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2018 A/L Batch Repeat Campaign
2018 A/L Batch Repeat Campaign
2018 A/L Batch Repeat Campaign
◆ It also gives attachment to the thoracic cage by way of ribs and through the rib cage to the
pectoral girdle & upper limbs.
◆ It is also attached at its lower end( sacrum) to the pelvic girdle and thereby to the lower limbs.
◆ The vertebral column contains the spinal cord within its vertebral canal.
> Flexibilty due to different types of intervertebral joints and curvatures of the column
> Strength due to bony vertebrae, intervertebral discs (2ry cartilagenous joints) and ligaments
associated with the column
✓ Intervertebral formen - between the superior & inferior intervertebral notches of pedicles of
adjacent vertebrae. The spinal nerve of the related spinal segment & segmental
arteries of the spinal cord pass through this. CHAT HERE
✓ Cervical- foramen
transversarium and bifid
spinous process
Axis C2
• dens from the superior surface of the body
• only posterior tubercle present
• massive spinous process
Vertebra Prominens C7
• thick long nearly horizontal spine, not bifid, ends in tubercle
• only posterior tubercle present
• Foramen transversarium doesn't transmit vertebral artery, only the vein
Thoracic
Typical thoracic vertebrae (T2- T8) Costal facets on body and transverse processes
Body • heart shaped
• Costal [demi] facets: Superior-larger
Inferior-smaller
Vertebral foramen • small, circular
T9
• Inferior costal facet missing
• Spine nearly horizontal
T10
• Superior costal facet complete
T11
• Superior costal facet complete
• Costal facets - no facet
T12
• Superior costal facet complete
• Costal facets - 3 tubercles (superior, inferior, lateral)
• Spine horizontal
Lumber
Typical lumber vertebrae (L1- L4) *No costal facet or foramina transeversaria
Body • Large
• Kidney shape
Vertebral foramen • Triangular (medium)
Transverse process • Thin, tapering
• Postero-superior root→ mammillary process
• postero-inferior root→ accessory process
Spinous process • Quadrilateral plate
Articular process • Very characteristic.
• Superior facets face laterally & interlock with upper facets.
Sacrum
Base • Sacral promontory – anteriorly
• Sacral canal – triangular
• Transverse process + costal elements – Ala
Apex • Oval facet for coccyx
Pelvic surface • Concave
• 4 transverse ridges
• 4 anterior sacral foramina
Dorsal surface • Median sacral crest – spines
• Sacral hiatus
• Articular processes - sup. of S1 – free
• Inf. of S5 - sacral cornua
• 4 dorsal sacral foramina
• lateral sacral crest – fusion of transverse processes
• Intermediate sacral crest – fusion of articular facets
I. Intervertebral joints
a) Zygapophyseal joints -
• Between superior & inferior articular facets
• Synovial joint
• Cervical region: articular facets lie obliquely
• Thoracic region: articular facets lie in an arc
• In lumbar region: articular facets interlock
01. Anterior longitudinal ligament - attached to body and intervertebral disc. More strongly to body.
Extend from base of skull to anterior of sacrum
02. Posterior longitudinal ligament - attached to body and intervertebral disc. More strongly to
disc.Starts from axis. Lines part of anterior surface of vertebral canal
04. Interspinous ligament - unites spinous processes along adjacent borders. Well developed in
lumbar region
07. ligamentum nuchae – extends from C7 spine to the external occipital protuberance.
Clinicals
• Death in execution is due to the rupture of the transverse ligament of dens, which then
compress the medulla oblongata & spinal cord
• Cervical spondylosis
• Due to the horizontal position of articular facets, dislocation occurs without fracture
Anterior margin - intervertebral disc & adjacent bodies of vertebra above & below
Clinical
• 1/5 of height of vertebral column – Intervertebral disc
01. Disc prolapse [slip disc]
Trauma Degenerative disease Sudden stress
03. Spondylosis
• Degenerating changes with ageing
04. Spondylolysis
• Inf. articular processes, spine & laminae vertebra separate from rest of body due to
fracture of pars interarticularis (loss of scotty dog appearance)
Common in L5
05. Spondylolisthesis
• Forward slippage of vertebral body
09. Spread of cancers – prostatic, breast & cervical cancers can spread into external vertebral
venous plexus via valveless connections & then into any part in the body
Clavicle
• Special features
- Only long bone which lies horizontally
- Subcutaneous throughout
- 1st bone to start ossifying
- Only long bone which has a membranous ossification
- Only long bone which has 2 primary centers of
ossification
- Generally, has no medullary cavity
- The supraclavicular nerves crossing it can be rolled
against the bone
Shaft
o Lateral 1/3
▪ Flattened from above downwards
▪ Anterior border concave forwards, posterior
border convex backwards
▪ Superior surface is subcutaneous, inferior
surface has an elevation – conoid tubercle, and
a ridge- trapezoid ridge
o Medial 2/3
▪ Rounded
▪ Anterior surface convex forwards
The ends
o Medial
▪ Sternal end
▪ Quadrangular
▪ Articulates with the clavicular notch of the manubrium to form the sternoclavicular
joint
▪ Articular surface extends up to the inferior aspect to articulate with the 1st costal
cartilage
o Lateral
▪ Acromial end
▪ Flatten from above downwards
▪ Has a facet for the acromion and forms the acromioclavicular joint
Attachments
• Margins of the lateral and medial articular surfaces give attachment to the joint capsules
Clinical
• Fracture
- Commonest site – junction between medial 2/3 & lat. 1/3 (weakest point) between
costoclavicular and coracoclavicular ligament
- Caused by falling on the outstretched hand
- Lat. fragment – displaces downwards by the weight of the upper limb
- Med. fragment – displaces upwards by the action of sternocleidomastoid
- Adductor muscles spasm – adduction of the arm
Dislocation
• Weight transmission
1. Scapula
2. Coracoclavicular ligament
3. Clavicle
4. Sternoclavicular joint to sternum or
5. Costoclavicular ligament to first rib
Side determination
2 surfaces
1. Costal – subscapular fossa. Directed medially and forwards. Have three longitudinal ridges.
2. Dorsal – spine of scapula is present. It divides the surface into supraspinous and infraspinous
fossae. Two fossae connected through spinoglenoid notch laterally.
3 borders
1. Superior- thin and short. Suprascapular notch present at the root of coracoid process
2. Lateral- thick. At the upper end the infraglenoid tubercle is present
3. Medial- thin.
3 processes
1. Spine- triangular. Has 3 borders and 2 surfaces. The posterior border is called the crest of
spine which has upper and lower lips.
2. Acromion- has medial and lateral borders. Has superior and inferior surfaces. Has an oval
facet for clavicle.
3. Coracoid- directed forwards and slightly laterally. Directly inferior to lateral part of the
clavicle. Bent. Has an atavistic type of epiphysis.
Muscle attachments
Clinical
• Winging of scapula
✓ Due to paralysis of serratus anterior
✓ Medial border becomes unduly prominent.
✓ Arm cannot be abducted beyond 90 degrees.
• Scaphoid scapula
✓ Development anomaly.
✓ Medial border is concave.
• Fracture
✓ Rare.
✓ Strong thick covering of muscles protects it.
✓ Only by direct and severe violence.
✓ Suprascapular nerve and vessels
Humerus
Side determination:
Upper end
Shaft
Lower end
Inferior surface- area for scaphoid and lunate which take part in forming the wrist joint
Clinical – Radius
Side determination
• The upper end is hook like with its concavity directed forwards
• Lateral border is sharp and crest like
• Pointed styloid process lies posteromedial to the rounded head of ulna at its lower end
Upper end
• Presents :
Olecranon process- projects up from the shaft
Coronoid process- just below olecranon process
Trochlear notch-articular surface for trochlear of humerus to form the elbow joint
Radial notch- for head of radius
Shaft
• 3 borders
• Lateral border is the sharpest
• Posterior border is subcutaneous and is not crossed and therefore can be exposed surgically
• Anterior border terminates at the medial side of styloid process
Lower end
Clinical-
Dislocation of the elbow by a fall on the outstretched hand with the elbow slightly flexed. -
• Fracture of the olecranon is common and is caused by fall on the point of the elbow
• Miner’s elbow / Student’s elbow
• Green stick fractures (common in children)-one side of bone is broken &other side only bent
Let’s start with the muscles categorized according to their relation to the axilla.
The nerve supply to each muscle is also included in the charts below for convenience but try
to understand that innervation after learning the brachial plexus.
As a base to build up your knowledge on any region of upper limb (lower limb too) first be
thorough with your muscles!
To understand their function , let’s take a brief look at movements of shoulder joint.:
Intramuscular injections -- to lower part of the deltoid muscle (avoid injury to axillary
nerve)
Clinical
1) Pectoralis Major-
clavicular head - the arm is abducted to 90
degrees or more
The patient pushes the arm forwards against
resistance.
sternocostal head- the arm is abducted to 60
degrees
Adduct against resistance.
The contracting heads can be seen and felt.
• (Pec. Major is the only muscle of the upper limb to be
supplied by all 5 segments of brachial plexus)
• Pec. Major testing ( alternative methods)
Clavicular head - attempt to lift a heavy table
- flex arm to a 90 against
resistance
2) Trapezius- The shoulder is shrugged against resistance and the upper border
of the muscle is seen and felt.
3) Latissimus Dorsi-
▪ The arm is abducted to a right angle
4) Serratus Anterior- With the arm flexed and the elbow extended the
outstretched hand is pushed against a wall. Paralysis results in ‘winged
scapula’, where the vertebral border becomes prominently raised off the
posterior chest wall.
B. Muscles of shoulder
2) Deltoid- The arm is abducted against resistance and the muscle is seen and
felt.
1. Sternoclavicular joint
2. Acromioclavicular joint
3. Shoulder joint
It is the most mobile and most frequently dislocated joint in the body. Its anatomical
structure has gained a wide range of mobility at the expense of stability.
• Type – Typical synovial, ball & socket, multiaxial
• Articular surfaces – Shallow, too small glenoid fossa ( 1/4th of the surface area of humeral
head(deepened by glenoidal labrum which is a fibrocartilaginous ring around the margin of
glenoid fossa ) & Head of humerus (1/3 of a sphere) covered by hyaline cartilage
• Capsule – Collagen
Pain sensitive
Strong but lax (doesn’t strengthen the joint enough)
Attachment
• Ligaments Extracapsular
*Transverse humeral ligament (bridges bicipital groove)
*Coracoacromial ligament
Superior
Intracapsular
*Glenohumeral lig. Middle
Inferior
• Blood supply -
Anterior &
posterior
circumflex
humeral
- Suprascapular
- Subscapular
Nerve supply - Axillary nerve, Musculocutaneous nerve, Suprascapular nerve
Factors contributing to mobility will contribute to reduced stability (increase the risk of
dislocation) and generally vice versa.
● Two gliding planes, one internal (the glenohumeral articulation) and one external (the
subcoracoid–subacromial–subdeltoid plane). Gliding is facilitated by
the synovial lined cavities of the glenohumeral joint and
the subcoracoid, subacromial and subdeltoid bursae, which are nearly always
contiguous.
● The synovial membrane lines the capsule and covers parts of the anatomical
neck.
● The curvature of the glenoid fossa is deepened by a fibrocartilaginous rim, the glenoid
labrum
● Humeral head is contained in a spherical space bounded medially by the glenoid fossa and
elsewhere by the deep surface of the fibrous capsule
● A fibrous capsule envelops the joint. It is lax however it is very tough. It is attached
medially to the glenoid neck at a variable distance from the glenoid labrum; it includes the
supraglenoid tubercle, to which the long head of biceps attaches, and which is therefore
intracapsular. Laterally, it is attached to the anatomical neck of the humerus, i.e. near the
articular margin,except inferomedially, where it descends more than 1 cm on the calcar
humerale. The fibres of the capsule are orientated in a spiral fashion, so that, in elevation of
the arm, the capsule tightens, so bringing the articular surfaces into closer apposition and
contributing to the concavity compression.
● The humeral head is held to the concave glenoid fossa by the compressive action of
the rotator cuff muscles – principle of “concavity compression”. The lateral part of the
external surface of the fibrous capsule is blended with the tendons of supraspinatus
(superiorly), infraspinatus and teres minor (posteriorly), subscapularis (anteriorly) – very
important factor in stability. They centre the head of the humerus in the glenoid fossa
through the entire
range of motion.
● Roughly spherical space bounded by the coracoid anteriorly; the coracoacromial
ligament anterosuperiorly; the acromion posteriorly – coracoacromial
arch/secondary socket
●
Further contributing to this is the spine of the scapula posteriorly, posterosuperiorly and
posterolaterally; and the deep surface of deltoid anterolaterally and laterally.
● Ligaments:
- Three glenohumeral ligaments (superior, middle and inferior), only visible
from within the joint, reinforce the capsule anteriorly and inferiorly.
- coracohumeral and
- transverse humeral
• Most stable in adduction and medial rotation: joint is in maximum congruity therefore
this is the preferred position of immobilization
• Least stable in abduction and lateral rotation: joint is in minimum congruity and most
likely to dislocate.
Movements of SJ
✓ The muscles that produce movements at the glenohumeral joint are principally
the scapulohumeral and thoracobrachial muscles.
Flexion - Flexion is carried out by pectoralis major (clavicular part), deltoid (anterior
fibres) and coracobrachialis, assisted by biceps.Sternocostal part of pectoralis major is a
major force in flexion forwards to the coronal plane from full extension.
Extension : Extension is carried out by deltoid (posterior fibres) and teres major, from
the dependant position. When the fully flexed arm is extended against resistance,
latissimus dorsi and the sternocostal part of pectoralis major act powerfully until the
arm reaches the coronal plane.
Adduction is carried out by the pectoralis major, latissimus dorsi, teres major and the
subscapularis
Medial rotation : Medial rotation is carried out by pectoralis major, deltoid (anterior
fibres), latissimus dorsi, teres major and, with the arm dependant, subscapularis.
Clinicals
• More prone to dislocation than any other joint
• Axillary nerve can be damaged during inferior dislocation of shoulder joint because this
nerve winds around the surgical neck of humerus. The consequences are;
• Subacromial bursitis - Tenderness over greater tuberosity beneath the Deltoid, disappears
when the arm is abducted
• Shoulder tip pain – due to irritation of respective dome of diaphragm (phrenic nerve
carrying impulses from peritoneum and supraclavicular nerves from skin above shoulder have
common C3 and C4 roots)
• Osteomyelitis of upper end of humerus can spread to shoulder joint by direct spread due
to the capsule attachment
Sternoclavicular Joint
• Type - Atypical Synovial, ball and socket
• Articular facets – covered by fibrocartilage
• Has complete articular disc
• Ligaments
1) Costoclavicular ligament
- Main stabilising factor
- It transmits the weight from clavicle to axial skeleton
2) Anterior and posterior sternoclavicular ligaments
3) Interclavicular ligament
Boundaries
Clavipectoral fascia
A thick sheet of connective tissue that clavicle to the floor of the axilla. It encloses subclavius
& pectoralis minor muscles and spans the gap between them (structures piercing this fascia
are listed later)
Deltopectoral fascia
Pectoral fascia (fascia overlying pec major muscle 0passes over the infraclavicular fossa and
deltopectoral groove to become continuous with fascia overlying deltoid. These are
collectively known as deltopectoral fascia. It curves around the lower edge of pec major to
become continuous with axillary fascia
AXILLARY ARTERY
Commences at the outer border of 1st rib as the continuation of subclavian artery and
continues as the brachial artery at the lower border of teres major.
The axillary artery is divided into 3 parts by the overlying pectoralis minor muscle;
✓ First part – above the muscle
✓ Second part – behind the muscle
✓ Third part – below the muscle
The 3 cords of brachial plexus derive their names ( medial, lateral & posterior according to
their relations to the 2nd part of axillary artey)
The axillary artery and the cords of brachial plexus in the axilla are enclosed within the
axillary sheath which is an extension of the prevertebral fascia of neck ( refer deep cervical
fascia in Head & Neck later)
✓ Thoracoacromial artery gives off 4 branches; pectoral, deltoid, acromial & clavicular
✓ Subscapular artery dicides into 2 branches; Thoracodorsal artery and circumflex
scapular artery
This anastomosis connects the 1st part of subclavian artery and 3rd part of
axillary artery.
This provides a collateral circulation when the subclavian artery is
obstructed.(eg; by a cervical rib)
- Cephalic vein passes in the deltopectoral groove and then pierces the clavipectoral
fascia to drain into the axillary vein.
- The vena comitantes of brachial artery join it near its commencement
3◊◊six divisions formed by each trunk dividing into an anterior and posterior
division; which link up again into:
The 5 roots – between scalenus anterior and scalenus middle in the posterior triangle of neck
✓ Posterior cord supplies the skin and muscles of the posterior aspect ( extensor
compartments) of the limb.
✓ Lateral and medial cords supply the anterior ( flexor) compartment structures .
Nerve Function
Lateral pectoral motor
Origin: Lateral cord Pectoralis major
Spinal segments:
C5 to C7
Musculocutaneous : motor
Origin: Lateral cord All muscles in the anterior compartment of
Spinal segments: the arm
C5 to C7 : sensory
Skin over lateral aspect of forearm
Lateral root of median nerve - it joins the medial root of median nerve of medial cord to
form the median nerve
Nerve Function
Medial pectoral : motor
Origin: Medial cord Pectoralis major, pectoralis minor
Spinal segments: C8, T1
Ulnar : motor
Origin: Medial cord All intrinsic muscles of the hand (except
Spinal segments: three thenar muscles and two lateral
(C7), C8, T1 lumbricals)
Function flexor carpi ulnaris and the medial half of
flfl exor
digitorum profundus in the forearm
: sensory
Skin over the palmar surface of the medial
one and one-half digits and associated
palm and wrist, and skin over the dorsal
surface of the medial one and one-half
digits
Medial root of median nerve – crosses laterally over the axillary artery and join the lateral
root of median nerve to form the median nerve
Function:
motor - All muscles in the anterior compartment of the forearm (except flfl exor carpi
ulnaris and medial half of flfl exor digitorum profundus), three thenar
muscles of the thumb and two lateral lumbrical muscles
sensory -Skin over the palmar surface of the lateral three and one-half digits and
over the lateral side of the palm and middle of the wrist
Median nerve is lateral to the axillary artery at its( nerve) commencement.
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Peripheral nerves given off by posterior cord
Nerve Function
Superior subscapular motor :
Origin: Posterior cord Subscapularis
Spinal segments: C5, C6
Axillary motor :
Origin: Posterior cord Deltoid, teres minor
Spinal segments: C5, C6
sensory :
Skin over upper lateral part of arm
Radial motor :
Origin: Posterior cord All muscles in the posterior compartments of
Spinal segments: arm and forearm
C5 to C8, (T1)
sensory :
Skin on the posterior aspects of the arm and
forearm, the lower lateral
surface of the arm, and the dorsal lateral
surface of the hand
1)Anterior (Pectoral) group •Along the lateral thoracic •Upper ½ of the anterior wall
vessels of the trunk
•Along lower border of pec •Major part of the breast
minor
2)Posterior (Scapular) group •Along subscapular vessels •upper ½ of the posterior
•On the posterior fold of wall of the trunk
Axilla •Axillary tail of the breast
3)Lateral group •Along the upper part of the •Upper limb
humerus
•Medial to axillary vein
4)Central group •Lie in the fat of the upper •Anterior, posterior & lateral
Axilla groups
•Floor of axilla
5)Apical (infraclavicular) •Lie deep to clavipectoral •Central group
group fascia •Upper part of the breast
•along the axillary vessels •The thumb and its web
CLINICAL
• Long thoracic , intercostobrachial nerve and thoracodorsal nerve can get damaged when
surgically removing axillary lymph nodes ( eg: during metastatic spread )
• C- Cephalic vein
• A- Acromiothoracic artery
• L- Lateral pectoral nerve
• L – Lymphatics
*Axillary sheath
Continuation of prevertebral fascia
Encloses brachial plexus, axillary artery. But NOT axillary vein.
Blood Supply
- Breast is extremely vascular
Arterial supply
1) Branches of axillary artery
I. Superior thoracic
II. Acromiothoracic - Pectoral branch
III. Lateral thoracic- Main
Nerve supply
- Ant. & lat. Cutaneous branches of 4, 5, 6 intercostal nerves
- Nerves DO NOT control the secretion of milk. Controlled by hormone, Prolactin
- Sensory fibers to the skin
- Autonomic fibers to the smooth muscle and blood vessels
Lateral
- Medial to the Axillary vein
Central
- In the fat of axilla
- receive lymph from anterior,
posterior, lateral groups
Apical
- Axillary vessels
- Receive lymph from central
and upper part of Breast
Developmental abnormalities
Clinical
-Superficial lymphatics communicate across the midline Cancer can spread from one breast
to another
Histology
Lactating phase
- Full of acini and minimum connective tissue
• Carrying angle – Disappear in full flexion. (Normally 5 - 15 away from the body, more in females.)
Factors forming the carrying angle is,
Medial flange of trochlea is 6mm deeper than the lateral flange
The superior articular surface of the coronoid process of ulna is placed
oblique to the long axis of the bone
• Dislocation – posteriorly triangular relationship (between 2 epicondyles and olecranon process) is lost
and coronoid may fracture
Posterior dislocation is common because capsule is weak and deep fascia is thin
• Subluxation - pulled elbow (radial head subluxate through the annular ligament)
Common in children
• Minors elbow (student’s elbow) – bursitis over the olecranon process.
• Tennis elbow- pain and tenderness over lateral epicondyle due to sprain of radial collateral, tearing of
fibers of extensor carpi radialis brevis, degenerative condition
• Golfers elbow - pain and tenderness over medial epicondyle. Microtrauma to medial epicondyle
• Cubital valgus: carrying angle more than 13o
• Cubital varus: carrying angle less than 13o
Interrosseus membrane
• Interrosseus membrane – downwards and medially from radius to ulnar
• Superior aperture- posterior interosseous vessels
• Inferior aperture- anterior interosseous vessels
• Other than providing attachments for muscles and binding bones, transmits forces from radius to ulna.
Arteries of Arm
Brachial artery
• Continuation of the axillary artery and terminate at
the neck of the radius dividing into 2 terminal
branches;radial and ulnar arteries.
• Superfical along it's whole course except at the
middle of the arm where it's crossed by median nerve
superficaly from lateral to medial (occasionally
deeply).-Brachial pulse
• Other named branches before it's termination are,
1) Profunda brachial artery -largest
a) Radial collateral
b) Medial collaterl
2) Nutrient artery to humerus
Subclavian Vein
1. Muscularcutaneous nerve
Lateral cord of brachial plexus > pierces coracobrachialis > passes in the plane between biceps
brachii and brachialis > pierces the deep fascia ( at the roof of cubital fossa) & continues as the
lateral cutaneous nerve of forearm
Posterior Cord
(Refer the figure at the end of “ at the level of insertion of coracobrachialis for the course of ulnar and
median nerve in the arm)
• Radial nerve
Divides into deep & superficial branches -At the level of lateral humeral epicondyle( before dividing
it innervates brachioradialis, extensor carpi radialis longus & lateral part of brachialis)
- superficial branch -cutaneous continuation of radial nerve & passes under the cover of
brachioradialis
- deep branch – innervates extensor carpi radialis brevis & supinator before disappearing between
the 2 heads of supinator into the posterior compartment of forearm. There it continues as the
posterior interosseous nerve.
Clinicals
Median cubital vein is chosen for intravenous
injections
Brachial artery is used to record blood
pressure ( Auscultatory method)
Venipuncture -1. Stability-fixed by
perforator
2.most superficial
3.seperated from brachial
artery by bicipital aponeurosis
Intermediate layer
Extensor compartment
Superficial layer
Muscle Origin Insertion Innervation Function
Brachioradial Proximal part of Lateral surface of Radial nerve (C5, Accessory flexor of elbow
is lateral supra- distal end of C6) before division joint when forearm is
epicondylar ridge of radius into superficial and midpronated
humerus and deep branches
adjacent
intermuscular septum
Extensor Distal part of lateral Dorsal surface of Radial nerve (C6, Extends and abducts the
carpi radialis supra-epicondylar base of C7) before division wrist
longus ridge of humerus and metacarpal 2 into superficial and
adjacent deep branches
intermuscular septum
Extensor Lateral epicondyle of Dorsal surface of Deep branch of Extends and abducts the
carpi radialis humerus and base of radial nerve (C7, wrist
brevis adjacent metacarpals 2 C8) before
intermuscular septum and 3 penetrating
supinator muscle
Extensor Lateral epicondyle of Four tendons Extends the index, middle,
digitorum humerus and which insert via ring and little fingers
adjacent extensor hoods Can also extend the wrist
intermuscular septum into the dorsal Posterior
and deep fascia aspects of the interosseous nerve
bases of the (C7, C8)
middle and distal
Deep layer
1) Pronator Teres- From the supine position the forearm is pronated against resistance and the muscle
palpated at the medial margin of the cubital fossa.
2) Flexor Carpi Radialis- The wrist is flexed and abducted against resistance and the tendon is easily
seen and felt.
3) Flexor Digitorum Superficialis- The fingers are flexed at the proximal interphalangeal joints against
resistance applied to the middle phalanges, while the distal interphalangeal joints are kept
extended.
4) Flexor Carpi Ulnaris- The wrist is flexed and adducted against resistance and the tendon palpated.
1) Flexor Digitorum Profundus- With the fingers extended and the hand lying supine on the table, the
distal interphalangeal joints are flexed against resistance with the middle phalanx held in extension.
2) Flexor Pollicis Longus- With the proximal phalanx of the thumb held steady, the distal phalanx is
flexed against resistance.
1) Brachioradialis- With the forearm in the midprone position the elbow is flexed against resistance;
the muscle can be seen and felt
Transverse
section of
the forearm
Radial artery
Ulnar artery
• Larger
• At the commencement it passes beneath the mucles of common flexor origin(deep to
pronator teres after passing through the cubital fossa).
• It gives off common interosseous artery at it’s commencement and it divide into anterior
and posterior branches, runs on the interosseoues membrane, join distal to it and supply the
carpal joints.
Posterior compartment
• Dislocated carpus may then reduce spontaneously and tilt it over; its distal surface facing forwards
(dislocation of the lunate)
• Bennet’s fracture – fracture of the base of the first metacarpal. Caused by a force along the axis of the bone.
Thumb cannot be opposed.is fixed semi flexed. Fist cannot be clenched
➢ Superficial fascia
• Dense fibrous bands
• Bind skin to palmar aponeurosis
• Contains a subcutaneous muscle, Palmaris brevis
➢ Deep fascia
• Wrist - flexor retinaculum
• Palm - palmar aponeurosis
• Deep fascia forms the fibrous flexor sheaths
Flexor Retinaculum
• Strong fibrous horizontal band which bridges the anterior concavity of the carpus.
• 2-3cm transversely and longitudinally
• Attachments of the flexor retinaculum
Laterally-tubercle of scaphoid & crest of trapezium
Medially-hook of hamate & pisiform bone
• Thenar and hypothenar muscles arise from the retinaculum
Extensor Retinaculum
Attachment – Laterally – Lower part of sharp anterior border of the radius
Medially – Styloid process of Ulna
Triquetral
Pisiform
Palmar aponeurosis
• The deep fascia in the central region of the palm, reinforced by a superficial layer of longitudinal fibers
continuous with the tendon of the palmaris longus muscle and by deeper transverse fibers
• Triangular in shape
• Proximal apex blends with flexor retinaculum & continuous with the tendon of palmaris longus
• Distally divides into 4 strips; 1 for each finger
▪ Distally divides into 2 layers
▪ Superficial layer – blends with skin
▪ Deep layer – 4 slips- blends with fibrous flexor sheaths
▪ No slip for thumb – more mobile (but plantar aponeurosis has)
• Fingers fibrous flexor sheaths (see grants pic)
Forms a blind fibro-osseous tunnel – tendons of FDS and FDP and
synovial sheath lie there.
• After exiting the carpal tunnel, the tendons of the flexor digitorum superficialis & profundus cross the palm &
enter fibrous sheaths on the palmar aspect of the digits.
