum.
The retropharyngeal space lies between the buccopharyngeal fascia (the
part of the pretracheal fascia posterior to the pharynx) and the prevertebral
fascia and extends from the base of the skull to the upper part of the
posterior mediastinum.
The prevertebral space is within the prevertebral layer as it splits into two
laminae, extending from the base of the skull and extends through the
posterior mediastinum to the diaphragm.
8/26/22, 5:04 PM Neck Triangles - MRCEM Success
Neck Triangles LAST UPDATED: 20TH

APRIL 2020
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The trapezius and sternocleidomastoid divide the neck into anterior and posterior
triangles on each side.
Anterior Triangle
Each anterior triangle is bounded:
medially by the median vertical line of the neck
laterally by the anterior margin of the sternocleidomastoid muscle
superiorly by the inferior margin of the mandible
The contents of the anterior triangle include muscles, nerves, arteries, veins and
lymph nodes:
Muscles
Suprahyoid muscles
Infrahyoid muscles
Nerves
Facial nerve
Glossopharyngeal nerve
Vagus nerve
Accessory nerve
Hypoglossal nerve
Arteries
Common carotid artery bifurcates into the external and internal carotid
artery
Veins
Internal jugular vein
Lymph nodes
Posterior Triangle
https://mrcemsuccess.com/explanation/neck-triangles/?_sft_qc=neck 2/3
8/26/22, 5:04 PM Neck Triangles - MRCEM Success
Each posterior triangle is bounded:

anteriorly by the posterior margin of the sternocleidomastoid
posteriorly by the anterior margin of the trapezius
basally by the middle one-third of the clavicle
apically by the occipital bone
ANTERIOR AND POSTERIOR TRIANGLES OF THE NECK. (IMAGE BY OLEK REMESZ (WIKI-PL:
OREM, COMMONS: OREM) MODIFIED BY USER:MADHERO88 (ORIGINAL IMAGE FILE:MUSCULI
COLI BASE.SVG) [CC BY 3.0], VIA WIKIMEDIA COMMONS)
https://mrcemsuccess.com/explanation/neck-triangles/?_sft_qc=neck 3/3
8/26/22, 5:05 PM Sternocleidomastoid Muscle - MRCEM Success
Sternocleidomastoid Muscle LAST UPDATED: 11TH

APRIL 2019
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Table: Overview of the Sternocleidomastoid Muscle

Muscle Sternocleidomastoid
Origin Sternal head: anterior manubrium of sternum
Clavicular head: medial one-third of clavicle
Insertion Sternal head: lateral one-half of superior nuchal line
Clavicular head: lateral mastoid process
Innervation Accessory nerve (and by branches of anterior rami of C2 – C3)
Action Acting unilaterally: lateral rotation of head towards
same side and rotation of head towards opposite side
Acting bilaterally: dorsal extension of head
Attachments
The sternocleidomastoid muscle has two heads; the sternal head originates from
the upper part of the anterior manubrium of the sternum and inserts onto the
lateral one-half of the superior nuchal line (occipital bone) and the clavicular head
originates from the superior surface of the medial one-third of the clavicle and
inserts onto the lateral surface of the mastoid process (temporal bone).
Function
Individually each muscle will tilt the head towards the shoulder on the same side
(lateral flexion) and rotate the head to turn to face the opposite side. Acting
together the muscles draw the head forward, through extension of the neck at the
atlanto-occipital joints (dorsal extension).
Innervation
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8/26/22, 5:05 PM Sternocleidomastoid Muscle - MRCEM Success
The sternocleidomastoid is innervated by the accessory nerve (CN XI) and by

branches of anterior rami of C2 - C3.
STERNOCLEIDOMASTOID MUSCLE. (IMAGE BY HENRY VANDYKE CARTER [PUBLIC DOMAIN],

https://mrcemsuccess.com/explanation/sternocleidomastoid-2/?_sft_qc=neck 3/3
8/26/22, 5:05 PM Deep Cervical Lymph Nodes - MRCEM Success
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Deep Cervical Lymph LAST UPDATED: 11TH

APRIL 2019
Nodes  Bookmark
The deep cervical nodes form a chain along the internal jugular vein and are
divided into upper and lower groups.
Jugulodigastric Node
The most superior node in the upper group (lying where the posterior belly of
the digastric muscle crosses the internal jugular vein) is the jugulodigastric
node which receives lymphatic drainage from the tonsils and tonsillar region.
Jugulo-omohyoid Lymph Node

The most superior node in the lower group (lying just inferior to the
intermediate tendon of the omohyoid muscle) is the jugulo-omohyoid node
which receives lymphatic drainage from the tongue.
https://mrcemsuccess.com/explanation/deep-cervical-lymph-nodes/?_sft_qc=neck 2/3
8/26/22, 5:05 PM Deep Cervical Lymph Nodes - MRCEM Success
DEEP CERVICAL LYMPH NODES. (IMAGE BY HENRY VANDYKE CARTER [PUBLIC

DOMAIN], VIA WIKIMEDIA COMMONS)
https://mrcemsuccess.com/explanation/deep-cervical-lymph-nodes/?_sft_qc=neck 3/3
8/26/22, 5:06 PM Phrenic Nerve - MRCEM Success
Phrenic Nerve LAST UPDATED: 11TH

FEBRUARY 2019
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The phrenic nerves are branches of the cervical plexus, arising on each
side as contributions from the anterior rami of C3 - C5 come together.
Passing around the upper lateral border of each anterior scalene muscle,
the phrenic nerves continue inferiorly across the anterior surface of the
anterior scalene muscle within the prevertebral fascia.
Leaving the lower edge of the anterior scalene muscle, each phrenic nerve
passes between the subclavian vein and artery to enter the thorax to
continue to the diaphragm.
https://mrcemsuccess.com/explanation/phrenic-nerve/?_sft_qc=neck 2/3
8/26/22, 5:06 PM Phrenic Nerve - MRCEM Success
ROOT OF THE NECK. (IMAGE MODIFIED BY FRCEM SUCCESS. ORIGINAL BY HENRY

VANDYKE CARTER [PUBLIC DOMAIN], VIA WIKIMEDIA COMMONS)
https://mrcemsuccess.com/explanation/phrenic-nerve/?_sft_qc=neck 3/3
8/26/22, 5:07 PM Recurrent Laryngeal Nerve - MRCEM Success
Recurrent Laryngeal Nerve LAST UPDATED: 11TH

APRIL 2019
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Right Recurrent Laryngeal Nerve

The right recurrent laryngeal nerve originates in the root of the neck, as a
branch of the right vagus nerve as it reaches the lower edge of the first part
of the subclavian artery. It passes around the subclavian artery and
travels upwards and medially in a groove between the trachea and the
oesophagus as it heads to the larynx.
https://mrcemsuccess.com/explanation/recurrent-laryngeal-nerve/?_sft_qc=neck 2/4
RIGHT RECURRENT LARYNGEAL NERVE. (IMAGE BY HENRY VANDYKE CARTER

[PUBLIC DOMAIN])
Left Recurrent Laryngeal Nerve

The left recurrent laryngeal nerve originates more inferiorly, from the left
vagus nerve as it crosses the arch of the aorta in the superior mediastinum. It
passes below and behind the arch of the aorta and then ascends beside the
trachea to the larynx.
LEFT RECURRENT LARYNGEAL NERVE. (IMAGE BY JKWCHUI (BASED ON DRAWING

BY TRUTH-SEEKER2004) [CC BY-SA 3.0
(HTTP://CREATIVECOMMONS.ORG/LICENSES/BY-SA/3.0)], VIA WIKIMEDIA
COMMONS)
Clinical Implications
Damage to the recurrent laryngeal nerves may result in hoarseness,
respiratory obstruction, inability to speak and loss of sensation below the
vocal cord.
Causes of damage include:
thyroid/parathyroid surgery
mediastinal lymphadenopathy
cricothyroidotomy
aneurysm of the aortic arch
lung cancer in the apex of the right lung
malignancy infiltrating into the 'aortopulmonary window'
8/26/22, 5:07 PM Suprahyoid and Infrahyoid Muscles - MRCEM Success
Suprahyoid and Infrahyoid LAST UPDATED: 11TH

APRIL 2019
Muscles  Bookmark
Suprahyoid Muscles
Muscles superior to the hyoid are called suprahyoid muscles and include the
stylohyoid, digastric, mylohyoid and geniohyoid muscles. The suprahyoid
muscles pass in a superior direction from the hyoid bone to the skull or
mandible and act to raise the hyoid bone, as occurs in swallowing.
https://mrcemsuccess.com/explanation/neck-muscles/?_sft_qc=neck&sf_paged=2 2/4
8/26/22, 5:07 PM Suprahyoid and Infrahyoid Muscles - MRCEM Success
SUPRAHYOID MUSCLES. (IMAGE BY HÄGGSTRÖM, MIKAEL. “MEDICAL GALLERY OF

MIKAEL HÄGGSTRÖM 2014”. WIKIVERSITY JOURNAL OF MEDICINE 1 (2).
DOI:10.15347/WJM/2014.008. ISSN 20018762. (IMAGE:GRAY386.PNG) [PUBLIC
Infrahyoid Muscles
Muscles inferior to the hyoid are the infrahyoid muscles and include the
omohyoid, sternohyoid, thyrohyoid and sternothyroid. The infrahyoid muscles
attach the hyoid bone to inferior structures and act to depress the hyoid
bone and the larynx. They also provide a stable point of attachment for the
suprahyoid muscles.
https://mrcemsuccess.com/explanation/neck-muscles/?_sft_qc=neck&sf_paged=2 3/4
8/26/22, 5:08 PM Thyroid Gland - MRCEM Success
Thyroid Gland LAST UPDATED: 11TH

APRIL 2019
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The thyroid gland is anterior in the neck, below and lateral to the thyroid
cartilage, and spanning between the C5 and T1 vertebrae.
It has two lateral lobes (which cover the anterolateral surfaces of the trachea,
cricoid cartilage and the lower part of the thyroid cartilage) connected by the
isthmus which crosses the anterior surface of the second and third tracheal
cartilages.
THYROID GLAND. (IMAGE BY OPENSTAX COLLEGE [CC BY 3.0

(HTTPS://CREATIVECOMMONS.ORG/LICENSES/BY/3.0)], VIA WIKIMEDIA COMMONS)
https://mrcemsuccess.com/explanation/thyroid-gland/?_sft_qc=neck&sf_paged=2 2/4
Relations
It lies deep to the sternohyoid, sternothyroid and omohyoid muscles, in the
visceral compartment of the neck, together with and anterior to the pharynx,
trachea and oesophagus, and surrounded by the pretracheal fascia.
Structures vulnerable in thyroid surgery include:
Thyroidea ima artery
Inferior thyroid vein
Anterior jugular vein
Recurrent laryngeal nerve
Cervical dome of the pleura
Oesophagus
Parathyroid glands
Blood Supply
The thyroid gland is supplied predominantly by the superior thyroid artery
(branch of the external carotid artery) and the inferior thyroid artery (branch
of the thyrocervical trunk from the subclavian artery). Occasionally a small
thyroidea ima artery arises from the brachiocephalic trunk or the arch of the
aorta and ascends to supply the thyroid gland.
Venous Drainage
The venous drainage of the thyroid is to the superior and middle thyroid veins
(draining to the internal jugular vein) and the inferior thyroid veins (draining to
the brachiocephalic veins).
Lymphatic Drainage
Lymphatic drainage of the thyroid gland is to nodes beside the trachea
(paratracheal nodes) and to deep cervical nodes inferior to the omohyoid
muscle along the internal jugular vein.
Recurrent Laryngeal Nerve

The thyroid gland is closely related to the recurrent laryngeal nerves. After
branching from the vagus nerve and looping around the subclavian artery on
the right and the arch of the aorta on the left, the recurrent laryngeal nerves
ascend in the neck in a groove between the trachea and oesophagus. They
pass deep to the posteromedial surface of the lateral lobes of the thyroid
gland and enter the larynx by passing deep to the lower margin of the inferior
constrictor of the pharynx.
The recurrent laryngeal nerve is the most commonly injured nerve during
thyroid surgery. The recurrent laryngeal nerves supply sensory innervation to
the laryngeal cavity below the level of the vocal folds and motor innervation
to all intrinsic muscles of the larynx except for the cricothyroid muscle.
8/26/22, 5:08 PM Trachea (Neck) - MRCEM Success
Anatomy Head and Neck Neck
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Trachea (Neck) LAST UPDATED: 11TH

APRIL 2019
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The trachea begins at vertebral level C6, where it is continuous with the larynx
above. The trachea lies directly anterior to the oesophagus and
travels inferiorly to pass through the thoracic inlet.
Cricothyrotomy
A cricothyrotomy is performed to provide a temporary emergency airway in
situations where there is obstruction at or above the level of the larynx, such
that oral/nasal endotracheal intubation is impossible e.g. as a result of
inhalation of a foreign body, severe oedema secondary to anaphylactic
reaction, or severe head and neck trauma.
Compared with an emergency tracheostomy, it is quicker and easier to perform
and associated with fewer complications. It involves making an opening in the
median cricothyroid ligament (the medial part of the cricothyroid membrane),
between the cricoid and thyroid cartilages of the larynx. The ligament can be
palpated in the midline and usually there are only small blood vessels,
connective tissue and skin overlying it.
https://mrcemsuccess.com/explanation/trachea-5/?_sft_qc=neck&sf_paged=2 2/4
STRUCTURE OF THE LARYNX (ANTERIOR VIEW). (IMAGE BY OLEK REMESZ (WIKI-PL:

OREM, COMMONS: OREM) [CC BY-SA 2.5-2.0-1.0], VIA WIKIMEDIA COMMONS)
Tracheostomy
At a lower level, the airway can be accessed surgically (or percutaneously)
through the anterior wall of the trachea by tracheostomy. Tracheostomy is
usually performed in non-emergency situations.
A small transverse incision is placed in the lower third of the neck anteriorly.
The strap (infrahyoid) muscles are deviated laterally and the trachea can be
easily visualised. Occasionally it is necessary to divide the isthmus of the
thyroid. An incision is typically made between the second and third or the third
and fourth tracheal rings and a small tracheostomy tube inserted.
This route of entry is complicated because large veins and part of the thyroid
gland overlie this region. Structures particularly vulnerable include the isthmus
of the thyroid, the jugular arch connecting the anterior jugular veins, the
inferior thyroid vein, the left brachiocephalic vein, the thyroidea ima artery, and
the recurrent laryngeal nerve (less commonly).
COMPLETED TRACHEOSTOMY: 1) VOCAL FOLDS, 2) THYROID CARTILAGE, 3) CRICOID

CARTILAGE, 4) TRACHEAL RINGS, 5) BALLOON CUFF. (IMAGE BY JEREMYKEMP
[COPYRIGHTED FREE USE], VIA WIKIMEDIA COMMONS)
8/26/22, 5:08 PM Subclavian Artery - MRCEM Success
Subclavian Artery LAST UPDATED: 12TH

FEBRUARY 2019
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The subclavian arteries on both sides arch upward out of the thorax to enter
the root of the neck.
The right subclavian artery begins posterior to the sternoclavicular joint as a
branch of the brachiocephalic trunk.
The left subclavian artery begins more inferiorly as a direct branch of the arch
of the aorta and ascends posterior to the left common carotid artery.
SUBCLAVIAN ARTERY. (IMAGE BY HENRY VANDYKE CARTER [PUBLIC DOMAIN], VIA

WIKIMEDIA COMMONS)
https://mrcemsuccess.com/explanation/subclavian-artery-3/?_sft_qc=neck&sf_paged=2 2/3
8/26/22, 5:08 PM Subclavian Artery - MRCEM Success
Each subclavian artery arches superiorly and laterally to pass anterior to the
extension of the pleural cavity in the root of the neck and posterior to the
anterior scalene muscle, becoming the axillary artery as it crosses the lateral
border of rib I.
ROOT OF THE NECK. (IMAGE MODIFIED BY FRCEM SUCCESS. ORIGINAL BY HENRY

https://mrcemsuccess.com/explanation/subclavian-artery-3/?_sft_qc=neck&sf_paged=2 3/3
8/26/22, 5:09 PM Subclavian Vein - MRCEM Success
Subclavian Vein LAST UPDATED: 11TH

APRIL 2019
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The subclavian veins begin at the lateral margin of rib I as continuations of the
axillary veins. Passing medially on each side, just anterior to the anterior
scalene muscles, each subclavian vein is joined by the internal jugular vein to
form the brachiocephalic vein.
Central Venous Cannulation

Central venous cannulation may be performed via the internal jugular vein or
subclavian vein.
To gain subclavian access, the clavicle is identified and the needle placed in
the infraclavicular region (in the midclavicular line or lateral to this line), aiming
superomedially. As the subclavian vein passes inferiorly, posterior to the
clavicle, it passes over the apex of the lung. Any misplacement of a needle into
or through this structure may puncture the apical pleura, producing a
pneumothorax. Inadvertent arterial puncture and vein laceration may also
produce a haemopneumothorax.
Cannulation of the internal jugular vein carries fewer risks but local
haematoma and damage to the carotid artery are important considerations.
https://mrcemsuccess.com/explanation/subclavian-vein/?_sft_qc=neck&sf_paged=2 2/2
8/26/22, 5:10 PM Sympathetic Trunk - MRCEM Success
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Sympathetic Trunk LAST UPDATED: 11TH

APRIL 2019
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The sympathetic trunks are two parallel cords that run from the base of the skull to
the coccyx. Along the way they are punctuated by ganglia, collections of neuronal
cell bodies outside of the CNS. The cervical part of the sympathetic trunk is anterior
to the longus colli and longus capitis muscles and posterior to the common carotid
artery in the carotid sheath.
There are three ganglia along the course of the sympathetic trunk in the cervical
region within which ascending preganglionic sympathetic fibres from upper
thoracic spinal cord levels synapse with postganglionic sympathetic fibres. The
postganglionic fibres are distributed from these ganglia in branches, called grey
rami communicantes, which connect with cervical spinal nerves C1 - C8.
https://mrcemsuccess.com/explanation/sympathetic-trunk/?_sft_qc=neck&sf_paged=2 2/4
CERVICAL GANGLIA OF THE SYMPATHETIC TRUNK. (IMAGE BY HENRY VANDYKE CARTER

[PUBLIC DOMAIN])
Superior Cervical Ganglion

The superior cervical ganglion is responsible for sympathetic innervation to the
structures in the head and neck. The superior cervical ganglion lies in the area of
vertebrae C1 - C2 and has branches to:
the internal and external carotid arteries
the cervical spinal nerves C1 - C4
the pharynx
the heart
Middle Cervical Ganglion

The middle cervical ganglion lies in the area of vertebra C6 and has branches to:
cervical spinal nerves C5 - C6

the heart
Inferior Cervical Ganglion

The inferior cervical ganglion lies in the area of vertebra C7 (anterior to the neck of
rib I, posterior to the first part of the subclavian artery), combines with the first
thoracic ganglion to form the cervicothoracic ganglion and has branches to:
spinal nerves C7 - T1
the vertebral and subclavian artery
the heart
This ganglion may also receive white rami communicantes from thoracic spinal
nerves T1 - T2.
Horner's Syndrome
The sympathetic fibres can be stretched or damage along their course and if
unilaterally disturbed may produce Horner's syndrome, a triad of partial ptosis (due
to paralysis of the superior tarsal muscle), miosis (due to paralysis of the dilator
pupillae muscle) and anhidrosis (due to loss of innervation to the sweat glands).
Secondary changes may also include ipsilateral vasodilation (due to loss of
sympathetic control of subcutaneous blood vessels) and enophthalmos (due to
paralysis of the orbitalis muscle).
Possible causes of Horner's syndrome include:
Apical lung tumour (Pancoast's tumour) eroding the cervicothoracic ganglion
Thyroid carcinoma
Penetrating injury to neck
Lymphadenopathy
Cervical rib
Injury to carotid arteries
8/26/22, 5:11 PM Pharynx - MRCEM Success
Pharynx LAST UPDATED: 11TH

APRIL 2019
ANATOMY / HEAD AND NECK / PHARYNX
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The pharynx is a musculofascial structure that connects the oral and nasal
cavities in the head to the larynx and the oesophagus in the neck.
Anatomical Location
The pharynx is attached above to the base of the skull, and is continuous below,
approximately at the level of vertebra C6, with the top of the oesophagus.
The pharynx is separated from the posterior vertebral column by a thin
retropharyngeal space, bordered anteriorly by the buccopharyngeal fascia and
posteriorly by the prevertebral fascia.
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8/26/22, 5:11 PM Pharynx - MRCEM Success
RELATIONS OF THE PHARYNX. (IMAGE BY OPENSTAX COLLEGE [CC BY 3.0], VIA

WIKIMEDIA COMMONS)
Arrangement
The walls of the pharynx are attached anteriorly to the margins of the nasal
cavities, oral cavity and larynx, dividing the pharynx into the continuous
nasopharynx, oropharynx and laryngopharynx respectively.
The posterior apertures of the nasal cavities open into the nasopharynx, the
oropharyngeal isthmus opens into the oropharynx and the superior aperture of
the larynx opens into the laryngopharynx.
The pharyngotympanic tubes (from the middle ear) open into the lateral walls of
the nasopharynx.
Muscles
The muscles of the pharyngeal wall are organised into two groups:
The three sheet-like constrictor muscles constrict the pharyngeal cavity
sequentially to move a bolus of food through the pharynx and into the
oesophagus during swallowing.
The three longitudinal muscles elevate the pharyngeal wall, or during
swallowing, pull the pharyngeal wall up and over a bolus of food being
moved through the pharynx into the oesophagus.
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8/26/22, 5:11 PM Soft Palate - MRCEM Success
Soft Palate LAST UPDATED: 22ND

DECEMBER 2019
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Soft Palate
The soft palate continues posteriorly from the hard palate and acts as a valve
that can be:
depressed to help close the oropharyngeal isthmus and seal off the oral
cavity from the oropharynx
elevated to separate the nasopharynx from the oropharynx.
The soft palate is formed and moved by five paired muscles.
Uvula
The small muscular projection that hangs from the posterior free margin of the
soft palate is the uvula.
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OROPHARYNX. (IMAGE BY HENRY VANDYKE CARTER [PUBLIC DOMAIN], VIA

WIKIMEDIA COMMONS)
Innervation
MOTOR:
All of the muscles of the soft palate are innervated by the vagus nerve (from
the pharyngeal plexus), except for the tensor veli palatini, which is innervated
by a branch of the mandibular nerve. Normally, the palate elevates evenly in
the midline. In a palsy of the vagus nerve, the uvula will deviate away from the
affected side.
SENSORY:
General sensation to the palate is supplied by the greater and lesser palatine
nerves and the nasopalatine nerve (general sensory fibres carried in all these
nerves originate in the pterygopalatine fossa from the maxillary nerve).
AUTONOMIC:
Parasympathetic fibres to glands and special afferent fibres carrying taste
from the soft palate are carried in the facial nerve and join the nerves in the
pterygopalatine fossa, as do the sympathetic fibres, ultimately derived from
the T1 spinal cord level.
8/26/22, 5:12 PM Tonsils - MRCEM Success
Tonsils LAST UPDATED: 11TH

APRIL 2019
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Technically, there are three sets of tonsils in the body: the adenoid tonsil, the
palatine tonsils, and the lingual tonsil.
TONSILS. (IMAGE BY BLAUSEN.COM STAFF. “BLAUSEN GALLERY 2014”. WIKIVERSITY

JOURNAL OF MEDICINE. DOI:10.15347/WJM/2014.010. ISSN 20018762. (OWN WORK)
[CC BY 3.0 (HTTP://CREATIVECOMMONS.ORG/LICENSES/BY/3.0)], VIA WIKIMEDIA
COMMONS)
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Lingual Tonsil
The lingual tonsil is a large collection of lymphoid tissue found on the
pharyngeal surface (posterior one-third) of the tongue.
Adenoid Tonsil
The adenoid (pharyngeal) tonsil is a large collection of lymphoid tissue in the
mucosa covering the roof of the nasopharynx.
Palatine Tonsils
The palatine tonsils are on the lateral walls of the oropharynx. On each side
there is a large ovoid collection of lymphoid tissue in the mucosa lining the
superior constrictor muscle, between the palatoglossal and palatopharyngeal
arches and just posterior to the oropharyngeal isthmus.
PALATINE TONSILS. (IMAGE MODIFIED BY FRCEM SUCCESS. ORIGINAL BY HENRY

Blood Supply
The palatine tonsils are highly vascular, receiving blood from the ascending
palatine and tonsillar branches of the facial artery, the descending palatine
branch of the maxillary artery, a palatine branch of the ascending pharyngeal
artery and a branch of the lingual artery.
Tonsillectomy may result in severe haemorrhage, which may occur from the
branches of the facial, ascending pharyngeal, maxillary and lingual arteries, or
from peritonsillar veins.
Lymphatic Drainage
The lymphatic drainage of the palatine tonsils drains through the pharyngeal
wall into the jugulodigastric nodes in the region where the facial vein drains
into the internal jugular vein, inferior to the posterior belly of the digastric
muscle.
8/26/22, 5:12 PM Cutaneous Innervation of Face - MRCEM Success
Cutaneous Innervation of LAST UPDATED: 16TH

JUNE 2022
Face  Bookmark
ANATOMY / HEAD AND NECK / FACE
The trigeminal nerve divides into three major divisions: the ophthalmic (V1),
maxillary (V2) and mandibular (V3) nerves which supply the skin of the face.
CUTANEOUS INNERVATION OF THE HEAD. (IMAGE BY PATRICK J. LYNCH, MEDICAL

ILLUSTRATOR [CC BY 2.5], VIA WIKIMEDIA COMMONS)
Ophthalmic Nerve
The ophthalmic nerve exits the skull through the superior orbital fissure to enter
the orbit. It gives rise to five cutaneous branches that supply the face:
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8/26/22, 5:12 PM Cutaneous Innervation of Face - MRCEM Success
the supraorbital nerve (innervating skin of the upper eyelid and conjunctiva
and the skin of the upper forehead extending back to the middle of the
scalp)
the supratrochlear nerve (innervating skin of the lower central part of the
forehead and conjunctiva and skin of the upper eyelid)
the infratrochlear nerve (innervating the medial half of the upper eyelid and
the skin in the area of the medial angle and the bridge of the nose)
the lacrimal nerve (innervating the lateral half of the upper eyelid and the
skin in the area of the lateral angle)
the external nasal nerve (innervating the anterior lower half of the nose).
Maxillary Nerve
The maxillary nerve exits the skull through the foramen rotundum and gives rise
to three cutaneous branches that supply the face:
the zygomaticotemporal nerve (innervating a small area of the anterior
temple above the zygomatic arch)
the zygomaticofacial nerve (innervating a small area of skin over the
zygomatic bone)
the infraorbital nerve (innervating the lower eyelid, the cheek, the side of
the nose and the upper lip).
Mandibular Nerve
The mandibular nerve exits the skull through the foramen ovale and gives rise to
three cutaneous branches that supply the face:
the auriculotemporal nerve (innervating the external acoustic meatus, the
surface of the tympanic membrane and a large area of the temple)
the buccal nerve (innervating the cheek)
the mental nerve (innervating the skin and mucous membranes of the
lower lip and the skin of the chin).
https://mrcemsuccess.com/explanation/trigeminal-nerve-anatomy/?_sft_qc=face 3/3
8/26/22, 5:13 PM Facial Muscles - MRCEM Success
Facial Muscles LAST UPDATED: 11TH

APRIL 2019
 Bookmark
The facial muscles act as muscles of facial expression, and as sphincters and dilators
of the orifices of the face.
The facial muscles are all innervated by the facial nerve (CN VII).
Table: Function of the Facial Muscles

Muscle Function
Orbicularis oculi Closes eyelids gentle and forcefully
Occipitofrontalis Raises eyebrows and wrinkles forehead
Orbicularis oris Closes lips and protrudes lips as in whistling
Buccinator Presses cheek against teeth, aids in forceful expulsion of
air from distended cheeks
Orbicularis Oculi
The orbicularis oculi is a large muscle located over the frontal and zygomatic bones
and is responsible for closure of the eyelids, both gently (palpebral part) and forcefully
as in screwing the eyes up (orbital part).
Occipitofrontalis
The occipitofrontalis is responsible for wrinkling the forehead, raising the eyebrows
and drawing the scalp backwards. It has two bellies, the occipital belly originating
from the superior nuchal line of the occipital bone and mastoid process of the
temporal bone, and the frontal belly originating from the skin of the eyebrows; both
heads insert onto the epicranial aponeurosis.
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8/26/22, 5:13 PM Facial Muscles - MRCEM Success
Orbicularis Oris
The orbicularis oris is a complex muscle consisting of fibres that completely encircle
the mouth, responsible for closing the lips and protruding the lips (as in whistling).
Buccinator
The buccinator originates from the posterior parts of the maxilla and mandible, deep
to the other facial muscles. Its muscle fibres run forwards to blend with those of the
orbicularis oris muscle and to insert into the modiolus, which is a small button-
shaped nodule of connective tissue at the interface between the muscles of the lips
and cheeks on each side. The buccinator is responsible for pressing the cheek against
the teeth which helps keeps the cheek taut and aids in mastication by preventing
food from accumulating between the teeth and cheek. The muscle also assists in the
forceful expulsion of air from the cheeks by compressing the distended cheeks.
MUSCLES OF THE FACE. (IMAGE BY OPENSTAX [CC BY 4.0], VIA WIKIMEDIA COMMONS)

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8/26/22, 5:13 PM Facial Vein - MRCEM Success
Facial Vein LAST UPDATED: 11TH

APRIL 2019
 Bookmark
The facial vein is the major vein draining the face. It originates near the medial
corner of the eye from the union of the supratrochlear and supraorbital veins,
receives tributaries draining the eyelids, the external nose, the lips, cheeks and chin
throughout its course, and drains into the internal jugular vein.
Connections
As it crosses the face, the facial vein has numerous connections:
near the medial corner of the orbit, it communicates with ophthalmic veins
in the area of the cheek, it communicates with veins passing into the
infraorbital foramen
it also communicates with veins passing into deeper regions of the face i.e.
the deep facial vein connecting with the pterygoid plexus of veins
Cavernous Sinus
All these venous channels have interconnections with the intracranial cavernous
sinus through emissary veins that connect intracranial with extracranial veins.
There are no valves in the facial vein, or any other venous channels in the head, so
blood can move in any direction. This means infections of the face, primarily above
the mouth, should be treated with caution to prevent the dissemination of
infectious material in an intracranial direction.
Although cavernous sinus thrombosis (CST) is rare, it most commonly has an
infectious aetiology (most commonly from spread of infection from the sinuses or
middle third of the face, or less commonly secondary to dental abscess or orbital
cellulitis).
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8/26/22, 5:13 PM Facial Vein - MRCEM Success
VEINS OF THE HEAD AND NECK. (IMAGE BY OPENSTAX COLLEGE [CC BY 3.0
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8/26/22, 5:14 PM Arterial Supply of Face - MRCEM Success
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Arterial Supply of Face LAST UPDATED: 6TH

NOVEMBER 2020
 Bookmark
Facial Artery
The facial artery, branch of the external carotid artery, is the major blood
vessel supplying the face.
After arising from the external carotid artery, the facial artery passes up
through the deep structures of the neck and appears at the lower border
of the mandible after passing posterior to the submandibular gland.
Curving around the inferior border of the mandible, just anterior to the
masseter muscle, the facial artery then enters the face where it runs
upwards and medially in a tortuous course. It passes along the side of the
nose and terminates as the angular artery at the medial corner of the eye.
Transverse Facial Artery

Another contributor to the vascular supply of the face is the transverse
facial artery, which arises from the superficial temporal artery within the
substance of the parotid gland.
Superficial Temporal Artery

The superficial temporal artery is the smaller of the two terminal branches
of the external carotid artery; it passes superiorly, just anterior to the ear,
divides into anterior and posterior branches and supplies almost the entire
lateral aspect of the scalp.
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8/26/22, 5:14 PM Arterial Supply of Face - MRCEM Success
BLOOD SUPPLY OF THE FACE. (IMAGE MODIFIED BY FRCEM SUCCESS. ORIGINAL

BY HENRY VANDYKE CARTER [PUBLIC DOMAIN], VIA WIKIMEDIA COMMONS)
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8/26/22, 5:15 PM Lymphatic Drainage of Face - MRCEM Success
RELATED TOPICS
Anatomy Head and Neck Face
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Lymphatic Drainage of LAST UPDATED: 11TH

APRIL 2019
Face  Bookmark
Lymphatic drainage of the face primarily moves towards three groups of lymph
nodes.
Submental Nodes
Submental nodes, inferior and posterior to the chin, drain lymphatics from the
medial part of the lower lip and chin bilaterally (in addition to the tip of the
tongue).
Submandibular Nodes
Submandibular nodes, superficial to the submandibular gland and inferior to
the body of the mandible, drain lymphatics from the medial corner of the orbit,
most of the external nose, the medial part of the cheek, the upper lip and the
lateral part of the lower lip.
Preauricular and Parotid Nodes

The preauricular and parotid nodes, anterior to the ear, drain lymphatics from
most of the eyelids, a part of the external nose and the lateral part of the cheek
(in addition to the external acoustic meatus and the posterior orbit).
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8/26/22, 5:15 PM Lymphatic Drainage of Face - MRCEM Success
LYMPHATIC DRAINAGE OF THE FACE. (IMAGE BY HENRY VANDYKE CARTER [PUBLIC

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8/26/22, 5:16 PM Cranial Nerve V: Trigeminal Nerve - MRCEM Success
Cranial Nerve V: Trigeminal LAST UPDATED: 23RD

APRIL 2020
Nerve  Bookmark
ANATOMY / CRANIAL NERVE LESIONS / HEAD AND NECK /
FACE
The trigeminal nerve (CN V) is the largest cranial nerve, originating from three sensory
nuclei and one motor nucleus extending from the midbrain to the medulla and exiting
the brainstem from the pons.
Table: Overview of the Trigeminal Nerve

Cranial Trigeminal Nerve (CN V)
Nerve
Key Arises from several nuclei in the brainstem, exits brainstem from
anatomy pons
Sensory Face, oral and nasal cavities, frontal sinus, external ear, afferent
function pathway of corneal reflex
Motor Muscles of mastication, tensor tympani, tensor veli palatini,
function mylohyoid, anterior belly of digastric, parasympathetic fibres to
lacrimal and nasal glands
Assessment Sensation of face, jaw jerk, corneal blink reflex, power/bulk of
muscles of mastication
Clinical Flaccid paralysis of muscles of mastication, jaw deviation towards
effects of affected side, loss of sensation to face, loss of afferent corneal
injury reflex, loss of jaw jerk
Causes of Trauma, anaesthetic block, tumours, cavernous sinus disease
injury
Anatomical Course
The trigeminal nerve is a mixed motor and sensory nerve. It has three main divisions:
V1 ophthalmic
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V2 maxillary
V3 mandibular
TRIGEMINAL NERVE. (IMAGE BY HENRY VANDYKE CARTER [PUBLIC DOMAIN], VIA WIKIMEDIA
COMMONS)
Function
The trigeminal nerve supplies:
Sensation to the face, mucous membranes of the nasal and oral cavities and
frontal sinus, teeth, hard palate, soft palate and deep structures of the head
(proprioception from muscles and the TMJ), the dura of the anterior and middle
cranial fossa and the external ear
The afferent pathway for the corneal reflex
The muscles of mastication (temporalis, masseter, lateral and medial pterygoids)
The tensor tympani muscle of the middle ear
The tensor veli palatini muscle of the soft palate
The mylohyoid and the anterior belly of the digastric muscles
Parasympathetic fibres to lacrimal and nasal glands
Assessment
The trigeminal nerve can be assessed by:
Testing sensation of the face (testing both light touch and pin prick)
Testing muscles of mastication by asking the patient to clench their teeth and
palpating for contraction in the temporalis and masseter muscle (or by asking the
patient to open their mouth and move their jaw from side to side)
Testing the corneal reflex
Testing the jaw reflex
Likely Causes of Disease or Injury

The trigeminal nerve may be damaged by:
Fractures of the middle third of the face (V2)
Trauma to the mandible (V3)
Anaesthetic block of the inferior alveolar nerve (V3)
Basal skull fractures
Tumours e.g. of the maxillary antrum and nasopharynx (V3)
Cavernous sinus pathology (V1)
Trigeminal neuralgia (sensory disorder characterised by severe shooting pains
usually in the distribution of V2 or V3)
All three branches have bilateral cortical representation so a unilateral central lesion, for
example a stroke, does not usually produce a deficit.
Common Clinical Effects

CN V palsy results in:
Flaccid paralysis of the muscles of mastication
Jaw deviation to the paralysed side (due to unopposed action of the opposite
lateral pterygoid)
Loss of sensation over the areas innervated by the three divisions of the
trigeminal nerve
Loss of the corneal reflex (afferent pathway)
Loss of jaw jerk
Paralysis of tensor tympani muscle leading to hypoacusis
8/26/22, 5:16 PM Cranial Nerve V2: Maxillary Nerve - MRCEM Success
Cranial Nerve V2: Maxillary LAST UPDATED: 11TH

APRIL 2019
Nerve  Bookmark
FACE / INFRATEMPORAL FOSSA
The maxillary nerve is the second branch of the trigeminal nerve.
Functional Overview
The maxillary nerve (via its branches) supplies sensation to:
the orbital wall
the sphenoidal and ethmoidal sinuses
the mucosa and glands of the hard palate and associated gingiva
the nasal cavity
the soft palate
the upper teeth and associated gingiva
the nasopharynx
skin over the temple and the zygomatic bone
the maxillary sinus
the lateral aspect of the external nose and part of the nasal septum
skin of the lower eyelid and its conjunctiva
skin over the cheek and upper lip and associated oral mucosa
part of the cranial dura mater.
It also supplies parasympathetic fibres to the lacrimal glands and nasal glands.
Anatomical Course
The maxillary nerve originates from the trigeminal ganglia in the cranial cavity and, after
passing through the lateral wall of the cavernous sinus, enters the pterygopalatine
fossa through the foramen rotundum.
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8/26/22, 5:16 PM Cranial Nerve V2: Maxillary Nerve - MRCEM Success
TRIGEMINAL NERVE. (IMAGE BY HENRY VANDYKE CARTER [PUBLIC DOMAIN], VIA WIKIMEDIA
COMMONS)
Branches
The maxillary nerve gives rise to numerous sensory branches:
In the cranium
Middle meningeal nerve
In the pterygopalatine fossa
Zygomatic nerve
Zygomaticotemporal nerve (innervating a small area of the anterior
temple above the zygomatic arch)
Zygomaticofacial nerve (innervating a small area of skin over the
zygomatic bone)
Nasopalatine nerve
Posterior superior alveolar nerve
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8/26/22, 5:16 PM Cranial Nerve VII: Facial Nerve - MRCEM Success
Cranial Nerve VII: Facial Nerve LAST UPDATED: 11TH

APRIL 2019
FACE  Bookmark
The facial nerve (CN VII) mediates facial movements, taste, salivation and lacrimation.
Table: Overview of the Facial Nerve

Cranial Facial Nerve (CN VII)
Nerve
Key Exits brainstem in cerebellopontine angle, enters internal
anatomy auditory meatus and facial canal, exits facial canal and skull via
stylomastoid foramen
Motor Muscles of facial expression, posterior belly of digastric muscle,
function stylohyoid muscle, stapedius muscle, parasympathetic
innervation to lacrimal, salivary, oral, pharyngeal and nasal
glands, efferent pathway of corneal blink reflex
Sensory Taste to anterior two-thirds of tongue
function
Assessment Facial movements, corneal blink reflex
Clinical Facial weakness, loss of efferent corneal reflex, impaired lacrimal
effects of fluid production, hyperacusis, impaired sense of taste to anterior
injury two-thirds of tongue, impaired salivation
Causes of Bell’s palsy, Ramsay-Hunt syndrome, Guillain-Barre syndrome,
injury mumps, middle ear disease, tumours, trauma
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Function
The facial nerve provides motor innervation to the muscles of facial expression, the
posterior belly of the digastric, the stylohyoid and the stapedius muscles. The chorda
tympani branch supplies taste to the anterior two-thirds of the tongue. The facial nerve
also carries parasympathetic innervation to the lacrimal glands, salivary glands, nasal,
palatine and pharyngeal mucous glands.
Anatomical Course
The facial nerve arises in the pons, leaves the brainstem in the cerebellopontine angle
and exits the posterior cranial fossa through the internal acoustic meatus in the
temporal bone before entering the facial canal still within the temporal bone where it
gives rise to three main branches:
The nerve to the stapedius (innervating the stapedius muscle)
The greater petrosal nerve (supplying parasympathetic innervation to the lacrimal
gland and the mucous glands of the oral cavity, nose and pharynx)
The chorda tympani (supplying taste to the anterior two-thirds of the tongue and
parasympathetic innervation to all salivary glands below the level of the oral
fissure)
The facial nerve exits the facial canal (and the basal skull) through the stylomastoid
foramen between the styloid and mastoid processes of the temporal bone, at which
point it gives off the posterior auricular nerve (innervating the occipital belly of the
occipitofrontalis muscle of the scalp and external ear muscles).
ANATOMICAL COURSE OF THE FACIAL NERVE. (IMAGE MODIFIED BY FRCEM SUCCESS. ORIGINAL
BY PATRICK J. LYNCH, MEDICAL ILLUSTRATOR (PATRICK J. LYNCH, MEDICAL ILLUSTRATOR) [CC
BY 2.5 (HTTP://CREATIVECOMMONS.ORG/LICENSES/BY/2.5)], VIA WIKIMEDIA COMMONS)
The facial nerve then gives off motor branches (innervating the posterior belly of the
digastric muscle and the stylohyoid muscle) before entering the deep surface of the
parotid gland.
Once in the parotid gland, the facial nerve divides into five terminal branches:
The temporal branch (innervating muscles in the temple, forehead and
supraorbital areas)
The zygomatic branch (innervating muscles in the infraorbital area, the lateral
nasal area and the upper lip)
The buccal branch (innervating muscles in the cheek, the upper lip and the corner
of the mouth)
The marginal mandibular branch (innervating muscles of the lower lip and chin)
The cervical branch (innervating the platysma muscle)
TERMINAL BRANCHES OF THE FACIAL NERVE. (IMAGE BY PATRICK J. LYNCH, MEDICAL

ILLUSTRATOR (PATRICK J. LYNCH, MEDICAL ILLUSTRATOR) [CC BY 2.5
(HTTP://CREATIVECOMMONS.ORG/LICENSES/BY/2.5)], VIA WIKIMEDIA COMMONS)
Assessment
The facial nerve can be assessed by:
Looking for symmetry in the face at rest
Asking the patient to perform the following movements
Raising their eyebrows
Closing their eyes tightly
Blowing out their cheeks
Smiling

Causes of CN VII palsy include:
Bell's palsy (idiopathic)
Ramsay-Hunt syndrome (herpes zoster infection of the CN VII motor ganglion)

Guillain-Barre syndrome
Botulism
Infection e.g. mumps, measles, chickenpox, otitis externa/media, encephalitis,
mastoiditis
Tumours e.g. parotid tumours, cerebellopontine angle tumours
Fractures of the petrous temporal bone
Blunt/penetrating trauma to the face or during parotid surgery
Penetrating injury to the middle ear or barotrauma
Brainstem injury
Upper motor neuron (UMN) facial nerve palsy warrants CT head to exclude
cerebrovascular events and other intracranial causes such as tumours, particularly
cerebellopontine angle tumours.

Injury to the facial nerve may result in:
Ipsilateral facial weakness with flattening of the nasolabial fold and dropping of
the corners of the mouth, drooping of the lower eyelid and inability to close the
eye
Loss of corneal reflex (due to paralysis of the orbicularis oculi muscle)
Impaired lacrimal fluid production (due to impaired function of the greater
petrosal nerve)
Hyperacusis (hypersensitivity to sound due to impaired function of the nerve to
the stapedius)
Impaired sense of taste to anterior two-thirds of tongue and impaired salivation
(due to impaired function of the chorda tympani)
If the damage is peripheral (LMN), the forehead will be involved and there will be an
inability to close the eyes or raise the eyebrows. If the damage is central (UMN) there is
forehead sparing as the frontalis and orbicularis oculi muscles are innervated bilaterally.
8/26/22, 5:17 PM External Nose - MRCEM Success
External Nose LAST UPDATED: 11TH

APRIL 2019
ANATOMY / HEAD AND NECK /
NOSE AND PARANASAL REGION  Bookmark
Blood Supply
The blood supply to the external nose is derived mainly from branches of the
ophthalmic and facial arteries.
Innervation
The cutaneous supply of the external nose is from:
the external nasal nerve (ophthalmic nerve) innervating the anterior
lower half of the nose
the infratrochlear nerve (ophthalmic nerve) innervating the bridge of the
nose
the infraorbital nerve (maxillary nerve) innervating the sides of the nose
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8/26/22, 5:18 PM Nasal Cavity - MRCEM Success
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Nasal Cavity LAST UPDATED: 11TH

APRIL 2019
The nasal cavities are separated from each other by a midline nasal septum,
from the oral cavity below by the hard palate and from the cranial cavity above
by parts of the frontal, palatine, ethmoid and sphenoid bones. The nasal cavity
is lined by ciliated epithelial cells which help trap and remove particulate
matter from the airway.
Boundaries
Table: Anatomical Boundaries of the Nasal Cavity

Space Nasal Cavity
Floor Hard palate (palatine process of maxilla and horizontal plate of
palatine bone)
Roof Frontal bone, nasal bone, cribriform plate of ethmoid bone,
sphenoid bone
Medial Thin nasal septum (formed primarily from perpendicular plate
wall of ethmoid bone, vomer and septal cartilage)
Lateral Ethmoid bone, nasal bone, palatine bone, sphenoid bone,
wall lacrimal bone, maxilla, conchae
Each nasal cavity has a floor, a roof, a medial and a lateral wall.
The floor of each nasal cavity consists of soft tissues of the external nose and
the upper surface of the palatine process of the maxilla and the horizontal
plate of the palatine bone (which together form the hard palate).
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The roof of the nasal cavity is formed:

anteriorly by the nasal spine of the frontal bone and the nasal bones, and
the lateral processes of the septal cartilage and cartilages of the
external nose
centrally by the cribriform plate of the ethmoid bone
posteriorly by the sphenoid bone and palatine bone.
The medial wall of the nasal cavity is the mucosa-covered surface of the thin
nasal septum.
Bony support for the lateral wall of the nasal cavity is provided by the ethmoid
bone, palatine bone, sphenoid bone, lacrimal bones and maxillae.
CORONAL SECTION OF NASAL CAVITIES. (IMAGE BY HENRY VANDYKE CARTER

Conchae
The lateral wall is characterised by three curved shelves of bone - the conchae
- which run one above the other and project medially and inferiorly across the
nasal cavity. These conchae increase the surface area of contact between
tissues of the lateral wall and respired air.
The conchae divide each nasal cavity into four air channels:
an inferior nasal meatus (between the inferior concha and the nasal
floor)
a middle nasal meatus
a superior nasal meatus
a sphenoethmoidal recess (between the superior concha and the nasal
roof).
The openings of the paranasal sinuses are on the lateral wall and roof of the
nasal cavities.
In addition the lateral wall also contains the nasolacrimal duct opening onto
the inferior nasal meatus, draining tears from the eye into the nasal cavity.
LATERAL WALL OF THE NASAL CAVITY. (IMAGE BY HENRY VANDYKE CARTER [PUBLIC
Innervation
The nasal cavities are innervated by:
The olfactory nerve - carrying olfaction
The trigeminal nerve - carrying general sensation, anteriorly by the
ophthalmic nerve and posteriorly by the maxillary nerve
The facial nerve - carrying parasympathetic fibres to the nasal glands
(which join branches of the maxillary nerve in the pterygopalatine fossa).
Blood Supply
The nasal cavities have a rich vascular supply to allow them to alter the
humidity and temperature of respired air.
Blood supply to the nasal cavity is by terminal branches of the maxillary and
facial arteries (from the external carotid artery) and ethmoidal branches of the
ophthalmic artery (from the internal carotid artery).
The vessels form extensive anastomoses with each other, particularly in the
anterior region of the medial wall where there are anastomoses between
branches of the greater palatine (maxillary artery), sphenopalatine (maxillary
artery), superior labial (facial artery) and anterior ethmoidal arteries
(ophthalmic artery) - this area is known as Little's area and is the major site of
epistaxis.
BLOOD SUPPLY OF THE NASAL CAVITY. (IMAGE BY ASATUR BASMAJIAN VIA

WIKIMEDIA COMMONS)
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Paranasal Sinuses LAST UPDATED: 11TH

APRIL 2019
There are four paired paranasal air sinuses - the ethmoidal cells and the
sphenoidal, maxillary and frontal sinuses - named according to the bone in which
the sinus is found. The paranasal sinuses develop as outgrowths from the nasal
cavities and erode into the surrounding bones.
Location
All of the paranasal sinuses are lined by respiratory mucosa, open into the nasal
cavities and are innervated by branches of the trigeminal nerve.
The frontal sinuses are the most superior of the sinuses and drain onto the
middle meatus of the lateral wall.
The maxillary sinuses are the largest of the paranasal sinuses and drain onto
the middle meatus of the lateral wall.
The ethmoidal cells drain into the superior or middle meatus.
The sphenoidal sinuses open into the sphenoethmoidal recess of the nasal
cavity.
Developmental Staging
PARANASAL SINUSES. (IMAGE BY OPENSTAX COLLEGE [CC BY 3.0], VIA WIKIMEDIA
COMMONS)
The maxillary sinus is the first sinus to develop and is filled with fluid at birth and
undergoes two phases of growth during years 0 - 3 and again at 6 - 12 years.
The frontal sinus is the last sinus to pneumatise; it is formed by the upward
movement of anterior ethmoid cells after age 2, growth increases at age 6 and
continues until late teenage years.
The sphenoid sinus starts to pneumatise at around 2 years of age and reaches its
full size by the late teenage years.
The ethmoid sinuses are present at birth and develop rapidly, continuing to grow
and pneumatise until the age of 12.

Anatomy Head and Neck
Orbit and Eye
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Bony Orbit LAST UPDATED: 11TH

APRIL 2019
ANATOMY / HEAD AND NECK / ORBIT AND EYE
 Bookmark
The bony orbit is formed from seven bones; the maxilla, zygomatic, frontal,
ethmoid, lacrimal, sphenoid, and palatine bones.
BONES OF THE ORBIT. (IMAGE BY OPENSTAX COLLEGE [CC BY 3.0], VIA

WIKIMEDIA COMMONS)
Together they give the bony orbit the shape of a pyramid, with its apex
extending in a posteromedial direction to become the optic foramen and
the wide base extending anteriorly onto the face as the orbital rim.
Orbital Rim
The orbital rim is formed
superiorly by the frontal bone
medially by the frontal process of the maxilla
inferiorly by the zygomatic process of the maxilla and the zygomatic
bone
laterally by the zygomatic bone, the frontal process of the zygomatic
bone and the zygomatic process of the frontal bone.
Foramina
The optic nerve and the ophthalmic artery enter the orbit through the optic
canal.
The trochlear, oculomotor, abducens and ophthalmic nerves and the
superior ophthalmic vein enter the orbit through the superior orbital fissure.
The inferior ophthalmic vein enters the orbit through the inferior orbital
fissure.

Orbit and Eye
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Eyeball LAST UPDATED: 6TH

NOVEMBER 2020
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The walls of the eyeball consist of three layers:

the outer fibrous layer of the sclera posteriorly and the cornea anteriorly
the middle vascular layer of the choroid posteriorly which is continuous
with the ciliary body and iris anteriorly
the inner retina.
The anterior and posterior chambers are the areas posterior to the cornea, and
anterior to the lens. The posterior four-fifths of the eyeball, from the lens to the
retina, is the vitreous chamber filled with the vitreous body, a transparent
gelatinous substance.
EYEBALL. (IMAGE BY OPENSTAX COLLEGE [CC BY 3.0], VIA WIKIMEDIA COMMONS)
Sclera and Cornea

The sclera is an opaque white layer of dense connective tissue that provides
attachment for the muscles involved in eyeball movement.
The transparent cornea is the anterior protrusion of the eyeball. It is continuous
with the sclera anteriorly and allows light to enter the eyeball.
This outer layer receives its sensory supply from branches of the trigeminal nerve,
which acts as the afferent pathway of the corneal blink reflex (the facial nerve is
the efferent pathway of the corneal blink reflex, mediated by the orbicularis oculi
muscle).
Choroid, Lens and Ciliary Body

The choroid is posterior and represents two-thirds of the vascular layer; it is a
thin, highly vascular, pigmented layer firmly attached to the retina internally and
loosely attached to the sclera externally.
The lens is a transparent, biconvex elastic disc attached to muscles associated
with the outer wall of the eyeball, which can change its refractive ability to
maintain visual acuity.
The ciliary body extends from the anterior border of the choroid and is composed
of the ciliary muscle and the ciliary processes, from which extends the lens
attached to the suspensory ligament of the lens. Contraction of the ciliary muscle
changes the shape of the lens to accommodate the lens for near vision. The
ciliary muscle is innervated by parasympathetic fibres of the oculomotor nerve.
Iris and Pupil

The iris, the coloured part of the eye with the central opening forming the pupil,
projects outwards from the ciliary body. Smooth muscle fibres within the iris
control the size of the pupil:
The sphincter pupillae muscle is innervated by parasympathetic fibres of
the oculomotor nerve which acts as the efferent pathway of the pupillary
light reflex (the optic nerve is the afferent pathway of the pupillary light
reflex). Loss of parasympathetic innervation results in a fixed dilated pupil.
The dilator pupillae muscle is innervated by postganglionic sympathetic
fibres arising from the superior cervical ganglion. Loss of sympathetic
innervation results in a constricted pupil (miosis).
Horner's syndrome results from damage to the sympathetic chain and is
characterised by the triad of miosis, partial ptosis (due to loss of innervation to
the superior tarsal muscle) and anhidrosis.
Chambers
The anterior chamber is the area of the eyeball directly anterior to the iris.
Posterior to the iris and anterior to the lens is the smaller posterior chamber. The
chambers are continuous with each other through the pupillary opening. They are
filled with aqueous humour, which is secreted into the posterior chamber, flows
into the anterior chamber and is absorbed into the canal of Schlemm. The
aqueous humour supplies nutrients to the avascular cornea and lens and
maintains intraocular pressure. If the normal cycle of production and absorption
is disturbed, this can cause glaucoma due to raised intraocular pressure.
Retina and Optic Disc
The inner layer of the eyeball is the retina, divided into the posterior optic part and
the non-visual part, which covers the internal surface of the ciliary body and the
iris.
The optic part of the retina consists of an outer pigmented layer firmly attached
to the choroid and the neural layer attached to the pigmented layer around the
optic nerve.
The optic disc is where the optic nerve leaves the retina. Lateral to the optic disc,
a small area is the macula lutea with its central depression, the fovea centralis.
This is the thinnest area of the retina and visual sensitivity is higher here than
elsewhere in the retina because it has fewer rods and more cones.
The retina is supplied by the central retinal artery from the ophthalmic artery.

RELATED TOPICS
Orbit and Eye
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Eyelids LAST UPDATED: 16TH

AUGUST 2020
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The upper and lower eyelids are anterior structures that protect the eyeball
when closed. The space between the eyelids is the palpebral fissure.
Layers
The layers of the eyelids consist of (from anterior to posterior)
skin
subcutaneous tissue
voluntary muscle
the orbital septum (an extension of periosteum which attaches to the
tarsus)
the tarsus (a plate of dense connective tissue which provide the major
support for the eyelid)
conjunctiva (a thin membrane, composed primarily of stratified
squamous epithelium, which covers the posterior surface of each eyelid
before reflecting onto the sclera of the eyeball).
The upper and lower eyelids are basically the same, except for the addition of
two muscles in the upper eyelid, the levator palpebrae superioris and the
superior tarsal muscle, and the inferior tarsal muscle in the lower eyelid.
LAYERS OF THE EYELIDS. (IMAGE BY HENRY VANDYKE CARTER [PUBLIC DOMAIN], VIA
WIKIMEDIA COMMONS)
Muscles
The orbicularis oculi muscle is innervated by the facial nerve and closes the
eyelids. Loss of function of the orbicularis oculi causes an inability to close the
eyelids tightly and a drooping of the lower eyelid (ectropion) resulting in
spillage of tears. This leads to drying of the cornea, with subsequent ulceration
and secondary infection.
The levator palpebrae superioris muscle originates from the roof of the orbit
and inserts into the superior tarsus. It is innervated by the oculomotor nerve
and acts to raise the upper eyelid. Loss of function of the levator palpebrae
superioris muscle results in a complete ptosis.
The superior tarsal muscle is a collection of smooth muscle fibres in
companion with the levator palpebrae superioris, innervated by postganglionic
sympathetic fibres from the superior cervical ganglion, which helps to maintain
upper eyelid opening. Loss of function of the superior tarsal muscle results in a
partial ptosis.
MUSCLES OF THE EYELIDS. (IMAGE BY HENRY VANDYKE CARTER [PUBLIC DOMAIN],

Innervation
The sensory innervation of the eyelids and conjunctiva is from:
the supraorbital nerve (ophthalmic nerve)
the supratrochlear nerve (ophthalmic nerve)
the infratrochlear nerve (ophthalmic nerve)
lacrimal branches (ophthalmic nerve)
the infraorbital nerve (maxillary nerve)
Glands
Embedded in the tarsal plates are modified sebaceous tarsal glands
(Meibomian glands) which empty an oily substance onto the free margin of
each eyelid that increases the viscosity of tears and decreases the rate of
evaporation of tears from the surface of the eyeball.
Blockage and inflammation of a tarsal gland is a chalazion and is on the inner
surface of the eyelid. External sebaceous and sweat glands associated with
the eyelash follicles may also become blocked and inflamed causing a stye on
the edge of the eyelid.

Orbit and Eye
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Lacrimal Apparatus LAST UPDATED: 11TH

APRIL 2019
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The lacrimal apparatus is involved in the production, movement and drainage

of fluid from the surface of the eyeball. It is made up of the lacrimal gland and
its ducts, the lacrimal canaliculi, the lacrimal sac and the nasolacrimal duct.
Flow
The lacrimal gland is anterior in the superolateral region of the orbit.
Numerous ducts empty the glandular secretions into the lateral part of
the conjunctiva.
Fluid is moved across the surface of the eyeball from lateral to medial as
the eyelids blink.
The fluid accumulates medially in the lacrimal lake and is drained from
the lake by the lacrimal canaliculi (ducts) through the lacrimal punctum.
Passing medially the lacrimal canaliculi join the lacrimal sac.
From the lacrimal sac, the fluid drains through the nasolacrimal duct,
emptying into the inferior nasal meatus of the nasal cavity.
LACRIMAL APPARATUS. (IMAGE BY HENRY VANDYKE CARTER [PUBLIC DOMAIN], VIA
WIKIMEDIA COMMONS)

Orbital Muscles LAST UPDATED: 4TH
NOVEMBER 2019
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Movements of the Eye

The six extraocular muscles are responsible for turning or rotating the eye about its vertical,
horizontal, and anteroposterior axes.
Table: Movements of the Eyeball

Action Description Primary Muscle(s)
Elevation Moving pupil superiorly Superior rectus and
inferior oblique
Depression Moving pupil inferiorly Inferior rectus and
superior oblique
Abduction Moving pupil laterally Lateral rectus
Adduction Moving pupil medially Medial rectus
Medial rotation Rotating upper part of pupil medially Superior oblique
(intorsion) towards nose
Lateral rotation Rotating upper part of pupil laterally Inferior oblique
(extorsion) towards temple
Orbital Muscles
ORIGIN:
The recti muscles all originate as a group from a common tendinous ring at the apex of the orbit
and form a cone of muscles as they pass forward to their attachment on the eyeball.
Table: Overview of the Orbital Muscles

STRUCTURE OF THE ORBITAL MUSCLES. (IMAGE BY OPENSTAX COLLEGE [CC BY 3.0], VIA WIKIMEDIA
COMMONS)
ACTION AND INNERVATION:
Extraocular Innervation Function Clinical Assessment

Muscle (direction to move eye when
testing muscle)
Superior Oculomotor Elevation, adduction Look out and up
rectus nerve and medial rotation of
eyeball
Inferior Oculomotor Depression, adduction Look out and down
rectus nerve and lateral rotation of
eyeball
Medial Oculomotor Adduction of eyeball Look in (in horizontal plane)
rectus nerve
Lateral Abducens Abduction of eyeball Look out (in horizontal plane)
rectus nerve
Superior Trochlear Depression, abduction Look in and down
oblique nerve and medial rotation of
eyeball
Inferior Oculomotor Elevation, abduction Look in and up
oblique nerve and lateral rotation of
eyeball
ASSESSMENT:
To test the muscles in isolation, the patient can be asked to move their eyeball in certain
directions. A lateral position of the eyeball is necessary for testing the inferior and superior recti,
whereas a medial position is necessary for testing the inferior and superior oblique. This first
movement (laterally or medially) brings the axis of the eyeball into alignment with the axis of the
muscle. If the extraocular muscle being tested is paralysed, the patient will be unable to perform
the movement and will complain of diplopia.
CLINICAL TESTING: DIRECTION TO MOVE EYE WHEN TESTING MUSCLES (IMAGE BY AU.YOUSEF [CC BY-SA
4.0 (HTTPS://CREATIVECOMMONS.ORG/LICENSES/BY-SA/4.0)], FROM WIKIMEDIA COMMONS)

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Blood Supply of Orbit LAST UPDATED:

11TH APRIL 2019
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Arterial Supply
The ophthalmic artery (branch of the internal carotid artery) is the prime
artery of blood supply to the orbit and supplies all the orbital muscles,
the lacrimal gland and the eyeball.
Venous Drainage
The venous drainage of the orbit is via the superior and inferior
ophthalmic veins. Because the ophthalmic veins communicate with the
cavernous sinus via emissary veins, they act as a route by which
infections can spread to the cranial cavity and can predispose to
cavernous sinus thrombosis.
Lymphatic Drainage
The lymphatic drainage of the orbit is to deep cervical nodes via the
preauricular and parotid groups.

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Hard Palate LAST UPDATED:

22ND DECEMBER
ANATOMY / HEAD AND NECK / 2019
MOUTH AND HARD PALATE
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The roof of the oral cavity consists of the palate - the anterior hard palate
and the posterior soft palate. The hard palate separates the oral cavity
from the nasal cavities.
Boundaries
The anterior three-quarters of the hard palate are formed by the palatine
processes of the maxillae and the posterior one-quarter is formed by the
horizontal plates of the palatine bones.
In the oral cavity, the hard palate is bordered by the upper alveolar arch
anteriorly and laterally. Posteriorly the hard palate is continuous with the
soft palate.
HARD PALATE. (IMAGE BY HENRY VANDYKE CARTER [PUBLIC DOMAIN], VIA
WIKIMEDIA COMMONS)
Blood Supply
The blood supply to the palate is derived from branches from the external
carotid artery: the greater palatine branch of the maxillary artery, the
ascending palatine branch of the facial artery and the palatine branch of
the ascending pharyngeal artery.
Lymphatic Drainage
Lymphatic vessels from the palate drain into the deep cervical nodes.
Innervation
SENSORY:
The hard palate is innervated by the greater palatine and nasopalatine
nerves and the soft palate is innervated by the lesser palatine nerve.
General sensory fibres carried in all these nerves originate in the
pterygopalatine fossa from the maxillary nerve.

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Teeth LAST UPDATED: 11TH

APRIL 2019
MOUTH AND HARD PALATE  Bookmark
The teeth are attached to sockets in the upper alveolar arch on the maxilla and
the lower alveolar arch on the mandible. The gingivae are specialised regions of
oral mucosa that surround the teeth and cover adjacent regions of the alveolar
bone.
Normal Dentition
In adults, there are 32 teeth, 16 in the upper jaw and 16 in the lower jaw. On each
side in both upper and lower arches, there are two incisors, one canine, two
premolars and three molar teeth. Two successive sets of teeth develop in
humans; deciduous teeth emerging between six months and two years of age,
and permanent teeth, which begin to emerge and replace the deciduous teeth at
around age six years.
NORMAL DENTITION. (IMAGE BY HENRY VANDYKE CARTER [PUBLIC DOMAIN], VIA
WIKIMEDIA COMMONS)
Innervation
All nerves that innervate the teeth and gingiva are branches of the trigeminal
nerve. The lower teeth are innervated by the inferior alveolar nerve (branch of the
mandibular nerve). The upper teeth are innervated by the anterior, middle and
posterior superior alveolar nerves (branches of the maxillary nerve).
Anaesthesia of the inferior alveolar nerve can be performed by placing the needle
lateral to the anterior arch of the fauces (palatoglossal arch) in the oral cavity and
advancing along the medial border around the inferior third of the ramus of the
mandible. It is also possible to anaesthetise the infraorbital and buccal nerves.
Tooth Structure
The portion of the tooth exposed to the oral cavity is the dental crown, and the
portion below the dental crown is the tooth root. The dental pulp cavity exists in
the centre of the tooth containing the pulp which consist of blood vessels, lymph
vessels and nerve fibres.
STRUCTURE OF A TOOTH. (IMAGE BY BLAUSEN.COM STAFF. “BLAUSEN GALLERY 2014”.
WIKIVERSITY JOURNAL OF MEDICINE. DOI:10.15347/WJM/2014.010. ISSN 20018762.
(OWN WORK) [CC BY 3.0], VIA WIKIMEDIA COMMONS)

Tongue LAST UPDATED: 11TH
APRIL 2019
The tongue is a muscular structure that forms part of the floor of the oral cavity
and part of the anterior wall of the oropharynx. The anterior two-thirds of the
tongue are in the oral cavity. The posterior root of the tongue is attached to the
mandible and the hyoid bone. The anterior wall of the oropharynx inferior to the
oropharyngeal isthmus is formed by the upper part of the posterior one-third of
the tongue.
A pair of mucosal pouches (valleculae), one on each side of the midline, between
the base of the tongue and epiglottis, are depressions formed between the
midline mucosal fold and two lateral folds that connect the tongue to the
epiglottis.
TONGUE. (IMAGE BY OPENSTAX [CC BY 4.0], VIA WIKIMEDIA COMMONS)

Papillae and Lingual Tonsil
The oral (anterior two-thirds) and pharyngeal (posterior one-third) surfaces are
separated by a V-shaped terminal sulcus of the tongue. The superior surface of
the oral part of the tongue is covered by papillae, the majority of which have taste
buds on their surface. The mucosa of the pharyngeal surface of the tongue is
irregular, because of the many small nodules of lymphoid tissue in the
submucosa, collectively known as the lingual tonsil.
PAPILLAE OF THE TONGUE. (IMAGE BY LESION (OWN WORK) [CC BY-SA 3.0], VIA
WIKIMEDIA COMMONS)
Innervation
General sensation from the anterior two-thirds of the tongue is carried by
the lingual nerve, branch of the mandibular nerve.
Taste from the anterior two-thirds of the tongue is carried by the chorda
tympani, branch of the facial nerve.
Taste and general sensation from the posterior one-third of the tongue is
carried by the glossopharyngeal nerve.
All muscles of the tongue are innervated by the hypoglossal nerve, except
for the palatoglossus, which is innervated by the vagus nerve.
Lymphatic Drainage
All lymphatics from the tongue ultimately drain into the deep cervical chain of
nodes along the internal jugular vein. The pharyngeal part of the tongue drains
through the pharyngeal wall directly into mainly the jugulo-omohyoid node of the
deep cervical chain. The oral part of the tongue drains both directly into the deep
cervical nodes and indirectly into these nodes by passing first through the
mylohyoid muscle and into submental and submandibular nodes.

Innervation of Oral Cavity LAST UPDATED: 11TH
APRIL 2019
Sensory
General sensory innervation of the oral cavity is carried predominantly by
branches of the trigeminal nerve:
The upper parts of the cavity, including the palate and upper teeth are
innervated by branches of the maxillary nerve.
The lower parts of the cavity, including the lower teeth and anterior two-
thirds of the tongue are innervated by branches of the mandibular nerve.
General sensation from the posterior one-third of the tongue is carried by the
glossopharyngeal nerve.
Motor
All muscles of the tongue are innervated by the hypoglossal nerve, except for the
palatoglossus, which is innervated by the vagus nerve.
All muscles of the soft palate are innervated by the vagus nerve, except for the
tensor veli palatini, which is innervated by a branch of the mandibular nerve.
The mylohyoid, which forms the floor of the oral cavity is also innervated by the
mandibular nerve (inferior alveolar branch).
Special: Taste
Taste from the anterior two-thirds of the tongue is carried by the chorda tympani
(branch of the facial nerve).
Taste (and sensation) from the posterior one-third of the tongue is carried by the
glossopharyngeal nerve.
Autonomic
Parasympathetic fibres to the glands within the oral cavity are carried by
branches of the facial nerve, which are distributed with branches of the
trigeminal nerve.
Sympathetic fibres in the oral cavity ultimately come from spinal cord level T1,
synapse in the superior cervical ganglion and are eventually distributed to the
oral cavity along branches of the trigeminal nerve or directly along blood vessels.

External Ear LAST UPDATED: 23RD
APRIL 2020
ANATOMY / HEAD AND NECK / EAR
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The external ear consists of the auricle (pinna) and the external acoustic meatus.
STRUCTURE OF THE EAR. (IMAGE BY OPENSTAX [CC BY 4.0], VIA WIKIMEDIA COMMONS)
Auricle
The auricle on the side of the head is a cartilaginous folded structure.
The outer, more superficial structures of the auricle are supplied by:
the great auricular nerve (from spinal nerves C2 - C3) inferiorly
the lesser occipital nerve (from spinal nerves C2 - C3) posterosuperiorly
the auriculotemporal nerve (branch of the mandibular nerve) anterosuperiorly.
The deeper parts of the auricle are supplied by the auricular branch of the vagus
nerve and a branch from the facial nerve (which contributes to the auricular branch
of the vagus nerve).
External Acoustic Meatus

The external acoustic meatus extends laterally from the deepest part of the concha
to the tympanic membrane (about 3 cm in length). Sensory innervation of the
external acoustic meatus is from the auriculotemporal nerve (branch of the
mandibular nerve) anteriorly and superiorly and the auricular branch of the vagus
nerve posteriorly and inferiorly.
Tympanic Membrane
The tympanic membrane separates the external acoustic meatus from the middle
ear. At the periphery of the tympanic membrane, a fibrocartilaginous ring attaches it
to the tympanic part of the temporal bone. At its centre, the lower end of the handle
of the malleus is attached on its internal surface forming the umbo of the tympanic
membrane.
TYMPANIC MEMBRANE. (IMAGE BY EMAD KAYYAM [CC BY-SA 3.0

(HTTPS://CREATIVECOMMONS.ORG/LICENSES/BY-SA/3.0)])
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Middle Ear LAST UPDATED:

29TH MAY 2019
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The middle ear is an air-filled cavity in the petrous temporal bone between
the tympanic membrane laterally and the lateral wall of the internal ear
medially.
STRUCTURE OF THE EAR. (IMAGE BY OPENSTAX [CC BY 4.0], VIA WIKIMEDIA

COMMONS)
Ossicles
Its basic function is to transmit vibrations of the tympanic membrane across
the cavity of the middle ear to the internal ear which it does through three
interconnected bones:
the malleus (connected to the tympanic membrane)
the incus (connected to the malleus)
the stapes (connected to the incus and attached to the lateral wall of
the internal ear at the oval window)
Relations
The middle ear communicates with the mastoid area posteriorly and the
nasopharynx (via the pharyngotympanic tube) anteriorly. The
pharyngotympanic tube equalizes pressure on both sides of the tympanic
membrane.
The mucous membrane lining the mastoid air cells is continuous with the
mucous membranes throughout the middle ear. Therefore infections in the
middle ear can easily spread into the mastoid area (and from here to the
middle cranial fossa).
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Inner Ear LAST UPDATED:

23RD APRIL 2020
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The internal ear consists of a series of bony cavities in the petrous part of
the temporal bone, bounded laterally by the middle ear and medially by
the internal acoustic meatus, and the membranous sacs and ducts within
these cavities.
The internal auditory meatus is a canal within the petrous part of the
temporal bone of the skull between the inner ear and the posterior cranial
fossa. The internal auditory meatus provides a passage through which the
vestibulocochlear nerve (CN VIII), the facial nerve (CN VII), and the
labyrinthine artery (an internal auditory branch of the anterior inferior
cerebellar artery in 85% of people) can pass from inside the skull to
structures of the inner ear and face. It also contains the vestibular
ganglion.
STRUCTURE OF THE EAR. (IMAGE BY OPENSTAX [CC BY 4.0], VIA WIKIMEDIA
COMMONS)
Function
The structures of the inner ear convey information to the brain about
balance and hearing. The cochlear duct is the organ of hearing. The
semicircular ducts and sacs (utricle and saccule) are the organs of
balance.

Masseter Muscle LAST UPDATED: 4TH
APRIL 2022
ANATOMY / HEAD AND NECK / PAROTID REGION
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The masseter muscle overlies the lateral surface of the ramus of the mandible.
Table: Overview of the Masseter Muscle

Muscle Masseter
Origin Zygomatic arch and maxillary process of zygomatic bone
Insertion Lateral surface of ramus of mandible
Action Elevation of mandible
Innervation Mandibular division of trigeminal nerve
Attachments
It originates from the zygomatic arch and the maxillary process of the
zygomatic bone and inserts onto the lateral surface of the ramus of the
mandible.
Function
The masseter muscle is a powerful muscle of mastication that elevates the
mandible.
Innervation
It is innervated by the mandibular division of the trigeminal nerve.
MUSCLES OF MASTICATION. (IMAGE BY OPENSTAX [CC BY 4.0], VIA WIKIMEDIA
COMMONS)

Parotid Gland LAST UPDATED: 11TH
APRIL 2019
ANATOMY / HEAD AND NECK / PAROTID REGION
 Bookmark
The parotid glands are the largest of the paired salivary glands and are enclosed
within the split investing layer of the deep cervical fascia. The parotid glands
produce watery saliva and salivary amylase required for food bolus formation
and oral digestion.
Anatomical Location
The parotid glands are anterior to and inferior to the lower half of the ear. They
extend down to the lower border of the mandible and up to the zygomatic arch.
Posteriorly they cover the anterior part of the sternocleidomastoid and continue
anteriorly to halfway across the masseter muscle.
RELATIONS OF THE PAROTID GLAND. (IMAGE BY HENRY VANDYKE CARTER [PUBLIC
Parotid Duct
The parotid duct leaves the anterior edge of the parotid gland midway between
the zygomatic arch and the corner of the mouth. It traverses the masseter
muscle and after crossing the medial border of the masseter, turns deeply into
the buccal fat pad and pierces the buccinator muscle. It opens into the oral
cavity near the second upper molar tooth.
Relations
Several major structures enter and pass through or just deep to the parotid
gland including:
The facial nerve (and its five terminal branches arising within the parotid
gland)
The external carotid artery (and its branches arising within the parotid
gland - the posterior auricular artery and its terminal branches the
maxillary and superficial temporal artery)
The retromandibular vein (formed within the parotid gland from the union
of the superficial temporal and maxillary vein).
Innervation
Sensory innervation of the parotid gland is provided by the auriculotemporal
nerve (branch of the mandibular nerve).
The auriculotemporal nerve also carries secretomotor parasympathetic fibres to
the parotid gland; these postganglionic parasympathetic fibres have their origin
in the otic ganglion (just inferior to the foramen ovale) which receives
preganglionic parasympathetic fibres from the glossopharyngeal nerve.
Sympathetic innervation originates from the superior cervical ganglion.
Parotitis refers to inflammation of the parotid gland, usually as a result of an
infection. The parotid gland is enclosed in a tough fibrous capsule which limits
swelling of the gland, resulting in pain which may be referred to the external ear.

Temporomandibular Joint LAST UPDATED: 5TH
OCTOBER 2019
TEMPOROMANDIBULAR JOINT  Bookmark
The temporomandibular joints allow opening and closing of the mouth and
complex chewing and side-to-side movements of the lower jaw. Opening of the
mouth involves both depression and protrusion of the mandible. Closing of the
mouth involves elevation and retraction of the mandible.
Table: Overview of the Temporomandibular Joint

Joint Temporomandibular Joint (TMJ)
Articulations Condylar head of mandible with articular fossa and
articular tubercle of squamous part of temporal bone
Stabilising Lateral ligament, sphenomandibular ligament,
factors stylomandibular ligament
Movements Elevation and depression, retraction and protraction, side
to side movements
Articulations
Each joint is synovial and formed between the condylar head of the mandible
and the articular fossa and articular tubercle of the squamous part of the
temporal bone.
ARTICULATIONS OF THE TEMPOROMANDIBULAR JOINT. (IMAGE BY HENRY VANDYKE
CARTER [PUBLIC DOMAIN], VIA WIKIMEDIA COMMONS)
Ligaments
The joint is stabilised by three extracapsular ligaments:
the lateral (capsular) ligament extending from the articular tubercles of the
temporal bone to the neck of the mandible
the sphenomandibular ligament extending from the spine of the sphenoid
bone at the base of the skull to the medial side of the ramus of the
mandible
the stylomandibular ligament extending from the styloid process of the
temporal bone to the posterior margin of the mandible.
EXTRACAPSULAR LIGAMENTS OF THE TEMPOROMANDIBULAR JOINT. (IMAGE BY HENRY
Movements
Table: Movements of the Temporomandibular Joint

Joint Muscles Involved
Movement
Depression Digastric, geniohyoid, mylohyoid, lateral pterygoid, (plus
gravity)
Elevation Temporalis, masseter, medial pterygoid
Protraction Lateral pterygoid, medial pterygoid
Retraction Geniohyoid, digastric, temporalis, masseter
Movements of the mandible include depression, elevation, protrusion and

retraction.
Movements of the mandible at the TMJ:
Depression is generated by the digastric, geniohyoid, mylohyoid muscles
on both sides, is normally assisted by gravity, and, because it involves
forward movement of the head of the mandible onto the articular tubercle,
the lateral pterygoid muscles are also involved.
Elevation is a very powerful movement generated by the temporalis,
masseter and medial pterygoid muscles.
Protraction is mainly achieved by the lateral pterygoid, with some
assistance by the medial pterygoid.
Retraction is carried out by the geniohyoid and digastric muscles and by
the posterior and deep fibres of the temporalis and masseter muscles
respectively.
The TMJ is less stable when the mouth is open. Anterior dislocation of the TMJ
can occur by yawning or taking a large bite. The head of the mandible slips out of
the mandibular fossa and is pulled anteriorly. The patient is unable to close their
mouth. Posterior dislocation is uncommon but may occur due to a blow to the
face. If traumatic, the facial and auriculotemporal nerves may be affected due to
their close proximity to the joint.
Temporal Fossa LAST UPDATED: 11TH
APRIL 2019
ANATOMY / HEAD AND NECK / SCALP
 Bookmark
The temporal fossa is the narrow fan-shaped space that covers the lateral
surface of the skull, superior to the infratemporal fossa and above the zygomatic
arch.
The zygomatic arch is formed by the zygomatic process of the temporal bone
and the temporal process of the zygomatic bone.
Table: Overview of the Temporal Fossa

Space Temporal Fossa
Superior Superior and inferior temporal lines
margin
Inferior Zygomatic arch laterally and greater wing of sphenoid bone
margin medially
Anterior Frontal process of zygomatic bone and zygomatic process of
margin frontal bone
Contents Temporalis muscle, deep temporal nerves,
zygomaticotemporal nerve, deep temporal arteries, middle
temporal artery
Boundaries
Its upper margin is defined by a pair of temporal lines that arch across the
skull from the zygomatic process of the frontal bone to the supramastoid
crest of the temporal bone.
Laterally it is limited by the temporal fascia, which is a tough aponeurosis
overlying the temporalis muscle and attached by its outer margin to the
superior temporal line and by its inferior margin to the zygomatic arch.
Anteriorly it is limited by the posterior surface of the frontal process of the
zygomatic bone and the posterior surface of the zygomatic process of the
frontal bone, which separate the temporal fossa from the orbit in front.
Its inferior margin is marked by the zygomatic arch laterally and by the
infratemporal crest of the greater wing of the sphenoid medially.
It communicates with the infratemporal fossa below through the gap between
the zygomatic arch and the more medial surface of the skull.
TEMPORAL FOSSA. (IMAGE MODIFIED BY FRCEM SUCCESS. ORIGINAL IMAGE BY ENGUSZ

AT HUNGARIAN WIKIPEDIA [CC-BY-SA-3.0], VIA WIKIMEDIA COMMONS)
Contents
Contents of the temporal fossa:
Temporalis muscle
Deep temporal nerves (branches of mandibular nerve) - innervate
temporalis muscle
Zygomaticotemporal nerve (branch of maxillary nerve) - supplies skin of
temple
Deep temporal arteries (branch of maxillary artery)
Middle temporal artery (branch of superficial temporal artery)

Temporalis Muscle LAST UPDATED: 11TH
APRIL 2019
 Bookmark
Table: Overview of the Temporalis Muscle

Muscle Temporalis
Origin Bony surface of temporal fossa superior to the
inferior temporal line
Insertion Coronoid process of mandible and along anterior
margin of ramus of mandible
Action Elevation of mandible, retraction of mandible, side-
to-side movements of mandible
Innervation Mandibular division of trigeminal nerve
Attachments
The temporalis muscle is a large fan-shaped muscle that fills much of the
temporal fossa. It originates from the bony surfaces of the temporal fossa
superiorly to the inferior temporal line and is attached laterally to the
surface of the temporal fascia. Distally it inserts onto the coronoid process
of the mandible and along the anterior margin of the ramus of the mandible
(almost to the last molar tooth).
Function
The temporalis is a powerful elevator of the mandible, acts to retract the
mandible and also participates in side-to-side movements of the mandible.
Innervation
It is innervated by the mandibular division of the trigeminal nerve.
COMMONS)

Cutaneous Innervation of LAST UPDATED:
19TH FEBRUARY
Scalp 2019
ANATOMY / HEAD AND NECK / SCALP  Bookmark
Anterior to the ears and the vertex the scalp is supplied by branches of the
trigeminal nerve:
The supratrochlear nerve supplies the front of the forehead near the
midline
The supraorbital nerve supplies the forehead as far back as the
vertex
The zygomaticotemporal nerve supplies the scalp over a small
anterior area of the temple
The auriculotemporal nerve supplies the scalp over the temporal
region and anterior to the ear extending superiorly near to the vertex.
Posterior to the ears and the vertex the scalp is supplied by cervical spinal
nerves C2 and C3:
The great auricular nerve (anterior rami of C2 - C3, from the cervical
plexus) supplies a small area of the scalp just posterior to the ear
The lesser occipital nerve (anterior ramus of C2, from the cervical
plexus) supplies an area of the scalp posterior and superior to the ear
The greater occipital nerve (posterior ramus of C2) supplies a large
part of the posterior scalp as far superiorly as the vertex
The third occipital nerve (posterior ramus C3) supplies a small area of
the lower part of the scalp.
CUTANEOUS INNERVATION OF THE HEAD. (IMAGE BY PATRICK J. LYNCH,
MEDICAL ILLUSTRATOR [CC BY 2.5], VIA WIKIMEDIA COMMONS)

Blood Supply of Scalp LAST UPDATED:
11TH APRIL 2019
 Bookmark
Arterial Supply
The arterial supply of the scalp is from branches of the external carotid
artery or the ophthalmic artery (branch of the internal carotid artery)
which form a rich anastomosing network.
The scalp has an extremely rich blood supply, so lacerations of the scalp
tend to bleed profusely. Scalp bleeding is predominantly arterial, firstly
because in the erect position venous pressure is extremely low and
secondly because the vessels do not retract and close when lacerated
because the dense connective tissue in which they are found holds
them open.
Arterial Supply of the Scalp. (Image by Internet Archive Book Images [No
restrictions], via Wikimedia Commons)
Venous Drainage
Veins draining the scalp follow the arterial pattern. The posterior
auricular vein drains the area of the scalp posterior to the ear. The
sigmoid sinus is connected with the exterior by the mastoid emissary
vein which joins the posterior auricular vein. In this way infections of the
ear or mastoid may spread intracranially.
VENOUS DRAINAGE OF THE SCALP. (IMAGE BY HENRY VANDYKE CARTER

Anatomy Head and Neck Larynx
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Larynx Structure LAST UPDATED: 11TH

APRIL 2019
ANATOMY / HEAD AND NECK / LARYNX
 Bookmark
The skeletal framework of the larynx is formed from three large unpaired
cartilages (cricoid, thyroid, and epiglottis), three smaller paired cartilages
(arytenoid, corniculate and cuneiform), joints, ligaments and membranes.
STRUCTURE OF THE LARYNX (POSTERIOR VIEW). (IMAGE BY HENRY VANDYKE CARTER

Cartilages
The cricoid cartilage is the most inferior of the laryngeal cartilages and
completely encircles the airway. The cricoid cartilage articulates with the base
of the arytenoid cartilages superiorly (forming the cricoarytenoid joint) and the
inferior horns of the thyroid cartilage posterolaterally (forming the cricothyroid
joint).
The thyroid cartilage is the largest of the laryngeal cartilages. The thyroid
cartilage articulates with the cricoid cartilage inferiorly and the hyoid bone
superiorly.
The epiglottis is attached to the posterior aspect of the thyroid cartilage and
projects posterosuperiorly. The upper margin of the epiglottis is behind the
pharyngeal part of the tongue.
The two arytenoid cartilages articulate inferiorly with the cricoid cartilage and
superiorly with the corniculate cartilages.
LARYNGEAL CARTILAGES. (IMAGE BY HENRY VANDYKE CARTER [PUBLIC DOMAIN], VIA

WIKIMEDIA COMMONS)
Joints
The cricothyroid and cricoarytenoid joints are the main laryngeal joints
allowing normal function.
Movements at the cricoarytenoid joints abduct and adduct the vocal ligaments.
Movements at the cricothyroid joint enable the thyroid cartilage to move
forward and tilt downwards on the cricoid cartilage which effectively lengthens
and puts tension on the vocal ligaments.
Cricothyroid Membrane
The cricothyroid membrane (conus elasticus) is attached to the arch of the
cricoid cartilage and extends superiorly to end in a free upper margin within the
space enclosed by the thyroid cartilage. This upper free margin attaches on
each side anteriorly to the thyroid cartilage and posteriorly to the vocal
processes of the arytenoid cartilage. The free margin between these two points
is thickened to form the vocal ligament which is under the vocal fold of the
larynx.
The cricothyroid membrane is also thickened anteriorly in the midline to form
the distinct median cricothyroid ligament, which spans the distance between
the arch of the cricoid cartilage and the thyroid cartilage up to the attachments
of the vocal ligaments. In emergency situations, when the airway is blocked
above the level of the vocal folds, the median cricothyroid ligament can be
perforated to establish an airway (cricothyrotomy).
STRUCTURE OF THE LARYNX (ANTERIOR VIEW). (IMAGE BY OLEK REMESZ (WIKI-PL:
OREM, COMMONS: OREM) [CC BY-SA 2.5-2.0-1.0], VIA WIKIMEDIA COMMONS)
Laryngeal Inlet
LARYNGOSCOPIC VIEW OF INTERIOR OF LARYNX. (IMAGE BY HENRY VANDYKE CARTER
ENTRANCE TO LARYNX (POSTERIOR VIEW). (IMAGE BY HENRY VANDYKE CARTER

Larynx Muscles LAST UPDATED: 11TH
APRIL 2019
ANATOMY / HEAD AND NECK / LARYNX
 Bookmark
The larynx is suspended from the superior hyoid bone and attached to the
trachea below by membranes and ligaments. It opens above into the
pharynx immediately posterior and slightly inferior to the tongue and the
oropharyngeal isthmus of the oral cavity, and blends inferiorly with the
trachea at the vertebral level C6.
RELATIONS OF THE LARYNX. (IMAGE BY HENRY VANDYKE CARTER [PUBLIC

DOMAIN])
Function
There are four principal roles of the larynx:
phonation
sphincteric to close the lower respiratory tract (for example during
swallowing)
coughing
breath-holding while straining (vocal cord adduction).
Intrinsic vs Extrinsic Muscles

The laryngeal muscles are divided into intrinsic and extrinsic groups.
The intrinsic muscles alter the size and shape of the laryngeal inlet and move
the vocal folds.
The extrinsic muscles are involved in elevation and depression of the larynx
to produce swallowing.
VOCAL CORDS. (IMAGE BY UNKNOWN [PUBLIC DOMAIN], VIA WIKIMEDIA COMMONS)
Innervation
Motor and sensory innervation of the larynx is provided by the vagus nerve
via its superior laryngeal and recurrent laryngeal branches.
The recurrent laryngeal nerves are sensory to the laryngeal cavity below the
level of the vocal folds and motor to all intrinsic muscles of the larynx except
for the cricothyroid muscle (innervated by the superior laryngeal branch of
the vagus nerve).
A lesion of the recurrent laryngeal nerve may cause respiratory obstruction,
hoarseness, inability to speak and loss of sensation below the vocal cord.
The superior laryngeal nerve supplies sensation to the mucous membrane
above the vocal cord and the taste buds on the epiglottis, and motor
innervation to the cricothyroid and the inferior pharyngeal constrictor
muscles.
A lesion of the superior laryngeal nerve may cause loss of sensation above
the vocal cord and taste on the epiglottis, and a weak hoarse voice.

Infratemporal Fossa LAST UPDATED: 11TH
APRIL 2019
INFRATEMPORAL FOSSA  Bookmark
The wedge-shaped infratemporal fossa lies inferior to the temporal fossa and
the skull base, between the ramus of the mandible laterally and the wall of the
pharynx medially.
Boundaries
Table: Anatomical Boundaries of the Infratemporal Fossa

Space Infratemporal Fossa
Roof Inferior surface of greater wing of sphenoid and temporal
bone
Lateral Medial surface of ramus of mandible
wall
Medial Lateral plate of pterygoid process, pharynx and soft palate
wall
Anterior Posterior surface of maxilla
wall
Contents Sphenomandibular ligament, medial and lateral pterygoid
muscles, maxillary artery, mandibular nerve, chorda
tympani nerve, lesser petrosal nerve, pterygoid venous
plexus
The roof is formed by the inferior surfaces of the greater wing of the
sphenoid and the temporal bone, and is open superiorly to the temporal
fossa.
The lateral wall is the medial surface of the ramus of the mandible.
The medial wall is formed anteriorly by the lateral plate of the pterygoid
process and more posteriorly by the pharynx and by the tensor and
levator veli palatini muscles of the soft palate.
The anterior wall is formed by part of the posterior surface of the
maxilla.
Posteroinferiorly, the infratemporal fossa is open to the neck.
LEFT INFRATEMPORAL FOSSA. (IMAGE BY HENRY VANDYKE CARTER [PUBLIC

Contents
Major contents of this fossa include:
the sphenomandibular ligament
the medial and lateral pterygoid muscles
the maxillary artery (and its branches including the middle meningeal
artery)
the mandibular nerve (and its sensory branches - the auriculotemporal,
buccal, lingual and inferior alveolar nerves)
the chorda tympani (branch of the facial nerve)
the lesser petrosal nerve (originating from the glossopharyngeal nerve)
the pterygoid plexus of veins
Infratemporal Fossa
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Pterygoid Muscles LAST UPDATED: 5TH

OCTOBER 2019
Function
The pterygoid muscles are muscles of mastication and serve the movement of
the temporomandibular joint.
The medial pterygoid muscle mainly elevates the mandible, closing the mouth.
Because it passes obliquely backward to insert into the mandible, it also
assists the lateral pterygoid in protruding the lower jaw.
Unlike the medial pterygoid muscle whose fibres tend to be oriented vertically,
those of the lateral pterygoid are oriented almost horizontally. As a result,
when the lateral pterygoid contracts it pulls the articular disc and head of the
mandible forward onto the articular tubercle and is therefore the major
protruder of the lower jaw.
When the lateral and medial pterygoid muscles contract on only one side, the
chin moves to the opposite side. When opposite movements at the two
temporomandibular joints are coordinated, a chewing movement results.
Innervation
Both the medial and lateral pterygoids are innervated by the mandibular
division of the trigeminal nerve.
COMMONS)

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Maxillary Artery LAST UPDATED: 11TH

APRIL 2019
The maxillary artery is the largest branch of the external carotid artery and a
major source of blood supply for the nasal cavity, the lateral wall and roof of
the oral cavity, all teeth and the dura mater in the cranial cavity.
It passes through and supplies the infratemporal fossa and then enters the
pterygopalatine fossa, where it gives origin to terminal branches.
Middle Meningeal Artery

The middle meningeal artery arises from the maxillary artery and ascends
vertically to enter the cranial cavity. Within the cranial cavity, the middle
meningeal artery and its branches travel in the outer layer of the dura mater,
where they can be damaged by lateral blows to the head. When the vessels
are torn, the leaking blood, which is under arterial pressure, separates the
dura from its attachment to bone, resulting in an extradural haematoma.
BRANCHES OF THE MAXILLARY ARTERY. (IMAGE BY MIKAEL HÄGGSTRÖM [PUBLIC

Pterygoid Venous Plexus LAST UPDATED: 12TH
FEBRUARY 2019
The pterygoid venous plexus is a network of veins between the medial and
lateral pterygoid muscles, and between the lateral pterygoid and temporalis
muscles.
It receives tributaries from veins draining regions supplied by the maxillary
artery (i.e. the nasal cavity, roof and lateral wall of the oral cavity, all teeth,
muscles of the infratemporal fossa, paranasal sinuses and nasopharynx). In
addition the inferior ophthalmic veins from the orbit can drain through the
inferior orbital fissure into the pterygoid plexus.
Small emissary veins often connect the pterygoid plexus in the infratemporal
fossa with the cavernous sinus in the cranial cavity. This gives a route of
spread of infection into the cranial cavity. Also, as there are no valves in the
veins of the head and neck, anaesthetic inadvertently injected under pressure
into the veins of the pterygoid plexus can backflow into tissues or into the
cranial cavity.
The pterygoid plexus connects posteriorly with the retromandibular vein in
the neck (via a short maxillary vein) and anteriorly with the facial vein on the
face (via a deep facial vein).

Pterygopalatine Ganglion LAST UPDATED: 12TH
FEBRUARY 2019
The pterygopalatine ganglion sits in the pterygopalatine fossa.

It receives preganglionic parasympathetic fibres from the facial nerve (via the
greater petrosal nerve). It also receives postganglionic sympathetic fibres
originating from the T1 spinal cord.
Postganglionic parasympathetic fibres, arising in the pterygopalatine ganglion,
join the general sensory branches of the maxillary nerve, as do the postganglionic
sympathetic fibres.
The three types of fibres leave the ganglion to supply the nose and palate by way
of branches of the maxillary nerve.
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Atlas and Axis LAST UPDATED: 11TH

APRIL 2019
VERTEBRAL COLUMN  Bookmark
Atlas
Vertebra C1 (the atlas) is distinguished by its lack of vertebral body,
essentially being composed of two lateral masses interconnected by an
anterior and posterior arch. Each lateral mass articulates above with an
occipital condyle of the skull and below with the superior articular facet of
vertebra C2 (the axis). The posterior surface of the anterior arch has an
articular facet for the dens of the axis.
The atlanto-occipital joints allow the head to nod up and down on the
vertebral column.
Axis
The axis is characterised by the large dens, which extends superiorly from
its vertebral body to articulate with the anterior arch of the atlas, and by its
bifid spinous process. The dens is held in position by the strong transverse
ligament of atlas posterior to it and spanning the distance between the
lateral masses of the atlas.
The atlanto-axial joints allow the head to rotate from side to side.
STRUCTURE OF THE CERVICAL VERTEBRAE. (IMAGE BY OPENSTAX COLLEGE [CC
BY 3.0], VIA WIKIMEDIA COMMONS)

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Vertebral Column Bones LAST UPDATED: 2ND

MAY 2019
VERTEBRAL COLUMN  Bookmark
The vertebral column consists of 33 vertebrae: seven cervical, twelve

thoracic, five lumbar, five fused sacral and four fused coccygeal vertebrae.
Structural Overview
A typical vertebra consists of a vertebral body and a vertebral arch.
The vertebral body is anterior and is separated from adjacent vertebral bodies
by fibrocartilaginous intervertebral discs. The size of the vertebral body
increases inferiorly as the amount of weight supported increases.
The vertebral arch is anchored to the posterior surface of the vertebral body
by two pedicles, which form the lateral pillars of the arch. The roof of the
vertebral arch is formed by the right and left laminae which fuse at the
midline.
A spinous process projects posteriorly and inferiorly from the roof of the
vertebral arch and is a site for muscle and ligament attachment.
On each side of the vertebral arch, a transverse process extends laterally
from the region where a lamina meets a pedicle and is a site for articulation
with ribs in the thoracic region. From the same region, a superior articular
process and an inferior articular process articulate with similar processes on
adjacent vertebrae.
The vertebral arches are aligned to form the lateral and posterior walls of the
vertebral foramen; the vertebral foramina of all the vertebrae together form
the vertebral canal.
VERTEBRAL COLUMN. (IMAGE BY JMARCHN (OWN WORK) [CC BY-SA 3.0], VIA
WIKIMEDIA COMMONS)

Intervertebral Disc LAST UPDATED: 11TH
APRIL 2019
ANATOMY / HEAD AND NECK / VERTEBRAL COLUMN
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Each vertebral body is separated from adjacent vertebral bodies by

fibrocartilaginous intervertebral discs.
Structure
The intervertebral disc consists of the outer annulus fibrosus, a complex series of
fibrous rings enclosing the central gelatinous nucleus pulposus.
INTERVERTEBRAL DISC. (IMAGE BY OPENSTAX COLLEGE [CC BY 3.0], VIA WIKIMEDIA

COMMONS)
Function
The intervertebral discs allows movements between the vertebrae and act as a
shock absorber.
Degenerative changes in the annulus fibrosus can lead to herniation of the
nucleus pulposus. A tear can occur within the annulus fibrosus through which the
nucleus pulposus can track into the intervertebral foramen or into the vertebral
canal, compressing the spinal nerve root. It commonly occurs posterolaterally
where the annulus fibrosus is not reinforced by the posterior longitudinal
ligament, and frequently affects the lumbar region.
The spinal cord only occupies about 2/3s of the space available to it in the
vertebral canal. The lower a nerve root, the more steeply it slopes down and the
further it has to travel before gaining its intervertebral foramen. Therefore, a
posterolateral herniation of the disc at the L4 - L5 level for example, would be
most likely to damage the fifth lumbar nerve root, not the fourth lumbar nerve
root, due to more oblique descending of the fifth lumbar nerve root within the
subarachnoid space.
INTERVERTEBRAL DISC HERNIATION. (IMAGE BY OPENSTAX COLLEGE [CC BY 3.0


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Vertebral Column Ligaments LAST UPDATED: 11TH

APRIL 2019
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Joints between vertebrae are reinforced by numerous ligaments.
Table: Ligaments of the Vertebral Column

Ligament Location Function
Anterior Extends from base of skull to Limits extension of vertebral
longitudinal sacrum, attached along its column, supports annulus
ligament length to vertebral bodies fibrosus anteriorly, resists
anteriorly gravitational pull
Posterior Extends from C2 to sacrum, Limits flexion of vertebral
longitudinal attached along its length to column, supports annulus
ligament vertebral bodies posteriorly fibrosus posteriorly, resists
gravitational pull
Ligamenta Pass between laminae of Resist separation of laminae in
flava adjacent vertebrae flexion and assist in extension
back to anatomical position
Supraspinous Passes between and connects Limits flexion of vertebral
ligament tips of spinous processes, column
extending from C7 to sacrum
Ligamentum Passes between and connects Supports head, resists flexion
nuchae tips of spinous processes, of neck and helps return head
extending from skull to spinous to anatomical position
process of C7
Interspinous Pass between spinous processes Limit flexion of vertebral
ligaments of adjacent vertebrae column
Anterior Longitudinal Ligament
The anterior longitudinal ligament is attached superiorly to the base of the skull and extends
inferiorly to attach to the anterior surface of the sacrum. Along its length it is attached to the
vertebral bodies and intervertebral discs anteriorly. The anterior longitudinal ligament acts to
limit extension of the vertebral column, support the annulus fibrosus anteriorly and resist
gravitational pull.
Posterior Longitudinal Ligament

The posterior longitudinal ligament is on the posterior surface of the vertebral bodies and
lines the anterior surface of the vertebral canal. It is attached along its length to the vertebral
bodies and intervertebral discs posteriorly. The posterior longitudinal ligament acts to
support the posterior aspect of the vertebral bodies and the annulus fibrosus and limit flexion
of the vertebral column.
Ligamenta Flava
The ligamenta flava, on each side, pass between the laminae of adjacent vertebrae, forming
part of the posterior surface of the vertebral canal. The ligamenta flava resist separation of
the laminae in flexion and assist in extension back to the anatomical position.
Supraspinous Ligament
The supraspinous ligament connects and passes along the tips of the vertebral spinous
processes from vertebra C7 to the sacrum. From vertebra C7 to the skull, the ligament is more
structurally distinct and referred to as the ligamentum nuchae.
Ligamentum Nuchae
The ligamentum nuchae is attached superiorly to the skull (from the external occipital
protuberance to the foramen magnum), inferiorly to the spinous process of C7 and between
these two points to the spinous processes of the cervical vertebrae. The ligamentum nuchae
supports the head, resists flexion and helps to return the head to the anatomical position. The
ligament provides attachment for adjacent muscles.
Interspinous Ligament
The interspinous ligaments pass between adjacent vertebral spinous processes, blending
posteriorly with the supraspinous ligament and anteriorly with the ligamenta flava on each
side.
LIGAMENTS OF THE VERTEBRAL COLUMN. (IMAGE BY HENRY VANDYKE CARTER [PUBLIC DOMAIN], VIA
WIKIMEDIA COMMONS)

Vertebral Column Muscles LAST UPDATED: 11TH
APRIL 2019
 Bookmark
Movements by the vertebral column include flexion, extension, lateral flexion and
rotation. Rotation occurs predominantly in the thoracic column. Flexion of the
vertebral column is provided predominantly by the rectus abdominis muscle
assisted for rotation by the obliques.
Back Muscles
Muscles of the back are organised into superficial, intermediate and deep groups.
Extrinsic muscles (innervated by anterior rami of spinal nerves)
The superficial group consists of muscles related to and involved with
movements of the upper limb.
The intermediate group consists of muscles attached to the ribs and
involved in respiratory function.
Intrinsic muscles (innervated by posterior rami of spinal nerves)
The deep group consists of muscles directly related to movements of
the vertebral column and head.
Deep Muscles
The deep muscles of the back include:
the splenius capitis and cervicis (extensors and rotators of the head and
neck)
the erector spinae and transversospinalis (extensors and rotators of the
vertebral column)
the short segmental muscles.
Erector Spinae
The erector spinae is the largest group of intrinsic back muscles, lying
posterolaterally to the vertebral column between the spinous processes medially
and the angles of the ribs laterally. The muscles in the erector spinae group are
the primary extensors of the vertebral column and head. Acting bilaterally, they
straighten the back, returning it to the upright position from the flexed position,
and pull the head posteriorly. Acting unilaterally, they bend the vertebral column
laterally.
ERECTOR SPINAE MUSCLES. (IMAGE BY HENRY VANDYKE CARTER [PUBLIC DOMAIN], VIA
WIKIMEDIA COMMONS)

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Vertebral Canal LAST UPDATED: 11TH

APRIL 2019
 Bookmark
The vertebral canal extends from the first cervical vertebra (C1) to the last
sacral vertebra (S5).
Boundaries
Superiorly the vertebral canal is continuous, through the foramen magnum of
the skull, with the cranial cavity.
The vertebral canal is bounded anteriorly by the vertebral bodies, intervertebral
discs and the posterior longitudinal ligament, laterally by the vertebral pedicles
and posteriorly by the vertebral laminae.
RELATIONS OF THE VERTEBRAL CANAL. (IMAGE BY UNKNOWN [PUBLIC DOMAIN], VIA
WIKIMEDIA COMMONS)
Contents
The vertebral canal contains the spinal cord and its protective membranes,
together with blood vessels, connective tissue, fat and spinal nerve roots. The
conus medullaris is the point below which the canal contains only the cauda
equina and filum terminale.
Meninges
The spinal cord is surrounded by a series of three spinal meninges consisting
of a dura, arachnoid and pia mater.
The bony walls of the spinal canal are separated from the meninges by the
epidural (extradural) space.
The subarachnoid space, containing CSF, is found between the arachnoid and
pia mater. The subarachnoid space around the spinal cord is continuous at the
foramen magnum with the subarachnoid space surrounding the brain.
MENINGES OF THE SPINAL CORD. (IMAGE BY MYSID [PUBLIC DOMAIN], VIA WIKIMEDIA
COMMONS)
Lumbar Puncture
In adults, the spinal cord typically ends between L1/L2 whereas the
subarachnoid space extends to approximately the lower border of vertebra S2.
As a result of this, CSF can be withdrawn from the subarachnoid space in the
lower lumbar region without endangering the spinal cord.
When performing a lumbar puncture, the needle passes between adjacent
vertebral spinous processes, through the supraspinous and interspinous
ligaments and through the ligamentum flavum to enter the extradural space.
The needle then continues through the dura and the arachnoid mater to enter
the subarachnoid space.
Layers penetrated during lumbar puncture:
Skin
Superficial fascia
Supraspinous ligament
Interspinous ligament
Ligamentum flavum (first 'give')
Extradural space
Dura mater (second 'give')
Subdural space
Arachnoid mater
Subarachnoid space (containing CSF)
LUMBAR PUNCTURE. (IMAGE BY GURCH [PUBLIC DOMAIN], VIA WIKIMEDIA COMMONS)

NEURO &
CRANIAL
NERVES
8/26/22, 12:00 AM Arterial Supply of Brain - MRCEM Success
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Arterial Supply of Brain LAST UPDATED: 30TH

MARCH 2020
ANATOMY / CENTRAL NERVOUS SYSTEM
 Bookmark
The brain receives its arterial supply from two pairs of vessels, the vertebral arteries and
the internal carotid arteries.
CEREBRAL BLOOD SUPPLY. (IMAGE BY RHCASTILHOS (GRAY519.PNG) [PUBLIC DOMAIN], VIA

WIKIMEDIA COMMONS)
Internal Carotid Arteries

The two internal carotid arteries arise from the common carotid arteries at the level of
vertebra C4 and enter the cranial cavity through the carotid canal in the temporal bone.
Entering the cranial cavity, each internal carotid artery gives off the following paired
branches:
The ophthalmic artery (supplying structures in the orbit and giving rise to the
central retinal artery supplying the retina)
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The posterior communicating artery (joining the posterior and middle cerebral
arteries)
The anterior choroidal artery (supplying parts of the optic pathway, the internal
capsule, the midbrain and the choroid plexus)
The anterior cerebral artery (supplying the medial cerebral hemisphere)
The anterior communicating artery (joining the two anterior cerebral arteries)
The middle cerebral artery (supplying the lateral cerebral hemispheres)
Vertebral Arteries
The two vertebral arteries, branches of the subclavian arteries, ascend through the
transverse foramina of the upper six cervical vertebrae before entering the cranial cavity
through the foramen magnum.
The vertebral arteries give rise to the following branches:
The single anterior spinal artery (supplying the anterior portion of the spinal cord)
The posterior inferior cerebellar arteries (supplying the cerebellum)
The posterior spinal arteries (supplying the posterior portion of the spinal cord) -
either a direct branch of the vertebral artery or of the posterior inferior cerebellar
artery
The basilar artery is formed by the joining of the two terminal vertebral arteries inferior to
the pons.
The basilar artery gives rise to the following paired branches:
Pontine arteries (supplying the pons and adjacent structures)
Labyrinthine artery (supplying the vestibular apparatus and cochlea)
Anterior inferior cerebellar artery (supplying the cerebellum)
Superior cerebellar artery (supplying the cerebellum)
Posterior cerebral artery (supplying the occipital lobe and the inferior temporal lobe)
Clinical Effects of Occlusion of the Cerebral Arteries

The middle cerebral artery is the largest branch of the internal carotid artery and supplies
the largest area of the cerebral cortex. It is the most commonly involved artery in stroke.
Pure anterior cerebral artery infarcts are rare because of the collateral circulation
provided by the anterior communicating artery.
Table: Clinical Effects of Occlusion of the Cerebral Arteries
Blood Territory of Clinical Effects of Occlusion

Vessel Supply
Anterior Medial FRONTAL LOBE: contralateral weakness in lower limb,
cerebral cerebral dysarthria/dysphasia, apraxia, urinary incontinence,
artery hemisphere personality change
including
the frontal PARIETAL LOBE: contralateral somatosensory loss in
lobe, the lower limb
superior
CORPUS CALLOSUM: dyspraxia and tactile agnosia
parietal lobe
and the
anterior
corpus
callosum
Middle Lateral FRONTAL LOBE: contralateral weakness (face/arm >
cerebral convexity of leg), contralateral somatosensory loss (face/arm >
artery cerebral leg), conjugate deviation of the eyes to affected side,
hemisphere expressive dysphasia, change in judgement, insight
including and mood
the frontal
lobe, TEMPORAL LOBE: deafness (if bilateral), receptive
superior dysphasia, auditory illusions and hallucinations,
temporal contralateral superior quadrantanopia
lobe, inferior
PARIETAL LOBE: loss of sensory discrimination,
parietal lobe
hemineglect, apraxia, contralateral inferior
and the
quadrantanopia
basal
ganglia and N.B. contralateral homonymous hemianopia will
internal occur if the entire optic radiation is affected, and
capsule global dysphasia will occur if both the Broca and
Wernicke speech areas are affected
Posterior Occipital OCCIPITAL LOBE: contralateral homonymous

cerebral lobe, inferior hemianopia with macular sparing (the macular area
artery temporal is additionally supplied by the middle cerebral artery),
lobe cortical blindness (if bilateral)
(including
hippocampal TEMPORAL LOBE: confusion, memory deficit
formation),
OCCIPITOTEMPORAL REGION: prosopagnosia, colour
thalamus
blindness
and the
posterior
aspect of
the corpus
callosum
and internal
capsule
CEREBRAL BLOOD SUPPLY. (IMAGE BY DERIVATIVE WORK: FRANK GAILLARD (TALK)

BRAIN_STEM_NORMAL_HUMAN.SVG: PATRICK J. LYNCH, MEDICAL ILLUSTRATOR
(BRAIN_STEM_NORMAL_HUMAN.SVG) [GFDL 1.3 (WWW.GNU.ORG/LICENSES/FDL-1.3.HTML), VIA
WIKIMEDIA COMMONS)
Circle of Willis
The arterial circle of Willis is positioned around the optic chiasm and is composed of the
following (left and right) arteries:
Anterior cerebral artery (branch of the internal carotid)
Anterior communicating artery (branch of the internal carotid)
Internal carotid
Posterior cerebral artery (branch of the basilar artery from the vertebral artery)
Posterior communicating artery (branch of the internal carotid)
Cerebral Aneurysm
Berry aneurysms tend to arise from the vessels in and around the circle of Willis. The most
frequent location is the anterior communicating artery (35%), followed by the internal
carotid artery (30%-including the carotid artery itself, the posterior communicating
artery, and the ophthalmic artery), the middle cerebral artery (22%), and finally, the
posterior circulation sites, most commonly the basilar artery tip.
Aneurysm of the anterior communicating artery may compress the optic chiasm and
cause a bitemporal hemianopia. Aneurysm of the posterior communicating artery may
cause an oculomotor nerve palsy. Rupture of berry aneurysm is a common cause of
spontaneous subarachnoid haemorrhage.
8/26/22, 12:00 AM Brain Overview - MRCEM Success
ANATOMY / CENTRAL NERVOUS SYSTEM LAST UPDATED: 19TH

FEBRUARY 2019
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The major parts of the developed brain are:

The cerebrum (cerebral hemispheres and diencephalon)
The brainstem (midbrain, pons and medulla)
The cerebellum
Embryologically these structures develop from three primary brain vesicles:
The forebrain (gives rise to the cerebral hemispheres and basal ganglia
and the diencephalon)
The midbrain (remains as the midbrain)
The hindbrain (gives rise to the pons, medulla and cerebellum)
OVERVIEW OF THE BRAIN. (IMAGE BY CANCER RESEARCH UK [CC BY-SA 4.0

(HTTPS://CREATIVECOMMONS.ORG/LICENSES/BY-SA/4.0)], VIA WIKIMEDIA COMMONS)
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8/26/22, 12:01 AM Brainstem - MRCEM Success
Brainstem LAST UPDATED: 11TH

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The brainstem comprises the midbrain, the pons and the medulla. It extends
from the tentorial aperture to the level of C1. The medulla passes out of the
cranial cavity via the foramen magnum and becomes the spinal cord as C1
roots emerge. The cells of the brainstem are predominantly clumped into
nuclei.
BRAINSTEM. (IMAGE BY OPENSTAX [CC BY 4.0

https://mrcemsuccess.com/explanation/brain3/?_sft_qc=central-nervous-system 2/6
Midbrain
The midbrain lies predominantly within the posterior cranial fossa. The
aperture in the tentorium cerebelli lies on its dorsal surface.
The midbrain receives its blood supply from the posterior cerebral and superior
cerebellar arteries (ex-basilar).
Dopaminergic cells sit within the midbrain within the substantia nigra; loss of
dopaminergic neurons is the basis of Parkinson’s disease.
Pons
The pons receives its blood supply from pontine branches of the basilar artery.
The pons houses nuclei of the trigeminal nerve, the abducens nerve, the facial
nerve and the vestibulocochlear nerve. This knowledge allows prediction of the
clinical effects of a pontine haemorrhage:
Abducens nucleus (lateral rectus paralysis)
Vestibular nuclei (nystagmus, nausea, vomiting, vertigo)
Cochlear nuclei (central nerve deafness)
Trigeminal nuclei (paralysis of muscles of mastication, jaw deviation, loss
of facial sensation)
Facial nucleus (facial nerve paralysis and loss of taste sensation from
anterior tongue)
BRAINSTEM NUCLEI. (IMAGE BY HENRY VANDYKE CARTER [PUBLIC DOMAIN], VIA

WIKIMEDIA COMMONS)
Medulla
The medulla oblongata is the upward continuation of the spinal cord. It
receives its blood supply from the posterior inferior cerebellar arteries and
branches of the vertebral and basilar arteries.
FORMATIO RETICULARIS OF THE MEDULLA OBLONGATA: 1. ANTERIOR MEDIAN

FISSURE. 2. FOURTH VENTRICLE. 3. FORMATIO RETICULARIS, WITH 3’, ITS INTERNAL
PART (RETICULARIS ALBA), AND 3’’, ITS EXTERNAL PART (RETICULARIS GRISEA). 4.
RAPHÉ. 5. PYRAMID. 6. LEMNISCUS. 7. INFERIOR OLIVARY NUCLEUS WITH THE TWO
ACCESSORY OLIVARY NUCLEI. 8. HYPOGLOSSAL NERVE, WITH 8’, ITS NUCLEUS OF
ORIGIN. 9. VAGUS NERVE, WITH 9’, ITS NUCLEUS OF TERMINATION. 10. LATERAL
DORSAL ACOUSTIC NUCLEUS. 11. NUCLEUS AMBIGUUS (NUCLEUS OF ORIGIN OF
MOTOR FIBERS OF GLOSSOPHARYNGEAL, VAGUS, AND CEREBRAL PORTION OF
SPINAL ACCESSORY). 12. GRACILE NUCLEUS. 13. CUNEATE NUCLEUS. 14. HEAD OF
POSTERIOR COLUMN, WITH 14’, THE LOWER SENSORY ROOT OF TRIGEMINAL NERVE.
15. FASCICULUS SOLITARIUS. 16. ANTERIOR EXTERNAL ARCUATE FIBERS, WITH 16’,
THE NUCLEUS ARCUATUS. 17. NUCLEUS LATERALIS 18. NUCLEUS OF FASCICULUS
TERES. 19. LIGULA.
Lateral medullary syndrome results from occlusion of the intracranial portion

of the vertebral artery (most commonly) or of the posterior inferior cerebellar
artery (PICA). The resultant structures affected are the:
Vestibular nuclei (nystagmus, nausea, vomiting, vertigo)
Inferior cerebellar peduncle (cerebellar signs)
Nucleus ambiguus of glossopharyngeal and vagus nerve (ipsilateral
laryngeal, pharyngeal and palatal paralysis with dysarthria, dysphagia,
dysphonia)
Spinothalamic tracts (contralateral loss of pain and temperature from
trunk and limbs)
Spinal trigeminal nucleus and tract (ipsilateral loss of pain and
temperature from face)
Descending sympathetic tract (ipsilateral Horner's syndrome)
Medial medullary syndrome results from occlusion of small perforating
branches from the vertebral or proximal basilar artery such as the anterior
spinal artery. The resultant structures affected are the:
Corticospinal tract (contralateral hemiparesis of trunk and extremities)
Medial lemniscus (contralateral loss of proprioception, two-point
discrimination and vibration of trunk and limbs)
Hypoglossal nerve roots (ipsilateral flaccid paralysis of tongue)
8/26/22, 12:02 AM Cerebellum - MRCEM Success
Cerebellum LAST UPDATED:

11TH APRIL 2019
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The infratentorial cerebellum consists of two lateral hemispheres and a

midline part. It, sits within the posterior cranial fossa and lies between
the temporal and occipital lobes and the brainstem.
CEREBELLUM. (IMAGE BY PATRICK J. LYNCH [CC BY 2.5

(HTTP://CREATIVECOMMONS.ORG/LICENSES/BY/2.5)], VIA WIKIMEDIA
COMMONS)
Function
The cerebellum has three primary functions:
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8/26/22, 12:02 AM Cerebellum - MRCEM Success
Maintenance of posture and balance

Maintenance of muscle tone
Coordination of voluntary motor activity
Therefore postural reflexes, truncal stability and synergistic muscular
movements all depend upon an intact cerebellum. Cerebellar lesions do
not cause paralysis but do lead to disturbance of balance and movement.
Blood Supply
The cerebellum receives its blood supply from the posterior inferior
cerebellar artery, the anterior inferior cerebellar artery and the superior
cerebellar artery. Interruption to the blood flow in any of the blood vessels
will lead to cerebellar signs.
Cerebellar dysfunction is characterised by DANISH signs:
Dysmetria (past-pointing) and Dysdiadochokinesia (inability to
perform rapid alternating movements)
Ataxia (lack of coordination of gait, trunk and limbs)
Nystagmus
Intention tremor
Slurred/Scanning/Staccato Speech
Hypotonia
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8/26/22, 12:02 AM Cerebral Hemispheres - MRCEM Success
Cerebral Hemispheres LAST UPDATED:

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The cerebral hemispheres are covered in a thin layer of grey matter called
the cerebral cortex which is folded into gyri (elevations) and separated by
sulci (depressions). The left and right hemispheres are partially separated
by a deep longitudinal fissure (and the falx cerebri of the dura mater
which extends into the fissure). The two cerebral hemispheres are
connected by a white matter structure, called the corpus callosum which
is composed primarily of commissural fibres.
CORPUS CALLOSUM. (IMAGE BY HENRY VANDYKE CARTER [PUBLIC DOMAIN],

Cerebral Lobes
The cerebral hemispheres fill the area of the skull above the tentorium
cerebelli and are subdivided into lobes based on their position relative to
the major sulci:
Frontal lobe – anterior to the central sulcus and superior to the
lateral sulcus (extends from the central sulcus to the frontal pole)
Parietal lobe – posterior to the central sulcus and superior to the
lateral sulcus (extends from the central sulcus to the occipital lobe,
lies superior to the temporal lobe)
Temporal lobe – inferior to the lateral sulcus (extends from the
temporal pole to the occipital lobe)
Occipital lobe – posteroinferior to the parieto-occipital sulcus
LOBES OF THE BRAIN. (IMAGE BY BRUCEBLAUS (OWN WORK) [CC BY 3.0

COMMONS)
Basal Nuclei
The basal nuclei (ganglia) are positioned within the lateral forebrain and
function as a supraspinal control centre for skeletal muscle movement.
They include the caudate nucleus, putamen and globus pallidum. The
basal nuclei are strongly interconnected with the cerebral cortex,
thalamus, and brainstem, as well as several other brain areas. The basal
nuclei are highlighted green in the image below.
Projection Fibres
The white matter of the cerebral hemispheres basically contains two
components; myelinated nerve fibres and neuroglia.
It consists of three types of tracts:
Commissural fibres which interconnect the corresponding regions
of the two cerebral hemispheres (i.e. the corpus callosum and
anterior commissure)
Association fibres which connect the various cortical regions
within a cerebral hemisphere allowing cortical coordination
Projection fibres which connect the cerebral cortex with the lower
part of the brain or brainstem and the spinal cord, in both
directions
Internal Capsule
Most projection fibres (both ascending and descending) pass through the
internal capsule, a layer of white matter which separates the caudate
nucleus and the thalamus medially from the lentiform nucleus (putamen
and globus pallidus) laterally. This is clinically important as the internal
capsule is particularly susceptible to infarction or compression from
haemorrhagic intraparenchymal bleeds. Capsular infarct can result in a
pure motor stroke with contralateral motor weakness and upper motor
neuron signs, or a mixed sensorimotor stroke.
SCHEMATIC ILLUSTRATION OF PROJECTION FIBERS. (IMAGE BY MOELLER K,

WILLMES K AND KLEIN E [CC BY 4.0
COMMONS)
8/26/22, 12:03 AM Cerebral Ventricles - MRCEM Success
Cerebral Ventricles LAST UPDATED: 11TH

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The ventricles are a set of communicating cavities within the brain that are
responsible for the production, transport and removal of cerebrospinal fluid
(CSF), which bathes the central nervous system.
In total there are four ventricles; right and left lateral ventricles, the third
ventricle and the fourth ventricle. In cross sectional radiology, the midline
cavities (third and fourth ventricles and the aqueduct) are symmetrical, but
the lateral ventricles (the cavities of the hemispheres) are not.
Lateral Ventricles
The lateral ventricles are C-shaped cavities located within their respective
hemispheres of the cerebrum. They are divided into a body, an anterior horn
(projecting into the frontal lobe), an inferior horn (projecting into the
temporal lobe) and a posterior horn (projecting into the occipital lobe). The
lateral ventricles are connected to the third ventricle by the interventricular
foramen (of Monro).
Third Ventricle
The third ventricle is a slit-like space in the sagittal plane, situated between
the right and left thalamus and superior to the hypothalamus. The third
ventricle is connected to the fourth ventricle by the cerebral aqueduct.
Fourth Ventricle
The fourth ventricle lies within the brainstem, at the junction between the
pons and the medulla oblongata.
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8/26/22, 12:03 AM Cerebral Ventricles - MRCEM Success
VENTRICULAR SYSTEM OF THE BRAIN. (IMAGE BY BRUCEBLAUS (OWN WORK) [CC

BY 3.0 (HTTP://CREATIVECOMMONS.ORG/LICENSES/BY/3.0)], VIA WIKIMEDIA
COMMONS)
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8/26/22, 12:04 AM Cerebrospinal Fluid - MRCEM Success
Cerebrospinal Fluid LAST UPDATED: 11TH

APRIL 2019
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Total CSF volume is about 130 ml, of which the majority is in the
subarachnoid space.
Function
CSF has three main functions:
1. Protection - acting as a cushion for the brain

2. Buoyancy - reducing the net weight of the brain to prevent excessive
pressure on the base of the brain
3. Chemical stability - creating the right chemical environment to allow
proper functioning of the brain
Production
CSF is secreted by the ventricular choroid plexuses, which are vascular
conglomerates of capillaries, pial and ependymal cells. The majority of CSF
arises from the plexuses of the lateral ventricles.
Flow
From the lateral ventricles, CSF passes through the interventricular foramina
to the third ventricle, then the cerebral aqueduct to the fourth ventricle.
From the roof of the fourth ventricle, the CSF drains via foramina into the
central spinal canal (bathing the spinal cord) and the subarachnoid cisterns
in the subarachnoid space located between the arachnoid mater and pia
mater (bathing the brain).
From the subarachnoid cisterns, CSF is reabsorbed by arachnoid
granulations, which protrude into the dura mater, into the dural venous
sinuses and from here back into the circulation.
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8/26/22, 12:04 AM Cerebrospinal Fluid - MRCEM Success
There is small but significant CSF drainage via the cribriform plate of the
ethmoid into the nasal tissues. Fracture of the cribriform plate results in CSF
rhinorrhoea.
CIRCULATION OF CEREBROSPINAL FLUID. (IMAGE BY OPENSTAX [CC BY 4.0

https://mrcemsuccess.com/explanation/cerebrospinal-fluid/?_sft_qc=central-nervous-system 3/3
8/26/22, 12:05 AM Frontal Lobe - MRCEM Success
Frontal Lobe LAST UPDATED: 19TH

FEBRUARY 2019
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The frontal lobe extends from the central sulcus to the frontal pole. It is separated
from the parietal lobe posteriorly by the central sulcus and from the temporal lobe
inferoposteriorly by the lateral sulcus.

https://mrcemsuccess.com/explanation/frontal-lobe/?_sft_qc=central-nervous-system 2/6
Function
Areas of the frontal lobe are responsible for:
Movement (planning and execution)
Higher intellect, problem solving and judgement
Attention and concentration
Behaviour, personality and mood
Language production
Continence
Cortical Areas
Table: Cortical Areas of the Frontal Lobe

Area Function Lesion
Primary motor Contralateral Contralateral UMN
cortex movement of voluntary weakness/paralysis
muscles
Premotor Role in coordination of Apraxia, UMN signs
cortex complex movements
Supplementary Role in programming Inability to plan sequence of
motor cortex complex motor complex movements
sequences
Frontal eye Conjugate deviation of Conjugate deviation of the
field the eyes to the eyes towards the side of the
opposite side lesion (and away from the
side of weakness)
Broca speech Speech production Expressive dysphasia
area (dominant
hemisphere)
Prefrontal Higher intellect, Inappropriate social behavior,
cortex problem-solving, difficulty in adaptation and
judgement, personality, loss of initiative, primitive
emotion and mood, reflexes, inability to
central control of concentrate, incontinence
micturition
The primary motor cortex is located in the precentral gyrus and is responsible
for voluntary movements of muscles of the opposite side of the body.
The premotor cortex plays a role in the control and coordination of proximal
and axial muscles, it prepares the motor cortex for specific movements in
advance of their execution.
The supplementary motor cortex is concerned with programming of complex
movements and regulates somatosensory input into the motor cortex.
The Broca speech area (in the dominant hemisphere only) is the 'expressive'
centre for the production of speech. It is connected to the Wernicke speech
area by the arcuate fasciculus.
The frontal eye field is involved in making eye movements to the contralateral
side.
The prefrontal cortex governs personality, emotional expression, initiative
and the ability to plan.
The cortical micturition centre, within the prefrontal cortex, is involved in the
cortical inhibition of the voiding of the bladder.
MOTOR AND SENSORY REGIONS OF THE CEREBRAL CORTEX. (IMAGE BY BLAUSEN.COM

STAFF. “BLAUSEN GALLERY 2014, VIA WIKIMEDIA COMMONS)
Blood Supply
The blood supply to the frontal lobe is from the anterior cerebral artery (supplying
the medial surface of the primary motor cortex which controls the lower limb) and
the middle cerebral artery (supplying the lateral surface of the primary motor cortex
which controls the face and upper limb).

(BRAIN_STEM_NORMAL_HUMAN.SVG) [GFDL 1.3 (WWW.GNU.ORG/LICENSES/FDL-
1.3.HTML), VIA WIKIMEDIA COMMONS)
Damage to the frontal lobe may cause a diverse range of presentations including:
contralateral weakness/paralysis in an UMN pattern (damage to the primary
motor cortex)
inability to plan sequence of complex movements (damage to the premotor
cortex and supplementary motor cortex)
conjugate eye deviation where both eyes look towards the side of the lesion
and away from the side of weakness (damage to the frontal eye field)
expressive dysphasia (damage to the Broca speech area)
personality, mood and behavioural change with loss of initiative and inability
to problem solve (damage to the prefrontal cortex)
primitive reflexes (damage to the prefrontal cortex)
anosmia (damage to the olfactory tract as a result of close proximity to
inferior frontal lobe)
incontinence (damage to the cortical micturition centre)
CORTICAL LANGUAGE AREAS. (IMAGE BY PETER HAGOORT [CC BY 3.0

8/26/22, 12:06 AM Occipital Lobe - MRCEM Success
Occipital Lobe LAST UPDATED: 11TH

APRIL 2019
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The occipital lobe rests inferiorly upon the tentorium cerebelli which segregates
the cerebrum from the cerebellum. The parieto-occipital sulcus separates the
occipital lobe from the parietal and temporal lobes anteriorly.

Cortical Areas
The primary visual cortex is located within the occipital lobe and together with
the visual association cortex is responsible for vision.
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Blood Supply
The blood supply to the occipital lobe is from the posterior cerebral artery, but
the occipital poles, serving macular vision, have additional supply from a branch
of the middle cerebral artery.

Damage to the occipital lobe can result in:
Contralateral homonymous hemianopia (with macular sparing)
Cortical blindness
Visual agnosia
Colour blindness
Visual illusions or hallucinations
Difficulty reading and writing
8/26/22, 12:06 AM Parietal Lobe - MRCEM Success
Parietal Lobe LAST UPDATED: 6TH

NOVEMBER 2019
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The parietal lobe lies between the frontal lobe anteriorly and the occipital lobe
posteriorly, from which it is separated by the central sulcus and parieto-occipital
sulcus, respectively. It sits superiorly in relation to the temporal lobe, being
separated by the lateral sulcus.

Function
Areas of the parietal lobe are responsible for:
Perceiving and interpreting sensation and proprioception
Language and calculation of numbers on the dominant hemisphere side
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Integration of somatosensory, visual and auditory information and

processing of visuospatial functions (e.g. 2-point discrimination) on the
non-dominant hemisphere side
Cortical Areas

Primary Sensation and Loss of sensation, difficulty
somatosensory proprioception, distinguishing left from right,
cortex and visuo-spatial sensory neglect, apraxia, loss of
somatosensory perception hand-eye coordination, tactile
association agnosia
cortex
Arcuate Connects Difficulties with reading, writing,
fasciculus audiovisual naming, maths
association areas
with Broca and
Wernicke speech
areas
Optic radiation Carries visual Contralateral homonymous
information to inferior quadrantanopia
primary visual
cortex
The primary somatosensory cortex is located in the postcentral gyrus and

is concerned with perceiving complex somatosensory stimuli from the
contralateral side of the face and body. Together with the somatosensory
association cortex, these areas are responsible for sensation and
proprioception, and visuo-spatial perception.
Pathways within the arcuate fasciculus are concerned with language as
they connect Broca's area (frontal lobe) with Wernicke's area (temporal
lobe).
The fibres of the upper part of the optic radiation (serving the lower
quadrant of the contralateral visual field) pass deep within the parietal
lobe.

Blood Supply
The blood supply to the parietal lobe is from the middle cerebral artery.

Clinical Implications:
Damage to the parietal lobe may result in:
Cortical contralateral sensory loss with loss of proprioception and two-
point discrimination
Apraxia
Tactile agnosia
Attention deficits e.g. contralateral hemispatial neglect syndrome (an
inability to perceive a contralateral stimulus when two simultaneous
sensory stimuli are applied with equal intensity to corresponding sites on
opposite sides of the body)
Visual field defect (contralateral homonymous inferior quadrantanopia)
8/26/22, 12:07 AM Spinal Cord - MRCEM Success
Spinal Cord LAST UPDATED: 27TH

JUNE 2020
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Extent
The spinal cord arises cranially as a continuation of the medulla oblongata
at the foramen magnum. It then travels inferiorly within the vertebral canal,
surrounded by the spinal meninges, before terminating as the conus
medullaris. The filum terminale is an extension of pia mater that extends
from the conus medullaris to the dural sac, and from the dural sac to the
coccyx.
EXTENT OF THE SPINAL CORD. (IMAGE BY HENRY VANDYKE CARTER [PUBLIC

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At birth, the conus medullaris lies at L3. By the age of 21, it sits at L1/L2, thus
the spinal cord only occupies about 2/3s of the space available to it in the
vertebral canal. The lower a nerve root, therefore, the more steeply it slopes
down and the further it has to travel before gaining its intervertebral
foramen. The lumbosacral nerve roots that arise from the end of the spinal
cord and descend through the subarachnoid space to exit through their
respective intervertebral or sacral foramina are bundled together forming
the cauda equina.
CAUDA EQUINA. (IMAGE MODIFIED BY FRCEM SUCCESS. ORIGINAL BY HENRY

Enlargements
During the course of the spinal cord, there are two points of enlargement:
The cervical enlargement is located in the region associated with the
origins of spinal nerves C5 to T1 (at the C3 - T1 vertebral level).
The lumbar enlargement is located in the region associated with the

origins of spinal nerves L1 to S3 (at the T11 - L1 vertebral level).
ENLARGEMENTS OF THE SPINAL CORD. (IMAGE BY HENRY VANDYKE CARTER

Internal anatomy
Internally the spinal cord has a small central canal (containing CSF)
surrounded by grey and white matter. The central grey matter is rich in nerve
cell bodies which are divided into three divisions (the anterior, posterior and
lateral horns), which in cross-section form the characteristic H-shaped
appearance in the central regions of the cord. The peripheral white matter
surrounds the grey matter and is rich in myelinated nerve cell processes,
which form large bundles or tracts that ascend and descend in the cord to
other spinal cord levels or the brain. The white matter is divided bilaterally by
sulci into three major divisions (the anterior, posterior and lateral columns).
INTERNAL ANATOMY OF THE SPINAL CORD. (IMAGE BY USER:POLARLYS (OWN

WORK) [GFDL (HTTP://WWW.GNU.ORG/COPYLEFT/FDL.HTML)], VIA WIKIMEDIA
COMMONS)
Blood Supply
The spinal cord is supplied primarily by branches of the vertebral artery:
The single anterior spinal artery is formed from the left and right
vertebral arteries and supplies the anterior two-thirds of the spinal
cord, including the anterior and lateral horns and the anterior and
lateral columns.
The paired posterior spinal arteries arise from either the posterior
inferior cerebellar artery or directly from the vertebral artery and
supply the posterior third of the spinal cord including the posterior
horns and columns.
Nerve Roots
The spinal nerves are formed by the union of posterior and anterior roots.
Spinal rootlets emerge from the spinal cord in the subarachnoid space and
amalgamate shortly afterwards into roots. Anterior roots (containing motor
nerve fibres) and posterior roots (containing the processes of sensory
neurons) then emerge from their individual intervertebral foramina.
After invaginating the dura, the roots combine into mixed spinal nerves
which divide into a posterior ramus (innervating intrinsic back muscles and
an associated strip of skin on the back) and an anterior ramus (innervating
the remaining muscles and skin of the trunk and limbs and the visceral
organs).
SPINAL NERVE ROOTS. (IMAGE BY MYSID (ORIGINAL BY TRISTANB) [GFDL

(HTTP://WWW.GNU.ORG/COPYLEFT/FDL.HTML)], VIA WIKIMEDIA COMMONS)
8/26/22, 12:09 AM Spinal Cord Tracts - MRCEM Success
Spinal Cord Tracts LAST UPDATED: 28TH

MARCH 2022
 Bookmark
The spinal cord has numerous groups of nerve fibers going towards and coming from the brain.
These ascending and descending tracts of the spinal cord are responsible for carrying motor and
sensory stimuli to and from the periphery.
ASCENDING AND DESCENDING TRACTS OF THE SPINAL CORD. (IMAGE BY POLARLYS AND MIKAEL
HÄGGSTRÖM [CC BY-SA 3.0 (HTTP://CREATIVECOMMONS.ORG/LICENSES/BY-SA/3.0)], VIA WIKIMEDIA
COMMONS)
Ascending Tracts
The ascending spinal cord tracts represent functional pathways that convey sensory information
from the periphery to higher levels.
Table: Ascending Tracts of the Spinal Cord
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Tract Location Function

Dorsal Column Posterior Transmits proprioception, vibration and fine-touch
Medial column sensation
Lemniscus
System
Anterior Anterior Transmits crude touch and pressure sensation
spinothalamic column
tract (decussates
in spinal cord)
Lateral Lateral Transmits pain and temperature sensation
spinothalamic column
tract (decussates (anterior
in spinal cord) aspect)
Posterior Lateral Transmits unconscious proprioceptive information to
spinocerebellar column the cerebellum, involved in fine coordination of posture
tract (posterior and movement of individual muscles of lower limb
aspect)
Anterior Lateral Transmits unconscious proprioceptive information to
spinocerebellar column the cerebellum, involved with coordination movement
tract (anterior and posture of the entire lower limb
aspect)
ASCENDING TRACTS OF THE SPINAL CORD. (IMAGE BY OPENSTAX COLLEGE [CC BY 3.0
Descending Tracts
The descending tracts are functional pathways concerned with somatic and visceral motor
activities.
Table: Descending Tracts of the Spinal Cord

Tract Location Function
Lateral corticospinal tract Lateral column Involved in voluntary skilled
(posterior aspect) motor activity of limbs
Anterior corticospinal tract Anterior column Involved with control of axial
(decussates in spinal cord) muscles
DESCENDING TRACTS OF THE SPINAL CORD. (IMAGE BY OPENSTAX COLLEGE [CC BY 3.0
Table: Clinical Effects of Lesions of the Spinal Cord
Spinal Cord Mechanism Tracts Clinical Features

Syndrome Affected
Complete Major trauma All tracts Death (C1 – C3), paralysis of
cord voluntary/automatic breathing
transection (above C5), quadriplegia (C4 –
C5), paraplegia (below T1), UMN
paralysis below lesion, complete
sensory loss below lesion,
urinary and faecal incontinence,
anhidrosis and loss of
vasomotor tone
Brown- Penetrating All tracts on Ipsilateral UMN paralysis below
Sequard trauma one side lesion, ipsilateral loss of
syndrome proprioception/vibration/fine
(hemisection) touch sensation below lesion,
contralateral loss of crude
touch/pain/temperature
sensation below lesion, bilateral
lower limb ataxia
Central cord Hyperextension Lateral Bilateral sensory loss and UMN
syndrome injury of corticospinal motor loss below lesion with
cervical spine tract, greater loss in upper limbs than
in patient with spinothalamic lower limbs, and greater loss of
pre-existing tract motor function than sensory
cervical function
stenosis
Anterior cord Occlusion of Corticospinal, Complete motor paralysis
syndrome anterior spinal spinothalamic (flaccid at level of lesion and
artery with and spastic below lesion), bilateral
infarction of spinocerebellar loss of pain and temperature
territory sensation at and below lesion
supplied due to interruption of
spinothalamic tract (but
retained proprioception and
vibratory sensation due to intact
dorsal columns), autonomic
dysfunction may manifest as
hypotension (either orthostatic
or frank hypotension), sexual
dysfunction, and/or bowel and
bladder dysfunction
INCOMPLETE LESIONS OF THE SPINAL CORD. (IMAGE BY FPJACQUOT, VIA WIKIMEDIA COMMONS)
8/26/22, 12:09 AM Temporal Lobe - MRCEM Success
Temporal Lobe LAST UPDATED: 11TH

APRIL 2019
 Bookmark
The temporal lobe extends from the temporal pole to the occipital lobe and lies
inferior to the frontal and parietal lobes, from which it is separated by the lateral
sulcus.

Cortical Areas
Table: Cortical Areas of the Temporal Lobe
https://mrcemsuccess.com/explanation/temporal-lobe/?_sft_qc=central-nervous-system&sf_paged=2 2/6

Wernicke’s speech Language Receptive dysphasia
area comprehension
Primary auditory Perception and Partial cortical deafness,
cortex and auditory recognition of auditory agnosia
association area auditory stimuli
Limbic association Memory, learning, Memory impairment,
cortex emotion increased aggression,
difficulty recognising
faces/objects
Optic radiation Carries visual Contralateral homonymous
information to superior quadrantanopia
primary visual
cortex
The Wernicke's speech area (in the dominant hemisphere only) is responsible
for comprehension of written and spoken language. It is connected to the
Broca's speech area by the arcuate fasciculus.
The primary auditory cortex and auditory association area are important for
perception and recognition of auditory stimuli.
The limbic association cortex is important in memory, learning and emotion.
The fibres of the lower part of the optic radiation (serving the upper quadrant
of the contralateral visual field) pass through the temporal lobe.

Blood Supply
The blood supply to the temporal lobe is from the posterior cerebral artery (medial
part of the lobe) and the middle cerebral artery (lateral part of the lobe).

Damage to the temporal lobe may result in:
Receptive dysphasia - damage to the Wernicke's speech area
Visual field defect (contralateral homonymous superior quadrantanopia) -
damage to the optic radiation
Memory impairment - damage to the limbic system
Emotional and behavioural disturbances - damage to the limbic system
Auditory agnosia - damage to the primary auditory cortex or auditory
association areas
Partial cortical deafness (due to bilateral cochlear representation) - damage
to the primary auditory cortex
CORTICAL LANGUAGE AREAS. (IMAGE BY PETER HAGOORT [CC BY 3.0

8/26/22, 12:10 AM Thalamus - MRCEM Success
Thalamus LAST UPDATED: 11TH

APRIL 2019
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The thalamus is a wedge-shaped structure around the third ventricle,

made up of at least 50 thalamic nuclei.
THALAMUS. (IMAGE BY HENRY VANDYKE CARTER [PUBLIC DOMAIN], VIA

WIKIMEDIA COMMONS)
Functions
The thalamus has many functions including:
translation of prethalamic inputs into readable form
process and relay of sensory information selectively to various parts
of the cerebral cortex
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8/26/22, 12:10 AM Thalamus - MRCEM Success
regulation of sleep and wakefulness

thalamo-cortico-thalamic circuits involved in consciousness,
arousal, level of awareness, and activity
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8/26/22, 12:11 AM Visual Pathway - MRCEM Success
Visual Pathway LAST UPDATED: 26TH

FEBRUARY 2020
ANATOMY / CENTRAL NERVOUS SYSTEM /
CRANIAL NERVE LESIONS  Bookmark
Visual Pathway
RETINAL BIPOLAR AND GANGLION CELLS:
There are two types of photoreceptors in the human retina, rods and cones. Rods
and cones are the first-order receptor cells that respond directly to light
stimulation. Bipolar neurons are the second-order neurons that relay stimuli from
the rods and cones to the retinal ganglion cells.
OPTIC NERVE:
The optic nerve is formed by the convergence of axons from the retinal ganglion
cells. The optic nerve leaves the bony orbit via the optic canal, a passageway
through the sphenoid bone. It enters the cranial cavity, running along the surface
of the middle cranial fossa (in close proximity to the pituitary gland).
OPTIC CHIASM:
Within the middle cranial fossa, the optic nerves from each eye unite to form the
optic chiasm.
OPTIC TRACTS:
At the optic chiasm, fibres from the medial (nasal) half of each retina crossover,
forming the right and left optic tracts.
The left optic tract contains fibres from the left lateral (temporal) retina and
the right medial retina.
The right optic tract contains fibres from the right lateral retina and the left
medial retina.
Each optic tract travels to its corresponding cerebral hemisphere to reach its lateral
geniculate nucleus (LGN) located in the thalamus where the fibres synapse.
OPTIC RADIATION:
Axons from the lateral geniculate nucleus (LGN) then carry visual information, via
the upper and lower optic radiations, to the visual cortex in the occipital lobe:
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The upper optic radiation carries fibres from the superior retinal quadrants
(corresponding to the inferior visual field quadrants) and travels through the
parietal lobe to reach the visual cortex.
The lower optic radiation carries fibres from the inferior retinal quadrants
(corresponding to the superior visual field quadrants) and travels through the
temporal lobe to reach the visual cortex of the occipital lobe.
VISUAL CORTEX:
At the visual cortex, the brain processes the sensory information and responds
appropriately.
VISUAL PATHWAY. (IMAGE BY MIQUEL PERELLO NIETO (OWN WORK) [CC BY-SA 4.0
(HTTP://CREATIVECOMMONS.ORG/LICENSES/BY-SA/4.0)], VIA WIKIMEDIA COMMONS)
Blood Supply
Table: Blood Supply of the Visual Pathway
Structure Blood Supply

Optic nerve (retinal and Central retinal artery (branch of the
orbital part) ophthalmic artery)
Optic nerve (intracranial Ophthalmic artery, anterior cerebral and
part) and optic chiasm anterior communicating arteries
Optic tract Posterior communicating artery and anterior
choroidal artery
Lateral geniculate nucleus Posterior cerebral artery and
anterior choroidal artery
Optic radiations Middle and posterior cerebral arteries,
anterior choroidal artery
Visual cortex Posterior cerebral artery (macular dually
supplied by middle cerebral artery)

Damage to the optic nerve may be caused by:
optic neuritis in multiple sclerosis or secondary to measles or mumps
optic nerve compression secondary to orbital cellulitis, glaucoma or ocular
tumours
optic nerve toxicity secondary to ethambutol, methanol and ethylene glycol
optic nerve damage secondary to orbital fracture or penetrating injury to the
eye
optic nerve ischaemia
Compression at the optic chiasm may occur due to:
pituitary tumour
craniopharyngioma
meningioma
optic glioma
aneurysm of the internal carotid artery
Damage to the visual tract central to the optic chiasm may be caused by:
cerebrovascular event
brain abscess
brain tumours
Table: Clinical Effects of Lesions of the Visual Pathway

Site of Lesion Visual Defect
Optic nerve Ipsilateral visual loss
Optic chiasm Bitemporal hemianopia
Optic tract Contralateral homonymous hemianopia
Parietal upper optic Contralateral homonymous inferior
radiation quadrantanopia
Temporal lower optic Contralateral homonymous superior
radiation quadrantanopia
Occipital visual cortex Contralateral homonymous hemianopia with
macular sparing
CLINICAL EFFECTS OF LESIONS OF THE VISUAL PATHWAY. (IMAGE MODIFIED BY FRCEM

SUCCESS. ORIGINAL BY KDS444 [PUBLIC DOMAIN], VIA WIKIMEDIA COMMONS)
8/26/22, 12:12 AM Cranial Nerve I: Olfactory Nerve - MRCEM Success
Cranial Nerve I: Olfactory LAST UPDATED: 11TH

APRIL 2019
Nerve  Bookmark
ANATOMY / CRANIAL NERVE LESIONS /
HEAD AND NECK / NOSE AND PARANASAL REGION
The olfactory nerve (CN I) is a sensory nerve responsible for the sense of smell.
Table: Overview of the Olfactory Nerve

Cranial Olfactory Nerve (CN I)
Nerve
Key Nerve fibres from nasal epithelium enter cranial cavity via
anatomy cribriform plate of ethmoid bone, fibres then enter olfactory
bulb in anterior cranial fossa, second-order neurons pass
posteriorly into olfactory tract which runs inferiorly to frontal
lobe
Function Sensory: sense of smell
Assessment Enquire about changes in smell/taste, formal assessment of
smell
Clinical Anosmia (loss of smell) and taste
effects of
injury
Causes of Local nasal disease, tumour of frontal lobe, meningitis,
injury trauma (e.g. fractured ethmoid bone, head injury)
Anatomical Course
The olfactory nerve consists of a collection of unmyelinated axons of bipolar
neurons located in the nasal mucosa which enter the skull via the foramina of the
cribriform plate of the ethmoid bone. Once in the cranial cavity, the fibres enter the
olfactory bulb which lies in the anterior cranial fossa and synapse, before second-
order neurons pass posteriorly into the olfactory tract which runs inferiorly to the
frontal lobe.
The olfactory nerve is the shortest cranial nerve and originates from the cerebrum;
it is one of two nerves that do not originate from the brainstem, the other being the
optic nerve.
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OLFACTORY NERVE. (IMAGE BY PATRICK J. LYNCH, MEDICAL ILLUSTRATOR (PATRICK J.

LYNCH, MEDICAL ILLUSTRATOR) [CC BY 2.5
Assessment
The olfactory nerve is usually tested by asking the patient if they have noticed any
change in their sense of smell or taste; it can be formally tested using recognisable
smells e.g. peppermint, asking the patient to close their eyes and examining each
nostril in turn.

Examples of causes of damage to the olfactory nerve include:
Local nasal disease
External pressure from a tumour of the frontal lobe
Meningitis
Trauma (most common, e.g. contrecoup injury from occipital head trauma,
direct coup injury from frontal head trauma, fracture of cribriform plate)
Trauma is the most common cause of olfactory nerve injury and the olfactory nerve
is the most commonly damaged nerve in head injury. All patients presenting with
olfactory nerve dysfunction, especially following trauma, should be considered for
CT scan.

Injury to the olfactory nerve causes anosmia (loss of sense of smell) with altered
sense of taste.
8/26/22, 12:12 AM Cranial Nerve II: Optic Nerve - MRCEM Success
Cranial Nerve II: Optic LAST UPDATED: 11TH

APRIL 2019
Nerve  Bookmark
HEAD AND NECK / ORBIT AND EYE
The optic nerve (CN II) is a purely sensory nerve, which carries visual
information from the retina to the visual cortex.
Table: Optic Nerve

Cranial Optic Nerve (CN II)
Nerve
Key Formed from convergence of axons of neurons in
anatomy ganglion layer of retina, surrounded by cranial meninges,
enters skull via optic canal of sphenoid bone, receives
blood supply from combination of anterior cerebral,
ophthalmic and central retinal arteries
Function Sensory: vision, afferent pathway of pupillary light reflex
Assessment Visual acuity (Snellen chart), colour vision (Ishihara
plates), pupillary light response, optic disc (fundoscopy),
visual fields (tests visual pathway)
Clinical Ipsilateral monocular visual loss, loss of colour vision,
effects of abnormal pupillary light reflex, visual field defects if
injury damage to visual pathway
Causes of Optic neuritis in multiple sclerosis, optic nerve
injury compression in orbital cellulitis or glaucoma, optic nerve
toxicity, trauma (e.g. orbital fracture, penetrating injury
to eye), ischaemia secondary to vascular disease
Anatomical Course
The optic nerve is not a true cranial nerve but rather an extension of the brain
carrying afferent fibres from the retina of the eyeball to the visual centres of
the brain. It is one of two cranial nerves that do not arise from the brainstem,
the other being the olfactory nerve.
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The optic nerve is surrounded by the cranial meninges, including the

subarachnoid space, which extend as far forwards as the eyeball. Any increase
in intracranial pressure will therefore result in increased pressure in the
subarachnoid space surrounding the optic nerve. This impedes venous return
along the retinal veins, causing oedema of the optic disc (papilloedema).
The optic nerve leaves the orbit through the sphenoidal optic canal.
The optic nerve receives its blood supply from the anterior cerebral,
ophthalmic and central retinal arteries.
OPTIC NERVE. (IMAGE BY OPENSTAX [CC BY 4.0

Assessment
To assess the optic nerve:
The patient should be asked if they have noticed any changes in their
vision
Visual acuity should be assessed with a Snellen chart

Visual fields should be assessed, testing each visual quadrant in turn
Colour vision should be assessed with Ishihara plates
Pupillary response should be tested using a swinging light to assess
direct and consensual reflexes (this tests both the afferent optic nerve
and the efferent oculomotor nerve)
The optic disc should be assessed using fundoscopy

Causes of damage to the optic nerve include:
Optic neuritis in multiple sclerosis or secondary to measles or mumps
Optic nerve compression secondary to orbital cellulitis, glaucoma or
ocular tumours
Optic nerve toxicity secondary to ethambutol, methanol and ethylene
glycol
Optic nerve trauma secondary to orbital fracture or penetrating injury to
the eye
Optic nerve ischaemia secondary to arterial disease

Lesions of the optic nerve result in:
Visual loss in the ipsilateral eye
Loss of colour vision in the ipsilateral eye
Abnormal pupillary light reflex
Loss of pupillary light reflex seen in complete transection of the
optic nerve:
Ipsilateral direct reflex lost
Contralateral consensual reflex lost
Contralateral direct reflex intact
Ipsilateral consensual reflex intact
Relative afferent pupillary defect (RAPD) seen in other optic nerve
disease:
Paradoxical direct and consensual dilatation when light is
shone in the affected eye directly after being shone in the
unaffected eye (the affected eye still senses light and
8/26/22, 12:13 AM Cranial Nerve III: Oculomotor Nerve - MRCEM Success
Cranial Nerve III: LAST UPDATED: 11TH

APRIL 2019
Oculomotor Nerve  Bookmark
The oculomotor nerve (CN III) is responsible for movements of the eyeball and
eyelid.
Cranial Oculomotor Nerve (CN III)

Nerve
Key Arises from midbrain, passes through lateral aspect of
anatomy cavernous sinus, exits skull through superior orbital
fissure
Function Motor: innervates four extraocular muscles (inferior
oblique, superior, inferior and medial rectus
muscles), levator palpebrae superioris muscle (elevation
of upper eyelid), sphincter pupillae muscle (pupillary
constriction), ciliary muscle (accommodation), efferent
pathway of pupillary light reflex
Assessment Eye movements, accommodation, pupillary light reflex
Clinical Depressed and abducted (down and out) eye, diplopia,
effects of ptosis, fixed and dilated pupil with loss of
injury accommodation and abnormal pupillary light reflex
Causes of Tumours, aneurysms (posterior
injury communicating), subdural or epidural haematoma,
diabetes mellitus
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Function
The oculomotor nerve is a motor nerve innervating all of the extraocular
muscles responsible for eyeball movements (except for the superior oblique
and lateral rectus muscles) and the levator palpebrae superioris muscle
responsible for elevation of the upper eyelid. It also provides the
parasympathetic supply to the sphincter pupillae (pupillary constriction) and
ciliary muscle (accommodation).
Anatomical Course
The oculomotor nerve arises from the anterior aspect of the midbrain and then
passes forwards between the posterior cerebral and superior cerebellar
arteries, very close to the posterior communicating artery. It pierces the dura
near the edge of the tentorium cerebelli, and passes through the lateral part of
the cavernous sinus (together with CN IV and VI nerves and the ophthalmic
division of CN V) to enter the orbit through the superior orbital fissure.
OBLIQUE SECTION THROUGH THE RIGHT CAVERNOUS SINUS. (IMAGE BY HENRY

At this point it divides into a superior branch innervating the superior rectus
and levator palpebrae superioris muscles and an inferior branch innervating
the inferior rectus, medial rectus and inferior oblique muscles and supplying
parasympathetic innervation to the sphincter pupillae and ciliary muscles. The
parasympathetic fibres pass on the periphery of the oculomotor nerve.
OCULOMOTOR NERVE. (IMAGE BY HENRY VANDYKE CARTER [PUBLIC DOMAIN], VIA

WIKIMEDIA COMMONS)
Assessment
The oculomotor nerve should be assessed by testing:
Ocular movements (which also tests the trochlear nerve (CN IV) and the
abducens nerve (CN VI))
Pupillary accommodation
Pupillary light reflex (which also tests the afferent optic nerve (CN II)).

Causes of CN III palsy:
Compressive aetiology
Tumours (commonly by compression against the fixed edge of the

tentorium as the medial part of the temporal lobe herniates down)
Aneurysms (carotid or posterior communicating artery)
Subdural or epidural haematoma
Trauma
Cavernous sinus disease
Ischaemic aetiology
Diabetes mellitus
Hypertension
Compressive causes of CN III palsy cause early pupillary dilatation because the
parasympathetic fibres run peripherally in the nerve and are easily
compressed. In diabetes mellitus the lesions are ischaemic rather than
compressive and therefore typically affect the central fibres resulting in
pupillary sparing.

CN III palsy results in:
A depressed and abducted eye (down and out pupil) due to unopposed
action of the lateral rectus and superior oblique muscles
Diplopia on looking up and in
Ptosis
Fixed pupillary dilatation
Loss of accommodation (cycloplegia)
Abnormal pupillary light reflex
Ipsilateral direct reflex lost
Contralateral consensual reflex intact
Contralateral direct reflex intact
Ipsilateral consensual reflex lost
8/26/22, 12:13 AM Cranial Nerve IV: Trochlear Nerve - MRCEM Success
Cranial Nerve IV: Trochlear LAST UPDATED: 11TH

APRIL 2019
Nerve  Bookmark
The trochlear nerve (CN IV) is a motor nerve supplying the superior oblique
muscle of the eye.
Table: Overview of the Trochlear Nerve

Cranial Trochlear Nerve (CN IV)
Nerve
Key Arises from midbrain, travels through lateral aspect of
anatomy cavernous sinus, exits skull through superior orbital
fissure
Function Motor: superior oblique muscle of eye (intorsion,
depression and abduction of eye)
Assessment Eye movements
Clinical Weakness of downward gaze (difficulty reading/walking
effects of downstairs), vertical diplopia, eye is extorted and may be
injury elevated (patient head tilts to opposite side to
compensate)
Causes of Idiopathic, trauma, microvasculopathy, cavernous sinus
injury disease, raised intracranial pressure
Anatomical Course
It is the smallest cranial nerve but has the longest cranial course. It arises from
the trochlear nucleus and decussates within the midbrain, emerging from the
posterior aspect of the midbrain. It runs anteroinferiorly within the
subarachnoid space before piercing the dura and travelling along the lateral
wall of the cavernous sinus, before entering the orbit of the eye via the
superior orbital fissure.
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TROCHLEAR NERVE. (IMAGE BY HENRY VANDYKE CARTER [PUBLIC DOMAIN], VIA

WIKIMEDIA COMMONS)
Function
The superior oblique primarily rotates the top of the eye towards the nose
(intorsion). Secondarily, it moves the eye downward (depression) and outward
(abduction). It prevents the unopposed action of the superior rectus which
would otherwise rotate the globe.
Assessment
The trochlear nerve should be assessed together with the oculomotor nerve
(CN III) and the abducens nerve (CN VI) by testing ocular movements.

Causes of damage include:
Idiopathic (most commonly)
Trauma
Microvasculopathy (associated with diabetes and hypertension)

Multiple sclerosis
Lesions in the midbrain
Cavernous sinus disease
Raised intracranial pressure

Trochlear palsy causes weakness of downward gaze. The patient complains of
difficulty reading or walking downstairs and of vertical diplopia. The eye is
extorted and may be elevated and the patient may head tilt to the opposite
side of the palsy to compensate.
8/26/22, 12:14 AM Cranial Nerve V: Trigeminal Nerve - MRCEM Success
Cranial Nerve V: Trigeminal LAST UPDATED: 23RD

APRIL 2020
Nerve  Bookmark
HEAD AND NECK / FACE
The trigeminal nerve (CN V) is the largest cranial nerve, originating from three
sensory nuclei and one motor nucleus extending from the midbrain to the
medulla and exiting the brainstem from the pons.
Table: Overview of the Trigeminal Nerve

Cranial Trigeminal Nerve (CN V)
Nerve
Key Arises from several nuclei in the brainstem, exits
anatomy brainstem from pons
Sensory Face, oral and nasal cavities, frontal sinus, external ear,
function afferent pathway of corneal reflex
Motor Muscles of mastication, tensor tympani, tensor veli
function palatini, mylohyoid, anterior belly of digastric,
parasympathetic fibres to lacrimal and nasal glands
Assessment Sensation of face, jaw jerk, corneal blink reflex,
power/bulk of muscles of mastication
Clinical Flaccid paralysis of muscles of mastication, jaw
effects of deviation towards affected side, loss of sensation to
injury face, loss of afferent corneal reflex, loss of jaw jerk
Causes of Trauma, anaesthetic block, tumours, cavernous sinus
injury disease
Anatomical Course
The trigeminal nerve is a mixed motor and sensory nerve. It has three main
divisions:
V1 ophthalmic
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V2 maxillary
V3 mandibular
TRIGEMINAL NERVE. (IMAGE BY HENRY VANDYKE CARTER [PUBLIC DOMAIN], VIA

WIKIMEDIA COMMONS)
Function
The trigeminal nerve supplies:
Sensation to the face, mucous membranes of the nasal and oral cavities
and frontal sinus, teeth, hard palate, soft palate and deep structures of
the head (proprioception from muscles and the TMJ), the dura of the
anterior and middle cranial fossa and the external ear
The afferent pathway for the corneal reflex
The muscles of mastication (temporalis, masseter, lateral and medial
pterygoids)
The tensor tympani muscle of the middle ear
The tensor veli palatini muscle of the soft palate
The mylohyoid and the anterior belly of the digastric muscles

Parasympathetic fibres to lacrimal and nasal glands
Assessment
The trigeminal nerve can be assessed by:
Testing sensation of the face (testing both light touch and pin prick)
Testing muscles of mastication by asking the patient to clench their
teeth and palpating for contraction in the temporalis and masseter
muscle (or by asking the patient to open their mouth and move their jaw
from side to side)
Testing the corneal reflex
Testing the jaw reflex

The trigeminal nerve may be damaged by:
Fractures of the middle third of the face (V2)
Trauma to the mandible (V3)
Anaesthetic block of the inferior alveolar nerve (V3)
Basal skull fractures
Tumours e.g. of the maxillary antrum and nasopharynx (V3)
Cavernous sinus pathology (V1)
Trigeminal neuralgia (sensory disorder characterised by severe shooting
pains usually in the distribution of V2 or V3)
All three branches have bilateral cortical representation so a unilateral central
lesion, for example a stroke, does not usually produce a deficit.

CN V palsy results in:
Flaccid paralysis of the muscles of mastication
Jaw deviation to the paralysed side (due to unopposed action of the
opposite lateral pterygoid)
Loss of sensation over the areas innervated by the three divisions of the
trigeminal nerve
Loss of the corneal reflex (afferent pathway)
Loss of jaw jerk

Paralysis of tensor tympani muscle leading to hypoacusis
8/26/22, 12:14 AM Cranial Nerve V1: Ophthalmic Nerve - MRCEM Success
Cranial Nerve V1: LAST UPDATED: 11TH

APRIL 2019
Ophthalmic Nerve  Bookmark
The ophthalmic nerve is a terminal branch of the trigeminal nerve.
Functional Overview
The ophthalmic division of the trigeminal nerve provides sensory innervation
to the following structures:
Forehead and scalp
Frontal, ethmoid and sphenoid sinuses
Upper eyelid and its conjunctiva
Cornea
Dorsum of the nose
Lacrimal gland
Parts of the meninges and tentorium cerebelli (recurrent tentorial
branch)
It also carries parasympathetic fibres to the lacrimal gland and sympathetic
fibres to the dilator pupillae muscle.
Anatomical Course
After arising from the trigeminal ganglion, the opthalmic nerve travels laterally
to the cavernous sinus and gives rise to the recurrent tentorial branch. The
nerve then exits the cranium via the superior orbital fissure, where it divides
into its three main branches.
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OPHTHALMIC NERVE. (IMAGE BY HENRY VANDYKE CARTER [PUBLIC DOMAIN], VIA

WIKIMEDIA COMMONS)
Branches
Frontal Nerve
Supraorbital branch (innervating skin of the upper eyelid and
conjunctiva and the skin of the upper forehead extending back to
the middle of the scalp)
Supratrochlear branch (innervating skin of the lower central part
of the forehead and conjunctiva and skin of the upper eyelid)
Lacrimal Nerve (innervating skin of the lateral half of the upper eyelid
and conjunctiva, and skin in the area of the lateral angle, carries
parasympathetic fibres to lacrimal gland)
Nasociliary Nerve
Anterior ethmoid nerve (innervating mucous membranes of the
frontal, ethmoid and sphenoid sinuses, and of the nasal cavity)
External nasal nerve (innervating the anterior part of the
nose)
Posterior ethmoid nerve (innervating mucous membranes of the

sphenoid sinus)
Infratrochlear nerve (innervating the medial half of the upper
eyelid and conjunctiva, the skin in the area of the medial angle and
the bridge of the nose)
Long ciliary nerves (sensory innervation to eye (cornea, ciliary
bodies, iris) and carries sympathetic fibres to dilator pupillae
muscle)
8/26/22, 12:16 AM Cranial Nerve VII: Facial Nerve - MRCEM Success
Cranial Nerve VII: Facial LAST UPDATED: 11TH

APRIL 2019
Nerve  Bookmark
HEAD AND NECK / FACE
The facial nerve (CN VII) mediates facial movements, taste, salivation and
lacrimation.
Table: Overview of the Facial Nerve
Cranial Facial Nerve (CN VII)
Nerve
Key Exits brainstem in cerebellopontine angle, enters
anatomy internal auditory meatus and facial canal, exits facial
canal and skull via stylomastoid foramen
Motor Muscles of facial expression, posterior belly of digastric
function muscle, stylohyoid muscle, stapedius muscle,
parasympathetic innervation to lacrimal, salivary, oral,
pharyngeal and nasal glands, efferent pathway of
corneal blink reflex
Sensory Taste to anterior two-thirds of tongue
function
Assessment Facial movements, corneal blink reflex
Clinical Facial weakness, loss of efferent corneal reflex, impaired
effects of lacrimal fluid production, hyperacusis, impaired sense of
injury taste to anterior two-thirds of tongue, impaired
salivation
Causes of Bell’s palsy, Ramsay-Hunt syndrome, Guillain-Barre
injury syndrome, mumps, middle ear disease, tumours, trauma
Function
The facial nerve provides motor innervation to the muscles of facial
expression, the posterior belly of the digastric, the stylohyoid and the
stapedius muscles. The chorda tympani branch supplies taste to the anterior
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two-thirds of the tongue. The facial nerve also carries parasympathetic

innervation to the lacrimal glands, salivary glands, nasal, palatine and
pharyngeal mucous glands.
Anatomical Course
The facial nerve arises in the pons, leaves the brainstem in the
cerebellopontine angle and exits the posterior cranial fossa through the
internal acoustic meatus in the temporal bone before entering the facial canal
still within the temporal bone where it gives rise to three main branches:
The nerve to the stapedius (innervating the stapedius muscle)
The greater petrosal nerve (supplying parasympathetic innervation to
the lacrimal gland and the mucous glands of the oral cavity, nose and
pharynx)
The chorda tympani (supplying taste to the anterior two-thirds of the
tongue and parasympathetic innervation to all salivary glands below the
level of the oral fissure)
The facial nerve exits the facial canal (and the basal skull) through the
stylomastoid foramen between the styloid and mastoid processes of the
temporal bone, at which point it gives off the posterior auricular nerve
(innervating the occipital belly of the occipitofrontalis muscle of the scalp and
external ear muscles).
ANATOMICAL COURSE OF THE FACIAL NERVE. (IMAGE MODIFIED BY FRCEM SUCCESS.

ORIGINAL BY PATRICK J. LYNCH, MEDICAL ILLUSTRATOR (PATRICK J. LYNCH,
MEDICAL ILLUSTRATOR) [CC BY 2.5
The facial nerve then gives off motor branches (innervating the posterior belly
of the digastric muscle and the stylohyoid muscle) before entering the deep
surface of the parotid gland.
Once in the parotid gland, the facial nerve divides into five terminal branches:
The temporal branch (innervating muscles in the temple, forehead and
supraorbital areas)
The zygomatic branch (innervating muscles in the infraorbital area, the
lateral nasal area and the upper lip)
The buccal branch (innervating muscles in the cheek, the upper lip and
the corner of the mouth)
The marginal mandibular branch (innervating muscles of the lower lip
and chin)
The cervical branch (innervating the platysma muscle)
TERMINAL BRANCHES OF THE FACIAL NERVE. (IMAGE BY PATRICK J. LYNCH,

MEDICAL ILLUSTRATOR (PATRICK J. LYNCH, MEDICAL ILLUSTRATOR) [CC BY 2.5
Assessment
The facial nerve can be assessed by:
Looking for symmetry in the face at rest
Asking the patient to perform the following movements
Raising their eyebrows
Closing their eyes tightly
Blowing out their cheeks
Smiling

Causes of CN VII palsy include:
Bell's palsy (idiopathic)

Ramsay-Hunt syndrome (herpes zoster infection of the CN VII motor
ganglion)
Guillain-Barre syndrome
Botulism
Infection e.g. mumps, measles, chickenpox, otitis externa/media,
encephalitis, mastoiditis
Tumours e.g. parotid tumours, cerebellopontine angle tumours
Fractures of the petrous temporal bone
Blunt/penetrating trauma to the face or during parotid surgery
Penetrating injury to the middle ear or barotrauma
Brainstem injury
Upper motor neuron (UMN) facial nerve palsy warrants CT head to exclude
cerebrovascular events and other intracranial causes such as tumours,
particularly cerebellopontine angle tumours.

Injury to the facial nerve may result in:
Ipsilateral facial weakness with flattening of the nasolabial fold and
dropping of the corners of the mouth, drooping of the lower eyelid and
inability to close the eye
Loss of corneal reflex (due to paralysis of the orbicularis oculi muscle)
Impaired lacrimal fluid production (due to impaired function of the
greater petrosal nerve)
Hyperacusis (hypersensitivity to sound due to impaired function of the
nerve to the stapedius)
Impaired sense of taste to anterior two-thirds of tongue and impaired
salivation (due to impaired function of the chorda tympani)
If the damage is peripheral (LMN), the forehead will be involved and there will
be an inability to close the eyes or raise the eyebrows. If the damage is central
(UMN) there is forehead sparing as the frontalis and orbicularis oculi muscles
are innervated bilaterally.
8/26/22, 12:16 AM Cranial Nerve VIII: Vestibulocochlear Nerve - MRCEM Success
Cranial Nerve VIII: LAST UPDATED: 20TH

AUGUST 2019
Vestibulocochlear Nerve  Bookmark
HEAD AND NECK / EAR
The vestibulocochlear nerve (CN VIII) is a sensory nerve which transmits

sensory information regarding head position and movement via the vestibular
nerve, and regarding the reception of sound via the cochlear nerve.
Table: Overview of the Vestibulocochlear Nerve
Cranial Vestibulocochlear Nerve (CN VIII)
Nerve
Key Comprised of vestibular and cochlear components
anatomy which combine in the pons, emerges from the brainstem
at the cerebellopontine angle, enters internal acoustic
meatus of temporal bone
Function Sensory: hearing and balance
Assessment Hearing, Weber and Rinne tests
Clinical Sensorineural deafness, tinnitus, vertigo, loss of
effects of equilibrium, nystagmus
injury
Causes of Infection, cerebellopontine angle tumours, basal skull
injury fracture, drugs
Anatomical Course
The vestibulocochlear nerve is comprised of two parts. The vestibular and
cochlear component combine in the pons to form the vestibulocochlear nerve
which emerges from the brainstem at the cerebellopontine angle to enter the
internal acoustic meatus of the temporal bone. Within the distal aspect of the
internal acoustic meatus, the vestibulocochlear nerve splits, forming the
vestibular nerve innervating the vestibular system and the cochlear nerve
innervating the cochlear.
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VESTIBULOCOCHLEAR NERVE. (IMAGE BY ZINA DERETSKY, NATIONAL SCIENCE

FOUNDATION [PUBLIC DOMAIN], VIA WIKIMEDIA COMMONS)
Assessment
The vestibulocochlear nerve can be assessed by:
Testing hearing by whispering numbers into each ear separately and
asking the patient to repeat it
Performing Rinne and Weber tuning fork tests to differentiate between
conductive and sensorineural hearing loss
Table: Rinne and Weber Tuning Fork Tests

Tuning Fork Test Weber’s test Rinne’s test
Screening Test of lateralisation Test of comparison of
to assess for perceived air
asymmetric conduction to bone
conductive or conduction to assess
Tuning Fork Test Weber’s test hearing
sensorineural Rinne’s test hearing
for conductive
loss loss
loss. loss.
Method Strike tuning fork, Start with ear that
place on midline of Weber test has
forehead and hold for lateralised to. Strike
up to 4 s. Ask patient tuning fork and hold
to report where the about 25 mm from ear
tone is heard: canal entrance for
centrally (in the head about 2 s. Immediately
or in both ears) or then place against the
towards the left or mastoid and hold for a
right. further 2 s. Ask patient
to report whether tone
is louder next to the
ear (Air conduction:
AC) or behind the ear
(Bone conduction:
BC).
Normal hearing Sound is heard AC > BC in both ears
centrally. (Rinne positive).
Unilateral Sound lateralised to In affected ear BC > AC
conductive hearing affected ear. (Rinne negative).
loss
In unaffected ear AC >
BC (Rinne positive).
Unilateral Sound lateralised In affected ear AC > BC

sensorineural to unaffected ear. (Rinne positive).
hearing loss
In unaffected ear AC >
BC (Rinne positive).
Bilateral hearing Sound is heard Sensorineural: AC > BC

loss centrally. in both ears (Rinne
positive).
Conductive: BC > AC in
both ears (Rinne
negative).