• These fibrous sheaths
➢ Begin proximally, anterior to the MP joints, and extend to the distal phalanges
➢ Are formed by annular ligaments & cruciate ligaments, which are attached posteriorly to the margins of the
phalanges and to the palmar ligaments associated with the MP & IP joints
➢ Hold the tendons to the bony plane & prevent the tendons from bowing when the digits are flexed
Clinical
Carpal tunnel syndrome
Symptoms caused by compression of the median nerve within the carpal tunnel due to any lesion diminishing
the size of the compartment
- dislocation of the lunate
- arthritis
- Edematous synovial sheaths
Boundaries
Contents
• Radial artery
• Superficial branch of radial nerve
• Cephalic vein
Clinicals
2) Volkmann’s contracture
• Follows ischemia and subsequent fibrosis and contraction of the long flexor and extensor muscles of the
forearm
• Deformities
➢ Flexion at the wrist - since the flexors of the wrist are bulkier than the extensors, their
fibrous contraction is greater
➢ Extension at the metacarpophalangeal joints - due to the contracture of the long flexors
inserted into the proximal phalanges
➢ Flexion at the interphalangeal joints - due to the contracture of long flexors; inserted into
the distal and middle phalanges
➢ Extrinsic muscles
➢ Intrinsic muscles
Thenar muscles
Muscle Nerve Action
Abductor pollicis Median nerve (recurrent abduction of thumb C/M & M/P joints
brevis branch) [associated with medial rotation]
Flexor pollicis Superficial - median flexion of thumb
brevis nerve deep head may be
by ulnar nerve
Opponens pollicis Median nerve (recurrent opposition - thumb [flexion, medial rotation]
branch)
Hypothenar muscles
Muscle Nerve Action
Opponens digiti minimi Ulnar nerve deep branch opposition with thumb,
lat. rotation
Flexor digiti minimi flexion of M/P joints
brevis
Abductor digiti minimi abduction of M/P joints
1) Flexion at the metacarpophalangeal and interphalangeal joints - by flexor pollicis longus and brevis
2) Extension at the metacarpophalangeal and interphalangeal joints - by extensor pollicis longus and
brevis
3) Palmar abduction (abduction) - by abductor pollicis brevis; thumb moves away from the index
finger in a plane perpendicular to the palm
4) Radial abduction (extension) - by abductor pollicis longus and extensor pollicis brevis
5) Adduction - by adductor pollicis; further transpalmar adduction is by flexor pollicis brevis
6) Opposition - a composite movement making the thumbnail lie parallel with the nail of the opposed
finger
6) The lumbricals and interossei are tested by asking the subject to flex the fingers at the
metacarpophalangeal joints against resistance
2. Radial bursa
• Synovial sheath of flexor pollicis longus tendon
• Extent – Upwards – 2”-3” into forearm
Downwards – up to distal phalanx of thumb
• Infection of the thumb may spread to the radial bursa
• At each of the skin crease of the fingers, the skin is bound down to the underlying
flexor sheath so that the pulp over each phalanx is in a separate compartment cut off
from its neighbors. So usually infection doesn’t spread much. Infection may however track from one space to
another along the neurovascular digital bundles if the infection is not treated well.
Thenar space infection (usually the infection in the web of thumb or untreated infection in the pulp
space of thumb or index finger)
• Rectangular
• Just above the wrist
• In front of pronator quadratus deep to long flexor tendons
• Extent
▪ Proximal - oblique origin of flexor digitorum superficialis
▪ Distal - Flexor retinaculum
• communicates with
- Midpalmar space
- Thenar space
• proximal part of ulnar & radial bursae protrudes into forearm space
• 3 web spaces lie in the distal part of the palm between the bases of proximal phalanges of four fingers
• Bounded by superficial transverse metacarpal ligament above & deep transverse metacarpal ligament below.
• Extend proximally up to the metacarpophalangeal joint.
• Contents from superficial to deep
- Superficial transverse metacarpal ligament
Web of thumb
- Lacks both superficial & deep transverse metacarpal ligaments
- Contain the heads of adductor pollicis & 1st dorsal interosseous
- Princeps pollicis & radialis indicis arteries
- Sensory loss over the skin in radial nerve palsy
Clinical:
01)T/F
a) Ulnar bursa encloses all flexor tendons
b) Infections of little finger and thumb can spread upto the forearm
c) Thick, creased skin in palmar surface increases grasping ability of hand
02)T/F
a) In whitlow distal 1/5th may get necrosed
b) In infections of mid palmar spaces swelling can be seen in the dorsal surface
c) Severe throbbing pain in pulp space infections is due to tight compartments formed by subcutaneous
fat
Superficial
Deep to palmar Superficial
arch to
- Palmaris brevis - Flexor digiti minimi
- Palmar - Flexor tendons of fingers
aponeurosis - Lumbricals
- Median nerve- digital branches
Branches – - to medial 3 ½ finger
3 common digital branches –joined to palmer metacarpal arteries from deep palmer arch
1 proper digital branch
DEEP
PALMAR
Deep to Superficial to
ARCH
-Metacarpals-shafts-proximal parts
-adductor pollicis- oblique head -interossei
-long flexor tendons of fingers
-lumbricals
❖ Deep branch of ulnar nerve lies within the concavity of arch
Branches
1. 3 palmar metacarpal arteries – join with lateral 3 digital branches to form
common digital branches,
Each common digital branch divides into proper digital branches & supply digits
Clinical
Allen’s test
• To test the patency of each ulnar & radial arteries, related to blood supply of the hand
Clench fist -> occlude radial & ulnar arteries -> fist is released -> skin of palm pale -> release one artery
Innervation of hand
Deep branch : Passes deep into the palm between abductor digiti minimi & flexor digiti
minimi to reach the surface of interossei.
Then arches within the concavity of deep palmar arch towards adductor policis muscle.
This branch (T1 myotome) gives motor supply to,
All interossei, all 3 hypothenar muscles, adductor policis, medial 2 lumbricals
Oher terminal branches of median nerve supply – lateral 2 lumbricals & lateral 3 ½ fingers (
including their nail beds)
• 3 parts – divided by Pec. Minor– 1st part above, 2nd part behind and 3rd part below Pec. Minor
SALSAP
1st part -skin -serratus ant. -lateral & pos. -Axillary vein
-superf. fascia -medial cord of cords of brachial
-deep fascia brachial plexus plexus
-pec major with medial
- clavipectoral pectoral nerve
fascia -1st intercostal sp.
2nd part -skin -post. Cord of -lateral cord of -Axillary vein
-superf. fascia brachial plexus brachial plexus -medial cord of
-deep fascia -subscapularis -coracobrachialis brachial plexus
-pec major -medial pectoral
-pec minor nerve
Clinicals
These are anastomosis between -1st part of Subclavian artery
-3rd part of Axillary Artery
They provide a collateral circulation when distal part of subclavian A. or proximal part of Axillary A. is blocked
Important in coarctation of the Aorta
2) Brachial Artery
• Continuation of the Axillary Artery.
• Extends from the lower border of Teres Major to neck of the radius.
• In the proximal arm, lies on medial side.
• In the distal arm, it moves laterally to assume a position midway between lateral epicondyle and the
medial epicondyle of the humerus.
• It crosses anteriorly to the elbow joint, lies immediately medial to the tendon of biceps brachii muscle.
Surface marking – Arm abducted to eight angle, line from middle of clavicle to the midpoint between
the humeral epicondyle. Readily palpable.
Branches
4) Ulnar Artery
• Main artery of forearm.
• Starts at the level of neck of Radius.
• Oblique in upper 1/3 & vertical in lower 2/3.
• Runs on medial side of forearm with ulnar nerve (in lower
part) under flexor carpi ulnaris muscle upon flexor
digitorum profundus.
• Median nerve crosses superficially to ulnar artery
separated by deep head of Pronator teres.
• Leaves forearm superficial to flexor retinaculum deep to
volar capal ligament
Superficial
Deep to palmar Superficial
arch to
- Palmaris brevis - Flexor digiti minimi
- Palmar - Flexor tendons of fingers
aponeurosis - Lumbricals
- Median nerve- digital branches
Branches – - to medial 3 ½ finger
3 common digital branches –joined by the palmer metacarpal arteries from deep palmer arch
1 proper digital branch
Surface marking_
1. Just lateral & distal to pisiform.
2. Medial to hook of hamate.
3. On the distal border of the thenar eminence in line with the 2 nd cleft
5) Radial Artery
• Main artery of hand.
• Starts at the level of neck of Radius.
• Lies laterally on muscles forming radial bed with superficial branch of radial nerve. (only in middle 1/3
of forearm)
• Medially related to brachioradialis in its whole length.
• Gives off a branch to assist in forming superficial palmar arch.
• Leave forearm by turning posteriorly then passes deep to the tendon of abductor pollicis longus and
extensor pollicis brevis to enter the anatomical snuffbox. (pulsation can be felt)
• Runs between two heads of the first dorsal interosseous muscle
• Lie deep to oblique head of adductor pollicis and then pass through two heads of adductor pollicis.
• Form the deep palmar arch, with the deep branch of ulnar artery.
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Branches
• in forearm -radial recurrent artery
-muscular branches
-palmar carpal branch – forms palmar carpal arch
-dorsal carpal branch – forms dorsal carpal arch
-Superficial palmar branch-arise just before winding backward
Pass through thenar muscles
Join superficial branch of Ulnar artery to complete the superficial palmer arch
• Dorsum of hand
- A branch to the lateral side of the dorsum of the thumb
- First dorsal metacarpal artery – for the adjacent sides of the thumb & index finger
• In the palm (deep to the oblique head of the adductor pollicis)
- Princeps pollicis artery-divides at the base of the proximal phalanx of the thumb into 2
branches for the palmar surface of the thumb
- Radialis indicis artery- descends between the 1st dorsal interosseous muscle and the
transverse head of the adductor pollicis to supply the lateral side of the index finger
DEEP
PALMAR
Deep to Superficial to
ARCH
-Metacarpals-shafts-proximal parts
-adductor pollicis- oblique head -interossei
-long flexor tendons of fingers
-lumbricals
Branches
Clinical
Allen’s test
• To test the patency of each ulnar & radial arteries, related to blood supply of the hand
Clench fist → occlude radial & ulnar arteries → fist is released → skin of palm pale → release one artery
Elbow Anastomosis
Wrist – radius (ant. Border) laterally Junction – upper 1/3 & lower 2/3 of
Flexor carpi radialis tendon medially forearm medial border
(Radial pulse felt) Lateral to pisiform
-runs along medial side of arm & forearm -lies in the roof of anatomical snuff box
-Pierces deep fascia at the middle of arm -Lateral border of upper limb
-Most of the blood drains into basilic vein via
-continues as axillary vein at the lower border median cubital vein
of teres major
-Can be used for emergency venous cut down at
the deltopectoral groove.
-It pierces clavipectoral fascia and drains into
axillary vein
Cervical Plexus
Brachial Plexus
Lumbar Plexus
Sacral Plexus
Plexus of nerves formed by the ant. Primary rami of the C5, C6, C7, C8, T1 nerve roots with contributions
from the C4 and T2 nerve roots.
Nerves from the BRACHIAL PLEXUS innervates all the muscles of the UPPER EXTREMITY
ROOTS between ant. & middle scaleni ( Floor of the Posterior Triangle )
The anterior divisions only innervate the anterior compartment of the upperlimb (flexor compartment)
The posterior divisions only innervate the posterior comaprtment of the upperlimb (extensor compartment)
Proximal nerve roots innervate the proximal segments and distal nerve roots innervate the distal segments
of the upper extremity
Shoulder – c5 & c6
Hand – c8 & t1
Identification of the components of the brachial plexus is mainly done in relation to the m shape at the 3rd
part of axilliary artery
3 MUSKATEERS – Musculocutaneous – C5 / C6 / C7
Cause Undue separation of head from shoulders Undue abduction of arm due to
( Lateral Flexion of Neck + Extension of Shoulder ) Birth injury (breech
Due to –birth injury - Pulled from the Head delivery)
fall on shoulder Pulled from the Upperlimb
anaesthesia Clutching something after fall from
a height
Cervical rib
Nerve roots C5, C6 T1, C8
Musculocutaneous Nerve –
Muscular to the Anterior Arm compartment ; Cutaneous anterolateral aspect of forearm
Damaged in Misplaced injection into deltoid as well. ( INJECTIONS must be placed 3 finger breaths
BELOW the acromion process )
Paralysis of deltoid.
Arm can’t be abducted beyond 15 degrees.
Sensory loss over lower half of deltoid. (regimental badge sign)
Greater tubercle becomes prominent. (atrophy of the deltoid) - flattened contour of
shoulder.
Root values are C5, C6, C7, C8, T1 anterior primary rami.
Origin by the union of medial root from medial cord & lateral root from lateral cord in axilla lateral
to the axillary artery, where medial root crosses 3rd part of axillary artery from medial to lateral and
join with lateral root to form the median nerve.
Nerve runs lateral to the 3rd part of the axillary artery.
In the upper part of arm, runs lateral to the brachial artery.
At the level of insertion of corachobrachialis, crosses brachial artery from lateral to medial
anteriorly.
In the lower part of the arm, runs medial to brachial artery.
Supplies Brachial artery.
Gives a motor branch to Pronator teres before leaving the arm.
In the cubital fossa, runs medial to brachial artery. (RTAN)
Gives motor branches to Flexor carpi radialis, Palmaris longus, Flexor digitorum superficialis.
TO ALL flexor muscles of the Forearm except the Flexor carpi ulnaris and Flexor digitorum
profundus to ulnar 2 fingers
Passes between two heads of pronator teres. (here ulnar artery lies deep to the deep head of
pronator teres)
Passes deep to the fibrous arch of flexor digitorum superficialis, on flexor digitorum profundus.
Sandwitched between FDS and FDP
In the forearm gives Anterior interosseous branch supplying lateral half of Flexor digitorum
profundus, Flexor policis longus, Pronator quadratus.
Continuation descends deep to flexor digitorum superficialis and adheres to it.
Supplies the whole of FDS - Flexor Digitorum Superficialis
At the lower border of forearm, gives Palmar cutaneous branch which goes superficial to flexor
retinaculum supplying lateral 3 and 1/2 of palm and Fingers including the nail beds
At wrist lies deep and lateral to the palmaris longus tendon.
Enters the Carpal tunnel just deep to the flexor retinaculum.
Lies between tendons of flexor digitorum superficialis and tendon of flexor carpi radialis.
Lies medial to the muscles of thenar eminence.
Gives off recurrent branch to thenar muscles. (Abductor pollicis brevis, Flexor pollicis brevis,
Opponens pollicis) – Median nerve has a Constant motor innervation of the APB
Divide into medial and lateral branches.
Gives Digital branches to 1st & 2nd lumbricals.
Cutaneous supply to Palmar surface of lateral 3 ½ digits with their nail beds & distal dorsal skin.
If damage is above the elbow. (Supracondylar fracture) = FDS and FDP to the RADIAL
2 fingers PARALYSED
Cutaneous loss-
Vasomotor changes-
Oedema
Pigmentation of skin
Friable nails
Dryness of skin
Trophic changes –
1) Unable to pick a pin with thumb & index finger. (Due to inability to oppose thumb)
2) Pen test for abductor pollicis brevis.
Lay the hand flat on a table, palm directed upwards. Patient is unable to touch a pen held in
front of the palm by a thumb.
Clinical -
Damage at wrist
Commonest.
Produces Ulnar claw hand. (Claw hand - Hyperextension at m/p joints due to
paralysis of interossei & lumbricals, Flexion at I/p joints)
Sensory loss – medial 1/3rd of palm & medial 1 ½ fingers including nail beds.
Ulnar paradox
If injured @elbow, clawing of fingers is less, because medial half of FDP is also paralysed.
If injured @wrist, clawing is more, because intact FDP flexes digits more.
Distal more clawing; Proximal less clawing.
Clinical Testing
1) Place the hand on a flat surface. ( To remove the
contribution from FLEXORS and EXTENSORS )
2) Place a paper between two fingers.
3) See how firmly it can be held.
ADDUCTION of FINGERS – Palmar IO - PAD
ABDUCTION of FINGERS – Dorsal IO - DAB
Radial Nerve
Main nerve of the posterior compartment of the upper limb ; Motor innervation to the Posterior &lower
lateral arm and Posterior forearm
Root values are C5, C6, C7, C8, T1 anterior primary rami.
Originates from the posterior cord posterior to the 3rd part of the axillary artery.
In the axilla gives motor branches to long head & medial head of Triceps and Posterior cutaneous
nerve of arm.
SUPPLIES all muscles of the EXTENSOR COMPARTMENT of ARM and EXTENSOR COMPARTMENT of
FOREARM
Passes through the lower triangular space (triangular interval) along with the profunda brachii
vessels.
Enters the posterior compartment of arm.
In the upper part of the arm, runs posterior to brachial artery.
Then enters the radial groove between medial and lateral head of triceps along with profunda
brachii vessels running downwards medial to lateral.
Gives motor branches to lateral & medial heads of Triceps brachii and Anconeus.
Cutaneous branches Lower lateral cutaneous nerve of arm and Posterior cutaneous nerve of
forearm.
Clinical -
IO and lumbricals provide connection between flexion and extension actions of the fingers
Increases the manual dexterity of the fingers
ED – Radial nerve
FDS – Median nerve
FDP – medial ½ - Median nerve
FDP – ulnar ½ - Ulnar nerve
Cutaneous innervation –
DERMATOMES & CUTANEOUS FILEDS of CUTANEOUS NERVE
Motor innervation –
MYOTOMES
Intercostobrachial nerve
This nerve is the lateral cutaneous branch of the second intercostal nerve.
Emerges from the second intercostal space anterior to the long thoracic nerve and crosses the axilla.
Supplies the skin of the axilla ( Arm pit skin )
It may be in contact with level I lymph nodes and be at risk during node excision.
The Thoraco - epigastric vein crossed posterior to the nerve and aids identification
DERMATOMES arranged around the VENTRAL AXIAL LINE anteriorly ( Refer the embryology of the upper -
limb )
MYOTOMES – Movements that are contributed by motor neurons originating from a single spinal nerve root
UPPER ROOTS supply PROXIMAL LIMB SEGMENTS & LOWER ROOTS supply DISTAL LIMB SEGMENTS
eg-
Hand – C8 & T1
Shoulder ; Arm – C5 & C6
Pubis
• The body of the pubis projects laterally as a superior ramus which joins the ilium and ischium at
the acetabulum
• Inferior ramus fuses with the ischial ramus medial to the obturator foramen.
• The symphyseal surface of the body forms the secondary cartilaginous joint that constitutes the
pubic symphysis
• The upper border of the body is the pubic crest.
• It is marked laterally by a prominence – the pubic tubercle.
• From the pubic tubercle two ridges diverge laterally onto the superior ramus.
• The upper ridge, sharp, is the pectineal line; it forms part of the pelvic brim and joins the arcuate
line of the ilium.
• Pectineus arises from the pectineal line and the adjacent surface of the superior ramus.
• The lower ridge, more rounded, is the obturator crest.
• Below the obturator crest on the pubic ramus is the obturator groove, which lodges the
obturator nerve.
• The pubic tubercle receives the attachment of the inguinal ligament,
Ischium
• The ischium is an L-shaped bone
• The body joins with pubis and ilium at the acetabulum and extends down to the ischial
tuberosity; it supports the sitting weight.
• The obturator membrane is attached to the margin of the foramen.
• Outer surface - obturator externus inner surface – obturator internus
• The spine of the ischium projects medially to divide the greater from the lesser sciatic notch
below it.
• The sacrospinous ligament is attached to it, contributing to conversion of the greater sciatic
notch into the greater sciatic foramen
• The lesser sciatic notch lies between the spine and the ischial tuberosity.
• It is bridged by the sacrotuberous ligament, which with the sacrospinous ligament converts the
notch into the lesser sciatic foramen
• Obturator internus emerges through this foramen into the buttock, and the internal pudendal
vessels and nerve pass forward into the perineum.
Femur
• Longest and strongest bone of the body
• Growth direction of long bones of lower limb– away from knee
• Ossifies from 1 primary center and 4 secondary centers
• Upper end
• Consists of head, neck, greater and lesser trochanters
• Head
• More than half a sphere
• Articulates with acetabulum to form hip
joint
• Contains a roughened pit behind and
below the center of the head called
fovea
• Neck
• Connects head with shaft
• Upper border is concave, horizontal and
meets shaft at greater trochanter
• Lower border is straight, oblique and
meets shaft near lesser trochanter
• Anterior surface is flat and meets shaft
at intertrochanteric line and is entirely
intracapsular
• Posterior surface is convex vertically
and concave horizontally and meets
shaft at intertrochanteric crest. Medial half is intracapsular
• Makes an angle with the shaft (125° in adults)
• Angle larger in males
• Angle facilitates movement of hip joint
• Intertrochanteric line
• Prominent roughened ridge
• Continuous below with spiral line
• Intertrochanteric crest
• Smooth rounded ridge
• Ends at lesser trochanter
• Rounded elevation present a little above the crest’s middle – quadrate tubercle
• Shaft
• Cylindrical (middle part triangular)
• Directed obliquely downwards and medially – therefore brings knees closer to center of gravity
• Lower end
• Widely expanded to form 2 large condyles
• Anteriorly the 2 condyles are united and are in line with the front of the shaft
• Posteriorly separated by a deep gap – Intercondylar fossa
• Walls of intercondylar fossa
• Lateral surface of medial condyle – large oval facet for posterior cruciate ligament
• Medial surface of lateral condyle – small oval facet for anterior cruciate ligament
• Articular surface partially covers 2 condyles
• Articular surface for patella
• Covers the anterior surface of both condyles
• Extends more on the lateral condyle than the medial condyle
• Surfaces of the medial and lateral condyles that articulate with the patella form a V-shaped trench
which faces anteriorly. Lateral surface of trench is larger and steeper
Clinicals
1. Fractures of the neck of the femur
Pertrochanteric – Extracapsular
Basal
Cervical. Intracapsular
Subcapital
2.Midshaft fractures
• Considerable shortening occurs
• Due to longitudinal contracture of surrounding muscles
• Proximal segment flexed by iliacus and psoas and
abducted by gluteus medius and minimus
• Distal segment pulled medially by adductors
Patella (Kneecap)
• Triangular in shape with its apex downwards
• Posterior surface is divided by a vertical ridge
• Largest sesamoid bone of the body
• Lies in the tendon of quadriceps tendon. Continues as ligamentum
patellae from apex
• When set on a table it rests on the larger lateral surface (side
• determination)
• Posterior surface is articular in its upper three-fourths and covered with
hyaline cartilage
• Separated from the skin by prepatellar bursa
Clinical
• Has a natural tendency to dislocate laterally
(Patellar ligament vertical, but pull of quadriceps is oblique)
But it is prevented by,
1. Bony factors: prominent articular surface of the lateral femoral condyle
2. Muscular factors: medial pull of the lower most fibres of vastus medialis which
Tibia
Side determination
UPPER END
Expanded side to side by 2 massive condyles
1)Medial condyle
• Larger
• Superior articular surface is oval, longer anteroposteriorly, concave
• with medial femoral condyle(central) and medial meniscus(peripheral)
2)Lateral condyle
• Superior articular surface is nearly circular
• With lateral femoral condyle(centre) and lateral meniscus(peripheral)
• Medial margin of articular surface is raised to cover the lateral Intercondylar tubercle
• Postero-inferior aspect articulates with the fibula. Fibula facet is flat, circular
• Superior to fibular facet groove for popliteus tendon
• Anterior aspect Smooth ‘Gerdy’s tubercle’ ITT
3)Intercondylar area
• Tibial plateau rough and elevated between
condylar surfaces Intercondylar eminence
• Intercondylar eminence grooved antero-
posteriorly Medial and Lateral Intercondylar
tubercle
• Horns of meniscus and cruciate ligaments attached
4)Tuberosity
• Upper Smooth Quadrate tubercle via patella
ligament
• Lower Rough Subcutaneous
Subcutaneous infrapatellar bursa
• Inferior Continuous with anterior border of
shaft
SHAFT
Triangular in Cross section
1)Borders
Anterior Sharp, crest-like, subcutaneous & forms shin
Tibial tubercle anterior border of medial malleolus
Medial convexity above behind it Tibialis anterior on upper 2/3 of ext/lateral
surface
Lower smooth deep fascia of leg
Posterior Oblique line in upper part Soleal line run to lateral border
Soleus Soleal line and mid 1/3 of posterior surface
Above soleal line Popliteus(medial)
Below soleal line Divided by vertical ridge into lateral and medial parts
Lateral Tibialis Posterior Medial FDL
Upper end of ridge Nutrient foramen Branch of Posterior tibial artery
LOWER END
Rectangular in cross section
Medially elongated Medial malleolus GSV and Saphenous nerve in front
Anterior bare Crossed by TA, EHL, Anterior tibial artery, Deep peroneal nerve, EDL, PT
Lateral Fibular notch(triangular) Inter tibiofibular ligament
Posterior Tibialis Posterior (which lies in a groove), FDL, FHL
Inferior Saddle shape articular surface from talus up to medial malleolus
Medial malleolus posterior sup and deep deltoid ligament
➢ Upper end of the shaft most common site for acute osteomyelitis.
(upper extremity of the tibial diaphysis is extracapsular; involvement of the knee
joint therefore only occurs in the late and neglected case.)
➢ Tibia-mostly fractured at - junction of upper 2/3 and lower 1/3
- poor blood supply Union is slow / nonunion
➢ commonest long bone to be fractured and to suffer compound injury. (Ellis)
➢ anteromedial surface- subcutaneous therefore a donor site for bone graft
Fibula
• Fibula is shorter than tibia.
• Head
-has a styloid process
-Tendon of biceps femoris insertion and fibular collateral ligament attachment
• Neck- Common peroneal nerve can be rolled against the neck
of the fibula, where it is commonly damaged (Foot drop)
• Shaft
• Lower end
-The fibula is subcutaneous for its terminal
5) Ligaments-
* iliofemoral ligament (strongest, anteriorly) – limits extension
Inverted “Y” shape, arise from anterior inferior iliac spine, inserted to each end of
trochanteric line
*pubofemoral ligament (inferiorly)
Arise from iliopubic junction
blend with capsule
*ischiofemoral ligament(posteriorly)(weakest)
Arise from ischium inserted onto the greater trochanter
*round ligament (ligamentum teres)
Tendon of obturator
6) Relations - internus
Medial & lateral rotation – vertical axis passes through head of femur and condyle
Shaft doesn’t rotate around its own axis
8) Blood supply:
Through ligamentum teres of femur- from obturator artery
Retinacular arteries- from trochanteric anastomosis (main in adults)
Trochanteric anastomosis – medial & lateral circumflex femoral arteries, inferior gluteal &
ascending branch of 1st perforating artery
Nutrient artery of femur
▪ Usually dislocated backwards- which is produced by force applied along femoral shaft when
hip is flexed
leads to damage of sciatic nerve. Due to its close relationship.
(Foot drop)
▪ When hip is in adducted position- backward dislocation without acetabular fracture
▪ When hip is in abducted position- backward dislocation with fracture of posterior acetabular
lip
▪ # safe area (eg for injections) --- upper outer quadrant of gluteal region
▪ Sciatic nerve which is related inferiorly to hip joint can be damaged in hip dislocations
▪ Disease of the hip joint may cause referred pain in knee joint & vice versa, due to common
nerve supply of two joints.
Trendelenburg’s test-
positive when abductors (gluteus medius & minimus) of opposite side are paralyzed (eg:- in poliomyelitis)
, dislocation, fracture of head of femur
Normally when body weight is supported on one limb, the glutei of the supported side rise the opposite
unsupported side of the pelvis.
Relations to piriformis
region
Below piriformis pudendal nerve
▪ Internal pudendal vessels
PIN ▪ Nerve to obturator internus
▪ Inferior gluteal vessels
▪ Inferior gluteal nerve
▪ Posterior cutaneous nerve of thigh
▪ Nerve to quadratus femoris
▪ Sciatic nerve
Lesser sciatic foramen
▪ Obturator internus muscle tendon
▪ Pudendal nerve
▪ Internal pudendal vessels Pass into perineum from gluteal region
Nerves
Posterior femoral cutaneous nerve / posterior cutaneous nerve of the thigh (S1, S2, S3)
▪ Runs medial or posterior to sciatic nerve
▪ Immediately deep to the deep fascia
▪ Branches
➢ Perineal branch
o Crosses the ischial tuberosity
o Enters the urogenital triangle
➢ Gluteal branches
o Supplies skin of posteroinferior quadrant of gluteal region
Clinical
Muscles
• Gluteus maximus
• Gluteus medius
• Gluteus minimus
Sacrotuberous ligament
▪ long and strong ligament
▪ Between ischial tuberosity and posterior
Iliac spines
Sacrospinous ligament
▪ Deep to sacrotuberous ligament
▪ Short triangular thick band
▪ Attached to, laterally – ischial spine
Medially – sacrococcygeal
junction
Clinical
1. Intramuscular injection- upper outer
quadrant of buttock to avoid injury to large
vessels and nerves which pass through the
lower region.
2. Paralysis of gluteus medius and minimus – bends or waddles on the paralysed side (lurching gait)
3. Trendelenberg’s test
• Normally the glutei of the supported side raise the opposite side of the pelvis.
• The unsupported side/opposite side of the pelvis drops in a paralysis of gluteus medius and minimus.
(Positive trendelenberg’s sign)
- Paralysis of gluteus minimus and medius
- Defects of the fulcrum ( congenital and pathological dislocation of the hip)
- Defects of weight ( ununited fracture of the neck of the femur)
2. Fascia lata
• Deep fascia of thigh
• Tough fibrous sheath
• Attachments
Superiorly-
Anterior – inguinal ligament & ASIS
Lateral – iliac crest (External lip)
Posterior (through gluteal fascia) – Sacrum, Coccyx, Sacrotuberous lig.
Medial – pubis. Pubic arch, Ischial tuberosity
Inferiorly front & sides –Subcutaneous bony prominences (Tibial condyles &
Fibular head)
1. Iliotibial tract
• Thigh – lateral side
• Thickened band of fascia lata
• Attachments
Superiorly 2 slips superficial lamina iliac crest – tubercle
• Importance
Insertion of - Gluteus maximus (3/4)
- Tensor fascia latae
Stabilize knee (in extension & partial flexion)
• Leaning forward with slightly flexed knees tract is the main antigravity support
2. Saphenous openings (3cm below and lateral to the pubic tubercle)
3. Lateral intermuscular septum (extending from the deep aspect of the iliotibial tract to the linea
aspera of the femur separating anterior and posterior compartments of the thigh
Vastus lateralis -anteriorly
Short head of biceps femoris- posteriorly
Q).T/F
a) Fascia lata stabilizes the knee joint in the extended position
b) Most parts of the gluteus maximus are attached to the gluteal tuberosity
c) Gluteus maximus is supplied by inferior gluteal nerve
d) Gluteus maximus has an origin from the sacrospinous ligament
e) Tensor fascia lata extends the knee.
Course
● Enters the thigh behind inguinal ligament at midinguinal point (Pubic symphysis & ASIS)
● Just below the inguinal ligament artery is lateral to vein
● Lies in lateral compartment of the femoral sheath
● Passes downwards & medially
-femoral triangle
-adductor canal (deep to Sartorius)
● Vein gradually crosses medial to lateral deep to artery
● Saphenous nerve crosses to medial superficially
rd rd
● through adductor hiatus (at junction of upper 2/3 & lower 1/3 of thigh)
● continues as popliteal artery
Branches
In femoral triangle – 4 superficial –
1. Superficial epigastric
• emerges through the saphenous opening. runs towards the umbilicus.
2. Superficial circumflex iliac
-2 deep-
1. Profunda femoris
2. Muscular branches
In adductor canal -
1. Muscular
2. Descending genicular
Branches Descending
4 perforating arteries
Clinical:
- Compress femoral artery -at midinguinal point
- Against head of femur
- To control bleeding from distal L.L
- Femoral artery pulsations – at the mid inguinal point (against the head of
femur/ psoas tendon)
- Femoral artery is superficial in the femoral triangle
- Easy exposure for ligature
- Cannulation(2nd only to radial artery)
Superficial veins
Great Saphenous vein
Longest vein in the body.
Course
Starts by union of medial marginal vein & the medial end of dorsal venous arch
Runs upwards in front of medial malleolus (constant position)
Crosses the lower third of the medial surface of the tibia obliquely along with the
saphenous nerve (In varicose surgery sensory loss in medial side of leg)
Along medial side of leg
To Posteromedial aspect of knee (hand’s breadth behind the medial border of the
patella)
Spirals forwards around the medial convexity of the thigh
Ends by passing through the Cribriform Fascia covering the saphenous opening.
(About 3 cm below and lateral to the pubic tubercle) Constant valve is present here
Receive 3 tributaries
1.Superficial circumflex iliac
2.Superficial epigastric
3.Superficial external pudendal
Pierces cribriform fascia
After piercing
Receives deep external pudendal
Opens into femoral vein (constant valve) (saphenofemoral junction)
• Up to 20 valves
• Incompetence of valves is a cause of varicosity of the vein.
• Unusually thick wall
• Accompanied by saphenous nerve (anterior to the vein)
Thoracoepigastric vein - connects o Lateral thoracic vein of
axillary vein Obstruction of inferior vena cava o
Superficial epigastric vein
Femoral nerve
Nerve of the extensor compartment of thigh
Root value - Posterior Divisions of Ant. Primary rami L2, L3, L4
Course
Starts from the lumbar plexus
Emerges at the lateral border of psoas major in abdomen then lies in the iliac fossa between
psoas and iliacus.
Enters thigh by passing deep to inguinal ligament, at the lateral edge of the femoral sheath,
which separates it from the femoral artery. (Lies behind iliacus fascia)
Lies between iliacus and psoas tendons in the femoral triangle
Not a content of the femoral sheath
Divides into branches immediately (~4cm distal to the inguinal lig)
Branches
• Iliacus is supplied by the nerve in the abdomen.
• As it enters the femoral triangle, it gives off the branch to Pectineus, which
passes behind the femoral sheath to reach the muscle.
Femoral nerve supplying quadriceps femoris is tested by patellar jerk (L3, L4)
Anterior Division
• Passes above and anterior to the obturator externus
• Then behind pectineus and adductor longus
• Over the ant. surface of adductor brevis
• After supplying gracilis, enters the subsartorial plexus ends by supplying
femoral artery (supplies skin over the medial side of thigh)
Posterior division
• Enters thigh, piercing obturator externus
• Passes vertically downwards on adductor magnus, deep to the other adductor
muscles.
Clinical
• Both femoral and obturator nerves supply knee joint and hip joint. Pain in the knee can be
referred to hip joint
• Due to deep position, damage due to trauma is rare, but may be involved in obstetrics processes
and pelvic disease. (Ovarian tumour causes pain referred to medial side of thigh)
Subsartorial plexus
✔ Medial cutaneous nerve of thigh
✔ Saphenous nerve
✔ Obturator nerve- anterior division
Supplies the overlying fascia lata and an area of skin above the medial side of the knee
Roof –
● Deep fascia [Fascia Lata] - Saphenous opening with cribriform fascia
● Superficial fascia
- Upper part of Great saphenous vein
- Superficial inguinal nodes
- Genitofemoral nerve - femoral branch(supplies the skin over the femoral triangle)
- Ilioinguinal nerve - branches
- Femoral artery- 3 superficial branches & accompanying 3 superficial veins
(superficial circumflex iliac, superficial epigastric, superficial external pudendal)
● Skin
Contents - 01. Femoral artery and branches [midinguinal point to the apex -6 Branches-3 superficial and 3
deep -superficial branches-superficial external pudendal
-superficial epigastric
-superficial circumflex iliac
-deep branches -profunda femoris
-deep external pudendal artery
-muscular branches]
02. Femoral vein and tributaries
[At base - medial to artery] Great saphenous vein
[At apex - post. to artery] Veins corresponding to branches of artery
(Receives greater saphenous vein, circumflex veins and corresponding branches of femoral
artery)
03. Femoral sheath
04. Nerves
A) Femoral nerve (in the groove between iliacus & psoas muscles outside the femoral sheath)
B)Nerve to the pectineus (branch of femoral nerve) -passes medially behind the femoral sheath
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C) Femoral branch of genitofemoral nerve
-pierces the anterior wall of the
femoral sheath
D) Lateral cutaneous nerve of the thigh-
can be compressed as it passes through
the inguinal ligament causing pain &
altered sensation (meralgia
paraesthitica)
05. Deep inguinal lymph nodes
Femoral artery lies in front of psoas major
tendon
Femoral vein lies in front of pectineus
Femoral nerve lies in the groove between iliacus and psoas muscles lateral to the femoral sheath
behind the iliac fascia
Femoral sheath
● Funnel shape sleeve of fascia
● It is asymmetrical
● Enclose upper 4cm of femoral vessels
Prolongation of Fascia transversalis=>Ant.
wall o Iliacus fascia=>Pos. wall
Inferiorly merges with adventitia of femoral
vessels
Nerve to pectineus
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Femoral lymph node of Cloquet/ Rosenmuller in the medial compartment
Femoral Canal
-Medial compartment of femoral sheath
-Conical
-wide above at the base and narrow below
-Base is also known as Femoral ring
Femoral ring-
Boundaries- Anteriorly - Inguinal lig. (medial part)
Posteriorly - Pectineal ligament
Medially - Lacunar ligament
(crescentic edge)
Laterally - septum separating from
femoral vein
Clinical
Femoral Hernia
➢ Abdominal contents bulge out through femoral canal
➢ More common in female
• Wider pelvis
• Smaller size of femoral vessels
In strangulation, have to enlarge femoral ring => By incising lacunar ligament
• Normally => No Danger
• Abnormal(accessory) obturator artery => Alarming hemorrhage
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Differentiating inguinal hernia from femoral hernia??
Neck of the Femoral hernial sac protrudes below and lateral to the pubic tubercle and neck of
the inguinal hernial sack protrudes above and medial to the pubic tubercle.
Femoral hernia is never found in the newborn (not congenital)
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Definition - Intermuscular space, triangular in cross section, on medial side of middle 1/3 of thigh
03. Saphenous nerve=>pierces roof to leave canal (Crosses anterior to femoral artery from lateral to
medial side, infrapatellar branch is given off before leaving the canal )
Clinical
Exposure and ligature of femoral artery in this canal for aneurysm of the popliteal artery
T/F
Saphenous nerve crosses femoral artery medial to lateral in the adductor canal
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Back of the thigh
∙ Long head of biceps femoris & semitendinosus have a common origin in medial facet of ischial
tuberosity ∙ Semimembranosus originates from the lateral facet of ischial tuberosity
6.T/F
a) Semimembranosus is inserted into posteromedial surface of medial
condyle of tibia
b) Reflected head of rectus femoris arises from a groove immediately
below the acetabulum
c) Semimembranosus is inserted posterior to gracilis & Sartorius into
the medial surface of tibia
d) Sciatic nerve innervates only the hamstring muscles
e) Hamstring muscles all arise from ischial tuberosity
f) All hamstring muscles are inserted to the bones of the leg
G) All the hamstrings are innervated by the tibial nerve
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Sciatic Nerve
Root values - ventral divisions of anterior primary rami L4, L5, S1, S2, S3 (tibial Part),
- dorsal divisions of anterior primary rami L4, L5, S1, S2 (common peroneal
part)
Course
In the pelvis
Lies in front of piriformis
Undercover of fascia
In the gluteal region
Enters through the greater sciatic foramen below piriformis (more
laterally than the inferior gluteal and pudendal nerves and vessels)
Posteriorly related to the capsule of hip joint
Passes vertically downwards on the posterior surface of Superior
Gemellus, Obturator Internus, Inferior Gemellus, Quadratus
femoris.
Pass midway between the ischial tuberosity and greater trochanter. No
branches given in this region
Enters back of thigh at the lower border of gluteus maximus.
Nerve to quadratus femoris is deep to the sciatic nerve.
Superficially lies the posterior cutaneous nerve of thigh.
In the thigh
❖ Lies under cover of the Gluteus Maximus, crossed posteriorly by the
long head of Biceps Femoris
❖ Runs vertically downwards up to the superior angle of popliteal fossa
the posterior surface of the adductor magnus, where it Terminates by
dividing into tibial and common peroneal nerves above the knee. (variable point)
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Branches -Articular branch to hip joint
-muscular branches
Patellar plexus
✔ Lateral cutaneous nerve of thigh
✔ Intermediate cutaneous nerve of thigh
✔ Medial cutaneous nerve of thigh
✔ Saphenous nerve
Lymph Drainage
∙ Distal group – Lies vertically along the terminal great saphenous vein
Below it,
● External genitalia,
● lower anal canal and perineum,
● uterus
− Upper lateral – buttock, flanking back below the waist
− Lower vertical (distal group) – Superficial lymphatics of the lower limb except posterolateral calf
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Deep lymph nodes
∙ ¾ nodes
– afferents from
* Popliteal nodes
- efferent to
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Popliteal fossa
Definition=> Diamond/Rhomboid shaped depression behind the knee joint, lower
part of femur and upper part of tibia
Boundaries=>
Superomedial
* Semitendinosus
* Semimembranosus (supplemented
by Gracilis, Sartorius, Adductor Magnus)
Superolateral
*Biceps femoris
Inferomedial
*Gastrocnemius medial head
Inferolateral
* Gastrocnemius lateral head
* Plantaris
Roof
Skin, superficial fascia and deep fascia
Contains
01. Short saphenous vein
02. Cutaneous nerves – 3
Medial cutaneous N. of thigh
Posterior cutaneous N. of thigh
Sural communicating N.
Floor
From above to downwards;
01.Femur popliteal surface
02. Knee joint – capsule & oblique popliteal ligament
03.Popliteal fascia covering popliteus
Contents
01. Popliteal artery &branches 05. Pos.cutaneous nerve of thigh
02. Popliteal vein & tributaries 06. Obturator nerve - genicular branch
03. Tibial nerve & branches [Sural N.] 07. Popliteal lymph nodes
04. Common peroneal nerve & branches 08. Fat
➢ Superficial to deep- N, V, A
➢ Medial to lateral- above- A, V, N
below- N, V, A
(popliteal vessels cross the tibial nerve anteriorly in the middle of fossa. Arrangement @ middle is N, V,
A behind forwards)
• Tibial nerve crosses fossa vertically downwards.
• Popliteal artery runs downwards and slightly laterally, divides at the lower border of popliteus
• Common peroneal nerve crosses the fossa obliquely along the medial border of biceps femoris.
• Clinical -Pulsation of popliteal artery – in aneurysms
Branches
Cutaneous - lateral cutaneous nerve of calf
Sural communicating nerve joins the sural nerve below the
gastrocnemius heads
Articular - sup. Lat genicular
inf. Lat genicular
recurrent genicular
POPLITEAL ARTERY
➢ continuation of femoral artery
➢ begins at adductor hiatus (hand’s breadth above the knee joint)
➢ descends downwards & laterally
➢ terminates at the fibrous arch of soleus. (hands breadth
below the knee joint)+lower border of the popliteus
➢ deepest of the large neurovascular structures
➢ It enters the fossa medial to the sciatic nerve and lies medial
to the tibial nerve
➢ Then passes downwards and convex laterally to lie lateral to
the tibial nerve
➢ Below the fibrous arch in soleus as the posterior tibial
artery – returns medial side of the nerve
➢ At all levels the popliteal vein lies between the artery and the nerve.
➢ It passes under the fibrous arch in soleus and divides into(terminates at the lower border of popliteus)
1. Anterior tibial artery
2. Posterior tibial artery
• 5 genicular branches
1. Medial superior genicular artery
2. Lateral superior genicular artery
3. Medial inferior genicular artery
4. Lateral inferior genicular artery
These four contribute to genicular anastomoses
5. Middle genicular artery
• pierces oblique popliteal ligament
• supply cruciate ligaments
• accompanied by
1. genicular branch of post division of Obturator Nerve
2. genicular branch of tibial nerve
Clinical:
-most prone to aneurysms
-used to record B.P in L.L
-Palpation against the popliteal surface of femur
Anterior Compartment
Course
o Runs vertically downwards on the interosseous membrane
o deep peroneal nerve reaches from the lateral side, runs in
front of it in middle of the leg, returns its lateral side again
below
o Accompanied by two venae comitantes on each side –
Anterior Tibial Veins
o Crossed anteriorly from lateral to medially by the flexor
hallucis longus tendon
o crosses the lower end of the tibia at the front of the ankle
joint, midway between the 2 malleoli.
Branches
1. Anterior recurrent Branch - genicular anastomoses
2. Posterior recurrent Branch - genicular anastomoses
3. Lateral malleolar branch
4. Medial malleolar branch
- Arises within peroneus longus, over the neck of the fibula at the
bifurcation of the common peroneal nerve.
- Spirals around the neck of the fibula, under cover of peroneus
longus muscle, pierces anterior intermuscular septum then pierces
fibers of the extensor digitorum longus and reaches the
interosseous membrane.
- Runs down lateral to the anterior tibial vessels
- Upper part lies between the extensor digitorum longus and Tibialis
Anterior, in the middle lies between the Extensor Hallucis
Longus(EHL) and Tibialis Anterior. (EHL crosses in front of the
neurovascular bundle to lie on its medialside)
- Ends by dividing into medial and lateral branches
Course
o runs down on tibialis posterior
o between flexor digitorum longus and flexor hallucis longus.
Branches
• Peroneal artery – Deep part of posterior compartment
- descends in a fibrous canal between flexor hallucis longus and tibialis posterior
- nutrient artery to fibula
- perforating branches pierces posterior intermuscular septum and supplies lateral
compartment
- gives lateral calcaneal branch may replace or supplement the dorsalis pedis artery.
• Nutrient artery – to tibia
• Circumflex fibular – laterally around the fibular neck to genicular anastomosis
• Muscular Branches – soleus, deep flexors
Tibial Nerve
Nerve of the flexor compartment of the leg
Larger subdivision of sciatic nerve
Rootvalues -ventraldivisionofventralramiL4,L5,S1,S2,S3
Course
▪ Descends vertically in the popliteal fossa
▪ Crosses popliteal vessels from lateral to medial side superficially
▪ Descends as the neurovascular bundle with post. tibial vessels (Post. Tibial artery first lies
lateral to it then passes ant. to it and continues down on its medial side.
▪ Lies superficial to tibialis posterior and deep to flexor digitorum longus
▪ Passes deep to the middle of the flexor retinaculum and
terminates by dividing into medial and lateral plantar nerves
3) Capsule: attached little beyond the margin of articular surface of tibia & femur. Attached to
the sides of patella and anteriorly deficient and replaced by
patella
quadriceps femoris
ligament of patella
2 constant gaps- suprapatellar bursa, popliteal tendon
Attached to periphery of menisci
Capsule strengthened by - පැක ො ISSO – patella retinacula, quadriceps femoris, iliotibial
tract, sartorius, semimembranosus, oblique
popliteal ligament (this is an expansion of
semimembranosus
4) Synovial membrane:
lines the non-articular surface of the joint cavity
Cruciate ligaments are not covered,
covers deep surface of the infra patella fat pad (ala fold)
infrapatellar fat pad- deep to ligamentum patellae
5) Relations:
Ant- prepatellar, subpatellar, infra patellar bursae and patellar plexus of nerves
Pos- muscle forming borders of popliteal fossa and contents of popliteal fossa
Medial- semitendinosus, tendon of Sartorius and gracilis, great saphenous vein with
saphenous nerve
Laterally- biceps femoris, common peroneal nerve, tendon of origin of popliteus
Bursae: 12 bursae.
capsule communicates –
Menisci
Ligaments
1. Intracapsular
Cruciate Ligament
• Strong fibrous connection between femur and tibia
• Determines Antero-posterior stability
• Intra-capsular extra-synovial
2. Extracapsular ligaments
Stability continued…
• Cruciate ligaments maintain anteroposterior stability
7) Blood supply:
*From thigh- descending genicular branch of femoral,
popliteal and lateral circumflex femoral
* From leg- circumflex fibular artery
recurrent branch of ant. Tibial artery
Genicular Anastomosis
• Around the patella and the femoral and tibial condyles
• Lateral superior genicular
• Lateral inferior genicular Popliteal
• Medial inferior genicular artery
• Medial superior genicular
• Middle genicular artery
• Anterior tibial recurrent Anterior tibial artery
• Posterior tibial recurrent
• Circumflex fibular → Posterior Tibial Artery
• Descending genicular → Femoral Artery
• Lateral circumflex femoral – descending branch
8)Nerve supply:
* obturator
*Femoral
*Tibial
*Common Peroneal
Clinical
01. Pott’s fracture
Pott’s fracture
• Most common ankle fracture.
• Tibia internally rotates with the foot rigidly held
01. spiral fracture of the lateral malleolus 1st degree
02. avulsion of the medial malleolus 2nd degree
03. posterior margin of the lower end of the tibia shears of against
the talus 3rd degree
02. Sprains of the ankle are almost always abduction sprains of subtalar joints. True sprains are
caused by forced plantarflexion
• Collateral ligaments of ankle joint can be sprained or completely torn by forcible abduction
or adduction
• Lateral collateral ligament is the most affected, because medial collateral ligament is
stronger.
**Avascular necrosis of the Talus- Occur due to forced dorsiflexion causing fracture of the neck of
talus. If arteries to body of talus go through neck only as in some cases, the body will get avascular
necrosis.
03. Dislocation of ankle joint is rare. Most stable when foot is dorsiflexed
2. base of the 5th metatarsal - easily felt on the lateral side of the foot and is
the site of insertion of peroneus brevis.
3. If the calcaneus carefully palpated→ the peroneal tubercle can be felt below
the tip of the lateral malleolus
Talonavicular & calcaneocuboid joints lie in one line and together called “Transverse
tarsal joint” (mid tarsal joint) here pronation and supination take place as hidden
movements for plantigrade contact (gripping) – reinforced by the bifurcate ligament
• Cuboideonavicular joint - Fibrous joint. No movement (All other joints are synovial)
• Cuneonavicular joint - Continue with 2nd and 3rd intermetatarsal joints
• Calcaneocuboid joint - long and short plantar ligaments on its plantar surface
• Tarso-metatarsal joints - Gliding and aid in pronation and supination. Synovial
**The tendon to the great toe is different from others and is named extensor hallucis brevis
1st layer
2nd layer
02) Flexor digitorum -lateral plantar nerve -straigthens the pull of long flexor
accessorius main trunk tendons
3rd layer
02) Adductor hallucis -lat. plantar nerve-deep branch -adduction-- great toe
03) Flexor digiti minimi lat. Plantar nerve-superf. Bran. -flexion of little toe
4th layer
Clinicals
Gait
• The gait cycle consists of one cycle of swing and stance by one limb.
o Begins with heel strike, when the heel strikes the ground and begins to assume the
body’s full weight
o Ends with push off, from the forefoot – a result of plantar flexion
o Occupy 60% of walking cycle
o Contains two periods
▪ Double stance period -- when both feet are on the ground
▪ Single stance period – when one foot is on the ground
➢ In running there is no period of double stance
o After the heel strikes, the forefoot must be lowered to the ground via plantar flexion
As one foot is raised from the ground, pelvis of the unsupported side drops
This is corrected by the gluteus medius and minimus of the opposite side
When these muscles are paralyzed
In one side – lurching gait
Both sides – waddling gait
(+ve Trendelenburg test)
• Walking up stairs
o Extension of the hip & knee joint in the leading limb to pull up the trunk to the
Step above
FEMORAL ARTERY
Course
➢ Enters the thigh behind inguinal ligament at midinguinal point (Pubic symphysis & ASIS)
➢ Just below the inguinal ligament artery is lateral to vein
➢ Lies in lateral compartment of the femoral sheath
➢ Passes downwards & medially
-femoral triangle
-adductor canal (deep to Sartorius)
➢ Vein gradually crosses medial to lateral deep to artery
➢ Saphenous nerve crosses to medial superficially
➢ through adductor hiatus (at junction of upper 2/3rd & lower 1/3rd of thigh)
➢ continues as popliteal artery
1. Superficial epigastric
• emerges through the saphenous opening.
• runs towards the umbilicus.
2. Superficial circumflex iliac
• pierces the fascia lata
• to the anastomosis at the anterior superior iliac spine.
3. Superficial external pudendal
• emerges from the saphenous opening
• in front of the spermatic cord (round ligament)
• to the penis and scrotum (labium majus).
-3 deep-
1. Profunda femoris
2. Muscular branches
3. Deep external pudendal
• pierces the fascia lata
• behind the spermatic cord (round ligament)
• to supply the skin of the scrotum (labium majus).
In adductor canal -
1. Muscular
2. Descending genicular
❖ Lateral circumflex femoral artery Transverse: Cruciate anastomosis, pierce Vastus lateralis
❖ 4 perforating arteries
Clinical:
Ascending branch
Ascending branch
Trochanteric
OBTURATOR ARTERY
➢ divides into anterior and posterior branches that encircle the foramen.
➢ anastomose with each other and with the medial circumflex artery
➢ Abnormal obturator artery replaces the pubic branch of inferior epigastric artery
Branches –
• 5 genicular branches
1. Medial superior genicular artery
2. Lateral superior genicular artery
3. Medial inferior genicular artery
4. Lateral inferior genicular artery
These four contribute to genicular anastomoses
Course
Branches
Course
Branches
Anastomosis
* 4th perforating artery popliteal artery (upper muscular branch)
Arteries of foot
Posterior tibial
Dorsalis Pedis
• Runs to 1st intermetatarsal space & passes down into the sole where it joins the lateral
plantar artery to complete plantar arch
• Palpated between tendons of extensor digitorum longus & extensor hallucis longus
• 3 branches
- 1st dorsal metatarsal artery
- Arcuate artery- 2, 3, 4 dorsal metatarsal arteries
- Lateral tarsal artery
a) The popliteal artery divides into anterior & posterior tibial arteries at the distal
border of popliteus.
b) The anterior tibial artery passes to the anterior compartment of the leg by piercing
the interosseous membrane.
c) The posterior tibial artery is the main artery of the foot.
d) The main blood supply of both tibia & fibula is from posterior tibial artery.
3 types deep
veins Superficial Veins
Perforating veins
Deep veins
• Ant. Tibial
• Post. Tibial
• Peroneal
• Popliteal
• Femoral
− Valves-more numerous
− Supported by surrounding
powerful muscles
− Accompany major arteries
− More efficient
− Most of the venous return
happens through the deep
vein system.
Superficial veins
− Great (long) saphenous vein
− Small (short) saphenous vein
- Drains into deep veins via
perforating veins
− Less valves
− Starts by union of medial marginal vein & the medial end of dorsal
venous arch
− Runs upwards in front of medial malleolus (constant position)
− Crosses the lower third of the medial surface of the tibia obliquely along
with the saphenous nerve (In varicose surgery sensory loss in medial
side of leg)
− Along medial side of leg
− To Posteromedial aspect of knee (hand’s breadth behind the medial border
of the patella)
− Spirals forwards around the medial convexity of the thigh
Course
− Starts – drains the lateral side of the dorsal venous arch of the foot and lateral margin of the foot.
− Ascends behind the lateral malleolus, accompanied by the Sural nerve. (lateral to the vein)
− Ascends in the subcutaneous fat along post. Aspect of leg up to midcalf level
− Pierces deep fascia (anywhere between midcalf to roof of the popliteal fossa)
− Drains into popliteal vein.
− It communicates by several channels with the great saphenous vein.
Perforating veins
Indirect direct
Through muscular veins 1) Hand’s breath above knee
Superficial veins deep veins ❖ Great saphenous vein femoral vein
2) Hand’s breath below knee
❖ Great saphenous vein post. Tibial v.
3) Hand’s breath above ankle
❖ Medially- great saphenous post. Tibial v.
❖ Laterally- small saphenous peroneal v.
General factors
Local factors
Clinicals
➢ Muscle pump
− Soleus (peripheral heart)
➢ Varicose veins & ulcers
− incompetence of
o valves of perforators or deep veins
o valves at termination of superficial
veins
➢ Deep vein thrombosis – may occur in deep veins of lower limb and pelvic veins
Valves of Lower limb may be destroyed leading to varicose veins
Superficial-Drains skin and superficial fascia Deep-drains deep structures of lower limb except
of lower limb and trunk below the gluteal region and upper part of posterior thigh
plane of umbilicus.
• Superficial inguinal lymph nodes 1.Deep inguinal lymph nodes
• About 10 nodes, T shaped arrangement
• Proximal group – Just distal to the • 4-5 nodes
inguinal ligament
• Medial to femoral vein
• Distal group – Lies vertically along the
• eg:- lymph node of
terminal great saphenous vein
Cloquet/Rosenmuller(within femoral
• Efferent – Pierce cribriform fascia and
canal)
terminate in deep inguinal nodes
- afferents from
* Superficial inguinal nodes
Proximal group
* Popliteal nodes
1. Upper medial – Umbilicus and anterior * Glans penis / clitoris (→Cloquet)
abdominal wall. * deep lymphatics – L.L.
Below it, - efferent to
External genitalia, lower anal * external iliac nodes
canal and perineum, uterus
2. Upper lateral – buttock, flanking back 2. Popliteal lymph nodes
below the waist
- near small saphenous vein termination
Lower vertical (distal group) – Superficial
- afferents from
lymphatics of the lower limb except
* territory of small saphenous vein
posterolateral calf * leg – deep parts
* heel of foot
* knee joint
-efferents to
*deep inguinal nodes
Superficial
Popliteal
Femoral nerve
Nerve of the extensor compartment of thigh
Root value - Posterior Divisions of Ant. Primary rami L2, L3, L4
Course
❖ Starts from the lumbar plexus
❖ Emerges at the lateral border of psoas major in abdomen then lies in the iliac fossa
between psoas and iliacus.
❖ Enters thigh by passing deep to inguinal ligament, at the lateral edge of the femoral
sheath, which separates it from the femoral artery. (Lies behind iliacus fascia)
❖ Lies between iliacus and psoas tendons in the femoral triangle
❖ Not a content of the femoral sheath
❖ Divides into branches immediately (~4cm distal to the inguinal lig)
Branches
• Iliacus is supplied by the nerve in the abdomen.
• As it enters the femoral triangle, it gives off the branch to Pectineus, which passes behind
the femoral sheath to reach the muscle.
(Separated by
Anterior division lateral circumflex artery) Posterior division
Obturator nerve
Nerve of the adductor compartment
Root values - Anterior Divisions of Ant.
primary Rami of L2, L3, L4 nerves.
Course
− Emerges on the medial border of psoas major within the abdomen
− Crosses the pelvic brim
− Runs forwards on the lateral wall of pelvis
− Enters thigh by passing through the obturator canal
− Divides into anterior and posterior divisions in the obturator canal
Anterior Division
• Passes above and anterior to the obturator externus
• Then behind pectineus and adductor longus
• Over the ant. surface of adductor brevis
• After supplying gracilis, enters the subsartorial plexus ends by
supplying femoral artery (supplies skin over the medial side of thigh)
Posterior division
• Enters thigh, piercing obturator externus
• Passes vertically downwards on adductor magnus, deep to the other
adductor muscles.
Branches
Anterior Posterior
Muscular Pectineus Adductor magnus(adductor part) Obturator
Adductor externus
longus
Gracilis Sometimes adductor brevis
Adductor brevis
Clinical
• Both femoral and obturator nerves supply knee joint and hip joint. Pain in the knee can be
referred to hip joint
• Due to deep position, damage due to trauma is rare, but may be involved in obstetrics processes and
pelvic disease. (Ovarian tumour causes pain referred to medial side of thigh)
Subsartorial plexus
❖ Medial cutaneous nerve of thigh
❖ Saphenous nerve
❖ Obturator nerve- anterior division
Supplies the overlying fascia lata and an area of skin above the medial side of the knee
Patellar plexus
❖ Lateral cutaneous nerve of thigh
❖ Intermediate cutaneous nerve of thigh
❖ Medial cutaneous nerve of thigh
❖ Saphenous nerve
Sciatic Nerve
➢ Nerve of the flexor compartment
➢ Thickest nerve in the body.