Possible causes of damage to the vestibulocochlear nerve include:
Infections e.g. vestibular neuritis, mastoiditis and herpes zoster

Cerebellopontine angle tumours (85% are acoustic neuromas, others
include meningiomas, cholesteatomas and primary malignancies of the
posterior fossa)
Tumours invading the temporal bone e.g. brainstem glioma
Vascular malformations at the cerebellopontine angle
Drugs e.g. aspirin, furosemide, phenytoin, cytotoxics, alcohol
Paget's disease
Fracture of the petrous temporal bone
Basal skull fracture

Damage to the vestibulocochlear nerve results in (ipsilateral):
Sensorineural deafness
Tinnitus
Loss of equilibrium
Nystagmus
Vertigo
8/26/22, 12:17 AM Cranial Nerve IX: Glossopharyngeal Nerve - MRCEM Success
Cranial Nerve IX: LAST UPDATED: 6TH

DECEMBER 2020
Glossopharyngeal Nerve  Bookmark
HEAD AND NECK / NECK
The glossopharyngeal nerve (CN IX) mediates taste, salivation and swallowing
(together with CN X).
Table: Overview of the Glossopharyngeal Nerve

Cranial Glossopharyngeal Nerve (CN IX)
Nerve
Key Originates from medulla, exits skull via jugular foramen
anatomy
Sensory Posterior one-third of tongue, tonsils, oropharynx, soft
function palate, middle ear, taste from posterior one-third of
tongue, visceral afferents from carotid body and sinus,
afferent pathway of gag reflex
Motor Stylopharyngeus muscle (facilitates swallowing),
function parasympathetic fibres to parotid gland
Assessment Gag reflex, swallowing
Clinical Loss of gag reflex, dysphagia, loss of carotid sinus reflex,
effects of loss of taste from posterior one-third of tongue
injury
Causes of Occipital condyle fractures, lateral medullary syndrome,
injury jugular foramen syndrome, carotid artery dissection
Anatomical Course
The glossopharyngeal nerve originates from the medulla and travels lateral in
the posterior cranial fossa before emerging from the cranial cavity via the
jugular foramen.
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GLOSSOPHARYNGEAL NERVE. (IMAGE BY HENRY VANDYKE CARTER [PUBLIC

Function
The glossopharyngeal nerve carries:
General visceral afferent fibres from the carotid body and sinus
General sensory afferent fibres from the posterior one-third of the
tongue, palatine tonsils, oropharynx, and mucosa of the middle ear,
pharyngotympanic tube and mastoid ear cells
Special afferent fibres for taste from the posterior one-third of the
tongue
Parasympathetic secretomotor fibres to the parotid salivary gland
Motor fibres to the stylopharyngeus muscle (elevates larynx and
pharynx facilitating swallowing)
Assessment
The glossopharyngeal nerve can be assessed together with the vagus nerve
(CN X) by:
Asking the patient to cough

Asking the patient to open the mouth wide and say 'ah' while visualising
the palate and posterior pharyngeal wall (the soft palate should move
upwards centrally)
Testing the gag reflex

Causes of damage to CN IX include:
Occipital condyle fractures
Lateral medullary syndrome
Ischaemia secondary to vertebral artery damage
Jugular foramen syndrome (palsy of CN IX, X, XI and XII caused by
tumours, meningitis and infection from the middle ear spreading into
the posterior fossa or trauma)
Carotid artery dissection
Isolated glossopharyngeal nerve palsy is rare. It is usually damaged with CN X
and XI, close to the jugular foramen.

CN IX palsy will result in:
Loss of gag reflex (afferent pathway)
Loss of carotid sinus reflex
Loss of taste from posterior one-third of tongue
Dysphagia
8/26/22, 12:17 AM Cranial Nerve X: Vagus Nerve - MRCEM Success
Cranial Nerve X: Vagus LAST UPDATED: 10TH

AUGUST 2019
Nerve  Bookmark
The vagus nerve (CN X) is a mixed motor and sensory nerve which mediates
phonation, swallowing, elevation of the palate and taste, and innervates
viscera of the neck, thorax and abdomen.
Table: Overview of the Vagus Nerve

Cranial Vagus Nerve (CN X)
Nerve
Key Originates in medulla, exits skull via jugular foramen,
anatomy descends in neck within carotid sheath
Sensory Larynx, laryngopharynx, external ear, external acoustic
function meatus, dura mater of posterior cranial fossa, thoracic
and abdominal viscera, taste around epiglottis and
pharynx
Motor Muscles of soft palate (except tensor veli palatini) ,
function muscles of pharynx (except stylopharyngeus), muscles
of larynx, palatoglossus muscle of tongue, visceral
efferent fibres to viscera of neck, thorax and abdomen,
efferent pathway of gag reflex
Assessment Ask patient to say ‘ahhh’ to look for uvular deviation, gag
reflex, swallowing, speech
Clinical Dysarthria, dysphonia, dysphagia, stridor, loss of gag
effects of reflex, uvular deviation away from affected side
injury
Causes of Trauma, neck surgery, tumours, aneurysms, jugular
injury foramen syndrome
Anatomical Course
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The vagus nerve originates in the medulla, exits the skull via the jugular
foramen (with CN IX and XI), then descends in the carotid sheath to innervate
the neck, chest and abdomen.
VAGUS NERVE. (IMAGE BY HENRY VANDYKE CARTER [PUBLIC DOMAIN], VIA

WIKIMEDIA COMMONS)
Function
The vagus nerve carries:
General sensory afferent fibres from the larynx, laryngopharynx, deeper
parts of the auricle, part of the external acoustic meatus and the dura
mater of the posterior cranial fossa
General visceral afferent fibres from the aortic body chemoreceptors
and aortic arch baroreceptors, and the pharynx, larynx, oesophagus,
trachea, heart and lungs and abdominal viscera as far as the mid-
transverse colon
Special afferent fibres for taste around the epiglottis and pharynx
Parasympathetic fibres to the pharynx, larynx, thoracic viscera, and

abdominal viscera as far as the mid-transverse colon
Motor fibres to the palatoglossus muscle of the tongue, the muscles of
the soft palate (except for the tensor veli palatini), the muscles of the
pharynx (except the stylopharyngeus), the muscles of the larynx and the
striated muscle of the upper oesophagus
General visceral efferent fibres to the viscera of the neck and the
thoracic and abdominal cavities as far as the mid-transverse colon
Assessment
The vagus nerve can be assessed together with the glossopharyngeal nerve
(CN IX) by:
Asking the patient to cough
Asking the patient to open the mouth wide and say 'ah' while visualising
the palate and posterior pharyngeal wall (the soft palate should move
upwards centrally)
Testing the gag reflex

The vagus nerve may be damaged by:
Trauma or neck surgery
Lateral medullary syndrome
Aortic aneurysms
Tumours (mediastinal or lung carcinoma)
Jugular foramen syndrome

Vagus nerve palsy results in:
Ipsilateral palatal weakness with nasal speech and nasal regurgitation of
food (the soft palate and uvula will move asymmetrically when the
patient says 'ahh' - away from the affected side)
Ipsilateral pharyngeal weakness with dysphagia
Ipsilateral laryngeal weakness with hoarseness, aphonia, and stridor
Loss of gag reflex (efferent pathway)
8/26/22, 12:17 AM Cranial Nerve XI: Spinal Accessory Nerve - MRCEM Success
Cranial Nerve XI: Spinal LAST UPDATED: 11TH

APRIL 2019
Accessory Nerve  Bookmark
The spinal accessory nerve (CN XI) is primarily a motor nerve innervating the
sternocleidomastoid and the trapezius muscles which mediate head and
shoulder movement.
Table: Overview of the Spinal Accessory Nerve

Cranial Spinal Accessory Nerve (CN XI)
Nerve
Key Originates from cervical segments C1 – C5/C6, enters
anatomy cranial cavity through foramen magnum, travels through
posterior cranial fossa and exits skull through jugular
foramen
Function Motor: sternocleidomastoid, trapezius
Assessment Test head rotation and shoulder shrug against
resistance
Clinical Inability to shrug ipsilateral shoulder, shoulder droop,
effects of inability to rotate head towards opposite side to the
injury lesion
Causes of Metastatic lymphadenopathy in neck, neck dissection
injury surgery, internal jugular vein cannulation, blunt or
penetrating neck trauma
Anatomical Course
It is a unique cranial nerve because its roots actually arise from motor neurons
in the upper five segments of the cervical spinal cord. The fibres leave the
lateral surface of the spinal cord, joining together as they ascend, and enter
the cranial cavity through the foramen magnum forming the accessory nerve.
The accessory nerve then continues through the posterior cranial fossa and
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exits the skull through the jugular foramen before descending in the neck
along the internal carotid artery to innervate the muscles.
SPINAL ACCESSORY NERVE. (IMAGE BY HENRY VANDYKE CARTER [PUBLIC DOMAIN],

A few rootlets arising from the medulla just inferior to the fibres that arise to
form the vagus nerve, may be referred to as the 'cranial' roots of the accessory
nerve. Leaving the medulla these fibres course with the 'spinal' roots of the
accessory nerve into the jugular foramen, at which point these cranial roots
join the vagus nerve. They are distributed to the pharyngeal musculature
innervated by the vagus nerve and are therefore usually described as being
part of the vagus nerve.
Assessment
The spinal accessory nerve is assessed by:
Testing the sternocleidomastoid by asking the patient to turn their head
to each side against resistance
Testing the trapezius by asking the patient to shrug their shoulders

against resistance

Damage can occur due to:
Metastatic disease in the neck with lymph node involvement
Neck dissection surgery
Cannulation of the internal jugular vein
Blunt or penetrating neck trauma

Clinical features of CN XI palsy include muscle wasting and paralysis of the
sternocleidomastoid and trapezius muscles resulting in the inability to rotate
the head to the side opposite the lesion and to shrug the ipsilateral shoulder
(resulting in shoulder droop) respectively.
8/26/22, 12:18 AM Cranial Nerve XII: Hypoglossal Nerve - MRCEM Success
Cranial Nerve XII: LAST UPDATED: 11TH

APRIL 2019
Hypoglossal Nerve  Bookmark
HEAD AND NECK / MOUTH AND HARD PALATE
The hypoglossal nerve (CN XII) is a purely motor nerve which innervates
muscles of the tongue.
Table: Overview of the Hypoglossal Nerve

Cranial Hypoglossal Nerve (CN XII)
Nerve
Key Arises from medulla, exits skull through hypoglossal
anatomy canal
Function Motor: all intrinsic and extrinsic muscles of tongue
(except for palatoglossus)
Assessment Power and symmetry of tongue, tongue protrusion to
look for deviation
Clinical Hemiparalysis of tongue with wasting and
effects of fasciculations, tongue deviation towards weak side
injury
Causes of Penetrating trauma, tumours, meningitis, extension
injury of middle ear infection
Anatomical Course
The hypoglossal nerve arises from the medulla and passes laterally across the
posterior cranial fossa within the subarachnoid space before emerging from
the cranial cavity via the hypoglossal canal. It then passes inferiorly to the
angle of the mandible and moves in an anterior direction to enter the tongue.
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HYPOGLOSSAL NERVE. (IMAGE BY HENRY VANDYKE CARTER [PUBLIC DOMAIN], VIA

WIKIMEDIA COMMONS)
Function
It innervates the hyoglossus, the genioglossus, the styloglossus and all of the
intrinsic muscles of the tongue (i.e. all the muscles of the tongue except for
the extrinsic palatoglossus muscle innervated by the vagus nerve).
Assessment
The hypoglossal nerve is assessed by:
Inspecting the tongue for any wasting or fasciculation
Asking the patient to protrude their tongue to look for deviation
Testing power of the tongue by asking the patient to push their tongue
against their cheek

Isolated hypoglossal nerve injury is relatively uncommon. Possible causes
include penetrating traumatic injuries, tumours (e.g. metastases,
neurofibroma, cerebellopontine angle lesions), meningitis and infection from
the middle ear spreading into the posterior fossa.

In CN XII palsy there is hemiparalysis of the tongue associated with muscle
wasting and fasciculations. The tongue deviates towards the weak side upon
protrusion due to the unopposed action of the opposite genioglossus.
8/26/22, 12:18 AM Cranial Nerve Overview - MRCEM Success
Something wrong?
Cranial Nerve Overview LAST UPDATED: 24TH

FEBRUARY 2019
CRANIAL NERVE LESIONS  Bookmark
There are 12 pairs of cranial nerves arising from the brain.
Cranial Nerve Origin Exit from Function

Skull
Olfactory Nerve Cerebrum Cribriform SA: smell
(I) Plate
Optic Nerve (II) Cerebrum Optic Canal SA: vision
Oculomotor Midbrain Superior GSE: levator palpebrae
Nerve (III) Orbital superioris, superior rectus,
Fissure inferior rectus, medial rectus,
inferior oblique
GVE: sphincter pupillae, ciliary
muscles
Trochlear Nerve Midbrain Superior GSE: superior oblique

(IV) Orbital
Fissure
Trigeminal Nerve Pons Superior GSA: sensory from most of
(V): Orbital head
Fissure (V1);
Foramen BE: temporalis, masseter,
Rotundum medial and lateral pterygoids,
(V2); tensor tympani, tensor veli
Foramen palatini, anterior belly of
Ovale (V3) digastric, mylohyoid
Abducens Nerve Pons Superior GSE: lateral rectus

(VI) Orbital
Fissure
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Skull
Facial Nerve (VII) Pons Internal GSA: sensory from external
Acoustic acoustic meatus and skin
Meatus; posterior to ear
Stylomastoid
Foramen SA: taste from anterior two-
thirds of tongue
GVE: lacrimal gland,
submandibular and sublingual
salivary glands, mucous
membranes of nasal cavity
and palate
BE: muscles of face and scalp,
stapedius, posterior belly of
digastric, stylohyoid
Vestibulocochlear Pons Internal SA: balance and hearing

Nerve (VIII) Acoustic
Meatus
Glossopharyngeal Medulla Jugular GVA: sensory from carotid
Nerve (IX) Foramen body and sinus, posterior one-
third of tongue, palatine
tonsils, upper pharynx, and
mucosa of middle ear and
pharyngotympanic tube
SA: taste from posterior one-
third of tongue
GVE: parotid salivary gland
BE: stylopharyngeus

Skull
Vagus Nerve (X) Medulla Jugular GSA: sensory from skin
Foramen posterior to ear and external
acoustic meatus, and dura in
posterior cranial fossa
GVA: sensory from aortic body
chemoreceptors and aortic
arch baroreceptors, mucous
membranes of pharynx,
larynx, oesophagus, bronchi,
lungs, heart, and abdominal
viscera of foregut and midgut
SA: taste from epiglottis
GVE: smooth muscle and
glands in pharynx, larynx,
thoracic viscera and
abdominal viscera in foregut
and midgut
BE: palatoglossus, muscles of
soft palate (except tensor veli
palatini), muscles of pharynx
(except stylopharyngeus),
muscles of larynx
Spinal Accessory Medulla Jugular BE: sternocleidomastoid and

Nerve (XI) Foramen trapezius
Hypoglossal Medulla Hypoglossal GSE: hyoglossus,
Nerve (XII) Canal genioglossus, styloglossus
and intrinsic muscles of
tongue
(GSA = General Somatic Afferent; GVA = General Visceral Afferent; SA = Special Afferent;
GSE = General Somatic Efferent; GVE: General Visceral Efferent; BE = Branchial Efferent)
CRANIAL NERVE ORIGINS (LEFT) AND CRANIAL NERVE EXITS (RIGHT). (IMAGE MODIFIED BY FRCEM
SUCCESS. ORIGINAL BY PATRICK J. LYNCH, MEDICAL ILLUSTRATOR (PATRICK J. LYNCH, MEDICAL
ILLUSTRATOR) [CC BY 2.5 (HTTP://CREATIVECOMMONS.ORG/LICENSES/BY/2.5)], VIA WIKIMEDIA
COMMONS)
THORAX
Diaphragm LAST UPDATED: 11TH
APRIL 2019
ANATOMY / THORAX / DIAPHRAGM
 Bookmark
The diaphragm is a musculotendinous structure that separates the

thoracic cavity from the abdominal cavity.
Table: Anatomical Overview of the Diaphragm

Structure Diaphragm
Primary Respiration – contraction of diaphragm flattens
function diaphragm increasing vertical dimension of thorax
(inspiration), relaxation of diaphragm elevates
diaphragm decreasing vertical dimension of thorax
(expiration)
Secondary Assists in straining movements by increasing intra-
functions abdominal pressure, acts as functional sphincter on
oesophagus preventing acid reflux
Peripheral Xiphoid process of sternum, costal cartilages ribs 7
attachments – 10, ends of ribs 11 and 12, arcuate ligaments and
lumbar vertebrae
Central Fuses with fibrous pericardium superiorly
attachment
Surface Anterior attachment: vertebral level T8/T9, Posterior
markings attachment: vertebral level T12, Right dome: 5th rib,
Left dome: 5th intercostal space, Central tendon:
xiphoid process
Openings Oesophageal opening at T10 (oesophagus, vagus
nerve), aortic opening at T12 (aorta, thoracic duct
and azygos vein), caval opening at T8 (inferior vena
cava and right phrenic nerve)
Innervation Phrenic nerve (C3 – C5)
Function
The diaphragm performs an important function in respiration; contraction
of the domes of the diaphragm in inspiration flattens the diaphragm,
increasing the vertical dimension of the thorax and vice versa in expiration,
with relaxation and elevation of the diaphragm reducing the vertical
dimension of the thorax.
The diaphragm is also involved in non-respiratory functions; helping to
expel vomit, faeces, and urine from the body by increasing intra-abdominal
pressure, and preventing acid reflux by exerting pressure on the
oesophagus as it passes through the oesophageal opening.
Attachments
The diaphragm is attached peripherally to:
the xiphoid process of the sternum and the costal cartilages of ribs 7
- 10 (the costal margin) anteriorly
the ends of ribs 11 and 12 laterally
the arcuate ligaments and vertebrae posteriorly.
From these peripheral attachments, muscle fibres converge to form the
central tendon which fuses with the fibrous pericardium superiorly.
DIAPHRAGM. (IMAGE BY OPENSTAX [CC BY 4.0
Diaphragmatic openings
Structures travelling between the thorax and abdomen must pass through
the diaphragm via three main openings.
The oesophageal opening at vertebral level T10 transmits:
the oesophagus
the anterior and posterior vagal trunks
oesophageal branches of the left gastric vessels
a few lymphatics.
The aortic opening at vertebral level T12 transmits:
the aorta
the thoracic duct
the azygos vein and sometimes the hemiazygos vein.
The caval opening at vertebral level T8 transmits:
the inferior vena cava
the right phrenic nerve.
Surface markings
In the medial sagittal plane, the diaphragm slopes inferiorly from its
anterior attachment to the xiphoid at approximately vertebral level T8/T9
to its posterior attachment to the median arcuate ligament at
approximately vertebral level T12.
At rest the right dome of the diaphragm lies slightly higher than the left;
this is thought to be due to the position of the liver. In normal expiration,
the normal upper limits of the superior margins are the fifth rib for the right
dome, the fifth intercostal space for the left dome and the xiphoid process
for the central tendon.
Innervation
The entire motor supply of the diaphragm is from the right and left phrenic
nerves (C3 - C5) which penetrate the diaphragm and innervate it from its
abdominal surface.
Damage to the phrenic nerve will result in hemiparalysis of the diaphragm.
Paralysis of the diaphragm produces a paradoxical movement. The affected
side of the diaphragm moves upwards during inspiration (as it is pushed
superiorly by the abdominal viscera that are being actively compressed by
the other half), and downwards during expiration.
A unilateral diaphragmatic paralysis is usually asymptomatic, and is most
often an incidental finding on x-ray. If both sides are paralysed, the patient
may experience poor exercise tolerance, orthopnoea and fatigue. Lung
function tests will show a restrictive deficit.

Diaphragmatic Hernia LAST UPDATED:
24TH JANUARY 2019
ANATOMY / THORAX / DIAPHRAGM
 Bookmark
Diaphragmatic hernias are defined as congenital or acquired defects in the

diaphragm. There are two main types of congenital diaphragmatic hernias;
Bochdalek hernias and Morgagni hernias.
Acquired diaphragmatic hernias include traumatic diaphragmatic rupture,
hiatus hernia and iatrogenic diaphragmatic hernias. Depending on the
location and size of the defect, retroperitoneal or intra-abdominal organs
and tissues can prolapse into the thoracic cavity due to the negative
intrathoracic pressure.
Diaphragmatic rupture usually results from blunt abdominal trauma, which
is typically associated with motor-vehicle accidents; the most commonly
herniated viscera are the stomach and colon on the left side, and the liver
on the right side.
In hiatus hernia, the stomach herniates through the oesophageal opening
of the diaphragm, typically resulting in symptoms of acid reflux.

Something wrong?
Cardiac Blood Supply LAST UPDATED: 6TH

JUNE 2019
ANATOMY / THORAX / HEART AND PERICARDIUM
 Bookmark
The right and left coronary arteries arise from the right and left aortic sinuses in the
initial portion of the ascending aorta and supply the muscle and other tissues of the
heart.
Territories of Supply
Although there is variation, in most people the territories of supply are as follows:
The right coronary artery supplies:
the right atrium
most of the right ventricle
the sinoatrial and atrioventricular nodes
the interatrial septum
a portion of the left atrium
the posteroinferior one-third of the interventricular septum
a portion of the posterior part of the left ventricle
The left coronary artery supplies:
most of the left atrium
most of the left ventricle
a portion of the right ventricle
most of the interventricular septum (including the atrioventricular bundle and
branches)
Branches
Table: Blood Supply of the Heart

Artery Territory of Supply
Right coronary Right atrium and ventricle, sinoatrial node, atrioventricular
artery node
Right marginal Inferior aspect of right ventricle
branch
Posterior Posterior aspect of right and left ventricles, posterior one-
interventricular third of interventricular septum
branch
Left coronary artery Via main branches below
Anterior Right and left ventricles, anterior two-thirds of
interventricular interventricular septum
branch
Left circumflex Left atrium and left ventricle
branch
The right coronary artery supplies the right atrium, the sinoatrial node and the
atrioventricular node (via the SA and AV nodal branches) and gives rise to two principal
branches:
the right marginal branch (supplying the inferior margin of the right ventricle and
the apex)
the posterior interventricular branch (supplying the posterior aspect of the right
and left ventricles and the posterior one-third of the interventricular septum).
The left coronary artery gives rise to two principal branches:
the anterior interventricular branch (supplying the right and left ventricles, the
apex and the anterior two-thirds of the interventricular septum)
the circumflex branch (supplying the left atrium and left ventricle).
CARDIAC BLOOD SUPPLY. (IMAGE BY OPENSTAX COLLEGE [CC BY 3.0

Cardiac Conduction System LAST UPDATED: 28TH
FEBRUARY 2019
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The cardiac conduction system initiates and coordinates contraction of the heart.
The sinoatrial node, the cardiac pacemaker, is located at the superior end of the
crista terminalis at the junction of the superior vena cava and the right atrium.
Impulses generated by the sinoatrial node are propagated by the atrial myocardium
to the atrioventricular node located near the opening of the coronary sinus, close to
the attachment of the septal cusp of the tricuspid valve and within the
atrioventricular septum. Here the impulse is briefly delayed before being spread to
the ventricles.
The atrioventricular bundle (bundle of His) is a direct continuation of the
atrioventricular node and continues along the lower margin of the membranous
part of the interventricular septum before dividing into the right and left bundles
which continue themselves as Purkinje fibres, the final component of the
conducting system.
CARDIAC CONDUCTION SYSTEM. (IMAGE BY OPENSTAX COLLEGE [CC BY 3.0

Cardiac Orientation LAST UPDATED: 11TH
APRIL 2019
 Bookmark
The general shape and orientation of the heart are that of a pyramid that has
fallen over and is resting on one of its sides.
The apex of this pyramid projects forwards, downwards and to the
left. The apex is formed by the inferolateral part of the left ventricle and
is positioned deep to the left fifth intercostal space in the midclavicular
line.
The base is facing posteriorly. The base is formed mostly by the left
atrium with a small portion of the right atrium and the proximal part of
the great veins, and is fixed posteriorly to the pericardial wall, opposite
the bodies of the T5 - T8 vertebrae (T6 - T9 when standing). The
oesophagus lies immediately posterior to the base.
Table: Surfaces and Borders of the Heart

Border/Surface Main Structure (Contributing Structures)
Apex Left ventricle
Base Left atrium (right atrium, proximal great
veins)
Anterior surface Right ventricle (right atrium, left ventricle)
Inferior surface Left and right ventricle
Left pulmonary surface Left ventricle (left atrium)
Right pulmonary Right atrium
surface
Inferior border Right ventricle (left ventricle)
Left border Left ventricle (left auricle)
Right border Right atrium
Superior border Both atria, roots of great vessels
Surfaces
There are four surfaces to the upturned pyramid:
The anterior (sternocostal) surface consists mostly of the right ventricle
with some of the right atrium and some of the left ventricle.
The inferior (diaphragmatic) surface consists of the left ventricle with a
small portion of the right ventricle separated by the posterior
interventricular groove.
The left pulmonary surface consists mainly of the left ventricle and a
portion of the left atrium.
The right pulmonary surface consists of the right atrium.
Borders
There are four main borders separating the surfaces of the heart:
The inferior border is formed mostly by the right ventricle and a small
portion of the left ventricle near the apex.
The left border is formed mostly by the left ventricle with a small portion
of the left auricle.
The right border is formed by the right atrium.
The superior border is formed by both atria and the roots of the great
vessels.
ORIENTATION OF THE HEART. (IMAGE MODIFIED BY FRCEM SUCCESS. ORIGINAL BY
MIKAEL HÄGGSTRÖM [PUBLIC DOMAIN], VIA WIKIMEDIA COMMONS)

Cardiac Surface Markings LAST UPDATED: 29TH
JANUARY 2019
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Table: Surface Markings of the Heart

Heart Surface Marking
Right upper limit Third costal cartilage
Left upper limit Second intercostal space
Right lower limit Sixth costal cartilage
Left lower limit Fifth intercostal space
The upper limit of the heart reaches as high as the third costal cartilage on the
right side of the sternum and the second intercostal space on the left side of
the sternum.
The lower limit of the heart extends from the sternal end of the right sixth
costal cartilage to the apex in the fifth intercostal space near the midclavicular
line.
The right margin of the heart therefore extends from the right third costal
cartilage to near the right sixth costal cartilage and the left margin of the heart
extends from the left second intercostal space to the apex located near the
midclavicular line in the fifth intercostal space.
SURFACE MARKINGS OF THE HEART. (IMAGE MODIFIED BY FRCEM SUCCESS.
ORIGINAL BY MIKAEL HÄGGSTRÖM[PUBLIC DOMAIN], VIA WIKIMEDIA COMMONS)

Cardiac Valves LAST UPDATED: 11TH
APRIL 2019
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Table: Surface Marking and Auscultation Positions of the Heart

Valves
Heart Surface Marking Auscultation
valve Position
Tricuspid Posterior to right half of sternum at Left of sternum
valve level of 4th ICS near 5th ICS
Mitral Posterior to left half of sternum at Left 5th ICS in
valve level of 4th costal cartilage midclavicular line
Pulmonary Posterior to third left Medial end of left
valve chondrosternal joint 2nd ICS
Aortic Posterior to left half of sternum at Medial end of
valve level of 3rd ICS right 2nd ICS
Surface Markings
The tricuspid valve is located posterior to the right half of the sternum at
the level of the fourth intercostal space.
The mitral valve is located posterior to the left half of the sternum at the
level of the fourth costal cartilage.
The pulmonary valve is located posterior to the third left chondrosternal
joint.
The aortic valve is located posterior to the left half of the sternum at the
level of the third intercostal space.
Auscultation Positions
Heart valves should be auscultated by positioning the stethoscope
downstream from the flow of blood through the valves.
The tricuspid valve is heard just to the left of the lower part of the
sternum near the fifth intercostal space.
The mitral valve is heard over the apex of the heart in the left fifth
intercostal space at the midclavicular line.
The pulmonary valve is heard over the medial end of the left second
intercostal space.
The aortic valve is heard over the medial end of the right second
intercostal space.
SURFACE MARKINGS OF THE HEART VALVES (AND AUSCULTATION POSITIONS).

(IMAGE MODIFIED BY FRCEM SUCCESS. ORIGINAL BY MIKAEL HÄGGSTRÖM [PUBLIC

Great Vessels LAST UPDATED: 11TH
APRIL 2019
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The pulmonary trunk and the ascending aorta are contained within the
pericardial sac, lined by serous pericardium and within a common sheath.
Ascending Aorta
The ascending aorta arises from the aortic orifice at the base of the left
ventricle, at the level of the lower edge of the third left costal cartilage,
posterior to the left half of the sternum. The ascending aorta ascends, moving
slightly forwards and to the right, before continuing as the arch of the aorta
posterior to the second right costal cartilage.
Pulmonary Trunk
The pulmonary trunk arises from the conus arteriosus of the right ventricle
slightly anterior to the aortic orifice, posterior to the left third costal cartilage.
The pulmonary trunk ascends, moving posteriorly and to the left, lying initially
anterior and then to the left of the ascending aorta, before bifurcating into the
right and left pulmonary arteries posterior to the left second intercostal space.
SECTIONAL ANATOMY OF THE HEART. (IMAGE BY BLAUSEN MEDICAL
COMMUNICATIONS, INC. [CC BY 3.0

Pericardial Aspiration LAST UPDATED: 1ST
JULY 2020
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Pericardiocentesis is a surgical puncture of the pericardial cavity for the

aspiration of fluid, which is necessary to relieve the pressure of accumulated
fluid in the heart.
Procedure
A needle is inserted into the pericardial cavity 1 - 2 cm inferior to the left of the
xiphochondral junction (between the xiphisternum and the left costal margin)
at a 45 degree angle and advance aiming toward the tip of the left scapula
(site marked by cross in image below).
SITE OF PERICARDIAL ASPIRATION. (IMAGE MODIFIED BY FRCEM SUCCESS. ORIGINAL

BY MIKAEL HÄGGSTRÖM [PUBLIC DOMAIN], VIA WIKIMEDIA COMMONS)
Complications
Complications of pericardiocentesis include:
Aspiration of ventricular blood instead of pericardial blood
Laceration of ventricular epicardium or myocardium
Laceration of coronary artery or vein
Ventricular fibrillation
Pneumothorax secondary to lung puncture
Puncture of great vessels with worsening pericardial tamponade
Mediastinitis secondary to oesophageal puncture
Peritonitis secondary to peritoneal puncture

Pericardium LAST UPDATED: 11TH
APRIL 2019
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The pericardium is a fibroserous sac surrounding the heart and the roots of the
great vessels in the middle mediastinum. It is composed of two main layers;
the fibrous pericardium and the serous pericardium.
PERICARDIUM. (IMAGE BY OPENSTAX COLLEGE [CC BY 3.0

Serous pericardium
The serous pericardium itself is divided into two parts which are continuous at
the roots of the great vessels; the parietal layer which lines the inner surface
of the fibrous pericardium and the visceral layer which lines the heart itself.
The parietal and visceral layer of serous pericardium are separated by the
pericardial cavity which normally contains a small amount of lubricating
serous fluid which reduces friction during normal movement of the heart.
Fibrous pericardium
The fibrous pericardium is a tough, inelastic sheath which fixes the heart in
position (through its attachments to the central tendon of the diaphragm, the
sternum and the tunica adventitia of the great vessels) and prevents sudden
overfilling and distension of the heart.
Cardiac tamponade is acute compression of the heart caused by rapid
accumulation of fluid or blood in the pericardial cavity from trauma (to the
heart, great vessels or pericardial vessels) or pericardial effusion. The
inflexibility of the fibrous pericardium results in increased intrapericardial
pressure, with subsequent compression of venous return and reduced cardiac
output.
Innervation
The pericardium receives its nerve supply from the vagus nerve, the
sympathetic trunks and the phrenic nerves.
Somatic sensation from the parietal pericardium is carried by somatic afferent
fibres in the phrenic nerves (C3 - C5); it is for this reason that pain related to a
pericardial problem may be referred to the supraclavicular region of the
shoulder or the lateral neck area dermatomes for spinal cord segments C3 -
C5.

Oesophagus (Thoracic) LAST UPDATED: 11TH
APRIL 2019
ANATOMY / THORAX / OESOPHAGUS
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The oesophagus is a muscular tube passing between the pharynx in the

neck and the stomach in the abdomen.
Anatomical extent
The oesophagus begins at the inferior border of the cricoid cartilage
opposite vertebra C6, pierces the diaphragm at the esophageal hiatus at
T10 and ends at the cardiac opening of the stomach opposite vertebra T11.
Structure
The oesophagus consists of an internal circular and external longitudinal
layer of muscle. The external longitudinal layer is comprised of different
muscle types in each third of the oesophagus; superior third - voluntary
striated muscle, middle third - voluntary striated and smooth muscle and
inferior third - smooth muscle.
Relations
The oesophagus descends on the anterior aspect of the bodies of the
vertebrae, immediately posterior to the trachea and the recurrent
laryngeal nerves, generally in the midline position. The oesophagus is
crossed anteriorly by the aortic arch. As it approaches the diaphragm, the
oesophagus moves anteriorly and to the left, crossing from the right side
of the thoracic aorta to eventually assume a position anterior to it, before
passing through the diaphragm.
Posterior to the oesophagus, the thoracic duct is on the right side
inferiorly but crosses to the left more superiorly (at T5). Other structures
posteriorly include portions of the hemiazygos veins and the right
posterior intercostal vessels.
Anterior to the oesophagus below the tracheal bifurcation are the right
pulmonary artery and the left main bronchus. The oesophagus then
passes immediately posterior to the left atrium, separated from it only by
pericardium. Inferior to the left atrium, the oesophagus is related to the
diaphragm.
RELATIONS OF THE OESOPHAGUS. (IMAGE BY ZOOFARI [CC BY-SA 3.0

COMMONS)
Points of constriction
As the oesophagus is a flexible muscular tube, it is compressed by
surrounding structures at four locations:
1) the junction of the oesophagus with the pharynx in the neck
(upper oesophageal sphincter formed by the cricopharyngeus
muscle)
2) in the superior mediastinum where the oesophagus is crossed by
the arch of the aorta
3) in the posterior mediastinum where the oesophagus is
compressed by the left main bronchus
4) in the posterior mediastinum at the oesophageal hiatus in the
diaphragm.
Clinically these compressions are important when passing instruments or
assessing swallowed objects.
Innervation
Oesophageal innervation is complex, oesophageal branches arise from the
vagus nerves and sympathetic trunks. The visceral afferents that pass
through the sympathetic trunks and the splanchnic nerves are the
primary participants in detection of oesophageal pain and transmission of
this information to various levels of the central nervous system.

Ribs LAST UPDATED: 11TH
APRIL 2019
ANATOMY / THORAX / OSTEOLOGY
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There are twelve pairs of ribs, each terminating anteriorly in a costal

cartilage.
True and False Ribs

The ribs are divided into 'true' and 'false' ribs based on their anterior
attachments:
The true ribs (1 - 7) attach directly to the sternum anteriorly.
The false ribs (8 - 12) can be further divided into those that attach
to the costal cartilage of the rib above them (8 - 10) and the floating
ribs (11 + 12) that do not have any anterior attachments.
ANTERIOR RIB JOINTS. (IMAGE BY OPENSTAX COLLEGE [CC BY 3.0
(HTTPS://CREATIVECOMMONS.ORG/LICENSES/BY/3.0)], VIA WIKIMEDIA
COMMONS)
Posterior Joints
Posteriorly, all of the ribs articulate with the thoracic vertebrae of the
spine.
Each typical rib forms two joints posteriorly:
the costotransverse joint (between the tubercle of the rib and the
transverse process of the corresponding vertebra)
the costovertebral joint (between the two facets on the head of the
rib and the superior costal facet on the body of the corresponding
vertebra, and the inferior costal facet on the body of the vertebra
above).
POSTERIOR RIB JOINTS. (IMAGE MODIFIED BY FRCEM SUCCESS. ORIGINAL BY

HENRY VANDYKE CARTER [PUBLIC DOMAIN], VIA WIKIMEDIA COMMONS)
Typical Ribs
The typical rib consists of a head, a neck and a body:
The head of the rib has two articular facets which articulate with the
superior costal facet on the body of the corresponding vertebra, and
the inferior costal facet on the body of the vertebra above.
The neck of the rib connects the head to the body. Where the neck
meets the body, there is a tubercle which articulates with the
transverse process of the corresponding vertebra.
The body of the rib is flat and curved.
The inferior margin of the internal surface of the body is marked by the
costal groove which protects the neurovascular structures which run
within it.
TYPICAL RIB. (IMAGE MODIFIED BY FRCEM SUCCESS. ORIGINAL BY HENRY

Atypical Ribs
Table: Distinguishing Features of the Atypical Ribs

Atypical Distinguishing Features
Rib
Rib 1 Shorter and wider, single facet for articulation with T1,
scalene tubercle
Rib 2 Flat, roughened area for attachment of serratus
anterior muscle
Rib 10 Single facet for articulation with T10
Rib 11 No neck, single facet for articulation with T11
Rib 12 No neck, single facet for articulation with T12
The atypical ribs consist of ribs 1, 2, 10, 11 and 12.

Rib 1 is shorter and wider than the other ribs. The head of rib 1 has
only one facet for articulation with the body of its own vertebra (T1);
it does NOT articulate with vertebrae C7. The superior surface of rib 1
is characterised by the scalene tubercle about midway along the
body, which separates two smooth grooves in the rib made by the
subclavian vein anteriorly and the subclavian artery posteriorly.
Like rib 1, rib 2 is flat but twice as long. It has a roughened area on
its upper surface where the serratus anterior muscle attaches.
The head of rib 10 only has a single facet for articulation with the
body of its own vertebra (T10).
Ribs 11 and 12 have no neck, and have only one facet for articulation
with the bodies of their own vertebrae (T11 and T12).

Lung LAST UPDATED:
30TH MARCH 2020
ANATOMY / THORAX / PLEURA AND LUNGS
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The lungs lie on either side of the mediastinum, each surrounded by a

pleural cavity. They are suspended from the mediastinum by the root of
the lung, a short tubular collection of structures.
Lung roots
The root is lined by a layer of mediastinal pleura that reflects onto the
surface of the lungs as visceral pleura. The region outlined by this pleural
reflection on the medial surface of the lung is the hilum, where structures
enter and leave.
The hila are located at the level of the 3rd - 4th costal cartilage anteriorly,
and the T5 - T7 vertebrae posteriorly.
Each lung root contains:
a pulmonary artery
two pulmonary veins
a main bronchus
bronchial vessels,
nerves and
lymphatics.
Generally the pulmonary artery is superior in the lung root, the pulmonary
veins are inferior and the bronchi are somewhat posterior in position.
In the mediastinum, the vagus nerves pass immediately posteriorly to the
lung roots, while the phrenic nerves pass immediately anterior to them.
On the right side, the lobar bronchus to the superior lobe branches from
the main bronchus in the root, whereas on the left, it branches within the
lung itself.
ROOT OF THE LUNG. (IMAGE MODIFIED BY FRCEM SUCCESS. ORIGINAL BY GRAY,
HENRY, 1825-1861; CARTER, H. V. (HENRY VANDYKE), 1831-1897; PICK, T.
PICKERING (THOMAS PICKERING), 1841-1919 [NO RESTRICTIONS], VIA
WIKIMEDIA COMMONS)
Relations
The medial surface of the right lung lies adjacent to:
the heart
the inferior vena cava
the superior vena cava
the azygos vein
the oesophagus
The medial surface of the left lung lies adjacent to:
the heart
the aortic arch
the thoracic aorta
the oesophagus.
The right and left subclavian arteries and veins arch over and are related
to the superior lobe of the right and left lung as they pass over the dome
of the cervical pleura and into the axilla.
RELATIONS OF THE LUNGS. (IMAGE BY HENRY VANDYKE CARTER [PUBLIC

Blood supply
The right and left pulmonary arteries originate from the pulmonary trunk
(at the vertebral level T4/T5) and carry deoxygenated blood to the lungs.
On each side a superior and inferior pulmonary vein carries oxygenated
blood from the lungs back to the heart.
The bronchi (down to the terminal bronchioles), lung roots, visceral pleura
and supporting lung tissues receive their nutrient blood supply from the
bronchial arteries, which arise from the descending aorta.
Lymphatics
The parenchyma of the lungs as well as the visceral pleura are drained by
a vast plexus of tiny lymph vessels which drain lymph from these areas
towards the hilum of the lung. All lobes of the lungs first drain into the
intrapulmonary nodes, located around the bifurcations of the branching
lobar bronchi, then onto the bronchopulmonary nodes, located at the
hilum of the lungs. From here, they drain first into the inferior and then the
superior tracheobronchial nodes, located inferior and superior to the
tracheal bifurcation respectively. Then they drain onto the paratracheal
nodes, running superiorly on either side of the trachea, and finally into the
right and left bronchomediastinal lymph trunks, located medially to the
superior portion of the azygos vein and anterior to the vertebral bodies of
the spinal column.
Knowledge of the lymphatics of the lung is very important in both the
staging and treatment of lung cancer. As lung cancer spreads and
metastasises from its primary tumor, it often does so via the lymphatic
system and usually proceeds in a sequential order. Hypothetically, the
sentinel lymph node is the first lymph node or group of lymph nodes
draining a cancer, and is also the first place where cancer cells are most
likely to spread. With other pathologies of the lung, the bronchopulmonary
nodes are those which most frequently become enlarged. On radiography
of the chest, this may be indicated as a classical hilar lymphadenopathy
which may be caused by inflammation, cancer or carcinoma or infection
such as tuberculosis.
Innervation
The nerve supply to the lungs is from the anterior and posterior pulmonary
plexus (networks of nerves derived from the sympathetic trunk and vagus
nerve).
The parasympathetic nerve supply, carried by the vagus nerve, stimulates
secretion from the bronchial glands, contraction of bronchial smooth
muscle, and vasodilation of the pulmonary vessels. The vagus nerve also
carries afferent fibres of pain, cough reflex and stretch of the lung (during
inspiration).
The sympathetic nerve supply stimulates relaxation of bronchial smooth
muscle, and vasoconstriction of the pulmonary vessels.

Lung Surface Anatomy LAST UPDATED:
25TH APRIL 2020
 Bookmark
The lungs lie on either side of the mediastinum, each surrounded by a

pleural cavity. The right lung is normally a little larger than the left lung
because the middle mediastinum, containing the heart, bulges more to
the left than to the right.
Lobes and Fissures

The right lung has three lobes and two fissures; the oblique fissure
separates the inferior lobe from the superior and middle lobe whilst the
horizontal fissure separates the superior lobe from the middle lobe.
The left lung has two lobes separated by the oblique fissure.
The oblique fissure may be an evolutionary development to permit greater
transmission of diaphragmatic excursions to the superior lobe. In this way
the upper lobe can expand to a relatively greater extent for a given
increase in the superoinferior diameter of the pleural cavity.
Surface Markings
The inferior margin of the lung in quiet respiration is a line that runs
between rib 6 in the midclavicular line, rib 8 in the midaxillary line and
vertebra T10 posteriorly.
In quiet respiration, the approximate position of the right oblique fissure
can be marked by a line on the thoracic wall that begins at the spinous
process of vertebra T4, crosses the fifth intercostal space laterally and
then follows the contour of rib 6 anteriorly. The horizontal fissure follows
the fourth intercostal space from the sternum until it meets the oblique
fissure as it crosses rib 5.
The oblique fissure in the left lung is slightly more oblique than the
corresponding fissure in the right lung. In quiet respiration, the
approximate position of the oblique fissure can be marked by a line on the
thoracic wall that begins between the spinous processes of vertebrae T3
and T4, crosses the fifth intercostal space laterally and then follows the
contour of rib 6 anteriorly.
SURFACE MARKINGS OF THE LUNGS. (IMAGE MODIFIED BY FRCEM SUCCESS.

ORIGINAL BY HENRY VANDYKE CARTER [PUBLIC DOMAIN], VIA WIKIMEDIA
COMMONS)
Auscultation
Visualisation of the lungs from the surface is of utmost importance for
auscultation:
Anteriorly:
The right side of chest mostly presents upper and middle
lobes divided by the horizontal fissure at about the 5th rib in
the midaxillary line to 4th rib in the sternum.
The left side of chest mainly presents upper lobe, that is
divided from the lower lobe by oblique fissure going from the
5th rib in the midaxillary line to the 6th rib at the midclavicular
line.
Posteriorly
With the exception of apices, the posterior aspect of chest on
each side mainly presents lower lobe stretching from spinous
process C7 to T10.
Right lateral
The lung is located deep to the area going from axilla to the
level of the 7th or 8th rib. The upper lobe is demarcated in the
level of the 5th rib in the midaxillary line and 6th rib in the
midclavicular line.
Left lateral
The lung is located deep to the area going from axilla to the
7th or 8th rib. The upper lobe is demarcated in the level of the
5th rib in the midaxillary line and 6th rib in the midclavicular
line.
Key Points:
The superior lobe of the right lung is perceptible above the 4th rib
anteriorly.
The middle lobe of the right lung is perceptible between the 4th and
the 6th rib anteriorly.
The superior lobe of the left lung is perceptible above the 6th rib
anteriorly.
The inferior lobes of the left and right lungs are best examined on
the back, notably in the region of the triangle of auscultation formed
by the lateral border of trapezius muscle, medial border of scapula,
and upper border of latissimus dorsi (because this area is free of
intervening muscle masses, respiratory sounds can be easily
detected)

Pleura LAST UPDATED: 11TH
APRIL 2019
 Bookmark
Each lung is surrounded by a pleura. The pleura consists of two parts, the
parietal pleura (which lines the thoracic cavity) and the visceral pleura
(which lines the lungs). The two parts of the pleura are continuous with
each other at the hilum of each lung. The potential space between these
two parts of the pleura is called the pleural cavity.
PLEURAL CAVITY. (IMAGE BY OPENSTAX COLLEGE [CC BY 3.0

(HTTPS://CREATIVECOMMONS.ORG/LICENSES/BY/3.0)], VIA WIKIMEDIA
COMMONS)
Pleural Cavity
The pleural cavity normally contains a small amount of lubricating fluid to
allow the visceral pleura attached to the lungs to smoothly slide over the
parietal pleura attached to the thoracic wall during respiration. The serous
fluid also produces a surface tension, pulling the parietal and visceral
pleura together. This ensures that when the thorax expands, the lung also
expands, filling with air.
Innervation
The parietal pleura is innervated by somatic afferent fibres. The costal
pleura (pleura related to the ribs and intercostal spaces) is innervated by
branches of the intercostal nerves, and pain is felt in relation to the
thoracic wall. The diaphragmatic pleura (covering the diaphragm) and the
mediastinal pleura (covering the mediastinum) are innervated mainly by
the phrenic nerves (C3 - C5), and pain is referred the the C3 - C5
dermatomes (lateral neck and supraclavicular region of shoulder).
Although the visceral pleura is innervated by visceral afferent fibres, pain
is not generally elicited from this tissue.
Surface Markings
Superiorly the pleural cavity projects as much as 3 - 4 cm above the first
costal cartilage but does not extend above the neck of rib 1.
Anteriorly the pleurae approach each other posterior to the upper part of
the sternum. At the lower part of the sternum the left pleura does not
come as close to the midline as the right pleura because the middle
mediastinum bulges to the left.
Inferiorly the pleura reflects onto the diaphragm above the costal margin.
The inferior margin of the pleural cavity is a line that runs between rib 8 in
the midclavicular line, rib 10 in the midaxillary line and vertebra T12
posteriorly.
The inferior margin of the lung in quiet respiration is a line that runs
between rib 6 in the midclavicular line, rib 8 in the midaxillary line and
vertebra T10 posteriorly.
The lungs therefore do not completely fill the pleural cavities, producing
two pleural recesses, the costomediastinal and costodiaphragmatic
recesses, in which fluids can collect.
The costomediastinal recess occurs on each side where the the costal
pleura is opposed to mediastinal pleura, particularly on the left side in the
region overlying the heart.
The costodiaphragmatic recess occurs between the costal and
diaphragmatic pleura. It is the region between the inferior margin of the
lung and the inferior margin of the pleural cavity and is clinically important
for pleural aspiration.
SURFACE MARKINGS OF THE PLEURA. (IMAGE BY HENRY VANDYKE CARTER


Tracheobronchial Tree LAST UPDATED:
28TH JANUARY 2019
 Bookmark
The trachea bifurcates into a left and right main bronchus at the level of
vertebra T4/T5. At the bifurcation of the main bronchi, a ridge of cartilage
called the carina runs anteroposteriorly between the openings of the two
bronchi.
Each main bronchus enters the root of a lung and passes through the
hilum into the lung itself. The right main bronchus is wider and takes a
more vertical course through the root and hilum than the left main
bronchus, therefore inhaled foreign bodies are more likely to lodge on the
right than the left.
The main bronchus divides into lobar bronchi (secondary bronchi) which
each supply a lobe. The lobar bronchi further divided into segmental
bronchi (tertiary bronchi) which supply bronchopulmonary segments (the
functional unit of the lung).
Within each bronchopulmonary segment, the segmental bronchi give rise
to multiple generations of divisions and ultimately to bronchioles (in order,
conducting bronchioles, terminal bronchioles, respiratory bronchioles).
The respiratory bronchioles continue as alveolar ducts and sacs, the walls
of which form alveoli.
TRACHEOBRONCHIAL TREE. (IMAGE BY LADYOFHATS [PUBLIC DOMAIN], VIA
WIKIMEDIA COMMONS)

Thoracic Inlet LAST UPDATED:
27TH FEBRUARY
ANATOMY / THORAX / THORACIC INLET 2020
 Bookmark
The thoracic inlet is bordered anteriorly by the manubrium of the sternum

and the first costal cartilages, laterally by the first ribs and posteriorly by
the body of vertebra T1.
THORACIC INLET. (IMAGE MODIFIED BY FRCEM SUCCESS. ORIGINAL BY HENRY

At the thoracic inlet, the superior aspects of the pleural cavities lie on
either side of the entrance to the mediastinum, extending approximately 2
- 3 cm above rib I and the costal cartilage into the neck.
Relations of Key Structures
The thoracic inlet is traversed in the median plane by (from anterior to
posterior):
the sternohyoid muscle
the sternothyroid muscle
the thymic remnants
the inferior thyroid veins
the trachea
the recurrent laryngeal nerves (in the tracheo-oesophageal sulcus)
the oesophagus
the thoracic duct (displaced slightly to the left)
the longus colli muscles
the anterior longitudinal ligament.
To the left, it is traversed by (from anterior to posterior):
the left brachiocephalic vein
the left vagus and left phrenic nerves
the left common carotid artery and the left subclavian artery.
To the right, it is traversed by (from anterior to posterior):
the right brachiocephalic vein
the right vagus and right phrenic nerves
the brachiocephalic trunk.

Dermatomal Supply of LAST UPDATED:
20TH FEBRUARY
Trunk 2019
ANATOMY / ABDOMEN /  Bookmark
ANTERIOR ABDOMINAL WALL / THORAX /
THORACIC WALL
Table: Dermatomal Supply of the Trunk

Dermatome Landmark
T1 Medial antecubital fossa
T2 Apex of axilla
T3 Third intercostal space
T4 Level of nipples (fourth intercostal space)
T5 Fifth intercostal space
T6 Level of xiphisternum
T7 One-quarter distance between xiphisternum and
umbilicus
T8 One-half distance between xiphisternum and
umbilicus
T9 Three-quarter distance between xiphisternum and
umbilicus
T10 Level of umbilicus
T11 Midway between umbilicus and inguinal ligament
T12 Midpoint of inguinal ligament
DERMATOME MAP. (IMAGE BY GRANT, JOHN CHARLES BOILEAU (AN ATLAS OF
ANATOMY, / BY REGIONS 1962) [PUBLIC DOMAIN], VIA WIKIMEDIA COMMONS)
The T3 dermatome is best tested at the midclavicular line and the third
intercostal space.
The T4 dermatome is best tested at the midclavicular line and the fourth
intercostal space, located at the level of the nipples.
The T5 dermatome is best tested at the midclavicular line and the fifth
intercostal space, located midway between the level of the nipples and
the level of the xiphisternum.
The T6 dermatome is best tested at the midclavicular line, located at the
level of the xiphisternum.
The T7 dermatome is best tested at the midclavicular line, one quarter the
distance between the level of the xiphisternum and the level of the
umbilicus.
Intercostal Space LAST UPDATED: 11TH
APRIL 2019
ANATOMY / THORAX / THORACIC WALL
 Bookmark
The intercostal space lies between adjacent ribs and mostly contains
intercostal muscles. Since there are 12 ribs on each side, there are 11
intercostal spaces, each numbered for the rib superior to it.
Intercostal nerves and major associated arteries and veins lie in the costal
groove along the inferior margin of the rib, lying in a plane between the
internal and innermost intercostal muscles.
COSTAL GROOVE OF CENTRAL RIB ON LEFT SIDE (INFERIOR VIEW). (ORIGINAL

IMAGE BY HENRY VANDYKE CARTER [PUBLIC DOMAIN], VIA WIKIMEDIA
COMMONS)
Clinical Significance
In each space, the vein is the most superior structure and is therefore
highest in the costal groove. The artery is inferior to the vein and the nerve
inferior to the artery and often not protected by the groove. Therefore the
nerve is the most vulnerable structure in a penetrating injury to the upper
aspect of the intercostal space. Small collateral branches of the major
intercostal nerves and vessels are often present superior to the inferior rib
below.
Any needle or tube (e.g. in needle thoracocentesis, pleural aspiration or
chest drain insertion) being inserted in the intercostal space should be
placed immediately above the superior margin of a rib to avoid injury to
the intercostal neurovascular bundle.

Resuscitative LAST UPDATED: 3RD
JULY 2020
Thoracotomy  Bookmark
The patient should be positioned in the supine position if not already so.
Time should not be wasted on full asepsis but a rapid application of skin
preparation is appropriate.
Using a scalpel and blunt forceps, bilateral 4 cm thoracostomies should be
made in the 5th intercostal space in the mid-axillary line, breaching the
intercostal muscles and parietal pleura.
The thoracostomies should be connected with a deep skin incision
following the 5th intercostal space.
Two fingers should be inserted into a thoracostomy to hold the lung out of
the way while cutting through all layers of the intercostal muscles and
pleura towards the sternum using heavy scissors. This should be
performed on the left and right sides leaving only a sternal bridge
between the two anterolateral thoracotomies.
The sternum or xiphoid should be divided using the heavy scissors. If
unable to cut through bone with scissors, a Gigli saw (serrated wire) may
be used.
The “clam shell” should be opened using one or two large self retaining
retractors/rib spreaders from the full thoracotomy set. If this is not
available, the incision can be held open manually by one or two gloved
assistants. The retractor should be opened to its full extent to provide
adequate exposure of the chest cavity with access to all areas. If exposure
is inadequate the incisions need to be extended posteriorly.
Once the chest is opened steps include:
Damage control maneuvers are used to manage hemorrhage that
will impede performance of pericardiotomy or aortic cross-clamping
The pericardial sac is opened, and temporising measures are used
to control any cardiac injuries, if present. Air embolism is managed if
identified
The aorta is cross-clamped to allow filling of the heart and facilitate
ongoing fluid resuscitation.
Open cardiac massage is initiated once the heart has filled
sufficiently
The thoracic structures are systematically explored, looking for any
additional bleeding or hematoma formation that might suggest
underlying injury

Thoracic Wall Movements LAST UPDATED: 11TH
APRIL 2019
 Bookmark
Movement of the ribs at the costovertebral joints in respiration results in

the 'pump handle' and 'bucket handle' movements:
Because the anterior ends of the ribs are inferior to the posterior
ends, when the ribs are elevated, the anterior end moves upwards
and forwards, moving the sternum upwards and forwards in turn.
This 'pump handle' upwards and forwards movement changes the
anteroposterior (AP) dimension of the thorax.
Because the middles of the shafts of the ribs are lower than either
the anterior or posterior end, elevation of the ribs also moves the
middles of the shafts laterally. This 'bucket handle' upwards and
lateral movement increases the lateral dimensions of the thorax.
Reversal of these movements i.e. depression of the ribs, will reduce the
anteroposterior and transverse dimensions of the thorax.
THORACIC MOVEMENTS. (IMAGE BY OPENSTAX COLLEGE [CC BY 3.0
COMMONS)
Inspiration
In inspiration, elevation of the sternal ends of the ribs ('pump handle'
movement), elevation of the lateral shafts of the ribs ('bucket handle'
movement) and depression of the diaphragm result in expansion of the
thorax in an anteroposterior, transverse and vertical direction
respectively. This results in an increased intrathoracic volume and
decreased intrathoracic pressure and thus air is drawn into the lungs.
Passive inspiration is produced by contraction of the diaphragm
(depressing the diaphragm) and the external intercostal muscles
(elevating the ribs).
The accessory respiratory muscles (including the sternocleidomastoid,
the scalene muscles and the serratus anterior amongst others) aid in
forceful inspiration.
Expiration
In expiration, depression of the ribs and elevation of the diaphragm result
in a reduction of the thorax in an anteroposterior, transverse and vertical
direction. This results in a decreased intrathoracic volume and increased
intrathoracic pressure and thus air is forced out of the lungs.
Passive expiration is produced primarily by relaxation of the inspiratory
muscles (diaphragm and external intercostal muscles) and the elastic
recoil of the lungs.
Forceful expiration is primarily produced by the deeper thoracic muscles
(internal and innermost intercostal muscles, subcostals and transversus
thoracis) aided by contraction of the abdominal wall muscles which
increase intra-abdominal pressure thus further reducing the volume of
the thorax.
Paradoxical Respiration
Normally as the diaphragm moves downwards in respiration, the
abdominal wall moves outwards (together with the chest wall), and the
reverse occurs in expiration.
In complete airway obstruction, the diaphragm will move down and the
abdominal wall out but as inspiratory effort continues against a closed
airway, increasing intrathoracic pressure will draw the chest wall
paradoxically inwards (against the opposing action of the intercostal
muscles). To the observer, in inspiration there is abdominal expansion with
chest collapse and during expiration the reverse is seen. As inspiratory
effort increases and expiration becomes active, the see-sawing pattern
becomes more pronounced.
Flail chest is a loss of stability of the thoracic cage that occurs when a
segment of the anterior or lateral thoracic wall moves freely because of
multiple rib fractures, allowing the loose segment to move paradoxically
inward on inspiration and outward on expiration. If a large enough
segment of the chest is affected, ventilation is impaired.

Thoracic Wall Muscles LAST UPDATED: 11TH
APRIL 2019
 Bookmark
The intercostal muscles are three flat muscles found in each intercostal
space that pass between adjacent ribs. As a group the intercostal muscles
provide structural support of the intercostal spaces during breathing and
can also act to move the ribs.
THORACIC WALL MUSCLES. (IMAGE BY CFCF (OWN WORK) [CC BY-SA 4.0
COMMONS)
The neurovascular bundles associated with the intercostal spaces pass
around the thoracic wall in the costal grooves in a plane between the
layers of the internal and innermost intercostal muscles. The intercostal
and transversus thoracis muscles are innervated by the intercostal nerves
(T1 - T11).
Table: Function of the Thoracic Wall Muscles

Muscle Function
External intercostal Move ribs superiorly, most active in
inspiration
Internal intercostal Move ribs inferiorly, most active in
expiration
Innermost Acts with internal intercostal muscles
intercostal
Transversus Depresses costal cartilages
thoracis
Internal Intercostal Muscles

The internal intercostal muscles lie deep to the external intercostal
muscles. They run posteroinferiorly from the rib above to the rib below,
and are continuous with the internal oblique muscle inferiorly. The internal
intercostal muscles act to move the ribs inferiorly and are most active
during expiration.
External Intercostal Muscles

The external intercostal muscles lie in the outer layer. They run
anteroinferiorly from the rib above to the rib below, and are continuous
with the external oblique muscle inferiorly. The external intercostal
muscles act to move the ribs superiorly and are most active in inspiration.
Innermost Intercostal Muscles
The innermost intercostal muscles are the deepest of the intercostal
muscles and are very similar to the internal intercostal muscles in terms of
structure and function.
Transversus Thoracis Muscle

The transversus thoracis muscle is also part of the innermost layer, and is
continuous inferiorly with the transversus abdominis muscle inferiorly.

Transverse Thoracic LAST UPDATED:
24TH FEBRUARY
Plane 2020
ANATOMY / THORAX / THORACIC WALL  Bookmark
The transverse thoracic plane lies at the level of the sternal angle (at the
level of the second intercostal cartilages) and the intervertebral disc
between T4 and T5.
A number of important structures are transected by the transverse
thoracic plane.
At the level of the transverse thoracic plane:
the ascending aorta ends and the aortic arch begins
the aortic arch ends and the descending aorta begins
the superior mediastinum becomes the inferior mediastinum
the trachea bifurcates into the right and left main bronchi
the pulmonary trunk bifurcates into the right and left pulmonary
arteries
the azygos vein ends by draining into the superior vena cava
the thoracic duct crosses the oesophagus posteriorly (from right to
left)
the left recurrent laryngeal nerve loops around the aortic arch

Thymus Gland LAST UPDATED:
19TH FEBRUARY
ANATOMY / THORAX / THYMUS 2019
 Bookmark
The thymus gland is the most anterior component of the superior

mediastinum lying immediately posterior to the manubrium of the
sternum.
The superior aspect of the thymus can reach as high as the thyroid gland
in the neck and the inferior aspect typically extends into the anterior
mediastinum over the pericardium.
The thymus is a large structure in the child, important in early
development of the immune system and begins to atrophy after puberty.
In adulthood it is usually replaced by adipose tissue and is barely
recognisable. Nevertheless, residual T-cell lymphopoiesis continues
throughout adult life.
Trachea (Thorax) LAST UPDATED: 11TH
APRIL 2019
ANATOMY / THORAX / TRACHEA
 Bookmark
The trachea arises at the lower border of the cricoid cartilage in the neck,
as a continuation of the larynx. It extends from vertebral level C6 to T4/T5
at which point it bifurcates into the right and left main bronchi (at the
level of the sternal angle).
TRACHEA. (IMAGE BY BLAUSEN.COM STAFF. “BLAUSEN GALLERY 2014”.

WIKIVERSITY JOURNAL OF MEDICINE. DOI:10.15347/WJM/2014.010. ISSN
20018762. (OWN WORK) [CC BY 3.0
COMMONS)
The trachea is formed anteriorly by 15 - 20 C-shaped rings of hyaline

cartilage which mechanically hold the airway open whilst allowing it
flexibility. The trachealis muscle connects the ends of the incomplete
rings and forms the posterior wall of the trachea. The trachealis muscle is
able to constrict the trachea, allowing air to be expelled with more force
e.g. during coughing.
The trachea and bronchi are lined by ciliated pseudostratified columnar
epithelium, interspersed by mucus-producing goblet cells. This mucous
membrane functions as the mucociliary escalator, trapping particles in
sticky mucus and sweeping it along the airway.
Relations
The trachea descends anterior to the oesophagus and inclines slightly to
the right.
In the thorax, anteriorly it is related to:
the thymic remnants
the left brachiocephalic vein
the aortic arch
the brachiocephalic trunk
the left common carotid artery
the deep cardiac plexus.
Laterally it is related to:
the pleura, the right vagus nerve and the brachiocephalic trunk on
the right
the left recurrent laryngeal nerve, the aortic arch and the left
common carotid and subclavian vessels on the left.
RELATIONS OF THE TRACHEA. (IMAGE BY ZOOFARI [CC BY-SA 3.0
COMMONS)

ABDOMEN
& PELVIS
8/26/22, 4:06 PM Abdominal Regions - MRCEM Success
Abdominal Regions LAST UPDATED: 8TH

JULY 2019
ANATOMY / ABDOMEN / ANTERIOR ABDOMINAL WALL
 Bookmark
ABDOMINAL REGIONS. (IMAGE BY OPENSTAX. [CC BY 3.0

Four-quadrant pattern
The abdominal wall may be divided into a simple four-quadrant topographical pattern
by a horizontal line passing through the umbilicus and the intervertebral disc between
vertebrae L3 and L4 (transumbilical plane) intersecting with the vertical median plane;
this forms the right upper, the left upper, the right lower and the left lower quadrants.
Nine-region pattern
The nine-region topographical description is based on two horizontal and two vertical
planes:
The two vertical planes pass on each side from the midpoint of the clavicle to
the midpoint of the inguinal ligament.
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The inferior horizontal plane (the intertubercular plane) connects the tubercles
of the iliac crests and passes posteriorly through the body of vertebra L5.
The superior horizontal plane may be taken as the subcostal or the transpyloric
plane:
The subcostal plane lies immediately inferior to the costal margins at the
lower border of the tenth costal cartilage and passes posteriorly through
the body of vertebra L3.
The transpyloric plane lies halfway between the jugular notch and the
pubic symphysis, intersecting with the costal margin at the ends of the
ninth costal cartilage and passing posteriorly through the body of vertebra
L1.
The nine regions are designated (read as if reading a book):
the right hypochondriac region
the epigastric region
the left hypochondriac region
the right lumbar region (or flank)
the umbilical region
the left lumbar region (or flank)
the right iliac region
the pubic (or hypogastric) region
the left iliac region
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8/26/22, 4:08 PM Anterior Abdominal Wall Muscles - MRCEM Success
Anterior Abdominal Wall LAST UPDATED: 11TH

APRIL 2019
There are five muscles in the anterolateral group of abdominal wall muscles; three flat
muscles whose fibres begin posterolaterally and pass anteriorly before being replaced by
an aponeurosis as the muscle continues towards the midline (external oblique, internal
oblique, transversus abdominis) and two vertical muscles enclosed by the tendinous
sheath formed by the aponeuroses of the flat muscles (rectus abdominis, pyramidalis).
ANTERIOR ABDOMINAL WALL MUSCLES. (IMAGE BY OPENSTAX COLLEGE [CC BY 3.0

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External oblique
The external oblique is the largest and most superficial of the anterior abdominal muscles,
lying just deep to the superficial fascia. The external oblique originates from the outer
surfaces of the lower eight ribs, its fibres running in an inferomedial direction before
inserting onto the lateral lip of the iliac crest.
The external oblique has a large aponeurotic component that covers the anterior part of
the abdominal wall and forms the linea alba at the midline, together with the aponeuroses
from the internal oblique and the transversus abdominis. The linea alba extends from the
xiphoid process to the pubic symphysis.
The lower free border of the external oblique aponeurosis forms the inguinal ligament on
each side (which runs between the anterior superior iliac spine laterally and the pubic
tubercle medially).
Internal oblique
The internal oblique muscle lies deep to the external oblique. Its fibres run in a
superomedial direction, originating from the thoracolumbar fascia, the iliac crest and the
lateral two-thirds of the inguinal ligament and inserting onto the inferior border of the
lower 3 - 4 ribs, the linea alba, the pubic crest and pectineal line.
Transversus abdominis
The transversus abdominis is the innermost of the flat anterior abdominal muscles, lying
deep to the internal oblique. It originates from the thoracolumbar fascia, the iliac crest,
the lateral one-third of the inguinal ligament and the 7th - 12th costal cartilages and
inserts onto the linea alba, the pubic crest and the pectineal line.
Rectus abdominis
The rectus abdominis is a long muscle that extends the length of the anterior abdominal
wall. It originates from the pubic crest, pubic tubercle and pubic symphysis and inserts
onto the costal cartilages of ribs 5 - 7 and to the xiphoid process. It is a paired muscle,
separated in the midline by the linea alba.
Function
The abdominal wall muscles form a firm, but flexible wall that keeps the abdominal viscera
within the abdominal cavity, protects the viscera from injury and helps maintain the
position of the viscera in the erect posture against the action of gravity.
The muscles act together to flex and rotate the vertebral column.
In addition, contraction of these muscles assists in forced expiration, and in coughing and
vomiting, by pushing the viscera upwards. All of these muscles are involved in any action
that increases intra-abdominal pressure, including childbirth, micturition and
defaecation.
Innervation
The anterior abdominal wall muscles are innervated by the anterior rami of T7 - T12 and L1.
8/26/22, 4:33 PM Rectus Sheath - MRCEM Success
Rectus Sheath LAST UPDATED: 11TH

APRIL 2019
 Bookmark
The rectus sheath is formed by the aponeuroses of the three flat anterior abdominal
wall muscles.
Derivation
The anterior wall of the sheath is formed by the aponeurosis of the external
oblique and half of the aponeurosis of the internal oblique (which splits at the
lateral margin of the rectus abdominis).
The posterior wall of the sheath is formed by the other half of the aponeurosis
of the internal oblique and by the aponeurosis of the transversus abdominis.
The rectus sheath completely encloses the upper three-quarters of the rectus
abdominis in the above formation but only covers the anterior surface of the lower
one-quarter of the muscle. At this point (midway between the umbilicus and the
pubic symphysis), the anterior wall is formed by the aponeuroses of all three
muscles, there is no posterior wall to the rectus sheath and the rectus abdominis
muscle is in direct contact with the transversalis fascia. Marking this point of
transition is the arcuate line.
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8/26/22, 4:33 PM Rectus Sheath - MRCEM Success
RECTUS SHEATH (ENCLOSING UPPER THREE-QUARTERS OF RECTUS ABDOMINIS MUSCLE).

(IMAGE BY HENRY VANDYKE CARTER [PUBLIC DOMAIN], VIA WIKIMEDIA COMMONS)
RECTUS SHEATH (COVERING LOWER ONE-QUARTER OF RECTUS ABDOMINIS MUSCLE).

(IMAGE MODIFIED BY FRCEM SUCCESS. ORIGINAL BY HENRY VANDYKE CARTER [PUBLIC
Contents
In addition to the rectus abdominis muscle, the rectus sheath also encloses:
the pyramidalis muscle
the superior and inferior epigastric vessels
the termination of intercostal nerves T7 - T11
the 12th thoracic nerve and the accompanying vessels
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8/26/22, 4:30 PM Peritoneum - MRCEM Success
Peritoneum LAST UPDATED: 3RD

APRIL 2020
ANATOMY / ABDOMEN /
TOPOGRAPHY OF ABDOMINAL CAVITY  Bookmark
The peritoneum is a continuous double-layered serous membrane. The parietal peritoneum

lines the walls of the abdominal cavity and the visceral peritoneum lines the viscera.
Between the parietal and visceral layers of peritoneum is a potential space, the peritoneal
cavity.
Intraperitoneal vs. Retroperitoneal

Abdominal viscera are either suspended in the peritoneal cavity by folds of peritoneum
called mesenteries (intraperitoneal viscera) or are outside the peritoneal cavity bound to the
posterior abdominal wall (retroperitoneal viscera). Retroperitoneal organs are only covered
in peritoneum on their anterior surface.
A useful mnemonic to help remember which abdominal organs are retroperitoneal is SAD
PUCKER:
Suprarenal glands
Aorta and Inferior vena cava
Duodenum (2nd and 3rd parts)
Pancreas (except for the tail)
Ureters (proximal) and Bladder
Colon (ascending and descending)
Kidneys
(O)esophagus
Rectum (lower two-thirds)
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8/26/22, 4:30 PM Peritoneum - MRCEM Success
PERITONEUM. (IMAGE BY OPENSTAX COLLEGE [CC BY 3.0

Innervation
The parietal peritoneum associated with the abdominal wall is innervated by somatic
afferents carried in branches of the associated spinal nerves and is therefore sensitive to
pressure, pain and temperature, and gives rise to well-localised pain. The diaphragmatic
peritoneum is supplied by the phrenic nerve (C3 - C5) and the remainder of the parietal
peritoneum is supplied segmentally by intercostal and lumbar nerves.
The visceral peritoneum is innervated by visceral afferents that accompany autonomic
nerves back to the CNS and therefore activation gives rise to referred and poorly localised
sensations of discomfort and to visceral motor activity.
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8/26/22, 4:30 PM Peritoneal Compartments - MRCEM Success
Peritoneal Compartments LAST UPDATED: 10TH

JUNE 2020
ANATOMY / ABDOMEN / TOPOGRAPHY OF ABDOMINAL CAVITY
 Bookmark
The peritoneal cavity is divided into the greater sac and the omental bursa (lesser sac).
Table: Anatomical Overview of the Abdominal Cavity

Structure Key anatomy
Peritoneal Divided into greater and lesser sacs
cavity
Greater sac Divided into supracolic and infracolic compartments by transverse
mesocolon, compartments connected by paracolic gutters
Supracolic Contains stomach, liver and spleen, lies under cover of costal limits of
compartment thoracic cage
Infracolic Divided into left and right parts by oblique attachment of mesentery,
compartment contains small intestine and ascending/descending colon, continuous
with pelvic cavity
Lesser sac Lies posterior to stomach and liver and anterior to pancreas,
(omental continuous with greater sac through epiploic foramen
bursa
Greater Descends from greater curvature of stomach and first part of
omentum duodenum, drapes inferiorly over transverse colon, jejunum and ileum,
folds back up and ascends to adhere to transverse colon/mesocolon
before arriving at posterior abdominal wall
Lesser Extends from lesser curvature of stomach and first part of duodenum
omentum to inferior surface of liver
Mesentery Connects jejunum and ileus to posterior abdominal wall, attaches
superiorly to duodenojejunal junction and passes oblique downwards
and to the right to end at ileocecal junction
Transverse Connects transverse colon to posterior abdominal wall, leaves
mesocolon posterior abdominal wall across anterior surface of head and body of
pancreas and passes outwards to surround transverse colon
Sigmoid Connects sigmoid colon to abdominal wall, V-shaped fold with apex
mesocolon near division of left common iliac artery, left limb descending along
medial border of left psoas major muscle and right limb descending
into pelvis to end at vertebral level S3
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Greater Sac
The greater sac accounts for most of the space in the peritoneal cavity, beginning superiorly
at the diaphragm and continuing inferiorly in the pelvic cavity. It is further divided into two
compartments by the transverse mesocolon:
The supracolic compartment lies above the transverse mesocolon and contains the
stomach, liver and spleen. It lies largely under cover of the costal limits of the thoracic
cage.
The infracolic compartment lies below the transverse mesocolon, is divided into left and
right parts by the oblique attachment of the mesentery and contains the small intestine
and the ascending and descending colon. The left infracolic compartment is continuous
with the pelvic cavity.
The supracolic and infracolic compartments are connected by the paracolic gutters which lie
between the posterolateral abdominal wall and the lateral aspect of the ascending or
descending colon.
The supracolic space can be arbitrarily divided into right and left supracolic spaces and
subspaces.
The left supracolic space has two subspaces:
Left subphrenic space
Left perihepatic space
The right supracolic space has three subspaces:
Right subphrenic space
Right subhepatic space
This is further divided into anterior and posterior spaces.
The posterior right subhepatic space (Morrison's pouch) separates the liver from
the right kidney. Fluid (e.g. ascites or haemoperitoneum) accumulates here as it is
the lowest dependant spaces of the peritoneal cavity from a wide range of
causes. It is also a preferential site for metastases and abscesses.
Lesser sac
Lesser Sac
The omental bursa (lesser sac) is a smaller subdivision of the peritoneal cavity posterior to the
stomach and liver and anterior to the pancreas, and is continuous with the greater sac
through the epiploic foramen.
PERITONEAL CAVITY. (IMAGE MODIFIED BY FRCEM SUCCESS. ORIGINAL BY HENRY VANDYKE CARTER
8/26/22, 4:30 PM Peritoneal Mesenteries - MRCEM Success
Peritoneal Mesenteries LAST UPDATED: 11TH

APRIL 2019
ANATOMY / ABDOMEN / TOPOGRAPHY OF ABDOMINAL CAVITY
 Bookmark

cavity
with pelvic cavity
Lesser sac Lies posterior to stomach and liver and anterior to pancreas,
(omental continuous with greater sac through epiploic foramen
bursa
Lesser Extends from lesser curvature of stomach and first part of duodenum
omentum to inferior surface of liver
Transverse Connects transverse colon to posterior abdominal wall, leaves
mesocolon posterior abdominal wall across anterior surface of head and body of
pancreas and passes outwards to surround transverse colon
medial border of left psoas major muscle and right limb descending
into pelvis to end at vertebral level S3
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Mesenteries are peritoneal folds that attach viscera to the posterior abdominal wall. They allow
some movement and provide a conduit for vessels, nerves and lymphatics to reach the viscera
and include:
the mesentery - associated with parts of the small intestine
the transverse mesocolon - associated with transverse colon
the sigmoid mesocolon - associated with the sigmoid colon.
Mesentery
The mesentery is a large, fan-shaped, double-layered fold of peritoneum that connects the
jejunum and ileum to the posterior abdominal wall. Its superior attachment is at the
duodenojejunal junction, just to the left of the upper lumbar part of the vertebral column. It
passes obliquely downwards and to the right, ending at the ileocaecal junction near the upper
border of the right sacroiliac joint.
Transverse Mesocolon
The transverse mesocolon is a fold of peritoneum that connects the transverse colon to the
posterior abdominal wall. It leaves the posterior abdominal wall across the anterior surface of
the head and body of the pancreas and passes outwards to surround the transverse colon. Its
anterior layer is adherent to the posterior layer of the greater omentum.
Sigmoid Mesocolon
The sigmoid mesocolon is an inverted V-shaped peritoneal fold that attaches the sigmoid
colon to the abdominal wall. The apex of the V is near the division of the left common iliac
artery, with the left limb of the descending V along the medial border of the left psoas major
muscle, and the right limb descending into the pelvis to end at the level of vertebra S3.
8/26/22, 4:31 PM Posterior Abdominal Wall Muscles - MRCEM Success
Posterior Abdominal Wall LAST UPDATED: 11TH

APRIL 2019
ANATOMY / ABDOMEN / POSTERIOR ABDOMINAL WALL
The most important muscles of the posterior abdominal wall are the psoas major, the iliacus
and the quadratus lumborum which each possess a strong fascial covering. Associated with
the psoas major muscle is the psoas minor muscle, which is sometimes absent.
Table: Function and Innervation of the Posterior Abdominal Wall Muscles
Muscle Extent Function Innervation
Psoas Originates from vertebrae T12 – L5, Flexes thigh Anterior
major covers anterolateral bodies of at hip joint rami L1 – L3
lumbar vertebrae and fills in spaces when trunk is
between vertebral bodies and stabilised,
transverse processes, passes flexes trunk
inferiorly along pelvic brim and against
attaches distally to lesser gravity when
trochanter of femur body is supine
Quadratus Fills space between rib 12 and iliac Depresses Anterior
lumborum crest on both sides of vertebral and stabilises rami of T12
column, overlapped medially by twelfth rib, and L1 – L4
psoas major muscle, lies medial to contributes to
transversus abdominis muscle lateral
bending of
trunk
Iliacus Fills iliac fossa on each side before Flexes thigh Femoral
passing inferiorly to join with psoas at hip joint nerve (L2 –
major muscle and attach distally to when trunk is L4)
lesser trochanter of femur stabilised,
flexes trunk
against
gravity when
body is supine
Psoas Major
The psoas major originates from the lateral bodies of, the transverse processes of and the
intervertebral discs between the T12 and L1 - L5 vertebrae, essentially covering the
https://mrcemsuccess.com/explanation/posterior-abdominal-wall-muscles/?_sft_qc=abdomen&sf_paged=3 2/4
anterolateral surface of the bodies of the lumbar vertebrae and filling in the spaces between
the vertebral bodies and the transverse processes. It passes inferiorly along the pelvic brim
and continues into the anterior thigh to attach to the lesser trochanter of the femur.
The psoas major flexes the thigh at the hip joint when the trunk is stabilised and flexes the
trunk against gravity when the body is supine.
It is innervated by the anterior rami of nerves L1 - L3.

The lumbar plexus forms within the psoas major muscle, anterior to its attachment to the
transverse
Quadratus process of the lumbar vertebrae.
Lumborum
The quadratus lumborum muscles essentially fill the space between rib 12 and the iliac crest
on both sides of the vertebral column. They are overlapped medially by the psoas major
muscles and along their lateral borders are the transversus abdominis muscles.
The quadratus lumborum muscles depress and stabilise the twelfth ribs and contribute to
lateral bending of the trunk. Acting together, the muscles may extend the lumbar part of the
vertebral column.
They are innervated by the anterior rami of T12 and L1 - L4.
Iliacus
The iliacus muscle fills the iliac fossa on each side, before passing inferiorly to join with the
psoas major muscle (forming the iliopsoas muscle) and attach to the lesser trochanter of the
femur.
Like the psoas major, the iliacus flexes the thigh at the hip joint when the trunk is stabilised
and flexes the trunk against gravity when the body is supine.
It is innervated by branches of the femoral nerve.
MUSCLES OF THE POSTERIOR ABDOMINAL WALL. (IMAGE BY OPENSTAX COLLEGE [CC BY 3.0
8/26/22, 4:27 PM Oesophagus (Abdominal) - MRCEM Success
Oesophagus (Abdominal) LAST UPDATED: 7TH

JUNE 2022
ANATOMY / ABDOMEN / GASTROINTESTINAL TRACT
 Bookmark
The abdominal oesophagus represents the short distal part (about 2 cm) of the
oesophagus located in the abdominal cavity.
Emerging through the right crus of the diaphragm at the level of vertebra T10, it passes
from the oesophageal hiatus to the cardiac orifice of the stomach just left of the midline
at the level of vertebra T11.
Factors guarding against gastric reflux

Anatomical factors that help guard against gastric reflux include:
The diaphragmatic pinchcock effect where at the oesophageal hiatus,
diaphragmatic crural fibres exert pressure on the oesophageal wall and serve as
an extrinsic sphincter
The lower oesophageal sphincter which is a high-pressure zone of smooth
muscle in the oesophageal wall maintained in a state of tonic contraction (except
during swallowing, belching or vomiting)
Intra-abdominal pressure which maintains the oesophagus in a state of collapse
when empty
The angle of His formed at the junction of the oesophagus and the gastric fundus,
which together with the posterolateral position of the gastric fundus, minimises
contact of gastric content with the gastro-oesophageal junction
The gastric mucosal rosette-like folds formed at the gastro-oesophageal junction
which compress against each other with increased intraabdominal pressure to
prevent reflux
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8/26/22, 4:27 PM Oesophagus (Abdominal) - MRCEM Success
ABDOMINAL OESOPHAGUS. (IMAGE MODIFIED BY FRCEM SUCCESS. [CC BY-SA 3.0

https://mrcemsuccess.com/explanation/oesophagus-abdominal/?_sft_qc=abdomen&sf_paged=3 3/3
8/26/22, 4:36 PM Stomach - MRCEM Success
Stomach LAST UPDATED: 4TH

JULY 2021
 Bookmark
The stomach is the most dilated part of the gastrointestinal tract and has a J-
like shape. The stomach is in the epigastric, umbilical and left hypochondrial
regions of the abdomen. It is an intraperitoneal organ.
SURFACE MARKINGS OF THE STOMACH. (IMAGE BY HENRY VANDYKE CARTER [PUBLIC

Anatomical Distinctions
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The stomach is divided into four regions:

the cardia which surrounds the opening of the oesophagus into the
stomach
the fundus which is the area above the level of the cardiac orifice
the body which is the largest central region of the stomach
the pyloric part which is divided into the pyloric antrum and the pyloric
canal which opens into the duodenum.
The most distal portion of the pyloric canal contains a thickened ring of gastric
circular muscle, the pyloric sphincter that surrounds the distal pyloric orifice.
The pyloric orifice is just to the right of the midline in the transpyloric plane. The
pyloric sphincter controls the exit of chyme from the stomach into the
duodenum. The sphincter is constricted by sympathetic stimulation and relaxed
by parasympathetic action. Parasympathetic fibres in the vagus nerve are also
secretomotor to gastric glands and motor to muscular wall of stomach.
STOMACH. (IMAGE MODIFIED BY FRCEM SUCCESS. ORIGINAL BY HENRY VANDYKE

Relations
The stomach lies inferior to the diaphragm.
The stomach lies posterior to:
the anterior abdominal wall
the left costal margin
the left lobe of the liver
The stomach lies anterior to the stomach bed formed by:
the diaphragm
the pancreas
the transverse mesocolon
the left colic flexure
the left kidney
the left adrenal gland
the spleen
RELATIONS OF THE STOMACH. (IMAGE BY HENRY VANDYKE CARTER [PUBLIC DOMAIN],

Blood supply
The arterial supply to the stomach is derived from all three branches (left
gastric, splenic and common hepatic branches) of the coeliac trunk.
8/26/22, 4:33 PM Small Intestine: Duodenum - MRCEM Success
Small Intestine: Duodenum LAST UPDATED: 11TH

APRIL 2019
 Bookmark
The small intestine is the longest part of the gastrointestinal tract and extends from
the pyloric orifice of the stomach to the ileocaecal fold, comprising the duodenum,
jejunum and ileum. The first part of the small intestine is the duodenum.
SMALL INTESTINE. (IMAGE BY BLAUSEN.COM STAFF (2014). “MEDICAL GALLERY OF

BLAUSEN MEDICAL 2014”. WIKIJOURNAL OF MEDICINE 1 (2). DOI:10.15347/WJM/2014.010.
ISSN 2002-4436. [CC BY 3.0 (HTTPS://CREATIVECOMMONS.ORG/LICENSES/BY/3.0)], FROM
WIKIMEDIA COMMONS)
Anatomical Position
https://mrcemsuccess.com/explanation/small-intestine-duodenum/?_sft_qc=abdomen&sf_paged=4 2/4
The duodenum is a C-shaped structure, adjacent to the head of the pancreas, and
above the level of the umbilicus. It is retroperitoneal except for its proximal part
which is connected to the liver by the hepatoduodenal ligament of the lesser
omentum.
Parts of the Duodenum

The superior (first) part extends from the pyloric orifice of the stomach to the
neck of the gallbladder, lies just to the right of the body of vertebra L1, and
passes anterior to the inferior vena cava and superior to the head of the
pancreas.
The descending (second) part is just to the right of the midline, extending
from the neck of the gallbladder to the lower border of vertebra L3 and lying
lateral to the head of the pancreas. This part contains the major duodenal
papilla which is the common entrance for the bile and pancreatic ducts.
The inferior (third) part is the longest section, crossing the inferior vena cava,
the aorta and the vertebral column at the level of vertebra L3 and lying
inferior to the pancreas.
The ascending (fourth) part passes upwards on, or to the left of the aorta to
approximately the upper border of vertebra L2 and terminates at the
duodenojejunal flexure.
RELATIONS OF THE DUODENUM. (IMAGE MODIFIED BY FRCEM SUCCESS. ORIGINAL BY

Blood supply
The arterial supply of the duodenum is primarily from the pancreaticoduodenal
arteries, branches of the superior mesenteric artery and the gastroduodenal artery
(branch of the common hepatic artery from the coeliac trunk).
8/26/22, 4:34 PM Small Intestine: Jejunum and Ileum - MRCEM Success
Small Intestine: Jejunum and LAST UPDATED: 11TH

APRIL 2019
Ileum  Bookmark
The small intestine is the longest part of the gastrointestinal tract and extends from
the pyloric orifice of the stomach to the ileocaecal fold, comprising the duodenum,
jejunum and ileum. The jejunum and ileum make up the last two sections of the
small intestine.
SMALL INTESTINE. (IMAGE BY BLAUSEN.COM STAFF (2014). “MEDICAL GALLERY OF

BLAUSEN MEDICAL 2014”. WIKIJOURNAL OF MEDICINE 1 (2). DOI:10.15347/WJM/2014.010.
ISSN 2002-4436. [CC BY 3.0 (HTTPS://CREATIVECOMMONS.ORG/LICENSES/BY/3.0)], FROM
WIKIMEDIA COMMONS)
https://mrcemsuccess.com/explanation/small-intestine-jejunum-and-ileum/?_sft_qc=abdomen&sf_paged=4 2/3
8/26/22, 4:34 PM Small Intestine: Jejunum and Ileum - MRCEM Success
Anatomical Position
The jejunum represents the proximal two-fifths. It is mostly in the left upper
quadrant of the abdomen and is larger in diameter and has a thicker wall than the
ileum.
The ileum makes up the distal three-fifths and is mostly in the right lower quadrant.
The ileum invaginates into the large intestine at the ileocaecal junction forming the
ileocaecal valve, which prevents reflux from the caecum to the ileum and regulates
the passage of contents from the ileum to the caecum.
The jejunum and ileum are intraperitoneal, attached to the posterior abdominal wall
by the mesentery.
Blood supply
The arterial supply to the jejunum and ileum is derived from the superior mesenteric
artery.
Innervation
Pain from the jejunum and ileum is referred to the periumbilical region.
https://mrcemsuccess.com/explanation/small-intestine-jejunum-and-ileum/?_sft_qc=abdomen&sf_paged=4 3/3
8/26/22, 4:34 PM Small Intestine: Meckel's Diverticulum - MRCEM Success
Small Intestine: Meckel’s LAST UPDATED: 27TH

FEBRUARY 2020
Diverticulum  Bookmark
Meckel's diverticulum is the most common congenital anomaly of the

gastrointestinal tract. It results from incomplete obliteration of the vitelline duct
leading to the formation of a true diverticulum of the small intestine.
Meckel's lies on the antimesenteric surface of the middle-to-distal ileum,
approximately 2 feet proximal to the ileocaecal junction. It appears as a blind-ended
tubular outpouching of bowel, about 2 inches long, occurring in about 2% of the
population, and may contain two types of ectopic tissue (gastric and pancreatic).
The rich blood supply to the diverticulum is provided by the superior mesenteric
artery.
Meckel's diverticula are uncommon and often clinically silent, particularly in the
adult. An asymptomatic Meckel's diverticulum may be discovered during abdominal
exploration for the evaluation of unrelated pathology. Less commonly, they are
found incidentally on diagnostic imaging. When symptomatic, Meckel's diverticulum
may present with abdominal pain or symptoms of gastrointestinal bleeding or bowel
obstruction.
Complications include haemorrhage, intussusception, diverticulitis, ulceration and
obstruction, and symptoms may mimic those of acute appendicitis.
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8/26/22, 4:34 PM Small Intestine: Meckel's Diverticulum - MRCEM Success
MECKEL’S DIVERTICULUM. (IMAGE BY RAZIEL AT FRENCH WIKIPEDIA (TRANSFERRED

FROM FR.WIKIPEDIA TO COMMONS.) [CC SA 1.0
(HTTP://CREATIVECOMMONS.ORG/LICENSES/SA/1.0/)], VIA WIKIMEDIA COMMONS)
https://mrcemsuccess.com/explanation/small-intestine-meckels-diverticulum/?_sft_qc=abdomen&sf_paged=4 3/3
8/26/22, 4:24 PM Large Intestine: Caecum - MRCEM Success
Large Intestine: Caecum LAST UPDATED: 25TH

JANUARY 2019
 Bookmark
LARGE INTESTINE. (IMAGE BY BLAUSEN.COM STAFF. “BLAUSEN GALLERY 2014”. WIKIVERSITY

JOURNAL OF MEDICINE. DOI:10.15347/WJM/2014.010. ISSN 20018762. (OWN WORK) [CC BY
3.0 (HTTP://CREATIVECOMMONS.ORG/LICENSES/BY/3.0)], VIA WIKIMEDIA COMMONS)
The intraperitoneal caecum is the first part of the large intestine. It is inferior to the
ileocaecal opening and lies in the right iliac fossa.
The caecum is continuous with the ascending colon at the entrance of the ileum and
is usually in contact with the anterior abdominal wall. It may cross the pelvic brim to
lie in the true pelvis.
The appendix is attached to the posteromedial wall of the caecum, just inferior to the
end of the ileum.
https://mrcemsuccess.com/explanation/large-intestine-caecum/?_sft_qc=abdomen&sf_paged=2 2/3
8/26/22, 4:25 PM Large Intestine: Colon - MRCEM Success
Large Intestine: Colon LAST UPDATED: 4TH

AUGUST 2022
 Bookmark

JOURNAL OF MEDICINE. DOI:10.15347/WJM/2014.010. ISSN 20018762. (OWN WORK) [CC BY
Anatomical Position
The colon continues from the caecum in the right groin as the ascending colon, which
passes upwards through the right flank and into the right hypochondrium.
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Just below the right lobe of the liver, it bends to the left forming the right colic flexure
(hepatic flexure), and crosses the abdomen as the transverse colon to the left
hypochondrium. The transverse colon is related superiorly to the liver, gallbladder,
greater curvature of the stomach and the lateral end of the spleen.
At this point, just below the spleen, it bends downwards forming the left colic flexure
(splenic flexure) and continues as the descending colon through the left flank and
into the left groin. The splenic flexure is higher and more posterior than the hepatic
flexure, and is attached to the diaphragm by the phrenicocolic ligament.
The colon enters the upper part of the pelvis as the sigmoid colon, which begins
above the pelvic inlet and extends to the level of vertebra S3 where it is continuous
with the rectum. This S-shaped structure is quite mobile except at its proximal and
distal end which are attached to the descending colon and rectum respectively.
Between these points, it is suspended by the sigmoid mesocolon.
The ascending and descending segments are retroperitoneal and the transverse and
sigmoid segments are intraperitoneal.
SURFACE MARKINGS OF THE LARGE INTESTINE. (IMAGE BY HENRY VANDYKE CARTER [PUBLIC
Relations
Table: Anatomical Relations of the Colon

Colon Anterior Relations Posterior Relations
Ascending Small intestine, Iliacus and quadratus lumborum, right
colon greater omentum, kidney
anterior abdominal
wall
Transverse Liver, gallbladder, Second part of duodenum, head of
colon stomach, greater pancreas, upper end of mesentery,
omentum, anterior duodenojejunal flexure, coils of
abdominal wall jejunum and ileum
Descending Small intestine, Iliacus and quadratus lumborum, left
colon greater omentum, kidney
anterior abdominal
wall
Sigmoid Bladder, uterus and Rectum, sacrum, ileum
colon upper vagina
Blood supply
The arterial supply to the colon is derived from the superior mesenteric artery
(caecum, appendix, ascending colon, hepatic flexure, proximal two-thirds of
transverse colon) and the inferior mesenteric artery (distal one-thirds of transverse
colon, splenic flexure, descending colon, sigmoid colon).
As the terminal vessels of the superior mesenteric and inferior mesenteric artery
approach the colon they split into many colic branches which anastomose with each
other. These anastomoses form a continuous arterial channel which extends the
length of the colon, the marginal artery.
At the junctional area of the supply of the superior and inferior mesenteric arteries,
the anastomosis may not be sufficient, thus the splenic flexure is most susceptible to
ischaemia.
Innervation
The visceral pain sensation from the ascending and transverse colon travels through
the lesser splanchnic nerve to the T10 - T11 spinal cord segments hence pain is
referred to the umbilical and hypogastric regions.
Pain from the descending and sigmoid colon is carried in the lumbar splanchnic
nerves to the L1 and L2 spinal cord segments hence pain is referred to the inguinal
region and thigh.
8/26/22, 4:24 PM Large Intestine: Appendix - MRCEM Success
Large Intestine: Appendix LAST UPDATED: 11TH

APRIL 2019
 Bookmark
LARGE INTESTINE. (IMAGE BY BLAUSEN.COM STAFF. “BLAUSEN GALLERY 2014”.

WIKIVERSITY JOURNAL OF MEDICINE. DOI:10.15347/WJM/2014.010. ISSN 20018762. (OWN
WORK) [CC BY 3.0 (HTTP://CREATIVECOMMONS.ORG/LICENSES/BY/3.0)], VIA WIKIMEDIA
COMMONS)
The appendix is a narrow, hollow, blind-ended tube. It has large aggregations of

lymphoid tissue in its walls and is suspended from the terminal ileum by the
mesoappendix.
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8/26/22, 4:24 PM Large Intestine: Appendix - MRCEM Success
Positions
The appendix is attached to the posteromedial wall of the caecum, just inferior to
the end of the ileum. Its point of attachment to the caecum is consistent with the
highly visible free taeniae leading directly to the base of the appendix but the rest
of its location is highly variable.
It may be:
1) posterior to the caecum or the lower ascending colon, or both, in a
retrocaecal or retrocolic position
2) suspended over the pelvic brim in a pelvic or descending position
3) below the caecum in a subcaecal position
4) anterior to the terminal ileum, possibly contacting with the body wall in a
pre-ileal position or posterior to the terminal ileum in a post-ileal position.
The most common position is retrocaecal, followed by pelvic. The retrocaecal
appendix is related anteriorly to the caecum and posteriorly to the psoas major and
iliacus muscle. The psoas sign may be positive in retrocaecal appendicitis; irritation
of the psoas muscle (hip flexor) gives rise to pain when the patient's right thigh is
extended from a flexed position as the muscle is stretched.
McBurney's Point
The surface projection of the base of the appendix is at the junction of the lateral
and middle one-third of a line from the anterior superior iliac spine to the umbilicus
(McBurney's point). People with appendicitis may describe pain at this location.
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8/26/22, 4:33 PM Rectum - MRCEM Success
Rectum LAST UPDATED: 11TH

APRIL 2019
 Bookmark
The rectum is continuous above with the sigmoid colon at the rectosigmoid junction at
about the level of vertebra S3, where the sigmoid mesocolon ends, and below with the
anal canal as this structure penetrates the pelvic floor to enter the perineum. The lower
part of the rectum is expanded to form the rectal ampulla.

JOURNAL OF MEDICINE. DOI:10.15347/WJM/2014.010. ISSN 20018762. (OWN WORK) [CC BY 3.0
Relations
The rectum is a retroperitoneal structure. It is the most posterior viscera in the pelvic
cavity, lying immediately anterior to, and following the concave contour of the sacrum.
https://mrcemsuccess.com/explanation/rectum/?_sft_qc=abdomen&sf_paged=4 2/5
The rectum lies posterior to the bladder, prostate and seminal vesicle in men and to the
uterus, vagina and cervix in women.
In men, the rectovesical septum lies between the fundus of the bladder and the ampulla
of the rectum and is closely associated with the seminal glands and prostate. In females,
the rectouterine pouch (pouch of Douglas) is a peritoneal recess between the rectum
and uterus.
RELATIONS OF THE RECTUM. (IMAGE BY OPENSTAX COLLEGE [CC BY 3.0

Digital Rectal Examination

In a PR/DRE the following structures may be palpated through the anterior rectal wall:
the vagina, cervix and retroverted uterus in women
the prostate, seminal vesicle and base of the urinary bladder in men
The bony structures that are palpated through the posterior rectal wall are the anterior
surface of the lower sacrum and coccyx and the ischial spine and tuberosity.
The anal mucosa and rectal walls themselves are also examined.
DIGITAL RECTAL EXAMINATION (IMAGE BY UNKNOWN ILLUSTRATOR [PUBLIC DOMAIN], VIA

WIKIMEDIA COMMONS)
Innervation
Sympathetic nervous supply to the rectum is from the lumbar splanchnic nerves (L1, L2)
and the inferior mesenteric plexus (upper rectum) and hypogastric plexuses (middle and
lower rectum).
Parasympathetic supply is from the pelvic splanchnic nerves (S2 - S4) and inferior
hypogastric plexus.
Visceral afferent fibres follow the parasympathetic supply to the S2 - S4 spinal sensory
ganglia.
8/26/22, 4:07 PM Anal Canal - MRCEM Success
Anal Canal LAST UPDATED: 11TH

APRIL 2019
 Bookmark
The anal canal is the last 4 cm of the adult gastrointestinal tract and begins at the
terminal end of the rectal ampulla, where it narrows at the pelvic floor. The anal canal
is divided into the upper two-thirds and the lower one-third by the pectinate (dentate)
line.
ANAL CANAL. (IMAGE BY CANCER RESEARCH UK [CC BY-SA 4.0

Anatomical Position
The anorectal junction is pulled forward by the action of the puborectalis muscle (part
of the levator ani muscle) and so the anal canal moves in a posterior direction as it
passes inferiorly through the pelvic floor.
https://mrcemsuccess.com/explanation/anal-canal/?_sft_qc=abdomen 2/4
As it passes through the pelvic floor, it is surrounded along its entire length by the
internal anal sphincter (involuntary) and external anal sphincter (voluntary), which
normally keep it closed.
The anal canal terminates as the anus after passing through the perineum.
RELATIONS OF THE ANAL CANAL. (IMAGE MODIFIED BY FRCEM SUCCESS. ORIGINAL BY

UNKNOWN [CC BY-SA 3.0 (HTTP://CREATIVECOMMONS.ORG/LICENSES/BY-SA/3.0)], VIA
WIKIMEDIA COMMONS)
Control of Defecation
Defecation is initiated by distension of the rectal ampulla which activates
visceral afferent impulses transmitted to the spinal cord by the pelvic splanchnic
nerve. Parasympathetic stimulation increases peristalsis and relaxes the internal anal
sphincter, facilitating defecation. Sympathetic stimulation causes a decrease in
peristalsis, and maintains tone in the internal anal sphincter, inhibiting defecation.
To facilitate defecation:
Intra-abdominal pressure is increased by breath-holding and contracting the

diaphragm and the abdominal muscles
The puborectalis muscle relaxes, decreasing the angle between the ampulla of
the rectum and the upper portion of the anal canal
The smooth muscle in the wall of the rectum contracts, the internal anal
sphincter relaxes, and the external anal sphincter relaxes
Lymphatic Drainage
Above the pectinate line, the anal canal drains to the internal iliac lymph nodes which
subsequently drain to the lumbar (para-aortic) nodes.
Below the pectinate line, the anal canal drains to the superficial inguinal nodes. These
nodes have efferent vessels that drain primarily into the external iliac nodes and
ultimately to the lumbar (para-aortic) nodes.
Innervation
Above the pectinate line, the anal canal receives innervation from the autonomic
nervous system via the inferior hypogastric plexus.
Below the pectinate line it is innervated by the somatic fibres of the pudendal nerve
(S2 - S4) which also innervates the external anal sphincter and most of the skin over
the perineum.
The anococcygeal nerves originate from the coccygeal plexus (S4 - C0) and innervate
skin in the anal triangle of the perineum.
8/26/22, 4:26 PM Liver - MRCEM Success
Liver LAST UPDATED: 22ND

NOVEMBER 2020
ANATOMY / ABDOMEN / LIVER AND BILIARY TRACT
 Bookmark
The liver is the largest visceral organ in the body and is primarily located in the right
hypochondrium and epigastric region, extending into the left hypochondrium.
Surface Markings
Most of the liver is under the right dome of the diaphragm and deep to the lower thoracic
wall. The inferior margin of the liver can be palpated descending below the right costal
margin on deep inspiration.
The inferior margin is indicated by a line that joins points at the right tenth costal
cartilage in the midaxillary line, the tip of the right ninth costal cartilage, the transpyloric
plane in the midline, the tip of the left eighth costal cartilage and the left fifth rib in the
midclavicular line.
The superior margin is indicated by a line that joins a point on the left fifth rib at the
midclavicular line to a corresponding point on the right side. The superior margin is
concave in its central part and crosses behind the xiphisternal joint.
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SURFACE MARKINGS OF THE LIVER. (IMAGE BY HENRY VANDYKE CARTER [PUBLIC DOMAIN], VIA
WIKIMEDIA COMMONS)
Anatomical Surfaces
The liver has a diaphragmatic surface in the anterior, superior, and posterior directions
and a visceral surface in the inferior direction.
The diaphragmatic surface of the liver is related anteriorly to the anterior abdominal wall
and rib cage and superiorly to the diaphragm.
The visceral surface of the liver is related to the oesophagus, right anterior part of the
stomach, superior part of the duodenum, lesser omentum, gallbladder, right colic flexure,
right transverse colon, right kidney and right adrenal gland.
DIAPHRAGMATIC SURFACE OF THE LIVER. (IMAGE BY HENRY VANDYKE CARTER [PUBLIC

INFERIOR SURFACE OF THE LIVER. (IMAGE MODIFIED BY FRCEM SUCCESS. ORIGINAL BY HENRY
Lobes
There are four anatomical lobes to the liver.
The liver is divided into the left and right lobe by falciform ligament.
The caudate lobe sits between the fissure for the ligamentum venosum and the
inferior vena cava.
The quadrate lobe is located between the gallbladder and the fissure for the
ligamentum teres.
The porta hepatis is the central intraperitoneal fissure of the liver that separates the
caudate and the quadrate lobes. The porta hepatis serves as the point of entry into the
liver for the hepatic arteries and portal vein, and the exit point for the hepatic ducts.
Functional Anatomy
Microscopically, hepatocytes are arranged into lobules which are the functional units of
the liver. Each lobule is hexagonal-shaped, and is drained by a venule in its centre, called
a central vein (which drains to the hepatic vein).

At the periphery of the hexagon are three structures collect0vely known as the portal
triad, comprising:
a portal arteriole (a branch of the hepatic artery),
a portal venule (a branch of the hepatic portal vein),
a bile duct.
The portal triad also contains lymphatic vessels and vagal parasympathetic nerve fibres.
The liver sinusoids serve as a location for mixing of the oxygen-rich blood from the
hepatic artery and the nutrient-rich blood from the portal vein.
FUNCTIONAL ANATOMY OF THE LIVER (IMAGE BY OPENSTAX COLLEGE [CC BY 3.0

Blood supply
The liver has a unique dual blood supply. The arterial supply to the liver is from the left
and right hepatic arteries derived from the hepatic artery proper, a branch of the
common hepatic artery from the coeliac trunk.

The hepatic portal vein (formed from the union of the superior mesenteric and splenic
vein posterior to the neck of the pancreas at the level of vertebra L2) supplies the liver
with deoxygenated blood carrying nutrients absorbed from the small intestine.
Venous drainage of the liver is achieved through three hepatic veins, which return the
venous blood to the inferior vena cava just inferior to the diaphragm.
Lymphatic drainage
The lymphatic vessels of the liver drain into hepatic lymph nodes which empty in the
coeliac lymph nodes.
8/26/22, 4:08 PM Biliary Tree - MRCEM Success
Biliary Tree LAST UPDATED: 11TH

APRIL 2019
 Bookmark
The biliary tree begins in the liver parenchyma with the formation of the left and right
hepatic duct which drain bile from the liver where it has been synthesised. These two
ducts meet to form the common hepatic duct which runs near the liver, with the hepatic
artery proper and portal vein in the free margin of the lesser omentum.
As the common hepatic duct descends, it is joined by the cystic duct, which is a
continuation of the neck of the gallbladder. The common hepatic duct and the cystic duct
combine to form the common bile duct. At this point the bile duct lies to the right of the
hepatic artery proper and usually to the right of, and anterior to, the portal vein in the free
margin of the lesser omentum.
As the common bile duct descends, it passes posterior to the first part of the duodenum
before joining with the pancreatic duct from the pancreas, forming the hepatopancreatic
ampulla (ampulla of Vater) at the major duodenal papilla, located in the second part of the
duodenum. Surrounding the ampulla is the sphincter of Oddi, a collection of smooth
muscle which can open to allow bile and pancreatic fluid to empty into the duodenum.
Common Bile Duct

The common bile duct can be divided into three main regions, based on its relation to the
duodenum:
The first supraduodenal region is the upper one-third which lies in the free margin
of the lesser omentum with the hepatic artery and portal vein. The common bile
duct lies anterior to the portal vein and to the right of the hepatic artery proper.
The second retroduodenal region is the middle one-third which lies posterior to the
first part of the duodenum. The gastroduodenal artery lies on its left aspect and the
portal vein on its posterior aspect.
The third infraduodenal region is the lower one-third which lies in a groove on the
posterior surface of the head of the pancreas, to the left of the second part of the
duodenum and anterior to the right renal vein and inferior vena cava.
https://mrcemsuccess.com/explanation/biliary-tree-3/?_sft_qc=abdomen 2/3
8/26/22, 4:08 PM Biliary Tree - MRCEM Success
BILIARY TREE. (IMAGE MODIFIED BY FRCEM SUCCESS. ORIGINAL BY JMARCHN (OWN WORK) [CC
BY-SA 3.0 (HTTP://CREATIVECOMMONS.ORG/LICENSES/BY-SA/3.0), VIA WIKIMEDIA COMMONS)
https://mrcemsuccess.com/explanation/biliary-tree-3/?_sft_qc=abdomen 3/3
8/26/22, 4:36 PM Spleen - MRCEM Success
Something wrong?
Spleen LAST UPDATED: 4TH

OCTOBER 2020
ANATOMY / ABDOMEN / PANCREAS AND SPLEEN
 Bookmark
The intraperitoneal spleen is situated principally in the left hypochondriac

region; it lies between the fundus of the stomach and the diaphragm. The
spleen cannot normally be palpated on clinical examination.
Functional Overview
The spleen is an organ of the reticuloendothelial system and acts:
to filter blood to remove old and defective blood cells
as a blood reservoir
to produce white blood cells
to produce an immune response
Relations
The spleen lies posterior to the stomach, superior to the left colic flexure and
lateral to the left kidney and tail of the pancreas.
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RELATIONS OF THE SPLEEN. (IMAGE BY HENRY VANDYKE CARTER [PUBLIC

Surface Markings
The spleen projects onto the left side and back in the area of ribs 9 - 11. The
spleen follows the contour of rib 10 and extends from the superior pole of the
left kidney to just posterior to the midaxillary line.
SURFACE MARKINGS OF SPLEEN (POSTERIOR VIEW). (IMAGE BY HENRY VANDYKE

SURFACE MARKINGS OF SPLEEN (LATERAL VIEW). (IMAGE BY HENRY VANDYKE

Splenic Rupture
This most commonly occurs due to localised trauma to the left upper
quadrant. It may be associated with left lower rib fractures. Because the
spleen has an extremely thin capsule it is susceptible to injury even when
there is no damage to surrounding structures and because the spleen is
highly vascular, when ruptured, it bleeds profusely into the peritoneal cavity.
8/26/22, 4:28 PM Pancreas - MRCEM Success
Pancreas LAST UPDATED: 11TH

APRIL 2019
ANATOMY / ABDOMEN / PANCREAS AND SPLEEN
 Bookmark
Anatomical Position
The pancreas lies mostly posterior to the stomach. It extends across the
posterior abdominal wall from the duodenum on the right, to the spleen on the
left. It lies in the epigastric region and left hypochondrium. The pancreas is a
retroperitoneal organ (except for a small part of its tail) and consists of a head,
uncinate process, neck, body and tail.
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SURFACE MARKINGS OF THE PANCREAS. (IMAGE BY HENRY VANDYKE CARTER [PUBLIC

Relations
The head of the pancreas lies within the C-shaped concavity of the
duodenum. The head is related anteriorly to the first part of the
duodenum, the transverse colon and coils of jejunum and posteriorly to
the common bile duct and the inferior vena cava and the termination of
the renal veins.
The uncinate process projects from the lower part of the head and passes
posterior to the superior mesenteric vessels.
The neck is anterior to the superior mesenteric vessels. Posterior to the
neck of the pancreas, the superior mesenteric and splenic veins join to
form the portal vein.
The body is elongated and extends from the neck to the tail of the
pancreas in the transpyloric plane (at the level of vertebra L1) to lie behind
the stomach and to the left of the superior mesenteric vessels.
The intraperitoneal tail passes between layers of the splenorenal
ligament. It is related to the left kidney posteriorly, the hilum of the spleen
laterally, the left colic flexure inferiorly and the stomach anteriorly.
RELATIONS OF THE PANCREAS. (IMAGE MODIFIED BY FRCEM SUCCESS. ORIGINAL BY

Pancreatic Duct
The pancreatic duct begins in the tail of the pancreas and passes to the right,
through the body and to the head where it turns inferiorly and joins the bile duct
forming the hepatopancreatic ampulla (ampulla of Vater) which enters the
second part of the duodenum at the major duodenal papilla. The accessory
pancreatic duct empties into the duodenum just above the major duodenal
papilla at the minor duodenal papilla.
PANCREATIC DUCT. (IMAGE MODIFIED BY FRCEM SUCCESS. ORIGINAL BY HENRY

Blood supply
The arterial supply to the pancreas is primarily derived from the splenic artery
from the coeliac trunk, assisted by branches from the gastroduodenal artery
(from the common hepatic artery from the coeliac trunk), and from the superior
mesenteric artery.
Venous drainage of the head of the pancreas is via pancreaticoduodenal veins
into the superior mesenteric vein and portal vein. Venous drainage of the body
and tail of the pancreas is via pancreatic veins into the splenic vein.
Lymphatics
Lymphatics draining the pancreas empty into the pancreaticosplenic nodes and
the pyloric nodes, which in turn drain into the superior mesenteric and celiac
pre-aortic lymph nodes.
Innervation
Visceral afferent fibres travel in the greater and lesser splanchnic nerves. The
segmental level of innervation is T6 - T10. Pain typically radiates to the middle of
the back due to irritation of the parietal peritoneum covering the pancreas.
8/26/22, 4:23 PM Kidney - MRCEM Success
Kidney LAST UPDATED: 11TH

APRIL 2019
ANATOMY / ABDOMEN / URINARY TRACT
 Bookmark
The kidneys are retroperitoneal organs. They lie in the extraperitoneal connective
tissue immediately lateral to the vertebral column in the upper left and right
abdominal quadrants.
Table: Anatomical Overview of the Kidneys

Viscera Kidney
Surface Extend between vertebrae T12 – L3, left kidney slightly higher
marking than right, renal hila at vertebral level L1
Anterior RIGHT: right adrenal gland, liver, second part of duodenum,
relations right colic flexure, segment of small intestine. LEFT: left
adrenal gland, spleen, pancreas, stomach, left colic flexure
and descending colon, duodenojejunal flexure and coils of
small intestine
Posterior Diaphragm, psoas major, quadratus lumborum and
relations transversus abdominis muscles
Structure Each kidney covered by fibrous capsule and surrounded by
renal fascia, kidney itself made up of outer renal cortex and
inner renal medulla, renal pelvis continuous with ureters
Blood Renal artery (branch of abdominal aorta arising at vertebral
supply level L1/L2 posterior to the pancreas), divides into segmental
arteries to supply renal parenchyma
Lymphatics Lumbar (para-aortic) lymph nodes
Innervation Via renal plexus, parasympathetic fibres from vagus nerve and
sympathetic fibres from thoracic splanchnic nerves
Surface Markings
The position of the kidneys varies with respiration and the position of the body. In
the supine position, the kidneys extend from approximately vertebra T12 superiorly
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to vertebra L3 inferiorly. The left kidney is a little higher than the right, reaching as
high as rib 11, compared to rib 12 for the right kidney (because of its relationship
with the liver). The hila of the kidneys and the beginning of the ureters are at the
level of the L1 vertebra.
SURFACE MARKINGS OF THE KIDNEYS (ANTERIOR VIEW). (IMAGE BY HENRY VANDYKE

SURFACE MARKINGS OF THE KIDNEYS (POSTERIOR VIEW). (IMAGE MODIFIED BY FRCEM

SUCCESS. ORIGINAL BY HENRY VANDYKE CARTER [PUBLIC DOMAIN], VIA WIKIMEDIA
COMMONS)
Relations
The anterior surface of the right kidney is related to the (superiorly to inferiorly):
right adrenal gland medially
liver
second part of the duodenum medially,
right colic flexure laterally
a segment of small intestine medially.
The anterior surface of the left kidney is related to the (superiorly to inferiorly):
left adrenal gland medially
spleen laterally
pancreas
stomach (the kidney forms part of the stomach bed)
left colic flexure and descending colon laterally
duodenojejunal flexure and coils of small intestine
Posteriorly both kidneys are related superiorly to the diaphragm and ribs and
inferiorly (moving from medial to lateral) the psoas major, quadratus lumborum and
transversus abdominis muscles. The pleural sacs and the costodiaphragmatic
recesses also extend posterior to the kidneys.
RELATIONS OF THE KIDNEYS. (IMAGE BY HENRY VANDYKE CARTER [PUBLIC DOMAIN], VIA
WIKIMEDIA COMMONS)
Functional Anatomy
Each kidney consists of an outer renal cortex and an inner renal medulla.
Extensions of the renal cortex (the renal columns) project into the inner aspect of
the kidney, dividing the renal medulla into the renal pyramids. The base of the renal
pyramids are directed outwards towards the renal cortex, while the apex of each
renal pyramid projects inwards towards the renal sinus, a cavity which is occupied
by the renal calyces, blood vessels, nerves and fat.
The apical projection of the renal pyramid is surrounded by a minor calyx into which
the collecting ducts drain. Several minor calyces unite to form a major calyx, and
two or three major calyces unite to form the renal pelvis, which is continuous with
the ureter.
FUNCTIONAL ANATOMY OF THE KIDNEY. (IMAGE BY OPENSTAX COLLEGE [CC BY 3.0

Renal Fascia
Each kidney is covered by a firm fibrous capsule and surrounded by the renal
fascia. The attachments of the renal fascia determine the path of extension of a
perinephric abscess. Fascia at the renal hilum attaches the renal vessels and ureter,
usually preventing the spread of pus to the contralateral side. However pus from an
abscess may force its way into the pelvis between the loosely attached anterior and
posterior layers of the renal fascia.
Blood Supply
The renal artery arises from the abdominal aorta just inferior to the origin of the
superior mesenteric artery just between vertebrae L1 and L2 and posterior to the
pancreas. Each renal artery enters the kidney via the renal hilum, dividing into
segmental branches. These branches undergo further divisions to supply the renal
parenchyma.
Lymphatic Drainage
The lymphatic drainage is to the lumbar (para-aortic) lymph nodes located at the
origin of the renal arteries.
Innervation
The kidneys receive autonomic nerve fibres via the renal plexus which contains
parasympathetic fibres from the vagus nerve and sympathetic fibres from the
thoracic splanchnic nerves.
8/26/22, 4:37 PM Ureter - MRCEM Success
Ureter LAST UPDATED: 11TH

APRIL 2019
 Bookmark
The ureters are muscular tubes that transport urine from the kidneys to the
bladder. They are continuous superiorly with the renal pelvis at the
ureteropelvic junction (at the level of the renal hilum, vertebra L1).
Anatomical Course
Inferior to the ureteropelvic junction, the ureters descend retroperitoneally on
the medial aspect of the psoas major muscle, anterior to the tips of the
transverse processes of the lower lumbar vertebrae. The ureters cross the
pelvic brim anterior to the bifurcation of the common iliac arteries to enter the
pelvic cavity and continue their journey down the lateral pelvic walls.
Within the pelvic cavity, the ureters are crossed by the uterine artery lateral to
the cervix in women, and by the ductus deferens just posterior to the bladder in
men.
At the level of the ischial spines, they turn anteromedially, moving in a
transverse plane towards the bladder. The ureters enters obliquely through the
base of the bladder at the level of the pubic tubercle.
The right ureter lies in close relation to the appendix, and thus be irritated in
acute appendicitis causing urinary frequency.
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CONSTRICTIONS OF THE URETER. (IMAGE MODIFIED BY FRCEM SUCCESS. ORIGINAL BY

JORDI MARCH I NOGUÉ [1] (OWN WORK) [CC BY-SA 3.0
(HTTP://CREATIVECOMMONS.ORG/LICENSES/BY-SA/3.0) OR GFDL
(HTTP://WWW.GNU.ORG/COPYLEFT/FDL.HTML)], VIA WIKIMEDIA COMMONS)
Constrictions
At three points along their course, the ureters are constricted;
the first point is at the ureteropelvic junction (where the renal pelvis
becomes continuous with the ureter)
the second point is where the ureter crosses the common iliac vessels at
the pelvic brim
the third point is at the vesicoureteric junction (where the ureter enters
the wall of the bladder)
Kidneys stones can become lodged at these constrictions.
Innervation
Visceral afferent fibres from the ureters enter the spinal cord at T11 - L2, with
ureteric pain (usually from ureteric distension) thus referred to the dermatomes
supplied by T11 - L2; the posterior and lateral abdominal wall below the ribs and
above the iliac crest, the pubic region, the scrotum in males, the labia majora in
females and the proximal anterior aspect of the thigh (loin to groin pain).
8/26/22, 4:06 PM Abdominal Aorta - MRCEM Success
Abdominal Aorta LAST UPDATED: 9TH

JULY 2020
 Bookmark
The abdominal aorta begins at the aortic hiatus of the diaphragm, anterior to the lower
border of vertebra T12. It descends through the abdomen, anterior to the vertebral
bodies, and by the time it ends at the level of vertebra L4 it is slightly to the left of the
midline.
Surface Anatomy
The main terminal branches of the abdominal aorta are the two common iliac arteries.
This bifurcation can be visualised on the anterior abdominal wall as a point
approximately 2.5 cm below the umbilicus.
SURFACE ANATOMY OF THE ABDOMINAL AORTA. (IMAGE MODIFIED BY FRCEM SUCCESS.

ORIGINAL BY HENRY VANDYKE CARTER [PUBLIC DOMAIN], VIA WIKIMEDIA COMMONS)
https://mrcemsuccess.com/explanation/abdominal-aorta/?_sft_qc=abdomen 2/4
Branches
The abdominal aorta gives rise to:
three anterior unpaired visceral branches
the coeliac trunk supplying the abdominal foregut (upper border of L1
vertebra)
the superior mesenteric artery supplying the abdominal midgut (lower
border of L1 vertebra)
the inferior mesenteric artery supplying the abdominal hindgut (L3
vertebra)
three lateral paired visceral branches
the middle suprarenal (adrenal) arteries
the renal arteries (L2 vertebra)
the gonadal arteries
posterior parietal branches
the inferior phrenic arteries (paired)
the lumbar arteries (paired)
the median sacral artery (single)
two terminal branches
left common iliac artery
right common iliac artery
BRANCHES OF THE ABDOMINAL AORTA. (IMAGE BY OPENSTAX COLLEGE [CC BY 3.0

8/26/22, 4:22 PM Inferior Vena Cava - MRCEM Success
Something wrong?
Inferior Vena Cava LAST UPDATED: 11TH

APRIL 2019
ANATOMY / ABDOMEN /
POSTERIOR ABDOMINAL WALL  Bookmark
The inferior vena cava returns blood from all structures below the
diaphragm to the right atrium of the heart.
It is formed from the union of the two common iliac veins at the level of
vertebra L5, just to the right of the midline.
Relations
It ascends through the posterior abdominal region anterior to the vertebral
column immediately to the right of the abdominal aorta, and continues
superiorly, leaving the abdomen by piercing the diaphragm at the level of
vertebra T8.
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RELATIONS OF THE INFERIOR VENA CAVA. (IMAGE BY HENRY VANDYKE CARTER

Tributaries
Tributaries to the inferior vena cava include the:
common iliac veins
lumbar veins
gonadal vein (right)
renal veins
suprarenal vein (right)
inferior phrenic veins
hepatic veins.
There are no tributaries from the abdominal part of the gastrointestinal

tract, the spleen, the pancreas or the gallbladder, because veins from these
structures are components of the portal venous system, which first pass
through the liver.
8/26/22, 4:20 PM Hepatic Portal Vein - MRCEM Success
Hepatic Portal Vein LAST UPDATED: 11TH

APRIL 2019
 Bookmark
The portal vein is the final common pathway for the transport of venous blood
from the spleen, pancreas, gallbladder and abdominal part of the gastrointestinal
tract.
It is formed from the union of the superior mesenteric and splenic vein posterior
to the neck of the pancreas at the level of vertebra L2.
HEPATIC PORTAL VEIN. (IMAGE BY HENRY VANDYKE CARTER [PUBLIC DOMAIN], VIA
WIKIMEDIA COMMONS)
https://mrcemsuccess.com/explanation/portal-vein/?_sft_qc=abdomen&sf_paged=2 2/3
8/26/22, 4:20 PM Hepatic Portal Vein - MRCEM Success
Portosystemic Anastomoses
The hepatic portal system drains deoxygenated nutrient-rich blood from the
visceral organs of the abdomen to the liver. Normally 100% of portal venous blood
flow is recovered from the hepatic veins. In patients with elevated portal vein
pressure e.g. from cirrhosis, there is significantly less blood flow to the liver and
the rest of the blood enters collateral channels which drain into the systemic
circulation at specific points.
Portosystemic anastomoses occur at certain specific points, the largest of these
being:
The gastroesophageal junction around the cardia of the stomach where the
left gastric vein and its tributaries from a portosystemic anastomosis with
tributaries to the azygos system of veins of the caval system
The anus where the superior rectal vein of the portal system anastomoses
with the middle and inferior rectal veins of the systemic venous system
The anterior abdominal wall around the umbilicus where the portal
paraumbilical veins anastomose with systemic veins on the anterior
abdominal wall
When pressure in the portal vein is elevated, venous enlargement (varices) tends
to occur at and around these sites producing:
oesophageal varices at the gastroesophageal junction
varices at the anorectal junction
caput medusae at the umbilicus
https://mrcemsuccess.com/explanation/portal-vein/?_sft_qc=abdomen&sf_paged=2 3/3
8/26/22, 4:20 PM Greater and Lesser Omentum - MRCEM Success
ANATOMY / ABDOMEN / TOPOGRAPHY OF ABDOMINAL CAVITY LAST UPDATED: 11TH

APRIL 2019
 Bookmark
The omenta are double layers of peritoneum that extends from the stomach and proximal part
of the duodenum to other organs.

cavity
with pelvic cavity
Lesser sac Lies posterior to stomach and liver and anterior to pancreas, continuous
(omental with greater sac through epiploic foramen
bursa
Lesser Extends from lesser curvature of stomach and first part of duodenum to
omentum inferior surface of liver
Transverse Connects transverse colon to posterior abdominal wall, leaves posterior
mesocolon abdominal wall across anterior surface of head and body of pancreas
and passes outwards to surround transverse colon
medial border of left psoas major muscle and right limb descending into
pelvis to end at vertebral level S3
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8/26/22, 4:20 PM Greater and Lesser Omentum - MRCEM Success
Greater Omentum
The greater omentum descends from the greater curvature of the stomach and first part of the
duodenum, drapes inferiorly over the transverse colon and the coils of the jejunum and ileum,
then folds back up posteriorly and ascends to become adherent to the peritoneum on the
superior surface of the transverse colon and the anterior layer of the transverse mesocolon
before arriving at the posterior abdominal wall.
The greater omentum is often referred to as the 'policeman of the abdomen' because of its
apparent ability to migrate to any inflamed area and wrap itself around the organ to wall off
inflammation. The greater omentum is also an important site for metastatic tumour spread;
direct omental spread by a transcoelomic route is common for carcinoma of the ovary.
Lesser Omentum
The lesser omentum is considerably smaller and extends from the lesser curvature of the
stomach and the first part of the duodenum to the inferior surface of the liver.
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8/26/22, 4:15 PM Gallbladder - MRCEM Success
Gallbladder LAST UPDATED: 11TH

APRIL 2019
 Bookmark
Anatomical Position
The gallbladder is a pear-shaped sac lying on the visceral surface of the right lobe of the
liver in a fossa between the right and quadrate lobes. It is an intraperitoneal structure
and lies in the right hypochondrium.
GALLBLADDER. (IMAGE BY OPENSTAX COLLEGE [CC BY 3.0

Surface Marking
The gallbladder is located at the junction of the right ninth costal cartilage and the
lateral border of the rectus abdominis muscle which is the site of maximal tenderness in
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8/26/22, 4:15 PM Gallbladder - MRCEM Success
the acute inflammation of the gallbladder.
Structure
The gallbladder has:
a rounded end, the fundus, which may project from the inferior border of the liver
a major part in the fossa, the body, which may lie against the transverse colon
and the superior part of the duodenum
and a narrow part, the neck, which tapers to become continuous with the cystic
duct.
The neck contains a mucosal fold, known as Hartmann's pouch, which is a common site
for gallstones to become lodged.
Relations
The gallbladder lies:
posterior and inferior to the liver
posterior to the anterior abdominal wall
anterior to the transverse colon and the proximal duodenum
superior to the biliary tree and the duodenum.
Innervation
Inflammation of the gallbladder may present with pain in the right upper quadrant and
also in the right shoulder due to irritation of the diaphragmatic peritoneum. N.B. Pain
arising from structures supplied by the phrenic nerve is often referred to other somatic
regions served by spinal nerves C3 - C5.
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8/26/22, 4:22 PM Inguinal Canal - MRCEM Success
Inguinal Canal LAST UPDATED: 11TH

APRIL 2019
ANATOMY / ABDOMEN / INGUINAL REGION
 Bookmark
The inguinal canal is a slit-like passage that extends in a downwards and medial
direction, just above and parallel to the lower half of the inguinal ligament. It
begins at the deep inguinal ring and continues for approximately 4 cm, ending at
the superficial inguinal ring.
Table: Anatomical Boundaries and Contents of the Inguinal Canal

Inguinal Anatomy
Canal
Position Between deep and superficial inguinal rings, just above and
parallel to lower half of inguinal ligament
Anterior Formed by external oblique aponeurosis (reinforced by
wall internal oblique muscle laterally)
Posterior Formed by transversalis fascia (reinforced by conjoint tendon
wall medially)
Roof Formed by transversus abdominis and internal oblique
muscles
Floor Formed by medial one-half of inguinal ligament (reinforced
by lacunar ligament medially)
Deep Opening in transversalis fascia, located just superior to mid-
inguinal inguinal point (midway between ASIS and pubic symphysis)
ring
Superficial Opening in external oblique aponeurosis, located just
inguinal superior to pubic tubercle
ring
Contents Genital branch of genitofemoral nerve, spermatic cord, round
ligament, ilioinguinal nerve
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INGUINAL CANAL. (IMAGE MODIFIED BY FRCEM SUCCESS. ORIGINAL BY HENRY VANDYKE

Roof, walls and floor

The anterior wall of the inguinal canal is formed along its entire length by the
aponeurosis of the external oblique muscle, and reinforced by the internal oblique
muscle laterally.
The posterior wall of the inguinal canal is formed along its entire length by the
transversalis fascia and reinforced by the conjoint tendon medially.
The roof of the inguinal canal is formed by arching fibres of the transversus
abdominis and internal oblique muscles.
The floor of the inguinal canal is formed by the medial one-half of the inguinal
ligament, reinforced medially by the lacunar ligament.
Deep inguinal ring

The deep inguinal ring, the opening in the transversalis fascia, is the beginning of
the inguinal canal.
The surface marking of the deep inguinal ring is commonly described as being
located at either:
the midpoint of the inguinal ligament (midway between the anterior
superior iliac spine and the pubic tubercle)
the mid‐inguinal point (midway between the anterior superior iliac spine
and the pubic symphysis)
It lies just above the inguinal ligament and immediately lateral to the inferior
epigastric vessels; the femoral artery can be palpated in the same position but
below the inguinal ligament.
Superficial inguinal ring

The superficial inguinal ring is the end of the inguinal canal.
The superficial inguinal ring is located just superior to the pubic tubercle. It is a
triangular opening in the aponeurosis of the external oblique, with its apex
pointing superolaterally and its base formed by the pubic crest.
Contents
The inguinal canal contains:
the genital branch of the genitofemoral nerve (within the spermatic cord in
men)
the spermatic cord in men
the round ligament in women
the ilioinguinal nerve (passes through part of the canal, exiting the
superficial inguinal ring with the other contents)
8/26/22, 4:23 PM Inguinal Hernia - MRCEM Success
Inguinal Hernia LAST UPDATED: 11TH

APRIL 2019
ANATOMY / ABDOMEN / INGUINAL REGION
 Bookmark
An inguinal hernia is the protrusion of a peritoneal sac through a weakened part of the
abdominal wall in the groin.
Table: Clinical Anatomy of Inguinal Hernia

Hernia Indirect Inguinal Direct Inguinal Hernia
Hernia
Aetiology Congenital – patent Acquired – weakened abdominal
processus vaginalis musculature
Mechanism Peritoneal sac Peritoneal sac herniates directly
herniates through through posterior wall of inguinal
deep inguinal ring canal
Relation to Lateral to inferior Medial to inferior epigastric
inferior epigastric vessels vessels
epigastric
vessels
Indirect Inguinal Hernia

In indirect inguinal hernias, the most common type, the peritoneal sac enters the
inguinal canal by passing through the deep inguinal ring, due to a patent embryonic
processus vaginalis. If the entire processus vaginalis remains patent, the peritoneal
sac may traverse the length of the canal, exit the superficial inguinal ring and continue
into the scrotum or labia majora.
Direct Inguinal Hernia

In direct inguinal hernias, the peritoneal sac passes directly through the posterior wall
of the inguinal canal. It usually occurs when abdominal musculature has been
weakened, in older men, following surgery or due to persistent raised intra-abdominal
pressure. This type of hernia does not traverse the inguinal canal, but may still exit the
superficial inguinal ring to enter the scrotum.
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8/26/22, 4:09 PM Dermatomal Supply of Trunk - MRCEM Success
Dermatomal Supply of Trunk LAST UPDATED: 20TH

FEBRUARY 2019
ANATOMY / ABDOMEN / ANTERIOR ABDOMINAL WALL /
THORAX / THORACIC WALL  Bookmark
Table: Dermatomal Supply of the Trunk

Dermatome Landmark
T1 Medial antecubital fossa
T2 Apex of axilla
T3 Third intercostal space
T4 Level of nipples (fourth intercostal space)
T5 Fifth intercostal space
T6 Level of xiphisternum
T7 One-quarter distance between xiphisternum and umbilicus
T8 One-half distance between xiphisternum and umbilicus
T9 Three-quarter distance between xiphisternum and umbilicus
T10 Level of umbilicus
T11 Midway between umbilicus and inguinal ligament
T12 Midpoint of inguinal ligament
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DERMATOME MAP. (IMAGE BY GRANT, JOHN CHARLES BOILEAU (AN ATLAS OF ANATOMY, / BY
REGIONS 1962) [PUBLIC DOMAIN], VIA WIKIMEDIA COMMONS)
The T3 dermatome is best tested at the midclavicular line and the third intercostal
space.
The T4 dermatome is best tested at the midclavicular line and the fourth intercostal
space, located at the level of the nipples.
The T5 dermatome is best tested at the midclavicular line and the fifth intercostal
space, located midway between the level of the nipples and the level of the
xiphisternum.
The T6 dermatome is best tested at the midclavicular line, located at the level of the
xiphisternum.
The T7 dermatome is best tested at the midclavicular line, one quarter the distance
between the level of the xiphisternum and the level of the umbilicus.
The T8 dermatome is best tested at the midclavicular line, one half the distance
between the level of the xiphisternum and the level of the umbilicus.
The T9 dermatome is best tested at the midclavicular line, three quarters of the
distance between the level of the xiphisternum and the level of the umbilicus.
The T10 dermatome is best tested at the midclavicular line, located at the level of the
umbilicus.
The T11 dermatome is best tested at the midclavicular line, midway between the level of
the umbilicus and the inguinal ligament.
The T12 dermatome is best tested at the midclavicular line, over the midpoint of the
inguinal ligament.
8/26/22, 4:26 PM Lumbar Plexus - MRCEM Success
Lumbar Plexus LAST UPDATED: 16TH

DECEMBER 2019
 Bookmark
The lumbar plexus is formed by the anterior rami of nerves L1 - L3 and most of the anterior
ramus of L4. It also receives a contribution from the T12 (subcostal) nerve. The lumbar
plexus forms within the substance of the psoas major muscle, anterior to its attachment to
the transverse processes of the lumbar vertebrae.
LUMBAR PLEXUS. (IMAGE MODIFIED BY FRCEM SUCCESS. ORIGINAL BY NINOVOLADOR (TALK)

DERIVATIVE WORK: MCSTROTHER (GRAY822_ES.SVG) [CC BY 3.0
Function of the Lumbar Nerves
Table: Function of the Lumbar Nerves
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Nerve Spinal Motor Sensory Function

Segment Function
Iliohypogastric L1 Internal Posterolateral gluteal skin and skin
nerve oblique and in pubic region
transversus
abdominis
Ilioinguinal L1 Internal Skin in upper medial thigh, and
nerve oblique and either skin over root of penis and
transversus anterior scrotum or mons pubis and
abdominis labium majus
Genitofemoral L1, L2 Male Skin of anterior scrotum or skin of
nerve cremasteric mons pubis and labium majus
muscle (genital branch), skin of upper
anterior thigh (genitofemoral nerve)
Lateral L2, L3 N/A Skin on lateral thigh to knee
cutaneous
nerve of thigh
Obturator L2 – L4 Obturator Skin on medial aspect of thigh
nerve externus,
gracilis and
adductor
muscles
Femoral nerve L2 – L4 Iliacus, Skin on anterior thigh and medial
pectineus, leg
sartorius
and
quadriceps
femoris
The iliohypogastric nerve is formed from the anterior rami of L1. It innervates the internal
oblique and the transversus abdominis and supplies posterolateral gluteal skin and skin over
the pubic region.
The ilioinguinal nerve is formed from the anterior rami of L1. It innervates the internal
oblique and transversus abdominis and supplies skin over the upper medial thigh and the
external genitalia.
The genitofemoral nerve is formed from the anterior rami of L1 and L2. Its genital branch
innervates the male cremaster muscle and supplies skin over the external genitalia and its
femoral branch supplies skin of the upper anterior thigh.
The lateral cutaneous nerve of the thigh (lateral femoral cutaneous nerve) is formed from
the anterior rami of L2 and L3. It supplies skin on the anterolateral thigh to the knee.
The obturator nerve is formed from the anterior rami of L2 to L4. It innervates the obturator
externus and the muscles in the medial compartment of the thigh and supplies skin on the
medial aspect of the thigh.
The femoral nerve is formed from the anterior rami of L2 to L4. It innervates the iliacus,
pectineus, sartorius and muscles in the anterior compartment of the thigh and supplies skin
on the anterior thigh and medial surface of leg.
8/26/22, 4:31 PM Pre-aortic and Para-aortic Lymph Nodes - MRCEM Success
Pre-aortic and Para-aortic LAST UPDATED: 11TH

APRIL 2019
Lymph Nodes  Bookmark
Table: Lymphatic Drainage of the Abdomen and Pelvis

Lymph Structures
Nodes
Coeliac Abdominal oesophagus, stomach, pancreas, liver, gallbladder, spleen,
duodenum proximal to major duodenal papilla
Superior Distal duodenum, jejunum, ileum, caecum, appendix, ascending colon,
mesenteric proximal two-thirds of transverse colon
Inferior Distal transverse colon, descending colon, sigmoid colon, proximal
mesenteric rectum
Lumbar Body wall, kidneys, adrenal glands, testes/ovaries, efferents of
(para- common iliac lymph nodes
aortic)
Pre-aortic Lymph Nodes

Lymphatic drainage of the abdominal part of the gastrointestinal tract, as low as the inferior
part of the rectum, as well as the spleen, pancreas, gallbladder and liver is through vessels
and nodes that eventually end in large collections of pre-aortic lymph nodes located at the
origins of the three anterior branches of the abdominal aorta.
The coeliac group of pre-aortic nodes receives lymph from structures of the foregut
(abdominal oesophagus, stomach, pancreas, liver, gallbladder, spleen and duodenum
proximal to the major duodenal papilla). The coeliac lymph nodes drain into the
cisterna chyli of the thoracic duct.
The superior mesenteric group receives lymph from structures of the midgut (distal
duodenum, jejunum, ileum, caecum, appendix, ascending colon, and proximal two-
thirds of transverse colon). The superior mesenteric nodes drain into the coeliac
nodes.
The inferior mesenteric group receives lymph from structures of the hindgut (distal
one-third of transverse colon, descending colon, sigmoid colon, and proximal rectum).
The inferior mesenteric nodes drain into the coeliac nodes.
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8/26/22, 4:31 PM Pre-aortic and Para-aortic Lymph Nodes - MRCEM Success
Para-aortic Lymph Nodes

Lumbar nodes (para-aortic nodes) are positioned on either side of the abdominal aorta and
receive lymphatics from:
the body wall
the kidneys
the adrenal glands
the efferents of the common iliac lymph nodes
the testes or ovaries.
The para-aortic lymph nodes form the right and left lumbar trunks, and the pre-aortic lymph
nodes form the intestinal trunk. These trunks come together to form the cisterna chyli,
posterior to the right side of the abdominal aorta and anterior to the bodies of vertebrae L1
and L2, which marks the beginning of the thoracic duct.
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8/26/22, 4:08 PM Bony Pelvis - MRCEM Success
Bony Pelvis LAST UPDATED: 21ST

SEPTEMBER 2020
ANATOMY / ABDOMEN / PELVIC CAVITY
 Bookmark
The bones of the pelvis consist of the right and left pelvic bones, the sacrum and the
coccyx.
Each pelvic bone is formed by three elements: the ilium (superiorly), the pubis
(anteroinferiorly) and the ischium (posteroinferiorly). The lateral surface of the pelvic bone
has a large articular socket, the acetabulum, which together with the head of the femur,
forms the hip joint.
BONES OF THE PELVIS. (IMAGE MODIFIED BY FRCEM SUCCESS. ORIGINAL BY FRED THE OYSTER
[CC BY-SA 4.0 (HTTP://CREATIVECOMMONS.ORG/LICENSES/BY-SA/4.0)], VIA WIKIMEDIA
COMMONS)
Articulations
The pelvic bones articulate posteriorly with the sacrum at the sacroiliac joints and
with each other anteriorly at the pubic symphysis.
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The sacroiliac joints are stabilised by three ligaments; the anterior,

interosseous and posterior sacroiliac ligaments.
The pubic symphysis is stabilised by two major ligaments; the superior and
inferior pubic ligaments.
The sacrum articulates superiorly with vertebra L5 at the lumbosacral joints and
inferiorly with the coccyx at the sacrococcygeal joint.
The lumbosacral joints are reinforced by strong iliolumbar and lumbosacral
ligaments that extend from the expanded transverse processes of vertebra
L5 to the ilium and the sacrum respectively.
The sacrococcygeal joint is stabilised by a series of sacrococcygeal
ligaments.
Sacrospinous and Sacrotuberous Ligaments

The sacrospinous and sacrotuberous ligaments are major components of the lateral
pelvic walls.
The sacrospinous ligament is triangular with its apex attached to the ischial spine and its
base attached to the related margins of the sacrum and coccyx.
The sacrotuberous ligament is also triangular with its apex attached to the medial margin
of the ischial tuberosity and its broad base attached to the posterior superior iliac spine of
the pelvic bone along the dorsal aspect and lateral margin of the sacrum, and onto the
dorsolateral surface of the coccyx.
These ligaments stabilise the sacrum on the pelvic bones by resisting the upward tilting
of the inferior aspect of the sacrum. They also convert the greater and lesser sciatic
notches of the pelvic bone into the greater foramina (superior to the sacrospinous
ligament and ischial spine) and lesser foramina (inferior to the sacrospinous ligament and
between the sacrospinous ligament and the sacrotuberous ligament).
SACROSPINOUS LIGAMENT (PURPLE) AND SACROTUBEROUS LIGAMENT (BLUE). (IMAGE MODIFIED

BY FRCEM SUCCESS. ORIGINAL BY HENRY VANDYKE CARTER [PUBLIC DOMAIN], VIA WIKIMEDIA
COMMONS)
8/26/22, 4:27 PM Ovary - MRCEM Success
Something wrong?
Ovary LAST UPDATED: 11TH

APRIL 2019
ANATOMY / ABDOMEN /
FEMALE REPRODUCTIVE SYSTEM  Bookmark
Ovaries are the site of egg production, which are ovulated into the peritoneal
cavity and normally directed into the adjacent openings of the uterine tube
by fimbriae on the ends of the uterine tubes.
Relations
The ovaries lies adjacent to the lateral pelvic wall just inferior to the pelvic
inlet. Each of the two ovaries is about 3 cm long and is suspended by a
mesentery (the mesovarium) that is a posterior extension of the broad
ligament. Its medial end is attached to the uterus by the ligament of the ovary
and its lateral end is related to the fimbriae of the uterine tube.
https://mrcemsuccess.com/explanation/ovaries/?_sft_qc=abdomen&sf_paged=3 2/4
OVARY (IMAGE MODIFIED BY FRCEM SUCCESS. ORIGINAL BY HENRY VANDYKE

Blood supply
The arterial supply to the ovaries is from the ovarian arteries, direct
branches from the anterolateral surfaces of the abdominal aorta.
Lymphatics
There are three main pathways for lymphatic flow from the ovaries: superiorly
to the para-aortic lymph nodes adjacent to the ovarian artery, inferiorly to the
medial group of superficial inguinal lymph nodes through the inguinal canal
alongside the round ligament, and horizontally to the opposite ovary across
the uterine fundus.
Innervation
Visceral afferent fibres usual follow the sympathetic fibres of the ovarian
plexus and lumbar splanchnic nerves to cell bodies in the T10 - T12 and L1
spinal sensory ganglia; pain is thus referred to the periumbilical region,
suprapubic region and groin. Additionally ovarian pain can also be referred to
the medial aspect of the thigh by route of the adjacent obturator nerve.
8/26/22, 4:40 PM Uterus - MRCEM Success
Uterus LAST UPDATED: 11TH

APRIL 2019
ANATOMY / ABDOMEN /
The uterus consists of a fundus (the rounded superior end above the level of origin
of the uterine tubes), a body (the main part of the uterus) and a cervix (the inferior
narrow part that projects into the vagina).
UTERUS. (IMAGE BY NIH MEDICAL ARTS [PUBLIC DOMAIN], VIA WIKIMEDIA COMMONS)
Relations
The uterus is related:
superiorly to the small intestine
anteriorly to the bladder and the vesicouterine pouch
https://mrcemsuccess.com/explanation/uterus-3/?_sft_qc=abdomen&sf_paged=5 2/4
posteriorly to the rectum and pouch of Douglas (rectouterine pouch)

laterally to the broad ligament, uterine vessels and ovaries (to which it is
attached by the ovarian ligament).
inferiorly to the vagina
FEMALE REPRODUCTIVE SYSTEM. (IMAGE MODIFIED BY FRCEM SUCCESS. ORIGINAL BY

BLAUSEN.COM STAFF. “BLAUSEN GALLERY 2014”. WIKIVERSITY JOURNAL OF MEDICINE.
DOI:10.15347/WJM/2014.010. ISSN 20018762. (OWN WORK) [CC BY 3.0
Blood supply
The uterus is supplied primarily by the uterine artery (branch of the internal
iliac artery) assisted by uterine branches of the ovarian artery (branch of the
abdominal aorta), vessels contained within the broad ligament. The uterine artery
anastomoses with the ovarian artery and so also contributes to the blood supply of
the ovary.
Innervation
The uterus receives its sympathetic supply primarily from the inferior hypogastric
plexus and its parasympathetic supply from the pelvic splanchnic nerves (S2 - S4),
with visceral afferent fibres usually following the sympathetic fibres to enter the
spinal cord via T10 - T12 and L1 nerve fibres.
8/26/22, 4:38 PM Uterine Tube - MRCEM Success
Uterine Tube LAST UPDATED: 11TH

APRIL 2019
ANATOMY / ABDOMEN /
Superiorly, uterine tubes project laterally from the uterus, extending to the lateral
pelvic wall, passing superior to the ovaries and opening into the peritoneal cavity
immediately lateral to the ovaries.
UTERINE TUBES. (IMAGE MODIFIED BY FRCEM SUCCESS. ORIGINAL BY BLAUSEN.COM

STAFF. “BLAUSEN GALLERY 2014”. WIKIVERSITY JOURNAL OF MEDICINE.
Divisions
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8/26/22, 4:38 PM Uterine Tube - MRCEM Success
Each uterine tube is approximately 10 - 12 cm long and has:

fimbriae (finger-like ciliated projections)
an infundibulum, (the funnel-shaped opening which curves around the
superolateral pole of the ovary and opens into the peritoneal cavity)
an ampulla (the elongated middle part)
an isthmus (the narrow proximal end which joins the body of the uterus).
Ectopic pregnancy most commonly occurs in the ampulla (70% of cases).
SITE OF ECTOPIC PREGNANCY. (IMAGE BY BRUCEBLAUS [CC BY-SA 4.0

(HTTPS://CREATIVECOMMONS.ORG/LICENSES/BY-SA/4.0)], FROM WIKIMEDIA COMMONS)
https://mrcemsuccess.com/explanation/uterine-tubes/?_sft_qc=abdomen&sf_paged=5 3/3
8/26/22, 4:39 PM Vagina - MRCEM Success
Vagina LAST UPDATED: 11TH

APRIL 2019
ANATOMY / ABDOMEN /
The vagina is a distensible fibromuscular tube, approximately 8 - 10 cm long, that

extends from the perineum through the pelvic floor and into the pelvic cavity.
Superiorly the vagina is related to the cervix. Inferiorly the vagina opens into the
vestibule of the perineum immediately posterior to the external opening of the
urethra.
Relations
The anterior wall of the vagina is related to the base of the bladder and to the
urethra (the urethra is fused to the anterior vaginal wall). Posteriorly the vagina is
related to the pouch of Douglas and rectum.
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8/26/22, 4:39 PM Vagina - MRCEM Success
FEMALE REPRODUCTIVE SYSTEM. (IMAGE MODIFIED BY FRCEM SUCCESS. ORIGINAL BY

BLAUSEN.COM STAFF. “BLAUSEN GALLERY 2014”. WIKIVERSITY JOURNAL OF MEDICINE.
Vaginal Examination
Digital vaginal examination allows palpation of the:
urethra and bladder through the anterior fornix of the vagina
the perineal body, rectum, coccyx and sacrum through the posterior fornix
ovaries, uterine tubes, ureters and ischial spines through the lateral
fornices
Bimanual examination allows palpation of the uterus and the ovaries and uterine
tubes.
https://mrcemsuccess.com/explanation/vagina/?_sft_qc=abdomen&sf_paged=5 3/4
8/26/22, 4:38 PM Urinary Bladder - MRCEM Success
Urinary Bladder LAST UPDATED: 11TH

APRIL 2019
 Bookmark
The bladder is the most anterior viscera in the pelvic cavity. When empty it is
entirely situated in the pelvic cavity, but when full expands superiorly into the
abdominal cavity. The bladder is a retroperitoneal structure and when full lies
adjacent to the anterior abdominal wall.
Structure
The empty bladder is shaped like a three-sided pyramid that has tipped over
to lie on its side and has an apex, a base, a superior surface and two
inferolateral surfaces.
The apex of the bladder is directed towards the top of the pubic
symphysis.
The triangular-shaped base (or fundus) of the bladder faces
posteroinferiorly. The two ureters enter the bladder at each of the
upper corners of the base, and the urethra drains inferiorly from the
lower corner of the base.
The inferolateral surfaces of the bladder are cradled between the
levator ani muscles of the pelvic diaphragm and the adjacent obturator
internus muscles above the attachment of the pelvic diaphragm.
The superior surface is slightly domed when the bladder is empty and
balloons upwards as the bladder fills.
Relations
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STRUCTURE OF THE URINARY BLADDER. (IMAGE BY OPENSTAX COLLEGE [CC BY 3.0

In the male the bladder is related:

anteriorly to the pubic symphysis
posteriorly to the rectovesical pouch and rectum
inferiorly to the prostate and the pelvic floor
superiorly to the peritoneum.
In the female the bladder is related:
anteriorly to the pubic symphysis
posteriorly to the vesicouterine pouch, the uterus, the cervix and the
vagina
superiorly to the uterus and the peritoneum
inferiorly to the pelvic floor.
RELATIONS OF THE URINARY BLADDER. (IMAGE BY OPENSTAX COLLEGE [CC BY 3.0

Innervation
The bladder receives efferent sympathetic fibres from the hypogastric
plexuses and nerves (T12 - L2).
The bladder receives efferent parasympathetic fibres from the pelvic
splanchnic nerves (S2 to S4).
The voluntary external urethral sphincter is innervated by the pudendal nerve
(S2 - S4).
Control of Micturition
8/26/22, 4:09 PM Ductus Deferens - MRCEM Success
Ductus Deferens LAST UPDATED: 11TH

APRIL 2019
ANATOMY / ABDOMEN / MALE REPRODUCTIVE SYSTEM
 Bookmark
Spermatozoa from the testis collects in the epididymis, the tail of which is continuous
with the ductus deferens.
Anatomical Course
The ductus deferens ascends in the scrotum as part of the spermatic cord and passes
through the inguinal canal in the anterior abdominal wall. After exiting the inguinal
canal through the deep inguinal ring, it enters the pelvic cavity and descends medially
on the pelvic wall, deep to the peritoneum, and crosses the ureter posterior to the
bladder. It continues inferomedially along the base of the bladder, anterior to the
rectum, almost to the midline where it is joined by the duct of the seminal vesicle to
form the ejaculatory duct.
The ejaculatory duct penetrates through the prostate gland to connect with the
prostatic urethra.
MALE REPRODUCTIVE SYSTEM. (IMAGE BY CFCF (OWN WORK) [CC BY-SA 3.0
https://mrcemsuccess.com/explanation/vas-ductus-deferens/?_sft_qc=abdomen 2/3
8/26/22, 4:28 PM Penis and Scrotum - MRCEM Success
Penis and Scrotum LAST UPDATED: 27TH

FEBRUARY 2020
ANATOMY / ABDOMEN /
MALE REPRODUCTIVE SYSTEM  Bookmark
Penis
STRUCTURE:
The penis is composed mainly of three masses of erectile tissue: the paired
corpora cavernosa and the single corpus spongiosum, which contains the
spongy urethra.
Because the anatomical position of the penis is erect, the paired corpora
cavernosa are defined as dorsal in the body of the penis and the single corpus
spongiosum as ventral. The nerves and vessels lie superficial to the corpus
cavernosum. The urethra lies within the corpus spongiosum.
CROSS-SECTION OF THE PENIS. (IMAGE BY MCSTROTHER (OWN WORK) [CC BY 3.0

INNERVATION:
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8/26/22, 4:28 PM Penis and Scrotum - MRCEM Success
The nerves supplying the penis are derived from the S2 - S4 spinal cord
segments and spinal ganglia, passing through the pelvic splanchnic and
pudendal nerves respectively. Sensory and sympathetic innervation is provided
primarily by the dorsal nerve of the penis, a terminal branch of the pudendal
nerve. Branches of the ilioinguinal nerve supply skin at the root of the penis.
LYMPHATIC DRAINAGE
The lymphatics from the penile skin and prepuce run proximally to join the
lymphatics from the scrotum and perineum draining into the superficial inguinal
nodes, especially the superomedial group. The lymphatics from the glans and
penile urethra drain primarily into the deep inguinal nodes.
Scrotum
INNERVATION:
The scrotum is innervated by nerves derived primarily from spinal roots L1 and
S2 - S3:
anterolaterally by the genital branch of the genitofemoral nerve (L1 -
L2)Penis and Scrotum,
anteriorly by scrotal branches of the ilioinguinal nerve (L1)
posteriorly by scrotal branches of the perineal nerve of the pudendal
nerve (S3)
inferiorly by perineal branches of the posterior femoral cutaneous nerve
(S2)
LYMPHATIC DRAINAGE:
The lymph drainage of the scrotum is to the superficial inguinal lymph nodes (in
contrast to that of the testes which is to the lumbar (para-aortic) nodes in the
abdomen).
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8/26/22, 4:34 PM Spermatic Cord - MRCEM Success
Spermatic Cord LAST UPDATED: 11TH

APRIL 2019
ANATOMY / ABDOMEN /
The spermatic cord begins to form proximally at the deep inguinal ring and
consists of structures passing between the abdominopelvic cavities and the
testes, and the three fascial coverings that enclose these structures.
Fascial Coverings
The structures of the spermatic cord enter the deep inguinal ring, proceed
down the inguinal canal, and exit from the superficial inguinal ring, having
acquired the three fascial coverings during their journey. Of the three fascial
layers:
the internal spermatic fascia arises from the transversalis fascia and is
attached to the margins of the deep inguinal ring
the cremasteric fascia, with the associated cremasteric muscle, arises
from the internal oblique muscle
the external spermatic fascia arises from the aponeurosis of the external
oblique muscle and is attached to the margins of the superficial inguinal
ring
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STRUCTURE OF THE SPERMATIC CORD. (IMAGE BY HENRY VANDYKE CARTER [PUBLIC

Contents
The structures in the spermatic cord include:
the ductus (vas) deferens
the artery to the ductus deferens (from the inferior vesical artery)
the testicular artery (from the abdominal aorta)
the pampiniform plexus of veins (testicular veins)
the cremasteric artery and vein (associated with the cremasteric fascia)
the genital branch of the genitofemoral nerve (innervation to the
cremaster muscle)
sympathetic and visceral afferent nerve fibres
lymphatics
remnants of the processus vaginalis.
CONTENTS OF THE SPERMATIC CORD. (IMAGE MODIFIED BY FRCEM SUCCESS.

8/26/22, 4:37 PM Testis and Epididymis - MRCEM Success
Testis and Epididymis LAST UPDATED: 11TH

APRIL 2019
ANATOMY / ABDOMEN /
The testis and epididymis are suspended in the scrotum by the spermatic cord.
The inferior pole of the testis is attached to the scrotal wall by the scrotal
ligament, which is the remnant of the gubernaculum testis.
TESTIS AND EPIDIDYMIS. (IMAGE MODIFIED BY FRCEM SUCCESS. ORIGINAL BY HENRY

Functional Anatomy
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Each testis is composed of seminiferous tubules (which produce spermatozoa)

and interstitial tissue (which secretes testosterone) surrounded by a thick
connective tissue capsule, the tunica albuginea. The spermatozoa collects in
the epididymis, the tail of which is continuous with the ductus deferens, which
transports the spermatozoa to the ejaculatory ducts in the pelvic cavity.
Development
The testes develop high on the posterior abdominal wall and then descend,
normally before birth, through the inguinal canal in the anterior abdominal wall
and into the scrotum of the perineum. During the descent, the testes carry their
vessels, lymphatics, nerves and ductus deferens with them. The spermatic cord
is the tube-shaped connection between the pouch in the scrotum and the
abdominal wall.
The sides and anterior aspect of the testis are covered by the serous tunica
vaginalis, derived from the embryonic processus vaginalis which is originally
connected to the abdominal cavity. Normally after testicular descent, the
connection closes, leaving a fibrous remnant. Failure of closure can result in the
development of an indirect inguinal hernia.
Blood supply
The testes receive their arterial supply from the testicular artery, direct branch
of the abdominal aorta, which travels in the spermatic cord.
Lymphatics
The lymph drainage of the testes is to the lumbar (para-aortic) nodes in the
abdomen, in contrast to that of the scrotum which drains to the superficial
inguinal nodes.
Innervation
The testes receive their autonomic nerve supply from the testicular plexus.
Visceral afferent fibres usually follow the sympathetic fibres to spinal cord
levels T10 - L1; pain is thus referred to the periumbilical region, suprapubic
region and groin.
The scrotum is innervated by nerves derived primarily from spinal roots L1 and
S2 - S3:
anterolaterally by the genital branch of the genitofemoral nerve (L1 - L2)
anteriorly by scrotal branches of the ilioinguinal nerve (L1)
posteriorly by scrotal branches of the perineal nerve of the pudendal
nerve (S3)
inferiorly by perineal branches of the posterior femoral cutaneous nerve
(S2)
8/26/22, 4:32 PM Prostate - MRCEM Success
Prostate LAST UPDATED: 11TH

APRIL 2019
ANATOMY / ABDOMEN / MALE REPRODUCTIVE SYSTEM
 Bookmark
The prostate is an unpaired accessory structure of the male reproductive system that
surrounds the prostatic urethra in the pelvic cavity. It typically weighs between 20 - 40 g
with an average size of 4 x 3 x 2 cm (its width being the greatest).
Function
Secretions from the prostate, together with secretions from the seminal vesicle,
contribute to the formation of semen during ejaculation.
The prostatic ducts open into the floor of the prostatic portion of the urethra.
The ejaculatory ducts (formed from the union of the ductus deferens with the duct of
the seminal gland) pass almost vertically in an anteroinferior direction through the
posterior aspect of the prostate to open into the prostatic urethra.
Relations
Structure
Lymphatic Drainage
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EJACULATORY DUCTS OPENING INTO THE PROSTATE. (IMAGE BY HENRY VANDYKE CARTER
[PUBLIC DOMAIN])
The prostate lies immediately inferior to the bladder and the internal urethral
sphincter, superior to the external urethral sphincter (with the levator ani muscle lying
inferolaterally to the gland) and anterior to the rectum. The urethra passes through the
prostate.
MALE REPRODUCTIVE SYSTEM. (IMAGE BY CFCF (OWN WORK) [CC BY-SA 3.0
Traditionally the prostate gland is divided anatomically into lobules, but more important
clinically is specific anatomical zones rather than lobes:
The transitional zone is the most central part of the gland that surrounds the
prostatic urethra and the area most prone to prostatic hyperplasia, resulting in
urinary symptoms.
The central zone encircles the transitional zone and encompasses the ejaculatory
ducts posterior to the prostatic urethra.
The peripheral zone is the outermost region of the prostate and the area most
prone to carcinomatous transformation. This is the zone palpated on PR
examination.
ZONES OF THE PROSTATE. (IMAGE MODIFIED BY FRCEM SUCCESS. ORIGINAL BY UNKNOWN

ILLUSTRATOR [PUBLIC DOMAIN OR PUBLIC DOMAIN], VIA WIKIMEDIA COMMONS)
The prostate gland has several lymphatic drainage pathways primarily to the
internal iliac nodes with some drainage to external iliac and presacral nodes.
8/26/22, 4:37 PM Urethra - MRCEM Success
Urethra LAST UPDATED: 11TH

APRIL 2019
 Bookmark
The urethra begins at the base of the bladder and ends with an external
opening in the perineum.
Female urethra
In women the urethra is short (about 4 cm long). It passes inferiorly through
the urogenital diaphragm into the perineum before opening in the vestibule
that lies between the labia minora. The inferior aspect of the urethra is bound
to the anterior surface of the vagina. The urethral opening is anterior to the
vaginal opening in the vestibule.
Male urethra
Beginning at the base of the bladder and passing inferiorly through the
prostate, the urethra passes through the deep perineal pouch and perineal
membrane and immediately enters the root of and travels the length of the
penis. The external urethral orifice is the sagittal slit at the end of the penis.
ANGLES:
The male urethra (spongy part) has two angles:
Infrapubic angle - where the urethra bends anteriorly in the root of the
penis after passing through the perineal membrane
Prepubic angle - where the urethra curves inferiorly when
passing from the root into the body of the penis
The infrapubic angle is a fixed angle, but the more distal prepubic angle can
be diminished by holding the penis upwards during urinary catheterisation.
This angle also disappears during erection.
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ANGLES OF THE MALE URETHRA. (IMAGE BY HENRY VANDYKE CARTER [PUBLIC

PARTS:
In men the urethra is long (about 20 cm) and is divided into four parts;
preprostatic, prostatic, membranous and spongy:
The preprostatic part is about 1 cm long, extending from the base of
the bladder to the prostate and is associated with the internal urethral
sphincter (which prevents retrograde movement of semen into the
bladder during ejaculation).
The prostatic part is about 3 - 4 cm long, is the widest part, and is
surrounded by the prostate. In this region the lumen of the urethra is
marked by a longitudinal midline fold of mucosa (the urethral crest).
Midway along its length the urethral crest is enlarged, marked by the
openings of the prostatic utricle and ejaculatory ducts. The prostatic

ducts empty into the prostatic sinuses on either side of the urethral
crest.
The membranous part is the narrowest part and passes through the
urogenital diaphragm. During its transit through the pelvic floor, in both
men and women, it is surrounded by skeletal muscle of the external
urethral sphincter.
The spongy part is the longest part and is surrounded by the corpus
spongiosum of the penis. It is enlarged to form a bulb at the base of
penis and again at the end. The bulbourethral glands open into the bulb
of the spongy urethra.
PARTS OF THE MALE URETHRA. (IMAGE MODIFIED BY FRCEM SUCCESS. ORIGINAL

UPPER
LIMB
8/24/22, 8:31 PM Anterior Arm Muscles - MRCEM Success
Anterior Arm Muscles LAST UPDATED: 8TH

APRIL 2019
ANATOMY / UPPER LIMB / ANTERIOR ARM
 Bookmark
The anterior compartment of the arm consists of three muscles.
Table: Function and Innervation of the Anterior Arm Muscles

Muscle Function Innervation
Coracobrachialis Flexion of arm Musculocutaneous nerve
Biceps brachii Flexion and Musculocutaneous nerve
supination of forearm
(primary), flexion of
arm (accessory)
Brachialis Flexion of forearm Musculocutaneous nerve;
small contribution by radial
nerve to lateral part of
muscle
Coracobrachialis
The coracobrachialis flexes the arm at the glenohumeral joint. It is innervated by
the musculocutaneous nerve.
Biceps brachii
The biceps brachii is primarily a powerful flexor of the forearm at the elbow joint
and supinator of the forearm. It is also an accessory flexor of the arm at the
glenohumeral joint (with the coracobrachialis muscle). It is innervated by the
musculocutaneous nerve.
Brachialis
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8/24/22, 8:31 PM Anterior Arm Muscles - MRCEM Success
The brachialis flexes the forearm at the elbow joint. It is innervated primarily by
the musculocutaneous nerve with a small contribution from the radial nerve.
ANTERIOR ARM MUSCLES: CORACOBRACHIALIS (GREEN), BICEPS BRACHII (RED),

BRACHIALIS (BLUE). (IMAGE MODIFIED BY FRCEM SUCCESS. ORIGINAL BY HENRY
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8/24/22, 8:42 PM Anterior Forearm Arteries - MRCEM Success
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Anterior Forearm Arteries LAST UPDATED:

10TH APRIL 2019
ANATOMY / UPPER LIMB / ANTERIOR FOREARM
 Bookmark
Radial Artery
The radial artery, branch of the brachial artery, passes along the lateral
aspect of the forearm, lying deep to the brachioradialis muscle proximally,
and distally being covered only by skin and fascia, making this an ideal
location to palpate the pulse or to gain arterial access (palpated just lateral
to the flexor carpi radialis tendon, while compressing the artery against the
radius bone). The radial artery enters the hand by curving around the lateral
side of the wrist, passing over the floor of the anatomical snuffbox and
penetrating the dorsolateral aspect of the hand between the bases of the
first and second metacarpal bones.
Ulnar Artery
The larger ulnar artery, also a branch of the brachial artery, enters the
forearm by passing deep to the pronator teres muscle and passes down the
medial side of the forearm between the flexor carpi ulnaris and the flexor
digitorum profundus muscles. The ulnar artery enters the hand, passing
lateral to the pisiform bone and superficial to the flexor retinaculum. The
ulnar artery gives rise to the common interosseous artery.
Carpal Arches
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8/24/22, 8:42 PM Anterior Forearm Arteries - MRCEM Success
The palmar and dorsal carpal arches are formed from anastomosis between
the carpal branches of the radial and ulnar arteries, and supply the wrist
and carpal bones.
Venae Comitantes
Deep veins of the anterior compartment generally accompany the arteries
and ultimately drain into brachial veins associated with the brachial artery
in the cubital fossa.
ARTERIES OF THE ANTERIOR FOREARM. (IMAGE BY HENRY VANDYKE CARTER

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8/24/22, 8:44 PM Anterior Forearm Muscles - MRCEM Success
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Anterior Forearm Muscles LAST UPDATED: 10TH

APRIL 2019
 Bookmark
The flexor muscles of the anterior forearm all originate from the medial humeral epicondyle.
Compartments
The anterior forearm is divided into:
The superficial compartment consisting of the:
flexor carpi ulnaris
flexor carpi radialis
palmaris longus
pronator teres
The intermediate compartment consisting of the:
flexor digitorum superficialis
The deep compartment consisting of the:
flexor digitorum profundus
flexor pollicis longus
pronator quadratus
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ANTERIOR FOREARM MUSCLES (SUPERFICIAL). (IMAGE BY HENRY VANDYKE CARTER [PUBLIC

ANTERIOR FOREARM MUSCLES (DEEP). (IMAGE BY HENRY VANDYKE CARTER [PUBLIC DOMAIN], VIA
WIKIMEDIA COMMONS)
Innervation
All of the muscles in the anterior forearm are innervated by the median nerve, except for the
flexor carpi ulnaris and the medial half of the flexor digitorum profundus which are
innervated by the ulnar nerve.
Function
Table: Function and Innervation of the Anterior Forearm Muscles

Flexor carpi Flexion and adduction of wrist Ulnar nerve
ulnaris
Flexor carpi Flexion and abduction of wrist Median nerve
radialis
Palmaris Flexion of wrist Median nerve
longus
Pronator teres Pronation of forearm Median nerve
Flexor Flexion of MCPJ and PIPJ of all Median nerve
digitorum four digits, flexion of wrist
superficialis
Flexor pollicis Flexion of MCPJ and IPJ of Median nerve
longus thumb
Flexor Flexion of MCPJ and DIPJ of all Lateral half by median nerve,
digitorum four digits, flexion of wrist medial half by ulnar nerve
profundus
Pronator Pronation of forearm Median nerve
quadratus
8/24/22, 8:45 PM Anterior Forearm Veins - MRCEM Success
Something wrong?
Anterior Forearm Veins LAST UPDATED:

10TH APRIL 2019
 Bookmark
The cephalic, basilic and median cubital veins are the main superficial veins
of the upper limb.
Cephalic Vein
The cephalic vein arises from the lateral aspect of the dorsal venous
network, ascends along the anterolateral border of the forearm and arm
and drains into the axillary vein.
Basilic Vein
The basilic vein arises from the medial aspect of the dorsal venous network,
ascends along the medial aspect of the forearm and arm and becomes the
axillary vein.
Medial Cubital Vein

The two superficial veins communicate via the median cubital vein which
passes obliquely across the anterior elbow in the antecubital fossa. The
median cubital vein is a common site of venepuncture.
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8/24/22, 8:45 PM Anterior Forearm Veins - MRCEM Success
ANTERIOR FOREARM VEINS. (IMAGE BY HENRY VANDYKE CARTER [PUBLIC

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8/24/22, 8:51 PM Axillary Nerve - MRCEM Success
Axillary Nerve LAST UPDATED: 28TH

JANUARY 2019
ANATOMY / UPPER LIMB / AXILLA /
INNERVATION OF UPPER LIMB  Bookmark
Table: Anatomical Overview of the Axillary Nerve

Nerve Axillary
Nerve C5 and C6
roots
Plexus Posterior cord
cords
Motor Deltoid, teres minor
Supply
Sensory Regimental badge area on lateral arm via superior lateral
supply cutaneous nerve of the arm
The axillary nerve arises from the posterior cord containing fibres from nerve
roots C5 and C6.
The axillary nerve and associated blood vessels (the posterior circumflex humeral
artery and vein) enter the deltoid by passing posteriorly around the surgical neck
of the humerus (where it is vulnerable to damage).
The axillary nerve innervates the teres minor and deltoid muscles and the skin
over the inferior portion of the deltoid, the 'regimental badge area' (via the
superior lateral cutaneous nerve of the arm).
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AXILLARY NERVE. (IMAGE BY HENRY VANDYKE CARTER [PUBLIC DOMAIN], VIA

WIKIMEDIA COMMONS)
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8/24/22, 8:33 PM Brachial Artery - MRCEM Success
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Brachial Artery LAST UPDATED: 8TH

APRIL 2019
 Bookmark
Anatomical Course
The brachial artery is a continuation of the axillary artery, beginning at
the lower border of the teres major muscle and ending just distal to the
elbow joint where it bifurcates into the radial and ulnar arteries. In the
proximal arm, the brachial artery lies on the medial side. In the distal arm,
it moves laterally to assume a position midway between the lateral and
medial epicondyle of the humerus, before crossing anteriorly to the
elbow joint.
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BRACHIAL ARTERY. (IMAGE BY HENRY VANDYKE CARTER [PUBLIC DOMAIN],

Palpation
The brachial artery is palpable along its length; in the proximal arm it can
be compressed against the medial humerus and in the antecubital fossa
it may be palpated immediately medial to the tendon of the biceps
brachii muscle.
Branches
The brachial artery gives rise to numerous branches including:
the profunda brachii (deep brachial) artery

muscular branches
nutrient branches
ulnar collateral branches
terminal branches (radial and ulnar arteries)
The brachial artery is accompanied by venae comitantes.
8/24/22, 8:51 PM Brachial Plexus - MRCEM Success
Brachial Plexus LAST UPDATED: 8TH

APRIL 2019
ANATOMY / UPPER LIMB / AXILLA
 Bookmark
BRACHIAL PLEXUS. (IMAGE BY MATTOPAEDIA AT EN.WIKIPEDIA DERIVATIVE WORK:

CAPTAIN-N00DLE (TALK), MISSMJ (BRACHIAL_PLEXUS.JPG) [PUBLIC DOMAIN], FROM
WIKIMEDIA COMMONS)
ROOTS:
The brachial plexus is formed by the union of the anterior rami of spinal nerves C5
- T1.
TRUNKS:
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8/24/22, 8:51 PM Brachial Plexus - MRCEM Success
In the inferior neck, the roots of the brachial plexus unite to form three trunks:
A superior trunk (from the union of the C5 and C6 roots)
A middle trunk (which is a continuation of the C7 root)
An inferior trunk (from the union of the C8 and T1 roots)
DIVISIONS:
Within the posterior triangle of the neck, the trunks divide into anterior and
posterior divisions.
CORDS:
Within the axilla, the divisions reunite to form three cords (named by their relation
to the axillary artery):
The lateral cord (from the anterior divisions of the superior and middle
trunks)
The medial cord (a continuation of the anterior division of the inferior trunk)
The posterior cord (from the posterior divisions of all three trunks)
NERVES:
The cords give rise to the major branches of the brachial plexus.
https://mrcemsuccess.com/explanation/brachial-plexus-2/?_sft_qc=axilla 3/3
8/24/22, 8:52 PM Humeral Circumflex Arteries - MRCEM Success
Humeral Circumflex LAST UPDATED:

25TH JANUARY 2019
Arteries  Bookmark
The circumflex humeral arteries arise from the axillary artery, encircle the
surgical neck of the humerus and give off branches supplying the shoulder.
The humeral circumflex arteries may be damaged by fracture of the
surgical neck of the humerus or by shoulder dislocation.
HUMERAL CIRCUMFLEX ARTERIES (ANTERIOR). (IMAGE BY HENRY VANDYKE

https://mrcemsuccess.com/explanation/circumflex-humeral-arteries/?_sft_qc=axilla 2/3
8/24/22, 8:52 PM Humeral Circumflex Arteries - MRCEM Success
HUMERAL CIRCUMFLEX ARTERIES (POSTERIOR). (IMAGE BY HENRY VANDYKE

https://mrcemsuccess.com/explanation/circumflex-humeral-arteries/?_sft_qc=axilla 3/3
8/24/22, 8:46 PM Median Nerve - MRCEM Success
Something wrong?
Median Nerve LAST UPDATED: 8TH

APRIL 2019
ANATOMY / UPPER LIMB / ANTERIOR ARM /
ANTERIOR FOREARM /  Bookmark
INNERVATION OF UPPER LIMB
The median nerve is formed from the medial and lateral brachial plexus
cords and contains fibres from all five roots (C5 - T1).
Table: Anatomical Overview of the Median Nerve

Nerve Median
Nerve C5 – T1
roots
Plexus Medial and lateral cords
cords
Motor All the anterior forearm muscles (except for the flexor
Supply carpi ulnaris and the medial half of the flexor digitorum
profundus), the thenar muscles (flexor pollicis brevis,
abductor pollicis brevis, opponens pollicis) and the lateral
two lumbricals
Sensory Lateral aspect of palm and palmar surface and fingertips
supply of lateral three and a half digits
Anatomical course
The median nerve originates in the axilla before passing down the medial
side of the arm (initially lateral to the brachial artery before crossing over to
https://mrcemsuccess.com/explanation/median-nerve-2/?_sft_qc=anterior-forearm 2/5
the medial side of the brachial artery). It enters the anterior compartment
of the forearm via the antecubital fossa, travelling between the flexor
digitorum profundus and flexor digitorum superficialis muscles, before
entering the hand via the carpal tunnel and bifurcating into its terminal
branches.
MEDIAN NERVE. (IMAGE BY HENRY VANDYKE CARTER [PUBLIC DOMAIN], VIA

WIKIMEDIA COMMONS)
Branches
Table: Branches of the Median Nerve
Branches of Origin Supply

Median
Nerve
Median Axilla Superficial and intermediate
nerve compartment of anterior forearm
(pronator teres, flexor carpi radialis,
palmaris longus, flexor digitorum
superficialis, NOT flexor carpi ulnaris)
Anterior Forearm Deep compartment of anterior forearm
interosseous (flexor pollicis longus, pronator
nerve quadratus, lateral half of flexor
digitorum profundus)
Palmar Forearm Skin over the lateral aspect of the palm
cutaneous
branch
Recurrent Hand Thenar muscles (flexor pollicis brevis,
branch of abductor pollicis brevis, opponens
median pollicis)
nerve
Palmar Hand Lateral two lumbricals and skin over the
digital palmar surface and fingertips of the
branch lateral three and a half digits
The median nerve directly innervates the pronator teres, the flexor carpi
radialis, the palmaris longus and the flexor digitorum superficialis. It gives
off no major branches in the arm, but gives rise to the anterior interosseous
nerve (innervating the flexor pollicis longus, the pronator quadratus, and
the lateral half of the flexor digitorum profundus) and the palmar cutaneous
nerve (innervating the lateral aspect of the palm) in the forearm.
In the hand the median nerve bifurcates into the recurrent branch of the
median nerve (innervating the thenar muscles) and the palmar digital
branch (innervating the lateral two lumbricals and the skin over the palmar
surface and fingertips of the lateral three and a half digits).
8/24/22, 8:35 PM Musculocutaneous Nerve - MRCEM Success
Musculocutaneous Nerve LAST UPDATED: 8TH

APRIL 2019
The musculocutaneous nerve originates from the lateral cord of the brachial
plexus, receiving fibres from C5 - C7.
Table: Anatomical Overview of the Musculocutaneous Nerve

Nerve Musculocutaneous
Nerve roots C5 – C7
Plexus Lateral
cords
Motor Anterior compartment of arm (coracobrachialis, biceps
Supply brachii, brachialis)
Sensory Lateral forearm (via the lateral cutaneous nerve of the
supply forearm)
Anatomical Course
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MUSCULOCUTANEOUS NERVE. (IMAGE BY HENRY VANDYKE CARTER [PUBLIC DOMAIN],

Function
It innervates all of the muscles in the anterior compartment of the arm (the
coracobrachialis, the biceps brachii and the brachialis muscles) and gives rise to
the lateral cutaneous nerve of the forearm, which supplies the skin on the lateral
surface of the forearm.
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8/24/22, 8:46 PM Radioulnar Joints - MRCEM Success
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Radioulnar Joints LAST UPDATED: 10TH

APRIL 2019
 Bookmark
RADIOULNAR JOINTS. (IMAGE BY OPENSTAX COLLEGE [CC BY 3.0

Proximal Radioulnar Joint
Table: Anatomical Overview of the Proximal Radioulnar Joint

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Joint Proximal Radioulnar

Type Synovial pivot
Articulations Head of radius with radial notch of ulna
Stabilising factors Annular ligament
Movements Pronation and supination
The proximal radioulnar joint is a pivot type synovial joint occurring between the
head of the radius and the radial notch of the ulnar. The radial head is held in
position by the annular ligament of the radius.
Distal Radioulnar Joint
Table: Anatomical Overview of the Distal Radioulnar Joint

Joint Distal Radioulnar
Type Synovial pivot
Articulations Head of ulna with ulnar notch of radius
Movements Pronation and supination
The distal radioulnar joint is a pivot type synovial joint occurring between the
head of the ulnar and the ulnar notch on the radius.
Movements
The radioulnar joints allow pronation and supination of the forearm.
Table: Movements of the Radioulnar Joints

Movement Main Muscles Involved Main Nerves Involved
Pronation Pronator quadratus, Median nerve
pronator teres
Supination Biceps brachii, supinator Musculocutaneous nerve,
radial nerve
8/24/22, 8:53 PM Subscapularis Muscle - MRCEM Success
Subscapularis Muscle LAST UPDATED: 8TH

APRIL 2019
 Bookmark
The subscapularis muscle forms the largest component of the posterior

wall of the axilla. Together with three muscles of the posterior scapula
region (the supraspinatus, infraspinatus and teres minor muscles) the
subscapularis is a member of the rotator cuff muscle group, which
stabilises the glenohumeral joint.
Table: Function and Innervation of the Subscapularis Muscle

Muscle Subscapularis
Origin Medial two-thirds of subscapular fossa
Insertion Lesser tubercle of humerus
Actions Medial rotation of arm at glenohumeral joint
Innervation Upper and lower subscapular nerves
Attachments
It originates from, and fills, the subscapular fossa on the anterior surface of
the scapula and inserts into the lesser tubercle of the humerus. The tendon
crosses immediately anterior to the joint capsule of the glenohumeral joint.
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8/24/22, 8:53 PM Subscapularis Muscle - MRCEM Success
Function
The subscapularis acts to medially rotate the arm at the glenohumeral joint.
To isolate the subscapularis muscle in examination, place the dorsum of the
patient's hand in full medial rotation on the lower back and ask them to
push their hand off the back (the 'lift-off' test). Loss of power suggests a
tear while pain on forced medial rotation suggests tendonitis.
Innervation
The subscapularis is innervated by the upper and lower subscapular nerves,
branches of the brachial plexus.
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8/24/22, 8:35 PM Supratrochlear and Infraclavicular Lymph Nodes - MRCEM Success
Supratrochlear and LAST UPDATED: 8TH

APRIL 2019
Infraclavicular Lymph Nodes  Bookmark
Supratrochlear Lymph Nodes

The supratrochlear lymph nodes lie subcutaneously above the medial epicondyle,
medial to the basilic vein. They drain the ulnar side of the forearm and the medial
hand. Differential diagnosis for enlarged lymph nodes includes skin infections,
skin malignancies and lymphoma.
Infraclavicular Lymph Nodes

The 2 - 3 infraclavicular (deltopectoral) lymph nodes lie in the deltopectoral
groove inferior to the clavicle, located superiorly and posteriorly to the axillary
artery. They primarily drain the radial side of the upper limb. Lymphadenopathy
here is highly suspicious for non-Hodgkin's lymphoma specifically, and for
malignancy in general.
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8/24/22, 8:35 PM Supratrochlear and Infraclavicular Lymph Nodes - MRCEM Success
LYMPHATIC DRAINAGE OF THE ARM. IMAGE BY HENRY VANDYKE CARTER [PUBLIC

DOMAIN], VIA WIKIMEDIA COMMONS
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8/24/22, 8:53 PM Teres Major Muscle - MRCEM Success
Teres Major Muscle LAST UPDATED: 8TH

APRIL 2019
 Bookmark
The teres major muscle passes from the inferior angle of the scapula to the
upper humerus and contributes to the posterior axillary skin fold laterally.
Table: Function and Innervation of the Teres Major Muscle

Muscle Teres Major
Origin Posterior surface of inferior angle of scapula
Distal Medial lip of intertubercular sulcus on humerus
Attachment
Function Medial rotation and extension of arm at
glenohumeral joint
Innervation Lower subscapular nerve
Origin
The teres major muscle originates from a large oval region on the posterior
surface of the inferior angle of the scapula.
Insertion
The broad cord-like muscle passes superiorly and laterally and ends as a
flat tendon that inserts onto the medial lip of the intertubercular sulcus on
the anterior surface of the humerus.
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8/24/22, 8:53 PM Teres Major Muscle - MRCEM Success
Function
The teres major medially rotates and extends the humerus at the
glenohumeral joint.
Innervation
The teres major muscle is innervated by the lower subscapular nerve.
TERES MAJOR MUSCLE. (IMAGE MODIFIED BY FRCEM SUCCESS. ORIGINAL BY

https://mrcemsuccess.com/explanation/teres-major-3/?_sft_qc=axilla 3/3
8/24/22, 8:47 PM Ulnar Nerve - MRCEM Success
Ulnar Nerve LAST UPDATED: 10TH

APRIL 2019
ANTERIOR FOREARM / INNERVATION OF UPPER LIMB  Bookmark
The ulnar nerve is a continuation of the medial cord of the brachial plexus,
containing fibres from the C8 - T1 nerve roots.
Table: Anatomical Overview of the Ulnar Nerve

Nerve Ulnar
Nerve C8 – T1
roots
Plexus Medial cord
cords
Motor All the intrinsic muscles of the hand (except for the thenar
Supply muscles and the lateral two lumbricals), the flexor carpi ulnaris
and the medial half of the flexor digitorum profundus
Sensory Medial half of palm, palmar and dorsal surface of medial one
supply and a half fingers and medial dorsum of hand
Anatomical course
The ulnar nerve descends down the medial side of the upper arm and passes
posterior to the medial epicondyle (where it is susceptible to damage) before
entering the anterior compartment of the forearm by passing between the two
heads of the flexor carpi ulnaris. It continues down the medial aspect of the
forearm.
The ulnar nerve emerges from beneath the flexor carpi ulnaris and becomes
superficial just proximal to the wrist where it passes superficial to the flexor
retinaculum, together with the ulnar artery, to enter the hand through a groove
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between the pisiform and the hook of the hamate where it bifurcates into its
terminal branches.
ULNAR NERVE. (IMAGE BY HENRY VANDYKE CARTER [PUBLIC DOMAIN], VIA WIKIMEDIA
COMMONS)
Branches
Table: Branches of the Ulnar Nerve
Branches Origin Supply

of Ulnar
Nerve
Muscular Forearm Flexor carpi ulnaris, medial half of flexor
branch digitorum profundus
Palmar Forearm Skin of medial half of palm
cutaneous
branch
Dorsal Forearm Skin of dorsum of medial one and a half fingers
cutaneous and associated dorsal hand area
branch
Deep Hand Hypothenar muscles (abductor digiti minimi,
branch flexor digiti minimi, opponens digiti minimi),
medial two lumbricals, adductor pollicis and
interossei
Superficial Hand Skin of palmar surface of medial one and a half
branch fingers
The ulnar nerve gives off no major branches in the arm.

Three branches arise in the forearm:
The muscular branch innervating the flexor carpi ulnaris and the medial half
of the flexor digitorum profundus
The palmar cutaneous branch supplying the skin of the medial half of the
palm
The dorsal cutaneous branch supplying the skin of the medial dorsum of
the hand and the dorsal surface of the medial one and a half fingers
The ulnar nerve terminates by bifurcating into:
A deep branch innervating the hypothenar muscles, the medial two
lumbricals, the adductor pollicis and the interossei
A superficial branch supplying the skin of the palmar surface of the medial
one and a half fingers
8/25/22, 9:04 PM Lymphatic Drainage of Breast - MRCEM Success
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Lymphatic Drainage of LAST UPDATED:

20TH FEBRUARY
Breast 2019
ANATOMY / UPPER LIMB / BREAST  Bookmark
The lymphatic drainage of the breast is of great clinical importance due

to its role in the metastasis of breast cancer cells.
There are three main groups of lymph nodes that receive lymph from
breast tissue:
Approximately 75% of lymphatic drainage is via lymphatic vessels
that drain laterally and superiorly into axillary lymph nodes.
Most of the remainder (20%) is into medial parasternal lymph
nodes, which lie deep to the anterior thoracic wall associated with
the internal thoracic artery.
Some drainage (5%) may follow the lateral branches of posterior
intercostal arteries and connect with posterior intercostal lymph
nodes situated near the heads and necks of ribs.
From here:
Axillary nodes drain into the subclavian trunks
Parasternal nodes drain into the bronchomediastinal trunks
Intercostal nodes drain either into the thoracic duct or into the
bronchomediastinal trunks
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8/25/22, 9:04 PM Lymphatic Drainage of Breast - MRCEM Success
LYMPHATIC DRAINAGE OF THE BREAST. (IMAGE BY HENRY VANDYKE CARTER

https://mrcemsuccess.com/explanation/lymphatic-drainage-of-the-breast/?_sft_qc=breast 3/3
8/25/22, 9:06 PM Digital Attachments of Long Extensor Tendons - MRCEM Success
Digital Attachments of LAST UPDATED: 29TH

JANUARY 2019
Long Extensor Tendons  Bookmark
ANATOMY / UPPER LIMB /
DIGITAL ATTACHMENT OF LONG TENDONS
Table: Digital Attachments of the Long Extensor Tendons

Muscle Distal Attachment
Tendon
Extensor Dorsal surface of base of 2nd metacarpal
carpi radialis
longus
Extensor Dorsal surface of base of 2nd and 3rd metacarpal
carpi radialis
brevis
Extensor Dorsal aspects of bases of middle and distal phalanges
digitorum of index, middle, ring and little fingers via extensor
hoods
Extensor Tubercle on base of 5th metacarpal
carpi ulnaris
Abductor Lateral side of base of 1st metacarpal
pollicis
longus
Extensor Dorsal surface of base of distal phalanx of thumb
pollicis
longus
Extensor Dorsal surface of base of proximal phalanx of thumb
pollicis
brevis
Extensor Extensor hood of index finger
indicis
Extensor Extensor hood of little finger
digiti minimi
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8/25/22, 9:06 PM Digital Attachments of Long Extensor Tendons - MRCEM Success
A detailed knowledge of the distal attachments of the extensor tendons is

important to allow understanding of the clinical effects of division/injury at
any given level of the finger.
The abductor pollicis longus is attached to the lateral side of the base of
the 1st metacarpal.
The extensor pollicis brevis is attached to the dorsal surface of the base
of the proximal phalanx of the thumb.
The extensor pollicis longus is attached to the dorsal surface of the base
of the distal phalanx of the thumb.
The extensor indicis inserts into the extensor hood of the index finger.
The extensor carpi radialis longus is attached to the dorsal surface of
the base of the 2nd metacarpal.
The extensor carpi radialis brevis is attached to the dorsal surface of the
bases of the 2nd and 3rd metacarpals.
The four tendons of the extensor digitorum insert via extensor hoods
into the dorsal aspects of the bases of the middle and distal phalanges
of the index, middle, ring and little fingers.
The extensor digiti minimi inserts, together with the tendon of the
extensor digitorum, into the extensor hood of the little finger.
The extensor carpi ulnaris is attached to the tubercle on the base of the
5th metacarpal.
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8/25/22, 9:06 PM Digital Attachments of Long Flexor Tendons - MRCEM Success
Digital Attachments of LAST UPDATED: 29TH

JANUARY 2019
Long Flexor Tendons  Bookmark
DIGITAL ATTACHMENT OF LONG TENDONS
The flexor muscles of the anterior forearm all originate from the medial
humeral epicondyle.
Table: Digital Attachments of the Long Flexor Tendons

Flexor Tendon Distal Attachment
Flexor pollicis longus Base of distal phalanx of thumb
Flexor digitorum Distal phalanges of all four digits
profundus
Flexor digitorum Middle phalanges of all four digits
superficialis
Flexor carpi ulnaris Pisiform, hook of hamate and 5th
metacarpal
Flexor carpi radialis Base of 2nd and 3rd metacarpal
Palmaris longus Palmar aponeurosis
A detailed knowledge of the distal attachments of the flexor tendons is

important to allow understanding of the clinical effects of division/injury at
any given level of the finger.
The flexor pollicis longus is attached distally to the base of the distal
phalanx of the thumb.
The flexor digitorum profundus is attached distally to the palmar
surface of the distal phalanges of all four fingers.
The flexor digitorum superficialis is attached distally to the palmar
surface of the middle phalanges of all four fingers.
The flexor carpi ulnaris is attached distally to the pisiform, hook of
hamate and 5th metacarpal.
The flexor carpi radialis is attached distally to the base of the 2nd and
3rd metacarpal.
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8/25/22, 9:06 PM Digital Attachments of Long Flexor Tendons - MRCEM Success
The palmaris longus distally blends with the fibres of the flexor
retinaculum which is continuous with the palmar aponeurosis.
DIGITAL ATTACHMENTS OF LONG FLEXOR TENDONS. N.B. SOME TERMINOLOGY IS

OUTDATED, BUT ATTACHMENTS ARE CORRECT. (IMAGE BY HENRY VANDYKE CARTER
https://mrcemsuccess.com/explanation/digital-attachments-of-long-flexor-tendons/?_sft_qc=digital-attachment-of-long-tendons 3/3
8/25/22, 9:07 PM Extensor Tendon Injury - MRCEM Success
Extensor Tendon Injury LAST UPDATED: 10TH

APRIL 2019
DIGITAL ATTACHMENT OF LONG TENDONS  Bookmark
Table: Clinical Features of Extensor Tendon Injury

Structure Terminal Central Slip of Extensor Tendon
Extensor
Tendon
Attachment Distal phalanx Middle phalanx
Movements Loss of Loss of extension at proximal
affected in extension at interphalangeal joint and flexion at
injury distal distal interphalangeal joint
interphalangeal
joint
Deformity Mallet deformity: Boutonniere deformity: Middle
in injury Distal phalanx phalanx held in fixed flexion with
held in fixed hyperextension of distal phalanx
flexion
The tendons of the extensor digitorum (and extensor pollicis longus) pass onto
the dorsal aspect of the digits and expand over the proximal phalanges to form
complex extensor hoods. The central slip inserts into the base of the middle
phalanx, and distally the tendon inserts into the distal phalanx of each digit.
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8/25/22, 9:07 PM Extensor Tendon Injury - MRCEM Success
EXTENSOR TENDONS. (IMAGE MODIFIED BY FRCEM SUCCESS. ORIGINAL BY HENRY

Central Slip
Division of the central slip of the extensor tendon will result in the Boutonniere
deformity, with loss of extension of the proximal interphalangeal joint and loss
of flexion of the distal interphalangeal joint. The middle phalanx is held in
forced flexion, with hyperextension of the distal phalanx.
Terminal Tendon
Division of the terminal extensor tendon will result in the Mallet deformity, with
loss of extension at the distal interphalangeal joint as in this case; the distal
phalanx is held in forced flexion due to unopposed action of the flexor
digitorum profundus muscle.

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Axillary Nerve LAST UPDATED: 28TH

JANUARY 2019
ANATOMY / UPPER LIMB / AXILLA /
Table: Anatomical Overview of the Axillary Nerve

Nerve Axillary
Nerve C5 and C6
roots
cords
Motor Deltoid, teres minor
Supply
Sensory Regimental badge area on lateral arm via superior lateral
supply cutaneous nerve of the arm
The axillary nerve arises from the posterior cord containing fibres from nerve
roots C5 and C6.
The axillary nerve and associated blood vessels (the posterior circumflex
humeral artery and vein) enter the deltoid by passing posteriorly around the
surgical neck of the humerus (where it is vulnerable to damage).
The axillary nerve innervates the teres minor and deltoid muscles and the skin
over the inferior portion of the deltoid, the 'regimental badge area' (via the
superior lateral cutaneous nerve of the arm).
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AXILLARY NERVE. (IMAGE BY HENRY VANDYKE CARTER [PUBLIC DOMAIN], VIA

WIKIMEDIA COMMONS)
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8/25/22, 9:10 PM Axillary Nerve Injury - MRCEM Success
Table: Clinical Features of Axillary Nerve Injury

Nerve Axillary
Mechanism Dislocation of the glenohumeral joint, fracture of the surgical
of injury neck of the humerus, trauma or surgery to the shoulder, incorrect
use of axillary crutches
Motor loss Loss of abduction of the arm at the glenohumeral joint and
weakness of lateral rotation
Sensory Lateral arm (regimental badge area)
loss
Signs Atrophy of deltoid – flattened shoulder appearance
Clinical Anatomy
The axillary nerve and associated blood vessels (the posterior circumflex humeral
artery and vein) enter the deltoid by passing posteriorly around the surgical neck of
the humerus.
Mechanism of Injury
The axillary nerve is most commonly damaged by direct trauma to the shoulder or
proximal humerus. Common mechanisms of injury include fracture of the surgical
neck of the humerus, shoulder dislocation or iatrogenic injury during shoulder surgery.
Clinical Features
Axillary nerve injury results in:
Weakness of abduction (due to paralysis of the deltoid muscle)
Weakness of lateral rotation (due to paralysis of the teres minor muscle)
Loss of sensation over the 'regimental badge area' on the lateral arm
Deltoid muscle atrophy giving a flattened shoulder appearance (in long-
standing cases)
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8/25/22, 9:11 PM Brachial Plexus Injury - MRCEM Success
Brachial Plexus Injury LAST UPDATED: 8TH

APRIL 2019
Brachial plexus injuries are usually the result of blunt trauma producing nerve
avulsions and disruption.
Table: Clinical Features of Brachial Plexus Injury

Brachial Erb’s palsy Klumpke’s palsy
plexus
injury
Mechanism Excessive increase in angle Sudden excessive
of injury between neck and abduction e.g. person
shoulder e.g. during breech catching something
delivery or from fall from overhead as they fall or
motorbike or horse during a difficult delivery
Nerve roots C5, C6 C8, T1
affected
Nerves Musculocutaneous, Ulnar and median nerves
affected axillary, suprascapular and
nerve to subclavius
Muscles Supraspinatus, All small muscles of
affected infraspinatus, subclavius, hand (flexor muscles in
biceps brachii, brachialis, forearm innervated by
coracobrachialis, deltoid different nerve roots)
and teres minor
Motor loss Abduction, flexion and Intrinsic hand
lateral rotation of arm, movements
flexion and supination of
forearm
Sensory Lateral arm Medial arm
loss
Deformities Waiter’s tip Claw hand
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8/25/22, 9:11 PM Brachial Plexus Injury - MRCEM Success
Klumpke's Palsy
Klumpke's palsy affects nerves derived from the C8 or T1 roots. It is much less
common than Erb's palsy. It usually occurs from sudden excessive abduction
of the arm e.g. catching something overhead when falling, or during a difficult
birth. All the small muscles of the hand are affected (the flexor muscles of the
forearm are spared as they are supplied by different roots). There is sensory
loss over the medial side of the arm and a characteristic 'claw hand'
appearance, where the metacarpophalangeal joints are hyperextended, and
the interphalangeal joints are flexed.
Erb's Palsy
Erb's palsy affects nerves derived from the C5 or C6 roots. It commonly result
from an excessive increase in the angle between the neck and the shoulder
e.g. a person thrown from a motorbike or horseback or during a difficult birth.
There is loss or weakness of abduction, lateral rotation and flexion of the arm
and flexion and supination of the forearm and loss of sensation on the lateral
arm. A characteristic 'Waiter's tip' deformity may be present where the limb
hangs limply by the side, medially rotated by the unopposed action of the
pectoralis major with the forearm pronated and extended and the wrist flexed.
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8/25/22, 9:12 PM Cutaneous Innervation of Upper Limb - MRCEM Success

APRIL 2019
Upper Limb  Bookmark
Table: Cutaneous Innervation of the Upper Limb

Cutaneous Nerve Origin Skin Supplied
Lateral Cervical plexus Upper half of deltoid
supraclavicular (C3, C4) muscle
nerve
Superior lateral Axillary nerve Lower half of deltoid
cutaneous nerve of muscle
the arm
Inferior lateral Radial nerve Lateral arm below
cutaneous nerve of deltoid muscle
the arm
Medial cutaneous Brachial plexus Medial arm
nerve of the arm (C8, T1)
Intercostobrachial Second intercostal Axilla
nerve nerve (T2)
Posterior cutaneous Radial nerve Posterior arm
nerve of the arm
Medial cutaneous Brachial plexus Medial forearm
nerve of the forearm (C8, T1)
Posterior cutaneous Radial nerve Posterior forearm
nerve of the forearm
Lateral cutaneous Musculocutaneous Lateral forearm
nerve of the forearm nerve
Superficial branch of Radial nerve Lateral dorsum of hand
radial nerve and lateral three and a
half digits
Palmar cutaneous Ulnar nerve Medial half of palm
Cutaneous Nerve
branch of ulnar Origin Skin Supplied
https://mrcemsuccess.com/explanation/cutaneous-supply-of-the-upper-limb-2/?_sft_qc=innervation-of-upper-limb 2/5
nerve
Dorsal cutaneous Ulnar nerve Medial dorsum of hand
branch of ulnar and medial one and a
nerve half fingers
Superficial branch of Ulnar nerve Palmar surface of
ulnar nerve medial one and a half
digits
Palmar cutaneous Median nerve Lateral half of palm
branch of median
nerve
Palmar digital Median nerve Palmar surface and
branch of median fingertips of lateral
nerve three and a half digits
CUTANEOUS INNERVATION OF UPPER LIMB. (IMAGE MODIFIED BY FRCEM SUCCESS.

Cutaneous Innervation of Arm

The lateral supraclavicular nerve, branch of the cervical plexus, supplies
the skin over the upper half of the deltoid muscle.
The superior lateral cutaneous nerve of the arm, branch of the axillary
nerve, supplies the skin over the lower half of the deltoid muscle
(regimental badge area).
The inferior lateral cutaneous nerve of the arm, branch of the radial
nerve, supplies the skin over the lateral side of the arm below the deltoid
muscle.
The medial cutaneous nerve of the arm, branch of the brachial plexus,
supplies the skin over the medial arm.
The intercostobrachial nerve, branch of the second intercostal nerve,
supplies the skin of the axilla.
The posterior cutaneous nerve of the arm, branch of the radial nerve,
supplies the skin over the posterior arm.
Cutaneous Innervation of Forearm

The medial cutaneous nerve of the forearm, branch of the brachial
plexus, supplies the skin over the medial aspect of the forearm.
The posterior cutaneous nerve of the forearm, branch of the radial
nerve, supplies the skin over the posterior forearm.
The lateral cutaneous nerve of the forearm, branch of the
musculocutaneous nerve, supplies the skin over the lateral aspect of the
forearm.
Cutaneous Innervation of Hand

The superficial branch of the radial nerve supplies the skin over the
lateral dorsum of the hand and the lateral three and a half digits.
The palmar cutaneous branch of the ulnar nerve supplies the skin over
the medial half of the palm.
The dorsal cutaneous branch of the ulnar nerve supplies the skin over
medial dorsum of the hand and the dorsum of the medial one and a half
fingers.
The superficial branch of the ulnar nerve supplies the skin over the
palmar surface of the medial one and a half fingers.
The palmar cutaneous branch of the median nerve supplies the skin over
the lateral half of the palm.
The palmar digital branch of the median nerve supplies the skin over the
palmar surface and the fingertips of the lateral three and a half digits.
8/25/22, 9:13 PM Dermatomal Supply of Upper Limb - MRCEM Success
Table: Dermatomal Supply of the Upper Limb

Dermatome Landmark
C2 Occipital Protuberance
C3 Supraclavicular Fossa
C4 Acromioclavicular Joint
C5 Lateral Antecubital Fossa
C6 Thumb
C7 Middle Finger
C8 Little Finger
T1 Medial Antecubital Fossa
T2 Apex of Axilla
DERMATOME MAP. (IMAGE BY GRANT, JOHN CHARLES BOILEAU (AN ATLAS OF ANATOMY, / BY
REGIONS 1962) [PUBLIC DOMAIN], VIA WIKIMEDIA COMMONS)
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8/25/22, 9:13 PM Dermatomal Supply of Upper Limb - MRCEM Success
The C2 dermatome is best tested at least one cm lateral to the occipital protuberance at
the base of the skull. Alternately, it can be located at least 3 cm behind the ear.
The C3 dermatome is best tested in the supraclavicular fossa, at the midclavicular line.
The C4 dermatome is best tested over the acromioclavicular joint.
The C5 dermatome is best tested on the lateral (radial) side of the antecubital fossa just
proximal to the elbow.
The C6 dermatome is best tested on the dorsal surface of the proximal phalanx of the
thumb.
middle finger.
little finger.
The T1 dermatome is best tested on the medial (ulnar) side of the antecubital fossa, just
proximal to the medial epicondyle of the humerus.
The T2 dermatome is best tested at the apex of the axilla.
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8/25/22, 9:13 PM Long Thoracic Nerve Injury - MRCEM Success
Long Thoracic Nerve Injury LAST UPDATED: 8TH

APRIL 2019
Clinical Anatomy
The long thoracic nerve is prone to injury due to its excessive length and
superficial location on the lateral thoracic wall on the external surface of the
serratus anterior muscle, just deep to skin and subcutaneous fascia.
Mechanism of Injury
Injury to this nerve may occur due to:
Trauma or surgery
A direct blow to the rib area
Overstretching or strenuous repetitive movements of the arms
Sustained bearing of excessive weight over the shoulder
Clinical Features
Damage to the long thoracic nerve results in weakness/paralysis of the
serratus anterior muscle.
Loss of function of this muscle causes the medial border, and particularly the
inferior angle, of the scapula to elevate away from the thoracic wall, resulting
in the characteristic 'winging' of the scapula. This deformity becomes more
pronounced if the patient presses the upper limb against a wall.
Furthermore, normal elevation of the arm is no longer possible.
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8/25/22, 9:13 PM Long Thoracic Nerve Injury - MRCEM Success
WINGING OF THE SCAPULA. (IMAGE BY KAURJMEB [CC BY-SA 2.0

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8/25/22, 9:14 PM Median Nerve Injury - MRCEM Success
Median Nerve Injury LAST UPDATED: 4TH

NOVEMBER 2019
Table: Clinical Features of Median Nerve Injury

Lesion Proximal (arm, elbow, proximal forearm) Distal
(wrist)
Mechanisms Supracondylar fracture, stab wound to Lacerations
arm or forearm just
proximal to
flexor
retinaculum
Motor Loss Forearm pronation, wrist flexion and Thumb
abduction, index and middle finger flexion,
flexion, thumb flexion, abduction and abduction
opposition and
opposition,
flexion of
index and
middle
finger
MCPJ
Sensory Lateral aspect of palm and palmar Lateral
Loss surface and fingertips of lateral three aspect of
and a half digits palm and
palmar
surface and
fingertips of
lateral three
and a half
digits
Signs Forearm rests in supination with wrist Thenar
in ulnar deviation and thumb extended, eminence
thenar eminence wasting, hand of wasting
Benediction (when asked to make a fist,
the patient will be able to flex the little
and ring fingers but not the index and
middle fingers)
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Proximal Median Nerve Injury

MECHANISM OF INJURY:
A proximal median nerve lesion at the elbow may occur due to supracondylar
fracture of the humerus or from deep penetrating wounds to the arm.
CLINICAL FEATURES:
Pronation of the forearm and flexion and abduction of the wrist are lost
due to paralysis of the flexors and pronators in the forearm. The forearm
thus often rests in supination with ulnar deviation of the wrist (due to
unopposed action of the flexor carpi ulnaris).
Flexion, abduction and opposition of the thumb at the MCPJ and IPJ are
lost due to paralysis of the thenar muscles and the flexor pollicis longus.
Flexion of the index and middle fingers at the IPJs is lost due to paralysis
of the flexor digitorum superficialis and the lateral half of the flexor
digitorum profundus.
Extension of the index and middle fingers at the IPJs is weakened due to
paralysis of the lateral two lumbrical muscles (but not lost due to
preservation of the interossei innervated by the ulnar nerve)
Flexion of the MCPJ of the index and middle fingers is lost due to
paralysis of the lateral two lumbrical muscles.
N.B. Flexion of the ring and little fingers at the MCPJ and DIPJ are
preserved as these are functions of the medial half of the flexor
digitorum profundus and the medial two lumbrical muscles, innervated
by the ulnar nerve (there may be weakness of flexion at the PIPJ of
these fingers due to paralysis of the flexor digitorum superficialis).
There is loss of sensation over the lateral aspect of the palm, and the
skin over the palmar surface and fingertips of the lateral three and a half
digits.
Distal Median Nerve Injury

Medial nerve lesion at the wrist often occurs due to lacerations just proximal to
the flexor retinaculum. Only the intrinsic hand muscles are affected.
CLINICAL FEATURES:
Loss of opposition, abduction and flexion of the MCPJ of the thumb

occurs due to paralysis of the thenar muscles.
Loss of flexion at the MCPJ of the index and middle finger and weakness
of extension at the IPJs of the index and middle finger occurs due to
paralysis of the lateral two lumbricals.
There is loss of sensation to the lateral palm and palmar surface and
fingertips of the lateral three and a half digits.

APRIL 2019
The musculocutaneous nerve originates from the lateral cord of the brachial
plexus, receiving fibres from C5 - C7.
Table: Anatomical Overview of the Musculocutaneous Nerve
Nerve C5 – C7
roots
Plexus Lateral
cords
Motor Anterior compartment of arm (coracobrachialis, biceps
Supply brachii, brachialis)
Sensory Lateral forearm (via the lateral cutaneous nerve of the
supply forearm)
Anatomical Course
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MUSCULOCUTANEOUS NERVE. (IMAGE BY HENRY VANDYKE CARTER [PUBLIC

Function
It innervates all of the muscles in the anterior compartment of the arm (the
coracobrachialis, the biceps brachii and the brachialis muscles) and gives rise
to the lateral cutaneous nerve of the forearm, which supplies the skin on the
lateral surface of the forearm.
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8/25/22, 9:15 PM Musculocutaneous Nerve Injury - MRCEM Success

JANUARY 2019
Injury  Bookmark
Table: Clinical Features of Musculocutaneous Nerve Injury

Mechanism Stab wound in axilla
of injury
Motor loss Weakness of flexion and supination of the forearm,
weakness of arm flexion
Sensory loss Lateral aspect of forearm
Injury to the musculocutaneous nerve is rare, as it is relatively protected in the

axilla.
The most common cause of injury is a stab wound in the axilla.
Flexion of the arm and flexion and supination of the forearm are weakened but
not lost entirely due to the actions of the pectoralis major and deltoid, the
brachioradialis and the supinator muscles respectively.
There is loss of sensation over the lateral aspect of the forearm.
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8/25/22, 9:16 PM Myotomes and Reflexes - MRCEM Success
Myotomes and Reflexes LAST UPDATED: 10TH

APRIL 2019
LOWER LIMB / INNERVATION OF LOWER LIMB /  Bookmark
UPPER LIMB / INNERVATION OF UPPER LIMB
Upper Limb
Table: Myotomes of the Upper Limb

Myotome Most Strongly Associated Movement
C5 Elbow flexion
C6 Wrist extension
C7 Elbow extension
C8 Finger flexion
T1 Finger abduction
Lower Limb
Table: Myotomes of the Lower Limb

L2 Hip flexion
L3 Knee extension
L4 Ankle dorsiflexion
L5 Great toe extension
S1 Ankle plantarflexion
S2 Knee flexion
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Reflexes
Table: Reflexes of the Upper and Lower Limb

Reflex Root Muscle
Biceps C5 – C6 Biceps brachii
Supinator C6 – C7 Brachioradialis
Triceps C7 – C8 Triceps brachii
Knee L3 – L4 Quadriceps
Ankle S1 Gastrocnemius
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8/25/22, 9:16 PM Radial Nerve - MRCEM Success
Radial Nerve LAST UPDATED: 8TH

APRIL 2019
INNERVATION OF UPPER LIMB / POSTERIOR ARM /  Bookmark
POSTERIOR FOREARM
The radial nerve is a continuation of the posterior cord, containing fibres from
C5 - T1.
Table: Anatomical Overview of the Radial Nerve

Nerve Radial
Nerve C5 – T1
roots
cords
Motor Triceps brachii, posterior compartment of forearm:
Supply superficial muscles (brachioradialis, extensor carpi radialis
longus and brevis, extensor digitorum, extensor digiti
minimi, extensor carpi ulnaris) and deep muscles (supinator,
abductor pollicis longus, extensor pollicis longus and brevis,
extensor indicis)
Sensory Lower lateral arm, posterior arm, posterior forearm, dorsum
supply of lateral hand and three and a half fingers
Anatomical course
The radial nerve enters the arm by crossing the lower margin of the teres
major muscle, where it lies posterior to the brachial artery. It enters the
posterior compartment of the arm, where it descends obliquely passing from
medial to lateral in the radial (spiral) groove of the humerus. After emerging
from the spiral groove, the radial nerve pierces the lateral intermuscular
septum and enters the anterior compartment of the arm, descending into the
cubital fossa where it lies between the brachialis and brachioradialis muscles.
The radial nerve enters the forearm after passing over the lateral epicondyle of
the humerus. Within the proximal forearm the nerve terminates by bifurcating
into the deep branch and the superficial branch.
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N.B. Once the deep branch of the radial nerve penetrates between the two
heads of the supinator muscle to access the posterior compartment of the
forearm, it becomes known as the posterior interosseous nerve.
RADIAL NERVE. (IMAGE BY HENRY VANDYKE CARTER [PUBLIC DOMAIN], VIA

WIKIMEDIA COMMONS)
Branches
Table: Branches of the Radial Nerve
Branches of Origin Supply

Radial Nerve
Radial nerve Axilla Triceps brachii, extensor carpi radialis
longus, brachioradialis
Posterior Axilla Skin of posterior arm
cutaneous
nerve of the
arm
Inferior Arm Skin over lateral aspect of lower arm
lateral
cutaneous
nerve of the
arm
Posterior Arm Strip of skin down middle of posterior
cutaneous forearm
nerve of the
forearm
Deep branch Forearm Posterior compartment of forearm:
which superficial muscles (extensor carpi radialis
continues as brevis, extensor digitorum, extensor digiti
the posterior minimi, extensor carpi ulnaris) and deep
interosseous muscles (supinator, abductor pollicis
nerve longus, extensor pollicis longus and
brevis, extensor indicis)
Superficial Forearm Skin of dorsum of the hand and lateral
branch three and a half fingers
In the arm, the radial nerve directly innervates the triceps brachii, the extensor
carpi radialis longus and the brachioradialis. In the forearm, the deep branch,
which continues as the posterior interosseous nerve, innervates the muscles
of the posterior compartment of the forearm and the superficial branch
supplies the skin of the dorsum of the hand and lateral three and a half fingers.
The radial nerve also gives rise to several cutaneous branches; the posterior
cutaneous nerve of the arm originating in the axilla, and the inferior lateral
cutaneous nerve of the arm and the posterior cutaneous nerve of the forearm
originating in the arm. These cutaneous branches supply skin over the
posterior surface of the arm, the lateral aspect of the arm and the skin down
the middle of the posterior forearm respectively.
8/25/22, 9:17 PM Radial Nerve Injury - MRCEM Success
Table: Clinical Features of Radial Nerve Injury

Lesion In axilla In spiral In forearm In forearm (deep
groove (superficial branch) branch)
Mechanism Glenohumeral Fracture of Stabbing/laceration Fracture of
joint midshaft of forearm radial head or
dislocation, of posterior
fracture of humerus dislocation
proximal of radius
humerus,
‘Saturday
night
syndrome’
Motor Loss Loss of Loss of None Weakness of
extension at extension extension at
elbow, wrist at wrist wrist and
and fingers and fingers fingers (extensor
(triceps carpi radialis
brachii spared)
spared)
Sensory Lower lateral Dorsum of Dorsum of lateral None
Loss arm, posterior lateral hand and three and
arm, posterior hand and a half fingers
forearm, three and a
dorsum of half fingers
lateral hand (cutaneous
and three and branches
a half fingers of arm and
forearm
spared)
Signs Wrist drop Wrist drop, None Wrist drop not
(unopposed weak hand typically seen
wrist flexion), grip (extensor carpi
weakness of radialis spared)
hand grip
(finger flexion
is weak as the
long flexor
tendons are
not under
tension)
Radial Nerve Injury in the Axilla

Radial nerve injury at the axilla may occur in glenohumeral joint dislocation, in fractures of the
proximal humerus, through incorrect use of axillary crutches, or due to 'Saturday Night' palsy.
CLINICAL FEATURES:
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8/25/22, 9:17 PM Radial Nerve Injury - MRCEM Success
Loss of extension of the forearm due to paralysis of the triceps brachii and loss of extension of the
wrist and fingers (predominantly MCPJs, as extension at the IPJs is primarily a function of the
lumbrical and interosseous muscles) and weakness of supination due to paralysis of the muscles
of the posterior compartment of the forearm. All four cutaneous branches of the radial nerve are
affected and there is loss of sensation over the lateral and posterior arm, the posterior forearm
and the dorsal surface of the hand and lateral three and a half digits. There is unopposed wrist
flexion, giving the appearance of wrist drop.
Radial Nerve injury in the Arm

The radial nerve in the arm is most susceptible to midshaft fractures of the humerus due to its
course in the spiral groove.
CLINICAL FEATURES:
Extension of the forearm is not affected as the triceps brachii is spared. There is loss of extension
of the wrist and MCPJs of the fingers and weakness of supination of the forearm. The cutaneous
branches of the arm and forearm have already arisen and sensation loss occurs only on the
dorsum of the lateral hand and three and a half digits.
Radial Nerve Injury in the Forearm

Radial nerve damage in the forearm may present as superficial branch or deep branch damage.
SUPERFICIAL BRANCH:
The superficial branch is most commonly damaged by stabbing or laceration to the forearm and
results in loss of sensation over the dorsum of the lateral hand and three and a half digits.
DEEP BRANCH:
The deep branch may be damaged by fracture of the radial head or posterior dislocation of the
radius and results in weakness of extension of the wrist and fingers, but not typically with wrist
drop (as the extensor carpi radialis is spared).
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8/25/22, 9:19 PM Ulnar Nerve Injury - MRCEM Success

Table: Clinical Features of Ulnar Nerve Injury

Lesion Proximal (at elbow) Distal (at
wrist)
Mechanism Fracture of medial epicondyle Laceration at
wrist
Motor Loss Wrist flexion and adduction, finger Finger
abduction and adduction, flexion of ring abduction
and little finger, abduction and opposition and
of little finger, thumb adduction, extension adduction,
of IPJs of all digits (less so at index and flexion of ring
middle finger due to sparing of lateral two and little
lumbricals) finger,
abduction
and
opposition of
little finger,
thumb
adduction,
extension at
IPJs
Sensory Medial half of palm, palmar and dorsal Palmar
Loss surface of medial one and a half fingers surface of
and medial dorsum of hand medial one
and a half
fingers
Signs Hand held in abduction (due to unopposed Claw hand
action of flexor carpi radialis), Froment’s (unopposed
sign (patient is asked to hold a piece of extension at
paper between thumb and flat palm as MCPJ and
paper is pulled away, patient will flex thumb unopposed
at IPJ to maintain hold – tests adductor flexion at
pollicis muscle), hypothenar eminence IPJs of ring
wasting, N.B. claw hand not typically seen and little
due to paralysis of the flexor digitorum finger),
profundus hypothenar
eminence
wasting,
Froment’s
sign
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Proximal Ulnar Nerve Injury

The ulnar nerve is most likely to be injured proximally by a medial epicondyle
fracture
CLINICAL FEATURES:
There is weak wrist flexion and adduction due to paralysis of the flexor carpi
ulnaris and the medial half of the flexor digitorum profundus; the hand may
be held in abduction (due to unopposed action of the flexor carpi radialis).
There is loss of abduction and adduction of the fingers due to paralysis of the
interossei.
There is loss of flexion at the MCPJ of the ring and little finger due to
paralysis of the medial two lumbricals and the flexor digiti minimi.
There is loss of flexion at the DIPJ of the ring and little finger due to paralysis
of the medial half of the flexor digitorum profundus (but flexion at the PIPJ is
likely preserved as this is a function of the flexor digitorum superficialis).
There is weakened extension at the IPJs of the ring and little finger due to
paralysis of the interossei and medial two lumbricals (and to a lesser extent at
the IPJs of the index and middle finger).
There is loss of abduction and opposition of the little finger due to paralysis of
the hypothenar muscles (hypothenar wasting may be seen).
There is loss of adduction of the thumb due to paralysis of the adductor
pollicis (Froment's sign).
There is loss of sensation to skin over the medial half of the palm, the palmar
and dorsal surface of the medial one and a half fingers and the
medial dorsum of the hand.
There is not typically a claw hand appearance (as may be seen in a lesion at
the wrist) due to paralysis of the flexor digitorum profundus.
Distal Ulnar Nerve Injury

A distal lesion most commonly occurs due to laceration at the wrist.
CLINICAL FEATURES:
Only intrinsic hand muscles are affected (the flexor carpi ulnaris and medial
half of the flexor digitorum profundus are spared).
A loss of sensation will only affect the palmar surface of the medial one and a
half fingers (the medial palm and the dorsum of the hand are spared).
A claw hand deformity may be seen due to unopposed extension at the MCPJ
(by the extensor digitorum) and unopposed flexion at the IPJs (by the FDP
and FDS) of the ring and little finger.
8/25/22, 9:21 PM Acromioclavicular Joint - MRCEM Success
Acromioclavicular Joint LAST UPDATED: 8TH

APRIL 2019
ANATOMY / UPPER LIMB / PECTORAL REGION
 Bookmark
Table: Anatomical Overview of the Acromioclavicular Joint

Joint Acromioclavicular
Type Plane type synovial joint
Articulations Lateral end of clavicle and acromion of scapula
Main stabilising Acromioclavicular ligament and coracoclavicular
factors ligament
Joint Articulations
The acromioclavicular joint is a plane type synovial joint, occurring between the
lateral end of the clavicle and the acromion of the scapula.
Joint Ligaments
The acromioclavicular joint is reinforced by two main ligaments; a small
acromioclavicular ligament and a much larger coracoclavicular ligament.
The strong coracoclavicular ligament (made up of two ligaments, the conoid and
trapezoid ligament) is the main stabilising force, and essentially suspends the
weight of the upper limb from the clavicle.
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8/25/22, 9:21 PM Acromioclavicular Joint - MRCEM Success
ACROMIOCLAVICULAR JOINT. (IMAGE BY HENRY VANDYKE CARTER [PUBLIC DOMAIN], VIA

WIKIMEDIA COMMONS)
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8/25/22, 9:24 PM Acromioclavicular Joint Dislocation - MRCEM Success
Acromioclavicular Joint LAST UPDATED: 24TH

JANUARY 2019
Dislocation  Bookmark
Dislocation of the acromioclavicular joint may result from a direct blow to the
joint, a hard fall onto the shoulder or from a fall onto an outstretched upper
limb. In acromioclavicular joint dislocation the acromion is forcibly pushed
inferiorly and medially with respect to the clavicle, and becomes more
prominent.
ACROMIOCLAVICULAR JOINT DISLOCATION. (IMAGE BY JAMES HEILMAN, MD [CC BY-

SA 4.0 (HTTPS://CREATIVECOMMONS.ORG/LICENSES/BY-SA/4.0)], FROM WIKIMEDIA
COMMONS)
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8/25/22, 9:25 PM Latissimus Dorsi Muscle - MRCEM Success
Latissimus Dorsi Muscle LAST UPDATED: 8TH

APRIL 2019
 Bookmark
The latissimus dorsi muscle forms much of the muscle mass underlying
the posterior axillary skin fold extending obliquely upwards from the trunk
to the arm.
Table: Function and Innervation of the Latissimus Dorsi Muscle

Muscle Latissimus Dorsi
Origin Spinous processes of lower 6 thoracic vertebrae and
related interspinous ligaments; via the
thoracolumbar fascia to the spinous processes of the
lumbar vertebrae, related interspinous ligaments and
iliac crest; lower 3 – 4 ribs
Insertion Floor of intertubercular sulcus
Function Adduction, medial rotation and extension of arm at
glenohumeral joint
Innervation Thoracodorsal nerve
Origin
The latissimus dorsi originates from the spinous processes of the lower six
thoracic vertebrae and related interspinous ligaments, via the
thoracolumbar fascia to the spinous processes of the lumbar vertebrae,
related interspinous ligaments and iliac crest and from the inferior 3 or 4
ribs.
Insertion
The muscle inserts onto the floor of the intertubercular sulcus of the
humerus.
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8/25/22, 9:25 PM Latissimus Dorsi Muscle - MRCEM Success
Function
The latissimus dorsi produces adduction, medial rotation and extension of
the humerus at the glenohumeral joint.
Innervation
The latissimus dorsi is innervated by the thoracodorsal nerve.
LATISSIMUS DORSI MUSCLE. (IMAGE BY MIKAEL HÄGGSTRÖM

(IMAGE:GRAY409.PNG) [PUBLIC DOMAIN OR PUBLIC DOMAIN], VIA WIKIMEDIA
COMMONS)
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8/25/22, 9:25 PM Pectoralis Major Muscle - MRCEM Success
Pectoralis Major Muscle LAST UPDATED: 8TH

APRIL 2019
 Bookmark
The pectoralis major is the largest and most superficial muscle of the
anterior wall. Its inferior margin underlies the anterior axillary fold, which
marks the anteroinferior border of the axilla.
Table: Function and Innervation of the Pectoralis Major Muscle

Muscle Pectoralis Major
Origin Clavicular head: Medial half of clavicle
Sternocostal head: Medial part of anterior thoracic
wall (anterior surface of sternum, first seven costal
cartilages, sternal end of sixth rib, aponeurosis of
external oblique)
Insertion Lateral lip of intertubercular sulcus of humerus

Function Flexion, adduction and medial rotation of arm at
glenohumeral joint
Innervation Medial and lateral pectoral nerves
Origin
The muscle has two heads:
the clavicular head originates from the anterior surface of the
medial half of the clavicle
the sternocostal head originates from the medial part of the anterior
thoracic wall (the anterior surface of the sternum, the first seven
costal cartilages, the sternal end of sixth rib and the aponeurosis of
the external oblique)
Insertion
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8/25/22, 9:25 PM Pectoralis Major Muscle - MRCEM Success
The muscle inserts into the lateral lip of the intertubercular sulcus of the
humerus.
Function
Acting together, the two heads of the pectoralis major flex, adduct and
medially rotate the arm at the glenohumeral joint.
Innervation
The pectoralis major is innervated by the medial and lateral pectoral
nerves which originate from the brachial plexus in the axilla.
PECTORALIS MAJOR MUSCLE. (IMAGE MODIFIED BY FRCEM SUCCESS. ORIGINAL

https://mrcemsuccess.com/explanation/pectoralis-major/?_sft_qc=pectoral-region 3/4
8/25/22, 9:25 PM Pectoralis Minor Muscle - MRCEM Success
Pectoralis Minor Muscle LAST UPDATED: 8TH

APRIL 2019
 Bookmark
The pectoralis minor is a small triangular-shaped muscle that lies deep to

the pectoralis major muscle and passes from the thoracic wall to the
coracoid process of the scapula.
Table: Function and Innervation of the Pectoralis Minor Muscle

Muscle Pectoralis Minor
Origin Anterior surfaces and superior borders of ribs 3 – 5
and from deep fascia overlying related intercostal
spaces
Distal Medial border and upper surface of coracoid process
Attachment of scapula
Actions Depresses tip of shoulder, protracts scapula
Innervation Medial pectoral nerve
Origin
The muscle originates as three muscular slips from the anterior surfaces
and upper margins of ribs 3 - 5 and from the fascia overlying muscles of
the related intercostal spaces.
Insertion
The muscle fibres pass superiorly and laterally to insert into the medial
and upper aspects of the coracoid process.
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8/25/22, 9:25 PM Pectoralis Minor Muscle - MRCEM Success
Function
The muscle protracts the scapula (by pulling the scapula anteriorly on the
thoracic wall) and depresses the lateral angle of the scapula.
Innervation
The muscle is innervated by the medial pectoral nerve, which originates
from the brachial plexus in the axilla.
PECTORALIS MINOR MUSCLE. (IMAGE MODIFIED BY FRCEM SUCCESS. ORIGINAL

https://mrcemsuccess.com/explanation/pectoralis-minor-notes/?_sft_qc=pectoral-region 3/4
8/25/22, 9:26 PM Serratus Anterior Muscle - MRCEM Success
Serratus Anterior Muscle LAST UPDATED:

16TH NOVEMBER
ANATOMY / UPPER LIMB / PECTORAL REGION 2020
 Bookmark
Table: Function and Innervation of the Serratus Anterior Muscle

Muscle Serratus Anterior
Origin Lateral surfaces of ribs 1 – 8/9 and deep fascia
overlying the related intercostal spaces
Distal Costal surface of medial border of scapula
Attachment
Function Protraction and rotation of scapula; keeps medial
border and inferior angle of scapula opposed to
thoracic wall
Innervation Long thoracic nerve
Origin
The serratus anterior muscle originates as a number of muscular slips
from the lateral surfaces of ribs 1 - 8/9 and the intervening deep fascia
overlying the related intercostal spaces.
Insertion
The muscle forms a flattened sheet, which passes posteriorly around the
thoracic wall to insert primarily on the costal surface of the medial border
of the scapula.
Function
The serratus anterior pulls the scapula forward over the thoracic wall and
facilitates scapular rotation. It also keeps the costal surface of the scapula
closely opposed to the thoracic wall.
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8/25/22, 9:26 PM Serratus Anterior Muscle - MRCEM Success
Innervation
The serratus anterior is innervated by the long thoracic nerve, which is
derived from the roots of the brachial plexus, passes through the axilla
along the medial and passes vertically down the serratus anterior muscle
on its external surface, just deep to skin and superficial fascia.
SERRATUS ANTERIOR MUSCLE. (IMAGE MODIFIED BY FRCEM SUCCESS.

COMMONS)
https://mrcemsuccess.com/explanation/serratus-anterior/?_sft_qc=pectoral-region 3/3
8/25/22, 9:26 PM Sternoclavicular Joint - MRCEM Success
Something wrong?
Sternoclavicular Joint LAST UPDATED: 8TH

APRIL 2019
 Bookmark
Table: Anatomical Overview of the Sternoclavicular Joint

Joint Sternoclavicular joint
Type Synovial saddle-shaped joint
Articulations Proximal end of the clavicle; manubrium of sternum
and first costal cartilage
Stabilisation Joint capsule, anterior and posterior
sternoclavicular ligaments, interclavicular ligament
and costoclavicular ligament
Joint Articulations
The sternoclavicular joint is a synovial saddle-shaped joint, occurring
between the proximal end of the clavicle and the manubrium of the
sternum and first costal cartilage.
Joint Ligaments
The sternoclavicular joint is surrounded by a joint capsule and reinforced
by four ligaments; the anterior and posterior sternoclavicular ligaments,
the interclavicular ligament and the costoclavicular ligament.
The strong costoclavicular ligament joins the proximal end of the clavicle
to the first rib and costal cartilage and is the main stabilising force for the
joint. Sternoclavicular joint dislocation is rare and requires significant
force.
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8/25/22, 9:26 PM Sternoclavicular Joint - MRCEM Success
STERNOCLAVICULAR JOINT. (IMAGE BY HENRY VANDYKE CARTER [PUBLIC

https://mrcemsuccess.com/explanation/sternoclavicular-joint-2/?_sft_qc=pectoral-region 3/3
8/25/22, 9:27 PM Trapezius Muscle - MRCEM Success
Trapezius Muscle LAST UPDATED: 8TH

APRIL 2019
 Bookmark
The trapezius muscle is responsible for the smooth contour of the lateral
side of the neck and over the superior aspect of the shoulder.
Table: Function and Innervation of the Trapezius Muscle

Muscle Trapezius
Origin Superior nuchal line, external occipital protuberance,
medial margin of ligamentum nuchae, spinous
processes of C7 – T12 and the related supraspinous
ligaments
Insertion Superior edge of crest of the spine of the scapula,
acromion and posterior border of lateral one-third of
clavicle
Function Elevation of scapula, rotation of scapula during
abduction of humerus above horizontal, retraction
and depression of scapula
Innervation Spinal accessory nerve
Origin
The trapezius muscle has an extensive origin from the axial skeleton,
originating from the superior nuchal line, the external occipital
protuberance, the medial margin of the ligamentum nuchae, the spinous
processes of C7 - T12 and the related supraspinous ligaments.
Insertion
The muscle inserts onto the skeletal framework of the shoulder (to the
superior edge of the crest of the spine of the scapula, the acromion and the
posterior border of the lateral one-third of the clavicle) along the inner
https://mrcemsuccess.com/explanation/trapezius-3/?_sft_qc=pectoral-region 2/4
8/25/22, 9:27 PM Trapezius Muscle - MRCEM Success
margins of a continuous U-shaped line of attachment orientated in the

horizontal plane, with the bottom of the U directed laterally.
Function
The trapezius is a powerful elevator of the shoulder and also rotates the
scapula to extend the reach superiorly (during abduction of the humerus
above horizontal). The middle fibres retract the scapula and the lower fibres
depress the scapula.
Innervation
The trapezius is innervated by the spinal part of the accessory nerve
(motor supply) and the anterior rami of C3 and C4 (sensory supply). These
nerves pass vertically along the deep surface of the muscle. The accessory
nerve can be evaluated by testing the function of the trapezius muscle,
most easily done by asking the patient to shrug their shoulders against
resistance.
https://mrcemsuccess.com/explanation/trapezius-3/?_sft_qc=pectoral-region 3/4
8/25/22, 9:29 PM Elbow Joint - MRCEM Success
Elbow Joint LAST UPDATED:

18TH OCTOBER 2019
ANATOMY / UPPER LIMB / POSTERIOR ARM
 Bookmark
Table: Anatomical Overview of the Elbow Joint

Joint Elbow
Type Synovial hinge joint
Articulations Trochlea of humerus with trochlear notch of ulna
and capitulum of humerus with head of radius
Stabilising Joint capsule, radial and ulnar collateral ligaments
factors
Movements Flexion and Extension
Joint Articulations
The elbow is a synovial hinge joint. It is formed by the articulations
between the trochlea of the humerus and the trochlear notch of the ulnar
and between the capitulum of the humerus and the head of the radius.
Joint Movements
The movements of the elbow joint are extension and flexion.
Table: Movements of the Elbow Joint

Flexion Biceps brachii, brachialis, Musculocutaneous
brachioradialis nerve, radial nerve
Extension Triceps brachii, Radial nerve
anconeus
https://mrcemsuccess.com/explanation/elbow-joint-3/?_sft_qc=posterior-arm 2/4
8/25/22, 9:29 PM Elbow Joint - MRCEM Success
Joint Ligaments
The collateral ligaments of the elbow are medial and lateral thickenings of
the joint capsule.
The radial collateral ligament arises from the lateral epicondyle of the
humerus and blends distally with the annular ligament of the radius.
The ulnar collateral ligament arises from the medial epicondyle and distally
attaches to the olecranon and coronoid process of the ulna.
The annular ligament is a strong band of fibres that encircles the head of
the radius, and retains it in contact with the radial notch of the ulna. The
annular ligament is attached by both its ends to the anterior and posterior
margins of the radial notch of the ulna.
ELBOW JOINT. (IMAGE BY OPENSTAX COLLEGE, CC BY 3.0

<HTTPS://CREATIVECOMMONS.ORG/LICENSES/BY/3.0>, VIA WIKIMEDIA
COMMONS)
https://mrcemsuccess.com/explanation/elbow-joint-3/?_sft_qc=posterior-arm 3/4
8/25/22, 9:40 PM Triceps Brachii Muscle - MRCEM Success
ANATOMY / UPPER LIMB / POSTERIOR ARM LAST UPDATED: 20TH

FEBRUARY 2019
 Bookmark
Table: Function and Innervation of the Triceps Brachii Muscle

Muscle Triceps Brachii
Function Extension of forearm at elbow (primary), extension and
adduction of arm at glenohumeral joint (via long head)
Innervation Radial nerve
The triceps brachii is the chief extensor of the forearm at the elbow joint and
acts as an accessory adductor and extensor of the arm at the glenohumeral
joint via its long head.
The triceps brachii muscle is innervated by the radial nerve.
https://mrcemsuccess.com/explanation/triceps-brachii-2/?_sft_qc=posterior-arm 2/3
8/25/22, 9:41 PM Anatomical Snuffbox - MRCEM Success
Anatomical Snuffbox LAST UPDATED: 10TH

APRIL 2019
ANATOMY / UPPER LIMB / POSTERIOR FOREARM
 Bookmark
The anatomical snuffbox is the triangular depression formed on the

posterolateral side of the dorsal wrist and 1st metacarpal by the extensor
tendons passing into the thumb.
Table: Anatomical Boundaries and Contents of the Anatomical

Snuffbox
Anatomical Structure(s)
Boundaries
Medial border Tendon of extensor pollicis longus
Lateral border Tendons of the abductor pollicis longus and extensor
pollicis brevis
Proximal Radial styloid process
border
Distal border 1st metacarpal
Floor Scaphoid and trapezium bones
Roof Skin
Contents Radial artery, terminal portion of the superficial
branch of the radial nerve, cephalic vein
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8/25/22, 9:41 PM Anatomical Snuffbox - MRCEM Success
Boundaries
It is bounded laterally by the tendons of the abductor pollicis longus and the
extensor pollicis brevis and medially by the tendon of the extensor pollicis
longus.
The floor of the anatomical snuffbox is formed by the scaphoid and trapezium
carpal bones. The radial styloid process can be palpated proximally and the
1st metacarpal can be palpated distally.
Contents
The radial artery crosses the floor of the anatomical snuffbox.
Subcutaneously terminal parts of the superficial branch of the radial nerve
and the origin of the cephalic vein pass over the anatomical snuffbox.
The anatomical snuffbox is important clinically as the scaphoid is palpable
within the snuffbox; localised pain and tenderness of the anatomical snuffbox
is most likely due to a scaphoid fracture.
https://mrcemsuccess.com/explanation/anatomical-snuffbox-2/?_sft_qc=posterior-forearm 3/4
8/25/22, 9:42 PM Extensor Retinaculum - MRCEM Success
Extensor Retinaculum LAST UPDATED: 10TH

APRIL 2019
 Bookmark
The extensor retinaculum (dorsal carpal ligament) lies obliquely across the
extensor surface of the wrist joint, and holds the extensor tendons in place
during movement of the wrist.
It is attached laterally to the anterolateral radius above the styloid process and
medially to the pisiform and triquetrum bones. It does NOT attach to the ulna.
Contents
The extensor tendons pass through the extensor tunnel, deep to the extensor
retinaculum, in six compartments lined by synovial sheaths:
The tendons of the extensor carpi ulnaris and extensor digiti
minimi have separate sheaths on the medial side of the wrist
The tendons of the extensor digitorum and extensor indicis share a
synovial sheath on the posterior surface of the wrist
The tendons of the abductor pollicis longus and extensor pollicis brevis,
the extensor carpi radialis longus and extensor carpi radialis brevis, and
the extensor pollicis longus have three separate sheaths on the lateral
side of the wrist
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8/25/22, 9:42 PM Extensor Retinaculum - MRCEM Success
EXTENSOR RETINACULUM. (IMAGE BY HENRY VANDYKE CARTER [PUBLIC DOMAIN],

DORSAL COMPARTMENTS OF WRIST: 1) EXTENSOR POLLICIS BREVIS AND ABDUCTOR

POLLICIS LONGUS TENDONS 2) EXTENSOR CARPI RADIALIS LONGUS AND BREVIS
TENDONS 3) EXTENSOR POLLICIS LONGUS TENDON 4) EXTENSOR DIGITORUM AND
https://mrcemsuccess.com/explanation/extensor-retinaculum-2/?_sft_qc=posterior-forearm 3/4
8/25/22, 9:43 PM Posterior Forearm Muscles - MRCEM Success
Posterior Forearm Muscles LAST UPDATED: 10TH

APRIL 2019
 Bookmark
The posterior forearm is divided into the superficial and deep groups:
The superficial group is made up of:
the brachioradialis
the extensor carpi radialis longus and brevis
the extensor digitorum
the extensor digiti mini
the anconeus
the extensor carpi ulnaris
The deep group is made up of:
the supinator
the abductor pollicis longus
the extensor pollicis longus and brevis
the extensor indicis
The muscles of the posterior forearm are all innervated by the radial nerve.
MUSCLES OF THE POSTERIOR FOREARM (SUPERFICIAL). (IMAGE BY HENRY VANDYKE CARTER [PUBLIC
https://mrcemsuccess.com/explanation/posterior-forearm-muscles/?_sft_qc=posterior-forearm 2/4
MUSCLES OF THE POSTERIOR FOREARM (DEEP). (IMAGE BY HENRY VANDYKE CARTER [PUBLIC DOMAIN],
Function
Table: Function and Innervation of the Posterior Forearm Muscles

Brachioradialis Flexion of elbow Radial
nerve
Extensor carpi radialis Extension and abduction of wrist Radial
longus nerve
Extensor carpi radialis Extension and abduction of wrist Radial
brevis nerve
Extensor digitorum Extension of all four fingers, extension of Radial
wrist nerve
Extensor digiti minimi Extension of little finger Radial
nerve
Extensor carpi ulnaris Extension and adduction of wrist Radial
nerve
Supinator Supination of forearm Radial
nerve
Abductor pollicis longus Abduction and extension of thumb Radial
nerve
Extensor pollicis longus Extension of thumb (CMCJ, MCPJ, IPJ) Radial
nerve
Extensor pollicis brevis Extension of thumb (CMCJ and MCPJ) Radial
nerve
Extensor indicis Extension of index finger Radial
nerve
8/25/22, 9:45 PM Deltoid Muscle - MRCEM Success
Deltoid Muscle LAST UPDATED: 8TH

APRIL 2019
ANATOMY / UPPER LIMB / SHOULDER
 Bookmark
The deltoid muscle is large and triangular shape, with its base attached to
the scapula and clavicle and its apex attached to the humerus.
Table: Function and Innervation of the Deltoid Muscle

Muscle Deltoid
Function Major abductor of shoulder
Innervation Axillary nerve
Function
The major function of the deltoid muscle is abduction of the arm
(beyond the initial 15 degrees achieved by the supraspinatus muscle).
Innervation
The deltoid is innervated by the axillary nerve, a branch of the posterior
cord of the brachial plexus.
https://mrcemsuccess.com/explanation/deltoid-3/?_sft_qc=shoulder 2/3
8/25/22, 9:45 PM Deltoid Muscle - MRCEM Success
DELTOID MUSCLE. (IMAGE MODIFIED BY FRCEM SUCCESS. ORIGINAL BY HENRY

https://mrcemsuccess.com/explanation/deltoid-3/?_sft_qc=shoulder 3/3
8/25/22, 9:45 PM Infraspinatus Muscle - MRCEM Success
Infraspinatus Muscle LAST UPDATED: 8TH

APRIL 2019
 Bookmark
The infraspinatus is part of the rotator cuff group.
Table: Function and Innervation of the Infraspinatus Muscle

Muscle Infraspinatus
Function Lateral rotation of arm at glenohumeral joint
Innervation Suprascapular nerve
Examination Infraspinatus Test: Position the patient with the arm
fully adducted, with the elbow flexed to 90 degrees.
Ask the patient to resist the medially directed force
to the arm. Test is positive if patient has pain or
weakness.
Function
It acts to laterally rotate the arm at the glenohumeral joint, together with
the teres minor muscle.
Innervation
It is innervated by the suprascapular nerve.
Examination
Infraspinatus Test: Position the patient with the arm fully adducted, with
the elbow flexed to 90 degrees. Ask the patient to resist the medially
directed force to the arm. The test is positive if the patient has pain or
weakness.
https://mrcemsuccess.com/explanation/infraspinatus-2/?_sft_qc=shoulder 2/3
8/25/22, 9:45 PM Infraspinatus Muscle - MRCEM Success
INFRASPINATUS MUSCLE. (IMAGE MODIFIED BY FRCEM SUCCESS. ORIGINAL BY

https://mrcemsuccess.com/explanation/infraspinatus-2/?_sft_qc=shoulder 3/3
8/25/22, 9:45 PM Rotator Cuff Injury - MRCEM Success
Rotator Cuff Injury LAST UPDATED:

25TH JANUARY 2019
 Bookmark
The two main disorders of the rotator cuff are impingement and
tendinopathy.
The supraspinatus muscle is the most commonly injured rotator cuff
muscle as it passes beneath the acromion and the acromioclavicular
ligament. This space is fixed, therefore any swelling of the supraspinatus
muscle, excessive fluid in the subacromial/subdeltoid bursa or
subacromial bony spurs, may produce significant impingement when the
arm is abducted. The blood supply to the supraspinatus tendon is
relatively poor and the tendon is susceptible to degenerative change,
which in turn, makes it more susceptible to trauma and partial or full-
thickness tears may occur. This will result in painful or weak abduction of
the arm at the shoulder.
https://mrcemsuccess.com/explanation/rotator-cuff-injury/?_sft_qc=shoulder 2/2
8/25/22, 9:46 PM Shoulder Joint - MRCEM Success
Shoulder Joint LAST UPDATED: 8TH

APRIL 2019
 Bookmark
Table: Anatomical Overview of the Shoulder Joint

Joint Shoulder (Glenohumeral)
Type Synovial ball and socket joint
Articulations Head of humerus and glenoid cavity of scapula
Stabilising Rotator cuff muscle tendons, long head of biceps brachii muscle
Factors tendon, coracoacromial arch, extracapsular ligaments
(glenohumeral ligaments, coracohumeral ligament, transverse
humeral ligament)
Movements Flexion, extension, abduction, adduction, medial rotation and
lateral rotation
Joint Articulations
The glenohumeral joint is a synovial ball and socket joint occurring between the head of
the humerus and the glenoid cavity of the scapula. The glenoid cavity is deepened and
expanded peripherally by a fibrocartilaginous collar (the glenoid labrum), which attaches
to the margin of the fossa, and is continuous superiorly with the tendon of the long head
of the biceps brachii.
https://mrcemsuccess.com/explanation/glenohumeral-joint-2/?_sft_qc=shoulder 2/6
GLENOHUMERAL JOINT. (IMAGE BY OPENSTAX COLLEGE [CC BY 3.0

Joint Movements
Movements at the joint include flexion, extension, abduction, adduction, medial rotation
and lateral rotation.
Table: Movements of the Shoulder Joint

Flexion Pectoralis major, deltoid, Pectoral nerves, axillary nerve,
coracobrachialis, biceps musculocutaneous nerve
brachii
Extension Deltoid and latissimus dorsi, Axillary nerve, thoracodorsal
teres major, triceps brachii nerve, lower subscapular nerve,
radial nerve
Abduction Deltoid and supraspinatus Axillary nerve, suprascapular
nerve
Adduction Pectoralis major, latissimus Pectoral nerves, thoracodorsal
dorsi, triceps brachii nerve, radial nerve
Medial Subscapularis, pectoralis Subscapular nerves, pectoral
Rotation major, latissimus dorsi, nerves, thoracodorsal nerve
teres major
Lateral Infraspinatus and teres Suprascapular nerve, axillary
Rotation minor nerve
Table: Muscular Innervation of the Shoulder Joint

Nerve Muscle(s) Shoulder Movements
Long thoracic Serratus Protraction and retraction of scapula
nerve anterior
Thoracodorsal Latissimus Adduction, medial rotation and extension of
nerve dorsi shoulder
Spinal Trapezius Elevation of scapula, rotation of scapula
accessory during shoulder abduction, retraction and
nerve depression of scapula
Suprascapular Supraspinatus; Initiation of abduction of shoulder to 15
nerve infraspinatus degrees; Lateral rotation of shoulder
Subscapular Subscapularis; Medial rotation of shoulder; Medial rotation
nerves teres major and extension of shoulder
Pectoral Pectoralis Flexion, adduction and medial rotation of
nerves major; shoulder; Depresses tip of shoulder and
pectoralis protracts scapula
minor
Axillary nerve Deltoid; teres Major abductor of shoulder; Lateral rotation
minor of shoulder
Joint Stability
The glenohumeral joint has a wide range of movements provided at the cost of skeletal
stability. Joint stability is provided by the rotator cuff muscles, the long head of the
biceps brachii muscle, related bony processes and extracapsular ligaments.
EXTRACAPSULAR LIGAMENTS:
The fibrous membrane of the joint capsule is thickened:
Anterosuperiorly in three locations to form the glenohumeral ligaments (superior,
middle and inferior) which pass from the superomedial margin of the glenoid
cavity to the lesser tubercle and inferiorly related anatomical neck of the humerus.
and act to reinforce the anterior part of the joint capsule.
Superiorly to form the coracohumeral ligament which passes between the base of
the coracoid process and the greater tubercle of the humerus, and acts to
strengthen the joint capsule superiorly.
Between the greater and lesser tubercles of the humerus to form the transverse
humeral ligament which bridges over the intertubercular sulcus. This holds the
synovial sheath and the tendon of the biceps brachii in place during movements of
the glenohumeral joint.
EXTRACAPSULAR LIGAMENTS OF SHOULDER JOINT. (IMAGE BY HENRY VANDYKE CARTER

CORACOACROMIAL ARCH:
The coracoacromial arch is formed superiorly by the acromion and the coracoid process
of the scapula with the coracoacromial ligament spanning between them. This structure
prevents superior displacement of the humerus.
ROTATOR CUFF:
Tendons of the rotator cuff muscles blend with the joint capsule and form a
musculotendinous collar that surrounds the posterior, superior and anterior aspects of
the glenohumeral joint. This cuff of muscles stabilises and holds the head of the
humerus in the glenoid cavity of the scapular without compromising the arms' flexibility
and range of motion.
BICEPS BRACHII TENDON:
The tendon of the long head of the biceps brachii muscle passes superiorly through the
joint and restricts upwards movement of the humeral head on the glenoid cavity.
8/25/22, 9:47 PM Shoulder Joint Dislocation - MRCEM Success
Shoulder Joint LAST UPDATED: 8TH

MAY 2022
Dislocation  Bookmark
Dislocation of the shoulder joint most commonly occurs in an anterior

direction.
Clinical Features
Severe shoulder pain
All movements limited and painful
Affected arm supported by unaffected arm
Loss of normal contour of deltoid (flattened shoulder)
Step-off deformity at acromion (with palpable gap inferior to
acromion)
Humeral head palpable anteriorly and below the coracoid process
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8/25/22, 9:47 PM Shoulder Joint Dislocation - MRCEM Success
ANTERIOR SHOULDER DISLOCATION. (IMAGE BY HELLERHOFF [CC BY-SA 3.0

(HTTPS://CREATIVECOMMONS.ORG/LICENSES/BY-SA/3.0)], FROM WIKIMEDIA
COMMONS)
Complications
Common complications of anterior shoulder dislocation include:
Axillary nerve damage (paralysis of the teres minor and deltoid with
weakness of lateral rotation and abduction, and loss of sensation
over 'regimental badge' area on lateral arm)
Posterior humeral circumflex vessel damage
Bankart lesion (avulsion of the glenoid labrum at the insertion of the
inferior glenohumeral ligament)
Rotator cuff damage
Shoulder joint instability
Injury to brachial plexus
https://mrcemsuccess.com/explanation/shoulder-joint-dislocation/?_sft_qc=shoulder 3/3
8/25/22, 9:47 PM Supraspinatus Muscle - MRCEM Success
Supraspinatus Muscle LAST UPDATED:

14TH JULY 2019
 Bookmark
The supraspinatus is part of the rotator cuff group of muscles.
Table: Function and Innervation of the Supraspinatus Muscle

Muscle Supraspinatus
Function Initiation of abduction of shoulder to 15 degrees
(and then assistance of deltoid with continued
abduction)
Innervation Suprascapular nerve
Examination Empty Can Test: Position the patient with arms
elevated to 90 degrees in the scapular plane, with
the elbow extended, and full medial rotation and
pronation of the forearm with thumbs pointing
downwards. Ask the patient to resist the downward
force being applied to the forearm. Test is positive
is patient has pain or weakness.
Function
The supraspinatus acts to initiate abduction of the arm to 15 degrees and
then assists the deltoid with continued abduction to 90 degrees.
Innervation
The supraspinatus is innervated by the suprascapular nerve.
Examination
The supraspinatus muscle can be assessed using the 'empty can' test. The
'empty can' test can be performed by positioning the patient with the arm
in 90 degrees of forward flexion, in the plane of the scapula
https://mrcemsuccess.com/explanation/supraspinatus-5/?_sft_qc=shoulder 2/3
8/25/22, 9:47 PM Supraspinatus Muscle - MRCEM Success
(approximately 30 degrees of abduction) and in full internal rotation with

the thumb pointing down (as if emptying a can). The patient is asked to
forward flex their arm against resistance, and the test is considered
positive if there is significant pain and/or weakness.
SUPRASPINATUS MUSCLE. (IMAGE MODIFIED BY FRCEM SUCCESS. ORIGINAL BY

https://mrcemsuccess.com/explanation/supraspinatus-5/?_sft_qc=shoulder 3/3
8/25/22, 9:48 PM Teres Minor Muscle - MRCEM Success
Teres Minor Muscle LAST UPDATED: 8TH

APRIL 2019
 Bookmark
The teres minor is part of the rotator cuff.
Table: Function and Innervation of the Teres Minor Muscle

Muscle Teres Minor
Function Lateral rotation of arm at glenohumeral joint
Innervation Axillary nerve
Examination Hornblower’s Test: Position the patient with the arm
elevated to 90 degrees in the scapular plane and
the elbow flexed to 90 degrees. Ask the patient to
laterally rotate the arm against resistance. Test is
positive if patient has pain or weakness.
Function
It acts to laterally rotate the arm at the glenohumeral joint, together with
the infraspinatus muscle.
Innervation
It is innervated by the axillary nerve.
Examination
Hornblower's Test: Position the patient with the arm elevated to 90
degrees in the scapular plane and the elbow flexed to 90 degrees. Ask the
patient to laterally rotate the arm against resistance. The test is positive if
the patient has pain or weakness.
https://mrcemsuccess.com/explanation/teres-minor-2/?_sft_qc=shoulder 2/3
8/25/22, 9:48 PM Teres Minor Muscle - MRCEM Success
TERES MINOR MUSCLE. (IMAGE MODIFIED BY FRCEM SUCCESS. ORIGINAL BY

https://mrcemsuccess.com/explanation/teres-minor-2/?_sft_qc=shoulder 3/3
8/25/22, 9:49 PM Carpal Tunnel - MRCEM Success
Carpal Tunnel LAST UPDATED:

10TH APRIL 2019
ANATOMY / UPPER LIMB / WRIST AND HAND
 Bookmark
Table: Anatomical Boundaries and Contents of the Carpal Tunnel

Anatomical Structure(s)
Boundaries
Roof Flexor retinaculum
Carpal arch Pisiform and hook of the hamate medially, tubercles
of the scaphoid and trapezium laterally
Contents Four tendons of flexor digitorum profundus, four
tendons of flexor digitorum superficialis, tendon of
flexor pollicis longus, median nerve
Anatomical Boundaries
The carpal tunnel is formed by a deep carpal arch and a superficial flexor
retinaculum.
The base of the carpal tunnel is formed medially by the pisiform and the
hook of the hamate and laterally by the tubercles of the scaphoid and
trapezium.
The flexor retinaculum is a thickened band of fibrous connective tissue on
the volar aspect of the hand, which bridges the gap between these carpal
bones and forms the roof of the carpal tunnel.
Contents
The following structures pass through the carpal tunnel:
the four tendons of the flexor digitorum profundus (FDP)
the four tendons of the flexor digitorum superficialis (FDS)
the tendon of the flexor pollicis longus (FPL)
the median nerve.
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8/25/22, 9:49 PM Carpal Tunnel - MRCEM Success
Free movement of the tendons in the carpal tunnel is facilitated by

synovial sheaths, which surround the tendons. All of the tendons of the
FDP and FDS are contained within a single synovial sheath with a separate
sheath enclosing the tendon of the FPL. The median nerve lies anterior to
the tendons in the carpal tunnel.
CARPAL TUNNEL. (IMAGE MODIFIED BY FRCEM SUCCESS. ORIGINAL BY HENRY

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8/25/22, 9:49 PM Carpal Tunnel Syndrome - MRCEM Success
Carpal Tunnel Syndrome LAST UPDATED:

16TH AUGUST 2020
 Bookmark
Carpal tunnel syndrome (CTS) is caused by compression of the median

nerve within the carpal tunnel at the wrist.
Aetiology
In most people the cause of carpal tunnel syndrome is not known
Factors that have strong evidence supporting an increased risk of
CTS include:
Activities with high hand/wrist repetition rate
Obesity
Clinical Features
Symptoms
Numbness, tingling and pain in distribution of the median
nerve (palmar surface and fingertips of lateral three and a half
digits - lateral palm is typically spared as the palmar
cutaneous branch of the median nerve does not pass through
the carpal tunnel)
Symptoms often worse at night
May be unilateral or bilateral
Pain may radiate up forearm
Loss of grip strength, clumsiness and reduced manual
dexterity
Signs
Sensory loss in distribution of the median nerve
Atrophy of thenar muscles
Reduced strength of thumb abduction
Positive Tinel's test (tapping lightly over the nerve at the wrist
elicits symptoms in the median nerve distribution
Positive Phalen's test (holding the wrist in flexion for 60s
elicits symptoms in the median nerve distribution)
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8/25/22, 9:49 PM Carpal Tunnel Syndrome - MRCEM Success
Positive carpal tunnel compression test (pressure over the

proximal end of the carpal ligament (proximal wrist crease)
with the thumbs elicits symptoms in the median nerve
distribution)
UNTREATED CARPAL TUNNEL SYNDROME. (IMAGE BY DR. HARRY GOUVAS, MD,

PHD [PUBLIC DOMAIN], VIA WIKIMEDIA COMMONS)
Management
Lifestyle modifications
Wrist splinting in neutral position
Corticosteroid injections
Carpal tunnel decompression surgery
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8/25/22, 9:49 PM Flexor Retinaculum - MRCEM Success
Flexor Retinaculum LAST UPDATED:

10TH APRIL 2019
 Bookmark
The flexor retinaculum (transverse carpal ligament) is a thickened band of

fibrous connective tissue on the volar aspect of the hand which forms the
roof of the carpal tunnel. The flexor retinaculum holds the flexor tendons
in place at the wrist and prevents them from bowstringing.
It is attached laterally to the scaphoid and trapezium and medially to the
pisiform and the hook of the hamate. The thenar and hypothenar muscles
arise from the flexor retinaculum.
Relations
The ulnar artery, ulnar nerve, and tendon of the palmaris longus
pass into the hand anterior to the flexor retinaculum, and therefore
do not pass through the carpal tunnel.
The flexor carpi radialis tendon passes through the lateral aspect of
the flexor retinaculum into the hand.
The four tendons of the flexor digitorum profundus, the four
tendons of the flexor digitorum superficialis, the tendon of the flexor
pollicis longus and the median nerve pass into the hand posterior to
the flexor retinaculum, within the carpal tunnel.
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8/25/22, 9:49 PM Flexor Retinaculum - MRCEM Success
FLEXOR RETINACULUM. (IMAGE MODIFIED BY FRCEM SUCCESS. ORIGINAL BY

https://mrcemsuccess.com/explanation/flexor-retinaculum-3/?_sft_qc=wrist-and-hand 3/3
8/25/22, 9:50 PM Flexor Sheath Infection - MRCEM Success
Flexor Sheath Infection LAST UPDATED:

12TH AUGUST 2019
 Bookmark
Infections may occur in the digital synovial sheath for example after a
puncture wound to a finger.
Infection in the middle three fingers is usually contained as they have
separate synovial sheaths.
The synovial sheath of the little finger is usually continuous with the
common flexor sheath (the ulnar bursa) and thus infection may spread to
this sheath and from here to the midpalmar space.
Infections in the thumb may spread to the midpalmar space via the
continuous synovial sheath of the flexor pollicis longus (the radial bursa).
FLEXOR SHEATHS. (IMAGE BY HENRY VANDYKE CARTER [PUBLIC DOMAIN], VIA

WIKIMEDIA COMMONS)
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8/25/22, 9:50 PM Hand Movements - MRCEM Success
Hand Movements LAST UPDATED:

29TH JANUARY 2019
 Bookmark
Hand movements are complex. The table below shows an overview of

hand and thumb movements and the main muscles bringing about these
movements.
Table: Movements of the Finger Joints

Finger Primary Muscle (Assisting Muscles)
Movements
Flexion of MCPJ Lumbricals (flexor digitorum superficialis,
of digits 2 – 5 flexor digitorum profundus, flexor digiti minimi,
interossei)
Flexion of PIPJ of Flexor digitorum superficialis (flexor digitorum
digits 2 – 5 profundus)
Flexion of DIPJ of Flexor digitorum profundus
digits 2 – 5
Extension of Extensor digitorum, extensor indicis, extensor
MCPJ of digits 2 digiti minimi
–5
Extension of PIPJ Lumbricals and interossei (extensor digitorum)
and DIPJ of digits
2–5
Adduction of Palmar interossei
digits 2 – 5
Abduction of Dorsal interossei
digits 2 – 4
Abduction of little Abductor digiti minimi
finger
Opposition of Opponens digiti minimi
little finger
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8/25/22, 9:50 PM Hand Movements - MRCEM Success
Table: Movement of the Thumb Joints

Thumb Movements Primary Muscle(s)
Flexion of thumb at MCPJ Flexor pollicis longus and
brevis
Flexion of thumb at IPJ Flexor pollicis longus
Extension of thumb at CMCJ and Extensor pollicis longus and
MCPJ brevis
Extension of thumb at IPJ Extensor pollicis longus
Abduction of thumb Abductor pollicis longus and
brevis
Adduction of thumb Adductor pollicis
Opposition of thumb Opponens pollicis
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8/25/22, 9:50 PM Hypothenar Muscles - MRCEM Success
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Hypothenar Muscles LAST UPDATED:

10TH APRIL 2019
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The hypothenar muscles are the opponens digiti minimi, the abductor
digiti minimi and the flexor digiti minimi, all innervated by the ulnar nerve.
HYPOTHENAR EMINENCE: ABDUCTOR DIGITI MINIMI (GREEN), FLEXOR DIGITI

MINIMI (RED), OPPONENS DIGITI MINIMI (BLUE). (IMAGE MODIFIED BY FRCEM
SUCCESS. ORIGINAL BY OPENSTAX [CC BY 4.0
COMMONS)
Function
Table: Function and Innervation of the Hypothenar Muscles
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8/25/22, 9:50 PM Hypothenar Muscles - MRCEM Success

Opponens digiti Laterally rotates little Ulnar nerve
minimi finger
Abductor digiti minimi Abducts little finger at Ulnar nerve
MCPJ
Flexor digiti minimi Flexes little finger at Ulnar nerve
brevis MCPJ
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8/25/22, 9:51 PM Interosseus Muscles - MRCEM Success
Interosseus Muscles LAST UPDATED:

10TH APRIL 2019
 Bookmark
Attachments
The interossei muscles originate from and lie between the
metacarpal bones.
The dorsal interossei insert into the extensor hoods and proximal
phalanges of the index, middle and ring finger.
The palmar interossei insert into the extensor hoods of the index,
ring and little finger.
Function
The four dorsal interossei act to abduct the index, middle and ring
fingers at the MCPJs (DAB).
The three palmar interossei act to adduct the index, ring and little
fingers at the MCPJs (PAD).
Because the interossei muscles insert into the extensor hoods, they
also contribute to the complex flexion and extension movements of
the interphalangeal joints of the digits.
Innervation
The interossei muscles are all innervated by the ulnar nerve.
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8/25/22, 9:51 PM Interosseus Muscles - MRCEM Success
INTEROSSEI MUSCLES. (IMAGE MODIFIED BY FRCEM SUCCESS. ORIGINAL BY

OPENSTAX [CC BY 4.0 (HTTP://CREATIVECOMMONS.ORG/LICENSES/BY/4.0)],
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8/25/22, 9:52 PM Lumbrical Muscles - MRCEM Success
Lumbrical Muscles LAST UPDATED:

10TH APRIL 2019
 Bookmark
The lumbrical muscles originate from the tendons of the flexor digitorum
profundus in the palm and insert into the extensor hoods of the medial four
fingers.
Function
The lumbrical muscles act to flex these fingers at the metacarpophalangeal
joints (MCPJs) and extend them at the interphalangeal joints (IPJs).
Innervation
The medial two lumbricals are innervated by the ulnar nerve and the lateral
two lumbricals are innervated by the median nerve.
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8/25/22, 9:52 PM Palmar Aponeurosis - MRCEM Success
Palmar Aponeurosis LAST UPDATED:

25TH JANUARY 2019
 Bookmark
The palmar aponeurosis is a thickened area of palmar fascia which is

continuous proximally with the palmaris longus tendon and the flexor
retinaculum. Distally, the palmar aponeurosis fans out into four slips which
become the fibrous digital sheaths.
The palmar aponeurosis protects the underlying soft tissue and long flexor
tendons. The fibrous digital sheaths cover the synovial sheaths which
contain the flexor tendons, maintaining the tension and preventing
bowstringing.
PALMAR APONEUROSIS. (IMAGE BY HENRY VANDYKE CARTER [PUBLIC DOMAIN],

https://mrcemsuccess.com/explanation/palmar-aponeurosis/?_sft_qc=wrist-and-hand 2/3
8/25/22, 9:53 PM Palmar Arches - MRCEM Success
Palmar Arches LAST UPDATED:

10TH APRIL 2019
 Bookmark
There are two palmar arches which supply the hand. Laceration to the
palmar arches results in profuse bleeding.
Superficial Palmar Arch

The ulnar artery forms the superficial palmar arch which communicates
laterally with a palmar branch of the radial artery. The superficial palmar
arch lies superficial to the long flexor tendons of the digits and just deep to
the palmar aponeurosis. It is located across the centre of the palm, about
level with the distal border of the extended thumb.
Deep Palmar Arch

The radial artery forms the deep palmar arch which communicates medially
with the deep palmar branch of the ulnar artery. The deep palmar arch lies
between the metacarpal bones and the long flexor tendons of the digits. It
is located approximately 1 cm proximal to the superficial palmar arch.
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8/25/22, 9:53 PM Palmar Arches - MRCEM Success
PALMAR ARCHES. (IMAGE BY RHCASTILHOS (GRAY1237.PNG) [PUBLIC DOMAIN],

https://mrcemsuccess.com/explanation/palmar-arches/?_sft_qc=wrist-and-hand 3/3
8/25/22, 9:53 PM Thenar Muscles - MRCEM Success
Thenar Muscles LAST UPDATED: 10TH

APRIL 2019
 Bookmark
The thenar eminence consists of the opponens pollicis, the abductor pollicis
brevis and the flexor pollicis brevis muscles.
The thenar muscles are all innervated by the median nerve.
THENAR EMINENCE. (IMAGE MODIFIED BY FRCEM SUCCESS. ORIGINAL BY OPENSTAX

COMMONS)
Function
Table: Function and Innervation of the Thenar Muscles

Opponens pollicis Medially rotates thumb Median nerve
Abductor pollicis brevis Abducts thumb at MCPJ Median nerve
Flexor pollicis brevis Flexes thumb at MCPJ Median nerve
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8/25/22, 9:53 PM Wrist Joint - MRCEM Success
Wrist Joint LAST UPDATED: 10TH

APRIL 2019
 Bookmark
Table: Anatomical Overview of the Wrist Joint

Joint Wrist joint
Type Synovial condyloid joint
Articulations Distal end of the radius and articular disc with scaphoid,
lunate and triquetrum
Stabilising Joint capsule, palmar radiocarpal, palmar ulnocarpal
factors and dorsal radiocarpal ligaments, radial and ulnar
collateral ligaments of the wrist joint
Movements Flexion and extension, abduction and adduction
Articulations
The wrist joint is a synovial condyloid joint occurring between the distal end of
the radius and the articular disc overlying the distal end of the ulna and
the scaphoid, lunate and triquetrum.
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8/25/22, 9:53 PM Wrist Joint - MRCEM Success
WRIST JOINT. (IMAGE MODIFIED BY FRCEM SUCCESS. ORIGINAL BY HENRY VANDYKE

Ligaments
The capsule of the wrist joint is reinforced by palmar radiocarpal, palmar
ulnocarpal and dorsal radiocarpal ligaments. The radial and ulnar collateral
ligaments of the wrist joint reinforce the medial and lateral sides of the wrist
joint.
Movements
The wrist joint allows movement around two axes; the hand can be abducted
and adducted, and flexed and extended at the wrist joint.
Table: Movements of the Wrist Joint

Movement Main Muscles Involved Main
Nerves
Involved
Flexion Flexor carpi radialis, flexor carpi ulnaris, Median
flexor digitorum profundus, flexor digitorum and
superficialis, palmaris longus ulnar
nerves
Extension Extensor carpi radialis longus and brevis, Radial
extensor carpi ulnaris, extensor digitorum nerve
Abduction Flexor carpi radialis, extensor carpi radialis Median
longus and brevis and
radial
nerves
Adduction Flexor carpi ulnaris, extensor carpi ulnaris Ulnar
and
radial
nerves

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LOWER
LIMB
8/25/22, 11:13 PM Ankle Joint - MRCEM Success
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Ankle Joint LAST UPDATED: 10TH

APRIL 2019
ANATOMY / LOWER LIMB / ANKLE AND FOOT JOINTS
 Bookmark
Table: Anatomical Overview of the Ankle Joint

Joint Ankle
Type Synovial hinge joint
Articulations Talus with the inferior tibia and talus with the medial
malleolus of the tibia and the lateral malleolus of the fibula
Stabilising Shape of talus bone and articulations with malleoli; Medial
factors and lateral collateral ligaments
Movements Flexion and extension
Joint articulations
The ankle joint is a hinge type synovial joint formed between the distal ends of the
tibia and fibula, and the superior part of the talus.
The tibia and fibula are bound together by strong tibiofibular ligaments forming a
deep bracket-shaped socket, which the talus bone then fits into. The talus bone
articulates with the tibia in two places; the inferior surface of the tibia forms the
roof of the socket and its medial malleolus articulates with the medial surface of the
talus bone. The lateral malleolus of the fibula articulates with the lateral surface of
the talus bone. The articulation of the talus with the inferior tibia forms the
weightbearing surface and the articulations of the talus with the malleoli act to
stabilise the joint.
The articular surface of the talus is much wider anteriorly than it is posteriorly,
therefore the bone fits more tightly in the socket when the foot is dorsiflexed (and
the wider surface of the talus moves into the ankle joint), making the joint more
stable in dorsiflexion. Conversely the ankle joint is weakest during plantarflexion
(when the narrower part of the talus is in the joint) and it is in this position that the
majority of ankle injuries occur - usually as a result of the sudden inversion of the
foot.
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Ligaments
The ankle joint is supported on each side by the medial (deltoid) and lateral
collateral ligaments.
The large strong deltoid ligament is triangular in shape, attached proximally to the
medial malleolus at its apex and its broad base attached distally to a line that
extends from the tuberosity of the navicular bone anteriorly to the medial tubercle
of the talus posteriorly. The medial ligament is subdivided into four parts: the
tibionavicular part, the tibiocalcaneal part, the posterior tibiotalar part and the
anterior tibiotalar part. It acts to prevent overeversion of the foot and helps
maintain the medial longitudinal arch.
The weaker lateral ligament is actually composed of three separate ligaments all
originating from the lateral malleolus; the anterior talofibular ligament (attaching to
the anterior talus), the posterior talofibular ligament (attaching to the posterior
talus) and the calcaneofibular ligament (attaching to the calcaneus). It resists
inversion of the foot and is frequently injured in ankle sprain inversion injuries. The
most commonly affected ligament is the anterior talofibular ligament followed by
the calcaneofibular ligament and then the posterior talofibular ligament.
ANKLE JOINT. (IMAGE BY OPENSTAX COLLEGE [CC BY 3.0

Joint movements
The ankle joint allows dorsiflexion and plantarflexion of the foot.
Table: Movements of the Ankle Joint

Movement Main Muscles Involved Main Nerves
Involved
Dorsiflexion Tibialis anterior, Extensor hallucis Deep fibular
longus, Extensor digitorum longus, nerve
Fibularis tertius
Plantarflexion Gastrocnemius, Plantaris, Soleus, Flexor Tibial nerve,
hallucis longus, Tibialis posterior, Superficial
Fibularis longus fibular nerve
8/25/22, 11:14 PM Foot Arches - MRCEM Success
Foot Arches LAST UPDATED: 10TH

APRIL 2019
ANATOMY / LOWER LIMB /
ANKLE AND FOOT JOINTS  Bookmark
The bones of the foot form longitudinal and transverse arches (relative to the
ground) which absorb and distribute weight bearing forces during standing
and moving.
The longitudinal arch is formed between the posterior end of the calcaneus
and the heads of the metatarsals and has a medial and lateral part.
Table: Constituent Bones and Prime Supporting Factors of the

Longitudinal Foot Arches
Arch Constituent Tarsal Prime Supporting Factors
Bones
Medial Calcaneus, talus, Spring ligament, deltoid
longitudinal navicular, three ligament, plantar aponeurosis
arch cuneiforms and and tendons of the tibialis
medial three anterior and tibialis posterior
metatarsal bones muscles
Lateral Calcaneus, cuboid Plantar aponeurosis, fibularis
longitudinal and lateral two longus tendon, long and short
arch metatarsal bones plantar ligament
Medial Longitudinal Arch

The higher medial longitudinal arch is formed and maintained by the
interlocking of the calcaneus, the talus, the navicular, the three cuneiforms
and the medial three metatarsal bones. The medial longitudinal arch is
supported by the spring ligament, the deltoid ligament, the plantar
aponeurosis, the small muscles in the sole of the foot and the tendons of the
tibialis anterior, tibialis posterior and flexor hallucis longus muscles which
provide passive and dynamic support.
Lateral Longitudinal Arch
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The lateral longitudinal arch is formed from the calcaneus, the cuboid and the
lateral two metatarsal bones. The lateral longitudinal arch is flatter than the
medial part and rests on the ground during standing. The lateral longitudinal
arch is supported by the the long and short plantar ligament and the fibularis
longus tendon together with the extensor tendons and the short muscles of
the little toe.
ARCHES OF THE FOOT: MEDIAL AND LATERAL VIEWS. (IMAGE BY OPENSTAX COLLEGE
COMMONS)
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8/25/22, 11:15 PM Foot Movements - MRCEM Success
Foot Movements LAST UPDATED: 11TH

APRIL 2019
ANATOMY / LOWER LIMB / ANKLE AND FOOT JOINTS
 Bookmark
Intertarsal joints
There are numerous synovial joints between the individual tarsal bones which allow
movements of the foot, the most important of these being:
the subtalar joint (between the inferior surface of the talus and the superior
surface of the calcaneus)
the talocalcaneonavicular (between the head of the talus and the calcaneus
and spring ligament below, and the navicular in front)
the calcaneocuboid joints (between the anterior calcaneus and the posterior
cuboid)
The talocalcaneonavicular joint and the calcaneocuboid joints are together often
referred to as the transverse tarsal joint.
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8/25/22, 11:15 PM Foot Movements - MRCEM Success
TARSAL BONES. (IMAGE BY OPENSTAX COLLEGE [CC BY 3.0

Joint Movements
The subtalar and transverse tarsal joints allow inversion and eversion of the foot.
Table: Movements of the Foot Joints

Inversion Tibialis anterior and Deep fibular nerve, Tibial nerve
posterior
Eversion Fibularis longus, brevis Superficial fibular nerve, Deep
and tertius fibular nerve
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8/25/22, 11:15 PM Spring Ligament - MRCEM Success
Spring Ligament LAST UPDATED: 25TH

JANUARY 2019
The spring ligament (plantar calcaneonavicular ligament) is a broad thick

ligament that extends from the calcaneus to the navicular bone. It supports
the head of the talus, stabilises the talocalcaneonavicular joint and resists
depression of the medial arch of the foot. The spring ligament takes the weight
of the body from the talus and transmits it to the forefoot.
SPRING LIGAMENT. (IMAGE MODIFIED BY FRCEM SUCCESS. ORIGINAL BY HENRY

https://mrcemsuccess.com/explanation/tarsal-joint-ligaments/?_sft_qc=ankle-and-foot-joints 2/2
8/25/22, 11:16 PM Tarsal Bones - MRCEM Success
Tarsal Bones LAST UPDATED: 10TH

APRIL 2019
There are three groups of bones in the foot: the seven tarsal bone, the five
metatarsal bones and the fourteen phalanges.
The tarsal bones are organised into three rows:
Proximal group: Talus and Calcaneus
Intermediate: Navicular
Distal group: Cuboid and Cuneiforms
TARSAL BONES. (IMAGE BY OPENSTAX COLLEGE [CC BY 3.0

https://mrcemsuccess.com/explanation/tarsal-bones/?_sft_qc=ankle-and-foot-joints 2/3
8/25/22, 11:16 PM Tarsal Bones - MRCEM Success
Articulations
Table: Articulations of the Tarsal Bones

Tarsal Bone Articulations
Talus Tibia and fibula superiorly, calcaneus inferiorly and
navicular anteriorly
Calcaneus Talus superiorly and cuboid anteriorly
Navicular Talus posteriorly and cuboid and three cuneiforms
anteriorly
Cuboid Calcaneus and navicular posteriorly, lateral cuneiform
medially and bases of lateral two metatarsals anteriorly
Lateral Navicular posteriorly, cuboid laterally and 3rd
cuneiform metatarsal anteriorly
Intermediate Navicular posteriorly and 2nd metatarsal anteriorly
cuneiform
Medial Navicular posteriorly and 1st metatarsal anteriorly
cuneiform
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8/25/22, 11:16 PM Anterior Leg Muscles - MRCEM Success
Anterior Leg Muscles LAST UPDATED: 11TH

APRIL 2019
ANATOMY / LOWER LIMB / ANTERIOR LEG
 Bookmark
The anterior compartment of the leg is made up of four muscles: the tibialis
anterior, the extensor hallucis longus, the extensor digitorum longus and the
fibularis tertius which collectively dorsiflex the foot at the ankle joint.
Table: Function and Innervation of the Anterior Leg Muscles

Tibialis Dorsiflexion and inversion of foot, Deep fibular
anterior support of medial arch of foot nerve
Extensor Extension of great toe and Deep fibular
hallucis dorsiflexion of foot nerve
longus
Extensor Extension of lateral four toes and Deep fibular
digitorum dorsiflexion of foot nerve
longus
Fibularis Dorsiflexion and eversion of foot Deep fibular
tertius nerve
Innervation
These muscles are all innervated by the deep fibular nerve.
Function
The tibialis anterior dorsiflexes the foot at the ankle, inverts the foot at the
intertarsal joints and provides dynamic support of the medial arch of the foot
while walking.
The extensor hallucis longus extends the great toe and dorsiflexes the foot at
the ankle joint.
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8/25/22, 11:16 PM Anterior Leg Muscles - MRCEM Success
The extensor digitorum longus extends the lateral four toes and dorsiflexes
the foot at the ankle.
The fibularis tertius, sometimes considered part of the extensor digitorum
longus, assists in dorsiflexion and eversion of the foot.
ANTERIOR LEG MUSCLES: TIBIALIS ANTERIOR (RED), EXTENSOR HALLUCIS LONGUS

(GREEN), EXTENSOR DIGITORUM LONGUS (BLUE), FIBULARIS TERTIUS
(YELLOW). (IMAGE MODIFIED BY FRCEM SUCCESS. ORIGINAL BY HENRY VANDYKE
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8/25/22, 11:17 PM Deep Fibular Nerve - MRCEM Success
Deep Fibular Nerve LAST UPDATED: 6TH

DECEMBER 2020
ANATOMY / LOWER LIMB / ANTERIOR LEG /
INNERVATION OF LOWER LIMB  Bookmark
The deep fibular nerve is a branch of the common fibular nerve.
Table: Anatomical Overview of the Deep Fibular Nerve

Nerve Deep Fibular
Nerve L4 -L5
roots
Motor Anterior compartment of leg
supply
Sensory Webspace between 1st and 2nd toes
supply
Injury Motor Loss: Loss of dorsiflexion of ankle and extension of
toes, foot drop with high-stepping gait, weakness of foot
inversion
Sensory Loss: Loss of sensation over webspace between 1st
and 2nd toes
Anatomical Course
https://mrcemsuccess.com/explanation/deep-fibular-nerve/?_sft_qc=anterior-leg 2/5
DEEP FIBULAR NERVE. (IMAGE BY HENRY VANDYKE CARTER [PUBLIC DOMAIN], VIA
WIKIMEDIA COMMONS)
Function
It innervates the anterior leg (tibialis anterior, extensor hallucis longus,
extensor digitorum longus, fibularis tertius) and the dorsal intrinsic muscles of
the foot. It supplies skin over the webspace between the 1st and 2nd toes.
Table: Motor Supply of the Deep Fibular Nerve
Muscle Function
Tibialis anterior Dorsiflexion and inversion of foot, support of
medial arch of foot
Extensor hallucis Extension of great toe and dorsiflexion of foot
longus
Extensor digitorum Extension of lateral four toes and dorsiflexion of
longus foot
Fibularis tertius Dorsiflexion and eversion of foot
CUTANEOUS INNERVATION OF LOWER LIMB. (IMAGE MODIFIED BY FRCEM SUCCESS.

8/25/22, 11:18 PM Tibial Arteries - MRCEM Success
Tibial Arteries LAST UPDATED:

11TH APRIL 2019
ANATOMY / LOWER LIMB / ANTERIOR LEG /
POSTERIOR LEG  Bookmark
After exiting the popliteal fossa between the gastrocnemius and

popliteus muscle, the popliteal artery bifurcates into the anterior and
posterior tibial arteries at the lower border of the popliteus.
Anterior Tibial Artery

The anterior tibial artery penetrates the interosseous membrane to enter
and supply the anterior compartment of the leg, continuing inferiorly into
the foot where it becomes the dorsalis pedis artery.
Posterior Tibial Artery

The posterior tibial artery descends through the deep region of the
posterior compartment of the leg, giving rise to its two major branches,
the circumflex fibular artery and the fibular artery and supplying the
posterior and lateral compartments of the leg before passing posterior to
the medial malleolus, and entering the sole of the foot via the tarsal
tunnel.
The posterior tibial pulse may be palpated posterior and inferior to the
medial malleolus, midway between the medial malleolus and the heel.
https://mrcemsuccess.com/explanation/tibial-arteries/?_sft_qc=anterior-leg 2/3
8/25/22, 11:18 PM Tibial Arteries - MRCEM Success
TIBIAL ARTERIES. (IMAGE MODIFIED BY FRCEM SUCCESS. ORIGINAL BY HENRY

https://mrcemsuccess.com/explanation/tibial-arteries/?_sft_qc=anterior-leg 3/3
8/25/22, 11:18 PM Anterior Thigh Muscles - MRCEM Success
Anterior Thigh Muscles LAST UPDATED:

10TH APRIL 2019
ANATOMY / LOWER LIMB / ANTERIOR THIGH
 Bookmark
The sartorius, iliacus, psoas major and pectineus (in addition to the
rectus femoris of the quadriceps femoris muscle) are all flexors of the
thigh at the hip joint.
Table: Function and Innervation of the Anterior Thigh Muscles

Sartorius Flexion, abduction and lateral Femoral
rotation at hip and flexion at knee nerve
Iliacus Flexion and lateral rotation at hip Femoral
nerve
Psoas Flexion and lateral rotation at hip Anterior
major rami L1 – L3
Pectineus Adduction and flexion at hip Femoral
nerve
Sartorius
The sartorius is innervated by the femoral nerve. It acts to flex the thigh
at the hip joint and flex the leg at the knee joint. It also abducts the thigh
and rotates it laterally, as when resting the foot on the opposite knee
when sitting.
Iliopsoas
The iliacus and psoas major muscles originate as separate muscles but
insert by a common tendon onto the femur and together are referred to
as the iliopsoas muscle, which is a powerful flexor of the thigh at the hip
joint and also contributes to lateral rotation of the thigh at the hip joint.
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8/25/22, 11:18 PM Anterior Thigh Muscles - MRCEM Success
The iliacus is innervated by the femoral nerve. The psoas major is

innervated by the anterior rami of spinal nerves L1 - L3.
Pectineus
The pectineus is innervated by the femoral nerve. It acts to adduct and
flex the thigh at the hip joint.
ANTERIOR THIGH MUSCLES: PECTINEUS (GREEN), SARTORIUS (BLUE), ILIACUS

(RED), PSOAS MAJOR (YELLOW). (IMAGE MODIFIED BY FRCEM SUCCESS.
COMMONS)
https://mrcemsuccess.com/explanation/anterior-thigh-muscles/?_sft_qc=anterior-thigh 3/3
8/25/22, 11:18 PM Deep and Superficial Inguinal Lymph Nodes - MRCEM Success
Deep and Superficial LAST UPDATED:

10TH APRIL 2019
Inguinal Lymph Nodes  Bookmark
The inguinal nodes are found in the upper aspect of the femoral triangle.
Superficial Inguinal Nodes

The superficial inguinal lymph nodes (about 10 in number) are located in
the superficial fascia, forming a line below the inguinal ligament, and
medially extending inferiorly along the terminal part of the great
saphenous vein. They receive lymph from the gluteal region, lower
abdominal wall, perineum and superficial regions of the lower limb.
Deep Inguinal Nodes

The deep inguinal lymph nodes (about 1 - 3 in number) lie medial to the
femoral vein within the femoral canal. They receive lymph from deep
lymphatics associated with the femoral vessels and from the glans penis
or clitoris in the perineum.
The inguinal lymph nodes drain to the external iliac lymph nodes
associated with the external iliac artery in the abdomen.
https://mrcemsuccess.com/explanation/lymphatic-drainage-of-lower-limb/?_sft_qc=anterior-thigh 2/3
8/25/22, 11:18 PM Deep and Superficial Inguinal Lymph Nodes - MRCEM Success
LYMPHATIC DRAINAGE OF LOWER LIMB. (IMAGE BY HENRY VANDYKE CARTER

https://mrcemsuccess.com/explanation/lymphatic-drainage-of-lower-limb/?_sft_qc=anterior-thigh 3/3
8/25/22, 11:19 PM Quadriceps Femoris Muscle - MRCEM Success
Quadriceps Femoris LAST UPDATED:

10TH APRIL 2019
Muscle  Bookmark
The quadriceps femoris is made up of four individual muscles; the rectus

femoris, the vastus medialis, the vastus intermedius (deep to the rectus
femoris) and the vastus lateralis which all insert onto the patella by the
common quadriceps femoris tendon. Because the vastus muscles insert
into the margins of the patella as well as into the quadriceps femoris
tendon, they stabilise the position of the patella during knee joint
movement.
Table: Function and Innervation of the Quadriceps Femoris

Muscles
Rectus femoris Flexion at hip and extension at Femoral
knee nerve
Vastus lateralis Extension at knee Femoral
nerve
Vastus medialis Extension at knee Femoral
nerve
Vastus Extension at knee Femoral
intermedius nerve
Function
The quadriceps femoris muscles are the main extensors of the leg at the
knee joint. The rectus femoris crosses both the knee and the hip joint (in
contrast to the vastus muscles which only cross the knee joint), and
therefore also assists in flexion of the thigh at the hip joint.
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8/25/22, 11:19 PM Quadriceps Femoris Muscle - MRCEM Success
Innervation
The quadriceps femoris muscles are innervated by the femoral nerve.
QUADRICEPS FEMORIS MUSCLES: RECTUS FEMORIS (RED), VASTUS MEDIALIS

(BLUE), VASTUS LATERALIS (GREEN). (IMAGE MODIFIED BY FRCEM SUCCESS.
COMMONS)
https://mrcemsuccess.com/explanation/quadriceps-femoris-2/?_sft_qc=anterior-thigh 3/3
8/25/22, 11:20 PM Saphenous Veins - MRCEM Success
Saphenous Veins LAST UPDATED: 10TH

APRIL 2019
ANATOMY / LOWER LIMB / ANTERIOR THIGH /
POPLITEAL FOSSA AND KNEE  Bookmark
The great and small saphenous veins originate from the medial and lateral sides
respectively of the dorsal venous arch in the foot.
Great Saphenous Vein

The great saphenous vein passes anterior to the medial malleolus, travels up the
medial side of the leg, knee and thigh to pass through the saphenous opening in
the deep fascia covering the femoral triangle and join with the femoral vein just
below the inguinal ligament.
Small Saphenous Vein

The small saphenous vein passes posterior to the lateral malleolus and up the
back of the leg to pierce the deep fascia and join the popliteal vein in the popliteal
fossa posterior to the knee.
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8/25/22, 11:20 PM Saphenous Veins - MRCEM Success
GREAT SAPHENOUS VEIN. (IMAGE BY HENRY VANDYKE CARTER [PUBLIC DOMAIN], VIA
WIKIMEDIA COMMONS)
SMALL SAPHENOUS VEIN. (IMAGE BY HENRY VANDYKE CARTER [PUBLIC DOMAIN], VIA
WIKIMEDIA COMMONS)
https://mrcemsuccess.com/explanation/saphenous-veins/?_sft_qc=anterior-thigh 3/3
8/25/22, 11:20 PM Dorsalis Pedis Artery - MRCEM Success
Dorsalis Pedis Artery LAST UPDATED:

24TH JANUARY 2019
ANATOMY / LOWER LIMB / DORSUM OF FOOT
 Bookmark
The dorsalis pedis artery begins as the anterior tibial artery crosses the
ankle joint.
It passes anteriorly over the dorsal aspect of the tarsal bones and then
passes inferiorly to join the deep plantar arch in the sole of the foot along
with branches from the posterior tibial artery.
The dorsalis pedis pulse can be palpated on the dorsal surface of the foot
between the tendon of the extensor hallucis longus and the tendon of the
extensor digitorum longus to the second toe.
DORSALIS PEDIS ARTERY. (IMAGE MODIFIED BY FRCEM SUCCESS. ORIGINAL BY

https://mrcemsuccess.com/explanation/dorsalis-pedis-artery/?_sft_qc=dorsum-of-the-foot 2/3
8/25/22, 11:21 PM Femoral Artery - MRCEM Success
Femoral Artery LAST UPDATED:

10TH APRIL 2019
ANATOMY / LOWER LIMB / FEMORAL TRIANGLE
 Bookmark
The major artery supplying the lower limb is the femoral artery.
Anatomical Course
The femoral artery is the continuation of the external iliac artery, beginning
as the vessel passes under the inguinal ligament to enter the femoral
triangle in the anterior thigh.
The femoral artery can be palpated in the femoral triangle as it passes over
the femoral head, just inferior to the inguinal ligament, midway between
the anterior superior iliac spine and the pubic symphysis (at the mid-
inguinal point).
The femoral vein lies immediately medial to this pulsation, which is an
important landmark for central venous line insertion. Medial to the femoral
vein is the femoral canal which contains lymphatics and lies immediately
lateral to the pubic tubercle. The femoral nerve lies lateral to the femoral
artery.
The femoral artery gives rise to the deep profunda femoris artery in the
femoral triangle which is a major source of blood supply to the medial and
posterior compartments of the thigh and the proximal femur.
After exiting the femoral triangle, the femoral artery continues down the
anterior surface of the thigh via the adductor canal. During its descent it
supplies the anterior thigh, giving rise to numerous superficial cutaneous
branches.
The femoral artery becomes the popliteal artery after entering the
posterior compartment of the thigh through the adductor hiatus just
proximal to the knee.
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8/25/22, 11:21 PM Femoral Artery - MRCEM Success
FEMORAL ARTERY. (IMAGE MODIFIED BY FRCEM SUCCESS. ORIGINAL BY HENRY

https://mrcemsuccess.com/explanation/femoral-artery-3/?_sft_qc=femoral-canal-and-femoral-ring 3/3
8/25/22, 11:21 PM Femoral Canal and Femoral Ring - MRCEM Success
Femoral Canal and LAST UPDATED:

13TH JUNE 2019
Femoral Ring  Bookmark
Femoral canal
The femoral canal lies between the femoral vein and the medial edge of the
femoral sheath. The femoral canal contains loose connective tissue,
lymphatic vessels, deep inguinal lymph nodes and empty space. The
femoral canal allows the femoral vein to expand, for example, when venous
return from the leg is increased, or when increased intra-abdominal
pressure causes a temporary stasis.
FEMORAL SHEATH OPEN TO REVEAL CONTENTS: FEMORAL ARTERY, FEMORAL

VEIN AND FEMORAL CANAL (IMAGE BY HENRY VANDYKE CARTER [PUBLIC
https://mrcemsuccess.com/explanation/femoral-canal-and-femoral-ring/?_sft_qc=femoral-canal-and-femoral-ring 2/4
8/25/22, 11:21 PM Femoral Canal and Femoral Ring - MRCEM Success
Femoral ring
Table: Anatomical Borders of the Femoral Ring

Femoral Ring Structure
Anterior border Inguinal ligament
Posterior border Pectineal ligament
Medial border Lacunar ligament
Lateral border Femoral vein
The femoral ring is formed by the proximal abdominal opening of the

femoral canal, and is important clinically, as it is a common site of hernia. It
is bordered anteriorly by the inguinal ligament, posteriorly by the pectineal
ligament, medially by the lacunar ligament and laterally by the femoral vein.
https://mrcemsuccess.com/explanation/femoral-canal-and-femoral-ring/?_sft_qc=femoral-canal-and-femoral-ring 3/4
8/25/22, 11:22 PM Femoral Nerve - MRCEM Success
Femoral Nerve LAST UPDATED:

10TH APRIL 2019
ANATOMY / LOWER LIMB / FEMORAL TRIANGLE /
INNERVATION OF LOWER LIMB  Bookmark
The femoral nerve arises from the lumbar plexus, receiving fibres from the
anterior rami of L2 - L4.
Table: Anatomical Overview of the Femoral Nerve

Nerve Femoral
Nerve L2 – L4
roots
Motor Iliacus, pectineus, sartorius, quadriceps femoris
supply
Sensory Skin over the anterior thigh, anteromedial knee, medial
supply leg and medial foot
Injury Motor Loss: Weak flexion at hip and loss of extension
at knee
Sensory Loss: Loss of sensation over anterior thigh,
anteromedial knee, medial leg and medial foot
Anatomical course
The femoral nerve descends from the lumbar plexus in the posterior
abdomen through the substance of the psoas major muscle, emerging
from the lower lateral border of the psoas major. Continuing its descent,
the femoral nerve lies between the lateral border of the psoas major and
the anterior surface of the iliacus muscle. It is deep to the iliacus fascia and
lateral to the femoral artery as it passes posterior to the mid-inguinal point
to enter the femoral triangle in the anterior compartment of the thigh,
before dividing into an anterior and posterior division.
https://mrcemsuccess.com/explanation/femoral-nerve-2/?_sft_qc=femoral-canal-and-femoral-ring 2/6
FEMORAL NERVE. (IMAGE BY HENRY VANDYKE CARTER [PUBLIC DOMAIN], VIA

WIKIMEDIA COMMONS)
Branches
Table: Branches of the Femoral Nerve
Branch Supply
Muscular branches in Iliacus and pectineus
abdomen
Anterior cutaneous Skin over anterior thigh
branches
Anterior muscular Sartorius
branches
Posterior muscular Quadriceps femoris muscles
branches
Posterior articular Hip and knee joint
branches
Saphenous nerve Skin over anteromedial knee, medial side
of leg and foot
In the abdomen it gives rise to branches that innervate the iliacus and
pectineus muscles.
The anterior division gives off anterior cutaneous branches (supplying skin
over the anterior and medial thigh) and muscular branches (innervating the
sartorius).
The posterior division gives off muscular branches (innervating the
quadriceps femoris muscles) and articular branches (supplying the hip and
knee joint), before continuing as the saphenous nerve (supplying skin over
the anteromedial knee and the medial side of the leg and foot).
Function
Table: Motor Supply of the Femoral Nerve
Muscle Function
Sartorius Flexion, abduction and lateral rotation at hip and
flexion at knee
Iliacus Flexion and lateral rotation at hip
Pectineus Adduction and flexion at hip
Rectus Flexion at hip and extension at knee
femoris
Vastus Extension at knee
lateralis
medialis
intermedius
8/25/22, 11:22 PM Femoral Sheath - MRCEM Success
Something wrong?
Femoral Sheath LAST UPDATED:

25TH JANUARY 2019
 Bookmark
The femoral sheath originates as a prolongation of extraperitoneal fascia

and encloses the femoral artery, femoral vein and femoral canal. The
femoral nerve does NOT lie within the sheath, but instead lies lateral to it.
The femoral sheath terminates inferiorly by blending with the adventitia of
the femoral vessels approximately 4 cm inferior of the inguinal ligament.
FEMORAL SHEATH OPEN TO REVEAL CONTENTS: FEMORAL ARTERY, FEMORAL

VEIN AND FEMORAL CANAL (IMAGE BY HENRY VANDYKE CARTER [PUBLIC
https://mrcemsuccess.com/explanation/femoral-sheath-3/?_sft_qc=femoral-canal-and-femoral-ring 2/3
8/25/22, 11:22 PM Femoral Triangle - MRCEM Success
Something wrong?
Femoral Triangle LAST UPDATED:

10TH APRIL 2019
 Bookmark
The femoral triangle is a wedge-shaped depression formed by muscles in

the upper thigh at the junction between the anterior abdominal wall and
the lower limb.
Table: Anatomical Boundaries and Contents of the Femoral

Triangle
Femoral Structure(s)
Triangle
Superior Inguinal ligament
border
Lateral border Medial sartorius muscle
Medial border Medial adductor longus muscle
Roof Fascia lata
Floor Pectineus, iliopsoas and adductor longus muscles
Contents Femoral nerve, femoral artery, femoral vein,
femoral canal
Borders
The femoral triangle is bordered superiorly by the inguinal ligament,
laterally by the medial border of the sartorius muscle and medially by the
medial border of the adductor longus muscle. The roof is formed by the
fascia lata and the floor is formed by the pectineus, iliopsoas and adductor
longus muscles.
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8/25/22, 11:22 PM Femoral Triangle - MRCEM Success
FEMORAL TRIANGLE. (IMAGE BY HENRY VANDYKE CARTER [PUBLIC DOMAIN], VIA

WIKIMEDIA COMMONS)
Contents
The contents of the femoral triangle include (from lateral to medial):
The femoral nerve
The femoral sheath containing:
The femoral artery
The femoral vein
The femoral canal containing:
Lymphatic vessels and deep inguinal nodes
https://mrcemsuccess.com/explanation/femoral-triangle-2/?_sft_qc=femoral-canal-and-femoral-ring 3/3
8/25/22, 11:23 PM Gluteal Muscles - MRCEM Success
Gluteal Muscles LAST UPDATED: 10TH

APRIL 2019
HIP JOINT AND GLUTEAL REGION  Bookmark
Table: Function and Innervation of the Gluteal Muscles

Gluteus Extension, lateral rotation and Inferior gluteal
maximus abduction at hip nerve
Gluteus Abduction and medial rotation at Superior gluteal
medius hip nerve
Gluteus Abduction and medial rotation at Superior gluteal
minimus hip nerve
Piriformis Lateral rotation and abduction at Branches from S1
hip and S2
Gluteus Maximus
The gluteus maximus is the main extensor of the thigh at the hip joint and
also acts to laterally rotate and abduct the thigh. Through its insertion into
the iliotibial tract, it also stabilises the knee and hip joints. The gluteus
maximus is innervated by the inferior gluteal nerve.
Gluteus Medius and Gluteus Minimus

The gluteus medius and gluteus minimus act to abduct and medially rotate
the thigh at the hip joint, and also act to secure the pelvis, reducing pelvic
drop on the opposite swing side during walking. They are both innervated by
the superior gluteal nerve.
Piriformis
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8/25/22, 11:23 PM Gluteal Muscles - MRCEM Success
The piriformis acts to abduct and laterally rotate the thigh at the hip joint. It is
innervated by the nerve to the piriformis, originating from the sacral plexus
(S1, S2).
The obturator internus, gemelli and quadratus femoris muscles act as
synergistic femoral lateral rotators and hip stabilisers.
GLUTEAL MUSCLES: GLUTEUS MAXIMUS (RED), GLUTEUS MEDIUS (GREEN),

GLUTEUS MINIMUS (BLUE), PIRIFORMIS (YELLOW). (IMAGE MODIFIED BY FRCEM
COMMONS)
https://mrcemsuccess.com/explanation/gluteal-muscles/?_sft_qc=hip-joint-and-gluteal-region 3/3
8/25/22, 11:23 PM Gluteal Quadrants - MRCEM Success
Gluteal Quadrants LAST UPDATED: 6TH

FEBRUARY 2019
The gluteal region can be divided into quadrants by 2 lines: one line
descending vertically from the highest point of the iliac crest, the other line
passing horizontally through the first line midway between the highest point
of the iliac crest and the ischial tuberosity. The sciatic nerve passes through
the lower inner quadrant.
Intramuscular injections in the buttocks should always be given in the upper
outer quadrant of the gluteal region to avoid damage to the sciatic nerve.
SAFE INJECTION SITE: UPPER OUTER QUADRANT. (IMAGE BY BRITISH COLUMBIA

INSTITUTE OF TECHNOLOGY (BCIT) [CC BY 4.0
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8/25/22, 11:25 PM Hip Joint - MRCEM Success
Hip Joint LAST UPDATED: 10TH

APRIL 2019
The hip joint is a multiaxial synovial ball and socket joint occurring between the
head of the femur and the acetabulum of the pelvis.
Table: Anatomical Overview of the Hip Joint

Joint Hip
Type Synovial ball and socket joint
Articulations Head of femur with acetabulum of pelvis
Stabilising Acetabular labrum, thickened fibrous capsule, extracapsular
factors ligaments (iliofemoral, ischiofemoral, pubofemoral), medial
rotator muscles (effectively ‘pull’ head of femur into
acetabulum)
Movements Flexion/Extension, Abduction/Adduction, Medial/Lateral
rotation, Circumduction
Blood supply Branches of obturator artery, medial and lateral circumflex
branches of profunda femoris artery and superior and
inferior gluteal arteries
Innervation Femoral nerve, obturator nerve, superior gluteal nerve and
nerve to the quadratus femoris
Joint articulations
The acetabulum is formed by the fusion of the three bones, the ilium, the ischium
and the pubis.
https://mrcemsuccess.com/explanation/hip-joint/?_sft_qc=hip-joint-and-gluteal-region 2/7
HIP JOINT. (IMAGE BY HENRY VANDYKE CARTER [PUBLIC DOMAIN], VIA WIKIMEDIA
COMMONS)
The rim of the acetabulum is raised slightly by the fibrocartilaginous acetabular

labrum which increases its depth, improving stability of the joint. The acetabular
labrum continues inferiorly as the transverse acetabular ligament which bridges
the acetabular notch and converts the notch into a foramen for the passage of
nutrient vessels and nerves.
Ligaments
The intracapsular ligament of the head of femur (ligamentum teres) runs from the
fovea on the head of the femur at one end to the acetabular fossa and the
transverse acetabular ligament on the other. It carries a small acetabular branch of
the obturator artery.
There are three main stabilising extracapsular ligaments; the iliofemoral (the largest
and strongest ligament), the pubofemoral and the ischiofemoral ligament.
The iliofemoral ligament is anterosuperior to the hip joint, attached proximally
to the ilium just below the anterior inferior iliac spine and distally to the
intertrochanteric line of the femur. This ligament specifically prevents

hyperextension and lateral rotation of the hip joint whilst standing.
The pubofemoral ligament is anteroinferior to the hip joint, attached to the
pelvis at the iliopubic eminence and adjacent bone and blending distally with
the articular capsule. This ligament prevents excessive abduction and
extension of the femur at the hip joint.
The ischiofemoral ligament is posterior to the hip joint, attached medially to
the ischium and laterally to the greater trochanter. This ligament prevents
excessive extension and medial rotation of the femur at the hip joint.
INTRACAPSULAR LIGAMENT OF HEAD OF FEMUR. (IMAGE BY HENRY VANDYKE CARTER

HIP JOINT LIGAMENTS (ANTERIOR VIEW). (IMAGE MODIFIED BY FRCEM SUCCESS. ORIGINAL
HIP JOINT LIGAMENTS (POSTERIOR VIEW). (IMAGE BY HENRY VANDYKE CARTER [PUBLIC
Blood supply
The hip joint receives its blood supply primarily from branches of the obturator
artery, the medial and lateral circumflex arteries (branches of the profunda femoris
artery) and the superior and inferior gluteal arteries. The articular branches of these
vessels form a network around the joint.
Innervation
The hip joint is innervated by articular branches from the femoral nerve (anteriorly),
obturator nerve (inferiorly), superior gluteal nerve (superiorly), and the nerve to the
quadratus femoris (posteriorly).
Joint movements
The hip joint allows the movements of flexion and extension, abduction and
adduction, medial and lateral rotation and circumduction.
Table: Movements of the Hip Joint

Movement Muscles Involved
Flexion Sartorius, Iliacus, Psoas major, Pectineus, Rectus femoris
Extension Hamstrings, Gluteus maximus
Abduction Gluteus maximus, medius and minimus, Obturator internus,
Gemelli, Piriformis, Sartorius
Adduction Adductor longus, magnus and brevis, Gracilis, Pectineus
Medial Gluteus medius and minimus, Adductor longus, magnus and
rotation brevis, Semitendinosus and Semimembranosus
Lateral Obturator externus, Sartorius, Iliacus, Psoas major, Biceps
rotation femoris, Piriformis, Gluteus maximus, Obturator internus,
Gemelli, Quadratus femoris
8/25/22, 11:26 PM Sciatic Nerve - MRCEM Success
Sciatic Nerve LAST UPDATED: 10TH

APRIL 2019
HIP JOINT AND GLUTEAL REGION /  Bookmark
INNERVATION OF LOWER LIMB / POSTERIOR THIGH
The sciatic nerve is derived from the lumbosacral plexus and receives fibres from L4
- S3.
Table: Anatomical Overview of the Sciatic Nerve

Nerve Sciatic
Nerve L4 – S3
roots
Motor Posterior thigh muscles, hamstring portion of adductor magnus,
supply all of the muscles in the leg and foot
Sensory Skin on the lateral leg and foot, the heel and the dorsum and sole
supply of the foot
Motor Weak extension of hip and flexion of knee, loss of dorsiflexion and
loss in plantarflexion of ankle, loss of inversion and eversion of foot, foot
injury drop with high-stepping gait
Anatomical Course
The sciatic nerve leaves the pelvis and enters the gluteal region via the greater
sciatic foramen inferior to the piriformis muscle before descending through the
gluteal region and entering the posterior thigh.
In the posterior compartment of the thigh, the sciatic nerve lies on the adductor
magnus muscle and is crossed by the long head of the biceps femoris muscle.
Within the posterior thigh, the sciatic nerve gives rise to branches to the hamstring
muscles and adductor magus.
The sciatic nerve terminates at the apex of the popliteal fossa by dividing into the
tibial (anterior divisions of L4 – S3) and the common fibular (posterior divisions of
L4 – S2) nerves.
https://mrcemsuccess.com/explanation/sciatic-nerve/?_sft_qc=hip-joint-and-gluteal-region 2/3
8/25/22, 11:26 PM Sciatic Nerve - MRCEM Success
SCIATIC NERVE. (IMAGE BY HENRY VANDYKE CARTER [PUBLIC DOMAIN], VIA WIKIMEDIA
COMMONS)
Function
Motor Supply:
The sciatic nerve innervates all of the muscles in the posterior compartment of the
thigh (biceps femoris, semimembranosus and semitendinosus) and the hamstring
portion of the adductor magnus. Through its terminal branches, it indirectly
innervates all of the muscles in the leg and the foot
Sensory Supply:
The sciatic nerve has no direct sensory function but through its terminal branches,
it indirectly supplies the skin of the lateral leg and foot, the heel and both the
dorsum and sole of the foot.
https://mrcemsuccess.com/explanation/sciatic-nerve/?_sft_qc=hip-joint-and-gluteal-region 3/3
8/25/22, 11:26 PM Superior Gluteal Nerve Injury - MRCEM Success
Superior Gluteal Nerve Injury LAST UPDATED: 20TH

FEBRUARY 2019
Damage to the superior gluteal nerve may occur in association with pelvic
fractures, with space-occupying lesions within the pelvis extending into the
greater sciatic foramen, and following hip surgery.
Trendelenburg's sign is seen in people with weak/paralysed abductor muscles of
the hip, namely the gluteus medius and gluteus minimus muscles innervated by the
superior gluteal nerve.
The Trendelenburg sign is said to be positive if, when standing on one leg (the
'stance leg'), the pelvis drops on the side opposite to the stance leg. The muscle
weakness is present on the side of the stance leg. Typically the patient may also
demonstrate a Trendelenburg gait.
POSITIVE TRENDELENBURG’S SIGN. (IMAGE BY FOTO H.-P.HAACK [CC BY-SA 3.0

https://mrcemsuccess.com/explanation/superior-gluteal-nerve-injury/?_sft_qc=hip-joint-and-gluteal-region 2/3
8/25/22, 11:27 PM Common Fibular Nerve - MRCEM Success
Common Fibular Nerve LAST UPDATED: 5TH

OCTOBER 2019
INNERVATION OF LOWER LIMB /  Bookmark
POPLITEAL FOSSA AND KNEE
The common fibular nerve, also known as the common peroneal nerve, is a
branch of the sciatic nerve receiving fibres from L4 - S2.
Table: Anatomical Overview of the Common Fibular Nerve

Nerve Common Fibular
Nerve L4 – S2
roots
Motor Directly: Short head of the biceps femoris
supply
Terminal Branches: All muscles in the anterior and lateral
compartments of the leg, all intrinsic dorsal foot muscles
Sensory Directly: Skin over the upper lateral leg

supply
Terminal Branches: Skin over the lateral aspect of the lower leg
and ankle, and dorsal aspect of the foot and toes (except for
the lateral side of little toe)
Injury Motor Loss: Loss of dorsiflexion of ankle and foot eversion,

weakness of foot inversion, loss of toe extension, foot drop
with high-stepping gait and loss of sensation in above
distribution
Sensory Loss: Loss of sensation in skin over the lateral aspect
of leg and ankle, and dorsal aspect of the foot and toes (except
for the lateral side of little toe)
Anatomical Course
The nerve arises at the apex of the popliteal fossa and follows the medial margin
of the biceps femoris tendon over the lateral head of the gastrocnemius muscle.
Here it gives rise to two cutaneous branches, the sural communicating nerve
which joins the sural nerve (branch of the tibial nerve), and the lateral sural
cutaneous nerve (supplying skin over the upper lateral leg).
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The common fibular nerve continues by wrapping around the neck of the fibula
and passing between the attachments of the fibularis longus muscle to enter
the lateral compartment of the leg where it divides into its terminal branches,
the superficial and deep fibular nerves.
COMMON FIBULAR NERVE. (IMAGE BY HENRY VANDYKE CARTER [PUBLIC DOMAIN], VIA
WIKIMEDIA COMMONS)
Branches
Table: Branches of the Common Fibular Nerve
Branch Supply
Muscular Short head of biceps femoris muscle
branch
Sural Joins sural nerve
communicating
nerve
Lateral sural Skin over upper lateral leg
cutaneous
nerve
Superficial Lateral compartment of leg and skin over lower
fibular nerve anterolateral leg, and dorsum of foot (except lateral
side of little toe and skin over webspace of 1st and 2nd
toe)
Deep fibular Anterior compartment of leg and skin over webspace
nerve between 1st and 2nd toes
Function
The common fibular nerve directly innervates the short head of the biceps
femoris muscle and supplies skin over the upper lateral leg via its lateral sural
cutaneous branch.
Through its terminal branches, the common fibular nerve innervates all of the
muscles in the anterior and lateral compartments of the leg and the dorsal
intrinsic foot muscles and skin over the anterolateral aspect of the lower leg and
the dorsal aspect of the foot and toes (except for the lateral side of the little toe,
supplied by the sural branch of the tibial nerve).
Table: Motor Supply of the Common Fibular Nerve
Muscle Function Branch

Tibialis Dorsiflexion and inversion of foot, Deep fibular
anterior support of medial arch of foot nerve
Extensor Extension of great toe and dorsiflexion Deep fibular
hallucis of foot nerve
longus
Extensor Extension of lateral four toes and Deep fibular
digitorum dorsiflexion of foot nerve
longus
Fibularis Dorsiflexion and eversion of foot Deep fibular
tertius nerve
Fibularis Plantarflexion and eversion of foot, Superficial
longus support of lateral and transverse arch fibular
nerve
Fibularis Eversion of foot Superficial
brevis fibular
nerve
8/25/22, 11:28 PM Cutaneous Innervation of Lower Limb - MRCEM Success

APRIL 2019
Lower Limb  Bookmark
INNERVATION OF LOWER LIMB
Table: Cutaneous Innervation of the Lower Limb

Nerve Origin Skin Supplied
Lateral cutaneous Lumbar Lateral thigh
nerve of thigh plexus (L2,
L3)
Anterior cutaneous Femoral nerve Anterior thigh and
nerve anteromedial knee
Cutaneous branch Obturator Medial thigh
nerve
Posterior cutaneous Sacral plexus Posterior thigh and upper
nerve of thigh (S1 – S3) leg
Saphenous nerve Femoral nerve Anteromedial knee, medial
leg and foot
Lateral sural Common Upper lateral leg
cutaneous nerve fibular nerve
Superficial fibular Common Lower anterolateral leg and
nerve fibular nerve dorsum of foot
Deep fibular nerve Common Webspace between 1st and
fibular nerve 2nd toe
Sural nerve Tibial nerve Lower posterolateral leg,
heel and foot
Medial calcaneal nerve Tibial nerve Medial side and sole of heel
Medial and lateral Tibial nerve Sole of foot anterior to heel
plantar nerves
https://mrcemsuccess.com/explanation/cutaneous-innervation-of-lower-limb-2/?_sft_qc=innervation-of-lower-limb 2/5

CUTANEOUS INNERVATION OF FOOT. (IMAGE MODIFIED BY FRCEM SUCCESS. ORIGINAL

Cutaneous Innervation of Thigh

The skin over the hip and gluteal region is supplied by the posterior and
anterior rami of lumbosacral nerves (L1 – S3).
The lateral cutaneous nerve of the thigh, nerve from the lumbar plexus,
supplies skin over the lateral thigh.
The anterior cutaneous nerve, branch of the femoral nerve, supplies skin
over the anterior thigh and anteromedial knee.
The obturator nerve supplies skin over the upper medial thigh.
The posterior cutaneous nerve of the thigh, nerve from the sacral plexus,
supplies skin over the posterior thigh and upper leg.
Cutaneous Innervation of Leg

The saphenous nerve, branch of the femoral nerve, supplies the skin over
the anteromedial knee, medial leg and the medial side of the foot as far
anteriorly as the head of the 1st metatarsal.

The lateral sural nerve, branch of the common fibular nerve, supplies the
skin over the upper lateral leg.
The superficial fibular nerve supplies the area of skin over the lower
anterolateral leg and the dorsum of the foot (except for the webspace
between the 1st and 2nd toe and the lateral side of the little toe).
The deep fibular nerve supplies the skin over the webspace between the
1st and 2nd toe.
The sural nerve, branch of the tibial nerve, supplies the skin over the lower
posterolateral leg, heel and foot.
The medial calcaneal nerve, branch of the tibial nerve, supplies the skin
over the medial side and sole of the heel.
The medial and lateral plantar nerves, branches of the tibial nerve, supply
the skin over the sole of the foot anterior of the heel.
8/25/22, 11:29 PM Dermatomal Supply of Lower Limb - MRCEM Success

INNERVATION OF LOWER LIMB
Table: Dermatomal Supply of the Lower Limb

Dermatome Landmark
L1 Upper Anterior Thigh
L2 Mid Anterior Thigh
L3 Medial Femoral Condyle
L4 Medial Malleolus
L5 Dorsum 3rd MTP Joint
S1 Lateral Heel
S2 Popliteal Fossa
S3 Ischial Tuberosity
S5 Perianal Area
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8/25/22, 11:29 PM Dermatomal Supply of Lower Limb - MRCEM Success
DERMATOME MAP. (IMAGE BY GRANT, JOHN CHARLES BOILEAU (AN ATLAS OF ANATOMY, /
BY REGIONS 1962) [PUBLIC DOMAIN], VIA WIKIMEDIA COMMONS)
The T12 dermatome is best tested at the midclavicular line, over the midpoint of the
inguinal ligament.
The L1 dermatome is best tested on the upper anterior thigh, at a point midway
between the key sensory points for T12 and L2.
The L2 dermatome is best tested on the anteromedial thigh, at the midpoint drawn
on an imaginary line connecting the midpoint of the inguinal ligament and the
medial femoral condyle.
The L3 dermatome is best tested at the medial femoral condyle above the knee.
The L4 dermatome is best tested over the medial malleolus.
The L5 dermatome is best tested on the dorsum of the foot at the third
metatarsophalangeal joint.
The S1 dermatome is best tested on the lateral aspect of the calcaneus.
The S2 dermatome is best tested at the midpoint of the popliteal fossa.
The S3 dermatome is best tested over the ischial tuberosity or infragluteal fold
(depending on the patient their skin can move up, down or laterally over the ischii).
The S4/S5 dermatome is best tested in the perianal area, less than one cm lateral
to the mucocutaneous junction.
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Myotomes and Reflexes LAST UPDATED: 10TH

APRIL 2019
ANATOMY / CENTRAL NERVOUS SYSTEM / LOWER LIMB
/ INNERVATION OF LOWER LIMB / UPPER LIMB /  Bookmark
Upper Limb
Table: Myotomes of the Upper Limb

C5 Elbow flexion
C6 Wrist extension
C7 Elbow extension
C8 Finger flexion
T1 Finger abduction
Lower Limb
Table: Myotomes of the Lower Limb

L2 Hip flexion
L3 Knee extension
L4 Ankle dorsiflexion
L5 Great toe extension
S1 Ankle plantarflexion
S2 Knee flexion
Reflexes
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Table: Reflexes of the Upper and Lower Limb

Reflex Root Muscle
Biceps C5 – C6 Biceps brachii
Supinator C6 – C7 Brachioradialis
Triceps C7 – C8 Triceps brachii
Knee L3 – L4 Quadriceps
Ankle S1 Gastrocnemius
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8/25/22, 11:30 PM Obturator Nerve - MRCEM Success
Obturator Nerve LAST UPDATED: 10TH

APRIL 2019
INNERVATION OF LOWER LIMB / MEDIAL THIGH  Bookmark
The obturator nerve arises from the lumbar plexus, formed from the anterior
rami of L2 - L4.
Table: Anatomical Overview of the Obturator Nerve

Nerve Obturator
Nerve L2 – L4
roots
Motor Medial thigh muscles (adductor longus, brevis and magnus,
supply gracilis, obturator externus)
Sensory Upper medial thigh
supply
Injury Motor Loss: Loss of hip adduction and difficulty walking with
lateral swinging of limb (due to unopposed abduction)
Sensory Loss: Loss of sensation over upper medial thigh
Anatomical Course
The obturator nerve descends along the posterior abdominal wall, passes
through the pelvic cavity and enters the medial thigh by passing through the
obturator canal.
Function
The obturator nerve innervates all of the muscles of the medial compartment
of the thigh (except for the hamstring part of the adductor magnus innervated
by the tibial portion of the sciatic nerve).
It also gives off a cutaneous branch that supplies skin on the medial side of the
upper thigh.
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8/25/22, 11:30 PM Obturator Nerve - MRCEM Success
Table: Motor Supply of the Obturator Nerve

Muscle Function
Adductor longus Adduction and medial rotation at hip
Adductor brevis Adduction at hip
Adductor magnus Adduction and medial rotation at hip
Obturator externus Lateral rotation at hip
Gracilis Adduction at hip and flexion at knee

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8/25/22, 11:30 PM Tibial Nerve - MRCEM Success
Tibial Nerve LAST UPDATED: 10TH

APRIL 2019
INNERVATION OF LOWER LIMB / POSTERIOR LEG  Bookmark
The tibial nerve is a branch of the sciatic nerve receiving nerve fibres from L4 -
S3.
Table: Anatomical Overview of the Tibial Nerve

Nerve Tibial
Nerve L4 – S3
roots
Motor All muscles in the posterior compartment of the leg and the
supply intrinsic muscles in the sole of the foot
Sensory Skin on the posterolateral side of the lower leg, the lateral
supply side of the ankle, foot and little toe, the medial side of the
heel and the sole of the heel, foot and toes
Injury Motor Loss: Weakness of flexion at knee, loss of
plantarflexion at ankle and flexion of toes, weakness of foot
inversion
Sensory Loss: Loss of sensation to the skin on the
posterolateral side of the lower leg, the lateral side of the
ankle, foot and little toe, the medial side of the heel and the
sole of the heel, foot and toes
Anatomical Course
It arises at the apex of the popliteal fossa before descending in the leg to enter
the popliteal fossa posterior to the knee. The tibial nerve then passes under
the tendinous arch formed by the two heads of the soleus muscle and then
descends through the deep region of the posterior compartment of the leg.
The tibial nerve passes through the tarsal tunnel, posterior to the medial
malleolus to enter to foot.
https://mrcemsuccess.com/explanation/tibial-nerve/?_sft_qc=innervation-of-lower-limb 2/5
TIBIAL NERVE. (IMAGE BY HENRY VANDYKE CARTER [PUBLIC DOMAIN], VIA

WIKIMEDIA COMMONS)
Branches
Table: Branches of the Tibial Nerve

Branch Supply
Muscular Posterior compartment of leg
branches
Sural nerve Skin on lower posterolateral leg, lateral side of ankle,
foot and little toe
Medial Skin on medial surface and sole of heel
calcaneal nerve
Plantar nerves Intrinsic muscles in sole of foot, skin over sole of
foot and toes
Through its muscular branches, the tibial nerve innervates all of the muscles in
the posterior compartment of the leg.
The tibial nerve gives rise to the sural nerve in the proximal leg which supplies
skin on the lower posterolateral surface of the leg, and the lateral side of the
ankle, foot and little toe, and the medial calcaneal nerve in the distal leg which
supplies skin on the medial surface and sole of the heel.
In the foot the tibial nerve divides into the medial and lateral plantar nerves
which innervate all of the intrinsic muscles of the sole of the foot and supply
skin over the medial and lateral sole of foot and toes respectively.
Function
The table below details the motor function of the tibial nerve.
Table: Motor Supply of the Tibial Nerve

Muscle Function
Gastrocnemius Plantarflexion of foot and flexion of leg
Plantaris Plantarflexion of foot and flexion of leg
Soleus Plantarflexion of foot
Flexor digitorum Flexion of lateral four toes
longus
Flexor hallucis Flexion of great toe and plantarflexion of foot
longus
Tibialis posterior Plantarflexion and inversion of foot, support of
medial arch

8/25/22, 11:31 PM Lateral Leg Muscles - MRCEM Success
Lateral Leg Muscles LAST UPDATED: 16TH

JUNE 2022
ANATOMY / LOWER LIMB / LATERAL LEG
 Bookmark
Table: Function and Innervation of the Lateral Leg Muscles

Muscle Function Innervation Distal
Attachment
Fibularis Plantarflexion and Superficial 1st
longus eversion of foot, support fibular metatarsal
of lateral and transverse nerve and medial
arches cuneiform
Fibularis Eversion of foot Superficial 5th
brevis fibular metatarsal
nerve
Function
The fibularis longus and brevis act together to evert the foot. The fibularis
longus also assists in plantarflexion of the foot and supports the arches of the
foot (mainly the lateral and transverse arches).
Innervation
Both the fibularis longus and brevis are innervated by the superficial fibular
nerve.
Attachments
Both tendons of the fibularis longus and brevis pass posterior to the lateral
malleolus in a shallow bony groove before swinging forward to enter the lateral
side of the foot. The fibularis brevis then curves forward across the lateral
surface of the calcaneus to attach to a tubercle on the lateral surface of the
base of the 5th metatarsal. The fibularis longus descends obliquely down the
lateral side of the foot before swinging under the foot to cross the sole and
attach to the inferior surfaces of the base of the 1st metatarsal and the medial
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8/25/22, 11:31 PM Lateral Leg Muscles - MRCEM Success
cuneiform bones. The fibularis tertius extends from the distal end of the fibula
to the dorsal base of the fifth metatarsal bone.
LATERAL LEG MUSCLES: FIBULARIS LONGUS (RED), FIBULARIS BREVIS (GREEN).

(IMAGE MODIFIED BY FRCEM SUCCESS. ORIGINAL BY HENRY VANDYKE CARTER
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8/25/22, 11:31 PM Superficial Fibular Nerve - MRCEM Success
Superficial Fibular Nerve LAST UPDATED: 6TH

DECEMBER 2020
INNERVATION OF LOWER LIMB / LATERAL LEG  Bookmark
The superficial fibular nerve is a branch of the common fibular nerve.
Table: Anatomical Overview of the Superficial Fibular Nerve

Nerve Superficial Fibular
Nerve L4 – S1
roots
Motor Lateral compartment of leg
supply
Sensory Lower anterolateral leg and dorsum of foot
supply
Injury Loss of eversion of the foot and loss of sensation over the
lower anterolateral leg and dorsum of foot
Anatomical Course
https://mrcemsuccess.com/explanation/superficial-fibular-nerve/?_sft_qc=lateral-leg 2/4
SUPERFICIAL FIBULAR NERVE. (IMAGE BY HENRY VANDYKE CARTER [PUBLIC

Function
It innervates the fibularis longus and the fibularis brevis in the lateral leg. It
supplies the skin over the lower anterolateral leg and the dorsum of the foot
(except for the webspace between the 1st and 2nd digit supplied by the deep
fibular nerve, and the lateral side of the little toe, supplied by the sural branch
of the tibial nerve).
Table: Motor Supply of the Superficial Fibular Nerve
Muscle Function
Fibularis Plantarflexion and eversion of foot, support of lateral and
longus transverse arch
Fibularis Eversion of foot
brevis

8/25/22, 11:32 PM Medial Thigh Muscles - MRCEM Success
Medial Thigh Muscles LAST UPDATED: 10TH

APRIL 2019
ANATOMY / LOWER LIMB / MEDIAL THIGH
 Bookmark
There are five muscles in the medial compartment of the thigh (adductor
longus, adductor brevis, adductor magnus, obturator externus, gracilis), which
collectively adduct the thigh at the hip joint.
Table: Function and Innervation of the Medial Thigh Muscles

Adductor Adduction and Obturator nerve
longus medial rotation
at hip
Adductor Adduction at hip Obturator nerve
brevis
Adductor Adduction and Adductor part: Obturator nerve
magnus medial rotation
at hip Hamstring part: Sciatic nerve (tibial
division)
Obturator Lateral rotation Obturator nerve

externus at hip
Gracilis Adduction at hip Obturator nerve
and flexion at
knee
Innervation
These muscles are all innervated by the obturator nerve (except for the
hamstrings portion of the adductor magnus, innervated by the tibial division of
the sciatic nerve).
Function
The adductor longus, brevis, and magnus are the prime adductors of the thigh
at the hip joint and also assist in medial rotation.
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The obturator externus muscle acts to laterally rotate the thigh at the hip joint.
The gracilis adducts the thigh at the hip joint and flexes the leg at the knee
joint.
Testing of the medial thigh muscles can be performed with the patient lying
supine and the knee straight. The patient is asked to adduct the thigh against
resistance and the strength assessed (if the adductors are normal the
proximal ends of the gracilis and adductor longus can easily be palpated).
MEDIAL THIGH MUSCLES: OBTURATOR EXTERNUS (YELLOW), ADDUCTOR LONGUS

(RED), ADDUCTOR BREVIS (GREEN), ADDUCTOR MAGNUS (BLUE). (IMAGE MODIFIED
BY FRCEM SUCCESS. ORIGINAL BY HENRY VANDYKE CARTER [PUBLIC DOMAIN], VIA
WIKIMEDIA COMMONS)
GRACILIS MUSCLE. (IMAGE MODIFIED BY FRCEM SUCCESS. ORIGINAL BY HENRY

8/25/22, 11:33 PM Patella - MRCEM Success
Patella LAST UPDATED: 10TH

APRIL 2019
ANATOMY / LOWER LIMB / PATELLAR REGION
 Bookmark
The patella is a sesamoid bone embedded in the quadriceps femoris tendon

which sits in the trochlear groove of the anterior femur. The patella acts to
magnify the force exerted by the quadriceps femoris and to redirect the
quadriceps force as it undergoes normal lateral tracking during flexion.
The medial and lateral patellar retinaculum are formed primarily from fibres of
the vastus medialis muscle, and the vastus lateralis muscle and iliotibial tract
respectively, and attach the patella margins to surrounding fascia.
The quadriceps femoris tendon is continuous distally with the patellar
ligament which is attached to the tibial tuberosity distally.
PATELLA. (IMAGE BY OPENSTAX COLLEGE [CC BY 3.0

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8/25/22, 11:33 PM Patella - MRCEM Success
Factors Preventing Lateral Patellar Draw

There are several structures that work together to keep the patella aligned and
stabilised on the femur to prevent excessive lateral movement of the patella:
The lateral femoral condyle on the lateral aspect of the trochlear groove
is normally slightly higher than the medial aspect, providing a buttress
to the patella on the lateral side.
The vastus medialis muscle on the medial thigh acts to draw the patella
in a medial direction. If the vastus medialis muscle is not strong enough,
the patella is much more susceptible to dislocation.
The medial patellofemoral ligament, extending from the medial aspect of
the patella to the medial femoral condyle, provides a significant force
(about 60%) against lateral displacement.
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8/25/22, 11:34 PM Knee Joint - MRCEM Success
Knee Joint LAST UPDATED: 10TH

APRIL 2019
ANATOMY / LOWER LIMB / POPLITEAL FOSSA AND KNEE
 Bookmark
Table: Anatomical Overview of the Knee Joint

Joint Knee
Type Modified hinge synovial joint
Articulations Femoral condyles with tibial condyles (tibiofemoral articulation)
and patella with anterior femur (patellofemoral articulation)
Stabilising Fibrous capsule, tibial spines, menisci, tibial/fibular collateral
factors ligament, anterior/posterior cruciate ligament, vastus medialis
and lateralis muscles, oblique popliteal ligament, iliotibial tract,
muscle tendons (hamstrings, gastrocnemius, sartorius, gracilis)
Movements Flexion/Extension, Medial/Lateral rotation in flexed position
Joint Articulations
The knee joint is formed from two articulations:
the main weight bearing tibiofemoral articulation between the two femoral
condyles and the adjacent surfaces of the superior aspect of the tibial condyles
the patellofemoral articulation between the anterior femur and the patella which
allows the pull of the quadriceps femoris muscle to be directed anteriorly over
the knee to the tibia without tendon wear
https://mrcemsuccess.com/explanation/knee-joint/?_sft_qc=popliteal-fossa-and-knee 2/6
KNEE JOINT. (IMAGE BY OPENSTAX COLLEGE [CC BY 3.0

Joint Movements
The knee joint is a modified hinge synovial joint, allowing mainly flexion and extension,
but also a small degree of medial and lateral rotation.
Table: Movements of the Knee Joint

Flexion Hamstrings, Gracilis, Sartorius, Sciatic nerve, Femoral
Gastrocnemius, Plantaris nerve, Obturator nerve
Extension Quadriceps femoris Femoral nerve
‘Screw-home’ Mechanism and ‘Locking’

When standing, the knee joint is 'locked' in position to reduce the amount of muscle
work needed to maintain the standing weight bearing position. This locking
mechanism occurs partly due to the change in the shape/size of the articulating
femoral surfaces (in the flexed position, the surfaces of the femoral condyles that
articulate with the tibia are curved/round, but in extension, the surfaces are flat, and
consequently the joint surfaces become larger and more stable in extension) and
partly due to medial rotation of the femur on the tibia in full extension; medial rotation
and full extension tightens all the associated ligaments (the screw home mechanism).
Contraction of the popliteus muscle 'unlocks' the knee by initiating lateral rotation of
the femur on the tibia, and allowing flexion.
Joint Capsule
The fibrous membrane of the knee joint is reinforced anteriorly by the tendinous
expansions of the vastus lateralis and vastus medialis muscles, anterolaterally by a
fibrous extension from the iliotibial tract and posteromedially by the oblique popliteal
ligament, an extension from the tendon of the semimembranosus muscle (the oblique
popliteal ligament resists hyperextension and lateral rotation of the leg). The upper
end of the popliteus muscle passes through an opening in the posterolateral aspect of
the fibrous membrane of the knee.
Menisci
The two menisci are C-shaped fibrocartilaginous structures that lie between the
femoral condyles and the tibia, attaching at each end to facets in the intercondylar
region of the tibial plateau. In addition, the medial meniscus is also attached around its
margin to the joint capsule and to the tibial collateral ligament, unlike the smaller, more
mobile lateral meniscus. This means any damage to the tibial collateral ligament
results in tearing of the medial meniscus. The menisci deepen the articular surface of
the tibia increasing stability of the joint, improve congruence between the femoral and
tibial condyles during joint movements and play an important role in shock absorption.
MENISCI. (IMAGE BY OPENSTAX COLLEGE [CC BY 3.0

Ligaments
COLLATERAL LIGAMENTS:
The tibial collateral ligament is attached proximally to the medial epicondyle of the
femur and distally to the medial tibia. The fibular collateral ligament is attached
proximally to the lateral condyle of the femur and distally to the lateral fibula. The tibial
and fibular collateral ligaments act to stabilise the knee joint medially and laterally
respectively, limiting extension and preventing adduction and abduction movements.
The tibial collateral ligament is also attached to the medial meniscus; this means any
damage to the tibial collateral ligament usually results in tearing of the medial
meniscus.
CRUCIATE LIGAMENTS:
The cruciate ligaments interconnect the adjacent ends of the femur and tibia and
maintain their opposed positions during movement.
The anterior cruciate ligament (the weaker of the two) attaches to the anterior
part of the intercondylar area of the tibia and ascends posteriorly to attach to
the lateral wall of the intercondylar fossa of the femur and acts to prevent
anterior displacement of the tibia relative to the femur. The ligament is lax
during flexion and taut during extension thus it may be torn when the knee is
hyperextended (or by the application of a large force to the back of the knee with
the joint partly flexed). The anterior drawer sign may be seen where there is
forward sliding of the tibia on the femur.
The posterior cruciate ligament (the stronger of the two) attaches to the
posterior part of the intercondylar area of the tibia and ascends anteriorly to
attach to the medial wall of the intercondylar fossa of the femur and acts to
prevent posterior dislocation of the tibia relative to the femur. The ligament is lax
during extension and taut during flexion and thus it may be torn in a
hyperflexion injury, where a large force is applied to the tibia when the knee is
flexed. The posterior drawer sign may be seen where there is backward sliding of
the tibia on the femur.
KNEE LIGAMENT INJURY:
The 'unhappy triad' typically occurs due to a lateral force to an extended knee, e.g. in a
football tackle. It refers to injury of the anterior cruciate ligament (due to forward
displacement of the tibia), the tibial collateral ligament (due to excessive abduction)
and the medial meniscus (due to its attachment on the tibial collateral ligament).
Bursae
The synovial membrane of the knee joint forms pouches in two locations to provide
low-friction surfaces for the movement of tendons associated with the joint:
The subpopliteal recess - extends posterolaterally and lies between the lateral
meniscus and the tendon of the popliteus muscle
The suprapatellar bursa extends superiorly between the distal end of the shaft
of the femur and the quadriceps femoris muscle and tendon
Other bursae associated with the knee, but not normally communicating with the
synovial joint, include the subcutaneous prepatellar bursa, the deep and
subcutaneous infrapatellar bursae separated by the patella ligament, and numerous
other bursae associated with tendons and ligaments around the knee
joint. Housemaid's knee is inflammation of the prepatellar bursa, and Clergyman's knee
is inflammation of the subcutaneous infrapatellar bursa.
8/25/22, 11:35 PM Popliteal Artery - MRCEM Success
Popliteal Artery LAST UPDATED: 25TH

JANUARY 2019
The femoral artery becomes the popliteal artery after entering the posterior
compartment of the thigh through the adductor hiatus just proximal to the
knee.
The popliteal artery is the deepest neurovascular structure in the popliteal
fossa. Palpation should be performed with the person in the prone position
with the knee flexed to relax the popliteal fascia and hamstrings. The popliteal
pulse is best felt in the midline, in the inferior part of the fossa where the
popliteal artery is related to the tibia.
After exiting the popliteal fossa between the gastrocnemius and popliteus
muscle, the popliteal artery bifurcates into the anterior and posterior tibial
arteries at the lower border of the popliteus.
POPLITEAL ARTERY. (IMAGE BY MIKAEL HÄGGSTRÖM, USED WITH PERMISSION.

(IMAGE:GRAY544.PNG) [PUBLIC DOMAIN OR PUBLIC DOMAIN], VIA WIKIMEDIA
https://mrcemsuccess.com/explanation/popliteal-artery-3/?_sft_qc=popliteal-fossa-and-knee 2/3
8/25/22, 11:37 PM Popliteal Fossa - MRCEM Success
Popliteal Fossa LAST UPDATED: 10TH

APRIL 2019
The popliteal fossa is a diamond-shaped space behind the knee joint.
Table: Anatomical Boundaries and Contents of the Popliteal Fossa

Popliteal Structure(s)
fossa
Superomedial Semimembranosus
border
Superolateral Biceps femoris
border
Inferomedial Medial head of gastrocnemius
border
Inferolateral Lateral head of gastrocnemius and plantaris
border
Floor Knee joint capsule and adjacent surfaces of femur and
tibia and popliteus muscle
Roof Deep fascia
Contents Popliteal artery, popliteal vein, tibial nerve, common
fibular nerve
Anatomical boundaries
The popliteal fossa is bordered:
superomedially by the semimembranosus
superolaterally by the biceps femoris
inferomedially by the medial head of the gastrocnemius
inferolaterally by the lateral head of the gastrocnemius and plantaris
The floor of the fossa is formed by the capsule of the knee joint and adjacent
surfaces of the femur and tibia, and more inferiorly by the popliteus muscle.
https://mrcemsuccess.com/explanation/popliteal-fossa-3/?_sft_qc=popliteal-fossa-and-knee 2/4
The roof is formed by deep fascia.
ANATOMICAL BOUNDARIES OF POPLITEAL FOSSA. (IMAGE BY HENRY VANDYKE

Contents
The major structures contained within the popliteal fossa are (from medial to
lateral):
the popliteal artery
the popliteal vein
the tibial nerve
the common fibular nerve
The small saphenous vein ascends in the superficial fascia on the back of the
leg to the knee where it penetrates the deep fascia and enters the popliteal
fossa to drain into the popliteal vein. One other structure that passes through
the roof of the fossa is the posterior cutaneous nerve of the thigh which
descends through the thigh superficial to the hamstring muscles, passes
through the roof of the popliteal fossa, and then continues inferiorly with the
small saphenous vein to supply skin on the upper half of the posterior leg.
CONTENTS OF POPLITEAL FOSSA. (IMAGE MODIFIED BY FRCEM SUCCESS. ORIGINAL

8/25/22, 11:37 PM Popliteus Muscle - MRCEM Success
Popliteus Muscle LAST UPDATED:

20TH FEBRUARY
ANATOMY / LOWER LIMB / 2019
POPLITEAL FOSSA AND KNEE
 Bookmark
The popliteus muscle is the smallest and most superior of the deep
muscles in the posterior compartment of the leg.
The popliteus muscle 'unlocks' the knee from the fully extended 'locked'
position by initiating lateral rotation of the femur on the fixed tibia and
hences assists in initiation of flexion of the leg at the knee joint. It
stabilises the knee by resisting lateral rotation of the tibia on the femur.
The popliteus muscle is also attached to the lateral meniscus in the knee
and draws it posteriorly during knee flexion thus preventing its
entrapment.
The popliteus is innervated by the tibial nerve.
https://mrcemsuccess.com/explanation/popliteus-3/?_sft_qc=popliteal-fossa-and-knee 2/3
8/25/22, 11:39 PM Posterior Leg Muscles - MRCEM Success
Posterior Leg Muscles LAST UPDATED: 11TH

APRIL 2019
ANATOMY / LOWER LIMB / POSTERIOR LEG
 Bookmark
The muscles of the posterior leg are divided into the superficial group (the
gastrocnemius, the plantaris and the soleus) and the deep group (the popliteus,
the flexor hallucis longus, the flexor digitorum longus and the tibialis posterior).
Table: Function and Innervation of the Posterior Leg Muscles

Gastrocnemius Plantarflexion of foot and flexion of Tibial nerve
leg
Plantaris Plantarflexion of foot and flexion of Tibial nerve
leg
Soleus Plantarflexion of foot Tibial nerve
Flexor Flexion of lateral four toes Tibial nerve
digitorum
longus
Flexor hallucis Flexion of great toe and Tibial nerve
longus plantarflexion of foot
Tibialis Plantarflexion and inversion of foot, Tibial nerve
posterior support of medial arch
Innervation
They are all innervated by the tibial nerve.
Function
The gastrocnemius plantarflexes the foot at the ankle and also flexes the leg at
the knee.
The plantaris plantarflexes the foot at the ankle and flexes the leg at the knee.
https://mrcemsuccess.com/explanation/posterior-leg-muscles/?_sft_qc=posterior-leg 2/4
The soleus plantarflexes the foot at the ankle.