➢ Main Branch of sacral plexus
Root values - ventral divisions of anterior primary rami L4, L5, S1, S2, S3 (tibial Part),
- dorsal divisions of anterior primary rami L4, L5, S1, S2 (common peroneal part)
➢ In the thigh
▪ Lies under cover of the Gluteus Maximus, crossed posteriorly by
the long head of Biceps Femoris.
▪ Runs vertically downwards up to the superior angle of popliteal
fossa on the posterior surface of the adductor magnus, where it
▪ Terminates by dividing into tibial and common peroneal nerves
above the knee. (variable point)
Branches -Articular branch to hip joint
-muscular branches
• Shooting pain over cutaneous distributions of sciatic nerve and its terminal branches
• Due to compression and irritation of nerve roots forming sciatic nerve (osteoarthritis, lumbar disc
prolapse, spondylolisthesis
Foot drop
Intramuscular injections
Gluteal region is a typical site for
intramuscular injections. Sciatic
nerve passes through this region and
it needs to be avoided. Safest place
to inject is the upper outer region of
the gluteal region.
Sleeping foot
- Compression of sciatic nerve (Since
sciatic nerve lies on femur between
qudratus femoris and adductor
magnus)
- Unusual stretching after sitting for a
long time
Clinical • Commonest nerve to be damaged in the lower limb. (fracture of neck of fibula, compression of
the nerve by a plaster on the leg)
- Site- as it winds around the neck of the fibula
• Effects of injury (talipes equinovarus)
o Paralysis of dorsiflexors of the foot ------- foot drop (unopposed action of plantar flexors)
o Paralysis of evertors -------- inversion of the foot
Sensory loss
Back of leg
Lateral side of leg
Most of dorsum of foot
Branches
Muscular -Tibialis Anterior (Muscles of the extensor compartment of leg)
-Extensor Hallucis longus
-Peroneus tertius
-Extensor digitorum brevis & longus
Cutaneous -dorsal digital nerves for the adjacent sides of the big toe and second toe
Branches
Segmental innervation
Clinical
Lateral cutaneous nerve of the thigh is sometimes compressed as it passes through the inguinal
ligament, causing pain and altered sensation in the lateral side of the thigh – Meralgia paresthetica.
Human DNA
Mitochondrial genes
• The only organelles outside the nucleus that have their
own DNA (extranuclear DNA)
• Circular double-stranded DNA (not linear)
• 2-10 copies (rings) per mitochondrion
• Unique sequences rather than repetitive
• Slightly different genetic code
• Exclusively transmitted to next generation by
mothers through oocytes.
Euchromatin: Forms the major portion of the chromosome body. Active; high proportion of coding
genes. Lightly stained.
Heterochromatin: Genes are absent or inactive. Darkly stained.
Depending on the position of the centromere, chromosomes have short arms(p) / long arms(q)
Metacentric –Centromere is in the middle (p=q), ex: - 1, 3, 16, 19 and 20
Submetacentric - Centromere is displaced from the center (p< q), ex: - 2,4,5,6-12,17,18 & X
Acrocentric- centromere is at one end (p<< q), ex: - 13-15,21,22 & Y
Telomeres
• Are ends of chromatids.
• Long arrays of tandem repeats.
• Specific telomeric proteins binds to this site forming a cap
Functions;
• prevent abnormal end to end fusion of chromosomes
• ensure complete replication of ends
• assist chromosome pairing during meiosis
• help to establish internal structure of the nucleus during interphase by linking the
chromosomes to the nuclear membrane
• may be involved in ageing process
• G banding: Uses the Trypsin and Giemsa • High resolution banding to detect
3 stain to detect numerical defects. © 2018 A/L Repeat Campaign
micro deletions.
• Light band: Active-lightly stained bands, • Detect structural defects.
G-C rich.
Other staining methods- fluorescent dyes and examination under UV light
MEIOSIS
• Before cell entering the meiosis, each chromosome will replicate its DNA
• Each chromosome resulting two sister chromatids
• In prophase l
• Chromosomes become visible as threads
• Homologous chromosomes pair
• Formation of synapsis
• Cross over of chromosomal material
• Further condensation of chromosomes
• Homologous pair begin to separate but held together at the point of cross over -
chiasmata
• Metaphase l
• Homologous pair position on either side of equatorial plane
• Spindle formation
• Independent assortment
• Anaphase l
• Homologous chromosomes separate from each other & move to the opposite poles of the
cell
• Telophase l
• Two haploid sets of chromosomes reach each pole & cytoplasm divide forming two new
daughter cells secondary oocyte & 1st polar body
• Enters meiosis ll following a brief interphase
Additionally,
Meiosis Prophase 1:
The process of meiosis differs in males and females. In males this is a continuous process which begins
in the mature seminiferous tubules of adolescents. In females by birth the process is arrested in
prophase 1 in a stage called Dictyotene. After menarche with each ovulation meiosis 1 is completed
and meiosis 2 begins. Meiosis 2 completes only following the entry of the spermatozoon into the egg.
PROPHASE I
METAPHASE I
ANAPHASE I
TELOPHASE I
division
METAPHASE II
ANAPHASE II
Mutations
Chromosomal Disorders
Numerical Anomalies
I. Polyploidy
Presence of more than 2 sets of chromosomes Ex: - Triploids - 69, XXX
69, XXY
69, XYY
Tetraploids
Imprinting is shown in triploidy [phenotypic expression varies depending on whether the extra set of
chromosomes are paternal or maternal in origin]
II. Trisomy
• Presence of 3 copies of a single chromosome
• Commonest cause is nondisjunction in meiosis I (80%)
• Secondly in meiosis II (20%)
• In either sex (oogenesis 80%, spermatogenesis 20%)
• In early mitotic division of the zygote or Anaphase lag.
• Most trisomic embryos are lost in early pregnancy. Usually only trisomies 13, 18 and 21
survive.
• Trisomy of the sex chromosomes have less severe effects on development; they survive.
Autosomal:
Sex chromosomes:
Triple X Syndrome
• Karyotype-[47, XXX]
• Affected girls are physically normal
• Taller than average
• Learning difficulties
• Usually arises form an error in meiosis I
III. Monosomy- Autosomal monosomies are lethal. Only monosomy X is compatible with life.
4. Mosaicism
• Presence of two or more cell lines with different karyotypes in a person
• Caused by chromosomal nondisjunction during mitosis
• Clinical feature depends on proportion of abnormality to normal cells
• The abnormal cell line may be confined to a particular tissue if the aberration took place in
the late embryonic or fetal development
1. Deletion
Leads to a loss of chromatin.
Terminal deletions – Break is at the end of an arm.
• Ex: - cri du chat syndrome: - deletion of tip of the
short arm of the chromosome [5p]
o Malformed larynx [cat-like cry].
o Low birth weight and failure to thrive. Round face,
low set ears, profound learning disability,
Hypertelorism, epicanthic folds
Micro deletions - Very small deletions detected only by special high resolution banding.
Deletion occurs in chromosome 15q
Paternal: Prader-Willi syndrome
Maternal: Angelman syndrome
Is an example of imprinting involving genes.
2. Duplication
Results in a gain of chromosome material by doubling in a
particular region.
3. Isochromosomes
Formed when a chromosome with two chromatids splits
at right angles to the normal length wise separation seen
in normal division. Chromosomes will have both short
arms or both long arms.
Ex: - 20% of Turner Syndrome individuals (one normal X
and another X which is an isochromosome for the long
arm – short arm monosomy and long arm trisomy)
Down syndrome (long arm trisomy and short arm
monosomy)
4. Inversion
Chromosomes break at two points & the intervening
broken segment turns 180 degrees to reverse the order of
chromatin.
Paracentric inversion - If the break points are on the same arm.
5. Translocation
Exchange of chromosomal material between chromosomes. 3 types:
II. Reciprocal
• Breakage and then exchange of segments of chromosomes. Point of exchange may be
anywhere along the chromosome.
• No loss of chromosomal material.
Ex: Philadelphia chromosome (Ph) – Deleted chromosome 22 in which the long arm has
been translocated to the long arm of chromosome 9. Used to indicate prognosis of
chronic myeloid leukemia (CML) & acute lymphocytic leukemia (ALL).
III. Insertional
• Insertion of a deleted segment of a chromosome interstitially or inside another
chromosome following a break at that point.
Other anomalies
Fragile X syndrome:
• Tip of the long arm of X is fragile.
• More common in males.
• Commonest inherited form of mental retardation.
• Moderate educational subnormality, speech delay, problems with social interactions.
• Triangular face, prominent mandible, closely set eyes, large ears, macro-orchidism.
• Females with fragile X are mentally normal.
Early development:
At the beginning of week 5, primordial germ cells migrate from endoderm cells of the yolk sac and infiltrate
primitive sex cords within mesodermal genital ridges which are products of coelomic epithelium.
Paired indifferent gonad is identical in males and females.
Birth defects
Genetic Non-genetic
(Mendelian
inheritance)
Autosomal dominant
Vertical inheritance –Transmission of the trait
continues from generation without skipping.
Both sexes are affected equally.
Every affected child has an affected parent except
for a new mutation.
Affected heterozygous + normal homozygous = risk
50%
1. New mutation
e.g .:- Achondroplasia, osteogenesis imperfecta
Isolated case
Increased paternal age
2. Reduced penetrance
e.g .:-multiple neurofibromatosis, marfan syndrome, BRCA, retinoblastoma
Percentage of carriers of a specific mutated gene/allele that expresses the relevant phenotypic
features.
If the frequency is less than 100%, reduced penetrance exists.
3. Variable expressivity
e.g.:-Marfan syndrome, multiple neurofibromatosis
a. Degree of expression of a trait.
b. The individuals of a family may show mild to moderate to severe forms of the disease.
4. Variation in age onset
e.g.:-adult polycystic kidney disease – May show cysts only in later life
Huntington’s disease - clinical features manifest in the 3rd or 4th decades of life
5. Variation in severity dependent on sex. ‘Anticipation’
Eg:- Huntington’s disease-manifests earlier if the affected parent is the father
Myotonic dystrophy- manifests earlier if the affected parent is the mother
6. Genetic heterogeneity
e.g.:-Retinitis pigmentosa – caused by both autosomal dominant and recessive inheritance
similar clinical picture produced by different mutations at the same locus or different loci
7. Influence of non-genetic factors
diet→expression of familial hypercholesterolemia
barbiturates→precipitate porphyria
8. Variable severity
a. All offspring will not have the entire severity of the disease
e.g.:-tuberous sclerosis
9. Phenocopy
It is an environmentally caused phenotype which resembles one produced by a mutant gene.
e.g: Warfarin induced embryonic defects resembling Conradi’s syndrome.
2 © 2018 A/L Repeat Campaign
Clinical examples for autosomal dominant
1) Huntington’s disease - Adult onset disease. Associated with choreiform movements and progressive loss
of mental activity, mood disturbances.
o Gene-short arm of chromosome 4 (4p)
o Anticipation
o Triplet repeat expansion (CAG)
2) Marfan syndrome
Long arm of chromosome 15 (15q)
Shows variable expression
Connective tissue disorder
Abnormal body proportions, Kyphosis, Scoliosis, Arachnodactyly, Mitral and Aortic valve
defects, dissecting aneurisms, Lens dislocations.
3) Familial hypercholesterolemia
Deletion of a gene producing LDL receptors
Increased serum cholesterol levels
Premature coronary artery disease
In autosomal dominance heterozygous normally survives. Homozygous does not survive. But in
hypercholesterolemia, homozygous also survives.
Autosomal Recessive
Only manifest in homozygous genes.
Horizontal inheritance.
Both sexes affected equally.
Normal parents, some normal offspring with affected
siblings among them.
Parental consanguinity increases the incidence.
Heterozygote male + heterozygote female →25% risk
Carriers – usually normal, exception-sickle cell anemia
Certain racial groups → recessive genes at higher
frequency
If the recessive genes are alleles, all the children of two
affected parents are affected.
Clinical examples
1) Homocystinuria –Deficiency of cystathione beta synthetase.
2) Cystic fibrosis - short arm of chromosome 7 (7p). Present with failure to thrive, chronic respiratory
infections and malabsorption. Secretions of the gut and lungs are thick and sweat is thick with high NaCl.
3) Phenylketonuria –Severe mental retardation due to accumulation of phenylalanine in blood, tissues and
urine. Mutation in long arm of chromosome 12.
4) Sickle cell anemia
- Mutant β-globin polypeptide chains on chromosome 11
- Glutamate is replaced with Valine at position 6 from the amino end
- Normal HbA/HbA
- Trait HbA/HbS
- Disease state HbS/HbS
5) Thalassemia
- Imbalance of synthesis of globin chains
- The excess accumulates in RBC, insoluble precipitates are formed causing hemolysis
- Causes anaemia leading to hyperplasia of bone marrow.
- 2 types (α & β)
Y-linked
-Directly from father to son.
-No father to daughter transmission
-Hairy ears, webbed toes.
-Only males are affected.
Multifactorial Inheritance
Genes + environment → final outcome – occurrence of the disease depends on the environmental
conditions at which both the parents and offspring live.
Accounts for the majority of congenital malformations and responsible for many normal variations in
humans.(Eg;- height)
Non-syndromal malformations
- ASD, tetralogy of Fallot, VSD, PDA.
- Anencephaly, meningocephalocele, spina bifida.
- Cleft lip with or without a cleft palate.
- Congenital hip dislocation.
- Diabetes mellitus
- Hypertension
- Alzheimer’s disease
The diseases tend to be familial
Mitochondrial Inheritance
Inheritance is matrilineal
- Only mothers transmit the condition to both sexes (as the zygote receives all of its
functional mitochondria from the oocyte.)
Tissue rich in mitochondria are mostly affected.
- Heart
- Striated muscle
- Kidney
- CNS
Dark-affected
Both 1 & 2 parents are affected but they
have an unaffected child.
This is possible in Autosomal dominant
disorders & that is enough to identify.
Pericardial
Peritoneal
large excretory
Thin cell layer ducts
(2 or 3) Robust e.g.:- Salivary
lining glands
Epithelia - glands
Exocrine glands
Structure
Simple
• Tubular cells secrete mucus and are pale staining.
• Acinar cells are serous secreting cells and are darkly staining
Sweat gland(coiled)
-Pancreas(compound)
Brunner’s glands of
duodenum(Compound
branched)
Connective tissue
Origin: - Mesoderm
Types: - Loose connective tissue
Dense connective tissue
Adipose tissue
Bone & cartilage
Cells of immune system
Composition: - 1. Cells
2. Extracellular matrix ( ECM> cells)
3. Blood vessels & lymphatics
II. Myofibroblasts
- Contractile function, tissue repair after damage
III. Adipocytes
Lipoblasts ==> Adipocytes
- Store energy
Ground substance
- Transparent molecules
- Semi fluid gel
- Fibers are embedded
- Formed by GAGs
Fibers
- Collagen (secreted as tropocollagen)& elastin
Collagen – Type 1 fibrous supporting tissue(dermis of
skin,tendons)Type 2 hyaline cartilage
Type 3 (reticulin) supporting framework (Of lymphoid tissue, bone marrow)
Basement membrane
Constituents- GAGs- heparin sulphate
Fibers- collagen type 4
Glycoproteins- fibronectin, laminin, entactin (Nidogen1)
Reticuloendothelial system/Macrophage phagocytic system
Function; - 1. Phagocytose particular matters, microorganism, affected cells
2. Store iron & certain metabolic products
Cell junctions
Tight junctions Adhering junctions Communication junctions
-Intestinal epithelium -In most tissues -Cardiac muscles
6. T/F
a) Type I collagen is found in bone.
Excitable Tissue
Muscles (Contractile Tissue)
Histology
1. Extremely elongated/tubular
2. Unbranched
3. Cylindrical cells
4. Flat, Peripheral multi nuclei
5. Cross striations
Functioning
Large motor nerves “motor unit”
(Fasciculation)
Histology Sarcomere
- Long cylindrical - mitochondria with closely packed cristae
- Branching fibers - glycogen granules
- Some striations - well developed sarcoplasmic reticulum
- 1 -2 central nuc. - T tubule system in Z line
- Intercalated discs
Junction between 2 cells
Contractile proteins
Actin (tropomyosin) & Myosin (only bind to actin) in
Criss-cross
Nerve system
1. Somatic 2.Autonomic
Neurons
Structure
Cell body Processes Nucleus – large,round
Nucleus Axons Prominent
Perikaryon Dendrites nucleolus
(Cytoplasm) Nissl bodies - RER
(Darkly stained)
*Lack in axons
Types
Axons
Synapses
Junction between terminals of neuron & either another neuron or muscle
Structure
- Nerve fibers form fascicles
- Surrounding layers of supporting tissue
- Rich blood supply
- Fibers follows a zig zag, longitudinal course (for stretching of the nerve)
- Supporting cells – schwann cells
Ganglia
- Aggregations of neuronal cell bodies located outside the CNS
- Cell bodies – surrounding satellite cells ( structural & metabolic support )
- Capsulated by supporting tissue
Meninges
1. Dura mater – Dense fibroelastic layer, lined by flat
cells
-Strongest layer
-Skull: - merges with the periosteum
Subdural space
2. Arachnoid mater – Cobweb like
- Pia + Arachnoid = Leptomeninges leptomeninges
(Both found together)
Subarachnoid space
3. Pia mater – Delicate, glia limitants- formed of collagen, elastin, fibroblasts
8. Regarding nerves
a) In unmyelinated nerves conduction is salutatory.
b) Action potential is generated in the cell body.
c) Myelin sheath of an axon is formed by several Schwann cells.
d) Myelin is absent in Ranvier nodes.
e) In the CNS the myelin sheath is formed by oligodendrocytes.
9. T/F
a) Has mesaxons wrapping spirally around the?
b) Have the axons in the extracellular compartment within the Schwann cell.
c) Ranvier nodes conduct impulses in a continuous manner.
d) Most of the nuclei which are seen in the fascicle belong to the neuron.
e) Wavy bands of nuclei are a characteristic feature.
Cartilage
Cells
Perichondrium
- At the periphery of mature cartilage tissue
-Zone of condense tissue
-Collagen fibers & spindle shaped fibroblasts
Types
1. Hyaline Cartilage
2. Fibro Cartilage
3. Elastic Cartilage
1. Hyaline Cartilage
- Translucent, homogenous appearance
- Small aggregations of chondrocytes
- Ground substance—collagen fibers (type 2)
3. Elastic Cartilage
- Equal to hyaline cartilage
- Many branching elastin fibers
- gives flexibility
Formation
- Mesenchymal cell
- Differentiate into chondroblasts
- They divide & secrets ground substance & fibers
- Clusters of mature cells—chondrocytes
Nutrition
Most of cartilage devoid of blood vessels
Substance diffuse through ECM
In thick cartilage-- “cartilage canals” convey small vessels into cartilage mass
Bone
Cells
1. Osteoblasts 2.Osteocytes
-Synthesize osteoid - assist in nutrition of bone
-Mediate the mineralization - large, inactive osteoblasts
- Inside the large lacunae
3. Osteoclasts
- Important in constant turnover & refreshing of bone
- Phagocytic cells formed by fusion of monocytes
- Large, multinucleated, eosinophilic cytoplasm
- present within Howship lacunae
Periosteum
- Condensed fibrous tissue
16 2018 A/L Repeat Campaign
- Inner layer – contain osteoprogenitor cells & osteoblasts
Sites: - outer shed of the bone
*Diaphysis
Types
1. Woven bone
-immature bone—fetal skeleton
-- fracture sites
2. Lamellar bone
Regular parallel bands of collagen sheets
Formation
1. Intra membranous ossification → membrane bone
Sites: - clavicle
Vault of skull
Mandible (most part)
Mesenchymal cells
Mesenchymal cells
Remolding of bone
Osteoclastic & osteoblastic activity
Repair of bone
13. Osteoclasts
b) Has mesenchymal origin.
c) Are within the howship’s lacunae.
d) Cytoplasm is basophilic.
e) Are multinuclear cells.
Spermatogenesis – All the events by which spermatogonia are transformed into spermatozoa
begins at puberty.
CLEAVAGE
BLASTOCYST FORMATION
• Fluid in the uterine
cavity penetrates the zona
pellucida into the intercellular
spaces of the inner cell mass.
• Intercellular spaces
become confluent and forms a single cavity – blastocoel
• At this time, the embryo is called the –
BLASTOCYST
BLASTOCYST
• Outer cell mass (trophoblast) flattens to form the epithelial wall of the blastocyst.
• Inner cell mass (embryoblast) is concentrated to a pole of the blastocyst.
• The fluid filled cavity between the abembryonic pole and the embryoblast is the blastocoel.
HATCHING
• The embryo getting out of the zona pellucida on the 5th day.
IMPLANTATION
• On the sixth day.
• Trophoblastic cells over the embryoblast pole penetrate into the uterine endometrium. (mucosa)
• The endometrium is in the – SECRETORY PHASE
• SECRETORY PHASE
o Coiled uterine glands
o Coiled uterine arteries
o Glycogen granules found in cells
• Implantation occurs usually in the posterior (or anterior) wall of the uterus.
(Where it becomes embedded between the openings of the glands)
At the beginning – Blastocyst is partially embedded in the endometrial stroma. The embryonic pole of
the blastocyst is facing the endometrium.
The blastocyst is more deeply embedded in the endometrium and the penetration defect is closed by
a fibrin coagulum by day 9. Later the coagulum is replaced by endometrial surface epithelium.
Also, on day 9 syncytial vacuoles appear at embryonic pole, thus called lacunar stage of trophoblast.
Days 11 & 12
Uteroplacental circulation is established.
Cytotrophoblast
1. Columns of cells develop into the syncytium. - day 13
2. Known as ‘Primary Villi’ (outer layer of syncytiotrophoblast surrounding core of cytotrophoblast)
Therefore, the extraembryonic coelom separates the cytotrophoblast (lined internally by the
extraembryonic somatopleuric mesoderm) from the primitive yolk sac and amniotic cavity. (lined
externally by the extraembryonic splanchnopleuric and somatopleuric mesoderms respectively)
BUT the germ disc is connected to the trophoblast by a ‘connecting stalk’ made of extraembryonic
mesoderm.
Therefore, the only place where the extraembryonic mesoderm traverses the chorionic
cavity/extraembryonic coelom is the ‘connecting stalk’ - later becomes the umbilical cord
Extraembryonic mesoderm lining the inside of the cytotrophoblast is called the – chorionic plate
Therefore the exocoelomic cysts are found in the chorionic cavity / extraembryonic coelom
Secondary yolk sac is smaller than the primitive yolk sac.
Normal site of pregnancy: Posterior or anterior wall of the uterus
Sites of ectopic pregnancies: abdominal cavity, ovary, uterine tubes
GASTRULATION
Process that establishes the three germ layers (ectoderm, mesoderm, and endoderm) of the embryo
Therefore now,
• The ectoderm is in continuation with the amnioblasts
• The mesoderm is in continuation with the extraembryonic mesoderm (both splanchnopleuric and
somatopleuric)
• The endoderm is in continuation with the cells of the secondary yolk sac
OROPHARYNGEAL MEMBRANE
• Tightly adherent ectoderm and endoderm
• Gives rise to the opening of the oral cavity in the
future
PRECHORDAL PLATE
• Derived from some of the cells that
migrate through the primitive node in
the midline
• Induction of the forebrain
development
• located between notochord and
oropharyngeal membrane
NOTOCHORD
• Represents the primitive skeletal
structure characteristic to the
chordates
• Development of the Notochord
PRIMITIVE CHORD
• A shallow groove in the ectoderm.
• The migratory gateway of epiblast cells which form mesoderm and endoderm
CLOACAL MEMBRANE
• Tightly adherent ectodermal and endodermal cells that later form the anal membrane and the
urogenital membrane (separated by the urorectal septum).
• After the appearance of the cloacal membrane the posterior wall of the yolk sac forms a small
diverticulum which extends into the connecting stalk called – allantoenteric diverticulum /
allantois
Secondary villus –
Mesodermal core, covered by
cytotrophoblast and
syncytium
Then differentiation of
mesodermal cells into blood
vessels, to form Tertiary villi
EXTRAEMBRYONIC CIRCULATION
o Blood and blood vessels are derived from the mesoderm
o Mesoderm in the core of secondary villi, chorionic plate, connecting stalk and intraembryonic
mesoderm are in continuity
o Therefore when blood vessels develop in each of the above structures, a connected
extraembryonic, and intraembryonic circulation is established
o I.e.; capillaries in tertiary villi ➔ capillaries in the chorionic plate ➔capillaries in the connecting
stalk ➔intraembryonic capillaries
o The connecting stalk will develop into the umbilical cord eventually
o Cytotrophoblastic cells penetrate the syncytium until it meets the decidua basalis of the
endometrium.
o Neighboring villi are connected forming a thin outer cytotrophoblast shell.
o These villi + cytotrophoblast shell firmly attaches the chorionic sac to the endometrium.
o Villi that extend from the chorionic plate to decidua basalis – anchoring/stem villi
o Villi branching from the sides of stem villi – free villi
Major features of the external body form can be recognized by the end of this period.
ECTODERM
Neurulation
o Ventral pathway
▪
Sensory ganglia
▪
Sympathetic neurons
▪
Enteric nervous system
▪
Schwann cells
▪ Cells of adrenal medulla
MESODERM
1. Paraxial mesoderm
2. Intermediate mesoderm
3. Lateral plate mesoderm
The mesoderm beside the midline thickens and forms the paraxial mesoderm.
Lateral plate mesoderm splits into two, giving rise to a cavity the intraembryonic cavity which becomes
continuous with the extraembryonic cavity.
The mesodermal layer continuous with the extraembryonic somatopleuric mesoderm (covering the amniotic cavity)
becomes the parietal/somatic mesoderm.
The mesodermal layer continuous with the extraembryonic splanchnopleuric mesoderm (covering the yolk sac)
becomes the splanchnic/visceral mesoderm.
The unsplit mesoderm connecting the lateral plate and paraxial mesoderm is called the intermediate mesoderm.
Paraxial mesoderm
Become organized into segments – somitomeres- mesodermal cells organized in concentric whorls. (In the 3rd
week)
Formation of somitomeres is cephalocaudal
From occipital region caudally somitomeres further organize into - somites at around 3 per day for 15 days
SOMITE DIFFERENTIATION
1. Presomite mesoderm – ball of mesoderm
2. Arrange into a donut shape by epithelization
3. Differentiation
a. Sclerotome – form the vertebrae and ribs
b. Dermatome – form the dermis of the back
c. Myotome – form segmental muscular component
INTERMEDIATE MESODERM
ENDODERM
Endoderm forms the ventral surface of the trilaminar germ disc, which is the roof of the yolk sac
1. Cephalic folding
• Cephalic part of the germ disc (head fold) folding towards the middle of the disc
• The endodermal germ layer is incorporated into the body to form the foregut
2. Caudal folding
• Caudal part of the disc (tail fold) including the connecting stalk fold towards the middle
• Endodermal germ layer is incorporated into the body to form the hind gut
• The allantois initially incorporated to the connecting stalk develops a connection with the hind gut forming
the cloaca – (discussed later in system based embryology)
3. Lateral folding
• Lateral parts of the germ disc fold toward the anteroposterior midline(axis)
After folding the yolk sac is connected to the midgut by the vitelline duct
Therefore the endoderm basically forms the epithelial lining of the primitive gut tube, intraembryonic portion
of allantois, and vitelline duct.
So far learnt -
• Tertiary (& some secondary) anchoring villi are extending from the chorionic plate to the
cytotrophoblastic shell
• Uteroplacental circulation established
o Cytological process of erosion of maternal blood vessels – endovascular invasion
▪
Cytotrophoblast cells undergo – epithelial to endothelial transition
▪
Invade terminal ends of maternal spiral arteries
▪
Create hybrid vessels (of maternal and fetal origin)
▪
Connect the vessels to ‘lacunae’ / intervillous spaces
▪
The hybrid vessels are large – sinusoids – low resistance
• Extraembryonic vascular system established
• Free villi extend from stem villi to intervillous spaces
o Develop as buds from stem villi
o Initial structure
▪ Vascular mesoderm covered by
Decidua Decidua Basalis (Maternal part of placenta Decidua capsularis (degenerate later,
– endometrium) fuse with decidua parietalis)
TWINS
1. Dizygotic twins
2. Monozygotic twins
Dizygotic Twins
Fertilization of two ova by two different spermatozoa
• Genetically different zygotes
• Can be of same or different sex
• No more than the resemblance of brothers and sisters – fraternal
• Implant separately in the uterus
• Has separate placenta and all other fetal membranes for each embryo
• BUT if implanted close together, placentae, chorionic sacs can fuse
o Erythrocyte mosaicism?
Monozygotic twins
Develops from a single fertilized ovum
• Identical (morphologically, genetically, of the same sex)
Depending on the stage of separation monozygotic twin placentae and fetal membranes differ
Separation at
• Two cell stage (Zygote divides to form two zygotes)
• Earliest separation
• Two zygotes
• Separate implantation
• Separate placentae
• Separate chorionic sacs
▪
As in dizygotic twins the placentae and chorionic sacs can fuse if implanted close
by
• Early blastocyst stage (separation occurs in the inner cell mass only)
• Common chorion
• Common placenta
• Separate amnions
• After the appearance of primitive streak, node (partial splitting of primitive node, streak)
• Conjoined twins (craniopagus, pygopagus, thoracopagus)
• Common chorion
• Common placenta
• Common amniotic cavity
• Unit change in pH changes [H+] by ten-fold (e.g. when pH increases by 1, [H+] decreases
by 10 times)
• Biological systems (e.g. enzymes) are extremely sensitive to changes in pH.