The flexor digitorum longus flexes the lateral four toes. It is involved with
gripping the ground during walking and propelling the body forward off the toes
at the end of the stance phase of gait.
The flexor hallucis longus flexes the great toe and contributes to plantarflexion
of the foot at the ankle joint.
The tibialis posterior inverts and plantarflexes the foot and provides dynamic
support to the medial arch of the foot during walking. The tibialis posterior
distally curves forward under the medial malleolus and enters the medial side of
the foot to attach to the medial tarsal bones, mainly to the tuberosity of the
navicular and adjacent region of the medial cuneiform.
POSTERIOR LEG MUSCLES (SUPERFICIAL): GASTROCNEMIUS (GREEN), SOLEUS (RED),

PLANTARIS. (IMAGE MODIFIED BY FRCEM SUCCESS. ORIGINAL BY HENRY VANDYKE
POSTERIOR LEG MUSCLES (DEEP): FLEXOR DIGITORUM LONGUS (GREEN), TIBIALIS

POSTERIOR (RED), FLEXOR HALLUCIS LONGUS (BLUE). (IMAGE MODIFIED BY FRCEM
COMMONS)
8/25/22, 11:40 PM Hamstring Muscles - MRCEM Success
Hamstring Muscles LAST UPDATED:

10TH APRIL 2019
ANATOMY / LOWER LIMB / POSTERIOR THIGH
 Bookmark
The hamstrings are composed of three individual muscles; the biceps

femoris, the semitendinosus and the semimembranosus.
Table: Function and Innervation of the Hamstring Muscles

Biceps femoris Flexion at knee, extension Sciatic
and lateral rotation at hip nerve
Semitendinosus Flexion at knee, extension Sciatic
and medial rotation at hip nerve
Semimembranosus Flexion at knee, extension Sciatic
and medial rotation at hip nerve
Function
The hamstrings act together to flex the leg at the knee joint and extend
the thigh at the hip joint. The biceps femoris also acts to laterally rotate
the thigh at the hip joint and the leg at the knee joint. The
semimembranosus and semitendinosus also act together to medially
rotate the thigh at the hip joint and the leg at the knee joint.
Innervation
The hamstring muscles are all innervated by the tibial division of the
sciatic nerve (L5 - S2), except for the short head of the biceps femoris
innervated by the common fibular division.
Assessment
https://mrcemsuccess.com/explanation/hamstrings-2/?_sft_qc=posterior-thigh 2/3
8/25/22, 11:40 PM Hamstring Muscles - MRCEM Success
To test the hamstrings the patient flexes their leg against resistance.
Normally these muscles, especially their tendons on each side of the
popliteal fossa, are prominent as they bend the knee.
HAMSTRINGS: BICEPS FEMORIS (RED), SEMITENDINOSUS (BLUE),

SEMIMEMBRANOSUS (GREEN). (IMAGE MODIFIED BY FRCEM SUCCESS.
COMMONS)
https://mrcemsuccess.com/explanation/hamstrings-2/?_sft_qc=posterior-thigh 3/3
8/25/22, 11:41 PM Plantar Foot Layers - MRCEM Success
Plantar Foot Layers LAST UPDATED:

29TH JANUARY
ANATOMY / LOWER LIMB / SOLE OF FOOT 2019
 Bookmark
The muscles of the sole of the foot are organised into four layers, from
superficial to deep. Detailed knowledge of the muscles which lie within a
given layer is not required, but the following is required knowledge and
has implications for the structures likely to compromised when the sole is
injured.
The plantar arteries and nerves lie between the first and second layers.
The long flexor tendons of the flexor hallucis longus and flexor digitorum
longus muscles lie within the second layer.
The tendons of the tibialis posterior and fibularis longus muscles are part
of the fourth layer.
MUSCLES OF THE FOOT. (IMAGE BY HENRY VANDYKE CARTER [PUBLIC

https://mrcemsuccess.com/explanation/layers-of-sole-of-foot/?_sft_qc=sole-of-the-foot 2/3
Something wrong?
Cellular Pathology LAST UPDATED: 27TH

APRIL 2019
PATHOLOGY / INFLAMMATORY RESPONSES
 Bookmark
Cellular Adaptations
Atrophy:
A reduction in size of a tissue or organ; this may occur through a
reduction in cell number be deletion (apoptosis) or a reduction in cell size
through shrinkage
Examples of physiological atrophy include: thymic atrophy during
adolescence and post-menopausal ovarian atrophy
Examples of pathological atrophy include: muscle atrophy following
denervation and cerebral atrophy due to cerebrovascular disease
Hypertrophy:
An increase in size of individual cells due to an increase in cell proteins
and organelles; seen in organs containing terminally differentiated cells
that cannot multiply e.g. cardiac and skeletal cells
Examples of physiological hypertrophy include: hypertrophy of the
myometrium of the uterus in pregnancy and muscles of a bodybuilder
Examples of pathological hypertrophy include left ventricular hypertrophy
due to hypertension
Hyperplasia:
An increase in cell number
Examples of physiological hyperplasia include endometrial and breast
lobules in response to cyclical oestrogen exposure
Examples of pathological hyperplasia include benign prostatic
hyperplasia (BPH)
Metaplasia:
A change in which one cell type is switched for another; thought to be the
result of progenitor cells differentiating into a new type of cell rather than
a direct morphogenesis of cells from one type to another; seen almost
exclusively in epithelial cells, often in response to chronic injury; may
develop into epithelial dysplasia and eventually carcinoma
Common sites of squamous metaplasia include the endocervix (creating
the transformation zone where cervical neoplasia occurs) and the bronchi
of smokers
Common sites of glandular metaplasia include the lower oesophagus in
severe reflux disease
Reversible vs Irreversible Cell Damage

Cells may be damaged either reversibly or irreversibly. There are no absolute
ultrastructural criteria by which reversible and irreversible cellular damage can
be distinguished, and there is a continuum from a reversible injured cell through
to an irreversibly damaged cell. Cell recovery is associated with removal of
damaged components by autophagy.
Features of cell damage that tend to be reversible include:
swelling of endoplasmic reticulum and some mitochondria
loss of ribosomes
cell stress response
Features of cell damage that tend to be irreversible include:
loss of nucleolus
no ribosomes
swelling of all mitochondria
nuclear condensation
membrane blebs and holes
lysosome rupture
fragmentation of all inner membranes
nuclear breakup
Cellular Death
Apoptosis:
A controlled form of cell death in which no cellular contents are released
from the dying cell, and thus no inflammatory reaction is seen
Apoptosis may occur physiologically or pathologically
Apoptosis may be induced in two main ways: by the engagement of
surface death receptors e.g. TNF-alpha (extrinsic pathway) or through
cellular injury (intrinsic pathway)
The end result is the activation of proteases enzymes called caspases
which dismantle the cell cytoplasm and nucleus
Apoptotic cells shrink down and fragment into apoptotic bodies, each of
which retains an intact cell membrane; apoptotic bodies are then
targeted or rapid removal by adjacent cells
Disordered apoptosis is thought to be central to a number of important
disease processes, particularly carcinogenesis
Necrosis:
A poorly controlled form of cell death in which membrane integrity is lost
with leakage of cellular contents and an inflammatory response
Coagulative necrosis is the most common form of necrosis characterised
by the loss of cell nuclei, but with general preservation of the underlying
architecture. Dead tissue is macroscopically pale and firm. This is the
classic pattern seen in myocardial infarction.
Liquefactive necrosis leads to complete loss of cellular structure and
conversion into a soft, semi-solid mass. This is typically seen in the brain
following cerebral infarction.
Caseous necrosis is most commonly seen in tuberculosis. Histologically,
the complete loss of normal tissue architecture is replaced by amorphous,
granular and eosinophilic tissue with a variable amount of fat and an
appearance reminiscent of cottage cheese.
Fibrinoid necrosis occurs in malignant hypertension where increased
arterial pressure results in necrosis of smooth muscle wall. Eosinophilic
and fibrinous deposits are seen.
Fat necrosis typically occurs following either direct trauma or from
enzymatic lipolysis in acute pancreatitis, where release of triglyceride
elicits a rapid inflammatory response and fat is phagocytosed by
neutrophils and macrophages with subsequent fibrosis.
Gangrenous necrosis is necrosis with putrefaction of tissues due to
exposure to air (dry gangrene) or infection (wet gangrene). The tissue is
black due to iron sulphide from degraded haemoglobin.

Plasma Autoantibodies LAST UPDATED: 1ST
APRIL 2020
 Bookmark
Autoimmune disease can be either organ-specific illnesses (e.g. thyroid disease,

type 1 diabetes mellitus, myasthenia gravis) or systemic illnesses (e.g.
rheumatoid arthritis (RA), systemic lupus erythematosus (SLE)). The cause of
autoimmune damage may be mainly due to either autoantibodies or
autoimmune T lymphocytes. Nearly all autoimmune diseases are associated
with circulating autoantibodies, which may also be found associated with non-
related illnesses and in healthy individuals. Autoantibodies are often detected
many years before the onset of disease.
Examples of autoantibodies and their associations include:
Rheumatology
Antinuclear antibodies
Raised ANAs are almost always present in SLE
It is also associated with drug-induced lupus erythematosus
(LE), systemic sclerosis (scleroderma), Sjögren's syndrome,
polymyositis and dermatomyositis, mixed connective tissue
disorder and autoimmune hepatitis
It may also be seen in Addison's disease, idiopathic
thrombocytopenic purpura (ITP), Hashimoto's thyroiditis,
autoimmune haemolytic anaemia and type 1 diabetes
mellitus
Rheumatoid factor
High levels are associated with RA and Sjögren's syndrome
Other disease associations include chronic hepatitis, chronic
viral infection, tuberculosis, leprosy, leukaemia,
dermatomyositis, infectious mononucleosis, systemic
sclerosis and SLE
Antiphospholipid antibodies
Anticardiolipin antibodies are the most commonly detected
antiphospholipid antibodies and are associated with primary
antiphospholipid syndrome (also present in some people with
SLE)
Antineutrophil cytoplasmic antibodies (ANCA)
Associated with necrotising vasculitis and vasculitis
associated with rheumatic and inflammatory bowel disease;
two main types:
C-ANCA (cytoplasmic): associated with granulomatosis with
polyangiitis (Wegener's granulomatosis), micropolyarterits,
Churg-Strauss syndrome, polyarteritis nodosa and RPGN
P-ANCA (perinuclear): associated with microscopic
polyangiitis, Churg-Strauss syndrome, anti-GBM disease,
crescenteric glomerulonephritis and granulomatosis with
polyangiitis (Wegener's granulomatosis)
Gastroenterology
Intrinsic factor antibodies associated with pernicious anaemia
Parietal cell antibodies associated with autoimmune gastritis
IgA anti-tissue transglutaminase (anti-tTG), anti-gliadin and
endomysial antibodies (EMAs) associated with coeliac disease
Antimitochondrial antibodies associated with primary biliary
cirrhosis
Anti-smooth muscle antibodies associated with autoimmune
hepatitis
Endocrinology
Glutamic acid decarboxylase (GAD), islet cell and insulin antibodies
associated with type 1 diabetes mellitus
Anti-thyroid peroxidase (TPO), TSH (thyrotropin) receptor and
thyroglobulin (TG) antibodies associated with autoimmune thyroid
disease
Antisperm antibodies associated with immunological infertility
Steroid cell antibodies associated with Addison's disease and
autoimmune gonadal failure
Neurology
Acetylcholine receptor antibodies associated with myasthenia
gravis
Antibodies associated with peripheral neuropathy
Nephrology
Anti-glomerular basement membrane (GBM) antibodies associated
with Goodpasture's syndrome
Cardiology
Cardiac muscle antibodies associated with heart failure,
myocarditis and dilated cardiomyopathy
Dermatology
Intra-epidermal/desmosome antibody (pemphigus antibody)
associated with pemphigus
Basement membrane zone antibody (pemphigoid antibody)
associated with pemphigoid

Acute Inflammation LAST UPDATED: 8TH
NOVEMBER 2021
 Bookmark
Inflammation is the response of living tissues to cellular injury. The purpose of

inflammation is to localise and eliminate the causative agent, limit tissue injury
and restore tissue to normality.
Causes
Physical agents (e.g. trauma, heat, cold, ultraviolet light, radiation)
Irritant chemicals (e.g. acids, alkali)
Microbial infections (e.g. pyogenic bacteria)
Immune-mediated hypersensitivity reactions
Tissue necrosis (e.g. myocardial infarction)
Classic Signs
Rubor (redness)
Calor (heat)
Dolor (pain)
Tumor (swelling)
Functio laesa (loss of function)
These classic signs are produced by a rapid vascular response and cellular
events. The main function of these events is to bring elements of the immune
system to the site of injury and prevent further tissue damage.
Vascular Response
Vasodilation
Vasodilation occurs resulting in increased blood flow to the injured
area (causing redness and heat)
Increased vascular permeability
Endothelial intracellular proteins contract under the influence of
chemical inflammatory mediators such as histamine, serotonin,
bradykinin, nitric oxide and leukotriene B4
Endothelial contraction results in increased fenestrations between
endothelial cells and increased permeability of vessels to plasma
proteins
Proteins leak out of the plasma into the interstitial space
Inflammatory oedema
The combined increase in plasma hydrostatic pressure and
decrease in plasma oncotic pressure causes net fluid movement
from plasma into tissues (causing oedema)
This has several advantages
Fluid increase in damaged tissue dilutes and modifies the
actions of toxins
Protein levels increase in the tissue - these include
protective antibodies and fibrin
Non-specific antibodies act as opsonins for neutrophil
mediated phagocytosis and function to neutralise
toxins
The formation of a fibrin net acts as a scaffold for
inflammatory cells, preventing the spread of
microorganisms
Circulation of the exudate into the lymphatic system assists
in antigen presentation and helps mount a specific immune
response
Cellular Events
Neutrophil polymorphs pass between endothelial cell junctions and invade
damaged tissue to combat the effects of injury. The movement of leucocytes
out of the vessel lumen is termed extravasation, and is achieved in five phases:
1. Margination to the plasmatic zone assisted by the slowing of blood

2. 'Rolling' of leucocytes due to the repeated formation and destruction of
transient adhesions with the endothelium
3. Adhesion of leucocytes to the vascular endothelium, due to the
interaction of paired molecules on the leucocyte and endothelial cell
surface
4. Transmigration of leucocytes passing between the endothelial cell
junctions, through the vessel wall into the tissue spaces
5. Chemotaxis of neutrophils migrating towards the site of tissue injury,
attracted by chemotaxins such as leukotrienes, complement
components and bacterial products
Activated neutrophils and monocytes, as well as mast cells, ingest debris and
foreign particles at the site of injury. Phagocytosis is assisted by opsonisation
with immunoglobulins and complement components. Acute inflammation
produces numerous dead bacteria and damaged and dying neutrophils,
macrophages and tissue cells situated in a fibrin-rich fluid. Together, this forms
the yellow fibrinopurulent exudate known as pus.

Chronic Inflammation LAST UPDATED: 12TH
AUGUST 2019
 Bookmark
Causes
Chronic inflammation usually develops as a primary response to:
Microorganisms resistant to phagocytosis or intracellular killing
mechanisms e.g. tuberculosis, leprosy
Foreign bodies, which can be endogenous (e.g. bone adipose tissue, uric
acid crystals) or exogenous (e.g. silica, suture materials, implanted
prostheses)
Some autoimmune diseases e.g. rheumatoid arthritis
Primary granulomatous diseases e.g. Crohn's disease, sarcoidosis
Inflammation becomes chronic when it occurs over a prolonged period of time
with simultaneous tissue destruction and attempted repair. It may occur
secondary to acute inflammation due to the persistence of the causative agent.
Mechanism
The site of chronic inflammation is dominated by:
Lymphocytes
Plasma cells for antibody production
Macrophages for phagocytosis (some macrophages fuse to form
multinucleate giant cells)
Macrophages in inflamed tissue are formed from the transformation of
monocytes. The number of macrophages gradually increases during acute
inflammation until they are the dominant cell type in chronic inflammation. These
macrophages are activated by numerous stimuli, including interferon-gamma
(IFNγ), which is produced by activated T-cells.
The macrophages gradually remove damaged tissue by phagocytosis and

produce growth factors to aid repair through fibrosis. This results in the
replacement of damaged tissue with granulation tissue, which consists of new
capillaries and new connective tissue formed from myofibroblasts and the
collagen that they secrete.
The prolonged presence of activated macrophages in chronic inflammation leads
to the overproduction of biologically active products resulting in tissue damage
and systemic effects.
Acute Inflammation Chronic Inflammation

Response Immediate reaction of Persistent reaction of
tissue to injury tissue to injury
Onset Rapid Slow
Immunity Innate Adaptive
Predominant Neutrophil Lymphocytes, plasma cells,
cell type macrophages
Duration Hours to weeks Weeks/months/years
Vascular Prominent Less important
response
Systemic Effects of Inflammation
Both acute and chronic inflammation can produce a number of systemic effects
including:
Fever
Neutrophils and macrophages produce pyrogens (e.g. IL-1) which act
on the hypothalamus
Constitutional symptoms
Malaise, nausea, anorexia
Lymphadenopathy
Reactive hyperplasia of the mononuclear phagocyte system
Haematological changes
Increased erythrocyte sedimentation rate (ESR), leucocytosis and
acute phase protein release (e.g. C-reactive protein, CRP)
Weight loss
Occurs in severe chronic inflammation such as tuberculosis
Special Types of Chronic Inflammation

Chronic suppurative inflammation
Follows failure of acute inflammatory response to clear an
inflammatory stimulus
Examples include:
Persistent bacterial infection that cannot be contained, as in
necrotising fasciitis where bacterial secretion of enzymes
facilitates the spread of infection through the connective
tissue
Abscess formation where a wall of fibrous tissue surrounds an
acute inflammatory focus, which develops a liquified centre full
of pus due to presence of dead and dying neutrophils and
bacteria
Granulomatous inflammation
Typically seen when an infective agent with a digestion-resistance
capsule (e.g. Mycobacterium tuberculosis) or a piece of inert foreign
material (such as suture or glass) is introduced into the tissue
A transient acute inflammatory response occurs and when this is
ineffective in eradicating the stimulus, chronic inflammation occurs;
IL-1 is important in initiating granuloma formation, IL-2 can cause
them to enlarge and TNF-α maintains them
A granuloma is a collection of five or more epithelioid macrophages,
with or without attendant lymphocytes and fibroblasts; epithelioid
macrophages are altered macrophages which have turned
themselves over to becoming giant phagocytosing and killing
machines, they often fuse to become multinucleate giant cells
Other causes include: infection (e.g. parasites, leprosy,
Cryptococcus), sarcoidosis, Crohn's disease, drugs, autoimmune
disease (e.g. rheumatoid arthritis), tumour related (e.g. Hodgkin
lymphoma)
Chemical Mediators of LAST UPDATED: 26TH
JUNE 2019
Inflammation  Bookmark
Several different inflammatory mediator systems interact to produce

inflammation:
The complement system
This cascading sequence of serum proteins is made of more than 20
components; the activated product on one protein activates another
The complement system has roles in: activation of phagocytes,
stimulating release of inflammatory mediators from mast
cells/basophils, chemotaxis of neutrophils/macrophages,
opsonisation of bacteria for phagocytosis, transport of immune
complexes and direct lysis of target cells
Kinins
Small vasoactive peptides e.g. bradykinin
Exert effect by increasing vascular permeability and producing pain
Kinin system is stimulated by activated coagulation factor XII
Prostaglandins and leukotrienes
Membrane phospholipid of neutrophils and mast cells are
metabolised during acute inflammation to form prostaglandins and
leukotrienes (from arachidonic acid)
Prostaglandins are chemotaxins for neutrophils and also increase
vascular permeability
Leukotrienes are vasoactive
Platelet activation factors
Platelet activation factors are released from mast cells and
neutrophils during degranulation
They induce platelet aggregation and degranulation, increase
vascular permeability, induce leucocyte adhesion to the endothelium
and stimulate synthesis of arachidonic acid derivatives
Vasoactive amines
Preformed inflammatory mediators that are rapidly released from
inflammatory cells
Examples are histamine and serotonin, released following
degranulation of mast cells
Cytokines
Family of chemical messengers, secreted by leucocytes, that act over
short distances by binding specific receptors on target cell surfaces
They include: interleukins (act between leucocytes), interferons
(inhibit replication of viruses within cells and activate macrophages
and natural killer cells), growth factors, and tumour necrosis factors
(kill tumour cells)
Tumour necrosis factor alpha (TNFα) and interleukin-1 (IL-1) are key
cytokines in acute inflammation
Effects include: induction of fever and acute phase response,
stimulation of leucocyte differentiation and maturation, leucocyte
recruitment and activation, increased antibody production
Nitric oxide
Potent vasodilator that is released from endothelial cells and
macrophages
Regulates inflammation, actively reducing the effect of other
proinflammatory mediators
Acute-phase proteins (APPs)
The acute phase response is a systemic reaction to infection or
tissue injury induced by increased circulating levels of IL-1, IL-6 and
TNFα produced by inflammatory cells and characterised by a rise in
APPs, fever, leucocytosis, thrombocytosis, anorexia and weight loss
APPs are mostly derived from the liver and examples include C-
reactive protein (CRP), serum amyloid-A protein (SAA) and fibrinogen.
CRP and SAA bind to bacterial cell walls and may act as opsonins
At the same time, the production of a number of other plasma
proteins is reduced; examples include albumin and transferrin
C-Reactive Protein
C-reactive protein (CRP) is as an acute phase protein produced by the liver. CRP
binds to phosphorylcholine found on the surface of many bacteria and opsonises
them for phagocytosis. C-reactive protein can be measured in the serum as a
nonspecific marker of inflammation. A high or increasing CRP suggests an acute
infection or inflammation but does not help in identifying its location or the
condition causing it. In people with chronic inflammatory conditions, high
concentrations of CRP suggest a flare-up or that treatment has not been
effective. When results fall below 10 mg/L, there is no longer clinically active
inflammation.
ESR has largely been superseded in clinical practice by measurement of CRP.
Both CRP and ESR are elevated in the presence of inflammation, but the
concentration of CRP rises and falls faster than ESR. CRP is not affected by as
many other factors as is ESR, making it a better marker of some types of
inflammation.
Erythrocyte Sedimentation Rate

The erythrocyte sedimentation rate (ESR) is an indirect nonspecific marker of
inflammation. The ESR measures the rate at which red blood cells fall (sediment)
when placed in a column for a period of one hour. Normally red cells fall slowly,
leaving little clear plasma. Increased levels of acute phase proteins, such as
fibrinogen, CRP or immunoglobulins, cause the red cells to fall more rapidly,
increasing the ESR. The ESR is particularly helpful in diagnosing and monitoring
treatment in two specific inflammatory diseases, temporal arteritis and
polymyalgia rheumatica.
ESR is raised with inflammation and infection but also with anaemia, renal
impairment, pregnancy and old age. People with multiple myeloma or
Waldenstrom’s macroglobulinaemia (tumours that make large amounts of
immunoglobulins) typically have very high ESR even if they don't have
inflammation. Although a low ESR is not usually important, it can be seen with
polycythaemia, with extreme leucocytosis, and with some protein abnormalities.

Immune Response LAST UPDATED: 26TH
JUNE 2019
PATHOLOGY / IMMUNE RESPONSES
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The white blood cells (leucocytes) may be divided into two broad groups: the
phagocytes and the lymphocytes. Phagocytes comprise the cells of the innate
immune system, which can act very quickly after an infection, whereas
lymphocytes mediate the adaptive immune response, which can develop
immunological memory. Phagocytes can themselves be divided into granulocytes
(neutrophils, eosinophils and basophils) and monocytes. The function of
phagocytes and lymphocytes in protecting the body against infection is closely
connected with two soluble protein systems of the body, immunoglobulins and
complement.
HAEMOPOIESIS. (IMAGE BY MIKAEL HÄGGSTRÖM AND A. RAD [CC BY-SA 3.0

(HTTP://CREATIVECOMMONS.ORG/LICENSES/BY-SA/3.0/)])
Physical defence against infection by bacteria, viruses, fungi and parasites is

provided by the skin and epithelial lining the airways and gut. Organisms evading
these defences are targeted by the immune system. The innate immune response
provides a rapid response and causes inflammation. It is not antigen specific and
the response does not improve with repeated exposure. The adaptive immune
response takes time to develop because it is specific for each different antigen, but
it is more potent and initial antigen exposure leaves memory cells thus subsequent
interactions with the same antigen produce a more rapid response.
Innate Immune Response

Tissue damage and invasion of phagocytes activates mast cells and resident
phagocytes, primarily macrophages and dendritic cells, which release inflammatory
mediators, cytokines and cytotoxic agents. Inflammatory mediators cause
vasodilation (heat and redness), stimulate nociceptors, (pain), and increase
endothelial permeability, leading to extravasation of protein and fluids and thus
oedema (swelling).
Cytokines (e.g. interleukin-8, IL-8) attract many more phagocytes, chiefly
neutrophils (chemotaxis); these leave the blood by squeezing between endothelial
cells. Phagocytes ingest microorganisms, and in the case of macrophages also
damaged cells and debris. Pathogens can be detected because they express
pathogen-associated molecular patterns (PAMPs) not found in mammals. PAMPs
are recognised by phagocyte pattern recognition receptors (PRRs). Injured,
infected or cancerous cells express PAMP-like molecules recognised by natural
killer cells, which kill the cells and activate macrophages to remove the debris. In
major infections, cytokines such as IL-1 cause fever; high temperatures may assist
the immune response.
Complement is an important non-cellular mechanism comprised of a cascade of
plasma proteins. On activation it coats and opsonises pathogens for phagocytosis,
kills by membrane rupture, recruits phagocytes and induces inflammation. It is
activated by some surface molecules and by antibodies that have 'tagged' a
pathogen as foreign.
Adaptive Immune Response

The adaptive response takes ~5 days to become effective, and peaks after 1-2
weeks. It involves a cell-mediated response involving T-cells and a humoral
response involving B-cells and antibodies.
Cell-Mediated Immunity:
Cell-mediated immunity is directed towards antigen within cells, which are made
visible by class I major histocompatibility complex (MHC I). MHC I is found on the
surface of cells and displays antigen to cytotoxic T cells, which proliferate on
recognising the antigen and destroy the infected cell.
Humoral Immunity:
Humoral immunity is particularly effective against extracellular pathogens, as it
involves secretion of antibodies into extracellular fluid. When an antigen binds to its
matching receptor on naive B-cells, the latter activate and undergo clonal
expansion. These differentiate into plasma cells which secrete antibody in massive
amounts. T helper cells substantially enhance the response if the antigen is a
protein. Memory cells which persist for years are also produced during clonal
expansion. These respond much more rapidly and powerfully to subsequent
exposures to the same pathogen and provide long-term immunity.
T helper cells only recognise protein antigens when they are presented to them by
class II major histocompatibility complex (MHC II) on antigen presenting cells
(APCs), which include dendritic cells, macrophages and activated B-cells. If they
recognise the antigen, the cell proliferates and releases cytokines which strongly
potentiate B-cell proliferation and performance. They also release cytokines that
regulate the activity of other immune cells.

Immunoglobulins LAST UPDATED: 26TH
JUNE 2019
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Immunoglobulin molecules are composed of two identical heavy and two identical
light chains linked by disulphide bridges. The heavy and light chains each have
highly variable regions, which give the immunoglobulin specificity, and constant
regions, in which there is virtual complete correspondence in amino acid sequence
in all antibodies of a given isotype.
(IMMUNOGLOBULIN STRUCTURE. (IMAGE BY USER JE AT UWO ON EN.WIKIPEDIA [PUBLIC

DOMAIN])
Types
There are five isotypes of immunoglobulin: IgG, IgA, IgM, IgE and IgD, which are
determined by the heavy chain (gamma, alpha, mu, epsilon or delta respectively);
the light chains are either kappa or lambda.
IgG is the most abundant in plasma (comprising 80% of normal serum
immunoglobulin) and the main circulatory Ig for the secondary immune
response; it is the only Ig that can cross the placenta.
IgM is the main Ig in the primary immune response and the most proficient at
complement fixation.
IgA is the major Ig in secretions, particularly from the gastrointestinal tract
(but also in saliva, tears, sweat and breast milk).
IgE is important for mast cell degranulation in allergic and antiparasitic
response.
IgD is expressed on naive B-cells and its function is not known.
Function
Antibodies:
Neutralise toxins and prevent attachment of pathogens
Target, opsonise or agglutinate (clump together) antigens for phagocytosis
Activate the complement cascade (leading to lysis or opsonisation of the
pathogen)
Act as antigen receptors on B lymphocytes
Activate antibody-dependent cell-mediated cytotoxicity by natural killer (NK)
cells or T cytotoxic cells
Provide mucosal immunity (IgA-mediated)
Stimulate degranulation of mast cells (IgE and IgG mediated)
Provide passive immunity to the newborn (through transplacental passage of
IgG and secretion of IgA in breast milk)

Lymphocytes LAST UPDATED: 10TH
JULY 2019
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In postnatal life, the bone marrow and thymus are the primary lymphoid
organs in which lymphocytes develop. The secondary lymphoid organs in
which specific immune responses are generated are the lymph nodes,
spleen and lymphoid tissues of the alimentary and respiratory tracts.The
adaptive immune response depends upon two types of lymphocytes, B and T cells,
which derive from the haemopoietic stem cell. Naive B and T cells which leave the
bone marrow and thymus are resting cells that are not in cell division. They
recirculate in the lymphatic system. Specialised macrophages called dendritic cells
(antigen presenting cells, APCs) process antigens before presenting them to B and
T cells. T and B cells undergo clonal expansion if they meet an APC that is
presenting an antigen that can trigger their antigen receptor molecules. At this
stage, lymphocytes can develop into effector cells (e.g. plasma cells, cytotoxic T
cells) or memory cells. Antigen-specific immune responses are generated in
secondary lymphoid organ and commence when antigen is carried into a lymph
node.
B Lymphocytes
B-cells (20% of lymphocytes) mature in the bone marrow and circulate in the
peripheral blood until they undergo recognition of antigen. B-cell immunoglobulin
molecules synthesised in the cell are exported and bound to the surface membrane
to become the B-cell receptor (BCR) which can recognise and bind to a specific
antigen (either free or presented by APCs). The BCR is also important for antigen
internalisation, processing and presentation to T helper cells. Most antibody
responses require help from antigen-specific T helper cells (although some
antigens such as polysaccharide can lead to T-cell independent B-cell antibody
production).
When the B-cell is activated, the receptor itself is secreted as free soluble
immunoglobulin and the B-cell matures into a memory B-cell or a plasma cell (a B-
cell in its high-rate immunoglobulin secreting state). Plasma cells are non-motile
and are found predominantly in the bone marrow or spleen. Most plasma cells are
short-lived (1 - 2 weeks) but some may survive much longer. A proportion of B-cells
persist as memory cells, whose increased number and rapid response underlies the
augmented secondary response of the adaptive immune system.
B-CELL ACTIVATION. (IMAGE BY FRED THE OYSTER [PUBLIC DOMAIN])
T Lymphocytes
T-cells (80% of lymphocytes) develop from cells that have migrated to the thymus
where they differentiate into mature T-cells during passage from the cortex to the
medulla. During this process, self-reactive T-cells are deleted whereas T-cells with
some specificity for host human leucocyte antigen (HLA) molecules are selected.
HLA molecules are glycoproteins expressed on the cell surface and consist of
cytoplasmic transmembrane and extracellular portions. T-cells have T-cell
receptors (TCR) which recognise antigen only when it is presented in association
with 'self' HLA molecules.
T-cells may be CD8 or CD4 receptor positive:
CD4+ T-cells (Helper T cells)
Recognise antigen only in association with HLA class II molecules
(found on antigen presenting cells (APCs) e.g. dendritic cells, B-cells;
present exogenous antigens that have been
phagocytosed/endocytosed into intracellular vesicles)
Form most of the circulating T-cell population (about 75%)
Secrete cytokines (e.g. IFN-gamma) which are required for recruitment
and activation of other immune cells such as macrophages, T cytotoxic
cells and NK cells and for the activation of and production of
immunoglobulin from B-cells
CD8+ T-cells (Cytotoxic T cells)
Recognise antigen only in association with HLA Class I molecules
(found on all nucleated cells; present endogenous antigens such as
those found in cells infected by viruses or intracellular bacteria.)
Comprise about 25% of peripheral T-cells
Responsible for cytotoxic killing of target cells
Phagocytes LAST UPDATED: 6TH
DECEMBER 2020
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Phagocytes can be divided into granulocytes (neutrophils, eosinophils and

basophils) and monocytes.
PHAGOCYTES. (IMAGE BY UNKNOWN. [PUBLIC DOMAIN])
Granulopoiesis
Granulocytes and monocytes are formed in the bone marrow from a common
precursor cell. The earliest recognisable granulocyte precursors are myeloblasts,
which undergo further differentiation into promyelocytes, myelocytes,
metamyelocytes and finally, mature granulocytes. The bone marrow normally
contains more myeloid cells than erythroid cells in the ratio of 2:1 to 12:1, the largest
proportion being neutrophils and metamyelocytes.
Many growth factors are involved in this process; they stimulate proliferation and
differentiation and affect the function of the mature cells on which they act. They
also inhibit apoptosis. Increased granulocyte (and monocyte) production in
response to an infection is induced by increased production of growth factors from
stromal cells and T lymphocytes, stimulated by endotoxin and cytokines such as IL-
1 or tumour necrosis factor (TNF).
Following their release from the marrow, granulocytes spend only 6-10 hours in the
circulation before entering tissues where they perform their phagocytic function.
They spend on average 4-5 days in the tissues before they are destroyed during
defensive action or as the result of senescence. In the bloodstream there are two
pools usually of about equal size: the circulating pool (included in the blood count)
and the marginating pool (not included in the blood count).
Neutrophils
Neutrophils are the most abundant peripheral blood leucocyte, comprising about
50 - 70% of circulating white cells. Neutrophils have a characteristic dense nucleus
consisting of between two and five lobes, and a pale cytoplasm with an irregular
outline containing many fine pink-blue or grey-blue granules. The granules are
divided into primary, which appear at the promyelocyte stage, and secondary,
which appear at the myelocyte stage and predominate in the mature nucleus. Both
types of granule are lysosomal in origin; the primary contains myeloperoxidase and
other acid hydrolases; the secondary contains lactoferrin, lysozyme and other
enzymes. The lifespan of neutrophils in the blood is only 6 – 10 hours. In response
to tissue damage, cytokines and complement proteins, neutrophils migrate from
the bloodstream to the site of insult within minutes, where they destroy pathogens
by phagocytosis.
Eosinophils
Eosinophils comprise 1 - 3% of circulating white cells. Eosinophils are similar to
neutrophils, except that the cytoplasmic granules are coarser and more deeply red
staining, and there are rarely more than three nuclear lobes. They are less motile,
but longer lived. They enter inflammatory exudates and have a special role in
allergic responses, defence against parasites and removal of fibrin formed during
inflammation. Thus they play a role in local immunity and tissue repair.
Basophils and Mast Cells

Basophils are only occasionally seen in normal peripheral blood comprising < 1% of
circulating white cells. However, they are the largest type of granulocyte. They have
many dark cytoplasmic granules which overlie the nucleus and contain heparin and
histamine. They have immunoglobulin E (IgE) attachment sites and their
degranulation is associated with histamine release. Basophils are very similar in
both appearance and function to mast cells.
Mast cells are resident in tissues and have an important function in allergy,
anaphylaxis and defence against parasites. Mast cells have granules containing
preformed mediators such as tryptase, histamine, serotonin and heparin and can
also secrete newly formed mediators such as prostaglandin D2, bradykinin,
cytokines and leukotrienes. Mast cell degranulation is triggered by cross-linking of
high affinity receptors for the Fc portion of IgE and results in: increased capillary
permeability, vasodilation, smooth muscle contraction, platelet aggregation and
activation, complement activation, increased mucus secretion and chemotaxis of
leucocytes.
Monocytes and Macrophages

Monocytes account for 5 - 10% of the peripheral white cell count. Monocytes are
usually larger than other peripheral blood leucocytes and have a large central oval
or indented nucleus with clumped chromatin. The abundant cytoplasm stains blue
and contains many fine vacuoles, giving a ground-glass appearance. Cytoplasmic
granules are also often present. Monocytes divide and differentiate from the
granulocyte macrophage progenitor into monoblasts, promonocytes, monocytes
and tissue macrophages (in increasing order of maturity). Monocytes spend only a
short time in the marrow and, after circulating for 20-40 hours, leave the blood to
enter the tissues where they become macrophages.
Macrophages form the reticuloendothelial system in the liver, spleen and lymph
nodes. The lifespan of macrophages may be as long as several months or even
years. In tissues the macrophages become self-replicating without replenishment
from the blood. They assume specific functions in different tissues e.g. Kupffer cells
in the liver, alveolar macrophages in the lung, intraglomerular mesangial cells in the
kidneys, microglial cells in the brain, Langerhans cells in the skin and histiocytes in
connective tissue. Macrophages may be activated by cytokines such as IFN-
gamma, contact with complement or direct contact with the target cell through
leucocyte adhesion molecules.
Normal Function
Neutrophils, eosinophils, basophils and monocytes all have phagocytic activity, but
neutrophils and monocytes are the main professional phagocytes. The normal
function of neutrophils and monocytes may be divided into three phases:
Chemotaxis (cell mobilisation and migration):
The phagocyte is attracted to bacteria or the site of inflammation by
chemotactic substances released from damaged tissues, by
complement components and by the interaction of leucocyte adhesion
molecules with ligands on the damaged tissues. The leucocyte
adhesion molecules also mediate recruitment and interaction with
other immune cells.
Phagocytosis:
The foreign material or dead/damaged host cells are phagocytosed.
Recognition of a foreign particle is aided by opsonisation with
immunoglobulin or complement because both neutrophils and
monocytes have Fc and C3b receptors. Macrophages have a central
role in antigen presentation: processing and presenting foreign
antigens on human leucocyte antigen (HLA) molecules to the immune
system. They also secrete a large number of growth factors and
chemokines which regulate inflammation and immune responses.
Killing and Digestion:
This occurs by oxygen-dependent and oxygen-independent pathways.
PROCESS OF PHAGOCYTOSIS: 1. A PARTICLE IS INGESTED BY A PHAGOCYTE AFTER
ANTIGENS ARE RECOGNIZED WHICH RESULTS IN THE FORMATION OF A PHAGOSOME. 2. THE
FUSION OF LYSOSOMES WITH THE PHAGOSOME CREATES A PHAGOLYSOSOME. THE
PARTICLE IS BROKEN DOWN BY THE DIGESTIVE ENZYMES FOUND IN THE LYSOSOMES. 3.
THE RESULTING WASTE MATERIAL IS DISCHARGED FROM THE PHAGOCYTE BY EXOCYTOSIS.
(IMAGE BY MANGO SLICES [CC BY-SA 4.0

Something wrong?
Hypersensitivity Reactions LAST UPDATED: 27TH

FEBRUARY 2020
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A group of diseases caused by an abnormal immune-mediated reaction. This may be

directed an an exogenous antigen from the environment or a self-antigen.
Type I Hypersensitivity
Type I hypersensitivity (immediate hypersensitivity) is mediated by IgE, with
immediate degranulation of mast cells and basophils. Overproduction of IgE in
response to innocuous environmental antigen occurs in allergy and atopic individuals.
Type I hypersensitivity reactions require an initial antigen exposure in order to
sensitise the immune system, where lots of IgE is produced in response to that
antigen. Mast cells have membrane receptors specific for the Fc portion of IgE, so that
mast cells become coated in IgE. Subsequent exposure to the same antigen cross-
linking mast cell surface IgE results in degranulation. Mast cells and basophils release
their contents within minutes of exposure to an allergen (early phase response). The
late phase response is mediated by eosinophils, responding to the same stimulus.
Examples of type I reactions include:
Allergic rhinitis
Allergic conjunctivitis
Allergic asthma
Systemic anaphylaxis
Angioedema
Urticaria
Penicillin allergy
Type II Hypersensitivity
Type II hypersensitivity (antibody-mediated hypersensitivity) occurs when antibody

(IgG or IgM) specific for cell surface antigens (either antibody to foreign cells or
autoantibody) is produced. Cell destruction then occur via complement fixation,
antibody-dependent cell-mediated cytotoxicity, and phagocytosis. Onset is normally
rapid.
Examples of type II reactions include:
Incompatible blood transfusions
Haemolytic disease of the newborn
Autoimmune haemolytic anaemias
Goodpasture's syndrome
Rheumatic heart disease
Bullous pemphigoid
Type III Hypersensitivity
Type III hypersensitivity (immune complex-mediated hypersensitivity) occurs when
antibodies (IgG) react to free soluble antigen by forming antibody-antigen complexes
called an immune complex. The immune complexes undergo opsonisation by
complement and then are transported to the spleen where they are phagocytosed. If
there is a rapid influx in antigen that overwhelms these mechanisms, then a type III
hypersensitivity reaction occurs. Sites of predilection for the deposition of immune
complexes include small blood vessels, kidneys and joints.
Examples of type III reactions include:
Extrinsic allergic alveolitis
Systemic lupus erythematosus (SLE)
Post-streptococcal glomerulonephritis
Reactive arthritis
Rheumatoid arthritis
Type IV Hypersensitivity
Type IV hypersensitivity (delayed T-cell-mediated hypersensitivity) is caused by
activated T lymphocytes that injure cells by direct killing or releasing cytokines that
activate macrophages. On first exposure to an antigen, a subset of T helper cells is
activated and clonally expanded (this takes 1 - 2 weeks). On subsequent exposure to
the same antigen, sensitised T helper cells secrete cytokines which attract and
activate phagocytic macrophages. The type IV reactions peaks at 48 - 72 hours after
contact with the antigen (time taken for recruitment and activation of macrophages).
Type IV reactions are important for clearance of intracellular pathogens.
Examples of type IV reactions includes:
Contact dermatitis
Hashimoto's thyroiditis
Primary biliary cholangitis
Tuberculin skin test (Mantoux test)
Chronic transplant rejection
Granulomatous inflammation (e.g. sarcoidosis, Crohn's disease)

Abnormal White Cell Count LAST UPDATED: 26TH
JUNE 2019
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Neutrophilia
Neutrophil leucocytosis is defined as a neutrophil count greater than 7.5 x 109/L.

Causes:
Bacterial infection
Inflammation and tissue necrosis (e.g. cardiac infarct, trauma, vasculitis,
myositis)
Metabolic disorders (e.g. uraemia, acidosis, eclampsia, gout)
Pregnancy
Acute haemorrhage or haemolysis
Neoplasms of all types
Drugs (e.g. corticosteroid therapy, lithium, tetracyclines)
Asplenia
Myeloproliferative disorders (e.g. CML, essential thrombocythaemia,
polycythaemia vera, myelofibrosis)
Rare inherited disorders
Neutropaenia
Neutropaenia is defined as a neutrophil count of < 1.8 x 109/L (except in black people
and in the Middle East where 1.5 x 109/L is normal). When the absolute count falls
below 0.5 x 19/L the patient is likely to have recurrent infections and when the count
falls to less than 0.2 x 109/L the risks are very serious. Neutropaenia may be selective
or part of a general pancytopaenia.
Causes:
Selective neutropaenia
Congenital causes
Acquired causes
Drug-induced (e.g. chemotherapy, chloramphenicol, co-
trimoxazole, phenytoin, carbamazepine, carbimazole, furosemide,
chloroquine, clozapine, some DMARDs)
Benign (racial or familial)
Cyclical
Immune (e.g. SLE, Felty's syndrome, hypersensitivity and
anaphylaxis)
Leukaemia
Infections (e.g. HIV, hepatitis, fulminant bacterial infection)
General Pancytopaenia
Hypersplenism, aplastic anaemia, malignant infiltration of bone marrow,
megaloblastic anaemia, chemotherapy, myelodysplasia
Monocytosis
A rise in blood monocyte count above 0.8 x 109/L is infrequent.

Causes:
Chronic bacterial infections (e.g. tuberculosis, brucellosis, bacterial endocarditis,
typhoid)
Connective tissue disease (e.g. SLE, rheumatoid arthritis)
Protozoan infection
Chronic neutropaenia
Malignancy
Eosinophilia
An eosinophil leucocytosis is defined as an increase in blood eosinophils above 0.4 x
109/L.
Causes:
It is most frequently due to:
Allergic diseases (e.g. bronchial asthma, hay fever, atopic dermatitis, urticaria)
Parasites (e.g. hookworm, ascariasis, tapeworm, schistosomiasis)
Skin diseases (e.g. psoriasis, pemphigus, urticaria, angioedema)
Drug sensitivity
Other causes include:
Recovery from acute infection
Vasculitis
Graft-versus-host disease
Hodgkin disease
Metastatic malignancy with tumour necrosis
Hypereosinophilic syndrome
Pulmonary syndromes
Myeloproliferative disorders
Basophilia
An increase in blood basophils above 0.1 x 109/L is uncommon.

Causes:
Myxoedema
Chickenpox infection
Ulcerative colitis
Lymphocytosis
Lymphocytosis often occurs in infants and young children in response to infections
that would normally produce a neutrophil reaction in adults.
Lymphocytosis occurs in:
Viral infections (e.g. infectious mononucleosis, HIV, rubella, mumps, viral
hepatitis, cytomegalovirus, herpes simplex or zoster)
Bacterial infections (e.g. pertussis, tuberculosis, toxoplasmosis, syphilis)
Chronic lymphoid leukaemias
Acute lymphoblastic leukaemias
Non-Hodgkin lymphoma
Thyrotoxicosis
Lymphopaenia
Lymphopenia occurs in:
Immunodeficiency (e.g. HIV infection)
Hodgkin lymphoma
Widespread irradiation
Severe bone marrow failure
Corticosteroid and other immunosuppressive drug therapy

Function of Spleen LAST UPDATED: 24TH
APRIL 2019
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Functions
Control of Red Cell Integrity:
The spleen has an essential role in the 'quality control' of red cells. Excess DNA,
nuclear remnants (Howell-Jolly bodies) and siderotic granules are removed in
the spleen. In the relatively hypoxic environment of the red pulp of the spleen,
the membrane flexibility of aged and abnormal red cells is impaired, and they are
trapped within the sinus where they are ingested by macrophages.
Immune Function:
Macrophages and dendritic cells in the spleen initiate an immune response to
antigens filtered from the blood and are involved in phagocytosis and antigen
presentation to B and T-cells to start adaptive immune responses. This
arrangement is particularly efficient at mounting an immune response to
encapsulated bacteria and explains the susceptibility of hyposplenic patients to
these organisms.
Extramedullary Haemopoiesis:
The spleen is a site of haemopoiesis in foetal life (around 3 – 7 months) but is not
a site of erythropoiesis in the normal adult. However, haemopoiesis may be re-
established in both the liver and the spleen as extramedullary haemopoiesis, in
disorders such as myelofibrosis or in chronic severe haemolytic and
megaloblastic anaemia. Extramedullary haemopoiesis may result from either
reactivation of dormant stem cells within the spleen or homing of stem cells
from the bone marrow to the spleen.
Splenomegaly
An enlarged spleen is often asymptomatic but if significant may cause
abdominal discomfort. Splenomegaly is usually felt under the left costal margin,
but massive splenomegaly may be felt as far as the right iliac fossa. The spleen
moves with respiration and a medial splenic notch may be palpable in some
cases.
In developed countries the most common causes of splenomegaly are infectious
mononucleosis, haematological malignancy and portal hypertension, whereas
malaria and schistosomiasis are more prevalent on a global scale. Chronic
myeloid leukaemia, primary myelofibrosis, malaria and leishmaniasis are potential
causes of massive splenomegaly.
Hypersplenism
Normally only approximately 5% of the total red cell mass is present in the
spleen, although up to half of the total marginating neutrophil pool and 30% of
the platelet mass may be located here. As the spleen enlarges, the proportion of
haemopoietic cells within the organ increases such that up to 40% of the red cell
mass, and 90% of platelets may be pooled in an enlarged spleen.
Hypersplenism is characterised by an enlarged spleen with reduction of at least
one cell line in the blood in the presence of normal bone marrow function.
Hypersplenism may be treated with splenectomy if symptomatic. It is followed
by a rapid improvement in the peripheral blood count.
Hyposplenism
Functional hyposplenism is characterised by the blood film findings of Howell-
Jolly bodies or siderotic granules on iron staining. The most frequent cause is
surgical removal of the spleen e.g. after traumatic rupture, but hyposplenism can
also occur in sickle cell anaemia, gluten-induced enteropathy, amyloidosis and
other conditions.
Patients with hyposplenism are at lifelong increased risk of infection from a
variety of organisms. This is seen particularly in children under 5 years and those
with sickle cell anaemia. The most characteristic susceptibility is to the
encapsulated bacteriae Streptococcus pneumoniae, Haemophilus influenzae
type B and Neisseria meningitidis. Streptococcus pneumoniae is a particular
concern and can cause a rapid and fulminant disease. Malaria and infection
caused by animal bites also tend to be more severe.
Measures to reduce the risk of serious infection include:
Patients should be informed about their increased susceptibility to
infection and advised to carry a card about their condition
Prophylactic oral penicillin is recommended usually for life
A supply of appropriate antibiotics should also be given for patients to take
in the event of onset of fever before medical care is available
Vaccination against pneumococcus, haemophilus, meningococcus and
influenza vaccination is recommended

Complement Cascade LAST UPDATED: 4TH
NOVEMBER 2019
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This consists of a series of plasma proteins constituting an amplification enzyme

system which is capable of lysis of bacteria/blood cells or opsonisation of
bacteria/cells for phagocytosis. The complement sequence consists of nine
major components, which are inactivated in turn and form a cascade, resembling
the coagulation sequence. The most abundant and pivotal protein is C3.
Opsonisation
Macrophages and neutrophils have C3b receptors and they phagocytose C3b-
coated cells. C3 deficiency thus leads to increased susceptibility of infection
with encapsulated organisms (e.g. S. pneumoniae, H. influenzae).
The early stages leading to coating of the cells with C3b can occur by two
different pathways:
The classical pathway usually activated by IgG or IgM coating of cells
The alternative pathway which is more rapid and activated by IgA,
endotoxin and other factors
Membrane Attack Complex

If the complement sequence goes to completion, there is generation of an active
phospholipase (the membrane attack complex, MAC) that punches holes in the
cell membrane causing cell lysis. The MAC appears to be the only way of killing
the Neisseria family of bacteria and thus C5 - C9 deficiency results in increased
susceptibility to Neisseria infections.
Anaphylactoids
The complement pathway also generates the biologically active fragments C3a
and C5a which are chemoattractant for neutrophils and monocytes and which
stimulate degranulation of mast cells and basophils.
Regulation
The complement pathway is regulated by complement inhibitors e.g. decay
accelerating factor or C1 inhibitor. Deficiency in C1 inhibitor results in hereditary
angioedema. Deficiency in complement decay-accelerating factor results in
paroxysmal nocturnal haemoglobinuria.
COMPLEMENT CASCADE. (IMAGE BY OPENSTAX COLLEGE [CC BY 3.0

(HTTPS://CREATIVECOMMONS.ORG/LICENSES/BY/3.0)])

Blood Groups LAST UPDATED: 4TH
JULY 2021
 Bookmark
Approximately 400 red blood cell group antigens have been described. Human
red blood cells carry many antigens on their surfaces. The most important of
these antigens belong to the ABO system and the rhesus (Rh) system. The D
antigen is the most important antigen of the rhesus system.
Immune Response
The ABO group antigens are unusual in that naturally occurring antibodies occur
in the plasma of subjects who lack the corresponding antigen, even if they have
not been exposed to that antigen previously. The most important of these
natural antibodies are anti-A and anti-B, which are usually IgM.
Immune antibodies develop in response to the exposure by transfusion or by
transplacental passage in pregnancy to red cells possessing antigens that the
subject lacks. These antibodies are commonly IgG, although some IgM may also
develop in the early phase of an immune response. Only IgG antibodies are
capable of transplacental passage and the most important immune antibody is
the Rh antibody, anti-D.
ABO
The protein that defines the ABO antigens is encoded from a single gene for
which there are three major alleles, A, B and O. The A and B alleles catalyse
addition of different carbohydrate residues to a basic antigenic glycoprotein or
glycolipid with a terminal l-fructose on the red cell, known as the H substance.
The O allele is non-functional and thus does not modify the H substance.
The ABO blood group phenotypes are O (genotype OO), A (genotype AA or AO), B
(genotype BB or BO) and AB (genotype AB).
Blood group O is the most common in the UK (46 %), followed by group A (42 %),
group B (9 %) and finally group AB (3 %).
Blood group O has no antigens, but both anti-A and anti-B antibodies and
thus is the universal donor.
Blood group AB has both A and B antigens but no antibodies and thus is
the universal recipient.
Blood group A has A antigens and anti-B antibodies and blood group B has
B antigens and anti-A antibodies.
BLOOD GROUPS. (IMAGE BY OPENSTAX COLLEGE [CC BY 3.0

Rh D
The RhD gene may be either absent or present, giving the RhD negative or RhD
positive phenotype respectively. About 85% of the UK population is Rh D
positive. Anti-D antibodies don't occur naturally, and are therefore immune
antibodies that result from previous transfusions or pregnancy. The indirect
Coombs test is used for routine antibody screening e.g. in pregnancy or prior to a
blood transfusion.
Rhesus Disease
A baby inherits its blood type from both parents. Therefore a mother who is RhD
negative can carry a baby who is RhD positive. During pregnancy small amounts
of fetal blood can enter the maternal circulation. The presence of fetal RhD-
positive cells in her circulation can cause a mother who is RhD negative to
mount an immune response, producing a template for the production of
antibodies as well as small amounts of antibodies against the RhD antigen (anti-
D antibodies). This process is called sensitisation or alloimmunisation.
Sensitisation can happen at any time during pregnancy, but is most common in
the third trimester and during childbirth. Sensitisation can follow events in
pregnancy, such as medical interventions (chorionic villus sampling,
amniocentesis or external cephalic version), terminations, late miscarriages,
antepartum haemorrhage and abdominal trauma. It can also occur in the
absence of an observed potentially sensitising event. Once sensitisation has
occurred it is irreversible.
The process of sensitisation has no adverse health effects for the mother and
usually does not affect the pregnancy during which it occurs. However, if the
mother is exposed to the RhD antigen during a subsequent pregnancy, the
immune response is quicker and much greater. The anti-D antibodies produced
by the mother can cross the placenta and bind to RhD antigen on the surface of
fetal red blood cells. These antibody-coated fetal red blood cells are removed
from the fetal circulation. Fetal anaemia results if the red blood cells are
removed faster than they are produced. Severe anaemia can lead to fetal heart
failure, fluid retention and swelling (hydrops), and intrauterine death.
When red blood cells are broken down, bilirubin is released. In utero this is
cleared by the placenta and is not harmful. However, after birth the neonatal
liver cannot cope with the excess production of bilirubin, and this leads to
jaundice (haemolytic disease of the newborn or HDN). Before birth, anaemia and
hydrops can be managed with intrauterine transfusions, but this carries a 2%
risk of fetal loss. When red blood cells are broken down, bilirubin is released. In
utero this is cleared by the placenta and is not harmful. However, after birth the
neonatal liver cannot cope with the excess production of bilirubin, and this leads
to jaundice (haemolytic disease of the newborn or HDN). Low levels of jaundice
are not harmful but, if left untreated, higher levels can result in damage to
specific areas of the neonatal brain, causing permanent brain damage
(kernicterus). This can lead to a range of neurodevelopmental problems, such as
cerebral palsy, deafness, and motor and speech delay. Postnatal jaundice can be
treated with phototherapy and exchange transfusion.
The risk of sensitisation can be reduced by administering anti-D immunoglobulin
to women in situations in which feto-maternal haemorrhage is likely (after
delivery, miscarriage, abortion, invasive procedures or abdominal trauma).
Potentially sensitising events introduce a quantity of fetal RhD antigen into the
maternal circulation. The anti-D immunoglobulin administered neutralises this
fetal antigen. In addition, anti-D immunoglobulin can be administered routinely
in the third trimester as prophylaxis against small amounts of feto-maternal
haemorrhage that can occur in the absence of observable sensitising events.
This is known as routine antenatal anti-D prophylaxis (RAADP).

Stages of Wound Healing LAST UPDATED: 8TH
NOVEMBER 2021
PATHOLOGY / WOUND HEALING
 Bookmark
The process of wound healing in the skin depends on the size of the injury; it
occurs by two mechanisms.
Healing by First Intention vs Secondary Intention

Healing by first intention can occur when the wound edges are opposed, the
wound is clean and uninfected and there is minimal loss of cells and tissue i.e.
surgical incision wound. The wound margins are joined by fibrin deposition,
which is subsequently replaced by collagen and covered by epidermal growth.
Healing by secondary intention occurs when wound margins are not opposed
due to extensive tissue damage and involves the following:
Tissue defect fills with granulation tissue
Epithelial regeneration to cover the surface
Granulation tissue eventually contracts resulting in scar formation;
myofibroblasts within granulation tissue are attached to each other and to
adjacent extracellular matrix, their contraction draws together the
surrounding matrix and thus reduces the size of the defect, but in doing
so produces a scar
Stages of Wound Healing

Acute wound healing has four main stages:
Haemostasis:
Endothelial damage results in platelet adhesion, activation and
aggregation with subsequent activation of the coagulation cascade and
fibrin deposition.
The blood clot seals the wound and creates a waterproof layer of fibrin and
fibronectin.
Tissue damage and microbes stimulate acute inflammation.
Inflammation:
Infiltration of inflammatory cells (initially predominantly neutrophils but
these are replaced by macrophages by day three) leads to phagocytosis of
pathogens, damaged cells and debris.
Basal epithelial cells from the edges secrete and respond to epithelial
growth factor (EGF); they proliferate and migrate under the clot, adhering
to fibronectin.
Platelets secrete platelet-derived growth factor (PDGF) into the wound
stimulating fibroblasts.
Proliferation:
New blood vessels bud off nearby capillaries stimulated by VEGF; at first
they are solid cords, later they develop a lumen.
Fibroblasts migrate to the wound (about 2 - 5 days after wounding),
proliferate and secrete extracellular matrix comprising mainly collagen
(type 3) and fibronectin to plug the gap.
Myofibroblasts contract, reducing the area required to heal.
Matrix metalloproteinases secreted by fibroblasts open paths in the
collagen matrix for cellular and vascular traffic and remodelling.
Remodelling:
Type 3 collagen is resorbed and replaced by scar tissue (type 1 collagen)
starting by day 5.
Mature collagen contracts.
Blood vessels regress.
Further wound contraction occurs reducing the total area of scarring by
50-70%.
Basic healing is complete by 5-10 days but maximal wound strength (80%
of normal) may take 12 weeks.
Factor Affecting Healing

The following are essential for good healing:
An adequate blood supply to deliver inflammatory cells to remove debris,
and to provide nutrition and oxygen to the regenerating tissue
Nutrients to supply building materials
Vitamins, especially vitamin C, used in the manufacture of tropocollagen
Immobilisation of the healing tissues
The absence of infection or other destructive processes
Viable cells that can undertake the process of clearing debris and
replacing the damage tissue
Local factors affecting Systemic factors affecting healing

healing
Tissue hypoxia Malnutrition (vitamin A, vitamin C and zinc
deficiency)
Excessive tension of Age
wound edges
Repeated trauma Immunodeficiency
Infection Glucocorticosteroid therapy
Presence of foreign Diabetes mellitus
material
Tissue necrosis Smoking
History of irradiation Obesity
Complications of Healing
Scar contractures e.g. burns or wounds over joints
Hypertrophic scarring
Keloid formation
Failure to heal (abscess or empyema formation)
Failure to unite (skin, muscle or fascia wound breakdown)
Traumatic neuroma
Fracture complications

Something wrong?
Tissue Regeneration and LAST UPDATED: 19TH

JUNE 2019
Repair  Bookmark
Healing is the process of replacing dead and damaging tissue with healthy
tissue; this may occur through regeneration or repair.
Regeneration vs Repair
Regeneration refers to total healing of a wound with restitution of the original
tissues in their usual amounts, arrangements and with normal function. This can
only occur if the connective tissue framework of the tissue is not disrupted and if
the tissue is capable of regeneration.
Repair refers to the process where the original tissue is not totally regenerated
and the defect is made good to a variable extent by scar tissue. This begins with
the formation of granulation tissue which is then converted into a collagen-rich
scar. Although the structural integrity is maintained, there is loss of function of
the tissue that is scarred.
Types of Cells
The regenerative capacity of cells can be categorised in three main ways:
Labile cells are constantly dividing and have a good capacity for
regeneration; this allows the replacement of ageing tissue such as the
surface epithelia of the skin, gastrointestinal tract and uterus; blood cells
are derived from labile cells of the bone marrow.
Stable cells are in a state of quiescence, meaning that the cells slowly
replicate to maintain tissue size; such tissue may rapidly regenerate if
stimulated e.g. liver, renal tubular epithelium, endocrine glands
Permanent tissues consist of cells that have left the cell cycle and so are
incapable of division and cannot be regenerated e.g. brain cells,
myocardial cells, skeletal muscle cells.
The ultimate consequence of tissue injury, therefore, depends on many factors.
Although labile and stable cells may be capable division, complex tissue
architecture might not be replaced.
Healing at Special Sites

Brain:
The brain undergoes liquefactive degeneration after major injury, such as
a stroke. Survivors have cystic spaces within their brains. In cases of acute
damage, the initial functional loss often exceeds the loss of actual nerve
tissue because of the reactive changes in the surrounding tissue. As these
changes diminish, some function may be restored. No significant
regeneration of neurons occurs (as these are permanent cells), but
'rewiring' of neuronal pathways is possible to a limited extent. Minor
injuries related to infective organisms may heal by 'gliosis', the nervous
system equivalent of scarring, by proliferation of astrocytes and the
production of fibrillary glial acidic protein.
Peripheral Nerves:
Axonal damage must be repaired by regeneration from the nerve cell body,
a slow process which proceeds at about 1 mm per day. Schwann cells can
regenerate myelin to form the nerves' insulation. Regeneration takes the
form of sprouting of the cut ends of the axons. The results depend on the
apposition of the distal remnant with the sprouting axons. The best results
are seen in crush injuries where the sheaths remain in continuity. The
muscle may have atrophied beyond repair by the time regeneration is
complete and so must be kept stimulated. When axonal fibres are
completely severed it is usually impossible for them to follow their original
route back to their target muscle. Proliferation at the site of injury may
cause a painful tumour-like nodule of nerve fibres and myelin - a traumatic
neuroma.
Muscle:
Smooth cells (stable cells) have the greatest capacity to regenerate of all
the muscle cell types. The smooth muscle cells themselves retain the
ability to divide, and can increase in number this way. As well as this, new
cells can be produced by the division of cells called pericytes that lie along
some small blood vessels.
Skeletal muscle contains numerous 'satellite cells' underneath the basal
lamina; these are mononucleated quiescent cells. When the muscle is
damaged, these cells are stimulated to divide. After dividing, the cells fuse
with existing muscle fibres, to regenerate and repair the damaged fibres.
The skeletal muscle fibres themselves cannot divide. However, muscle
fibres can lay down new protein and enlarge (hypertrophy).
Cardiac muscle cells (permanent cells) cannot regenerate and scarring is
normal after damage such as a myocardial infarction.

Stages of Fracture Healing LAST UPDATED: 24TH
APRIL 2019
 Bookmark
Bone fractures heal by granulation tissue formation with fibrous repair, followed
by new bone formation in the fibrous granulation tissue.
Stages of Bone Healing

1. Haematoma Formation (Day 1)
Haematoma formation due to tearing of medullary blood vessels.
Blood clot fills gap and swells and lifts periosteum - stretching or
tearing cause severe pain and encourage immobilisation.
2. Organisation (Days 1-7)

Migration of neutrophils and macrophages into fracture with
organisation of haematoma within about 24 hours.
Capillaries and fibroblasts proliferate forming fibrovascular
granulation tissue.
Periosteal cells activated by PDGF, FGF and other factors in the
blood clot.
New osteoprogenitor cells (derived from mesenchymal precursor
cells) mature into osteoblasts which migrate into granulation
tissue.
3. Callus Formation (Weeks 2-3)

Osteoblasts deposit large quantities of osteoid collagen in a
haphazard way producing a woven bone pattern.
Fracture is bridged on outside by external callus (may contain
cartilage) and it is bridged in medullary cavity by internal callus
(rarely contains cartilage).
However, direct ossification may occur between fractured ends if
they are closely apposed.
4. Remodelling (3 weeks-3 months)
About 3 weeks post fracture, callus is well established and
undergoes remodelling.
Osteoclastic resorption and osteoblastic osteoid synthesis
removes surplus calcified callus, replacing bulky, woven bone with
compact, organised, lamellar cortical bone.
Process takes several months.
5. Completion
Formation of new lamellar trabecular bone is complete.
The marrow space is repopulated to normal by fat and
haemopoietic cells.
Bone is orientated in a direction determined by stresses to which it
is exposed with mobilisation.
However, even after remodelling, cortical irregularities and minor
marrow space fibrosis persist at site of fracture.
Complications of Bone Healing

Bones show a great capacity for healing but certain complications can occur:
Malunion
Poor anatomical alignment of fractures results in deformity,
angulation or displacement
Delayed union
This is common and defined as 25% longer than average time
Non-union
If union has not occurred within 1 year; the defect is typically filled
with fibrous tissue/fibrosus ankylosis
Causes of Complications
Efficient healing requires optimal conditions. Factors that prevent efficient
healing are:
Poor apposition of fractured bone ends
Inadequate immobilisation
Interposition of foreign bodies or soft tissues
Infection
Corticosteroid therapy
Poor general nutritional status
Poor blood supply

Abnormal Bleeding LAST UPDATED: 19TH
JUNE 2019
PATHOLOGY / HAEMATOLOGY /
COAGULATION DISORDERS  Bookmark
Abnormal bleeding may result from:

Vascular disorders
Thrombocytopaenia
Defective platelet function
Defective coagulation
Clinical Features
The pattern of bleeding is relatively predictable depending on the aetiology. Vascular
and platelet disorders tend to be associated with bleeding from bleeding from
mucous membranes and into the skin, whereas in coagulation disorders the bleeding
is often into joints or soft tissue.
Platelet/Vessel Wall Coagulation

Disease Disease
Mucosal Bleeding Common Rare
Petechiae Common Rare
Deep haematomas Rare Characteristic
Bleeding from skin Persistent Minimal
cuts
Gender Equal >80% male
Screening Tests
A number of simple tests are employed to assess the platelet, vessel wall and
coagulation components of haemostasis.
Blood count and blood film examination
Platelet count
Screening tests of coagulation (see table below)
Prothrombin time (may be expressed as international normalised ratio
INR)
Activated partial thromboplastin time (APTT)
Thrombin (clotting) time
Specific assays of coagulation factors
Tests of platelet function
Platelet aggregation tests
Platelet adhesion assays
Platelet function analysis-100 (PFA-100) test
Tests of fibrinolysis
Thromboelastography (TEG) or thromboelastometry (ROTEM)
D-dimer
Screening Normal Abnormalities Causes

Test Time Indicated by
Prolongation
Thrombin Time 14 - 16 Deficiency/abnormality DIC, heparin
(TT) seconds of fibrinogen or therapy
inhibition of thrombin
Prothrombin 10 - 14 Deficiency/inhibition of Liver disease,
Time (PT) seconds coagulation factors: VII, warfarin therapy,
X, V, II, fibrinogen DIC
(extrinsic and common
pathway)
Activated 30 - 40 Deficiency/inhibition of Haemophilia,
Partial seconds coagulation factors: XII, Christmas
Thromboplastin XI, IX, VIII, X, V, II, disease, DIC, liver
Time (APTT) fibrinogen (intrinsic and disease, warfarin
common pathway) therapy, heparin
therapy
Fibrinogen x Fibrinogen deficiency DIC, liver disease
Quantitation

Acquired Coagulation LAST UPDATED: 25TH
JUNE 2019
Disorders  Bookmark
COAGULATION DISORDERS
The acquired coagulation disorders are more common than the inherited disorders.
Unlike the inherited disorders, multiple clotting factor deficiencies are usual.
Acquired coagulation disorders:
Deficiency of vitamin K-dependent factors
Haemorrhagic disease of the newborn
Biliary obstruction
Malabsorption of vitamin K
Vitamin K antagonist therapy (e.g. warfarin)
Liver disease
Disseminated intravascular coagulation (DIC)
Inhibition of coagulation
Specific inhibitors e.g. antibodies against factor VIII
Non-specific inhibitors e.g. antibodies found in SLE
Miscellaneous
Diseases with M protein production
L-Asparaginase
Therapy with heparin, defibrinating agents or thrombolytics
Massive transfusion syndrome
Vitamin K deficiency
Fat-soluble vitamin K is obtained from green vegetables and bacterial synthesis in the
gut. Deficiency may present in the newborn (haemorrhagic disease of the newborn) or
in later life.
Deficiency may be caused by an inadequate diet, malabsorption or inhibition of
vitamin K by drugs such as warfarin. The activity of factors II, VII, IX and X are vitamin
K dependent as well as that of protein C and protein S. Both PT and APTT are
prolonged.
Liver Disease
Multiple haemostatic abnormalities in liver disease contribute to a bleeding tendency
and may exacerbate haemorrhage from oesophageal varices:
Biliary obstruction impairs absorption of vitamin K and thus synthesis of factors
II, VII, IX and X
Severe hepatocellular disease often results in reduced levels of factor V and
fibrinogen and increased amounts of plasminogen activator
Decreased thrombopoietin production from the liver contributes to
thrombocytopaenia
Functional abnormality of fibrinogen is found in many patients
Hypersplenism associated with portal hypertension results in splenic
sequestration of platelets and thrombocytopaenia
DIC may occur
The net haemostatic imbalance in liver disease may be prothrombotic or
haemorrhagic
Disseminated Intravascular Coagulation

Pathogenesis:
DIC is characterised by a widespread inappropriate intravascular deposition of fibrin
with consumption of coagulation factors and platelets. This may occur as a
consequence of many disorders that release procoagulant material into the
circulation or cause widespread endothelial damage or platelet aggregation.
Increased activity of thrombin in the circulation overwhelms its normal rate of
removal by natural anticoagulants. In addition to causing increased deposition of
fibrin in the microcirculation and widespread platelet aggregation to the vessels,
intravascular thrombin formation interferes with fibrin polymerisation. Intense
fibrinolysis is stimulated by thrombi on vascular walls and the release of fibrin
degradation products again interferes with fibrin polymerisation. The combined
action of thrombin and plasmin causes depletion of fibrinogen and all coagulation
factors, compounded by thrombocytopaenia caused by platelet consumption.
Causes:
Infection
Gram-negative and meningococcal septicaemia, falciparum malaria
Malignancy
Leukaemia, Adenocarcinoma
Obstetric complications
Amniotic fluid embolism, premature separation of placenta, eclampsia,
retained placenta
Hypersensitivity reactions
Anaphylaxis, incompatible blood transfusion
Widespread tissue damage
Surgery, trauma, burns
Vascular abnormalities
Leaking prosthetic valves, cardiac bypass surgery, vascular aneurysms
Miscellaneous
Liver failure, pancreatitis, snake bites, hypothermia, heat stroke, acute
hypoxia, massive blood loss
Clinical Features:
These are usually dominated by bleeding, particularly from venepuncture sites or
wounds. There may be generalised bleeding in the gastrointestinal tract, the
oropharynx, into the lungs, the urogenital tract and from the vagina in obstetric
cases. Less frequently, microthrombi may cause skin lesions, renal failure, gangrene
of the fingers or toes, or cerebral ischaemia.
Laboratory Findings:
Low platelet count
Low fibrinogen concentration
Prolonged PT
Prolonged TT
Prolonged APTT
High levels of FDPs (e.g. D-dimers)
Features of haemolysis
Management:
Pathology Haematology Malignancy
Something wrong?
Acute Leukaemia LAST UPDATED:

3RD JUNE 2020
MALIGNANCY  Bookmark
The leukaemias are a group of disorders characterised by the
accumulation of malignant clonal white cells in the bone marrow
and blood.
Acute leukaemias are usually aggressive diseases in which
malignant transformation occurs in the haemopoietic stem cell
or early progenitors. Genetic damage is believed to involve
several key biochemical steps resulting in:
An increased rate of proliferation
Reduced apoptosis
A block in cellular differentiation
Together, these events cause accumulation in the bone marrow
of early haemopoietic cells called blast cells. The dominant
clinical feature of acute leukaemia is usually bone marrow failure
caused by accumulation of blast cells, although organ infiltration
also occurs.
Acute leukaemia is normally defined as the presence of over 20%
of blast cells in the bone marrow at clinical presentation
(although it can be diagnosed with less than 20% blasts if
specific leukaemia-associated cytogenetic or molecular genetic
abnormalities are present). The lineage of the blast cells is
defined by microscopic examination (morphology),
immunophenotypic (flow cytometry), cytogenetic and molecular
analysis. This will define whether the blasts are of myeloid or
lymphoid lineage and also localise the stage of cellular
differentiation.
Acute Myeloid Leukaemia

Incidence:
Acute Lymphoblastic Leukaemia

Acute myeloid leukaemia (AML) is the most common form of
acute leukaemia in adults and becomes increasingly common
with age, with a median onset of 65 years. It forms only a minor
fraction (10 - 15%) of childhood leukaemia.
Clinical Features:
The clinical features of AML are dominated by the pattern of bone
marrow failure caused by the accumulation of malignant cells
within marrow. Infections are frequent and anaemia and
thrombocytopaenia are often profound. Tumour cells can
infiltrate a variety of tissues.
Investigation:
Haematological investigations reveal a normochromic
normocytic anaemia with thrombocytopenia in most cases. The
total white cell count is usually increased and blood film
examination typically shows a variable number of blast cells. The
bone marrow is hypercellular and typically contains many blast
cells.
Management:
General supportive therapy for bone marrow failure
Insertion of central venous cannula, blood product
support, prevention of tumour lysis syndrome,
prompt treatment of fever
Specific therapy of AML
Determined by age and performance status of
patient as well as the genetic lesions within the
tumour; aim of treatment in acute leukaemia is to
induce complete remission (less than 5% blasts in
the bone marrow, normal peripheral blood counts
and normal clinical status) and then to consolidate
this with intensive therapy, hopefully eliminating the
disease; allogeneic stem cell transplantation is
considered in poor prognosis cases or for patients
who have relapsed
Prognosis:
The outcome for an individual patient with AML will depend on a
number of factors including age and white cell count at
presentation. However, the genetic abnormalities in the tumour
are the most important determinant. The prognosis for patients
with AML has been improving steadily, particularly for those
under 60 years of age, and approximately one-third of patients of
this group can expect to achieve long-term cure. For the elderly,
the situation is poor and less than 10% of those over 70 years of
age achieve long-term remission.
Incidence:
Acute lymphoblastic leukaemia (ALL) is caused by an
accumulation of lymphoblasts in the bone marrow and is the
most common malignancy of childhood. The incidence of ALL is
highest at 3 - 7 years, with 75% of cases occurring before the age
of 6. There is a secondary rise after the age of 40 years. 85% of
cases are of B-cell lineage and have an equal sex incidence;
there is a male predominance for the 15% of T-cell lineage.
Clinical features:
Bone marrow failure
Anaemia
pallor
lethargy
dyspnoea
Neutropaenia
fever
malaise
recurrent infections (mouth, throat, skin,
respiratory, perianal or other)
Thrombocytopaenia
spontaneous bruising
purpura
bleeding gums
menorrhagia
Organ infiltration
Tender bones
Lymphadenopathy
Splenomegaly
Hepatomegaly
Meningeal syndrome (headache, nausea and
vomiting, blurred vision and diplopia)
Testicular swelling or signs of mediastinal
compression
Investigations:
Haematological investigations reveal a normochromic
normocytic anaemia with thrombocytopenia in most cases. The
total white cell count may be decreased, normal or increased.
The blood film typically shows a variable number of blast cells.
The bone marrow is hypercellular with >20% blast cells. Lumbar
puncture for CSF examination is not generally performed as it
may promote the spread of tumour cells to the CNS. Initial
assessment of the CSF should always be combined with the
concurrent administration of intrathecal chemotherapy.
Biochemical tests may reveal a raised serum uric acid, serum
lactate dehydrogenase or, less commonly, hypercalcaemia, Liver
and renal functions tests are performed as a baseline before
treatment begins. Radiography may reveal lytic bone lesions and
a mediastinal mass caused by enlargement of the thymus and/or
mediastinal lymph nodes.
Management:
General supportive therapy for bone marrow failure
Insertion of central venous cannula, blood product
support, prevention of tumour lysis syndrome,
prompt treatment of fever
Specific therapy of ALL in children
Chemotherapy +/- radiotherapy; treatment is guided
by age, gender and white cell count at presentation;
aim of treatment in acute leukaemia is to induce
complete remission (less than 5% blasts in the bone
marrow, normal peripheral blood counts and normal
clinical status) and then to consolidate this with
intensive therapy, reducing the tumour burden to
very low levels or hopefully eliminating the disease
Specific therapy of ALL in adults
Prognosis:
There is great variation in the chance of individual patients
achieving a long-term cure based on a number of biological
variables. Approximately 25% of children relapse after first-line
therapy and need further treatment but overall 90% of children
can expect to be cured. The cure rate in adults drops significantly
to less than 5% over the age of 70 years.

Anaemia of Chronic LAST UPDATED:
15TH JULY 2019
Disease  Bookmark
PATHOLOGY / HAEMATOLOGY / ANAEMIA
Anaemia of chronic disease is a common normochromic or mildly

hypochromic anaemia, occurring in patients with different
inflammatory and malignant diseases.
Causes
Chronic infections
Especially osteomyelitis, bacterial endocarditis, TB,
chronic abscesses, bronchiectasis, chronic UTI, HIV, AIDs,
malaria
Chronic inflammatory disorders
Rheumatoid arthritis, polymyalgia rheumatica, systemic
lupus erythematosus, scleroderma, inflammatory bowel
disease, thrombophlebitis
Malignancy
Especially metastatic, lymphoma
Other
Congestive heart failure
Pathogenesis
Hepcidin, released by the liver in response to inflammatory cytokines,
reduces iron absorption and iron release by macrophages into plasma.
Increased level of cytokines also interact directly with accessory
marrow stromal cells, macrophages and erythroid progenitors to
reduce erythropoiesis, iron utilisation and response to erythropoietin.
Laboratory Features
Normocytic or mildly microcytic anaemia
Moderate anaemia (> 90 g/L), severity correlates to severity of
underlying disease
Reduced serum iron
Reduced total iron binding capacity (TIBC)
Reduced transferrin saturation
Normal or raised ferritin (adequate iron stores in bone marrow
but stainable iron absent from erythroblasts)
Raised ESR and CRP
Management
The anaemia is corrected by successful management of the
underlying disease and does not respond to iron therapy.
Recombinant erythropoietin may improve anaemia in patients with
e.g. rheumatoid arthritis, cancer and myeloma.

Anaemia Overview LAST UPDATED: 16TH
AUGUST 2022
 Bookmark
Anaemia is defined as a reduction in haemoglobin concentration below the normal

range for the age and sex of the individual. Women tend to have lower haemoglobin
than men.
Normal Values
Although laboratory values vary, typical values would be less than 135 g/L in adult
males and less than 115 g/L in adult females. From the age of 2 years to puberty, less
than 110 g/L indicates anaemia, and at birth less than 140 g/L indicates anaemia.
Anaemia may occur from an actual reduction in total circulating haemoglobin mass,
or with an increase in plasma volume e.g. in pregnancy, causing a dilutional anaemia.
Likewise, a reduction in plasma volume may mask anaemia or even cause an
apparent polycythaemia. After acute major blood loss, anaemia is not immediately
apparent because total blood volume is reduced and it takes up to a day for plasma
volume to be replaced and hence the degree of anaemia to become apparent. The
initial clinical features in acute haemorrhage are therefore a result of reduction in
blood volume rather than that of anaemia.
Clinical Features
When anaemia develops slowly, the associated symptoms are often very mild as the
body has time to adapt to the fall in haemoglobin. This involves mechanisms such as
an increase in red cell 2,3 -diphosphoglycerate (2,3 - DPG), which shifts the oxygen
dissociation curve to the right, allowing enhanced delivery of O2 to the tissues, and
an increase in stroke volume and heart rate.
In acute onset anaemia, a lack of physiological adaptation leads to more marked

symptoms and signs. Significant symptoms may also occur in more mild anaemia in
older patients with impaired cardiovascular reserve.
Non-specific symptoms of anaemia include:
fatigue
dizziness
headache
palpitations
tinnitus
shortness of breath on exertion
worsening of angina, congestive heart failure or intermittent claudication
Non-specific signs of anaemia include:
pallor of mucous membranes or nail beds (if Hb < 90 g/L)
tachycardia
bounding pulse
wide pulse pressure
flow murmurs
cardiomegaly
in severe cases, signs of congestive cardiac failure
Causes
Anaemia can be classified according to the red cell size or mean cell volume (MCV),
into microcytic, normocytic and macrocytic anaemia. This classification is not
perfect, as some conditions can straddle two categories e.g. anaemia of chronic
disease is usually normocytic, but may be microcytic or there may be combined
macrocytic and microcytic causes cancelling each other out to produce an apparent
normocytic anaemia.
Microcytic anaemia (MCV < 78 fl)
Iron deficiency
Thalassaemia
Other haemoglobin defects
Anaemia of chronic disease (some cases)
Congenital sideroblastic anaemia
Normocytic anaemia (MCV 78 - 98 fl)
Most haemolytic anaemias
Anaemia of chronic disease (most cases)
Mixed cases
Macrocytic anaemia (MCV > 98 fl)
Megaloblastic anaemia
Vitamin B12 deficiency
Folate deficiency
Other causes
Alcohol, liver disease, hypothyroidism, reticulocytosis, cytotoxic
drugs, aplastic anaemia, pregnancy, myelodysplastic syndromes,
myeloma, neonatal
Typical Investigations
Full blood count
Stained blood film
Haemoglobin electrophoresis or high performance liquid chromatography
(HPLC)
Haematinic levels (B12, folate, ferritin, iron and iron-binding capacity)

Antiplatelet and Anticoagulant LAST UPDATED: 25TH
JUNE 2019
Drugs  Bookmark
PATHOLOGY / HAEMATOLOGY / COAGULATION DISORDERS
Antiplatelets
Aspirin irreversibly inhibits cyclo-oxygenase impairing platelet synthesis of the
prostaglandin thromboxane A2, preventing platelet aggregation.
Dipyridamole inhibits both the reuptake of adenosine and phosphodiesterase, preventing
the degradation of cAMP and thus blocking the platelet aggregation response to ADP.
Clopidogrel inhibits the binding of ADP to its platelet receptor, preventing platelet
aggregation.
Abciximab, eptifibatide and tirofiban are GPIIb/IIIa inhibitors, inhibiting platelet
aggregation by preventing the binding of fibrinogen, von Willebrand factor and other
adhesive molecules.
ASPIRIN ANTIPLATELET EFFECT. (IMAGE BY VTVU [CC BY-SA 3.0

Anticoagulants
Unfractionated heparin potentiates the activity of antithrombin, which then inactivates
thrombin, factor Xa and other proteases.
Low molecular weight heparin (LMWH) preparations inhibit factor Xa directly. Inhibition of
factor Xa prevents thrombin generation and thrombus development.
Warfarin is a coumarin derivative that acts by inhibiting vitamin-K dependent clotting
factors (factors VII, IX, X and II) as well as the anticoagulant proteins C and S.
Apixaban, dabigatran, edoxaban and rivaroxaban are new anticoagulants with a novel
mode of action:
Apixaban, edoxaban and rivaroxaban are direct and reversible inhibitors of factor
Xa.
Dabigatran is a reversible inhibitor of free thrombin, fibrin-bound thrombin, and
thrombin-induced platelet aggregation.

Chronic Leukaemia LAST UPDATED: 25TH
APRIL 2019
PATHOLOGY / HAEMATOLOGY / MALIGNANCY
 Bookmark
The leukaemias are a group of disorders characterised by the accumulation of

malignant clonal white cells in the bone marrow and blood.
The chronic leukaemias are distinguished from acute leukaemias from their slower
progression. Chronic leukaemias can be broadly subdivided into myeloid and
lymphoid groups.
Chronic Myeloid Leukaemia

Incidence:
Chronic myeloid leukaemia (CML) is a clonal disorder of a pluripotent stem cell. The
disease accounts for around 15% of leukaemias and may occur at any age. The
diagnosis of CML is rarely difficult and is assisted by the characteristic presence of
the Philadelphia (ph) chromosome. This disease occurs in either sex, most frequently
between the ages of 40 and 60 years. However, it may occur in children and
neonates, and in the very elderly. There is a genetic predisposition to development of
the disease.
Clinical Features:
In up to 50% of cases the diagnosis is made incidentally from a routine blood count.
In those cases where the disease presents clinically, the following features may be
seen:
Symptoms related to hypermetabolism
weight loss
lethargy
anorexia
night sweats
Splenomegaly
Features of anaemia
pallor
dyspnoea
tachycardia
Features of abnormal platelet function
bruising
epistaxis
menorrhagia
haemorrhage
Gout or renal impairment caused by hyperuricaemia from excessive purine
breakdown
Visual disturbance and priapism (rare)
Investigations:
Leucocytosis is the main feature, with a complete spectrum of myeloid cells
seen in the peripheral blood. The levels of neutrophils and myelocytes exceed
those of blast cells and promyelocytes.
Increased circulating basophils are a characteristic feature.
Normochromic normocytic anaemia is usual.
Platelet count may be increased (most frequently), normal or decreased.
Bone marrow is hypercellular with granulopoietic predominance.
Serum uric acid is usually raised.
Ph chromosome on cytogenetic analysis (98% of cases)
Management
Tyrosine kinase inhibitors (TKI) are the mainstay of treatment and several
different drugs are now available, largely replacing chemotherapy treatment
Allogeneic stem cell transplantation is a potentially curative treatment for CML
but because of the risks associated with the procedure, it is usually reserved
for TKI failures or patient's presenting in accelerated phases.
Prognosis:
The clinical outlook is very good and 90% of patients can expect long-term control of
disease.
Chronic Lymphocytic Leukaemia

Incidence:
Chronic lymphocytic leukaemia (CLL) is the most common of the chronic lymphoid
leukaemias and has a peak incidence between 60 and 80 years of age. It is the most
common form of leukaemia within Europe and the USA but less frequent elsewhere.
The CLL tumour cell is a mature B-cell with weak surface expression of
immunoglobulin (IgM or IgD). CLL cells typically exhibit impaired apoptosis and a
prolonged lifespan, and this is reflected in their accumulation in the blood, bone
marrow, liver, spleen and lymph nodes. The mean age at diagnosis is 72 years, with
only 15% of cases before 50 years of age. The male: female ratio is approximately 2:1.
Clinical Features
Over 80% of cases are diagnosed from the results of a routine blood test,
usually taken for another reason.
Enlargement of cervical, axillary or inguinal lymph nodes is the most frequent
clinical sign.
Features of anaemia and thrombocytopenia may be present
Splenomegaly and, less commonly, hepatomegaly are common in later stages
Immunosuppression is often a significant problem with recurrent infection
Investigations:
Lymphocytosis
CLL tumour cells
Normochromic normocytic anaemia
Thrombocytopenia
Bone marrow aspiration shows up to 95% lymphocytic replacement of normal
marrow elements
Reduced concentrations of serum immunoglobulins are found
Autoimmunity directed against cells of the haemopoietic system is common
Management:
It is very difficult to cure CLL and so the approach to therapy is generally
conservative, aiming for symptom control rather than a normal blood count. Indeed,
chemotherapy given too early in the disease can shorten rather than prolong life
expectancy. Many patients never need treatment but treatment may be given for
troublesome symptoms or if the lymphocyte count rises rapidly. Use of
chemotherapy and an anti-CD20 monoclonal antibody establishes disease remission
but is not curative.
Haemolytic Anaemia LAST UPDATED: 12TH
AUGUST 2019
 Bookmark
Haemolytic anaemias are caused by a shortened red cell lifespan. Because of

erythropoietic hyperplasia and anatomical extension of bone marrow, red cell
destruction may be increased several-fold before the patient becomes anaemic.
Causes
Hereditary causes:
Red cell membrane e.g. hereditary spherocytosis, hereditary elliptocytosis
Red cell metabolism e.g. glucose-6-phosphate dehydrogenase (G6PD)
deficiency, pyruvate kinase deficiency
Haemoglobin synthesis e.g. thalassaemia, sickle cell disease
Acquired causes:
Autoimmune e.g. warm or cold antibody type (characterised by a positive
direct Coombs test and divided into 'warm' and 'cold' types according to
whether the antibody reacts more strongly with red cells at 37 degrees Celsius
or 4 degrees Celsius)
Alloimmune e.g. haemolytic disease of the newborn or haemolytic transfusion
reactions
Red cell fragmentation syndromes e.g. DIC, TTP, HUS
Infections e.g. malaria
Drug or chemical-associated
Secondary to liver or renal disease
Paroxysmal nocturnal haemoglobinuria
Pathophysiology
Physiological red cell destruction is normally extravascular in the macrophages of
the reticuloendothelial system. Globin is degraded to amino acids, haem to
protoporphyrin, carbon monoxide and iron. Protoporphyrin is metabolised to
biliverdin, and then bilirubin, conjugated to a glucuronide in the liver, excreted in
faeces (as stercobilinogen) and, after reabsorption, in urine as urobilinogen.
Pathological red cell destruction is also usually extravascular. However it may also be
intravascular. Some haemoglobin may then appear in plasma, where it is toxic and
may cause fever, rigors and tissue damage. It is excreted unchanged in the urine and
may cause renal damage. It is also partly reabsorbed by the renal tubules and broken
down in the tubular cells to haemosiderin which appears in the urine.
Causes of intravascular haemolysis:

Haemolytic transfusion reactions
G6PD deficiency
Red cell fragmentation syndromes
Some severe autoimmune haemolytic anaemias
Some drug-and infection-induced haemolytic anaemias
Clinical Features
Anaemia
Jaundice (caused by unconjugated bilirubin in plasma, bilirubin is absent from
urine)
Pigment gallstones
Splenomegaly
Ankle ulcers
Expansion of marrow with, in children, bone expansion e.g. frontal bossing in
beta-thalassaemia major
Aplastic crisis caused by parvovirus
Megaloblastic anaemia caused by folate deficiency
Laboratory Features
Haemoglobin may be normal or reduced
Reticulocyte count is raised
Blood film shows polychromasia and altered red cell shape
Bone marrow shows increased erythropoiesis
Serum indirect (unconjugated) bilirubin is raised
Urine urobilinogen is raised
Serum haptoglobin is absent
Lactate dehydrogenase is raised
+/- Features of intravascular haemolysis
Haemoglobinaemia
Methaemalbuminaemia
Haemoglobinuria (dark urine)
Haemosiderinuria

Inherited Coagulation LAST UPDATED: 24TH
APRIL 2019
Disorders  Bookmark
COAGULATION DISORDERS
Hereditary deficiencies of each of the coagulation factors have been described.
Haemophilia A (factor VIII) deficiency, haemophilia B (Christmas disease, factor IX
deficiency) and von Willebrand disease (VWD) are the most frequent; the others are
rarer.
Haemophilia A
Haemophilia A is the most common of the hereditary clotting factor deficiencies.
The inheritance is sex-linked but up to one-third of patients have no family history
and these cases result from recent mutation. The defect is an absence or low level
of plasma factor VIII.
Inheritance:
The inheritance is X-linked recessive; therefore (assuming the other parent is a
non-carrier):
Sons of a female carrier have a 50% chance of developing the disease
Daughters of a female carrier have a 50% chance of being a carrier
All sons of a male haemophiliac will be unaffected
All daughters of a male haemophiliac will be a carrier
X-LINKED RECESSIVE INHERITANCE PATTERN. (IMAGE BY NATIONAL INSTITUTES OF
HEALTH DERIVATIVE WORK: DRSRISENTHIL [PUBLIC DOMAIN])
Clinical Features:
Infants may develop profuse post-circumcision haemorrhage or joint and soft

tissue bleeds and excessive bruising when they start to become active. Recurrent
painful haemarthroses and muscle haematomas dominate the clinical course of
severely affected patients and if inadequately treated, lead to progressive joint
deformity and disability. Local pressure can cause entrapment neuropathy or
ischaemic necrosis. Prolonged bleeding occurs after dental extractions or post-
trauma. Spontaneous haematuria and gastrointestinal haemorrhage may occur.
The clinical severity of the disease correlates inversely with the factor VIII level.
Operative and post-traumatic haemorrhage are life-threatening both in severely
and mildly affected patients. Haemophilic pseudotumours are large encapsulated
haematomas with progressive cystic swelling from repeated haemorrhage. Due to
blood product transfusions, many patients were infected with HIV and hepatitis C
during the 1980s.
Laboratory Findings:
Prolonged APTT
Normal PT
Low Factor VIII
Haemophilia B (Christmas Disease)

Haemophilia B is due to a factor IX deficiency. The inheritance and clinical features
are identical to that of haemophilia A. The two disorders can only be distinguished
by specific coagulation factor assays. The incidence is one-fifth of that of
haemophilia A. Laboratory findings demonstrate prolonged APTT, normal PT and
low factor IX.
Von Willebrand Disease

Von Willebrand disease (VWD) results from either a reduced level or abnormal
functioning of von Willebrand factor (VWF) resulting from a wide variety of genetic
mutations.
VWF is produced both in endothelial cells and megakaryocytes. VWF has two roles:
it promotes platelet adhesion to subendothelium and to each other at high shear
rates and it is the carrier molecule for factor VIII, protecting it from premature
destruction. The latter property explains the reduced factor VIII levels found in
VWD.
VWD is the most common inherited bleeding disorder. Usually the inheritance is
autosomal dominant, and the severity of the bleeding is highly variable. Women are
more badly affected than men at a given VWF level. Typically there is mucous
membrane bleeding (e.g. epistaxis, menorrhagia), excessive blood loss from
superficial cuts and abrasions, and operative and post-traumatic haemorrhage.
Haemarthroses and muscle haematomas are rare.
Laboratory findings typically show (although again, this varies depending on VWD
type):
Abnormal PFA-100 test
Low factor VIII levels (if low a factor VIII/VWF binding assay is performed)
Prolonged APTT (or normal)
Normal PT
Low VWF levels
Defective platelet aggregation
Normal platelet count

Iron Deficiency Anaemia LAST UPDATED: 16TH
JULY 2019
 Bookmark
Iron deficiency anaemia is the most common cause of microcytic anaemia and of any
anaemia worldwide.
Causes
Inadequate Intake:
Dietary iron deficiency is fairly uncommon in the UK
Growing children and elderly people with iron-poor diets may become
deficient
Excessive requirements:
Pregnancy, menstruation, lactation
Times of rapid growth in children
Exfoliative skin disease
Malabsorption:
Drugs e.g. tetracyclines, quinolones, antacids and proton pump
inhibitors
Partial or total gastrectomy
Coeliac disease, inflammatory bowel disease (IBD), gastritis
Excessive loss:
Blood loss from the gastrointestinal (GI) tract is the most common cause
of iron deficiency anaemia in adult men and postmenopausal women.
Blood loss due to menorrhagia is the most common cause of iron
deficiency anaemia in pre-menopausal women.
In tropical countries, infestation of the gut is a common cause of iron
deficiency, especially with hookworm and schistosomiasis.
Clinical Features
General features of anaemia
Specific features of iron deficiency:
koilonychia (spoon-shaped nails with longitudinal ridging)
angular cheilitis (ulceration at the corners of the mouth)
atrophic glossitis (painful smooth red tongue)
pica (unusual dietary cravings)
hair thinning
Laboratory Findings
Hypochromic microcytic anaemia
Blood film appearances: hypochromic/microcytic cells,
anisocytosis/poikilocytosis, target cells, 'pencil' cells
Iron status
↓ Serum ferritin
↓ Serum iron
↑ Transferrin
↓Transferrin saturation
↑ Total iron binding capacity (TIBC)
Ferritin, Transferrin and Iron Levels

The key parameters of iron status are the serum ferritin, transferrin and iron levels.
Ferritin is the main storage protein for iron and therefore roughly correlates with the
amount of tissue-storage iron. However ferritin is also an acute phase reactant,
which is typically raised in infection and inflammation. Thus normal serum ferritin
levels may be found in the presence of reduced iron stores in for example infection
or malignancy.
Serum iron also falls in the context of iron deficiency, but there is often marked
diurnal and day-day changes in serum iron concentration, making it an unreliable
indicator of iron status when assayed alone. Serum iron can however be interpreted
in the context of the transferrin concentration, to give a measure of transferrin
saturation.
Transferrin, synthesised in the liver, is generally increased in states of iron
deficiency, and together with the reduced serum iron, this leads to an increased total
iron binding capacity (TIBC) and a reduction in transferrin saturation (where levels <
20% generally represent iron depletion). This can also be unreliable in isolation as
chronic liver disease and chronic inflammatory states will cause the serum
transferrin level to fall, while its production is often increased in women taking the
OCP.

Iron Requirements LAST UPDATED: 4TH
JUNE 2020
 Bookmark
Iron is contained in haemoglobin, the reticuloendothelial system (as ferritin and

haemosiderin), muscle (myoglobin), plasma (bound to transferrin) and cellular
enzymes (e.g. cytochromes, catalase). The total amount of iron in the body is about 3
- 4 g, of which about two-thirds is in haemoglobin.
Iron Intake and Absorption

The average Western diet contains 10 - 15 mg/day of iron and typically about 5 - 10%
of this is absorbed through the upper small intestine to make up for daily loss.
Dietary iron may be in the form of haem or non-haem iron. Haem iron is degraded
after absorption through the cell surface to release Fe2+. Most non-haem iron is in
the form Fe3+, which is reduced at the luminal surface to the more soluble Fe 2+,
facilitated by hydrochloric acid in gastric secretions (and enhanced by ascorbic
acid). Fe2+ is taken from the intestinal lumen into the cell across the enterocyte
apical membrane by the divalent metal transporter (DMT1).
In the enterocyte, Fe2+ is then either stored in enterocyte epithelial cells as ferritin,
or released into portal plasma via the transmembrane protein ferroportin at the
basolateral membrane.
Iron Transport and Storage
On entry to portal plasma, Fe2+ is reoxidised to Fe3+ and then bound to the transport
protein transferrin. Iron is transferred to the bone marrow for erythropoiesis or to the
liver or other parenchymal cells for storage as ferritin or haemosiderin.
Reticuloendothelial cells (macrophages) also gain iron from the breakdown of
haemoglobin of senescent red blood cells, and can release this to plasma transferrin
for transfer to other tissues.
Iron Regulation
Iron absorption is tightly regulated as excess iron is potentially toxic, and the body
has no physiological mechanism for upregulating excretion.
Iron absorption can be increased when body stores are low or when there is a need
to increase erythropoiesis e.g. an increase in absorption may be seen about 3 - 4
days following haemorrhage.
Hepcidin is the main hormonal regulator of iron homeostasis; it lowers cell levels of
ferroportin, the protein that allows iron entry into the portal circulation from
duodenal enterocytes and into the blood circulation from macrophages. Hepcidin
therefore reduces both iron absorption and iron release from macrophages.
Synthesis of hepcidin is suppressed by iron deficiency and increased erythropoiesis
but upregulated in inflammation and iron overload.
IRON HANDLING. (IMAGE BY UNKNOWN, [CC BY-SA 3.0

HTTPS://IT.WIKIPEDIA.ORG/WIKI/FILE:METABOLISMO_DEL_FERRO.JPG])

Lymphoma LAST UPDATED: 25TH
APRIL 2019
 Bookmark
Lymphomas are a group of diseases caused by malignant lymphocytes that

accumulate in lymph nodes and other lymphoid tissue and cause the characteristic
clinical feature of lymphadenopathy.
The major subdivision of lymphomas is into Hodgkin lymphoma (HL) and non-
Hodgkin lymphoma (NHL) and this is based on the histological presence of Reed-
Sternberg cells present in HL.
Hodgkin Lymphoma
Incidence:
Hodgkin lymphoma can present at any age but is rare in children and has a peak
incidence in young adults. There is an almost 2 : 1 male predominance.
Clinical Features:
Lymphadenopathy
Most patients present with painless, asymmetrical, firm and discrete
enlargement of superficial lymph nodes
Cervical nodes are involved in 60-70% of cases, axillary nodes in 10-15%
and inguinal nodes in 6-12%
Typically the disease is localised initially to a single peripheral lymph
node region and its subsequent progression is by contiguity within the
lymphatic system
Retroperitoneal nodes are also often involved but usually only diagnosed
by CT scan
Modest splenomegaly occurs during the course of the disease in 50% of
patients; the liver may also be enlarged
Mediastinal involvement is found in up to 10% of patients at presentation (may
be associated with pleural effusions or superior vena cava obstruction)
Cutaneous HL occurs as a late complication in approximately 10% of patients
Constitutional symptoms are prominent in patients with widespread disease
Fever (occurs in 30% of patients)
Pruritus (occurs in 25% of patients)
Alcohol-induced pain in areas where disease is present
Other symptoms including weight loss, night sweats, fatigue, weakness,
anorexia and cachexia
Investigations:
Normochromic normocytic anaemia is most common; bone marrow failure
involvement is unusual in early disease, but if it occurs bone marrow failure
may develop with leucoerythroblastic anaemia
One-third of patients have a neutrophilia; eosinophilia is frequent
Advanced disease is associated with lymphopenia and loss of cell-mediated
immunity
Platelet count is normal or increased in early disease and reduced in later
stages
ESR and CRP are usually raised (ESR is useful in monitoring disease progress)
Serum LDH is raised initially in 30-40% of cases
Diagnosis is made by histological examination of an excised lymph node
The distinctive multinucleate polypoid RS cell is central to the diagnosis
of the four classic types of HL (95% of cases)
Management:
The selection of appropriate treatment depends on the stage and grade of the
disease
Staging is performed by history, clinical examination and blood tests together
with PET and CT scans
Treatment is with chemotherapy alone or a combination of chemotherapy with
radiotherapy; the response to treatment can be monitored by CT and PET
scans; disease relapse can be treated with chemotherapy and sometimes with
stem cell transplantation
Prognosis:
The prognosis depends on age, stage and histology
Overall approximately 85% of patients are cured
Non-Hodgkin Lymphoma
Non-Hodgkin lymphomas (NHL) are a large group of clonal lymphoid tumours, about
85% of B-cell and 15% of T or NK (natural killer) cell origin. Their clinical presentation
and natural history are much more variable than Hodgkin lymphoma. They are
characterised by an irregular pattern of spread and a significant proportion of
patients develop disease outside of the lymph nodes.
Clinical features:
Superficial lymphadenopathy (typically asymmetric and painless)
Constitutional symptoms (fever, night sweats, weight loss)
Oropharyngeal involvement (sore throat, noisy or obstructed breathing)
Symptoms due to anaemia, neutropaenia or thrombocytopaenia
Abdominal disease (hepatosplenomegaly, involvement of retroperitoneal or
mesenteric nodes)
Infiltration of other organs (skin, brain, testis or thyroid)
Investigations:
Whole lymph node biopsy, or more usually trucut biopsy of lymph node or of
other involved tissue (e.g. bone marrow or extranodal tissue) is the definitive
investigation; morphological examination of the biopsy is assisted by
immunophenotypic, and in some cases, genetic analysis
Blood tests
PET/CT imaging
Management:
When treatment is started it is usually in the form of a combination of
chemotherapy drugs together with a monoclonal antibody directed against
the tumour cell
However, various new drugs have been developed which may change the
management of disease in future years

Megaloblastic Anaemia LAST UPDATED: 4TH
AUGUST 2019
 Bookmark
Megaloblastic anaemia is characterised by an abnormal appearance of the bone

marrow erythroblasts in which nuclear development is delayed and nuclear
chromatin has a lacy open appearance.
Pathophysiology
Megaloblastic anemia results from inhibition of DNA synthesis during red blood cell
production. When DNA synthesis is impaired, the cell cycle cannot progress from the
growth stage to the mitosis stage. This leads to continuing cell growth without
division, which presents as macrocytosis. The defect in red cell DNA synthesis is
most often due to hypovitaminosis, specifically vitamin B12 deficiency or folate
deficiency.
Vitamin B12 and Folate Requirements

Vitamin B12 is found exclusively in food of animal origin. Dietary vitamin B12 is
cleaved from food proteins by gastric acid and bound to R protein found in saliva and
in gastric secretions which protects it from digestion in the stomach. Vitamin B12 is
cleaved from R protein by the action of pancreatic proteases, and subsequently
binds to intrinsic factor secreted by gastric parietal cells. Receptors for the intrinsic
factor-B12 complex are present in the membrane of epithelial cells of the terminal
ileum, which bind the complex and allow uptake of vitamin B12. Vitamin B12 is then
transported across the basal membrane of the epithelial cells into the plasma, where
it is bound to transcobalamin II and taken up by the tissues. Normal body stores are
largely in the liver with an enterohepatic circulation. Stores of vitamin B12 are
normally adequate for 2 - 4 years and so features of deficiency take years to appear.
Folate is an essential vitamin found in most foods, especially liver, green vegetables
and yeast. The normal daily diet contains 200 - 250 μg, of which about 50% is
absorbed. Daily adult requirements are about 100 μg. Absorption of folate is
principally from the duodenum and jejunum. Stores of folate are normally only
adequate for 4 months and so features of deficiency may be apparent after this time.
Causes of Vitamin B12 and Folate Deficiency
Causes of vitamin B12 deficiency:
Inadequate intake e.g. vegan diet
Malabsorption
Gastric causes
Pernicious anaemia
Gastrectomy
Congenital intrinsic factor deficiency
Atrophic gastritis
H.pylori infection
Intestinal causes
Fish tapeworm infestation
Overgrowth of intestinal flora
Ileal resection
Crohn's disease
Coeliac disease
Causes of folate deficiency:
Inadequate intake
Old age, alcoholism, institutions, poverty
Excessive requirement
Physiological
Pregnancy, lactation, prematurity
Pathological
Haemolytic anaemia, myelofibrosis, malignancy, inflammatory
disease
Malabsorption
Coeliac disease, Crohn's disease, jejunal resection, tropical sprue
Excessive urinary loss
Congestive heart failure, chronic dialysis
Drugs
Anticonvulsants, sulfasalazine
Mixed
Liver disease, alcoholism
Clinical Features
General features of anaemia
Increased incidence of foetal neural tube defects in pregnancy
Megaloblastic anaemia:
Lemon yellow tinge (combination of pallor and jaundice) caused by
ineffective erythropoiesis
Glossitis
Angular cheilitis
B12 deficiency:
Symmetrical neuropathy affecting the pyramidal tracts and posterior
columns of the spinal cord (subacute combined degeneration of the
cord) and the peripheral nerves (patients present with tingling in feet,
difficulty in gait, visual or psychiatric disorders)
Laboratory Features
Megaloblastic anaemia is characterised by:
Macrocytic anaemia with oval macrocytes and hypersegmented neutrophils
Moderate reduction in leucocyte and platelet counts
Raised serum bilirubin (indirect) and lactate dehydrogenase (LDH) (due to
haemolysis of defective red cells)
Low B12 +/- folate
Hypercellular bone marrow, increased proportion of early cells, megaloblastic
erythropoiesis and giant metamyelocytes

Multiple Myeloma LAST UPDATED: 25TH
APRIL 2019
 Bookmark
Multiple myeloma is a neoplastic disease characterised by plasma cell accumulation

in bone marrow, the presence of monoclonal protein in the serum and/or urine and,
in symptomatic patients, related tissue damage.
Incidence
98% of cases of myeloma occur over the age of 40 years with a peak incidence
between 65 and 70 years. The disease is twice as common in black individuals
compared to those of white or Asian origin.
Clinical Features
A useful acronym for tissue damage in myeloma is CRAB:
Hypercalcaemia
Renal impairment (proteinaceous deposits from light chain proteinuria,
hypercalcaemia, uric acid, amyloid and pyelonephritis may all contribute to
renal failure)
Anaemia
Bone pain (especially backache, resulting from vertebral collapse and
pathological fractures)
Other features include:
Amyloidosis (features include macroglossia, carpal tunnel syndrome,
diarrhoea)
Hyperviscosity syndrome (features include purpura, haemorrhages, visual
disturbance, CNS symptoms, neuropathies and heart failure)
Recurrent infections (related to deficient antibody production, abnormal cell-
mediated immunity and neutropaenia)
Abnormal bleeding tendency (resulting from paraprotein interfering with
platelet function and coagulation factors and from thrombocytopaenia in
advanced disease)
Peripheral neuropathy
Deep vein thrombosis
Laboratory Findings
Presence of a paraprotein in serum/urine (the paraprotein is IgG in 60% of
cases, IgA in 20% and light chain only in almost all the rest)
Elevated serum immunoglobulin-free light chains (κ or λ light chain proteins,
synthesised by plasma cells, that have not been paired with heavy chains; they
are normally made in small quantities and filtered from the serum into the
kidney but they are produced by almost all malignant plasma cells and so the
serum free light chain assay is useful in diagnosis and monitoring of myeloma
Bence-Jones protein (free light chains) in urine
Reduced serum IgG, IgA and IgM levels (immunoparesis)
Normochromic normocytic or macrocytic anaemia
Marked Rouleaux formation on blood film
Neutropaenia and thrombocytopaenia in advanced disease
High ESR
Increased plasma cells in the bone marrow (usually more than 20%), often with
abnormal forms
Hypercalcaemia (45% of patients)
Elevated creatinine (20% of cases)
Low serum albumin in advanced disease
Osteolytic lesions (60% of patients), osteoporosis (20% of patients) or
pathological fractures/vertebral collapse on radiological investigation
Raised serum β2-microglobulin (useful indicator of prognosis)
Management
The life expectancy of patients with myeloma has improved markedly in recent years
with the introduction of new drugs such as proteasome inhibitors and
immunomodulatory agents. The major initial treatment decision is between the use
of intensive combination chemotherapy (mostly for patients aged less than 70 years
old) or non-intensive therapy for older patients.
Prognosis
The outlook for patients with myeloma is improving markedly. The overall median
survival is now 7-10 years and in younger (less than 50 years) patients it can be over
Platelet Bleeding Disorders LAST UPDATED: 22ND
NOVEMBER 2021
PATHOLOGY / HAEMATOLOGY / COAGULATION DISORDERS
 Bookmark
Abnormal bleeding associated with thrombocytopaenia or abnormal platelet function is

characterised by spontaneous skin purpura, mucosal haemorrhage and prolonged bleeding
after trauma.
Thrombocytopaenia
Thrombocytopaenia may occur from:
Failure of platelet production (most common)
Selective megakaryocyte depression
Rare congenital defects
Drugs, chemicals, viral infections
Part of general bone marrow failure
Cytotoxic drugs, radiotherapy
Aplastic anaemia
Megaloblastic anaemia
HIV
Leukaemia, myelodysplasia, myelofibrosis, myeloma, marrow infiltration
Increased destruction of platelets
Immune
Autoimmune, idiopathic, post-transfusional, feto-maternal
Associated with infections or systemic disease
Drug-induced (e.g. heparin)
Thrombotic thrombocytopaenic purpura (TTP)
Abnormal distribution of platelets
Splenomegaly e.g. liver disease
Dilutional loss
Massive transfusion of stored blood to bleeding patients
Disorders of platelet function are suspected in patients who show skin and mucosal
haemorrhage despite a normal platelet count and normal levels of von Willebrand factor.
Platelet Function Disorders
Disorders of platelet function are suspected in patients who show skin and mucosal
haemorrhage despite a normal platelet count and normal levels of von Willebrand factor.
These disorders may be inherited or acquired:
Inherited platelet disorders
Glanzmann's disease
Bernard-Soulier syndrome
Storage pool diseases
Acquired platelet disorders
Antiplatelet drugs
Aspirin
Dipyridamole
Clopidogrel and prasugrel
Abciximab, eptifibatide and tirofiban
Hyperglobulinemia (associated with multiple myeloma or Waldenstrom's disease)
Myeloproliferative and myelodysplastic disorders
Uraemia
Diagnosis
Patients with suspected platelet or blood vessel abnormalities should initially have a blood
count and blood film examination. Bone marrow examination is often needed in
thrombocytopaenic patients to determine whether or not there is a failure of platelet
production. The marrow may also reveal one of the conditions associated with defective
production.
In patients with thrombocytopaenia, normal haemoglobin and white cell counts, a negative
drug history, normal or excessive numbers of marrow megakaryocytes, and no other marrow
abnormality or splenomegaly, ITP is the usual diagnosis. Screening tests for DIC are also
useful, as are tests for underlying disease such as SLE or HIV.
When the blood count, including platelet count and blood film examinations are normal, PFA-
100 test is used to detect abnormal platelet function. In most patients with abnormal platelet
function demonstrated by the PFA-100 test, the defect is acquired and associated either with
systemic disease (e.g. uraemia), or with aspirin therapy. If von Willebrand disease is
suspected, assay of VWF and coagulation factor VIII are required.
Immune Thrombocytopaenic Purpura
Immune thrombocytopaenic purpura (ITP) may be divided into chronic and acute forms.
Chronic ITP:
Chronic ITP is a relatively common disorder. The highest incidence is in women aged 15 - 50
years. It is the most common cause of thrombocytopaenia without anaemia or neutropaenia.
It is usually idiopathic but it may been seen in association with other conditions.
Platelet autoantibodies (usually IgG) result in the premature removal of platelets from the
circulation by macrophages of the reticuloendothelial system. In many causes the antibody is
directed against the glycoprotein IIb/IIIa or Ib complex. The normal platelet lifespan of 10
days is reduced to a few hours. Total megakaryocyte mass and platelet turnover are
increased to approximately five times normal.
The onset is often insidious with petechial haemorrhage, easy bruising, and menorrhagia and
the course of the disease is characteristically relapsing and remitting. Many asymptomatic
cases are discovered by routine blood count. Laboratory findings demonstrate: low platelet
count, abnormally large platelets on blood film and normal/increased megakaryocytes in
bone marrow biopsy.
Acute ITP:
Acute ITP is most common in children. In approximately 75% of cases, the episode follows
vaccination or infection such as chicken pox or glandular fever. Most cases are caused by
non-specific immune complex attachment to platelets. Acute ITP usually has a very sudden
onset and the symptoms usually disappear in less than 6 months (often within a few weeks).
It is usually a self-limiting condition and over 80% of children recover without treatment; in 5
- 10% of cases a chronic form of the disease develops.
Thrombotic Thrombocytopaenic Purpura

Thrombotic thrombocytopaenic purpura (TTP) may be congenital or acquired. There is a
deficiency of the ADAMTS13 metalloprotease which breaks down von Willebrand factor (VWF)
multimers anchored to endothelial cells. Acquired TTP follows the development of an
inhibitory IgG autoantibody, the presence of which may be stimulated by infection,
autoimmune disease, connective tissue disease, certain drugs, stem cell transplantation or
cardiac surgery.
TTP has traditionally been described as a pentad of thrombocytopaenia, microangiopathic
haemolytic anaemia, neurological abnormalities, renal failure and fever. The microvascular
thrombosis consumes platelets, causes variable degrees of tissue ischaemia and infarction
and is responsible for the microangiopathic haemolytic anaemia (cells fragment as they
circulate through the partially occluded vessels). Increasing platelet aggregation onto the
VWF multimers has the potential to form large occlusive platelet thrombi which have the
potential to embolise. Thrombocytopaenia, schistocytes in the blood film and a particularly
high LDH are sufficient to suggest the diagnosis.
Haemolytic uraemic syndrome (HUS) in children has many common features but organ
damage is limited to the kidneys and ADAMTS13 levels are normal. There is also usually
diarrhoea and epileptic seizures may occur. Many cases are associated with E.coli 0157
infection. It is classically associated with the triad of: microangiopathic haemolytic anaemia,
thrombocytopaenia and acute kidney injury (AKI).

Sickle Cell Disease LAST UPDATED: 24TH
APRIL 2019
 Bookmark
Sickle cell disease is a group of haemoglobin disorders resulting from the

inheritance of the sickle β-globin gene. Homozygous sickle cell anaemia (Hb SS)
is the most common severe syndrome. The carrier state is widespread, found in
up to 30% of West African people, maintained at this level due to the protection
against falciparum malaria that is afforded by the carrier state. The mutant gene
also occurs in other parts of the world where malaria is present e.g. the Middle
East, Far East and Indian subcontinent.
Pathophysiology
Point mutation in the β-globin gene results in substitution of valine for
glutamic acid in the sixth position of the β-globin chain, Hb S is formed
Hb S is insoluble in its deoxygenated state; the insoluble chains crystallise
in red cells causing sickling and vascular occlusion
Clinical Features
Features of sickle cell disease include:
Anaemia (symptoms are usually mild because the O2 dissociation curve of
Hb S is shifted to the right)
Vaso-occlusive crisis
Sickling causes blockage of small vessels
Common precipitants are infection, dehydration, acidosis and
deoxygenation
Abdominal pain is caused by infarction affecting abdominal organs
Bone pain may occur in the back, pelvis, ribs and long bones
Infarction may affect the central nervous system, lungs, spleen or
kidneys
Hand-foot syndrome in children caused by infarction of metaphyses
of small bones is frequently the first presentation of the disease
Acute sickle chest syndrome is the most common cause of death in
adults and children (dyspnoea, falling arterial PO2, chest pain,
pulmonary infiltrates on CXR)
Visceral sequestration crisis
Sickling with pooling of red cells in the liver, spleen or lungs
Aplastic crisis
Usually following infection with B19 parvovirus
Temporary arrest of erythropoiesis, rapidly causing severe anaemia
requiring transfusion
Increased susceptibility to infection
Splenic function is reduced because infarction leads to hyposplenism
Pneumococcal infections may lead to pneumonia and meningitis
Infarction of intestinal mucosa predisposes to Salmonella infection
and osteomyelitis
Other clinical features:
Pigment gallstones with cholecystitis
Chronic leg ulcers
Avascular necrosis of the femoral and humeral heads or other bones
Cardiomyopathy
Pulmonary hypertension
Proliferative retinopathy
Priapism
Renal papillary necrosis
Stroke
Laboratory Findings
The haemoglobin is usually 60 - 90 g/L
Sickle cells and target cells occur in the blood
Features of splenic atrophy may be present (e.g. Howell-Jolly bodies)
Screening tests for sickling are positive when the blood is deoxygenated
Haemoglobin electrophoresis demonstrates abnormal Hb
Management
Prophylactic - avoid factors known to precipitate crises
Folic acid
Good general nutrition and hygiene
Pneumococcal, Haemophilus and meningococcal vaccination and regular
oral penicillin
Crises - treat with rest, warmth, rehydration, analgesia and antibiotics as
required; transfusion with blood products if symptomatic; exchange
transfusion may be needed particularly if there is neurological damage, a
visceral sequestration crisis or repeated painful crises
Special care taken in pregnancy or with anaesthesia
Transfusions - sometimes given repeatedly as prophylaxis to patients
having frequent crises or who have had major organ damage
Hydroxycarbamide - can increase Hb F levels and improve the clinical
course of children or adults
Stem cell transplantation - can cure the disease, with 80% disease free
New potential drugs to enhance Hb F synthesis or to increase the solubility
of Hb S

Thalassaemia LAST UPDATED: 24TH
APRIL 2019
 Bookmark
The thalassaemias are a heterogeneous group of genetic disorders that result

from a reduced rate of synthesis of alpha (α) or beta (β) globin chains. β-
thalassaemia is more common in the Mediterranean region while α-thalassaemia
is more common in the Far East.
Deficiency of one globin chain results in the compensatory production of the
other, an excess of α or β chains results in abnormal aggregation within red cell
precursors, predisposing them to phagocytosis by macrophages in the
reticuloendothelial system.
Alpha-Thalassaemia
Normally, there are four α-globin genes. The severity of α-thalassaemia depends
on the number of α-genes deleted or, less frequently, dysfunctional.
Hydrops Foetalis:
Loss of all four α-genes
Foetus is unable to make either HbF or HbA haemoglobin
Death occurs in utero
Haemoglobin H disease
Loss/dysfunction of three α-genes
Marked microcytic, hypochromic anaemia with splenomegaly
α-thalassaemia traits
Loss/dysfunction of one or two genes

Mild anaemia occurs in some cases
Beta-Thalassaemia
β-thalassaemia major
Pathophysiology:
Complete or almost complete failure of β-globin chain
synthesis, severe imbalance of α:β-chains with deposition of α-
chains in erythroblasts, ineffective erythropoiesis and
extramedullary haemopoiesis
Clinical features:
Severe anaemia (becoming apparent at 3 - 6 months when the
switch from γ-chain to β-chain synthesis normally occurs)
Failure to thrive, intercurrent infection, pallor, mild jaundice
Enlargement of liver and spleen (due to excessive red cell
destruction, extramedullary haemopoiesis and later due to
transfusion related iron overload)
Expansion of bones (due to marrow hyperplasia, especially of
the skull, resulting in bossing, 'hair-on-end- appearance on x-
ray, thalassaemic facies)
Features of iron overload (as a result of blood transfusions and
increased iron absorption)
Laboratory findings
Severe microcytic anaemia
Blood film shows hypochromic, microcytic cells, target cells,
erythroblasts and myelocytes
Bone marrow is hypercellular with erythroid hyperplasia
DNA analysis reveals specific mutations/deletions
Beta-thalassaemia minor
Variable syndrome, milder than thalassaemia major, with later onset
Characterised by moderate hypochromic microcytic anaemia
requiring either few, or no transfusions
Clinical features as described above may occur
Beta-thalassaemia trait
Characterised by mild hypochromic, microcytic anaemia with raised
red cell count and raised haemoglobin A2.

Vascular Bleeding Disorders LAST UPDATED: 24TH
APRIL 2019
The vascular disorders are a heterogeneous group of conditions characterised by

easy bruising and spontaneous bleeding from small vessels.
The underlying abnormality is either in the vessels themselves or in the
perivascular connective tissues. Mosts cases of bleeding caused by vascular
defects alone are not severe. Frequently the bleeding is mainly in the skin causing
petechiae, ecchymoses or both. In some disorders there is also bleeding from
mucous membranes.
In these conditions the standard screening tests are normal. The bleeding time is
usually normal and the other tests of haemostasis are also normal.
Vascular defects may be inherited or acquired:
Inherited vascular disorders
Hereditary haemorrhagic telangiectasia
Connective tissue disorders e.g. Ehlers-Danlos syndromes
Giant cavernous haemangioma
Acquired vascular disorders
Simple easy bruising
Senile purpura
Purpura associated with infection
Henoch-Schonlein syndrome
Scurvy
Steroid purpura
Tranexamic acid and aminocaproic acid are useful antifibrinolytic drugs that may
reduce bleeding from vascular disorders, but are relatively contraindicated in the
presence of haematuria because they might lead to clots obstructing the renal
tract.

Venous Thrombosis LAST UPDATED: 25TH
JUNE 2019
There are three main components important in venous thrombus formation

described by Virchow's triad:
Decreased rate of blood flow (e.g. by venous insufficiency, prolonged
immobility or varicose veins)
Hypercoagulability of blood (e.g. by hyperviscosity or thrombophilia
disorders)
Vessel wall damage (e.g. by sepsis, indwelling venous catheter or by
previous thrombosis)
Risk Factors for Venous Thrombosis
Inherited risk factors:
Factor V Leiden (most common)
Prothrombin variant
Protein C or protein S deficiency
Antithrombin deficiency
Acquired risk factors include:
Lupus anticoagulant
Oestrogen therapy (OCP and HRT)
Heparin-induced thrombocytopaenia
Pregnancy and puerperium
Surgery (especially abdominal, hip and knee surgery)
Major trauma
Malignancy (especially of the ovary, brain and pancreas)
Acutely ill hospitalised medical patients
Hyperviscosity, polycythaemia
Stroke
Pelvic obstruction
Nephrotic syndrome
Dehydration
Varicose veins
Previous venous thrombosis
Age
Obesity
Behcet's disease
Approximately one-third of patients who suffer DVT or PE have an identifiable

heritable risk factor, although additional risk factors are usually present when
they develop the thrombosis. The history of a spontaneous DVT in a close relative
increases an individual's risk of DVT even if no known genetic predisposition can
be identified.
Factor V Leiden
Factor V Leiden gene mutation is the most common inherited cause of an
increased risk of venous thrombosis. Activated protein C normally breaks down
activated factor V and so should slow the clotting reaction and prolong the APTT,
but a mutation in the factor V gene makes factor V less susceptible to cleavage by
activated protein C, resulting in increased levels of activated factor V.
Heterozygotes for factor V Leiden are at an approximately five- to eight- fold
increased risk of venous thrombosis compared to the general population (but only
10% of carriers will develop thrombosis in their lifetime). Homozygotes have a 30 -
140-fold increased risk. The incidence of factor V Leiden in patients with venous
thrombosis is approximately 20 - 40%. It does not increase the risk of arterial
thrombosis.
Diagnosis of Venous Thrombosis

Deep Vein Thrombosis (DVT):
Clinical Suspicion
DVT is suspected in patients with a painful swollen limb
Signs may include unilateral thigh or calf swelling or tenderness,
changes to skin colour, and venous distension
Plasma D-dimer concentration
The concentration of fibrin degradation products (FDPs) is raised
when there is a fresh thrombosis; this may be used to exclude
diagnosis when used in conjunction with a clinical probability tool
Compression ultrasound
This is a reliable and practical method for patients with suspected
DVT in the legs and other sites
Pulmonary Embolism (PE):
Clinical Suspicion
PE is suspected in patients with shortness of breath and pleuritic
chest pain
Signs may include tachycardia, tachypnoea, hypoxia and pyrexia
Chest x-ray
This is often normal but may show evidence of pulmonary infarction
or pleural effusion
Electrocardiogram
This may show right heart strain in severe cases
Plasma D-dimer concentration
This may be used to exclude diagnosis when used in conjunction with
a clinical probability tool
Ventilation perfusion (VQ) scintigraphy
This detects areas of the lungs being ventilated but not perfused
Computed tomography pulmonary angiography (CTPA)
Fine slices of the lung are scanned by spiral CT to identify filling
defects in the pulmonary arteries

Cell Structure LAST UPDATED: 11TH
APRIL 2019
PHYSIOLOGY / BASIC CELLULAR /
CELL STRUCTURE AND FUNCTION  Bookmark
About half of each cell is filled with cytosol, a viscous, protein-rich fluid between the
internal structures which consist of organelles, which are themselves enclosed by lipid
membranes, and components of the cytoskeleton which provide structural stability.
CELL STRUCTURE. (IMAGE BY CNX OPENSTAX [CC BY 4.0

Nucleus
The nucleus contains most of the cell's genetic material organised as chromosomes. It
also contains the nucleolus, a membrane-less structure which is responsible for the
production of ribosomes.
Mitochondria
Mitochondria are responsible for the production of chemical energy in the form of ATP
by oxidative phosphorylation, which is then used by all energy-requiring reactions.
Mitochondria are also involved in other cellular processes, including Ca2+ homeostasis
and signalling. Mitochondria contain a small amount of maternal DNA.
Endoplasmic reticulum
The smooth endoplasmic reticulum serves as a store for intracellular Ca2+ and is the
major site of lipid production (including triglyceride, steroid and phospholipid
synthesis).
The rough endoplasmic reticulum has ribosomes bound to its outer surface, which are
responsible for protein assembly and post-translational processing of proteins. This
includes trimming amino acid chains to the right length, protein folding, addition of
polysaccharide chains and identification of improperly folded proteins, which are
tagged for subsequent destruction by lysosomes.
Golgi apparatus
The Golgi apparatus packages proteins for delivery to specific intracellular destinations
or into vesicles which can then be secreted from the cell for extracellular action.
Lysosomes
Lysosomes, containing digestive enzymes, are responsible for the digestion and
breakdown of unwanted and defective proteins, the recycling of raw materials and the
prevention of accumulation of waste.

Cell Membrane Structure LAST UPDATED: 11TH
APRIL 2019
Human cells are enclosed by a plasma membrane composed of a phospholipid bilayer with
embedded proteins which provide signalling, transport and structural functions. such as ion
channels, receptors and enzymes.
CELL MEMBRANE STRUCTURE. (IMAGE MODIFIED BY FRCEM SUCCESS. ORIGINAL BY CNX OPENSTAX
[CC BY 4.0 (HTTP://CREATIVECOMMONS.ORG/LICENSES/BY/4.0)], VIA WIKIMEDIA COMMONS)
Bilayer Structure
Membrane lipids comprise a hydrophilic head and two hydrophobic fatty acid tails and are
arranged in a bilayer such that the hydrophobic tails face inwards, with the hydrophilic
heads facing externally. This means that lipid-soluble substances such as cholesterol
incorporate into the membrane, whilst molecules with both hydrophobic and hydrophilic
domains such as proteins can be tethered part in and part out of the membrane.
The membrane is selectively permeable; lipid-soluble molecules such as O2 and CO2, and
small molecules such as water and urea can readily pass through the lipid bilayer, but larger
molecules such as glucose, and polar molecules such as ions cannot, and their transport is
mediated by transporter and ion channel membrane proteins.
PHOSPHOLIPID BILAYER. (IMAGE BY OPENSTAX [CC BY 4.0

Glycocalyx
Most cells are also covered by a thin gel-like layer called the glycocalyx, containing
glycoproteins and carbohydrate chains extending from the lipid membrane, which protects
the membrane and plays a role in cell-cell interaction.
Membrane Proteins
Peripheral membrane proteins associated with cell signalling include enzymes bound to the
inner surface such as phospholipases, which produce arachidonic acid, and adenylyl
cyclase which generates the second messenger cyclic adenosine monophosphate (cAMP).
cAMP activates protein kinase enzymes to initiate numerous changes in cell function by
phosphorylating membrane and intracellular proteins.
Transmembrane proteins penetrate the entire thickness of the bilayer, and include ion
channel proteins and receptors such as G-protein-coupled receptors (GPCRs). On binding
the appropriate molecule, GPCRs activate specific membrane-associated GTP-binding
proteins, which cleave guanosine triphosphate (GTP) to guanosine diphosphate (GDP), and
Cellular Respiration LAST UPDATED: 30TH
AUGUST 2019
Cellular respiration is the process by which cells obtain energy in the form of adenosine
triphosphate (ATP). ATP transfers chemical energy from the energy rich substances in the cell
to the cell's energy requiring reactions e.g. active transport, DNA replication and muscle
contraction.
Cellular respiration is essentially a three step process:
1. Glycolysis
2. The Krebs cycle
3. The electron transfer system
CELLULAR RESPIRATION. (IMAGE BY REGISFREY (OWN WORK) [CC BY-SA 3.0

Respiratory Substrates
The main respiratory substrate used by cells is 6-carbon glucose. Respiration is a series of
reactions in which 6-carbon glucose is oxidised to form carbon dioxide. The energy released
due to the oxidation of glucose is used to synthesise ATP from adenosine diphosphate (ADP)
and inorganic phosphate (Pi).
Fats and proteins can also be used as respiratory substrates. When fats are being used as the
primary energy source, in the absence of glucose, an excess amount of acetyl-CoA is produced,
and is converted into acetone and ketone bodies. This can occur in starvation, fasting or in
diabetic ketoacidosis. Proteins are used as an energy source only if protein intake is very high,
or if glucose and fat sources are depleted.
Glycolysis
Glycolysis takes place in the cytoplasm of the cell and does not require oxygen. Glycolysis is the
breakdown of 6-carbon glucose into two 3-carbon pyruvic acid (pyruvate) units. The hydrogens
removed join with the hydrogen carrier NAD to form NADH2. Although some energy is needed to
start glycolysis there is an overall net gain of 2 ATP. The pyruvic acid (3C) then enters the matrix
of the mitochondrion where it is oxidised (i.e. 2H removed) and a carbon dioxide is lost, forming
acetyl CoA (2C).
Krebs Cycle
The Krebs cycle takes place in the matrix of the mitochondrion and requires oxygen. The Krebs
cycle begins when the 2-carbon acetyl CoA joins with a 4-carbon compound to form a 6-
carbon compound called citric acid. Citric acid (6C) is gradually converted back to the 4-carbon
compound ready to start the cycle once more. The carbons removed are released as CO2. The
hydrogens which are removed join with NAD to form NADH2.
Electron Transfer System

Most of the energy produced during respiration is made by the electron transfer system. The
electron transfer system is a system of hydrogen carriers located in the inner mitochondrial
membrane. The NADH2 molecules produced during glycolysis and the Krebs cycle transfer the
hydrogens to the electron transfer system. In doing so, a H+ ion gradient is generated across
the inner membrane which drives ATP synthase. Oxygen is the final hydrogen acceptor and the
H+ ions and O2 combine to form water.
Anaerobic Respiration
When anaerobic respiration occurs there is no oxygen to act as the final hydrogen acceptor and
so the hydrogen cannot pass through the electron transfer system. As a result, both the Krebs
cycle and the electron transfer system stages cannot take place. The only ATP produced is
formed during glycolysis, that is, 2 ATP per glucose molecule (compared to the 38 molecules of
ATP produced during aerobic respiration).
The pyruvic acid produced following glycolysis is converted to lactic acid in a process called
lactic acid fermentation. No energy is generated in this process but it allows ongoing glycolysis
and ATP synthesis (which would otherwise stop) via the regeneration of NAD+ from NADH. The
anaerobic pathway is reversible with lactic acid being converted back to pyruvic acid when
oxygen is present.
Anaerobic respiration produces an oxygen debt. This is the amount of oxygen needed to oxidise
lactic acid to carbon dioxide and water. The existence of an oxygen debt explains why we
continue to breathe deeply and quickly for a while after exercise.

Something wrong?
Cell Membrane Transport LAST UPDATED: 3RD

OCTOBER 2021
Proteins provide several routes for the movement of materials across membranes:
Large pores, constructed of several protein subunits that allow the bulk flow
of water, ions and sometimes larger molecules
Transporter (carrier) proteins, some of which use direct or indirect metabolic
energy to move molecules against electrochemical gradients
Ion channels, specialised to allow the passage of particular ion species across
the membrane under defined conditions
Diffusion
Diffusion is the passive movement of ions across a cell membrane down their
electrochemical or concentration gradient through ion channels.
Ion channels are transmembrane proteins which provide a charged, hydrophilic
pore through which ions can move across the lipid bilayer. Ion channels are
selective for particular ions and their pores may be opened or closed; in this way ion
channels confer upon the cell the ability to closely control the movement of ions
across the membrane.
The transition between an open and closed ion channel state is called gating, and is
brought about by a change in the conformation of the protein subunits that opens
or closes the ion-permeable pore. Ion channels can be voltage-gated (regulated
according to the potential difference across the cell membrane) or ligand-gated
(regulated by the presence of a specific signal molecule).
Facilitated Diffusion
Facilitated diffusion is the process of spontaneous passive transport of molecules
or ions down their concentration gradient across a cell membrane via specific
transmembrane transporter (carrier) proteins. The energy required for
conformational changes in the transporter protein is provided by the concentration
gradient rather than by metabolic activity.
DIFFUSION ACROSS CELL MEMBRANE. (IMAGE BY LADYOFHATS MARIANA RUIZ VILLARREAL

Active Transport
Primary active transport uses chemical energy in the form of ATP to pump ions
against their electrochemical gradient. The Na+/K+ -ATPase antiporter pump uses
metabolic energy to move 3 Na+ ions out of the cell for every 2 K+ ions in, against
their respective electrochemical gradients. This allows the cell to maintain a high
concentration of K+ ions and a low concentration of Na+ ions intracellularly.
PRIMARY ACTIVE TRANSPORT. (IMAGE BY CLOD94 VIA WIKIMEDIA COMMONS)
Secondary active transport relies on an electrochemical gradient (usually the Na+

electrochemical gradient) created by primary active transport to pump another ion
(or molecule) against its electrochemical or concentration gradient. There is no
direct coupling of ATP but the initial Na+ electrochemical gradient that drives the
secondary active transport is set up by a process that requires metabolic energy.
Examples include the sodium/calcium exchanger, or the sodium/glucose
symporter.
Diffusion and Permeability LAST UPDATED: 11TH
APRIL 2019
VESSEL FLUID DYNAMICS  Bookmark
Passive diffusion refers to movement down a concentration gradient and accounts

for movement across small distances e.g. within the cytosol or across membranes.
Diffusion Within a Solution

The rate of diffusion in a solution is described by Fick's law which states:
Js = -DA (ΔC/Δx)
where,
Js = Amount of substance transferred per unit time
ΔC = Difference in concentration
Δx = Diffusion distance
A = Surface area over which diffusion occurs
D = Diffusion coefficient
The diffusion coefficient is a measure of how easy it is for the substance to diffuse -
it is related to temperature, solvent viscosity and the size of the molecule.
Diffusion Across a Membrane

Diffusion across a membrane is also affected by the permeability (p) of the
membrane. The permeability is related to the membrane thickness and
composition, and the diffusion coefficient of the substance.
Therefore Fick's equation for diffusion across a membrane can be rewritten as:
Js = -pAΔC
where,
Js = Amount of substance transferred per unit time
ΔC = Difference in concentration across the membrane
A = Membrane area over which diffusion occurs
Osmosis and Tonicity LAST UPDATED: 11TH
APRIL 2019
PHYSIOLOGY / BASIC CELLULAR / FLUID SPACES
 Bookmark
Definition
Osmosis is the passive movement of water across a semipermeable membrane from
regions of low solute concentration to those of higher solute concentration.
Biological membranes are semipermeable in that they usually allow the free
movement of water but restrict the movement of solutes.
The creation of osmotic gradients in this way is the primary method of movement of
water within the body, and thus the osmotic potential of body fluids is tightly
regulated by homeostatic control mechanisms.
Tonicity
Tonicity is a measure of the relative effective osmotic potentials of two solutions
separated by a semipermeable membrane. Tonicity is usually used to describe the
effective osmotic potential of a solution relative to plasma.
A fluid at the same osmotic potential as plasma is said to be isotonic; one at higher
potential is hypertonic and one at lower potential is hypotonic.
Taking on board fluids of differing osmotic potentials has distinct effects on the
distribution of water between cells and extracellular fluids.
Fluid Water Movement

Hypertonic Extracellular fluid becomes more concentrated relative to
fluid intracellular fluid, osmotic potential draws water out of cells,
cells lose water and shrink (crenation)
Isotonic Extracellular and intracellular fluid are isotonic, no osmotic
fluid potential generated, no net movement of water
Hypotonic Extracellular fluid diluted relative to intracellular fluid, osmotic
fluid potential draws water into cells, cells swell and may burst
Osmolarity and Osmolality LAST UPDATED: 4TH
APRIL 2019
 Bookmark
The osmotic potential of a solution depends on the concentration of

osmotically active particles in the solution. It can be expressed as osmolarity or
osmolality.
Osmolality
The osmolality is the concentration of a solution expressed as the total number
of solute particles per kilogram weight of solvent. The normal serum osmolality
is between 275 - 295 mosmol/kg.
Serum osmolality can be measured directly or it can be calculated
(approximately) if the concentrations of the major solutes are already known.
The equation for calculating serum osmolality is = 2[Na+] + 2[K+] + [Glucose] +
[Urea].
Osmolal gap
The osmolal gap is the apparent difference between the measured and the
calculated osmolality. The normal osmolal gap is < 10.
Osmolal gaps of > 10 are considered abnormal and represent the presence of
an osmotically active substance in the blood. A raised osmolal gap can be
caused by toxic alcohols (e.g. ethanol, methanol or ethylene glycol ingestion);
sugars (e.g. mannitol, sorbitol); and lorazepam infusions (which contain
propylene glycol).
There may also be a discrepancy where there is a gross increase in plasma
protein or triglyceride concentration, both of which decrease the plasma water
per unit volume and give a pseudohyponatraemia which in turn will lead to an
erroneously low calculated osmolality.
Osmolarity
The osmolarity is the concentration of a solution expressed as the total
number of solute particles per litre of solution. Its measurement or calculation
has been largely replaced by osmolality.
For a given solution, osmolarity is always slightly less than osmolality because
the total solvent weight (the divisor used for osmolality) excludes the weight of
any solutes, whereas the total solution volume (used for osmolarity) includes
solute content. Changes in volume, and thus osmolarity, are affected by
changes in water content, as well as temperature and pressure. In contrast,
the weight of a solvent and thus osmolality, is independent of temperature and
pressure and is therefore relatively easier to determine. In practice, there is
negligible difference between the absolute values of the different
measurements.

Isometric vs Isotonic Contraction LAST UPDATED: 11TH
APRIL 2019
SKELETAL MUSCLE PHYSIOLOGY  Bookmark
Isometric Contraction
Isometric contraction occurs when the two ends of the muscle are held at a fixed distance
apart, and stimulation of the muscle causes the development of tension within the muscle due
to the tension being transferred to elastic filaments within the muscle without a change in
muscle length e.g. holding a weight with an outstretched hand.
Isotonic Contraction
In isotonic contraction one end of the muscle is free to move and the muscle length
changes. There are two types of isotonic contraction - concentric and eccentric.
In concentric movements the muscle shortens as the muscle fibres contract, thereby
generating force e.g. repeatedly lifting a weight.
In eccentric movements the muscle lengthens in a controlled manner, due to the resistance
being greater than the force the muscle is producing e.g. lowering a weight gently.
In practice, most contractions are made up of both isometric and isotonic contractions.
ISOMETRIC VS ISOTONIC CONTRACTION. (IMAGE BY OPENSTAX [CC BY 4.0

Haemoglobin LAST UPDATED: 24TH
APRIL 2019
BLOOD AND BLOOD FLOW  Bookmark
Red blood cells contain the specialised protein haemoglobin which is responsible for
carrying oxygen and carbon dioxide in the blood. Haemoglobin is composed of four
polypeptide globin chains each with its own iron containing haem molecule.
Haemoglobin Synthesis
Haemoglobin synthesis occurs in immature red blood cells. Haem synthesis occurs
largely in the mitochondria by a series of biochemical reactions commencing with the
condensation of glycine and succinyl coenzyme A under the action of the key rate-
limiting enzyme delta-aminolevulinic acid (ALA) synthase; ultimately protoporphyrin
combines with iron in the ferrous (Fe2+) state to form haem. The globin chains are
synthesised by ribosomes in the cytosol.
Haemoglobin Degradation
Red cells are destroyed by macrophages in the liver and spleen after ~ 120 days. The
haem group is split from the haemoglobin and converted to biliverdin and then bilirubin.
The iron is conserved and recycled to plasma via transferrin or stored in macrophages
as ferritin and haemosiderin. An increased rate of haemoglobin breakdown results in
excess bilirubin and jaundice.
Types of Haemoglobin
There are three types of haemoglobin in normal adult blood: haemoglobin A, A2 and F.
Normal adult haemoglobin (HbA) makes up about 96 - 98 % of total adult
haemoglobin, and consists of two alpha (α) and two beta (β) globin chains.
Haemoglobin A2 (HbA2), a normal variant of adult haemoglobin, makes up about
1.5 - 3.5 % of total adult haemoglobin and consists of two α and two delta (δ)
globin chains.
Foetal haemoglobin (HbF) makes up about 0.5 - 0.8 % of total adult haemoglobin
and consists of two α and two gamma (γ) globin chains.
Hb Structure Normal adult %
HbA α2β2 96 - 98%
HbA2 α2δ2 1.5 - 3.5%
HbF α2γ2 0.5-0.8%
Foetal haemoglobin is the main Hb in the later two-thirds of foetal life and in the
newborn until approximately 12 weeks of age. Foetal haemoglobin has a higher affinity
for oxygen than adult haemoglobin.
STRUCTURE OF HAEMOGLOBIN. (IMAGE BY OPENSTAX COLLEGE [CC BY 3.0


The normal haemostatic response to vascular damage depends on a closely linked interaction
between the blood vessel wall, circulating platelets and blood coagulation factors.
Platelet Production
Platelets are produced in the bone marrow by fragmentation of the cytoplasm of
megakaryocytes, derived from the common myeloid progenitor cell. The time interval from
differentiation of the human stem cell to the production of platelets averages 10 days.
Thrombopoietin is the major regulator of platelet formation and 95% of this is produced by the
liver.
The normal platelet count is approximately 150 - 450 x 109/L and the normal platelet lifespan
is 10 days. Under normal circumstances, about one-third of the marrow output of platelets
may be trapped at any one time in the normal spleen.
PLATELET PRODUCTION. (IMAGE BY パタゴニア [CC BY-SA 3.0

Platelet Structure
Platelets are extremely small and discoid. The platelet surface coat has glycoproteins that are
particularly important in platelet adhesion and aggregation. Adhesion to collagen is facilitated
by glycoprotein Ia. Glycoproteins Ib and IIb/IIIa are important in the attachment of platelets to
von Willebrand factor (VWF) and hence to vascular subendothelium. The binding site for IIb/IIIa
is also the receptor for fibrinogen, which, like VWF, is important in platelet-platelet
aggregation.
The platelet plasma membrane invaginates into the platelet interior to form a canalicular
system which provides a large reactive surface area to which the plasma coagulation proteins
may be selectively absorbed. Plasma membrane phospholipids are particularly important in
the conversion of factor X to Xa and prothrombin (factor II) to thrombin (IIa).
Platelets contain three types of storage granule;
1. dense granules containing ADP, ATP, serotonin and calcium

2. alpha granules containing clotting factors, von Willebrand factor (VWF), platelet-
derived growth factor (PDGF) and other proteins
3. lysosomes containing hydrolytic enzymes
Platelets are also rich in signalling and cytoskeletal proteins, which support the rapid switch
from quiescence to activation that follows vessel damage. During the release reaction, the
contents of the granules are discharged into the open canalicular system.
PLATELET STRUCTURE. (IMAGE BY DR GRAHAM BEARDS [CC BY-SA 3.0
Platelet Function
The primary function of platelets is the formation of a platelet plug during the primary
haemostatic response to vascular injury via adhesion, aggregation and activation. The
immobilisation of platelets at the sites of vascular injury requires specific platelet-vessel wall
(adhesion) and platelet-platelet (aggregation) reactions, both partly mediated through VWF.
Platelet aggregation is characterised by cross-linking of platelets through active GPIIb/IIIa
receptors with fibrinogen bridges.
Primary activation by various agonists (e.g. thrombin) induces intracellular signalling, leading
to the release of alpha granule contents. These have an important role in platelet aggregate
formation and stabilisation and, in addition, the ADP released from dense granules has a major
positive feedback role in promoting platelet activation.
Thromboxane A2 (TXA2), produced by platelets, is important in secondary amplification of
platelet activation to form a stable platelet aggregate. TXA2 lowers platelet cAMP levels and
initiates the platelet release reaction; it also has powerful vasoconstrictive activity.
After platelet aggregation and release, the exposed membrane phospholipid is available for
two reactions in the coagulation cascade. The first involves factors IXa, VIIIa and X in the
formation of factor Xa. The second results in the formation of thrombin from the interactions
of factors Xa, Va and prothrombin.
PDGF found in the alpha granules of platelets stimulates vascular smooth muscle cells to
multiply and thus may hasten vascular healing following injury.
PRIMARY HAEMOSTASIS. (IMAGE BY OPENSTAX COLLEGE [CC BY 3.0

Natural Inhibitors of Platelet Function

The release reaction is inhibited by substances that increase the level of platelet cAMP.
Prostacyclin (PGI2), synthesised by endothelial cells, is one such substance. PGI2 has the
opposing effects of TXA2; it is a potent inhibitor of platelet adhesion and aggregation on
normal vascular endothelium (and a potent vasodilator). Nitric oxide is constitutively released
from endothelial cells and also from macrophages and platelets; it inhibits platelet activation
and promotes vasodilation.
Haemopoiesis LAST UPDATED: 15TH
JULY 2019
Haemopoiesis Sites
Haemopoiesis in the foetus occurs firstly in the yolk sac, and later in the liver and
spleen, which are the major haemopoietic organs from about 6 weeks until 6 - 7 months
gestation, at which point the bone marrow becomes the most important site. In normal
childhood and adult life, haemopoiesis is restricted to the bone marrow.
Haemopoietic Stem Cells

All blood cells develop from haemopoietic stem cells (HSCs). Haemopoiesis occurs when
HSCs bind, via cell surface receptors, to adhesion molecules and to fixed or secreted
cytokines and growth factors. This binding triggers a cascade of phosphorylation
reactions which transmits a signal to the nucleus to upregulate gene transcription. This
signal promotes haemopoiesis by activating pathways that lead to cell proliferation,
differentiation, maturation, inhibition of apoptosis (programmed cell death) or activation
of mature cells.
HSCs give rise to two major lineages, the lymphoid lineage in which a common lymphoid
progenitor gives rise to B-cells, T-cells and natural killer (NK) cells, and a myeloid lineage
in which a common myeloid progenitor gives rise to erythrocytes, platelets,
granulocytes and monocytes.
HAEMOPOIESIS. (IMAGE BY UNKNOWN [CC-BY-SA-3.0
(HTTP://CREATIVECOMMONS.ORG/LICENSES/BY-SA/3.0/)], VIA WIKIMEDIA COMMONS)

Haemostasis LAST UPDATED: 25TH
JUNE 2019
Vasoconstriction
Immediate vasoconstriction of the injured vessel and reflex constriction of adjacent
small arteries and arterioles is responsible for an initial slowing of blood flow to the area
of injury. Where there is widespread damage, this vascular reaction prevents
exsanguination. The reduced blood flow allows contact activation of platelets and
coagulation factors.
Platelet Reactions and Primary Haemostatic Plug Formation

Following a break in the endothelial lining, there is an initial adherence of platelets (via
GPIa and GPIb receptors) to exposed connective tissue, mediated by von Willebrand
factor (VWF). Under conditions of high shear stress (e.g. arterioles), the exposed
subendothelial matrix is initially coated with VWF. Collagen exposure and thrombin
generated through activation of tissue factor produced at the site of injury cause the
adherent platelets to release their granule contents and also activate platelet
prostaglandin synthesis, leading to the formation of thromboxane A2 (TXA2). Released
ADP causes platelets to swell and aggregate; TXA2 and serotonin (5-HT) also enhance
the vasoconstriction.
Platelet rolling in the direction of blood flow over exposed VWF with activation of
GPIIb/IIIa receptors results in firmer binding. Additional platelets from the circulating
blood are drawn to the area of injury. This continuing platelet aggregation promotes the
growth of the haemostatic plug which soon covers the exposed connective tissue. The
unstable primary haemostatic plug produced by these platelet reactions in the first
minute or so following injury is usually sufficient to provide temporary control of
bleeding. The highly localised enhancement of platelet activation by ADP and TXA2
results in a platelet mass large enough to plug the area of endothelial injury.
Stabilisation of the Platelet Plug by Fibrin

Definitive haemostasis is achieved when fibrin, formed by blood coagulation, is added to
the platelet mass and by platelet-induced clot retraction. Vascular injury results in the
initiation and amplification of the coagulation cascade. Platelet aggregation and release
reactions accelerate the coagulation cascade by providing abundant membrane
phospholipid. The thrombin generated by the coagulation cascade converts soluble
plasma fibrinogen into fibrin monomers, potentiates platelet aggregation and secretion
and also activates factor XI and XIII and cofactors V and VIII. The fibrin monomers
spontaneously polymerise to a fibrous mesh of fibrin, entrapping the platelets and other
blood cells. The fibrin polymer is finally cross-linked by factor XIIIa to create a tough
network of fibrin fibres, and a stable clot. Clot retraction occurs, mediated by GPIIb/IIIa
receptors which link the cytoplasmic actin filaments to surface-bound fibrin polymers,
making it tougher and assisting repair by drawing the edges of the wound together.
HAEMOSTASIS. (IMAGE BY OPENSTAX COLLEGE [CC BY 3.0

Homeostasis LAST UPDATED: 30TH
AUGUST 2019
PHYSIOLOGY / BASIC CELLULAR / HOMEOSTASIS
 Bookmark
Normal functioning of proteins is essential for life. Seemingly small changes in the
external environment (particularly in temperature and pH) can irreversibly
denature proteins that are essential for normal physiological function. As long as
conditions are maintained within the normal physiological range within the internal
environment, the cells of the body continue to live and function properly.
Definition
Homeostasis is defined as 'the property of a system in which variables are regulated so
that internal conditions remain stable and relatively constant'. Homeostasis preserves
protein functionality and maintains most physiological systems in the body.
Set Point
The 'set point' is a narrow range of values within which normal physiological function
occurs. The set point can under certain circumstances be reset to meet physiological
requirements e.g. acclimatisation at high altitude.
Negative Feedback
The most common type of regulation is by negative feedback e.g. control of body
temperature, acid-base balance and blood pressure.
A negative feedback system comprises three components:
A detector (often neural receptor cells) to measure the variable in question and to
provide input to the comparator
A comparator (usually a neural assembly in the central nervous system) to receive
input from the detector, to compare the variable against the set point and to
determine the need for a response
An effector (usually muscular or glandular tissue) that is activated by the
comparator to enact the appropriate response to restore the variable to its set
point
The term 'negative feedback' refers to the fact that effectors always act to move the
variable in the opposite direction to the change that was originally detected.
Due to the inherent time delay between detecting a change in a variable and effecting a
response, negative feedback mechanisms cause oscillations in the variable they
control. This delay means that feedback control always causes the variable to overshoot
the set point slightly activating the opposite restorative mechanism to induce a smaller
overshoot in that direction, until the oscillations fall within the range of values that are
optimal for physiological function.
NEGATIVE FEEDBACK LOOP. (IMAGE MODIFIED BY FRCEM SUCCESS. ORIGINAL BY OPENSTAX

Positive Feedback
Some physiological systems use positive feedback mechanisms e.g. hormonal control
of childbirth (where pressure on the cervix causes increased release of oxytocin
increasing uterine contraction) or initiation of an action potential (where a sodium influx
causes depolarisation which causes further sodium channel opening).
Positive feedback systems are less common in the body due to their inherent instability
and risk of uncontrolled amplification. Positive feedback mechanisms require a
mechanism to break the feedback loop ( such as by birth of the child in the first example
above and by inactivation of sodium channels in the second).
POSITIVE FEEDBACK LOOP. (IMAGE BY OPENSTAX [CC BY 4.0


Red Blood Cells LAST UPDATED: 4TH
AUGUST 2019
Erythropoietin
The glycoprotein hormone erythropoietin (EPO) promotes the production of red cells.
About 90% of erythropoietin is produced in the peritubular complex of the kidney and
10% in the liver and other organs. Erythropoietin secretion is stimulated by reduced O2
supply to the kidney receptor. Thus the principal stimuli to red cell production are tissue
hypoxia and reduced haemoglobin concentration (anaemia). Increased pathological
secretion may occur in polycystic kidney disease and renal cell carcinoma. Decreased
secretion may occur in advanced chronic kidney disease or in polycythaemia vera.
Recombinant erythropoietin is available for treating anaemia in end-stage chronic
kidney disease.
Red Cell Production

Red blood cells are formed from committed stem cells in a process called erythropoiesis
which occurs in the bone marrow in adults, and the liver and spleen in the foetus.
Erythropoietin increases the number of committed stem cells and promotes production
of red cells. Stem cells differentiate into erythroblasts (early normoblasts) which are
relatively large and nucleated. As differentiation proceeds, the cells shrink and
haemoglobin is synthesised, which requires iron, folate and vitamin B12. In the late
normoblast the nucleus breaks up and disappears and the reticulocyte is formed.
About 2 x 1011 red cells are produced from the marrow each day. The spleen also holds a
reserve of red cells that can be released following blood loss.
Reticulocytes
Reticulocytes do not have a cell nucleus, but they have a network of ribosomal RNA
which allows continued synthesis of haemoglobin. Normally about 1 - 2% of circulating
red cells are reticulocytes, which are characterised by their slightly larger size compared
to mature erythrocytes and cresyl blue staining (due to residual RNA).
The reticulocyte count is a measure of new red cell production by the bone marrow. It is
raised after haemorrhage or haemolysis when extra red cell production is needed. It is
low if the marrow is incapable of normal red cell production, for example in:
General bone marrow failure (e.g. malignant infiltration, aplastic anaemia)
Impaired red blood cell production (e.g. deficiency of iron, vitamin B12 or folate)
Lack of erythropoietin stimulus (e.g. chronic kidney disease)
Chronic systemic disease
An isolated reticulocytosis without anaemia is relatively common as a direct toxic effect
of alcohol.
Erythrocytes
The reticulocytes are released from the marrow into the peripheral blood, where after
about 1 - 2 days, they lose their remaining ribosomes and become mature erythrocytes,
at which point haemoglobin synthesis can no longer take place.
Mature erythrocytes are biconcave discs with no nucleus, ribosomes or mitochondria but
with the ability to generate energy as ATP by the anaerobic glycolytic pathway. The red
cell membrane consists of a bipolar lipid layer with a membrane skeleton of penetrating
and integral proteins anchoring carbohydrate surface antigens. The shape and flexibility
of red cells allows them to deform easily and pass through capillaries.
Erythrocytes have a normal lifespan of about 120 days.
Red Cell Degradation

Senescent red cells are destroyed extravascularly by macrophages in the
reticuloendothelial system (in the bone marrow, liver and spleen).
Approximately 10 - 15% of developing erythroblasts die within the marrow without
producing mature cells; this is termed ineffective erythropoiesis and may be more
marked in certain disease.
LIFECYCLE OF A RED BLOOD CELL. (IMAGE BY OPENSTAX COLLEGE [CC BY 3.0

Coagulation Cascade LAST UPDATED: 11TH
APRIL 2022
Blood coagulation involves a biological amplification system in which a few initiation

substances sequentially activate by proteolysis a cascade of circulating precursor
proteins (the coagulation factor enzymes) which culminates in the generation of
thrombin; this, in turn, coverts soluble plasma fibrinogen into fibrin. Fibrin enmeshes the
platelet aggregates at the sites of vascular injury and converts the unstable primary
platelet plug into a firm, definitive and stable haemostatic plug.
The generation of thrombin is a complex network of amplification and negative
feedback loops to ensure a localised and limited production. Generation of thrombin is
dependent on three enzyme complexes, each consisting of protease, cofactor,
phospholipids and calcium. The operation of this enzyme cascade requires local
concentration of circulating coagulation factors at the site of injury. Surface-mediated
reactions occur on exposed collagen, platelet phospholipid and tissue factor.
Initiation
Coagulation is initiated after vascular injury by the interaction of the membrane bound
tissue factor (TF, factor III), exposed and activated by vascular injury, with plasma factor
VII. The factor VIIa-tissue factor (extrinsic factor Xase) complex activates both factor IX
and factor X. The factor Xa, in the absence of its cofactor, forms small amounts of
thrombin from prothrombin. This is insufficient to initiate significant fibrin
polymerisation; amplification is needed. The initiation pathway is rapidly inactivated by
tissue factor pathway inhibitor (TFPI).
Amplification
The amplification phase takes place on the surface of platelets. The small amount of
thrombin generated during the initiation phase activates nearby platelets and also
cofactor V on their surface. Cofactor VIII is normally bound to plasma von Willlebrand
factor (VWF), which protects it from degradation. Thrombin cleaves factor VIII from VWF
and activates it, when it also binds to the platelet surface. The end product is a large
number of activated platelets covered with active cofactors.
Propagation
Thrombin activates a short cascade that leads to activation of factor IX (also activated
by the extrinsic factor Xase). The intrinsic Xase, formed by IXa and VIIIa on phospholipid
surface in the presence of Ca2+, activates sufficient Xa. Factor Xa, in combination with
Va, phospholipid and Ca2+, forms the prothrombinase complex and results in the
explosive generation of thrombin. Thrombin hydrolyses fibrinogen to form fibrin
monomers which link spontaneously to form a loose insoluble fibrin polymer. Factor XIII
is also activated by thrombin and stabilises the fibrin monomers with the formation of
covalent bond cross-links.
COAGULATION CASCADE. (IMAGE BY OPENSTAX COLLEGE [CC BY 3.0


Something wrong?
Relative Fluid Distribution in LAST UPDATED: 11TH

APRIL 2019
Fluid Spaces  Bookmark
An 'average' person (70 kg male) contains about 40 litres of water in total, separated into
different fluid compartments by biological semipermeable membranes; plasma cell
membranes between extracellular and intracellular fluid, and capillary walls between
interstitial and intravascular fluid.
Distribution of Fluid
FLUID SPACES. (IMAGE MODIFIED BY FRCEM SUCCESS. ORIGINAL IMAGE BY OPENSTAX COLLEGE
Around two-thirds of the total fluid (27 L) is intracellular fluid (ICF) and one-third of this
(13 L) is extracellular fluid (ECF). The ECF can be further divided into intravascular fluid
(3.5 L) and interstitial fluid (9.5 L). Transcellular fluid refers to any fluid that does not
contribute to any of the main compartments but which are derived from them e.g.
gastrointestinal secretions and cerebrospinal fluid, and has a collective volume of
approximately 2 L.
Fluid Space Volume

Intravascular fluid 3.5 L
Interstitial fluid 9.5 L
Intracellular fluid 27 L
Total 40 L
Plasma Oncotic Pressure

The main difference between interstitial and intravascular fluid is that intravascular fluid
contains more protein than interstitial fluid which under normal circumstances does not
penetrate the capillary wall. The presence of protein in plasma exerts an osmotic force
(plasma oncotic pressure) which counteracts the hydrostatic pressure imposed on
plasma by the action of the heart, allowing only a small net movement of water out of
plasma into the interstitial space, which is absorbed by the lymphatic system.

Relative Ionic Distribution in LAST UPDATED: 11TH
APRIL 2019
Fluid Spaces  Bookmark
The extracellular and the intracellular fluid compartments differ markedly in terms of the
concentrations of the ions that are dissolved in them. It should be noted that, within any
one compartment, there must be electrical neutrality, i.e. the total number of positive
charges must equal the total number of negative charges.
Intracellular vs Extracellular Fluid

The most important difference is the relative concentrations of the cations:
Sodium (Na+) is the principal extracellular cation; approximately 140 mmol/L (93%)
is extracellular and 10 mmol/L (7%) intracellular.
Potassium (K+) is the principal intracellular cation; approximately 4 mmol/L is
extracellular (3%) and 140 mmol/L intracellular (97%).
Of the other cations, most Ca2+ in the cell is transported actively either out of the cell or
into the endoplasmic reticulum and mitochondria, leaving very low levels of free Ca2+ in
the intracellular fluid. Mg2+ is a predominantly intracellular ion.
Intracellularly the main anions are protein and phosphate, whereas extracellularly the
main anions are chloride (Cl-) and bicarbonate (HCO3-).
Physiology Basic Cellular
Skeletal Muscle Physiology
Something wrong?
Motor Unit LAST UPDATED:

15TH MAY 2019
Definition
In normal skeletal muscle, muscle fibres never contract as isolated
individuals. Several contract at almost the same time as they are all
supplied by the same alpha-motor neuron. The single motor neuron and all
the fibres it innervates is called the motor unit. This is the smallest part of
a muscle that can be made to contract independently from other parts of
the muscle.
Motor Unit Recruitment

The number of muscle fibres supplied by a single motor neurone is
correlated with the precision required of that muscle, for example the total
number of muscle fibres is small in muscles such as the extraocular
muscles that provide fine smooth movements, but large in muscles such
as the gluteus maximus that needs to generate powerful but coarse
movements.
Each motor unit contracts in an all or nothing fashion, i.e. if a motor unit is
excited, it will stimulate all of its muscle fibres to contract. The force of
contraction of a muscle is controlled by varying the motor unit recruitment
(spatial summation), and by varying the firing rate of the motor units
(temporal summation).
Spatial Summation
Spatial summation is the recruitment of additional motor units to generate
more force; there is a recruitment order of the motor units in that the
smallest cells discharge first and the largest last (size principle). During a
gradual increase in contraction of a muscle, the first units start to
discharge and increase their firing rate, and, as the force needs to
increase, new units are recruited and, in turn, also increase their firing
rate.
Temporal Summation
Increasing the firing rate of motor units is temporal summation where the
tension developed by the first action potential has not completely decayed
when the second action potential and twitch is grafted onto the first and
so on. If the muscle fibres are stimulated repeatedly at a faster frequency,
a sustained contraction results where it is not possible to detect individual
twitches. This is called tetany. The tension of tetany is much greater than
the maximum tension of a single, double or triple twitch.
For most motor units, the firing rate for a steady contraction is between 5
and 8 Hz. Because the unitary firing rates for each motor unit are different
and not synchronised, the overall effect is a smooth force profile from the
muscle.

Something wrong?
Resting Membrane LAST UPDATED: 30TH

AUGUST 2019
Potential  Bookmark
ACTION POTENTIAL
Electrical events in biological tissues are caused by the movement of ions

across the membrane.
A membrane potential is a property of all cell membranes, but the ability to
generate an action potential is only a property of excitable tissues.
The value of the membrane potential depends on the relative membrane
permeability to the ions in the extracellular fluid (mainly Na+ and Cl-) and the
intracellular fluid (mainly K+). In most neurons the resting potential has a value
of approximately -70 mV. A cardiac myocyte has a resting potential of about
-90 mV.
The resting membrane is more permeable to K+ and Cl- than to other ions. The
cell contains negatively charged molecules (e.g. proteins) which cannot cross
the membrane. This fixed negative charge attracts K+, leading to accumulation
of K+ within the cell. However, the consequent increase in the K + concentration
gradient drives K+ back out of the cell. This means fewer K + ions move into the
cell than are required to achieve electrical neutrality with the fixed negative
charges and the inside of the cell therefore remains negatively charged
compared to the outside, causing a potential difference across the membrane.
These fixed anions also attract Na+ and the electrochemical gradient for Na+ is
strongly inwards, however the resting membrane is relatively impermeable to
Na+ and only a small amount of Na+ can leak in. A consequence of this setup is
that if Na+ permeability were suddenly increased to more than that of K +, the
membrane potential will depolarise; this is the basis of the action potential.
RESTING MEMBRANE POTENTIAL. (IMAGE BY SYNAPTIDUDE, VIA WIKIMEDIA
COMMONS)

Sarcomere LAST UPDATED: 18TH
JULY 2021
The sarcomere is the functional unit of the muscle.

Each muscle fibre is divided at regular intervals along its length into sarcomeres separated
by Z-lines.
The I-band extends from either side of the Z-line to the start of the thick myosin filament
(i.e. it is the zone of thin actin filaments that is not superimposed by thick myosin
filaments).
The A-band extends along the whole length of the myosin filament. The A-band therefore
does not shorten in muscle contraction, as the myosin filament does not shorten itself
(rather the sarcomere shortens as the myosin and actin filaments slide over one another).
The H-zone is at the centre of the sarcomere ending at the start of the actin filaments (i.e.
it is the zone of thick myosin filaments that is not superimposed by thin actin filaments).
The M-line is a disc of filaments in the middle of the H-zone that holds the myosin filament
in position so that each one is surrounded by six actin filaments.
STRUCTURE OF THE SARCOMERE. (IMAGE BY OPENSTAX [CC BY 4.0

Something wrong?
Skeletal Muscle Structure LAST UPDATED: 11TH

APRIL 2019
The skeletal muscles and skeleton function together as the musculoskeletal system.
Gross Structure
The connective tissue surrounding the whole muscle is called the epimysium. The
connective tissue that extends beyond the body of the muscle eventually blends into a
tendon, which is attached to bone or cartilage. Skeletal muscle is composed of numerous
parallel, elongated, multinucleated cells called muscle fibres (or myofibres) each enclosed by
endomysium, which are grouped together to form fascicles. Each fascicle is surrounded by
perimysium.
STRUCTURE OF SKELETAL MUSCLE. (IMAGE BY UNKNOWN, VIA WIKIMEDIA COMMONS)
Muscle Fibres
Beneath the endomysium is the sarcolemma, an elastic sheath that projects into the cell as
invaginations called T-tubules which wrap around the sarcomeres, particularly where the
thin and thick filaments overlap. Each muscle fibre is composed of myofibrils separated by
sarcoplasm and arranged in a parallel fashion along the long axis of the cell. Each myofibril is
further subdivided into thick myosin and thin actin myofilaments which are responsible for
the cross-striations.
SKELETAL MUSCLE FIBRE. (IMAGE BY BLAUSEN.COM STAFF (2014). "MEDICAL GALLERY OF BLAUSEN
MEDICAL 2014". WIKIJOURNAL OF MEDICINE 1 (2). DOI:10.15347/WJM/2014.010. ISSN 2002-4436.
(OWN WORK) [CC BY 3.0 (HTTP://CREATIVECOMMONS.ORG/LICENSES/BY/3.0)], VIA WIKIMEDIA
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Skeletal Excitation-
Contraction Coupling
Physiology
MRCEM Success
KEYWORDS
Excitation-Contraction Coupling
Sarcolemma Sarcoplasmic Reticulum
Skeletal Muscle T-Tubules
RELATED TOPICS
Skeletal Muscle Physiology
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Skeletal Excitation-Contraction LAST UPDATED: 28TH
FEBRUARY 2019
Coupling  Bookmark
SKELETAL MUSCLE PHYSIOLOGY
Muscle contraction occurs when the concentration of intracellular Ca 2+ rises.

An action potential travels down tube-shaped invaginations of the sarcolemma called T-
tubules which penetrate throughout the muscle fibre and lie adjacent to the terminal
cisternae of the sarcoplasmic reticulum.
Voltage changes in the T-tubules results in the opening of sarcoplasmic reticulum
Ca2+ channels and the release of stored Ca2+ into the sarcoplasm.
Thus muscle contraction occurs via excitation-contraction coupling.
EXCITATION-CONTRACTION COUPLING. (IMAGE BY OPENSTAX [CC BY 4.0


Sliding Filament Theory LAST UPDATED: 11TH
APRIL 2019
Myofilaments
The thin filament consists of two intertwining strands of actin with smaller strands of
tropomyosin and troponin between the intertwining strands. The thick filament is composed
predominantly of myosin. Each molecule is club shaped, with a thin tail, comprising two
coiled peptide chains and a head made up of two heavy peptide chains and four light
peptide chains. The ATPase activity of the myosin molecule is concentrated in the head. The
thin tails of the myosin form the bulk of the thick filaments, whereas the heads project
outwards to form cross bridges between the thick filaments and their neighbouring thin
filaments.
MYOFILAMENTS. (IMAGE BY OPENSTAX [CC BY 4.0

Muscle Contraction
The contraction of muscle is triggered by the release of Ca 2+ from the sarcoplasmic

reticulum where it is stored bound to calsequestrin. This raises the concentration of calcium
which saturates the binding sites on troponin. This results in a shift of tropomyosin,
exposing actin binding sites thus allowing myosin cross-bridges to form with actin.
Myosin cross bridges attaches attach to the actin filament. The myosin head pivots and
bends as it pulls on the actin filament sliding it towards the M line. Release of ADP and Pi
from the myosin head frees the head for another molecule of ATP. As new ATP attaches to
the myosin head, the cross bridge detaches and frees the myosin head for further binding.
ATP is hydrolysed to ADP and Pi, returning the myosin head to the 'cocked' position.
This mechanism is called the sliding filament theory. The muscle fibre itself does not
shorten in contraction, but the sarcomere shortens as the thick and thin filaments slide over
one another. This constant interaction of the thin and thick filaments, binding, tilting,
releasing and rebinding and sliding over one another using cross-bridges will continue as
long as Ca2+ remains high. The duration of the contraction is dependent on the rate at
which the sarcoplasmic reticulum pumps back the Ca2+ into the terminal cisternae.
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Generation of Action LAST UPDATED: 11TH

APRIL 2019
Potentials  Bookmark
AUTONOMIC NERVOUS SYSTEM
Once triggered an action potential will travel over the entire surface of an excitable
cell and will always have the same amplitude. An action potential is an all or nothing
response; because the size of the action potential is constant, the intensity of the
stimulus is coded by the frequency of firing of a neuron.
Threshold Potential
Action potentials are initiated in nerves by activation of ligand-gated Na+ channels

by neurotransmitters. Opening of these Na+ channels results in a small influx of
sodium and depolarisation of the negative resting membrane potential (-70 mV).
If the stimulus is sufficiently strong, the resting membrane depolarises enough to
reach threshold potential (generally around -55 mV), at which point an action
potential can occur.
Depolarisation
Voltage-gated Na+ channels open, causing further depolarisation and activating

more voltage-gated Na+ channels and there is a sudden and massive sodium influx,
driving the cell membrane potential to about +40 mV.
Repolarisation
The spike of the action potential is transient because as the membrane potential
becomes positive, the voltage-gated Na+ channels inactivate preventing further
sodium influx.
Voltage-gated K+ channels are also activated, causing the K+ permeability to again
be much greater than that for Na+, and the potassium efflux leads to repolarisation.
Delayed closure of these rectifier K+ channels causes a transient hyperpolarisation.
Refractory Period
Following the action potential, Na+ channels remain inactive for a time in a period
known as the absolute refractory period where they cannot be opened by any
amount of depolarisation.
Following this there is a relative refractory period where the temporary
hyperpolarisation makes the cell more difficult to depolarise and an action potential
can be generated only in response to a larger than normal stimulus.
The refractory period limits the frequency at which action potentials can be
generated, and ensures that, once initiated, an action potential can travel only in
one direction.
ACTION POTENTIAL. (IMAGE BY UNKNOWN. [CC-BY-SA-3.0
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Propagation of Action
Potentials
Physiology
MRCEM Success
KEYWORDS
Action Potential Myelin
Nodes of Ranvier Saltatory Conduction
RELATED TOPICS
Action Potential
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Propagation of Action LAST UPDATED: 25TH
FEBRUARY 2019
Potentials  Bookmark
PHYSIOLOGY / BASIC CELLULAR / ACTION POTENTIAL
An action potential is a self-propagating response, successive depolarisation moving along

each segment of an unmyelinated nerve until it reaches the end. It is all-or-nothing and
does not decrease in size.
Conduction in myelinated fibres is much faster, up to 50 times that of the fastest
unmyelinated nerve. Myelinated fibres are insulated except at areas devoid of myelin called
nodes of Ranvier. The depolarisation jumps from one node of Ranvier to another by a
process called saltatory conduction.
Saltatory conduction not only increases the velocity of impulse transmission but also
conserves energy for the axon because depolarisation only occurs at the nodes and not
along the whole length of the nerve fibre.
Larger diameter myelinated nerve fibres conduct nerve impulses faster than small
unmyelinated nerve fibres.
SALTATORY CONDUCTION. (IMAGE BY HELIXITTA (OWN WORK) [CC BY-SA 4.0


Flow through a tube is dependent on the pressure differences across the ends of the tube (P1 - P2) and
the resistance to flow provided by the tube (R).
Darcy's law states that: Flow = (P1 - P2)/R.
Resistance is due to frictional forces and is determined by the length of the tube (L), the radius of the tube
(r) and the viscosity of the fluid flowing down that tube (V).
Poiseuille's law states: R = (8VL)/(πr4).
Combining these equations shows us that flow ∝ (radius) 4. Therefore the radius of the tube has the largest
effect on resistance and therefore flow; the constriction of an artery by 20% will decrease the blood flow
by ~ 60%. This explains why smaller gauge cannulas (with larger diameters) have a faster rate of flow.
Fluids with higher viscosity also have a slower rate of flow. Plasma has a similar viscosity to water, but
blood contains cells which effectively increase the viscosity by three- to four-fold. Changes in cell number
e.g. polycythemia, therefore affect blood flow.
Turbulent vs Laminar Flow

Frictional forces at the sides of a vessel cause a drag force on the fluid touching them, creating a velocity
gradient where the flow is greatest at the centre. This is termed laminar flow which for the most part is the
normal physiological flow. A consequence of the velocity gradient is that blood cells tend to move away
from the sides of the vessel and accumulate towards the centre, aligning themselves to the flow, which
effectively reduces blood viscosity and minimises resistance.
At high velocities, especially in large arteries or where the velocity increases sharply at points of sudden
narrowing in the vessels, or across valves, laminar blood flow may become disrupted and flow may become
turbulent.
Turbulent blood flow is multidirectional and travels at different velocities leading to increased resistance
and additional shear stress on the vessel wall. This may result in damage to endothelium or existing
plaques resulting in an increased tendency to thrombus formation. Clinically turbulence may be heard as a
murmur or a bruit. Turbulent blood flow may sometimes occur due to elevated cardiac output, even across
anatomically normal cardiac valves, resulting in physiological murmurs e.g. in pregnancy.
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Wall Tension LAST UPDATED: 21ST

FEBRUARY 2019
VESSEL FLUID DYNAMICS  Bookmark
Pressure across the wall of a flexible tube (transmural pressure) tends to

extend it, and increases wall tension.
This can be described by Laplace's Law:
Pt = (Tw)/r
where,
Pt = Transmural Pressure
T = Wall Tension
w = Wall Thickness
r = Radius
Thus, a small bubble with the same wall tension as a larger bubble will
contain a greater pressure, and will collapse into the larger bubble if they are
joined. In the lung, small alveoli would collapse into larger ones were it not
for surfactant, which reduces the surface tension more strongly as the size
of the alveolus decreases.
Laplace's Law also means that a large dilated heart (e.g. heart failure) has to
develop more wall tension (contractile force) in order to obtain the same
ventricular pressure, making it less efficient.

Autonomic Nervous System LAST UPDATED: 30TH
AUGUST 2019
AUTONOMIC NERVOUS SYSTEM  Bookmark
The autonomic nervous system mediates homeostatic reflexes, allows the integration
and modulation of function by central mechanisms in the brain in response to external
and internal stimuli, and provides the efferent arm for the involuntary control of most
organs. It is divided into the sympathetic and the parasympathetic nervous systems
which work in concert, but often antagonistically. Both contain preganglionic
neurons originating in the central nervous system that synapse with non-myelinated
postganglionic neurons in peripheral ganglia; postganglionic neurons innervate the
target organ or tissue.
Preganglionic Neurons
Sympathetic preganglionic neurons originate in the lateral horn of segments T1 - L2 of
the spinal cord and exit the cord via the ventral horn on their way to the paravertebral or
prevertebral ganglia.
Parasympathetic preganglionic neurons originate in the brainstem from which they run
in cranial nerves III, VII, IX and X and also from the second and third sacral segments of
the spinal cord.
Both sympathetic and parasympathetic preganglionic neurons release acetylcholine
into the synapse, which acts on cholinergic nicotinic receptors on the postganglionic
fibre. The postganglionic neurotransmitters and receptors depend on the system and
organ.
Postganglionic Neurons
Parasympathetic peripheral ganglia are generally found close to or within their target,
whereas sympathetic peripheral ganglia are located largely in two sympathetic chains
on either side of the vertebral column (paravertebral ganglia), or in diffuse prevertebral
ganglia of the visceral plexuses of the abdomen and pelvis. An exception is the
sympathetic innervation of the adrenal gland, where sympathetic preganglionic fibres
directly innervate the adrenal medulla.
Sympathetic postganglionic neurons terminate in the effector organs where they
release the catecholamine noradrenaline (norepinephrine), which acts on alpha and
beta adrenergic receptors which are linked via G-proteins to cellular effector
mechanisms. A few sympathetic neurons release acetylcholine at the effector (e.g.
sweat glands) and are thus known as sympathetic cholinergic neurons.
Parasympathetic postganglionic neurons release acetylcholine, which acts on
cholinergic muscarinic receptors.
Principle Effects
AUTONOMIC NERVOUS SYSTEM. (IMAGE BY GEO-SCIENCE-INTERNATIONAL VIA WIKIMEDIA

COMMONS)

Neuromuscular Junction LAST UPDATED: 30TH
AUGUST 2019
For skeletal muscle to contract, there must be neuronal activation to the muscle
fibres themselves from either higher centres in the brain or via reflex pathways
involving either the spinal cord or brainstem.
The neurons that innervate skeletal muscles are called alpha-motor neurons.
Each motor axon splits into a number of branches that make contact with the
motor end plate of individual muscle fibres at the neuromuscular junction (NMJ).
The role of the NMJ is the one-to-one transmission of excitatory impulses from
the alpha-motor neuron to the muscle fibres it innervates.
The motor neuron axon terminal has a large number of vesicles containing the
neurotransmitter acetylcholine (ACh). When an action potential reaches the
prejunctional membrane, the opening of voltage-gated Ca2+ channels increases
the permeability to Ca2+ ions and the sudden Ca2+ influx causes the release of
acetylcholine by exocytosis.
Acetylcholine diffuses across the synaptic cleft between the nerve and the
muscle cells, and stimulates a large number of cholinergic nicotinic receptors on
the post-junctional membrane. These receptors contain an integral ion channel,
which opens and allows the influx of small cations, mainly Na+. This movement of
positively charged ions generates an end plate potential (EPP) that is above
threshold for triggering a self-propagating action potential in the muscle fibre.
NEUROMUSCULAR JUNCTION. (IMAGE BY OPENSTAX [CC BY 4.0

Neurochemical Synaptic LAST UPDATED: 25TH
FEBRUARY 2019
Transmission  Bookmark
ACTION POTENTIAL
Action potentials in incoming neurons are transmitted by the release of

neurotransmitters that bind to receptors on the postganglionic neuron or effector
tissue. Between neurons (e.g. in ganglia), this occurs within the synapse, where
the axon terminates in a bouton separated from the target by a synaptic cleft.
The neurotransmitter is synthesised and stored in vesicles in the terminal bouton
of the preganglionic neuron. The arrival of an action potential at the nerve ending
causes opening of voltage-gated Ca2+ channels in the presynaptic membrane,
and a subsequent influx of Ca2+, which causes the neurotransmitter-containing
vesicle to fuse with the presynaptic membrane and release its contents into the
synaptic cleft. The neurotransmitter then diffuses across the synaptic cleft to
bind with receptors on the postsynaptic membrane of the dendrite and activate
the response. Neurotransmitter release can be suppressed by feedback onto
presynaptic inhibitory receptors.
After activation at the postsynaptic membrane, neurotransmitters must be
removed from the synaptic cleft. In cholinergic synapses, cholinesterase rapidly
breaks down acetylcholine into choline and acetate which are then recycled. In
adrenergic synapses, most noradrenaline is taken up by the nerve ending and
recycled. Excess noradrenaline and sympathomimetic amines such as tyramine
are metabolised in the neuron by mitochondrial monoamine oxidase (MAO).
Noradrenaline and other catecholamines in the circulation are metabolised
sequentially by catechol-O-methyltransferase (COMT) and MAO.
NEUROCHEMICAL SYNAPTIC TRANSMISSION. (IMAGE BY UNKNOWN [CC BY-SA 4.0

Functional Anatomy of Heart LAST UPDATED: 21ST APRIL
2019
PHYSIOLOGY / CARDIOVASCULAR / CARDIAC OUTPUT
 Bookmark
Heart Chambers
The heart consists of four chambers - two thin-walled atria and two muscular ventricles. The atria are
separated from the ventricles by a band of fibrous connective tissue called the annulus fibrosus,
which provides a skeleton for the attachment of muscle and cardiac valves, and prevents electrical
conduction between the atria and ventricles (except at the atrioventricular node).
Heart Valves
Blood flows from the right atrium into the right ventricle via the tricuspid atrioventricular valve and
from the left atrium into the left ventricle via the mitral atrioventricular valve.
Blood is ejected from the right ventricle through the pulmonary semilunar valve into the pulmonary
artery and from the left ventricle via the aortic semilunar valve into the aorta.
SECTIONAL ANATOMY OF THE HEART. (IMAGE BY BLAUSEN MEDICAL COMMUNICATIONS, INC. [CC BY 3.0
Heart Wall
The walls of the heart are formed from myocardium, and the left side has more muscle than the right
(as the systemic circulation has greater resistance to flow, the left ventricle requires more force).
The inner surface of the heart is covered by the endocardium which provides an anti-thrombogenic
surface. The outer surface is covered by epicardium, a layer of mesothelial cells. The whole heart is
enclosed in a thin fibrous sheath, the pericardium.
HEART WALL. (IMAGE BY OPENSTAX COLLEGE [CC BY 3.0


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CVS Systemic Overview LAST UPDATED: 2ND

MAY 2019
PHYSIOLOGY / CARDIOVASCULAR /
CARDIAC OUTPUT  Bookmark
Definitions
The total blood volume in the circulatory system of a healthy adult is about 5
L.
The stroke volume is the volume of blood ejected per beat. It is usually about
70 mL/beat at rest.
The heart rate is the number of beats per minute. It is usually about 70
beats/minute at rest.
The cardiac output is the volume of blood pumped out of heart via the aorta
per minute.
Cardiac output (CO) = Stroke volume x Heart rate = 70 mL/beat x 70
beats/min = 4900 mL/min
Therefore cardiac output is usually about 5 L/minute at rest in humans.
Mean Arterial Pressure (MAP)

During systole, the pressure in the left ventricle increases and blood is
ejected into the aorta. The rise in pressure stretches the elastic walls of the
aorta and large arteries and drives blood flow. Systolic pressure is the
maximum arterial pressure during systole. During diastole, arterial blood
flow is partly maintained by elastic recoil of the walls of large arteries. The
minimum pressure reached before the next systole is the diastolic pressure.
The difference between the systolic and diastolic pressure is the pulse
pressure.
The mean arterial pressure (MAP) cannot be calculated by averaging these
pressures, because for about 60% of the time, the heart is in diastole. It is
instead estimated as the diastolic + one-third of the pulse pressure, e.g. =
80 + 1/3(110 - 80) = 90 mmHg where BP 110/80 mmHg.
Normal Pressures in the Circulation

The mean arterial pressure (MAP) at the start of the arterioles is about 65
mmHg. The pressure on the arterial side of capillaries is about 25 mmHg,
and on the venous side is about 15 mmHg. Venules converge into veins and
finally the vena cava. The pressure in the vena cava at the level of the heart
(the central venous pressure) is usually close to 0 mmHg.

PHYSIOLOGY / CARDIOVASCULAR / CARDIAC CYCLE LAST UPDATED: 28TH
FEBRUARY 2019
 Bookmark
The myocardium is composed of cardiac muscle cells called myocytes. The cells are striated due to the
arrangement of the thick and thin filaments which make up the bulk of the muscle, although they are less
organised than in skeletal muscle. The myocytes are small and branched, with a single nucleus and are
rich in mitochondria. The normal pumping action of the heart is dependent on the synchronised
contraction of all cardiac cells.
Cardiac myocyte contraction is not dependent on an external nerve supply but instead the heart
generates its own rhythm (inherent rhythmicity). The nerves innervating the heart only speed up or slow
down the rhythm and can modify the force of contraction.
The synchronicity between myocytes occurs because all the adjacent cells are linked to one another at
their ends by specialised gap junctions (formed of connexons), within the intercalated discs, which
essentially provide a low-resistance pathway between cells. Gap junctions allow action potentials to
spread rapidly from one cell to another and allows the myocardium to act as a functional syncytium. The
intercalated discs also provide structural attachments (desmosomes) between myocytes to distribute
force.
Although a rise in intracellular [Ca2+] initiates contraction in the same way as in skeletal muscle, the
mechanisms leading to the rise in intracellular [Ca2+] are fundamentally different.
CARDIAC MYOCYTE MICROSTRUCTURE. (IMAGE BY OPENSTAX CNX [CC BY 3.0

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Characteristics of Special LAST UPDATED: 21ST

APRIL 2019
Circulations  Bookmark
PERIPHERAL VASCULAR SYSTEM
Skeletal Muscle Circulation

The skeletal muscle circulation normally receives about 15 - 20% of the cardiac output,
but this may rise to > 80% during exercise. Skeletal muscle provides a major contribution
to the total peripheral resistance and sympathetic regulation of muscle blood flow is
important in the baroreceptor reflex. At rest most capillaries are not perfused as their
arterioles are constricted. Capillaries are recruited during exercise by metabolic
hyperaemia, caused by release of K+ and CO2 from the muscle and adenosine. This
overrides sympathetic vasoconstriction in working muscle; the latter reduces flow in
non-working muscle conserving cardiac output.
Pulmonary Circulation
The pulmonary circulation is not controlled by either autonomic nerves or metabolic
products, and the most important mechanism regulating flow is hypoxic pulmonary
vasoconstriction, in which small arteries constrict in response to hypoxia (in contrast to
elsewhere in the body).
If an area of lung is poorly ventilated and the alveolar partial pressure of oxygen is low,
pulmonary blood vessels are constricted and blood is diverted to areas of the lung that
are better ventilated, thus maintaining optimal ventilation-perfusion matching. This
effect is accentuated by high alveolar PCO2.
The response is unhelpful in the presence of global lung hypoxia, at altitude or in

respiratory failure, where it may contribute to the development of pulmonary
hypertension and right-sided heart failure (cor pulmonale).
Cutaneous Circulation
The main function of the cutaneous circulation is thermoregulation. Arteriovenous
anastomoses (AVAs) directly linked arterioles and venules, allowing a high blood flow into
the venous plexus and thus radiation of heat. AVAs are mostly found in the hands, feet
and areas of the face.
Temperature is sensed by peripheral thermoreceptors and the hypothalamus
coordinates the response.
When temperature is low, sympathetic stimulation of alpha-adrenergic receptors causes
vasoconstriction of cutaneous vessels minimising loss of body heat (a similar response
occurs in the baroreceptor reflex). Piloerection traps insulating air.
Increased temperatures reduce sympathetic adrenergic stimulation, causing
vasodilation and allowing more blood to flow to the skin and radiate its heat to the
environment, whereas activation of sympathetic cholinergic fibres promotes sweating
and the release of bradykinin, which also causes vasodilation.
Cerebral Circulation
The brain receives around 15% of the total cardiac output and has a high capillary
density.
The endothelial cells of the capillaries of the blood-brain barrier have very tight
junctions, and contain membrane transporters that control the movement of
substances, such as ions, glucose and amino acids, and tightly regulate the composition
of cerebrospinal fluid. This is continuous except where substances need to be absorbed
or released e.g. pituitary gland, choroid plexus.
The autoregulation of cerebral blood flow can maintain a constant flow for blood
pressures (MAP) between 50 and 170 mmHg. CO2 and K+ are particularly important
metabolic regulators in the brain, with increasing concentration causing vasodilation
and a functional hyperaemia.
Hyperventilation reduces blood PCO2 and can cause fainting due to cerebral
vasoconstriction.
Coronary Circulation
The heart has a high metabolic demand and its high capillary density allow it to extract
an unusually large fraction (about 70%) of oxygen from the blood.
In exercise, the reduced diastolic interval and increased oxygen consumption demand a
greatly increased blood flow which is achieved by metabolic hyperaemia mediated by
adenosine, K+ and hypoxia. This overrides the vasoconstriction mediated by sympathetic
nerves acting at alpha-adrenergic receptors and is assisted by circulating adrenaline
which causes vasodilation by acting on beta-adrenergic receptors.

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Pressures, Volumes and Key LAST UPDATED: 31ST

JANUARY 2022
Events in Cardiac Cycle  Bookmark
PHYSIOLOGY / CARDIOVASCULAR / CARDIAC CYCLE
The cardiac cycle describes the events that occur during one beat of the heart.
CARDIAC CYCLE. (IMAGE MODIFIED BY FRCEM SUCCESS. ORIGINAL BY DANIELCHANGMD REVISED

ORIGINAL WORK OF DESTINYQX; REDRAWN AS SVG BY XAVAX [CC BY-SA 2.5
At the start of the cardiac cycle, towards the end of diastole, the whole of the heart is
relaxed. The atrioventricular (AV) valves are open because the atrial pressure is still slightly
greater than the ventricular pressure. The semilunar valves are closed, as the pressure in the
pulmonary artery and aorta is greater than the ventricular pressures. The cycle starts when
the sinoatrial node (SAN) initiates atrial systole.
Diastole: Atrial Systole (AV valves open, Semilunar valves closed)
Atrial depolarisation causes the P wave on the ECG and initiates atrial contraction (atrial
repolarisation is too diffuse to be seen on the ECG).
As the atria contract, the atrial pressure increases which forces more blood flow across the
open AV valves, leading to rapid flow of blood into the ventricles. There are no valves
between the veins and atria and atrial systole causes a small pressure rise in the great veins
(the a wave on the JVP waveform).
At rest, atrial contraction only contributes the last 15 - 20% of the final ventricular volume,
as most of the ventricular filling has occurred passively in diastole due to venous pressure.
The proportion of atrial contribution increases with heart rate as diastole shortens and there
is less time for passive ventricular filling.
The end-diastolic volume (EDV) is usually about 120 - 140 mL, and the end-diastolic
pressure is less than 10 mmHg (and higher in the left ventricle than the right due to the
thicker and therefore stiffer left ventricle).
In ventricular hypertrophy, filling of the 'stiff' ventricle by atrial systole causes a fourth heart
sound, which is not audible in normal adults.
Systole: Isovolumetric Contraction (All valves closed)

Ventricular depolarisation causes the QRS complex on the ECG, and triggers excitation-
contraction coupling and myocyte contraction.
The ventricular pressure rises sharply during contraction and the AV valves close as soon as
this is greater than the atrial pressure (causing the first heart sound). Because the mitral
valve closes before the tricuspid valve, the first heart sound may be split.
For a short period, as the forces are developing, both the AV and the semilunar valves are
closed as the ventricular pressure is still less than that in the pulmonary artery and aorta,
and no ejection occurs. This is isovolumetric contraction.
The increasing pressure makes the AV valves bulge into the atria, causing a small atrial
pressure wave (the c wave of the JVP waveform).
Systole: Ventricular Ejection (Semilunar valves open, AV valves closed)

When the ventricular pressure exceeds that in the pulmonary artery and the aorta, the
semilunar valves open and blood is ejected, initially rapidly (rapid ejection phase) and then
more slowly (reduced ejection phase).
Atrial pressure initially decreases as the atrial base is pulled downward during ejection,
expanding the atrial chamber (the x descent of the JVP waveform). Atrial filling begins in the
rapid ejection phase and continues during the reduced ejection phase and atrial pressure
begins to rise (the v wave of the JVP waveform).
During the second half of ejection, the ventricles stop actively contracting, the ventricular
pressure starts to decrease and the muscle starts to repolarise; this causes the T wave on
the ECG, which marks the end of both ventricular contraction and rapid ventricular ejection.
The ventricular pressure during the reduced ejection phase begins to decrease. Aortic
pressure also decreases because of the runoff of blood from large arteries into smaller
arteries. The ventricular pressure falls slightly below that in the aorta, but initially blood
continues to flow out of the ventricle because of momentum; eventually the ventricular
pressure falls sufficiently and the semilunar valves close.
The amount of blood ejected is the stroke volume (SV), and is usually about 70 mL (therefore
about 50 mL is left; this is the end-systolic volume). The proportion of EDV that is ejected
(i.e. the SV/EDV) is the ejection fraction and this is normally about 0.6.
Diastole: Isovolumetric Relaxation (All valves closed)

Closure of the semilunar valves causes a small increase in aortic pressure (the dicrotic
notch on the arterial waveform), and the second heart sound. Inspiration delays closure of
the pulmonary valve and thus causes splitting of the second heart sound.
Immediately after the closure of the semilunar valves, the ventricles rapidly relax and
ventricular pressure decreases rapidly but the AV valves remain closed as initially the
ventricular pressure is still greater than atrial pressure. This is isovolumetric relaxation.
Atrial pressure continues to rise because of venous return, with the v wave of the JVP
waveform peaking during this phase. As the ventricles continue to relax, the ventricular
pressure falls below that of the atrial pressure and the AV valves open.
Diastole: Ventricular Filling (AV valves open, Semilunar valves closed)

When the AV valves open, the atrial pressure falls (the y descent of the JVP waveform) and
the ventricles refill, initially rapidly (the rapid filling phase) and then more slowly as the
ventricles expand, become less compliant, and ventricular pressures rise (the reduced filling
phase). Rapid flow of blood from the atria into the ventricles causes the third heart sound,
which is normal in children but, in adults, is associated with disease such as ventricular
dilation.
Diastole is usually twice the length of systole at rest, but decreases with increased heart
rate. During systole, contraction of the ventricles compresses the coronary arteries and
suppresses blood flow. This is particularly evident in the left ventricle, where during systole
the ventricular pressure is the same as or greater than that in the arteries and as a result
more than 85% of left ventricular perfusion occurs during diastole. This becomes a problem
if the heart rate is increased as the diastolic interval is shorter and can result in ischaemia.
Valve Opening/Closure during Cardiac Cycle
Cardiac Cycle Atrioventricular Valves Semilunar Valves

Phase
Atrial systole Open (atrial pressure > Closed (arterial pressure >
ventricular pressure) ventricular pressure)
Isovolumetric Closed (ventricular pressure > Closed (arterial pressure >
contraction atrial pressure) ventricular pressure)
Ventricular Closed (ventricular pressure > Open (ventricular pressure >
ejection atrial pressure) arterial pressure)
Isovolumetric Closed (ventricular pressure > Closed (arterial pressure >
relaxation atrial pressure) ventricular pressure)
Ventricular Open (atrial pressure > Closed (arterial pressure >
filling ventricular pressure) ventricular pressure)
JVP Waveform during Cardiac Cycle
JVP Phase of Physiology

waveform Cardiac Cycle
a wave Atrial systole Occurs due to right atrial contraction
(end diastole)
c wave Isovolumetric Occurs due to the bulging of the tricuspid valve into
contraction the right atrium during right isovolumetric
(early systole) ventricular contraction
x descent Rapid Occurs due to a combination of right atrial
ventricular relaxation, the downward displacement of the
ejection (mid tricuspid valve during right ventricular contraction,
systole) and the ejection of blood from both the ventricles
JVP Phase of Physiology
waveform Cardiac Cycle
v wave Ventricular Occurs due to right atrial filling from venous return
ejection and
isovolumetric
relaxation
(late systole)
y descent Ventricular Occurs due to opening of the tricuspid valve and the
filling (early subsequent rapid inflow of blood from the right
diastole) atrium to the right ventricle
Heart Sounds during Cardiac Cycle
Heart Phase of Mechanical Event

Sound Cardiac
Cycle
First Start of Caused by closure of the atrioventricular (mitral and
heart systole tricuspid) valves
sound
Second End of Caused by closure of the semilunar (aortic and
heart systole pulmonary) valves
sound
Third Early Caused by rapid flow of blood from the atria into the
heart diastole ventricles during the ventricular filling phase
sound
Fourth Late Caused by filling of an abnormally stiff ventricle in atrial
heart diastole systole
sound
ECG Deflections during Cardiac Cycle
ECG Event
P wave Atrial depolarisation
QRS complex Ventricular depolarisation
T wave Ventricular repolarisation
Conducting System of Heart LAST UPDATED: 7TH
JUNE 2022
 Bookmark
The cardiac conduction system initiates and coordinates contraction of the heart.
Sinoatrial Node
The heartbeat is initiated by spontaneous depolarisation of the sinoatrial node (SAN), a
region of specialised myocytes in the right atrium. The rate is modulated by the
autonomic nervous system. Action potentials in the SAN activate adjacent atrial
myocytes and a wave of depolarisation and contraction therefore spreads through atrial
muscle. This is prevented from reaching the ventricles directly by the annulus fibrosus.
CARDIAC CONDUCTION SYSTEM. (IMAGE BY OPENSTAX COLLEGE [CC BY 3.0

Atrioventricular Node
The impulse generated by the SAN is then channelled through the atrioventricular node
(AVN), located between the right atrium and ventricle near the atrial septum. The AVN
contains small cells and thus conducts slowly and delays the impulse for about 120 ms
allowing time for atrial contraction to complete ventricular filling.
Conduction of the Impulse

Once ventricular filling is complete, the impulse is then transmitted by specialised, wide,
fast conducting myocytes in the bundle of His, the left and right bundles, and the
Purkinje fibres, by which it is distributed over the inner surface of both ventricles. From
here a wave of depolarisation and contraction moves from myocyte to myocyte across
the endocardium until the whole ventricular mass is activated.
Pathophysiology
Because the SAN is responsible for the rest of the heart's electrical activity, it is called
the primary pacemaker. The SAN will normally discharge at a rate of 60-100 bpm. If the
SAN does not function properly or the impulse generated in the SAN is blocked before it
travels down the electrical conduction system, a group of cells further down the heart
will become its pacemaker.
The AVN is the secondary pacemaker and will normally discharge at about 40-60 beats
per minute. The left and right branches of the bundle of His, and the Purkinje fibers, will
also produce a spontaneous action potential at a rate of 20-40 beats per minute, so if
the SAN and AVN both fail to function, these cells can become pacemakers. It is
important to realise that these cells will be initiating action potentials and contraction at
a much lower rate.
The SAN controls the rate of contraction for the entire heart muscle because its cells
have the quickest rate of spontaneous depolarisation, thus they initiate action potentials
the quickest. The action potential generated by the SAN passes down the electrical
conduction system of the heart, and depolarises the other potential pacemaker cells to
initiate action potentials before these other cells have had a chance to generate their
own spontaneous action potential, thus they contract and propagate electrical impulses
to the pace set by the cells of the SAN. This is the normal conduction of electrical activity
in the heart.
Electrocardiogram (ECG) LAST UPDATED: 28TH
FEBRUARY 2019
 Bookmark
The wave of depolarisation through the heart causes local currents in surrounding fluid
which are detected at the body surface as small changes in voltage. This forms the basis of
the ECG.
The classical ECG records voltage between the left and right arm (lead I), the right arm and
left leg (lead II) and the left arm and left leg (lead III). This is represented by Einthoven's
triangle.
The size of the voltage at any time depends on the quantity of muscle depolarisation and
the direction in which the wave of depolarisation is travelling. Thus lead II normally shows
the largest deflection during ventricular depolarisation, as the muscle mass is greatest and
depolarisation travels from apex to base, more or less parallel to a line from the left hip to
the right shoulder.
EINTHOVEN'S TRIANGLE. (IMAGE BY NPATCHETT (OWN WORK) [CC BY-SA 4.0

Capillaries and the smallest venules are formed from a single layer of endothelial cells
supported on the outside by a basal lamina containing collagen. The luminal surface is
covered by the glycoprotein network called the glycocalyx.
Capillary Permeability
Capillaries throughout the body vary in their permeability based on the size of their
pores. There are three basic types:
Continuous capillaries, found in the skin, lungs, muscles and CNS, are the most
selective with low permeability, as junctions between the endothelial cells are
very tight, restricting the flow of molecules with MW > 10,000.
Fenestrated capillaries, found in renal glomeruli, endocrine glands and intestinal
villi, are more permeable with less tight junctions, and the endothelial cells are
also punctured by pores which allow large amounts of fluids or metabolites to
pass.
Discontinuous capillaries, found in the reticuloendothelial system (bone marrow,
liver and spleen), have large gaps between endothelial cells and are permeable
to red blood cells.
TYPES OF CAPILLARY. (IMAGE BY OPENSTAX COLLEGE [PUBLIC DOMAIN], VIA WIKIMEDIA

COMMONS)
Transcapillary Exchange
Water, gases and other substances cross the capillary wall mainly by diffusion down
their concentration gradients.
Non-polar lipophilic substances e.g. CO2 and O2 can cross the endothelial lipid bilayer
membrane easily. The membrane is however more impermeable to hydrophilic
molecules such as glucose and polar molecules and ions. Such substances mainly
cross the wall of continuous capillaries through the gaps between endothelial cells,
slowed down by tight junctions between cells and by the glycocalyx so that diffusion is
much slower than for lipophilic substances.
This small pore system also prevents the diffusion of substances greater than 10,000
Da such as plasma proteins. Plasma proteins can cross the capillary wall, but
extremely slowly; this may involve large pores through endothelial cells, such as in
fenestrated capillaries or large spaces between endothelial cells, such as in
discontinuous capillaries.

Something wrong?
Inotropic Effects on Heart LAST UPDATED: 28TH

FEBRUARY 2019
CARDIAC CYCLE  Bookmark
Factors that affect intracellular [Ca2+] and hence cardiac contractility are
called inotropes.
Sympathetic stimulation increases cardiac muscle contractility because it
causes release of noradrenaline. Noradrenaline is a positive inotrope; it binds
to β1-adrenoceptors on the membrane and causes increased Ca2+ entry via L-
type channels during the AP and thus increases Ca2+ release from the SR.
Noradrenaline also increases Ca2+ sequestration into the SR and thus more
Ca2+ is available for the next contraction.
Cardiac glycosides (e.g. digoxin) slow the removal of Ca2+ from the cell by
inhibiting the membrane Na+ pump which generates the Na + gradient
required for driving the export of Ca2+; consequently the removal of Ca2+ from
the myocyte is slowed and more Ca2+ is available inside the myocyte for the
next contraction.
Acidosis is negatively inotropic, largely because H+ competes for Ca2+ binding

sites.

Sinoatrial Node Action Potential LAST UPDATED: 21ST APRIL
2019
 Bookmark
Pacemaker Potential
The action potential (AP) of the sinoatrial node (SAN) differs from that in ventricular muscle.
The resting potential of the SAN is about - 60 mV, and it decays steadily with time until it reaches
a threshold potential of about - 40 mV, when an action potential is initiated.
The upstroke of the AP is slow, as it is not due to activation of fast Na + channels like cardiac
myocytes, but instead slow L-type Ca2+ channels; the SA node contains no functional fast
Na+ channels. The slow upstroke means that conduction between nodal myocytes is slow, which
is particularly important at the atrioventricular node (which has a similar AP to the SAN).
The rate of decay of the SAN resting potential determines the rate of AP and therefore of heart
rate; it is therefore called the pacemaker potential. The pacemaker potential decays because of a
slowly reducing outward K+ current set against a slow inward Na+ leak through slow
Na+ channels (and to a lesser extent, a slow inward Ca2+ leak through T-type
Ca2+ channels). Factors that affect these currents alter the rate of decay and the time to reach
threshold and thus heart rate and are called chronotropic agents.
SINOATRIAL NODE ACTION POTENTIAL. (IMAGE BY OPENSTAX COLLEGE [CC BY 3.0

Chronotropic Agents
Noradrenaline (the sympathetic neurotransmitter) is a positive chronotrope and causes a faster
rate of decay and thus heart rate whereas acetylcholine (the parasympathetic neurotransmitter)
is a negative chronotrope and lengthens the time to reach threshold and decreases heart rate.
Other Cardiac Action Potentials

Other atrial cells, the AV node, the bundle of His and Purkinje system may also exhibit decaying
resting potentials that can act as pacemakers. However the SAN is normally fastest and
predominates - this is called overdrive suppression.

Something wrong?
Ventricular Myocyte Action LAST UPDATED: 21ST

APRIL 2019
Potential  Bookmark
The resting potential of ventricular myocytes is about -90 mV. An action potential (AP)
is initiated when the myocyte is depolarised to a threshold potential of about -65 mV,
as a result of transmission from an adjacent myocyte via gap junctions.
Depolarisation
Fast voltage-gated Na+ channels are activated and a Na+ influx depolarises the
membrane rapidly to about +30 mV. This initial depolarisation is similar to that in nerve
and skeletal muscle, and assists the transmission to the next myocyte.
Na+ channels and currents rapidly inactivate, but in cardiac myocytes, the initial
depolarisation activates voltage-gated Ca2+ channels (slow L-type channels,
threshold approximately - 45 mV) through which Ca2+ floods into the cell. The
resulting influx of Ca2+ prevents the cell from repolarising and causes a plateau phase,
that is maintained for about 250 ms until the L-type channels inactivate. The cardiac
AP is thus much longer than that in nerve or skeletal muscle.
Repolarisation
Repolarisation occurs due to activation of voltage-gated K + rectifier channels and a K+

efflux. As the AP lasts almost as long as contraction, its refractory period prevents
another AP being initiated until the muscle relaxes, thus cardiac muscle cannot exhibit
tetanus.
VENTRICULAR MUSCLE ACTION POTENTIAL. (IMAGE MODIFIED BY FRCEM SUCCESS. ORIGINAL
BY UNKNOWN [CC-BY-SA-3.0 (HTTP://CREATIVECOMMONS.ORG/LICENSES/BY-SA/3.0/), VIA
WIKIMEDIA COMMONS)
Other Cardiac Action Potentials

Atrial myocytes have a similar but more triangular AP compared to the ventricles (less
plateau). Purkinje fibres in the conduction system are also similar to ventricular
myocytes, but have a spike at the peak of the upstroke reflecting a larger Na+ current
that contributes to their fast conduction velocity.

Cardiac output is determined by the heart rate and stroke volume. Stroke volume is
dependent on the filling pressure (the preload), the cardiac muscle force (the
contractility) and the pressure against which the heart has to pump (the afterload).
Frank-Starling Relationship
The volume of blood in the ventricle at the start of systole, the end-diastolic volume
(EDV), depends on the end-diastolic pressure (EDP) and the compliance of the
ventricular wall. Right ventricular EDP is dependent on right atrial and hence central
venous pressure (CVP). If EDP (and thus EDV) is increased, the force of the following
contraction, and thus stroke volume increases; this is known as the Frank-Starling
relationship.
Starling's law of the heart states that 'the energy released during contraction depends
on the initial fibre length'. An increase in EDV causes an increase in ventricular fibre
length, which produces an increase in developed tension and results in an increased
force of systolic contraction. As muscle is stretched, more myosin cross-bridges can
form, increasing force. However, cardiac muscle has a much steeper relationship
between stretch and force than skeletal muscle, because in the heart stretch also
increases the Ca2+ sensitivity of troponin, so more force is generated for the same
intracellular Ca2+.
The most important consequence of Starling's law is that output is matched between
the right and left ventricles. It thus explains how CVP, although only perceived by the
right ventricle, also influences left ventricular function and cardiac output, and why
postural hypotension and haemorrhage reduce cardiac output. It also allows the heart
to sustain output when afterload is increased, or contractility is reduced, as both lead to
accumulation of venous blood and a raised EDP, which increases ventricular force and
restores stroke volume.
Factors affecting the Frank-Starling Curve

The Frank-Starling curve is affected by:
Preload
Increases in preload cause a rightward shift along the curve
Decreases in preload cause a leftward shift along the curve
Contractility
Increases in contractility shift the curve upwards and to the left
Decreases in contractility shift the curve downwards and to the right
Afterload
Increases in afterload shift the curve downwards and to the right
Decreases in afterload shift the curve upwards and to the left
FRANK-STARLING CURVE. (IMAGE BY OPENSTAX COLLEGE [PUBLIC DOMAIN], VIA WIKIMEDIA

COMMONS)
Preload
Preload can be defined as the initial stretching of the cardiac myocytes prior to
contraction. Preload, therefore, is related to muscle sarcomere length. Because
sarcomere length cannot be determined in the intact heart, other indices of preload are
used such as ventricular end-diastolic volume or pressure. When venous return to the
heart is increased, the end-diastolic pressure and volume of the ventricles are
increased, which stretches the sarcomeres, thereby increasing their preload.
Ventricular filling and therefore preload is increased by:
Increased central venous pressure which can result from:
Decreased venous compliance caused by venoconstriction
Increased thoracic blood volume caused by either an increase in total blood
volume or an increase in venous return (augmented by increased
respiratory activity, increased skeletal muscle pump activity or by gravity in
head-down tilt).
Increased ventricular compliance
Increased atrial activity caused by sympathetic stimulation or from increased
filling of the atria
Reduced heart rate (which increases ventricular filling time)
Ventricular filling and therefore preload is decreased by:
Decreased central venous pressure caused by:
Reduced blood volume e.g. haemorrhage
Gravity causing blood to pool in lower limbs when standing
Impaired atrial activity e.g. in atrial fibrillation
Tachycardia which reduces ventricular filling time
Decreased ventricular compliance e.g. ventricular hypertrophy
Inflow (mitral and tricuspid) valve stenosis which reduces ventricular filling
Contractility
Contractility (inotropy) is the intrinsic ability of cardiac muscle to develop force at a
given muscle length. It is determined by the intracellular [Ca2+] and can be estimated by
the ejection fraction. Increases in contractility cause an increase in stroke
volume/cardiac output for any level of right atrial pressure or end-diastolic volume, and
hence shift the Starling curve upwards. Decreases in contractility cause a decrease in
stroke volume/cardiac output for any level of right atrial pressure or end-diastolic
volume and hence shift the Starling curve downwards.
Afterload
Afterload is determined by the resistance to outflow from the ventricle, which for the
left ventricle is mainly determined by the aortic pressure, and for the right, the
pulmonary artery pressure.
An increase in afterload (e.g. hypertension, valve stenosis) means that the ventricles
must eject blood against a higher pressure, resulting in a decrease in stroke volume and
a downward shift of the Starling curve.
This decrease in stroke volume however results in an increase in end-systolic volume.
As a result, blood accumulates on the venous side and filling pressure rises. This will
result in a secondary increase in preload and a rightward shift along the Starling curve;
cardiac output is restored at the expense of an increased EDP.

Capillary Filtration LAST UPDATED: 6TH
JUNE 2019
PERIPHERAL VASCULAR SYSTEM  Bookmark
The capillary wall is very permeable to water. Water tends to flow from a low to a high
osmotic pressure, but from a high to a low hydrostatic pressure. The net flow of water
across the capillary wall is therefore determined by the balance between the hydrostatic
pressure which tends to drive water out of the capillaries and the oncotic pressure which
tends to draw water into the capillaries from the interstitial space.
(IMAGE BY KES47 [PUBLIC DOMAIN], VIA WIKIMEDIA COMMONS)
Starling's Equation
Starling's equation tells us that the net flow of water across the capillary wall is
proportional to (Pc - Pi) - (πp - πi), where (Pc - Pi) is the difference in hydrostatic
pressure between the capillary and interstitial space and (πp - πi) is the difference in
osmotic pressure between plasma and interstitial fluid. A positive value means there is a
net fluid movement out of the capillary (filtration), a negative value means there is a net
fluid movement into the capillary (absorption).
Oncotic Pressure
Across capillary walls, unlike proteins, most ions and small molecules diffuse easily and
thus the crystalloid osmotic pressure they exert is roughly the same on either side of the
capillary wall; for this reason, the osmotic force across the capillary wall is largely
determined by protein concentration in the blood. Plasma protein concentration is
normally much higher than interstitial protein concentration because very little protein is
filtered; plasma colloid osmotic pressure is therefore higher than interstitial colloid
osmotic pressure and tends to draw fluid intravascularly.
Hydrostatic Pressure
Capillary hydrostatic pressure normally varies from about 35 mmHg at the arteriolar end
to about 15 mmHg at the venous end, whereas the interstitial hydrostatic pressure is
normally close to 0 mmHg (or is slightly negative). The greater hydrostatic pressure inside
the capillary tends to drive filtration of water out of the capillary into the tissues.
Net Filtration
Normally overall the hydrostatic pressure along the length of the capillary is greater than
plasma oncotic pressure and thus there is a small net filtration of fluid from the capillary
into the interstitial space; of about 4000 L of plasma entering the capillaries daily as the
blood recirculates, a net filtration of 8 L occurs. Although arteriolar constriction will
reduce capillary hydrostatic pressure and therefore lead to the reabsorption of fluid, this
will normally be transient due to the concentration of interstitial fluid, i.e. the increased
interstitial oncotic pressure.
A reduction in plasma protein (e.g. starvation), or a loss of endothelium integrity with
diffusion of protein into the interstitial space (e.g. inflammation, ischaemia), will reduce
(πp - πi), leading to enhanced filtration and loss of fluid into the tissues. Increased
filtration is also caused by high venous pressures.
CAPILLARY EXCHANGE. (IMAGE BY OPENSTAX COLLEGE [CC BY 3.0


Oedema LAST UPDATED: 28TH
FEBRUARY 2019
Oedema is swelling of the tissues due to excess fluid in the interstitial space.
This may be caused by increased filtration, resulting in fluid overwhelming the lymphatic
system, or due to obstruction or dysfunction of the lymphatic system itself.
A reduction in plasma protein (e.g. starvation), or a loss of endothelium integrity with
diffusion of protein into the interstitial space (e.g. inflammation, ischaemia), will reduce the
oncotic pressure gradient, leading to enhanced filtration and loss of fluid into the tissues.
Reduced venous drainage (increased venous pressure) will increase capillary hydrostatic
pressure with a similar effect. Standing without moving the legs prevents the operation of
the muscle pump leading to local venous pressure rises and leg oedema. In congestive heart
failure, reduced cardiac function results in increased pulmonary and central venous
pressures, leading to pulmonary oedema and peripheral oedema respectively.
Mechanism of Causes
Oedema
Increased capillary Caused by increased venous pressures e.g. by
hydrostatic pressure gravitational forces, volume expanded states, in heart
failure or with venous obstruction
Decreased Caused by decreased protein concentration in blood e.g.
plasma oncotic nephrotic syndrome, protein malnutrition, liver failure
pressure
Increased capillary Caused by proinflammatory mediators or by damage to
permeability (leading to the structural integrity of capillaries so that they become
reduced oncotic more 'leaky' e.g. in tissue trauma, burns and severe
pressure gradient) inflammation
Lymphatic obstruction Caused by, for example, filariasis or following lymph node
dissection, surgery or radiation therapy

Lymphatic Capillaries LAST UPDATED: 28TH
FEBRUARY 2019
Normally, filtration of fluid out of the capillaries is slightly greater than absorption of fluid
into the capillaries. Fluid filtered by the microcirculation (about 8 L per day) is returned to
the circulation by the lymphatic system.
Lymphatic capillaries are blind-ended tubes walled with endothelial cells which allow the
entry of fluid, protein and bacteria, but prevent their exit. Lymphatic capillaries drain into
collecting lymphatics and then into larger lymphatic vessels, both containing smooth
muscle and unidirectional valves.
From here, lymph is propelled by smooth muscle constriction and compression of the
vessels by body movements into afferent lymphatics and then the lymph nodes, where
bacteria and other foreign materials are removed by phagocytes. Most fluid is
reabsorbed here by capillaries, with the remainder returning via efferent lymphatics and
the thoracic duct into the subclavian veins.
The lymphatic system plays a major role in the body's immune defence and is also
important for absorption and transport of fats.
LYMPHATIC CAPILLARIES. (IMAGE BY OPENSTAX COLLEGE [CC BY 3.0

Cardiac Excitation-Contraction LAST UPDATED: 21ST
APRIL 2019
Coupling  Bookmark
Cardiac muscle contracts when intracellular Ca2+ rises (> 100 nmol/L).
Contraction
Although Ca2+ entry during the action potential (AP) is essential for contraction, it only accounts
for about 25% of the rise in intracellular Ca2+. The rest is released from Ca 2+ stores in the
sarcoplasmic reticulum (SR).
APs travel down invaginations of the sarcolemma called T-tubules, which are close to, but do not
touch, the terminal cisternae of the SR. During the AP plateau, Ca2+ enters the cell and activates
Ca2+ sensitive Ca2+ release channels in the sarcoplasmic reticulum allowing stored Ca2+ to flood
into the cytosol; this is called Ca2+-induced Ca2+ release. The amount of Ca2+ released is
dependent on how much is stored, and on the size of the initial Ca2+ influx during the AP.
EXCITATION-CONTRACTION COUPLING. (IMAGE BY OPENSTAX [CC BY 4.0

Relaxation
In relaxation, about 80% of Ca2+ is rapidly pumped back into the SR (sequestered) by Ca2+
ATPase pumps. The Ca2+ that entered the cell during the AP is transported out of the cell
primarily by the Na+/Ca2+ exchanger in the membrane which pumps one Ca 2+ ion out in
exchange for three Na+ ions in, using the Na+ electrochemical gradient as an energy source. This
is relatively slow and continues during diastole.
Treppe Effect
When more action potentials occur per unit time, more Ca2+ enters the cell during the AP
plateau, more Ca2+ is stored in the SR, more Ca2+ is released from the SR and thus more Ca 2+ is
left inside the cell and greater tension is produced during contraction. Increased heart rate
increases the force of contraction in a stepwise fashion as intracellular [Ca2+] increases
cumulatively over several beats.

Something wrong?
ANS Effects on Heart LAST UPDATED: 2ND

MAY 2019
CARDIAC OUTPUT  Bookmark
Both the heart rate and contractility can be modulated by the autonomic
nervous system.
Sympathetic Stimulation
Sympathetic stimulation increases heart rate and cardiac
contractility. Activation of sympathetic nerves also causes arterial and
venous vasoconstriction. Arterial vasoconstriction increases total peripheral
resistance (TPR) and thus reduces flow, so downstream pressure and
venous return will fall. Venoconstriction does not significantly impede flow
because venous resistance is low compared to arteries, but it reduces their
compliance and hence capacity. Thus vasoconstriction has the same effect
as increasing blood volume, and increases CVP. Sympathetic stimulation
thus increases cardiac output by increasing heart rate, contractility and
CVP, and increases blood pressure by increasing TPR and cardiac output.
Parasympathetic Stimulation
Parasympathetic stimulation causes a marked decrease in heart rate
(negative chronotropic effect) but only a slight decrease in heart muscle
contractility (negative inotropic effect) as parasympathetic ventricular
innervation is sparse.

Something wrong?
Baroreceptor Reflex LAST UPDATED: 21ST

APRIL 2019
PHYSIOLOGY / CARDIOVASCULAR / CARDIAC OUTPUT
 Bookmark
Mean arterial pressure (MAP) = Cardiac output (CO) x Total peripheral resistance (TPR).
Cardiac output is itself dependent on the central venous pressure (CVP), which in turn
is highly dependent on the blood volume. Alterations of any of these variables may
change MAP.
Postural Hypotension
On standing from a prone position, gravity causes blood to pool in veins in the legs.
Central venous pressure (CVP) falls, causing a fall in stroke volume and cardiac output
(due to Starling's law) and thus a fall in blood pressure. Normally this fall in BP is rapidly
corrected by the baroreceptor reflex which causes venoconstriction (partially restoring
CVP), and an increase in heart rate and contractility, so restoring cardiac output and
blood pressure. Impaired autonomic nervous activity in the elderly accounts for the
greater likelihood of postural hypotension. Any symptoms of dizziness, blurred vision
or syncope is due to a transient fall in cerebral perfusion that occurs before cardiac
output and MAP can be corrected.
Baroreceptor Reflex
Arterial baroreceptors are located in the carotid sinus and aortic arch, and detect the
mean arterial pressure (MAP).
A decrease in MAP (such as in postural hypotension, or haemorrhage) reduces arterial
stretch and decreases baroreceptor activity, resulting in decreased firing in afferent
nerves travelling via the glossopharyngeal nerve (carotid sinus) and vagus nerve
(aortic arch) to the medulla where the activity of the autonomic nervous system is
coordinated.
Sympathetic nerve activity consequently increases, causing an increase in heart rate
and cardiac contractility, peripheral vasoconstriction with an increase in TPR, and
venoconstriction with an increase in CVP and thus an increase in cardiac output and
blood pressure. Parasympathetic activity (vagal tone) decreases, contributing to the
rise in heart rate. MAP therefore returns to normal. An increase in MAP has the
opposite effect.
The baroreceptors are most sensitive between 80 and 150 mmHg and their sensitivity
is increased by a large pulse pressure. They also show adaptation; if a new pressure is
maintained for a few hours, activity slowly moves towards normal. The baroreceptor
reflex is important for buffering short-term changes in MAP e.g. with postural
changes, or when muscle blood flow increases rapidly in exercise.
BARORECEPTOR REFLEX. (IMAGE BY OPENSTAX COLLEGE [CC BY 3.0


Vascular System Structure LAST UPDATED: 21ST
APRIL 2019
The vascular system consists of arteries and arterioles that take blood from the heart
to the tissues, thin-walled capillaries and postcapillary venules that allow the diffusion
of gases and metabolites, and venules and veins that return blood to the heart. The
blood pressure, vessel diameter and wall thickness vary throughout the circulation.
Varying amounts of smooth muscle are contained within the vessel walls, allowing
them to constrict and alter their resistance to flow.
Arteries and Arterioles

Large arteries are elastic and partially damp out oscillations in pressure produced by
pumping of the heart; stiff arteries (e.g. age, atherosclerosis) result in larger
oscillations. The major arteries are conductance vessels and divide repeatedly into
smaller muscular arterioles.
Smaller arteries and arterioles contain relatively more muscle and are resistance
vessels, responsible for controlling tissue blood flow through constriction. Each small
arteriole feeds many capillaries via several terminal arterioles.
Microcirculation
The microcirculation consists of the terminal arterioles and the exchange vessels, the
capillaries and small postcapillary venules, which have no smooth muscle or valves
and which provide the exchange surface between blood and tissues.
Venules and Veins

Small venules rejoin into larger venules which ultimately drain into veins. Veins have a
larger diameter than equivalent arteries and provide less resistance. They have thin
distensible walls and contain about 70% of the total blood volume at any one time.
Large veins are capacitance vessels and act as a blood volume reservoir; when
required they can constrict and increase the effective blood volume. Large veins in the
limbs contain one-way valves, and when muscle activity intermittently compresses
these veins, they act as a pump and assist venous return to the heart.
OVERVIEW OF THE VASCULAR SYSTEM. (IMAGE BY KELVINSONG (OWN WORK) [CC BY-SA 3.0

Vascular Tone Regulation LAST UPDATED: 21ST
APRIL 2019
Basis of Vasoconstriction
Most vasoconstrictors bind to G-protein coupled receptors which mediate elevation in
intracellular [Ca2+], leading to vascular smooth muscle contraction. Important
vasoconstrictors include endothelin-1, angiotensin II and noradrenaline.
The increase in intracellular [Ca2+] is brought about by release of Ca2+ from the
sarcoplasmic reticulum and by depolarisation and entry of Ca2+ via L-type voltage-
gated Ca2+ channels. Most types of vascular smooth muscle do not generate action
potentials, but instead depolarisation is graded, allowing graded entry of Ca2+.
Basis of Vasodilation
Vasodilation occurs by decreasing intracellular [Ca2+] through sequestration by the

sarcoplasmic reticulum Ca2+ ATPase and by removal from the cell by a plasma
membrane Ca2+ ATPase and Na+/Ca2+ exchange.
Most endogenous vasodilators cause relaxation by increasing cyclic guanosine
monophosphate (cGMP) (e.g. nitric oxide) or cyclic adenosine monophosphate (cAMP)
(e.g. prostacyclin, beta-adrenergic receptor agonists), which activate protein kinases
causing substrate level phosphorylation. L-type Ca2+ channel blocker drugs are
clinically effective vasodilators.
Endothelial Function
The endothelium plays a vital role in regulation of vascular tone (as well as regulation
of haemostasis, angiogenesis and inflammatory response).
In response to substances in the blood, endothelial damage or changes in blood flow, it
can synthesise several important substances; nitric oxide and prostacyclin are
important vasodilators and endothelin-1 and thromboxane A2 are potent
vasoconstrictors.
Nitric oxide (NO) production by the endothelium is increased by factors that elevate
intracellular Ca2+, including local mediators such as bradykinin, histamine and
serotonin, and some neurotransmitters (e.g. substance P). Increased flow (shear
stress) also stimulates NO production and additionally activates prostacyclin
synthesis. The basal production of NO continuously modulates vascular resistance.
Nitric oxide also inhibits platelet activation and thrombosis.
Endothelin-1 (ET-1) is an extremely potent vasoconstrictor peptide which is released
from the endothelium in the presence of many other vasoconstrictors, including
angiotensin II, antidiuretic hormone (ADH) and noradrenaline, and may be increased in
disease and hypoxia.
The eicosanoids prostacyclin (PGI2) and thromboxane A2 (TXA2) are synthesised by
the cyclooxygenase pathway from arachidonic acid, which is made from membrane
phospholipids by phospholipase A2.
Vasoconstricting Agents Vasodilating Agents

Endothelin-1 Nitric oxide
Thromboxane A2 Prostacyclin
Angiotensin II Beta-agonists
Noradrenaline (alpha 1-receptors) Calcium-channel blockers

Adrenal Function LAST UPDATED: 2ND
MAY 2019
PHYSIOLOGY / ENDOCRINE / ADRENAL FUNCTION
 Bookmark
The adrenal glands are located on the superior pole of each kidney. The glands are
retroperitoneal, covered in perinephric fat and enclosed in renal fascia. The adrenal
gland is divided into two functionally distinct regions; the larger outer region
(comprising about 90% of the gland) called the adrenal cortex and the inner, much
smaller region called the adrenal medulla.
ADRENAL GLAND. (IMAGE BY OPENSTAX COLLEGE [CC BY 3.0

Adrenal Cortex
The adrenal cortex is functionally and anatomically divided into three zones of tissue
which each secrete different steroid hormones:
The outer zona glomerulosa secretes mineralocorticoid (aldosterone) which
regulates salt and water homeostasis.
The zona fasciculata secretes glucocorticoid (cortisol and its analogues) which
regulates carbohydrate metabolism and the response to stress.
The inner zona reticularis secretes the androgen dehydroepiandrosterone
(DHEA) which has effects on the maintenance of secondary sexual
characteristics.
The release of cortisol and DHEA is stimulated by adrenocorticotropic (ACTH)
hormone from the anterior pituitary, which in turn is released in response to
corticotropin-releasing hormone (CRH) from the hypothalamus.
The secretion of aldosterone, in contrast, is mainly regulated by the renin-angiotensin
system, in response to low circulating blood volume, hyponatraemia or hyperkalemia.
Adrenal Medulla
The adrenal medulla produces catecholamines, and is controlled by and functions in
concert with the sympathetic nervous system.

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Aldosterone LAST UPDATED: 2ND

MAY 2021
PHYSIOLOGY / ENDOCRINE / ADRENAL FUNCTION /
RENAL / MECHANISM OF FILTRATION  Bookmark
Aldosterone is secreted by the zona glomerulosa of the adrenal cortex.
Stimulating Factors
Aldosterone release is stimulated by:
Angiotensin II (secondary to a fall in blood volume, blood pressure or plasma
[Na+])
High plasma [K+]
ACTH
N.B. ACTH is less important as a regulator, so pituitary failure does not severely
impair aldosterone secretion.
Function
Aldosterone acts mainly at the renal distal convoluted tubule (DCT) to
cause sodium retention and potassium loss. It increases the synthesis of transport
mechanisms in the distal nephron including the Na+ pump, Na+/H+ antiporter, and
Na+ and K+ channels in principal cells, and H+ ATPase in intercalated cells. Na+ (and
thus water) reabsorption and K+ and H+ secretion are thereby enhanced.
RENIN-ANGIOTENSIN-ALDOSTERONE SYSTEM. (IMAGE BY MIKAEL HÄGGSTRÖM [PUBLIC

Adrenal Insufficiency LAST UPDATED: 21ST
APRIL 2019
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Primary Adrenal Insufficiency

Primary insufficiency of the adrenal cortex, called Addison's disease, arises as a
result of a destructive process in the adrenal gland or genetic defects in steroid
synthesis. All three zones of the adrenal cortex are typically affected.
Causes
Causes of primary adrenal insufficiency include:
Autoimmune adrenalitis (over 70% of cases in the developed world)
Genetic e.g. congenital adrenal hyperplasia/hypoplasia
Iatrogenic e.g. bilateral adrenalectomy, drugs
Infarction/haemorrhage e.g. antiphospholipid syndrome, anticoagulants
Infection e.g. TB, fungal, AIDS
Infiltration e.g. amyloidosis, haemochromatosis
Malignancy e.g. lung, breast or kidney (symptomatic adrenal insufficiency
uncommon)
Clinical Features
Symptoms/Signs:
Onset is usually gradual and symptoms may be non-specific
Fatigue, weakness, anorexia, weight loss, nausea and abdominal pain
Dizziness and postural hypotension (due to mineralocorticoid deficiency)
Increased pigmentation (due to ACTH excess from reduced cortisol negative
feedback leading to melanocyte stimulation)
Reduced libido and loss of axillary/pubic hair in women (due to androgen
deficiency)
Typical Biochemistry:
Hyponatraemia (due to mineralocorticoid deficiency)
Hyperkalaemia (due to mineralocorticoid deficiency)
Hypoglycaemia (due to glucocorticoid deficiency)
Low morning cortisol
Elevated ACTH
Elevated plasma renin
Synacthen test (cortisol post Synacthen < 500 nmol/L)
Positive adrenal autoantibodies
Management
Patients with primary adrenal failure need lifelong glucocorticoid and
mineralocorticoid replacement therapy, typically given as hydrocortisone and
fludrocortisone. Patients should be advised to increase the dose of their
glucocorticoid at times of illness and glucocorticoids need to be administered IV/IM
during surgery or in cases of prolonged vomiting/diarrhoea. Patients should be
provided with a steroid emergency card, encouraged to wear medical alert jewellery,
and be provided with emergency contact details for their endocrine team.
An acute exacerbation of Addison's disease is called an adrenal crisis. It is a life-
threatening emergency characterised by hypotensive hypovolaemic shock and
hypoglycaemia. The mainstay of treatment is rehydration and urgent systemic
glucocorticoid therapy.
Acute adrenal failure may also occur if long-term high-dose steroid treatment is
stopped abruptly (as the prolonged steroid treatment has suppressed the HPA axis
and natural ACTH release). Patients taking long-term steroids should thus be
instructed not to stop their steroids abruptly, at least until an adequate adrenal
reserve has been demonstrated.
Secondary Adrenal Insufficiency

Secondary adrenal insufficiency can arise as the result of any cause of
hypopituitarism. Patients display similar features as above with the exception that
pigmentation is absent as ACTH is not raised, and mineralocorticoid deficiency is
not a feature, because aldosterone secretion is not significantly influenced by
ACTH.
Hyperaldosteronism LAST UPDATED: 24TH
APRIL 2020
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Hyperaldosteronism can be defined as excessive levels of aldosterone which may

be independent of the renin-angiotensin axis (primary hyperaldosteronism) or due
to high renin levels (secondary hyperaldosteronism).
Pathophysiology
Excessive aldosterone levels act at the distal renal tubule, promoting sodium
retention, which results in water retention and volume expansion with
hypertension. There is also excretion of potassium, resulting in hypokalaemia.
Causes of Primary Hyperaldosteronism

Adrenal adenoma (Conn's syndrome, accounts for >80% of cases of
hyperaldosteronism)
Adrenal hyperplasia
Familial hyperaldosteronism
Adrenal carcinoma
Features of Primary Hyperaldosteronism

Hypertension
Hypokalaemia
Metabolic alkalosis
Hypernatraemia (may be high end of normal or only mildly raised)
Aldosterone levels high
Renin levels low
Management of Primary Hyperaldosteronism

Medical management is used in the period prior to surgery - which is the definitive
treatment. Medical management involves the use of aldosterone antagonists e.g.
spironolactone. Surgical treatment involves adrenalectomy.
Catecholamines LAST UPDATED: 21ST
APRIL 2019
 Bookmark
The chromaffin cells of the medulla secrete noradrenaline (20%) and adrenaline
(80%), stimulated by sympathetic preganglionic neurones located in the spinal
cord.
Derivation and Degradation

These catecholamine hormones are derived from tyrosine by a series of steps
catalysed by specific enzymes. The production of the rate-limited enzyme,
phenylethanolamine-N-methyltransferase, is stimulated by cortisol, providing a
direct link between the functioning of the adrenal medulla and cortex.
Catecholamines are broken down extracellularly and in the liver by catechol-O-
methyltransferase (COMT) and intracellularly by monoamine oxidase (MAO).
Effects of Adrenaline
These catecholamines act on alpha- and beta- G-protein coupled receptors ,
having the same effect in tissues as the stimulation of sympathetic nerves.
Noradrenaline has equal potency at all adrenoceptors, but adrenaline at normal
plasma concentrations will only activate beta-receptors (higher levels do stimulate
alpha-receptors).
Actions of adrenaline:
Cardiovascular system
Increased rate and force of cardiac contraction
Vasoconstriction of vessels in skin, mucous membranes and
splanchnic bed
Vasodilation of skeletal muscle vessels
Increased cardiac output and blood pressure
Respiratory system
Bronchodilation
Increased ventilation rate
Gastrointestinal system
Smooth muscle relaxation
Contraction of sphincters
Metabolism
Decreased insulin release
Increased glucagon release
Increased thermogenesis
Increased glycolysis
Increased lipolysis
Eye
Pupillary dilation

Phaeochromocytoma LAST UPDATED: 21ST
APRIL 2019
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Phaeochromocytomas are catecholamine-secreting tumours which occur in about

0.1% of patients with hypertension. In about 90% of cases they arise from the
adrenal medulla. The remaining 10%, which arise from extra-adrenal chromaffin
tissue, are termed paragangliomas.
Clinical Features
Common presenting symptoms include one or more of headache, sweating, pallor
and palpitations. Less commonly, patients describe anxiety, panic attacks and
pyrexia. Hypertension, whether sustained or episodic, is present in at least 90% of
patients. Left untreated phaeochromocytoma can occasionally lead to hypertensive
crisis, encephalopathy, hyperglycaemia, pulmonary oedema, cardiac arrhythmias,
or even death. Patients with undiagnosed phaeochromocytoma having routine
surgery can develop severe hypertension or sudden death.
Diagnosis
Diagnosis relies on the biochemical confirmation of elevated catecholamines or
their metabolites (metanephrines), followed by radiological localisation of the
tumour.
Management
The definitive treatment is surgical excision. In advance of the surgery, it is
mandatory that all patients are protected from the effects of catecholamine excess
by alpha-blockade with or without beta-blockade. Alpha-blockade, conventionally
administered as oral phenoxybenzamine, should be commenced before beta-
blockade in order to avoid unopposed alpha-adrenergic stimulation and the risk of
hypertensive crisis. Beta-blockers can be introduced subsequently to control reflex
tachycardia.
Cortisol LAST UPDATED: 21ST
APRIL 2019
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Cortisol and its analogues have powerful effects on glucose metabolism and all
collectively classified as glucocorticoids (although they do have some
mineralocorticoid action). Cortisol is secreted from the zona fasciculata of the
adrenal cortex.
Regulation of Cortisol Secretion in Health

Cortisol release is stimulated by adrenocorticotropic hormone (ACTH) from the
anterior pituitary, which in turn is released in response to corticotropin-releasing
hormone (CRH) from the hypothalamus. Cortisol has a negative feedback effect on
the hypothalamus and the anterior pituitary gland, inhibiting release of CRH and
ACTH respectively.
The effects of cortisol are mediated by intracellular receptors that translocate to
the cell nucleus after binding the hormone.
Cortisol is released during the course of normal physiological activity in a pulsatile
pattern. Cortisol release displays a circadian rhythm, with the highest levels in the
early morning.
Regulation of Cortisol Secretion in Stress

The primary stimulus for the increased release of glucocorticoids is stress, which is
the result of exposure to adverse situations.
Stress response:
The stress response is driven by the amygdala, part of the forebrain that stimulates:
activity in the hypothalamic CRH neurons
activity in the sympathetic nervous system
activity in the parasympathetic nerves that cause acid secretion in the
stomach
the feeling of fear
The actions of the two parts of the adrenal gland are complementary in response to
stress. Catecholamines are released from the adrenal medulla to produce a rapid
increase in cardiac output and the mobilisation of metabolic fuels. Corticosteroids
produce a slower, more sustained response.
REGULATION OF CORTISOL SECRETION. (IMAGE MODIFIED BY FRCEM SUCCESS. ORIGINAL

BY CAMPOS-RODRÍGUEZ R, GODÍNEZ-VICTORIA M, ABARCA-ROJANO E, PACHECO-YÉPEZ J,
REYNA-GARFIAS H, BARBOSA-CABRERA RE, DRAGO-SERRANO ME [CC BY 3.0
Effects of Cortisol
Cortisol acts to:
raise plasma glucose by stimulating glycolysis and gluconeogenesis in the
liver and inhibiting peripheral glucose uptake into storage tissues
Cushing’s Syndrome LAST UPDATED: 21ST
APRIL 2019
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Cushing's syndrome is the name given to the clinical symptoms and signs
induced by chronic glucocorticoid excess.
Cushing's disease refers to the specific condition of excess corticosteroids as a
result of an ACTH-secreting pituitary adenoma, leading to bilateral adrenal
hyperplasia and excess cortisol secretion. Cushing's disease is also associated
with hyperpigmentation due to the melanocyte-stimulating action of ACTH.
Causes
This may occur due to:
1. Excess secretion of ACTH

ACTH secreting pituitary adenoma (Cushing's disease)
Ectopic ACTH e.g. lung cancer
2. Excess secretion of cortisol

Adrenal adenoma or carcinoma
3. Exogenous steroids
Clinical Features
Plethoric moon face
Central obesity
Impaired glucose tolerance or diabetes
Hypertension
Menstrual irregularity, erectile dysfunction
Osteoporosis and kyphosis
Purple striae and tendency to bruise easily
Proximal myopathy
Hirsutism and frontal alopecia
Ankle oedema
Interscapular fat pad
Acne
Musculoskeletal aches and pains
Depression
Poor wound healing
Polycythaemia
CLINICAL FEATURES OF CUSHING'S SYNDROME. (IMAGE BY MIKAEL HÄGGSTRÖM (OWN

WORK) [CC0], VIA WIKIMEDIA COMMONS)
Management
If an adrenal tumour is found, adrenalectomy is the treatment of choice. In
ectopic ACTH, appropriate treatment of the underlying malignancy and medical
control of cortisol levels are needed. In Cushing's disease, trans-sphenoidal
removal of the pituitary adenoma is indicated. Medical treatment (e.g.
metyrapone which blocks cortisol production) can be used pre-operatively if
symptoms are severe, or there is uncontrolled hypokalaemia, diabetes and
hypertension.

Endocrine Pancreas LAST UPDATED: 19TH
APRIL 2020
PHYSIOLOGY / ENDOCRINE / PANCREATIC FUNCTION
 Bookmark
The endocrine pancreas refers to those cells within the pancreas that synthesise
and secrete hormones.
The endocrine portion of the pancreas takes the form of many small clusters of
cells called islets of Langerhans or, more simply, pancreatic islets. Humans have
roughly one million islets.
Pancreatic islets house five main cell types, each of which produces a different
endocrine product:
Alpha cells producing glucagon
Beta cells producing insulin (most abundant cells)
Delta cells producing somatostatin
Epsilon cells producing ghrelin
PP cells (gamma cells or F cells) producing pancreatic polypeptide
Islets are richly vascularised, allowing their secreted hormones ready access to
the circulation. Although islets comprise only 1-2% of the mass of the pancreas,
they receive about 10 to 15% of the pancreatic blood flow. Additionally, they are
innervated by parasympathetic and sympathetic neurons, and nervous signals
clearly modulate secretion of insulin and glucagon.
OVERVIEW OF PANCREAS LOCALISATION AND ANATOMY. (IMAGE ADAPTED AND MODIFIED
FROM AN OPENSTAX COLLEGE RESOURCE, AVAILABLE FROM
HTTPS://WWW.RESEARCHGATE.NET/FIGURE/OVERVIEW-OF-PANCREAS-LOCALIZATION-
AND-ANATOMY-THE-PANCREAS-IS-COMPOSED-OF-AN-ENDOAND_FIG3_328475917)

Glucagon Physiology LAST UPDATED: 9TH
JULY 2020
 Bookmark
Glucagon is produced by α cells, located peripherally within the islets of

Langerhans, in the endocrine tissues of the pancreas.
Glucagon release patterns tend to be the mirror image of those of insulin. Low
blood glucose initiates glucagon release directly and also drives nervous and
hormonal release of catecholamines which activate beta-adrenoceptors on α
cells to augment glucagon release.
Glucagon acts on guanosine triphosphate-binding protein (G-protein) coupled
receptors that stimulate the production of intracellular cyclic adenosine
monophosphate (cAMP). In liver cells, this results in the inhibition of glycogen
synthesis and the activation of glycogen breakdown systems. Similar effects are
obtained in muscle cells to increase circulating levels of glucose.
There are interactions between glucagon and insulin within the islets: insulin
inhibits release of glucagon, but glucagon stimulates the release of insulin, an
effect that ensures a basal level of insulin release regardless of glucose levels.
Comparison between Insulin and Glucagon
Hormone Insulin Glucagon

Cell Type Beta-cells Alpha-cells
Factors ↑ Blood glucose ↓ Blood glucose
that ↑ Amino acids ↑ Amino acids
Increase ↑ Fatty acids Cholecystokinin
Secretion Glucagon Catecholamines
Secretin Acetylcholine
Acetylcholine
Factors ↓ Blood glucose ↑ Blood glucose
that Somatostatin Insulin
Decrease Catecholamines Somatostatin
Secretion Fatty acids,
ketoacids
Mechanism Acts on tyrosine kinase receptor Acts on G-protein
of Action to activate intracellular pathway coupled receptor to
that results in translocation of stimulate production
GLUT-4 transporter to plasma of cAMP
membrane
Major ↑ Glucose uptake into ↓ Glycogenesis

Actions cells ↑ Glycogenolysis
↑ Glycogenesis ↑
↓ Glycogenolysis Gluconeogenesis
↓ Gluconeogenesis ↓ Fatty acid
↑ Protein synthesis synthesis
↓ Protein degradation ↑ Lipolysis
↑ Fat deposition ↑ Ketoacid
↓ Lipolysis production
↓ Ketoacid production
↑ K+ uptake into cells
Overall ↓ [Glucose] ↑ [Glucose]

Effect on ↓ [Amino acid] ↑ [Fatty acid]
Blood ↓ [Fatty acid] ↑ [Ketoacid]
Levels ↓ [Ketoacid]
↓ [K+]

Insulin Physiology LAST UPDATED: 2ND
MAY 2019
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Insulin is produced by β cells, located centrally within the islets of Langerhans, in

the endocrine tissues of the pancreas.
Insulin is a polypeptide hormone consisting of two short chains (A and B) linked by
disulphide bonds. Proinsulin is synthesised as a single-chain peptide. Within
storage granules, a connecting peptide (C peptide) is removed by proteases to yield
insulin. The C peptide is packaged and secreted along with insulin, and its
concentration is used to monitor β cell activity in diabetic patients who receive
exogenous insulin.
Insulin release is stimulated initially during eating by the parasympathetic nervous
system and gut hormones such as secretin, but most output is driven by the rise in
plasma glucose concentration that occurs after a meal. Circulating fatty acids,
ketone bodies and amino acids augment the effect of glucose.
The major action of insulin is to stimulate glucose uptake, with the subsequent
manufacture of glycogen and triglycerides by adipose, muscle and liver cells.
The effects of insulin are mediated by the receptor tyrosine kinase. The enzyme
activates an intracellular pathway that results in the translocation of the glucose
transporter GLUT-4 and to a lesser extent GLUT-1 to the plasma membrane of the
affected cell, to facilitate the entry of glucose. Insulin thus decreases plasma
glucose.
Insulin release is reduced as the blood glucose concentration falls, and is further
inhibited by catecholamines acting at β cell alpha-2-adrenoceptors.
INSULIN SIGNAL TRANSDUCTION PATHWAY. (IMAGE BY JAMES FOREMAN, USED WITH
PERMISSION. [CC0], FROM WIKIMEDIA COMMONS)
Comparison between Insulin and Glucagon

Cell Type Beta-cells Alpha-cells
Factors ↑ Blood glucose ↓ Blood glucose
that ↑ Amino acids ↑ Amino acids
Increase ↑ Fatty acids Cholecystokinin
Secretion Glucagon Catecholamines
Secretin Acetylcholine
Acetylcholine
Factors ↓ Blood glucose ↑ Blood glucose
that Somatostatin Insulin
Decrease Catecholamines Somatostatin
Secretion Fatty acids,
ketoacids
Mechanism Acts on tyrosine kinase receptor Acts on G-protein
of Action to activate intracellular pathway coupled receptor to
that results in translocation of stimulate production
GLUT-4 transporter to plasma of cAMP
membrane
Major ↑ Glucose uptake into cells ↓ Glycogenesis

Actions ↑ Glycogenesis ↑ Glycogenolysis
Glycogenolysis ↑
↓ Gluconeogenesis Gluconeogenesis
↑ Protein synthesis ↓ Fatty acid
↓ Protein degradation synthesis
↑ Fat deposition ↑ Lipolysis
↓ Lipolysis ↑ Ketoacid
↓ Ketoacid production production
↑ K+ uptake into cells
Overall ↓ [Glucose] ↑ [Glucose]

Effect on ↓ [Amino acid] ↑ [Fatty acid]
Blood ↓ [Fatty acid] ↑ [Ketoacid]
Levels ↓ [Ketoacid]
↓ [K+]

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Diabetes Mellitus LAST UPDATED: 21ST

APRIL 2019
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Diabetes mellitus is a metabolic disorder characterised by persistent

hyperglycaemia which is a result of defects in insulin secretion, insulin action or
both.
Classification
Diabetes mellitus is broadly classified as type 1 or type 2 (although rarer causes of
diabetes exist):
Type 1 (5 - 10%)
Autoimmune destruction of beta-cells of the pancreas results in
absolute insulin deficiency with patients requiring insulin to survive
In absence of insulin action in muscle and adipose tissue, glucose is
not transported into cells by the GLUT4 transporter
Type 2 (90 - 95%)
Caused by both insulin resistance and a defect in insulin secretion as a
result of beta-cell dysfunction
Insulin resistance occurs in skeletal muscle, adipose tissue and liver,
resulting in reduced glucose uptake in skeletal muscle, impaired
inhibition of hepatic glucose output and increased fatty acid
production in adipose tissue, which stimulates gluconeogenesis and
triglyceride synthesis
Risk factors include obesity, lack of physical activity, increasing age,
dyslipidaemia, hypertension, certain ethnic groups, genetic
predisposition
Clinical Features
T1DM:
Osmotic symptoms
Thirst, polydipsia, polyuria
Dehydration, hypovolaemia, drowsiness
Blurred vision
Cutaneous Candida infections
Catabolic symptoms
Muscle wasting, fatigue and weight loss
Diabetic ketoacidosis (approx 25% of children with T1DM present in DKA)
Aetiology
Impairment of glucose utilisation in the peripheral tissues leads
to increased gluconeogenesis and glycogenolysis in the liver
with consequent worsened hyperglycaemia.
Simultaneous counter-regulatory hormone hypersecretion
(including cortisol, glucagon and catecholamines) in tandem with
insulin deficiency causes release of free fatty acids into the
circulation as a result of lipolysis in adipose tissue.
Free fatty acids undergo oxidation in the liver to produce ketone
bodies and subsequent ketonaemia. As ketone bodies are weakly
acidic, this causes increased plasma hydrogen ion
concentrations and metabolic acidosis.
Characterised by the biochemical triad:
Hyperglycaemia (> 11 mmol/L)
Ketonaemia (> 3 mmol/L)
Acidosis (pH < 7.3 +/- HCO3 < 15 mmol/L)
Clinical features
Symptoms
Polyuria, polydipsia, thirst, lethargy, weight loss, nausea,
vomiting, anorexia, abdominal pain, dehydration,
headache, altered mental state
Signs
Dry mucous membranes, ketotic breath, tachycardia,
hypotension, Kussmaul breathing, focal signs of
precipitant e.g. infection
Management
Fluid replacement
Insulin (+ glucose)
Monitoring of [K+] (+/- replacement)
Treat underlying cause
T2DM:
One-third of cases are detected incidentally
Diagnosis is often delayed for many years and the patient can therefore
present with complications from prolonged hyperglycaemia
Only about half of patients present with the classic symptoms of thirst,
polydipsia, polyuria and tiredness secondary to hyperglycaemia, although
these symptoms are less marked than in T1DM
Hyperglycaemic hyperosmolar state (up to 25% of patients with T2DM
present as HHS)
Aetiology
Prolonged hyperglycaemia from insulin resistance or insulin
deficiency results in an osmotic diuresis with renal sodium and
potassium loss.
This results in extracellular volume depletion and dehydration,
with a raised serum osmolality.
Ketosis/ketonaemia does not typically occur in HHS, because
some insulin is still present and hyperosmolality can inhibit
lipolysis.
Characterised by triad:
Hypovolaemia
Marked hyperglycaemia (> 30 mmol/L) without significant
hyperketonaemia or acidosis
Osmolality > 320 mosmol/kg
Clinical features
Polydipsia, polyuria, impaired cognitive function, tachycardia,
hypotension, seizures
Management
Treat underlying cause
Fluid replacement (+/- insulin)
Correct electrolyte imbalance
Treat with prophylactic anticoagulation
Diagnosis
Glucose concentration criteria:
In symptomatic individuals (e.g. thirst, polyuria, polydipsia and
unexplained weight loss):
A random venous plasma glucose concentration ≥ 11.1 mmol/L OR
A fasting plasma glucose concentration ≥ 7.0 mmol/L OR
Two-hour plasma glucose concentration ≥ 11.1 mmol/L after 75g
anhydrous glucose in an oral glucose tolerance test (OGTT)
In asymptomatic individual:
At least one of the above criteria fulfilled on two separate
occasions
HbA1c criteria:
HbA1c ≥ 48 mmol/mol (6.5%) confirmed with second sample unless
individual is symptomatic with plasma glucose ≥ 11.1 mmol/L when
confirmation is not needed
N.B. Not to use in children and young people, type 1 DM, symptom onset
within 2 months, pregnancy, drugs causing hyperglycaemia (e.g.
steroids) or blood conditions affecting Hb (e.g. haemolytic anaemia)
Complications
Macrovascular
Ischaemic heart disease
Angina, ACS
Cerebrovascular ischaemia
TIA, stroke
Peripheral vascular disease
Intermittent claudication, acute ischaemic limb, foot ulcer
Microvascular
Autonomic neuropathy
Resting tachycardia, postural hypotension, cardiac ischaemia,
sudden cardiac death
Gastroparesis, constipation/diarrhoea, oesophageal dysmotility
Erectile dysfunction, neuropathic bladder
Mononeuropathies
Often cranial nerves III and VI, median, ulnar and radial nerves
Diabetic peripheral neuropathy
Glove and stocking distribution, foot ulceration
Diabetic nephropathy
CKD
Diabetic retinopathy
Blindness
Hypoglycaemia
Hypoglycaemia occurs when plasma glucose falls below 4 mmol/L. It commonly
occurs as a result of insulin therapy; it can also occur with certain oral
hypoglycaemic agents.
In individuals without diabetes, the normal response to hypoglycaemia comprises
reduced insulin secretion from the pancreas and increased glucagon release. A
number of counter-regulatory hormones, including noradrenaline, cortisol and
growth hormone, are also released. In patients with diabetes, these responses are
reduced, especially with recurrent hypoglycaemia and with increased duration of
disease - this can result in hypoglycaemic unawareness.
Clinical features of hypoglycaemia:
Autonomic symptoms
Sweating, feeling hot, anxiety/agitation, palpitations, shaking,
paraesthesia, dizziness
Neuroglycopaenic symptoms
Weakness, blurred vision, difficulty speaking, poor concentration, poor
coordination, drowsiness, confusion, seizures, coma
Other symptoms
Nausea, fatigue, hunger
Any suspected hypoglycaemia should be managed as an emergency, and treated
immediately to return blood glucose to the normal range.
Something wrong?
Pituitary Gland LAST UPDATED: 21ST APRIL

2019
PHYSIOLOGY / ENDOCRINE / PITUITARY FUNCTION
 Bookmark
Anatomical Location
The pituitary gland lies immediately beneath the hypothalamus in a bony hollow of the sphenoid bone
(the sella turcica), and it is covered by the fibrous diaphragma sellae of the dura mater. The optic chiasm
lies directly superior to the anterior pituitary. The posterior pituitary is connected to the median
eminence of the hypothalamus by the pituitary stalk (also known as the infundibulum). The cavernous
sinuses (including cranial nerves III - VI) lie lateral to the pituitary gland. The pituitary gland is primarily
divided into two sub glands, the anterior pituitary (adenohypophysis) and the posterior pituitary
(neurohypophysis).
ANATOMICAL LOCATION OF THE PITUITARY GLAND. (IMAGE BY OPENSTAX COLLEGE [CC BY 3.0
Anterior Pituitary Gland

Anterior pituitary hormones are released under the control of hypothalamic releasing or inhibiting
hormones originating from small neurons with their cell bodies in the hypothalamus and released into
the blood at the median eminence. These hypothalamic hormones are transported directly to the
anterior pituitary via hypophyseal portal vessels and act to stimulate or inhibit release of anterior
pituitary hormones by the activation of receptors on specific groups of pituitary cells.
The anterior pituitary hormones (and the hormones released by their target organs) inhibit further
release of hypothalamic and anterior pituitary hormones by negative feedback mechanisms.
The following hormones are secreted from the anterior pituitary gland:
Follicle-stimulating hormone (FSH)
Prolactin
Thyroid-stimulating hormone (TSH)
Adrenocorticotropic hormone (ACTH)
Luteinising hormone (LH)
Growth hormone (GH)
This can be remembered using the mnemonic: Fresh Pituitary Tastes Almost Like Guinness.
FUNCTION OF THE ANTERIOR PITUITARY GLAND. (IMAGE BY OPENSTAX COLLEGE [CC BY 3.0
Posterior Pituitary Gland

The posterior pituitary gland secretes two peptide hormones:
Oxytocin
Antidiuretic hormone (ADH)
The posterior pituitary is really a direct extension of the hypothalamus. Oxytocin and ADH are
manufactured in the cell bodies of large neurons in the hypothalamus and are transported down the
axons of these cells to their terminals on capillaries originating from the inferior hypophyseal artery
within the posterior pituitary gland. When these neurons are activated, they release oxytocin or ADH
into the general circulation from whence they can reach the relevant target tissues to produce the
required effect.
ADH release is controlled by negative feedback mechanisms based on plasma osmolality and blood
volume, oxytocin however is involved in positive feedback mechanisms.
FUNCTION OF THE POSTERIOR PITUITARY GLAND. (IMAGE BY OPENSTAX COLLEGE [CC BY 3.0

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Hypothalamic-Pituitary Axis LAST UPDATED: 13TH

MARCH 2019
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Pituitary Hormone Hypothalamic Target Effect

Releasing/Inhibiting Organ
Factors
Growth hormone Stimulated by Liver, bone, Direct effect (regulates
(GH) growth hormone- muscles growth and metabolic
releasing hormone rate)
(GHRH)
Inhibited by
somatostatin (also
called growth
hormone–inhibiting
hormone (GHIH))
Adrenocorticotropic Stimulated by Adrenal Stimulates release of
hormone (ACTH) corticotropin- gland cortisol
releasing hormone
(CRH)
Follicle-stimulating Stimulated by Gonads Stimulates release of
hormone (FSH) and gonadotropin- testosterone/oestrogen
luteinising hormone releasing hormone and production of
(LH) (GnRH) eggs/sperm
Thyroid-stimulating Stimulated by Thyroid Stimulates release of
hormone (TSH) thyrotropin gland thyroid hormones
releasing hormone (T4/T3)
(TRH)
Prolactin Weakly stimulated Mammary Direct effect
by TRH, oxytocin glands (stimulates lactation)
and ADH
Inhibited by
dopamine (also
called prolactin-
inhibiting
hormone (PIH))
Antidiuretic From posterior Kidneys Direct effect (regulates
hormone (ADH) pituitary water balance)
Pituitary Hormone Hypothalamic Target Effect
Releasing/Inhibiting Organ
Factors
Oxytocin From posterior Female Direct effect
pituitary reproductive (stimulates milk
system ejection in suckling and
uterine contractions in
childbirth)
HYPOTHALAMUS-PITUITARY AXIS. (IMAGE BY OPENSTAX COLLEGE [CC BY 3.0


Antidiuretic Hormone LAST UPDATED: 21ST
APRIL 2019
PHYSIOLOGY / ENDOCRINE / PITUITARY FUNCTION /
RENAL / MECHANISM OF FILTRATION  Bookmark
Extracellular fluid osmolality must be closely regulated as alterations cause the

swelling or shrinking of cells and can lead to cell death. Osmoreceptors in the
anterior hypothalamus control water intake by altering thirst and control renal
water excretion by altering antidiuretic hormone (ADH) release. A rise in
osmolality triggers ADH release and stimulates thirst; a fall has the opposite
effect.
Synthesis
Antidiuretic hormone is synthesised in the hypothalamus and transported to the
posterior pituitary within nerve fibres where it is stored in secretory granules.
Action
ADH binds V2 receptors on renal principal cells in the late distal tubule and
collecting ducts, raising cAMP levels and causing intracellular vesicles to fuse
with the apical membrane. In their membrane these vesicles have water channels
called aquaporins, which increase the water permeability allowing greater water
reabsorption and concentration of urine.
ADH also binds to V1 receptor receptors on vascular smooth muscle, causing
vasoconstriction and enhancing the effect of aldosterone on sodium reabsorption
in the distal tubule.
Metabolism
ADH is rapidly removed from plasma, falling by about 50% in about 10 minutes,
mainly due to metabolism in the liver and kidneys.
Stimulating Factors
ADH release is stimulated primarily by raised plasma osmolality detected by
osmoreceptors in the anterior hypothalamus. Other factors that increase ADH
release include: extracellular fluid volume depletion, angiotensin II, nausea, pain,
stress, exercise, emotion, hypoglycaemia.
Inhibiting Factors
ADH release is inhibited by low plasma osmolality, alcohol, caffeine,
glucocorticoids and atrial natriuretic peptide (ANP).
Hormone Stimulation Inhibition Action Clinical Excess Clinical
Deficiency
ACTH CRH Cortisol Acts on adrenal cortex Cushing's disease Secondary
to stimulate release of adrenal
glucocorticoids which insufficiency
regulate metabolism
and stress response
TSH TRH Thyroxine Acts on thyroid gland to Secondary Secondary
stimulate release of hyperthyroidism hypothyroidism
thyroid hormones
which regulate
metabolism
FSH/LH GnRH Prolactin, Acts on gonads to Infertility Gonadal
oestrogen/testosterone stimulate production of insufficiency
oestrogen/testosterone
and production of
eggs/sperm
GH GHRH Somatostatin Acts on liver, bone and Acromegaly in Adult GH
muscles to stimulate adults or gigantism deficiency
production of IGFs in children syndrome in
which stimulate body adults
growth and a higher or dwarfism in
metabolic rate children
Prolactin PRH, TRH Dopamine Acts on mammary Hyperprolactinemia Failure of
glands to promote milk postpartum
production lactation
ADH Raised Low plasma osmolality, Acts on kidneys to SIADH Central
plasma alcohol, caffeine, promote water diabetes
osmolality glucocorticoids and retention and on insipidus
atrial natriuretic vascular system to
peptide (ANP) cause vasoconstriction
Oxytocin Stretch Stress Acts on female / /
receptors in reproductive system to
nipple and trigger uterine
cervix contractions during
childbirth and milk
ejection during suckling
Anterior Pituitary Hormones

ACTH
Adrenocorticotropic hormone (ACTH) acts on the adrenal cortex to stimulate glucocorticoid and androgen release.
ACTH secretion is stimulated by corticotropin-releasing hormone (CRH) from the hypothalamus.
ACTH secretion is inhibited by cortisol.
ACTH deficiency results in secondary adrenal insufficiency.
Excess levels of ACTH due to a functioning pituitary adenoma results in Cushing's disease.
TSH
Thyroid-stimulating hormone (TSH) acts on the thyroid gland to stimulate thyroid hormone (T3 and T4) release.
TSH secretion is stimulated by thyrotropin-releasing hormone (TRH) from the hypothalamus.
TSH secretion is inhibited by raised serum levels of T3 or T4, somatostatin, dopamine, glucocorticoids, acute non-thyroidal illness
and increased human chorionic gonadotropin (e.g. in early pregnancy).
TSH deficiency results in secondary hypothyroidism.
Excess TSH (extremely rare) results in secondary hyperthyroidism.
FSH/LH
The gonadotropins, luteinising hormone (LH) and follicle stimulating hormone (FSH) act via G-protein coupled receptors on the
gonads. In the male, LH acts to stimulate production of testosterone, which acts in concert with FSH to support
spermatogenesis. In the female, LH and FSH are essential for normal menstruation and reproduction.
LH/FSH secretion is stimulated by gonadotropin-releasing hormone (GnRH) from the hypothalamus. GnRH is released in a
pulsatile fashion, which is essential for normal reproductive activity.
LH/FSH secretion is inhibited by prolactin (via GnRH) and sex steroids.
LH/FSH deficiency results in gonadal insufficiency (decreased sex steroids).
Excess levels of FSH/LH (extremely rare) results in infertility.
Growth Hormone
Growth hormone (GH) acts on the liver to stimulate insulin-like growth factor (IGF) production to promote skeletal and muscular
growth and protein synthesis.
GH secretion is stimulated by growth hormone-releasing hormone (GHRH) from the hypothalamus.
GH secretion is inhibited by growth hormone-inhibiting hormone (somatostatin) and IGF-1.
Excess levels of GH results in acromegaly in adults and gigantism in children (if excess GH occurs prior to epiphyseal fusion).
GH deficiency results in dwarfism in children or adult GH deficiency syndrome in adults.
Prolactin
Prolactin acts on the mammary glands and reproductive organs to promote growth of these organs and initiate lactation.
Prolactin secretion is stimulated by prolactin-releasing factor (PRF) and thyrotropin-releasing hormone (TRH) from the
hypothalamus.
Prolactin secretion is inhibited by dopamine secreted by the hypothalamus.
Prolactin levels rise physiologically in pregnancy, puerperium, and breast stimulation.
Excess levels of prolactin may be caused by a prolactinoma (prolactin-secreting pituitary adenoma); compression of the pituitary
stalk by a pituitary or hypothalamic tumour preventing normal dopaminergic inhibition of prolactin release; PCOS; severe
hypothyroidism (due to increased synthesis of TRH); drugs e.g. dopamine antagonists, antipsychotics
Hyperprolactinaemia causes symptoms such as oligomenorrhoea/amenorrhoea, galactorrhoea, loss of libido, erectile
dysfunction and infertility (via inhibition of the release of GnRH from the hypothalamus).
Prolactin deficiency results in failure of postpartum lactation.
Posterior Pituitary Hormones

ADH
Antidiuretic hormone (ADH) acts on the kidneys to increase water permeability in the distal nephron allowing greater water
reabsorption and concentration of urine. ADH also acts on vascular smooth muscle, causing vasoconstriction.
ADH release is stimulated mainly by raised plasma osmolality detected by osmoreceptors in the anterior hypothalamus. Other
stimuli to ADH release include volume depletion, angiotensin II, hypoxia, hypercapnia, adrenaline, cortisol, sex steroids, pain,
trauma, temperature and psychogenic stimuli.
ADH release is inhibited by low plasma osmolality, alcohol, caffeine, glucocorticoids and atrial natriuretic peptide (ANP).
ADH deficiency results in central diabetes insipidus.
Excess levels of ADH results in syndrome of inappropriate ADH secretion (SIADH).
Oxytocin
Oxytocin acts on the mammary glands to stimulate milk ejection, and the uterus to stimulate uterine contraction in childbirth.
Oxytocin release is stimulated by stretch receptors in the nipple and the cervix and by oestrogen.
Oxytocin release is inhibited by stress.
Something wrong?
Syndrome of Inappropriate LAST UPDATED: 21ST

APRIL 2019
Antidiuretic Hormone  Bookmark
Secretion (SIADH)
Diagnosis
Syndrome of inappropriate ADH (SIADH) is characterised by:
euvolaemic hypo-osmolar hyponatraemia in the context of:
a low serum osmolality (< 275 mosmol/kg)
urine osmolality > 100 mosmol/kg and
urine sodium > 30 mmol/L.
SIADH can only be diagnosed after the exclusion of hypothyroidism, total salt
depletion and ACTH deficiency. ACTH deficiency appears identical to SIADH
because it causes reduced excretion of free water, because cortisol deficiency
leads to increased ADH activity. This is different from hyponatraemia caused by
mineralocorticoid deficiency in Addison's disease.
Causes
The potential causes of SIADH are vast including:
Malignancy:
lung, lymphoma, gastrointestinal/pancreatic malignancy,
genitourinary malignancy
Neurological:
malignancy, infection, trauma, haemorrhage
Pulmonary:
pneumonia, TB, abscess, malignancy
Drugs:
SSRIs, tricyclic antidepressants, anticonvulsants
Miscellaneous:
idiopathic, HIV, MS, Guillain-Barre, Acute Intermittent Porphyria
Idiopathic SIADH is a diagnosis of exclusion.
Management
Reversal or treatment of the cause of SIADH and fluid restriction are the key
aspects of management. Strict fluid restriction (1 - 1.5 L/day) is poorly tolerated
and difficult to achieve. Drug treatment of SIADH includes demeclocycline and
ADH antagonists. Demeclocycline reduces renal response to ADH but its use is
limited by side effects and unpredictable pharmacokinetics. ADH antagonists
directly block ADH action and are of use in specific clinical situations.

Diabetes Insipidus LAST UPDATED: 21ST
APRIL 2019
 Bookmark
Diabetes insipidus (DI) may result from a deficiency of ADH secretion (cranial DI)
or from an inappropriate renal response to ADH (nephrogenic DI).
As a result, fluid reabsorption at the kidneys is impaired, resulting in large
amounts of hypotonic, dilute urine being passed with a profound unquenchable
polydipsia.
Biochemical Features
The biochemical hallmarks of DI are:
High plasma osmolality (> 295 mOsm/kg)
Low urine osmolality (< 300 mOsm/kg)
Hypernatraemia (> 145 mmol/L)
High urine volume
Causes
Cranial (ADH deficiency)
Inflammatory hypophysitis
Histiocytosis X
Post-pituitary surgery
Nephrogenic (ADH resistance)
Metabolic or electrolyte disturbance
Renal disease
Drugs e.g. lithium
An ADH stimulation test can distinguish between cranial and nephrogenic DI, as
nephrogenic DI shows an inability to concentrate urine even after administration
of synthetic ADH.
Management
Patients with confirmed cranial DI should be investigated for pituitary disease,
and managed as appropriate. Cranial DI typically responds well to synthetic ADH
administration and results in good clinical improvement.
In nephrogenic DI, the underlying cause should be considered and reversed
where possible. If symptoms persist, patients should drink according to thirst and
keep up with water loss. Specific measures to treat nephrogenic DI include the
use of low salt, low protein diet, diuretics and NSAIDs.

Hyponatraemia LAST UPDATED: 16TH
JULY 2020
 Bookmark
Hyponatraemia is defined as a serum sodium concentration < 135 mmol/L. A level

< 125 mmol/L is considered severe. Hyponatraemia results from a relative excess
of body water to sodium.
Clinical Features
The rate of change of sodium is more important than the absolute sodium value
so patients with chronic hyponatraemia can be asymptomatic, while patients with
a sudden drop can be very unwell.
Early symptoms are headache, nausea, vomiting and general malaise. Later signs
are confusion, agitation and drowsiness. Acute severe hyponatraemia leads to
seizures, respiratory depression, coma and death. This is due to swelling of brain
cells when water moves from the extracellular to the intracellular compartment
because of differences in the osmolality between brain and plasma, resulting in
cerebral oedema and raised intracranial pressure.
Diagnostic Approach
Drug history
Hydration status
Plasma osmolality
Urine osmolality
Urine sodium
Thyroid function
Assessment of cortisol reserve
Plasma osmolality
Hyponatraemia of any cause is associated with a low plasma osmolality.
If the plasma osmolality is normal, then the possibility of pseudohyponatraemia
should be considered; this is an artifactual result due to a reduction in plasma
water caused by marked hyperlipidaemia or hyperproteinaemia e.g. in multiple
myeloma.
If the plasma osmolality is high, then the possibility of hyperosmolar
hyponatraemia should be considered; this may be due to hyperglycaemia or
administration of mannitol amongst other causes and reflects the shift of water
out of cells into the extracellular fluid in response to osmotic effects.
Urine osmolality
Once hypotonic hyponatraemia has been confirmed, urine osmolality should be
checked.
Low urine osmolality (< 100 mosmol/kg):
Primary polydipsia
Inappropriate administration of IV fluids
Malnutrition - low salt diet
Normal urine osmolality (> 100 mosmol/kg):
Urinary Na+ < 30 mmol/L

Patient hypovolaemic (true volume depletion or third space loss)
Gastrointestinal salt loss - severe diarrhoea and vomiting
Transdermal salt loss - sweating, extensive skin burns
Third space loss - pancreatitis, bowel obstruction, sepsis
Diuretics
Patient hypervolaemic (intravascular depletion in fluid overloaded
state)
Congestive cardiac failure
Cirrhosis
Nephrotic syndrome
Urinary Na+ > 30 mmol/L
Patient euvolaemic (normal circulating volume)
SIADH
ACTH deficiency
Severe hypothyroidism
Patient hypovolaemic (low circulating volume)
Addison's disease
Cerebral salt-wasting
Renal salt-wasting
Vomiting (causes loss of hydrogen ions and a metabolic
alkalosis which is corrected by the renal excretion of sodium
bicarbonate)
However, if the individual is using diuretics, or there is evidence of kidney disease,
all causes should be considered, as these can cause a low or a high urinary
sodium concentration.
Management
Treatment is cause-specific. Appropriate fluid replacement in patients with
hypovolaemic hyponatraemia with normal saline typically leads to improvement.
In patients with hypervolaemic hyponatraemia, specialist treatment of the
underlying condition is indicated.
In acute severe hyponatraemia with neurological compromise, the use of
hypertonic saline should be considered whatever the cause, with specialist input
and careful monitoring. Correction should not be too rapid, especially in chronic
hyponatraemia, as this may result in central pontine myelinolysis.

Hypernatraemia LAST UPDATED: 21ST
APRIL 2019
 Bookmark
Hypernatraemia is an increase in the serum sodium concentration > 145 mmol/L. It

is less common than hyponatraemia in clinical practice but it is a sign of significant
disease. Hypernatraemia may arise from either sodium gain or much more
commonly from water deficit (both are associated with a raised plasma osmolality).
Causes
Hypernatraemia can be thought of in relation to actual total body sodium:
Hypotonic fluid loss
The most common group of patients are those with hypernatraemia with decreased
total body sodium through loss of both water and sodium, but with a greater
proportion of water loss which may result from:
Renal losses e.g. osmotic diuresis secondary to uncontrolled diabetes
mellitus, mannitol, or renal disease
Skin losses e.g. burns, excessive sweating in hot climate or exercise
Gastrointestinal losses e.g. vomiting, diarrhoea, fistulae
Pure water depletion
Patients with hypernatraemia with normal total body sodium have a pure water
deficit which may result from:
Inadequate water intake e.g. unconscious patient, dementia, disordered thirst
perception in hypothalamic lesion
Extra-renal loss e.g. hyperventilation, hyperthyroidism, mucocutaneous loss
Renal loss e.g. diabetes insipidus or chronic kidney disease
Salt gain
Hypernatraemia with an actual increase in total body sodium is rare. Mild true
hypernatraemia may be caused by primary hyperaldosteronism, but this is not
typical. Other causes include acute salt poisoning e.g. intravenous sodium
bicarbonate, hypertonic saline, high sodium feeds in infants, near drowning in salt
water, salt ingestion.
Assessment and Management
When assessing patients with hypernatraemia:
If the hypernatraemia is mild (Na ? 150 mmol/L) and the patient has obvious
signs of dehydration it is likely the ECF volume is reduced and that the patient
has lost both sodium and water. Treatment should aim to replace the deficit
of fluid by infusing isotonic saline, or if the deficit is large, hypotonic saline.
With more severe hypernatraemia (150 - 170 mmol/L), pure water loss is likely
if the clinical signs of dehydration are mild in relation to the degree of
hypernatraemia - this is because pure water loss is distributed evenly
throughout the body compartments and the sodium content of the ECF is
unchanged. Treatment should be aimed at replacing water either orally, or
with 5% dextrose.
With gross hypernatraemia ( > 180 mmol/L), an excess of sodium is likely, the
patient may present with signs of fluid overload. Treatment may be with
diuretics, or rarely, by renal dialysis.
Acute severe hypernatraemia

This is a medical emergency and requires inpatient management in a high
dependency setting. Seizures and intracranial vascular haemorrhage as a result of
brain cell crenation can occur. The cause is most commonly excessive water loss
and the key aspect of treatment is aggressive fluid replacement (typically with
normal saline as this is relatively hypotonic). If urine osmolality is low, DI should be
considered and a trial of synthetic ADH given. In patients with known DI, it is
essential to ensure synthetic ADH is given parenterally and that close fluid balance
is observed.

Something wrong?
Thyroid Function LAST UPDATED: 2ND

MAY 2019
PHYSIOLOGY / ENDOCRINE / THYROID FUNCTION
 Bookmark
Anatomical Location
The thyroid gland is attached to the anterior surface of the trachea just below the
larynx. It has a right and left lobe joined by a central isthmus. Thyroid lesions can be
distinguished from other neck lumps by their movement on swallowing. The
recurrent laryngeal nerve lies laterally on each side and the parathyroid glands lie
posteriorly - both may be damaged during thyroid surgery. The thyroid gland has a
rich vascular supply from the inferior and superior thyroid arteries.
ANATOMY OF THE THYROID GLAND. (IMAGE BY OPENSTAX COLLEGE [CC BY 3.0

Production and Transport of Thyroid Hormones

Thyroid tissue is made up of colloid which contains iodinated thyroglobulin.
Thyroglobulin is synthesised by the surrounding follicular cells and is the large
Hyperthyroidism LAST UPDATED: 21ST
APRIL 2019
 Bookmark
The overproduction of T3 and T4 leads to hyperthyroidism.
Causes
Graves disease (autoimmune thyroid disease)
Results from the production of TSH receptor stimulating antibodies
Most common cause of hyperthyroidism
Nodular thyroid disease
Results from autonomous secretion of T3 and/or T4, either from a
solitary toxic nodule or numerous nodules within a multinodular goitre
Second most common cause of hyperthyroidism
Thyroiditis (e.g. viral, postpartum, drugs)
Results from inflammation of the thyroid gland causing a destructive
release of thyroxine
Less common
Clinical Features
Symptoms
Weight loss (often with increase appetite)
Insomnia, irritability and anxiety
Heat intolerance
Palpitations
Tremor
Pruritus
Increased bowel frequency and loose motions
Menstrual disturbance
Reduced fertility
Signs
General
Resting tachycardia (sinus rhythm or AF)
Warm peripheries
Proximal myopathy
Resting tremor
Hyperreflexia
Lid lag
Hypertension and flow murmur
Agitation and restlessness
Goitre
Graves disease
Thyroid eye disease (in order of increasing severity)
Dry/gritty eyes
Eyelid swelling, chemosis and periorbital oedema
Proptosis and lid retraction
Diplopia
Exposure keratopathy and compressive optic neuropathy
Skin changes
Pretibial myxoedema
Thyroid acropachy
PROPTOSIS AND LID RETRACTION IN GRAVES DISEASE. (IMAGE BY JONATHAN TROBE, M.D.
- UNIVERSITY OF MICHIGAN KELLOGG EYE CENTER (THE EYES HAVE IT) [CC BY 3.0
THYROID ACROPACHY AND PRETIBIAL MYXOEDEMA. (IMAGE BY HERBERT L. FRED, MD AND
HENDRIK A. VAN DIJK (HTTP://CNX.ORG/CONTENT/M14924/LATEST/) [CC BY 2.0
Investigations
T3, T4 and TSH
Elevated T4 and T3 with suppressed TSH = Primary hyperthyroidism
Elevated T3 with suppressed TSH = T3 toxicosis
Normal T4 and T3 with suppressed TSH = Subclinical hyperthyroidism
Elevated T4 and T3 with non-suppressed TSH = Consider assay
interference or secondary hyperthyroidism e.g. TSHoma or thyroid
hormone resistance
Thyroid antibodies (e.g. thyroid peroxidase (TPO) and TSH receptor
stimulating antibodies)
Thyroid ultrasound scan
Hypothyroidism LAST UPDATED: 21ST
APRIL 2019
 Bookmark
Hypothyroidism is characterised by reduced circulating T3 and T4.
Causes
Primary hypothyroidism
Autoimmune (atrophic and Hashimoto's)
Iatrogenic (thionamides, radioactive iodine, surgery, radiation)
Hypothyroid phase of thyroiditis
Drugs (lithium, amiodarone, interferon)
Iodine deficiency
Secondary hypothyroidism
TSH deficiency secondary to hypothalamic-pituitary disease
Clinical Features
Symptoms
Weight gain
Cold intolerance
Fatigue
Constipation
Depression
Muscle cramps
Carpal tunnel syndrome
Reduced fertility
Signs
Alopecia
Bradycardia
Dry skin
Brittle nails
Peri-orbital myxoedema
Goitre
Pre-tibial myxoedema
CLINICAL FEATURES OF HYPOTHYROIDISM. (IMAGE BY MIKAEL HÄGGSTRÖM, USED WITH

PERMISSION. [CC0], FROM WIKIMEDIA COMMONS)
Investigations
T3, T4 and TSH
Low T4 with elevated TSH = Primary hypothyroidism
Normal T4 with elevated TSH = Subclinical hypothyroidism
Low T4 with non-elevated TSH = Secondary hypothyroidism (exclude
pituitary disease)
Thyroid antibodies (e.g. TPO antibodies)
Management
Thyroxine replacement to normalise TFTs and resolve symptoms
Myxoedema Coma
Myxoedema coma is a rare medical emergency with a high mortality requiring
treatment in a high dependency setting characterised by:
Hypotension
Pericardial effusion
Bradycardia
Reduced consciousness
Hypoventilation
Hyponatraemia
Renal impairment
Coagulopathy

Parathyroid Hormone LAST UPDATED: 6TH
DECEMBER 2021
PHYSIOLOGY / ENDOCRINE / CALCIUM AND BONE
 Bookmark
Parathyroid hormone (PTH) is a peptide hormone synthesised by the chief cells of

the parathyroid glands, located immediately behind the thyroid gland.
Release of PTH
PTH is released in response to:
decreasing plasma [Ca2+] concentration

increasing blood [PO43-] concentration (indirectly by its binding to ionised
calcium and thereby effective reduction of plasma calcium levels).
PTH release is thus inhibited by normal blood calcium levels and also by
hypomagnesaemia.
Effects of PTH
PTH acts to:
BONE:
increase calcium and phosphate resorption from bone (via immediate
stimulation of osteocytic osteolysis and later, by upregulation of
osteoclast activity)
KIDNEYS:
increase calcium reabsorption in the distal tubule of the nephron (by
activating Ca2+ entry channels in the apical membrane and the
Ca2+ ATPase pump in the basolateral membrane)
increase phosphate excretion by inhibiting reabsorption in the proximal
tubule of the nephron
inhibit renal bicarbonate reabsorption stimulating a metabolic acidosis
which favours dissociation of calcium from plasma proteins
stimulate 1-alpha-hydroxylase in the kidneys to produce more
activated vitamin D
GUT:
indirectly increase calcium and phosphate absorption in the small
intestine (via activated vitamin D)
Overall PTH acts to increase plasma calcium levels and decrease plasma phosphate
levels.
CALCIUM AND BONE PHYSIOLOGY. (IMAGE BY OPENSTAX COLLEGE [CC BY 3.0


Phosphate Handling LAST UPDATED: 21ST
APRIL 2019
PHYSIOLOGY / ENDOCRINE / CALCIUM AND BONE /
RENAL / CALCIUM BALANCE  Bookmark
Phosphate is abundant in the body and is an important intracellular and

extracellular anion (but is predominantly intracellular). About 65% of dietary
phosphate is absorbed, mainly in the duodenum and jejunum by a transcellular
process which is enhanced by vitamin D.
Ca2+ and PO43- precipitate to form insoluble calcium phosphate and their
concentrations in the blood are close to the saturation point at which calcium
phosphate complexes precipitate out of solution onto the bone matrix. Therefore
an increase in one of the ions results in the precipitation of some calcium
phosphate and thus some of the other ion is removed from the solution;
Ca2+ and PO43- concentrations are thus inversely proportional.
Renal Phosphate Handling
Unbound PO43- is filtered freely at the glomerulus and there is reabsorption

along the nephron. The maximum rate of reabsorption is limited and and excess
filtered phosphate above a threshold level is excreted. Of filtered phosphate, 80%
is reabsorbed in the proximal tubule by a transcellular process. The distal tubules
reabsorb a further 10% of the filtered phosphate and the collecting ducts a
further 2 - 3%.
PO43- renal excretion is regulated by:
PTH (increases excretion by inhibiting reabsorption in the proximal tubule)

activated vitamin D (decreases excretion by increasing reabsorption in the
distal tubule)
acidosis (increases excretion)
glucocorticoids (increases excretion)
calcitonin (increases excretion)
Something wrong?
Calcium Handling LAST UPDATED: 24TH

NOVEMBER 2020
PHYSIOLOGY / ENDOCRINE / CALCIUM AND BONE /
RENAL / CALCIUM BALANCE  Bookmark
Normal Values of Calcium and Rationale for Corrected Calcium

Values
RCEM defines the normal value for total serum calcium as 2.1 - 2.5 mmol/L. This
is the sum of free ionised calcium and calcium bound to albumin.
This total serum calcium measurement must be adjusted for albumin levels (as
patients with a low albumin have total serum calcium lower than the reference
range yet have normal free ionised calcium and vice versa). 0.02 mmol/L should
be added to the calcium concentration for every g/L that albumin is below 40
and 0.02 mmol/L should be subtracted for every g/L that albumin is above 40.
Corrected calcium = Measured calcium + [(40 g/l - albumin) x 0.02]
Calcium Absorption
Calcium rich foods include: cheese, milk, yoghurt, fish and some vegetables and
nuts. Of dietary calcium, about 25 - 30% is absorbed by the gut. Ca2+ is absorbed
throughout the small intestine but mainly in the duodenum and proximal
jejunum. Absorption occurs by a transcellular process involving intracellular
calcium-binding proteins called calbindins. Gut absorption is increased by
activated vitamin D.
Physiological Actions of Calcium

Calcium is essential for:
enzymatic reactions
intracellular signalling
nerve conduction
skeletal, cardiac and smooth muscle contraction
the release of neurotransmitters
the release of hormones
secretion from exocrine glands
blood clotting
bone mineralisation
Transport of Calcium in the Blood

Only unbound ionised calcium is physiologically active.
Free intracellular Ca2+ must be maintained at a very low level; most is bound to
proteins or stored in the endoplasmic reticulum and mitochondria.
Blood calcium levels in the extracellular fluid are kept within a very narrow range
to maintain normal physiological processes:
about 45% of serum calcium is bound to albumin
about 5% is complexed to other ions and
about 50% is free ionised Ca2+.
Ionised calcium binds to negatively charged sites on protein molecules,
competing with hydrogen ions for the same binding sites on albumin and other
calcium-binding proteins. This binding is pH dependent and alters the level of
ionised calcium in the blood. An increase in pH, alkalosis, promotes increased
protein binding, which decreases free calcium levels. Acidosis, on the other
hand, decreases protein binding, resulting in increased free calcium levels.
Renal Calcium Handling

Calcium that is not protein bound is freely filtered in the glomerulus, and there is
reabsorption along the nephron.
About 70% is reabsorbed in the proximal tubule.
About 20% is reabsorbed in the thick ascending limb of the loop of Henle.
This reabsorption is mainly passive and paracellular and driven by sodium
reabsorption. Sodium reabsorption causes water reabsorption, which
raises tubular calcium concentration, causing calcium to diffuse out of the
tubules. The positive lumen potential also encourages calcium to leave
the tubule.
About 5 - 10% is reabsorbed in the distal convoluted tubule.
Less than 0.5% is reabsorbed in the collecting ducts.
Calcium reabsorption in the distal nephron is active and transcellular and
is the major target for hormonal control.
Something wrong?
Vitamin D LAST UPDATED: 21ST

APRIL 2019
 Bookmark
Vitamin D2 (ergocalciferol), derived from plants and yeasts and Vitamin D3
(cholecalciferol), derived from animal (particularly dairy) products, are obtained
in the diet and absorbed in the small intestine. Vitamin D3 can also be
manufactured from cholesterol within the body, via a reaction that is enabled by
ultraviolet irradiation of the skin.
Production of Activated Vitamin D

The D vitamins are converted to calcifediol (25-hydroxycholecalciferol) by
vitamin D 25-hydroxylase in the liver.
This is further converted to activated vitamin D (calcitriol or 1, 25 -
dihydroxycholecalciferol) by 1-alpha-hydroxylase in the cells of the renal
proximal tubule. This final reaction is the slowest step in the process and
therefore regulates the speed of the entire chain of reactions.
The enzyme 1-alpha-hydroxylase is stimulated by parathyroid hormone (PTH)
and thus this final step is regulated by PTH.
Calcitonin LAST UPDATED: 13TH
MARCH 2019
 Bookmark
Calcitonin is secreted by the parafollicular cells (C-cells) of the thyroid gland.
Calcitonin is secreted in response to rising or high levels of plasma Ca2+ ions and
acts to lower circulating levels of calcium.
Calcitonin acts on the kidneys to inhibit renal reabsorption of calcium and
phosphate and on the bones to inhibit bone resorption by osteocytes.
CALCIUM AND BONE PHYSIOLOGY. (IMAGE BY OPENSTAX COLLEGE [CC BY 3.0

Vitamin D Deficiency LAST UPDATED: 15TH
MARCH 2019
 Bookmark
Without activated vitamin D, calcium uptake from the gut is severely impaired
to the point at which intake of the hormone is insufficient to maintain body
stores. This leads to the increased release of PTH and resorption of bone.
A lack of vitamin D in children leads to inadequate calcification of bones,
which become malformed (rickets). Vitamin D deficiency in adults leads to
bone wasting resulting in soft malleable bone (osteomalacia).
Vitamin D deficiency can occur in:
dietary deficiency
malabsorption e.g. coeliac disease
lack of sun exposure
chronic kidney disease
liver failure

Osteomalacia LAST UPDATED: 21ST
APRIL 2019
 Bookmark
Osteomalacia is a disorder of mineralisation of bone matrix leading to soft

malleable bone. Rickets is a disorder of defective mineralisation of cartilage in
the epiphyseal growth plates of children.
Osteomalacia is caused by impaired bone metabolism primarily due to
inadequate levels of available phosphate, calcium, and vitamin D, or because of
resorption of calcium. The most common cause of osteomalacia is a deficiency
of vitamin D.
Clinical Features
Features of osteomalacia include:
Bone pain (particularly bone, pelvis, ribs)
Neuromuscular dysfunction (particularly in the gluteal muscles, leading to
waddling gait)
Pseudofractures on x-ray (looser zones)
Elevated alkaline phosphatase, hypocalcaemia and low phosphate due to
secondary hyperparathyroidism
Features of rickets include:
Bowing of tibia
Poor growth
Pain in spine, pelvis, legs
Projection of sternum and chest wall deformities
Back deformities e.g. kyphosis
Management
Management includes reversal of risk factors, increased dietary intake,
correction of hypocalcaemia and vitamin D replacement.
Osteoporosis LAST UPDATED: 21ST
APRIL 2019
 Bookmark
Osteoporosis is a disease characterised by reduced bone mass and increased

bone fragility resulting in an increased risk of fracture after minimal trauma
(particularly of the hip, spine and distal radius). It is very common in
postmenopausal women.
Bone densitometry, measured by dual energy X-ray absorptiometry (DXA) scan,
is the mainstay of diagnosis. Osteoporosis, defined according the the T score,
occurs when bone density is >2.5 standard deviations below normal peak bone
mass.
Risk Factors for Primary Osteoporosis

This is multifactorial, usually resulting from a combination of oestrogen
deficiency and aging. Risk factors include:
Oestrogen deficiency
Ageing
Family history
Smoking
Alcohol
Vitamin D deficiency
Causes of Secondary Osteoporosis

(Consider when osteoporosis occurs in non-'at risk' groups including men and
premenopausal women)
Hypogonadism
Hyperthyroidism
Hyperparathyroidism
Cushing's syndrome
Exogenous steroids
Hyperprolactinaemia
Management
Clinical risk prediction of fracture is a better guide to treatment than DXA
scanning alone. Algorithms exist to calculate the 10 -year fracture risk e.g. the
FRAX score.
Non-pharmacological
Balanced diet
Exercise
Smoking cessation
Falls prevention
Avoidance of excessive alcohol intake
Avoidance of drugs that cause osteoporosis e.g. corticosteroids
Pharmacological
Calcium and vitamin D supplementation
Bisphosphonates
Selective oestrogen receptor modulators (SERMs)
Parathyroid hormone
Hormone replacement therapy (HRT)

Structure of Gut Wall LAST UPDATED: 21ST
APRIL 2019
PHYSIOLOGY / GASTROINTESTINAL / GUT WALL
 Bookmark
The gastrointestinal system is essentially a muscular tube which maintains the same
basic structure throughout its length, although this is modified as function varies.
Layers
The layers that comprise this basic structure (from innermost to outermost) are:
The innermost mucosa composed of:
the epithelial layer (which has either secretory or absorptive functions)
the lamina propria (consisting of loose connective tissue, blood vessels
and lymph tissues)
the muscularis mucosa (a thin layer of smooth muscle)
The submucosa (containing a second layer of connective tissue, larger blood
vessels and lymphatic vessels and the submucosal plexus)
The muscularis externa composed of
the inner circular muscle layer (which, when it contracts, produces a
constriction of the lumen)
the outer longitudinal muscle layer (which, when it contracts, results in
shortening of the GI tract)
the myenteric plexus which lies between these two layers of muscle
The outermost serosa (another connective tissue layer covered with squamous
mesothelial cells)
Innervation
There are two intrinsic nerve plexuses which function as the enteric nerve system,
the activity of which is moderated by extrinsic innervations and hormones.
The submucosal plexus (Meissner's plexus) is located in the submucosal layer. The
submucosal plexus only has parasympathetic input and provides secretomotor
innervation to the mucosa, mainly regulating epithelial cell and submucosal blood
vessel function.
The myenteric plexus (Auerbach's plexus) is located between the circular and
longitudinal muscle layers of the muscularis externa. The myenteric plexus provides
motor innervation to the smooth muscle layers via sympathetic and parasympathetic
input, mainly regulating intestinal motility and sphincter function.
STRUCTURE OF THE GUT WALL. (IMAGE BY GORAN TEK-EN [CC BY-SA 3.0

Gastric Mucosal Barrier LAST UPDATED: 21ST
APRIL 2019
Mechanisms  Bookmark
PHYSIOLOGY / GASTROINTESTINAL / STOMACH
Mechanisms to protect the gastric mucosa include:

Secretion of mucus by mucous neck cells and goblet cells which forms a
water-insoluble gel that coats the gastric mucosa protecting it from the
acidic gastric contents and autodigestion by e.g. pepsin
Secretion of HCO3- by surface epithelial cells which forms part of the
mucosal gel layer raising the pH around the mucus layer
A compact epithelium lining with tight junctions between cells and fast cell
turnover
Production of prostaglandins which inhibit acid secretion and increase
mucus and HCO3- secretion
IgA secretion which helps prevent against invasion by ingested
microorganisms
Mucosal protection may be impaired by:
Excess acid secretion e.g. Zollinger-Ellison syndrome
NSAIDs which inhibit prostaglandin production and hence reduce mucus
secretion
Helicobacter pylori infection
Hypercalcaemia
Alcohol
Chronic nicotine exposure in smoking

Function of Stomach LAST UPDATED: 28TH
NOVEMBER 2019
 Bookmark
The stomach receives food and fluid from the oesophagus, mixes it with digestive
juices to form chyme and releases its contents into the duodenum. The stomach
acts as a reservoir for food as it is very distensible; when empty it has a volume of
about 50 mL but it has capacity of up to 3 - 4 L.
There are two sphincters at each of the gastric orifices, the lower oesophageal
sphincter protects the oesophagus from reflux of the gastric contents and the
pyloric sphincter controls the flow of gastric contents into the duodenum.
Functions
The main functions of the stomach are to:
Store food temporarily (as it can be ingested more rapidly than it can be
digested)
Chemically and mechanically digest food using acids, enzymes and
churning movements
Regulate the release of the resulting chyme into the small intestine
Secrete intrinsic factor which is essential for absorption of vitamin B12
Gastric Cell Types
Cell Type Function

Parietal cell Secretes HCl and intrinsic factor
Chief cell Secretes pepsinogen
G cell Secretes gastrin
Enterochromaffin-like cell Secretes histamine
Surface mucous cell Secretes mucus
GASTRIC CELLS. (IMAGE BY OPENSTAX COLLEGE [CC BY 3.0

Gastric Emptying LAST UPDATED: 21ST
APRIL 2019
 Bookmark
Gastric Motility
Mixing of the food with gastric secretions takes place in the distal body and
antrum of the stomach where the muscularis externa layer is thicker. The stomach
has an additional inner oblique smooth muscle layer (in addition to the inner
circular layer and outer longitudinal layer), allowing peristaltic contractions and
thorough mixing. Gastric contractions are increased by vagal stimulation and
decreased by sympathetic stimulation.
Gastric Emptying
The presence of chyme in the pyloric antrum distends it and causes antral
contractions and opening of the pyloric sphincter. The rate of gastric emptying is
regulated, which leads to a precise supply of chyme to the intestine at an
appropriate rate for digestion. Gastric emptying varies with different food
types; carbohydrates are emptied more quickly, proteins more slowly and fatty
foods even more so, liquids empty more rapidly than solid foods.
Gastric emptying is increased by:
Distension of the pyloric antrum
A fall in the pH of chyme in the stomach
Parasympathetic stimulation
Gastric emptying is decreased by:
Enterogastric inhibitory reflexes stimulated by
Distension of the duodenum
The presence of fats in the duodenum (by stimulating release of
cholecystokinin)
A fall in the pH of chyme in the duodenum
An increase in the osmolality of chyme in the duodenum
Irritation of the mucosal lining of the duodenum
Hormones
Cholecystokinin
Secretin
Gastric emptying can also be delayed pathologically by mechanical obstruction
e.g. tumours or stenosis or by non-mechanical causes e.g. myotonic dystrophy or
autonomic neuropathy.

Gastric Juice LAST UPDATED: 18TH
APRIL 2019
 Bookmark
The average adult produces 2 - 3 L of gastric fluid every 24 hours.

Gastric fluid contains:
Mucus
Hydrochloric acid (HCl)
Digestive enzymes
pepsinogen
gastric lipase
Intrinsic factor
Mucus
Mucus is secreted by surface mucous cells. The alkaline, mucin-rich fluid forms a
water-insoluble gel that adheres to the surface of the stomach lumen and plays an
important role in protection of the stomach against its acid contents and
autodigestion by pepsin. In addition, local mediators, such as prostaglandins, are
released when the mucosa is irritated, and these increase the thickness of the
mucus layer and stimulate the production of bicarbonate which neutralises acid.
Hydrochloric Acid
Hydrochloric acid is secreted by gastric parietal cells.
Digestive Enzymes
Proteins in food are broken down into polypeptides in the stomach by enzymes
called pepsins. Pepsin is secreted in the form of its inactive precursor, pepsinogen,
from chief cells in the gastric mucosa, and is converted to its active form by the
acid environment in the stomach.
Gastric lipase is of little physiological importance except in pancreatic
insufficiency.
Intrinsic Factor
Intrinsic factor is produced by parietal cells, and is essential for vitamin B12
absorption. Intrinsic factor binds to vitamin B12, allowing it to escape degradation
in the stomach and intestine and to be safely transported to the terminal ileum
where it is absorbed.

Phases of Gastric Secretion LAST UPDATED: 21ST
APRIL 2019
 Bookmark
Stimulation of gastric secretion occurs in three phases.
Cephalic Phase
The cephalic phase is the shortest phase and is initiated by the sight, smell and
taste of food, mediated by the activation of the vagus nerve and its action on the
enteric plexus. It usually begins before the meal and lasts up to 30 minutes into
the meal.
Acid secretion is upregulated by acetylcholine released from postganglionic
parasympathetic fibres in the myenteric plexus which acts directly by stimulating
parietal cells and indirectly by stimulating the release of gastrin (from antral G -
cells) and histamine (from enterochromaffin-like cells) which themselves also
upregulate acid secretion from parietal cells.
Gastric Phase
The gastric phase is the longest phase, lasting for up to 3 hours after the start of
the meal. It is triggered by distension of the stomach and the chemical
composition of the food. Most acid secretion takes place during this phase, and
the food in the stomach is converted to chyme.
Mechanoreceptors in the stomach wall are stretched and set up local myenteric
and central vagovagal cholinergic reflexes. Both cause the release of acetylcholine
which stimulates the release of gastrin, histamine, and in turn, acid, pepsinogen
and mucus. Stimulation of the vagus nerve also stimulates the release of gastrin-
releasing peptide (GRP), which mainly acts directly on G-cells to release gastrin.
Whole proteins do not affect gastric secretions directly but the presence of their
break-down products, amino acids and peptides, directly stimulates gastrin
release from antral G-cells.
A low pH in the stomach inhibits gastrin secretion, therefore when the stomach is
empty or when acid has been secreted for some time after food has entered it,
there is inhibition of acid secretion. However, when food first enters the stomach,
the pH rises, and this leads to release of the inhibition and causes a maximum
secretion of gastrin. Thus gastric acid secretion is self-regulating.
Intestinal phase
The intestinal phase is brought about by chyme entering the duodenum through
the pyloric sphincter. Initially, there is a continuation of gastric stimulation due to
the activation of intestinal G cells by amino acids and peptides in chyme with
subsequent gastrin release.
However, this is short lived as the duodenum becomes more distended with
further gastric emptying and a series of reflexes is initiated which inhibits further
release of gastric secretion.
Secretin is released in response to acid stimulation which reaches the
stomach via the bloodstream and inhibits the release of gastrin.
The presence of fatty acids in the duodenum itself stimulates the release of
gastric inhibitory peptide (GIP) and cholecystokinin (CCK), which inhibit the
release of both gastrin and acid.
Together with mechanoreceptors in the duodenum via vagal and local reflex
pathways, the release of secretin and cholecystokinin also plays a role in the
regulation of gastric emptying.
Stimulating Factors
Gastrin secretion is stimulated by:
The presence of small peptides and amino acids in chyme
Gastric distension
Vagal stimulation directly via acetylcholine and indirectly via gastrin-releasing peptide (GRP)
Raised gastric pH
Inhibiting Factors
Gastrin secretion is inhibited by:
Low gastric pH (negative feedback mechanism)
Somatostatin
Secretin
Gastric inhibitory polypeptide (GIP)
Cholecystokinin
Function
Gastrin acts to:
Stimulate acid secretion from parietal cells (both directly and indirectly by stimulating release
of histamine from ECL cells)
Stimulate pepsinogen secretion from chief cells
Increase gastric motility
Stimulate growth of gastric mucosa
Hormone Released Stimulated by: Inhibited by: Acts to:

from:
from:
Gastrin G-cells in The presence of small Low gastric pH, Stimulate
the pyloric peptides and amino somatostatin, acid
antrum acids in the stomach, secretin, secretion
gastric distension, cholecystokinin, from
raised gastric pH, gastric gastric
vagal stimulation inhibitory parietal
polypeptide cells,
stimulate
pepsinogen
from
gastric
chief cells,
increase
gastric
motility,
stimulate
growth of
gastric
mucosa
Cholecystokinin I-cells in The presence of fatty Somatostatin Increase
(CCK) the acids/monoglycerides production
duodenum and small of bile,
and peptides/amino acids stimulate
jejunum in the duodenum release of
stored bile,
increase
pancreatic
bicarbonate
secretion,
stimulate
pancreatic
enzyme
secretion,
inhibit
gastric
emptying,
inhibit
gastric acid
production,
stimulate
pepsinogen
secretion
from:
Secretin S-cells in A low pH and the Somatostatin Inhibit
the presence of fatty gastric acid
duodenum acids in the secretion,
duodenum inhibit
gastric
emptying,
stimulate
pepsinogen
secretion,
stimulate
pancreatic
bicarbonate
secretion,
increase
pancreatic
enzyme
secretion,
increase
bile
production
Gastric K-cells in The presence of fatty Somatostatin Inhibit
inhibitory the acids, amino acids gastric acid
polypeptide duodenum and orally secretion,
(GIP) and administered glucose stimulate
jejunum in the duodenum insulin
release

Somatostatin LAST UPDATED: 5TH
MARCH 2019
PHYSIOLOGY / GASTROINTESTINAL / PANCREAS /
SMALL INTESTINE / STOMACH  Bookmark
Somatostatin is secreted from D-cells in the pyloric antrum, the duodenum and
pancreatic islets.
Somatostatin is secreted by cells throughout the GI tract in response to H+ in the
lumen.
Somatostatin secretion is inhibited by vagal stimulation.
Somatostatin acts to inhibit gastric acid secretion both directly at the parietal cell
via a G-protein coupled receptor and indirectly via inhibition of gastrin and
histamine secretion.
Somatostatin also acts to inhibit secretion of all GI hormones including:
Insulin
Glucagon
Cholecystokinin
Secretin
Gastric inhibitory polypeptide (GIP)
Somatostatin thus mediates:
Decreased gastric and intestinal motility
Decreased gastric and intestinal secretions
Decreased pancreatic exocrine function
Decreased pancreatic endocrine function
Decreased bile production and release

Saliva LAST UPDATED: 16TH
DECEMBER 2019
PHYSIOLOGY / GASTROINTESTINAL /
MOUTH AND OESOPHAGUS  Bookmark
Sites of Production
Three main pairs of glands: the parotid, submandibular and sublingual glands
secrete saliva. About 1 - 2 L of saliva is produced per day, and almost all is
swallowed and absorbed.
Salivary gland Contribution at Contribution when

rest stimulated
Parotid gland 20% 50%
Submandibular 65% 30%
gland
Sublingual gland 7-8% 10%
Minor glands 7-8% 10%
SALIVARY GLANDS. (IMAGE BY BLAUSEN.COM STAFF (2014). "MEDICAL GALLERY OF
BLAUSEN MEDICAL 2014". WIKIJOURNAL OF MEDICINE 1 (2).
DOI:10.15347/WJM/2014.010. ISSN 2002-4436. (OWN WORK) [CC BY 3.0
Composition
Saliva is hypotonic and alkaline, and contains a mixture of both inorganic and
organic constituents. Saliva composition varies according to the rate and site of
production, but the main components are:
Water (99%)
Mucus
Digestive enzymes e.g. amylase, lingual lipase
Antibacterial enzymes e.g. lysozyme
Secretory immunoglobulins e.g. IgA
Electrolytes (high K+ and HCO3- concentration)
Control of Secretion
Secretion of saliva is under the control of the autonomic nervous system. There is
a baseline level of secretion (about 0.5 mL/min) due to ongoing low-level
parasympathetic stimulation which prevents the mouth and pharynx from drying
out. On top of the baseline, increases in salivary secretion can occur in response
to food activating gustatory receptors or mastication activating mucosal
mechanoreceptors or in response the sight, smell and anticipation of food.
However salivation is initiated, the impulses to the salivary glands travel via the
autonomic nerves.
The sympathetic control of salivary production is via the superior cervical
ganglion. Sympathetic innervation causes increased protein secretion resulting
in increased production of a thick mucoid saliva. There is variable sympathetic
innervation between the salivary glands and generally this system is far less
important than the parasympathetic innervation in terms of regulating
production of saliva.
The parasympathetic outflow is coordinated via centres in the medulla, and
innervation occurs via the facial and glossopharyngeal nerves. This results in the
following effects: increased production of saliva by acinar cells, increased
secretion of bicarbonate by ductal cells, increased blood flow to the salivary
glands and contraction of myoepithelium to increase the rate of expulsion of
saliva. Overall, increased parasympathetic stimulation results in an increased flow
of saliva that is more watery in composition. Saliva production is decreased by
inhibition of the parasympathetic nervous system e.g. by sleep, dehydration,
anticholinergic drugs and fear.
Function
Functions of saliva in health include:
General cleansing and protection of the buccal cavity by washing away
food particles
Moistening of the buccal cavity for speech
Lubrication of ingested food for bolus formation and swallowing
Dissolving of chemicals in food allowing them to interact more efficiently
with taste buds
Dilution and neutralisation of acid in food (and produced by bacteria)
Mastication LAST UPDATED: 4TH
MARCH 2019
Mastication is the process of systematic mechanical breakdown of food in the

mouth. Mastication breaks up large food particles, mixing them with salivary
secretions and aiding subsequent digestion. Certain foods require more chewing
than others e.g. red meat or chicken compared to fish, eggs or rice in order to be
fully digested and absorbed by the gastrointestinal tract.
Mastication involves the coordinated activity of the teeth, jaw muscles,
temporomandibular joint, tongue and other structures such as the lips, palate and
salivary glands.
During mastication, three main pairs of glands secrete saliva; the parotid,
submandibular and sublingual glands.
At rest, saliva is predominantly produced by the submandibular gland (65%, with
only 20% from the parotid gland), but when stimulated, saliva is increasingly
produced by the parotid gland (50%, compared to only 30% from the
submandibular gland). The parotid gland produces a more watery proteinaceous
saliva, rich in electrolytes and enzymes with little mucus, compared to the
submandibular gland.
Following mastication, the tongue propels the bolus of food along the palate
towards the pharynx, initiating the swallowing reflex.

Something wrong?
Swallowing LAST UPDATED: 21ST

APRIL 2019
Swallowing is the controlled transport of a food bolus from mouth to stomach,

involving a sequential reflex, which is coordinated by the swallowing centre in the
medulla and pons and consists of three phases: the buccal, pharyngeal and
oesophageal phases. Fibres in the vagus and glossopharyngeal nerves carry
information between the gastrointestinal tract and the brainstem.
Buccal Phase (voluntary)

During the buccal phase, food is chewed and mixed with saliva to form a food
bolus. Tongue movements then push this food bolus upwards and backwards
against the hard palate, forcing it into the pharynx.
Pharyngeal Phase (involuntary)

The pharyngeal phase lasts about 1 second and is initiated by the food bolus
stimulating mechanoreceptors in the pharynx and firing impulses via the
glossopharyngeal nerve (CN IX) and the vagus nerve (CN X) to the swallowing
centre.
In the pharyngeal phase:
The soft palate elevates, closing off the nasopharynx
The base of the tongue retracts, pushing the bolus against the pharyngeal
walls
Laryngeal muscles contract to close the glottis and elevate the larynx,
closing off the airway
Breathing is inhibited
The tip of the epiglottis moves over the tracheal opening, closing off the
airway
The pharyngeal constrictor muscles contract sequentially from top to
bottom, squeezing the bolus downwards
The upper oesophageal sphincter relaxes to permit the food bolus to enter
the oesophagus
As the bolus enters the oesophagus, these changes reverse, the larynx opens and
breathing continues.
Oesophageal Phase (involuntary)

The oesophageal phase involves transport of the bolus along the oesophagus to
the stomach by peristalsis. A coordinated wave of relaxation in front of the food
bolus and contraction behind the bolus of the circular and longitudinal muscles of
the oesophagus propels the food bolus along. Gravity accelerates the movement.
The lower oesophageal sphincter relaxes as the food bolus approaches the lower
end of the oeosphagus, opening and allowing the bolus to pass into the stomach.
The sphincters and the peristaltic waves are principally controlled by activity in
the vagus nerve and aided by a high degree of coordination of the activity within
the enteric nerve plexuses within the tract itself.
PHASES OF SWALLOWING. (IMAGE BY BOUMPHREYFR [CC BY-SA 3.0

Bile LAST UPDATED: 21ST
APRIL 2019
LIVER AND GALLBLADDER  Bookmark
Bile is an aqueous, alkaline greenish-yellow liquid containing bile acids,

cholesterol, phospholipids, bile pigments, electrolytes, mucus and water.
Function
Bile functions to eliminate endogenous and exogenous substances from the
liver, to neutralise gastric acid in the small intestine, and to emulsify fats in the
small intestine and facilitate their digestion and absorption.
Production
Bile is secreted by hepatocytes. It is isotonic and resembles plasma ionically.
This fraction of bile is called the bile acid-dependent fraction. As it passes
along the bile duct, the bile is modified by epithelial cells lining the duct by the
addition of water and bicarbonate ions; this fraction is called the bile acid-
independent fraction. Overall, the liver can produce 500 - 1000 mL of bile per
day. The bile is either discharged directly into the duodenum or stored in the
gallbladder. The bile acid-independent fraction is made at the time it is
required i.e. during digestion of chyme. The bile acid-dependent fraction is
made when the bile salts are returned from the GI tract to the liver, and is then
stored in the gallbladder until needed.
Storage
The gallbladder not only stores bile but concentrates it by removing non-
essential solutes and water, leaving bile acids and pigments, mainly by active
transport of Na+ into the intercellular spaces of the lining cells which, in turn,
draws in water, HCO3- and Cl- from the bile and into the extracellular fluid.
Within a few minutes of a meal, particularly when fatty foods have been
consumed, the gallbladder contracts and releases bile into the bile duct. The
sphincter of Oddi is relaxed, allowing the bile to pass into the duodenum
through the ampulla of Vater. The gallbladder empties completely 1 h after a
fat-rich meal, and maintains the level of bile acids in the duodenum above that
necessary for the function of the micelles.
Regulation
The formation of bile is stimulated by:
Bile salts
Secretin
Glucagon
Gastrin
The release of bile stored in the gallbladder is stimulated by:
Cholecystokinin
Vagal stimulation (to a lesser extent)

Something wrong?
Bile Acids LAST UPDATED: 6TH

DECEMBER 2020
Bile acids are detergents which emulsify lipids. They have a hydrophobic and a
hydrophilic end and in aqueous solution, bile salts orient themselves around
droplets of lipid forming micelles to keep the lipid droplets dispersed.
Production
Bile acids are synthesised from cholesterol by hepatocyte and excreted into
bile. Synthesis of new bile acids occurs as needed to replace bile acids that are
excreted in the faeces.
The principal primary bile acids are cholic acid and chenodeoxycholic acid. They
are made more soluble by conjugation with taurine or glycine in the liver.
Enterohepatic Circulation
Of the bile acids excreted into the intestine, about 95% are reabsorbed into the
portal circulation by active transport mechanisms in the distal ileum and
recycled by the liver.
Many of the bile salts are reabsorbed unaltered, some are converted by
intestinal bacteria into secondary bile acids (deoxycholic acid and lithocholic
acid) and then reabsorbed and a small proportion escapes reabsorption and is
excreted in the faeces.
Function
The main functions of bile acids are:
Emulsification of lipids to increase the surface area available for digestion
by pancreatic lipase
Micelle formation to facilitate lipid transport and absorption
Stimulation of bile production by osmotically attracting water and
electrolytes into the bile canaliculi
Regulation of bile acid synthesis via negative feedback

Function of Liver LAST UPDATED: 21ST
APRIL 2019
Functional Anatomy
The liver consists of four lobes, each made up of hexagonal lobules, the
functional unit of the liver. Each lobule consists of a central vein that eventually
becomes part of the hepatic vein. Surrounding the central vein are single
columns of hepatocytes radiating outwards; between the hepatocytes are small
canaliculi which drain into the bile duct on the periphery of the lobule. At each
of the six corners of the lobules lies a 'portal triad' comprising branches of the
hepatic artery, the portal vein and the bile duct.
FUNCTIONAL ANATOMY OF THE LIVER. (IMAGE BY OPENSTAX COLLEGE [CC BY 3.0

Function of Exocrine LAST UPDATED: 21ST
APRIL 2019
Pancreas  Bookmark
PHYSIOLOGY / GASTROINTESTINAL / PANCREAS
The exocrine pancreas secretes a major digestive fluid called pancreatic juice, which
is secreted into the duodenum via the pancreatic duct. When food is present in the
duodenum the sphincter of Oddi relaxes, allowing both bile and pancreatic secretions
to enter the duodenum.
FUNCTIONAL ANATOMY OF THE PANCREAS. (IMAGE BY OPENSTAX COLLEGE [CC BY 3.0

Pancreatic Juice
The pancreas secretes about 1 L of fluid per day. The bulk of the fluid is a sodium and
bicarbonate rich hypertonic alkaline fluid secreted by pancreatic ductal cells, which
together with secretions from the gallbladder and the intestinal juices, neutralises
acid entering the duodenum from the stomach.
Digestive Enzymes
The acinar cells secrete a small volume of fluid rich in digestive enzymes.
These enzymes include:
Pancreatic amylase
Pancreatic lipase
Ribonuclease and deoxyribonuclease
Proteolytic enzymes including trypsin, chymotrypsin, elastase and
carboxypeptidase
Most of the proteolytic enzymes are secreted in an inactive proenzyme form to
protect the pancreas from autodigestion, and are activated in the duodenum.
Regulation of Secretions
Pancreatic exocrine secretion is controlled by:
Parasympathetic stimulation which enhances secretion of both the enzyme
and aqueous components
Sympathetic stimulation which inhibits pancreatic secretion
Secretin which stimulates secretion of the alkaline-rich fluid from ductal cells
Cholecystokinin which stimulates secretion of the enzyme-rich fluid from
acinar cells
Somatostatin which inhibits secretion from both acinar and ductal cells

Stimulating Factors
Cholecystokinin release is stimulated by:
The presence of small peptides and amino acids in the duodenum
The presence of fatty acids and monoglycerides in the duodenum
Inhibitory Factors
The release of cholecystokinin is inhibited by somatostatin.
Function
CCK acts to:
Increase production of bile
Stimulate release of stored bile via contraction of the gallbladder and relaxation of the
sphincter of Oddi
Potentiate secretin-induced stimulation of pancreatic HCO3- secretion
Stimulate pancreatic enzyme secretion
Inhibit gastric emptying
Inhibit gastric acid production
Stimulate secretion of pepsinogen from chief cells

from:
polypeptide cells,
stimulate
pepsinogen
from
gastric
chief cells,
increase
gastric
motility,
stimulate
growth of
gastric
mucosa
from:
stored bile,
increase
pancreatic
bicarbonate
secretion,
stimulate
pancreatic
enzyme
secretion,
inhibit
gastric
emptying,
inhibit
gastric acid
production,
stimulate
pepsinogen
secretion
duodenum inhibit
gastric
emptying,
stimulate
pepsinogen
secretion,
stimulate
pancreatic
bicarbonate
secretion,
increase
pancreatic
enzyme
secretion,
increase
bile
production
from:
release

Stimulating Factors
Secretin secretion is stimulated by:
A low pH in the duodenum
The presence of the products of fat digestion in the duodenum
Inhibitory Factors
Secretin release is inhibited by somatostatin.
Function
Secretin acts to:
Decrease gastric acid secretion by gastric parietal cells (through inhibition of gastrin release)
Inhibit gastric emptying
Stimulate the release of pepsinogen by gastric chief cells
Stimulate pancreatic HCO3- secretion
Potentiate cholecystokinin-induced stimulation of pancreatic enzyme secretion
Stimulate HCO3- and H2O secretion by the liver and increase bile production

from:
polypeptide cells,
stimulate
pepsinogen
from
gastric
chief cells,
increase
gastric
motility,
stimulate
growth of
gastric
mucosa
from:
stored bile,
increase
pancreatic
bicarbonate
secretion,
stimulate
pancreatic
enzyme
secretion,
inhibit
gastric
emptying,
inhibit
gastric acid
production,
stimulate
pepsinogen
secretion
duodenum inhibit
gastric
emptying,
stimulate
pepsinogen
secretion,
stimulate
pancreatic
bicarbonate
secretion,
increase
pancreatic
enzyme
secretion,
increase
bile
production
from:
release

Function of Small Intestine LAST UPDATED: 28TH
NOVEMBER 2019
PHYSIOLOGY / GASTROINTESTINAL / SMALL INTESTINE
 Bookmark
The small intestine is the main site for digestive and absorptive processes. Motility of
the small intestine (via peristalsis and segmental contraction) facilitates mixing of
intestinal contents, the bringing of the intestinal contents into contact with the
absorptive intestinal brush border and the forward propulsion of the contents. The
small intestine absorbs water, electrolytes, carbohydrates, amino acids, minerals, fats
and vitamins.
Duodenal Chyme
The chyme that first enters the duodenum is acidic, hypertonic and only partially
digested. There is an osmotic movement of water across the freely permeable wall
which leads to the contents becoming isotonic, and addition of both bicarbonate from
the pancreas and bile from the liver which neutralises the acidity, allowing further
digestion of the chyme performed by the addition of enzymes from the pancreas, liver
and intestine itself.
Functional Anatomy
The mucosa of the small intestine has a much greater surface area for absorption than
in other parts of the gastrointestinal tract.
Factors increasing the surface area include:
The small intestine is very long - about 5 m in length.
The inner wall of the small intestine is covered by numerous folds of mucous
membrane called plicae circulares.
The lining of the small intestine is folded into many finger-like projections called
villi.
The surface of the villi is covered with a layer of epithelial cells which, in turn,
have many small projections called microvilli that project towards the lumen of
the intestine (forming the brush border).
The microvilli are covered by a glycocalyx which contains many enzymes which are
involved in digestion and transport. Each villus contains a single, blind-ended
lymphatic vessel called a lacteal and also a capillary network, via which nutrients are
absorbed.
FUNCTIONAL ANATOMY OF THE SMALL INTESTINE. (IMAGE BY OPENSTAX COLLEGE [CC BY 3.0
Water Absorption and the Sodium Pump

As the contents of the intestine are isotonic with body fluids and mostly have the
same concentration of the major electrolytes, their absorption is active. Water cannot
be moved directly, but follows osmotic gradients set up by the transport of ions,
primarily mediated by the sodium pump.
Na+/K+ ATPase located on the basolateral membrane of the epithelial cells pumps
three Na+ ions from the cell in exchange for two K+ ions, against their respective
concentration gradients. This leads to a low intracellular concentration of Na+ and a
high intracellular concentration of K+. The low intracellular concentration of Na+
ensures a movement of Na+ from the intestinal contents into the cell down its
concentration gradient by both membrane channels and transporter protein
mechanisms. Na+ is then rapidly pumped again by the basolateral sodium pump. K+
leaves the cell across the basolateral membrane down its concentration gradient
linked to an outward movement of Cl- against its concentration gradient (Cl- having
entered the cell across the luminal membrane down its concentration gradient).
These movements set up an osmotic gradient between the lumen and the blood,
leading to water absorption following the movement of Na+ and Cl- across the luminal
membrane. Up to 9 L of water is absorbed from the gastrointestinal tract per day, most
of it from the small intestine, especially the jejunum.

Carbohydrate Handling LAST UPDATED: 21ST
APRIL 2019
 Bookmark
Carbohydrates are the main energy source of most diets. They provide 17 kJ (4 kcal) of
energy per gram. Carbohydrate is digested in the mouth and small intestine.
Dietary Carbohydrate
Most dietary carbohydrate is in the form of polysaccharides. The principal ingested
polysaccharides are starch which is derived from plant sources and glycogen which is
derived from animal sources. Other sources of carbohydrate are monosaccharides
(glucose, fructose and galactose) and disaccharides (maltose, sucrose and lactose).
Dietary fibre consists of indigestible carbohydrate (found in plant foods) such as
cellulose, lignin and pectin. Although it does not provide energy, fibre adds bulk to the
bowel contents and increases gut motility (and decreases absorption of toxic
compounds due to its binding properties, including some carcinogens).
Carbohydrate Digestion
Polysaccharides are digested by amylases, produced initially by salivary glands and
later by the pancreas, to produce maltose, maltotriose and limit dextrins with short
branches. These are broken down further by enzymes released from the intestinal
brush border (maltase, isomaltase, sucrase and lactase) into the final products of
carbohydrate digestion, the monosaccharides (glucose, fructose and galactose),
which can be absorbed by the enterocyte.
The monosaccharides are transported across the apical membrane of the enterocyte
by means of cotransporter molecules, such as the sodium-glucose co-transporter
(SGLT-1), that link their inward movement with that of Na+ down its concentration
gradient (the Na+ gradient being maintained by the Na+/K+ ATPase pump). At the
basolateral membrane, monosaccharides leave the cell either by simple or facilitated
diffusion down the concentration gradient and enter the circulation via the rich
capillary network in the villus.
CARBOHYDRATE HANDLING. (IMAGE BY SONABI (OWN WORK) [CC BY-SA 4.0

Fat Handling LAST UPDATED: 15TH
MAY 2019
 Bookmark
Dietary Fat
Dietary fat is chiefly composed of triglycerides (esters of free fatty acids and glycerol
which may be saturated or unsaturated). The essential fatty acids are linoleic acid and
alpha-linolenic acid, which cannot be manufactured in the body. The body is efficient
at manufacturing fats (triglycerides, sterols and phospholipids) and will lay down
subcutaneous fat stores. Dietary fat provides 37 kJ (9 kcal) of energy per gram. Fats
are digested almost entirely in the small intestine and are only released from the
stomach into the duodenum at the rate at which they can be digested.
Fat Digestion
Lingual and gastric lipase begin the hydrolysis of triglycerides (although this is not
physiologically significant unless pancreatic lipase is deficient).
In the duodenum fat is emulsified by bile acids, a process where larger lipid droplets
are broken down into much smaller droplets providing a greater surface area for
enzymatic digestion. Pancreatic lipase digests triglycerides into monoglycerides and
free fatty acids. These breakdown products form tiny particles with the bile acids
called micelles.
Micelles are arranged so that hydrophobic lipid molecules lie in the centre, surrounded
by bile acids arranged such the outer region is hydrophilic. This arrangement allows
the micelles to enter the aqueous layers surrounding the microvilli, and the products
of fat digestion (fatty acids and monoglycerides), cholesterol and fat-soluble vitamins
can then diffuse passively into the enterocytes, leaving the bile salts within the lumen
of the gut where they are reabsorbed from the ileum or excreted in faeces.
STRUCTURE OF A MICELLE. (IMAGE BY BILE1.PNG: FRANK BOUMPHREY, MD DERIVATIVE WORK:
HAZMAT2 (THIS FILE WAS DERIVED FROM BILE1.PNG:) [CC BY-SA 3.0
Fat Absorption
Once inside the epithelial cell, lipid is taken into the smooth endoplasmic reticulum
where much of it is re esterified. Dietary and synthesised lipids are then incorporated
into chylomicrons in the Golgi body, which are exocytosed from the basolateral
membrane to enter lacteals. Some small-chain fatty acids may be absorbed directly
into the blood.
FAT HANDLING. (IMAGE BY OPENSTAX COLLEGE [CC BY 3.0
Chylomicrons
From lacteals, chylomicrons pass into the lymphatic system and eventually reach the
bloodstream via the thoracic duct. Chylomicrons consist mainly of triglyceride with
small amounts of cholesterol and cholesteryl esters in the centre with a phospholipid
coat studded with apolipoproteins.
Protein is composed of amino acids linked by peptide bonds. Nine amino acids are essential
(required from the diet) for protein synthesis and nitrogen balance, the other necessary amino
acids can be manufactured in the body. Proteins provide about the same amount of energy as
carbohydrate but are not as easily utilised. The protein requirement of a normal healthy adult
is about 40 g/day. Protein is digested in the stomach and small intestine.
Protein Digestion
Digestion of dietary protein begins in the stomach where pepsin hydrolyses protein to
polypeptides, and continues in the duodenum where pancreatic proteases (trypsin and
chymotrypsin) continue the process of hydrolysis forming oligopeptides.
These are further broken down into small peptides and amino acids by pancreatic
carboxypeptidases and aminopeptidases located on luminal membrane epithelial cells. Free
amino acids are absorbed by secondary active transport coupled with Na+ transport. Amino
acids cross the basal membrane into the capillaries by facilitated diffusion.
PROTEIN HANDLING. (IMAGE BY SONABI (OWN WORK) [CC BY-SA 4.0

Iron Handling LAST UPDATED: 21ST
APRIL 2019
SMALL INTESTINE  Bookmark
The total amount of iron in the body is about 3 - 4 g, of which about two-
thirds is in haemoglobin.
Iron Absorption
Iron exists in two forms, the ferrous state (Fe 2+) or the ferric state (Fe3+). Most
dietary iron is in the form Fe3+, which is reduced by ferrireductase in the
mucosa assisted by ascorbic acid and HCl in gastric secretions to the more
soluble Fe2+ and then absorbed by the duodenum and jejunum.
Fe2+ is taken across the enterocyte apical membrane by the divalent metal
transporter (DMT1). In the enterocyte, Fe2+ is oxidised to Fe3+ and then either
stored in enterocyte epithelial cells bound to apoferritin, or released into the
plasma via the molecule ferroportin on the basolateral membrane.
Iron Transport
Iron in the plasma is bound to the transport protein transferrin. Iron is
transferred to the bone marrow for erythropoiesis or to the liver or other
parenchymal cells for storage as ferritin or haemosiderin. The iron released
from the breakdown of senescent red blood cells, some of which is stored by
the macrophages in the liver and spleen, provides most of the iron on
transferrin, only a small proportion of transferrin iron comes from dietary iron.
Regulation of Iron Absorption

The normal Western diet contains about 10 - 20 mg of iron per day and
typically about 5 - 10% of this is absorbed (to replace that lost by intestinal
epithelial cell shedding). Iron absorption is tightly regulated as excess iron is
potentially toxic, and the body has no physiological mechanism for
upregulating excretion.
Iron absorption can be increased when body stores are low or when there is a
need to increase erythropoiesis e.g. an increase in absorption may be seen
about 3 - 4 days following haemorrhage.
Hepcidin is the main hormonal regulator of iron homeostasis; it inhibits iron
release from macrophages in the reticuloendothelial system and from
intestinal epithelial cells and inhibits intestinal iron absorption. Hepcidin is
suppressed by erythropoietin, ineffective erythropoiesis, pregnancy and
hypoxia, but upregulated in inflammation and iron overload.

Vitamin B12 Handling LAST UPDATED: 5TH
MARCH 2019
On ingestion, vitamin B12 is bound to R protein found in saliva and gastric

secretions, which protects it from digestion in the stomach.
Once vitamin B12 has been separated from R protein in the duodenum by the
action of pancreatic proteases, vitamin B12 binds to intrinsic factor (IF)
secreted by gastric parietal cells.
Receptors for the IF-B12 complex are present in the membrane of epithelial
cells of the terminal ileum, which bind the complex and allow uptake of
vitamin B12 across the apical membrane by endocytosis. Vitamin B12 is then
transported across the basal membrane into the portal blood where it is
bound to transcobalamin II and processed by the liver.
In pernicious anaemia, there are autoantibodies against gastric parietal cells
and intrinsic factor, resulting in vitamin B12 deficiency anaemia.

Vitamins LAST UPDATED: 21ST
APRIL 2019
Vitamins are classified as fat soluble or water soluble. Vitamins A, D, E and K

are fat soluble, the other vitamins (B and C) are water soluble .
Absorption of fat-soluble vitamins is dependent upon absorption of dietary
fat, and they are stored in fatty tissue in the body, mainly in the liver. Sources
of fat-soluble vitamins include meat, fish and vegetable oil.
The water-soluble vitamins are mainly absorbed by diffusion or mediated
transport (other than vitamin B12). Body stores of water-soluble vitamins
(other than vitamin B12) are smaller than the stores of fat-soluble vitamins.
Sources of water-soluble vitamins include milk, meat, fruit and vegetables.
Clinical effects of vitamin deficiency include:
Vitamin C deficiency - Scurvy
Thiamine (Vitamin B1) deficiency - Beriberi/Wernicke-Korsakoff
syndrome
Vitamin B12 deficiency - Megaloblastic anaemia/Subacute combined
degeneration of spinal cord
Folate (B9) deficiency - Megaloblastic anaemia
Vitamin D deficiency - Osteomalacia/Rickets
Vitamin K deficiency - Defective clotting
Vitamin A deficiency - Blindness

Something wrong?
Function of Large Intestine LAST UPDATED: 21ST

APRIL 2019
LARGE INTESTINE  Bookmark
The large intestine extends from the ileocaecal valve to the anus.
Ileocecal Valve
Approximately 1.5 L of chyme enters the large intestine per day through the
ileocaecal sphincter. Distension of the terminal ileum results in the opening of
the ileocaecal sphincter and distension of the caecum causes it to close allowing
regulation of flow into the colon to maximise the function of the large intestine,
which is to concentrate faeces by absorbing water and electrolytes. The initial
1.5 L is reduced to about 150 g of faeces consisting of 100 mL of water and 50 g
of solids.
Functional Role of Taenia Coli

The muscle layers of the large intestine are slightly different from those found in
the rest of the GI tract. It still has a powerful circular muscle layer but the
longitudinal smooth muscle layer is concentrated into three bands called the
teniae coli. These bands are shorter than the circular muscle layer and gather the
caecum and colon into a series of pouch-like folds called haustra.
The caecum and ascending and transverse colon are innervated by
parasympathetic branches of the vagus nerve; the descending and sigmoid
colon, rectum and anal canal are innervated by parasympathetic branches of the
pelvic splanchnic nerves. These parasympathetic fibres innervate intramural
plexuses. The sympathetic nerves via the superior mesenteric plexus, and via the
inferior mesenteric and superior hypogastric plexuses, innervate the proximal
and distal parts of the large intestine respectively.
FUNCTIONAL ANATOMY OF THE LARGE INTESTINE. (IMAGE BY UNKNOWN [PUBLIC
Handling of Chyme
Movement of chyme through the large intestine involves both mixing (via
haustral segmental contractions) and propulsion (via peristalsis). Haustration
aids the exposure of chyme to the mucosal surface and helps the reabsorption
of water and electrolytes. Chyme usually remains in the colon for up to 20 h.
Parasympathetic stimulation causes segmental contraction whereas stimulation
of sympathetic fibres stops colonic activity.
Water Absorption
The chyme that initially enters the large intestine is isotonic, however in the
colon, more water than electrolytes is absorbed, and the fluid becomes
hypertonic, leading to water being absorbed against a concentration gradient.
The process of water absorption is controlled by Na+/K+ ATPases located in the

basolateral and lateral membranes of the epithelial cells. Na+ is pumped into
extracellular spaces and tight junctions at the luminal membrane prevent the
diffusion of Na+ and Cl- back from the extracellular space into the lumen. This
leaves a hypertonic solution close to the lumen, causing water to follow by
osmosis.
The electrolytes are absorbed by a variety of mechanisms (similar to those of the
small intestine), with essentially a net movement of K+ and HCO3- into the lumen
of the large intestine, because of the potential difference set up by the
asymmetrical absorption of Na+ and Cl- across the epithelium.
Intestinal Flora
Commensal intestinal bacterial flora have a role in:
Keeping pathogenic bacteria at bay by competing for space and nutrient
Converting conjugated bilirubin to urobilinogen (some of which is
reabsorbed and excreted in urine) and stercobilinogen which is excreted in
the faeces
The synthesis of vitamins K, B12, thiamine and riboflavin
The breakdown of primary bile acids to secondary bile acids
The breakdown of cholesterol, some food additives and drugs

Something wrong?
Defecation Reflex LAST UPDATED: 8TH

NOVEMBER 2021
LARGE INTESTINE  Bookmark
Colonic Mass Movement

Colonic mass movement describes the intense contraction that begins halfway
along the transverse colon and pushes the intestinal contents in the proximal
colon towards the rectum. It occurs shortly after a meal due to distension of the
stomach and duodenum as part of the gastrocolic reflex and if faeces is present
in the rectum, stimulates the urge to defecate.
Defecation Reflex
The internal and external anal sphincters usually keep the anal canal closed and
are controlled both reflexly and voluntarily. The internal sphincter is made up of
circular smooth muscle innervated by the autonomic fibres, and the more distal
external sphincter is composed of striated muscle innervated by motor fibres
from the pudendal nerve.
When a critical mass of faeces is forced into the rectum, the desire for
defaecation is experienced.
Distention of the rectum causes firing of afferent cholinergic parasympathetic
fibres which are transmitted to spinal control centres resulting in contraction of
the rectum, relaxation of the internal anal sphincter and initially contraction of
the external anal sphincter. This initial contraction is soon followed by a reflex
relaxation of the external sphincter initiated by an increase in the peristaltic
activity in the sigmoid colon and pressure in the rectum.
This reflex relaxation of the external anal sphincter can be overridden by higher
brain centre activity, leading to voluntary control over the sphincter which can
delay the expulsion of faeces. The prolonged distension of the rectum then leads
to a reverse peristalsis, which empties the rectum into the colon and removes
the urge to defecate until the next mass movement and/or a more convenient
time.
When a person decides to defecate i.e. when the external sphincter is voluntarily
relaxed, an increase in intra-abdominal pressure must be achieved to expel
faeces. Thus a breath is taken in and the glottis closes over the trachea, the
respiratory muscles contract on lungs filled with air and the abdominal muscles
contract which increases both the intrathoracic and intra-abdominal pressures,
the pelvic floor muscles relax which straightens the rectum and faeces can be
expelled.

Something wrong?
Overview of Nephron LAST UPDATED: 21ST

APRIL 2019
PHYSIOLOGY / RENAL / FUNCTIONAL ANATOMY
 Bookmark
Each kidney has about 800,000 nephrons, the functional unit of the kidney.
There are two types of nephrons, cortical nephrons (85% of nephrons) and
juxtamedullary nephrons (15% of nephrons).
Functional Anatomy
Each nephron consists of a renal corpuscle (Bowman's capsule and glomerulus)
and a tubule (proximal tubule, loop of Henle, distal tubule and collecting duct):
Cortical nephrons have their renal corpuscles in the outer part of the
cortex and relatively short loops of Henle.
Juxtamedullary nephrons have their corpuscles in the inner third of the
cortex, close to the corticomedullary junction, with long loops of Henle
extending into the renal medulla.
The glomerulus is formed by the invagination of a ball of capillaries into the
Bowman's capsule, the blind end of the nephron.
The convoluted proximal tubule continues from the renal corpuscle and
straightens before becoming the loop of Henle.
The distal tubule is the continuation of the loop of Henle, ending in the collecting
ducts.
The collecting ducts empty into papillary ducts at the apices of the renal
pyramids.
Functions
Main functions:
Glomerulus: Filtration
Proximal tubule: Reabsorption
Loop of Henle: Urine concentration
Distal tubule and collecting duct: Water homeostasis and acid-base
balance
OVERVIEW OF THE NEPHRON. (IMAGE BY HOLLY FISCHER [CC BY 3.0


The juxtaglomerular apparatus (JGA) is located where the renal tubule passes back up into the
cortex and lies adjacent to the renal corpuscle and arterioles of its own nephron.
Cell Types
The juxtaglomerular apparatus consists of three main cell types:
Juxtaglomerular (granular) cells
Macula densa tubular cells
Extraglomerular mesangial cells
Juxtaglomerular cells are specialised smooth muscle cells found mainly in the walls of the afferent
arterioles which synthesise renin.
The macula densa is an area of specialised columnar tubular epithelial cells located at the junction
of the thick ascending limb of the loop of Henle and the early distal tubule which senses and
responds to changes in tubular ion concentration (particularly changes in the concentration of
Na+ ions).
Contractile extraglomerular mesangial cells are found outside the glomerulus in association with
the JGA. Their role is uncertain.
JUXTAGLOMERULAR APPARATUS. (IMAGE BY MKOMORNICZAK -TALK- (POLISH WIKIPEDIST) [CC BY-SA 3.0
The kidneys receive about 20% of total cardiac output ( ~1 L/min).
Functional Anatomy
The renal artery enters via the hilus and divides into two or three segmental arteries which
further divide into interlobar arteries running between the renal pyramids to the
corticomedullary border, where they split into arcuate arteries. The arcuate arteries curve
parallel to the outer surface of the kidney and give rise to the interlobular arteries which
ascend into the cortex and feed the afferent arterioles of the glomerulus. The capillaries of the
glomerulus are the site of filtration, and drain into the efferent arteriole. Afferent and efferent
arterioles provide the major resistance to renal blood flow.
In the outer two-thirds of the cortex, the efferent arterioles branch into a network of
peritubular capillaries which supply all cortical parts of the nephrons. Capillaries close the
corticomedullary border in the inner third of the cortex, loop into the medulla to form the vasa
recta surrounding the loop of Henle. The vasa recta and peritubular capillaries drain into the
renal veins.
STRUCTURAL ARRANGEMENT OF THE RENAL BLOOD SUPPLY. (IMAGE BY OPENSTAX COLLEGE [CC BY
Regulation of Renal Blood Flow
Autoregulation
The myogenic mechanism: where an increase in intravascular pressure stimulates
stretch receptors in the vessel wall causing a reflex smooth muscle contraction
and hence vessel vasoconstriction and reduced flow.
The tubuloglomerular feedback mechanism: where an increase in tubular flow rate
(with a resultant increase in tubular NaCl concentration detected by the macula
densa) causes the juxtaglomerular apparatus to release adenosine which
produces afferent arteriolar vasoconstriction and reduces GFR.
Renin-Angiotensin II system
The juxtaglomerular apparatus releases renin in response to a drop in afferent
arteriolar pressure, a fall in tubular flow rate, or a fall in tubular NaCl concentration
at the macula densa.
Other stimuli include sympathetic nerve stimulation of beta1-adrenergic
receptors on granular cells and a fall in angiotensin II levels.
Renin promotes the production of angiotensin II which acts to vasoconstrict
afferent and efferent arterioles (the dominant effect is on efferent arteriolar
constriction so the GFR is increased).
Prostaglandins
Many peripheral vasoconstrictors stimulate the renal production of vasodilating
prostaglandins such as PGE2 and PGI2 (prostacyclin) which protect the kidney
from severe vasoconstriction.
Vasoactive peptides
Bradykinin, released in the distal tubule and glomerulus, promotes prostaglandin
synthesis and vasodilation.
Natriuretic peptides, released from cardiac cells, produce systemic vasodilation.
Endothelin, produced in renal vascular endothelial cells and tubules, is a potent
vasoconstrictor.
Vasopressin (ADH) promotes vasoconstriction and antidiuretic action.
Adrenomedullin promotes renal vasodilation and is produced in the kidney.
Other regulatory pathways
Renal nerves contain sympathetic neurons which release noradrenaline which
causes constriction of both afferent and efferent arterioles and promotes renin
release.
Dopamine at low doses has a vasodilatory effect. At higher concentrations
dopamine causes renal vasoconstriction and promotes renin release.
Nitric oxide is a potent vasodilator that is synthesised in the macula densa,
endothelium and mesangial cells and upregulated in response to mechanical
shear stress.
Vasodilators Vasoconstrictors
Prostaglandins Angiotensin II
Nitric oxide Endothelin
Bradykinin Vasopressin
Low-dose dopamine Noradrenaline

PHYSIOLOGY / RENAL / FUNCTIONAL ANATOMY LAST UPDATED: 21ST APRIL
2019
 Bookmark
Macroscopic Structure of the Kidney

Each kidney is surrounded by a fibrous renal capsule. Internally each kidney is divided into two main
layers, the dark outer renal cortex and the inner lighter renal medulla made up of the renal
pyramids. The cortex contains the glomerulus and proximal and distal tubules of the nephrons,
whilst the loop of Henle and collecting ducts descend into the medulla.
The renal vessels, lymphatics and nerves enter the medial border of the kidney via the hilum.
The ureters arise from the renal pelvis and emerge from the hilum before continuing to the bladder.
Within the kidney, the outer border of the renal pelvis divides into two or three major calyces, each
of which further subdivide into minor calyces, which are each indented by a renal papilla, the apex
of the medullary pyramid, and it is here that the collecting ducts of the renal nephron empty the
urine.
MACROSCOPIC STRUCTURE OF THE KIDNEY. (IMAGE BY OPENSTAX COLLEGE [CC BY 3.0

Functions of the Kidney
The kidney is important for the following actions:
Excretion of waste products and drugs in urine
Regulation of body fluid and ionic composition
Regulation of acid-base balance
Metabolism of certain proteins e.g. insulin, PTH and calcitonin
Hormone production
Renin
Activated vitamin D
Erythropoietin
Prostaglandins

Something wrong?
Renal Handling of Water LAST UPDATED: 21ST

APRIL 2019
and Urea  Bookmark
PHYSIOLOGY / RENAL /
MECHANISM OF FILTRATION
Renal Handling of Water

The kidney regulates body water and sodium content in parallel to maintain
body volume and osmolality (normally 285 - 295 mOsmol/kg).
In the glomerulus, water and ions are freely filtered. As the filtrate moves
along the tubules, ions are reabsorbed and water follows by osmosis. Water
reabsorption is influenced by the water permeability of the tubular
epithelium and the osmotic gradient across the epithelium.
Proximal tubule:
The proximal tubule is highly water permeability and about 65% of filtered
water is reabsorbed here by osmosis, following the reabsorption of ions.
Loop of Henle:
In the loop of Henle, the descending limb is permeable to water, but not
ions, whereas the ascending limb is permeable to ions but not water.
Sodium and chloride are transported out of the thick ascending limb into
the medullary interstitium. This raises the osmolality of the interstitium
which promotes water movement out of the descending limb. Within the
loop, the transport of water and ions is separated with reabsorption of
about 25% of filtered sodium and chloride but only 10% of filtered water,
producing a dilute urine and a hypertonic medullary interstitium.
Distal tubule:
The distal convoluted tubule has low water permeability and does not
reabsorb water. However, reabsorption of ions further dilutes the tubular
fluid.
Collecting ducts:
The hypotonic urine passes down the collecting ducts, where water
permeability is controlled by antidiuretic hormone (ADH).
Role of Urea
Urea is freely filtered at the glomerulus. In the proximal tubule, about 50%
of the filtered urea is reabsorbed passively, mainly through paracellular
routes.
Urea is secreted into the ascending limb from the medullary interstitium
down its concentration gradient, increasing tubular urea concentration.
The distal tubule, cortical collecting ducts and the outer medullary ducts
are impermeable to urea. As it continues along the nephron, tubular urea
therefore becomes more concentrated as further solutes and water are
reabsorbed, and thus in the inner medullary collecting ducts (which are
permeable to urea), urea is passively reabsorbed by urea transporters
(activated by ADH) into the medullary interstitium.
The recycling of urea between the medullary collecting ducts and the
ascending limb plays an important role in the creation of a hypertonic
medullary interstitium, accounting for about half of the medullary
interstitial osmolality that drives water reabsorption from the descending
limb and medullary collecting duct. ADH increases the permeability of the
inner medullary collecting ducts to urea, further increasing the medullary
osmolality and allowing further concentration of urine.