• Partial pressure of a gas in solution = pressure the gas would exert if it were the
only occupant of the given volume of fluid
• The total pressure of a mixture of gases in solution = sum of the partial pressures
of each gas
• Conjugate Acid-Base pair: A proton donor and its corresponding proton acceptor
HA ⇌H+ + A−
Acid dissociation constant = Ka
[𝐻+][𝐴−]
𝐾𝑎 = [𝐻𝐴]
• Weak acids (e.g. aspirin, pKa ≈ 3.5) are in the unionized form in the stomach (due to its
highly acidic pH)
2 2018 A/L Batch Repeat Campaign
• Unionized form of a drug (i.e. HA) is more soluble in phospholipid bilayer
• Therefore, will cross the cell membranes more rapidly and move into blood
• In the blood, at physiological pH, they are in the ionized form (i.e. A–) and do not flow
back into the stomach
Buffers
• Substances that resist pH changes
• Combinations of H+ donors and H+ acceptors (weak acids or weak bases)
• Mixture of weak acid/base and its conjugate base/acid
• The H (acid) combines with weak acids (conjugate base) in free solution
+
• Buffers work by accepting H+ when they are in excess and donating H+ to the solution
when they are depleted
• Buffering capacity depends on the type of buffer and the molarity of the solution
• Optimum activity of buffer occurs when pH = pKa (i.e. when [A-] = [HA])
• Maximum buffering capacity in the pH range (pKa ± 1)
• Conjugate acid-base pairs act as buffer when pH = pKa
• Buffering system in the body – controlled by kidney
Acids are made during metabolism - metabolic reactions produce CO and other acids; CO is
2 2
• the pH of the blood can change therefore the excess H generated due to acids need to
+
Buffering is a quick response to maintain pH, by temporarily holding the H by the buffer
+
system. Excretion of the H is the more long-term mechanism which also takes a little longer
+
to happen.
CO + H O
2 2 H2CO3– H + HCO
+
3
-
• Bicarbonate diffuses back into plasma and is transported to lungs, while some is
transported by RBC.
• HCO3- plasma (2/3) >RBC (1/3).
• Formation of HCO3- inside the RBC increases the osmotic gradient into the red
cells, so water flows in therefore cell size increase therefore PCV increases .
• Cl moves into RBC and ensures electrical negativity (as Na and K cannot easily cross
-
RBC membrane): the chloride shift results in venous plasma having 2% less chloride
than arterial plasma. The chloride shift also balances the charge when HCO3-
moves to plasma. (opposite occurs in lungs)
• Affinity for H+ is high in Deoxy haemoglobin and is important to carry oxygen and
CO by taking both O and H .
2 2
+
In the Lungs
• Reverse process occurs by chloride leaving RBC, reformation of HC03-and enters
alveoli, converted by carbonic anhydrase to CO and diffuses into alveolar air, which
2
• Oxyhaemoglobin (in the lungs) has low affinity for CO , which enables release and
2
excretion.
Haldane effect (mirrors the Bohr effect for O ) – at a given partial pressure of CO ,
2 2
releasing oxygen increases affinity for CO and when haemoglobin is oxygenated, it has
2
1. Across the difference in partial pressures between arterial and venous blood which is
40mmHg to 46mmHg, the almost linear steep dissociation curve ensures that for
2. 1mmHg change in pressure, 0.7mL CO per 100ml blood is unloaded.
2
3. Ensures a minimal pH change between arterial and venous blood when loading and
unloading.
Consequently, pH falls.
ACID-BASE BALANCE:
Is the regulation of hydrogen ion concentration in body fluids- homeostatic control of
hydrogen ions
Protein buffers
● Hb buffers H+ by H+ joining with histidine during the transport of the HCO3- until
either CO2 is excreted in the lungs or H+ is excreted in the kidney
● CO2 diffuses into renal tubule cells and via carbonic anhydrase H2CO3 is produced.
● H2CO3<—>HCO3- + H+ which is transported into blood.
● H+ excreted in urine (almost all)
● The pH of urine is 4.5 and therefore the H+ will not diffuse back into tubules once
secreted.
● Indirect reabsorption of bicarbonate from the PCT since renal tubule cells are
impermeable to HCO3-
● H+ +HCO3-< —>H2CO3<—>CO2+ H20 in the lumen catalyzed by carbonic
dehydrase(CA)
● This CO2 diffuses into the tubule cell where CA works again.
● The HCO3- diffuses into the blood. Therefore,1 molecule (net) of HCO3- is transferred
from urine to blood.
The urine can only accommodate a small % of free H+ in solution, therefore they should bind
with other buffering bases to be excreted. Such major buffers are phosphates and NH3, other
minor buffers include urate and citrate.
RESPIRATORY ACIDOSIS
Caused by retention of carbon dioxide where blood paCO2 rises and pH falls
Associated with impaired efficiency of gaseous exchange
Renal compensation is important
RESPIRATORY ALKALOSIS
Caused by hyperventilation which causes blood paCO2 to fall and pH to rise Metabolic
compensation usually slight.
METABOLIC ACIDOSIS
Caused by excessive production of hydrogen ions eg in diabetic ketosis, increased
lactic acid production following shock, or any situation where tissue perfusion is
compromised.
Loss of bicarbonate from fluid of small intestines due to diarrhea or other causes of loss of
intestinal contents
Respiratory compensation is important - occurs with rapid breathing to washout CO2
METABOLIC ALKALOSIS
Caused by loss of acidic fluids by vomiting gastric contents (or by excessive oral intake of
bicarbonate)
Respiratory compensation is often slight
Introduction
Functions
Isomerism
Isomers
• Isomers are molecules that have the same molecular formula, but have a different arrangement
of the atoms in space. (different structures)
Eg: Glucose, Fructose Galactose, Mannose (Same chemical formula C6 H12 O6)
Epimers
Enantiomers
• Asymmetric carbon –
o A carbon linked to four different atoms or groups farthest from the carbonyl carbon
o Also called chiral carbon
Optical activity
• When a plane polarized light is passed through a solution containing monosaccharides the light
will either be rotated towards right or left.
• This rotation is because of the presence of asymmetric carbon atom.
• If it is rotated towards left- levorotatory (-)
• If it is rotated towards right- dextrorotatory(+
carbohydrates
simple complex
carbohydrates carbohydrates
Simple carbohydrates
Monosaccharides
Cannot hydrolyze
disaccharides
• Can be hydrolyzed.
• reducing sugars (except sucrose)
• contains glycosidic bonds
E.g.
Glu+Glu
Sucrose
Glu+fru
Glu+ gal
Glycosidic bond
• Bond formed between the anomeric carbon of a carbohydrate and the hydroxyl oxygen atom of
an alcohol (O-glycosidic bond) or the nitrogen of an amine (N-glycosidic bond)
• Glycosidic bonds between monosaccharides yield oligo- and polysaccharides
• After glycosidic bond formation, the ring formation involving the anomeric carbon is stabilized
with no potentially free aldehyde or keto groups
• sweet taste
Complex carbohydrates
Polysaccharides
Some functions:
Glycosaminoglycans
properties
• Hyaluronic acid
• Chondroitin sulfate/Dermatan sulfate
• Keratan sulfate
• Heparin/Heparan sulfate
Hyaluronic acid
Chondroitin sulfate
Important in
• Anticoagulation,
• Wound healing
• Thromboprophylaxis
. • Binds LDL
Keratan sulfate
Heparin
Heparan sulphate
Heparin
¢ Stroke after cerebral venous sinus thrombosis, potential early cardiogenic re-embolization
Inulin
Dextran
• Used in certain IV fluids (intravenous fluids) to solubilize other factors such as iron (iron dextran) –
imferon
Glycoproteins
• Used as a parenteral source of calories & water for parenteral nutrition & hydration
• Hypertonic dextrose injections (>5%) are used to provide adequate calories in minimal volume of
water
• 10-25% dextrose injections are used to restore blood glucose concentration in treatment of acute
symptomatic hypoglycemia
• May be admixed with amino acid injections or other compatible IV fluids to provide parenteral
nutrition
Cellulose
• Wound dressing
• Tissue engineering
Hyaluronic acid
• Week attractions between FA chains, chain length, presence, number, position and
confirmation of double bonds affect the melting point. (length melting point - due to
number of vanderwaals interactions)
• Trans double bonds increase the melting point of unsaturated fatty acids.
Eg: margarine, elaidic acid (natural trans unsaturated)
The straighter the molecule, the easier it is to pack densely in a solid.
Double bonds induce ‘kinks’ in FA chain, preventing orderly packing in lipid phases.
As the degree of unsaturation increases, -the more pronounced is the bending (packing difficult)
-the melting points of fatty acids become lower increasing the fluidity of unsat. FA containing
lipids.
cannot be synthesized in the body – humans cannot form double bond beyond carbon in the FA
➢ α Linolenic - ω 3 series
➢ Linoleic - ω 6 series
TAG
(triglycerides) Sphingolipids Steroid
Phosphoglycerolipids
sphingosine
(glycerophopholipds)
FA X Glycerol
Cholesterol
Sphingosine+FA = ceramide
FA FA phosphoric
alcohol
Phosphosphingolipids Glycosphingolipids
• Lecithin
sphingosine sphingosine
Cholin alcohol – neural transmission
FA phosphoric FA Sugar (one or more) Most abundant phospholipid in cell
membrane
alcohol • Blood group antigens Lung surfactant – dipalmytoyl lesithin
• Ceramide (spingosine + FA) • Cardilopin
➢ Galactosylceramide – brain Only in mitochondria
• Sphingomyaline
nervous tissue Alteration cause
➢ Myalinesheath in
➢ Glucosyl ceramide -extra mito.dysfunction
brain and nervous
neural tissue • Inositol
system (no glycerol)
• Gangliosides - receptor Precursor of 2nd messengers
• Cell surface receptors for
cholera and tetanus
• Major glycolipids in animal
tissue
• Common in cell membrane
(outer leaflet)
TAG
• storage lipids
• neutral fat
• TAG are a much more efficient form of energy storage than glycogen
• hydrophobic / non polar/water insoluble (important for storage)
• high energy molecule 9kcal/g
• anhydrous (tend to associate with each other and & other hydrophobic groups)
• C1 & C2 of glycerol is not identical &they are enzyme specific
Membrane lipids
Phospholipids
1) Steroids
2) Cholesteryl ester
• Hydrophobic
Cholesterol FA
Amino acids
❖ Amino acids are classified according the properties of the side chain (R group)
➢ Some AA are not found in proteins but found in the free state in cells or as derivatives.
Eg: - Derivatives (epinephrine, norepinephrine)
❖ Ketogenic AA
➢ Amino acids that only yield acetyl CoA & they can’t be used for gluconeogenesis.
➢ But can be used for ketogenesis
Eg: - Lysine & Leucine Refer
➢ Amino acids that yield both acetyl CoA & TCA cycle intermediates
Eg: - trypsine, tyronine, Phe, Ile
• Metabolism of all AA except branched chain AA (Val, Leu, Ile) takes place in Liver
Isoelectric pH (pI)
• pH at which zwitter ion predominates with equal but very small amounts of cationic &
anionic forms.
• A zwitter ion is a dipolar ion with two or more functional groups one is (+) charged and
other one is (-) charged. (At pI - no net charge)
• Do not move in an electric field For mono amino, mono carboxylic amino acids:
• solubility is least PI = pk1+pk2
Cystinuria
➢ An inherited abnormality in
reabsorption of Cystine, Orn, Arg,
Lys (COAL) in kidney tubule.
➢ It leads to increased excretion of
these AA in urine.
➢ Clinical features due to precipitation
of Cystein in renal tracts
1) Glutathione
• Antioxidant
• AA transporter
• Glutamine, Cysteine, Glycine
Protein structure
2) Secondary
• Structure that arises as a result of interactions between backbone groups that are close to one
another in protein
• Helix and alpha chain are not same
3) Tertiary
Fibrous Globular
➢ Structural
proteins ➢ functional
➢ Insoluble ➢ compact, tight
➢ Long half life packing in core
➢ Secondary structure ➢ Secondary, tertiary &
➢ No defined tertiary quaternary structure
Intermediate structure
structure ➢ Soluble in water
Eg: - α keratin, Eg: - Hb, myoglobin,
collagen, elastin lysosome,
Eg: - fibrinogen ribonuclease
• Some globular proteins have both α helical and B pleated sheet (higher amount of B
pleated sheet) structures in the same molecule
Lysozyme
Domains
• Distinct 3-dimensional structural units of a polypeptide chain which may have separate
functions.
• Often encoded by different exons
• A chain with a domain folds independently of others
• Each domain has a characteristic of a small compact globular protein structurally
independent of the others.
• Core of domain is composed of super secondary structures(motifs).
1. Charged nature
• Mainly from charged R groups and to a lesser extent COOH or NH2, can exist as cations,
anions or zwitter ions, depending on pH
• IpH depending on nature of R groups
• At IpH solubility and osmotic pressure are minimum
Alkaline medium negative ions react with Zn2+/Ba2+ deproteinising body fluid
2. Buffering action
• pH = pK buffering is maximum
• Imidazole of His important in buffering action of Hb (Globin is rich in His, pka = 7)
Prion diseases
• Natural non infectious form is alpha helical found in human brain cells
• Prion protein is a causative agent of transmissible spongiform encephalopathies
• Infectious beta pleated sheet act as a template and convert naturally occurring non infectious
prion protein alpha helical structure to beta pleated sheet
• Insoluble aggregates of fibrils
Amyloidosis
Collagen
Synthesis of collagen
Collagen diseases
Plasma protein
❖ Functions
1. Control of fluid distribution - albumin maintains colloid osmotic pressure
2. Transport (albumin, others) - bilirubin, free FA, Ca2+, Zn2+, fat soluble vitamins &
hormones (others - thyroid hormones, lipids, irons)
3. Haemostasis (enzymatic activity)
4. Defense - Immunoglobulins (γ globulins), acute phase proteins (inflammatory
responses in severe conditions)
Electrophoresis
• Plasma lipoprotein
➢ Separate as for serum proteins but stain for lipids (Eg: - Sudan red)
Extracellular Intracellular
Synthesized and retained in Synthesized in the cell but secreted
the cell for the use of cell itself out from the cell to work externally
Ex: Catalase Ex: Amylase, Trypsin
2H2O2--> 2H2O + O2
1 2018 A/L Batch Repeat Campaign
Enzymes can be used to identify diseases
Enzymes present in blood
Plasma specific enzymes: include: Present in salivary glands, gastric oxyntic glands and
Serine protease procoagulants such pancreas; α-amylase in salivary glands and pancreas, lactate
as thrombin, factor XII, Factor X and dehydrogenase enzyme and alkaline phosphatase etc.
others.
Enzyme Nomenclature
• Adding a suffix to the name of the substrate (ex: Arginine – Arginase)
• Traditional names (ex: Pepsin, renin)
• Naming by groups that catalyze similar reactions (ex: Lipase, proteinase)
• Systematic naming – has 02 parts → substrate + type of reaction
(Ex: lactate dehydrogenase)
Structure of enzyme
Globular complex protein structure made up of long linear chain of amino acids
Becomes ‘complementary’
when it binds to substrate
Enzyme specificity
• Ability of an enzyme to choose exact substrate from a group of similar chemical molecules
• It is a molecular recognition mechanism
• Operates through structural and conformational complementarity between enzyme and
substrate
• Enzymes show different degree of specificity towards their substrate
1. Substrate Specific for one substrate • Lactase on β 1-4 glycosidic bond
specificity and one reaction • Maltase on α 1-4 glycosidic bond
❖ How do enzymes increase reaction rate? By binding with substrate & increase the rate of
chemical reaction by lowering its activation energy.
A catalyst,
• do not undergo permanent change
• will not change the ΔG of the reaction
• will not change the equilibrium constant of the reaction
Co-enzymes
Co-factors
Small organic molecules derived from vitamins
Coenzymes
Pyridoxal Phosphate (PLP) Vit B6 Family Prosthetic group for number of enzymes
All 3 forms are converted especially reactions involving amino acids
to active form
Biotin Biotin Prosthetic group for carboxylation
Carries activated CO2
Eg: Pyruvate carboxylase
Acetyl CoA carboxylase
Coenzyme A Vit B5/Pantothenic acid is Has 3 major components
a component Thiol group carries acyl compounds; acyl
group transfer reactions
Eg: Succinyl CoA, Fatty acyl CoA and Acetyl
CoA
Tetrahydrofolate (THF) Folate Important in one- carbon transfer reactions
5’ Deoxyadenosylcobalamin Vit B12
and Methyl cobalamin
• Concentration of the E
• Concentration of the S
• pH of the reaction
• Temperature of the reaction Will determine the 3D conformation
• Electrolyte composition of the medium
1. Substrate concentration
2. Enzyme concentration
• Rate of the reaction increases with the enzyme concentration
[𝑺] k1 k2
𝑽𝒐 = 𝑽𝒎𝒂𝒙 E+S ES E+P
𝑲𝒎 + [𝑺] k-1
𝐾−1 + 𝐾2
𝐾𝑚 =
𝐾1
Any substrate that can diminish the velocity of an enzyme catalyzed reaction is called
“inhibitor”.
Enzyme
inhibition
Reversible Irreversible
inhibition inhibition
Reversible Inhibition
Competitive Non-Competitive
Active Site Active on active site Not on Active site
Structure of inhibitor Structural analogues. Substrate and Unrelated molecules
inhibitor are chemically similar and
have similar shapes. Thus S & I
competes for the active site.
Effect on Active site Inhibitor does not change Inhibitor changes the
active site shape of the active site
Excess of Substrate Inhibition relieved No effect
E+S ⇌ ES ⇌ E+P E+S ⇌ ES ⇌ E+P
+I +I +I
EI EI ESI
Inhibitor binds with Enzyme Enzyme or ES complex
Km ↑ (∴ Substrate binding is affected) Unchanged
Affinity ↓ Unchanged
Competitive Inhibitors
1) Statins
➢ Statins (ex: Atorvastatin and Pravastatin) are structural
analogues of natural substrate for HMG CoA Reductase.
➢ Inhibit De novo Cholesterol synthesis, thereby lowering
plasma cholesterol levels.
2) Sulfa drugs
Alcohol dehydrogenase
Methanol Formic acid → Metabolic acidosis and tissue injury
-
Ethanol
Summary
Irreversible Inhibition
• Inhibitor covalently binds to the enzyme and modifies key amino acid residues needed
for enzymatic activity.
• The catalytic activity of the enzyme is completely lost.
• It can only be restored by synthesizing the enzyme.
(-)
Acetylcholinesterase
Acetylcholine Choline + Acetate
2. Suicide inhibitors
• An unusual group of irreversible inhibitors.
• Inhibitor is a relatively inert molecule.
• Binds with the active site of enzyme.
• Transformed into a reactive compound. (intermediate)
• The intermediate forms a covalent linkage with active site.
• Inactivates the enzyme.
• Enzyme loses its original form.
Adenosine
Inosine Guanine
Allopurinol Oxypurinol
• Series of steps found in biochemical reactions that occur to create and use energy in a living
cell
• 02 types
o Anabolic pathways – energy is generally absorbed
o Catabolic pathways – energy is generally released
• Metabolism - sum of all chemical changes occurring in a cell, tissue and the body.
• The product of one reaction in a pathway serves as the substrate for the following reaction.
• Enzymes can be involved at every step in a reaction pathway.
• Those enzymes can be located adjacent to each other (in an organelle or in the membrane
of an organelle) → speeds up the reaction
• Intermediate products do not accumulate so that the equilibrium will not attain. Thus, the
reactions will proceed in the “preferred” direction. → more efficient
Metabolic Flux
• “Flow of metabolites through a reaction pathway”
• Modulated by extracellular signals (ex: hormones)
• It will lead to,
1 Varying [E] within the cell
2 Subcellular location of the enzyme
3 Changing the activity of the enzyme present in the cell
4 Cofactor balance of enzyme reaction
Control Mechanism
Control enzyme
Enzyme on or off
kinetics
Effector molecules
Often low Mol. Weight organic compounds
Proteins and metal ions can also act as effector
molecules
2. Via phosphorylation
• Phosphorylation of enzymes by specific protein kinases is a widespread mechanism for
regulation of enzyme activity
• It is a reversible means of regulation
• Plays a central role in signal transduction in eukaryotes
• The phosphorylation occurs mainly on Ser/Thr and on Tyr residues
Reaction pathways
Reversible reactions (A ⇄ B)
▪ The Substrate and the Product it forms is at near equilibrium
▪ Can quickly restore the levels of S and P to near equilibrium status and the direction of the
reaction will be governed by their concentration
Irreversible reactions (B → C)
▪ The steady state concentration of S and P are far from the equilibrium.
▪ Reaction goes in one direction
Phosphofructokinase I is an example
of allosteric activation and inhibition
The individual enzymes differ as to whether it is their phosphorylated or the dephosphorylate form
is active
Ex:
Glycogen synthase is active in the dephosphorylated form
Glycogen phosphorylase is active in the phosphorylated form
ISOENZYMES
Enzymes that differ in amino acid sequence but catalyze the same chemical reaction.
Activity is regulated & organ localization can be different
Has different regulatory properties
Clinical importance assessing damage to specific organs due to different tissue distribution
1. Creatin kinase(CK)
2. Lactate dehydrogenase(LDH)
Has two isoenzymic chains H chain – cardiac muscle; M chain – in skeletal muscle
Isoform Present in
LDH1 Heart, RBC, Renal cortex
LDH2 Heart, RBC, Renal cortex
LDH3 Lung, Lymphoid tissue, Pancreas
LDH4 Liver, Skeletal Muscle
LDH5 Liver, Skeletal Muscle
Regulation of isoenzymes
Many regulatory enzymes (irreversible) in metabolic pathways exist as isozymes to serve
optimally to the tissue need and its environment
Have different regulatory properties according to tissue.
Eg: in glycolytic pathway
Hexokinase / Glucokinase – liver and other glycolytic cells
Phosphofructokinase- 2 (PFK2) - liver and cardiac / skeletal muscle
Pyruvate kinase – liver and other tissues
Lactate dehydrogenase (LDH) (not irreversible enzyme – cardiac and skeletal muscle
Eg: other enzymes
Glycogen phosphorylase- liver and muscle
Pyruvate dehydrogenase- Skeletal muscle and other tissues
Metabolic channeling
The product of one reaction is directly transferred to the next active site in the pathway
1. Increases the rate of reaction vastly because of the decrease in transit time for intermediates
between enzymes by producing local high concentration of intermediates
2. Protect chemically labile intermediates from degradation by the outside environment.
Achieved via,
1. Multienzyme complexes
Different enzymes that catalyse sequential reactions in a pathway are bound together
Ex: Pyruvate dehydrogenase complex in conversion of Pyruvate to Acetyl CoA
2. Multifunctional enzymes
Different activities found on a single multifunctional polypeptide chain
Ex: Fatty acid synthase (bifunctional) in the synthesis of Fatty acid
DNA polymerase I tri functional enzyme
Structure
Lipid bilayer
Held together by non-covalent interactions
Components proteins
Carbohydrates covalently linked to proteins (glycoproteins)
Lipids (glycolipids)
Only in outer leaflet.
Cholesterol
Phosphatidylinositol
Hydrophilic head →
➢ PI - minor phospholipid critical for signaling
exposed to water
Lipids are amphipathic
Hydrophobic tails →
in interior
When mixed with
water Unsaturated tail → cis double
bond → forms kinks
Saturated tail
Micelles /emulsions Lipid bilayers Liposomes → can be made from
solutions of pure phospholipids.
Enzymes
Used in DNA to target
delivery of Anticancer tissues.
drugs
1 2018 A/L Batch Repeat Campaign
Micelles
2. Membrane proteins.
Peripheral proteins Peripheral membrane proteins are found on the outside and
→
inside surfaces of membranes, attached either to
integral proteins or to phospholipids. Unlike
integral membrane proteins, peripheral membrane
proteins do not stick into the hydrophobic core of
Two classes
the membrane, and they tend to be more loosely attached.
• Transporter
• Enzyme binding site Outside
• Cell surface receptor
• Cell surface identity marker
• Cell adhesion Inside
• Attachment to cytoskeleton Glycophorin
1) Asymmetry
2) Fluidity
• Flippase actively maintains the concentrations of PS and PE in inner membrane. Cell damage
leads to loss of membrane asymmetry
• Carbohydrates mainly in outer leaflet
❖ Phosphatidylserine
➢ Anionic-Gives negative charge to cytoplasmic side of the membrane.
2) Fluidity
Amount of cholesterol
(Fluidity Buffer)
I. Type of phospholipids
a) Saturation
✓ Unsaturated - high fluidity
II.Amount of cholesterol
➢ Broadens the melting temperature
Q. Briefly explain the role of cholesterol in maintaining the fluidity of the bio membranes.
➢ The steroid cholesterol is wedged between phospholipid molecules in plasma membrane of
animal cells.
➢ - OH groups of cholesterol are aligned with the polar head of phospholipids in the
membrane
➢ It acts as fluidity buffer
➢ At warm temperatures it controls the movement of phospholipids and reduces fluidity
➢ At cool temperatures it maintains fluidity by preventing tight packing
3) Flexibility
• Permits shape change without loss of integrity
4) Dynamic
I. Uncatalyzed
II. Catalyzed
➢ Individual fatty acyl chains are hysrolyzed from the
1. A catalyst-a protein- is involved – it lipids and replaced by new fatty acyl chains
uses ATP flippase-moves phospholipids ➢ The membrane phospholipids also moves
from outer to inner leaflet, this
movement is fast
3. Scramblase – do not need ATP but a fast movement does both above movements (inner to outer/outer to
inner)These movements causes the lipid bilayer a moving /fluid structure ‘Fluid Mosaic Structure’ –this is
really important for the membrane homeostasis
Protein mobility
1. Rotational mobility
2. Lateral diffusion
• Protein mobility can vary greatly.
➢ Some proteins are free to move
➢ Some adhered to structures in the cytoplasm or extracellular spaces
Biological membrane allow the small non polar molecules to pass through it easily and fast. e.g. the gases like
oxygen and carbon dioxide
The large non-polar molecules pass through it but slowly. e.g. benzene
The large polar molecules do not pass through the (lipid part of the) membrane. e.g. glucose
The charges molecules do not pass through the (lipid part of the) membrane. e.g. Cl-, Na+, amino acids
MEMBRANE TRANSPORT
Ion channels - allow passage of ions which are associated with water
Gap junctions
✓ Transport ions connect the cytoplasm of two cells by 2 CONNEXONS
✓ A connexon is made by 6 connexin proteins
✓ Opening of gap junctions is inhibited by intracellular Ca2+.
Aquaporin
✓ Transport water (too narrow for ion transportation)
✓ Tetrameric transmembrane protein
• Uniport
➢ Transport single solute
➢ Eg- GLUT 1 glucose carrier
• Symport / cotransport
➢ Two different solutes to be
transported
➢ Gradient of one substrate drive
uphill transport of co-substance
➢ Eg: - Glucose-Na+ symport
• Antiport
➢ Exchange one solute for another
Eg: -
Na+- H+ exchanger,
Cl-/HCO- exchanger
bands protein in RBC membrane
➢ Symport and antiport are secondary active
transport methods
2) Active transport
Na+ / K+ ATPase
• Na+/K+ ATPase binds 3 intracellular Na+
• ATP phosphorylates protein with bound sodium
• Phosphorylation causes conformational changes reducing its affinity to Na+, then 3 Na+
diffuses out
• New conformation has higher affinity to extracellular K+
• Binding of 2 K+ facilitates dephosphorylation of protein
• Required to maintain osmotic balance and cell volume
❖ Digitalis inhibits this pump, Careful use as a therapeutic benefit for heart patients
Q. Explain the molecular mechanism of acidification of the stomach lumen by parietal cells in the
gastric lining
➢ Omeprazole inhibits the H+/K+
ATPase pump and used for gastric
ulcers
➢ In the healthy state there are glucose-dependent and glucose independent methods of
absorbing Na+ in the gut
➢ In diarrhoea glucose independent method is inactivated
➢ The Na+ in the intestinal lumen is transported into the enterocytes via the Sodium Glucose
Cotransporter (SGLT-1) which is a symport
➢ Therefore, glucose must be present (along with Na+) in the ORT fluid
➢ Na+ that enters the cell is then pumped into the blood using ATP by the Na +/K+ ATPase
pump
➢ Glucose enters the blood from the enterocytes via the GLUT-2 transporter
➢ Since both Na+ and glucose are osmotically active substances, water will also move in from
the lumen to the enterocytes and then to the blood
➢ Therefore, both lost water and electrolytes (Na+) are replaced due to ORT
Bulk transport - ENERGY REQUIRING
• Two types
1) endocytosis
2) exocytosis
1) Endocytosis
Key Functions
ECM components are secreted by the surrounding cells (osteoblasts, chondroblasts) & assembled
outside the cells.
Composition of ECM
1. Protein
Adhesive proteins
-adhesive proteins - Fibronectin, Laminin, Fibrillin
2. Water
Glycosaminoglycans
Cartilage
ECM of cartilage
3 types of cartilage
Protein
Structural proteins
1. Collagen
• Proteins (Organic matrix) are synthesized first and then the minerals are added.
• The vast majority of the organic matrix is collagen which provides tensile strength.