Sodium Handling LAST UPDATED: 21ST
APRIL 2019
PHYSIOLOGY / RENAL / MECHANISM OF FILTRATION
 Bookmark
Sodium is the major extracellular cation and its concentration is tightly controlled.
Na+ is freely filtered at the glomerulus, a large amount is absorbed in the proximal
tubules and the loop of Henle, and the little that is left is reabsorbed in a precisely
regulated manner by the distal tubules and collecting ducts to maintain accurate
salt balance.
The basolateral membranes of the tubular cells contain Na +/K+ ATPases that
actively pump sodium into the peritubular interstitial fluid. From here, sodium ions
pass freely into the blood. The continual pumping of sodium out of the cells and
its subsequent removal by the blood creates a Na+ gradient between the tubular
filtrate and the cell cytoplasm. This gradient allows Na+ from the filtrate to enter
the cells passively at their apical membrane, provided that suitable channels or
transporters are present.
Sodium Handling in the Proximal Tubule

Of the filtered sodium, about 65% is reabsorbed in the proximal tubule.
In the early tubule, the sodium gradient drives the cotransport of sodium with
bicarbonate, amino acids, glucose or other organic molecules. The
Na+/H+ exchanger uses the sodium gradient to drive sodium reabsorption from
the filtrate and H+ secretion into the filtrate. As carbonic anhydrase is present in
the cell cytoplasm and tubular lumen, the secretion of H+ is equivalent to the
reabsorption of bicarbonate. The apical secretion of H+ is balanced by the
basolateral exit of bicarbonate with sodium.
Chloride concentration rises along the proximal tubule. When the positively
charged sodium ions leave the lumen with neutral organic molecules, the lumen
is left with a negative charge. This repels negatively charged chloride ions which
leave the lumen through the paracellular route between cells. By the time the
filtrate reaches the late proximal tubule, most organic molecules and bicarbonate
Sodium
have alreadyHandling in the
been removed andLoop
sodiumofions
Henle
are reabsorbed mainly with chloride
ions.
About 25% of filtered sodium is reabsorbed in the the loop of Henle.
The thin descending limb is permeable to water but not to sodium, so water
leaves the tubule passively to enter the hypertonic medullary interstitium. In
contrast, the thin ascending limb is permeable to sodium but not to water and as
there is a high tubular concentration of NaCl, both ions diffuse out.
In the thick ascending limb, the Na +/K+/2Cl- cotransporter uses the sodium
gradient to actively reabsorb one sodium, one potassium and two chloride ions.
As the potassium ions can re-enter the tubule via an ROMK channel, the net
effect is the removal of one sodium and two chloride ions, leaving the tubular
lumen positively charged. This positive potential drives the paracellular transport
of positively charged ions, including sodium, potassium, calcium, magnesium and
ammonium.
Sodium Handling in the Distal Nephron

The early distal tubule reabsorbs a further 5% of the filtered sodium, mainly via
the Na+/Cl- symporter. As the fluid in the lumen in this portion of the nephron is
negative, there is also some paracellular movement of negatively charged
chloride ions.
About 2 - 5% of filtered sodium is reabsorbed in the late distal tubule and
collecting ducts. Sodium reabsorption by principal cells and chloride reabsorption
by intercalated cells are the final stages in sodium chloride reabsorption before
urine leaves the kidney.

Proximal Tubule LAST UPDATED: 21ST
APRIL 2019
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The proximal tubule continues from the renal corpuscle. The wall of the proximal
tubule is composed of a single layer of columnar epithelial cells which
interdigitate extensively at the basal surface increasing their surface area and are
connected by tight junctions at their luminal surface limiting diffusion through
gaps between cells. The luminal surface of each cell is made up of millions of
microvilli, forming a dense brush border that increases the surface area available
for reabsorption of tubular filtrate.
The main function of the proximal tubule is reabsorption. The proximal tubule
reabsorbs most glucose, amino acids, phosphate and bicarbonate together with
about 60 - 70% of filtered Na+, K+, Ca2+, Cl-, urea and water.
Sodium
The concentration of Na+ in the filtrate is ~ 140 mmol/L, but is much lower in the
cytosol of epithelial cells, which is also negatively charged. Tubular Na+ is thus
absorbed into the epithelial cells of the proximal tubule down its electrochemical
gradient, providing the driving force for the secondary transport of other
substances. About 80% of the Na+ is reabsorbed via the Na +/H+ antiporter (this
secretion of H+ is critical for HCO3- reabsorption) and some is coupled with the
transport of other substances e.g. glucose, amino acids and phosphate ions.
Na+ is removed from tubular cells into the interstitial fluid by Na +/K+ ATPase
pumps on the basolateral membrane, thus maintaining the electrochemical
gradient for reabsorption of further Na+. However only about 20% of transported
Na+ diffuses into the capillaries, as there is a significant back flux into the tubule
via paracellular pathways.
Water
Water is reabsorbed by osmosis via both transcellular and paracellular pathways,
following absorption of Na+ and HCO3- as the osmolality of the peritubular
interstitial fluid increases and the osmolality of the tubular fluid decreases. The
reabsorption of water increases tubular concentration of Cl-, K+, Ca2+ and urea
which are therefore reabsorbed into the peritubular space passively down their
concentration gradients, largely via paracellular pathways, although the route for
Ca2+ may be transcellular.
Glucose
Glucose is reabsorbed by cotransport with Na+ across the apical membrane of

epithelial cells and then diffuses out of the cells into the peritubular interstitium.
FUNCTION OF THE PROXIMAL TUBULE. (IMAGE BY OPENSTAX COLLEGE [CC BY 3.0

The loop of Henle consists of a single layer of flattened squamous cells (transitioning to
columnar cells in the thick ascending segment), which form a thin-walled hairpin-shaped
tube. At the point at which the loop associates with the juxtaglomerular apparatus after re-
entering the cortex, the wall is formed from modified macula densa cells.
About 25% of filtered Na+ and Cl-, and 15% of filtered water and cations such as K+, Ca2+,
Mg2+ are reabsorbed in the loop of Henle.
The generation of high osmolality in the medulla depends on the differential permeabilities
to water and solutes in different regions, the active transport of ions in the thick ascending
limb and the countercurrent multiplier. Tubular fluid is isotonic with plasma when it enters
the loop of Henle, hypertonic at the tip of the hairpin (where it reaches equilibrium with the
hypertonic interstitial fluid), and hypotonic when it leaves to enter the distal nephron.
Differential Permeabilities to Water and Solutes in Different Regions

The thin descending limb of the loop of Henle is permeable to water and impermeable
to NaCl and urea.
The thin ascending limb is impermeable to water, but highly permeable to urea and
NaCl.
The thick ascending limb is impermeable to water and actively reabsorbs NaCl from
tubular fluid.
PERMEABILITIES OF THE LOOP OF HENLE. (IMAGE BY OPENSTAX COLLEGE [CC BY 3.0
Active Transport of Ions in the Thick Ascending Limb
In the thick ascending limb, Na+ and Cl- ions are actively reabsorbed from the tubular fluid
via the Na+/K+/2Cl- symporter on the apical membrane. The Na + ions are primarily
transported across the basolateral membrane by Na+ pumps and the Cl- ions by diffusion. K+
leaks back into the tubular fluid via apical ROMK K+ channels creating a positive charge that
drives the reabsorption of cations (Na+, K+, Ca2+, Mg2+) through paracellular pathways. As
the thick ascending limb is impermeable to water, the reabsorption of ions reduces the
tubular fluid osmolality, and increases the interstitial fluid osmolality, creating an osmotic
difference.
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Distal Collecting System LAST UPDATED: 21ST

APRIL 2019
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The distal nephron consists of the late distal tubule and the collecting ducts.
The distal tubule is functionally similar to the cortical collecting ducts. Both
contain principal cells which respond to antidiuretic hormone (ADH) and
intercalated cells which secrete H+ ions (involved in acid-base balance).
About 7% of filtered NaCl and about 8 - 17% of water is reabsorbed in the distal
tubule and collecting duct.
Water Permeability
Fluid entering the distal tubule is hypotonic. More Na+ is reabsorbed in
principal cells via the Na+ channel ENaC which is inhibited by atrial natriuretic
peptide (ANP); expression of ENaC and thus Na+ reabsorption is increased by
aldosterone. The movement of Na+ through ENaC is charge compensated by
the opposite movement (secretion) of K+ through ROMK channels.
The distal tubule and cortical collecting duct are impermeable to water except
in the presence of antidiuretic hormone (ADH), which causes water channels
(aquaporins) to insert into the apical membrane. In the presence of ADH, water
diffuses into the cortical interstitium, and the tubular fluid becomes more
concentrated. The fluid differs from plasma as large quantities of Na+, K+, Cl-
and HCO3- have been reabsorbed, their place having been taken by urea. This
is concentrated as water is reabsorbed, because the distal tubule and cortical
collecting duct are impermeable to urea.
The medullary collecting duct also becomes permeable to water in the

presence of ADH. Water is reabsorbed due to the high osmolality of the
medullary interstitium. Although only 15% of nephrons have loops of Henle that
pass deep into the medulla and so contribute to the high medullary osmolality,
the collecting ducts of all nephrons pass through the medulla and therefore
concentrate urine.
Urea
The medullary collecting duct is relatively permeable to urea, which diffuses
down its concentration gradient into the medulla and then into the ascending
loop of Henle. Urea is therefore 'trapped' and partially recycled, so maintaining
a high concentration and providing ~50% of the osmolality in the medulla. ADH
increases the permeability of the medullary collecting duct to urea and hence
its reabsorption by activating epithelial uniporters; this further increases the
medullary osmolality and allows the production of more concentrated urine.
Potassium
Potassium has been largely reabsorbed by the time the distal tubule is
reached, and so excretion is regulated by secretion in the late distal tubule. K+
is actively transported into principal cells by basolateral Na+ pumps and
passively secreted via ROMK channels and K+/Cl- cotransport; the former is
promoted by the negative luminal charge caused by reabsorption of Na+
through ENaC. Secretion is therefore driven by the concentration gradient
between the cytosol and tubular fluid. However, secreted K+ will reduce the
gradient unless it is washed away and so K+ excretion is increased as tubular
flow increases; diuretics therefore often lead to K+ loss. K+ secretion is
increased by aldosterone which enhances Na+ pump activity and apical
membrane K+ permeability. Perturbations of K+ homeostasis are often
associated with acid-base disorders.
Calcium
Calcium reabsorption in the distal tubule is regulated by parathyroid hormone
and activated vitamin D.
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Glomerular Filtration Rate LAST UPDATED: 21ST

APRIL 2019
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Glomerular Filtration Rate

The glomerular filtration rate (GFR) is the amount of ultrafiltrate produced from
plasma flowing through the glomerulus per unit time.
The normal glomerular filtration rate is about 120 mL/min. The total amount
filtered per day is about 180 L/day.
The normal renal plasma flow (RPF) is about 600 mL/min.
Therefore the filtration fraction (FF = GFR/RPF), the proportion of plasma that
is filtered, is about 20%.
Factors Determining the GFR

The GFR is dependent on the difference between the hydrostatic and oncotic
pressures in the glomerular capillaries and Bowman's capsule, as determined
by Starling's equation.
The glomerular capillary pressure is greater than that elsewhere (~45 mmHg)
because of the unique arrangement of afferent and efferent arterioles, with low
afferent but high efferent resistances. As the pressure in the Bowman's
capsule is ~10 mmHg, the net hydrostatic force driving filtration is ~35 mmHg.
This is opposed by the oncotic pressure of capillary plasma (~25 mmHg); the
filtrate oncotic pressure is essentially zero (no protein).
Therefore, GFR = [Glomerular capillary hydrostatic pressure (Pc) - Bowman's
capsule hydrostatic pressure (Pb)] - Capillary oncotic pressure (?c) = 35 mmHg
- 25 mmHg = 10 mmHg
It should be noted that as fluid is filtered and plasma proteins are not filtered,
the oncotic pressure in the capillary will rise as blood traverses the glomerulus,
reducing (but not abolishing) filtration. It is this raised oncotic pressure
(together with a relatively low hydrostatic pressure) that promotes
reabsorption in the peritubular and vasa recta capillaries.
FACTORS DETERMINING THE GLOMERULAR FILTRATION RATE. (IMAGE BY OPENSTAX

COLLEGE [CC BY 3.0 (HTTP://CREATIVECOMMONS.ORG/LICENSES/BY/3.0)], VIA
WIKIMEDIA COMMONS)
Regulation of Glomerular Filtration Rate

Glomerular capillary hydrostatic pressure and thus GFR is strongly dependent
on the relative resistance of the afferent and efferent arterioles. High pressure
Structure of the Glomerulus
The glomerulus is a ball of capillaries surrounded by the Bowman's capsule.
The glomerulus is interspersed with mesangial cells which act to:
provide structural support for the capillaries
exhibit phagocytic activity
secrete extracellular matrix
secrete prostaglandins
help regulate blood flow through the glomerular capillaries through their
contractile activity
STRUCTURE OF THE GLOMERULUS. (IMAGE BY OPENSTAX COLLEGE [CC BY 3.0

Glomerular Filtration Barrier
Plasma is selectively filtered through the glomerular capillary wall into the Bowman's
capsule. The solution that arrives in the Bowman's capsule is called ultrafiltrate
which then passes into the proximal tubule.
Selective filtration is dependent on the filtration barrier, which has three main layers:
1. The glomerular capillary endothelium

Perforated by pores (fenestrations) which allow plasma components
with a molecular weight of < 7000 Da to pass freely.
2. A specialised capillary basement membrane

Layer of connective tissue containing negatively charged
glycoproteins, thought to be the main site of ultrafiltration.
3. Modified epithelial lining of the Bowman's capsule

Single layer of specialised cells called podocytes which have long
extensions that engulf the capillaries and numerous foot-like
processes (pedicels) directly contacting the basement membrane. The
regular gaps between pedicles are called filtration slits. Across these
slits, a protein network forms slit pores in the epithelial lining which
prevent the passage of larger molecules through this final layer.
Podocytes maintain the basement membrane and, like mesangial cells,
may be phagocytic and partially contractile.
GLOMERULAR FILTRATION BARRIER. (IMAGE MODIFIED BY FRCEM SUCCESS. ORIGINAL
IMAGE BY MKOMORNICZAK [CC BY-SA 3.0 (HTTP://CREATIVECOMMONS.ORG/LICENSES/BY-
SA/3.0)], VIA WIKIMEDIA COMMONS)
Factors affecting Permeability of the Filtration Barrier

Molecular weight is the main factor in determining whether a substance is filtered or
not - molecules < 7000 Da in molecular weight pass freely e.g. glucose, amino acids,
urea, ions but larger molecules are increasingly restricted up to 70 kDa, above which
filtration is insignificant.
Negatively charged molecules are further restricted, as they are repelled by negative
charges, particularly in the basement membrane. Albumin has a molecular weight of
69 kDa and is negatively charged, thus only very small amounts are filtered (and all of
the filtered albumin is reabsorbed in the proximal tubule), whereas small molecules
such as ions, glucose, amino acids and urea pass the filter without hindrance. This
means that ultrafiltrate is virtually protein free, but otherwise has an identical
composition of that of plasma.
Creatinine Clearance LAST UPDATED: 10TH
MARCH 2019
MECHANISM OF FILTRATION  Bookmark
Clearance is defined as the volume of plasma that is cleared of a substance

per unit time.
Clearance of substance = (Urine concentration of substance x Urine flow
rate)/Plasma concentration of substance.
Clearance of a substance can provide an accurate estimate of the glomerular
filtration rate (GFR) provided that the substance is:
1. freely filtered
2. not reabsorbed in the nephron
3. not secreted in the nephron
4. not synthesised or metabolised by the kidney
Inulin is such a substance but measurement of inulin clearance is

complicated and not used in routine clinical practice.
Creatinine (which is steadily released from skeletal muscle) clearance can be
used because it is freely filtered and not reabsorbed, and there is very little
secretion, allowing relatively accurate approximation of the GFR (except when
plasma creatinine or GFR is abnormally low).
In practice, GFR is usually estimated from the plasma creatinine using a
formula e.g. the MDRD equation making an adjustment for age, sex and race.

Physiology Renal
Mechanism of Filtration
Something wrong?
Renal Tubular Transport LAST UPDATED: 2ND

MAY 2019
Modes of Tubular Transport

Reabsorption and secretion involves the transport of substances across the
tubular epithelium; this occurs either by diffusion through tight junctions and
lateral intercellular spaces (paracellular pathway), driven by concentration,
osmotic or electrical gradients, or by transport through the epithelial cells
themselves (transcellular pathway).
The latter usually involves an active process on either the apical or basolateral
cell membrane, with passive diffusion across the opposite membrane driven
by the concentration gradient so created.
The movement of solutes between the peritubular space and capillaries is by
bulk flow and diffusion; the movement of water is influenced by Starling's
forces.
Active transport involves transporter proteins, and may be primary (which
uses ATP directly as an energy source) or secondary (which uses the
concentration gradient created by primary active transport as an energy
source)
The rate of diffusion across cell membranes is enhanced by ion channels and
uniporters which effectively increase membrane permeability to specific
substances; this is termed facilitated diffusion, and may be modulated by
hormones or drugs.
Maximal Tubular Transport

There is a limit to the rate at which any transporter can operate and so for any
substance, there is a maximum rate of absorption or secretion, called the
tubular transport maximum (Tm).
Glucose is normally completely reabsorbed in the proximal tubule via
secondary active transport by the Na+/glucose symporter and none excreted
in the urine. However, when filtrate glucose concentration rises above the
renal threshold concentration, the transporters start to saturate and glucose
appears in the urine. Once tubular maximum transport is reached, excretion
increases linearly with filtration. The threshold concentration for glucose (~ 11
mmol/L) is somewhat lower than that required to reach tubular transport
maximum (~21 mmol/L) because of the variation in transport maxima between
nephrons; this is called splay.

Physiology Renal
Mechanism of Filtration
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Renin-Angiotensin- LAST UPDATED: 21ST

APRIL 2019
Aldosterone System  Bookmark
MECHANISM OF FILTRATION
As plasma osmolality is strongly regulated by the osmoreceptors and ADH,

changes in the major osmotic component of extracellular fluid, i.e. Na+, will
result in changes in extracellular volume. The control of total body
Na+ content by the kidney is therefore the main regulator of body fluid volume.
Sensing Blood Volume

Atrial and other cardiopulmonary stretch receptors detect a fall in central
venous pressure (CVP) which reflects the blood volume. A fall in blood volume
sufficient to reduce the blood pressure activates the baroreceptor reflex.
In both cases, increased sympathetic stimulation causes:
peripheral vasoconstriction increasing the total peripheral resistance
renal vasoconstriction decreasing the GFR
stimulation of ADH release increasing water reabsorption
stimulation of granular cells to release renin
Renin
Renin is produced by granular cells of the juxtaglomerular apparatus and
released in response to:
A fall in extracellular fluid volume, central venous pressure or arterial
blood pressure
Decreased perfusion pressure and thus wall tension in the renal afferent
arterioles
Decreased tubular NaCl concentration detected by the cells of the
macula densa
A reduced glomerular filtration rate (GFR)
Renin cleaves plasma angiotensinogen (produced in the liver) into angiotensin

I. Angiotensin I is converted by angiotensin-converting enzyme (ACE) on
pulmonary endothelial cells to angiotensin II.
Angiotensin II
Angiotensin II is the primary hormone for Na+ homeostasis and has several
important functions.
Angiotensin II acts to:
Stimulate release of aldosterone from the zona glomerulosa of the
adrenal cortex (which in turn acts to increase sodium reabsorption)
Cause systemic vasoconstriction
Cause vasoconstriction of the renal arterioles (predominant efferent
effect thus intraglomerular pressure is stable or increased, thereby
tending to maintain or even raise the GFR)
Directly increase Na+ reabsorption from the proximal tubule (by
activating Na+/H+ antiporters)
Stimulate synthesis and release of ADH from the hypothalamus and
posterior pituitary respectively
Stimulate the sensation of thirst
Potentiate sympathetic activity (positive feedback)
Inhibit renin production by granular cells (negative feedback)
Aldosterone
Aldosterone acts mainly at the renal distal convoluted tubule (DCT) to cause
sodium retention and potassium loss. It increases the synthesis of transport
mechanisms in the distal nephron including the Na+ pump, Na+/H+ symporter,
and Na+ and K+ channels in principal cells, and H+ ATPase in intercalated
cells. Na+ (and thus water) reabsorption and K + and H+ secretion are thereby
enhanced.
RENIN-ANGIOTENSIN-ALDOSTERONE SYSTEM. (IMAGE BY A. RAD (OWN WORK) CC-

BY-SA-3.0 (HTTP://CREATIVECOMMONS.ORG/LICENSES/BY-SA/3.0/)], VIA
WIKIMEDIA COMMONS)

Atrial Natriuretic Peptide LAST UPDATED: 21ST
APRIL 2019
Atrial natriuretic peptide (ANP) is released from cardiac atrial muscle cells in
response to atrial stretch caused by an increase in intravascular fluid volume
and is also produced in collecting duct cells.
Function
ANP acts to:
Inhibit Na+ reabsorption in the distal nephron (through inhibition of
ENaC in principal cells)
Suppress the production of renin
Suppress the production of aldosterone
Suppress the production of ADH
Cause renal vasodilation, increasing the glomerular filtration rate
The net result is increased excretion of water and Na+ and hence reduced
blood volume.

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Diuretic Therapy LAST UPDATED: 21ST

APRIL 2019
 Bookmark
Loop Diuretics
Loop diuretics e.g. furosemide are the most potent diuretics.
They inhibit the Na+/K+/2Cl- symporter in the thick ascending limb of the loop of
Henle. This binding inhibits sodium, potassium, and chloride reabsorption, causing
diuresis with loss of these electrolytes. The transcellular voltage difference falls, and
paracellular calcium and magnesium reabsorption are also reduced.
Salt reabsorption in the ascending limb normally concentrates the medullary
interstitium, and by blocking this process, loop diuretics reduce the ability of the
kidney to concentrate urine. Increased sodium delivery to the principal cells in the
collecting duct increases potassium secretion in return for sodium reabsorption.
Thiazide Diuretics
Thiazide diuretics e.g. bendroflumethiazide inhibit the apical Na+/Cl- cotransporter

in the early distal tubule. More sodium is then delivered to the principal cells of the
collecting duct. Some of this excess sodium is exchanged for potassium, causing
hypokalaemia. Reduced sodium reabsorption lowers intracellular sodium
concentration, promoting basolateral sodium-calcium exchange and therefore
calcium reabsorption.
Osmotic Diuretics
Osmotic diuretics e.g. mannitol are filtered in the glomerulus and then cannot be
reabsorbed effectively. As the filtrate passes along the nephron, water is reabsorbed
and the concentration of the osmotic diuretic rises until its osmotic effect opposes
further water reabsorption. Sodium is then reabsorbed without water. Eventually
sodium reabsorption is also inhibited because the sodium gradient between filtrate
and plasma increases to the point at which sodium leaks back into the lumen.
Potassium-Sparing Diuretics
Aldosterone promotes sodium reabsorption and potassium secretion by increasing
transcription of the ENaC channel and the Na+/K+ ATPase. Aldosterone antagonists
e.g. spironolactone block aldosterone receptors so reducing Na+ reabsorption and
K+ secretion in the distal nephron.
Carbonic Anhydrase Inhibitors

Carbonic anhydrase inhibitors e.g. acetazolamide block the reaction of carbon
dioxide and water and so prevent Na+/H+ exchange and bicarbonate reabsorption.
The increased bicarbonate levels in the filtrate oppose water reabsorption. Proximal
tubule sodium reabsorption is also reduced because it is partly dependent on
bicarbonate reabsorption.

Potassium Handling LAST UPDATED: 21ST
APRIL 2019
PHYSIOLOGY / RENAL / POTASSIUM BALANCE
 Bookmark
Potassium is the major intracellular cation. The potassium concentration inside cells
is around 150 mmol/L, compared with around 4 mmol/L (3.0 - 4.5 mmol/L) in
extracellular fluid. The K+ gradient across the cell membrane largely determines the
electrical potential across that membrane. As this electrical potential influences the
electrical excitability of tissues such as nerves and muscles, including the cardiac
muscle, potassium levels must be precisely controlled within safe limits.
The average daily intake of potassium in the diet is around 40 - 120 mmol, but the
kidney filters around 800 mmol each day. To maintain potassium balance, the kidney
therefore excretes only 5 - 15% of the filtered potassium. Potassium is freely filtered
in the glomerulus, almost entirely reabsorbed before the filtrate reaches the
collecting tubules, and is then secreted into the collecting duct before being
excreted in urine.
Renal Potassium Handling
K+ is freely filtered at the glomerulus.

Proximal tubule:
Approximately 65 - 70% of filtered K+ is reabsorbed in the proximal tubule. Potassium

reabsorption is tightly linked to that of sodium and water. The reabsorption of sodium
drives that of water, which may carry some potassium with it. The potassium
gradient resulting from the reabsorption of water from the tubular lumen drives the
paracellular reabsorption of potassium and may be enhanced by the removal of
potassium from the paracellular space via the Na+/K+ ATPase pump. In the later
proximal tubule, the positive potential in the lumen also drives the potassium
reabsorption through the paracellular route.
Loop of Henle:
Some K+ moves into the filtrate in the thin descending limb of the loop of Henle, but
this is counterbalanced by movement of K+ out of the loop and into the medullary
collecting ducts. The net result is some recycling of this potassium across the
medullary interstitium. Around 30% of filtered K+ is reabsorbed in the thick
ascending limb of the loop of Henle, primarily via the luminal
Na+/K+/2Cl- cotransporter, but there is also significant paracellular reabsorption,
encouraged by the positive potential in the tubular lumen.
Distal tubule:
The distal tubule can reabsorb more potassium and 95% of filtered K+ is reabsorbed
in a sodium-dependent fashion before the filtrate reaches the collecting ducts.
Collecting tubule and ducts:
In the distal nephron, the principal cells secrete potassium, whereas the intercalated
cells reabsorb potassium; potassium secretion far outweighs its reabsorption in this
part of the nephron, and it is here that regulation of potassium excretion primarily
occurs (mainly as a result of changes in potassium secretion by the principal cells).
Reabsorption of K+ by intercalated cells is driven by the apical H+/K+ ATPase pump;

K+ leaves these cells through basolateral potassium channels.
Secretion of K+ by principal cells is driven by the basolateral Na+/K+ ATPase pump;

K+ is secreted into the lumen through apical K+ channels or via K+/Cl- cotransporters
down a concentration gradient. The negative potential in the tubular lumen due to
Na+ reabsorption also promotes K+ secretion (thus increased sodium reabsorption
promotes potassium secretion). As potassium secretion is occurring down a
concentration gradient, it can continue only if the concentration of potassium in the
filtrate is kept low, hence an increased tubular flow rate results in increased
K+ secretion and excretion (seen in hypokalaemia secondary to diuretic therapy).
Control of Renal Potassium Excretion
Aldosterone: A rise in [K+] in the extracellular fluid of the adrenal cortex

directly stimulates aldosterone release. Aldosterone promotes the synthesis of
Na+/K+ ATPases and the insertion of more Na+/K+ ATPases into the
basolateral membrane, and also stimulates apical sodium and potassium
channel activity, overall acting to increase sodium reabsorption and potassium
secretion.
pH changes: Potassium secretion is reduced in acute acidosis and increased in
acute alkalosis. A higher pH increases the apical K+ channel activity and the
basolateral Na+/K+ ATPase activity – both changes that promote K+ secretion.
Flow rates: Increased flow rates in the collecting duct reduce K+ concentration
in the lumen and therefore enhance K+ secretion. Increased flow also activates
BK potassium channels, and ENaC channels which promote potassium
secretion and sodium reabsorption respectively.
Sodium delivery: Decreased Na+ delivery to the collecting ducts results in less
Na+ reabsorption and hence a reduced gradient for K+ secretion.
ADH: ADH reduces urinary flow rates that would reduce potassium secretion,
however it also stimulates the apical potassium channel activity, which helps
maintain normal potassium secretion.
Magnesium: Intracellular magnesium can bind and block K+ channels inhibiting
K+ secretion into the tubules. Therefore magnesium deficiency reduces this
inhibitory effect and so allows more potassium to be secreted into tubules and
can cause hypokalaemia.

Hypokalaemia LAST UPDATED: 21ST
APRIL 2019
 Bookmark
RCEM defines normal values for total serum potassium as 3.0 - 4.5 mmol/L.
Causes
Causes of hypokalaemia can be divided into:
Increased loss
Renal loss:
Thiazide or loop diuretics
Renal tubular acidosis
Hypomagnesaemia
Hyperaldosteronism
Transporter mutations (rare)
Drugs such as penicillins, aminoglycosides, amphotericin
GI loss:
Diarrhoea, vomiting
Transcellular shift of K+ into cells
Metabolic alkalosis
Insulin excess or overdose
Catecholamines in acute stress e.g. acute MI
Beta-2 sympathomimetics
Decreased intake
Inadequate replacement whilst NBM or on TPN, malnutrition, anorexia
nervosa, hypocaloric diets
Clinical Features
Clinical features of hypokalaemia may include:
Asymptomatic
Muscle weakness
Muscle cramps, rhabdomyolysis and myoglobinuria
Ascending paralysis resulting in respiratory failure
Constipation
Gut ileus with distension, anorexia, nausea and vomiting
Impaired ADH action with polyuria and polydipsia
ECG changes and cardiac arrhythmias
ECG Changes
Hypokalaemia increases automaticity and delays repolarisation of cardiac cells. This
predisposes the heart to dysrhythmias such as ectopic beats, atrioventricular block
and atrial and ventricular fibrillation.
Classic ECG changes:
Progressive lengthening of the PR interval
ST segment depression
Flattening of the T wave
Prominent U waves
Prolongation of QT interval

Hyperkalaemia LAST UPDATED: 21ST
APRIL 2019
 Bookmark
RCEM defines normal values for total serum potassium as 3.0 - 4.5 mmol/L.
Causes
The causes of hyperkalaemia may be divided into:
Renal retention
Renal failure
Hypoaldosteronism (e.g. Addison's disease)
K+ sparing diuretics
ACE inhibitors/ARBs
NSAIDs
Trimethoprim and pentamidine therapy
Increased intake
Excess dietary K+
Transcellular shift of K+ out of cells
Metabolic acidosis
Insulin deficiency
Beta-blockers
Cellular injury/rhabdomyolysis
Tumour lysis syndrome, trauma, burns, crush syndrome,
chemotherapy
Pseudohyperkalaemia
Prolonged tourniquet time
Difficulty collecting the sample
Test tube haemolysis
Length of storage of the specimen
Sample from limb receiving IV fluids containing potassium
Clinical Features
Clinical features of hyperkalaemia may include:
Asymptomatic
Paraesthesia
Muscle weakness or paralysis
Cardiac conduction abnormalities and dysrhythmias
ECG Changes
Hyperkalaemia causes a rapid reduction in resting membrane potential leading to
increased cardiac depolarisation and muscle excitability. This in turn results in ECG
changes which can rapidly progress to ventricular fibrillation or asystole.
Classic ECG changes:
Tall peaked T waves
Shortening of the QT interval
Lengthening of the PR interval
Widening of the QRS complex
Loss of the S-T segment
Loss of p waves
Sine wave appearance

Renal Regulation of Acid- LAST UPDATED: 21ST
APRIL 2019
Base Balance  Bookmark
PHYSIOLOGY / RENAL / ACID-BASE BALANCE
The pH of arterial blood is normally 7.35 - 7.45 ([H+] = 35 - 45 nmol/L).
Metabolism produces ~ 60 mmol H+ per day, most of which is excreted through

the lungs as CO2, formed by the reaction of H+ with HCO3-. The kidneys conserve
and replace HCO3- lost in this way, and fine tune H + excretion. Physiological
buffers maintain a low free [H+] and prevent large swings in pH.
Buffers
Buffers are weak acids or bases that can donate or accept H + ions respectively
and therefore resist changes in pH. Buffering does not alter the body's overall
H+ load, ultimately the body must get rid of H+ by renal excretion if the buffering
capacity of the body is not to be exceeded and a dangerous pH reached.
At a given [H+], a defined amount of buffer exists as acid (HA) and a defined
amount as base (A-). The ratio of buffer pairs at a given [H+] is defined by the
dissociation constant (pK) for that buffer pair. For a given acid-base pair, altering
the ratio of the acid to the base alters the pH.
pK = ([H+][A-])/[HA], or pH = pK + log([A-]/[HA] (the Henderson-Hasselbalch

equation).
Thus an increase in [A-] or a decrease in [HA] will increase pH and a decrease in

pH will decrease the ratio [A-]/[HA].
Bicarbonate and carbonic acid (formed by the combination of CO2 with water,
potentiated by carbonic anhydrase) are the most important buffer pair in the
body, although haemoglobin provides about 20% of buffering in the blood, and
phosphate and proteins provide intracellular buffering. Buffers in urine, largely
phosphate, allow the excretion of large quantities of H+.
The bicarbonate system is physiologically effective because CO2 and HCO3- are
precisely controlled by the lungs and the kidneys respectively.
Proximal Tubule
Bicarbonate is freely filtered at the glomerulus. Less than 0.1% of filtered
bicarbonate is normally excreted in the urine (if plasma [HCO3-] increases,
maximum tubular transport is exceeded and some HCO3- is excreted in urine).
About 80% of bicarbonate is reabsorbed in the proximal tubule.
HCO3- is not transported directly, tubular HCO3- associates with H+ secreted by

epithelial Na+/H+ antiporters to form carbonic acid (H2CO3) which readily
dissociates to form carbon dioxide and water in the presence of carbonic
anhydrase. CO2 and water diffuse into the tubular cells, where they recombine to
form carbonic acid which dissociates to H+ and HCO3-.
This HCO3- is transported into the interstitium largely by Na +/HCO3- symporters

on the basolateral membrane (and H+ is secreted back into the lumen). For each
H+ secreted into the lumen, one Na+ and one HCO3- are reabsorbed into the
plasma. H+ is recycled so there is little net secretion of H+ at this stage. A further
10 - 15% of HCO3- is similarly reabsorbed in the thick ascending limb of the loop of
Henle.
BICARBONATE HANDLING IN THE PROXIMAL TUBULE. (IMAGE BY M. KOEPPEN, VIA
WIKIMEDIA COMMONS)
Ammonia
The body can excrete acid by the urinary loss of H+ ions associated with a buffer
(predominantly sodium phosphate) or by the excretion of H+ ions as ammonium
ions.
Ammonia is produced in tubular cells by the metabolism of glutamine, which
leads to the generation of HCO3- and glucose. NH3 diffuses into the tubular fluid,
or as NH4+ is transported by the Na +/H+ antiporter. In the tubular fluid, NH 3 gains
H+ to form NH4+ which cannot diffuse through membranes. About 50% of
NH4+ secreted by the proximal tubule is reabsorbed in the thick ascending limb,
where it substitutes for K+ in the Na+/K+/2Cl- symporter and passes into the
medullary interstitium. Here NH4+ dissociates into NH3 and H+ and NH3 re-enters
the collecting duct by diffusion. The secretion of H+ in the collecting duct leads to
conversion back to NH4+ which is trapped in the lumen and excreted.
Anion Gap LAST UPDATED: 21ST
APRIL 2019
 Bookmark
Definition
The anion gap is the difference between the measured cations and the measured
anions in plasma. As plasma is always electrically neutral, the anion gap
determines the presence of unmeasured anions. These are usually proteins,
organic acids, sulphate and phosphate.
The anion gap can be calculated as: ([Na+] + [K+]) - ([Cl-] + [HCO3-])
The normal anion gap is normally between about 6 - 16 mmol/L.
Clinical Relevance
In metabolic acidosis:
An increased anion gap occurs if a new acid is added to the body. This
dissociates producing free H+ (which uses up bicarbonate) and anions
(which take the place of the bicarbonate).
A normal anion gap occurs if there is a simple loss of bicarbonate. This
causes a compensatory rise in plasma chloride concentration so the anion
gap is normal (thus is sometimes referred to as hyperchloraemic acidosis).
Causes of Increased Anion Gap Metabolic Acidosis

MUDPILES can be used to remember some of the causes of a raised anion gap
acidosis:
Methanol
Uraemia (in renal failure)
Diabetic ketoacidosis
Propylene glycol overdose
Infection/Iron overdose/Isoniazid/Inborn errors of metabolism
Lactic acidosis
Ethylene glycol overdose
Salicylate overdose
Causes of Normal Anion Gap Metabolic Acidosis

FUSEDCARS can be used to remember some of the causes of a normal anion gap
acidosis:
Fistula (pancreaticoduodenal)
Ureteroenteric conduit
Saline administration
Endocrine (hyperparathyroidism)
Diarrhoea
Carbonic anhydrase inhibitors (e.g. acetazolamide)
Ammonium chloride
Renal tubular acidosis
Spironolactone

Acid-Base Disturbance LAST UPDATED: 21ST
APRIL 2019
 Bookmark
Total body pH can be regulated by controlling the ratio of PaCO2 (acid) to [HCO3-]
(base) in plasma. Ventilation controls the CO2 level and the kidney controls the
HCO3- level. Disorders of acid-base metabolism can therefore arise from either
excess acid or base, or from diseases altering CO2 or HCO3- levels.
pH ∝ [HCO3-]/PaCO2
In a respiratory acid-base disturbance, the primary disorder alters the CO2 level
whereas in a metabolic acid-base disturbance, the primary disorder alters the
HCO3- level either directly, or by the addition of acid or base to the body. In a
mixed disorder, there may be both respiratory and metabolic disturbances. When
either the HCO3- or CO2 levels change, the pH can be brought back towards
normal by altering the other buffer partner in the same direction.
Normal ABG Values

RCEM defines the normal values for blood gases as:
pH = 7.35 - 7.45
pO2 (on air) = 11 - 14 kPa
pCO2 = 4.5 - 6.0 kPa
HCO3- = 24 - 30 mmol/L
BE = +/- 2 mmol/L
Acid-base disturbance
Metabolic Primary Compensatory Change
Disturbance Change
Metabolic ↓[HCO3-] ↓PaCO2 (increased ventilation)
acidosis (↓pH)
Metabolic ↑[HCO3-] ↑PaCO2 (decreased ventilation)
alkalosis (↑pH)
Respiratory ↑PaCO2 ↑[HCO3-] (increased renal
acidosis (↓pH) bicarbonate reabsorption)
Respiratory ↓PaCO2 ↓[HCO3-] (decreased renal
alkalosis (↑pH) bicarbonate reabsorption)
Base Excess
Base excess is defined as the amount of strong acid that must be added to each
litre of fully oxygenated blood to return the pH to 7.40 at a temperature of 37 °C
and a pCO2 of 40 mmHg (5.3 kPa).
A base deficit (i.e. a negative base excess) can be correspondingly defined in

terms of the amount of strong base that must be added.
The predominant base contributing to base excess is bicarbonate. A typical
reference range for base excess is -2 to +2 mmol/L.
The base excess increases (or becomes more positive) in metabolic alkalosis or in
compensation for a respiratory acidosis.
The base excess decreases (or becomes more negative) in metabolic acidosis or
in compensation for a respiratory alkalosis.
Metabolic Acidosis
Metabolic acidosis arises from the gain of acid or the loss of base as bicarbonate.
increased production of H+ e.g. lactic acidosis, ketoacidosis (DKA, alcohol,

starvation)
ingestion of H+ or of drugs that are metabolised to acids e.g. salicylate
overdose, ethylene glycol poisoning
impaired renal excretion of H+ e.g. acute or chronic renal failure
loss of HCO3- in the urine e.g. renal tubular acidosis
loss of HCO3- in the gastrointestinal tract e.g. chronic diarrhoea, ileal
conduits, fistulae, small intestinal/pancreatic/biliary drains
The compensatory response to metabolic acidosis is hyperventilation, since the
increased [H+] acts as a powerful stimulant of the respiratory centre. The deep,
rapid and gasping respiratory pattern is called Kussmaul breathing. At low pH, the
blood pressure falls as a result of reduced peripheral resistance and impaired
myocardial contractility. Pulmonary oedema and ultimately ventricular arrest can
occur.
Metabolic Alkalosis
Metabolic alkalosis arises from addition of bicarbonate to the blood or from loss of
H+ ions from the body.
loss of H+ in the gastrointestinal tract e.g. vomiting, pyloric stenosis, NGT

drainage
loss of H+ in the kidneys e.g. diuretic therapy
ingestion of absorbable alkali e.g. sodium bicarbonate, antacid overdose
increased renal HCO3- reabsorption e.g. primary hyperaldosteronism,
secondary to volume depletion, secondary to hypokalaemia
Metabolic alkalosis is associated with hypoventilation and features of
hypocalcaemia (due to a decrease in the unbound plasma Ca2+ concentration)
and hypokalaemia (due to a shift of potassium into cells) e.g. muscle cramps,
weakness, tetany, paraesthesia.
Respiratory Alkalosis
In a respiratory alkalosis, the primary disorder is a decrease in pCO2 resulting from
hyperventilation. Respiratory alkalosis is much less common than acidosis, and it
is usually acute and uncompensated.
Causes include:
hysterical overbreathing
mechanical over-ventilation in a ventilated patient
raised intracranial pressure
pregnancy
thyrotoxicosis
sepsis
salicylate overdose
hyperthermia
liver failure
hypoxia-induced e.g. altitude acclimatisation
Clinically, there is neuromuscular irritability, with perioral and extremity
paresthesia, muscle cramps, tinnitus, hyperreflexia, tetany and seizures. Cerebral
vasoconstriction with reduced blood flow and cardiac dysrhythmias can occur.
Respiratory Acidosis
Respiratory acidosis results from a primary decrease in ventilation as a result of
depression of the respiratory centre e.g. opioid overdose, a physical impediment
to breathing such as neurological, muscular or chest wall disease, or lung
disease or injury e.g. COPD, asthma, pulmonary oedema.
An acute rise in plasma CO2 is usually associated with a fall in oxygen levels,
dyspnoea, reduced consciousness, and eventually coma. CO2 causes
vasodilation, which may increase cerebral blood flow causing headaches and
increased intracranial pressure. Systemic vasodilation reduces blood pressure,
and large rises in plasma CO2 levels reduce cardiac contractility.

Lung Volumes LAST UPDATED: 11TH APRIL
2019
PHYSIOLOGY / RESPIRATORY /
LUNG VOLUMES AND PRESSURES  Bookmark
LUNG VOLUMES. (IMAGE BY VIHSADAS AT EN.WIKIPEDIA DERIVATIVE WORK: RSCOTTWEEKLY

(LUNGVOLUME.JPG) [CC BY-SA 3.0 (HTTP://CREATIVECOMMONS.ORG/LICENSES/BY-SA/3.0)], FROM
WIKIMEDIA COMMONS)
Volumes
The tidal volume (TV) is the volume of air drawn into and out of the lungs during normal breathing,
i.e. the volume change of the lung between a resting inspiration and a resting expiration.
The inspiratory reserve volume (IRV) is the volume of air that can be inspired at the end of a
normal inspiration, i.e. the difference in volume between a resting and maximum inspiration.
The expiratory reserve volume (ERV) is the volume of air that can be expelled at the end of a
normal expiration, i.e. the difference in volume between a resting and maximum expiration.
The residual volume (RV) is the volume of air remaining in the lungs after a maximal expiration.
Capacities
The vital capacity (VC) is the maximum tidal volume when an individual breathes in and out as far
as possible i.e. the volume change of the lung between a maximum inspiration and a maximum
expiration.
VC = IRV + TV + ERV.
The inspiratory capacity (IC) is the volume of air that can be breathed in by a maximum inspiration
at the end of a resting expiration.
IC = TV + IRV.
The functional residual capacity (FRC) is the volume of air remaining in the lungs at the end of a
resting expiration.
FRC = ERV + RV.
The total lung capacity (TLC) is the volume of air in the lungs after a maximum inspiration.
TLC = VC + RV.
Measuring Lung Volumes and Capacities

Lung volumes vary with age, sex and height.
Most lung volumes (except RV) can be measured directly using spirometry.
Residual volume (and thus FRC and TLC) can be measured using helium dilution or body
plethysmography.
Lung Volume Typical Value (70 kg Male)

Tidal volume (TV) 500 mL
Vital capacity (VC) 5500 mL
Inspiratory reserve volume (IRV) 3300 mL
Expiratory reserve volume (ERV) 1700 mL
Total lung capacity (TLC) 7300 mL
Functional residual capacity (FRC) 3500 mL
Residual volume (RV) 1800 mL
Functional Residual Capacity LAST UPDATED: 21ST
APRIL 2019
Definition
The volume left in the lungs at the end of a normal breath is called the functional
residual capacity (FRC). At FRC, the respiratory muscles are relaxed and its volume is
determined by the elastic properties of the chest wall (tending to spring outwards)
and the lungs (tending to collapse).
If the elastic recoil of either the lungs or chest wall is abnormally large or small, the
FRC will be abnormal. In fibrosis, the lungs are stiff and have decreased compliance,
and so the FRC is reduced. In emphysema, there is loss of alveolar tissue, and with it
elastic recoil of the lungs and hence the FRC is increased. As such, patients with
emphysema often have noticeably broader chests due to the relatively unopposed
outward recoil of the chest wall.
Factors Affecting FRC

Factors increasing FRC:
Emphysema
Air trapping in asthma
Ageing (due to loss of elastic properties)
Increasing height of patient
Factors decreasing FRC:
Restrictive ventilatory defects e.g. pulmonary fibrosis
Posture - lying supine
Increased intra-abdominal pressure (e.g. obesity, pregnancy, ascites)
Reduced muscle tone of diaphragm e.g. muscle relaxants in
anaesthesia, neuromuscular disease

Physiology Respiratory
Lung Volumes and Pressures
Something wrong?
Dead Space LAST UPDATED: 11TH

APRIL 2019
Total Ventilation (minute ventilation) = Tidal Volume (TV) x Respiratory Rate

(RR)
With each tidal volume, about one third of the total amount of gas flowing
into the airway and lung does not participate in gas exchange. This is the
physiological dead space. Dead space can thus be defined as the volume of
gas in the respiratory tract which does not take part in gas exchange.
Anatomical Dead Space

The anatomical dead space includes the respiratory tract down to and
including the terminal bronchioles. These conducting airways have a
function in warming, filtering and humidifying inspired air. The anatomical
dead space is normally about 150 mL. Fowler's method is used to measure
anatomical dead space.
Alveolar Dead Space

The alveolar dead space refers to alveoli incapable of gas exchange; in
health, it is negligible but it may become significant in V/Q mismatch, for
example in pulmonary embolism where certain alveoli lose their blood
supply and no longer take part in gas exchange.
Physiological Dead Space
The physiological dead space is the sum of the anatomical and alveolar
dead space (in health, all alveoli take part in gas exchange, so physiological
dead space = anatomical dead space). The Bohr equation is used to
measure physiological dead space.

Something wrong?
Alveolar Pressure LAST UPDATED: 21ST

APRIL 2019
At Rest
At rest (before inspiration begins), alveolar pressure equals atmospheric
pressure. Because lung pressures are expressed relative to atmospheric
pressure, alveolar pressure is said to be zero.
The lung volume at rest is the functional residual capacity (FRC). At FRC, the
opposing forces of the lungs trying to collapse and the chest wall trying to
expand create a negative pressure in the intrapleural space between them.
Inspiration
During inspiration, the inspiratory muscles contract, the chest wall is
expanded and intrapleural pressure falls (making it more negative). This
increases the pressure gradient between the intrapleural space and alveoli,
stretching the lungs. The alveoli expand and alveolar pressure falls, creating
a pressure gradient between the mouth and alveoli and causing air to flow
into the lungs.
Expiration
During expiration alveolar pressure becomes greater because alveolar gas is
compressed by the elastic forces of the lung. Alveolar pressure is now higher
than atmospheric pressure, the pressure-gradient is reversed and air flows
out of the lungs. Intrapleural pressure also rises, returning to its resting
value during a normal expiration.
In quiet breathing, intrapleural pressure remains negative for the whole of
the respiratory cycle, whereas alveolar pressure is negative in inspiration
and positive during expiration. If ventilation is increased, the changes of
intrapleural and alveolar pressure are greater. In forced expiration (e.g.
coughing or sneezing), intrapleural pressure becomes positive.
Dynamic Compression
The lungs never fully empty. Physiologically this is important as a completely
deflated lung with collapsed alveoli requires significantly more energy to
inflate. Even with a maximum expiration, there is still a residual volume of air
in the lungs. This occurs because as the expiratory muscles contract during
forced expiration, all the structures within the lungs, including the airways,
are compressed by the positive intrapleural pressure (dynamic
compression). Consequently the smaller airways collapse before the alveoli
empty completely and some air remains within the lungs.
In patients with COPD, dynamic compression limits expiratory flow even in
tidal breathing - this is because there is a loss of radial traction due to
destruction of lung architecture meaning the airways are more readily
compressed, and there is increased lung compliance, leading to lower
alveolar pressure and less force driving air out of the lungs.

Respiratory Epithelial LAST UPDATED: 30TH
MARCH 2020
Function  Bookmark
PHYSIOLOGY / RESPIRATORY / LUNG MECHANICS
Mucociliary Clearance
The respiratory tract from the trachea down until the respiratory bronchioles is
lined with ciliated columnar epithelial cells. Goblet cells and submucosal glands
secrete a thick, gel-like mucus. Synchronous beating of the cilia moves the
mucus and associated debris to the mouth where it is swallowed or expectorated,
a process known as mucociliary clearance.
Impaired Mucociliary Clearance

Factors that increase the viscosity of the mucus (e.g. cystic fibrosis, asthma,
inflammation or poor humidity) or factors that impair ciliary activity (e.g. smoking,
pollutants, infection or general anaesthetics) lead to defective mucociliary
clearance and recurrent infections.
Mucus contains substances that protect the airway from pathogens and from
destructive proteases released from dead bacteria and immune cells e.g. alpha-1-
antitrypsin, lysozyme, IgA. Genetic deficiency of alpha-1-antitrypsin leads to
early-onset emphysema as a result of uninhibited protease activity in the lung
resulting in destruction of elastin in the alveoli.
Epithelial Cells
The single layer of epithelial cells forming the walls of the alveoli and alveolar
ducts are non ciliated squamous cells, predominantly very thin type I alveolar
pneumocytes joined by tight junctions lying on a basement membrane. These
form the gas exchange surface with the pulmonary capillary endothelium.
A few type II alveolar pneumocytes make up a small proportion of the alveolar
surface area and secrete surfactant which bathes the alveoli, reducing the
surface tension and preventing alveolar collapse.
Macrophages in the airways ingest foreign materials and destroy pathogens. In
the alveoli, alveolar macrophages take the place of cilia by clearing debris.
STRUCTURE OF AN ALVEOLUS. (IMAGE MODIFIED BY FRCEM SUCCESS. ORIGINAL

SOURCED FROM WIKIMEDIA COMMONS.)

Lung Compliance LAST UPDATED: 11TH
APRIL 2019
 Bookmark
In order for inspiration to occur, the respiratory muscles must overcome the
impedance offered by the lungs and chest wall, mainly in the form of frictional
airway resistance and elastic resistance to stretching of the lung and chest wall
tissues and the fluid lining the alveoli.
Compliance describes the distensibility or ease of stretch of lung tissue when an
external force is applied to it. Like lung volumes, compliance is affected by a
person's age, sex and height.
Static Compliance
The static compliance (CL) of the lungs is defined as the change in lung volume
per unit change in distending pressure.
Compliance = ΔV/ΔP
The distending pressure is the transmural pressure difference across the lung,
which equals alveolar - intrapleural pressure.
Alveolar pressure cannot easily be measured, but when no air is flowing, alveolar
pressure must be zero (i.e. equal to atmospheric pressure). The transmural
pressure is then equal to the intrapleural pressure.
Intrapleural pressure can be measured with an oesophageal balloon. The subject
breathes in steps and measurements are taken while the breath is held and
plotted as a static pressure-volume (P-V) curve. The static lung compliance is the
slope of the steepest part of this static P-V curve in the region just above the
functional residual capacity.
The pressure-volume curve demonstrates hysteresis where the inspiratory curve

is slightly different from the expiratory curve even at the same volumes. This is
because expiration is deemed a passive process due to the elastic recoil of the
lung whereas there is a need to overcome surface tension forces when inflating
the lungs.
Dynamic Compliance
Dynamic compliance is measured during continuous breathing and therefore
includes a component due to airway resistance. The dynamic pressure-volume
loop has a point at each end where the flow is zero: the slope of the line between
these points is the dynamic compliance. In health, dynamic compliance is similar
to static compliance but is some diseases it may be lower. Between the two zero
flow points, the dynamic P-V loop appears fatter than the static P-V loop, as
intrapleural pressure must change more to drive airflow. In fact, the area of the
dynamic loop is a measure of the work done against airway resistance.
Factors Affecting Compliance

Compliance changes at different lung volumes. Initially at lower lung volumes the
compliance of the lung is poor and greater pressure change is required to cause a
change in volume. This occurs if the lungs become collapsed for a period of time.
At functional residual capacity (FRC) compliance is optimal since the elastic recoil
of the lung tending towards collapse is balanced by the tendency of the chest
wall to spring outwards. At higher lung volumes the compliance of the lung again
becomes less as the lung becomes stiffer. At all volumes, the base of the lung has
a greater compliance than the apex.
Other factors increasing compliance:
Old age
Emphysema
Other factors decreasing compliance:
Pulmonary fibrosis
Pulmonary oedema
Atelectasis
Extremes of lung volumes
Expiratory Flow Rates LAST UPDATED: 19TH
APRIL 2020
 Bookmark
Lung volumes can be measured with spirometry. Airway resistance and lung compliance can
be assessed indirectly by measuring the forced expiratory flows and volumes.
Peak Expiratory Flow Rate

The easiest and quickest measurement is the peak expiratory flow rate (PEFR). PEFR is
reduced if airway resistance is increased in obstructive disease and is commonly used to
monitor asthma. It is dependent on the initial lung volume and therefore on the patient's age,
sex and height.
NORMAL VALUES FOR PEAK EXPIRATORY FLOW (EXAMPLE). (IMAGE BY HÄGGSTRÖM, MIKAEL (2014).
"MEDICAL GALLERY OF MIKAEL HÄGGSTRÖM 2014". WIKIJOURNAL OF MEDICINE 1 (2).
DOI:10.15347/WJM/2014.008. ISSN 2002-4436. PUBLIC DOMAIN)
Forced Vital Capacity
The forced vital capacity (FVC) is the volume of air that can forcibly be blown out after a
maximum inspiration.
Forced Expiratory Volume

The forced expiratory volume in 1 second (FEV1) is the volume of air that can forcibly be blown
out after maximal inspiration in one second.
This is normally expressed as a ratio to FVC to correct for lung volume.
FEV1/FVC Ratio
The FEV1/FVC ratio is usually 0.75 - 0.90.
The FEV1/FVC ratio can be used to distinguish between obstructive (increased airway
resistance) and restrictive (decreased lung compliance) disease.
In obstructive disease, slowing of expiratory flow means that a low proportion of the FVC is
expired in the first second and thus the FEV1/FVC ratio is reduced (normally < 0.7).
In restrictive disease, FEV1 and FVC are both reduced, but the FEV1/FVC ratio is normal or
even increased due to greater elastic recoil.
Disease Obstructive Restrictive Disease

Disease
Pathophysiology Increased Impaired ability of the lungs to expand caused
airway by decreased lung compliance
resistance
caused by
narrowing of
the airways
Examples COPD, asthma, Intrinsic causes: interstitial lung disease,
emphysema, pulmonary oedema, pneumonia, parenchymal
bronchiectasis lung tumours; Extrinsic causes: pleural
effusion, pleural adhesions, pneumothorax,
chest wall deformities, neuromuscular disease,
connective tissue disease, obesity or
pregnancy
FVC Normal or low Low (< 0.8)
Disease Obstructive Restrictive Disease
Disease
FEV1 Low (< 0.8) Low (<0.8)
FEV1/FVC ratio Low (< 0.7) Normal or high (>0.7)
Vital capacity Low Low
Residual volume High Normal or low
Total lung Normal or high Low
capacity

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Alveolar Interface LAST UPDATED: 21ST

APRIL 2019
 Bookmark
Alveolar Air-Fluid Interface

The surface tension of the fluid lining the alveoli contributes to lung
compliance, as the attraction of water molecules for each other at the air-
fluid interface creates a collapsing pressure that is directly proportional to
surface tension and inversely proportional to alveolar radius.
This is a manifestation of Laplace's law which states that the pressure (P) in
a bubble (or alveolus) is proportional to the surface tension (T)/radius (r). A
small bubble will therefore have a higher collapsing pressure than a larger
one, and be more difficult to keep open. The inward force created by this
surface tension also tends to suck fluid into the alveoli (transudation).
In the lungs, pulmonary surfactant secreted by type II pneumocytes aims to
minimise these problems.
Pulmonary Surfactant
Pulmonary surfactant is a mixture of phospholipids that floats on the
alveolar fluid surface and reduces surface tension. As the alveoli shrink
during expiration, the effective concentration of surfactant increases,
further lowering the surface tension (which more than balances the
increased tendency for alveoli to collapse as they shrink). Alveolar stability is
also aided by the connection and mutual pull of neighbouring alveoli, a
phenomenon known as alveolar interdependence.
Surfactant prevents alveolar collapse, increases lung compliance and
prevents transudation of fluid into alveoli. Infant respiratory distress
syndrome, with stiff lungs, lung collapse and transudation, occurs in
premature babies (< 34 weeks gestation) due to a deficiency of surfactant
production.

Physiology Respiratory
Lung Mechanics
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Airway Resistance LAST UPDATED: 11TH

APRIL 2019
 Bookmark
Airflow is driven by and is directly proportional to, the mouth-alveolar

pressure gradient generated by the respiratory muscles.
Flow through airways is described by Darcy's law: Flow = (P1 - P2)/R where
P1 is the alveolar pressure, P2 is the mouth pressure and R is the resistance
to airflow.
Airway resistance is primarily determined by the airway radius according to
Poiseuille's law, and whether the flow is laminar or turbulent. The major site
of airway resistance is the medium-sized bronchi. The smallest airways
would seem to offer the highest resistance, but they do not because of their
branching parallel arrangement.
Factors Affecting Airway Resistance

Factors causing bronchoconstriction:
Via muscarinic receptors
Parasympathetic stimulation
Stimulation of irritant receptors
Inflammatory mediators e.g. histamine, prostaglandins,
leukotrienes
Beta-blockers
Factors causing bronchodilation:
Via beta2-adrenoceptors
Sympathetic stimulation
Adrenaline (epinephrine)
Beta2-adrenergic agonists e.g. salbutamol
Anticholinergic and muscarinic antagonists e.g. ipratropium
Pollutants, and substances released from mast cells and eosinophils can
increase airway resistance via bronchoconstriction, mucosal oedema,
mucus hypersecretion, mucus plugging and epithelial shedding - all of
which are important in asthma.

Ventilation-Perfusion LAST UPDATED: 8TH
AUGUST 2021
Mismatch  Bookmark
VENTILATION-PERFUSION RELATIONSHIP
At rest, total alveolar ventilation and total pulmonary blood flow are similar, each
being around 5 L/min. To achieve efficient gas exchange, it is essential that the
flow of gas (ventilation, V) and the flow of blood (perfusion, Q) are closely matched
throughout all regions of the lung. Ideally, local ventilation-perfusion (V/Q) ratios
should be as close to 1 as possible.
V/Q Mismatch
When there are significant regional variations in ventilation or perfusion, this is
referred to as ventilation-perfusion (V/Q) mismatch.
There are two extremes of V/Q mismatch:
1. Dead space
Lung region with normal alveolar ventilation but absent perfusion
Caused by large pulmonary embolus for example
Q = 0, therefore V/Q = ∞
The Po2 and Pco2 of alveolar gas will approach their values in
inspired air
2. True shunt
Lung region with normal perfusion but absent alveolar ventilation
Caused by complete collapse or consolidation of a lung region for
example
V = 0, therefore V/Q = 0
The Po2 and Pco2 of pulmonary capillary blood (and, therefore, of
systemic arterial blood) will approach their values in mixed venous
blood
Effect of V/Q Mismatch on Arterial Gases
Regions of the lung with V/Q > 1 have excessive ventilation relative to perfusion
with a dead space effect, and blood derived from them will have raised PaO2 and
low PaCO2. This may be seen in emphysematous areas where capillaries are
destroyed or where pulmonary emboli are partially blocking blood flow.
Regions of the lung with V/Q < 1 have reduced ventilation relative to perfusion
with a shunt effect, and blood derived from them will have low PaO2 and raised
PaCO2. This may be seen when airways are partly blocked by bronchoconstriction,
inflammation or secretions.
Regions of high V/Q cannot compensate for regions of low V/Q and the net effect
of mixing blood from areas with V/Q mismatch is a low PaO2 and a normal/low
PaCO2. Hypoxic vasoconstriction helps to reduce the severity of V/Q mismatching
by diverting blood from regions with low V/Q ratios to regions that are better
ventilated.
For an alveolus with a V/Q between 0-1 (V/Q mismatch but not true shunt), there
is perfusion but relatively less ventilation, therefore blood passing through this
alveolus will be partially oxygenated and increasing oxygen fraction can
significantly improve arterial oxygen content (assuming no diffusion limitation).
However in a true shunt (V/Q = 0) increasing oxygen fraction has no effect
because the oxygen-enriched air fails to reach the shunted blood.
Gravitational Effects on V/Q Mismatch
Both ventilation and perfusion increase towards the lung base, because of the
effects of gravity, but the gravitational effects are greater on perfusion than
ventilation and therefore there is a regional variation in V/Q ratio from lung apex
(high V/Q) to lung base (low V/Q). In young people, this gravitational effect is
modest and has little effect on blood gases, but the V/Q mismatch increases with
age and contributes to the reduction in PaO2 seen in the elderly.
Regional ventilation and perfusion can be visualised by inhalation and infusion of

appropriate radioisotopes on a V/Q scan.
A-a gradient
The cause of a hypoxia can be classified by the alveolar-arterial PO2 gradient (A-a
gradient). The alveolar gradient is calculated as PAO2 – PaO2.
A normal A-a gradient is seen in alveolar hypoventilation or low inspired PO2 (e.g.
at high altitude). An increased A-a gradient reflects a diffusion defect (rare), V/Q
mismatch or a right-to-left shunt.
In healthy young people, there is a small A-a gradient (< 2 kPa) arising from the
normal anatomical right-to-left shunts. The normal value for the A-a gradient
increases with age.

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Right to Left Shunt LAST UPDATED: 11TH

APRIL 2019
VENTILATION-PERFUSION RELATIONSHIP  Bookmark
Anatomical Right to Left Shunts

Part of the venous effluent of the bronchial and coronary circulations
bypasses the lungs and enters the pulmonary vein and left ventricle
respectively. Oxygenated blood from the lungs is therefore diluted by
venous blood. In healthy people, these anatomical shunts are equivalent to
2% or less of the cardiac output but they explain why arterial PO2 is less
than alveolar PO2 even though pulmonary capillary blood equilibrates with
alveolar air.
Right to Left Shunts in Disease

Shunting may become significant in some disease states when regions of
the lung are not ventilated (e.g. atelectasis, pulmonary oedema,
pneumonia) or due to cyanotic congenital heart disease where blood
bypasses the pulmonary circulation completely (e.g. tetralogy of Fallot).
The shunted blood will not have been oxygenated or been able to offload
CO2 and thus its levels of PO2 and PCO2 are that of mixed venous blood.
Changes in PCO2 and PO2 stimulate the chemoreceptors and increase
ventilation, so that arterial PCO2 returns to normal. However, increased
ventilation cannot increase blood O2 content, as the haemoglobin of the
blood passing through the lungs is already close to saturation. Thus right to
left shunts commonly result in a low arterial PO2 but a normal or low PCO2.
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Lung Receptors LAST UPDATED: 11TH

APRIL 2019
CONTROL OF RESPIRATION  Bookmark
Various types of lung receptors provide feedback from the lungs to the
respiratory centre.
Stretch Receptors
Stretch receptors are located in smooth muscle of the bronchial walls. Their
afferent nerves ascend via the vagus nerve. Stimulation of stretch receptors
causes short, shallow breaths, and delay of the next inspiratory cycle. These
receptors are largely responsible for the Hering-Breuer reflex where excessive
lung inflation inhibits inspiratory muscle activity to prevent over inflation.
Juxtapulmonary (J) Receptors

Juxtapulmonary or 'J' receptors are located on alveolar and bronchial walls
close to the capillaries. Their afferents are small unmyelinated C-fibres or
myelinated nerves in the vagus nerve. Activation causes depression of somatic
and visceral activity by producing apnoea or rapid shallow breathing, a fall in
heart rate and blood pressure, laryngeal constriction and relaxation of skeletal
muscles via spinal neurones. J receptors are stimulated by increased alveolar
wall fluid, pulmonary congestion and oedema, microembolism and inflammatory
mediators. J receptors are thought to be involved in the sensation of dyspnoea
in lung disease.
Irritant Receptors
Irritant receptors are located throughout airways between epithelial cells, with
rapidly adapting afferent myelinated fibres in the vagus nerve. Receptors in the
trachea lead to cough, those in the lower airway to hyperpnoea. Stimulation also
causes reflex bronchial and laryngeal constriction. Irritant receptors are
stimulated by irritant gases, smoke and dust, rapid inflation/deflation, airway
deformation, pulmonary congestion and inflammation. Irritant receptors are
responsible for deep augmented breaths or sighs seen every 5 - 20 minutes at
rest, which reverse the slow collapse of the lungs that occurs in quiet breathing.

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Chemoreceptors LAST UPDATED: 11TH

APRIL 2019
CONTROL OF RESPIRATION  Bookmark
Chemical control of ventilation is mediated via central and peripheral

chemoreceptors which detect arterial PCO2 and pH (central and peripheral) and
PO2 (peripheral only), and modulate ventilation via a distributed network of
neurones in the brainstem.
Factors Affecting Ventilation

PCO2 is the most important factor. An increase in PACO 2 causes ventilation to rise
in an almost linear fashion.
A metabolic acidosis (e.g. lactic acidosis in strenuous exercise) causes the
relationship between PCO2 and ventilation to shift to the left (where ventilation
increases more for any given rise in PACO2) and a metabolic alkalosis causes a
shift to the right.
PO2 normally stimulates ventilation only when it falls below around 8 kPa.
However, when a fall in PO2 is accompanied by an increase in PCO2, the resultant
increase in ventilation is far greater than would be expected from the effects of
either alone; there is thus a synergistic relationship between PO2 and PCO2.
Central Chemoreceptors
The central chemoreceptor consists of a diffuse collection of neurones located
near the ventrolateral surface of the medulla. These are sensitive to the pH of the
surrounding cerebrospinal fluid (CSF), thus indirectly respond to blood PCO2 (but
do not respond to changes in PO2).
CSF is separated from the blood by the blood-brain barrier. This barrier is
impermeable to polar molecules such as H+ and HCO3- but CO2 can diffuse across
it easily. The pH of CSF is therefore determined by the arterial PCO2 and the CSF
HCO3- and is not affected by blood pH. Stimulation of the central chemoreceptor
by a fall in CSF pH (with a rise in blood PCO2) causes an increase in ventilation to
blow off CO2; the response is delayed because CO2 has to diffuse across the blood-
brain barrier.
The central chemoreceptor is responsible for about 80% of the ventilatory
response to changes in PCO2 in humans.
Peripheral Chemoreceptors
The peripheral chemoreceptors are found within the carotid body, innervated by
the glossopharyngeal nerve and located at the bifurcation of the common carotid
arteries, and the aortic bodies, innervated by the vagus nerve and located on the
aortic arch. The aortic bodies are functionally less important. Carotid bodies
respond to increased PCO2 and decreased blood pH in addition to reduced PO2.
They are responsible for about 20% of the ventilatory response to increased PCO2.

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Central Control of LAST UPDATED: 11TH

APRIL 2019
Respiration  Bookmark
CONTROL OF RESPIRATION
Control of breathing involves a central pattern generator that sets the basic
rhythm and pattern of ventilation and controls the respiratory muscles. It is
modulated by higher centres and feedback from central and peripheral
chemoreceptors and peripheral mechanoreceptors.
Brainstem and Central Pattern Generator

The brainstem includes diffuse groups of respiratory neurones in the pons and
medulla that act together as the central pattern generator.
The medulla contains dorsal and ventral respiratory groups that receive input
from the chemoreceptors and lung receptors and drive the respiratory muscle
motor neurones. The medullary respiratory groups also provide ascending
input to, and receives descending input from the pneumotaxic centre in the
pons.
The pneumotaxic centre receives input from the hypothalamus and higher
centres, coordinates medullary homeostatic functions with factors such as
emotion and temperature and affects the pattern of breathing.
Voluntary control of breathing is mediated by motor neurones from the cortex
contained in the pyramidal tracts, which bypass the pneumotaxic and
medullary respiratory centres.

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Gas Transport LAST UPDATED: 11TH

APRIL 2019
GAS TRANSPORT IN LUNGS  Bookmark
Fractional Concentration and Partial Pressure of Gases in a

Gas Mixture
Dalton's law states that when two or more gases, which do not react
chemically, are present in the same container, the total pressure is the sum of
the partial pressures of each gas.
In the atmosphere, the partial pressure of a gas is the contribution to
barometric pressure exerted by that gas. The total pressure exerted by the
atmosphere at sea level is 760 mmHg (101 kPa).
The partial pressure of each gas is determined by the fractional concentration
of that gas. Dried air contains 21% oxygen, 78.1% nitrogen and 0.9% inert gases
such as helium and argon. The small amount of CO2 in air (< 0.04 %) is usually
ignored.
Therefore the partial pressure of oxygen in dry inhaled air = 0.21 x 760 (101) =
159 mmHg (21.2 kPa) and the partial pressure of nitrogen = 0.78 x 760 (101) =
593 mmHg (78.8 kPa).
At altitude, the oxygen fraction is unaltered but the barometric pressure and
thus partial pressure of oxygen is reduced.
Oxygen and Carbon Dioxide Partial Pressures in Respiration

Typical values for a resting young healthy male (in kPa) are shown below:
Inhaled air: PO2 21.2, PCO2 0.0
Inspired air in airways (after humidification): PO2 19.9, PCO2 0.0
Alveolar air (after equilibrium with pulmonary capillaries): PO2 13.3, PCO2
5.3
Exhaled air (after mixing with anatomical dead space air): PO2 15.5, PCO2
4.3
Gases Dissolved in Body Fluids

If a gas is exposed to a liquid to which it does not react, gas particles will move
into that liquid. Henry's law states that the number of molecules dissolving into
the liquid is directly proportional to the partial pressure at the surface of the
gas.
The constant of proportionality is the solubility of the gas in the liquid, and it is
determined by the gas, the liquid and the temperature:
Content of dissolved gas X in liquid Y = (Solubility of X in Y) x (Partial pressure
of X at surface)

Gas exchange between alveolar air and blood in the pulmonary capillaries takes
place by diffusion across the alveolar-capillary membrane. Diffusion occurs from
an area of high partial pressure to an area of low partial pressure, thus the
driving force for diffusion is the alveolar-capillary partial pressure gradient.
Diffusion occurs until equilibrium is reached, but random movement of particles
continues to occur and this is known as dynamic equilibrium.
Fick's Law
Diffusion occurs across a membrane and is therefore governed by Fick's law.
The rate of gas flow = permeability x surface area of gas exchange x difference in
partial pressures (where permeability depends on the membrane thickness, gas
molecular weight and it's solubility in the membrane).
Fick's law tells us that the rate of diffusion of a gas increases:
the larger the surface area involved in gas exchange
the greater the partial pressure gradient across the membrane
the thinner the membrane
the more soluble the gas in the membrane
the lower the molecular weight of the gas
Although CO2 is larger than O2, it is is much more soluble and diffuses 20 times
more rapidly. The average surface area of the alveolar-capillary membrane is
about 50 - 100 m2, and the average thickness is 0.4 mm. This allows an
enormous surface area for gas exchange and a very short diffusion distance.
Transfer Factor
For gas transfer across the lungs, the permeability and surface area are
commonly combined as the diffusing capacity (or transfer factor) for that gas, a
measure of the alveolar-capillary membrane function.
The diffusing capacity for oxygen (DLO2) cannot be measured directly but the
rate of diffusion in the lungs can be estimated by measuring the diffusing
capacity of the lungs for carbon monoxide (DLCO).
Factors affecting transfer factor:
DLCO is reduced by reduced alveolar-capillary membrane area (as in
emphysema, pulmonary embolism or lung resection).
DLCO is reduced by increased membrane thickness (as in pulmonary
oedema or pulmonary fibrosis).
DLCO is reduced in anaemia.
DLCO is increased in polycythaemia.
DLCO is increased in exercise (due to increased pulmonary blood volume
increasing the effective area).
DLCO is not affected by hypoventilation.
Limitations of Gas Transfer

The rate of transfer of a gas may be diffusion or perfusion limited.
The solubility of nitrous oxide in the blood is low and it does not undergo
chemical combination with any component of blood, thus the partial pressure in
the blood rapidly reaches equilibrium with alveolar air, there is no alveolar-
capillary partial pressure gradient and diffusion ceases along the capillary;
uptake can only be increased by increased capillary blood flow and thus transfer
is perfusion-limited.
Carbon monoxide is rapidly taken up and bound tightly to haemoglobin thus
pulmonary capillary PCO changes little and the alveolar-capillary partial pressure
gradient is maintained along the capillary. Improved ease of diffusion, with
reduced thickness or increased area of the alveolar-capillary membrane would
increase CO uptake, and thus transfer is diffusion-limited.
Oxygen transfer lies between these two extremes, but is normally perfusion-
limited.

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Oxygen Transport LAST UPDATED: 11TH

APRIL 2019
GAS TRANSPORT IN CIRCULATION  Bookmark
The solubility of oxygen in blood plasma is low and only a very small percentage
of the body's requirement can be carried in the dissolved form (< 10 mL),
therefore most oxygen is carried bound to haemoglobin in red blood cells.
Haemoglobin
Each gram of haemoglobin binds with up to 1.34 mL oxygen, so with a
haemoglobin concentration of 150 g/L, blood contains a maximum of 200 mL/L
oxygen bound to haemoglobin; this is the oxygen capacity, which varies with
[Hb]. The actual amount of oxygen bound to haemoglobin depends on the
PO2. Low PO2 in tissue capillaries promotes oxygen release from haemoglobin,
whereas the high PO2 in pulmonary capillaries promotes oxygen binding.
Each molecule of haemoglobin can bind up to four molecules of oxygen, at which

point it is said to be saturated. Haemoglobin binds oxygen in a cooperative
fashion; this means as each oxygen molecule binds, there is a conformational
change in its protein structure and its affinity for oxygen increases, making it
easier to bind the next oxygen molecule.
Oxygen-Haemoglobin Dissociation Curve

The oxygen dissociation curve is a graph that plots the proportion of
haemoglobin in its oxygen-laden saturated form on the vertical axis against the
partial pressure of oxygen on the horizontal axis.
Cooperative binding is responsible for the steepness of the oxygen-haemoglobin
dissociation curve in the middle. The curve flattens again at partial pressures
above about 8 kPa because there are few unfilled haemoglobin binding sites.
Thus for a normal arterial PO2 (about 13 kPa) and [Hb], the blood is about 97%
saturated and any increase in PO2 will have little effect on the blood oxygen
content. On the steep part of the curve however (< 8 kPa), small changes in PO2
will have large effects on the blood oxygen content. The PO2 at which the
haemoglobin is 50% saturated is known as the P50 (the P50 is higher for a right-
shifted curve and lower for a left-shifted curve).
OXYGEN-HAEMOGLOBIN DISSOCIATION CURVE. (IMAGE MODIFIED BY FRCEM SUCCESS.

ORIGINAL BY PETER SOUTHWOOD (OWN WORK) [CC0], VIA WIKIMEDIA COMMONS)
Factors Affecting Oxygen-Haemoglobin Curve

The affinity of haemoglobin for oxygen, and hence the position of the
dissociation curve, varies with local conditions.
A decreased affinity of haemoglobin for oxygen (and hence increased ease of
dissociation), shown by a right shift in the oxygen dissociation curve, is caused
by a fall in pH, a rise in PCO2 (the Bohr effect) and an increase in temperature.
These changes occur in metabolically active tissues such as in exercise, and
encourage oxygen release. The metabolic by-product 2,3-diphosphoglycerate
(2,3 -DPG) also causes a right shift; 2, 3 -DPG may also be raised in chronic
anaemia, chronic lung disease, or at high altitude.
Conversely, an increased affinity of haemoglobin for oxygen, shown by a left shift
in the oxygen dissociation curve, is caused in the lungs by a rise in pH, a fall in
PCO2 and a decrease in temperature.
Anaemia
In anaemia, at any given PO2, the oxygen capacity is reduced because of the
reduced concentration of haemoglobin binding sites. The dissociation curve
would not be altered if it was drawn as Saturation (y-axis) versus PO2 (x-axis) but
if drawn as Oxygen content (y-axis) versus PO2(x-axis), the oxygen content value
at each PO2 would be reduced. In chronic anaemia, red cell 2,3 -DPG levels rise
and the curve will be right shifted.
Carbon Monoxide
Carbon monoxide (CO) binds 240 times more strongly than O 2 to haemoglobin
and by occupying O2-binding sites, reduces oxygen capacity. CO also increases
oxygen affinity, shifting the oxygen haemoglobin curve to the left and making O2
release to tissues more difficult.
Foetal Haemoglobin
Foetal haemoglobin (HbF) binds 2, 3 -DPG less strongly than does adult
haemoglobin (HbA), and so the HbF dissociation curve lies to the left of that for
HbA, reflecting its higher oxygen affinity. This helps transfer oxygen from mother
to foetus.
ADULT VS FOETAL OXYGEN-HAEMOGLOBIN DISSOCIATION CURVE. (IMAGE BY OPENSTAX

COLLEGE [CC BY 3.0 (HTTP://CREATIVECOMMONS.ORG/LICENSES/BY/3.0)], VIA
WIKIMEDIA COMMONS)

Carbon Dioxide Transport LAST UPDATED: 11TH
APRIL 2019
GAS TRANSPORT IN CIRCULATION  Bookmark
Carbon dioxide is transported in the blood from tissues to the lungs in three ways
as bicarbonate ions, as carbamino compounds with proteins or simply dissolved
in plasma.
Bicarbonate Ions
About 60% of CO2 is transported in the form of bicarbonate ions.
CO2 generated in the tissues and water combine to form carbonic acid which
readily dissociates to form HCO3- and H+. The first part of this reaction is very
slow in plasma, but is accelerated dramatically by the enzyme carbonic
anhydrase present in red blood cells. Bicarbonate is therefore formed
preferentially in red cells, from which it freely diffuses down its concentration
gradient into plasma where it is transported to the lungs. The red cell membrane
is impermeable to H+ ions which remain in the cell. To maintain electroneutrality,
Cl- ions diffuse into the cell to replace HCO 3-, an effect known as the chloride
shift. Deoxygenated haemoglobin acts as a buffer for H+, allowing the reaction to
continue.
In the lungs, all of the above reactions occur in reverse. Oxygenated haemoglobin
does not bind H+ as well as it is more acidic and so in the lungs H + dissociates
from haemoglobin and shifts the CO2-HCO3- equation to the left, assisting CO2
unloading from the blood. This contributes to the Haldane effect which states
that for any given PCO2, the CO2 content of deoxygenated blood is greater than
that of oxygenated blood.
Carbamino Compounds
About 30% of CO2 is transported as carbamino compounds. CO2 combines rapidly
with terminal amine groups on proteins to form carbamino compounds, primarily
with haemoglobin forming carbaminohaemoglobin. Reduced haemoglobin forms
carbamino compounds more readily than oxygenated haemoglobin and this also
contributes to the Haldane effect.
Dissolved Carbon Dioxide

CO2 is 20 times more soluble than O 2 in plasma and about 10% of CO2 is
transported dissolved in solution.
TRANSPORT OF CARBON DIOXIDE. (IMAGE BY OPENSTAX COLLEGE [CC BY 3.0


Barriers to Infection LAST UPDATED: 8TH
NOVEMBER 2021
MICROBIOLOGY / PRINCIPLES /
NATURAL AND INNATE IMMUNITY  Bookmark
Anatomical Barriers
Anatomical barriers to infection include:
tight junctions between cells of the skin and mucosal membranes
the flushing action of tears, saliva and urine
the mucociliary escalator in the respiratory tract (together with the
actions of coughing and sneezing)
the acidic pH of gastric and vaginal secretions
the acidic pH of the skin (maintained by lactic acid and fatty acids in
sebum)
enzymes such as lysozyme found in saliva, sweat and tears
pepsin present in the stomach
biological commensal flora formed on the skin and the respiratory,
gastrointestinal and genitourinary tracts which protect the host by
competing with pathogenic bacteria for nutrients and attachment sites
and by producing antibacterial substances
Skin as a Barrier
The skin provides a physical barrier to infection, with secreted sebum and fatty
acids inhibiting bacterial growth.
Some pathogens can penetrate intact skin e.g. Leptospira and Treponema, or
are introduced via the bite of a vector e.g. in malaria or dengue fever.
Some organisms colonise mucosal surfaces and use this route to gain access
to the body e.g. Streptococcus pneumoniae.
If skin integrity is broken e.g. by intravenous cannulation, blood-borne viruses
such as hepatitis B and HIV can be transmitted.
Diseases of the skin such as eczema, psoriasis or burns, permit colonisation
and invasion by pathogens e.g. Staphylococcus epidermidis.

Normal Bacterial Flora LAST UPDATED: 16TH
MARCH 2019
NATURAL AND INNATE IMMUNITY  Bookmark
The normal flora provides protection against infection by competing with

pathogens for colonisation sites and resources and by producing antibacterial
substances (bacteriocins) that suppress other bacteria. The natural flora varies
depending on the location in the body.
Body Site Normal Flora

Nasopharynx Streptococci, Staphylococci, Haemophilus, Neisseria,
Corynebacteria, Moraxella, Mixed anaerobes, Candida,
Actinomyces
Skin Staphylococci, Streptococci, Corynebacteria,
Propionibacteria, Yeasts
Bowel Staphylococci, Enterobacteriaceae, Enterococci,
Candida, Bacteroides, Bifidobacteria, Clostridium,
Peptostreptococci, Lactobacilli
Vagina Lactobacilli, Staphylococci, Streptococci,
Corynebacteria, Candida, Actinomyces, Mycoplasma
hominis
Antibiotics suppress normal flora which allows for colonisation and infection by
opportunistic pathogens such as Candida albicans or Clostridium difficile.

Sources and Spread of LAST UPDATED: 21ST
APRIL 2019
Infection  Bookmark
CONTROLLING INFECTION
Sources of Infection
Infection is caused either by organisms from the host's normal flora
(endogenous infection) or by organisms transmitted from another source
(exogenous infection).
Endogenous infection will only occur if circumstances permit. For example:
Inhalation of stomach contents may cause aspiration pneumonia.
Staphylococcus aureus normally found in the nose may cause infection
if inoculated into a surgical wound or cannulation site.
N.B. Neutropenic patients are especially prone to infection from
conditional pathogens.
Examples of exogenous infections include:
Salmonella enterica spread via ingested poultry.
Legionella pneumophila spread via poorly maintained air-conditioning
cooling towers.
Spread of Infection
Examples of routes of transmission of infection include:
Route of Transmission Examples

Airborne Mycoplasma tuberculosis, Measles
virus
Route of Transmission Examples
Respiratory droplet Neisseria meningitidis, Influenza
virus
Faecal-oral Salmonella enterica, Campylobacter
jejuni
Sexual Neisseria gonorrhoea, HIV
Vector-borne Plasmodium falciparum
Transcutaneous (through intact Leptospira spp., Treponema
skin) pallidum
Percutaneous (through Staphylococcus epidermidis
breached skin)

Hospital Acquired Infection LAST UPDATED: 21ST
APRIL 2019
CONTROLLING INFECTION  Bookmark
A hospital acquired infection (HAI) is defined as an infection which was not

present or incubating at the time of hospital admission. Infection is a major cause
of mortality and morbidity in patients admitted to hospital.
Spread of Infection
Spread may occur via:
food supply (issues of hygiene standards, temperature of food, transport to
ward)
air supply (via theatre air supply and air conditioning systems)
fomites (any inanimate object that may act as a vehicle for transmission
e.g. MRSA on a stethoscope, Pseudomonas spp. on vases)
water supply (Legionella pneumophila may colonise the system in
redundant areas of lukewarm pipework and be transmitted to the air
conditioning system - to reduce this risk hot water supplies should be
maintained at temperatures above 45°C and cold water supplies below
20°C)
Risk Factors for Infection

Patient centred risk factors include:
Underlying illness or treatment e.g. immunosuppressive drugs
Antibiotic therapy
Patients tend to be older and less mobile
Patients tend to be kept in close contact with other patients/staff
Patients have less access to washing facilities
Invasive devices e.g. indwelling urinary catheters provide a route for
ascending infections into the bladder due to urinary stasis with secondary
bacterial colonisation
Control of Hospital LAST UPDATED: 21ST
APRIL 2019
Acquired Infection  Bookmark
CONTROLLING INFECTION
Good Clinical Practice

Infected patients should be isolated in a side room with dedicated hand
washing and toilet facilities.
Staff should be 'bare below the elbows' at all times.
Staff should use disposable plastic aprons and gloves for touching the
patient, which should be discarded after use.
Hands should be washed with liquid soap and dried with disposable
towels after seeing the patient.
For diseases spread via the respiratory route, the use of facemasks
should be considered.
Definitions
Important definitions:
Cleaning is the removal of foreign material from areas or objects to a point
at which they are visually free from debris.
Disinfection is the reduction in the number of infectious particles.
Disinfectants are substances which kill or inhibit microbes.
Sterilisation is the inactivation of all infectious agents and is achieved
mainly via autoclaving or irradiation.
Methods of disinfection:
Iodine is a slow-acting skin anti-bacterial disinfectant.
Chlorhexidine is an anti-staphylococcal agent.
Isopropyl alcohol (alcohol gel) is not effective against C. difficile spores, so
the use of soap and water is essential.

Pathogens and LAST UPDATED: 21ST
APRIL 2019
Pathogenicity  Bookmark
MECHANISMS OF DISEASE
Definitions
Humans encounter bacteria, viruses and parasites that do not cause disease.
An infection occurs when microorganisms cause disease.
Important definitions:
A pathogen is an organism that is capable of causing disease.
A commensal is an organism that is part of the normal flora.
Colonisation is a normal state and is not pathological.
Pathogenicity is the ability to cause disease.
Virulence is the ability to cause severe disease.
Infection describes a microbe-induced state of disease.
Types of Pathogen
Obligate pathogens cannot survive long outside of the human body and must
cause disease in order to be transmitted.
Conditional pathogens may cause disease only if certain conditions are met. For
example, Bacteroides fragilis is a normal gut commensal, but if it invades the
peritoneal cavity, it will cause severe infection, or Neisseria meningitidis, a
normal nasopharynx commensal, may cause meningitis by direct or
haematogenous spread.
Opportunistic pathogens usually cause infection only when the host defences
are compromised. For example, Pneumocystis jiroveci may cause lung infection
in a host who has severely compromised T-cell immunity as seen in HIV
infection.
Pathogen Examples
Obligate HIV, Mycobacterium tuberculosis, Treponema pallidum,
Neisseria gonorrhoeae
Conditional Bacteroides fragilis, Neisseria meningitidis,
Staphylococcus aureus
Opportunistic Candida albicans, Pneumocystis jiroveci, Pseudomonas
aeruginosa

Mechanisms of LAST UPDATED: 21ST
APRIL 2019
Attachment, Invasion and  Bookmark
Persistence
MECHANISMS OF DISEASE
Mechanisms of Attachment
Microorganisms must attach themselves to host tissues to colonise them and
each organism has a different strategy.
For example:
Microorganism Mechanism of Attachment

Neisseria Adheres to the genital mucosa using fimbriae
gonorrhoeae
Influenza Attaches by its haemagglutinin antigen
Giardia lamblia Attaches to gut mucosa via a specialised sucking
disc
HIV Binds strongly to CD4 antigen
Plasmodium Causes red cell protein expression facilitating
falciparum cerebral malaria
Mechanisms of Immune Evasion

Once past natural barriers, to survive in the human host, microorganisms must
overcome the host immune defences.
For example:
Microorganism Mechanism of Evading Host Defence
Neisseria Secretes an IgA protease that degrades host
meningitidis immunoglobulin
Staphylococcus Expresses protein A, which binds host
aureus immunoglobulin, preventing opsonisation and
complement activation
Streptococcus Has a polysaccharide capsule which inhibits
pneumoniae phagocytosis by neutrophils
Vibrio cholerae Motile by virtue of its flagellum, increasing its
virulence
Gram-negative Lipopolysaccharide coat makes them resistant to the
organisms effect of complement
Trypanosoma Alter surface antigens to evade antibodies
spp.
Mechanisms of Damaging Host

In addition to these mechanisms, some microorganisms have the ability to
generate damaging exotoxins:
Vibrio cholerae (causing cholera) produces exotoxin which binds to gut
epithelial cells, activating adenylyl cyclase and resulting in sodium and
chloride efflux from the cell, ultimately causing profuse watery diarrhoea.
Clostridium tetani (causing tetanus) produces the exotoxin
tetanospasmin which has the ability to disrupt neurological signalling and
integrity causing its neurotoxic effects.

Principles of Investigation LAST UPDATED: 21ST
APRIL 2019
PRINCIPLES OF INVESTIGATION  Bookmark
Specimen Types
Examples of specimens required to diagnose infection:
Infection Specimen
UTI Midstream Specimen of Urine (MSSU)
Skin wound Wound swab
Meningitis CSF and blood
Nonspecific pyrexia Blood culture and serology
Pneumonia Blood and sputum
Specimen Culture
Specimen culture allows amplification of organism quantity to allow reliable
detection. There are liquid medium and solid medium types of culture.
Specimen Examination
Specimens may be examined under microscopy:
Stool may be examined directly under light microscopy to detect parasites
in stool.
Special stains can be used to help identify certain organisms under light
microscopy. For example:
Giemsa staining can be used to identify malaria
Ziehl-Neelsen staining can be used to identify Mycobacterium
tuberculosis
Gram staining is used to differentiate between two large groups of
bacteria based on their different cell wall constituents (staining
purple/blue if Gram-positive and red if Gram-negative)
Immunofluorescence microscopy may be used to identify respiratory
syncytial virus (RSV).
Infection Investigation
Stool: parasites Direct light microscopy
CSF: bacteria Gram stain
Sputum: TB Ziehl-Neelsen stain
Blood: malaria Giemsa stain
Sputum: RSV Fluorescence microscopy
Serology
Infection can also be diagnosed by detecting the immune response to the
pathogen (the serology); for example the trend of rising or falling antibodies, or by
the presence of a specific antibody or antigen. These techniques are used for
organisms that are difficult to grow, such as viruses e.g. HIV, Hepatitis B.
Molecular Techniques
Nucleic acid amplification techniques (NAATs) detect specific regions of the
genome from the pathogen and are useful to detect organisms that are slow-
growing or difficult to grow e.g. Mycobacterium tuberculosis or Chlamydia
trachomatis.

United Kingdom LAST UPDATED: 8TH
NOVEMBER 2021
Immunisation Schedule  Bookmark
PRINCIPLES OF IMMUNISATION / PHARMACOLOGY /
IMMUNOGLOBULINS AND VACCINES
Routine Immunisation Schedule
Vaccine Schedule
Diphtheria, tetanus, polio 2, 3, 4 months, preschool and 14 years
Pertussis 2, 3, 4 months and preschool
Hib 2, 3, 4 and 12 months
Pneumococcal 3 and 12 months
Rotavirus 2 and 3 months
MenB 2, 4 and 12 months
MMR 12 months and preschool
MenC 12 months
MenACWY 14 years
Hepatitis B 2, 3 and 4 months
At 2 months the following vaccines are given:
Diphtheria, tetanus, pertussis, polio, Haemophilus influenzae type b
(Hib) and hepatitis B
Rotavirus gastroenteritis
Meningococcal group B
Diphtheria, tetanus, pertussis, polio, Hib and hepatitis B (2nd dose)
Pneumococcal (13 serotypes)
Rotavirus (2nd dose)
Diphtheria, tetanus, pertussis, polio, Hib and hepatitis B (3rd dose)
Meningococcal group B (2nd dose)
Hib (4th dose) and Meningococcal group C
Pneumococcal (13 serotypes) (2nd dose)
Measles, mumps and rubella
Meningococcal group B (3rd dose)
In preschool children (aged 3 years 4 months old) the following vaccines are
given:
Diphtheria, tetanus, pertussis and polio (4th dose)
Measles, mumps and rubella (2nd dose)
In boys and girls aged 12 - 13 the HPV vaccine is offered.
At 14 years (school year 9) the following vaccines are given:
Meningococcal groups A, C, W and Y disease
Tetanus, diphtheria and polio
At 65 years, the pneumococcal (23 serotypes) vaccine is offered.
In patients aged 65 years and older, the influenza vaccine is offered
annually.
At 70 years, the shingles vaccine is offered.
Age Diseases Protected Against Vaccine Given

2 months Diphtheria, tetanus, DTaP/IPV/Hib/HepB
pertussis, polio, MenB
Haemophilus influenzae Rotavirus
type b (Hib) and
hepatitis B
Meningococcal group B
(MenB)
Rotavirus
gastroenteritis
pertussis, polio, Hib and Pneumococcal
hepatitis B conjugate
Pneumococcal (13 vaccine (PCV)
serotypes) Rotavirus
Rotavirus
pertussis, polio, Hib and MenB
hepatitis B
MenB
One year Hib and MenC Hib/MenC
Pneumococcal PCV booster
Measles, mumps and MMR
rubella MenB booster
MenB
Eligible Influenza (each year Live attenuated
Paediatric from September) influenza vaccine
Age Group LAIV
Three Diphtheria, tetanus, DTaP/IPV
years four pertussis and polio MMR
months old Measles, mumps and
(preschool) rubella
Boys and Cervical cancer and HPV (two doses 6-
girls aged genital warts caused by 24 months apart)
12 to 13 human papillomavirus
years (HPV) types 16 and 18
(and genital warts
caused by types 6 and
11)
Fourteen Tetanus, diphtheria and Td/IPV
years old polio MenACWY
(school Meningococcal groups
year 9) A, C, W and Y disease
65 years Pneumococcal (23 serotypes) Pneumococcal
old polysaccharide vaccine
(PPV)
65 years of Influenza (each year from Inactivated influenza
age and September) vaccine
older
70 years Shingles Shingles
old
Selective Immunisation Schedules

BCG vaccine should be given to infants in areas of the country with TB
incidence ≥ 40/100,000, or to infants with a parent or grandparent born in a
high incidence country.
Influenza vaccine should be given to pregnant women during flu season at
any stage of pregnancy, and to at risk children from 6 months to 17 years of
age.
Pertussis vaccine should be given to pregnant women from 16 weeks
gestation.
Hepatitis B vaccine should be given to babies born to hepatitis B infected
mothers at birth, four weeks and 12 months old.
Additional vaccines may be required for individuals with underlying medical
conditions.
https://www.gov.uk/government/publications/the-complete-routine-
immunisation-schedule
Occupational Vaccinations
Healthcare workers are additionally strongly advised to have:
Hepatitis B vaccine
BCG vaccine
Varicella vaccine (if non-immune)
Influenza vaccine (annually)

Acute Epiglottitis LAST UPDATED: 21ST
APRIL 2019
MICROBIOLOGY / INFECTIONS
 Bookmark
Infective Agents
Haemophilus influenzae type b
Clinical Features
High fever
Painful throat causing child to drool saliva and be reluctant to talk, eat or
drink
Stridor
Complications
Bacteraemia
Airway obstruction
Diagnosis
Clinical
Treatment
Senior support
Airway management
Antibiotic therapy
Cefotaxime (or ceftriaxone) first line
Chloramphenicol if history of immediate hypersensitivity to penicillin

Acute Otitis Media LAST UPDATED: 21ST
APRIL 2019
 Bookmark
Acute otitis media is an inflammation in the middle ear associated with effusion
and accompanied by an ear infection.
Infective Agents
Viral (> 50% of cases)
Respiratory syncytial virus (RSV)
Rhinovirus
Bacterial
Haemophilus influenzae
Streptococcus pneumoniae
Moraxella catarrhalis
Streptococcus pyogenes
Clinical Features
Pain in affected ear – pulling, tugging or rubbing of ear
Fever
Irritability, crying, poor feeding
Red and bulging tympanic membrane
Complications
Rupture of tympanic membrane with pus discharge
Hearing loss
Rarely mastoiditis, meningitis, intracranial abscess, sinus thrombosis, facial
nerve paralysis
Diagnosis
Clinical or microscopy, culture and sensitivity of specimen
Treatment
Pain relief
Antibacterial therapy should be offered to children with acute otitis media
who are systemically very unwell, have signs and symptoms of a more
serious illness, or those who are at high-risk of serious complications due to
pre-existing comorbidities. Antibacterial therapy should also be considered
if otorrhoea (discharge following perforation of the eardrum) is present, or in
children under 2 years of age with bilateral otitis media.
When antibiotics are indicated:
Amoxicillin first line (suggested duration of treatment 5 days)
Consider co-amoxiclav if worsening symptoms despite 2 - 3 days of
treatment
If penicillin allergic, clarithromycin or erythromycin

Acute Tonsillitis LAST UPDATED: 5TH
AUGUST 2019
 Bookmark
Tonsillitis is inflammation due to infection of the tonsils. It is a very common

condition, most frequent in children aged 5 – 10 years and young adults between
15 – 25 years.
Clinical Features
Patients may complain of pain in the throat, pain on swallowing, pain referred to
the ears, headache and a high temperature. Nausea, vomiting, and abdominal pain
are common in children. On examination, the throat is red, the tonsils are swollen
and may be coated or have white flecks of pus on them (exudative). Patients are
usually pyrexial and may have swollen and tender anterior cervical glands.
Causes
The most common bacterial cause of tonsillitis is group A beta-haemolytic
streptococcus (GABHS), also called Streptococcus pyogenes (15 – 30% of sore
throats in children and 10% in adults).
Common viral causes of a sore throat include:
Rhinovirus, coronavirus, parainfluenza virus: the common cold (25% of sore
throats)
Influenza types A and B: influenza
Adenovirus: pharyngoconjunctival fever (4% of sore throats)
Epstein-Barr virus: infectious mononucleosis (< 1 % of sore throats)
Herpes simplex virus type 1 (and more rarely type 2): acute herpetic
pharyngitis (2% of sore throats)
Investigations
Investigations are not performed routinely.
Management
Pain and fever should be treated with paracetamol or an NSAID such as ibuprofen.
In most patients, no or delayed antibiotic prescribing is recommended. Sore throat
due to a viral or bacterial cause is a self-limiting condition. Symptoms resolve
within 3 days in 40% of people, and within 1 week in 85% of people, irrespective of
whether or not the sore throat is due to a streptococcal infection
The NICE guidelines suggests that indications for immediate antibiotics include:
Features of marked systemic upset secondary to the acute sore throat
Unilateral peritonsillitis
A history of rheumatic fever or valvular heart disease
An increased risk of severe infection or developing complications (such as a
child with diabetes mellitus or immunodeficiency)
Acute tonsillitis with three or four Centor criteria present (i.e. likely bacterial
infection)
The likelihood of the presence of bacterial infection is based on the Centor Criteria:
History of fever
Tonsillar exudate
No cough
Tender anterior cervical lymphadenopathy
Patients with one or none of these criteria are unlikely to have GABHS.
Consideration of antibiotic prescription should be limited to patients with three or
four criteria.
If antibiotics are to be used, first line is a 10 day course of phenoxymethylpenicillin.
Amoxicillin or ampicillin should be avoided if there is a possibility of glandular
fever. If penicillin-allergic, a 5 day course of clarithromycin is recommended.
Complications
Complications of streptococcal pharyngotonsillitis include:
Local extension:
Otitis media
Acute sinusitis
Peritonsillar abscess (quinsy)
Peritonsillar cellulitis
Parapharyngeal abscess
Retropharyngeal abscess
Mastoiditis
Streptococcal pneumonia
Systemic
Metastatic infection (e.g. brain abscess, endocarditis, meningitis,
osteomyelitis or liver abscess)
Streptococcal toxic shock syndrome
Scarlet fever
Rheumatic fever

Cellulitis LAST UPDATED: 21ST
APRIL 2019
 Bookmark
Infective Agents
Staphylococcus aureus (including MRSA)
Pseudomonas aeruginosa
Gram-negative coliforms (immobile patients)
Risk Factors
Pre-existing skin conditions e.g. eczema
Skin wound e.g. burn, insect bite, cannula insertion site
Peripheral vascular disease
Diabetes mellitus
Clinical Disease
Cellulitis
Erythematous (indistinct margins), swollen, painful lesion that
spreads, typically occurring on the limbs.
Erysipelas
Appears similar to cellulitis but the border is distinct and is typically on
the face, shin or foot
Diagnosis
Clinical diagnosis
Swab lesions for M, C & S
Blood cultures
Treatment
Erysipelas
Phenoxymethylpenicillin or benzylpenicillin
If severe infection, replace phenoxymethylpenicillin or benzylpenicillin
with high-dose flucloxacillin
Suggested duration of treatment at least 7 days
If penicillin-allergic, clindamycin or clarithromycin (or azithromycin or
erythromycin)
Cellulitis
High-dose flucloxacillin
If streptococcal infection confirmed, replace flucloxacillin with
phenoxymethylpenicillin or benzylpenicillin
If Gram-negative bacteria or anaerobes suspected, use broad-
spectrum antibacterials
If penicillin-allergic, clindamycin or clarithromycin (or azithromycin or
erythromycin) or vancomycin (or teicoplanin)
Animal/human bite (for both prophylaxis and treatment of infected bite
wound)
Cleanse wound thoroughly.
For tetanus-prone wound, give human tetanus immunoglobulin (with
a tetanus-containing vaccine if necessary, according to immunisation
history and risk of infection).
Consider rabies prophylaxis for bites from animals in endemic
countries.
Assess risk of blood-borne viruses (including HIV, hepatitis B and C)
and give appropriate prophylaxis to prevent viral spread.
First line: Co-amoxiclav
If penicillin-allergic, doxycycline + metronidazole

Infective Encephalitis LAST UPDATED: 18TH
JUNE 2019
 Bookmark
Encephalitis is inflammation within the substance of the central nervous system.
Infective Agents
Herpes simplex virus (most common cause)
Temporal lobe is most frequently affected
Virus replication in neurons, followed by the oedema associated with
the inflammatory response accounts for the haemorrhagic necrosis
and space-occupying nature of this form of the disease
Varicella zoster virus
Cytomegalovirus
Arbovirus
Mumps
Measles
Clinical Disease
Fever
Headache
Neck stiffness
Impaired consciousness
Focal neurological signs
Seizures
Diagnosis
Lumbar puncture
Viral encephalitis leads to a lymphocytosis with normal CSF/plasma
glucose ratio
Elevated CSF to serum antibody ratios indicate CSF infection with the
respective organism
PCR analysis of CSF can be used to diagnose most viral infections
Blood FBC, biochemistry, film, serology and cultures
CT/MRI head may demonstrate focal lesions
EEG
Treatment
Treatment of herpes simplex encephalitis is with intravenous aciclovir

Infective Endocarditis LAST UPDATED: 21ST
APRIL 2019
 Bookmark
Infective Agents
Bacteria
Staphylococcus aureus (intravenous drug use, indwelling vascular
catheters, prosthetic or native valves)
Coagulase-negative Staphylococcus spp. (neonates and prosthetic
heart valves)
Alpha-haemolytic streptococci (dental conditions or procedures)
Streptococcus agalactiae
Enterococcus spp. (gastric surgery or pathology)
HACEK organisms:
Haemophilus spp.
Actinobacillus actinomycetemcomitans
Cardiobacterium hominis
Eikenella corrodens
Kingella kingae
Fungi
Candida spp.
Aspergillus spp.
Histoplasma spp.
Pathogenesis
There are two main risk factors for infective endocarditis:
Bacteraemia
IVDU
dental treatment or poor hygiene
infections e.g. skin, UTI, respiratory
cardiac surgery e.g. pacemaker insertion
venous procedures e.g. cannula or central venous line insertion
Abnormal cardiac epithelium
Heart valve disease
Rheumatic heart disease
Prosthetic heart valves
Structural defects e.g. VSD, PDA, calcified aortic stenosis,
hypertrophic cardiomyopathy
Previous episode of infective endocarditis
Structurally weakened and damaged endocardium is susceptible to colonisation
with an infective organism, especially if a thrombus has already been deposited.
This process of infection and deposition of thrombus continues, forming the
characteristic vegetation lesion. As the disease progresses, the valve is destroyed
and regurgitation or obstruction develops. Thrombi from the vegetation can
embolise to distant sites. In addition, infective organisms can enter the circulation
and form immune complexes.
Clinical Disease
Symptoms
Systemic features: fever and night sweats, malaise, weight loss
Haematuria
Arthralgia
Symptoms of heart failure
Signs
Clubbing
New/changed murmur
Splenomegaly
Osler's nodes (painful, red, raised lesions on pulps of fingers)
Janeway lesions (red painless macules on palm)
Splinter haemorrhages (small, straight lesions under the nails)
Roth's spots (red lesions with central pale zone seen on fundoscopy)
Petechiae on skin
Complications
Right-hand side (associated with IVDU)
Pulmonary embolism
Lung abscess
Left-hand side
Renal failure (immune complex deposition or decreased renal blood
flow)
Stroke (thrombotic embolism or cerebral haemorrhage)
Distal gangrene (embolism or vasculitis)
Gastrointestinal/splenic embolism
Diagnosis
Urine dipstick - microscopic haematuria
Blood tests (FBC, U&Es, CRP/ESR) - anaemia, neutrophil leucocytosis, raised
inflammatory markers
Blood cultures (three separate sets)
Echocardiography (transesophageal or transthoracic) - vegetations or valve
dysfunction
Chest x-ray - signs of heart failure
Treatment
Infection Treatment
Initial 'blind' Amoxicillin
therapy for Consider adding low-dose gentamicin
native-valve If penicillin-allergic, or if MRSA suspected, or if
endocarditis severe sepsis, use vancomycin + low-dose
gentamicin
If severe sepsis with risk factors for Gram-
negative infection, use vancomycin + meropenem
Initial 'blind' Vancomycin + rifampicin + low-dose gentamicin
therapy for
prosthetic-valve
endocarditis
Infection Treatment
Native-valve Flucloxacillin (suggested duration of treatment 4
endocarditis weeks, at least 6 weeks if secondary lung abscess
caused by or osteomyelitis also present)
Staphylococci If penicillin-allergic or if MRSA, use vancomycin +
spp. rifampicin
Prosthetic-valve Flucloxacillin + rifampicin + low-dose gentamicin
endocarditis (suggested duration of treatment at least 6
caused by weeks)
Staphylococci If penicillin-allergic or if MRSA use vancomycin +
spp. rifampicin + low-dose gentamicin
Endocarditis Fully-sensitive species:
caused by benzylpenicillin (suggested duration of treatment
Streptococcus 4 - 6 weeks, 6 weeks for prosthetic valve
spp. endocarditis)
Less-sensitive species: benzylpenicillin + low-
dose gentamicin
If penicillin-allergic, vancomycin (or teicoplanin) +
low-dose gentamicin
Endocarditis Amoxicillin + low dose gentamicin or
caused by benzylpenicillin + low-dose gentamicin
Enterococci spp. (suggested duration of treatment 4 - 6 weeks, 6
weeks for prosthetic valve endocarditis)
If penicillin-allergic or penicillin-resistant,
vancomycin (or teicoplanin) + low-dose
gentamicin
If gentamicin resistant add streptomycin (if
susceptible) for 2 weeks
Endocarditis Amoxicillin + low-dose gentamicin (suggested
caused by duration of treatment 4 weeks, 6 weeks for
HACEK prosthetic valve endocarditis)
microorganisms: If amoxicillin-resistant, ceftriaxone (or
cefotaxime) + low-dose gentamicin
Prevention
Patients at risk of endocarditis should be:
advised to maintain good oral hygiene;
told how to recognise signs of infective endocarditis, and advised when to
seek expert advice.
Antibacterial prophylaxis and chlorhexidine mouthwash are not recommended for
the prevention of endocarditis in patients undergoing dental procedures.

MICROBIOLOGY / INFECTIONS LAST UPDATED: 16TH
JUNE 2022
 Bookmark
Infective Agents
Viral causes
Enteroviruses (Coxsackievirus, poliovirus and Enterovirus)
Varicella zoster virus
Herpes simplex virus
Mumps virus
Bacterial causes vary by age:
Age Pathogens
Neonate (< 1 Group B Streptococcus, Escherichia coli, Listeria
month) monocytogenes
Children (< 15 years) Streptococcus pneumoniae, Neisseria meningitidis,
Adult (< 55 years) Streptococcus pneumoniae, Neisseria meningitidis
Adult (> 55 years) Streptococcus pneumoniae, Neisseria meningitidis,
Listeria monocytogenes
Immunosuppressed Mycobacterium tuberculosis, Cryptococcus
Clinical Disease
Headache
Photophobia
Fever
Neck stiffness
Poor feeding/irritability
Altered consciousness or confusion
Kernig's sign (extension of flexed knee causes pain and resistance to
movement)
Brudzinski's sign (passive neck flexion causes bilateral hip and knee flexion)
Bulging fontanelle
Diagnosis
Lumbar puncture for CSF analysis, Gram-stain, microscopy and culture
Blood for culture, rapid antigen detection and glucose determination
CT head to exclude encephalitis
CSF Interpretation
Physical characteristics
Opening pressure: normally 10 - 20 cm H2O, may be elevated in infection
or bleed
Colour: clear and colourless is normal
Turbidity: cloudy or turbid CSF may indicate the presence of WBCs, RBCs,
microorganisms or an increase in protein levels
Viscosity: ‘thick’ CSF may be seen in infection
Biochemistry
CSF glucose: usually about 2/3s that of serum glucose, may be decreased
in bacterial or TB infection but usually remains normal in viral infection
CSF protein: increase in protein may be seen in infection
CSF lactic acid: usually raised in bacterial infection, but normal in viral
infection
CSF lactate dehydrogenase (LDH): usually raised in bacterial infection,
but low or normal in viral infection
CSF xanthochromia (bilirubin): seen following subarachnoid haemorrhage
Microscopy
CSF RBC count: presence of red blood cells may indicate bleeding into the
CSF or a ‘traumatic tap’
CSF WBC count: raised in infection or inflammation of the CNS
CSF WBC differential: neutrophils increased in bacterial infection, an
increase in lymphocytes with viral or TB infection
Microbiology
CSF Gram stain
CSF culture and sensitivity
CSF viral PCR testing
Other specific tests depending on which organisms are suspected
CSF Normal Bacterial Viral TB

Analysis (adults)
Appearance Clear and Turbid Normal Fibrin web
colourless
WCC (mm3) 0-5 High High High
Predominant - Neutrophils Lymphocytes Lymphocytes
cell type
Glucose 2.5 - 4.4 Low Normal Low
(mmol/L) mmol/L
CSF:Serum 0.6
Ratio
Protein (g/L) 0.2 - 0.4 High Normal or High

High
Treatment
Infection Treatment
Initial Benzylpenicillin should be given immediately if
empirical meningococcal disease is suspected in the community
treatment for In hospital, if aetiology unknown:
suspected For child < 3 months, cefotaxime + amoxicillin
meningitis For adult and child 3 months - 50 years,
ceftriaxone
For adult > 50 years, ceftriaxone + amoxicillin
Consider adding vancomycin if prolonged or
multiple use of other antibacterials in the last 3
months, or if travelled, in the last 3 months, to
areas outside the UK with highly penicillin- and
cephalosporin-resistant pneumococci
Meningitis Benzylpenicillin or cefotaxime/ceftriaxone (suggested
caused by duration 7 days)
Meningococci If penicillin allergic, chloramphenicol
spp.
Infection Treatment
Meningitis Cefotaxime/ceftriaxone (suggested duration 14 days)
caused by Consider adjunctive treatment with dexamethasone
Pneumococci If microorganism penicillin-sensitive, replace
spp. cefotaxime with benzylpenicillin
If microorganism highly penicillin and cephalosporin
resistant, add vancomycin +/- rifampicin
Meningitis Cefotaxime/ceftriaxone (suggestive duration 10 days)
caused by Consider adjunctive treatment with dexamethasone
Haemophilus If penicillin allergic or microorganism resistant to
influenzae cefotaxime, chloramphenicol
For H. influenzae type b give rifampicin for 4 days
before hospital discharge to those under 10 years of age
or to those in contact with vulnerable household
contacts
Meningitis Amoxicillin (or ampicillin) + gentamicin (suggested
caused by duration of treatment 21 days)
Listeria If penicillin allergic, co-trimoxazole

Myocarditis LAST UPDATED: 21ST
APRIL 2019
 Bookmark
Infective Agents
Viral
Coxsackievirus (most common cause)
Parvovirus B19
Herpesviridae
Echovirus
Adenovirus
Rubella
Bacterial
Mycoplasma pneumoniae
Corynebacterium diphtheriae (toxin-mediated)
Immune-mediated
Group A streptococcal infection (rheumatic fever)
Clinical Disease
Flu-like symptoms associated with fatigue, exertional dyspnoea, palpitations
and precordial pain
Tachycardia, dysrhythmia or cardiac failure may be present
ECG may show T-wave inversion, prolongation of the PR or QRS interval,
extrasystoles or heart block
Chest x-ray may show cardiomegaly
Cardiac enzymes may be elevated
Diagnosis
Viruses may be detected in faecal, nasopharyngeal and throat specimens in
nucleic acid amplification tests (NAATs).
Treatment
Treatment is supportive.

Osteomyelitis LAST UPDATED: 20TH
APRIL 2022
 Bookmark
Infective Agents
Staphylococcus aureus (most common)
Escherichia coli
Salmonella spp. (in sickle cell disease)
Mycobacterium tuberculosis
Pathogenesis
Haematogenous spread - distant infection causes bacteraemia and
subsequent osteomyelitis
Adjacent joint infection - septic arthritis can spread from the joint to the
bone
Direct infection - trauma, surgery or a deep ulcer can infect adjacent bone
Clinical Disease
Systemic features: fever, malaise
Localised pain over bone
Erythema, swelling and pus drainage through sinuses
Pathological fractures
Diagnosis
Clinical diagnosis
X-ray - changes only visible after 7 - 10 days, bone destruction and joint
effusions
MRI - bone destruction, effusions and joint damage
Swab pus for M, C & S
Blood cultures
Treatment
Immobilise bone
Antibiotic therapy
Flucloxacillin first line (clindamycin if penicillin allergic)
Vancomycin (or teicoplanin) if MRSA suspected
Consider adding fusidic acid or rifampicin for initial 2 weeks
Suggested duration of treatment 6 weeks for acute infection
Surgical therapy
Drainage and excision of the sequestrum

Pelvic Inflammatory Disease LAST UPDATED: 8TH
APRIL 2019
 Bookmark
Infectious Agents
Chlamydia trachomatis
Mixed anaerobic infection
Clinical Disease
Symptoms
Fever
Pelvic or lower abdominal pain
Deep dyspareunia
Abnormal vaginal bleeding (intermenstrual or postcoital)
Abnormal vaginal or cervical discharge
Right upper quadrant pain due to perihepatitis (Fitz-Hugh-Curtis
syndrome)
Signs
Lower abdominal or pelvic tenderness
Adnexal, cervical motion or uterine tenderness
Abnormal cervical or vaginal discharge
Complications
Tubal infertility
Ectopic pregnancy
Chronic pelvic pain
Diagnosis
Clinical diagnosis
Endocervical and high vaginal swabs should be taken for nucleic acid
amplification tests (NAATs)
Treatment
Contact tracing recommended
First Line: Doxycycline + metronidazole + single-dose of i/m ceftriaxone or
ofloxacin + metronidazole
Suggested duration of treatment 14 days (except i/m ceftriaxone)
In severely ill patients initial treatment with doxycycline + i/v ceftriaxone +
i/v metronidazole, then switch to oral treatment with doxycycline +
metronidazole to complete 14 days’ treatment

Pneumonia LAST UPDATED: 19TH
JANUARY 2020
 Bookmark
Infective Agents
Community acquired pneumonia
Streptococcus pneumoniae (most common)
Hospital acquired pneumonia (develops at least 24 hours after hospital
admission)
Gram-negative bacilli e.g. Escherichia coli and Klebsiella pneumoniae
Atypical pneumonia
Legionella pneumophila
Chlamydophila pneumoniae
Chlamydophila psittaci
Clinical Features
Symptoms
Systemic features: fever, myalgia, arthralgia, rigors, headache
Cough (+/- productive)
Dyspnoea
Pleuritic chest pain
Signs
Dull percussion note over infected area
Reduced chest expansion on affected side
Bronchial breathing
Crackles
Increased tactile fremitus and vocal resonance
Tachypnoea and tachycardia
Specific Pneumonias
More common in younger patients (school age and young adults)
Outbreaks occur approximately every 4 years in the UK
Flu-like illness followed by dry cough associated with extrapulmonary
complications such as erythema multiforme and SJS, autoimmune
haemolytic anaemia, pericarditis and myocarditis,
meningoencephalitis
Legionella pneumophila
Outbreaks among patients staying at institutions with contaminated
water tanks
Flu-like illness before developing a dry cough and shortness of breath,
associated with renal failure, gastrointestinal upset, confusion and
hyponatraemia
Chlamydia psittaci (psittacosis)
Linked with exposure to infected birds
Flu-like illness, dry cough, high temperature, photophobia and neck
stiffness
Klebsiella pneumoniae
Associated with older patients, diabetes mellitus and alcoholism
Sudden onset flu-like illness, high fever and productive cough with
blood-tinged sputum (red currant jelly sputum)
Diagnosis
Chest x-ray – consolidation +/- pleural effusion
Sputum for M, C & S
Urinary antigens for L. pneumophila and M. pneumoniae
Blood cultures
Bloods (FBC, U&Es, LFTs, CRP)
Serology for atypical organisms
Assessment of CAP
In adults, severity is assessed by clinical judgement guided by mortality risk score
(CURB65):
Confusion (abbreviated mental test, AMT score ≤ 8)
Urea (> 7 mmol/L)
Respiratory rate (≥ 30/min)
Blood pressure (< 90 systolic or ≤ 60 diastolic)
65 (age ≥ 65 years)
Patients are stratified for risk of death as follows:
0 or 1: low risk (less than 3% mortality risk)
2: intermediate risk (3‑15% mortality risk)
3 to 5: high risk (more than 15% mortality risk).
Treatment of CAP
Use clinical judgement in conjunction with the CURB65 score to guide the
management of community‑acquired pneumonia, as follows:
consider home‑based care for patients with a CURB65 score of 0 or 1
consider hospital‑based care for patients with a CURB65 score of 2 or more
consider intensive care assessment for patients with a CURB65 score of 3 or
more.
Infection First Choice Antibiotic

Low- Amoxicillin
severity Alternative in penicillin allergy or if amoxicillin
community unsuitable (for example, atypical pathogens
acquired suspected): Doxycycline, clarithromycin or
pneumonia erythromycin (in pregnancy)
Infection First Choice Antibiotic
Moderate- Amoxicillin
severity With clarithromycin or erythromycin (in pregnancy) if
community atypical pathogens suspected
acquired Alternative in penicillin allergy (guided by
pneumonia microbiological results when available): doxycycline or
clarithromycin
High- Co-amoxiclav with clarithromycin or erythromycin (in
severity pregnancy)
community Alternative in penicillin allergy (guided by
acquired microbiological results when available): levofloxacin
pneumonia

Urinary Tract Infection LAST UPDATED: 16TH
NOVEMBER 2020
 Bookmark
Urinary-tract infection is more common in women than in men; when it occurs in

men there is frequently an underlying abnormality of the renal tract. Recurrent
episodes of infection are an indication for radiological investigation especially in
children in whom untreated pyelonephritis may lead to permanent kidney damage.
Infective Agents
Escherichia coli (most common)
Staphylococcus saprophyticus (especially in sexually active young women)
Proteus mirabilis
Klebsiella pneumoniae
Pseudomonas aeruginosa (particularly in long term catheters)
Staphylococcus epidermidis
Enterococcus faecalis
Risk Factors
Poor hygiene
Sexual activity in females
Outflow obstruction e.g. BPH or prostate cancer, vaginal prolapse in elderly
women, renal calculi, urethral strictures, bladder tumours
Neurogenic bladder
Immunocompromised e.g. chemotherapy, diabetes mellitus
Pregnancy
Urethral catheters
Dehydration
Clinical Disease
Lower UTI
urinary frequency or urgency
dysuria
suprapubic discomfort
Acute pyelonephritis
fever, rigors
loin pain
renal angle tenderness
signs of septicaemia
Acute prostatitis
fever, rigors
Urinary voiding symptoms or acute urinary retention
Perineal or suprapubic pain (penile pain, low back pain, pain on
ejaculation, and pain during bowel movements can also occur)
Tender prostate on examination
Diagnosis
Dipstick test for leucocyte esterase, nitrites and blood
If both dipstick tests are negative, a UTI is unlikely.
If the leucocyte esterase test alone is positive, a UTI is moderately likely.
If the nitrite test is positive, with or without a positive leucocyte
esterase test, a UTI is highly likely.
Midstream urine (MSU) for culture, microscopy and sensitivities (M, C & S)
before starting antibacterial therapy:
in men;
in pregnant women;
in children under 3 years of age;
in patients with suspected upper urinary-tract infection;
complicated infection, or recurrent infection;
if resistant organisms are suspected;
if urine dipstick testing gives a single positive result for leucocyte
esterase or nitrite;
if clinical symptoms are not consistent with results of dipstick testing.
Further investigation in men or children
Treatment
Treatment should not be delayed while waiting for results. The antibacterial chosen
should reflect current local bacterial sensitivity to antibacterials.
Empirical treatment for lower UTI
Trimethoprim or nitrofurantoin first line
Amoxicillin or oral cephalosporin alternatively
Suggested duration 7 days (a 3-day course is usually adequate for
uncomplicated UTI in women)
Treatment for acute pyelonephritis
Oral cefalexin, ciprofloxacin or co-amoxiclav for patients who can be
managed at home
Intravenous cephalosporin or quinolone if unwell, gentamicin can also
be used
Suggested duration 10 - 14 days
Treatment for prostatitis
Ciprofloxacin or ofloxacin (suggested duration 14 days)

Septic Arthritis LAST UPDATED: 21ST
APRIL 2019
 Bookmark
Infective Agents
Staphylococcus aureus (most common)
Enterobacteriaceae
Pathogenesis
Haematogenous spread - distant infection causes bacteraemia and
subsequent septic arthritis
Direct infection - trauma, surgery or a deep ulcer can infect an adjacent joint
Risk factors:
Elderly
Diabetes mellitus
IV drug user
Recent joint surgery
Immunocompromised
Endocarditis or recent bacteraemia
Prosthetic or damaged joints (knee most commonly affected)
Clinical Disease
Acute onset of painful, swollen, hot, erythematous joint with reduced range of
movement secondary to pain +/- systemic features
Diagnosis
Joint aspiration for Gram stain, M, C & S
Cloudy or purulent joint fluid, raised WCC (usually > 50,000), neutrophilia,
low glucose and Gram-stain may suggest infection that can be
confirmed by culture or NAAT
Blood cultures
X-ray may show periarticular soft-tissue swelling
Treatment
Immobilise joint and start physiotherapy early
Antibiotic therapy
Flucloxacillin first line (suggested duration of treatment 4 – 6 weeks,
longer if infection complicated).
If penicillin allergic, clindamycin
If MRSA suspected, vancomycin or teicoplanin
If gonococcal arthritis or Gram-negative infection suspected,
cefotaxime or ceftriaxone
Surgical therapy
Aspiration and irrigation of joint to reduce inflammatory damage

Staphylococcus Aureus LAST UPDATED: 21ST
APRIL 2019
MICROBIOLOGY / PATHOGENS /
STREPTOCOCCI AND STAPHYLOCOCCI  Bookmark
Microorganism Staphylococcus Aureus

Gram stain Gram positive
Shape Cocci (clusters)
Catalase Positive
Coagulase Positive
Oxygen Facultative anaerobe
requirements
Additional Produces exotoxin
features
Reservoir Skin, nasopharynx and fomites
Common Skin & joint infections, device related infection, infective
diseases endocarditis, toxic shock syndrome, scalded
skin syndrome, toxic epidermal necrolysis, food poisoning
Staphylococcus aureus is a catalase-positive, coagulase-positive, beta-haemolytic,
Gram positive coccus found in grape-like clusters.
Transmission
Asymptomatic carriage of S. aureus is found in up to 40% of healthy people, in the
nose, skin, in particular the axilla and perineum, in the gastrointestinal tract and the
vagina. Organisms may spread and cause endogenous infection where there is
lowered host resistance.
Exogenous spread is via direct skin contact or indirect contact by clothing or other
fomites or by respiratory droplet transmission.
Clinical Disease
Staphylococcus aureus causes a wide range of infectious diseases:
Primary skin infection (e.g. impetigo, paronychia, abscess, cellulitis)
Secondary skin infections (e.g. in eczema, surgical wounds, intravenous
devices)
Pneumonia (may follow influenza or measles, typically cavitating)
Endocarditis (most common cause of acute IE, rapid and destructive,
associated with intravenous drug use or colonisation of intravenous devices)
Osteomyelitis
Septic arthritis
Septicaemia
Exotoxin-mediated syndromes include:

Scalded skin syndrome
Toxic shock syndrome
Food poisoning
Methicillin Resistant Staphylococcus Aureus (MRSA) is increasingly prevalent and
causes the same range of infections as susceptible isolates. Hospital acquired MRSA
is associated with antibiotic use, prolonged hospitalisation, surgical site infection,
intensive care, haemodialysis and device related infections.
Treatment
Flucloxacillin is usually the antibiotic of choice to treat methicillin-susceptible
strains and vancomycin or teicoplanin the agents of choice to treat MRSA.
Prevention
Patients colonised with MRSA should be isolated in a side room with barrier nursing.
Carriage may be eliminated by using topical chlorhexidine body wash and mupirocin
nasal ointment.

Staphylococcus Epidermidis LAST UPDATED: 16TH
MARCH 2019
Microorganism Staphylococcus Epidermidis

Shape Cocci (clusters)
Catalase Positive
Coagulase Negative
Oxygen requirements Facultative anaerobe
Additional features /
Reservoir Skin and nasopharynx
Common diseases Prosthetic joint, valve, and line related infections
Staphylococcus epidermidis is an important pathogen involving prosthetic implants,
intravascular lines, ventriculoperitoneal shunts and cardiac valves.
Staphylococcus epidermidis is part of the normal flora of the skin and nasopharynx,
and infection is usually endogenous.
Device removal is usually required for treatment of infections, as well as appropriate
antibiotics.

Streptococcus Pneumoniae LAST UPDATED: 21ST
APRIL 2019
Microorganism Streptococcus Pneumoniae

Shape Cocci (diplococci)
Catalase Negative
requirements
Haemolysis Alpha-haemolytic
Additional Encapsulated
features
Reservoir Nasopharynx
Common Pneumonia, meningitis, sinusitis, otitis media, cellulitis,
diseases deep abscesses
Transmission
Streptococcus pneumoniae is an encapsulated diplococci. It is often found in the
normal respiratory flora, particularly in children, smokers and in crowding. Person-
to-person spread may occur via the respiratory droplet route although infection is
usually endogenous.
Risk Factors
Risk factors for infection include:

disturbed consciousness predisposing to aspiration e.g. in general
anaesthesia, alcoholism, convulsions
preceding respiratory viral infections e.g. common cold, influenza
chronic respiratory disease or malignancy
comorbidities e.g. valvular and ischaemic heart disease
diabetes mellitus
chronic renal failure
immune deficiencies e.g. asplenia/hyposplenia, hypogammaglobulinaemia,
HIV, complement deficiency
Clinical Disease
It primarily causes disease of the airways (pneumonia, empyema, COPD
exacerbation) and associated tissues (otitis media, sinusitis, mastoiditis). It is the
most common cause of community acquired pneumonia.
Direct or haematogenous spread can give rise to meningitis; it is one of the most
common causes of acute bacterial meningitis in children and adults in the UK.
Less commonly it can cause cellulitis, abscesses, peritonitis and endocarditis.
Treatment
Penicillins, macrolides or tetracyclines are usually the treatment of choice for
respiratory infections, but third generation cephalosporins (e.g. cefotaxime) are
often used for meningitis and where high-level penicillin or cephalosporin resistance
occurs, a glycopeptide (e.g. vancomycin) should be added.

Streptococcus Pyogenes LAST UPDATED: 21ST
APRIL 2019
Microorganism Streptococcus Pyogenes

Shape Cocci (chains)
Catalase Negative
Haemolysis Beta-haemolytic (Group A)
Additional features Produces haemolytic exotoxin
Common diseases Acute tonsillitis, skin & soft tissue infections,
necrotising fasciitis
Toxin-mediated reactions Scarlet fever, toxic shock syndrome
Post-infectious immune- Rheumatic fever, erythema nodosum, acute
mediated reactions glomerulonephritis
Transmission
Streptococcus pyogenes (Group A beta-haemolytic streptococci) is carried
asymptomatically in the nasopharynx of 5 - 30% of the population, more commonly
in children. Spread occurs via respiratory droplets or by direct contact with infected
wounds on the skin.
Clinical Disease
Streptococcus pyogenes causes a wide range of infectious disease including:
Local nasopharyngeal spread
Pharyngitis
Tonsillitis
Peritonsillar abscess
Sinusitis
Otitis media
Pneumonia (rarely)
Meningitis
Skin and soft tissue infection
Impetigo
Erysipelas
Wound infections
Necrotising fasciitis
Septic arthritis
Osteomyelitis
Toxin-mediated reactions
Scarlet fever
Streptococcal toxic shock syndrome
Puerperal fever
Postinfectious immune-mediated sequelae
Rheumatic fever
Erythema nodosum
Treatment
Benzylpenicillin is usually the treatment of choice. Amoxicillin or
phenoxymethylpenicillin may be used for oral therapy in less severe infections.
Macrolides are an alternative for patients with allergy.

Streptococcus Spp. LAST UPDATED: 21ST
APRIL 2019
Streptococcus Pyogenes
Microorganism Streptococcus Pyogenes

Catalase Negative
Haemolysis Beta-haemolytic (Group A)
Additional features Produces haemolytic exotoxin
Common diseases Acute tonsillitis, skin & soft tissue infections,
necrotising fasciitis
Toxin-mediated reactions Scarlet fever, toxic shock syndrome
Post infectious immune- Rheumatic fever, erythema nodosum, acute
mediated reactions glomerulonephritis
Streptococcus Pneumoniae

Catalase Negative
requirements
Additional Encapsulated
features
Common Pneumonia, meningitis, sinusitis, otitis media, cellulitis,
diseases deep abscesses
Streptococcus Viridans
Microorganism Streptococcus Viridans

Catalase Negative
Reservoir Mouth
Common diseases Dental abscess, infective endocarditis

Viridans Group Streptococci LAST UPDATED: 16TH
MARCH 2019
(VGS)  Bookmark
STREPTOCOCCI AND STAPHYLOCOCCI
Microorganism Viridans Group Streptococci (VGS)

Catalase Negative
Reservoir Mouth
Common diseases Dental abscess, endocarditis

Campylobacter Jejuni LAST UPDATED: 21ST
APRIL 2019
GRAM-NEGATIVE GASTROINTESTINAL DISEASE  Bookmark
Microorganism Campylobacter Jejuni

Gram stain Gram negative
Shape Rod (spiral flagellate)
Oxygen Microaerophilic
requirements
Oxidase Positive
Reservoir Multiple animals and fowl - contaminated food
Transmission Oral-faecal route
Diseases Acute bloody diarrhoea (dysentery), Guillain Barre
syndrome
Campylobacter spp. are a common cause of acute infective gastroenteritis,
particularly in children, with Campylobacter jejuni responsible for 90% of
Campylobacter gastroenteritis.
Transmission
Campylobacter spp. are found in human and animal gastrointestinal tracts. Infection
typically follows ingestion of contaminated meat (most frequently undercooked
poultry), unpasteurised milk or contaminated water, following which the
microorganism invades and colonises the mucosa of the small intestine.
Clinical Disease
Clinical features typically include:
Fever
Flu-like illness
Abdominal pain/cramps (children may be misdiagnosed with acute
appendicitis or intussusception)
Profuse and occasionally bloody diarrhoea
Nausea and vomiting
Diagnosis
Diagnosis is made from culture of a stool specimen.
Treatment
Diarrhoea is usually self-limiting and treatment supportive but antibiotics may be
indicated in severe infection or in immunocompromised patients; first line is
clarithromycin (or azithromycin or erythromycin), ciprofloxacin is an alternative.
Complications
Immune-mediated complications include (typically occurring 1 - 2 weeks after
onset):
Reactive arthritis (usually of the ankles, knees and wrists)
Reiter's syndrome (triad of reactive arthritis, conjunctivitis and urethritis)
Guillain-Barre syndrome (an autoimmune ascending peripheral neuropathy)
Prevention
Prevention of Campylobacter infection is dependent on good animal husbandry and
abattoir practices, proper sewage disposal and good food and personal hygiene in
shops, dairies and at home.

Helicobacter Pylori LAST UPDATED: 25TH
JULY 2020
GRAM-NEGATIVE GASTROINTESTINAL DISEASE  Bookmark
Microorganism Helicobacter Pylori

Shape Rod (spiral flagellate)
Oxygen requirements Microaerophilic
Oxidase Positive
Reservoir Gastric mucosa
Diseases Peptic ulcer disease, gastric malignancy
Pathogenesis
Helicobacter pylori is a motile Gram-negative spiral bacillus that lives only on gastric
mucosa, and may be transmitted via the faecal-oral route.
Helicobacter pylori infection causes inflammation of the mucosal lining of the
stomach, depleting the layer of protective alkaline mucus and altering gastric
acidity. H. pylori expresses urease, which raises the pH in the surrounding area and
protects the bacterium from the effects of gastric acid.
Clinical Disease
H. pylori infection is often asymptomatic, but may cause dyspepsia or gastritis and
predisposes to peptic ulceration and gastric malignancy.
Diagnosis
Investigations for diagnosis:
Urea breath test (PPI must be stopped 14 days prior to testing and withhold
testing for 28 days after treatment with an antibiotic)
Stool antigen test (PPI must be stopped 14 days prior to testing and withhold
testing for 28 days after treatment with an antibiotic)
Serology for IgG antibodies (unhelpful where patients have previously been
treated for H. pylori infection)
Gastric biopsy
Treatment
Treatment is with a one week triple-therapy twice-daily dosing regimen that
comprises a proton pump inhibitor (e.g. lansoprazole 30 mg, omeprazole 20 mg or
pantoprazole 40 mg), amoxicillin (1 g) and either clarithromycin (500 mg) or
metronidazole (500 mg).

Neisseria Spp. LAST UPDATED: 21ST
APRIL 2019
MICROBIOLOGY / PATHOGENS / NEISSERIA
 Bookmark
Neisseria Meningitidis
Microorganism Neisseria Meningitidis

Oxygen Obligate aerobe
requirements
Additional features Encapsulated, Ferments glucose and maltose
Transmission Direct contact or respiratory droplet
Diseases Meningitis and meningococcal sepsis (notifiable
diseases)
Risk factors Smoking, winter, complement deficiencies (C5 - C9)
Neisseria Gonorrhoeae
Microorganism Neisseria Gonorrhoeae

requirements
Additional Only ferments glucose
features
Transmission Sexual and peripartum
Diseases Urethritis, epididymo-orchitis, UTI, PID, septic arthritis,
endocarditis, neonatal conjunctivitis

Neisseria Meningitidis LAST UPDATED: 21ST
APRIL 2019
 Bookmark
Microorganism Neisseria Meningitidis

requirements
Additional features Encapsulated, Ferments glucose and maltose
Transmission Direct contact or respiratory droplet
Diseases Meningitis and meningococcal sepsis (notifiable
diseases)
Risk factors Smoking, winter, complement deficiencies (C5 - C9)
Transmission
Asymptomatic carriage of Neisseria meningitidis in the nasopharynx and upper
respiratory tract is common (in about 5 - 10% of the population). Spread largely
occurs from close (e.g. kissing) contact with saliva or respiratory secretions.
Epidemiology
Infection is most common in the winter, with epidemics occurring about every 10 -
12 years. Most invasive infections in the UK are caused by serogroups B or C,
serogroup B most commonly since the introduction of the MenC vaccination in 1999.
The new MenB vaccine was added to the UK routine immunisation schedule in
September 2015.
Pathogenesis
N. meningitidis has three important virulence factors:
A polysaccharide capsule that resists phagocytosis by PMNs (this capsule is
the antigen that defines the serologic groups, that is detected in CSF and that
is used in vaccines)
Endotoxin (LPS) which activates complement and stimulates cytokine release
resulting in fever and shock
An IgA protease that helps the bacteria attach to the membranes of the upper
respiratory tract by cleaving secretory IgA
Immunity against N. meningitidis is dependent on complement activation and
formation of the membrane attack complex (MAC), therefore individuals with
complement deficiencies, particularly C5 - C9, have an increased risk of developing
meningococcal bacteraemia.
Risk Factors
Risk factors for disease:
Environmental risk factors
Overcrowding e.g. military recruits, university students
Respiratory viral infections e.g. influenza
Damage to the upper respiratory tract caused by smoking, low humidity,
dust or trauma
Winter season
Host risk factors
Infants and young children (highest incidence in infancy < 5 years,
second smaller peak at 14 - 19 years)
Older age (> 65 years)
Complement deficiency
Hyposplenia/asplenia
Clinical Disease
The two most important manifestations of disease are meningitis and
meningococcal septicaemia. Meningococcal meningitis is characterised by fever,
headache, neck stiffness, photophobia and reduced consciousness and
meningococcal septicaemia by a non-blanching petechial rash and signs of septic
shock.
Treatment
Treatment of meningococcal disease should be given as soon as the diagnosis is
suspected, and without waiting for investigations.
If meningococcal disease is suspected out of hospital, patients should receive a
single dose of parenteral (IM or IV) benzylpenicillin as soon as possible before urgent
transfer to hospital (as long as this does not delay the transfer).
In hospital, benzylpenicillin or cefotaxime (or ceftriaxone) are the antibiotics of
choice for meningococcal disease. Chloramphenicol may be considered in severe
penicillin allergy.
To eliminate nasopharyngeal carriage, ciprofloxacin, or rifampicin, or ceftriaxone
may be used.
Diagnosis
Definitive diagnosis is made from smear and cultures of blood and CSF aspirate;
rapid antigen detection or NAAT of CSF and blood are sensitive and reliable.
CSF analysis typically shows:
cloudy turbid appearance
raised WCC
predominantly neutrophils
high protein
low glucose (typically < 40% of serum glucose)
Gram-negative diplococci seen under microscopy
Prevention
Prophylaxis against meningococcal disease should be considered with rifampicin or
ciprofloxacin, regardless of meningococcal vaccination status, for all household and
other intimate contacts of an index case and for individuals who have had transient
close contact with an index case where they have been directly exposed to large
particle droplets/secretions from the respiratory tract.
Vaccinations available against N. meningitidis are shown below:
Serotype Vaccine
MenB 2, 4 and 12 months
MenC 1 year
Men ACWY 14 years

Neisseria Gonorrhoeae LAST UPDATED: 21ST
APRIL 2019
 Bookmark

requirements
Additional Only ferments glucose
features
Diseases Urethritis, epididymo-orchitis, PID, septic arthritis,
endocarditis, neonatal conjunctivitis
Transmission
Neisseria gonorrhoeae causes gonorrhoea, a sexually transmitted infection most
common in individuals between 15 and 35 years of age, and may also cause
ophthalmia neonatorum through peripartum transmission.
Clinical Disease
The organism adheres to the genitourinary epithelium via pili, then invades the
epithelial layer, triggering a local acute inflammatory response. It may affect the
mucous membranes of the urethra, endocervix, rectum, oropharynx, and
conjunctiva.
Clinical features may include:
Local infection
Acute painful urethritis, dysuria and purulent urethral discharge in men
(urethral infection is symptomatic in about 90% of men)
Vaginal discharge, irregular bleeding, dyspareunia and dysuria in women
(but endocervical/urethral infection is asymptomatic in about 50% of
cases)
Pharyngitis in pharyngeal infection
Anal pruritus, pain, tenesmus, discharge or bleeding in rectal infection
Purulent conjunctivitis in ocular infection
Disseminated infection
Gonococcal bacteraemia
Septic arthritis
Dermatitis (pustular rashes)
Gonococcal endocarditis
Reactive arthritis
Complications include:
Men
Epididymo-orchitis, penile lymphangitis, periurethral abscess, acute
prostatitis, seminal vesiculitis, urethral scarring and stricture causing
bladder outflow obstruction
Women
Bartholin's abscess, pelvic inflammatory disease, infertility, chronic
pelvic pain, ectopic pregnancy, perihepatitis, pregnancy-related
complications
Diagnosis
Diagnosis is with NAAT, microscopy or culture of a first pass urine sample or urethral
swab in men and urethral or endocervical swabs in women +/- rectal/pharyngeal
swabs if indicated.
Treatment
If diagnosis is suspected from clinical features, the patient should be treated
empirically whilst waiting for laboratory confirmation. Choice of alternative
antibacterial regimen depends on locality where infection acquired.
First line treatment for uncomplicated anogenital and pharyngeal disease is with
ceftriaxone 500 mg IM as a single dose, plus azithromycin 1 g orally as a single dose
(to cover for concomitant chlamydia infection).
A test of cure and contact tracing is recommended for all people who have been
treated for gonorrhoea.
Prevention
Prevention of gonorrhoea involves the use of condoms, avoidance of high risk sexual
behaviour and the prompt treatment of symptomatic patients and their contacts.

Pseudomonas Aeruginosa LAST UPDATED: 21ST
APRIL 2019
MICROBIOLOGY / PATHOGENS / PSEUDOMONAS
 Bookmark
Microorganism Pseudomonas Aeruginosa

Shape Rod
requirements
Oxidase Positive
Additional Non-fermenting, often multidrug resistant
features
Reservoir Soil, water, intestinal flora, fomites
Transmission Direct and indirect contact spread
Disease Nosocomial infection (mainly pneumonia, UTI and wound
infection), colonisation of cystic fibrosis and burns
patients, sepsis, 'hot tub rash', otitis externa, ecthyma
gangrenosum, infective endocarditis, corneal infections
Risk factors Cystic fibrosis, burns, IV drug users, diabetes mellitus,
neutropenia, immunosuppression, indwelling urinary
catheters
Most pseudomonas spp. are aerobic, motile, Gram-negative bacilli that cause
opportunistic infections, particularly in a healthcare environment in patients with
lowered host defences (especially in intensive care units and in neutropenic
patients).
P. aeruginosa is the primary human pathogen. P. aeruginosa produces damaging
cytotoxins and proteases and has other adaptive mechanisms that increase its
virulence.
Transmission
Moist places such as sink-traps, drains and flower vases can harbour P. aeruginosa
and it has a remarkable ability to withstand disinfectant. It may be spread via direct
contact or indirect contact on the hands of healthcare workers or by contaminated
equipment, via ingestion of contaminated food or via inhalation of aerosols.
Clinical Disease
Pseudomonas aeruginosa is implicated in:
Hospital-acquired septicaemia (with high mortality, neutropenic patients at
particular risk)
Catheter-related urinary tract infection
Respiratory infection
Chronic pulmonary infection in cystic fibrosis
Ventilator-associated pneumonia
Hospital acquired pneumonia
Skin and soft tissue infection
Colonisation and chronic infection of venous ulcers
Colonisation of burns and secondary septicaemia
Surgical site infection
Hot tub rash (acute self-limiting folliculitis)
Ecthyma gangrenosum (a destructive skin complication of septicaemia)
Osteomyelitis
Septic arthritis
Ocular infection
Rapidly progressive corneal infection (in contact lens wearers)
Ear infection
Otitis externa
Malignant otitis externa (in diabetics or patients with HIV)
Infective endocarditis (in IV drug users)
Meningitis
Diagnosis
Diagnosis is by culture on selective media.
Treatment and Prevention

Organisms are often multidrug resistant, therefore treatment is guided by
sensitivities.
Prevention of infection can be achieved by maintaining good hygiene and
handwashing practice, minimising unnecessary antibiotic use, minimising the use of
medical devices and using sterile medicated solutions.

Escherichia Coli LAST UPDATED: 6TH
DECEMBER 2020
KLEBSIELLA AND ENTEROBACTERIAE  Bookmark
Microorganism Escherichia coli

Shape Rod
requirements
Oxidase Negative
Additional Lactose-fermenting, produces exotoxin
features
Reservoir Intestinal flora, contaminated food and water
Transmission Faecal-oral, peripartum
Diseases UTI, diarrhoea, peritonitis, wound infections, abdominal
sepsis, neonatal meningitis N.B. E.coli O157 is associated
with HUS and TTP
Transmission
Escherichia coli is a facultatively anaerobic, Gram-negative bacilli that forms a
consistent component of the normal intestinal flora. Transmission is via the faecal-
oral route or via local spread of flora (eg. UTI).
Pathogenesis
Strains of E. coli possess a range of different pathogenic mechanisms (including pili,
a capsule, endotoxin and exotoxins) that enable them to cause a diverse range of
infectious diseases.
Certain uropathic strains are characterised by pili with adhesion proteins that bind to
specific receptors on the urinary tract epithelium. The motility of E. coli aids its ability
to ascend the urethra into the bladder or ascend the ureter into the kidney.
Clinical Disease
It is the most common cause of uncomplicated urinary tract infection in adults
(about 70 - 95% of cases), primarily occurring as an endogenous infection. It is also
the most common cause of nosocomial urinary tract infections, associated with the
use of indwelling urinary catheters.
E. coli is an important pathogen in neonatal meningitis and septicaemia associated
with a high mortality. Exposure of the newborn to E. coli occurs during birth as a
result of colonisation of the vaginal canal. It may also cause meningitis or brain
abscess following neurosurgical procedures, especially when prosthetic devices are
inserted. Enterobacteriaceae are often found as part of the polymicrobial flora of
brain abscess.
Some strains of E. coli, acquired through ingestion of contaminated food and water,
may cause a exotoxin-mediated watery diarrhoea (very common cause of traveller's
diarrhoea), an enteroinvasive shigellosis-like disease or a haemorrhagic
dysentery. Antibiotic therapy is not usually indicated in diarrhoeal diseases.
E. coli serotype O157 (mainly found in undercooked beef) causes a bloody diarrhoea
associated with haemolytic uraemic syndrome (particularly in children),
characterised by haemolytic anaemia, thrombocytopenia and acute renal failure.
E.coli may also be implicated in peritonitis, pneumonia (hospital acquired and
neonatal), wound infection and septicaemia.

Klebsiella Spp. LAST UPDATED: 21ST
APRIL 2019
Microorganism Klebsiella spp.

Shape Rods
Oxygen Facultative anaerobes
requirements
Oxidase Negative
Additional Lactose-fermenting
features
Reservoir Intestine, nasopharynx and skin flora
Diseases UTI, pneumonia, meningitis, otitis media, nosocomial
infections
Transmission
Klebsiella spp. are facultatively anaerobic Gram-negative rods, frequently found in
the human gastrointestinal and upper respiratory tracts but also present in soil and
water. Transmission is via respiratory droplet or local spread of flora.
Clinical Disease
These organisms are usually opportunistic pathogens that cause nosocomial
infections, particularly ventilator-associated pneumonia, catheter-associated
urinary tract infection, device-related and wound infection, septicaemia and
meningitis (neonatal). Outbreaks of infection in high-dependency patients is
associated with septicaemia and high mortality.
Klebsiella pneumoniae is an important respiratory tract pathogen outside hospitals
as well, carried in the respiratory tract of about 10% of healthy individuals. Patients
frequently have predisposing conditions such as advanced age, chronic respiratory
disease, diabetes mellitus or alcoholism. Community acquired pneumonia with K.
pneumoniae is a rare, severe infection characterised by thick, bloody sputum (red
currant jelly sputum), associated with complications such as necrosis and abscess
formation and poor outcomes.

Salmonella Enterica LAST UPDATED: 21ST
APRIL 2019
Microorganism Salmonella Enterica

Shape Rod
requirements
Oxidase Negative
Reservoir Cattle, pigs, poultry, humans
Transmission Faecal-oral route
Diseases Food poisoning, enteric fever, septicaemia,
osteomyelitis
Salmonella species are facultatively anaerobic Gram-negative bacilli. Salmonella
enterica is the primary pathogen in humans, and has a number of pathogenic
serovars (serotypes) including Salmonella typhi (responsible for typhoid fever).
Transmission
Salmonella enterica is a commensal of animal gastrointestinal tracts. Transmission is
primarily by the faecal-oral route, usually from ingestion of contaminated foods e.g.
poultry, eggs, undercooked meat, milk or water.
Patients at risk of infection include those with reduced gastric acid secretion (for
example following gastrectomy, or the use of acid-suppressing drugs) and those
who are immunocompromised or asplenic.
Clinical Disease
There are three main types of Salmonella infections: enterocolitis, enteric fever (such
as typhoid fever) and septicaemia with metastatic infections.
Enterocolitis:
Enterocolitis is characterised by invasion of the epithelial and subepithelial tissue of
the small and large intestines, usually presenting as an acute self-limiting
gastroenteritis with nausea/vomiting, abdominal pain, fever and diarrhoea, following
an incubation period of about 12 - 48 hours. Usually the disease only lasts a few days
and does not require medical care but fluid and electrolyte replacement may be
required.
Enteric fever:
In enteric fever, infection begins in the small intestine but few gastrointestinal
symptoms occur. Enteric fever is characterised by invasion of the intestinal wall, with
spread to local lymph nodes and infection of the reticuloendothelial system and
gallbladder, where the bacteria continue to multiply before passing into the blood
causing a bacteraemia (associated with the onset of fever and other symptoms).
Patients may present with fever, systemic upset, abdominal pain, alteration of bowel
habit (both constipation and diarrhoea may occur), splenomegaly and a rash of 'rose
spots'.
From the gallbladder, a further invasion of the intestine occurs; the bacteria multiply
in the mononuclear phagocytes of Peyer's patches and cause ulceration that may be
complicated by haemorrhage or perforation. Some patients may become chronic
carriers, with gallbladder and bowel colonisation, with ongoing excretion of bacteria
in the faeces for a long time. Cholecystectomy may be necessary to abolish the
chronic carrier state.
Septicaemia:
Septicaemia accounts for only about 5 - 10% of Salmonella infections and typically
occurs in patients with an underlying chronic disease (e.g. malignancy, sickle cell
disease) or in a child with enterocolitis. Bacteraemia results in the seeding of many
organs, with osteomyelitis, pneumonia and meningitis as the most common
sequelae.
Treatment
Salmonella enterocolitis is usually self-limiting and does not require treatment. In
severe or invasive infection, first line treatment is with ciprofloxacin or cefotaxime.
Infections from Middle-East, South Asia, and South-East Asia may be multiple-
antibacterial-resistant and sensitivity should be tested. First line treatment of
typhoid fever is with cefotaxime (or ceftriaxone). Azithromycin is an alternative in
mild or moderate disease caused by multiresistant organisms. Ciprofloxacin is an
alternative if the microorganism is sensitive.
Prevention
Salmonellosis is a notifiable disease and an investigation to determine its source
should be undertaken.
Prevention of infection can usually be achieved with public health and personal
hygiene measures: clean water, good animal husbandry and abattoir practices,
proper sewage treatment, sanitation and hygienic handling of foodstuffs,
pasteurisation of milk and proper cooking of poultry, eggs and meat.
A vaccination is available against Salmonella typhi, which should be given to
individuals who are travelling to high-risk areas (Asia, Africa, Central and South
America).

Chlamydia Trachomatis LAST UPDATED: 21ST
APRIL 2019
MICROBIOLOGY / PATHOGENS / CHLAMYDIA
 Bookmark
Microorganism Chlamydia trachomatis

Features Obligate intracellular bacterium
Reservoir Individuals with asymptomatic genital tract infection
Diseases Chlamydia, trachoma, conjunctivitis, ophthalmia
neonatorum, pneumonia
Members of the Chlamydia spp. are small, nonmotile, Gram-negative, obligate
intracellular organisms that grow in the cytoplasm of host cells.
Chlamydia trachomatis is implicated predominantly in infections of the genital tract
(chlamydia, lymphogranuloma venereum) but also of the eye (conjunctivitis,
trachoma, ophthalmia neonatorum) and occasionally of the lungs (typically neonatal
pneumonia). Chlamydia trachomatis infects only humans and is primarily
transmitted sexually or peripartum.
Clinical Disease
Chlamydia is the most common sexually transmitted infection in the UK and the
most common preventable cause of infertility worldwide. It is most commonly
asymptomatic (in approx. 50% of men and 80% of women), but may present with
pelvic pain, vaginal discharge, dysuria, intermenstrual/postcoital bleeding or
dyspareunia in women, or with urethritis with dysuria and urethral discharge in men.
Diagnosis
Diagnosis is usually by nucleic acid amplification tests (NAATs) although enzyme
immunoassays (EIAs) and cell culture techniques are available. Samples should be
taken as vulvovaginal/endocervical swabs or first-void urine samples in women or
first-void urine samples in men. Pharyngeal or rectal swabs may be required as
indicated.
Treatment
First line treatment for uncomplicated genital chlamydia infection is with
azithromycin (single 1 g dose) or doxycycline (100 mg bd for 7 days). Erythromycin is
an alternative.
Contact tracing is recommended.
Complications
Complications of chlamydia include:
Women
Pelvic inflammatory disease
Perihepatitis as part of Fitz-Hugh and Curtis syndrome
Ectopic pregnancy
Tubal infertility
Chronic pelvic pain
If pregnant - premature rupture of membranes, preterm delivery and low
birth weight
Neonatal ophthalmic infection/pneumonia secondary to peripartum
transmission
Men
Urethral stricture and scarring
Epididymo-orchitis
Prostatitis
Immune-mediated
Reactive arthritis (Reiter’s syndrome is a triad of urethritis, arthritis and
conjunctivitis which can be triggered by chlamydial infection)
Prevention
Prevention of infection can be achieved by the use of condoms, prompt treatment of
both the patient and their sexual contacts, and screening for and treatment of
concomitant STIs.
Ophthalmia Neonatorum
Ophthalmia neonatorum refers to any conjunctivitis occurring in the first 28 days of
life. Conjunctivitis appears in about 20 - 50% of infants exposed to C. trachomatis
infecting the cervix at birth; chlamydia is the single most common cause of
ophthalmia neonatorum in the UK (although gonorrhoeal conjunctivitis has more
severe sequelae). Affected babies present with mucopurulent discharge from one or
both eyes usually within 5 – 14 days. There may be associated preseptal cellulitis
and, less commonly, rhinitis, otitis and pneumonitis. Complications can include
keratitis, conjunctival scarring and permanent visual impairment.
Chlamydial Pneumonias
Chlamydia trachomatis can also cause pneumonia, primarily in infants and young
children.
Two other chlamydial organisms may also cause pneumonia in humans:
Chlamydophila pneumophila infects only humans, is transmitted by aerosol and may
cause upper and lower respiratory tract infections, especially bronchitis and
pneumonia in young adults.
Chlamydophila psittaci infects birds and many mammals. Humans are infected
primarily by inhaling organisms in dry bird faeces. Psittacosis may be asymptomatic
or may produce high fever and pneumonia associated with headache, altered mental
state, and hepatosplenomegaly.

Clostridium Spp. LAST UPDATED: 23RD
APRIL 2020
CLOSTRIDIAL INFECTION  Bookmark
Clostridial toxins
Clostridia produce the largest number of toxins of any bacterial class. The common
source of entry in humans is the gastrointestinal tract or trauma.
Species-specific toxin expression:
Botulism (C. botulinum)
Colitis (C. difficile)
Tetanus (C. tetani)
Septic abortion (C. sordellii)
Gas gangrene (C. perfringens, C. novyi, C. septicum, C. sordellii, C.
histolyticum)
Clostridial food poisoning (C. perfringens)
Clostridium Perfringens
Microorganism Clostridium Perfringens

Shape Rod
Oxygen requirements Obligate anaerobe
Additional features Spore-forming, Produces exotoxin
Reservoir Soil & intestinal flora
Diseases Gas gangrene, food poisoning
Clostridium Tetani
Microorganism Clostridium Tetani

Shape Rod
Additional features Spore-forming, Produces tetanospasmin
Reservoir Soil, dust & intestinal flora
Diseases Tetanus
Clostridium Difficile
Microorganism Clostridium Difficile

Shape Rod
Oxygen Obligate anaerobe
requirements
Additional Spore-forming, Produces Toxin A (enterotoxin) and Toxin
features B (cytotoxin)
Reservoir Intestinal flora & environment
Diseases Pseudomembranous colitis

Clostridium Tetani LAST UPDATED: 18TH
JUNE 2019

Shape Rod
Additional features Spore-forming, Produces tetanospasmin
Reservoir Soil, dust & intestinal flora
Diseases Tetanus
Clostridium tetani is the causative agent of tetanus.
Transmission
Clostridium tetani is found in the human intestinal flora, but infection seems to be
predominantly derived from animal faeces and soil.
Transmission occurs from spores contaminating open wounds. Germination of
clostridial spores and their outgrowth depend upon reduced oxygen tension in
devitalised tissue and non-viable material in a wound.
Pathogenesis
C. tetani produces the exotoxins tetanolysin and tetanospasmin. Tetanospasmin
impairs the membrane of synaptic vesicles, preventing the release of the inhibitory
neurotransmitter GABA at the presynaptic membrane; motor neurons are left under
no inhibitory control and undergo sustained excitatory discharge, causing the
characteristic spasms and spastic paralysis of tetanus. The toxin acts on the spinal
cord, the brainstem, the peripheral nerves, the neuromuscular junction and directly
on muscles.
Clinical Disease
The period between injury and the first signs is usually about 3 - 21 days (average 10
days).
The onset of signs and symptoms following a prodromal fever, malaise and
headache, is typically gradual and descending, usually starting with some stiffness
or pain near a recent wound.
Pain, stiffness and muscle spasm in the face, jaw (lockjaw), neck, back and abdomen
may follow; perioral muscle spasm causes risus sardonicus (a grin-like expression),
and spasms of the back muscles can produce arching of the back with an extended
neck (opisthotonus).
swallowing difficulties
aspiration pneumonia
laryngospasm
respiratory failure
autonomic dysfunction
OPISTHOTONUS. (IMAGE BY CHARLES BELL [PUBLIC DOMAIN], VIA WIKIMEDIA COMMONS)
Treatment
Management of infection
Wound debridement (removes spores and necrotic tissue, eradicating
the anaerobic conditions that facilitate clostridial growth)
Antibiotic therapy (metronidazole is the antibiotic of choice)
Intravenous human tetanus immunoglobulin (neutralises unbound toxin,
reducing the duration and severity of tetanus)
Tetanus toxoid immunisation (stimulates long-term humoral and cellular
immunity)
Control of muscle spasm
Benzodiazepines and other sedatives
Non-depolarising neuromuscular blocking agents
Baclofen
Supportive care
Airway support with prevention of aspiration
Mechanical ventilation
Nutritional support
VTE prophylaxis
Physiotherapy
Ulcer prevention
Immunisation Schedule
Tetanus Routine Childhood Immunisation Schedule:
Dose Time Vaccination type

1st dose 2 months As DTaP/IPV/Hib
2nd dose 3 months As DTaP/IPV/Hib
3rd dose 4 months As DTaP/IPV/Hib
4th dose (1st booster) 3.5 - 5 years (preschool) As DTaP/IPV
5th dose (2nd booster) 13 - 18 years As Td/IPV
If the primary course is interrupted it should be resumed but not repeated, allowing
an interval of one month between the remaining doses.

Clostridium Perfringens LAST UPDATED: 21ST
APRIL 2019
Microorganism Clostridium Perfringens

Shape Rod
Additional features Spore-forming, Produces exotoxin
Reservoir Soil & intestinal flora
Diseases Gas gangrene, food poisoning
Clostridium perfringens is capsulated and produces a range of exotoxins. It is
implicated in gas gangrene and enterotoxin-mediated food-poisoning.
Transmission
It is commonly present in the normal intestinal flora, in faeces and in soil and it may
cause endogenous or exogenous infection. Transmission may occur via wound
contamination with soil or gastrointestinal contents, or via ingestion of
contaminated food.
Clostridial Gas Gangrene

C. perfringens is the most common organism implicated in gas gangrene, although
gas gangrene is almost always a polymicrobial infection involving anaerobes and
facultative organisms. The condition is prevented by good management of
potentially infected, devitalised wounds.
Pathogenesis
Predisposing factors to gas gangrene include:
Tissue damage with contamination with clostridial spores and pyogenic
organisms
Presence of foreign bodies including soil
Impaired tissue perfusion with tissue hypoxia
Host factors e.g. vascular insufficiency, diabetes mellitus, old age, debility,
major surgery to the hip or lower limb
When clostridial infection has been initiated in a focus of devitalised tissue (by
germination of clostridial spores), the organisms multiply rapidly and produce a
range of exotoxins, resulting in tissue damage and necrosis, creating a more
anaerobic environment and further progression of infection.
Clinical Disease
The disease usually occurs within 3 days of injury, and is characterised by:
pain in the wound,
rapidly spreading oedema,
myositis,
necrosis of tissues,
gas production with crepitus,
and profound toxaemia.
GAS GANGRENE. (IMAGE BY ENGELBERT SCHRÖPFER, STEPHAN RAUTHE AND THOMAS
MEYER. [CC BY 2.0 (HTTP://CREATIVECOMMONS.ORG/LICENSES/BY/2.0)], VIA WIKIMEDIA
COMMONS)
Diagnosis
Diagnosis of gas gangrene is clinical and treatment must not wait for laboratory
confirmation.
Management
Management of gas gangrene should involve:
prompt and radical surgical debridement of necrotic and devitalised tissue,
fasciotomy to release tension,
removal of foreign bodies,
thorough wound cleansing and packing (wound left open),
appropriate antibiotic therapy (e.g. combination of penicillin, gentamicin and
metronidazole),
and consideration of hyperbaric oxygen therapy.

MICROBIOLOGY / PATHOGENS / CLOSTRIDIAL INFECTION LAST UPDATED: 8TH
SEPTEMBER 2021
 Bookmark
Microorganism Clostridium Difficile

Shape Rod
Oxygen Obligate anaerobe
requirements
Additional features Spore-forming, Produces Toxin A (enterotoxin) and Toxin B
(cytotoxin)
Reservoir Intestinal flora & environment
Diseases Pseudomembranous colitis
Pathogenesis and Clinical Disease

C. difficile causes pseudomembranous colitis, an acute inflammatory diarrhoeal disease and
an important cause of morbidity and mortality in hospitals.
C. difficile is normally found in the gut flora but its growth is normally suppressed by more
dominant anaerobes. Broad-spectrum antibiotics disturb the normal gut flora and can result
in C. difficile overgrowth. C. difficile spores can be transmitted via the faecal-oral route.
C. difficile produces exotoxins A (an enterotoxin) and B (a cytotoxin) which cause intestinal
fluid secretion and tissue damage resulting in profuse watery diarrhoea, abdominal cramps,
fever, rigors and sepsis.
Possible complications of pseudomembranous colitis include:
Toxic megacolon
Bowel perforation
Dehydration and AKI
Electrolyte disturbance
Systemic toxicity
Diagnosis
Diagnosis is with ELISA detection of toxins in stool.
Stopping the implicated antibiotic
Clindamycin, cephalosporins, fluoroquinolones and co-amoxiclav are
particularly high risk
Appropriate antibiotic therapy
First-line antibiotic for a first episode of mild, moderate or severe C. difficile
infection: Vancomycin 125 mg orally four times a day for 10 days
Second-line antibiotic for a first episode of mild, moderate or severe C. difficile
infection if vancomycin is ineffective: Fidaxomicin 200 mg orally twice a day for
10 days
Antibiotics for life-threatening C. difficile infection: Seek urgent specialist
advice, which may include surgery. Antibiotics that specialists may initially offer
are: Vancomycin 500 mg orally four times a day for 10 days with metronidazole
500 mg intravenously three times a day for 10 days
Fluid and electrolyte management
Rapid and strict isolation with barrier nursing
Enhanced ward cleaning and attention to hand hygiene
C. difficile spores are resistant to alcohol hand gel, so strict handwashing with
soap

Malaria LAST UPDATED: 6TH
DECEMBER 2020
MICROBIOLOGY / PATHOGENS / MALARIA
 Bookmark
Malaria is an infection of red blood cells caused by a protozoan parasite. Endemic

malaria is predominantly found in the tropics and subtropics.
Species
There are four different Plasmodium species relevant in humans:
Plasmodium falciparum
Plasmodium vivax
Plasmodium ovale
Plasmodium malariae
Some red blood cell defects (e.g. sickle cell disease, thalassaemia and glucose 6-
phosphate dehydrogenase deficiency) confer some protection against P.
falciparum malaria.
Life Cycle
Transmission
The Plasmodium spp. is transmitted to the human host by the bite of
the female Anopheles mosquito, which injects sporozoites present in
its salivary glands into the bloodstream.
Hepatic stage
The sporozoites travel to the liver where they invade, replicate and
mature in liver parenchymal cells over 1 - 2 weeks (asymptomatic
period) to form hepatic schizonts.
The hepatic schizonts subsequently rupture releasing merozoites
into the bloodstream.
Some sporozoites from latent hepatic schizonts (hypnozoites) that
can reactivate months to years later (P. ovale and P vivax only).
Erythrocytic stage
The released merozoites invade erythrocytes and multiply rapidly
forming erythrocytic schizonts.
The erythrocytic schizont subsequently ruptures releasing more
merozoites into the bloodstream and resulting in destruction of the
RBC, provoking an acute inflammatory response with release of
cytokines responsible for most of the clinical features of malaria.
Reproductive stage
Some merozoites develop into gametocytes which can reenter the
Anopheles mosquito when an infected individual is rebitten, and
develop in the mosquito gut into sporozoites, which migrate to the
insect's salivary glands.
LIFE CYCLE OF PLASMODIUM FALCIPARUM. (IMAGE BY CDC/ALEXANDER J. DA SILVA,

PHD/MELANIE MOSER [PUBLIC DOMAIN], VIA WIKIMEDIA COMMONS)
Clinical Features
Clinical features vary widely, and depend on the causative species.
Malaria is characterised by rigors, fever and sweating associated with headache,
myalgia, malaise, cough, abdominal pain, diarrhoea and vomiting. Signs may
include anaemia, jaundice and hepatosplenomegaly.
P. falciparum is responsible for most fatalities, associated with rapidly progressive
disease.
Complications
Complications of malaria may include:
Cerebral malaria
Circulatory shock
Severe anaemia
Renal impairment
Acute haemolysis with associated renal failure (Blackwater fever)
Acute respiratory distress syndrome
Hypoglycaemia
Metabolic acidosis
Nephrotic syndrome
Splenic rupture
Septicaemia
Diagnosis
Malaria should be considered in all acutely unwell or pyrexic travellers returning
from endemic areas.
Diagnosis is with serial blood film examination - three negative malaria smears 12
- 24 hours apart blood films are required to exclude a diagnosis. Thick blood film is
used for malaria diagnosis and thin blood film to diagnose the species of
Plasmodium.
Newer, more rapid antigen detection tests may also be used.
Treatment
Specialist advice should be sought.
If the infective species is not known, or if the infection is mixed, initial treatment
should be as for falciparum malaria. Falciparum malaria can progress rapidly in
unprotected individuals and antimalarial treatment should be considered in those
with features of severe malaria and possible exposure, even if the initial blood
tests for the organism are negative.
FALCIPARUM MALARIA:
Falciparum malaria (malignant malaria) is caused by Plasmodium falciparum. In
most parts of the world P. falciparum is now resistant to chloroquine which
should not therefore be given for treatment.
Quinine, Malarone® (atovaquone with proguanil hydrochloride), or Riamet®
(artemether with lumefantrine) can be given by mouth if the patient can swallow
and retain tablets and there are no serious manifestations (e.g. impaired
consciousness); quinine should be given by intravenous infusion if the patient is
seriously ill or unable to take tablets. Mefloquine is now rarely used for treatment
because of concerns about resistance.
Oral quinine is given by mouth for 5–7 days, together with or followed by either
doxycycline for 7 days or clindamycin for 7 days [unlicensed]. If the parasite is
likely to be sensitive, pyrimethamine with sulfadoxine as a single dose
[unlicensed] may be given (instead of either clindamycin or doxycycline) together
with, or after, a course of quinine.
Alternatively, Malarone®, or Riamet® may be given instead of quinine. It is not
necessary to give clindamycin, doxycycline, or pyrimethamine with sulfadoxine
after Malarone® or Riamet® treatment.
If the patient is seriously ill or unable to take tablets, or if more than 2% of red
blood cell are parasitized, quinine should be given by intravenous infusion
[unlicensed] (until patient can swallow tablets to complete the 7-day course
together with or followed by either doxycycline or clindamycin).
Specialist advice should be sought in difficult cases (e.g. very high parasite count,
deterioration on optimal doses of quinine, infection acquired in quinine-resistant
areas of south east Asia) because intravenous artesunate may be available for
‘named-patient’ use.
FALCIPARUM MALARIA IN PREGNANCY:
Falciparum malaria is particularly dangerous in pregnancy, especially in the last
trimester. The adult treatment doses of oral and intravenous quinine (including
the loading dose) can safely be given to pregnant women. Clindamycin should be
given after quinine [unlicensed indication]. Doxycycline should be avoided in
pregnancy (affects teeth and skeletal development); pyrimethamine with
sulfadoxine, Malarone®, and Riamet® are also best avoided until more
information is available. Specialist advice should be sought in difficult cases (e.g.
very high parasite count, deterioration on optimal doses of quinine, infection
acquired in quinine-resistant areas of south east Asia) because intravenous
artesunate may be available for ‘named patient’ use.
NON-FALCIPARUM MALARIA
Non-falciparum malaria is usually caused by Plasmodium vivax and less
commonly by P. ovale and P. malariae. P. knowlesi is also present in the Asia-
Pacific region. Chloroquine is the drug of choice for the treatment of non-
falciparum malaria (but chloroquine-resistant P. vivax has been reported in the
Indonesian archipelago, the Malay Peninsula, including Myanmar, and eastward to
Southern Vietnam).
For the treatment of chloroquine-resistant non-falciparum malaria, Malarone®
[unlicensed indication], quinine, or Riamet® [unlicensed indication] can be used;
as with chloroquine, primaquine should be given for radical cure.
Chloroquine alone is adequate for P. malariae and P. knowlesi infections but in the
case of P. vivax and P. ovale, a radical cure (to destroy parasites in the liver and
thus prevent relapses) is required. This is achieved with primaquine [unlicensed]
given after chloroquine, with the dose dependent on the infecting organism. For a
radical cure, primaquine [unlicensed] is then given for 14 days, with the dose also
dependent on the infecting organism.
NON-FALCIPARUM MALARIA IN PREGNANCY
The adult treatment doses of chloroquine can be given for non-falciparum
malaria. In the case of P. vivax or P. ovale, however, the radical cure with
primaquine should be postponed until the pregnancy is over; instead chloroquine
should be continued, given weekly during the pregnancy.

Legionella Pneumophila LAST UPDATED: 21ST
APRIL 2019
MICROBIOLOGY / PATHOGENS / LEGIONELLA
 Bookmark
Microorganism Legionella Pneumophila

Shape Rod (coccobacilli)
Oxygen requirements Obligate aerobes
Additional features Fastidious organisms
Reservoir Contaminated water and air-conditioning units
Transmission Aerosol
Disease Pneumonia
Legionella spp. are obligate aerobic, water-borne Gram-negative coccobacilli.
Legionella pneumophila is the most frequent pathogen implicated in human
disease, causing about 90% of pneumonia attributed to Legionella spp.
Transmission
Legionella spp. are predominantly found in environmental water sources such as
warm springs, domestic water supplies, water-cooling towers, air-conditioning
systems, swimming pools and hot tubs. Multiplication typically occurs at
temperatures between 20 - 40°C. Transmission is via inhalation of aerosols
generated from, for example, showers, taps and air-conditioning systems;
person-to-person spread does not typically occur.
Host risk factors include:
male patients
older patients
previous lung disease
smoking
high alcohol intake
immunosuppression
Clinical Disease
Clinical features may vary in severity and include:
Pontiac fever
mild upper respiratory tract influenza-like illness
Legionnaires disease
severe pneumonia with high mortality
presents with a dry cough, progressive dyspnoea and a high fever
associated with systemic features such as nausea and vomiting,
diarrhoea, headache, malaise, confusion and renal failure
N.B. hyponatraemia is an important laboratory finding that occurs
more often in Legionella pneumonia than in pneumonia caused by
other bacteria
Diagnosis
Diagnosis may be by:
Legionella antigen detection in urine (a rapid and specific method)
Legionella culture of sputum or bronchoalveolar fluid
Direct immunofluorescence of respiratory specimens
Serology (Legionella antibodies take at least 8 days to develop - only really
useful for retrospective diagnosis)
Blood cultures for bacteraemia
Treatment
For low and moderate severity community acquired Legionella pneumonia, an oral
fluoroquinolone or macrolide is recommended. For the management of high
severity or life threatening Legionella pneumonia, both a quinolone and macrolide
may be used together, or rifampicin may be added in for the first few days.
Suggested duration of treatment is usually 7 - 10 days.
Prevention
Legionellosis is a notifiable disease. Legionellosis is prevented by adequate
maintenance of air conditioning systems and ensuring hot-water supplies are
above 45°C to prevent multiplication.