ECM , cells
Polysaccharides
Elastin
Structure
Role of vitamin C
(Fe 2+ Fe3+)
Types of collagen
• 19 types
• 90% - type 1,2,3,4
2. osteogenesis imperfecta
• Defect in synthesis of collagen. Often type I collagen.
• Defective ∝ chains. Inadequate bone mineralization.
• Brittle bones - High frequency of fractures
3. Scurvy
Vitamin D
Sterol-7-dehydrocholesterol (epidermis)
(UV light)
Cholecalciferol
Function – as a hormone
kidney
1-25 dihydroxy cholecalciferol Ca, PO43- reabsorption
bone mineralization
bone resorption
Calcium
Beta-glycerol phosphate
Alkaline phosphatase
Free phosphate
Vitamin k
1. osteoporosis
• Porous bones
• Progressive systemic skeletal disease
• Low bone mass and microarchitectural deterioration of bone tissue
• Increased bone fragility, increased fracture risk
• Osteopenia – a mild form of osteoporosis
Osteoporosis Osteomalacia
Definition Decreased bone mass Demineralized bones
Pathophysiology Lack of calcium Lack of vitamin D
Radiography Osteopenia Pseudofractures /fractures,
looser zones
Calcium Normal Low / normal
Phosphate Normal Low / normal
PTH Normal High / normal
Alkaline phosphate Normal High
3. Rickets
• Seen only in children.
• Caused by failure of osteoid to calcify in growing person – in cartilaginous growth plate.
• Due to Vitamin D deficiency (inadequate intake, metabolism, and lack of exposure to
sunlight)
• Before contraction begins ATP binds to the head of the cross bridges. ATPase activity in myosin
head cleaves ATP and causes a conformational change in head. This stored energy brings out power
stroke to slide actin filaments over myosin.
• New ATP molecule binds to the head causing detachment of actin and myosin filaments.
• ATP is used to pump back Ca2+ from sarcoplasm to the sarcoplasmic reticulum following
contraction.
• ATP is used to maintain Na+/K+ pumps etc. to maintain the ionic environment of the cell in order to
propagate muscle fiber action potentials.
ATP
Glycogen - lactic acid 30-40 seconds Glycogen stores Intermediate athletic activity
system (100m/ 200m sprints)
Aerobic system Hours Glucose (from Prolonged athletic activities
glycogen), amino
acids, fatty acids
1) Phosphagen system
o Creatine phosphate (CP) is stored in muscles
o CP contsins a high energy bond.
o Bond is cleaved reversibly to reconstitute ATP.
• When ATP production fails to keep up with the ATP usage muscle fatigue occurs.
• Reduced ability to contract
• May result from shortage of fuel substrates.
• Nitrogenous Base
o Purines (bicyclic)
▪ Adenine (A)
▪ Guanine (G)
• Pyrimidines (monocyclic)
o Cytosine (C)
o Thymine (T) - only in DNA
o Uracil (U) - only in RNA
• Phosphate group - ribose & 2’deoxyribose
• Nucleotide = Nucleoside (2C, 3C, 5C or phosphate) + Phosphate group (one or more) (Ester bond)
Eg: - Deoxyadenosine triphosphate - dATP
Adenosine triphosphate – ATP
DNA
Structure of DNA (Watson & Crick Model)
• a polymer of deoxyribonucleoside monophosphates
• 2 polynucleotide chains coiled around a common axis (a few viruses that contain single-
stranded (ss) DNA)
• Double helical (for replication, transcription)
• Antiparallel
5’ 3’
3’ 5’
• Complementary (not identical)
• Right-handed coiling
• 10 bp/turn,20' A diameter
• Sugar phosphate backbone outside
• Hydrophilic
• Polar sugar molecules
• Negatively charged phosphate groups - Polyanionic
backbone
• Make railing
• Bases inside
• Hydrophobic
• stacked inside the helix
• perpendicular to sugar-phosphate backbone
• Make steps with H bonds
• When DNA double helix is viewed from outside 2 groves can be observed
1. Major groove
2. Minor groove Important in bindings to regulatory proteins
and small molecules –drugs/ dyes etc.
• Transitions between the B and Z helical forms play a role in regulating gene expression.
Denaturation of DNA
• Separation of two strands of the duplex DNA by breaking H
bonds
• a reversible process
1. increase in temperature (Melting)
2. increase in pH (alkali)
3. by specific enzymes
• Phosphodiester bonds are not broken
• Temperature at which ½ of DNA molecule are unwound = Melting temperature (Tm): 50% ds DNA;
50% ss DNA
• denaturation, can be monitored by measuring the absorbance at 260 nm
• The denatured DNA exhibits stronger UV absorption,
showing a hyperchromic shift during "melting".
• DNA denaturation occurs over a narrow temperature
range
• Because there are 3 H bonds between G and C but 2 H
bond between A and T
Tm of DNA that contains high GC content > Tm of DNA
that contains high AT content
Renaturation
• Process where the denatured complementary strands of DNA forms the duplex DNA.
• Slow cooling of denatured DNA allows renaturation.
Hybridization
• Denatured DNA when cooled in the presence of exogenous DNA, strand of DNA forms the duplex
DNA.
• Depends on
1. Favorable temperature of the solution
2. Salt-ion concentration
• Even if two sequences do not match perfectly, they can be hybridized. Used in disease diagnosis
(DNA annealing)
DNA PACKAGING
• Human genome (in diploid cells) = 6 x 109 bp = ∼2 m/cell
• Very thin (2.0 nm), extremely fragile
• Diameter of nucleus = 5-10 µm
• DNA binding proteins - compact double helical DNA into eukaryotic nucleus.
• Resulting DNA-protein complex – chromatin in the interphase nucleus
• Chromatin can be packaged into a much smaller volume than DNA alone.
Histones
Non-histone proteins
• Main packaging proteins
• Many different types of proteins (~100
• 4 major types/5 classes
types)
H1, H2A, H2B, H3, H4
• Diverse functions
• Rich in basic amino acids Lysine and
• Highly species / organ specific
Arginine
• Major =
• (+)vely charged
Topoisomerases, Scaffold proteins, Gene
• form ionic bonds with negatively regulatory proteins
charged DNA
• 2 groups
Linker histone –
• Less conserved
Core histones –
• contacts the exit & entry of the DNA
• forms the core of the nucleosome strand on the nucleosome
• Help fold DNA into nucleosomes • Help pack nucleosomes to form higher
• Highly conserved order structures
H2A, H2B, H3, H4 H1
• H1 is the most tissue-specific and
Nucleosomes (unit of DNA packaging) species-specific of the histones
30 nm fibre:
• coil of nucleosomes with 6/turn
• Most of chromatin in a typical interphase nucleus – found as 30-nm fibers
• According to one of the models - 30 nm fibers fold into series of radial
loops to forms the metaphase chromosomes
metaphase chromosome: Higher-level DNA supercoiling of the 30-nm fiber produces the metaphase
chromosome
• When DNA is wrapped very tightly: difficult for transcription factors or other DNA binding proteins to bind
to the DNA
Methylation Acetylation
Histone acetyltransferases (HAT), removes +
charges on lysine
Interaction with DNA
further condensation of DNA around histones relaxes chromatin condensation
prevents binding of transcription factors (TF) exposes DNA for TF binding
gene repression gene expression
Supercoiling of DNA
• Supercoiling = coiling of a coil as DNA is a coil (= helix)
• Packaging involves bending / twisting of the DNA helix (coil) =
supercoiling
Topoisomerases
• mutations in any of the genes coding for topoisomerases are usually lethal
• therefore, targets for antibiotics and other drugs
Key features of DNA Replication, (DNA – only molecule that can duplicate itself)
• Semi-conservative - new strand built on parent strand, so, each DNA molecule consists of
one old (parental) strand and one new (daughter) strand.
(Advantage – Replication errors can be repaired)
• Bi-directional - The two replication forks move in opposite directions.
• Semi-discontinuous
Concept of Template
• If the sequence on one strand is given, then the sequence of the other strand is
automatically determined. (complementary base pairing)
DNA Polymerase
• Uses DNA as a template to synthesize new DNA by catalyzing chain growth (phosphodiester
bonds) only in 5´ to 3 direction.
´
• only able to “read” the parental nucleotide sequences in the 3'→5' direction
• This requires,
• A template
• A primer with a free 3´ OH
1 2018 A/L Batch Repeat Campaign
•
Deoxynucleotides in the form of tri-Phosphates (PP released in reaction)
DNA polymerase has nuclease activity too.
1. 3´ to 5´exonuclease activity - Proofreading activity
• Removing wrong nucleotides & replace
• Ensures replication fidelity
2. 5´ to 3´exonuclease activity
• Removes nucleotides from 5´end.
• This is used in removal of RNA primer and DNA repair.
3’ to 5’ exonuclease 5’ to 3’ exonuclease
• Important for proof reading function of DNA • Important for removal of “RNA
polymerase I primers”
• Can remove wrong nucleotides and replace • Removes nucleotides from 5’ end
• Removes only mismatching points • Removes matching pairs also
• Removes only one nucleotide • Can remove a large part
• Only remove deoxyribonucleotides • Remove both deoxyribo and
ribonucleotides
Topoisomerases
• DNA supercoils are removed by reversibly cleaving one or two strands.
• Separation of DNA strands causes topological strain on the rest of the DNA strand.
• positive supercoils appear ahead of the replication fork while negative supercoils appear behind
the replication fork
• Topoisomerases relieve this strain by maintaining DNA in the negative supercoiled state
• Type 1 topoisomerase cleaves only one strand and it is ATP independent. (one → indepen.)
• Type 2 topoisomerases can cleave both strands and it is ATP dependent.
• DNA gyrase is a special type two topoisomerase enzyme which found in E-coli. It can introduce
negative supercoils.
• Quinoline drug is a topoisomerase inhibitor
DNA ligase
• Seals nicks(gaps) between DNA fragments
• catalyze formation of 3´ to 5´ phosphodiester
bonds in an ATP dependent reaction.
Replication Process
• Replication occurs in 3 stages,
1. Initiation
2. Elongation
3. Termination
Elongation
• Mainly done by DNA polymerase - III,
❖ Reads the template from 3´ to 5´ end.
❖ Synthesize new DNA strand in 5´ to 3´ end. (Polymerase activity)
❖ Has proofreading activity. (3´ to 5´ exonuclease activity)
❖ Synthesizes DNA from both strands simultaneously
❖ High processivity / high fidelity – remains bound to the template strand as it moves along,
and does not diffuse away and then rebind
❖ Processivity is the result of - β subunit forming a ring that encircles and moves along the
template strand of the DNA, serving as a sliding DNA clamp
❖ High rate of synthesis
❖ Two DNA strands grow in opposite directions.
Energy of Replication
• The nucleotide substrates are 5'-deoxyribo
nucleoside triphosphates
• The nucleotides arrive as nucleosides - DNA bases
with P–P–P
• DNA bases arrive with their own energy source for
bonding
• Pyrophosphate (PPi) is released when each new
deoxynucleoside monophosphate is added to the
growing chain
• Hydrolysis of PPi to 2Pi break down 2 high-energy bonds release the energy
DNA polymerase - I,
• 5´ to 3´ exonuclease activity – hydrolytically remove the RNA primer in the 5'→3' direction
• 5´ to 3´ polymerase activity – extends strand up to adjacent Okazaki fragment and replaces
RNA primer with DNA, because new lagging strand consists with RNA-DNA unjoined pieces of
RNA-DNA combinations.
• 3´ to 5´ exonuclease activity – proofreading
Telomerase,
• Ribonucleoprotein complex
• Has a C-rich RNA template - base-pairs with the GT-rich, single-stranded 3'-end of telomeric DNA
• Has Reverse Transcriptase activity - uses the RNA template to synthesize DNA in the usual 5'→3'
direction
• Has other proteins for binding of DNA.
• Telomerase recognizes the G rich single stranded 3´ end of the parent strand and elongates it by
copying its RNA template. It contains both template and enzyme activity.
Retroviruses
• ssRNA genome containing viruses
• reverse transcriptase, uses the viral RNA as a template for the 5’→3’ synthesis of viral DNA
• Viral DNA then becomes integrated into host chromosomes
• HIV Reverse transcriptase is 10 times less accurate than other reverse transcriptase enzymes,
therefore they have very high rate of evolution
RNA
1. RNA – Translated into proteins
• mRNA 5%
2. Structural / Functional RNA - Not translated
• rRNA - An integral component of ribosome 80% [Some rRNAs functions as catalysts
(rybozymes)]
• tRNA - Involve in translation 15%
• snRNA - (Small nuclear RNA)- Forms complexes with proteins used in Eukaryotic RNA
processing (eg; Exon splicing and intron removal)
• miRNA/siRNA - (Micro RNA/ Small Interfering RNA)- Short RNA sequences that bind to 3’
UTR target mRNAs and results in gene silencing
Transcription
The synthesis of RNA molecules using DNA strands as templates so that the genetic information
is transferred from DNA to RNA.
▪ The whole genome of DNA needs to be replicated but only a small portion of genome is
transcribed in response to the development requirement, physiological needs and
environmental changes.
▪ DNA regions that can be transcribed into RNA are called structural genes.
➢ Promoter - The nucleotide sequence upstream of a gene, that acts as a signal for RNA
Polymerase binding
➢ Exons - coding DNA segments of eukaryotic genes.
➢ Introns - non-coding DNA segments of eukaryotic genes. (intervening sequences)
(Transcripted but not translated. They are removed to produce mature mRNA)
• The enzyme responsible for the RNA synthesis is DNA dependent RNA polymerase.
• But RNA polymerase is 100% processive.
• Multiple subunit protein.
• 3 types
Enzyme Transcription
RNA Polymerase I rRNA
RNA Polymerase II mRNA, some SnRNAs
RNA Polymerase III tRNA, SnRNA, ScRNA
• Unlike prokaryotic RNA polymerases eukaryotic RNA polymerase 2 can’t recognize the
promoter.
• Therefore, transcription factors do it
Eg: TF II D
Operon
• Each transcriptable region is called operon.
• One operon includes several structural genes and upstream regulatory sequences (or
regulatory regions).
1) Initiation
2) Elongation
3) Termination
• Bubble moves forwards by unwinding in front & rewinding behind the DNA strand.
• DNA-RNA base pairing CG GC TA AU
Promoters
Transcription Bubble
PROKARYOTES EUKARYOTES
• Transcription & Translation occurs • Transcription in the Nucleus
simultaneously Translation in the cytosol
• One type of RNA polymerase • 3 types of RNA polymerase
• Polycistronic - mRNA codes for more • Monocistronic - mRNA codes only for one
than one gene gene
• Most part of DNA is accessible to • Only small amounts are accessible
transcription
• mRNA doesn’t show post • All mRNA, tRNA, rRNA undergo post
transcriptional modification transcriptional modification
Inhibitors of Transcription
INHIBITOR EFFECT
• Rifampicin (on prokaryotes) • Inhibit transcription by binding to
RNA polymerase (prevent chain
extension beyond 8 nucleotides)
• Blocks initiation
• Actinomycin D (on both • Intercalate between DNA base pairs.
prokaryotes and eukaryotes) – • Stop movement of RNA polymerase.
Cancer drugs • RNA elongation inhibitor.
• Both prokaryotes & eukaryotes
• α amanitin (on eukaryotes) – poisonous • Eukaryotic RNA polymerase II inhibitor
mushrooms
1) mRNA
Modification Function
1) Addition of the 7-methylguanosinecap at the • Prevent nucleases from destroying the
5’position (5’capping) transcript
• Occur at the beginning of transcription • Ribosome recognition
• Enzyme - Guanylyl transferase • Transfer of the transcript to the cytoplasm
2) tRNA
• Remove introns
• 3’ end is cut off and replaces by a CCA sequence
• Removal of the leader sequence
• Some base modifications
3) rRNA
Replication Transcription
• Template Both strands Single strand
• Substrate dNTP NTP
• Primer Yes No
• Enzyme DNA Polymerase RN Polymerase
• Product dsDNA ssRNA
• Base Pairs A-T, G-C A-U, T-A, G-C
transcription translation
DNA mRNA Protein
THE GENE
• Genetic code-information in the cell is stored in the form of linear sequence of nucleotides in
DNA
• The code has 4 different letters- A, C, G & T (4 bases)
• The code is composed of triplet codes/codons. eg - AGC, CTC, TGG
• Each codon codes for one amino acid.
• There are 64 different codons. ( 𝟒𝟑 = 𝟔𝟒 )
• But only 61 of them code for amino acids. (rest of them are stop codons) (61 codons-->20 AAs)
• A series of codons in DNA that coding for a protein is a GENE.
• Universal (almost) - The code is almost the same for all the living organisms.
wobble hypothesis
➢ Pairing of 3rd base in codon (wobble base) with 1st base of anticodon isn’t strong, but
other 2 base pairs follow strong Watson & crick pairs.
➢ Genetic Code 61 codons Coding for 20 amino acids
➢ All 61 codons do not have individual tRNA to pair.
➢ Therefore, more than one tRNA can bring one amino acid, because non tradition base pair
can occur.
e.g. - anticodon- (3’) XYU (5’)
codon - (5’) YXA (3’) or (5’) YXG (3’)
➢ So the 1 base of the anticodon determines the number of codons read by a given tRNA
st
Ribosomes
Small subunit
➢ mRNA binding site
Large subunit
➢ A site (Aminoacyl tRNA binding site)
➢ P site (Peptidyl tRNA binding site)
➢ E site (tRNA exit site)
1) Initiation
➢ fMet-tRNA binds to AUG forming 30S initiation complex (fMet-tRNA is the only tRNA which
goes into the P site)
➢ 50S subunit binds to 30S initiation complex forming 70S initiation complex.
• Ribosomes add 1 AA at a time to carboxylic end of growing polypeptide chain, GTP required
• Ribosome translocates by 3 bases after peptide bond formed.
• New charged tRNA aligns in the A site.
• Peptide bond between amino acids in A and P sites is formed by peptidyl-transferase.
• Ribosome translocates by three more bases.
• The uncharged tRNA in the P site is moved to the E site.
❖ Translocation: translocation of the new peptidyl t-RNA with its mRNA codon in the A site
into the free P site occurs.
❖ Now the A site is free for another cycle of Aminoacyl tRNA codon recognition and
elongation. Each translocation event moves mRNA one codon length through the
ribosomes.
❖ Translocation requires
➢ in prokaryotes: EF-G-GTP
➢ in eukaryotes: EF-2-GTP
3) Termination
Prokaryotes Eukaryotes
• 70s ribosomes • 80s ribosome
• Prokaryotic mRNA is polycistronic. • Eukaryotic mRNA is monocistronic.
• Initiator Met-tRNAi or Met-tRNAf • Initiating tRNA carries methionine
carries formyl- methionine
• Prokaryotic mRNA has specific purine rich • No specific purine-rich sequence.40s subunit
‘Shine Delgano sequence’ on the mRNA. binds to 5’ cap region and scan for the first AUG
• Fewer translation factors • Many translation factors
• Elongation GTP driven translocation • Similar to prokaryotes but specific elongation
factors
• Termination carries out by 2 release • Termination in eukaryotes is carried out by a
factors single released factor eRF 1
Antibiotics that inhibit ribosomal protein synthesis
Chaperones
• Proteins in the cell which assist the covalent folding or unfolding
• They guide folding of proteins present in cytosol, lumen of RER, mitochondria, etc.
• Chaperones promote the assembly of protein complexes from subunits.
• Prevent the aggregation of unfolded proteins.
Protein folding
➢ BiP (hsp) helps to fold protein correctly.
ATP
Open state confirmation, BiP-ATP
BiP weakly binds to target protein
hsp 40;
helps to hydrolyze ATP to ADP
conformational changes that causes BiP-ADP
BiP to clamp tightly to hydrophobic
region of the protein
This process is repeated over and over until protein is folded into its final form.
PTMs in Prokaryotes,
• Protein folding
• Removal of the Signal Peptide
• Removal of Formyl – Methionine from the N terminal
PTMs in Eukaryotes,
• Protein folding
• Removal of the Signal Peptide
• Removal of Methionine from the N terminal (initial Amino Acid)
1) Proteolytic cleavage
2) Disulphide bond formation
3) Glycosylation
4) Methylation
5) Phosphorylation
6) Lysosomal targeting of enzymes
7) Ubiquitination
8) S-Nitrosylation
9) Acylation
10) Sulfation
11) Vitamin C- dependent modification (Hydroxylation)
12) Vitamin K dependent modifications
2) Covalent attachments
a) Hydroxylation
Eg: In collagen synthesis; hydroxylation of selected proline and lysine residues of pro α chains.
Prolyl hydroxylase
Proline Hydroxy proline
Vit C= Ascorbic acid
Lysyl hydroxylase
Lysine Hydroxy Lysine
Vit.C = Ascorbic acid
➢ Ascorbic acid is required for this process. So, Vit.C deficiency leads to scurvy.
b) Glycosylation
• Enzymatic addition of oligosaccharide molecules into the peptide chain about 50% of
eukaryotic proteins are glycosylated
• Attached glycosyl residue determines the function of the glycoprotein
• predominated by mannose, glucose, galactose, GALNAC, GLCNAC, NANA
Eg:
❖ In collagen synthesis
❖ Glycation of Hb
[Fructosamine] α Average blood glucose concentration over the previous 1-2 weeks
Fructosamine
c) Phosphorylation
• Selected serine side chains of Histone proteins are phosphorylated → DNA packaging is
altered.
Glycogen synthase Glycogen synthase
(Active) (Inactive)
Eg:
• Insulin – 2 interchain S-S bonds
1 intrachain S-S bonds
S-Nitrosylation
NO is a chemical messenger. It reacts with free cysteine residues to form
S-nitro thiols (SNOs).
S-Nitrosylation is a critical PTM used by cells to;
➢ stabilize proteins
➢ regulate gene expression
➢ provide NO donors
• Lysosomal enzymes are synthesized in RER and modified in the Golgi apparatus.
• A carbohydrate moiety, mannose-6-phosphate label (man 6-PO4) is tagged to direct these
hydrolytic enzymes to lysosomes.
• Man 6-PO4 is bound by a specific glycosyltransferase or phosphotransferase.
• Man 6-PO4 acts as a Targeting signal that is identified by receptor that target the protein into
lysosomes.
Defective phosphotransferase in the Golgi → cannot add PO43-to the mannose residue.
Enzymes are not targeted to direct it to lysosome but excreted outside the cell.
Partly digested materials (oligosaccharides, lipids, GAGs, etc.) accumulated within lysosomes.
➢ Defective lysosomal enzymes are found in high concentrations in the blood and urine.
(lysosomal enzymes are normally found only within lysosomes.)
Signal hypothesis
• This explains how proteins destined for secretion are synthesized.
• Free ribosomes in the cytosol are directed to the ER by the presence of a signal peptide in the
protein being synthesized.
➢ Signal peptide; ~18-36 AAs near the N-terminal of the chain
Absent in the mature protein
Direct the ribosome to ER
Protein synthesis in ER
• ER synthesize proteins which are to be exported out of the cell (Eg: Insulin, Collagen)
• Signal hypothesis → Explains how proteins destined for secretion, are synthesized
• Signal sequence,
➢ Free ribosomes in the cytosol are directed to the ER by the presence of a signal
peptide in the protein being synthesized.
➢ Absent in the mature protein.
Prokaryotes
➢ are unicellular or colonial
➢ evolved to quickly exploit transient resources
➢ gene regulation is to allow cells to adjust to changing conditions
➢ different genes are active in the same cell at different times
Eukaryotes
➢ are multicellular organisms
➢ evolved the ability to maintain a stable internal environment -Homeostasis
➢ gene regulation is to allow specialization / differentiation & division of labor among the cells
➢ different genes are active in different cells at the same time
c) Inducible genes
➢ genes that are transcribed & translated at higher levels in response to an inducible factor
d) Repressible genes
➢ genes whose transcription & translation decreases in response to a repressing signal
➢ Induction or repression can be due to,
1. environmental change
2. position of the cell cycle
Chromatin Structure
2) Heterochromatin
• highly condensed regions which contain the transcriptionally inactive genes
• difficult to access by RNA Polymerase
• two forms of Heterochromatin,
1. Constitutive Heterochromatin
➢ permanent organization
➢ contain no genes
Eg: Centromeric & Telomeric regions of human Y chromosome
2. Facultative Heterochromatin
➢ not permanent
➢ contain genes that are inactive in some cells or at some periods of the cell cycle
Eg: Barr body formation in females (X inactivation)
Chromatin Modifications
➢ Histone modifications
• Histone proteins in a nucleosome should move (rearrange) to express or depress a gene, but
this movement is dependent on signals found on both the histone proteins & on the DNA.
➢ These tags do not alter the DNA base sequence, but they alter the gene expression by changing
the arrangement of histone proteins
➢ DNA Methylation
• Methylation occurs within very specific regions called CpG islands. These are stretches with
a high frequency of Cytosine (C) & Guanine (G) dinucleotide DNA pairs found in the
Promoter regions of genes (~ 56 % of human genes).
2) Hypo methylation
Eg: Proto oncogenes leads to cancer
Non-communicable diseases
• epigenetic modifications occur in response to cellular environment, such modifications
occurring at key stages in fetal development are now thought to play a role in subsequent
development of Obesity, Diabetes & etc. later in life.
Eg: Exposure of fetus to high glucose environment in mother with Gestational Diabetes
Mellitus (GDM).
Genomic imprinting
• epigenetic mechanism, where one allele of a gene is silenced by methylation, in a parent of
origin specific manner.
• Mutations to unimprinted (expressed) allele, may lead to diseases.
Eg: Prader-Willi Syndrome
Angelman Syndrome
Enhancers/silencers
Cis acting sequences
➢ Distal control element act on more than one
promotor
➢ Regulatory DNA sequences that
increase/decrease transcription of genes in
vicinity
➢ 15-25 bp
promoters ➢ Upstream/downstream or within the gene
➢ Bind with transcription factors
➢ Found upstream
➢ Enhancers/silencers for regulatory proteins or
➢ Proximal control element
specific transcription factor s are called as
➢ Determines the strength of the promoter
response elements
Activators Co-activators
➢ Bind to enhancers & stimulate transcription ➢ Proteins, which serve as a physical bridge
➢ 2 domains between the activator & the RNA
• DNA binding domain polymerase.
Eg: Zn finger motif ➢ They consist of 2 types of binding sites
leucine zipper 1) polymerase binding sites
homeodomain, 2) Activator binding sites
basic helix-turn-helix Eg: Histone Acetyl Transferases(HATs)
• Transcription factor binding domain
✓ Binding sites for Coactivators
✓ Variable
✓ Increase transcription by 100-fold
• HRE is a common cis acting regulatory element present in genes, which need to coordinate their
expression, to affect a particular response.
• HREs bound by particular trans-acting factors under particular conditions to effect gene
expression.
Eg: lipid soluble hormones bind to specific soluble intracellular receptors, which functions as
trans-acting factors to a particular HRE.
➢ Steroid hormones, thyroid hormones, retinoic acid, calcitriol
❖ Post transcriptional regulation, allow a cell to fine-tune gene expression. There are various
regulatory mechanisms of gene expression at this level.
• RNA editing
➢ modification of nucleotide sequence after transcription.
Eg:
• mRNA stability
➢ length of time an mRNA remains in the cytosol before it is degraded, influences how much
proteins are produced from that mRNA.
➢ binding of proteins called RNA binding proteins (RBPs) to the regions of the RNA just
upstream or downstream of the protein coding region, can influence its’ stability.
➢ These regions in the RNA that are not translated into proteins, are called the Untranslated
regions (UTRs).
➢ They are not introns, but these are the regions that regulate,
✓ mRNA localization
✓ stability
✓ protein translation
❖ Excess free Iron (Fe) in cell causes cell damage, so cellular iron uptake & storage must be
tightly regulated, because there is no proper excretory method of Iron, in humans.
➢ Mechanism of gene silencing mediated by short non-coding micro RNAs. They decrease
expression of mRNA by,
✓ Repression of translation
✓ Increased degradation
➢ Micro RNAs are derived from longer dsRNAs, which are cleaved by an endonuclease (Dicer) &
associate with cytosolic protein complex (RISC).
➢ They bind to complementary sequences in target mRNAs to exert their silencing effect.
➢ The use of short regulatory RNAs to block the translation appears to be important for
developmental regulation.
➢ Increase or decrease in miRNAs play a role in diseases by altering gene expression.
• In prokaryotes, regulation of gene expression mainly done via operons, but eukaryotes lack
operons.
• Operon is a functioning unit of DNA containing a cluster of genes which are acting together &
expressed under the control of a single promoter.
Eg: Lac Operon - contains 3 genes
Try Operon - contains 5 genes
DNA
Gene density
❖ Average 10 genes/ Mbp
❖ Very low compared to other organisms
❖ Gene density varies between chromosomes
1. Highest: chromosome 19 (Also 17, 22)
2. Lowest: chromosome 13 and Y (Also 4,18 )
Genome Proteome
❖ Alternative splicing
❖ Variation in gene regulation
❖ Post transcriptional modification
CpG islands
• Stretches of CH repeating
sequences near gene rich areas.
• Form a barrier between genes and
junk DNA.
• Methylation of CpG islands
represses gene expression.
2. Pseudogenes (5%)
• Related to functional genes
3. Repeated sequences
• Repetitive elements differ in their
o Position in the genome
o Sequence
o Size
o Number of copies
o Presence or absence of coding regions within
• Some are extremely well conserved between species while others are highly variable.
• Located at relatively specific chromosome domains
o Centromeres
o Sub telomeric regions
• Human variations
1. Simple tandem repeat length polymorphism
2. Single nucleotide polymorphism ( SNP)
Uses: Uses:
• Gene mapping • Finding chromsomal locations for disease
• DNA profiling and paternity testing associated sequences
• Forensic testing • Tracing human history
• Conformation of relatedness • Mapping migrations of human populations
• Dead body identification
• Application of genomic information about an individual as a part of clinical care. It may be either
diagnostic or therapeutic procedures.
Benefits:
Genome sequencing
• Sanger's method
• Dideoxynucleotides are used
• Steps involved are,
o Denaturation of ds DNA
o Annealing ss DNA with a primer
o Extension by a DNA polymerase and 4 types of deoxynucleotides
o Termination of elongation due to ddNTP
▪ ddNTP lacks a 3’-OH therefore chain elongation stops.
▪ 4 different types of ddNTP are added to 4 different samples
o Bands with same terminal nucleotide can be separated and the sequence can be read by
▪ Agarose gel electrophoresis
▪ Autoradiography
• Isolated from bacteria (they are present in bacteria for protection form foreign genes.
Bacterial (their own) DNA protected by methylation)
• Recognise specific DNA sequences
o most of them are palindromic (read the same forwards &
backwards eg: 1221)
o sequences are 4 to 8 base pairs long
o Cleave at specific sites within / close to recognition sequence
o Both strands are cleaved (cut)
o A type of Endonucleases – a site in the “middle” of the nucleic acid is cut, not
an end
• Two types of Restriction enzymes are identified,
o 1. Cut DNA resulting in sticky ands
o 2. Cut DNA resulting in flushed (blunt) ends
• Many different enzymes with different names are
identified (eg: EcoR1, HaeIII etc.) Each enzyme
identify a different sequence
3. Gel Electrophoresis
Individual DNA fragments resulted can be isolated by electrophoresis
Two complementary DNA strands getting attached together by complementary base pairing is called
ANNEALING. If the 2 strands are originally from the same molecule (a dsDNA after denaturation), the
process of annealing is termed as RENATURATION. If the 2 strands are of different origins, the
annealing process is termed HYBRIDIZATION.
HYBRIDIZATION CAN OCCUR BETWEEN DNA/DNA, DNA/RNA OR RNA/RNA
How is it done?
A labelled fragment of DNA is mixed with the separated fragments. If the sequence we
expect is there, it will anneal (hybridize), and can be detected.
• Probe is a ss fragment of DNA • Fragments in the gel are ds • Forms stable base paired hybrids
• It is complementary to the DNA • They are heated and Factors decreasing hybridization
sequence we need to identify denatured
• single stranded DNA are
Temperature
• It is also labelled – with
radioactive P for identification available for hybridization Presence of denaturing agents
of its presence/absence with a now eg: urea/formamide
X-ray film Presence of high molecular weight
• It need not to be 100% polymers
complementary. More GC eg: dextran sulphate
content, more chance of
Shear forces
annealing
Factors increasing hybridization
salt conc.-NaCl, Na citrate,
morpholinoethanesulfonic acid
Hybridization is also used DIRECTLY on extracted DNA to detect presence/absence of parasitic DNA
2) RFLP analysis
RFLP analysis is based on, polymorphism of DNA.
When the frequency of a specific allele/variant is >1%, it is called a polymorphism.
(Else mutation)
1 2 3 4 5 6 7 8 9 1 2 3 4 5 6 7 8 9 fragment
Jothipala Jothipala
Dhanapala Dhanapala
fragment
Jothipala
The repeat sequence is
identified beforehand with a
probe so that we can chose a
suitable restriction enzyme
Dhanapala
Probe with sequence homology to repeat unit Probes are designed from unique sequences adjacent to repeat unit
• This give rise to fragments of varying lengths, and the set of fragments generated is
unique to a person. Therefore used in DNA fingerprinting.
• As 50% of genes are transmitted from each parent to child, fragment lengths show
similarities between parents and children. – paternity testing
• In forensic applications - DNA extract from hair, blood, semen, or other biological
materials found at the scene of a violent crime -> RFLP done -> fingerprint ->
compared with sample at site & sample from suspect
Denaturation
dsDNA is denatured by heat
(1 minute at 94°C)
Gene Cloning
Obtain DNA Put into a cloning Introduce into host Amplification and
fragments vector cells (transformation) screening of target
(plasmind/virus) gene
•DNA is obtained • the cloning vector is cut •Plasmids and
open by the same •Vectors contain an
(can be DNA or viral vectors
restriction enzyme used
(bacteriophage) origin of
cDNA) above (or else not replications in
•DNA thus complementary) "infect" the host
• donor DNA mixed with cell with foreign their sequence
obtained is
cleaved by a
vectors DNA •therefore can self
• 2 fragments ligated by
restriction DNA ligase join •the host cell can replicate
enzyme compatible terminals by be a bacterium, amplifying the
forming phosphodiestaer yeat, plant or foreign DNA we
bonds animal cell need
• Vectors, •as the vectors
• are self replicating
• small
contain antibiotic
• high copy number resistant genes,
• contain, antibiotic host cells are
resistant genes cultures in an
• origin of replication
• multiple cloning site =
antibiotic
polylinker = a DNA containing
segment containing 2 or medium
more sites for
restriction digestion •cells containing
• universal primer binding the vector ( so the
sites
• Strong/ inducible
gene) survie.
promoters others lyse
DNA
DNA Damage
Repaired DNA
DNA replication
Normal DNA DNA mutations
Different types of mutations
DNA damage
• DNA damages can occur due to various reasons, but they can be mainly categorized into,
1) Endogenous damages
2) Exogenous damages
➢ If these damages occur in germ cells, they are inherited by offspring if not repaired, but
unrepaired damages in somatic cells affects individual only.
a) Base damage
❖ Modification of bases
2. Adenine Hypoxanthine
• Deaminated A pairs with C
4.5-Methylcytosine Thymine
➢ Tautomerization - rare condition which can convert bases into their isoforms.
Eg:
1. Thymine
• Keto form Enol form
• Tautomerized T pairs with G
2. Cytosine
• Amino form Imino form
• Tautomerized C pairs with A
❖ Loss of bases
b) Replication errors
• Replication errors are the main source of mutations because DNA polymerase is not
perfect.
• Replication errors can be due to,
➢ Base pair mismatch - a wrong base can be added by DNA polymerase during replication.
➢ Insertions or deletions - repeat sequence regions are more prone due to strand slippage
by DNA polymerase
Eg: - Single nucleotide repeat
• DNA polymerase do make mistakes at a rate of about 1 per every 100,000 nucleotides.
c) Recombination errors
d) By products of metabolism
a) Chemicals (mutagens)
❖ Aflatoxins
Food borne secondary toxic metabolites produced during the growth of Aspergillus flavus and
A.parasiticus group of fungi.
❖ Food preservatives
❖ Benzopyrene
b) Radiation
Radiation
❖ UV radiation
• cannot penetrate beyond the outer layer of the skin, so it mainly leads to
formation of pyrimidine (Thymine - Thymine) dimers.
• ROS may result from long range UV irradiation (300-400nm) which can cause
Single stranded DNA breaks.
❖ Ionizing radiation
• penetrate the whole body, so they can cause both somatic & germ line mutations.
Eg: -
➢ α, β, γ particles
➢ X rays
1) Direct damage
• Cleavage of one or both DNA (can leads to rearrangements, deletions & chromosomal loss)
• Damage or loss of bases
• Cross linking of DNA to itself or proteins
2) Indirect damage
• water dissociates to H* & OH* (radiolysis of water) under α radiation
• free radicals cause DNA / RNA damage leading to cell death
❖ Medical radiation from x-ray machines. Eg: Computer Axial Tomography, Mammography
There is no safe threshold.
Eg: replication of a
✓ Unprepared
misincorporation
✓ Deaminated cytosine
Damage Removal
• Repair double strand breaks caused by high energy radiation and oxygen free radicals
➢ Few bases lost, if wrong ends are joined, Crossing over/strand exchange
mutations can happen
Resulting gap in sister chromatid filled by
polymerase
• Bloom’s syndrome
Defect in a type of Helicase needed in recombination during cell division
Autosomal recessive
Internal Environment
In a multicellular organism, it is the interstitial fluid or tissue fluid.
There are various physiological arrangements which serve to restore the normal state once it is
disturbed.
Eg: Plasma [H+]
Plasma [H+]
There are various Control Systems to make this happen. They maintain a variable at a particular set
point.
-Gets inputs from set point & feedback
from the sensor. If the set point changes with
Set point
-Detects the error
time of the system is called
-Output to effector.
a “servo mechanism”.
Controller
Inputs Set point-
Output
Feedback
Feedback =error
signals
Sensor
Effector
-Continuous
monitoring of the -Receives output of the
variable controller
-Detects disturbance -Applies necessary correction
-Sends feedback to
controller Response
Controlled
variable
Correction
Disturbance(s)
In each case positive feedback is useful, the positive feedback itself is part of an overall
negative feedback process.
Measured by GAIN
=
Not 100% effective.
4. A 25-year-old person was admitted to the hospital after a road traffic accident. He has lost blood.
His systolic pressure was 90mmHg at the time of admission (normal systolic point is 120mmHg).
Deviation of blood pressure from the set point would,
a) Be due to decreased volume in the intra vascular compartment
b) Larger in the absence of a regulatory system
c) Be detected by the sensors in the circulatory system
d) Blood pressure can be normal by positive feedback
e) Can be normal 100% by negative feedback
Sarcopenia
ECF ICF
1/3 of TBW or 2/3 of TBW or
20% of BW 40% of BW
Transcellular fluid belongs to ECF & includes CSF, secretions in gut, fluids in joints and eye.
Blood-8% of the BW
1) Age - age TBW (Infants – 70%, Young adults – 60%, Old – 50%)
2) Gender - F – 50% < M – 60% (low percentage of fat)
3) Fat content - Fat TBW
Water Balance
In a healthy person,
Water gain = water output
3L/day = 3L/day
Distribution of electrolytes
Measurement of electrolytes
SI unit – mmol/L
Traditional unit – mEq/L
Severe Vomiting : H+ ↓
Cation concentration: Plasma > ICF
Anion concentration: ICF > ECF
ICF cation exchange > ICF anion exchange
pH : ICF < ECF (due to metabolism)
2+
50% of the Ca in the plasma are bound to protein.
100
TBV -
100−
×
Interstitial fluid - ECF - plasma
Mechanisms
Filtration
Glomerular Solvent Drag
filtration 1.Transport of
nutrients
2.RBCs in blood
Diffusion
1. Simple :
Gases-O2, CO2
Lipid Soluble Substances Active Transport
2.Facilitated : Glucose 1. Primary : Na+ /K+ ATPase
Mechanisms 2. Secandary :
Na+/glucose (SGLT)
Na+ /bile salt co-transporters
Exocytosis
Nerve Impulse Endocytosis
Transmission Osmosis
Phagocytocis
Pinocytosis
1) Diffusion
Net flux of
-solute particles
-from areas of high
-to areas of low concentrations
Types of diffusion
a. Simple Diffusion
b. Facilitated Diffusion
c. Nonionic diffusion
HA H+ + A-
H+ X
A- X
Exocytosis Endocytosis
3) Filtration
Diffusion of solvent from a region of low solute [conc.]/ low osmotic pressure to a region of high
solute [conc.]/ high osmotic pressure across a semi permeable membrane.
Pressure necessary to be applied to a solution to prevent the inward flow of solvent across a
semipermeable membrane by osmosis
Depends on no. of dissolved particles
Osmole = amount of solute that dissociates in solution to form 1 mole
Glucose 1 mol/L =1osmol / L
NaCl 1mol/L = 2 osmol/L
Tonicity
Osmolality of a solution relative to plasma
Isotonic - same as plasma
{0.9% Saline, 5% Dextrose, king coconut water}
Hypertonic - greater than plasma
Hypotonic - lesser than plasma
2. Assuming complete dissociation into Na+ & Cl- a solution of 5.85 g NaCl in litre of water
a) will have an osmolality of 0.1 osmole
b) will contain 0.1 mole of Na+ per litre
c) would be more concentrated than ECF
d) would have higher H+ concentration than ECF
e) will cause hemolysis of a normal red cells added to the solution in a few seconds
This suggests capillary walls acts like semi permeable membranes. Impermeable to colloids.
So, COP develops. COP due to plasma colloids is called the oncotic pressure.
Capillary permeability
Available surface area
Hydrostatic P =
∆P = ↓(11-9) mmHg
= ↓ 2 mmHg
Oedema
Generalized Localized
1. ↑ venous pressure 1. ↑ venous pressure in local
In right heart failure obstruction
↑ R atrial pressure. Late pregnancy (IVC)
2. Capillary filtration
a) decreases if interstitial oncotic pressure increases
b) is normally smaller in magnitude than capillary reabsorption
c) is the main mechanism of cerebro-spinal fluid formation
d) will decrease if the capillary hydrostatic pressure decreases
e) is increased in protein malnutrition
Neurones Muscles
Neurones
Structural Classification
1. Unipolar
2. Bipolar – retina
3. Pseudounipolar – Sensory
neurone
4. Multipolar – motor
Functional components of a
neurone
A receptor zone - Dendrites or
the cell body integration of
multiple local potentials
generated by synaptic
connections
Cell body
Generator of propagated
impulse - Initial segment or the
1st node of Ranvier
Pathway to transmit the
impulse - axon
Nerve endings to release the
neurotransmitters – axon
terminal
Glial cells
Microglia – Derived from macrophages Removes debris resulting from infection + diseases
Macroglia
1. Oligodendrocytes – Forms myelin sheath in CNS. A single cell can form myelin sheaths of multiple neurones
by emitting branches.
2. Schwann cells – forms myelin sheath in PNS. A single cell contributes only to one neurone.
3. Astrocytes
a. Only found in blood brain barrier
b. Trophic to nerves (produce neutrophins)
c. Take up K+ and neurotransmitters
Macroglia also secrete nerve growth factors.
Multiple sclerosis – Myelin destruction in CNS
Guillain barre syndrome – Myelin destruction in PNS
Membrane potential is the electrical potential energy difference between the inside and outside of a cell
Resting membrane potential (RMP) is the membrane potential when not transmitting an impulse
In neurons its value is usually -70 mV (inside the cell membrane compared to outside)
– Due to different concentrations of ions across the membrane
– Different permeability for different ions
The bulk solution inside and outside is electrically neutral
The potential difference exists only across the cell membrane
Main determinant of RMP is the movement of K+ through K+ leak channels
Therefore, changes in extracellular [K+] have major effects on RMP
Negativity inside is maintained by Na+/K+ ATPase pump Ion concentrations when R.M.P is -70 mV
– An electrogenic pump
– Inhibited by Ouabain and Digitalis Extracellular Intracellular
At rest the membrane is impermeable to proteins Na - 150
+ Na+ - 15
Due to leak channels, the membrane is K+ - 5.5 K+ - 150
– Slightly permeable to Na+ Cl- - 125 Cl- - 9
– Highly permeable to K+ (impermeable
to proteins)
Membrane potential is basically determined by the highly permiable K+ ions.
– Freely permeable to Cl- (No net movement as
Electrical responses of nerve to a
its equilibrium potential is -70 mV)
stimulus
K+ diffuses “out” of the cell along its concentration
gradient Propagated action Local, non-propagated
+
Na diffuses “in” to the cell along its concentration potential potential
gradient
Receptor potential
If ion leakage across the membrane continues unopposed, it would proceed
until concentration gradients are balanced by the electrical gradient
But, Na+/K+ ATPase pumps 3Na+ out & brings 2K+ in, per turn End plate potential
(Na+/K+ ATPase pump act as an electrogenic pump because it generates
electronegative potential Synaptic potential
This maintains the concentration gradients of K+ and Na+
(but contribution of Na+/K+ ATPase pump for RMP is a very small value of -5mV)
Therefore, the membrane potential is maintained at RMP
Changes in membrane potential that reach the threshold level can be propagated along a nerve fibre
Threshold is usually 15 to 20 mV above RMP (about -55 mV)
Depolarization leads to ; Local non-propagated / Synaptic / Generator / Electrogenic / Propagated action potentials.
Action Potential
B. Repolarization
Resistance for Na+ influx
Hyperpolarization
increases as membrane
potential becomes more
positive, reversing the
electrical gradient for Na+.
Voltage gated Na+ channels
close 1/104 s after they open.
Na+ INFLUX stops.
When MP rises from -70mV to 0mV, voltage gated K+ channels open.
– They are slow to open and slow to close.
Opening of K+ channels coincide with the closure of Na+ channels.
Resulting K+ EFFLUX makes the membrane potential negative again.
After depolarization, K+ voltage gated channels close via a negative feedback mechanism
C. Hyperpolarization
K+ efflux lasts longer than needed to restore membrane potential to RMP.
Therefore, the membrane is hyperpolarized.
When K+ channels close, K+ EFFLUX stops.
Membrane stops becoming more negative.
RMP is restored. But a large amount of Na+ remains within the cell & a large amount of K+ has escaped.
Na+ / K+ ATPase corrects the ionic distribution.
Absolute Relative
• Time period from reaching the firing level to the first • Time period from the last 2/3 of repolarization to
1/3 of repolarization the beginning of after-depolarization
• Does not respond to any stimuli • Only suprathreshold stimuli can evoke an AP
1. In a nerve cell
a) K+ efflux contributes to repolarization.
b) Initial rapid depolarization is due to opening of Na+ channels.
c) High Na+ concentration in ECF increases the magnitude of action potential.
d) Conductance of fibre type A is faster than type C.
e) Slightly higher cation concentration in the interstitial space affects the RMP of the cell.
Longer the time of application of the stimulus Smaller the required minimum strength of the stimulus
Shorter the time of application of the stimulus Greater the required minimum strength of the stimulus
Very slowly increasing current No AP
o Slow opening of voltage gated Na+ channels and slow opening of voltage gated K+ channels coincide.
Na+ influx is balanced by K+ efflux.
Clinical relevance
Demyelination (Eg: Multiple sclerosis) – Conduction velocity is decreased
Axonopathy – Reduction of amplitude. Later the velocity also reduced.
Injury to nerves – PNS likely to regenerate, CNS mostly degenerated.
Local anaesthesia – Blocks only C fibres
Neutrophins
Nerve growth factor (NGF)
Necessary for the growth & maintenance of sympathetic and other sensory neurones
Reduce apoptosis of neurons
Produced in structures innervated by them. Eg: muscles. In the CNS, produced by astrocytes
Transported retrogradely to the nerve cell body
Local potentials
Can be subdivided into,
1. Receptor potential
2. End-plate potential
3. Synaptic potential
When stimulus act on the unmyelinated nerve end or receptor changes occur in
receptor membrane
Opening of Na+/Ca2+ channels, inhibition of K+ channels or inhibition of Na+/K+
ATPase pump leads to produce non-propagated receptor potential
When this receptor potential reaches the threshold, An AP is generated in the 1st
node of Ranvier
Ach binds to the muscle type nicotinic-cholinergic receptors in the motor end
Local plate
This opens a gate within the ligand gated channels which are equally permeable
Potentials to Na+ & K+
Depolarization & causes a local graded potential on the end plate
Synaptic potential
Synaptic Potentials
Single stimulus does not produce an action potential in postsynaptic membrane, instead it produces a transient
depolarization or transient hyperpolarization
1. Summation
Summation of synaptic
potentials
Spatial Temporal
Many presynaptic terminals are stimulated at the same Successive discharges from a single presynaptic
time. terminal,
The depolarization induced at several points on the neuron If they occur rapidly enough, can add to one-
spread to trigger zone before decaying out another and summate
The potentials summate to elicit an AP
4. Inhibition
a. Presynaptic b. Postsynaptic
Inhibitory interneuron-GABA
Motor neurone
Synaptic Plasticity
Changes in the function of synapses due to past experience
Basis of learning and memory
Ex : Post tetanic potentiation, Habituation, Sensitisation, Long term potentiation, Long term depression.
1. T/F
a) Decrease in ECF [K+] hyperpolarize the nerve axons
b) Chronaxie is a time measurement
c) Rheobase the minimum strength of a stimulus to initiate an action potential
d) A slight increase in extracellular Na+ is enough to depolarize the membrane
e) Increased extra cellular Ca2+ increases the excitability of the nerve membrane
4. Saltatory conduction
a) Occurs only in myelinated fibres.
b) Does not depend on depolarization of the nerve cell membrane.
c) Velocity decreases as the temperature rises.
d) Transmits impulses with a velocity proportionate to fibre diameter.
e) Produces a great voltage change in the membrane than in non-saltatory conduction
Acetylcholine receptors
Z lines move closer. ‘A’ band remain constant. All others get shorter.
Functional unit of muscle – motor unit (=single motor neurone and all the muscle fibers innervated by it)
Neurone All the muscle fibers in one motor unit are innervated by one
motor neuron.
Relaxation
Ca2+ pumped in to SR by Ca2+ - Mg2+ ATPase pump (SERCA) (this pump needs ATP, therefore ATP dependent
process)
Release of Ca2+ from troponin C
Interaction between actin-myosin stops.
If Ca2+ transport into reticulum is inhibited, relaxation does not occur, resulting in sustained contraction called
contracture.
Electrical response
Mechanical response-
Starts 2ms after the onset of depolarization
before repolarization is complete
Muscle twitch – a single action potential causes a brief contraction followed by relaxation
Summation of Contraction
a) Tetanus - when there are repeated stimulations with a high frequency, individual responses fuse into a
single continuous contraction.
b) Treppe (Staircase phenomenon) – Maximal stimuli given at a frequency just below the tetanizing frequency
Increase in tension develop in each twitch. After a few contractions uniform tension per contraction is
reached (due to progressive increase in Ca2+ in the sarcoplasm)
E.g.- when muscle begins to contract after a long period of rest initial strength is little, after strength of
contraction increase to a plateau.
Tension
Time
In isometric contraction,
Tension α cross linkages between actin & myosin
Too shortened – distance thin filaments can more reduced
Too stretched – overlap of thin & 2 thick filaments reduced
Results of denervation
Muscle atrophy
Fibrillation – Fine irregular contractions of individual fibers, cannot be seen by naked eye but can be
observed by electromyography
Denervation hypersensitivity – due to increased sensitivity to circulating Ach
Fasciculations – Jerky, visible contractions of groups of muscle fibers that occur as a result of pathological discharge
of spinal motor neurones
CARDIAC MUSCLE
Visceral smooth muscle/ Single unit smooth muscles Multi-unit smooth muscle
Tunica media of blood vessels has both visceral and multi-unit smooth muscle types.
Lacks visible cross striations as actin and myosin filaments are not arranged in regular arrays.
Troponin is absent, but tropomyosin is present
Poorly developed sarcoplasmic reticulum
Few mitochondria
Depends mostly on glycolysis
Spikes
Ionic fluxes
Binding of Ach. muscarinic receptor
Increased influx of Ca2+ into cells from ECF through voltage gated Ca2+ channels
Activation of calmodulin dependent myosin light chain kinase
Phosphorylation of myosin light chains
Binding of myosin to actin and increased myosin ATPase activity
Contraction
Dephosphorylation of myosin by various phosphatases
Relaxation or sustained contraction due to latch bridge mechanism
E.g.: - vascular smooth muscles
Varicosities - Dilated areas of nerve fibers innervating smooth muscles that release neurotransmitters.
Dephosphorylated myosin cross-bridges remain attached to actin for some time after the cytoplasmic Ca2+
concentration falls. This produces sustained contraction with little expenditure of energy.
Important in vascular smooth muscle.
Action of catecholamines and acetylcholine on smooth muscle (Reverse happens in some smooth
muscles.)
Catecholamines Acetylcholine
Membrane potential become more negative Membrane potential becomes less negative
Spikes decrease in frequency Spikes more frequent
Muscle relaxes Muscle tone increases
α action – increased Ca2+ efflux from cells By phospholipase C and IP3, increase intracellular Ca2+
β action – via cAMP increased intracellular binding of Ca2+ concentration
Function of the nerve supply to smooth muscle is not to initiate activity but to modify it.
Mysthenia gravis – Autoimmune disorder that destroys muscle type nicotinic Ach receptors. What happens?
Lambert-Eaton syndrome – Autoimmune disease. Patients develop antibodies against voltage gated Ca2+
channels in the nerve endings.
To head arise in superior, middle and stellate To Head - cranial nerves III, VII, IX
ganglion & travel with blood vessels
To Thorax and upper abdomen - Cranial nerve X
Parts of uterus and male genital tract from
To sacral region S2-S4 spinal nerves
collateral ganglia
Short preganglionic and long postganglionic fibers Long preganglionic and short postganglionic fibers
Ganglion in sympathetic chain and superior, middle Near the viscera/ inside the viscera
& stellate ganglion
ACETYLCOLINE NOADRENALINE
Effects are localized and short term Spread further than Ach more prolonged &
(Acetylcholinesterase) diffuse action
Receptors Receptors
Nicotinic Alpha receptors-α1, α2
muscarinic Beta receptors-β1, β2
Receptors
Most of the organs are supplied by both divisions of The ANS but few organs are supplied only by
one division of ANS
❖ Exclusively by sympathetic-blood vessels, sweat glands, pilomotor muscles
Parasympathetic action
Acetylcholine - Muscarinic receptor
01. Decrease heart rate
02. Bronchoconstriction and increase
mucous secretion
03. Increase motility and secretion and decrease sphincter tone in GIT
04. Increase gastric acid secretion (M3)
Sympathetic action
Norepinephrine α1 1. Vasoconstriction.
(More affinity to α ®) 2. Inhibit mucous secretion in respiratory tract.
Epinephrine β1 1. Increase heart rate.
(More affinity to β ®) 2. Increase myocardial contractility
β2 1. Bronchodilation
2. Increase mucous secretion in respiratory tract.
3. Vasodilation in liver and skeletal muscles.
2. Submucosal plexus
• Located between circular & luminal mucosa
• Regulate the blood flow & epithelial cell functions
Although the enteric NS can function autonomously, normal digestive function often requires
communication between the CNS & the enteric NS
Borders
Anterior-sternum
Posterior-12 thoracic vertebrae &
intervening intervertebral discs
On each side- 12 ribs with their
costal cartilages+ intercostal muscles
Shape
Adult
Transverse section - kidney shape
Transverse diameter> antero-posterior diameter
Ribs - oblique ribs
Thoracic & abdominal respiration
Infant
Transverse section – circular
Transverse diameter< antero-posterior diameter
Ribs - horizontal ribs
Purely abdominal respiration
Typical rib
Anterior end
concave depression
attach with costal
cartilages
Posterior end
Head – 2 facets & a crest in between
Upper facet – body of the higher vertebra (MCQ point)
Crest – intra articular ligament
Lower facet – body of the numerically corresponding vertebra
Neck – 2 surfaces
Anterior – smooth related to costal pleura
Posterior – rough inferior costotransverse ligament
Superior border or crest superior costotransverse ligament
Atypical ribs
1st rib
Shortest, broadest, most curved, flattest
Shaft has no twist
Flattened from above downwards
Upper surface – 2 shallow grooves for the subclavian artery and vein.
Separated by scalene tubercle near the inner border
Lower surface – no subcostal groove
Superior surface
In between insertion of scalenus anterior to
the scalene tubercle
Subclavian vein - anteriorly
Subclavian artery & the lowest trunk of
the brachial plexus - posteriorly
Medially
Apex of the lung & cervical pleura
Suprapleural membrane is attached
Neck
From Medial to Lateral
S – Sympathetic trunk (Stellate ganglion)
V – 1st posterior intercostal Vein
A – Superior intercostal Artery
N – T1 Nerve (Larger portion of T1 nerve to form inferior trunk of brachial plexus)
Pressure on
1) Lowest trunk of brachial plexus (T1) -
Parasthesia along the ulnar border of forearm -
Wasting of intrinsic muscles of the hand
B) COSTAL CARTILAGES
Hyaline cartilage
In old age – progressive ossification
Add resilience to the thoracic cage - Protects sternum & ribs
C) STERNUM
3 parts- manubrium, body, xiphoid process
Clavicle
Jugular Notch
Manubriosternal joint
4 © 2018 A/L Repeat Campaign
Manubrium opposite toT3/T4
Body – opposite to T5 - T8
4 sternebrae - fused between puberty & 25 years Lateral border – notched
Articulate with part of 2nd, 3rd- 7th costal cartilages
Lower end – secondary cartilaginous xiphisternal joint
Xiphoid - Cartilage
May ossify at adult life (40)
Overlies the Epigastric fossa
Ligaments
1. capsular
2. Superior, Inferior, lateral costotransverse
RESPIRATORY MOVEMENTS
Antero-posterior diameter
Mainly ribs 2-6 (partly 7-10)
Pump handle movement
Forward movement of manubrio-sternum
Axis of rotation – costovertebral joints
-Costotransverse joints
Intercostal spaces
Intercostal muscles
3 layers – external intercostals Subcostalis
Internal intercostals
Tranversus thoracis Sternocostalis
Innermost intercostals
CLINICALS
Pus from the vertebral column tends to track around the thorax along the course of the
neurovascular bundle,
Dorsal primary ramus
2 cutaneous branches
Intercostal vein
Anterior intercostal veins
- Upper 6 spaces internal thoracic vein
- Lower 3 spaces musculophrenic vein
Tracheobronchial nodes
Lower 4 spaces upper spaces
Brachiocephalic nodes
Cisterna chyli Right Left
Bronchomediastinal trunk right lymphatic duct thoracic duct
Right Left
Neurovascular bundle
From above downwards - V A N
AZYGOS VEIN
Formation
Formed by right subcostal vein, ascending lumbar vein + lumber azygos.