Bordetella Pertussis LAST UPDATED: 10TH
AUGUST 2019
MICROBIOLOGY / PATHOGENS / PERTUSSIS
 Bookmark
Microorganism Bordetella Pertussis

Shape Rod (coccobacilli)
requirements
Additional features Fastidious organism, encapsulated, produces
exotoxin
Transmission Respiratory droplet route
Diseases Whooping cough
Transmission
Bordetella pertussis causes whooping cough, and is spread via the respiratory
droplet route.
Pathogenesis
B. pertussis express fimbriae that aid their adhesion to the ciliated epithelium of
the upper respiratory tract, and produce a number of exotoxins, causing the
characteristic thickened bronchial secretions, paralysis of cilia and
lymphocytosis.
Clinical Disease
The incubation period is about 7 - 10 days (range 5 - 21 days) and whooping
cough is considered to be infectious for 3 weeks after the initial onset of
symptoms. In the absence of an adequate vaccination programme, epidemics of
whooping cough occur in children approx. every 3 - 4 years.
A 1 - 2 week cold-like prodromal illness (catarrhal phase) occurs before the
paroxysmal phase which is characterised by repeated paroxysmal, prolonged
severe coughing fits. Typically, paroxysms consist of a short expiratory burst
followed by an inspiratory gasp, causing the 'whoop' sound. The paroxysms may
be severe enough to cause cyanosis in children, and are frequently associated
with post-tussive vomiting. This phase can last for up to 3 months, during which
there is a gradual improvement in cough frequency and severity. Leucocytosis
with marked lymphocytosis is common during this phase of the illness.
Secondary bacterial bronchopneumonia
Secondary bacterial otitis media
Apnoea following coughing spasms
Seizures
Encephalopathy
Unilateral hearing loss
Complications due to violent prolonged coughing
Pneumothorax, abdominal hernia formation, rectal prolapse, rib
fracture, herniation of lumbar intervertebral discs, urinary
incontinence, subconjunctival haemorrhage, facial/truncal
petechiae, post-coughing vomiting leading to
dehydration/malnutrition
Clinical Diagnosis
Whooping cough should be suspected if a person has an acute cough that has
lasted for 14 days or more without another apparent cause, and has one or more
of the following features:
Paroxysmal cough.
Inspiratory whoop.
Post-tussive vomiting.
Undiagnosed apnoeic attacks in young infants.
Clinical suspicion should be raised if the person is not fully immunized, or has
been in contact with a person who is confirmed or suspected of having whooping
cough.
Consider an alternative cause if symptoms are atypical, but be aware that very
young children, adults, and people who have some immunity (due to prior
infection or vaccination) may present with atypical symptoms (cough without
whoop in infants and adults, apnoea in infants, or milder illness).
Laboratory Diagnosis
Whooping cough is a notifiable disease. If there is any suspicion of infection
because of clinical features, a notification form should be completed and sent to
the local Public Health England (PHE) centre within 3 days.
The local health protection team can advise on appropriate tests for confirmation
and surveillance. This will depend on the person's age, the duration of symptoms,
and on local laboratory facilities.
If the cough is of 2 weeks’ duration or less, culture of a nasopharyngeal
aspirate or nasopharyngeal/pernasal swabs is recommended for people of
all ages. However, a negative result does not exclude pertussis.
Real-time PCR testing of nasopharyngeal or throat swabs can also be used
to confirm infection in people of all ages with symptoms of less than three
weeks' duration.
If the cough is of more than 2 weeks’ duration, anti-pertussis toxin
immunoglobulin G (IgG) serology may be employed in people aged over 17
years. Anti-pertussis toxin IgG detection in oral fluid can be used in children
aged 5 to 16 years.
Be aware that serology and oral fluid test results may be confounded by
receipt of a primary or booster dose of pertussis-containing vaccine within
the last year. It is also more difficult to recover the organism in vaccinated
compared with unvaccinated children, which may affect culture results.
Thus, whooping cough is confirmed when a person with clinical features of

pertussis has:
Bordetella pertussis isolated from a nasopharyngeal aspirate or
nasopharyngeal/pernasal swab,or
Detection by real-time PCR of the pertussis toxin S1 promoter region (ptxA-
pr), and the insertion element IS481, or
Anti-pertussis toxin IgG detected in serum or oral fluid in the absence of
vaccination within the past year.
Management
Arrange admission if the person:
Is 6 months of age or younger and acutely unwell.
Has significant breathing difficulties (for example apnoea episodes, severe
paroxysms, or cyanosis).
Has a significant complication (for example seizures or pneumonia).
Note: inform the hospital of the need for appropriate isolation before the
person is admitted.
If admission is not needed, prescribe an antibiotic if the onset of cough is within
the previous 21 days.
A macrolide antibiotic is recommended first-line:
Prescribe clarithromycin for infants less than 1 month of age.
Prescribe azithromycin or clarithromycin for children aged 1 month or older,
and non-pregnant adults.
Prescribe erythromycin for pregnant women.
Offer information and advice to the person and their family/carers:
Advise rest, adequate fluid intake, and the use of paracetamol or ibuprofen
for symptomatic relief.
Inform the person that, even with antibiotic treatment, whooping cough is
likely to cause a protracted non-infectious cough that may take several
weeks to completely resolve. Symptoms are likely to be less severe and
resolve more quickly if the person has been immunized or has had pertussis
before.
Advise the person to seek medical advice if they develop clinical features of
any complications.
Advise that children and healthcare workers who have suspected or
confirmed whooping cough should stay off nursery, school, or work until 48
hours of appropriate antibiotic treatment has been completed, or 21 days
after onset of symptoms if not treated.
People who work in other settings should avoid contact with infants under
one year of age who are unvaccinated or partially vaccinated until 48 hours
of appropriate antibiotic treatment has been completed, or 21 days after
onset of symptoms if not treated.
Prevention
The routine childhood vaccination schedule for pertussis is shown below:
Time frame Vaccine

2 months DTaP/IPV/Hib
Preschool DTaP/IPV

Mycobacterium LAST UPDATED: 21ST
APRIL 2019
Tuberculosis  Bookmark
MICROBIOLOGY / PATHOGENS / TUBERCULOSIS
Tuberculosis (TB) is caused by Mycobacterium tuberculosis, spread via the

airborne route and characterised by chronic granulomatous inflammation. The
lung is the usual primary site of infection, and most infections resolve with local
scarring.
Microorganism Mycobacterium Tuberculosis

Gram stain Weakly Gram positive, or does not stain (strictly
classified as neither)
Shape Rod
Oxygen Aerobic
requirements
Additional Acid fast organism (Ziehl-Neelsen stain)
features
Transmission Airborne route
Disease Tuberculosis
Risk Factors
Risk factors for developing active TB include:
Children < 5 years old
HIV/AIDs
Malignancy
Renal failure
Diabetes mellitus
Immunosuppressants
Social risk factors e.g. homelessness, institutions, overcrowding, prisons
Alcohol or drug misuse
Pathogenesis
Mycobacterium tuberculosis bacilli are ingested by alveolar macrophages but
have the ability to escape the phagolysosome to survive and multiply in the
cytoplasm of the macrophage. Some bacilli are carried in phagocytic cells to the
hilar lymph nodes where additional foci of infection develop. The initial focus of
infection in the lungs together with the enlarged hilar lymph nodes forms the
primary complex. The intense immune response this generates causes local
tissue destruction and granuloma formation resulting in lung cavitation and
cytokine-mediated systemic effects e.g. fever, weight loss.
In about 5 - 10% of patients, the infection is not controlled (progressive primary
TB) and it may give rise to progressive local lesions with symptoms specific to the
site involved, such as the central nervous system, peripheral lymph nodes, bones
and joints, pericardium and genitourinary system, or it may disseminate
throughout the body via haematogenous spread (miliary TB).
Latent TB occurs when the Mycobacterium bacteria remain dormant, and is
asymptomatic and noninfectious. Latent TB infection may be detected by using
the tuberculin skin test (TST) or an interferon-gamma release assay (IGRA). It is
estimated that about one third of the world's population has latent TB infection.
There is a 10% lifetime risk of reactivation of latent TB, particularly if immunity is
impaired, resulting in post-primary TB. Reactivation usually occurs in the apex of
the lungs and can spread locally or to distant sites.
Immunity against TB is dependent on effective T-cell function, so if compromised
such as in HIV infection, individuals are more likely to develop symptomatic
infection, reactivation of latent disease, and extrapulmonary TB.
Clinical Disease
Clinical features of active TB (progressive primary or post-primary) include:
Pulmonary features
Persistent cough
Breathlessness
Haemoptysis
Pleuritic chest pain
Systemic features
Fever
Weight loss
Night sweats
Anorexia
Malaise
Clubbing
Lymphadenopathy (typically painless rubbery lymph node swelling, often
affecting the cervical or supraclavicular lymph node chains)
Bone/joint involvement: Bone or joint pains, back pain (Pott's disease), joint
swelling, paravertebral/psoas abscess, kyphosis, paraplegia
Gastrointestinal involvement: Abdominal or pelvic pain, anorexia and
weight loss, irregular bowel habit, bowel obstruction, fistula or perforation
Genitourinary/renal involvement: dysuria, frequency, haematuria, flank
pain, sterile pyuria, prostatitis, epididymo-orchitis, endometritis, salpingitis
CNS involvement: Headache, fever, vomiting, irritability, confusion, altered
consciousness, cranial nerve palsies, seizures
Skin involvement: Erythema nodosum, lupus vulgaris
Pericardium involvement: Breathlessness, chest pain, ankle swelling,
cardiac tamponade
Miliary disease may occur without evidence of active pulmonary disease
Investigations
Three sputum samples for AFB smear (Ziehl-Neelsen stain), culture and
sensitivities
CXR typically shows upper lobe involvement with cavitation, consolidation,
fibrosis and calcification in chronic disease in addition to hilar/paratracheal
lymphadenopathy and pleural effusion
Bronchoalveolar lavage is an option if sputum is absent/negative
Consider system-specific investigations for suspected extrapulmonary TB
e.g. urine sample, pleural fluid, ascitic fluid, CSF
Management
TB is a notifiable disease
Antibiotic drug treatment (6 months) - the standard unsupervised six
month treatment regimen may be used during pregnancy and
breastfeeding (but streptomycin should not be used in pregnancy); renal
and hepatic function should be monitored during treatment
Initial Phase (2 months)
Isoniazid
Rifampicin
Pyrazinamide
Ethambutol
Continuation Phase (4 months)
Isoniazid
Rifampicin
Infection control
Risk assessment for HIV infection
Specialist coordination of care – people at risk of poor adherence to
treatment may have directly observed therapy (DOT)
Contact tracing and consideration of TB prophylaxis for susceptible close
contacts (with isoniazid, rifampicin or both)

Measles LAST UPDATED: 21ST
APRIL 2019
MEASLES, MUMPS AND RUBELLA  Bookmark
Virus Measles
Incubation 9 - 12 days
period
Relation of Patients are infectious from about 3 days before rash
infectivity to emerges to 4 days after
rash
Relation of Natural infection is followed by lifelong immunity
infection to
immunity
Clinical 2 - 4 day prodromal phase (fever, coryza, cough,
features conjunctivitis), Koplik spots (white papules on buccal
mucosa), maculopapular rash appearing first behind the
ears and spreading to whole body, rash resolves after 7 -
10 days
Complications Secondary bacterial infection (pneumonia, bronchitis,
otitis media), encephalitis, subacute sclerosing
panencephalitis
Diagnosis ELISA and immunofluorescence of saliva/blood, viral
culture of buccal/nasopharyngeal swab
Treatment Supportive treatment, notifiable disease
Vaccination MMR vaccine given at one year and at preschool age
Transmission and Epidemiology

Measles is transmitted by the respiratory droplet route. The incubation period is
about 9 - 12 days and individuals are infectious for about 3 days before the rash
emerges. Natural infection is followed by lifelong immunity.
Mortality is rare, but is higher in patients who have HIV, are immunocompromised,
malnourished, or are under 2 years old. Measles is rare in countries with a
vaccination programme (but has become more prevalent of late due to a failure of
uptake of vaccination).
Clinical Features
A prodromal 2 - 4 day coryzal illness (fever, cough, conjunctivitis, irritability)
normally occurs associated with Koplik's spots (small white papules found on the
buccal mucosa near the first premolars), before a morbilliform maculopapular
rash appears, first behind the ears and then spreading downwards to whole
body. The rash peels off or fades about about 7 - 10 days.
Complications
Complications may include:
secondary bacterial infection
pneumonia
otitis media
bronchitis
encephalitis
subacute sclerosing panencephalitis
a rare, progressive, fatal encephalitis that develops 7 - 10 years after
infection, usually in children who had a primary infection before the
age of 2
a progressive loss of neurological function results in spasticity,
seizures and eventually death
Diagnosis
Measles is unlikely in a fully immunised individual. Following assessment, if a
diagnosis of measles is considered likely, it is essential to notify the local Health
Protection Unit (HPU), and the infection should be confirmed through laboratory
investigation. Investigations may include ELISA, immunofluorescence of saliva or
blood or viral culture of buccal or nasopharyngeal swab.
Treatment
Treatment is supportive and measles will usually resolve over a course of 7 - 10
days. Antivirals may be considered in patients at particularly high risk.
Prevention
Infected patients should be isolated to prevent spread. Patients are considered
infectious for 3 days before the rash emerges and are advised to stay away from
school/nursery/work for four days from onset of the rash.
The measles, mumps and rubella vaccination is given at 1 year and at preschool
age (three years, four months old).

Mumps LAST UPDATED: 21ST
APRIL 2019
Virus Mumps
period
infection to
immunity
Clinical Non-specific features (fever, malaise, myalgia, headache)
features associated with bilateral tender parotitis, usually resolves
after about 7 - 10 days
Complications Meningitis, post meningitis deafness, encephalitis,
orchitis (+ infertility), oophoritis, pancreatitis
Diagnosis NAAT, culture or serology
Treatment Supportive, notifiable disease
Vaccination MMR vaccine given at one year and preschool age

Mumps usually occurs in childhood. The incubation period is about 14 - 24 days.
Subclinical infection is common, especially in children. It is transmitted primarily
by the respiratory droplet route. Natural infection is followed by lifelong immunity.
Epidemics can re-emerge if vaccination coverage falls.
Clinical Features
Clinical features usually include non-specific features such as fever, malaise,
myalgia and headache associated with parotid gland inflammation (parotitis).
Parotitis is usually bilateral and tender, lasting for about 7 - 10 days.
Complications
aseptic meningitis
post meningitis sensorineural deafness
encephalitis
orchitis (and subsequent infertility)
oophoritis
pancreatitis (although complications in a post-vaccine era are rare)
Diagnosis
Diagnosis is usually clinical, but should be confirmed by NAAT or culture of saliva
or serology.
Treatment
Treatment is supportive with bed rest and isolation to prevent spread. There are
no specific treatments available.
Prevention
Infected individuals should be advised to stay away from school/nursery/work for
five days after onset of facial swelling.
The MMR vaccine is given at one year, and at preschool age (three years four
months old).

Rubella LAST UPDATED: 4TH
JULY 2020
Virus Rubella
Transmission Respiratory droplet route or transplacentally
period
Relation of Patients are infectious from 7 days before the rash
infectivity to appears and until 4 days after the rash appears
rash
infection to
immunity
Clinical Prodromal phase (fever, malaise, sore throat) precedes
features fine red maculopapular rash (appearing first on the face
and spreading downwards) associated with
lymphadenopathy (suboccipital and postauricular nodes)
and arthralgia, symptoms last 7 - 10 days
Complications Arthritis, encephalitis, congenital rubella syndrome
(deafness, cataracts, cardiac defects, microcephaly,
cognitive impairment, intrauterine growth restriction)
Diagnosis ELISA or NAAT of saliva
Treatment Supportive, notifiable disease
Vaccination MMR vaccine given at one year and preschool age

Rubella is rare in countries with a vaccination programme. Transmission is by the
respiratory droplet route and transplacentally. The incubation period is 14 -
21 days. Patients are infectious from 7 days before the rash appears until 4 days
after the rash resolves. Natural infection is followed by lifelong immunity.
Clinical Features
Symptoms are often mild, and up to 50% of infections may be subclinical or
inapparent.
A prodrome of mild low-grade fever, malaise and sore throat usually precedes
development of a widespread fine red maculopapular rash (usually appears first
on the face, and then spreads to trunk and limbs, fades in 3 - 5 days) associated
with lymphadenopathy (suboccipital and postauricular nodes) and arthralgia.
Complications
arthritis
encephalitis
congenital rubella syndrome
maternal infection may cause foetal death or severe abnormalities
such as sensorineural deafness, cataracts, cardiac defects,
microcephaly, intrauterine growth restriction and cognitive
impairment; the risk is highest during the first trimester and
decreases in subsequent trimesters
Diagnosis
Diagnosis is with ELISA or NAAT of saliva.
Treatment
Treatment is supportive. There are no specific treatments for rubella.
Prevention
Infected individuals should stay away from school for 4 days from onset of the
rash.
The MMR vaccine is given at 1 year and at preschool age (three years four months
old).

Rotavirus LAST UPDATED: 21ST
APRIL 2019
GASTROINTESTINAL VIRUSES  Bookmark
Virus Rotavirus
Epidemiology Most common cause of infantile gastroenteritis, peak in
children aged 6 months - 2 years, seasonal peaks in winter
Transmission Faecal-oral route
period
Clinical Fever, vomiting, watery diarrhoea, lasting for about 3 - 8
features days
Diagnosis Clinical, can be confirmed with ELISA, NAAT or cell culture
of stool sample
Treatment Supportive, fluid replacement
Prevention Infection control measures, childhood vaccine given at 2
and 3 months
Epidemiology
Rotavirus is the most common cause of infantile gastroenteritis, occurring
predominantly in children between 6 months - 2 years old, with seasonal peaks in
winter. Transmission occurs via the faecal-oral route. Infection in adults is
uncommon because immunity is long lasting.
Clinical Features
Rotavirus is able to survive stomach acid, before infecting and replicating in small
intestinal enterocytes. The damaged cells are sloughed into the lumen, causing
release of the virus; poor sodium and glucose absorption by the immature cells
that replace the damaged cells results in impaired fluid absorption and a resultant
watery diarrhoea.
The onset of symptoms is abrupt, after a short incubation period of 1 - 2 days.
Fever, vomiting and watery diarrhoea are seen in the majority of infected children,
lasting for about 3 - 8 days.
Diagnosis
Diagnosis is usually clinical but it can be confirmed with ELISA, NAAT or virus cell
culture of stool sample.

Treatment is supportive with fluid replacement. Risk of infection can be reduced
by provision of adequate sanitation. A rotavirus vaccine was introduced to the
routine childhood immunisation schedule in July 2013, given at 2 and 3 months.

Norovirus LAST UPDATED: 21ST
APRIL 2019
GASTROINTESTINAL VIRUSES  Bookmark
Virus Norovirus
Epidemiology Most common cause of viral infectious gastroenteritis in UK,
can occur at any age, typically associated with outbreaks in
institutions
Transmission Faecal-oral route, direct or indirect contact
Incubation 24 - 48 hours
period
Clinical Nausea, vomiting, watery diarrhoea, symptoms last about 12 -
features 60 hours
Diagnosis Clinical, confirmed with NAAT of stool sample
Treatment Supportive, fluid replacement
Prevention Isolation, ward closure, good hand-washing technique
Epidemiology
Norovirus is the most common cause of viral infectious gastroenteritis in the UK. In
contrast to rotavirus infection, norovirus infection can occur in people of all ages
because immunity to it is not long lasting.
Norovirus is typically associated with outbreaks of acute self-limiting diarrhoea and
vomiting (sometimes projectile) in hospitals, care home, schools, nurseries and in
other confined communities. Infection is transmitted primarily by the faecal-oral
route but it can also be transmitted by contact with an infected person, consumption
of contaminated food or water, or contact with contaminated surfaces or objects.
Clinical Features
The incubation period is usually about 24 - 48 hours and the duration of symptoms
about 12 - 60 hours. Nausea and vomiting is followed by watery diarrhoea which may
be associated with fever, headache and myalgia.
Virus replication occurs in the mucosal epithelium of the small intestine resulting in
flattening of the villi and hyperplasia of crypt cells.
Diagnosis
Diagnosis is usually clinical but laboratory diagnosis is important for epidemiological
purposes and can be confirmed with NAAT from stool samples.

Treatment is supportive with fluid replacement. Prevention is by isolation, ward
closure, and good hand-washing technique.

Hepatitis A LAST UPDATED: 21ST
APRIL 2019
MICROBIOLOGY / PATHOGENS / HEPATITIS
 Bookmark
Transmission
Hepatitis A transmission is by the faecal-oral route; the virus is excreted in bile and
shed in the faeces of infected people. Faecal shedding has been demonstrated for
2 - 3 weeks before and about a week after, the onset of jaundice. The incubation
period is about 2 - 6 weeks.
Institutional outbreaks may occur in summer, and point-source outbreaks follow
faecal contamination of water or food e.g. oysters.
Clinical features
Hepatitis A is the most common cause of infective hepatitis worldwide.
Asymptomatic infection is more common in children, with the risk of symptomatic
disease increasing with age. Most people made an uneventful recovery.
Prodromal phase (duration 2 days - 2 weeks)
Flu-like symptoms (headache, malaise, fever, myalgia)
Gastrointestinal symptoms (anorexia, nausea/vomiting, diarrhoea,
RUQ discomfort)
Icteric phase (duration 1 - 3 weeks)
Jaundice, pruritus, anorexia, hepatomegaly, hepatic tenderness
Chronic hepatitis and carrier state does not occur and complete immunity is
attained after infection.
Diagnosis
Anti-HAV IgM antibodies are diagnostic, appearing before jaundice develops,
and persisting for about 3 months.
Anti-HAV IgG antibodies denote current or past hepatitis A infection, or
immunity from previous vaccination, conferring lifelong immunity.
Serum transaminases and bilirubin levels are elevated.
Treatment
Treatment is supportive, antiviral agents have no beneficial clinical effect.
Prevention
Reduction of transmission is achieved with adequate sanitation and good personal
hygiene.
Vaccination against hepatitis A is recommended for travellers to high prevalence
areas, patients with chronic liver infections or severe liver disease, individuals who
are at risk due to sexual behaviour or IV drug abuse, and individuals with high risk
occupations e.g. individuals who work with primates, sewage workers, laboratory
staff who work directly with the virus.
Immunisation should be considered for prevention of secondary cases in close
contacts of confirmed cases of hepatitis A. Intramuscular normal immunoglobulin
is recommended for use in addition to hepatitis A vaccine for close contacts of
confirmed cases of hepatitis A who have chronic liver disease or HIV infection, or
who are immunosuppressed or over 50 years of age.

Hepatitis B LAST UPDATED: 16TH
APRIL 2022
 Bookmark
Transmission
Hepatitis B virus (HBV) is transmitted sexually, vertically from mother to child or
through blood (e.g. needlestick injuries, IV drug users, blood products).
Clinical Features
HBV has a long incubation period (2 - 6 months).
Initial infection may be asymptomatic, particularly in children or may be associated
with a prodromal phase characterised by malaise, anorexia, myalgia, nausea and
weakness.
Acute hepatitis of variable severity develops insidiously signalled by the
appearance of jaundice and right upper quadrant abdominal pain; hepatocellular
damage is detectable biochemically with elevated transaminase levels before the
onset of clinical jaundice. Fulminant disease with acute liver failure carries a 1 - 2%
mortality.
In about 90% of people, lifelong immunity is achieved after clearing the infection.
About 10% of patients develop chronic hepatitis which may be complicated by
cirrhosis or hepatocellular carcinoma. Congenital infection carries a very high risk
of chronic infection and hepatocellular carcinoma, whereas only about 5% of
people infected as healthy adults develop chronic infection.
Diagnosis
Serology:
Antigens
Hepatitis B surface antigen (HBsAg)
acute infection (present in blood 6 weeks to 3 months after
acute infection)
presence for greater than 6 months signifies chronic hepatitis B
infection
Hepatitis B envelope antigen (HBeAg)
high level of viral replication and high infectivity
Antibodies
Anti-hepatitis B core antibody (anti-HBc)
IgM: acute viral replication and diagnostic
IgG: previous exposure (chronic state or cleared infection)
Anti-hepatitis B surface antibody (anti-HBs)
hepatitis B immunity (cleared infection or vaccination)
Anti-hepatitis B envelope antibody (anti-HBe)
decreased infectivity (absence = high infectivity)
Disease State Serology

Acute hepatitis B HBsAg, HBeAg, anti-HBc IgM
Chronic hepatitis B (inactive) HBsAg (>6/12), anti HBe, anti-HBc IgG
Chronic hepatitis B (active) HBsAg (>6/12), HBeAg, anti-HBc IgG
Immunity following infection Anti-HBs, anti-HBe, anti-HBc IgG
Immunity due to vaccination Anti-HBs
Treatment
Treatment is supportive for acute infection; acute hepatitis B is a notifiable
disease. Treatment with antivirals should be considered in chronic infection as
responders have a reduced risk of liver damage and liver cancer in the long term.
HBeAg seroconversion is often taken as a mark of treatment success.
Prevention
In August 2017 the UK introduced the hexavalent (DTaP/IPV/Hib/HepB)
combination vaccine into the routine childhood immunisation.
Individuals at high risk should be immunised with HBV vaccine (inactivated
HBsAg). High risk groups include healthcare workers, IV drug users, babies born to
HBV-infected mothers, individuals with chronic liver or renal disease, or those
receiving regular blood transfusions.
Hepatitis B immunoglobulin is available to be given at the same time as
vaccination for non-immune people who have been exposed to potentially
infected blood or body fluid.
Hepatitis D
Hepatitis D virus is transmitted in the same way as HBV and either with HBV or as a
superinfection in an individual infected with HBV. HDV is associated with severe
hepatitis and an accelerated progression to liver failure, cirrhosis and
hepatocellular carcinoma.

Hepatitis C LAST UPDATED: 21ST
APRIL 2019
 Bookmark
Transmission
Transmission is mainly through infected blood.
Risk factors include:
healthcare workers
blood transfusion recipients
intravenous drug users
Sexual transmission and vertical transmission do occur but are
uncommon.
Clinical Features
Infection may cause a mild hepatitis but many cases are asymptomatic;
fulminant disease is rare. In about 20% of cases infection is cleared by the
immune system but patients are not immune to future HCV infection.
HCV infection persists in up to 80% of patients, who are at high risk
of developing cirrhosis, liver failure and hepatocellular carcinoma between
10 - 30 years later.
Diagnosis
Diagnosis is by detection of anti-HCV IgG antibodies which indicate if a
person has ever been infected with HCV (resolved or current infection). If
the antibody test is positive, HCV RNA should be tested for, which if
positive indicates that a person has current infection with active hepatitis
C.
Treatment
Hepatitis C is a notifiable disease.
Treatment is with combination therapy initiated by a specialist, usually
with ribavirin and pegylated interferon, and often combined with a newer
medication such as simeprevir or sofosbuvir; response is best in patients
with particular genotypes and those with low initial viral loads but about
70- 90% will clear the virus.
Liver transplantation is the treatment of choice for people with end-stage
liver disease.
There is no HCV vaccine available currently.

Herpes Viruses LAST UPDATED: 16TH
MARCH 2019
MICROBIOLOGY / PATHOGENS / HERPES VIRUSES
 Bookmark
Herpesvirus Infectious Disease

Herpes simplex Herpes labialis, gingivostomatitis, keratitis,
type 1 encephalitis, meningitis
Herpes simplex Genital herpes, neonatal infection, encephalitis,
type 2 meningitis
Varicella zoster Chickenpox, shingles
virus
Cytomegalovirus Congenital infection, mononucleosis-like syndrome,
encephalitis, pneumonitis, hepatitis, retinitis
Epstein-Barr Infectious mononucleosis (glandular fever)
virus
Human Roseola infantum
herpesvirus 6
Human Roseola infantum
herpesvirus 7
Human Kaposi's sarcoma
herpesvirus 8

Herpes Simplex LAST UPDATED: 21ST
APRIL 2019
 Bookmark
Herpes simplex virus may be subtype 1 or type 2; HSV-1 is generally associated

predominantly with the mouth, eye, and central nervous system and HSV-2 is
found most often in the anogenital tract, although this is not mutually exclusive.
Pathogenesis
Herpes simplex is transmitted through direct contact. It invades skin locally
producing skin vesicles by its cytolytic activity. Local multiplication is followed by
viraemia and systemic infection (although this may go unnoticed) and
subsequent lifelong latent infection.
The virus enters peripheral sensory nerves in primary infection and migrates
along axons to sensory ganglia in the CNS where it remains latent. Reactivation
may be triggered by physical factors e.g. injury, hormones, UV light, or
psychological stress.
Cell-mediated immunity, especially the action of cytotoxic T-cells, is essential in
the control of herpesvirus infections and patients with T-cell deficiency are at
particular risk of reactivation and severe infection.
Clinical Disease
Clinical manifestations include:
HSV-1
acute febrile vesicular gingivostomatitis (more common in younger
children)
herpes labialis (cold sores)
genital herpes (although usually HSV-2)
HSV keratoconjunctivitis (corneal dendritic ulcers may lead to
scarring and blindness)
HSV-2
genital herpes (painful shallow ulcers affecting the genitals, rectum,
mouth and oropharynx associated with lymphadenopathy, dysuria,
fever, myalgia and headache)
herpes labialis (although usually HSV-1)
neonatal herpes (vertical perinatal transmission leads to skin, eye and
mucous membrane disease, disseminated disease or neonatal
encephalitis)
HSV-1 and HSV-2
systemic infection (common among immunocompromised)
herpetic whitlow (primary skin infection typically occurring on the
hands and fingers following direct contact with the virus)
eczema herpeticium (infection of eczema lesions)
herpes simplex meningitis (uncommon, usually self-limiting)
herpes simplex encephalitis (most frequent cause of infectious
encephalitis, may be severe, predilection for temporal lobe, treated
with intravenous aciclovir)
Diagnosis
Diagnosis of herpes simplex by nucleic acid amplification testing (NAAT) of vesicle
fluid, genital or mouth swabs is the most sensitive and specific method of
diagnosis, although the virus grows readily and can be visualised by electron
microscopy (EM).
The ratio between serum and CSF antibody may indicate local production and can
help in the diagnosis of HSV encephalitis. CT/MRI of the brain may detect
temporal lobe lesions that are typical of herpes encephalitis.
Treatment
Treatment of herpes simplex infection should start as early as possible and
usually within 5 days of the appearance of the infection.
In individuals with good immune function, mild infection of the eye (ocular
herpes) and of the lips (herpes labialis or cold sores) is treated with a topical
antiviral drug. Primary herpetic gingivostomatitis is managed by changes to diet
and with analgesics. Severe infection, neonatal herpes infection or infection in
immunocompromised individuals requires treatment with a systemic antiviral
drug. Primary or recurrent genital herpes simplex infection is treated with an
antiviral drug given by mouth. Persistence of a lesion or recurrence in an
immunocompromised patient may signal the development of resistance.
Specialist advice should be sought for systemic treatment of herpes simplex
infection in pregnancy.

Varicella Zoster Virus (VZV) LAST UPDATED: 1ST
AUGUST 2020
 Bookmark
Varicella zoster virus (VZV) causes chickenpox and shingles.
Transmission
Transmission is by direct contact or airborne spread from patients with vesicles,
and it is very contagious to non-immune individuals. The incubation period is
about 10 - 21 days. Recovery provides lifelong immunity.
Clinical Disease
Infection is commonest in children aged 4 - 10 years. Infection can also occur in
adults and is usually more severe.
Chickenpox usually presents with mild systemic symptoms, and a widespread
itchy rash; lesions appear in crops, affecting all regions of the body, including the
oropharynx and genitourinary tract, and progress through macules and papules
to vesicular eruptions which rupture, crust and spontaneously heal. The rash lasts
for about 7 - 10 days.
Secondary skin infection with S. aureus or S. pyogenes
Thrombocytopenic purpura
VZV pneumonitis (high mortality, high risk in immunocompromised and
pregnant women)
Meningitis
Postinfectious encephalitis
Congenital varicella syndrome
Maternal transmission with severe neonatal infection
After primary infection, VZV remains latent in sensory ganglia and in about 20% of
patients will reactivate resulting in shingles, a painful vesicular rash in the related
dermatome. Ocular damage may follow involvement of the ophthalmic division of
the trigeminal nerve. Shingles usually affects older people and the
immunocompromised. Shingles lesions are infectious to non-immune individuals
who are at risk of developing chickenpox. Shingles can not be contracted directly
from chickenpox, or from other cases of shingles. Up to 10% of shingles episodes
will be followed by postherpetic neuralgia.
Diagnosis
Chickenpox and shingles are usually diagnosed clinically, but laboratory diagnosis
can be made with NAAT, microscopy, culture and serology.
Treatment
Chickenpox:
Regardless of immune function and the use of any immunoglobulins, neonates
with chickenpox should be treated with a parenteral antiviral to reduce the risk of
severe disease. Oral therapy in children is not recommended as absorption is
variable. Chickenpox in otherwise healthy children between 1 month and 12 years
is usually mild and antiviral treatment is not usually required.
Chickenpox is more severe in adolescents and adults than in children; antiviral
treatment started within 24 hours of the onset of rash may reduce the duration
and severity of symptoms in otherwise healthy adults and adolescents. Antiviral
treatment is generally recommended in immunocompromised patients and those
at special risk (e.g. because of severe cardiovascular or respiratory disease or
chronic skin disorder); in such cases, an antiviral is given for 10 days with at least
7 days of parenteral treatment.
Pregnant women who develop severe chickenpox may be at risk of complications,
especially varicella pneumonia. Specialist advice should be sought for the
treatment of chickenpox during pregnancy.
Shingles:
In herpes zoster (shingles) systemic antiviral treatment can reduce the severity
and duration of pain, reduce complications, and reduce viral shedding. Treatment
with the antiviral should be started within 72 hours of the onset of rash and is
usually continued for 7–10 days. Immunocompromised patients at high risk of
disseminated or severe infection should be treated with a parenteral antiviral
drug.
Chronic pain which persists after the rash has healed (postherpetic neuralgia)
requires specific management.
Prevention
Although the usual exclusion period is 5 days, all lesions should be crusted over
before children return to nursery or school.
Non-immune individuals who have been exposed to chickenpox and are at special
risk of complications (e.g. neonates, pregnant women and immunocompromised
individuals) may require prophylaxis with varicella-zoster immunoglobulin.
A live attenuated-virus vaccine is available and recommended for non-immune
healthcare workers.

Human Immunodeficiency LAST UPDATED: 6TH
DECEMBER 2020
Virus (HIV)  Bookmark
MICROBIOLOGY / PATHOGENS / HIV
Epidemiology and Transmission

HIV transmission occurs:
by inoculation via a contaminated needle, instrument, blood, or blood
product; through direct exposure of mucous membranes or an open wound
to infected bodily fluids; or by a human bite that breaks the skin
sexually (in semen, preseminal fluid, rectal fluid and vaginal fluids through
vaginal, anal or oral sex)
vertically from mother to child (before or during birth, or in breast milk)
In developed countries, the main risk groups are intravenous drug users, men
who have sex with men (MSM) and individuals who have a current/former partner
from or themselves are from an area with high HIV prevalence.
In developing countries, HIV spread is mainly via heterosexual sexual
transmission, vertical transmission and through unscreened transfusions or use
of contaminated medical equipment. The majority of vertical transmission occurs
during labour; appropriate antiretroviral medication and caesarean section
dramatically reduces the risk.
Pathogenesis
HIV mainly infects CD4+ T helper cells. Viral replication results in progressive T-
cell depletion and impaired cell-mediated immunity with subsequent secondary
opportunistic infections and increased risk of malignancy. B-cell function is also
reduced as a result of lack of T-cell stimulation.
Clinical Features
Incubation period
2 - 4 weeks (all tests will be negative)
Seroconversion illness (2 - 3 week duration)
Fever, myalgia, lymphadenopathy, pharyngitis, maculopapular rash,
headache (may be mistaken for glandular fever)
Latent disease
Duration of this varies widely between people with some progressing
to AIDS within 1–2 years ('rapid progressors') and others maintaining
effective immune function more than 10 years later ('slow
progressors')
Disease progression
Development of acquired immune deficiency syndrome (AIDS)
Defined as CD4 count < 200 cells/uL or development of AIDS-defining
illness
Common secondary infections in patients with HIV or AIDS:
Bacterial
Mycobacterium tuberculosis (TB)
Listeria monocytogenes
Streptococcus pneumoniae
Salmonella spp.
Viral
Herpes simplex
Cytomegalovirus
Varicella zoster virus (shingles)
Measles
Fungal
Cryptococcus neoformans (meningitis)
Pneumocystis jiroveci (pneumonia)
Candida spp.
Protozoan
Toxoplasma gondii
Malignancy
Kaposi sarcoma
Non-Hodgkin's lymphoma
Diagnosis
Diagnosis
Combined HIV antibody and p24 antigen test
If the test is positive, a second sample is required for confirmation
Monitoring
HIV viral load (PCR) and CD4+ count
There is a window of three months after primary infection (during seroconversion)
where the the intial HIV test may be negative, and any negative test should be
repeated after this period.
Treatment
There is no cure for infection caused by the human immunodeficiency virus (HIV)
but a number of drugs slow or halt disease progression. Antiretroviral therapy
(ART) has had a huge positive impact on HIV-related morbidity and mortality, and
aims to reduce viral load to undetectable levels by limiting viral replication, but is
also associated with serious adverse effects. HIV mutates as it replicates so drugs
are used in combinations of 3 or more to reduce drug resistance.
Treatment aims to prevent the mortality and morbidity associated with chronic
HIV infection whilst minimising drug toxicity. Although it should be started before
the immune system is irreversibly damaged, the need for early drug treatment
should be balanced against the risk of toxicity. Commitment to treatment and
strict adherence over many years are required; the regimen chosen should take
into account convenience and patient tolerance. The development of drug
resistance is reduced by using a combination of drugs; such combinations should
have synergistic or additive activity while ensuring that their toxicity is not
additive. It is recommended that viral sensitivity to antiretroviral drugs is
established before starting treatment or before switching drugs if the infection is
not responding.
Antiretroviral drugs are classified into 5 groups depending on how they act:
Nucleoside/tide reverse transcriptase inhibitors (NRTIs).
Non-nucleoside reverse transcriptase inhibitors (NNRTIs).
Protease inhibitors (PIs).
Integrase inhibitors (IIs).
Entry inhibitors (EIs).
Adverse effects of ART include:
Hypersensitivity
Psychiatric — nightmares, sleep disturbance, mood or behaviour changes
Hyperlipidaemia (common)
Lipodystrophy (changes in the distribution of body fat) and lipoatrophy
(loss of subcutaneous fat)
Type 2 diabetes mellitus
Fanconi’s syndrome (dysfunction of the proximal tubule), ureteric colic,
renal and ureteric stones
Lactic acidosis and hepatic toxicity
Bone marrow suppression
Pancreatitis

Influenza LAST UPDATED: 21ST
APRIL 2019
RESPIRATORY VIRUSES  Bookmark
Epidemiology
Antigenic drift occurs via gradual genetic change allowing the virus to change its
surface antigens, undermining previous humoral immunity and thus resulting in
seasonal epidemics (in winter in the UK).
Antigenic shift is where different strains of a virus combine via genetic
reassortment to form a new subtype with new antigens (e.g. human with avian or
pig influenza strains) and this can result in pandemics. Pandemics typically occur
every 10 - 40 years.
Transmission
Transmission is by respiratory droplet spread or direct contact with respiratory
secretions of someone with the infection. The incubation period lasts 1 - 4 days
and patients are infectious for about 3 days, starting 1 day before symptoms
emerge.
Clinical Features
Clinical features usually include headache, myalgia, fever and cough, lasting for 3
- 4 days.
Complications
primary viral or secondary bacterial pneumonia (more common in the
elderly and in patients with cardiopulmonary disease, S. aureus commonly
implicated)
exacerbations of asthma and COPD
myocarditis
encephalitis
meningitis
otitis media
sinusitis
febrile convulsions
Diagnosis
Diagnosis is usually clinical. Rapid laboratory diagnosis can be made with direct
immunofluorescence or NAAT detection.
Treatment
Treatment is usually supportive. In patients who are at particular risk of
complications, influenza can be treated with neuraminidase inhibitors zanamivir
and oseltamivir, which decrease severity and shorten the duration of symptoms.
Prevention
Inactivated viral vaccines are prepared annually based on predictions of the strain
most likely to be prevalent and are recommended annually for certain patients
including:
people over 65 years old
healthcare professionals
pregnant women
people with chronic disease e.g. cystic fibrosis, renal disease, heart disease,
asthma
immunocompromised individuals e.g. asplenism, HIV/AIDs, chemotherapy

Parainfluenza LAST UPDATED: 21ST
APRIL 2019
Epidemiology
Parainfluenza virus infection, spread via the respiratory droplet route, peaks in
winter, with the highest rates occurring in children less than 3 years old. The
incubation period is about 2 - 6 days.
Clinical Features
It is a common, self-limiting condition which usually lasts about 4 - 5 days, during
which children are distressed, coryzal and febrile.
It is the most common cause of croup (laryngotracheobronchitis). Croup occurs
most commonly in children aged 6 months to 6 years. Croup is characterised by a
barking cough, inspiratory stridor, hoarse voice and respiratory distress due to
upper airway obstruction.
Rarely bronchiolitis, bronchopneumonia or acute epiglottitis may develop,
signalled by reduced air entry and cyanosis.
Diagnosis
Diagnosis is clinical. Laboratory diagnosis can be made with direct
immunofluorescence or NAAT detection.
Treatment
Treatment is supportive. More severe croup may require oral
dexamethasone/prednisolone or nebulised adrenaline.

Respiratory Syncytial Virus LAST UPDATED: 21ST
APRIL 2019
(RSV)  Bookmark
RESPIRATORY VIRUSES
Epidemiology and Transmission

Respiratory syncytial virus predominantly infects children during the first 3 years of
life, with annual epidemics in the winter months. It spreads easily in the hospital
environment, and in the elderly, frail or in those with respiratory tract disease.
Transmission is via the respiratory droplet route and the incubation period is about
4 - 5 days.
Clinical Features
It initially presents with coryza, and in 40% of cases bronchitis develops in older
children and bronchiolitis in the very young (most commonly 2 - 6 months). Infants
with bronchopulmonary dysplasia or congenital heart disease are at particularly
high risk.
Children with bronchiolitis are febrile and tachypnoeic with a dry cough and
difficulty feeding. Examination may reveal chest hyperinflation, respiratory distress,
wheezing and fine end-inspiratory crepitations. Chest x-ray may show
hyperinflation and increased peribronchial markings (although CXR should only
performed if there is diagnostic uncertainty or an atypical course).
Diagnosis
Diagnosis is usually clinical. Rapid laboratory diagnosis can be made with
immunofluorescence, ELISA, NAAT or viral culture of nasopharyngeal aspirate.
Treatment
Most infants with acute bronchiolitis will have mild self-limiting illness and can be
treated at home. Severe disease can develop quickly but with appropriate
supportive treatment (humidified oxygen, nutrition and fluid support), mortality is
low. Severely ill or immunocompromised patients may benefit from aerosolized
ribavirin.

Rhinovirus LAST UPDATED: 21ST
APRIL 2019

Rhinovirus is the principal cause of the common cold. More than 100
serological types exist and thus immunity after infection remains
poor. Infection occurs worldwide with peak incidence in the autumn and
winter months.
Transmission is by direct contact or respiratory droplet spread. It has a short
incubation period of about 24 - 72 hours and patients are infectious while
symptoms are present.
Clinical Features, Diagnosis and Treatment

The virus infects the upper respiratory tract, causing symptoms of headache,
nasal discharge, fever and upper respiratory tract inflammation. It may be
followed by a secondary bacterial infection such as otitis media or sinusitis.
Diagnosis is clinical and treatment is supportive.

Candida LAST UPDATED: 21ST
APRIL 2019
YEASTS AND FUNGI  Bookmark
Transmission
Candida spp. are normally widely distributed in the environment. They form
part of the normal commensal flora of the skin, gastrointestinal tract and
female genital tract and infection is usually endogenous. Infections can occur
when normal bacterial flora is disrupted e.g. following treatment with broad-
spectrum antibiotics, in pregnancy, in diabetes mellitus or when immunity is
altered. Most infections are caused by Candida albicans.
Clinical Disease
Skin
Cutaneous candidiasis
Candidal paronychia
Nappy rash
Oral
Oral candidiasis (commonly associated with inhaled
corticosteroids)
Genitourinary tract
Vulvovaginal candidiasis (thrush)
UTI (colonises catheters)
Gastrointestinal
Candidal oesophagitis (can be severe in immunocompromised
patients)
Systemic infection
Common in neutropenic patients, or patients in intensive care
(e.g. line associated infection).
Diagnosis
Diagnosis is by microscopy (Gram-positive spores and pseudohyphae), culture
or NAAT of specimens of skin, nails or oral or vaginal swabs. Given its
widespread distribution in normal flora, the significance of each isolate is
determined in relation to the overall clinical picture.
Treatment
Vulvovaginal or cutaneous candidiasis - topical clotrimazole or oral
fluconazole
Oral candidiasis - nystatin mouthwash or oral fluconazole
Invasive candidiasis - systemic fluconazole, echinocandin e.g.
caspofungin or amphotericin

Cryptococcus LAST UPDATED: 21ST
APRIL 2019
MICROBIOLOGY / PATHOGENS / YEASTS AND FUNGI
 Bookmark
Cryptococcus neoformans typically causes infection in patients with lymphoma,

those taking steroid or cytotoxic therapy, those with T-cell deficiency e.g. AIDS
and those with intense exposure, such as pigeon fanciers.
Transmission
Cryptococcus neoformans is found in bird droppings and transmission is by
inhalation of spores, thus the lung is the primary site of infection.
Clinical disease
Cryptococcosis
Neurological: meningitis (typically chronic lymphocytic meningitis)
Pulmonary: ranges from minor flu-like symptoms to pneumonia or
respiratory distress syndrome
Diagnosis
Diagnosis is by direct microscopy of CSF, antigen detection with the latex-
agglutination test or culture.
Treatment
Treatment of cryptococcal meningitis is with intravenous amphotericin and
flucytosine for 2 weeks followed by oral fluconazole for 8 weeks or until cultures
are negative. Following successful treatment, fluconazole can be used for
prophylaxis against relapse until immunity recovers.

EVIDENCE
BASED
MEDICINE
Absolute and Relative Risk LAST UPDATED: 21ST
APRIL 2019
EVIDENCE BASED MEDICINE / STATISTICS
 Bookmark
Outcome event No outcome event Total

Treatment a b a+b
Control c d c+d
Total a+c b+d n=a+b+c+d
N.B. The 'outcome event' always refers to the worst outcome
Absolute Risk and Absolute Risk Reduction

The absolute risk (AR) is the risk of an outcome event occurring over a set time
period (the incidence rate of the outcome event). It is calculated by dividing the
number of outcome events that occur by the total number of people at risk of that
event occurring.
The absolute risk reduction (ARR) is the difference between the absolute risk of
outcome event in the control group (ARC) and the absolute risk of outcome event
in the treatment group (ART).
ARC = c/(c + d)
ART = a/(a+b)
ARR = ARC – ART
Relative Risk and Relative Risk Reduction

The relative risk (RR) is the ratio of the risk of outcome event in the treatment
group compared to the risk of outcome event in the control group.
RR = ART/ARC
A risk ratio of 1 indicates no difference in risk between groups.
If the risk ratio of an outcome event is > 1, the rate of that event is increased
in the treatment group compared to the control group.
If the risk ratio is < 1, the rate of that outcome event is reduced in the
treatment group compared to the control group.
The relative risk reduction (RRR) is the proportional reduction in rates of outcome
event between the control group and the treatment group.
RRR = (ARC - ART)/ARC or 1 – RR
Number Needed To Treat

The number needed to treat (NNT) is the number of patients who need to be
treated with the intervention, compared with the control, in order for one extra
patient to experience a beneficial effect.
It is the reciprocal of the absolute risk reduction and therefore gives us
information about absolute benefit.
NNT = 1/ARR
NNT is always a number between 1 and infinity. The ideal NNT is 1, where everyone
that receives the treatment receives benefit. In theory, the higher the NNT, the
less effective the treatment, because more people need to receive the treatment
to see a benefit in one but NNT should be interpreted in clinical context.
Comparisons between NNTs can only be made if the baseline risks are the same.
A negative number would indicate that the treatment has a harmful effect and
would therefore represent the number needed to harm (NNH), defined as the
number of patients who need to be treated for one extra patient to experience a
harmful effect. The lower the NNH, the higher the rate of harmful effects. The
NNH:NNT ratio is indicative of the risk/benefit ratio.

Correlation LAST UPDATED: 21ST
APRIL 2019
 Bookmark
When there is a linear relationship between two variables, there is said to be

correlation.
Correlation Tests
Correlation tests are used to evaluate the strength of a linear relationship
between two variables measured in a single group, without making any
implication about cause and effect in that relationship.
The Pearson's correlation coefficient can be used if the values are sampled from
normal populations, otherwise the non-parametric equivalent, the Spearman's
rank correlation coefficient, can be used.
If it is believed that the relationship between a dependent and an independent
variable is nonlinear, it might be necessary to transform the data using logarithms
or square roots.
Correlation Coefficient
The strength of a relationship is given by the correlation coefficient (r), which can
be between -1.0 and +1.0.
A positive correlation coefficient means that the two variables are directly
proportional e.g. height and weight in healthy growing children.
A negative correlation coefficient means that the two variables are inversely
proportional e.g. socio-economic class and mortality.
If there is a perfect relationship between the two variables, then r = 1 (+ or -). The
closer that r is to 1, the greater the strength of correlation (and the closer the
points are to a straight line).
If there is no correlation between two variables, then r = 0. The closer that r is to 0,
the weaker the correlation.
Generally:
r = 0 - 0.2: very low correlation (probably meaningless)
r = 0.2 - 0.4: low correlation (might warrant further investigation)
r = 0.4 - 0.6: reasonable correlation
r = 0.6 - 0.8: high correlation
r = 0.8 - 1.0: very high correlation (check for errors or other reasons for such
high correlation)
The square of the correlation coefficient (r2 )is the coefficient of determination, an
estimate of the percentage variation in one variable that is explained by the other
variable. This is useful when interpreting clinical relevance.
CORRELATION COEFFICIENTS. (IMAGE BY KIATDD (OWN WORK) [CC BY-SA 3.0


The choice of the most appropriate statistical method will depend on the shape of the distribution of
data.
Distribution of data is usually unimodal (one peak) but may be bimodal (two peaks) or uniform (no
peaks, each value equally likely).
UNIMODAL DISTRIBUTION. (IMAGE BY NIST [PUBLIC DOMAIN], VIA WIKIMEDIA COMMONS)
BIMODAL DISTRIBUTION. (IMAGE BY TUNGSTEN (OWN WORK) [PUBLIC DOMAIN], VIA WIKIMEDIA COMMONS)
Skewed Distribution
When the distribution is unimodal, the main aim is to see where the majority of the data values lie,
relative to the maximum and minimum values.
A unimodal distribution may be symmetrical, positively skewed (skewed to the right) or negatively
skewed (skewed to the left):
A symmetrical distribution is centred around a midpoint, with each side being a mirror-image of
the other; mean = median = mode.
In a positive skew, the right tail is longer and the mass of distribution is concentrated on the
left; mean > median > mode.
In a negative skew, the left tail is longer and the mass of distribution is concentrated on the
right; mean < median < mode.
SKEWED DISTRIBUTIONS. (IMAGE BY RODOLFO HERMANS (GODOT) AT EN.WIKIPEDIA. [CC BY-SA 3.0
Normal (Gaussian) Distribution

Many continuous variables, such as height, have a normal distribution in the population.
The normal distribution is:
bell-shaped (unimodal)
symmetrical about its mean (and the mean and median are equal)
completely described by two parameters, the mean and the standard deviation of the
population
shifted to the right if the mean is increased and to the left if the mean is decreased (for a
constant standard deviation)
flattened as the standard deviation is increased but becomes more peaked as the standard
deviation is decreased (for a fixed mean)
Continuous variables in a normal distribution are evaluated using parametric methods. (Continuous
variables that are not normally distributed or for which no assumptions about distribution can be
made are evaluated using non-parametric methods.)
If a distribution appears to be positively or negatively skewed it can often be transferred to a normal
distribution by taking the logarithm, reciprocal or square root of each observation.
NORMAL DISTRIBUTION. (IMAGE BY SHISHIRDASIKA (OWN WORK) [CC BY-SA 3.0

Binomial Distribution
Categorical data have a binomial (or if more than two categories, multinomial) distribution. The
probability of the number of successes in a sequence of individual observations (e.g. heads vs. tails in
a series of coin tosses) is plotted against the sample size. If the sample size is large enough, the shape
will look similar to a normal distribution.
Poisson Distribution
Categorical data about the number of some discrete event occurring over a specified time e.g. number
of seizures per year follow the Poisson distribution. This distribution usually arises in the context of an
event with a low probability in a very large population, and in which there is no theoretical limit to the
number of events that could occur.
Epidemiological Data LAST UPDATED: 21ST
MARCH 2019
 Bookmark
Epidemiology is the scientific study of the distribution, causes and control of diseases
in the population.
The incidence of a disease is the number of new cases of a condition over a given time
period, given as a percentage of the population.
The point prevalence of a disease is the existing number of cases of a condition at a
single point in time, given as a percentage of the population. Period prevalence of a
disease can be assessed using repeated cross-sectional studies to find out the
proportion of a population that has the disease over a given time period.
With chronic diseases, the incidence will be lower than the prevalence. With short-term
illnesses e.g. the common cold, the incidence will be greater than the prevalence.
The mortality rate is a type of incidence rate defined as the total number of deaths
attributed to a disease in a given time period in a population.
The morbidity rate is the rate of occurrence of new non-fatal cases of the disease in a
defined population at risk over a given time period.
The median survival denotes how long patients survive with a disease. It is the time
period at which 50% of the patients are expected to be alive.

Forest Plots LAST UPDATED: 21ST
APRIL 2019
 Bookmark
The results of a meta-analysis are presented as a forest plot of pooled results, which
provides graphical representation of the strength of evidence of the constituent
trials.
Heterogeneity
Forest plots provides visual evidence of heterogeneity if present. Heterogeneity
occurs when there is more variation between studies than would be expected by
chance alone, even after allowing for random variation.
Heterogeneity is indicated if the confidence interval of a study does not overlap with
any of the confidence intervals of the other studies. If the horizontal lines all overlap
to some extent the trials are homogenous, where the observed differences are due
to random variation.
Interpretation
The left-hand column lists the names of the studies, commonly in chronological
order from the top downwards.
The right-hand column is a plot of the measure of effect size, for example an odds
ratio (OR), for each of these studies, represented by a square:
The midpoint of the square represents the effect size.
The width of the horizontal lines extending from the square represents the
95% confidence interval for this effect size.
The area of each square is proportional to the weight given to that study in the
meta-analysis (studies with larger sample sizes, and more effect sizes are
given more weight).
The overall meta-analysed summary effect size is plotted as a diamond:
The midpoint of the diamond represents the summary effect size.
The lateral points represent the 95% confidence interval for this estimate.
There may be an ascending dotted line from the upper point of the diamond.
There is a vertical line of no effect which intersects the horizontal axis at the point at
which there is no difference between the interventions.
If the confidence intervals for individual studies overlap with this line, it
demonstrates that at the given level of confidence the effect size does not
differ from no effect for that individual study and therefore the results are not
statistically significant. If the horizontal line does not cross the line, the results
are statistically significant.
The same applies for the summary measure of effect: if the points of the
diamond overlap the line of no effect the summary effect size cannot be said
to differ from no effect at the given level of confidence and the results are not
statistically significant.
FOREST PLOT. (IMAGE BY JAMES GRELLIER (OWN WORK) [CC BY-SA 3.0

Hypothesis Testing LAST UPDATED: 21ST
APRIL 2019
 Bookmark
Hypothesis testing involves making estimates or predictions about something

unknown using some prior knowledge, thus moving from descriptive statistics to
inferential statistics. It necessitates making assumptions and therefore dealing
with error and significance.
Null Hypothesis
The null hypothesis assumes that there is no true difference between two
groups of data and that any difference observed in the results of two groups of
data is due to chance.
The alternative hypothesis assumes that there is a true difference between two
groups of data, and is by default accepted if the null hypothesis is rejected.
Tests can either be one- or two- tailed, depending on the null hypothesis being
tested. A one-tailed hypothesis specifies the direction of a difference or
correlation (e.g. treatment A is not superior to treatment B) and can be tested
with a smaller sample than a two-tailed hypothesis (treatment A is equivalent to
treatment B).
P Value
To test a null hypothesis, a p value is calculated using a statistical significance
test.
The p value gives the probability of observing a difference between the two
groups if the null hypothesis is true. In other words, the probability that any
observed difference has happened by chance and not by any true difference.
The larger the p value, the more likely it is that the data have arisen by chance
alone, that the null hypothesis is true and that they do not represent a real
difference between the groups.
The smaller the p value, the less likely it is that the difference has happened by
chance, the greater the evidence against the null hypothesis and so the higher
the statistical significance of the finding.
Statistical Significance
It is important that the null hypothesis should only be rejected when a chance
error is very unlikely as we do not want to conclude that a treatment is effective
when it is not. For medical interventions, it is conventional to set the significance
level at 0.05 which means that the null hypothesis should be rejected in favour of
the alternative hypothesis if p < 0.05.
A p value < 0.05:
is statistically significant
means that the probability of obtaining a given result by chance is less than
1 in 20
means the null hypothesis is rejected
means there is evidence of an association between a variable and an
outcome
A p value > 0.05:
is statistically non-significant
means that the probability of obtaining a given result by chance is more
than 1 in 20
means that the null hypothesis is accepted
means that an association between a variable and an outcome has not
been proved
Clinical vs Statistical Significance

It is important to appreciate that statistical significance does not imply clinical
significance. If a study is too small, the results are unlikely to be statistically
significant even if the intervention actually works. Conversely a large study may
find a statistically significant difference that is too small to have any clinical
relevance.
Even if we ensure that every member of the population has a known and equal
chance of being included in a sample, it does not follow that a series of samples
drawn from one population will be identical. They will show chance variations
from one to another, and the variation may be slight or considerable. For
example, a series of samples of the body temperature of healthy people would
show very little variation from one another, but the variation between samples
of systolic blood pressure would be considerable. Thus the variation between
samples depends partly on the amount of variation in the population from which
they are drawn. The variation between samples also depends partly on the size
of the sample. If a series of samples are drawn from the population, the larger
the sample size, the more chance of the sample accurately representing the
population.
To generalise the result from a random sample to the target population two
concepts need to be understood:
Standard Error
Confidence Intervals
Standard Error of the Mean

The standard error of the mean (SEM) is a measure of the expected spread of
sample means (i.e. how much the mean varies on repeated sampling) and gives
us a measure of the precision of the sample mean as an estimate of the true
population mean.
The SEM for a data sample = σ/√n, where σ = standard deviation and n = sample
size.
A large SEM indicates the estimate is imprecise and small SEM indicates that
the estimate is precise. The SEM is reduced if the size of the sample is increased
or the data is less variable.
N.B. Standard deviation is a measure of variation between individual
observations in a sample whereas standard error is a measure of precision of an
estimate of the population parameter in that sample. Standard deviation is
therefore unaffected by sample size, whereas standard error will decrease as
sample size increases.
Confidence Intervals
The SEM is not, by itself, particularly useful, but it is used to calculate
confidence intervals for the sample mean.
The 95% confidence interval for the mean is the mean +/- 1.96 SEM.
This is the range in which we can be 95% confident that the true population
mean lies.
Changing the multiplier from 1.96 to 2.58 includes exactly 99% of the
distribution.
The width of the confidence interval depends on the size of the SEM, which in
turn depends on the sample size and the variability of the data; a narrow
confidence interval shows a more precise estimate. The upper and lower limits
of the confidence intervals provide a way of assessing whether results are
clinically important.
When quoted alongside a difference between two groups (e.g. mean difference),
a confidence interval that includes 0 is statistically non-significant.
When quoted alongside a ratio (e.g. relative risk, odds ratio), a confidence
interval that includes 1 is statistically non-significant.
N.B. Confidence intervals can also be calculated for single observations in a
normally distributed sample. A 95% confidence interval is the mean +/- 1.96 σ,
and this is the range within which we can be 95% confident that any given value
from our sample will fall.

Interquartile Range LAST UPDATED: 21ST
APRIL 2019
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It is useful to have some measure of the variation of observations about the

mean or median. Measures of variation differ whether the data is normally
distributed or non-normally distributed:
In a normally distributed data set, the mean and standard deviation are
used to describe variation.
In a non-normally distributed data set, the median and interquartile range
are used to describe variation.
Range
The range states the difference between the largest and smallest values in the
data set and can be given as two numbers or a single value.
The range however does not give much indication of the average spread of
observations about the mean and provides a misleading measure of spread if
there are outliers.
Interquartile Range
A more robust approach is to determine the interquartile range, which is largely
unaffected by sample size, and usually unaffected by outliers.
The interquartile range (IQ) is a measure of spread given by the difference
between the first quartile (the value below which 25% of the observations lie)
and the third quartile (the value below which 75% of the observations lie). It
focuses on the spread of the middle 50% of the values in an ordered data set.
Box and Whisker Plot

A boxplot is a vertical or horizontal rectangle used to display the interquartile
range, with the ends of the rectangle corresponding to the upper and lower
quartiles of the data values. The box contains 50% of the data values. A line
drawn through the rectangle corresponds to the median value. Whiskers,
starting at the ends of the rectangle usually indicate the minimum and
maximum values, therefore the entire box and whisker plot represents the
range. Any outliers can be plotted independent of the box and whisker plot.
BOX AND WHISKER PLOT. (IMAGE MODIFIED BY FRCEM SUCCESS. ORIGINAL BY

MADYNO (OWN WORK) [CC BY-SA 3.0 (HTTP://CREATIVECOMMONS.ORG/LICENSES/BY-
SA/3.0)], VIA WIKIMEDIA COMMONS)
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Measures of Central LAST UPDATED: 21ST
APRIL 2019
Tendency  Bookmark
There are three measures of central tendency: mean, median and mode.
Normal distribution: Mean = median = mode
Positive skew: Mean > median > mode
Negative skew: Mean < median < mode
Mean
The mean is the arithmetic average, calculated by summing all of the values of
a data set and dividing this sum by the number of observations in the data set.
The mean is used in normally distributed data as it uses all of the data set and
roughly reflects the sampling distribution. However the mean is distorted by
outliers and skewed data, where the median should be used instead.
Median
The median is the middle value of a data set that has been placed in numerical
order starting with the smallest value and ending with the largest value. With
an even number of data values, the median is the average of the two values
that lie on either side of the midline. It is the point which has half of the
observations above it and half of the observations below it.
The median is similar to the mean if the data is symmetrical, less than the
mean if the data are skewed to the right and greater than the mean if the data
are skewed to the left.
The median is not distorted by outliers or skewed data but ignores most of the
data values and so it can be shown to be less efficient than the mean.
Mode
The mode is the value that is observed most frequently in a data set.
The mode is rarely used as a summary measure. It is easily determined for
categorical data but ignores most of the information and does not reflect
sampling distribution.

Risk and Odds LAST UPDATED: 2ND
MAY 2019
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Risk Ratio
Risk Ratio is used to compare the risk in two different groups of people. It is
used in prospective cohort studies where the risk of developing a disease in a
group of people who have been exposed to a risk factor or treatment is
compared to a group who have not (i.e. the probability of disease given
exposure). It is calculated by dividing the risk of developing the disease in the
exposed/treated group by the risk of developing the disease in the
unexposed/control group.
A risk ratio of 1 indicates no difference in risk between groups.
If the risk ratio is > 1, the rate of that disease is increased in the exposed
group compared to the control group.
If the risk ratio is < 1, the rate of that disease is reduced in the exposed
group compared to the control group.
Risk ratios are frequently given with their 95% confidence intervals (CIs) - if
the CI for a risk ratio does not include one (no difference in risk), it is
statistically significant.
Worked example of Risk Ratio in a Cohort Study
Disease Present Disease Absent Total

Exposure a b a+b
No Exposure c d c+d
The risk ratio of developing a disease in people who have been exposed
compared to people who have not = Risk of disease in the exposed group/Risk
of disease in the unexposed group
Risk of disease in the exposed group = a/(a+b)
Risk of disease in the unexposed group = c/(c+d)
Risk Ratio = [a/(a+b)] / [c/(c+d)]
Odds Ratios
The odds of an event are calculated by dividing the number of times an event
happens by the number of times it does not happen.
Odds ratios are used in retrospective case-control studies, where they are
used to compare past exposure in patients who already have a certain
disease with patients who do not have the disease (i.e. the probability of
exposure given disease). They are calculated by dividing the odds of having
been exposed to a risk factor in the case group by the odds of having been
exposed in the control group.
An odds ratio of 1 indicates no difference in risk between groups.
If the odds ratio is > 1, the rate of exposure is increased in patients who
have the disease compared to those who don't.
If the odds ratio is < 1 the rate of exposure is reduced in patients who
have the disease compared to those who don't.
Odds ratios are frequently given with their 95% CIs - if the CI for a odds
ratio does not include one (no difference in odds), it is statistically significant.
Worked Example of Odds Ratio in a Case-Control Study
Case Control Total

Exposed a b a+b
Not Exposed c d c+d
Case Control Total
The odds ratio of people with a disease having been exposed compared to
people without the disease = Odds of exposure in the case group/odds of
exposure in the control group
Odds of people with the disease having being exposed = a/c
Odds of people without the disease having being exposed = b/d
Odds ratio = [a/c] / [b/d]

Sample Size and Power LAST UPDATED: 21ST
MARCH 2019
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The sample size for a study is not chosen at random. Ideally a clinical trial
should be large enough to reliably detect the smallest possible difference in
the outcome measure, with treatment, that is considered clinically
worthwhile.
The power of a study is the probability of correctly rejecting the null
hypothesis when it is false. It is the probability that the study would detect a
statistically significant difference if a true difference exists. As the power
increases, the chance of making a type II error decreases.
The power of a study = 1 - β. Typically β is arbitrarily set at 0.2, meaning that a
study has 80% power (0.8 of a chance) to detect a specified degree of
difference at a specified degree of significance.
A power of 0.8 is generally accepted as being adequate in most research
studies: a study power set at 80% accepts a likelihood of 1 in 5 (20%) of
missing a statistically significant difference where one exists.
The determinants of power are:
the sample size (the power increases with sample size)
the variability of the observations (the power increases as the variability
decreases)
the effect size of interest (the power is greater for a larger expected
effect size)
and the significance level, ? (the power is greater if the significance level
is larger); therefore the probability of a type I error increases as the
probability of a type II error decreases.
Inspection of the confidence intervals for the effect of interest gives an
indication of whether the power of the test was adequate; a wide confidence
interval suggests low power. The most common reason for type II error is that
the study is too small.
Standard Deviation LAST UPDATED: 21ST
APRIL 2019
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It is useful to have some measure of the variation of observations about the

mean or median. Measures of variation differ whether the data is normally
distributed or non-normally distributed:
In a normally distributed data set, the mean and standard deviation are
used to describe variation.
In a non-normally distributed data set, the median and interquartile
range are used to describe variation.
Normal (Gaussian) Distribution

The normal distribution is:
bell-shaped (unimodal)
symmetrical about its mean (and the mean and median are equal)
completely described by two parameters, the mean and the standard
deviation of the population
shifted to the right if the mean is increased and to the left if the mean is
decreased (for a constant standard deviation)
flattened as the standard deviation is increased but becomes more
peaked as the standard deviation is decreased (for a fixed mean)
Standard Deviation
The variance indicates the dispersion of the values around the mean. The
variance is equal to the average distance by which each individual
observation differs from the mean value.
The standard deviation is the square root of the variance and provides a
measure of the spread of sample values around the sample mean. It is
calculated by taking the square root of the average squared difference
between each value and the mean and is approximately equivalent to the
average difference between the sample value and the mean. A data set with a
larger standard deviation has a wider spread of data and vice versa.
Standard deviation (SD, σ) is used for describing the variability of normally-
distributed data, for non-normally distributed data, the interquartile range is a
better measure.
If we know the mean and standard deviation of a set of normally distributed
observations, we can estimate the range of values that would be expected to
include certain proportions of observations:
A range of one SD above and below the mean (+/- 1 SD) includes 68.2%
of the sample values
+/- 2 SD includes 95.4% of the values
+/- 3 SD includes 99.7% of the values
STANDARD DEVIATION ABOUT THE MEAN. (IMAGE BY DAN KERNLER (OWN WORK) [CC
BY-SA 4.0 (HTTP://CREATIVECOMMONS.ORG/LICENSES/BY-SA/4.0)], VIA WIKIMEDIA
COMMONS)
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Statistical Tests LAST UPDATED: 21ST
APRIL 2019
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Significance tests are mathematical functions which compute an observed

value of a test statistic from experimental data. The p value required to
determine significance is derived from this test statistic.
The type (categorical or quantitative) and distribution (normal, non-normal) of
data, the number of samples, and whether the data is paired or unpaired
determines which significance test should be used. In practice, computer
programs are used to do these calculations.
Unpaired data refers to data from two groups which have different members.
Paired data refers to data from the same individuals taken at different time
points.
Parametric and Non-Parametric Tests

Parametric tests are used to compare samples of normally distributed data.
Non-parametric testing is used to compare samples of non-normally
distributed data.
Parametric tests (normal data) Non-parametric tests (non-

normal data)
Unpaired student t-test: used to Mann Whitney U-test: used to
compare the means of two compare the medians of two
independent groups of values unpaired groups of values
Paired student t-test: used to Wilcoxon matched pairs: used
compare the means of values obtained to compare the medians of
from a single group at two different two paired groups of values
points in time
Parametric tests (normal data) Non-parametric tests (non-
normal data)
One-way Analysis of variance Kruskal-Wallis test: used to
(ANOVA): used to compare the means compare the medians of
of more than two unpaired groups of more than two unpaired
values groups of values
Repeated-measures ANOVA: used to Friedman's test: used to
compare the means of more than two compare the medians of
paired groups of values more than two paired groups
of values
Tests for Categorical Data

The chi-squared test is used to compare the proportions of two or more
unpaired groups with a particular attribute e.g. the proportion of people
suffering a stroke in two groups receiving a statin or no statin to see if they
are statistically different. An odds ratio of 1, or whose 95% CI includes the
value of 1, implies that there is no difference between the two groups.
For small-sized samples (fewer than five observations in any variable), Fisher's
exact test can be used.
The McNemar's test is used to compare proportions of two or more paired
groups of values.

Survival analysis studies the time between entry into a study and a subsequent
occurrence of an event (e.g. death). Survival analysis may be applied to data
from longitudinal cohort studies or from interventional studies.
Problems with analysing data relating to the time between one event and
another include:
All times to an event occurring will differ, but it is unlikely these times are
normally distributed.
The subjects may have entered the study at different times, so there are
unequal observation periods.
Some patients may not reach the endpoints of a study within the time
period.
Some patients may leave a study, not experience the event or be lost to
follow-up (data for these individuals is referred to as censored).
This means it is difficult to determine mean survival times because we do not
have all the survival data.
Kaplan-Meier Survival Curves

The Kaplan-Meier survival curve looks at event rates over the study period,
rather than just at a specific time point. The survival curve is plotted by
calculating the proportion of patients who remain alive (survivors) in the study
each time an event (e.g. a death) occurs, taking into account censored
observations. The survival curve will not change at the time of censoring, but
only when the next event occurs. Censored patients are assumed to have the
same survival prospects as those who continue in the study.
Time is plotted on the x axis, and the proportion of people who have not
experienced an event (survivors) on the y axis. A cumulative curve is achieved
with steps each times an event occurs. Small vertical ticks on the curve
indicates the times at which patients are censored.
The survival curve can be used to calculate:
The median survival time, which is the time interval indicated by a survival
probability of 50%, that is, the time taken for 50% of the subjects to
survive.
The survival time, which is the time taken for a certain proportion of the
population to survive.
The survival probability at a given time point, which is the probability that
an individual will not have developed an event.
A plot of control and intervention/exposure groups on the same graph allows
direct comparison.
KAPLAN-MEIER SURVIVAL CURVE. (IMAGE MODIFIED BY FRCEM SUCCESS. ORIGINAL BY

DEANNE TAYLOR (MADE AND ORIGINAL TO SUBMITTER) [PUBLIC DOMAIN], VIA
WIKIMEDIA COMMONS)

Type I and Type II Errors LAST UPDATED: 21ST
APRIL 2019
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Type I Error
A type I error occurs when the null hypothesis is wrongly rejected when it is
actually true and we conclude that there is a difference of effect when in
reality there is none (a false positive result).
The probability of making a type I error is denoted by alpha (α), the
predetermined significance level of the test (conventionally α = 0.05).
A p value < 0.05 means that the probability of obtaining a given result
by chance is less than 1 in 20. This is statistically significant and
means the null hypothesis is rejected and there is evidence of an
association between a variable and an outcome.
A p value > 0.05 is statistically non-significant and the null hypothesis
is accepted. An association between a variable and an outcome has
not been proved.
Type II Error
A type II error occurs when the null hypothesis is wrongly accepted when it
is actually false and we conclude that there is no evidence of a difference in
effect when one really exists (a false negative result).
The probability of making a type II error is denoted by beta (β).
Type II errors can be avoided at the design stage of the study by power
calculations that give an indication of the minimum sample size required so
that one can be reasonable likely to detect an effect of a given size.
The purpose of most studies is to collect data to obtain information about a
particular area of research. Data comprises observations on one or more
variables e.g. gender, height. The most appropriate statistical method used
to analyse data is dependent on the type of data collected.
Data may be categorical or quantitative (numerical). In general it is easier to
summarise categorical variables, and so quantitative variables are often
converted to categorical ones for descriptive purposes. However,
categorising a continuous variable reduces the amount of information
available, and statistical tests will in general be more sensitive (have more
power) for a quantitative variable than the corresponding categorical one.
Categorising data is therefore useful for summarising results, but not for
statistical analysis.
Categorical Data
Categorical data occurs when each individual can only belong to one of a
number of distinct categories of the variable.
Categorical data may be nominal or ordinal.
Ordinal data is data that is ordered in some way e.g. disease staging
system, pain scoring system.
Nominal data is data where the categories have names but are not
ordered in any way e.g. blood group, marital status, gender.
A categorical variable is binary or dichotomous when there are only two
categories e.g. yes/no, male/female.
Quantitative Data
Quantitative data occurs when the variable takes some numerical value.
Quantitative data may be discrete or continuous.
Discrete data is counted data that can only take whole numerical
values e.g. number of children, number of days missed from work per
year.
Continuous data is measured data where there is no limitation on the
value that the variable can take e.g. weight, height.
Age is often treated as discrete data (taken as age at last birthday) but is
technically continuous.

Something wrong?
Interventional Trials LAST UPDATED: 21ST

APRIL 2019
EVIDENCE BASED MEDICINE / STUDY METHODOLOGY
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Interventional trials are used to test a hypothesis that a particular healthcare

intervention is different from another, or from no intervention. Interventional
studies provide the most convincing evidence for any hypothesis as it is generally
possible to control for confounding factors that may affect outcome. Randomised
control trials (RCTs) are the gold standard for studying treatment effects, providing
a reliable measure of efficacy and allowing for meta-analysis but they are difficult,
time-consuming and expensive to set up. There can also be ethical problems in
giving different treatments to two groups.
Phases
Phase I: the first stage of human testing where a small group of healthy
volunteers is given the intervention under close monitoring to evaluate
safety, tolerability and pharmacodynamics
Phase II: larger trials in both healthy volunteers and patients in which safety
and tolerability continue to be assessed, but efficacy is also evaluated
Phase III: even larger multicentre randomised controlled trials (RCTs) to
definitively assess efficacy against the gold standard, interventions with
satisfactory results will get marketing authorisation
Phase IV: post-marketing surveillance trials in which safety data continue to
be collected, and specific issues, such as drug interactions and pregnancy
may be evaluated, even after the intervention is licensed
The sample size in a phase II or III clinical trial is critical and must be determined
knowing the incidence of the disease in question, the potential effect of the
intervention (estimated from earlier studies), the significance level deemed
acceptable, and the variance of the outcome measure.
Randomisation
Randomisation to study groups removes any allocation bias. It also may improve the
chance of having comparably matched groups by randomly distributing
confounding variables between the treatment arms, depending on the
randomisation strategy.
Blinding
Open trial: everybody knows which intervention is being given.
Single blind trial: either the subject or the researcher is not blinded. This is
usually either because the placebo does not perfectly mimic the intervention,
or because the researcher has to know the full facts.
Double blind: both the subject and researcher are blinded. This usually
achieves the highest standard of scientific rigor.
Cross-Over Study
Each patient receives both (or all) of the interventions being compared, and
therefore acts as their own control (although comparison takes place at different
time points). The order in which they receive the interventions must be randomised
and there is usually a 'washout period' between different drugs. This is only suitable
for chronic disease that is not curable but for which treatment may give short-lived,
temporary relief. Fewer patients are required because many between-patient
confounders are removed, thus they are often used to study rare diseases.
Follow-Up
The follow-up period must be long enough to allow outcomes of the trial to occur,
which requires prior knowledge about the natural history of the condition being
studied. Drop-out rates must be sufficiently low so as not to bring into doubt the
results of the trial.
An intention to treat (ITT) analysis is one in which all patients are included in the
analysis, classified according to the group into which they were randomised, even if
they were withdrawn from the study and did not actually receive the treatment, did
not comply with treatment or drop-out. Intention to treat analysis is a more reliable
estimate of true treatment effectiveness by replicating what happens in the ‘real
world’ (e.g. noncompliance and protocol violations commonly affect therapies).
This type of analysis is in contrast to ‘per protocol’ analysis (where analysis includes
only those patients who completed the treatment originally allocated) and ‘as
treated’ analysis (where analysis classifies patients based on the actual treatment
they received and not the treatment they were originally allocated to).

Observational Studies LAST UPDATED: 8TH JULY
2019
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Case-control Study
A case-control study is a longitudinal, retrospective, observational study which investigates the
relationship between a risk factor and one or more outcomes. This is done by selecting patients
who already have a specific disease (cases), matching them to patients who do not (controls) and
then collecting data from the patients to compare past exposure to a possible risk factor. The
usual outcome measure is the odds ratio.
Advantages:
relatively quick
relatively cheap and easy to perform
particularly suitable for studying associations between an exposure and an outcome when
the outcome is uncommon or if the outcome occurs decades after exposure
a wide range of risk factors can be investigated in each study
Disadvantages:
subject to recall bias
unlike in a whole population study, absolute risk cannot be quantified
temporal relationship between exposure and outcome can be difficult to establish
unsuitable for rare risk factors
prone to confounding
Cohort Study
A cohort study is a longitudinal, prospective, observational study that follows a defined group
(cohort) matched to unexposed controls for a set period of time and investigates the effect of
exposure to a risk factor on a particular future outcome. The usual outcome measure is the
relative risk (risk ratio).
Advantages:
ideal for studying associations between an exposure and an outcome when the exposure
is uncommon
the time sequence of events can be assessed
they can provide information on a wide range of disease outcomes
the absolute and relative risk of disease can be measured directly
they can give a direct estimation of disease incidence rates
Disadvantages:
costly and can take long periods of time if the outcome is delayed
subject to subject-selection and loss to follow-up bias
large sample size required for rare outcome of interest so it is not useful for rare diseases
prone to confounding
Cross-sectional Study
The above study designs are longitudinal where a sample of individuals are investigated at
different time points.
Cross-sectional studies aim to provide data about population health, normal ranges of biological
parameters, and disease prevalence or severity by observing the entire population, or a
representative subset, at a single point in time.
In this kind of study we can determine prevalence (total number of cases of a condition existing
within a population).
Cross-sectional studies are relatively simple and quick to perform and can be used to study
multiple outcomes, but are subject to confounding and recall bias and are not suitable for
studying rare diseases. Cross-sectional studies cannot be used to assess causation or to
consider trends over time.
Comparison of Observational Studies
Study Case-control Cohort Cross- Interventional

sectional
sectional
Features Retrospective, Prospective, Cross- Randomised
longitudinal, longitudinal, sectional control trials
observational observational observational (RCTs)
study used to study used to study used to
investigate investigate provide a
past exposure the effect of snapshot of
to a risk factor an exposure population
on a current to a risk health,
outcome, factor on a biological
usual future parameters
outcome outcome, and disease
measure = usual prevalence by
odds ratio outcome observing the
measure = entire
risk ratio population or
a
representative
subset at a
single point in
time
Advantages Relatively Suitable for Relatively Gold standard
quick, cheap studying a simple and for studying
and easy to rare quick to treatment
perform; wide exposure; perform; can effects;
range of risk time study multiple provide
factors can be sequence of outcomes; reliable
investigated; events can relatively measure of
suitable for be assessed; cheap efficacy; allow
studying a wide range of for meta-
rare outcome disease analysis; can
or when the outcomes control for
outcome is can be confounding
delayed studied; variables
absolute and
relative risk
of disease
can be
measured
directly; can
give a direct
estimate of
disease
incidence
rates
sectional
Disadvantages Subject to Costly and Subject to Difficult, time-
recall bias; can take long recall bias; not consuming
absolute risk periods of suitable for and expensive
cannot be time if rare diseases; to set up; may
quantified; outcome is cannot be be ethical
temporal delayed; used to assess problems in
relationship subject to causation or giving two
cannot be subject to consider different
established; selection and trends over treatments to
unsuitable for loss to time two groups
rare risk follow-up
factors bias; not
suitable for
rare diseases

Types of Bias LAST UPDATED: 21ST
APRIL 2019
 Bookmark
Bias is the term used to describe an error at any stage of the study that was not due to
chance. Bias leads to the systematic difference between the results from a study and
the true states of affair. Bias may be introduced at all stages of the research process,
from study design, through to analysis and publication. Bias can create a spurious
association or mask a real association.
Good research design can reduce the effect of bias (e.g. blinding, randomisation) but
they cannot eliminate it completely. Increasing the sample size does not reduce bias.
Selection Bias
Selection bias occurs when patients included in the study are not representative of
the population to which the results will be applied. It may be sampling bias, introduced
by the researches, or response bias, introduced by the study population. Selection bias
can happen not only at the recruitment stage of a study but also when subjects are
allocated to different arms.
Sampling bias:
Berkson (admission rate) bias - arises when the sample population is taken from
a hospital setting, but the hospital cases do not reflect the rate or severity of the
condition in the population.
Diagnostic purity bias - arises when comorbidity is excluded in the sample
population, such that the sample population does not reflect the true complexity
of cases in the population.
Neyman (incidence/prevalence) bias: arises when the prevalence of a condition
does not reflect its incidence. Usually this is due to a time gap between onset of
a condition and the actual selection of the study population, such that some
individuals with the condition are not available for selection.
Membership bias: arises when membership of a group is used to identify study
individuals.
The healthy entrant effect - arises where mortality and morbidity rates are lower
in the initial stages of a longitudinal study than in the general population
because the individuals included in the study are disease-free at its outset.
Lead-time bias - occurs in studies assessing changes in survival over time
where the development of more accurate diagnostic procedures may mean that
patients entered later into the study are diagnosed at an earlier stage resulting
in an apparent increase in survival from time of diagnosis
Response bias:
Occurs when individuals volunteer for studies but they differ in some way from
the population.
Allocation bias:
Occurs where there is a systematic difference between the patients allocated to
the intervention or to the control group
Performance Bias
Measurement bias - occurs where a systematic error is introduced by an
inaccurate measurement tool
Misclassification bias - occurs when a categorical exposure and/or outcome
variable is incorrectly classified
Central tendency bias - arises when using a scale where responders tend to
move towards the midpoint of the scale (e.g. no opinion)
Observation Bias
Interviewer bias - arises when the researcher is not blinded, and this alters the
researchers approach to the subject and the recording of results
Reporting/response bias - occurs when participants give answers in the
direction they perceive are of interest to the researcher or under-report socially
unacceptable factors
Hawthorne bias - a type of reactivity in which individuals modify or improve an
aspect of their behaviour in response to their awareness of being observed
Recall bias - occurs where there are differences in the accuracy or
completeness of recollections by study participants e.g. somebody who
develops a disease is more likely to recall a previous exposure to a risk factor
than someone who does not have the disease
Attrition Bias
Attrition bias occurs where those who drop-out or are lost to follow-up in a
longitudinal study differ in a systematic way from those not lost to follow-up. Thus
those left at the end of the study might not be representative of the study sample that
was randomised at the start.
Reporting Bias
Bias may also occur after performing a study.
Funding bias is where there is a tendency to report findings in the direction favoured
by the funding body and publication bias is where there is a tendency to publish only
those papers that report positive, statistically significant or topical results. Excluding
studies in a foreign language is another form of reporting bias.
Funnel plots are used to demonstrate the existence of publication bias in meta-
analysis. Funnel plots are scatter plots of treatment effects estimated from individual
studies on the x axis and some measure of study size on the y axis. Each point on the
graph represents one of the studies. A symmetrical inverted funnel shape indicates an
absence of publication bias. If there is publication bias, there will be asymmetry of the
open wide end due to the absence of small negative results.
FUNNEL PLOT ON RIGHT SIDE DEMONSTRATING PUBLICATION BIAS, FUNNEL PLOT ON LEFT
SIDE IN ABSENCE OF BIAS.

Systematic Review LAST UPDATED: 21ST
APRIL 2019
EVIDENCE BASED MEDICINE / CRITICAL APPRAISAL
 Bookmark
A systematic review (SR) is a formalised and stringent process of searching and

identifying, critically evaluating, and selecting for inclusion based on predefined
quality criteria, all relevant studies (both published and unpublished) surrounding
a particular clinical question. Systematic reviews are the gold-standard source of
research evidence in the hierarchy of research evidence.
Systematic review achieves:
refinement and reduction - large quantities of information are refined and
reduced to a manageable size
efficiency - SR is quicker and less costly to perform than a new study, it can
prevent others from embarking on an unnecessary study and can shorten
time between medical developments and their implementation
generalisability and consistency - results can often be generalised to a
wider population in a broader setting than would be possible from a single
study, consistencies in the results from different studies can be assessed
and inconsistencies determined
reliability - SR aims to reduce errors and so tends to improve the reliability
and accuracy of recommendations
power and precision (meta-analysis has greater power to detect effects of
interest and provides more precise estimates than a single study)
Meta-Analysis
A meta-analysis the quantitative assessment of a systematic review. It involves
combining the results of independent studies with common features to produce a
more powerful overall estimate of effect. A meta-analysis can provide conclusive
evidence for or against an intervention, even when individual studies are
inconclusive.
In meta-analysis of RCTs, the outcome data from each trial are usually illustrated
as a series of odd ratios with their confidence intervals on a graph known as a
forest plot.
PHARMACOLOGY
Benzodiazepines LAST UPDATED: 4TH
APRIL 2019
PHARMACOLOGY / ANAESTHESIA /
CENTRAL NERVOUS SYSTEM  Bookmark
Mechanism of action
Benzodiazepines are gamma-aminobutyric acid (GABA) receptor agonists which
enhance inhibitory synaptic transmission throughout the central nervous system, with
sedative, hypnotic, anxiolytic, anticonvulsant, and muscle relaxant properties.
Indications
Benzodiazepines are indicated for the short-term relief (two to four weeks only) of anxiety
that is severe, disabling, or causing the patient unacceptable distress, occurring alone or
in association with insomnia or short-term psychosomatic, organic, or psychotic illness.
The use of benzodiazepines to treat short-term ‘mild’ anxiety is inappropriate.
Benzodiazepines should be used to treat insomnia only when it is severe, disabling, or
causing the patient extreme distress.
Prescribing of these drugs is widespread but dependence (both physical and
psychological) and tolerance may occur. Therefore hypnotics and anxiolytics should be
reserved for short courses to alleviate acute conditions. Withdrawal of a benzodiazepine
should be gradual because abrupt withdrawal may produce confusion, toxic psychosis,
convulsions, or a condition resembling delirium tremens.
Benzodiazepines possess useful properties for premedication including relief of anxiety,
sedation, and amnesia; short-acting benzodiazepines taken by mouth are the most
common premedicants. Benzodiazepines are also used in intensive care units for
sedation, particularly in those receiving assisted ventilation.
Contraindications
Benzodiazepines are contraindicated in:

Respiratory depression
Marked neuromuscular respiratory weakness, such as unstable myasthenia gravis
Obstructive sleep apnoea syndrome (symptoms may be aggravated)
Severe hepatic impairment (the elimination half-life of diazepam may be prolonged;
increased risk of coma)
Phobic or obsessional states, chronic psychosis or hyperkinesis (paradoxical
reactions may occur)
Cautions
Benzodiazepines should be used with caution in:
Respiratory disease
Muscle weakness and myasthenia gravis (symptoms may be aggravated)
Organic brain disease
Severe renal impairment (increased cerebral sensitivity to diazepam; a reduced
dose may be appropriate)
Dependent, obsessive-compulsive, or avoidant-type personality disorders (may
increase the risk of dependency)
Frailty and the elderly (increased falls risk; a reduced dose may be appropriate)
A history of drug and/or alcohol misuse or dependency (increased risk of
dependency)
Patients taking other central depressants concomitantly e.g. alcohol, barbiturates
Side Effects
Adverse effects include:
Drowsiness and lightheadedness
Confusion and ataxia (especially in the elderly), amnesia, muscle weakness
Headache, vertigo, tremor, dysarthria, hypotension, decreased libido, erectile
dysfunction, gynaecomastia, urinary retention
Paradoxical effects such as talkativeness, excitement, irritability, aggression, anti-
social behaviour, and suicidal ideation
Withdrawal symptoms, for example anxiety, depression, anorexia, impaired
concentration, insomnia, abdominal cramps, palpitations, tremor, tinnitus and
perceptual disturbances
Tolerance and dependence (people who use benzodiazepines longer term can
develop tolerance and eventual dependence)
Toxicity
Features of benzodiazepine toxicity include:
drowsiness
ataxia
dysarthria
nystagmus
occasionally respiratory depression and coma
Flumazenil is used to antagonise the effects of benzodiazepines. It can be used to reduce
the sedative effects of benzodiazepines in anaesthesia, intensive care, diagnostic
procedures and in overdose.
Type Examples
Midazolam has a short duration of action (< 6 hours), lorazepam and temazepam have an
intermediate duration of action (12 - 18 hours) and diazepam and chlordiazepoxide have a
long duration of action (24 - 48 hours). Shorter-acting compounds may be preferred in
patients with hepatic impairment but they carry a greater risk of withdrawal symptoms.
Chlordiazepoxide is routinely used for symptoms associated with acute alcohol
withdrawal.
Diazepam is used to produce mild sedation with amnesia. It is a long-acting drug with
active metabolites and a second period of drowsiness can occur several hours after its
administration.
Temazepam is given by mouth for premedication and has a shorter duration of action and
a more rapid onset than oral diazepam; anxiolytic and sedative effects last about 90
minutes although there may be residual drowsiness.
Lorazepam produces more prolonged sedation than temazepam and it has marked
amnesic effects.
Midazolam is a water-soluble benzodiazepine that is often used in preference to
intravenous diazepam; recovery is faster than from diazepam, but may be significantly
longer in the elderly, in patients with a low cardiac output, or after repeated dosing.
Midazolam is associated with profound sedation when high doses are given intravenously
or when it is used with certain other drugs.

Etomidate LAST UPDATED: 4TH
APRIL 2019
PHARMACOLOGY / ANAESTHESIA
 Bookmark
Etomidate is an intravenous anaesthetic agent used for induction, associated

with rapid recovery without a hangover effect. Etomidate suppresses
adrenocortical function, particularly during continuous administration, and it
should not be used for maintenance of anaesthesia. It should be used with
caution in patients with underlying adrenal insufficiency, for example, those with
sepsis.
Pharmacokinetics
The induction dose for an adult is 0.3 mg/kg. Following injection, redistribution
occurs rapidly. Metabolism occurs via ester hydrolysis in both the plasma and the
liver. Metabolites are excreted via urine and bile; 2% remains unchanged.
Side Effects
Etomidate causes less hypotension than thiopental sodium and propofol during
induction. However, it is associated with a high incidence of extraneous muscle
movements, which can be minimised by an opioid analgesic or a short-acting
benzodiazepine given prior to induction. Pain on injection is common and there is
a high rate of thrombophlebitis in the postoperative period. Postoperative nausea
and vomiting commonly occur. Respiratory depression can also occur.
Etomidate causes the least cardiovascular depression of the intravenous
induction agents, with only a small reduction in the cardiac output and blood
pressure. In the past, etomidate was widely used to induce anaesthesia in the
shocked, elderly or cardiovascularly unstable patient. However, more recently it
has become less popular as a single induction dose blocks the normal stress-
induced increase in adrenal cortisol production for 4 - 8 hours, and up to 24
hours in elderly and debilitated patients. Although no increase in mortality has
been identified following a single dose during induction of anaesthesia, the use of
etomidate has declined due to a perceived potential morbidity.
Flumazenil LAST UPDATED: 4TH
APRIL 2019
 Bookmark
Flumazenil is a benzodiazepine antagonist used for the reversal of the

sedative effects of benzodiazepines after anaesthesia, sedation and similar
procedures.
Flumazenil has a shorter half-life and duration of action than diazepam or
midazolam so patients may become resedated.
Flumazenil should not be used in life-threatening conditions (e.g. raised
intracranial pressure, status epilepticus) controlled by benzodiazepines as
this would render further treatment, if required, ineffective.

Ketamine LAST UPDATED: 21ST
SEPTEMBER 2020
 Bookmark
Ketamine has hypnotic, analgesic and local anaesthetic properties. Ketamine is

an NMDA receptor antagonist, but it may also have other actions. Ketamine
produces so-called ‘dissociative’ anaesthesia. Transient psychotic effects
including alterations in mood state, floating sensations, vivid dreams and
hallucinations are common during emergence from ketamine anaesthesia. These
usually resolve on full wakening. Benzodiazepine premedication e.g. with
diazepam or midazolam reduces this delirium, which also occurs less often in
children and the elderly.
The onset of action is slower than other induction drugs (1 - 2 min for IV use), and
the end point can be difficult to judge with patients staring into the distance for a
short period of time. The duration of action of a single dose is approximately 5 -
10 minutes. Recovery is relatively slow.
Uses
Ketamine has a unique combination of cardiovascular effects. Unlike other
induction drugs it has sympathetic effects with increased heart rate, increased
blood pressure and an increased cardiac output; this makes ketamine useful in
the shocked, unwell patient. It is used mainly for paediatric anaesthesia,
particularly when repeated administration is required (such as for serial burns
dressings).
Ketamine has a minimal effect on respiratory drive and protective airway reflexes
remain well preserved, this makes ketamine an ideal anaesthetic drug to be used
in the prehospital environment. Ketamine is also a bronchial smooth muscle
relaxant and therefore has a special role in the management of severe asthma.
Contraindications
Ketamine is contraindicated in acute porphyrias, head trauma, stroke and raised
intracranial pressure, hypertension and severe cardiac disease.
Side Effects
There is a high incidence of extraneous muscle movements and postoperative
nausea and vomiting. Other common side effects include hypertension,
tachycardia and transient psychotic effects.

Local Anaesthetics LAST UPDATED: 4TH
APRIL 2019
 Bookmark
Local anaesthetic drugs act by causing a reversible block to conduction along

nerve fibres. The drugs penetrate the nerve in a non-ionised lipophilic form, but
once inside the axon, some ionised molecules are formed and these block the
voltage-gated Na+ channels, preventing the sodium current and generation of
action potentials.
They vary widely in their uses, potency, toxicity, duration of action, stability,
solubility in water, and ability to penetrate mucous membranes.
Lidocaine
Lidocaine is the most widely used local anaesthetic. It acts rapidly and when
administered with adrenaline the block lasts about 90 minutes. Lidocaine is
effectively absorbed from mucous membranes and can therefore be used as a
surface anaesthetic in concentrations up to 10%. Except for surface anaesthesia
and dental anaesthesia, solutions should not usually exceed 1% in strength.
Lidocaine also has class 1b antiarrhythmic properties (blocks inactivated voltage-
gated Na+ channels) and may be given intravenously in the treatment of
ventricular arrhythmias.
Prilocaine
Prilocaine hydrochloride is a local anaesthetic of low toxicity which is similar to
lidocaine hydrochloride but is more extensively metabolised and is less toxic in
equipotent doses.. It is most frequently used for intravenous regional anaesthesia
(i.e. Bier's block). Bier's block anaesthesia is an intravenous regional anaesthesia
technique in which an extremity (usually the arm) is anaesthetised by injecting a
local anaesthetic solution (typically prilocaine) into a vein after the limb has been
exsanguinated and a tourniquet placed on it. The tourniquet prevents a
potentially toxic dose of local anaesthetic from leaving the extremity and blood
from entering it, giving the patient an anaesthetised extremity and the surgeon a
bloodless field.
EMLA
EMLA cream, an effective topical local anaesthetic, is a 50/50 mixture of 2.5%
prilocaine and 2.5% lidocaine.
Bupivacaine
Bupivacaine has a longer duration of action than the other local anaesthetics, up
to 8 hours when used for nerve blocks. It has a slow onset, taking up to 30
minutes for full effect. It is often used in lumbar epidural blockade and is
particularly suitable for continuous epidural analgesia in labour, or for
postoperative pain relief. It is the principal drug used for spinal anaesthesia.
Vasoconstrictors
Local anaesthetics cause dilatation of blood vessels. The addition of a
vasoconstrictor such as adrenaline/epinephrine to the local anaesthetic
preparation diminishes local blood flow, slowing the rate of absorption and
thereby prolonging the anaesthetic effect. Great care should be taken to avoid
inadvertent intravenous administration of a preparation containing
adrenaline/epinephrine, and it is not advisable to give adrenaline/epinephrine
with a local anaesthetic injection in digits or appendages because of the risk of
ischaemic necrosis.
Adrenaline/epinephrine must be used in a low concentration when administered
with a local anaesthetic. Care must also be taken to calculate a safe maximum
dose of local anaesthetic when using combination products. In patients with
severe hypertension or unstable cardiac rhythm, the use of
adrenaline/epinephrine with a local anaesthetic may be hazardous; for these
patients an anaesthetic without adrenaline/epinephrine should be used.
Toxicity
Toxic effects after administration of local anaesthetics are a result of excessively
high plasma concentrations; severe toxicity usually results from inadvertent
intravascular injection or too rapid injection. Following most regional anaesthetic
procedures, maximum arterial plasma concentration of anaesthetic develops
within about 10 to 25 minutes, so careful surveillance for toxic effects is
necessary during the first 30 minutes after injection.
Local anaesthetics depress other excitable tissues producing:
Central nervous system effects (with increasing toxic doses)
Sedation, lightheadedness, anxiety and restlessness
Twitching, tremor and visual disturbance
Convulsions and coma, with respiratory depression resulting from
medullary depression
Cardiovascular effects
Vasodilation (partly by direct action on blood vessels and partly by
blocking their sympathetic nerve supply) with hypotension
Myocardial depression with bradycardia

Muscle Relaxants LAST UPDATED: 4TH
APRIL 2019
 Bookmark
Neuromuscular blocking drugs used in anaesthesia are also known as muscle

relaxants. By specific blockade of the neuromuscular junction they enable light
anaesthesia to be used with adequate relaxation of the muscles of the abdomen
and diaphragm. They also relax the vocal cords and allow the passage of a
tracheal tube. Their action differs from the muscle relaxants used in
musculoskeletal disorders that act on the spinal cord or brain.
Patients who have received a neuromuscular blocking drug should always have
their respiration assisted or controlled until the drug has been inactivated or
antagonised. They should also receive sufficient concomitant inhalational or
intravenous anaesthetic or sedative drugs to prevent awareness.
Non-Depolarising Agents
Non-depolarising muscle relaxant drugs e.g. atracurium compete with
acetylcholine (ACh) molecules released from the presynaptic membrane at the
neuromuscular junction (NMJ), by binding with the ACh receptors on the
postsynaptic membrane of the motor endplate, blocking the action of ACh and
preventing depolarisation and muscle contraction.
None of these drugs cross the blood-brain barrier as they are water-soluble polar
molecules and therefore have no effect on the central nervous system; they have
no sedative or analgesic effects and are not considered to trigger malignant
hyperthermia.
Non-depolarising neuromuscular blocking drugs have a slower onset of action
than suxamethonium chloride and can be classified by their duration of action as
short-acting (15 - 30 mins), intermediate-acting (30 - 40 mins) and long-acting
(60 - 120 mins), although duration of action is dose-dependent.
Atracurium besilate is a benzylisoquinolinium neuromuscular blocking drug with
an intermediate duration of action. It undergoes non-enzymatic metabolism
which is independent of liver and kidney function, thus allowing its use in patients
with hepatic or renal impairment. Cardiovascular effects such as flushing,
tachycardia, hypotension and bronchospasm are associated with significant
histamine release; histamine release can be minimised by administering slowly or
in divided doses over at least 1 minute.
All non-depolarising drugs should be used with care in patients suspected to be
suffering with myasthenia gravis or myasthenic syndrome, as patients with these
conditions are extremely sensitive to their effects.
Neostigmine, an anticholinesterase, is used specifically for reversal of non-
depolarising (competitive) blockade. It acts within one minute of intravenous
injection and its effects last for 20 to 30 minutes; a second dose may then be
necessary.
Depolarising Agents
Depolarising muscle relaxants produce what appears to be a "persistent"
depolarisation at the NMJ by binding to ACh receptors and mimicking the effect
of ACh but without dissociating from the receptors and being rapidly hydrolysed
by acetylcholinesterase. Propagation of an action potential is prevented by the
area of inexcitability that occurs around the ACh receptors. Suxamethonium is
the only depolarising muscle relaxant with clinical usefulness, has the most rapid
onset of action of any of the neuromuscular blocking drugs and is ideal if fast
onset and brief duration of action are required.
Unlike the non-depolarising neuromuscular blocking drugs, its action cannot be
reversed and anticholinesterases such as neostigmine actually potentiate the
neuromuscular block. Recovery from suxamethonium is spontaneous; the drug is
normally hydrolysed rapidly (5 - 10 mins) by plasma pseudocholinesterase.
Reduced plasma cholinesterase synthesis in end-stage hepatic disease or
congenital deficiency may increase the duration of action resulting in prolonged
paralysis with apnoea.
Suxamethonium should be given after anaesthetic induction because paralysis is
usually preceded by painful muscle fasciculations due to the initial endplate
depolarisation; asynchronous muscle fibre twitches cause damage which can
result in muscle pains the next day, and also potassium release and
hyperkalaemia. While tachycardia occurs with single use, bradycardia may occur
with repeated doses in adults and with the first dose in children. Premedication
with glycopyrronium bromide or alternatively atropine sulfate, reduces
bradycardia, excessive salivation and other muscarinic effects associated with
suxamethonium use.
Malignant hyperthermia is a rare but often fatal complication in susceptible
patients that results from a rapid increase in muscle metabolism. About 50% of
patients are genetically predisposed. It is characterised by tachycardia and,
among other manifestations, intense muscle spasm that results in a rapid and
profound hyperthermia.

Naloxone LAST UPDATED: 4TH
APRIL 2019
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Opioid toxicity can cause coma, respiratory depression, and pinpoint pupils.
Naloxone is a specific antagonist of mu(μ)-opioid receptors. Naloxone
hydrochloride will immediately reverse opioid-induced respiratory depression
but will also antagonise the analgesic effect. It will also precipitate a
withdrawal syndrome when dependence has occurred.
Naloxone should only be given by subcutaneous or intramuscular routes if
intravenous route is not feasible; intravenous administration has more rapid
onset of action. The BNF recommends naloxone 0.4 mg to 2 mg intravenously
in adults, repeated every 2 – 3 minutes up to a maximum of 10 mg. If
respiratory depression does not improve, then question the diagnosis. In
practice, most overdoses will respond to 400 micrograms to 800 micrograms
naloxone.
Since naloxone has a shorter duration of action than many opioids (1 - 2
hours), close monitoring and repeated injections may be necessary if
respiratory function deteriorates. When repeated administration of naloxone
is required, it can be given by continuous intravenous infusion instead and
the rate of infusion adjusted accordingly.
The effects of some opioids, such as buprenorphine and tramadol, are only
partially reversed by naloxone. Methadone has a very long duration of action;
patients may need to be monitored for long periods following large overdoses
(up to 72h).

Nitrous Oxide LAST UPDATED: 4TH
APRIL 2019
 Bookmark
Nitrous oxide is used for maintenance of anaesthesia and, in sub-anaesthetic

concentrations, for analgesia.
Uses
For anaesthesia, nitrous oxide is commonly used in a concentration of around
50 - 66% in oxygen in association with other inhalational or intravenous
agents. Nitrous oxide cannot be used as the sole anaesthetic agent due to
lack of potency, but is useful as part of a combination of drugs since it allows
reduction in dosage of other agents.
For analgesic purposes without the induction of anaesthesia, a mixture of
nitrous oxide and oxygen containing 50% of each gas (Entonox®, Equanox®)
is used. Self-administration using a demand valve is popular in obstetric
practice, for changing painful dressings, as an aid to postoperative
physiotherapy, and in emergency ambulances.
Contraindications
Nitrous oxide must not be used in patients with an air-containing closed
space as nitrous oxide diffuses into these spaces with a resulting increase in
pressure. This includes conditions such as pneumothorax, the presence of
intracranial air after head injury, entrapped air following recent underwater
dive, recent intraocular gas injection or intestinal obstruction. Nitrous oxide
also increases cerebral blood flow and should be avoided in patients with, or
at risk of, raised intracranial pressure.
Side Effects
Hypoxia can occur immediately following the administration of nitrous oxide;
additional oxygen should always be given for several minutes after stopping
the flow of nitrous oxide.
Exposure to nitrous oxide for prolonged periods, either by continuous or by
intermittent administration, may result in megaloblastic anaemia as a result
of interference with the action of vitamin B12; neurological toxic effects can
occur without preceding overt haematological changes. Depression of white
cell formation may also occur.

Propofol LAST UPDATED: 21ST
JUNE 2020
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Propofol is a short-acting drug with a rapid onset, and a rapid recovery with
less hangover effect than the other intravenous anaesthetics. It can produce
hypotension and respiratory depression to a greater extent than other
intravenous anaesthetic agents.
Uses
Propofol is the most widely used intravenous anaesthetic in the UK. It can be
used for induction or maintenance of anaesthesia in adults and children, but
it is not generally used in neonates. It can also be used for sedation during
procedures and sedation for adults in intensive care. Propofol reduces airway
and pharyngeal reflexes, therefore it is the ideal drug to use with the
laryngeal mask airway (LMA).
Administration
The induction dose in an unpremedicated young adult is 2 – 2.5 mg/kg body
weight. Premedication with opioid or benzodiazepine markedly reduces the
dose of propofol needed to induce anaesthesia. Elderly patients need a
smaller dose whereas children need a larger dose.
After induction with propofol, anaesthesia can be maintained in one of two
ways; using a volatile inhalational agent or using an infusion of propofol.
Pharmacokinetics
When a single induction dose of 2 mg/kg is injected, there is a rapid rise in
the blood levels of propofol and loss of consciousness occurs within 20 - 40
s. Clinically this will be manifest by loss of verbal contact with the patient.
Blood levels peak around 90 - 100 s. Blood levels then rapidly decline due to
the redistribution and elimination of the propofol. The distribution half life of
propofol is 2 to 8 min; elimination half life can be up to 6 h. Return of
consciousness occurs within 10 min.
Propofol is very rapidly cleared from the blood and has a clearance rate of 1.5
to 2.2 L/min. It is rapidly metabolised in the liver. There are two metabolic
pathways involved – conjugation to glucuronide and hydroxylation to quinol
which is subsequently glucuronidated. Clearance of propofol from the plasma
is greater than would be expected if it were only metabolised in the liver,
therefore there are probably extra-hepatic sites of its metabolism. Less than
1% of a dose is excreted unchanged by the kidneys.
Pharmacodynamics
Central nervous system
Sedation, loss of consciousness and anaesthesia
Antiemetic effects
Reduced cerebral metabolism and blood flow with consequent
reduction in intracranial pressure and cerebral perfusion
pressure
Reduced intraocular pressure
Reduced systolic, diastolic and mean blood pressure (due to
vasodilation and a reduction in pre- and afterload)
Slightly negative inotropic effect
Heart rate remains mostly unchanged
Respiratory system
Decreased tidal volume and respiratory rate producing
respiratory depression
Decreased ventilatory response to carbon dioxide
Reduced upper airway reflexes
Cautions
In hypotensive states, the blood flow to fat and muscle is reduced thus the
volume of distribution is reduced and patients will be more sensitive to the
effects of propofol. Propofol itself can produce hypotension and great
caution must be exercised in giving propofol to hypotensive patients. If a
patient is in a state of shock, it is advisable not to use propofol for induction
of anaesthesia.
Side Effects
Possible side effects include:
Hypotension
Bradycardia
Tachycardia
Arrhythmias
Pruritus and/or rash
Nausea and/or vomiting
Pain on injection
Excitation phenomena such as involuntary movements
Headache
Transient apnoea
Propofol infusion syndrome (prolonged infusion of propofol doses
exceeding 4 mg/kg/hour may result in potentially fatal effects,
including metabolic acidosis, arrhythmias, cardiac failure,
rhabdomyolysis, hyperlipidaemia, hyperkalaemia, hepatomegaly, and
renal failure)

Thiopental Sodium LAST UPDATED: 4TH
APRIL 2019
 Bookmark
Thiopental sodium, a barbiturate, was the most commonly used intravenous

induction agent until the introduction of propofol. It is still commonly used in the
UK and is the preferred drug for rapid sequence induction of anaesthesia.
Induction is generally smooth and rapid but dose-related cardiovascular and
respiratory depression can occur. Recovery after a single dose is rapid due to
redistribution, however, metabolism is slow and sedative effects can persist for
24 hours. Repeated doses have a cumulative effect and recovery is much slower.
Administration
The induction dose of thiopental for a healthy young adult is 4 - 5 mg/kg body
weight. Thiopental is prepared as a 2.5 % solution. The recommended induction
dose should be given over a period of about 20 s. If the thiopental is injected more
rapidly the onset of anaesthesia is quicker and the cardiovascular and respiratory
depression greater.
A reduced dose may be required in:
Conditions associated with low plasma protein such as malnutrition,
chronic renal failure and cirrhosis
The elderly
Hypothyroidism
An increased dose may be required in:
Children
Chronic alcohol abuse
Long term treatment with drugs that induce the cytochrome P450 enzyme
system in the liver
Pharmacokinetics
After a single induction dose of 4 mg/kg body weight, there is a rapid rise in the
plasma level of thiopental. The plasma level peaks at around 90 to 100 s and then
decreases rapidly due to redistribution. Redistribution occurs quickly to the
vessel rich group (e.g. liver, kidney, brain) of tissues and then to muscle and
fat. The level in the muscles peaks at around 20 min and in the fat at around 45
min. Loss of consciousness occurs in about 30 s (one arm-brain circulation time)
and return of consciousness occurs within 10 min.
Thiopental is metabolised only very slowly and metabolism plays no part in the
return of consciousness. Metabolism of thiopental occurs in the liver. It is mainly
broken down into inactive carboxylic acid analogues which are excreted by the
kidneys. A small fraction of thiopental undergoes desulphuration to pentobarbital
which is a long acting hypnotic. The distribution half life is 2 - 8 min and
elimination half life is about 10 h.
Pharmacodynamics
Central nervous system
Loss of consciousness and anaesthesia
Reduced cerebral metabolism with a consequent reduction in
cerebral blood flow and intracranial pressure
Anticonvulsant effects (may be used in refractory status epilepticus)
Reduced intraocular pressure
Reduced systolic, diastolic and mean blood pressure (due to
vasodilation and a decrease in preload and afterload); fall in BP is less
than with propofol but can be significant in patients who have
cardiac disease or are hypovolaemic
Heart rate may increase slightly at induction
Respiratory system
Reduced respiratory rate and tidal volume with respiratory
depression and transient apnoea
Sensitised laryngeal and pharyngeal reflexes (may result in
laryngospasm in response to surgical stimulation, presence of
secretions, or the insertion of oral airway or laryngeal mask airway at
too light a plane of anaesthesia)
Decreased ventilatory response to hypoxia (can precipitate
bronchospasm in susceptible patients)
Cautions
Barbiturates induce hepatic enzymes. The enzyme gamma aminolevulinic acid
synthetase, which produces porphyrins, can be induced and in susceptible
patients an attack of acute intermittent porphyria can occur. Thiopental is
absolutely contraindicated in these patients.
Side Effects
Extravasation of thiopental during injection can lead to tissue damage.
Accidental intra-arterial injection causes vasospasm and may lead to
thrombosis and tissue necrosis.
Involuntary muscle movements on induction
Cough and laryngospasm
Arrhythmias
Hypotension
Headache

ACE Inhibitors LAST UPDATED: 17TH
APRIL 2019
PHARMACOLOGY / CARDIOVASCULAR
 Bookmark
Mechanism of Action
Angiotensin-converting enzyme inhibitors (ACE inhibitors) e.g. captopril inhibit
the conversion of angiotensin I to angiotensin II, and thus have a vasodilatory
effect, lowering both arterial and venous resistance. The cardiac output increases
and, because the renovascular resistance falls, there is an increase in renal blood
flow. This latter effect, together with reduced aldosterone release, increases Na+
and H2O excretion, contracting the blood volume and reducing venous return to
the heart.
Blocking ACE also diminishes the breakdown of the potent vasodilator bradykinin
which is the cause of the persistent dry cough. Angiotensin-II receptor blockers
do not have this effect, therefore they are useful alternative for patients who have
to discontinue an ACE inhibitor because of persistent cough.
Indications
ACE inhibitors have many uses and are generally well tolerated. They are
indicated for:
Heart failure
Hypertension
Diabetic nephropathy
Secondary prevention of cardiovascular events
Contraindications
ACE inhibitors should be avoided in:
History of angioedema associated with previous exposure to an ACE
inhibitor
Recurrent angioedema
Bilateral renal artery stenosis
Pregnancy and breastfeeding
Cautions
The use of ACE inhibitors is cautioned in:
Renal impairment
Afro-Caribbean patients (may respond less well to ACE inhibitors)
Peripheral vascular disease or generalised atherosclerosis (risk of clinically
silent renovascular disease)
Primary aldosteronism (patients may respond less well to ACE inhibitors)
History of idiopathic or hereditary angioedema
Patients with hypertrophic cardiomyopathy
Patients with severe or symptomatic aortic stenosis (risk of hypotension)
Concomitant treatment with NSAIDs increases the risk of renal damage, and with
potassium-sparing diuretics (or potassium-containing salt substitutes) increases
the risk of hyperkalaemia. Hyperkalaemia and other side effects of ACE inhibitors
are more common in the elderly and in those with impaired renal function and the
dose may need to be reduced.
Side Effects
Side effects of ACE inhibitors may include:
Deterioration in renal function
Hyperkalaemia
Hypotension
Persistent dry cough
Angioedema (non-allergic drug reaction)
Dizziness and headaches (usually secondary to hypotension)
Other common adverse effects include abdominal discomfort, dyspepsia,
diarrhoea, nausea and vomiting, rash (in particular maculopapular rash),
myalgia, muscle spasms, dyspnoea, chest pain, and fatigue

Adenosine LAST UPDATED: 6TH
JUNE 2021
 Bookmark
Adenosine is usually the treatment of choice for terminating paroxysmal

supraventricular tachycardia.
Mechanism of Action
Adenosine stimulates A1-adenosine receptors and opens acetylcholine sensitive
K+ channels, increasing K+ efflux. This hyperpolarises the cell membrane in the
atrioventricular node and, by inhibiting the calcium channels, slows conduction in
the AVN. As it has a very short duration of action (half-life only about 8 - 10
seconds), most side effects are short lived.
Administration
For a regular narrow-complex tachycardia the first step is to attempt vagal
manoeuvres. If this is unsuccessful and the tachyarrhythmia persists, 6 mg
intravenous adenosine should be administered into a central/large vein over 2
seconds, followed by 12 mg after 1 - 2 minutes if required, then a further 18 mg
after 1 - 2 minutes if required (max 36 mg, as per the 2021 ALS Guidelines).
The effects of adenosine are potentiated by dipyridamole, therefore if it is
essential to give adenosine in a patient taking dipyridamole the dose should be
quartered.
The patient should be warned that they will feel unwell and may experience chest
discomfort for a few seconds following the injection. An ECG (preferably multi-
lead) should be recorded during the injection. If adenosine is contraindicated, or
fails to terminate a regular narrow-complex tachycardia, the administration of
verapamil 2.5 - 5 mg IV over 2 mins should be considered.
Contraindications
Adenosine is contraindicated in:
Asthma and COPD (can cause bronchospasm)
Decompensated heart failure
Long QT syndrome
Second- or third-degree AV block and sick sinus syndrome (unless
pacemaker fitted)
Severe hypotension
Side Effects
Common side effects of adenosine include:
Apprehension
Dizziness, flushing, headache, nausea, dyspnoea
Angina (discontinue)
AV block, sinus pause and arrhythmia (discontinue if asystole or severe
bradycardia occur)

Amiodarone LAST UPDATED: 17TH
APRIL 2019
 Bookmark
Amiodarone hydrochloride is used in the treatment of arrhythmias, particularly

when other drugs are ineffective or contraindicated. However, its long-term use is
often restricted by serious adverse effects such as photosensitivity, thyroid
disorders, corneal microdeposits, neuropathy and pulmonary alveolitis.
Mechanism of Action
Amiodarone has blocking actions on several channels (e.g. K+ and inactivated
Na+ channels) and beta-adrenoceptors. It acts by slowing repolarisation and
prolonging the action potential and refractory period in all cardiac tissues,
depressing sinus node automaticity and slowing conduction.
Indications
Amiodarone can be used for paroxysmal supraventricular, nodal and ventricular
tachycardias, atrial fibrillation and flutter, and ventricular fibrillation. It can also be
used for tachyarrhythmias associated with Wolff-Parkinson- White syndrome.
Intravenous injection of amiodarone hydrochloride can be used in
cardiopulmonary resuscitation for ventricular fibrillation or pulseless tachycardia
unresponsive to other interventions.
Contraindications
Amiodarone is contraindicated in:
Severe conduction disturbances (unless pacemaker fitted)
Sinus node disease (unless pacemaker fitted)
Iodine sensitivity
Sinoatrial heart block (except in cardiac arrest)
Sinus bradycardia (except in cardiac arrest)
Thyroid dysfunction
Intravenous use should be avoided in cardiomyopathy, congestive heart failure,
circulatory collapse, severe arterial hypotension and severe respiratory failure.
Cautions
Amiodarone should be used with caution in:
Acute porphyrias
Conduction disturbances (in excessive dosage)
Elderly
Heart failure
Hypokalaemia
Severe bradycardia (in excessive dosage)
Severe hepatocellular toxicity
Concomitant therapy with drugs that prolong the QT interval
Side Effects
Common side effects of amiodarone include:
Bradycardia
Nausea and vomiting
Thyroid disorders - hypothyroidism and hyperthyroidism
Persistent slate grey skin discoloration
Photosensitivity
Pulmonary toxicity (including pneumonitis and fibrosis)
Hepatotoxicity
Corneal microdeposits (sometimes with night glare)
Sleep disorders

Aspirin (Antiplatelet) LAST UPDATED: 7TH
JUNE 2022
 Bookmark
Antiplatelet drugs decrease platelet aggregation and inhibit thrombus formation

in the arterial circulation, because in faster-flowing vessels, thrombi are
composed mainly of platelets with little fibrin.
Mechanism of Action
Aspirin irreversibly inhibits cyclooxygenase and blocks the platelet production of
thromboxane A2 (TXA2), a powerful inducer of platelet aggregation. The
endothelial cells of the vascular wall produce a prostaglandin, prostacyclin (PGI2),
which is a physiological antagonist of TXA2, causing inhibition of platelet
aggregation. Platelets cannot synthesise new enzyme but the vascular
endothelial cells can, and the balance is shifted to the anti-aggregatory effects of
PGI2.
Indications
Low-dose aspirin may be indicated in:
Primary prevention of cardiovascular events in some people when the risk
is particularly high
Secondary prevention of cardiovascular events in people with:
Angina
Myocardial infarction
Stroke and transient ischaemic attack
Peripheral arterial disease
Atrial fibrillation (although anticoagulants are usually used)
Contraindications
Low-dose aspirin should be avoided in:
People with a history of true hypersensitivity to aspirin or salicylates
(symptoms of hypersensitivity to aspirin or salicylates include
bronchospasm, urticaria, angioedema, and vasomotor rhinitis)
People with active pathological bleeding, such as peptic ulcer or
intracranial haemorrhage
People with suspected stroke, until intracranial haemorrhage has been
excluded by brain imaging
People with haemophilia or another haemorrhagic disorder (including
thrombocytopenia)
Children younger than 16 years of age (due to risk of Reye's syndrome)
Cautions
Low-dose aspirin should be used with caution in:
People who may be at high risk of increased bleeding — for example those
receiving treatment with warfarin, NSAIDs, corticosteroids, or other drugs
known to increase bleeding
People with asthma (may precipitate bronchospasm)
People with uncontrolled blood pressure
If using for primary prevention of cardiovascular events, do not
initiate aspirin until blood pressure is less than 150/90 mmHg
For secondary prevention, benefits of antiplatelet treatment
outweigh risks, and treatment should not be delayed while
controlling blood pressure
Side Effects
Low-dose aspirin may result in:
Increased absolute risk of major bleeding, major gastrointestinal bleeding,
and intracranial bleeding
Gastrointestinal adverse effects including bleeding, ulceration and
dyspepsia
Bronchospasm and asthma attacks in patients with asthma
Interactions
The risk of bleeding is increased when low-dose aspirin is combined with other
drugs that can increase the risk of bleeding such as other antiplatelet drugs,
NSAIDs, oral and parenteral anticoagulants, selective serotonin reuptake
inhibitors (SSRIs) and corticosteroids. Consider the need for gastroprotection
with a proton pump inhibitor (such as omeprazole) or a histamine antagonist
(such as ranitidine).

Atropine LAST UPDATED: 17TH
APRIL 2019
 Bookmark
Atropine is used in sinus, atrial or nodal bradycardia or AV block, when the

haemodynamic condition of the patient is unstable because of the bradycardia.
The dose in this case is 500 micrograms intravenously, repeated if necessary to a
maximum of 3 mg. Doses greater than 3 mg can cause a paradoxical slowing of
the heart rate.
Asystole during cardiac arrest is usually caused by primary myocardial pathology
rather than excessive vagal tone and there is no evidence that routine use of
atropine is beneficial in the treatment of asystole or PEA.
Mechanism of Action
Atropine antagonises the action of the parasympathetic neurotransmitter
acetylcholine at muscarinic receptors. Therefore it blocks the effect of the vagus
nerve on both the sinoatrial and atrioventricular node, increasing sinus
automaticity and facilitating AV node conduction.
Contraindications
Antimuscarinics should be avoided in:
Gastrointestinal obstruction, intestinal atony or paralytic ileus
Myasthenia gravis
Prostatic enlargement, significant bladder outflow obstruction or urinary
retention
Severe ulcerative colitis or toxic megacolon
Side Effects
Side effects of atropine are dose-related and include:
Dilation of pupils with loss of accommodation
Blurred vision
Dry mouth
Urinary retention
Constipation
Drowsiness
Acute confusion
Skin dryness and flushing
Tachycardia, palpitations and arrhythmias

Beta-Blockers LAST UPDATED: 23RD
APRIL 2020
 Bookmark
Beta-blockers block the beta-adrenoceptors in the heart, peripheral vasculature,

bronchi, pancreas and liver.
Therapeutic Effects
Reduce blood pressure
Reduce heart rate, contractility and cardiac output
Increase AV conduction time, refractoriness and suppress
automaticity
Eye
Reduce intraocular pressure
Respiratory system
Cause bronchoconstriction
Type Examples
Many beta-blockers are now available and in general they are all equally effective.
There are, however, differences between them, which may affect choice in
treating particular diseases or individual patients.
Sotalol hydrochloride, a non-cardioselective beta-blocker with additional class III
antiarrhythmic activity, is used for prophylaxis in paroxysmal supraventricular
arrhythmias. It also suppresses ventricular ectopic beats and nonsustained
ventricular tachycardia. It has been shown to be more effective than lidocaine in
the termination of spontaneous sustained ventricular tachycardia due to
coronary disease or cardiomyopathy. However, it may prolong the QT-interval and
induce torsade de pointes in susceptible patients.
Labetalol has, in addition to other beta-blocker effects, an arteriolar vasodilating
action by diverse mechanisms, and thus lowers peripheral resistance. Labetalol is
useful for treating hypertensive emergencies and in the treatment of
hypertension of pheochromocytoma.
Esmolol hydrochloride is a relatively cardioselective beta-blocker with a very
short duration of action, used intravenously for the short-term treatment of
supraventricular arrhythmias, sinus tachycardia, or hypertension, particularly in
Indications
the perioperative period.
Beta-blockers may be indicated in:

Hypertension
Pheochromocytoma (only with an alpha-blocker)
Angina
Secondary prevention after ACS
Arrhythmias including atrial fibrillation
Heart failure
Thyrotoxicosis
Anxiety
Prophylaxis of migraine
Essential tremor
Glaucoma
Contraindications
Beta-blockers are contraindicated in people with:
A history of asthma or bronchospasm.
Beta-blockers can precipitate bronchospasm and should therefore
usually be avoided in patients with a history of asthma. When there is
no suitable alternative, it may be necessary for a patient with well-
controlled asthma, or chronic obstructive pulmonary disease
(without significant reversible airways obstruction), to receive
treatment with a beta-blocker for a co-existing condition (e.g. heart
failure or following myocardial infarction). In this situation, a
cardioselective beta-blocker should be selected and initiated at a low
dose by a specialist; the patient should be closely monitored for
adverse effects. Atenolol, bisoprolol fumarate, metoprolol tartrate,
nebivolol, and (to a lesser extent) acebutolol, have less effect on the
beta2 (bronchial) receptors and are, therefore, relatively
cardioselective, but they are not cardiospecific. They have a lesser
effect on airways resistance but are not free of this side-effect.
Reversible or severe COPD
Known intolerance or hypersensitivity to beta-blockers
Severe or symptomatic bradycardia (heart rate less than 60 beats per
minute)
Sinoatrial block, second- or third-degree heart block (unless there is a
pacemaker in place)
Severe or uncontrolled heart failure
Severe or symptomatic hypotension (systolic blood pressure less than 90
mmHg)
Severe peripheral arterial disease (including intermittent claudication) or
Raynaud's syndrome
Sick sinus syndrome
Cardiogenic shock or phaeochromocytoma (without a concomitant alpha-
blocker)
Frequent episodes of hypoglycaemia
Cautions
Beta-blockers should be used with caution in people with:
Heart failure with chronic kidney disease (CKD), hypotension, ischaemic
heart disease, or less severe peripheral arterial disease
Prinzmetal's angina
Current or recent (within 4 weeks) exacerbation of heart failure
First-degree atrioventricular heart block
Portal hypertension (risk of deterioration in liver function)
Diabetes mellitus (affects carbohydrate metabolism and symptoms of
hypoglycaemia may be masked)
COPD
Myasthenia gravis
Psoriasis
Thyrotoxicosis (symptoms may be masked)
People who wear contact lenses (reduced secretion of lacrimal fluid)
Chronic kidney disease
Side Effects
Deteriorating symptoms of heart failure (such as symptoms of fluid
overload and fatigue)
Hypotension and bradycardia
Dizziness, headache, and syncope
Nausea, vomiting, diarrhoea, and constipation
Sexual dysfunction including erectile dysfunction and loss of libido
Cold extremities, paraesthesia, and numbness (more common in people
with peripheral arterial disease)
Effect on carbohydrate metabolism (hypo- or hyperglycaemia in people
with or without diabetes mellitus)
Effect on metabolic and autonomic response to hypoglycaemia (possible
masking of hypoglycaemia warning signs such as tremor and tachycardia)
Fatigue and asthenia (lack of energy and strength)
Sleep disturbance, nightmares, and depression
Bronchospasm
Reduction of secretion of lacrimal fluid (may affect people who wear
contact lenses)

Calcium Channel Blockers LAST UPDATED: 17TH
APRIL 2019
 Bookmark
Calcium channel blockers are widely used in the treatment of angina (second line
to beta-blockers) and also for hypertension, heart failure and arrhythmias.
Type Examples
Calcium channel blockers vary widely in their predilection for the various possible
sites of action and in their therapeutic effects and may be divided into the
dihydropyridine type (e.g. amlodipine, nifedipine and nimodipine) and the rate-
limiting non-dihydropyridine type (e.g. verapamil, diltiazem).
Verapamil: Verapamil is used for the treatment of angina, hypertension, and
arrhythmias. Verapamil is highly negatively inotropic and reduces cardiac output,
slows the heart rate and may impair atrioventricular conduction. It may
precipitate heart failure, exacerbate conduction disorders, and cause
hypotension at high doses and should not be used with beta-blockers.
Constipation is the most common side effect.
Nifedipine: Nifedipine relaxes vascular smooth muscle and dilates coronary and
peripheral arteries. Nifedipine has less myocardial effects than verapamil and has
no antiarrhythmic properties but has more influence on the vessels. Unlike
verapamil it rarely precipitates heart failure because any negative inotropic effect
is offset by a reduction in left ventricular work.
Nimodipine: Nimodipine is related to nifedipine but the smooth muscle relaxant
effect preferentially acts on cerebral arteries. It is used solely for the prevention
and treatment of vascular spasm following aneurysmal subarachnoid
haemorrhage.
Mechanism of Action
Calcium channel blockers inhibit L-type voltage-sensitive calcium channels in
arterial smooth muscle, causing relaxation and vasodilation. They also block
calcium channels within the myocardium and conducting tissues of the heart
which produces a negative inotropic effect by reducing calcium influx during the
plateau phase of the action potential.
The dihydropyridines have relatively little effect on the heart because they have a
much higher affinity for inactivated channels found more frequently in vascular
muscle. Furthermore, at clinical doses, vasodilation results in a reflex increase in
sympathetic tone that counteracts the mild negative inotropic effect.
The non-dihydropyridines are rate-limiting calcium-channel blockers that

depress the sinus node and slow conduction in the atrioventricular node, causing
a mild resting bradycardia.
Contraindications
Verapamil:
Acute porphyrias
Atrial flutter or fibrillation associated with accessory conducting pathways
(e.g. Wolff-Parkinson-White-syndrome)
Bradycardia
Cardiogenic shock
History of heart failure (even if controlled by therapy)
History of significantly impaired left ventricular function (even if controlled
by therapy)
Hypotension
Second- and third-degree AV block
Sick sinus syndrome
Sinoatrial block
Nifedipine:
Acute attacks of angina
Cardiogenic shock
Significant aortic stenosis
Unstable angina
Within 1 month of myocardial infarction
Nimodipine:
Unstable angina
Within 1 month of myocardial infarction
Side Effects
Gastrointestinal adverse effects - constipation, nausea, vomiting,
dyspepsia
Cardiovascular adverse effects - Bradycardia, AV block, reflex tachycardia,
palpitations
Vasodilatory adverse effects - flushing, dizziness, headache, postural
hypotension, ankle swelling (more common with dihydropyridine calcium-
channel blockers and often improve with continued use, although ankle
swelling often persists)
Lethargy, fatigue

Clopidogrel LAST UPDATED: 17TH
APRIL 2019
 Bookmark
Antiplatelet drugs decrease platelet aggregation and inhibit thrombus formation

in the arterial circulation, because in faster-flowing vessels, thrombi are
composed mainly of platelets with little fibrin.
Mechanism of Action
Clopidogrel, a thienopyridine derivative, inhibits the binding of ADP to its platelet
receptor (P2Y12 ADP-receptor), inhibiting platelet adhesion and aggregation.
Indications
Clopidogrel is used for:
the prevention of atherothrombotic events in patients with a history of
symptomatic ischaemic disease
the management of ACS (in combination with low-dose aspirin)
the prevention of atherothrombotic events in percutaneous coronary
intervention (in combination with low-dose aspirin)
the prevention of atherothrombotic and thromboembolic events in patients
with atrial fibrillation (who cannot take warfarin) and in stroke (in patients
who cannot take aspirin)
Contraindications
Clopidogrel should be avoided in:
People with active pathological bleeding, such as peptic ulcer or
intracranial haemorrhage
People with severe hepatic impairment
Women who are pregnant or breastfeeding
Clopidogrel should be used with caution in people who may be at high risk of
increased bleeding, for example those receiving treatment with warfarin, other
anti-platelets or other drugs known to increase gastrointestinal bleeding (such as
NSAIDs, SSRIs and corticosteroids).
Side Effects
Clopidogrel is associated with an increased risk of bleeding (for example
gastrointestinal bleeds)
Other common adverse effects include diarrhoea, abdominal pain, and
dyspepsia
Clopidogrel is known to cause pruritus and urticaria, but these adverse
reactions are generally uncommon
Gynaecomastia is a rare adverse effect of clopidogrel
Thrombotic thrombocytopenic purpura is a very rare adverse effect of
clopidogrel, and it sometimes occurs after a short exposure to clopidogrel

Digoxin LAST UPDATED: 17TH
APRIL 2019
 Bookmark
Digoxin is a cardiac glycoside that increases the force of myocardial contraction

(positive inotrope), and slows the heart rate (negative chronotrope). Digoxin has a
narrow therapeutic index; digoxin toxicity can occur even when the serum digoxin
concentration is within the therapeutic range (between 0.7 - 2.0 mcg/L).
Mechanism of Action
Inotropic effect:
Digoxin directly inhibits membrane Na+/K+ ATPase, which is responsible for
Na+/K+ exchange across the myocyte cell membrane. This increases intracellular
Na+ and produces a secondary increase in intracellular Ca2+ that increases the
force of myocardial contraction. The increase in intracellular Ca2+ occurs
because the decreased Na+ gradient across the membrane reduces the extrusion
of Ca2+ by the Na+/Ca2+ exchanger that normally occurs during diastole. Digoxin
and K+ ions compete for the receptor on the outside of the muscle cell
membrane, and so the effects of digoxin may be dangerously increased in
hypokalaemia.
Chronotropic effect:
Digoxin stimulates vagal activity , causing the release of ACh, which slows the
heart rate, slows atrioventricular conduction and prolongs the refractory period in
the AVN and bundle of His. By delaying AV conduction, digoxin increases the
degree of block, and slows and strengthens the ventricular beat.
Indications
Digoxin is most useful for controlling the ventricular response in persistent and
permanent atrial fibrillation and atrial flutter. Digoxin is usually only effective for
controlling the ventricular rate at rest, and should therefore only be used as
monotherapy in predominantly sedentary patients with non-paroxysmal atrial
fibrillation. It is now rarely used for rapid control of heart rate, as even with
intravenous administration, response may take many hours.
Digoxin also has a role in the management of heart failure; digoxin improves
symptoms of heart failure and exercise tolerance and reduces hospitalisation due
to acute exacerbations but it does not reduce mortality. Digoxin is reserved for
patients with worsening or severe heart failure due to left ventricular systolic
dysfunction refractory to combination therapy with first-line agents.
Contraindications
Digoxin is contraindicated in:
Supraventricular arrhythmias associated with accessory conduction
pathways e.g. Wolff-Parkinson-White syndrome
Ventricular tachycardia or fibrillation
Heart conduction problems e.g. second degree or intermittent complete
heart block
Hypertrophic cardiomyopathy (unless concomitant atrial fibrillation and
heart failure but should be used with caution)
Cautions
Digoxin should be used with caution in:
Hypercalcaemia (risk of digitalis toxicity)
Hypokalaemia (risk of digitalis toxicity; diuretics may predispose to
hypokalaemia)
Hypomagnesaemia (risk of digitalis toxicity)
Hypoxia (risk of digitalis toxicity)
Recent myocardial infarction
Severe respiratory disease
Sick sinus syndrome
Thyroid disease
Constrictive pericarditis
Renal impairment (reduce dose and monitor plasma-digoxin concentration;
toxicity increased by electrolyte disturbances)
Elderly people (reduce dose)
Concomitant drug therapy with drugs which may increase plasma
concentration of digoxin e.g. amiodarone, antimicrobials, calcium-channel
blockers, spironolactone
Side Effects
The adverse effects of digoxin are frequently due to its narrow therapeutic
window and include:
Cardiac adverse effects
Sinoatrial and atrioventricular block
Premature ventricular contractions
PR prolongation and ST-segment depression
Nausea, vomiting and diarrhoea
Blurred or yellow vision
CNS effects
weakness, dizziness, confusion, apathy, malaise, headache,
depression, psychosis
Thrombocytopenia and agranulocytosis (rare)
Gynaecomastia in men in prolonged administration
Digoxin Toxicity
Unwanted effects of digoxin depend on both the plasma concentration of digoxin
(increasing risk of toxicity through the range 1.5 - 3 mcg/L) and on the sensitivity
of the conducting system or of the myocardium, which is often increased in heart
disease. Hypoxia, hypercalcaemia, hypokalaemia and hypomagnesaemia
predispose to digoxin toxicity. Care should also be taken in the elderly who are
particularly susceptible to digoxin toxicity.
If toxicity occurs, digoxin should be withdrawn. Digoxin-specific antibody
fragments are indicated for the treatment of known or strongly suspected life-
threatening digoxin toxicity associated with ventricular arrhythmias or
bradyarrhythmias unresponsive to atropine sulfate and when measures beyond
the withdrawal of digoxin and correction of any electrolyte abnormalities are
considered necessary.
Fibrinolytics LAST UPDATED: 17TH
APRIL 2019
 Bookmark
The value of thrombolytic drugs for the treatment of myocardial infarction has
been established. Streptokinase and alteplase have been shown to reduce
mortality. Reteplase and tenecteplase are also licensed for acute myocardial
infarction. Fibrinolytic therapy carries a risk of bleeding, including cerebral
haemorrhage, and not all patients can be given this treatment safely.
Mechanism of Action
Fibrinolytic drugs act as thrombolytics by activating plasminogen to form
plasmin, which degrades fibrin and so breaks up thrombi.
Alteplase should be given within 6 – 12 hours of symptom onset, reteplase and
streptokinase within 12 hours of symptom onset, but ideally all should be given
within 1 hour; use after 12 hours requires specialist advice.
Contraindications
Absolute
Previous haemorrhagic stroke
Ischaemic stroke during the previous 6 months
Central nervous system damage or neoplasm
Recent (within 3 weeks) major surgery, head injury or other major
trauma
Active internal bleeding or gastrointestinal bleeding within the past
month
Known bleeding disorder
Relative
Refractory hypertension (SBP > 180 mmHg)
Transient ischaemic attack during the previous 6 months
Oral anticoagulant treatment
Pregnancy or less than 1 week postpartum
Traumatic CPR
Non-compressive vascular puncture
Active peptic ulcer disease
Advanced liver disease
Infective endocarditis
Previous allergic reaction to fibrinolytic drug to be used
Side Effects
Bleeding (serious bleeding calls for discontinuation of the thrombolytic and
may require administration of coagulation factors and antifibrinolytic
drugs)
Nausea and vomiting
Further embolism (either due to clots that break away from the original
thrombus or to cholesterol crystal emboli)
Hypotension
Streptokinase
Streptokinase (SK) is a single chain polypeptide, derived from beta-haemolytic
streptococci. Its lack of fibrin specificity makes it a less desirable thrombolytic
drug than tPA compounds because it produces more fibrinogenolysis.
Streptokinase is antigenic, and so should not be given to patients who have
already been exposed, due to the development of antibodies (after about 4 - 5
days). Prolonged persistence of antibodies to streptokinase can reduce the
effectiveness of subsequent treatment; therefore, streptokinase should not be
used again beyond 4 days of first administration of streptokinase. Minor allergic
reactions may occur in up to 10% of patients - anaphylaxis occurs in less than
0.5% of cases. Hypotension may occur during infusion which usually responds to
fluids or slowing of the infusion.
Alteplase
Alteplase is a recombinant tissue-type plasminogen activator (tPA), a naturally
occurring fibrin-specific enzyme that has selectivity for activation of fibrin-bound
plasminogen. It has a short half-life of 3 - 4 minutes and must be given by
continuous intravenous infusion but is not associated with antigenic or
hypotensive effects, and can be used in patients when recent streptococcal
infections or recent use of streptokinase contraindicates the use of
streptokinase.
Reteplase and Tenecteplase

Reteplase and tenecteplase are genetically engineered forms of human tPA and
have a longer half-life, higher specificity for fibrin, and greater resistance to
plasminogen activator inhibitor-1 than native tPA. The increase in half-life
permits administration as a bolus rather than by continuous infusion.

Flecainide LAST UPDATED: 17TH
APRIL 2019
 Bookmark
Indications
Flecainide acetate is an orally active class Ic antiarrhythmic and may be of value
for serious symptomatic ventricular arrhythmias. It may also be indicated for
junctional re-entry tachycardias and for paroxysmal atrial fibrillation. However, it
has a negative inotropic action and can precipitate serious arrhythmias in a small
minority of patients (including those with otherwise normal hearts).
Contraindications
Flecainide is contraindicated in:
Abnormal left ventricular function
Atrial conduction defects (unless pacing rescue available)
Bundle branch block (unless pacing rescue available)
Distal block (unless pacing rescue available)
Haemodynamically significant valvular heart disease
Heart failure
History of myocardial infarction and either asymptomatic ventricular
ectopics or asymptomatic non-sustained ventricular tachycardia
Long-standing atrial fibrillation where conversion to sinus rhythm not
attempted
Second-degree or greater AV block (unless pacing rescue available)
Sinus node dysfunction (unless pacing rescue available)
Cautions
Flecainide should be used with caution in:
Atrial fibrillation following heart surgery
Elderly (accumulation may occur)
Patients with pacemakers (especially those who may be pacemaker
dependent because stimulation threshold may rise appreciably)
Side Effects
Common side effects of flecainide include:
Asthenia
Dizziness
Dyspnoea
Fatigue
Fever
Oedema
Pro-arrhythmic effects
Visual disturbances

Glycoprotein IIb/IIIa LAST UPDATED: 17TH
APRIL 2019
Inhibitors  Bookmark
Glycoprotein IIb/IIIa inhibitors prevent platelet aggregation by blocking the

binding of fibrinogen to receptors on platelets.
Abciximab is a monoclonal antibody which binds to glycoprotein IIb/IIIa receptors
and to other related sites; it is licensed as an adjunct to unfractionated heparin
and aspirin for the prevention of ischaemic complications in high-risk patients
undergoing percutaneous transluminal coronary intervention. Abciximab should
be used once only (to avoid additional risk of thrombocytopenia).
Eptifibatide (in combination with unfractionated heparin and aspirin) and tirofiban
(in combination with unfractionated heparin, aspirin, and clopidogrel) also inhibit
glycoprotein IIb/IIIa receptors; they are licensed for use to prevent early
myocardial infarction in patients with unstable angina or non-ST-segment-
elevation myocardial infarction.
Tirofiban is also licensed for use in combination with unfractionated heparin,
aspirin, and clopidogrel, for the reduction of major cardiovascular events in
patients with ST-segment elevation myocardial infarction intended for primary
percutaneous coronary intervention.
Abciximab, eptifibatide and tirofiban should be used by specialists only.

Heparin LAST UPDATED: 19TH
JUNE 2019
 Bookmark
The main use of anticoagulants is to prevent thrombus formation or extension of

an existing thrombus in the slower-moving venous side of the circulation, where
the thrombus consists of a fibrin web enmeshed with platelets and red cells.
Anticoagulants are of less use in preventing thrombus formation in arteries, for in
faster-flowing vessels thrombi are composed mainly of platelets with little fibrin.
Mechanism of Action
Unfractionated heparin potentiates the activity of antithrombin III, causing
inactivation of thrombin. The heparin-antithrombin III complex also inhibits factor
Xa and some other factors.
Low molecular weight heparin (LMWH) preparations inhibit only factor Xa.
PT and APTT may both be prolonged but the PT less so.
Contraindications
Heparins are contraindicated:
In people with current (or history of) heparin-induced thrombocytopenia
In people with acute bacterial endocarditis
In people with active major bleeding, and conditions with a high risk of
uncontrolled bleeding, including recent haemorrhagic stroke, major trauma,
recent brain, spinal cord or eye surgery, haemophilia and thrombocytopenia
In people with active gastric or duodenal ulceration
Side Effects
Bleeding
Heparin-induced thrombocytopenia (immune-mediated effect that usually
develops after 5 - 10 days, signs may include a 30% reduction of platelet
count, thrombosis, or skin allergy; if HIT is suspected or confirmed, heparin
should be discontinued and an alternative anticoagulant given)
Hyperkalaemia (due to inhibition of aldosterone secretion; patients with
diabetes mellitus, chronic renal failure, acidosis, raised plasma potassium
or those taking potassium-sparing drugs seem to be more susceptible)
Osteoporosis (risk lower with LMWH)
Alopecia
Injection site reactions
Lidocaine LAST UPDATED: 17TH
APRIL 2019
 Bookmark
Intravenous lidocaine hydrochloride can be used for the treatment of ventricular

tachycardia in haemodynamically stable patients, and ventricular fibrillation and
pulseless ventricular tachycardia in cardiac arrest refractory to defibrillation,
however it is a second-line choice (behind amiodarone).
Mechanism of Action
Lidocaine is a class Ib agent which blocks inactivated voltage-dependent Na+
channels, making it highly selective for damaged tissues. In normal cardiac
tissues, lidocaine has little effect because it dissociates rapidly from the Na+
channels which therefore recover during diastole. However, in ischaemic areas,
where anoxia causes depolarisation and arrhythmogenic activity, many Na+
channels are inactivated and therefore susceptible to lidocaine.
Contraindications
Intravenous lidocaine is contraindicated in:
All grades of atrioventricular block
Severe myocardial depression
Sinoatrial disorders
Cautions
Intravenous lidocaine should be used with caution in:
Acute porphyria (consider infusion with glucose for its anti-
porphyrinogenic effects)
Congestive cardiac failure (consider lower dose)
Post cardiac surgery (consider lower dose)
Side Effects
Common side effects of intravenous lidocaine include:
Bradycardia and hypotension (may lead to cardiac arrest)
Dizziness, drowsiness, paraesthesia, confusion (particularly if injection too
rapid)
Convulsions

Life Support Algorithms LAST UPDATED: 24TH
JUNE 2020
 Bookmark
Basic Life Support

For chest compressions in adult basic life support the heel of one hand
should be placed over the middle of the lower half of the patient's sternum
with the other hand on top.
The sternum should be depressed to a depth of 5 - 6 cm.
Chest compressions should be performed at a rate of 100 - 120 per minute.
Thirty compressions should be given before two breaths and that ratio
continued (30:2).
The person giving CPR should be changed every 2 minutes if possible to
avoid exhaustion and poor quality chest compressions.
Interruptions should be minimised (pauses should be < 5 seconds).
Advanced Life Support

In adult advanced life support, basic life support should continue whilst the
defibrillator pads are attached and the airway managed.
The pads should be positioned one to the right of the upper sternum below
the clavicle and the other in the left midaxillary line in the 5th intercostal
space.
Chest compressions should be paused briefly (< 5 secs) to assess the
rhythm and then continued as the defibrillator charges if a shockable
rhythm is identified or continued for a further two whole minutes if a non-
shockable rhythm is identified.
When delivering a shock, everybody should be clear of the patient (and any
GTN patches and oxygen sources removed).
Once the shock has been delivered, compressions should resume
immediately and continue for a further two minutes before checking the
rhythm again or feeling for a pulse.
Shockable Rhythm (ventricular fibrillation or pulseless
ventricular tachycardia)
IV adrenaline 1 mg (10 mL of 1:10,000 solution) should be given after 3
shocks and every 3 - 5 minutes/after alternate shocks thereafter.
IV amiodarone 300 mg should be given after 3 shocks. A further dose of IV
amiodarone 150 mg may be considered after a total of five defibrillation
attempts. Lidocaine (1 mg kg<sup>-1</sup>) may be used as an alternative
if amiodarone is not available but may not be given if amiodarone has been
given already.
Non-shockable Rhythm (asystole or pulseless electrical

activity)
IV adrenaline 1 mg should be given as soon as IV access is achieved and
then given every 3 - 5 minutes thereafter.

Loop Diuretics LAST UPDATED: 17TH
APRIL 2019
 Bookmark
Indications
Loop diuretics are powerful diuretics used in acute pulmonary oedema due to left
ventricular failure; intravenous administration produces relief of breathlessness
and reduces preload sooner than would be expected from the time of onset of
diuresis.
They are also used in oedema in patients with chronic heart failure; diuretic-
resistant oedema can be treated with a loop diuretic combined with a thiazide or
related diuretic.
If necessary, a loop diuretic can be added to antihypertensive treatment to
achieve better control of blood pressure in those with resistant hypertension, or
in patients with impaired renal function or heart failure.
Mechanism of Action
Loop diuretics inhibit the Na+/K+/2Cl- symporter on the luminal membrane in the
thick ascending limb of the loop of Henle, thus preventing reabsorption of NaCl
and water. These agents reduce reabsorption of Cl- and Na+ and increase Ca2+
excretion and loss of K+ and Mg2+.
Furosemide and bumetanide are similar in activity; both act within 1 hour of oral
administration and diuresis is complete within 6 hours so that, if necessary, they
can be given twice in one day without interfering with sleep. Following
intravenous administration furosemide has a peak effect within 30 minutes. The
diuresis associated with these drugs is dose related.
Contraindications
Loop diuretics are contraindicated in:
Hypovolaemia and dehydration
Severe hypokalaemia or severe hyponatraemia
Anuria, acute kidney injury or chronic kidney disease due to
nephrotoxic drugs
Comatose and pre-comatose states associated with liver cirrhosis
Cautions
Loop diuretics can exacerbate diabetes (but hyperglycaemia is less likely than
with thiazides) and gout.
If there is an enlarged prostate, urinary retention can occur, although this is less
likely if small doses and less potent diuretics are used initially.
Hypotension, hypovolaemia and electrolyte disturbance should be corrected
before initiation of treatment.
Hepatorenal syndrome; hypoproteinaemia may reduce diuretic effect and
increase risk of side-effects.
Lower initial doses of diuretics should be used in the elderly because they are
particularly susceptible to the side effects.
Side Effects
Adverse effects of loop diuretics include:
Mild gastrointestinal disturbances, pancreatitis and hepatic
encephalopathy
Hyperglycaemia
Acute urinary retention
Water and electrolyte imbalance
Hyponatraemia, hypocalcaemia, hypokalaemia, hypomagnesaemia,
hypochloraemia
Hypotension, hypovolaemia, dehydration, and venous thromboembolism
Metabolic alkalosis
Hyperuricaemia
Blood disorders (bone marrow suppression, thrombocytopenia, and
leucopenia)
Visual disturbance, tinnitus and deafness
Hypokalaemia
Hypokalaemia can occur with both thiazide and loop diuretics. The risk of
hypokalaemia depends on the duration of action as well as the potency and is
thus greater with thiazides than with an equipotent dose of a loop diuretic.
Hypokalaemia is dangerous in severe cardiovascular disease and in patients also
being treated with cardiac glycosides. Often the use of potassium-sparing
diuretics avoids the need to take potassium supplements. In hepatic failure,
hypokalaemia caused by diuretics can precipitate encephalopathy, particularly in
alcoholic cirrhosis.

Management of Acute LAST UPDATED: 13TH
FEBRUARY 2020
Coronary Syndrome  Bookmark
Clinical Features
In a patient with chest pain, acute coronary syndrome should be suspected if:
Pain in the chest or other areas (for example the arms, back, or jaw) lasts
longer than 15 minutes
Chest pain is associated with nausea and vomiting, sweating or
breathlessness, or a combination of these
Chest pain is associated with haemodynamic instability (for example the
person has a systolic blood pressure less than 90 mmHg)
Chest pain is of new-onset, or is the result of an abrupt deterioration of stable
angina; with pain occurring frequently with little or no exertion, and often
lasting longer than 15 minutes
The patient’s response to GTN should not be used to confirm or exclude a
diagnosis of ACS
Investigations
ECG
A normal ECG does not exclude ACS
Typical ECG findings:
Regional ST-segment elevation (2 mm ST-elevation in two
contiguous chest leads or 1 mm ST-elevation in two contiguous
limb leads)
New LBBB
Regional ST-segment depression (> 0.5 mm) or deep T wave
inversion (> 2 mm deep)
Pathological Q waves
Serum troponin (I or T)
A detectable troponin level indicates damage to the myocardium
If initial troponin is raised (on admission or at 6 hours after symptom
onset), repeat troponin measurement 10 – 12 hours after onset of
symptoms
Troponin is normally detectable within 12 hours following ACS and
becomes undetectable 1 – 2 weeks afterwards
Other conditions can also cause an increase in troponin e.g.
arrhythmias, pericarditis, pulmonary embolism, myocarditis
Consider a chest x-ray to exclude complications of ACS such as pulmonary
oedema, or to exclude alternative diagnoses such as pneumothorax or
pneumonia
A diagnosis of myocardial infarction is defined as the detection of the rise and/or fall
of cardiac biomarkers (preferably troponin) with at least 1 value above the 99th
percentile of the upper reference limit, together with evidence of myocardial
ischaemia with at least one of the following:
Symptoms of ischaemia
ECG changes indicative of ischaemia (new ST-T changes or new LBBB)
Development of pathological Q waves in the ECG
Imaging evidence of new loss of viable myocardium or new regional wall
motion abnormality
ECG Lead Changes
A septal infarct shows changes in the V1 - V2 leads, and typically involves the
left anterior descending artery.
An anterior infarct shows changes in the V2 - V5 leads, and typically involves
the left anterior descending artery.
An anteroseptal infarct shows changes in the V1 - V4 leads and typically
involves the left anterior descending artery.
An anterolateral infarct shows changes in leads I, aVL, V3 - V6 (and reciprocal
changes in leads II, III, aVF) and typically involves the left anterior descending
or the left circumflex artery.
An inferior infarct shows changes in leads II, III, aVF (and reciprocal changes in
leads I, aVL) and typically involves the right coronary artery.
A posterior infarct shows reciprocal changes in leads V1 - V3 and requires
placement of posterior leads (V7 - V9) to identify ST-elevation - it typically
involves the right coronary artery or the left circumflex artery.
Location of MI ECG Leads Coronary Vessel
Septal V1 - V2 LAD
Anterior V2 - V5 LAD
Anteroseptal V1 - V4 LAD
Anterolateral V3 - V6, I, aVL (R: II, III, aVF) LAD or left circumflex
Inferior II, III, aVF (R: I, aVL) RCA
Posterior R: V1 - V3 (P: V7 - V9) RCA or left circumflex
Management
If ACS is suspected:
Oxygen to maintain saturations of 94 – 98% (or 88 – 92% in patients at risk of
hypercapnic respiratory failure)
Glyceryl trinitrate (GTN) (1 – 2 doses of sublingual 400 microgram spray or 300
microgram tablet)
Analgesia e.g. IV diamorphine 2.5 – 5 mg, given slowly over 5 minutes
Antiemetic e.g. IV metoclopramide 10 mg
Aspirin 300 mg (unless there is clear evidence of allergy)
If pain is ongoing, consider intravenous GTN (10 – 200 micrograms/min) or
isosorbide mononitrate (2 – 10 mg/hr) IV infusion
For diagnosed NSTEMI/Unstable angina (in addition to aspirin 300 mg):
Fondaparinux (2.5 mg SC) for patients without a high bleeding risk, unless
coronary angiography is planned within 24 hours
Unfractionated heparin is an alternative to fondaparinux if angiography is
planned within 24 hours of admission (or for patients with significant renal
impairment)
For patients at low risk (mortality < 3%) offer 300 mg loading dose of
clopidogrel only to those who may undergo percutaneous coronary
intervention (PCI) within 24 h of admission to hospital
For patients at higher risk (mortality > 3%) offer 300 mg loading dose of
clopidogrel to all patients; consider adding a glycoprotein IIb/IIIa inhibitor
(intravenous eptifibatide or tirofiban) if angiography is scheduled within 96
hours of hospital admission
ADP receptor blocker alternatives to clopidogrel 300 mg include prasugrel 60
mg or ticagrelor 180 mg
Additional drug therapy may include beta-blockers (diltiazem is alternative),
ACE inhibitors and statins
For diagnosed STEMI (in addition to aspirin 300 mg):
Start antiplatelets/antithrombotics as per local protocol
For patients undergoing primary PCI:
All patients undergoing primary PCI should receive a platelet ADP
receptor blocker e.g. clopidogrel 600 mg, ticagrelor 180 mg or
prasugrel 60 mg
Anticoagulation with unfractionated or low molecular weight
heparin (LMWH) is given in the catheter lab, and in high risk cases
a glycoprotein IIb/IIIa inhibitor may also be given. Bivalirudin, a
direct thrombin inhibitor, may be chosen as an alternative to
heparin
For patients undergoing fibrinolysis:
Patients undergoing fibrinolysis should receive: clopidogrel 300
mg od and antithrombin therapy (unfractionated heparin, LMWH
or fondaparinux)
Offer coronary angiography, with follow-on primary PCI if indicated, as the
preferred coronary reperfusion strategy for people with acute STEMI if
presentation is within 12 hours of onset of symptoms AND primary PCI can be
delivered within 120 minutes of the time when fibrinolysis could have been
given
Consider coronary angiography, with follow-on primary PCI if indicated, for
people with acute STEMI presenting more than 12 hours after the onset of
symptoms if there is evidence of continuing myocardial ischaemia or of
cardiogenic shock
For those who undergo fibrinolysis (indicated in those presenting within 12
hours of onset of symptoms in whom primary PCI cannot be delivered in a
reasonable timeframe), repeat an ECG 60 – 90 minutes after administration.
For those with residual ST-segment elevation, offer immediate coronary
angiography, with follow-on rescue PCI, if indicated
Treatment of patients with atrial fibrillation aims to reduce symptoms and prevent
complications, especially stroke. Atrial fibrillation may be managed by either
controlling the ventricular rate (rate control) or by attempting to restore and
maintain sinus rhythm (rhythm control).
New-Onset Atrial Fibrillation

All patients with adverse features suggesting life-threatening haemodynamic
instability (shock, syncope, heart failure, myocardial ischaemia) caused by new onset
atrial fibrillation should undergo emergency electrical cardioversion with
synchronised DC shock without delaying to achieve anticoagulation.
In patients presenting acutely (< 48 hrs) with new onset AF but without adverse
features, immediate treatment options include rate control with drug therapy,
rhythm control using drugs to achieve chemical cardioversion, rhythm control by
synchronised cardioversion and treatment to prevent complications (e.g.
anticoagulation).
For rate-control, the usual drug of choice is a beta-blocker. Diltiazem may be
used in patients in whom beta-blockade is contraindicated or not tolerated.
Digoxin may be used in patients with heart failure. Amiodarone may be used to
assist with rate control but is most useful in maintaining rhythm control.
For rhythm-control, chemical cardioversion may be appropriate. Class 1c
antiarrhythmic drugs such as flecainide or propafenone may be used but are
contraindicated in the presence of heart failure, left ventricular impairment,
ischaemic heart disease or prolonged QT-interval. Amiodarone (300 mg
intravenously over 20 - 60 mins followed by 900 mg over 24 h) may be used to
attempt chemical cardioversion but is less often effective and takes longer to
act.
Electrical cardioversion remains an option in this setting and will restore sinus
rhythm in more patients than chemical cardioversion.
The longer a person remains in AF, the greater is the likelihood of atrial thrombus
developing. In general, people who have been in AF for > 48 h should not be treated
by cardioversion (electrical or chemical) until they have been fully anticoagulated for
at least 3 weeks, or unless transoesophageal echocardiography has detected no
evidence of atrial thrombus.
Long-Term Management
In general, rate control is the preferred first line drug treatment strategy for atrial
fibrillation in most patients except in patients with:
new onset atrial fibrillation
heart failure secondary to atrial fibrillation
atrial flutter suitable for an ablation strategy
atrial fibrillation with a reversible cause
or if rhythm control is more suitable based on clinical judgement.
Rate control may be achieved with a beta-blocker or a rate limiting non-
dihydropyridine calcium channel blocker e.g. verapamil or diltiazem.
Digoxin is usually only effective for controlling the ventricular rate at rest, and should
therefore only be used as monotherapy in predominantly sedentary patients with
non-paroxysmal atrial fibrillation or in combination therapy in resistant
cases. Digoxin is also used when atrial fibrillation is accompanied by congestive
heart failure.
If symptoms are not controlled with a combination of two drugs, a rhythm-control
strategy should be considered.
All patients with AF should be assessed and managed for risk of stroke and
thromboembolism, and risk of bleeding if anticoagulation is being considered.

Management of LAST UPDATED: 4TH
AUGUST 2021
Bradyarrhythmias  Bookmark
The approach to the management of bradyarrhythmias should follow the

Resuscitation Council guidelines.
If there are no adverse features (shock, syncope, myocardial ischaemia or heart
failure) and no risk of asystole (recent asystole, Mobitz II AV block, complete heart
block with broad QRS, ventricular pause > 3 seconds), immediate treatment can be
delayed and the patient assessed to try and identify the cause of the bradycardia.
If there are adverse features or a risk of asystole, atropine 500 mcg IV bolus should
be given. If there is an unsatisfactory response, this can be repeated every 3 - 5
mins up to a maximum dose of 3 mg. Atropine should be used cautiously in the
presence of acute myocardial ischaemia or myocardial infarction as the resulting
increase in heart rate may worsen ischaemia or increase the size of the infarct.
If bradycardia with adverse features persists despite atropine, consider cardiac
pacing. If pacing cannot be achieved promptly, consider the use of second line
drugs, seek expert help to select the most appropriate choice e.g. glucagon,
aminophylline, isoprenaline, adrenaline, dopamine, glycopyrrolate.
For a patient with bradycardia and adverse features, if there is no response to
atropine, or if atropine is contraindicated, transcutaneous pacing should be initiated
immediately. In the presence of life-threatening, extreme bradycardia, percussion
pacing should be used as an interim measure until transcutaneous pacing is
achieved.
Expert help should be sought and ultimately transvenous pacing arranged.

APRIL 2019
Pheochromocytoma  Bookmark
Long term management of pheochromocytoma involves surgery. However surgery

cannot take place until there is adequate blockade of both alpha- and beta-
adrenoceptors. Alpha-blockers are used in the short-term management of
hypertensive episodes in pheochromocytoma. Once alpha blockade is established,
tachycardia can be controlled by the cautious addition of a beta-blocker; a
cardioselective beta-blocker is preferred.
Phenoxybenzamine hydrochloride, a powerful alpha-blocker, is effective in the
management of phaeochromocytoma but it has many side-effects. Phentolamine
mesilate is a short-acting alpha-blocker used mainly during surgery of
phaeochromocytoma; its use for the diagnosis of phaeochromocytoma has been
superseded by measurement of catecholamines in blood and urine.

Management of Severe LAST UPDATED: 17TH
APRIL 2019
Hypertension  Bookmark
Hypertensive Urgency
Severe hypertension (blood pressure ≥ 180/110 mmHg) without acute target organ
damage is defined as hypertensive urgency.
Blood pressure should be reduced gradually over 24 – 48 hours with oral
antihypertensive therapy, such as labetalol hydrochloride, or the calcium channel
blockers amlodipine or felodipine.
Hypertensive Emergency
A hypertensive emergency is defined as severe hypertension with acute damage to
the target organs (e.g. signs of papilloedema or retinal haemorrhage, or the presence
of clinical conditions such as acute coronary syndromes, acute aortic dissection,
acute pulmonary oedema, hypertensive encephalopathy, acute cerebral infarction,
intracerebral or subarachnoid haemorrhage, eclampsia, or rapidly progressing renal
failure).
Prompt treatment with intravenous antihypertensive therapy is generally required;
over the first few minutes or within 2 hours, blood pressure should be reduced by 20
– 25 %. When intravenous therapy is indicated, treatment options include sodium
nitroprusside, nicardipine, labetalol, glyceryl trinitrate, phentolamine, hydralazine, or
esmolol; choice of drug is dependent on concomitant conditions and clinical status
of the patient.
If blood pressure is reduced too quickly in the management of hypertensive crises,
there is a risk of reduced organ perfusion leading to cerebral infarction, blindness,
deterioration in renal function, and myocardial ischaemia.

Management of Shock LAST UPDATED: 17TH
APRIL 2019
 Bookmark
Shock is a medical emergency associated with a high mortality. The underlying

causes of shock such as haemorrhage, sepsis, or myocardial insufficiency should be
corrected. The profound hypotension of shock must be treated promptly to prevent
tissue hypoxia and organ failure. Volume replacement is essential to correct the
hypovolaemia associated with haemorrhage and sepsis but may be detrimental in
cardiogenic shock.
Inotropic Sympathomimetics
Depending on haemodynamic status, cardiac output may be improved by the use of
sympathomimetic inotropes such as adrenaline/epinephrine, dobutamine or
dopamine.
In septic shock, when fluid replacement and inotropic support fail to maintain blood
pressure, the vasoconstrictor noradrenaline/norepinephrine may be considered. In
cardiogenic shock peripheral resistance is frequently high and to raise it further may
worsen myocardial performance and exacerbate tissue ischaemia.
Dobutamine directly stimulates the beta1-adrenergic receptors in the heart
and increases contractility and cardiac output with little effect on the rate. In
addition action on beta2-receptors causes vasodilation.
Dopamine is a neurotransmitter and a metabolic precursor of the
catecholamines. It acts on beta1-receptors in cardiac muscle increasing
cardiac contractility, and increases renal perfusion by stimulating dopamine
receptors in the renal vasculature. This is of benefit in cardiogenic shock
where deterioration of renal function is common.
Epinephrine increases blood pressure by stimulating the rate and force of the
heartbeat (beta1-effects). Stimulation of vascular alpha-receptors causes
vasoconstriction (viscera, skin) but beta-2 receptor stimulation causes
vasodilation (skeletal muscle) and the total peripheral resistance may actually
decrease.
Norepinephrine has little or no effect on the vascular beta2-receptors, and so
the alpha-mediated vasoconstriction is unopposed. The resulting rise in blood
pressure reflexively slows the heart.
The use of sympathomimetic inotropes and vasoconstrictors should preferably be
confined to the intensive care setting and undertaken with invasive haemodynamic
monitoring.
Vasoconstrictor Sympathomimetics
Vasoconstrictor sympathomimetics, such as ephedrine and metaraminol, raise blood
pressure transiently by acting on alpha-adrenergic receptors to constrict peripheral
vessels. They are sometimes used as an emergency method of elevating blood
pressure where other measures have failed. Their use is limited as although they
raise the blood pressure they also reduce organ perfusion.

AUGUST 2021
Tachyarrhythmias  Bookmark
The approach to the management of tachycardias should follow the Resuscitation

Council guidelines.
If the patient has adverse features:

Adverse features:
Shock (hypotension, pallor, sweating, cold extremities, confusion, impaired
consciousness)
Syncope (transient loss of consciousness)
Heart failure (pulmonary oedema, raised JVP, peripheral oedema,
hepatomegaly)
Myocardial ischaemia (ischaemic chest pain, ischaemic changes on ECG)
If any adverse features are present, emergency cardioversion with a synchronised
DC shock is indicated. If cardioversion fails to terminate the arrhythmia and adverse
features persist, amiodarone 300 mg IV over 10 – 20 mins should be given and
further cardioversion attempted. The loading dose of amiodarone can be followed by
an infusion of 900 mg over 24 h, given via a large vein.
If the patient has no adverse features:

If the patient is stable, the QRS duration should be considered.
If the QRS duration is 0.12 seconds or greater, it is a broad-complex
tachycardia.
If the QRS complex is less than 0.12 seconds, it is a narrow-complex
tachycardia.
Broad-complex tachycardia
Broad-complex tachycardias are mostly ventricular in origin but may be a
supraventricular rhythm with aberrant conduction.
A regular broad-complex tachycardia is likely to be ventricular tachycardia or a
regular supraventricular rhythm with bundle branch block.
A ventricular tachycardia (or broad-complex tachycardia of uncertain
origin) should be treated with amiodarone 300 mg IV over 10 - 60 min,
followed by an infusion of 900 mg over the next 24 hours.
If previously confirmed as SVT with bundle branch block, the patient
should be treated as for narrow-complex tachycardia.
A stable patient with an irregular broad-complex tachycardia is most likely to
be in AF with bundle branch block, although AF with ventricular pre-excitation
or polymorphic VT (torsades de pointes) is a possibility.
Expert help should be sought for the assessment and treatment of
irregular broad-complex tachycardia.
Torsade de pointes VT should be treated by stopping all drugs known to
prolong the QT interval, correcting electrolyte abnormalities, and giving
magnesium sulfate 2 g IV over 10 minutes. Expert help should be sought
as other treatment options including overdrive pacing may be required
to prevent relapse once the arrhythmia has been corrected.
Narrow-complex tachycardia
The narrow-complex tachycardias are supraventricular in origin.
A regular narrow-complex tachycardia may represent paroxysmal SVT or atrial
flutter with 2:1 conduction, it may be difficult to differentiate between the two.
The first step in treatment of regular narrow-complex tachycardias is to
attempt vagal manoeuvres (carotid sinus massage or Valsalva
manoeuvre).
If the tachyarrhythmia persists, adenosine 6 mg IV should be given as a
rapid bolus using a large cannula and a large vein. The patient should be
warned that they will feel unwell and may experience chest discomfort
for a few seconds following the injection. An ECG (preferably multi-lead)
should be recorded during the injection.
If the ventricular rate slows transiently and then speeds up again, this
may indicate atrial activity such as atrial flutter or other atrial
tachycardia, and this should be treated accordingly.
If there is no response (i.e. no transient slowing or termination of the
tachyarrhythmia) to adenosine 6 mg IV, a 12 mg IV bolus should be given
and if there is no response, one further 18 mg IV bolus given (max 36
mg). Lack of response to adenosine will occur if the bolus is given too
slowly or into a peripheral vein.
If adenosine is contraindicated, or fails to terminate a regular narrow-
complex tachycardia, the administration of verapamil 2.5 - 5 mg IV over
2 mins should be considered.
Irregular narrow-complex tachycardia is most likely to be AF with fast
ventricular response or, less commonly, atrial flutter with variable AV
conduction.
Immediate treatment options include rate control with drug therapy,
rhythm control using drugs to achieve chemical cardioversion, rhythm
control by synchronised cardioversion and treatment to prevent
complications (e.g. anticoagulation). Expert help should be sought in
determining the most appropriate treatment for the individual patient.

Mannitol LAST UPDATED: 17TH
APRIL 2019
 Bookmark
Mannitol is an osmotic diuretic that can be used to treat cerebral oedema and
raised intraocular pressure.
Mechanism of Action
Mannitol is an easily filtered, poorly reabsorbed solute that alters the diffusion of
water relative to sodium by 'binding' water. As a result, net reabsorption of Na+ is
reduced.
Contraindications
Mannitol is contraindicated in:
Anuria
Intracranial bleeding (except during craniotomy)
Severe cardiac failure
Severe dehydration
Severe pulmonary oedema
Side Effects
Common side effects include:
Fluid and electrolyte imbalance
Hypotension
Thrombophlebitis

Nitrates LAST UPDATED: 17TH
APRIL 2019
 Bookmark
Nitrates are useful in the management of angina. Although they are potent
coronary vasodilators, the main benefit derives from a reduction in venous return
which in turn reduces left ventricular effort, decreasing oxygen demands and
relieving anginal pain.
Vasodilators can also act in heart failure by arteriolar dilatation which reduces
both peripheral vascular resistance and left ventricular pressure during systole
resulting in improved cardiac output. They can also cause venous dilatation which
results in dilatation of capacitance vessels, increase of venous pooling, and
diminution of venous return to the heart (decreasing left ventricular end-diastolic
pressure).
Mechanism of Action
Initial metabolism of these drugs releases nitrite ions, which undergoes
intracellular conversion to nitric oxide (NO). Nitric oxide then activates guanylyl
cyclase, causing an increase in the intracellular concentration of cGMP in the
vascular smooth muscle cells. cGMP activates protein kinase G, an enzyme that
ultimately causes vascular smooth muscle relaxation.
Type Examples
Sublingual glyceryl trinitrate (GTN) is one of the most effective drugs for providing
rapid relief of angina, although its effects only last for 20 - 30 minutes. It may be
administered as sublingual tablets or by sublingual administration using aerosol
spray.
If sublingual glyceryl trinitrate is required more than twice a week, then combined
therapy is required, where beta-blockers or calcium-channel blockers are taken in
addition to nitrates which are reserved for acute attacks. If necessary, a long-
acting nitrate is added.
Long-acting nitrates are more stable and may be effective for several hours,
depending on the drug and the preparation (sublingual, oral, modified release).
Isosorbide dinitrate is widely used; duration of action of up to 12 hours is claimed
for modified-release preparations. The use of isosorbide mononitrate, which is the
main active metabolite of the dinitrate, avoids the variable absorption and
unpredictable first-pass metabolism of the dinitrate.
Glyceryl trinitrate or isosorbide dinitrate may be tried by intravenous injection
when the sublingual form is ineffective in patients with chest pain due to
myocardial infarction or severe ischaemia. Intravenous injections are also useful
in the treatment of congestive heart failure.
Side Effects
Side effects such as dizziness, flushing, tachycardia, throbbing headache and
postural hypotension may limit therapy, especially when angina is severe or when
patients are unusually sensitive to the effects of nitrates. Prolonged high dosage
may cause methaemoglobinaemia as a result of oxidation of haemoglobin.
Contraindications
Nitrates should not be used in people with:
Acute myocardial infarction (MI) with low filling pressure, acute circulatory
failure, (shock, vascular collapse), or very low blood pressure
Hypertrophic obstructive cardiomyopathy (HOCM), constrictive pericarditis,
cardiac tamponade, low cardiac filling pressures, or aortic/mitral valve
stenosis
Diseases associated with a raised intracranial pressure (for example
following a head trauma, including cerebral haemorrhage)
Severe anaemia
Closed angle glaucoma
Severe hypotension, or hypovolaemia

Sodium Nitroprusside LAST UPDATED: 17TH
APRIL 2019
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Sodium nitroprusside decomposes in the blood to release nitric oxide, an unstable

compound that causes vasodilation.
Indications
Sodium nitroprusside is indicated for
Hypertensive emergencies
Controlled hypotension in anaesthesia during surgery
Acute or chronic heart failure
Contraindications
It is contraindicated in
Compensatory hypertension
Leber’s optic atrophy
Severe vitamin B12 deficiency
Cautions
It is should be used with caution in
Elderly
Hyponatraemia
Hypothermia
Hypothyroidism
Impaired cerebral circulation
Ischaemic heart disease
Side Effects
Side effects associated with over rapid reduction in blood pressure include:
headache, dizziness, nausea, retching, abdominal pain, perspiration, palpitation,
anxiety, retrosternal discomfort; the infusion rate should be reduced if any of these
side effects occur.
Side effects caused by excessive plasma concentration of the cyanide metabolite
include tachycardia, sweating, hyperventilation, arrhythmias, marked metabolic
acidosis; the drug should be discontinued and the cyanide antidote given if these
effects occur.

Statins LAST UPDATED: 17TH
APRIL 2019
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Statins may be used for primary or secondary prevention of cardiovascular

disease and for treatment of primary or familial hypercholesterolaemia.
Statins are more effective than other lipid-regulating drugs at lowering LDL-
cholesterol concentration but they are less effective than the fibrates in reducing
triglyceride concentration. However, statins reduce cardiovascular disease events
and total mortality irrespective of the initial cholesterol concentration.
Mechanism of Action
Statins competitively inhibit 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA)
reductase, an enzyme involved in cholesterol synthesis. Inhibition of HMG CoA
reductase reduces low-density lipoprotein (LDL) cholesterol levels by slowing
down the production of cholesterol in the liver and increasing the liver's ability to
remove the LDL cholesterol already in the blood.
Indications
Statins should be offered to all patients, including the elderly, with cardiovascular
disease such as those with coronary heart disease (including history of angina or
acute myocardial infarction) or occlusive arterial disease (including peripheral
vascular disease, non-haemorrhagic stroke, or transient ischaemic attacks). The
use of statins should be considered in patients with a high risk of developing
cardiovascular disease (primary prevention) which can be assessed using risk
calculators.
Contraindications
Statins should be avoided in:
People with active liver disease
People with transaminase (alanine aminotransferase or aspartate
aminotransferase) levels that are three or more times the upper limit of
normal
Pregnant or breastfeeding women (discontinue 3 months before
attempting to conceive)
Cautions
Statins should be used with caution in people:
With a history of liver disease
Who consume high level of alcohol
With predisposing factors for rhabdomyolysis such as older age (> 70 years),
concomitant use with an interacting drug, renal impairment,
hypothyroidism, and personal or familial history of hereditary muscular
disorders
Side Effects
Adverse effects of statins include:
Headache
Epistaxis
Gastrointestinal disorders (such as constipation, flatulence, dyspepsia,
nausea, and diarrhoea)
Musculoskeletal and connective tissue disorders (such as myalgia,
arthralgia, pain in the extremity, muscle spasms, joint swelling, and back
pain)
Hyperglycaemia and diabetes
Myopathy and rhabdomyolysis
Interstitial lung disease
Hepatotoxicity
Muscle Effects
The risk of myopathy, myositis, and rhabdomyolysis associated with statin use is
rare. Although myalgia has been reported commonly in patients receiving statins,
muscle toxicity truly attributable to statin use is rare.
Muscle toxicity can occur with all statins, however the likelihood increases with
higher doses and in certain patients. Statins should be used with caution in
patients at increased risk of muscle toxicity, including those with a personal or
family history of muscular disorders, previous history of muscular toxicity, a high
alcohol intake, renal impairment or hypothyroidism.
There is an increased incidence of myopathy if a statin is given with a fibrate, with
lipid-lowering doses of nicotinic acid, with fusidic acid, or with drugs that
increase the plasma-statin concentration, such as macrolide antibiotics
(erythromycin and clarithromycin), imidazole and triazole antifungals, and
ciclosporin; close monitoring of liver function and, if muscular symptoms occur, of
creatine kinase is necessary.

Thiazide Diuretics LAST UPDATED: 17TH
APRIL 2019
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Thiazide diuretics are moderately potent diuretics, and are used to relieve
oedema in chronic heart failure, and in the management of hypertension. They
act within 1 to 2 hours of oral administration and most have a duration of action of
12 to 24 hours.
Mechanism of Action
Thiazides act mainly on the early segments of distal tubule where they inhibit
NaCl reabsorption by binding to the the Na+/Cl- cotransporter. Excretion of Cl-,
Na+ and accompanying water is increased. The increased Na+ load in the distal
tubule stimulates Na+ exchange with K+ and H+, increasing their excretion and
causing hypokalaemia and a metabolic alkalosis. Excretion of Ca2+ is reduced.
Indications
Bendroflumethiazide is used for oedema in mild or moderate heart failure.
Combination diuretic therapy (with loop and thiazide diuretics) may be effective in
patients with oedema resistant to treatment with one diuretic.
Thiazide diuretics are licensed for the treatment of hypertension but are no
longer considered the first line diuretic for this indication. In the management of
hypertension a low dose of a thiazide produces a maximal or near-maximal blood
pressure lowering effect, with very little biochemical disturbance. Higher doses
cause more marked changes in plasma potassium, sodium, uric acid, glucose, and
lipids, with little advantage in blood pressure control.
Contraindications
Thiazide diuretics are contraindicated in:
Addison’s disease
Hypercalcaemia
Hyponatraemia
Refractory hypokalaemia
Symptomatic hyperuricaemia
Severe hepatic impairment (may precipitate encephalopathy)
Cautions
Thiazide diuretics should be used with caution in:
Diabetes mellitus (may exacerbate)
Gout (may exacerbate)
Systemic lupus erythematosus (may exacerbate)
Hyperaldosteronism
Malnourishment
Nephrotic syndrome
Side Effects
Lower initial doses of diuretics should be used in the elderly because they are
particularly susceptible to the side effects. The dose should then be adjusted
according to renal function.
Common side effects of thiazide diuretics include:
Excessive diuresis
Postural hypotension, dehydration, renal impairment
Acid-base and electrolyte imbalance
Hypokalaemia, hyponatraemia, hypomagnesaemia, hypercalcaemia,
hypochloraemic alkalosis
Metabolic imbalance
Hyperuricaemia and gout
Impaired glucose tolerance and hyperglycaemia
Altered plasma-lipid concentrations
Mild gastrointestinal disturbances
Hypokalaemia
Hypokalaemia can occur with both thiazide and loop diuretics. The risk of
hypokalaemia depends on the duration of action as well as the potency and is
thus greater with thiazides than with an equipotent dose of a loop diuretic.
Hypokalaemia is dangerous in severe cardiovascular disease and in patients also
being treated with cardiac glycosides. Often the use of potassium-sparing
diuretics avoids the need to take potassium supplements.

Warfarin LAST UPDATED: 6TH
DECEMBER 2020
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The main use of anticoagulants is to prevent thrombus formation or extension of

an existing thrombus in the slower-moving venous side of the circulation, where
the thrombus consists of a fibrin web enmeshed with platelets and red cells.
Anticoagulants are of less use in preventing thrombus formation in arteries, for in
faster-flowing vessels thrombi are composed mainly of platelets with little fibrin.
Mechanism of Action
Warfarin is a vitamin K antagonist and will reduce the activity of vitamin-K
dependent clotting factors (factors VII, IX, X and II) and of protein C and S.
Both the PT and APTT are usually prolonged but the PT is grossly prolonged and
the APTT only mildly.
Indications
Warfarin is licensed for:
Prophylaxis of systemic embolism in people with rheumatic heart disease
and atrial fibrillation
Prophylaxis after insertion of prosthetic heart valves
Prophylaxis and treatment of venous thrombosis and pulmonary embolism
Transient attacks of cerebral ischaemia
Warfarin takes at least 48 to 72 hours for the anticoagulant effect to develop and
if an immediate effect is required, heparin must be given concomitantly and
continued for at least 5 days and until the INR is greater or equal to 2.0 for more
than 24 hours. The duration of treatment is dependent on the indication.
Contraindications
Haemorrhagic stroke
Clinically significant bleeding
Within 72 hours of major surgery with risk of severe bleeding
Within 48 hours postpartum
Pregnancy
Untreated bleeding disorders for example, thrombocytopenia, haemophilia,
liver failure and renal failure
Potential bleeding lesions for example; active peptic ulcer; oesophageal
varices; aneurysm; proliferative retinopathy; recent organ biopsy; recent
trauma or surgery to head, orbit, or spine; recent stroke; confirmed
intracranial or intraspinal bleed
Cautions
Warfarin should be used with caution in any patient at increased risk of
haemorrhage with risk factors including:
People aged over 65 years
Previous bleeding episode, history of gastrointestinal bleeding or anaemia
Recent ischaemic stroke, hypertension, heart disease, cerebrovascular
disease, renal disease, liver disease, active peptic ulcer
Recent or imminent surgery or trauma
Excessive alcohol intake, frequent or significant falls
Regular use of NSAIDs or other drugs that increase risk of bleeding
Side Effects
The most common adverse effect of warfarin is bleeding
Other common adverse effects of warfarin include nausea, vomiting,
diarrhoea, jaundice, hepatic dysfunction, pancreatitis, pyrexia, alopecia,
purpura, and rash
Skin necrosis is a rare but serious adverse effect of warfarin; treatment
with warfarin should be stopped if warfarin related skin necrosis is
suspected
Calciphylaxis is a rare, but a very serious condition that causes vascular
calcification and cutaneous necrosis
Monitoring
The prothrombin time, reported as the INR is used to monitor warfarin therapy;
the target INR is dependent on the indication.
Warfarin may need to be omitted for a couple of doses if the INR rises above the
target range or even reversed if the INR is > 8.0 or there are signs of bleeding.
Phytomenadione (vitamin K) can be given as a specific antidote to warfarin or in
cases of major bleeding, dried prothrombin complex (factors II, VII, IX, and X); if
dried prothrombin complex is unavailable, fresh frozen plasma can be given but is
less effective.
Scenario Management
INR 5.0 - Withhold 1 - 2 doses of warfarin and reduce subsequent
8.0, no maintenance dose
bleeding
INR 5.0 - Stop warfarin, give phytomenadione intravenously, restart
8.0, minor warfarin when INR < 5.0
bleeding
INR > 8.0, Stop warfarin, give phytomenadione orally, restart warfarin
no bleeding when INR < 5.0
INR > 8.0, Stop warfarin, give phytomenadione intravenously, repeat
minor dose if INR still too high after 24 h, restart warfarin when
bleeding INR < 5.0
Major Stop warfarin, give phytomenadione intravenously, give
bleeding dried prothrombin complex
Drug Interactions
Increased anticoagulant Decreased anticoagulant effect

effect
Acute alcohol Tricyclic antidepressants (can increase or
consumption decrease)
Amiodarone St John's wort
Increased anticoagulant Decreased anticoagulant effect
effect
Antibiotics(co-trimoxazole, Vitamin K-containing vitamin complexes,
metronidazole, quinolones, some enteral feeds, mineral supplements,
macrolides) and green vegetables
Antidepressants (SSRIs, Rifampicin
SNRIs, TCAs)
Azoles Carbamazepine
Cranberry juice Phenobarbital
Corticosteroids Primidone
Fibrates Azathioprine
NSAIDs Phenytoin
Thyroxine Griseofulvin

Antiemetics LAST UPDATED: 3RD
APRIL 2020
PHARMACOLOGY / CENTRAL NERVOUS SYSTEM
 Bookmark
Antiemetics should only be prescribed when the cause of the vomiting is known,
as otherwise they may delay or mask an underlying diagnosis which should be
treated first, particularly in children.
Antihistamines (Histamine-H1 receptor antagonists)

Antihistamines e.g. cyclizine, are effective against nausea and vomiting caused
by many different conditions, including motion sickness and vertigo. These
agents act by inhibiting histamine pathways, and cholinergic pathways involved
in transmission from the vestibular apparatus to the vomiting centre.
There is no evidence that any one antihistamine is superior to another but their
duration of action and incidence of adverse effects differ. Adverse effects include
drowsiness and antimuscarinic effects such as blurred vision, dry mouth, urinary
retention, constipation and confusion.
Phenothiazines
The phenothiazines e.g. prochlorperazine are dopamine-D2 receptor antagonists
and act centrally by blocking the chemoreceptor trigger zone. They are of
particular use in the treatment of nausea and vomiting caused by neoplastic
disease, radiation sickness or by other drugs such as opioids, general
anaesthetics, and cytotoxics.
Adverse actions include anticholinergic effects such as drowsiness, dry mouth,
and blurred vision, extrapyramidal effects, and postural hypotension.
Phenothiazines can all induce acute dystonic reactions such as facial and skeletal
muscle spasms and oculogyric crises; children (especially girls, young women,
and those under 10 kg) are particularly susceptible.
Some phenothiazines are available as rectal suppositories, which can be useful in
patients with persistent vomiting or with severe nausea; prochlorperazine can
also be administered as a buccal tablet which is placed between the upper lip and
the gum.
Metoclopramide
Metoclopramide is an effective antiemetic and its activity closely resembles that
of the phenothiazines (dopamine antagonist); it also acts directly on the
gastrointestinal tract as a prokinetic and therefore may be superior in treating
nausea associated with gastroduodenal, hepatic and biliary disease. It is
contraindicated in gastrointestinal obstruction/perforation.
Metoclopramide is commonly associated with extrapyramidal effects and
hyperprolactinemia and thus its use must be limited to short-term use.
Metoclopramide can induce acute dystonic reactions involving facial and skeletal
muscle spasms and oculogyric crises. These dystonic effects are more common
in the young (especially girls and young women) and the very old; they usually
occur shortly after starting treatment with metoclopramide and subside within 24
hours of stopping it. Injection of an antiparkinsonian drug such as procyclidine
will abort dystonic attacks.
Domperidone acts at the chemoreceptor trigger zone. It has the advantage over
metoclopramide hydrochloride and the phenothiazines of being less likely to
cause central effects such as sedation and dystonic reactions because it does
not readily cross the blood-brain barrier.
Ondansetron
Ondansetron is a serotonin-5HT3 receptor antagonist which acts both at the
chemoreceptor trigger zone and peripherally. Because it has fewer unwanted
actions, it is widely used to prevent or reduce nausea or vomiting associated with
cancer chemotherapy and general anaesthesia. The most common adverse
effects of these drugs are headache and mild constipation.

Antipsychotics LAST UPDATED: 4TH
APRIL 2019
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Mechanism of Action
The first generation antipsychotic drugs act predominantly by blocking dopamine
D2 receptors in the brain. First generation antipsychotic drugs are not selective
for any of the four dopamine pathways in the brain and so can cause a range of
side effects, particularly extrapyramidal symptoms and elevated prolactin.
The second generation antipsychotic drugs (sometimes referred to as atypical
antipsychotic drugs) act on a range of receptors in comparison to the first
generation antipsychotic drugs and tend to cause less extrapyramidal side
effects.
There is little meaningful difference in efficacy between each of the antipsychotic
drugs (other than clozapine), and response and tolerability to each antipsychotic
drug varies. There is no first-line antipsychotic drug which is suitable for all
patients.
Side Effects
Side effects of antipsychotic drugs are common and include:
Extrapyramidal effects (due to blockage of dopamine receptors in the basal
ganglia)
Sedation (due to blockage of H1-receptors)
Hyperprolactinaemia (because dopamine usually inhibits prolactin release)
Sexual dysfunction
Reduced bone mineral density
Galactorrhoea
Breast enlargement/gynecomastia in men
QT-interval prolongation
Tachycardia
Arrhythmias
Hypertension
Postural hypotension
Increased risk of stroke and VTE
Anticholinergic effects
Dry mouth
Blurred vision
Urinary retention
Constipation
Cutaneous flushing
Hyperglycaemia, dyslipidaemia and weight gain
Temperature dysregulation
Neuroleptic malignant syndrome
Hyperthermia
Fluctuating level of consciousness
Muscle rigidity
Autonomic dysfunction (pallor, tachycardia, labile blood pressure,
sweating, and urinary incontinence)
Blood dyscrasias
Extrapyramidal Effects
Antipsychotic drugs also block dopamine receptors in the basal ganglia and this
frequently results in distressing and disabling extrapyramidal side-effects.
Extrapyramidal side effects include:
Parkinsonian symptoms (tremor, bradykinesia and rigidity)
Dystonia (acute dystonic reactions may require treatment with
antimuscarinic drugs)
Dyskinesia
Akathisia (motor restlessness)
Tardive dyskinesia (rhythmic, involuntary movements of tongue, face, and
jaw)
Tardive dyskinesia is the most serious manifestation of extrapyramidal
symptoms; it is of particular concern because it may be irreversible on
withdrawing therapy and treatment is usually ineffective. Tardive dyskinesia
occurs fairly frequently, especially in the elderly, and treatment must be carefully
and regularly reviewed.

Aspirin (Analgesic) LAST UPDATED: 25TH
JULY 2020
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Mechanism of Action
Aspirin is a non-steroidal anti-inflammatory drug (NSAID). Aspirin irreversibly
inhibits cyclooxygenase (COX) enzymes and the resulting inhibition of
prostaglandin synthesis results in analgesic, antipyretic and to a lesser extent
anti-inflammatory actions. Low-dose aspirin also has an important antiplatelet
activity through inhibition of thromboxane-A2 synthesis. The inhibition of
prostaglandin synthesis in the gastric mucosa can result in gastrointestinal
damage.
Indications
Aspirin is well absorbed orally and has a duration of action of about 4 hours.
Aspirin is indicated for headache, transient musculoskeletal pain, dysmenorrhoea,
and pyrexia. Aspirin is a first-line option for the management of migraine. In most
circumstances where analgesia is required, other nonsteroidal anti-inflammatory
drugs (such as ibuprofen) are preferred to aspirin, because they are better
tolerated.
Contraindications
Aspirin (at analgesic doses) is contraindicated in:
People with a history of true hypersensitivity to aspirin or salicylates
(symptoms of hypersensitivity to aspirin or salicylates include
bronchospasm, urticaria, angioedema, and vasomotor rhinitis)
People with previous or active peptic ulceration
People with haemophilia or another bleeding disorder
Children younger than 16 years of age (risk of Reye's syndrome)
People with gout, or a history of gout (aspirin increases the level of uric
acid)
People with severe cardiac failure (analgesic dose)
People with severe hepatic impairment (increased risk of gastrointestinal
bleeding)
People with severe renal impairment (increased risk of deterioration of
renal function and GI bleeding)
N.B. Owing to an association with Reye’s syndrome, aspirin-containing
preparations should not be given to children under 16 years, unless specifically
indicated, e.g. for Kawasaki disease.
Cautions
Aspirin (at analgesic doses) should be used with caution in:
People who may be at high risk of increased bleeding — for example those
receiving treatment with warfarin, NSAIDs, SSRIs, corticosteroids, or other
drugs known to increase bleeding
People with asthma or allergic disease (may precipitate bronchospasm)
People with uncontrolled blood pressure
People with thyrotoxicosis
People with G6PD deficiency
People with dehydration or renal impairment
Elderly people (at higher risk of complications)
Side Effects
Increased risk of bleeding
Gastrointestinal adverse effects including irritation, bleeding, ulceration
and dyspepsia
Bronchospasm and asthma attacks in patients with asthma
Skin reactions in hypersensitive patients
Overdose
The main features of salicylate poisoning are hyperventilation, tinnitus, deafness,
vasodilatation, and sweating. Coma is uncommon but indicates very severe
poisoning.
Carbamazepine LAST UPDATED: 4TH
APRIL 2019
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Indications
Carbamazepine is a drug of choice for simple and complex focal seizures and is a
first-line treatment option for generalised tonic-clonic seizures. It is also used in
trigeminal neuralgia and diabetic neuropathy. Carbamazepine may exacerbate tonic,
atonic, myoclonic and absence seizures and is therefore not recommended if these
seizures are present. It is essential to initiate carbamazepine therapy at a low dose
and build this up slowly.
Mechanism of Action
Carbamazepine, lamotrigine, valproate and phenytoin act by producing a use-
dependent block of neuronal Na+ channels. Their anticonvulsant action is a result of
their ability to prevent high-frequency repetitive activity. The drugs bind
preferentially to inactivated (closed) Na+ channels, stabilising them in the
inactivated state and preventing them from returning to the resting (closed) state,
which they must re-enter before they can again open.
Contraindications
Carbamazepine is contraindicated in:
People with known hypersensitivity to carbamazepine or structurally related
drugs
People with atrioventricular block (may suppress AV conduction and
ventricular automaticity)
People with a history of bone marrow depression (risk of agranulocytosis and
aplastic anaemia)
People with a history of acute porphyrias
People taking a monoamine oxidase inhibitor (risk of serotonin syndrome)
Side Effects
Common adverse effects include nausea and vomiting, sedation, dizziness,
headache, blurred vision and ataxia. These adverse effects are dose related and are
most common at the start of treatment.
Other adverse effects include:
Allergic skin reactions (and rarely, more serious dermatological conditions)
Hyponatraemia (avoid concomitant use with diuretics)
Leucopenia, thrombocytopenia and other blood disorders
Hepatic impairment
Monitoring
Serum carbamazepine levels should not be routinely monitored unless toxicity is
suspected. A full blood count, liver function tests, and urea and electrolyte
measurements should be done before starting treatment and every 6 months during
treatment.
Interactions
The plasma concentration of carbamazepine may be increased by the concomitant
use of:
Macrolide antibiotics (clarithromycin and erythromycin)
Azole antifungals
Cimetidine
Selective serotonin reuptake inhibitors (SSRIs)
Carbamazepine is an enzyme-inducing drug which may accelerate the metabolism
of some drugs resulting in their reduced therapeutic effect, such as:
Corticosteroids
Doxycycline
Oral contraceptives
Thyroid hormones
Tricyclic antidepressants
Simvastatin
Warfarin
Lithium LAST UPDATED: 4TH
APRIL 2019
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Indications
Lithium salts are used in the prophylaxis and treatment of mania, hypomania and
depression in bipolar disorder and in the prophylaxis and treatment of recurrent
unipolar depression.
Contraindications
Lithium is contraindicated in:
Addison’s disease
Cardiac disease associated with rhythm disorders
Family or personal history of Brugada syndrome
Low sodium (including people that are dehydrated and those on low sodium
diets)
Untreated hypothyroidism
Clinically significant renal impairment
Cautions
Lithium should be used with caution in:
Cardiac disease
Concurrent ECT (may lower seizure threshold)
Diuretic treatment (risk of toxicity)
Elderly (reduce dose)
Epilepsy (may lower seizure threshold)
Myasthenia gravis
Psoriasis (risk of exacerbation)
QT interval prolongation
Interactions
Caution with concomitant use of drugs and any therapy that may lower seizure
threshold.
Caution with concomitant use of drugs that prolong the QT interval.
Lithium toxicity is made worse by sodium depletion, therefore concurrent use of
diuretics (particularly thiazides) is hazardous and should be avoided. Thiazide
diuretics also cause a rapid increase in serum lithium levels by reducing clearance
of lithium.
Concomitant NSAIDs may increase serum lithium levels.
Side Effects
Initial adverse effects of lithium therapy include nausea, diarrhoea, vertigo,
muscle weakness, and a dazed feeling. These effects often resolve with
continued therapy. Fine hand tremors, polyuria, and polydipsia may persist.
Adverse effects tend to be directly related to plasma levels. Longer-term adverse
effects include thyroid dysfunction, hyperparathyroidism, nephrotoxicity, renal
tumours and rhabdomyolysis.
Lithium Monitoring
Lithium has a narrow therapeutic index. Samples should be taken 12 hours after
the dose to achieve a serum-lithium concentration of 0.4 – 1 mmol/litre (lower
end of the range for maintenance therapy and elderly patients).
Routine serum-lithium monitoring should be performed weekly after initiation
and after each dose change until concentrations are stable, then every 3 months
thereafter. Additional serum-lithium measurements should be made if a patient
develops significant intercurrent disease or if there is a significant change in a
patient’s sodium or fluid intake.
Renal function should be monitored at baseline and every 6 months thereafter
(more often if there is evidence of deterioration or if the patient has other risk
factors, such as starting ACE inhibitors, NSAIDs, or diuretics).
A lithium treatment pack should be given to patients on initiation of treatment
with lithium. The pack consists of a patient information booklet, lithium alert card,
and a record book for tracking serum-lithium concentration.
Lithium Toxicity
Most cases of lithium intoxication occur as a complication of long term therapy
and are caused by reduced excretion of the drug because of a variety of factors
including dehydration, deterioration of renal function, infections, and co-
administration of diuretics or NSAIDs (or other drugs that interact).
Lithium toxicity occurs at serum lithium concentrations of approximately 1.5
mmol/L and above, but may occur despite an apparently normal plasma level.
Features of toxicity include:
Increasing gastrointestinal disturbances (vomiting, diarrhoea, anorexia)
Visual disturbances
Polyuria and incontinence
Muscle weakness and tremor
Tinnitus
CNS disturbances (dizziness, confusion and drowsiness increasing to lack
of coordination, restlessness, stupor)
Abnormal reflexes and myoclonus
Hypernatraemia
With severe overdose (serum-lithium concentration > 2 mmol/L) seizures, cardiac
arrhythmias (including sinoatrial block, bradycardia and first-degree heart block),
blood pressure changes, electrolyte imbalance, circulatory failure, renal failure,
coma and sudden death may occur.
There is no specific antidote to lithium toxicity. In secondary care the treatment is
supportive and lithium levels are normally rechecked every 6 – 12 hours. Osmotic
or forced alkaline diuresis may be required, however peritoneal or haemodialysis
may be used if levels are above 3 mmol/L.

Management of Status LAST UPDATED: 11TH
APRIL 2019
Epilepticus  Bookmark
Immediate emergency care and treatment should be given to children, young

people and adults who have prolonged (lasting 5 minutes or more) or repeated (3
or more in an hour) convulsive seizures.
Immediate Emergency Care

Immediate measures to manage status epilepticus include positioning the patient
to avoid injury, securing the airway, supporting respiration including the provision
of oxygen, maintaining blood pressure, obtaining intravenous access, and the
correction of any hypoglycaemia. Parenteral thiamine should be considered if
alcohol abuse is suspected.
First Line Treatment

Seizures lasting longer than 5 minutes should be treated urgently with
intravenous lorazepam first-line, repeated once after 10 minutes if seizures recur
or fail to respond. Patients should be monitored for respiratory depression and
hypotension. Administer a maximum of two doses of the first-line treatment
(including pre-hospital treatment).
Intravenous diazepam is effective but it carries a high risk of thrombophlebitis so
should only be used if if intravenous lorazepam is not immediately available.
Absorption of diazepam from intramuscular injection or from suppositories is too
slow for treatment of status epilepticus. When facilities for resuscitation are not
immediately available or if unable to secure immediate intravenous access,
diazepam can be administered as a rectal solution or midazolam oromucosal
solution can be given into the buccal cavity.
Drug Child 1 month - 11 years Child Adults
12
years
- 17
years
IV 100 micrograms/kg (max. per dose 4 4 mg 4 mg
lorazepam mg)
IV 300 - 400 micrograms/kg (max. per 10 10 mg
diazepam dose 10 mg) mg
Rectal 5 - 10 mg (5 mg in children < 1 years) 10 - 10 - 20
diazepam 20 mg (10
mg mg in
elderly)
Buccal 1 - 2 months: 300 10 10 mg
midazolam micrograms/kg (max. per dose mg
2.5 mg)
3 - 11 months: 2.5 mg
1 - 4 years: 5 mg
5 - 9 years: 7.5 mg
10 - 11 years: 10 mg
Second Line Treatment
If, after initial treatment with benzodiazepines, seizures recur or fail to respond 25
minutes after onset, phenytoin sodium, fosphenytoin sodium, or phenobarbital
sodium should be used.
Phenytoin sodium dosing:
Child 1 Child 12 - 17 Adults

month - 11 years
years
Child 1 Child 12 - 17 Adults
month - 11 years
years
Loading Loading dose Loading dose of 20 mg/kg (max. per
dose 20 20 mg/kg, dose 2 g), to be given at a rate not
mg/kg, then then (by exceeding 1 mg/kg/minute (max. 50 mg
(by slow intravenous per minute), then (by intravenous
intravenous infusion or by infusion or by slow intravenous injection
injection or slow or by mouth) maintenance 100 mg every
by intravenous 6 - 8 hours adjusted according to
intravenous injection) up plasma concentration monitoring.
infusion) 2.5 to 100 mg 3 -
- 5 mg/kg 4 times a day.
twice daily.
Alternatively, fosphenytoin sodium (a pro-drug of phenytoin), can be given more
rapidly and when given intravenously causes fewer injection-site reactions than
phenytoin sodium. Doses of fosphenytoin sodium should be expressed in terms
of phenytoin sodium.
Treating Refractory Convulsive Status Epilepticus

If these measures fail to control seizures 45 minutes after onset, anaesthesia
with thiopental sodium, midazolam, or propofol in adults, and midazolam or
thiopental sodium in children, should be instituted with full intensive care
support.

Opioids LAST UPDATED: 4TH
APRIL 2019
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Mechanism of Action
Opioid analgesics are usually used to relieve moderate to severe pain particularly
of visceral origin. Opioid analgesics mimic endogenous opioid peptides by causing
prolonged activation of opioid receptors that are widely distributed throughout
the central nervous system, primarily the mu(μ)-receptors which are the most
highly concentrated in brain areas involved in nociception.
Activation of these opioid receptors produces a range of central effects including
analgesia, respiratory depression (direct inhibition of respiratory centre in
brainstem), euphoria, sedation, postural hypotension (depression of the
vasomotor centre), miosis (IIIrd nerve nucleus stimulation), nausea/vomiting
(stimulation of chemoreceptor trigger zone) and constipation (decreased GI
motility).
Repeated use of opioid analgesics can result in tolerance and dependence,
although this is less relevant in the acute clinical context. Opioid dependant
patients may require much higher doses of opioids to control their pain.
Morphine
Morphine is the most valuable opioid analgesic for severe pain although it
frequently causes nausea and vomiting. In addition to relief of pain, morphine also
confers a state of euphoria and mental detachment. The efficacy of other opioids
are often measured against morphine.
Tramadol
Tramadol may be prescribed for the treatment of moderate to severe pain, and
may have special use for neuropathic pain. Tramadol hydrochloride produces
analgesia by two mechanisms: an opioid effect and an enhancement of
serotonergic and adrenergic pathways. It has fewer of the typical opioid side-
effects (notably, less respiratory depression, less constipation and less addiction
potential); psychiatric reactions have been reported.
Codeine
Codeine phosphate is a weak opioid and can be used for the relief of mild to
moderate pain where other painkillers such as paracetamol or ibuprofen have
proved ineffective.
Codeine is metabolised to morphine which is responsible for its therapeutic
effects. Codeine 240 mg is approximately equivalent to 30 mg of morphine. The
capacity to metabolise codeine can vary considerably between individuals; there
is a marked increase in morphine toxicity in people who are ultra rapid
metabolisers, and reduced therapeutic effect in poor codeine metabolisers.
Codeine is contraindicated in patients of any age who are known to be ultra-rapid
metabolisers of codeine (CYP2D6 ultra-rapid metabolisers).
Codeine is also contraindicated in children under 12, and in children of any
age who undergo the removal of tonsils or adenoids for the treatment of
obstructive sleep apnoea due to reports of morphine toxicity.
Contraindications
Opioids should be avoided in people who have:
A risk of paralytic ileus (opioids reduce gastric motility)
Acute respiratory depression
An acute exacerbation of asthma (opioids can aggravate
bronchoconstriction as a result of histamine release)
Conditions associated with increased intracranial pressure (opioids can
interfere with pupillary response making neurological assessment difficult
and may cause retention of carbon dioxide aggravating the increased
intracranial pressure)
Cautions
Opioids should be used with caution in:
Elderly people (more susceptible to side effects)
People with hypothyroidism and adrenocortical insufficiency (opioids can
affect endocrine function and lead to hypogonadism and adrenal
insufficiency)
People with moderate-to-severe chronic kidney disease (adverse effects
may be increased because elimination time is prolonged)
People with impaired respiratory function, asthma, COPD or acute
respiratory depression (risk of respiratory depression)
People with hepatic impairment (adverse effects such as sedation and
constipation can precipitate hepatic encephalopathy)
People with prostatic hyperplasia (urinary retention has been reported)
People with obstructive or inflammatory bowel bowel disorders (opioids
reduce gastric motility)
People with diseases of the biliary tract (ureteric or biliary spasm has been
reported)
People with chronic constipation (opioids reduce gastric motility)
People with convulsive disorders (tramadol may reduce seizure threshold)
Side Effects
All opioids have the potential to cause:
Gastrointestinal effects
Nausea, vomiting, constipation, difficulty with micturition, biliary
spasm
Central nervous system effects
Sedation, euphoria, respiratory depression, miosis
Peripheral vasodilation, postural hypotension
Dependence and tolerance
In addition tramadol can cause:
Convulsions (mainly after high doses or during concomitant therapy with
other drugs that reduce seizure threshold or induce convulsions such as
SSRIs and TCAs)
Psychiatric reactions including hallucinations and confusion
Hypoglycaemia
Hyponatraemia
Interactions
All opioids interact with central nervous system depressants such as sedatives or
hypnotics, phenothiazines or alcohol. Concomitant use may potentiate the
effects of CNS depressants and cause respiratory depression or sedation.
Tramadol has also been reported to increase the anticoagulant effects of warfarin
and concomitant use of tramadol with MAOIs may precipitate the serotonin
syndrome.
Overdose
In overdose opioids cause coma, respiratory depression, and pinpoint pupils
(miosis). Naloxone is a specific antagonist at opioid receptors and reverses
respiratory depression caused by opioid drugs.

Paracetamol LAST UPDATED: 4TH
APRIL 2019
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Mechanism of Action
Paracetamol is a non-opioid analgesic, similar in efficacy to aspirin, with
antipyretic properties but no anti-inflammatory properties. It is well absorbed
orally and does not cause gastric irritation. Paracetamol is a suitable first-line
choice for most people with mild-to-moderate pain, and for combination therapy.
Contraindications and Cautions

There are no contraindications to the use of paracetamol.
Paracetamol should be used with caution in:
Alcohol dependence
Dehydration
Chronic malnutrition
Hepatic impairment
People who weigh < 50 kg
Side Effects
Adverse effects are rare with paracetamol. However, paracetamol doses greater
than the maximum daily dose of 4 grams can lead to hepatotoxicity (and, less
frequently, acute kidney injury). In some people this may be fatal.
Overdose
Overdose with acetaminophen results in accumulation of a minor metabolite, N-
acetyl-p-benzoquinone, which is responsible for hepatotoxicity. When the
enzymes for glucuronide and sulfate conjugation of acetaminophen and the
reactive metabolite become saturated, an alternative glutathione conjugation
pathway (cytochrome P-450 dependent) becomes more important. If hepatic
glutathione is depleted, such as may occur with alcohol consumption, the
reactive metabolite accumulates and may cause hepatic damage by interaction
with cellular macromolecules, such as DNA and RNA.
People who have taken an overdose of paracetamol (accidentally or intentionally)
may require urgent admission to hospital, depending on the quantity of
paracetamol taken and the presence of risk factors for liver damage, including:
alcohol dependence, pre-existing liver disease, malnutrition, and the use of liver
enzyme inducing drugs (such as rifampicin, carbamazepine, and phenytoin).
Early symptoms of paracetamol toxicity are nausea, vomiting, and abdominal pain
which usually settle within 24 hours. Symptoms of liver damage include right
subcostal pain and tenderness. Liver damage peaks 3 to 4 days after paracetamol
ingestion. The person may develop encephalopathy, bleeding, hypoglycaemia,
and cerebral oedema.

Phenytoin LAST UPDATED: 4TH
APRIL 2019
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Indications
Phenytoin is licensed for tonic-clonic and focal seizures but may exacerbate
absence or myoclonic seizures and should be avoided if these seizures are
present. It is also used in status epilepticus refractory to benzodiazepines, given
intravenously.
Mechanism of Action
dependent block of neuronal Na+ channels. Their anticonvulsant action is a result
of their ability to prevent high-frequency repetitive activity. The drugs bind
inactivated state and preventing them from returning to the resting (closed)
state, which they must re-enter before they can again open.
It has a narrow therapeutic index and the relationship between dose and plasma
drug concentration is non-linear; small dosage increases in some patients may
produce large increases in plasma concentration with acute toxic side-effects.
Similarly, a few missed doses or a small change in drug absorption may result in a
marked change in plasma-drug concentration. Monitoring of plasma drug
concentration improves dosage adjustment; the usual total plasma-phenytoin
concentration for optimum response is 10 – 20 mg/litre (or 40 – 80 micromol/
litre).
Contraindications
Phenytoin is contraindicated in acute porphyrias. Intravenous phenytoin is
additionally contraindicated in second- and third-degree heart block, sinoatrial
block, sinus bradycardia and Stokes-Adams syndrome.
Side Effects
Generally
Nausea and vomiting
Drowsiness, lethargy, and loss of concentration
Headache, dizziness, tremor, nystagmus and ataxia
Gum enlargement or overgrowth
Coarsening of facial features, acne and hirsutism
Skin rashes
Blood disorders
Intravenously
Alterations in respiratory function or respiratory arrest
Arrhythmias, hypotension and cardiovascular collapse
CNS depression
Symptoms of phenytoin toxicity include nystagmus, diplopia, slurred speech,
ataxia, confusion, and hyperglycaemia.
Interactions
Phenytoin is an enzyme-inducing drug and can accelerate the metabolism of
certain drugs result in reduced therapeutic effect of that drug, such as
corticosteroids, warfarin, doxycycline, oral contraceptive pill and thyroid
hormones amongst others.

Sodium Valproate LAST UPDATED: 4TH
APRIL 2019
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Indications
Sodium valproate is effective in controlling tonic-clonic seizures, particularly in
primary generalised epilepsy. It is a drug of choice in primary generalised tonic-
clonic seizures, focal seizures, generalised absences and myoclonic seizures, and
can be tried in atypical absence seizures. It is recommended as a first-line option
in atonic and tonic seizures.
Mechanism of Action
dependent block of neuronal Na+ channels. Their anticonvulsant action is a result
of their ability to prevent high-frequency repetitive activity. The drugs bind
inactivated state and preventing them from returning to the resting (closed)
state, which they must re-enter before they can again open.
Sodium valproate has widespread metabolic effects and monitoring of liver
function tests and full blood count is essential. Valproate should not be used in
female children, in females of childbearing potential, and pregnant females,
unless alternative treatments are ineffective or not tolerated, because of its high
teratogenic potential.
Contraindications
Sodium valproate is contraindicated in:

Acute liver disease
Acute porphyrias
Known or suspected mitochondrial disorders (higher rate of acute liver
failure and liver-related deaths)
Personal or family history of severe, drug-related hepatic dysfunction
Side Effects
Gastric irritation, and hyperammonaemia both of which can lead to intense
nausea
Lethargy and confusion
Weight gain
Hair loss, with curly regrowth
Peripheral oedema
Very rarely, fulminant hepatic failure
Hyperandrogenism in women
Thrombocytopenia, leucopenia and red cell hypoplasia
Pancreatitis
Hepatic impairment
Interactions
Valproate is highly protein-bound (up to 94%), and other drugs that are also
highly protein bound (e.g. aspirin) may displace valproate from albumin and
precipitate toxicity.
Other less strongly protein-bound drugs (for example warfarin) can be displaced
by valproate; this may lead to higher free levels and increased therapeutic effect
or toxicity of the concomitant drug.
Valproate is metabolised by the liver, so drugs that inhibit cytochrome P450
enzymes (for example erythromycin, fluoxetine, and cimetidine) can increase
valproate levels.

Tricyclic Antidepressants LAST UPDATED: 7TH
JUNE 2022
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Mechanism of Action
Tricyclic antidepressants (TCAs) e.g. amitriptyline block the reuptake of both
serotonin and noradrenaline, although to different extents. TCAs have similar
efficacy to selective serotonin reuptake inhibitors (SSRIs) but are more likely to be
discontinued because of side effects; toxicity in overdosage is also a problem. SSRIs
are less sedating and have fewer antimuscarinic and cardiotoxic effects than TCAs,
and hence are usually considered first line for depression.
Contraindications
TCAs should be avoided in:
Acute porphyrias
Arrhythmias or heart block
Manic phase of bipolar disorder
Immediate recovery period after myocardial infarction
Severe liver disease
Concomitant therapy with an MAOI
Prostatism
Narrow angle glaucoma or other cause of increased intraocular pressure
Interactions
Concomitant therapy with other sedating drugs or alcohol may have a synergistic
sedative effect.
Concomitant therapy with antihistamines and antipsychotics may have a synergistic
antimuscarinic effect.
There is an increased risk of ventricular arrhythmias when TCAs are given with
antiarrhythmics.
There is an increased risk of serotonin syndrome when TCAs are given with
serotonergic drugs or dopaminergic drugs.
TCAs may enhance or reduce the anticoagulant effect of warfarin.
Side Effects
Anticholinergic effects
Dry mouth
Blurred vision
Dilated pupils
Urinary retention
Constipation
Absent bowel sounds
Pyrexia
Myoclonic twitching
CNS effects
Drowsiness
Coma
Convulsions
Pyramidal signs
Rigidity
Delirium
Ophthalmoplegia
Sinus tachycardia
Prolonged PR/QRS/QT
ST/T wave changes
Heart block
Vasodilatation
Hypotension
Cardiogenic shock
Ventricular fibrillation/tachycardia
Hepatic impairment
Narrow-angle glaucoma

Corticosteroids LAST UPDATED: 3RD
APRIL 2019
PHARMACOLOGY / ENDOCRINE
 Bookmark
In comparing the relative potencies of corticosteroids in terms of their anti-

inflammatory effects, it is worth noting that high glucocorticoid activity in itself is of
no advantage unless it is accompanied by relatively low mineralocorticoid activity.
Anti-Inflammatory Potency
Equivalent anti-inflammatory doses of corticosteroids:
Prednisolone 5 mg = Dexamethasone 750 micrograms = Hydrocortisone 20 mg
This does not take into account their mineralocorticoid effects, nor their duration of
action.
Side Effects
Overdose or prolonged use can exaggerate some of the normal physiological actions of
corticosteroids leading to mineralocorticoid and glucocorticoid side effects.
Mineralocorticoid side effects are most marked with fludrocortisone, but are significant
with hydrocortisone, negligible with the high potency glucocorticoids, betamethasone
and dexamethasone, and occur only slightly with methylprednisolone and
prednisolone.
Mineralocorticoid side effects include:
hypertension
sodium retention
water retention and oedema
potassium loss
calcium loss
Glucocorticoid side effects include:

weight gain
hyperglycaemia and diabetes
osteoporosis and osteoporotic fractures
muscle wasting (proximal myopathy)
peptic ulceration and perforation
psychiatric reactions
Side effects can be minimised by using the lowest effective dose for the minimum
period possible. The suppressive action of a corticosteroid on cortisol secretion is least
when it is given as a single dose in the morning. Whenever possible local treatment
with creams, intra-articular injections, inhalations, eye drops, or enemas should be
used in preference to systemic treatment.
Adrenal Suppression
During prolonged therapy with corticosteroids, particularly with systemic use, adrenal
atrophy develops and can persist for years after stopping. Abrupt withdrawal after a
prolonged period can lead to acute adrenal insufficiency, hypotension, or death.
Patients removed from long-term glucocorticoid therapy must be weaned off the drug
over several days, using progressively lower doses to allow recovery of adrenal
responsiveness.
To compensate for a diminished adrenocortical response caused by prolonged
corticosteroid treatment, any significant intercurrent illness, trauma, or surgical
procedure requires a temporary increase in corticosteroid dose, or if already stopped, a
temporary reintroduction of corticosteroid treatment.
Patients on long-term corticosteroid treatment should carry a steroid treatment card
which gives guidance on minimising risk and provides details of prescriber, drug,
dosage and duration of treatment.
Infections
Prolonged courses of corticosteroids increase susceptibility to infections and severity
of infections; clinical presentation of infections may also be atypical.
Unless they have had chickenpox, patients receiving oral or parenteral corticosteroids
for purposes other than replacement should be regarded as being at risk of severe
chickenpox. Manifestations of fulminant illness include pneumonia, hepatitis and
disseminated intravascular coagulation; rash is not necessarily a prominent
feature. Passive immunisation with varicella–zoster immunoglobulin is needed for
exposed non–immune patients receiving systemic corticosteroids or for those who
have used them within the previous 3 months. Confirmed chickenpox warrants
specialist care and urgent treatment. Corticosteroids should not be stopped and
dosage may need to be increased.
Patients taking corticosteroids should be advised to take particular care to avoid
exposure to measles and to seek immediate medical advice if exposure occurs.
Prophylaxis with intramuscular normal immunoglobulin may be needed.
Hydrocortisone
The relatively high mineralocorticoid activity of hydrocortisone, and the resulting fluid
retention, makes it unsuitable for disease suppression on a long-term basis. However,
hydrocortisone can be used for adrenal replacement therapy (together with
fludrocortisone). Hydrocortisone is primarily used on a short-term basis by
intravenous injection for the emergency management of some conditions such as
acute asthma and allergic/anaphylactic reactions as an adjunct to adrenaline. The
relatively moderate anti-inflammatory potency of hydrocortisone also makes it a
useful topical corticosteroid for the management of inflammatory skin conditions
because side effects (both topical and systemic) are less marked. Hydrocortisone
acetate or one of the synthetic analogues is also generally used for local injection.
Prednisolone
Prednisolone, an intermediate-acting agent, has predominantly glucocorticoid activity
with only minimal mineralocorticoid activity. Prednisolone is the corticosteroid most
commonly used by mouth for long-term disease suppression, for example in
rheumatoid arthritis and temporal arteritis.
Dexamethasone
Dexamethasone has a very high glucocorticoid activity in conjunction with
insignificant mineralocorticoid activity. This makes it particularly suitable for high-dose
therapy in conditions where fluid retention would be a disadvantage such as in the
management of raised intracranial pressure or cerebral oedema secondary to
malignancy. Dexamethasone also has a long duration of action and this, coupled with
its lack of mineralocorticoid action makes it particularly suitable for suppression of
corticotropin secretion in congenital adrenal hyperplasia. In most individuals a single
dose of dexamethasone at night, is sufficient to inhibit corticotropin secretion for 24
hours. This is the basis of the ‘overnight dexamethasone suppression test’ for
diagnosing Cushing’s syndrome.
Glucagon Therapy LAST UPDATED: 28TH
MARCH 2019
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Glucagon, a polypeptide hormone produced by the alpha cells of the islets of

Langerhans, increases plasma-glucose by mobilising glycogen stored in the liver.
Glucagon promotes glycogenolysis and gluconeogenesis and may be used to
treat hypoglycaemia.
Glucagon may also be used as an antidote in beta-blocker overdose and in
anaphylaxis in patients on beta-blockers that fail to respond to adrenaline.
Cautions
Glucagon may take up to 15 minutes to have an effect and will be less effective in
alcoholics, prolonged starvation and severe liver disease when glycogen stores
are depleted. In this situation or if prolonged treatment is required, IV glucose is
better. Glucagon may also be less effective in patients prescribed sulfonylurea
therapy.
Contraindications
Glucagon is contraindicated in pheochromocytoma.
Side Effects
Common: Nausea
Uncommon: Vomiting
Rare: Abdominal pain, hypertension, hypotension, tachycardia

Insulin Therapy LAST UPDATED: 28TH
MARCH 2019
 Bookmark
Action
Insulin plays a key role in the regulation of carbohydrate, fat, and protein
metabolism.
Insulin acts to:
Increase cellular glucose uptake
Decrease gluconeogenesis
Increase glycogenesis/decrease glycogenolysis
Increase lipogenesis/decrease lipolysis
Increase protein synthesis/decrease proteolysis
Increase cellular potassium uptake
Insulin is needed for all patients with type 1 DM and some patients with type 2 DM
where other methods have failed to achieve good control, and temporarily in the
presence of intercurrent illness or perioperatively.
Administration
Insulin is inactivated by gastro-intestinal enzymes, and must therefore be given
by injection; the subcutaneous route is ideal in most circumstances. Insulin is
usually injected into the upper arms, thighs, buttocks, or abdomen; absorption
from a limb site may be increased if the limb is used in strenuous exercise after
the injection. Generally subcutaneous insulin injections cause few problems;
lipodystrophy may occur but can be minimised by using different injection sites in
rotation. Local allergic reactions are rare.
Preparations
Insulin preparations can be divided into three types:
1. those of short duration which have a relatively rapid onset of action,
namely soluble insulin (most appropriate form of insulin for use in DKA -
given as intravenous solution) and the rapid-acting insulin analogues
(insulin aspart, insulin glulisine, and insulin lispro)
2. those with an intermediate action (e.g. isophane insulin)
3. those whose action is slower in onset and lasts for long periods (e.g.
protamine zinc insulin, insulin detemir, and insulin glargine)
Soluble insulin: When injected subcutaneously, soluble insulin has a rapid onset
of action (30 to 60 minutes), a peak action between 2 and 4 hours, and a duration
of action of up to 8 hours. When injected intravenously, soluble insulin has a very
short half-life of only about 5 minutes and its effect disappears within 30
minutes.
The rapid-acting human insulin analogues have a faster onset and shorter
duration of action than soluble insulin; as a result, compared to soluble insulin,
fasting and preprandial blood-glucose concentrations are a little higher,
postprandial blood-glucose concentration is a little lower, and hypoglycaemia
occurs slightly less frequently.
When given by subcutaneous injection, intermediate- and long-acting insulins
have an onset of action of approximately 1–2 hours, a maximal effect at 4–12
hours, and a duration of 16–42 hours.
Treatment Regimes
The aim of treatment is to achieve the best possible control of blood-glucose
concentration whilst avoiding disabling hypoglycaemia. Mixtures of insulin
preparations may be required and appropriate combinations have to be
determined for the individual patient.
Insulin regimes should be tailored to the requirements of the individual and may
include:
once/twice daily SC injections (often with a premixed solution of short-
acting insulin or rapid-acting insulin analogue with an intermediate-acting
or long-acting insulin)
multiple daily SC injections (with a short-acting insulin or a rapid-acting
insulin analogue given before meals with intermediate-acting or long-
acting insulin once or twice daily)
continuous subcutaneous insulin infusion
Insulin requirements may be increased by infection, stress, accidental or surgical
trauma, and during puberty. Requirements may be decreased in those with
certain endocrine disorders (e.g. Addison’s disease, hypopituitarism), or in coeliac
disease.
Implications of Diabetes on Driving

Loss of warning of hypoglycaemia among insulin-treated patients can be a
serious hazard, especially for drivers and those in dangerous occupations. Very
tight control of diabetes leads to increased risk of hypoglycaemic episodes and
an increase in the frequency of hypoglycaemia episodes may blunt
hypoglycaemic awareness. Beta-blockers can also blunt hypoglycaemic
awareness. Drivers with diabetes may be required to notify the DVLA of their
condition, depending on their treatment, the type of licence, and whether they
have diabetic complications.
Oral Antidiabetic Drugs

Oral antidiabetic drugs are used for the treatment of type 2 diabetes mellitus.
They should be prescribed only if the patient fails to respond adequately to at
least 3 months’ restriction of energy and carbohydrate intake and an increase in
physical activity. They should be used to augment the effect of diet and exercise,
and not to replace them.

Management of Diabetic LAST UPDATED: 11TH
AUGUST 2022
Ketoacidosis  Bookmark
Diabetic ketoacidosis (DKA) consists of the biochemical triad of ketonaemia

(ketosis), hyperglycaemia, and acidaemia.
Pathophysiology
DKA usually occurs as a consequence of absolute or relative insulin deficiency
that is accompanied by an increase in counter-regulatory hormones (i.e.
glucagon, cortisol, growth hormone, catecholamines). This type of hormonal
imbalance enhances hepatic gluconeogenesis and glycogenolysis resulting in
severe hyperglycaemia. Enhanced lipolysis increases serum free fatty acids that
are then metabolised as an alternative energy source in the process of
ketogenesis. This results in accumulation of large quantities of ketone bodies and
subsequent metabolic acidosis. Fluid depletion occurs due to osmotic diuresis
secondary to hyperglycaemia, vomiting, and inability to take in fluid due to a
diminished level of consciousness.
Diagnosis
Diagnostic criteria (all three must be present):
Capillary blood glucose > 11 mmol/L
Ketonaemia > 3 mmol/L or Ketonuria > ++
Bicarbonate (HCO3-) < 15 mmol/L and/or venous pH < 7.3
Management (adults)
Intravenous fluids
Initial fluids:
Systolic BP < 90 mmHg on admission
500 mL 0.9% sodium chloride should be given
intravenously over 10 – 15 minutes and repeated if blood
pressure remains < 90 mmHg whilst awaiting senior
input. Most people require 500-1000 mL given rapidly.
Consider involving the ITU/critical care team.
Once systolic BP > 90 mmHg, 1 L 0.9% sodium chloride
should be given over the next 60 minutes. The addition
of potassium is likely to be required in this second litre of
fluid.
Systolic BP ≥ 90 mmHg on admission.
1 L 0.9% sodium chloride should be given over the first 60
minutes.
Continuing fluids:
Regime:
0.9% sodium chloride 1L with potassium chloride over
next 2 hours
next 2 hours
next 4 hours
More cautious fluid replacement in young people aged 18-25
years, elderly, pregnant, heart or renal failure. (Consider HDU
and/or central line).
Accurate fluid balance chart, minimum urine output 0.5
ml/kg/hr.
Potassium replacement:
Potassium chloride should be included in the fluids unless
anuria is suspected, and adjusted according to plasma-
potassium concentration (measured at 60 minutes, 2 hours,
and 2 hourly thereafter; and hourly if outside the normal
range).
Potassium levels:
K+ Level >5.5 = nil replacement
K+ level 3.5 - 5.5 = 40 mmol/L replacement
K+ level <3.5 = senior review
Other electrolytes:
Venous blood gas for pH and bicarbonate should be checked at
60 minutes, 2 hours and 2 hourly thereafter.
Plasma electrolytes should be checked 4 hourly.
Insulin
An intravenous insulin infusion should be started at a concentration
of 1 unit/mL, infused at a fixed rate of 0.1 units/kg/hour using 50
units human soluble insulin (Actrapid® or Humulin S®) made up to
50 ml with 0.9% sodium chloride solution.
Established subcutaneous long-acting insulin therapy should be
continued during the treatment of DKA at usual dose and time.
Blood ketone and blood glucose concentrations should be checked
hourly and the insulin infusion rate adjusted accordingly. Blood
ketone concentration should fall by at least 0.5 mmol/litre/hour OR
bicarbonate should rise by at least 3 mmol/L/hour and blood glucose
concentration should fall by at least 3 mmol/litre/hour.
The insulin infusion should be continued until blood ketone
concentration is below 0.6 mmol/litre, blood pH is above 7.3 and/or
venous bicarbonate is over 18 mmol/L and the patient is able to eat
and drink; ideally the insulin infusion should be stopped about an
hour after giving subcutaneous fast-acting insulin and a meal.
Glucose
Once blood-glucose concentration falls below 14 mmol/litre, glucose
10% should be given by intravenous infusion (into a large vein
through a large-gauge needle) at a rate of 125 mL/hour, in addition to
the sodium chloride 0.9% infusion.
Consider reducing the rate of intravenous insulin infusion to 0.05
units/ kg/hour when glucose falls below 14 mmol/L.

MARCH 2019
Hypoglycaemia  Bookmark
Management (adults)
In adults who are conscious, cooperative and can swallow:
Give 15 - 20 g quick acting carbohydrate of the patient’s choice
where possible e.g. 90 – 120 mL of Lucozade or 5 – 7 Dextrosol
tablets
Repeat capillary blood glucose 10 – 15 minutes later
If blood glucose is still < 4.0 mmol/L, repeat step 1 (no more than 3
treatments in total)
If blood glucose remains < 4.0 mmol/L after 45 minutes or 3 cycles,
consider:
1 mg glucagon IM
IV 10% glucose infusion at 100ml/hr
In adults who are conscious but uncooperative:
Give either 1.5 – 2 tubes Glucogel/Dextrogel (may repeat up to 3
times)
If this is ineffective give glucagon 1 mg IM (may only give once)
If blood glucose level remains less than 4.0 mmol/L after 45 minutes
(or 3 cycles), consider IV 10% glucose infusion at 100ml/hr
In adults who are unconscious:
Give either:
1 mg glucagon intramuscularly (if not effective after 10 - 15
minutes, IV glucose should be given)
75 – 80 ml of 20% glucose intravenously over 10 - 15 minutes
150 – 160 ml of 10% glucose intravenously over 10 - 15 minutes
Once blood glucose is > 4.0 mmol/L and the patient recovered, give a long acting
carbohydrate of the patient’s choice where possible e.g. two biscuits, one slice of
bread. Note that patients given glucagon require a larger portion of long acting
carbohydrate to replenish glycogen stores (double the suggested amount).
If the hypoglycaemia was due to sulfonylurea or long acting insulin therapy then
be aware that the risk of hypoglycaemia may persist for up to 24 - 36 hours
following the last dose, especially if there is concurrent renal impairment.

Management of Thyroid LAST UPDATED: 27TH
FEBRUARY 2020
Disease  Bookmark
Antithyroid Drugs
Antithyroid drugs are used for hyperthyroidism either to prepare patients for
thyroidectomy or for long-term management. In the UK carbimazole is the most
commonly used drug. Propylthiouracil should be reserved for patients who are
intolerant of carbimazole or for those who experience sensitivity reactions to
carbimazole, and for whom other treatments are inappropriate. Both drugs act
primarily by interfering with the synthesis of thyroid hormones.
Over-treatment with antithyroid drugs can result in the rapid development of
hypothyroidism and should be avoided particularly during pregnancy because it
can cause foetal goitre.
A combination of carbimazole with levothyroxine sodium daily, may be used in a
blocking-replacement regimen; therapy is usually given for 18 months. The
blocking-replacement regimen is not suitable during pregnancy.
Iodine has been used as an adjunct to antithyroid drugs for 10 to 14 days before
partial thyroidectomy; however, there is little evidence of a beneficial effect.
Iodine should not be used for long-term treatment because its antithyroid action
tends to diminish.
Radioactive sodium iodide (131I) solution is used increasingly for the treatment of
thyrotoxicosis at all ages, particularly where medical therapy or compliance is a
problem, in patients with cardiac disease, and in patients who relapse after
thyroidectomy.
Propranolol hydrochloride is useful for rapid relief of thyrotoxic symptoms and
may be used in conjunction with antithyroid drugs or as an adjunct to radioactive
iodine. Beta-blockers are also useful in neonatal thyrotoxicosis and in
supraventricular arrhythmias due to hyperthyroidism. Propranolol hydrochloride
has been used in conjunction with iodine to prepare mildly thyrotoxic patients for
surgery but it is preferable to make the patient euthyroid with carbimazole.
Laboratory tests of thyroid function are not altered by beta-blockers. Most
experience in treating thyrotoxicosis has been gained with propranolol
hydrochloride but nadolol is also used.
Thyrotoxic crisis (‘thyroid storm’) requires emergency treatment with intravenous
administration of fluids, propranolol hydrochloride and hydrocortisone (as sodium
succinate), as well as oral iodine solution and carbimazole or propylthiouracil
which may need to be administered by nasogastric tube.
Thyroid Hormones
Thyroid hormones are used in hypothyroidism (myxoedema), and also in diffuse
non-toxic goitre, Hashimoto’s thyroiditis (lymphadenoid goitre), and thyroid
carcinoma. Neonatal hypothyroidism requires prompt treatment for normal
development. Levothyroxine sodium (thyroxine sodium) is the treatment of
choice for maintenance therapy.
In infants and children with congenital hypothyroidism and juvenile myxoedema,
the dose of levothyroxine sodium should be titrated according to clinical
response, growth assessment, and measurements of plasma thyroxine and
thyroid-stimulating hormone.
Liothyronine sodium has a similar action to levothyroxine sodium but is more
rapidly metabolised and has a more rapid effect. Its effects develop after a few
hours and disappear within 24 to 48 hours of discontinuing treatment. It may be
used in severe hypothyroid states when a rapid response is desired.
Liothyronine sodium by intravenous injection is the treatment of choice in
hypothyroid coma. Adjunctive therapy includes intravenous fluids,
hydrocortisone, and treatment of infection; assisted ventilation is often required.

Adrenaline Therapy LAST UPDATED: 3RD
APRIL 2019
PHARMACOLOGY / RESPIRATORY
 Bookmark
Adrenaline is a catecholamine that acts on both alpha and beta receptors and
increases both heart rate and contractility (beta1 effects); it can cause
peripheral vasodilation (a beta2 effect) or vasoconstriction (an alpha effect).
Adrenaline is used in cardiopulmonary resuscitation, in the emergency
management of acute allergic and anaphylactic reactions and in the
management of severe croup (as a nebuliser solution).
Mechanism of Action in Anaphylaxis

As an alpha-receptor agonist, adrenaline reverses peripheral vasodilation and
increased vascular permeability reducing hypotension and oedema.
As a beta-receptor agonist it dilates bronchial airways, increases the force and
rate of myocardial contraction, and suppresses histamine and leukotriene
release.
Adrenaline also alleviates pruritus, urticaria, and angioedema and may relieve
gastrointestinal and genitourinary symptoms associated with anaphylaxis
because of its relaxer effects on the smooth muscle of the stomach, intestine,
uterus and urinary bladder.
Adrenaline increases glycogenolysis, reduces glucose uptake by tissues, and
inhibits insulin release in the pancreas, resulting in hyperglycemia and
increased blood lactic acid.
Interactions
Severe anaphylaxis in patients taking beta-blockers may not respond to
adrenaline—consider bronchodilator therapy. Furthermore, adrenaline can
cause severe hypertension and bradycardia in those taking non-cardioselective
beta-blockers.
Antihistamines LAST UPDATED: 21ST
NOVEMBER 2021
 Bookmark
Antihistamines are competitive inhibitors at the H1-receptor (in contrast to H2

receptor antagonists used to decrease gastric acid secretion). They act to relax
histamine-induced bronchoconstriction, block the vasodilator effect of
histamine, inhibit histamine-induced increases in capillary permeability and
block mucus secretion and sensory nerve stimulation.
Pharmacokinetics
Histamine (H1)-receptor antagonists are well absorbed after oral administration.
The effects of these agents are usually seen in 30 minutes (with maximal
effects at 1 – 2 h); the duration of action is 3 – 8 hours for first-generation
compounds and 3 – 24 hours for second-generation compounds.
H1-receptor antagonists are metabolised in the liver; many induce microsomal
enzymes and alter their own metabolism and that of other drugs.
Indications
Allergic rhinitis and conjunctivitis
Urticarial rashes, pruritus, insect bites and stings
Angioedema
Nausea/vomiting and prevention of motion sickness
Insomnia
Chlorphenamine
All older antihistamines cause sedation but alimemazine tartrate and
promethazine may be more sedating whereas chlorphenamine maleate and
cyclizine may be less so. This sedating activity is sometimes used to manage
the pruritus associated with some allergies or used to manage occasional
insomnia. There is little evidence that any one of the older, 'sedating'
antihistamines is superior to another and patients vary widely in their response.
Cetirizine
The newer antihistamines e.g. cetirizine cause less sedation and psychomotor
impairment than the older antihistamines because they are much less lipid
soluble and penetrate the blood brain barrier only to a slight extent.
Cautions
Antihistamines should usually be avoided in acute porphyrias (although some
antihistamines are thought to be safe).
Antihistamines should be used with caution in epilepsy, prostatic hypertrophy,
urinary retention, hepatic impairment and susceptibility to angle-closure
glaucoma.
Side Effects (significantly reduced with second-generation

agents)
Elderly patients and children are more susceptible to side effects.
Common side effects of antihistamines may include:
Anticholinergic effects (blurred vision, dry mouth, urinary retention)
Headache
Gastrointestinal disturbances
Psychomotor impairment (sedation, dizziness and loss of appetite)
Drowsiness may affect performance of skilled tasks (e.g. cycling or driving);
sedating effects are enhanced by alcohol and opioid analgesics.

Inhaled Antimuscarinics LAST UPDATED: 28TH
MARCH 2019
 Bookmark
Ipratropium bromide, a short-acting antimuscarinic bronchodilator, causes

bronchodilation by blocking the cholinergic nerves in the airways.
Indications
Ipratropium bromide can provide short-term relief in chronic asthma, but short-
acting beta-2 agonists act more quickly and are preferred. Ipratropium bromide
by nebulisation can be added to other standard treatment in life-threatening
asthma or if acute asthma fails to improve with standard therapy.
The aerosol inhalation of ipratropium bromide may be used for short-term relief
in mild COPD in patients who are not using a long-acting antimuscarinic
drug. Its maximal effect occurs 30 – 60 minutes after use; its duration of action
is 3 to 6 hours and bronchodilation can usually be maintained with treatment 3
times a day.
Cautions
Ipratropium bromide should be used with caution in:
Men with prostatic hyperplasia and bladder-outflow obstruction
(worsened urinary retention has been reported in elderly men)
People with chronic kidney disease (CKD) stages 3 and above (because of
the risk of drug toxicity)
People with angle-closure glaucoma (nebulised mist of antimuscarinic
drugs can precipitate or worsen acute angle-closure glaucoma)
Interactions
There are no important drug interactions with inhaled muscarinic antagonists.
Side Effects
Inhaled antimuscarinics are generally well tolerated as they are poorly absorbed
systemically.
Their adverse effects include:
Dry mouth and abnormal taste in the mouth
Nasal congestion and dryness of nasal mucosa
Acute angle-closure glaucoma (reported in people on nebulised
ipratropium)

Inhaled Corticosteroids LAST UPDATED: 28TH
MARCH 2019
 Bookmark
Corticosteroids reduce airway inflammation and hence oedema and mucus

secretion.
Indications
Regular use of inhaled corticosteroids (e.g. beclomethasone) reduces the risk of
exacerbation of asthma.
An inhaled corticosteroid is used regularly for prophylaxis of asthma when
patients require a beta-2 agonist more than twice a week, or if symptoms
disturb sleep at least once a week, or if the patient has suffered an exacerbation
in the last 2 years requiring a systemic corticosteroid. Corticosteroid inhalers
must be used regularly for maximum benefit; alleviation of symptoms usually
occurs 3 to 7 days after initiation.
Current and previous smoking reduces the effectiveness of inhaled
corticosteroids and higher doses may be necessary.
Contraindications
There are no contraindications to the use of inhaled corticosteroids.
Inhaled corticosteroids should be used with caution in people with tuberculosis
(potential for exacerbation or reactivation) or in untreated systemic fungal,
bacterial, parasitic or viral infection.
Side Effects
Local adverse effects of inhaled corticosteroids include:
Oral candidiasis, sore mouth, dysphonia, hoarseness (patients should be
advised to rinse their mouth with water after inhalation)
Paradoxical bronchospasm (very rare and usually mild)
Systemic adverse effects may occur rarely, particularly if high doses are
prescribed for long periods of time or in concomitant use of other corticosteroid
preparations.
Systemic effects include:
Reduced bone mineral density predisposing the person to osteoporosis
Bruising, cataract, and glaucoma
Adrenal suppression , adrenal crisis, coma, and death — very rarely, this
has been reported in children taking long-term inhaled corticosteroids
Psychological and behavioural changes (such as psychomotor
hyperactivity, sleep disorders, anxiety, depression, and aggression)
Growth suppression in children – this does not seem to occur with
recommended doses of inhaled corticosteroids
Systemic Corticosteroid Therapy in Asthma

Systemic corticosteroid therapy may be necessary during episodes of stress,
such as severe infection, or if the asthma is worsening, when higher doses are
needed and access of inhaled drug to small airways may be reduced; patients
may need a reserve supply of corticosteroid tablets.
An acute attack of asthma should be treated with a short course of an oral
corticosteroid (e.g. prednisolone) or intravenous corticosteroid (e.g.
hydrocortisone) if oral intake is not possible, starting with a high dose. An oral
corticosteroid should normally be taken as a single dose in the morning to
reduce the disturbance to circadian cortisol secretion.

Management of Acute LAST UPDATED: 3RD
APRIL 2019
Asthma  Bookmark
Asthma is a common chronic inflammatory condition of the airways

characterised by bronchoconstriction. The most frequent symptoms are cough,
wheezing, chest tightness, and shortness of breath. The bronchoconstriction is
usually reversible (either spontaneously or with the aid of medication) leading to
intermittent symptoms, but in some patients with chronic asthma the
inflammation may result in irreversible airway obstruction. Occasionally, asthma
symptoms can get gradually or suddenly worse provoking an acute asthma
attack that, if severe, may require hospitalisation.
Classification of Acute Asthma in Adults

The nature of treatment required for the management of acute asthma depends
on the level of severity, described as follows:
Severity Criteria
Moderate Increasing symptoms
PEFR > 50 - 75% of best or predicted
No features of acute severe asthma
Severe Any one of:
PEFR 33 - 50% of best or predicted
Respiratory rate ≥ 25 breaths/minute
Heart rate ≥ 110 beats/minute
Inability to complete sentences in one breath
Severity Criteria
Life- Any one of the following in someone with severe asthma:
threatening
PEFR < 33% of best or predicted
SpO2< 92% or PaO2 < 8 kPa
Normal PaCO2 (4.6 - 6.0 kPa)
Silent chest
Cyanosis
Poor respiratory effort
Arrhythmia
Hypotension
Exhaustion
Altered conscious level
Near-fatal Respiratory acidosis (increased arterial PaCO2) and/or
requiring mechanical ventilation with increased inflation
pressures
BTS/SIGN Management of Acute Asthma in Adults

Patients with moderate asthma should be treated at home or in primary care
according to response to treatment, while patients with severe or life-
threatening acute asthma should start treatment as soon as possible and be
admitted to hospital immediately following initial assessment.
Management of acute asthma:
Oxygen therapy:
Give controlled supplementary oxygen therapy for all hypoxaemic
patients with severe acute asthma to maintain saturations of 94 –
98% (unless patient at risk of hypercapnic respiratory failure)
High-dose inhaled short-acting beta2-agonists are the first line
treatment (salbutamol or terbutaline):
A pressurised metered dose inhaler with spacer device is
preferred in patients with moderate to severe asthma (4 puffs
initially, followed by 2 puffs every 2 minutes according to response,
up to 10 puffs, whole process repeated every 10 – 20 minutes if
necessary)
The oxygen-driven nebulised route is recommended for patients
with life-threatening features or poorly responsive severe
asthma (salbutamol 5 mg at 15 - 30 minute intervals)
Consider continuous nebulisation in patients with severe acute
asthma that is poorly responsive to initial bolus dose (salbutamol at
5 - 10 mg/hour)
Reserve intravenous route for those in whom inhaled therapy
cannot be used reliably
Ipratropium bromide (muscarinic antagonist):
Add nebulised ipratropium bromide (0.5 mg 4 – 6 hourly) to
nebulised beta2-agonist treatment for patients with acute severe
or life threatening asthma or those with a poor initial response to
beta2-agonist therapy to provide greater bronchodilation
Steroid therapy:
Steroids reduce mortality, relapses, subsequent hospital admission and
requirement for β2 agonist therapy. The earlier they are given in the acute
attack the better the outcome.
Give steroids in adequate doses (prednisolone 40 - 50 mg) to all
patients with an acute asthma attack; steroid tablets are as
effective as injected steroids, provided they can be swallowed and
retained
Continue oral prednisolone (40 – 50 mg) daily for at least five days
or until recovery (steroids can usually be stopped abruptly, dose
does not need tapering)
Parenteral hydrocortisone (100 mg every 6 h, 400 mg daily) or
intramuscular methylprednisolone (160 mg) are alternatives in
patients who are unable to take oral prednisolone
Magnesium sulphate:
Nebulised magnesium is not recommended for treatment in adults
with acute asthma
Consider giving a single dose of IV magnesium sulphate (1.2 - 2 g IV
infusion over 20 minutes) to patients with acute severe asthma
who have not had a good initial response to inhaled bronchodilator
therapy
Aminophylline:
Intravenous aminophylline is not likely to result in any additional
bronchodilation compared to standard care with inhaled
bronchodilators and steroids and may cause side effects such as
arrhythmias and vomiting.
However, some patients with near-fatal asthma or life-threatening
asthma with a poor response to initial therapy may gain additional
benefit from IV aminophylline (5 mg/kg loading dose over 20
minutes unless on maintenance oral therapy, then continuous
infusion of 0.5 – 0.7 mg/kg/hr)
Intravenous magnesium sulphate or aminophylline should only be used
following consultation with senior medical staff
Routine prescription of antibiotics is not indicated for patients with acute
asthma
Drug Dose
Oxygen Give controlled supplementary oxygen therapy for all
hypoxaemic patients with acute severe asthma to
maintain saturations of 94 - 98%
Salbutamol pMDI + spacer (moderate/severe asthma): 4 puffs
initially, followed by 2 puffs every 2 minutes, up to
10 puffs, whole process repeated every 10 - 20
minutes if necessary
Oxygen-driven nebuliser (life-threatening or
poorly responsive severe asthma): salbutamol 5
mg at 15 - 30 minute intervals
Continuous nebulisation (asthma that is poorly
responsive to initial bolus dose): salbutamol at 5 -
10 mg/hour
Reserve intravenous route in those in whom
inhaled therapy cannot be used reliably
Ipratropium Add nebulised ipratropium bromide 0.5 mg 4 - 6 hourly
bromide to nebulised beta2-agonist treatment for patients with
acute severe or life threatening asthma or those with a
poor initial response to beta2-agonist therapy
Drug Dose
Steroid Oral prednisolone 40 - 50 mg daily for 5 days (or
until recovery)
Intravenous hydrocortisone 100 mg every 6 h
(400 mg daily) until patients can take oral therapy
Intramuscular methylprednisolone 160 mg in
patients unable to take oral therapy
Magnesium Nebulised magnesium is not recommended for
sulphate treatment in adults with acute asthma
Consider giving a single dose of IV magnesium
sulphate 1.2 - 2 g IV infusion over 20 minutes to
patients with acute severe asthma who have not
had a good initial response to inhaled
bronchodilator therapy
Aminophylline Some patients with near-fatal asthma or life-
threatening asthma with a poor response to initial
therapy may gain additional benefit from IV
aminophylline 5 mg/kg loading dose over 20 minutes
unless on maintenance oral therapy, then continuous
infusion of 0.5 - 0.7 mg/kg/hr
Antibiotics Not routinely prescribed in acute asthma
Patient Disposal
Patients whose PEFR is > 75% of predicted or best one hour after initial
treatment may be discharged from ED (unless there are other reasons why
admission is appropriate). It is essential that the patient’s primary care practice
is informed within 24 hours of discharge from the emergency department or
hospital following an asthma attack.
Admit all patients:
with any features of life-threatening or near-fatal asthma attack
with any feature of severe asthma attack persisting after initial treatment
Refer to ITU any patient:
requiring ventilatory support
with acute severe or life-threatening asthma, who is failing to respond to
therapy, as evidenced by:
deteriorating PEF
persisting or worsening hypoxia
hypercapnia
ABG analysis showing decreased pH or increased H+
exhaustion, feeble respiration
drowsiness, confusion, altered conscious state
respiratory arrest
https://www.brit-thoracic.org.uk/quality-improvement/guidelines/asthma/

NOVEMBER 2021
Anaphylaxis  Bookmark
Pathophysiology
Anaphylaxis is a severe, potentially life-threatening, generalised type I
hypersensitivity reaction. It occurs when an antigen binds to specific IgE
immunoglobulins on mast cells triggering degranulation and release of
inflammatory mediators (e.g. histamine, prostaglandins, and leukotrienes).
Patients with pre-existing asthma, especially poorly controlled asthma, are at
particular risk of life-threatening reactions.
Anaphylaxis can be triggered by any of a very broad range of triggers, but those
most commonly identified include food, drugs, latex and venom. Of foods, nuts
are the most common cause; muscle relaxants, antibiotics, NSAIDs and aspirin
are the most commonly implicated drugs. Food is the commonest trigger in
children and drugs the commonest in adults. A significant number of cases are
idiopathic.
Clinical Features
Severe anaphylaxis is characterised by sudden onset and rapidly developing,
life-threatening airway, breathing and circulation problems associated with skin
and/or mucosal changes.
Airway
Pharyngeal or laryngeal oedema with hoarseness and stridor
Breathing
Bronchospasm with tachypnoea, dyspnoea, wheeze, hypoxia,
cyanosis, respiratory arrest
Circulation
Peripheral vasodilation with hypotension, tachycardia, signs of
peripheral shut-down (e.g. pale, clammy), shock, cardiac arrest
Disability
Decreased brain perfusion leads to confusion, agitation and loss of
consciousness
Exposure
In about 80% of cases there are associated skin and mucosal
changes such as flushing, pruritus, urticaria and angioedema; skin
and/or mucosal changes can be absent or subtle in up to 20% of
reactions
Gastrointestinal symptoms
Nausea, vomiting, abdominal pain, diarrhoea, incontinence
Most reactions occur over several minutes; rarely, reactions may be slower in
onset. The speed of onset of the reaction depends on the trigger e.g.
intravenous medications will cause a more rapid onset than stings which in turn
will cause a more rapid onset than ingestion of food.
Reactions can vary greatly, from hypotension alone, to reactions with
predominantly asthmatic features, to cardiac/respiratory arrest. Skin or
mucosal changes alone are not a sign of an anaphylactic reaction.
Immediate Drug Treatment

Oxygen
Initially give 100% high flow oxygen using a mask with an oxygen
reservoir
Once pulse oximetry is feasible target an SpO2 of 94 - 98%
Adrenaline
This is the most important drug for treatment of anaphylaxis and
works best when given as early as possible after the onset of the
reaction:
The intramuscular route is best for most individuals; the best site
for IM injection is the anterolateral aspect of the middle third of the
thigh.
As an alpha-receptor agonist, it reverses peripheral vasodilation
and reduces oedema. As a beta-receptor agonist it dilates bronchial
airways, increases the force of myocardial contraction, and
suppresses histamine and leukotriene release.
For adults, the initial dose is 0.5 mg = 500 micrograms = 0.5 mL of
1:1000 adrenaline. After the initial dose of adrenaline, further doses
can be given at about 5 min intervals according to the patient's
response.
If features of anaphylaxis persist despite 2 doses of IM adrenaline,
the refractory anaphylaxis algorithm should be followed, and an
adrenaline infusion started with expert support.
Nebulised adrenaline may be effective as an adjunct to treat upper
airway obstruction caused by laryngeal oedema, but only after
treatment with IM (or IV) adrenaline and not as an alternative.
Recommended doses are 5 mL of 1 mg ML (1:1000) adrenaline.
Adrenaline remains the first line vasopressor for treatment of
anaphylaxis. Consider other vasopressors and inotropes (e.g.
noradrenaline, vasopressin, metaraminol and glucagon) when initial
resuscitation with adrenaline and fluids has not been successful.
Only use these drugs in specialist settings where there is
experience in their use.
Intravenous fluid
A rapid IV fluid challenge (crystalloid 10 mL/kg in a child or 500 -
1000 mL in an adult) should be administered and the response
monitored; further doses can be given if necessary.
There is no evidence to support the use of colloid over crystalloid
fluid in resuscitation, therefore crystalloid fluid (Hartmann's
solution or 0.9% saline) should be given as colloids have a higher
risk of hypersensitivity reactions.
Updates in ALS 12th edition (2021):
Antihistamines
Antihistamines are not recommended for the treatment of
anaphylaxis. They are of no benefit in treating life-
threatening symptoms of anaphylaxis and their use may
delay more appropriate treatment. Antihistamines may be
helpful in alleviating cutaneous symptoms but should only be
given after the patient has been stabilised. In this context,
use a non-sedating oral antihistamine, such as cetirizine.
Corticosteroids
The routine administration of corticosteroids is not advised.
Consider giving steroids after initial resuscitation for
refractory reactions or ongoing asthma/resistant shock.
Steroids should not be given preferentially to adrenaline. The
evidence that corticosteroids help shorten protracted
symptoms or prevent biphasic reactions is very weak. Oral
corticosteroids may be indicated where an acute asthma
exacerbation may have contributed to the severity of the
anaphylaxis. Steroids should be given via the oral route
where possible.
Age group IM adrenaline (1:1000)

Adult 500 mcg (0.5 mL)
Child > 12 years 500 mcg (0.5 mL)
Child 6 - 12 years 300 mcg (0.3 mL)
Child 6 months - 6 years 150 mcg (0.15 mL)
Child < 6 months 100-150 mcg (0.1 - 0.15 mL)
Investigations
Emergency treatment should not be delayed and should be based on a clinical
diagnosis of anaphylaxis. In addition to the usual investigations appropriate for
a medical emergency, the specific test to help confirm the diagnosis of
anaphylaxis is measurement of mast cell tryptase. Tryptase is a major
component of mast cell granules, therefore in anaphylaxis mast cell
degranulation leads to markedly increased blood tryptase concentration.
Tryptase concentration in the blood may not increase significantly until 30
minutes or more after the onset of symptoms and peaks 1 - 2 hours after onset.
Ideally three timed samples are taken, the initial sample as soon as feasible after
resuscitation has started, the second sample 1 - 2 hours (but no later than 4 h)
after the start of the symptoms and the third sample either at 24 h or in
convalescence (for baseline levels).
Discharge and Follow-Up

All patients should be reviewed by a senior clinician and a decision made about
the need for further treatment and duration of observation. There is no reliable
way of predicting who will have a biphasic reaction so decisions about
discharge must be made for each patient by an experienced clinician. Prior to
discharge, a healthcare with the appropriate skills should offer people the
following:
Information about anaphylaxis, including the signs and symptoms, and
the risk of a biphasic reaction (with clear instructions about returning to
hospital if symptoms return)
Information about what to do if anaphylaxis occurs
Consideration of an adrenaline auto-injector or a replacement
Advice about how to avoid the suspected trigger
Information about the need for referrals to specialist allergy service
Information about patient support groups

Oxygen Therapy LAST UPDATED: 28TH
MARCH 2019
 Bookmark
Oxygen should be regarded as a drug. It is prescribed for hypoxaemic patients

to increase alveolar oxygen tension and decrease the work of breathing. The
concentration of oxygen required depends on the condition being treated; the
administration of an inappropriate concentration of oxygen can have serious
or even fatal consequences.
High Concentration Oxygen Therapy

In most acutely ill patients with a normal or low arterial carbon dioxide
(PaCO2), oxygen saturation should be 94 – 98% oxygen saturation. However,
in some clinical situations such as cardiac arrest and carbon monoxide
poisoning it is more appropriate to aim for the highest possible oxygen
saturation until the patient is stable.
Low Concentration Oxygen Therapy

A lower target of 88 – 92% oxygen saturation is indicated for patients at risk of
hypercapnic respiratory failure e.g. patients with COPD. Until blood gases can
be measured, initial oxygen should be given using a controlled concentration
of 28% or less, titrated towards the SpO2 of 88 - 92%. The aim is to provide the
patient with enough oxygen to achieve an acceptable arterial oxygen tension
without worsening carbon dioxide retention and respiratory acidosis.
Long Term Oxygen Therapy

Long-term administration of oxygen (usually at least 15 hours daily) prolongs
survival in some patients with COPD. Assessment for long-term oxygen
therapy requires measurement of arterial blood gas tensions. A nasal cannula
is usually preferred for long-term oxygen therapy from an oxygen
concentrator. It can, however, produce dermatitis and mucosal drying in
sensitive individuals.
Giving oxygen by nasal cannula allows the patient to talk, eat, and drink, but
the concentration of oxygen is not controlled; this may not be appropriate for
acute respiratory failure. Increased respiratory depression is seldom a
problem in patients with stable respiratory failure treated with low
concentrations of oxygen although it may occur during exacerbations;
patients and relatives should be warned to call for medical help if drowsiness
or confusion occur.
Intermittent Oxygen Therapy

Oxygen is occasionally prescribed for short-burst (intermittent) use for
episodes of breathlessness not relieved by other treatment in patients with
severe chronic obstructive pulmonary disease, interstitial lung disease, heart
failure, and in palliative care.
Ambulatory Oxygen
Ambulatory oxygen is prescribed for patients on long-term oxygen therapy
who need to be away from home on a regular basis. Patients who are not on
long-term oxygen therapy can be considered for ambulatory oxygen therapy if
there is evidence of exercise-induced oxygen desaturation and of
improvement in blood oxygen saturation and exercise capacity with oxygen.

Selective Beta-2 Agonists LAST UPDATED: 28TH
MARCH 2019
 Bookmark
Selective beta-2 agonists act directly on beta-2 receptors, causing smooth

muscle relaxation and dilation of the airways.
Indications
Mild to moderate symptoms of asthma respond rapidly to the inhalation of a
selective short-acting beta2 agonist such as salbutamol or terbutaline
sulfate. Short-acting beta-2 agonists have a rapid onset of action (15
minutes) and their effects last for up to 4 hours. Salbutamol or terbutaline
sulfate can be given intravenously for severe or life-threatening acute
asthma; patients should be carefully monitored and the dose adjusted
according to response and heart rate.
Short acting beta-2 agonists are used for immediate relief of asthma
symptoms, while some long-acting beta-2 agonists (e.g. salmeterol) are
added to an inhaled corticosteroid in patients requiring prophylactic
treatment.
Cautions
Beta-2 agonists should be used with caution in people with:
Cardiovascular disease including arrhythmias and hypertension (beta-2
agonists may cause an increased risk of arrhythmias and significant
changes to blood pressure and heart rate)
Diabetes (risk of hyperglycaemia and ketoacidosis, especially with
intravenous use)
Hyperthyroidism (beta-2 agonists may stimulate thyroid activity)
Hypokalaemia (potentially serious hypokalaemia may result from beta-
2 agonist therapy; this effect may be potentiated in severe asthma
by concomitant treatment with theophylline, corticosteroids, diuretics
and by hypoxia)
Susceptibility to QT-interval prolongation
Convulsive disorders
Interactions
Hypokalaemia may be potentiated by concomitant treatment with
theophylline and its derivatives, corticosteroids, and diuretics. This in turn
may predispose to toxicity in patients taking digoxin.
Side Effects
Side effects are usually dose related and include:
Fine tremor — occurs particularly in the hands and is usually worse in
the first few days of treatment.
Palpitations and tachycardia
Headache
Seizure
Anxiety
Hypokalaemia
Cardiac arrhythmia and paradoxical bronchospasm (rare)
Acute angle-closure glaucoma

Theophylline LAST UPDATED: 28TH
MARCH 2019
 Bookmark
Theophylline may have an additive bronchodilation effect when used in

conjunction with small doses of beta-2 agonists. Theophylline is a xanthine
which inhibits phosphodiesterase resulting in increased tissue concentrations
of cyclic adenosine monophosphate (cAMP).
Theophylline is metabolised in the liver, and has a narrow therapeutic index.
The plasma theophylline concentration is increased in heart failure, hepatic
impairment, in viral infections, in fever and in the elderly. A reduction in
dosage may be necessary to avoid toxic accumulation. The plasma
theophylline concentration is decreased in smokers, and by alcohol
consumption.
Indications
It is used as a bronchodilator in asthma and stable COPD. It is not generally
effective in exacerbations of chronic obstructive pulmonary disease, but is
used rarely for severe or life-threatening acute asthma given by injection as
aminophylline, a mixture of theophylline with ethylenediamine, which is 20
times more soluble than theophylline alone.
Contraindications
Theophylline should not be prescribed to:
People with porphyria
People with hypersensitivity to xanthines
Children concomitantly receiving ephedrine
Infants under 6 months of age
Cautions
Theophylline should be used with caution in people with:
Cardiac arrhythmias or other cardiac disease
Hepatic impairment
Epilepsy
Hypertension
Hyperthyroidism
Peptic ulcer
Risk of hypokalaemia
Interactions
Hypokalaemia may be potentiated by concomitant therapy with beta-2
agonists, corticosteroids and diuretics.
Excretion of lithium may be potentiated by concomitant therapy with
theophylline.
There is an increased risk of convulsions when theophylline is given with
quinolones.
Examples of enzyme-inhibiting Examples of enzyme-inducing

drugs (raise plasma drugs (lower plasma
theophylline level) theophylline level)
Erythromycin Primidone
Clarithromycin Phenobarbital
Ciprofloxacin Carbamazepine
Fluconazole Phenytoin
Verapamil Ritonavir
Allopurinol Rifampicin
Cimetidine St John's Wort
Side Effects
Side effects include:
Tachycardia, palpitations and arrhythmias
CNS stimulation, tremor, headache, insomnia and convulsions
Gastric irritation, nausea, vomiting and diarrhoea
Hypokalaemia (potentially serious hypokalaemia may result from beta-2
agonist therapy; this effect may be potentiated in severe asthma by
concomitant treatment with theophylline and its derivatives,
corticosteroids, and diuretics, and by hypoxia)
Monitoring Requirements
In most individuals, a plasma-theophylline concentration of 10 – 20 mg/litre
(55 – 110 micromol/litre) is required for satisfactory bronchodilation, although
a lower plasma-theophylline concentration of 5 – 15 mg/litre may be effective.
Adverse effects can occur within the range 10 – 20 mg/litre and both the
frequency and severity increase at concentrations above 20 mg/litre.
Plasma-theophylline concentration is measured 5 days after starting oral
treatment and at least 3 days after any dose adjustment.
Overdose
Theophylline in overdose can cause vomiting (which may be severe and
intractable), agitation, restlessness, dilated pupils, sinus tachycardia, and
hyperglycaemia. More serious effects are haematemesis, convulsions, and
supraventricular and ventricular arrhythmias. Severe hypokalaemia may
develop rapidly.

Something wrong?
Intravenous Replacement LAST UPDATED: 26TH

MARCH 2019
Therapy  Bookmark
PHARMACOLOGY / FLUIDS AND ELECTROLYTES
Solutions of electrolytes are given intravenously to meet normal fluid and electrolyte
requirements or to replenish substantial deficits or continuing losses when the
patient is nauseated or vomiting and is unable to take adequate amounts by
mouth. When intravenous administration is not possible, fluid (as sodium chloride
0.9% or glucose 5%) can also be given by subcutaneous infusion.
Sodium Chloride
Normal saline (sodium chloride 0.9%) contains:
Na+ 150 mmol/L

Cl- 150 mmol/L
Sodium chloride in isotonic solution (0.9%) provides the most important extracellular
ions in near physiological concentrations and is indicated in sodium depletion which
can arise from such conditions as gastroenteritis, diabetic ketoacidosis, ileus, and
ascites.
Chronic hyponatraemia arising from inappropriate secretion of antidiuretic hormone
should ideally be corrected by fluid restriction. If sodium chloride is required for
acute or chronic hyponatraemia, regardless of the cause, the deficit should be
corrected slowly to avoid the risk of osmotic demyelination syndrome and the rise in
plasma sodium concentration should not exceed 10 mmol/L in 24 hours. In severe
hyponatraemia, sodium chloride 1.8 % may be used cautiously.
Hartmann's Solution
Hartmann’s solution (compound sodium lactate) can be used instead of isotonic
sodium chloride solution during or after surgery, or in the initial management of the
injured or wounded; it may reduce the risk of hyperchloraemic acidosis.
Hartmann's solution contains:
Na+ 131 mmol/L

K+ 5 mmol/L
HCO3- 29 mmol/L
Cl- 111 mmol/L
Glucose
Ca2+ 2 mmol/L
Glucose solutions (5%) are used mainly to replace water deficit. Average water
requirements in a healthy adult are 1.5 to 2.5 litres daily and this is needed to balance
unavoidable losses of water through the skin and lungs and to provide sufficient for
urinary excretion. Dehydration may occur when these losses are not compensated
for by intake e.g. in coma, or in the elderly. Excessive loss of water without loss of
electrolyte is uncommon, occurring in fevers, hyperthyroidism, diabetes insipidus
and hypercalcaemia.
Glucose solutions are also used to correct and prevent hypoglycaemia and to provide
a source of energy in those too ill to be fed adequately by mouth.
Glucose solutions are also given in regimens with calcium and insulin for the
emergency management of hyperkalaemia. They are also given after correction of
hyperglycaemia during treatment of diabetic ketoacidosis, when they must be
accompanied by continuing insulin infusion.
Potassium Chloride Mixtures

Potassium chloride with sodium chloride intravenous infusion is the initial treatment
for the correction of severe hypokalaemia and when sufficient potassium cannot be
taken by mouth. Repeated measurement of plasma-potassium concentration is
necessary to avoid the development of hyperkalaemia, particularly in renal
impairment. Initial potassium replacement therapy should not involve glucose
infusions, because glucose may cause a further decrease in the plasma-potassium
concentration.
Sodium Bicarbonate
Sodium bicarbonate is used to control severe metabolic acidosis (pH < 7.1)
particularly that caused by loss of bicarbonate (as in renal tubular acidosis or from
excessive gastrointestinal losses). Mild metabolic acidosis associated with volume
depletion should first be managed by appropriate fluid replacement because acidosis
usually resolves as tissue and renal perfusion are restored.
In more severe metabolic acidosis or when the acidosis remains unresponsive to
correction of anoxia or hypovolaemia, sodium bicarbonate (1.26%) can be infused
over 3 – 4 hours with plasma-pH and electrolyte monitoring. In severe shock, for
example in cardiac arrest, metabolic acidosis can develop without sodium or volume
depletion; in these circumstances sodium bicarbonate is best given as a small
volume of hypertonic solution, such as 50 mL of 8.4% solution intravenously.
Albumin
Albumin solutions, prepared from whole blood, contain soluble proteins and
electrolytes but no clotting factors, blood group antibodies, or plasma
cholinesterases thus may be given without regard to the recipient’s blood group.
Albumin is usually used after the acute phase of illness to correct a plasma-volume
deficit; hypoalbuminaemia itself is not an appropriate indication and the use of
albumin solution in acute plasma or blood loss is wasteful where plasma substitutes
should be used instead.
Concentrated albumin solution (20%) can be used under specialist supervision in
patients with an intravascular fluid deficit and oedema because of interstitial fluid
overload, to restore intravascular plasma volume with less exacerbation of the salt
and water overload than isotonic solutions. Concentrated albumin solution may also
be used to obtain a diuresis in hypoalbuminaemic patients (e.g. in hepatic cirrhosis).
Plasma Substitutes
Dextran and gelatin may be used at the outset to expand and maintain blood volume
in shock arising from conditions such as burns or septicaemia; they may also be
used as an immediate short-term measure to treat haemorrhage until blood is
available. Dextran and gelatin are rarely needed when shock is due to sodium and
Acute severe hyperkalaemia is characterised by a plasma-potassium concentration above
6.5 mmol/litre or the presence of ECG changes. ECG changes observed in hyperkalaemia may
include tall peaked T waves, flattening or loss of P waves, broadening of QRS complexes, PR
prolongation and bradycardia.
Emergency Management
1. Reduce cardiac cell membrane excitability:
10 ml calcium gluconate 10% by slow intravenous injection over 5 minutes
ECG changes should improve within 1 - 3 minutes, but only has a transient
effect of about 30 minutes
If there is no improvement, a further 10 ml should be given every 5 - 10
minutes until the ECG normalises (max 3 doses in total)
If the patient is taking digoxin, the calcium gluconate should be given slowly
(mixed with 100 ml 5% glucose and given over 20 minutes) as rapid calcium
administration may precipitate myocardial digoxin toxicity
2. Transcellular shift from extracellular to intracellular space:

Intravenous infusion of insulin-glucose given as 10 units of Actrapid added to 50 ml
of glucose 50% infused over 30 minutes
Potassium should decrease by about 0.6 - 1.0 mmol/L in 15 minutes and the
reduction lasts for about 60 minutes
This is repeated if necessary or a continuous infusion initiated
Nebulised salbutamol 10 mg
Reduces potassium by about 0.5 - 1.0 mmol/L in 15 - 30 minutes and lasts for
about two hours
Should be used with caution in patients with ischaemic heart disease and
history of cardiac arrhythmias
Response is attenuated in patients on beta-blockers and digoxin
The correction of causal or compounding acidosis with sodium bicarbonate infusion

should be considered (if pH < 7.2)
Correction of acidosis promotes intracellular uptake of K+
3. Reduce total body potassium:

Any potassium supplements should be stopped, as well as any drugs that might
precipitate hyperkalaemia (e.g. digoxin, beta-blockers)
Consider low potassium diet
Urinary potassium loss should be promoted with the use of appropriate fluids or
diuretics to maintain good urine output
Calcium resonium 15 g PO TDS
Ion-exchange resin that exchanges sodium for potassium as it passes
through the intestine
Should be given with regular laxatives to prevent constipation
Each gram removes approximately 1 mmol/L of potassium but onset is slow,
taking 2 - 6 hours or longer
Contraindicated in patients with pre-existing hypercalcaemia
If the patient does not respond to the above measures dialysis will be required. Dialysis is likely to
be needed if potassium is very high (> 7.5 mmol/L), if the patient is oligo/anuric, if the patient is
already on long term dialysis or if the patient has advanced CKD.
Treatment Administration Mechanism Time to Duration Achievable

of Action Onset of reduction
of Action of serum
Action K+
Calcium 15 g PO TDS Ion- 2-6 4-6 Unknown
resonium exchange hours or hours
resin that longer
exchanges
sodium for
potassium
as it passes
through
intestine
Calcium 10 ml calcium Antagonises 1-3 30 N/A
gluconate gluconate 10% cardiac minutes minutes
by IV injection membrane
over 5 mins excitability
Insulin- 10 units Increases Within 60 0.6 - 1
glucose Actrapid in 50 intracellular 15 minutes mmol/L
infusion ml glucose 50% uptake of K+ minutes
infused over 30 via Na-K
mins ATP pump
Nebulised 10 mg Increases Within 1-3 0.5 - 1
salbutamol nebulised intracellular 30 hours mmol/L
uptake of K+ minutes
via Na-K
ATP pump
Treatment Administration Mechanism Time to Duration Achievable
of Action Onset of reduction
of Action of serum
Action K+
Sodium 1.26% 500 ml IV Corrects After 60 Unknown Unknown
bicarbonate over 2 hours acidosis and minutes
thus
promotes
intracellular
uptake of K+

Management of Thiamine LAST UPDATED: 27TH
MARCH 2019
Deficiency  Bookmark
Deficiency of the B vitamins, other than vitamin B12, is rare in the UK and is
usually treated by preparations containing thiamine (B1), riboflavin (B2), and
nicotinamide.
The severe deficiency states Wernicke’s encephalopathy and Korsakoff’s
psychosis, especially as seen in chronic alcoholism, are best treated initially by
the parenteral administration of B vitamins (Pabrinex®), followed by oral
administration of thiamine in the longer term.
Administration
For prophylaxis of Wernicke's encephalopathy 1 pair of ampoules of Pabrinex I/V
high Potency are given once daily for at least 3 – 5 days by intravenous infusion
or deep muscular injection.
Oral thiamine should be continued long-term in harmful drinkers if they are
malnourished or at risk of malnourishment or if they have decompensated liver
disease.
CHM Advice
Although potentially serious allergic adverse reactions may rarely occur during, or
shortly after, parenteral administration of thiamine, the CHM has recommended
that:
this should not preclude the use of parenteral thiamine in patients where
this route of administration is required, particularly in patients at risk of
Wernicke-Korsakoff syndrome where treatment with thiamine is essential
intravenous administration should be by infusion over 30 minutes
facilities for treating anaphylaxis should be available when parenteral
thiamine is administered
Oral Rehydration Therapy LAST UPDATED: 3RD
APRIL 2019
 Bookmark
As a worldwide problem diarrhoea is by far the most important indication for fluid
and electrolyte replacement.
Mechanism of Action
Intestinal absorption of sodium and water is enhanced by glucose (and other
carbohydrates). Replacement of fluid and electrolytes lost through diarrhoea can
therefore be achieved by giving solutions (e.g. Dioralyte) containing sodium,
potassium, and glucose or another carbohydrate such as rice starch.
Oral rehydration solutions should:
enhance the absorption of water and electrolytes;
replace the electrolyte deficit adequately and safely;
contain an alkalinising agent to counter acidosis;
be slightly hypo-osmolar (about 250 mmol/litre) to prevent the possible
induction of osmotic diarrhoea;
be simple to use in hospital and at home;
be palatable and acceptable, especially to children;
be readily available.
Administration
Rehydration should be rapid over 3 to 4 hours (except in hypernatraemic
dehydration in which case rehydration should occur more slowly over 12 hours).
The patient should be reassessed after initial rehydration and if still dehydrated
rapid fluid replacement should continue.
Once rehydration is complete further dehydration is prevented by encouraging
the patient to drink normal volumes of an appropriate fluid and by replacing
continuing losses with an oral rehydration solution.
Potassium Supplements LAST UPDATED: 26TH
MARCH 2019
 Bookmark
Indications
Compensation for potassium loss is particularly necessary:
in those taking digoxin or antiarrhythmic drugs, where potassium depletion
may induce arrhythmias
in patients in whom secondary hyperaldosteronism occurs, e.g. renal artery
stenosis, cirrhosis of the liver, nephrotic syndrome, and severe heart failure
in patients with excessive losses of potassium in the faeces, e.g. chronic
diarrhoea associated with intestinal malabsorption or laxative abuse
Other groups which may be prone to hypokalaemia include:
the elderly who frequently take inadequate amounts of potassium in the
diet (although this must be balanced with the risks of renal insufficiency)
patients on long-term drug therapy with drugs known to cause
hypokalaemia e.g. corticosteroids, or diuretics
Administration
Potassium salts may be given by mouth to prevent deficiencies or to treat
established deficiencies of mild or moderate degree. Potassium salts cause
nausea/vomiting and poor compliance is a major limitation to their effectiveness.
In established hypokalaemia, larger oral or intravenous doses may be required;
hypokalaemia is frequently associated with chloride depletion and metabolic
alkalosis and this must also be corrected.

Proton Pump Inhibitors LAST UPDATED: 26TH
MARCH 2019
PHARMACOLOGY / GASTROINTESTINAL
 Bookmark
Mechanism of Action
Proton pump inhibitors act by directly inhibiting the H+/K+ ATPase (proton) pump
on gastric parietal cell luminal membranes and thus inhibiting acid secretion.
Indications
Proton pump inhibitors may be indicated for:
treatment of gastric and duodenal ulcers
eradication of Helicobacter pylori in combination with antibacterials
treatment of dyspepsia and GORD
post-endoscopic treatment of severe peptic ulcer bleeding (an intravenous
high dose PPI reduces risk of rebleeding and the need for surgery)
treatment and prevention of NSAID-associated ulcers
cystic fibrosis (reduces degradation of pancreatic enzyme supplements)
Zollinger-Ellison syndrome (controls excessive gastric acid secretion)
Cautions
Proton pump inhibitors:
can increase the risk of fractures (particularly when used at high doses for
over a year in the elderly or used in those at risk of osteoporosis)
may increase the risk of gastrointestinal infections (including Clostridium
difficile infection)
may mask the symptoms of gastric cancer (in patients with 'alarm features',
gastric malignancy should be ruled out before starting treatment)
can cause false negative H. pylori test results (and should be stopped at
least 2 weeks before testing)
Side Effects
Common side effects (usually mild and reversible) include:
abdominal pain
constipation
diarrhoea
flatulence
headache
nausea
vomiting
dizziness
skin rashes
Possible adverse effects of long-term PPI treatment:
Hypomagnesaemia (measurement of serum magnesium concentrations
should be considered before and during prolonged treatment with a PPI,
especially when used with other drugs that cause hypomagnesaemia or
with digoxin)
Rebound acid hypersecretion and protracted dyspepsia after stopping
prolonged treatment
Interstitial nephritis
Vitamin B12 deficiency
Administration
Omeprazole:
H. pylori eradication regimen dose: 20 mg od
Healing peptic ulcer: 20 mg od (40 mg od may be used in severe or
recurrent cases)
Healing NSAID-associated ulcer: 20 mg od
Prophylaxis for NSAID-associated ulcer: 20 mg od
Major peptic ulcer bleeding (following endoscopic treatment): Initially
80 mg, to be given over 40–60 minutes, then (by continuous intravenous
infusion) 8 mg/hour for 72 hours, subsequent dose then changed to oral
therapy
Management of Dyspepsia LAST UPDATED: 27TH
MARCH 2019
and GORD  Bookmark
Dyspepsia is upper abdominal discomfort or pain which may be described as a

burning sensation, a heaviness, or an ache. It is often related to eating and may
be accompanied by other symptoms such as nausea, fullness in the upper
abdomen, or belching. The most common causes of dyspepsia are gastro-
oesophageal reflux disease (GORD), peptic ulcer disease and non-ulcer
(functional) dyspepsia.
Patients with dyspepsia/GORD should be advised that symptoms may improve if
they:
lose weight (if they are overweight)
stop smoking
reduce alcohol consumption
reduce intake of any food or drink associated with worsening symptoms
avoid having meals within 3 - 4 hours of going to bed
raise the height of the head of the bed by a few inches

Antacids LAST UPDATED: 26TH
MARCH 2019
 Bookmark
Indications
Antacids are used for symptomatic relief in dyspepsia and in GORD.
Mechanism of Action
Antacids work by neutralising gastric acid and raising the luminal pH. However,
the effect is only for a relatively short period, requiring frequent administration.
Antacids do promote ulcer healing, but less well than antisecretory drugs.
Administration
Antacids are best taken when symptoms occur or are expected, usually between
meals and at bedtime. Liquid preparations are more effective than tablet
preparations.
Interactions
Antacids should preferably not be taken at the same time as other drugs since
they may impair absorption. Antacids may damage enteric coatings designed to
prevent dissolution in the stomach.
Side Effects
Aluminium- and magnesium-containing antacids (e.g. aluminium hydroxide,

magnesium carbonate), being relatively insoluble in water, are long acting if
retained in the stomach. Magnesium-containing antacids tend to be laxative
whereas aluminium-containing antacids tend to be constipating; antacids
containing both magnesium and aluminium may reduce these colonic side
effects.
Contraindications
Antacids are contraindicated in hypophosphataemia.
Alginates
Alginates taken in combination with an antacid increases the viscosity of
stomach contents and can protect the oesophageal mucosa from acid reflux.
Some alginate-containing preparations e.g. Gaviscon form a viscous gel raft that
floats on the surface of the stomach contents, thereby reducing symptoms of
reflux.

Antimuscarinics LAST UPDATED: 15TH
MAY 2019
 Bookmark
Indications
Antimuscarinics reduce intestinal motility (by acting on acetylcholine receptors
and relaxing smooth muscle) and can be used as antispasmodics for the
management of irritable bowel syndrome. Hyoscine butylbromide is advocated as
a gastrointestinal antispasmodic, but it is poorly absorbed and thus has limited
clinical utility.
Other indications for antimuscarinic drugs include arrhythmias, asthma and
airways disease, motion sickness, parkinsonism, urinary incontinence, to cause
mydriasis and cycloplegia, premedication, and as an antidote to organophosphate
poisoning.
Cautions
Antimuscarinics should be used with caution in:
acute myocardial infarction
arrhythmias (may be worsened)
autonomic neuropathy
cardiac insufficiency (due to association with tachycardia)
cardiac surgery (due to association with tachycardia)
children (increased risk of side effects)
conditions characterised by tachycardia
congestive heart failure (may be worsened)
coronary artery disease (may be worsened)
diarrhoea
elderly (especially if frail)
gastro-oesophageal reflux disease
hiatus hernia with reflux oesophagitis
hypertension
hyperthyroidism (due to association with tachycardia)
individuals susceptible to angle-closure glaucoma
prostatic hyperplasia
pyrexia
ulcerative colitis
Contraindications
Antimuscarinics are contraindicated in:
gastrointestinal obstruction
intestinal atony
myasthenia gravis
paralytic ileus
prostatic enlargement
pyloric stenosis
severe ulcerative colitis
significant bladder outflow obstruction
toxic megacolon
urinary retention
Side Effects
Many drugs have antimuscarinic effects; concomitant use of two or more such
drugs can increase side effects such as dry mouth, urine retention, and
constipation.
Side effects of antimuscarinics include:
dilation of pupils with loss of accommodation (cycloplegia) and photophobia
resulting in blurred vision ("Blind as a bat")
dry mouth, eyes and skin ("Dry as a bone")
elevated temperature ("Hot as a hare")
skin flushing ("Red as a beet")
confusion or agitation particularly in the elderly ("Mad as a hatter")
reduced bronchial secretions
transient bradycardia followed by tachycardia, palpitation and arrhythmias
urinary retention
constipation
Acute Diarrhoea LAST UPDATED: 26TH
MARCH 2019
 Bookmark
Acute Diarrhoea
The priority in the management of acute diarrhoea, such as in gastroenteritis, is
the prevention or reversal of fluid and electrolyte depletion. This is particularly
important in infants, and in frail and elderly patients. Oral rehydration
preparations may be used, or in more severe cases patients may be admitted to
hospital and given intravenous fluid and electrolyte replacement.
Antimotility Drugs
Antimotility drugs can relieve symptoms of acute diarrhoea by decreasing
intestinal secretion and motility, prolonging intestinal transit time and
facilitating water reabsorption (e.g. loperamide acting on opioid mu-receptors).
They may be used in the management of uncomplicated acute diarrhoea in
adults but are not recommended for acute diarrhoea in young children.
Antimotility drugs are contraindicated in active ulcerative colitis, antibiotic-
associated colitis and conditions where abdominal distension develops or where
inhibition of peristalsis should be avoided.
Antispasmodics
Antispasmodics are occasionally of value in treating abdominal cramp
associated with diarrhoea in adults but they should not be used for primary
treatment.
Antispasmodics and antiemetics should be avoided in young children with
gastroenteritis because they are rarely effective and have troublesome side
effects.
MARCH 2019
Inflammatory Bowel Disease  Bookmark
Aminosalicylates, corticosteroids and drugs that affect the immune response are
used in the management of inflammatory bowel disease.
Patients who present with acute exacerbations of a known inflammatory bowel
disease often require specialist advice and input.
Management of Acute Exacerbations

Acute mild to moderate disease affecting the rectum (proctitis) or the
rectosigmoid is treated initially with local application of an aminosalicylate;
alternatively, a local corticosteroid can be used but it is less effective. A
combination of a local aminosalicylate and a local corticosteroid can be
used for proctitis that does not respond to a local aminosalicylate alone.
Diffuse inflammatory bowel disease or disease that does not respond to
local therapy requires oral treatment:
Mild disease affecting the proximal colon can be treated with an oral
aminosalicylate alone; a combination of a local and an oral
aminosalicylate can be used in proctitis or distal colitis.
Refractory or moderate inflammatory bowel disease usually requires
adjunctive use of an oral corticosteroid such as prednisolone for 4 –
8 weeks.
Severe inflammatory bowel disease or disease that is not responding
to an oral corticosteroid requires hospital admission and treatment
with an intravenous corticosteroid (such as hydrocortisone or
methylprednisolone); other therapy may include intravenous fluid and
electrolyte replacement, and possibly parenteral nutrition. Specialist
supervision is required for patients who fail to respond adequately to
these measures.

Active Immunity LAST UPDATED: 26TH
MARCH 2019
PHARMACOLOGY /
IMMUNOGLOBULINS AND VACCINES  Bookmark
Active immunity can be acquired by natural disease or by vaccination.

Vaccines stimulate production of antibodies and other components of the immune
response.
Types of Vaccine
Vaccines may consist of:
1. A live attenuated form of a virus or bacteria

2. Inactivated preparations of the virus or bacteria
3. Detoxified exotoxins produced by the microorganism
4. Extracts of a microorganism, which may be derived from the organism (e.g.
pneumococcal capsular polysaccharide) or produced by recombinant DNA
technology (e.g. hepatitis B surface antigen)
Vaccine Type Type Examples

Live attenuated BCG, MMR, varicella-zoster, rotavirus, influenza (nasal
spray), polio (oral)
Inactivated Hepatitis A, influenza, polio, pertussis, rabies
preparation
Detoxified Tetanus, diphtheria
exotoxins
Extracts Men A & C, pneumococcus, Hib, hepatitis B
Key Differences
Vaccine Type Live Attenuated Inactivated

Vaccine Type Live Attenuated Inactivated
Cell-mediated Yes Weak or
immunity none
Humoral IgA and IgG IgG
immunity
Duration of Boosting often unnecessary Boosting
response often
required
Immunogenicity Potent Poor (often
requires
adjuvant)
Safety of Possible reversion to virulence, Safe if
vaccine possible spread to non-immune completely
individuals, unsafe in inactivated
immunocompromised individuals (and
pregnant women)
Stability at Low High
room
temperature
Contraindications
Vaccines are contraindicated in individuals with an allergy to a vaccine component
or a history of a reaction to a previous dose of vaccine.
Immunocompromised individuals should not be given live vaccines. Live vaccines
should not be administered routinely to pregnant women because of the
theoretical risk of fetal infection but where there is a significant risk of exposure to
disease, the need for vaccination usually outweighs any possible risk to the fetus.
Vaccination may be postponed if the individual is suffering from an acute illness;

however, it is not necessary to postpone immunisation in patients with minor
illnesses without fever or systemic upset.
Side Effects
Common side effects of vaccines include: fatigue; fever; gastrointestinal
disturbances; headache; irritability; loss of appetite; lymphangitis; malaise and
myalgia. Anaphylaxis, angioedema, bronchospasm and hypersensitivity reactions
may occur very rarely. Induration, inflammation, pain, redness and sterile abscess
may develop at the injection site.
Post-Immunisation Pyrexia
In infants the parent should be advised that if pyrexia develops after childhood
immunisation, and the infant seems distressed, paracetamol can be given or
ibuprofen can be used if paracetamol is unsuitable. They should be warned to seek
medical advice if the pyrexia persists.

Pharmacology
Immunoglobulins and Vaccines
Something wrong?
Passive Immunity LAST UPDATED: 26TH

MARCH 2019
PHARMACOLOGY / IMMUNOGLOBULINS AND VACCINES
 Bookmark
Passive immunity to a disease can be obtained by injected immunoglobulin preparations

made from the plasma of immune individuals with adequate levels of antibody to that
disease. This confers immediate protection but the duration of immunity varies according
to the dose and the type of immunoglobulin; where necessary passive immunity can be
repeated.
Two types of human immunoglobulin preparation are available, normal immunoglobulin
and disease-specific immunoglobulins:
Normal immunoglobulin for intramuscular administration is available from some regional
Public Health laboratories for protection of contacts and the control of outbreaks of:
hepatitis A
measles
rubella (to a lesser extent)
Disease specific immunoglobulins are available for:
hepatitis B
rabies
tetanus
varicella-zoster
Normal Immunoglobulin
Indications for hepatitis A:
Prevention of infection in close contacts of confirmed cases of hepatitis A who
have/are:
chronic liver disease
HIV infection
immunosuppressed
over 50 years of age
Prophylaxis of infection in immunosuppressed people travelling to high risk areas
(where antibody response to vaccine may be inadequate)
Indications for measles:
Prevention or attenuation of an attack of measles in individuals who do not have
adequate immunity, in infants under 9 months and in non-immune pregnant
women who have been in contact with a confirmed case of measles or who are
associated with a local outbreak
Contraindications: people with selective IgA deficiency who have known antibody against
IgA
Cautions: agammaglobulinaemia, hypogammaglobulinaemia, when given intravenously in
patients at risk of thromboembolic events; it should not be given at the same time as live
virus vaccines as it may interfere with the immune response.
Side effects: arthralgia; chills; diarrhoea; dizziness; fever; headache; low back pain;
muscle spasms; myalgia; nausea; acute renal failure; anaphylaxis; aseptic meningitis;
cutaneous skin reactions; hypotension
Hepatitis B Immunoglobulin (HBIG)

Hepatitis B immunoglobulin (HBIG) may be indicated for the prevention of infection in
laboratory and other personnel who have been accidentally inoculated with hepatitis B
virus, and in infants born to mothers who have become infected with this virus in
pregnancy or who are high-risk carriers. It may be given at the same time, but not the
same site as the hepatitis B vaccine.
Tetanus Immunoglobulin
Tetanus immunoglobulin should be used in addition to wound cleansing for tetanus prone
wounds and, where appropriate, antibacterial prophylaxis and a tetanus-containing
vaccine. Tetanus immunoglobulin, together with metronidazole and wound cleansing,
should also be used for the treatment of established cases of tetanus.
Varicella-Zoster Immunoglobulin (VZIG)

Varicella-zoster immunoglobulin (VZIG) is recommended for individuals who are at
increased risk of severe varicella and who have no antibodies to varicella– zoster virus and
who have significant exposure to chickenpox or herpes zoster. This includes:
neonates whose mothers develop chickenpox in the period 7 days before to 7 days
after delivery
susceptible neonates exposed in the first 7 days of life
susceptible neonates or infants exposed whilst requiring intensive or prolonged
special care nursing
susceptible women exposed at any stage of pregnancy providing VZIG is given
within 10 days of contact
immunocompromised individuals
Anti-D Immunoglobulin
Anti-D (Rh0) immunoglobulin is prepared from plasma taken from rhesus-negative
donors who have been immunised against the anti-D antigen. It is used to prevent a
rhesus-negative mother from forming antibodies to foetal rhesus-positive cells which
may pass into the maternal circulation and thus to prevent haemolytic disease of the
newborn.
It should be administered to the mother following any sensitising episode (e.g. abortion,
miscarriage and birth); it should be injected within 72 hours of the episode but even if a
longer period has elapsed it may still give protection and should be administered. Anti-D
immunoglobulin is also given when significant feto-maternal haemorrhage occurs in
rhesus-negative women during delivery. The dose of anti-d (Rh0) immunoglobulin is
determined according to the level of exposure to rhesus-positive blood.
Use of routine antenatal anti-D prophylaxis should be given irrespective of previous anti-
D prophylaxis for a sensitising event early in the same pregnancy. Similarly, postpartum
anti-D prophylaxis should be given irrespective of previous routine antenatal anti-D
prophylaxis or antenatal anti-D prophylaxis for a sensitising event in the same pregnancy.
Anti-D immunoglobulin is also given to women of childbearing potential after the
inadvertent transfusion of rhesus-incompatible blood components.

Management of Tetanus-Prone LAST UPDATED: 11TH
JUNE 2019
Wounds  Bookmark
PHARMACOLOGY / IMMUNOGLOBULINS AND VACCINES
Tetanus is an acute disease caused by the action of the tetanus neurotoxin

(tetanospasmin) produced by the bacterium Clostridium tetani, an anaerobic spore
forming bacillus. Tetanus spores are widespread in the environment, including in soil and
manure. They can survive hostile conditions for long periods of time. Transmission occurs
when spores are introduced into the body, often through a puncture wound but also
through trivial, unnoticed wounds, through injecting drug use, and occasionally through
abdominal surgery. The bacteria grow anaerobically at the site of the injury and have an
incubation period of between four and 21 days (most commonly about ten days).
Definition of tetanus-prone wounds

Tetanus-prone wounds include:
puncture-type injuries acquired in a contaminated environment and likely therefore
to contain tetanus spores e.g. gardening injuries
wounds containing foreign bodies
compound fractures
wounds or burns with systemic sepsis
certain animal bites and scratches - although smaller bites from domestic pets are
generally puncture injuries animal saliva should not contain tetanus spores unless
the animal has been routing in soil or lives in an agricultural setting
High risk tetanus-prone wounds are any of the above with either:
heavy contamination with material likely to contain tetanus spores e.g. soil, manure
wounds or burns that show extensive devitalised tissue
wounds or burns that require surgical intervention that is delayed for more than six
hours are high risk even if the contamination was not initially heavy
Thorough cleaning of wounds is essential.
Clean wounds are defined as:
wounds less than 6 hours old, non-penetrating with negligible tissue damage
Management of tetanus-prone wounds

Immunisation Status Clean Tetanus Prone High Risk
Wound Wound Tetanus Prone
Wound
Those aged ≥ 11, who have None None Required None Required
received an adequate Required
priming course of tetanus
vaccine with the last dose
within 10 years
Children aged 5-10 years
who have received priming
course and preschool
booster
Children under 5 years
who have received an
adequate priming course
Those who have received None Immediate Immediate

an adequate priming Required reinforcing reinforcing
course of tetanus vaccine dose of vaccine dose of vaccine
but the last dose was > 10 & one dose of
years ago human tetanus
immunoglobulin
Children aged 5-10 years at a different
who have received an site
adequate priming course
but no preschool booster
Those who have not Immediate Immediate Immediate

received an adequate reinforcing reinforcing reinforcing
priming course of tetanus dose of dose of vaccine dose of vaccine
vaccine vaccine & one dose of & one dose of
human tetanus human tetanus
Includes uncertain immunoglobulin immunoglobulin
immunisation status and/ at a different at a different
or born before 1961 site site
Important considerations:
An adequate priming course is defined as at least 3 doses of tetanus vaccine at
appropriate intervals. (N.B. This definition of “adequate course” is for the risk
assessment of tetanus-prone wounds only. The full UK schedule is five doses of
tetanus containing vaccine at appropriate intervals.)
The dose of human tetanus immunoglobulin (IM-TIG) is normally 250 IU by
intramuscular injection, or 500 IU if more than 24 hours have elapsed since injury or
there is a risk of heavy contamination or following burns.
In the absence of IM-TIG, the human normal immunoglobulin (HNIG) product
Subgam 16% can be used instead.
Tetanus vaccine should be injected at a different site from immunoglobulin so that
it is not 'neutralised' by the passive immunisation.
Patients who are severely immunosuppressed may not be adequately protected
against tetanus, despite having been fully immunised. In the event of an exposure
they may require additional boosting and/or immunoglobulin.
For those whose immunisation status is uncertain, and individuals born before 1961
who may not have been immunised in infancy, a full course of immunisation is likely
to be required.
For those who are incompletely immunised, further doses should be offered to
complete the recommended schedule to protect against future exposures.

Post-Exposure Prophylaxis LAST UPDATED: 26TH
MARCH 2019
against Rabies  Bookmark
PHARMACOLOGY /
IMMUNOGLOBULINS AND VACCINES
Following potential exposure to rabies, the wound or site of exposure (e.g.

mucous membrane) should be cleansed under running water and washed for
several minutes with soapy water as soon as possible after exposure. Disinfectant
and a simple dressing can be applied, but suturing should be delayed because it
may increase the risk of introducing rabies virus into the nerves.
Post-exposure prophylaxis against rabies depends on the level of risk in the
country, the nature of exposure, and the individual’s immunity. In each case,
expert risk assessment and advice on appropriate management should be
obtained.
There are no specific contraindications to the use of rabies vaccine for post-
exposure prophylaxis and its use should be considered whenever a patient has
been attacked by an animal in a country where rabies is enzootic, even if there is
no direct evidence of rabies in the attacking animal. Because of the potential
consequences of untreated rabies exposure and because rabies vaccination has
not been associated with fetal abnormalities, pregnancy is not considered a
contraindication to post-exposure prophylaxis.
For post-exposure prophylaxis of fully immunised individuals (who have
previously received pre-exposure or post-exposure prophylaxis with cell-derived
rabies vaccine), 2 doses of cell-derived vaccine are likely to be sufficient; the first
dose is given on day 0 and the second dose is given between day 3–7. Rabies
immunoglobulin is not necessary in such cases.
Post-exposure treatment for unimmunised individuals (or those whose
prophylaxis is possibly incomplete) comprises 5 doses of rabies vaccine given
over 1 month (on days 0, 3, 7, 14, and the fifth dose is given between day 28–30);
also, depending on the level of risk (determined by factors such as the nature of
the bite and the country where it was sustained), rabies immunoglobulin is given
to unimmunised individuals on day 0 or within 7 days of starting the course of
rabies vaccine. The immunisation course can be discontinued if it is proved that
the individual was not at risk.

Aciclovir LAST UPDATED: 26TH
MARCH 2019
PHARMACOLOGY / INFECTIONS
 Bookmark
Mechanism of Action
Aciclovir is active against herpesviruses but does not eradicate them. It acts
to inhibit viral DNA synthesis.
Indications
Uses of aciclovir include systemic treatment of varicella–zoster (in
chickenpox and shingles) and the systemic and topical treatment of herpes
simplex infections of the skin and mucous membranes. It is used by mouth
for severe herpetic stomatitis. Aciclovir eye ointment is used for herpes
simplex infections of the eye; it is combined with systemic treatment for
ophthalmic zoster. Aciclovir has good CSF penetration and is administered
intravenously for the treatment of herpes simplex encephalitis.
Cautions
Aciclovir should be used with caution in the elderly and in patients with
renal impairment due to a risk of neurological reactions.
Side Effects
Aciclovir is generally well tolerated. Common side effects of systemic
aciclovir include abdominal pain, diarrhoea, fatigue, headache, nausea,
photosensitivity, pruritus, rash, urticaria, vomiting.
Reversible renal insufficiency (crystalline nephropathy) or neurotoxicity,
including tremor, delirium, and seizures, may develop without adequate
Aminoglycosides LAST UPDATED: 26TH
MARCH 2019
 Bookmark
Mechanism of Action
Aminoglycosides interfere with bacterial protein synthesis; they bind to the
bacterial 30S subunit and inhibit binding of the aminoacyl-tRNA, in addition
to causing misreading of the mRNA so that non-functional proteins are
synthesised .
Aminoglycosides are active against some Gram-positive and many Gram-
negative organisms. The aminoglycosides are not absorbed from the gut
and must therefore be given by injection for systemic infections.
Gentamicin is the aminoglycoside of choice in the UK and is used widely for
the treatment of serious infections. It has a broad spectrum but is inactive
against anaerobes and has poor activity against haemolytic streptococci
and pneumococci. When used for the blind therapy of undiagnosed serious
infections it is usually given in conjunction with a penicillin or metronidazole
(or both).
Indications
Indications include:
Gram-positive bacterial endocarditis or HACEK endocarditis (in
combination with other antibiotics)
Septicaemia
Listeria meningitis (with amoxicillin)
Biliary tract infection
Peritonitis (with metronidazole or clindamycin)
Hospital acquired pneumonia
Surgical prophylaxis
Contraindications
Gentamicin is contraindicated in myasthenia gravis and should be used with
caution in renal disease which may result in accumulation and a greater risk
of toxic side effects.
Side Effects
The main adverse effects are:
Ototoxicity (auditory and vestibular damage due to damage to CN VIII)
Nephrotoxicity (acute tubular necrosis, occurs most commonly in
elderly)
Impaired neuromuscular transmission (may cause a transient
myasthenic syndrome)
Serum Monitoring
Gentamicin has a narrow therapeutic index with toxic effects being dose
dependent.
Loading and maintenance doses of gentamicin may be calculated on the
basis of the patient’s weight and renal function; adjustments are then made
according to serum gentamicin concentrations.
Serum concentration monitoring avoids both excessive and subtherapeutic
concentrations thus preventing toxicity and ensuring efficacy. Serum-
aminoglycoside concentrations should be monitored in patients receiving
parenteral aminoglycosides and must be determined in the elderly, in
obesity, and in cystic fibrosis, or if high doses are being given, or if there is
renal impairment.
In patients with normal renal function, aminoglycoside concentrations
should be measured after 3 or 4 doses of a multiple daily dose regimen and
after a dose change.
For multiple daily dose regimens, blood samples should be taken
approximately 1 hour after intramuscular or intravenous administration
(‘peak’ concentration) and also just before the next dose (‘trough’
concentration). If the pre-dose (‘trough’) concentration is high, the interval
between doses must be increased. If the post-dose (‘peak’) concentration is
high, the dose must be decreased.
For once daily dose regimens, local guidelines on serum concentration
monitoring should be consulted.

Cephalosporins LAST UPDATED: 26TH
MARCH 2019
 Bookmark
Mechanism of Action
The cephalosporins are broad-spectrum beta-lactam antibiotics that attach to
penicillin binding proteins to interrupt cell wall synthesis, leading to bacterial cell
lysis and death.
They are used for the treatment of septicaemia, pneumonia, meningitis, biliary
tract infections, peritonitis, and urinary tract infections. Cephalosporins
penetrate the cerebrospinal fluid poorly unless the meninges are inflamed;
cefotaxime and ceftriaxone are suitable cephalosporins for infections of the CNS
(e.g. meningitis).
Side Effects
The principal side effect of the cephalosporins is hypersensitivity. Patients with a
history of anaphylaxis, urticaria, or rash immediately after penicillin use should
not receive a penicillin or other beta-lactam antibiotics; about 0.5 – 6.5 % of
penicillin-sensitive patients will also be allergic to the cephalosporins.
Gastrointestinal effects such as diarrhoea, nausea and vomiting are common with
cephalosporins. Antibiotic-associated colitis may occur, more commonly with
second- and third-generation cephalosporins.
Cefalexin
The orally active first generation cephalosporin, cefalexin is useful for urinary
tract infections which do not respond to other drugs or which occur in pregnancy,
respiratory tract infections, otitis media, sinusitis, and skin and soft-tissue
infections.
Cefuroxime
The second generation cephalosporin, cefuroxime is less susceptible than the
earlier cephalosporins to inactivation by beta-lactamases. It is therefore active
against certain bacteria which are resistant to the other drugs and has greater
activity against Haemophilus influenzae.
Cefuroxime is indicated first line for community acquired septicaemia, early-
onset hospital acquired pneumonia and acute pyelonephritis.
Cefotaxime and Ceftriaxone

The third generation cephalosporins, cefotaxime and ceftriaxone have greater
activity than the second generation cephalosporins against certain Gram-
negative bacteria e.g. N. gonorrhoeae, N. meningitidis. However, they are less
active than cefuroxime against Gram-positive bacteria, most notably
Staphylococcus aureus. Their broad antibacterial spectrum may encourage
superinfection with resistant bacteria or fungi (e.g. C. difficile colitis).
Cefotaxime (or ceftriaxone) are indicated first line in:
Blind treatment of meningitis in patients > 3 months (with amoxicillin if
patient > 50 years)
Meningitis caused by meningococci
Meningitis caused by pneumococci
Meningitis caused by H. influenzae
Severe or invasive salmonellosis
Typhoid fever
Gonorrhoea
Gonococcal arthritis
Haemophilus influenzae epiglottitis
Ceftriaxone has a longer half-life and therefore needs to be given only once daily.
The calcium salt of ceftriaxone forms a precipitate in the gallbladder which may
rarely cause symptoms but these usually resolve when the antibiotic is stopped.

Chloramphenicol LAST UPDATED: 26TH
MARCH 2019
 Bookmark
Mechanism of Action
Chloramphenicol is a potent broad-spectrum antibiotic that interferes with
bacterial protein synthesis.
Indications and Side Effects

Due to its risk of serious adverse effects including aplastic anaemia, peripheral
neuropathy and optic neuritis, when given systemically, it has limited use. It is
reserved for the treatment of typhoid fever and Haemophilus influenzae
meningitis, but a wide-spectrum cephalosporin is usually preferred.
Chloramphenicol eye drops are widely used topically for superficial bacterial eye
infections - given as 1 drop every 2 hours or 3 - 4 times daily, and then the
frequency reduced as the infection is controlled, continuing treatment for 48
hours after healing.

Fusidic Acid LAST UPDATED: 26TH
MARCH 2019
 Bookmark
Indications
Fusidic acid is a narrow spectrum antibiotic used for staphylococcal
infections, primarily topically for minor staphylococcal skin (impetigo) or eye
infection. It is sometimes used orally for penicillin-resistant staphylococcal
infection, including osteomyelitis or endocarditis, in combination with other
antibacterials.
To avoid the development of resistance, fusidic acid should not be used for
longer than 10 days and local microbiology advice should be sought before
using it in hospital.
Side Effects
Topical treatment can cause local skin irritation, sensitisation, erythema,
contact dermatitis, or pruritus but topical side effects are rare.
Common side effects of oral treatment include abdominal pain, diarrhoea,
dizziness, drowsiness, dyspepsia, nausea and vomiting. Elevated liver
enzymes, hyperbilirubinaemia and jaundice can occur—these effects are
usually reversible following withdrawal of therapy.

Macrolides LAST UPDATED: 26TH
MARCH 2019
 Bookmark
The macrolides have an antibacterial spectrum that is similar but not identical
to that of benzylpenicillin (i.e. narrow spectrum, mainly active against Gram-
positive organisms); they are thus an alternative in penicillin-allergic patients
or for penicillin-resistant staphylococci. However, they are not effective in
meningitis because they do not penetrate the CNS adequately.
Macrolides are usually given orally, but erythromycin and clarithromycin can
be given intravenously if necessary.
Mechanism of Action
Erythromycin inhibits protein synthesis by binding irreversibly to the bacterial
50S ribosomal subunit. It inhibits aminoacyl translocation and the formation
of initiation complexes.
Indications
Indications for the macrolides include campylobacter enteritis, respiratory
infections (including pneumonia, whooping cough, Legionella, chlamydia, and
mycoplasma infection), Lyme disease and skin infections. Erythromycin is also
used in the treatment of early syphilis, uncomplicated genital chlamydial
infection, and non-gonococcal urethritis but has poor activity against
Haemophilus influenzae.
Clarithromycin is an erythromycin derivative with slightly greater activity than
the parent compound. Tissue concentrations are higher than with
erythromycin. It is given twice daily. Clarithromycin is also used in regimens
for Helicobacter pylori eradication.
Cautions
Erythromycin is metabolised by the liver and dosage reduction in renal failure
is usually unnecessary unless the renal failure is severe. Macrolides are very
safe drugs.
Macrolides should be used with caution in myasthenia gravis, hepatic
impairment or in electrolyte disturbances or conditions that predispose to QT-
interval prolongation (as macrolides themselves can cause QT-interval
prolongation).
Side Effects
Macrolides commonly cause nausea, vomiting, diarrhoea, and abdominal
discomfort. Gastrointestinal side effects are mild and less frequent with
azithromycin and clarithromycin than with erythromycin.
Less common side effects include hepatotoxicity, cholestatic jaundice, rash,
reversible hearing loss (sometimes with tinnitus). Other adverse effects
reported rarely or very rarely include pancreatitis, QT interval prolongation,
arrhythmias, Stevens-Johnson syndrome, and toxic epidermal necrolysis.
Interactions
Erythromycin and clarithromycin inhibit cytochrome P450-mediated
metabolism of warfarin, phenytoin and carbamazepine and may lead to
accumulation of these drugs.
There is an increased risk of myopathy (due to cytochrome P450 enzyme
CYP3A4 inhibition) if erythromycin or clarithromycin is taken with atorvastatin
or simvastatin.
Erythromycin increases plasma concentrations of theophylline,
and theophylline may also reduce absorption of oral erythromycin.
All macrolides can prolong the QT-interval and concomitant use of drugs that
prolong the QT interval is not recommended.

Metronidazole LAST UPDATED: 26TH
MARCH 2019
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Mechanism of Action
Metronidazole, of the nitroimidazole class, is a bacterial nucleic acid synthesis
inhibitor. It has high activity against anaerobic bacteria and protozoa.
Metronidazole is well absorbed orally and the intravenous route is normally
reserved for severe infections.
Indications
Clostridium difficile colitis
Helicobacter pylori eradication (with clarithromycin/amoxicillin and PPI)
Bacterial vaginosis
Pelvic inflammatory disease (with doxycycline and ceftriaxone or
ofloxacin)
Peritonitis (with cephalosporin or gentamicin)
Acute oral infections
Tetanus
Rosacea and acne (topical)
Surgical prophylaxis
Protozoal infections
Amoebic dysentery
Giardiasis
Trichomoniasis
Interactions
Metronidazole can cause a disulfiram-like reaction with alcohol causing
symptoms such as flushing, headaches, dizziness, nausea/vomiting,
tachypnoea and tachycardia.
Metronidazole enhances the anticoagulant effect of warfarin. If concurrent
use cannot be avoided, consider reducing the warfarin dosage appropriately.
Side Effects
Common adverse effects include a metallic taste and gastrointestinal
irritation (in particular nausea and vomiting). These are more common at
higher doses. Patients should be advised that metronidazole should be taken
with or after food.

Notifiable Diseases LAST UPDATED: 15TH
JUNE 2021
 Bookmark
List of notifiable diseases:

Acute encephalitis
Acute infectious hepatitis
Acute meningitis
Acute poliomyelitis
Anthrax
Botulism
Brucellosis
Cholera
COVID-19
Diphtheria
Enteric fever (typhoid or paratyphoid fever)
Food poisoning
Haemolytic uraemic syndrome (HUS)
Infectious bloody diarrhoea
Invasive group A streptococcal disease
Legionnaires’ disease
Leprosy
Malaria
Measles
Meningococcal septicaemia
Mumps
Plague
Rabies
Rubella
Severe Acute Respiratory Syndrome (SARS)
Scarlet fever
Smallpox
Tetanus
Tuberculosis
Typhus
Viral haemorrhagic fever (VHF)
Whooping cough
Yellow fever

Nystatin LAST UPDATED:
26TH MARCH 2019
 Bookmark
Indications
Oral Candidiasis
Cautions
Contact with eyes should be avoided
Side Effects
Frequency not known: Abdominal distress; angioedema; diarrhoea; face
oedema; nausea; sensitisation; skin reactions; Stevens-Johnson
syndrome; vomiting

Penicillins LAST UPDATED: 20TH
DECEMBER 2019
 Bookmark
Mechanism of Action
Penicillins are beta-lactam antibiotics that inhibit bacterial cell wall synthesis by
inactivating bacterial transpeptidases and preventing the cross-linking of
peptidoglycan polymers that is essential for bacterial cell wall integrity. This
results in loss of rigidity and a susceptibility to rupture. The major cause of
resistance is the production of beta-lactamases (penicillinases) that are
produced by certain strains of bacteria.
Penicillins diffuse well into body tissues and fluids, but penetration into the
cerebrospinal fluid is poor except when the meninges are inflamed.
Side Effects
Common side effects include: Anaphylaxis; angioedema; diarrhoea (very common,
occurs most commonly with broad-spectrum antibiotics, may be associated with
colitis); fever; hypersensitivity reactions; joint pains; rashes; serum sickness-like
reaction; urticaria
Rare side effects include: Cerebral irritation (may result from excessively high
doses or in patients with severe renal failure); CNS toxicity (including
convulsions); coagulation disorders; encephalopathy; haemolytic anaemia;
interstitial nephritis; leucopenia; thrombocytopenia
Allergy
The most important side effect of the penicillins is hypersensitivity which can be
fatal. Allergic reactions to penicillins occur in 1 – 10% of exposed individuals;
anaphylactic reactions occur in fewer than 0.05% of treated patients. Patients
with a history of atopic allergy are at higher risk of anaphylactic reactions to
penicillins.
Patients with a history of anaphylaxis, urticaria, or rash immediately after
penicillin use should not receive a penicillin or other beta-lactam antibiotics;
about 0.5 – 6.5 % of penicillin-sensitive patients will also be allergic to the
cephalosporins.
Patients with a history of a more minor rash (i.e. non-confluent, non-pruritic rash
restricted to a small area of the body) or delayed reaction (rash occurring more
than 72 hours after penicillin administration), may not be truly allergic and may be
considered for penicillin or beta-lactam treatment in severe infection (although
possibility of allergy should be borne in mind). Other beta-lactam antibiotics
(including cephalosporins) can be used in these patients.
Indications
First Line Antibiotic Indications

Ampicillin or amoxicillin Blind therapy for native valve endocarditis;
endocarditis caused by enterococci (with low-
dose gentamicin); endocarditis caused by
HACEK organisms (with low-dose gentamicin);
blind treatment of meningitis in adults > 50
years (with cefotaxime/ceftriaxone);
meningitis caused by Listeria (with
gentamicin); otitis media; sinusitis; oral
infection; exacerbation chronic bronchitis;
low-severity community acquired pneumonia;
moderate-severity community acquired
pneumonia (with clarithromycin)
Co-amoxiclav Severe or resistant otitis media; resistant
sinusitis; severe or resistant dental infection;
high-severity community acquired pneumonia
(with clarithromycin); hospital acquired
pneumonia (non severe signs or symptoms and
not at higher risk of resistance); animal and
human bite wounds
First Line Antibiotic Indications
Flucloxacillin Native valve endocarditis caused by
staphylococci; prosthetic valve endocarditis
caused by staphylococci (with rifampicin and
low-dose gentamicin); spreading/severe otitis
externa; osteomyelitis; septic arthritis;
widespread impetigo; severe erysipelas;
cellulitis; mastitis during breastfeeding
Benzylpenicillin Meningococcal disease (prehospital);
endocarditis caused by streptococci (with or
without low-dose gentamicin); endocarditis
caused by enterococci (with low-dose
gentamicin); meningitis caused by
meningococci; erysipelas
Phenoxymethylpenicillin Erysipelas, acute tonsillitis
Piperacillin/tazobactam Community acquired septicaemia, hospital
acquired septicaemia; peritonitis; hospital
acquired pneumonia (severe signs or
symptoms or at higher risk of resistance);
complicated infections involving the urinary
tract, skin and soft tissues, or intra-abdomen
Benzylpenicillin
Benzylpenicillin sodium remains an important and useful antibiotic but is
inactivated by bacterial beta-lactamases. It is effective for many streptococcal
(including pneumococcal), gonococcal, and meningococcal infections and also
for anthrax, diphtheria, gas-gangrene, and leptospirosis. Pneumococci,
meningococci, and gonococci which have decreased sensitivity to penicillin have
been isolated; benzylpenicillin sodium is no longer the drug of first choice for
pneumococcal meningitis. Although benzylpenicillin sodium is effective in the
treatment of tetanus, metronidazole is preferred. Benzylpenicillin is inactivated
by gastric acid and absorption from the gastrointestinal tract is low; therefore it
must be given by injection.
If meningococcal disease (meningitis with non-blanching rash or meningococcal
septicaemia) suspected, benzylpenicillin sodium should be given before transfer
to hospital, so long as this does not delay the transfer. If a patient with suspected
bacterial meningitis without non-blanching rash cannot be transferred to
hospital urgently, benzylpenicillin sodium should be given before the transfer.
Phenoxymethylpenicillin
Phenoxymethylpenicillin (penicillin V) is less active than benzylpenicillin but has a
similar antibacterial spectrum. It is gastric-acid stable and therefore suitable for
oral administration, but should not be used for serious infections because
absorption can be unpredictable and plasma concentrations variable.
It is given primarily for respiratory tract infections in children, for streptococcal
tonsillitis and for continuing treatment after one or more injections of
benzylpenicillin when clinical response has begun. It is also used for prophylaxis
against streptococcal infections following rheumatic fever and against
pneumococcal infections following splenectomy or in sickle-cell disease. It
should not be used for meningococcal or gonococcal infections.
Flucloxacillin
Flucloxacillin is unique in that it is beta-lactamase stable and it can be used in
infections caused by beta-lactamase producing staphylococci e.g. S. aureus. It is
acid-stable and can therefore be given by mouth as well as by injection.
It is used first line for treatment of widespread impetigo infection, cellulitis,
mastitis, osteomyelitis, septic arthritis, severe erysipelas, severe/spreading otitis
externa and infective endocarditis caused by staphylococci.
The most common adverse effects of flucloxacillin include nausea, vomiting, skin
rash, and diarrhoea. Cholestatic jaundice and hepatitis may occur very rarely, up
to two months after treatment with flucloxacillin has been stopped.
Administration for more than 2 weeks and increasing age are risk factors.
Ampicillin
Ampicillin is active against certain Gram-positive and Gram-negative organisms
but is inactivated by penicillinases. Ampicillin is associated with high levels of
resistance, therefore it is often not appropriate for blind treatment of infection. It
is principally indicated for the treatment of exacerbations of chronic bronchitis
and middle ear infections, both of which may be due to Streptococcus
pneumoniae and H. influenzae, and for urinary tract infections.
Maculopapular rashes commonly occur with ampicillin (and amoxicillin) but are
not usually related to true penicillin allergy. They almost always occur in patients
with glandular fever; thus broad-spectrum penicillins should not be used for blind
treatment of a sore throat. The risk of rash is also increased in patients with acute
or chronic lymphocytic leukaemia or in cytomegalovirus infection.
Amoxicillin
Amoxicillin is a derivative of ampicillin and has a similar antibacterial spectrum. It
is better absorbed than ampicillin when given orally, producing higher plasma and
tissue concentrations; unlike ampicillin, absorption is not affected by the
presence of food in the stomach. The adverse effects of amoxicillin are mainly
gastrointestinal and mild and include nausea, vomiting and diarrhoea.
Amoxicillin is used first line for low to moderate severity community acquired
pneumonia, exacerbations of chronic bronchitis, for acute otitis media, for acute
sinusitis, for oral infections/dental abscess, for Listeria meningitis (in
combination with another antibiotic), for infective endocarditis (in combination
with another antibiotic) and for H. Pylori eradication (in combination with
metronidazole/clarithromycin and a proton pump inhibitor).
Co-amoxiclav
Co-amoxiclav consists of amoxicillin with the beta-lactamase inhibitor clavulanic
acid. Clavulanic acid itself has no significant antibacterial activity but, by
inactivating beta-lactamases, it makes the combination active against beta-
lactamase-producing bacteria that are resistant to amoxicillin. These include
resistant strains of Staph. aureus, E. coli, and H. influenzae, as well as many
Bacteroides and Klebsiella spp, causing infections such as respiratory tract
infections, bone, joint and soft tissue infections, genitourinary and abdominal
infection. Co-amoxiclav should be reserved for infections likely, or known, to be
caused by amoxicillin-resistant beta-lactamase-producing strains.
The most common adverse effects of co-amoxiclav include nausea, vomiting, skin
rash and diarrhoea. Pseudomembranous colitis should be considered if a person
develops severe diarrhoea during or after treatment with co-amoxiclav.
Cholestatic jaundice can occur either during or shortly after the use of co-
amoxiclav. An epidemiological study has shown that the risk of acute liver toxicity
was about 6 times greater with co-amoxiclav than with amoxicillin. Cholestatic
jaundice is more common in patients above the age of 65 years and in men; these
reactions have only rarely been reported in children. Jaundice is usually self-
limiting and very rarely fatal.
Antipseudomonal Penicillins
Piperacillin, a ureidopenicillin, is only available in combination with the beta-
lactamase inhibitor tazobactam. Ticarcillin, a carboxypenicillin, is only available in
combination with the beta-lactamase inhibitor clavulanic acid. Both preparations
have a broad spectrum of activity against a range of Gram-positive and Gram-
negative bacteria, and anaerobes. Piperacillin with tazobactam has activity
against a wider range of Gram-negative organisms than ticarcillin with clavulanic
acid and it is more active against Pseudomonas aeruginosa. These antibacterials
are not active against MRSA. They are used in the treatment of septicaemia,
hospital-acquired pneumonia, and complicated infections involving the urinary
tract, skin and soft tissues, or intra-abdomen. For severe pseudomonas
infections these antipseudomonal penicillins can be given with an
aminoglycoside (e.g. gentamicin) since they have a synergistic effect.
Quinolones LAST UPDATED: 26TH
MARCH 2019
 Bookmark
Mechanism of Action
Quinolones interfere with bacterial nucleic acid synthesis. Ciprofloxacin is well
absorbed orally and can be given intravenously. It is eliminated mainly by the
kidneys.
Indications
Ciprofloxacin is active against both Gram-positive and Gram-negative bacteria. It is
particularly active against Gram-negative bacteria, including salmonella, shigella,
campylobacter, Neisseria, and pseudomonas. Ciprofloxacin has only moderate
activity against Gram-positive bacteria such as Streptococcus pneumoniae and
Enterococcus faecalis; it should not be used for pneumococcal pneumonia. It is
active against chlamydia and some mycobacteria. Most anaerobic organisms are not
susceptible.
Ciprofloxacin can be used for respiratory tract infections (but not for pneumococcal
pneumonia), urinary tract infections (including acute pyelonephritis and prostatitis),
biliary tract infections, infections of the gastrointestinal system (including typhoid
fever), bone and joint infections, gonorrhoea and septicaemia caused by sensitive
organisms.
CSM Advice
The CSM has warned that quinolones may induce convulsions in patients with or
without a history of convulsions; taking NSAIDs at the same time may predispose to
this. Convulsions may occur because the quinolones are GABA antagonists.
Tendon damage (including rupture) has also been reported rarely in patients taking
quinolones, typically occurring within 48 hours of starting treatment. Quinolones are
therefore contraindicated in patients with a history of tendon disorders related to
quinolone use and should be used with caution in patients over 60 years of age (who
are more prone to tendon damage) and in those taking concomitant corticosteroids
(which also predispose to tendon damage). If tendinitis is suspected, the quinolone
should be stopped immediately.
Contraindications
Quinolones are contraindicated in patients with a history of tendon disorders related
to quinolone use.
Quinolones should be used with caution in:
conditions that prolong the QT interval (including electrolyte disturbance)
concomitant use with other drugs known to prolong the QT interval
epilepsy or conditions that predispose to seizures
G6PD deficiency
myasthenia gravis
renal impairment (reduce dose)
children/adolescents (may be at risk of arthropathy)
Side Effects
Common side effects include diarrhoea, dizziness, headache, nausea and vomiting.
Ciprofloxacin can occasionally cause drowsiness and may impair the performance of
skilled tasks such as driving.
Other adverse effects include:
Tendon damage (including rupture)
Seizures (in patients with and without epilepsy)
Photosensitivity
Antibiotic-associated colitis
Interactions
Ciprofloxacin increases plasma concentrations of theophylline.
There is an increased risk of convulsions when quinolones are given with NSAIDs or
theophylline.
Tetracyclines LAST UPDATED: 26TH
MARCH 2019
 Bookmark
Mechanism of Action
Tetracyclines bind reversibly to the 30S subunit of bacterial ribosomes, preventing
the binding of aminoacyl tRNA to the acceptor site on the mRNA–ribosome complex
and addition of amino acids to the growing peptide, thus inhibiting bacterial protein
synthesis.
The tetracyclines are orally active, broad spectrum antibiotics but increasing
bacterial resistance and the development of safer drugs has reduced their
usefulness. Absorption from the gut is variable and is reduced by calcium ions (e.g.
milk), magnesium ions (e.g. antacids), food and iron preparations. They can also be
administered parenterally.
Indications
They remain the treatment of choice for infections caused by chlamydia (trachoma,
psittacosis, salpingitis, pelvic inflammatory disease, urethritis, and
lymphogranuloma venereum), rickettsia (including Q-fever), brucella (doxycycline
with either streptomycin or rifampicin), and the spirochaete, Borrelia burgdorferi
(Lyme disease).
They are also used in respiratory and genital mycoplasma infections, in acne and
rosacea, in destructive (refractory) periodontal disease, in exacerbations of chronic
bronchitis (because of their activity against Haemophilus influenzae), in community
acquired pneumonia, and for leptospirosis in penicillin hypersensitivity (as an
alternative to erythromycin).
Doxycycline may also used for malaria prophylaxis and as an adjunct to quinine in
the treatment of Plasmodium falciparum malaria.
Microbiologically, there is little to choose between the various tetracyclines, the only
exception being minocycline which has a broader spectrum but is no longer
recommended because of side effects including dizziness and vertigo.
Contraindications
Tetracyclines are contraindicated in children under 12 years (deposition in growing
bone and teeth by binding to calcium causes staining and occasionally dental
hypoplasia) and in pregnant women (may cause impaired skeletal development and
discolouration of teeth). They should also be avoided in people with liver disease,
systemic lupus erythematosus, myasthenia gravis and porphyria.
Side Effects
The most common are gastrointestinal adverse effects such as nausea, vomiting and
diarrhoea. Less frequently, they may cause photosensitivity (patients should be
advised to avoid exposure to sunlight or sunlamps). At high doses, most
tetracyclines can cause hepatic damage. Severe adverse effects are unusual with a
short course. However, benign intracranial hypertension has rarely been reported
following treatment with a tetracycline; treatment should be discontinued in a
patient complaining of headache and visual disturbance.

Trimethoprim LAST UPDATED: 26TH
MARCH 2019
 Bookmark
Mechanism of Action
Trimethoprim inhibits bacterial metabolism. It is well absorbed orally and is effective
in most patients with simple lower urinary tract infections.
A combination of trimethoprim and sulfamethoxazole (co-trimoxazole) may produce
a synergistic action and increased activity against certain bacteria. Co-trimoxazole
has an important use in the treatment of Pneumocystis jiroveci pneumonia.
Contraindications
Trimethoprim is contraindicated in blood dyscrasias and should be used with caution
in the elderly and neonates as it predisposes to folate deficiency. The risk of folate
deficiency is also increased when trimethoprim is combined with certain drugs e.g.
methotrexate.
There is a teratogenic risk in first trimester (folate antagonist) and manufacturers
advise to avoid during pregnancy. However the NICE CKS guidelines state that
trimethoprim can be used during pregnancy (although it should not be used first-line
when other alternatives are available); if trimethoprim is used during the first
trimester, it should be co-prescribed with folic acid 5 mg daily.
The dose should be reduced in severe renal impairment as the drug is predominantly
excreted by the kidney.
Side Effects
The most common side effects are allergic reactions and skin rashes. Much less
common are more serious reactions such as Stevens-Johnsons syndrome and
various blood dyscrasias.

Vancomycin LAST UPDATED: 8TH
SEPTEMBER 2021
 Bookmark
Mechanism of Action
Vancomycin is a glycopeptide antibiotic which acts by inhibiting peptidoglycan
formation and is active against aerobic and anaerobic Gram-positive bacteria
including multi resistant staphylococci.
Vancomycin binds to the terminal end of the growing peptidoglycan to prevent
further elongation and cross-linking due to inhibition of transglycosylase; this
results in decreased cell membrane activity and increased cell lysis.
For systemic infection vancomycin must be given by intravenous injection as it is not
absorbed orally. Penetration into cerebrospinal fluid is poor. It is given orally for
pseudomembranous colitis caused by Clostridium difficile infection.
Indications
C. difficile colitis
Infections due to Gram-positive bacteria including endocarditis, osteomyelitis,
septicaemia, pneumonia, septic arthritis and soft-tissue infection where MRSA
is suspected/demonstrated
Peritonitis associated with peritoneal dialysis
Septicaemia related to vascular catheter
Surgical prophylaxis (when high risk of MRSA)
Cautions
Vancomycin should be avoided if there is a history of deafness, and should be used
with caution in the elderly. The dose should be reduced in renal impairment, and the
plasma-vancomycin, renal function and auditory function monitored regularly.
Side Effects
Side effects include:
Blood disorders including neutropenia
Nephrotoxicity (acute interstitial nephritis)
Ototoxicity (discontinue if tinnitus occurs)
Rarely anaphylactoid reaction, cardiac arrest or 'red man' syndrome (flushing
of the upper body) on rapid infusion
Monitoring
All patients require plasma-vancomycin measurement (after 3 or 4 doses if renal
function normal, earlier if renal impairment).
All patients require blood counts, urinalysis, and renal function tests. Auditory
function should be monitored in the elderly.

Non-Steroidal Anti- LAST UPDATED: 26TH
MARCH 2019
Inflammatory Drugs (NSAIDs)  Bookmark
PHARMACOLOGY / MUSCULOSKELETAL
Mechanism of Action
NSAIDs reduce the production of prostaglandins by inhibiting the cyclooxygenase (COX)
enzymes with analgesic, antipyretic and anti-inflammatory effects. The two main types
of COX enzyme are COX-1 (which produces prostaglandins that help to maintain gastric
mucosal integrity and platelet-initiated blood clotting) and COX-2 (which produces
prostaglandins that mediate pain and inflammation). NSAIDs vary in their selectivity for
inhibiting different types of COX; specific inhibition of COX-2 (e.g. celecoxib and
etoricoxib) is associated with less gastrointestinal intolerance.
Therapeutic Effects
In single doses NSAIDs have analgesic activity comparable to that of paracetamol,
therefore given their side effect profile, paracetamol is preferred, particularly in the
elderly. In regular full dosage NSAIDs have both a lasting analgesic and an anti-
inflammatory effect making them useful for the management of continuous or regular
pain associated with inflammation e.g. inflammatory arthritides. Pain relief starts soon
after taking the first dose and a full analgesic effect should normally be obtained within a
week, whereas an anti-inflammatory effect may not be achieved (or may not be clinically
assessable) for up to 3 weeks.
Choice of NSAID
Ibuprofen has fewer side effects than other non-selective NSAIDs but its anti-
inflammatory properties are weaker, making it unsuitable for conditions where
inflammation is prominent e.g. acute gout.
Naproxen has good efficacy with a relatively low incidence of side effects (but more than
ibuprofen); it is recommended first line treatment in acute gout.
Diclofenac is similar in efficacy to naproxen but is associated with a higher incidence of
cardiovascular adverse events (and is in fact contraindicated in people with ischaemic
heart disease, cerebrovascular disease, peripheral arterial disease and mild, moderate, or
severe heart failure).
Mefenamic acid has only minor anti-inflammatory properties and is typically used in the
management of painful dysmenorrhoea. It has occasionally been associated with
diarrhoea and haemolytic anaemia which require discontinuation of treatment.
Risk of NSAID-induced GI adverse events NSAIDs

Lowest risk Ibuprofen
Intermediate risk Naproxen, diclofenac, indometacin
Highest risk Piroxicam, ketoprofen, ketorolac
Contraindications
NSAIDs are contraindicated in people with:
A history of hypersensitivity or severe allergic reaction to aspirin or any other
NSAID
Severe heart failure (NSAIDs may impair renal function)
Liver fibrosis, cirrhosis or acute liver failure (risk of variceal bleeding, hepatorenal
syndrome and encephalopathy)
Severe hepatic impairment (e.g. liver enzyme levels more than three times the
upper limit of the normal range; serum albumin less than 25 g/L)
Current treatment for gastrointestinal bleeding, symptomatic peptic ulcer, or
gastrointestinal perforation or obstruction
Coxibs and diclofenac are also contraindicated in people with ischaemic heart
disease, cerebrovascular disease, peripheral arterial disease, mild, moderate, or
severe heart failure
Renal failure, with estimated glomerular filtration rate (eGFR) less than 30–15
mL/min/1.73 m2, or creatinine clearance less than 30–20 mL/min, or dehydration
(relative)
Cautions
NSAIDs should be used with caution in:
People with asthma (patients should be offered a trial to assess effect on asthma
control)
The elderly (increased risk of serious adverse effects such as gastrointestinal
bleeding and perforation, which may be fatal)
People with a history of peptic ulceration (standard NSAIDs contraindicated), or
those at high risk of gastrointestinal adverse effects
People with inflammatory bowel disease (NSAIDs may increase the risk of
developing or cause exacerbations of ulcerative colitis or Crohn's disease)
People with hepatitis or cholestasis (increased risk of gastrointestinal bleeding
and fluid retention)
Renal impairment (avoid if possible, sodium and water retention may occur leading
to a deterioration in renal function and, possibly renal failure)
People with heart failure (NSAIDs may impair renal function)
People with hypertension (NSAIDs may impair renal function)
In a women trying to conceive (NSAIDs may impair female fertility)
Adverse Effects
Adverse effects may be minimised by selecting an appropriate NSAID and using the
lowest effective dose for the shortest duration necessary to control symptoms.
Side effects of NSAIDs include:
The most common adverse effects of NSAIDs are dyspepsia and other upper
gastrointestinal complications such as ulcer, perforation, obstruction or bleeding
(especially if risk factors are present - see below)
Less commonly NSAIDs may cause cardiovascular and renal complications such as
myocardial infarction, stroke, cardiac failure, hypertension, and renal failure (the
risk is increased in people with IHD, CVD, PAD, CKD, HF or HTN, risk factors for
cardiovascular disease and people > 65 years)
Prolonged bleeding (for example after surgery) because of platelet inhibition
Asthma (NSAIDs may exacerbate or precipitate asthma. Stop NSAID if it is
suspected to have precipitated bronchospasm)
Severe skin reactions and angioedema (stop NSAID)
Very rarely, NSAIDs can precipitate severe hepatic reactions such as hepatitis, liver
necrosis, or hepatic failure (stop NSAID)
Risk Factors for Increased Risk of Gastrointestinal Adverse Effects

People are at high risk of serious NSAID–induced gastrointestinal adverse events if they
have one or more of the following risk factors:
Using the maximum recommended dose of an NSAID
Aged 65 years or older
History of gastroduodenal ulcer, GI bleeding, or gastroduodenal perforation
Concomitant use of medications that are known to increase the likelihood of upper
GI adverse events (e.g. anticoagulants, aspirin, corticosteroids, and
antidepressants (selective serotonin reuptake inhibitors, venlafaxine, or
duloxetine))
Serious comorbidity, such as cardiovascular disease, hepatic or renal impairment,
diabetes, or hypertension
Requirement for prolonged NSAID use including people with osteoarthritis or
rheumatoid arthritis of any age and people aged 45 years or older with chronic low
back pain
The presence of Helicobacter pylori infection
Excessive alcohol use
Heavy smoking
Prevention and Management of Gastrointestinal Adverse Effects

Preventing gastrointestinal adverse effects
Consider prescribing:
An alternative to an NSAID e.g. paracetamol +/- codeine
The lowest dose of NSAID for the shortest period of time
Only one NSAID at a time (avoid concomitant use with aspirin)
A COX-2 selective NSAID (but increased cardiovascular risk)
If the person is at an increased risk of GI adverse events and requires an
NSAID, co-prescribe a proton pump inhibitor (PPI) for gastroprotection (e.g.
omeprazole 20 mg od, lansoprazole 15 - 30 mg od)
Managing gastrointestinal adverse effects
Where possible the NSAID should be withdrawn if an ulcer occurs
The ulcer should be treated with a PPI (a H2-receptor antagonist or
misoprostol are alternatives)
On healing the patient should be tested for H. pylori and treated if required
If treatment with NSAID needs to continue, options include:
On healing continue PPI
Switch to selective COX-2 inhibitor

Management of Gout LAST UPDATED: 27TH
MARCH 2019
PHARMACOLOGY / MUSCULOSKELETAL
 Bookmark
Gout is a disorder of purine metabolism characterised by a raised uric acid level in

the blood (hyperuricaemia) and the deposition of urate crystals in joints and other
tissues, such as soft connective tissues or the urinary tract.
NSAIDs
Acute attacks of gout are usually treated with an NSAID such as diclofenac,
indometacin, or naproxen. Treatment should be started as soon as possible and
continued until 48 hours after the attack has resolved. A PPI should be co-
prescribed for gastric protection in people at high risk of gastrointestinal adverse
events.
Colchicine
Colchicine is an alternative in patients in whom NSAIDs are contraindicated, not
tolerated or ineffective. Although its use is limited by toxicity at higher doses, it is
useful in patients with heart failure or those taking anticoagulants.
The dose is 500 micrograms 2 - 4 times a day until the symptoms are relieved or
diarrhoea or vomiting occurs (max 6 mg per course and do not repeat treatment
within 3 days).
Colchicine should be avoided in people with blood dyscrasias and bone marrow
disease.
Common side effects of colchicine include:
abdominal pain
nausea and vomiting
diarrhoea
Side effects are dose dependent and may be severe enough to limit treatment.
Corticosteroids
Oral or parenteral corticosteroids are an effective alternative in those who cannot
tolerate or who are resistant to NSAIDs and colchicine. Intra-articular injection of
a corticosteroid can be used occasionally in acute monoarticular gout.
Allopurinol
Allopurinol is not effective in treating an acute attack and may prolong it
indefinitely if started during the acute episode, but should be continued during an
acute attack if the patient is already established on long term therapy.
Long term treatment (prevention) of gout may be indicated in patients with
frequent recurrence of acute attacks of gout, the presence of tophi, or signs of
chronic gouty arthritis. Allopurinol reduces uric acid formation from purines and
may be used to prevent further attacks of gout by correcting hyperuricaemia. The
initiation of treatment may precipitate an acute attack, and should be covered
with an NSAID or colchicine, continued for at least one month after the
hyperuricaemia has been corrected.

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ANATOMY

Anterior Scalene Muscle LAST UPDATED: 19TH

ANTERIOR SCALENE MUSCLE. (IMAGE BY USER:MIKAEL HÄGGSTRÖM (IMAGE:GRAY387.PNG)

Neck Spaces and Fascia LAST UPDATED: 20TH

LAYERS OF THE DEEP CERVICAL FASCIA: INVESTING LAYER (BLUE), PREVERTEBRAL

Neck Triangles LAST UPDATED: 20TH

Each posterior triangle is bounded:

Sternocleidomastoid Muscle LAST UPDATED: 11TH

Table: Overview of the Sternocleidomastoid Muscle

The sternocleidomastoid is innervated by the accessory nerve (CN XI) and by

STERNOCLEIDOMASTOID MUSCLE. (IMAGE BY HENRY VANDYKE CARTER [PUBLIC DOMAIN],

Deep Cervical Lymph LAST UPDATED: 11TH

Jugulo-omohyoid Lymph Node

DEEP CERVICAL LYMPH NODES. (IMAGE BY HENRY VANDYKE CARTER [PUBLIC

Phrenic Nerve LAST UPDATED: 11TH

ROOT OF THE NECK. (IMAGE MODIFIED BY FRCEM SUCCESS. ORIGINAL BY HENRY

Recurrent Laryngeal Nerve LAST UPDATED: 11TH

Right Recurrent Laryngeal Nerve

RIGHT RECURRENT LARYNGEAL NERVE. (IMAGE BY HENRY VANDYKE CARTER

Left Recurrent Laryngeal Nerve

LEFT RECURRENT LARYNGEAL NERVE. (IMAGE BY JKWCHUI (BASED ON DRAWING

Suprahyoid and Infrahyoid LAST UPDATED: 11TH

SUPRAHYOID MUSCLES. (IMAGE BY HÄGGSTRÖM, MIKAEL. “MEDICAL GALLERY OF

Thyroid Gland LAST UPDATED: 11TH

THYROID GLAND. (IMAGE BY OPENSTAX COLLEGE [CC BY 3.0

muscle along the internal jugular vein.

Recurrent Laryngeal Nerve

Anatomy Head and Neck Neck

Trachea (Neck) LAST UPDATED: 11TH

STRUCTURE OF THE LARYNX (ANTERIOR VIEW). (IMAGE BY OLEK REMESZ (WIKI-PL:

COMPLETED TRACHEOSTOMY: 1) VOCAL FOLDS, 2) THYROID CARTILAGE, 3) CRICOID

Subclavian Artery LAST UPDATED: 12TH

SUBCLAVIAN ARTERY. (IMAGE BY HENRY VANDYKE CARTER [PUBLIC DOMAIN], VIA

ROOT OF THE NECK. (IMAGE MODIFIED BY FRCEM SUCCESS. ORIGINAL BY HENRY

Subclavian Vein LAST UPDATED: 11TH

Central Venous Cannulation

Sympathetic Trunk LAST UPDATED: 11TH

CERVICAL GANGLIA OF THE SYMPATHETIC TRUNK. (IMAGE BY HENRY VANDYKE CARTER

Superior Cervical Ganglion

Middle Cervical Ganglion

cervical spinal nerves C5 - C6

Inferior Cervical Ganglion

Pharynx LAST UPDATED: 11TH

RELATIONS OF THE PHARYNX. (IMAGE BY OPENSTAX COLLEGE [CC BY 3.0], VIA

Soft Palate LAST UPDATED: 22ND

OROPHARYNX. (IMAGE BY HENRY VANDYKE CARTER [PUBLIC DOMAIN], VIA

Tonsils LAST UPDATED: 11TH

TONSILS. (IMAGE BY BLAUSEN.COM STAFF. “BLAUSEN GALLERY 2014”. WIKIVERSITY

PALATINE TONSILS. (IMAGE MODIFIED BY FRCEM SUCCESS. ORIGINAL BY HENRY

Cutaneous Innervation of LAST UPDATED: 16TH

CUTANEOUS INNERVATION OF THE HEAD. (IMAGE BY PATRICK J. LYNCH, MEDICAL

Facial Muscles LAST UPDATED: 11TH

Table: Function of the Facial Muscles

Facial Vein LAST UPDATED: 11TH

Arterial Supply of Face LAST UPDATED: 6TH

Transverse Facial Artery

Superficial Temporal Artery

BLOOD SUPPLY OF THE FACE. (IMAGE MODIFIED BY FRCEM SUCCESS. ORIGINAL

Lymphatic Drainage of LAST UPDATED: 11TH

Preauricular and Parotid Nodes

LYMPHATIC DRAINAGE OF THE FACE. (IMAGE BY HENRY VANDYKE CARTER [PUBLIC

Cranial Nerve V: Trigeminal LAST UPDATED: 23RD

Table: Overview of the Trigeminal Nerve

Parasympathetic fibres to lacrimal and nasal glands