CLINICALS
SVC obstruction – azygos vein transmits blood from the upper half of the body to
unobstructed part of the SVC or to the IVC.
Thoracoepigastric vein (Superficial vein formed by anastomoses between lateral
thoracic vein of axillary vein and superficial epigastric vein of greater saphenous
vein) opens up.
HEMIAZYGOS VEIN
Formed by the left ascending lumbar & left subcostal
9-11 left posterior intercostal veins
DIAPHRAGM
- dome shaped fibromuscular septum
- partition between the thorax & abdomen
- chief muscle of respiration
- 2 parts: peripheral muscular
Central tendon (aponeurosis)
- Normal - Right dome upper border of the 5th rib
- left dome lower border of the 5th rib
- In forced expiration - Right dome 4th intercostal space
- Left dome 5th rib
- In forced inspiration – Right dome 6th rib
Muscular fibers (origin)
- Sternal – 2 small slips from the back of the xiphisternum
- Costal – inner aspect of lower 6 ribs & costal cartilages
Median arcuate ligament: medial margins of 2 cruratendinous arch in front of the Aorta
Medial arcuate ligament: thickening of psoas fascia
Medially- side of body of L1
Laterally- transverse process of L1
Nerve supply
Entire motor supply: phrenic nerves (C3, C4, C5)
Sensory: central- phrenic
Peripheral (including crura) - lower 6 intercostal nerves
Blood supply
Superior phrenic
Inferior phrenic
Muscular phrenic
Lower intercostal arteries
CLINICAL
*paradoxical movements
*referred pain
Position
- Highest in supine position
- Lowest while sitting
- Intermediate while standing
CLINICALS
Diaphragmatic hernia
Congenital hernia– unusual to occur
1. Anteriorly – through foramen of Morgagni (retrosternal); between xiphoid & costal
margin
2. Posteriorly – through the foramen of Bochdalek (pleuroperitoneal canals) - posterolateral
hernia
3. through a deficiency of the whole central tendon (central hernia)
4. congenitally large oesophageal hiatus
Irritation of diaphragm can cause referred pain in the shoulder tip (via root values C3, C4 and C5
Pulmonary/Visceral Pleura
▪ From splanchnopleuric mesoderm.
▪ Firmly adherent to the lung.
▪ Covers the surfaces & fissures of lungs except along the pulmonary ligament & hilum of
the lung.
▪ Pain insensitive – autonomic supply (T2-T5 sympathetic,
Vagus parasympathetic)
▪ Supplied by – bronchial arteries
▪ Drained by – Bronchial veins
▪ Lymphatic drainage - Broncho pulmonary lymph nodes/tracheobronchial lymph nodes
1. Costomediastinal recess
▪ Between costal & mediastinal pleurae.
▪ obvious in regions of cardiac notch of the
Left lung.
▪ Filled by anterior margins of the lungs
even during quiet breathing.
2. Costodiaphragmatic Recess
▪ Vertically 5 cm.
▪ extends from 8-10 ribs along the
midaxillary line.
▪ between costal & diaphragmatic pleura.
3. Pulmonary Ligament
➢ Parietal Pleura extend downwards beyond the
root.
➢ Provide a dead space for pulmonary veins and lung roots.
Root of lung-structures that connect lung to
mediastinum.
Hilum-site where structures enter & leave the lung
Clinicals
➢ Paracentesis thoracis
Tube thoracostomy-chest tube insertion into plural cavity to drain air, blood, bile,
pus or other fluids.
Ex: pneumothorax
Done at safe triangle
Boundaries of safe triangle:
1…………………………………………..........................……..
…………………….……………………………………………………
2…………………………………………………………………………
..…………………………………………………………………………
3………..………………………………………………………………
………………..………………………………………………………..
Needle/Syringe insertion
During any of these procedure needle or tube pass above upper border of the rib. (lower part of the
intercostal space)
Why?
……………………………………………………………………………………………………………………………………………..……………
………………………………………………………………………………………………………………………………………………..…………
Referred pain
Diaphragmatic pleura
Fissures
Oblique fissure – Cuts into whole thickness of lung, except at hilum
Due to; lower lobe more posterior than others
o 2cm lateral to the T3 spine
o 5th rib in the mid axillary line
o 6th costal cartilage 3 inches (7.5cm) from midline
OR
Full abduction of the shoulder
o Oblique fissure corresponds to the position of the medial border of the scapula
o The right oblique fissure (T4 Inferior border) is at a lower level than the left oblique fissure
(T3 spinous process) posteriorly
Lingula – Tongue shaped projection of left lung below the cardiac notch.
Contents
1. Principal bronchus on the left, eparterial and hyparterial bronchi on the right.
2. One pulmonary artery.
3. Two pulmonary veins; superior and inferior.
4. Bronchial arteries; one on the right and two on the left.
5. Bronchial veins.
6. Anterior and posterior pulmonary plexuses of nerves.
7. Lymphatics of the lungs.
8. Bronchopulmonary lymph nodes.
9. Areolar tissue.
Anterior
- phrenic nerve
- pericardiophrenic vessels on both sides
- anterior pulmonary plexuses
*on the right – svc, right atrium
Posterior
- Vagus nerve
- posterior pulmonary plexus on both sides
*on the left – descending thoracic aorta
Superior
On the right – terminal part of the azygos vein
On the left – arch of aorta
Inferior
Pulmonary ligament
Hilum
Lies opposite the bodies of T5, T6, T7 vertebrae
Behind 3rd and 4th costal cartilages
Contents;
▪ bronchial vessels
A – Right 1, left 2
V
▪ lymphatics
▪ bronchopulmonary lymph nodes
Pulmonary nodes
Bronchopulmonary nodes
Paratracheal nodes
Clinicals
Auscultation of lung
1. Upper lobe – 4th rib on both sides
2. Lower lobe – back
3. Middle lobe – between 4th & 6th ribs on both sides
Secondary/lobar bronchi
One for each lung lobe (2 for left & 3 for right)
Tertiary /segmental bronchi
10 for each side one for each segment
Divide repeatedly
Terminal bronchioles
Respiratory bronchioles
Alveolar ducts
Components of pulmonary unit
Atria
Air saccules
Alveoli
Bronchi Eparterial
Right principal bronchus – divides before enter lungs
Hyparterial
➢ Wider
➢ Shorter
➢ Nearly 5 cm
➢ Downwards & outwards below the arch of aorta
➢ Pulmonary artery anteriorly & above
➢ Esophagus posteriorly
➢ Narrower, longer, more oblique
➢ Angle with tracheal bifurcation - 45°
Bronchopulmonary segments
Definition - a segment of lung supplied by a single segmental (IIIry) bronchus
Features
• 10 in each lung.
• Independent respiratory unit. (surgical, functional, structural)
• Each segment has its own separate artery.
• Veins lie in the intersegmental planes, can isolate a particular segment along the veins
• Bronchopulmonary segment is not a bronchovascular segment (as it doesn’t have its
own vein).
● Pyramidal, apex directs towards root.
Clinicals
✓ Bronchoscopy
✓ Widening and distortion of the angle between the primary bronchi
- Carina
- Carcinoma of tracheobronchial lymph nodes around the bifurcation of the trachea.
- Bronchial infections are restricted to specific bronchopulmonary segment.
Trachea
Pericardium
Transverse sinus
• Horizontal gap
• Lies between arterial & venous tubes
• Bounded
o Anteriorly → arterial tube
o Posteriorly → superior vena cava
o Inferiorly → left atrium
• When the pericardium is opened anteriorly during
a surgery, a finger placed in the transverse sinus
separates arteries from veins.
• A hand placed under the apex and moved
superiorly, slips into the oblique sinus.
Oblique sinus
• A recess between left atrium and parietal
pericardium
• Bounded,
o Anteriorly → left atrium
o Posteriorly → parietal pericardium
o On right & left → reflections of the
pericardium
Clinical
Pericardial effusion (Cardiac tamponade)
Heart
Position
❖ behind the body of the
sternum,
❖ In the middle mediastinum,
❖ In front of the T5-T8
vertebral bodies,
❖ 2/3 of the heart - to the left
of the midline
External features
a) Apex
Eentirely by left ventricle
b) Surfaces
• Anterior / sternocostal surface
o Mainly right ventricle & right atrium (left
ventricle, left auricle)
o Area of superficial cardiac dullness – A
part of the anterior surface that is not
covered by the lungs
• Posterior/base
o Left atrium (mainly) & small part of
right atrium
• Inferior/ diaphragmatic
o Right 1/3 of right ventricle, left 2/3 of left ventricle, on central tendon of diaphragm
• Left surface →
• Mainly left ventricle, Upper end by left auricle
c) Borders
• Right → right atrium only (acute border)
• Left → left ventricle, partly by left auricle (obtuse border)
Grooves
Surface marking
1) 2nd left costal cartilage
2) 3rd right costal cartilage 0.5 inch from sternal angle
th
3) 6 right costal cartilage
4) 5th left intercostal space – 3.5 inches (9cm) from midline
Chambers of Heart
Left atrium
• Posterior surface forms the anterior wall of the oblique sinus
• Greater part of interior is smooth walled (derived from absorbed pulmonary veins)
• Fossa lunata on the septal wall
• Two pairs of pulmonary veins open on each side of posterior wall
• Musculi pectinati are present only in auricle (derived from primitive atrial chamber)
Left ventricle
• The interior has 02 parts
o Upper smooth part (aortic vestibule) → gives origin to ascending aorta (Derived from mid
part of bulbus cordis)
o Lower rough part with trabeculae carneae (Derived from primitive ventricle)
• Contains 02 well developed papillary muscles (anterior & posterior)
• 2 orifices → Left atrioventricular orifice/bicuspid (mitral) valve
Aortic orifice/semilunar valve
• Interventricular septum → Upper part is thin & membranous
Lower part is thick and muscular
• The cavity of the left ventricle is circular in cross section
1) Atrioventricular valves
Tricuspid valve - between right atrium and right ventricle
Bicuspid valve/ Mitral valve - between left atrium and left ventricle
The mitral valve is more prone to valvular disease
Structure
• Components
2) Semilunar valves
Aortic valve - between left ventricle and ascending aorta
Pulmonary valve - between right ventricle and pulmonary trunk
• Valves prevent back flow of blood – Chordae tendinae prevent eversion of cusps
• Normal heart sounds are produced by closure of heart valves
Auscultation
Conducting system
SA node
• “Pacemaker” of the heart, Horse shoe
shaped
• Situated at the atrio-caval junction in the
upper part of the sulcus terminalis
• Supplied by right coronary artery (60%)
AV node
• Situated in lower posterior part of interatrial
septum just above the opening of coronary sinus
AV bundle of His → Only muscular connection between atrial and ventricular musculatures
Winds around the inferior border of the heart Right marginal artery
Distribution
➢ Right atrium
➢ Right ventricle except a small area near the anterior IV groove.
➢ Left ventricle near the posterior ventricular groove.
Distribution
➢ Left atrium
➢ Left ventricle except for a small area
near posterior IV grove.
➢ Right ventricle – small area near
anterior IV groove
➢ A part of the left bundle branch
➢ Anterior 2/3 of IV septum.
Cardiac dominance
• The artery giving the posterior interventicular branch is the dominant artery.
• In 90% cases, right coronary artery is the dominant artery.
• Rest 10%, is left dominant.
1. Coronary sinus
Largest vein of the heart
Situated In left posterior coronary sulcus
Opens into posterior wall of right atrium
It receives;
Accompanies
➢ Great cardiac vein - First anterior IV artery; then left coronary artery
➢ Middle cardiac vein - Posterior IV artery
➢ Small cardiac vein - Right coronary artery
(Right marginal vein may drain into this)
➢ Posterior vein of left ventricle
➢ Right marginal vein - Marginal artery of right coronary artery
➢ Oblique vein of left atrium (derived from left common cardinal vein)
Cardiothoracic ratio
• It is a useful index of cardiac size evaluation, and a value of 50% is generally considered to
indicate the upper limit of normal.
• It is measured by taking the sum of the measurements from the midline to the furthest point
on the right side of the heart & from the midline to the furthest point on the left side of the
heart, and dividing by the transverse diameter of the thoracic wall.
Boundaries of mediastinum.
Anterior – Sternum
Posterior – 12 thoracic vertebrae
Superior – Superior thoracic aperture
Inferior – Inferior thoracic aperture
On each side - mediastinal pleurae
Divisions
Imaginary plane through sternal angle of Louis &
lower border of T4 divides mediastinum into
Mediastinum
Plane passes through the bifurcation of trachea, concavity of aortic arch, just above the
pulmonary trunk.
On the plane
-azygos vein enters the superior vena cava
-thoracic duct reaches left side of esophagus in its passage upwards
-ligamentum arteriosum with left recurrent laryngeal nerve recurving below it
-tracheobronchial lymph nodes
-superficial & deep cardiac plexus
Superior mediastinum
Boundaries
- anterior - manubrium sterni
- posterior- upper 4 thoracic vertebrae (Much longer)
- superior- superior thoracic aperture
- inferior- imaginary plane through sternal angle and lower border of T4
- on each side- mediastinal pleura
CLINICALS
Inferior mediastinum
- Right + left brachiocephalic vein = SVC (behind the sternal end of the right fist
costal cartilage)
- *no valves
- Tributaries:
Azygos - second right costal cartilage
CLINICALS
Obstruction of SVC
Above azygos opening – through azygos
Below azygos opening – through IVC
Aorta
1.Ascending aorta
Lower border of 3rd costal cartilage
Forwards, upwards to the right
Ends at sternal angle (upper border of 2nd right costal cartilage)
Branches: right & left coronary arteries Originates from the aortic sinuses which are
above the aortic cusps
2.Arch of aorta
nd
Begins at upper border of right 2 sternochondral joint
Upwards, backwards to the left across the bifurcation of trachea
Downwards behind left bronchus- reach the body of T4 just left of midline
Arches over root of left lung(Left primary bronchus) and pulmonary trunk bifurcation
Ends at the sternal angle
The convexity reaches as high as midpoint of manubrium
Relations:
Anteriorly to the left
Left phrenic nerve, cardiac nerves, vagus
Left superior intercostals vein-deep to phrenic nerve & superficial to vagus
Left lung & pleura
Remains of thymus
Superiorly
- 3 branches of aorta – brachiocephalic, left common carotid, left subclavian
-All of these crossed by the left brachiocephalic vein close to origin
Branches
O 9 pairs of posterior intercostals arteries
o Pair of subcostal artery
o 2 left bronchial arteries
o Oesophageal branches
o Pericardial branches
o Mediastinal branches
o Superior phrenic arteries
CLINICALS
Aortic aneurysm
Coarctation of aorta
Oesophagus
25cm long muscular tube
Begins in midline – C6 – lower border of the cricoid cartilage --->Inclines slightly to
left of midline--->enters thoracic inlet--->superior mediastinum--->at level of T5
returns to midline--->at T7 deviates to left--->curves forward.
{Curvatures -2 side to side curvatures (to the left)
-anteroposterior curvature corresponding to the curvature of
cervicothoracic spine}
Traverses the superior & posterior mediastina.
Pierces the diaphragm – T10
Ends at the cardiac orifice of the stomach (T11)
Relations:
Cervical
Anterior – trachea, thyroid gland
Posterior – C6,C7,prevertebral fascia
On each side- Common carotid arteries
Recurrent laryngeal nerves
Left subclavian artery
Terminal part of thoracic duct
Thoracic
Anterior : -Trachea
-Just below bifurcation of trachea crossed anteriorly by Left bronchus
& Right Pulmonary artery
-Pericardium with left atrium
-Diaphragm
Posterior–
Vertebral column
Thoracic duct(first on its right, At T5 crosses to left behind oesophagus)
More
posterior
Azygos vein &its tributaries
plane Right posterior intercostal arteries
Level of T7 – descending thoracic aorta pass behind to it
To the right –
o right lung & pleura
o Azygos vein – arches over Right primary bronchus
o Right vagus
To the left
o in the superior mediastinum,
o Left subclavian artery
o Aortic arch
o Left recurrent laryngeal nerve
o Thoracic duct
o Left pleura & lung
-In the posterior mediastinum
Descending thoracic aorta
The left lung & pleura
Blood supply
Arterial supply:
Cervical - inferior thyroid arteries
Thoracic - oesophageal branches of aorta
Abdominal - oesophageal branches of left gastric artery
Venous drainage:
Cervical – inf. thyroid vein/brachiocephalic veins
Thoracic – azygos vein
Abdominal – partly azygos, partly left gastric (Portosystemic anastomosis)
Lymphatic drainage:
Periesophageal lymphatic plexus
Cervical – deep cervical nodes supraclavicular
Thoracic – post. mediastinal nodes & tracheobronchial nodes
Abdominal – left gastric nodes & coeliac nodes
Nerve supply:
Parasympathetic - below the root of the lung vagi form a plexus on it
Sympathetic – middle cervical & thoracic ganglia
CLINICALS
Barium swallow
Indentations – aortic arch, left bronchus, Left atrium
Oesophageal varices in portal hypertension
Left atrial enlargement – mitral stenosis
Achalasia cardia – lower esophageal sphincter fails to open up during swallowing
Dysphagia -difficulty in swallowing (can be caused by mediastinal syndrome)
Thoracic duct
45cm long (L2 to root of neck)
Beaded appearance - presence of valves
Continuation of cisterna chyli
Ascends through the aortic opening of the diaphragm (T12)
Runs through posterior mediastinum behind oesophagus in front of vertebral bodies
Crosses from right to left (T5)
Azygous Aorta
Cardiac plexus
Right phrenic nerve- related medially with venous structures (lateral to right
brachiocephalic vein, svc, pericardium over right atrium, IVC--> passing through
central tendon)
Left phrenic nerve- related medially to arterial structures. (Lateral to
Left common carotid, left subclavian arteries, lateral to superior intercostal vein-->in
front of vagus-->laterally down the pericardium over left ventricle -->towards apex of
the heart-->piercing left muscular part of the diaphragm.)
Vagus nerves
Lymphocytes
T cells
4. Memory T cells
B cells
Adult
thymus
Structure:-
✓ Lobulated.
✓ Invested by loose collagenous capsule.
✓ Interlobular septae arise from the capsule.
✓ No afferent lymphatics.
✓ Outer cortex – deeply basophilic
✓ Inner medulla – eosinophilic
✓ Immature T lymphocytes enter thymus through Post capillary venules
✓ Thymic epithelium forms blood thymic barrier.
✓ Cortex
- Highly cellular. T cells present.(maturing thymocytes)
- they are supported on a cytoreticulum formed by thymic
epithelial cells, they are APCs.
- Mitotic figures present.
- Undergo further maturation as they move deeper. (Cortex
to medulla)
✓ Medulla
- Dominant feature – Epithelial component
- Hassall’s corpuscles present
- contain dendritic cells
✓ Hassall’s corpuscles
- Lamellated.
- 1st appear in fetal life.
- Increase in number and size with age.
- Formed from degenerating keratinized epithelial cells.
- Unique to medulla
• At the end of their journey through thymus mature T cells enter blood vessels and
lymphatics. Post capillary venules which are found in corticomedullary junction allow
their passage into and out of the thymus.
• Thymus secretes hormones throughout life.(Thymosine)
Structure:-
✓ Bean shaped.
✓ Surrounded by collagenous capsule.
✓ Trabeculae extend from the capsule
✓ Afferent lymphatics pierce the capsule.
✓ Cortex
- Highly cellular/densely staining
- Densely packed with lymphocytes
- Has proliferating B lymphocytes, helper T cells follicular dendritic cells
and macrophages
- Lymphoid follicles are present in the superficial part
- Deep cortex / Paracortex is devoid of lymphoid follicles
(no much lymphoid nodules but has lymphoid tissue rich in T cells)
- Cortical sinuses are found in the cortical cell mass
✓ Medulla
- Less cellular.
- Pale staining.
- Medullary cords are extensions of cortical cell mass.
- Medullary sinuses converge upon hilum.
✓ All the sinuses kept patent by a skeleton of reticulin fibers
✓ Blood supply
- High endothelial venules are the site of entry of most circulating
lymphocytes in to the node
- Are specialized post capillary venules which are located in paracortex
- HEV lined by tall cuboidal cells
✓ 3 functional compartments are found within a node
a) Lymphatic sinuses
b) Blood vessels
c) Interstitial compartment
PALATINE TONSIL
• Organized lymphoid tissue is found in all parts of GI tract except in the stomach.
• Largest aggregates are Peyer’s patches of SI. (non encapsulated)
• Peyer’s patches are least numerous in duodenum & most prominent in terminal ileum.
(in both mucosa and submucosa)
• Epithelium overlying is specialized for antigen uptake. E.g.: M cells (contain microfolds,
not microvilli)
• HEV (High endothelial Venules) present.
APPENDIX
P – paranchyma
VS – venous sinuses E – endothelial cells
Structure:-
✓ Surrounded by a thin fibroelastic outer capsule.
✓ Trabeculae extend into parenchyma.
✓ Macroscopically-white nodules in a red matrix
✓ White nodules represent white pulp and it is embedded in the red
pulp
✓ Red matrix represent red pulp.
✓ But when stained , red pulp stains lightly and white pulp stains darkly
(microscopically)
✓
✓ White pulp
- contains lymphoid aggregations.
- is of two types T cells & B cells.
- small fraction (5-20%) of total mass.
- T cell areas surround central arteries forming
periarteriolar lymphoid sheath (mainly TH cells).
- B cells form follicles.
✓ Red pulp
- is vascular tissue.
- consists of parenchyma with an interconnected network
of venous sinuses.
- parenchyma is composed of macrophages of sheathed
capillaries, other macrophages & blood cells.
- vascular sinuses are lined by stave cells.
Conduction:
simply the transmission of air from the atmosphere in to the alveoli. So the tract is adapted
to prevent collapsing while air is flowing, adjust its diameter and maintain the stretch ability
by several structural components.
Conditioning:
Is mainly done by the respiratory epithelium and its specialized cells. Warming of the air is
done by the countercurrent mechanism that occurs between blood and air. (Temperature
exchanges)
Regional differences
Respiratory epithelium
Lined by pseudostratified columnar epithelium and it has special cells in it helping the
conditioning of air.
❖ Goblet cell – produce mucus
❖ Serous cell – secrete serous secretions and it humidifies the inhaled air by
evaporation.
❖ APUD cell – secrete hormones (dispersed endocrine system)
❖ Clara cell - produce surfactant
❖ Brush cell
Trachea Bronchioles
Has C shaped cartilage rings No cartilage
Circular lumen Star shaped lumen
Smooth muscles are not prominent Smooth muscles are prominent and they are
comparatively . arranged spirally like a braid.
C cartilage
Star shaped
lumen
Trachea
P1 – Type 1 pneumocyte
P2 – Type 2 pneumocyte
Surface epithelium
Pleura
• Lined by mesothelium – flattened cuboidal cells with surface microvilli
• Outer parietal pleura
• Inner visceral pleura – contains fibrous septa, lymph vessels, blood vessels and
capillaries
Conducting System
• Modified cardiac muscle fibres, subendocardial purkinje fibres (larger than normal
muscle fibres)
• Has no T tubule system
• Connect with each other by desmosomes, gap junctions rather than intercalated discs
Pericardium
• Consists of outer fibrous pericardium and inner
serous pericardium
• Fibrous pericardium is made of fibrous tissue
• Serous pericardium is a thin double layered membrane lined by mesothelium
• Outer layer of serous pericardium – parietal pericardium is fused with the
fibrous pericardium
• Inner layer of serous pericardium – visceral pericardium (epicardium) is
fused to the heart
• Mesothelial cells are flattened epithelial cells that secrete a fluid for
lubrication
Myocardium – Cardiac muscle
Endocardium
• Line the cavities of the heart and
continuous with blood vessels
• Consists of simple squamous epithelium
• Sub epithelial layer (beneath the epithelium) consists of fibrous tissue and
elastic fibres to prevent endocardial damage during contraction
Heart valves
• Lined by thin endothelium layer with a fibro-elastic tissue core (collagen and
elastin)
• Surfaces are covered by a thin layer of endothelium
• Avascular
• A sinus is present around the valve to facilitate opening and closing of the valve
• Central fibroelastic core – lamina fibrosa
Tunica intima
− Consists of endothelium and subendothelium
− Endothelium is a single layer of simple squamous epithelial cells lying on a
basement membrane
− Intercellular junctions connect the cells together
− Cytoplasm contains membrane bound organelles that store and secrete
substances important in blood clotting
− Sub endothelium consists of fibroblasts and myointimal cells
− Fibroblasts secrete collagen fibres
− Myointimal cells have a contractile function and responsible for lipid
accumulation with age
Tunica media
− Consists of smooth muscle, collagen and elastin
− Smooth muscles contain receptors for adrenal medullary hormones to
control the diameter of the vessels
− Elastic arteries have a high content of elastin fibres and low content of
smooth muscles. Elastin fibres are arranged as sheets with collagen in
between
− Muscular arteries have a high content of smooth muscles and elastin fibres
are arranged in two well defined sheets
1.Internal elastic lamina – between tunica intima and media
2.External elastic lamina – between tunica media and tunica adventitia
Tunica adventitia
− A fibrous connective tissue, consists of collagen and elastin
− Vasa vasorum are small arteries in the adventitia of large arteries (eg:-
aorta) that supply the thick wall. They penetrate outer half of tunica
media
Arterioles
Micro-circulation
Sinusoids
• Arterioles
− Smooth muscles > elastin
− Major site of controlling peripheral resistance
• Micro-circulation
− Composed of smallest blood vessels (small arterioles,
metarterioles, capillaries, venules, AV shunts)
− Capillaries contain only a tunica intima with a single layer
of flattened endothelial cells resting on a basement
membrane and pericytes
− Nuclei bulge in to the lumen
− Pericytes are flattened cells with a contractile function. They surround
the endothelial cells
− At origin of each capillary, Pre-capillary sphincter found
Capillaries
• Metarterioles
− Larger diameter capillaries
− Discontinuous outer layer of smooth muscles
− Make direct communication on between arterioles & venules
Venous system
Venules
Post capillary venules size increases
Collecting venules tunica media acquire more smooth muscles
Muscular venules Usually thickest layer is adventitia
Veins
Lymphatic system
• Wall structure is similar to veins
• Contain valves
• Endothelium – extremely thin cell cytoplasm
− Basement membrane is rudimentary or absent
− No pericytes
➢ space created between the two layers of lateral plate mesoderm constitutes the primitive body
cavity
➢ Visceral (splanchnic) layer of lateral plate mesoderm Visceral layer of pleural pericardial
and peritoneal cavity
• Visceral (splanchnic) layer of lateral plate mesoderm and underlying endoderm are called the
splanchnopleure.
Cantrell pentalogy — spectrum of abnormalities due to closure defect begins at the caudal end
of the sternum and extends into the upper abdomen
1- Cleft sternum
2- Ectopia cordis
3- Omphalocele and gastroschisis
4- Diaphragmatic hernia
5- Congenital heart defects (VSD, TOF) & pericardial defects / absence of pericardium
Development of diaphragm
Diaphragm is derived from 4 components.
1- Septum transversum
• Is a thick plate of mesoderm occupying the space between the thoracic cavity and the
stalk of the yolk sac.
• Derived from visceral mesoderm surrounding the heart.
• It is developed at cervical segments.
• And during cephalocaudal folding it descends to thoracic level.
• By dragging its nerve supply from C3, C4, C5, spinal segments (phrenic nerve).
• And forms the central tendon of the diaphragm.
2- Pleuroperitoneal membranes
• Closes the foetal communication between pleural and peritoneal cavities. Form a part of
the diaphragm
3- Dorsal mesentery of the esophagus forms the crura of the diaphragm.
4- Fetal body wall forms the peripheral muscular rim.
Respiratory system
4th week of gestation
Fuse
Development of Larynx
➢ Cartilages and muscles of larynx – 4th and 6th pharyngeal arches
➢ Internal lining endoderm
➢ Rapid proliferation of the mesenchyme results in the change of the appearance of the
laryngeal opening from sagittal slit to T shaped opening.
➢ Innervation Superior laryngeal nerve and recurrent laryngeal nerve.
➢ Mesenchyme of two arches transforms into thyroid, arytenoid and cricoid cartilages.
➢ At about the time that the cartilages are formed, the laryngeal epithelium also proliferates
rapidly, resulting in a temporary occlusion of the lumen.
➢ Subsequently, vacuolization and recanalization produce a pair of lateral recesses, the laryngeal
ventricles. These recesses are bounded by folds of tissue that differentiate into the false and
true vocal cords
3 2
Secondary bronchi
Maturation of lungs
Last 2 months
• Number of alveoli increases steadily
• Amount of surfactant increases in last 2 weeks
After birth
• Growth of lung is due to an increase in number of respiratory bronchioles and alveoli
(due to increase in size)
• New alveoli are formed (5/6 of adult alveoli) during 1st 10 years of postnatal life)
• Heart, all blood vessels and all blood cells originate from mesoderm.
• Cardiac progenitor cells which are in the splanchnic layer of the lateral plate
mesoderm forms cardiac myoblasts.
• Also, blood islands (blood islands - The innermost cells of these blood islands are
hematopoietic cells that give rise to the
blood cell lines. The outermost cells
give rise to the endothelial cell layer
of blood vessels) which appear in the
mesoderm
• A horse-shoe shaped cluster of cells called the primary
heart field is formed.
• These cells form the atria, left ventricle & part of the right ventricle.
• The secondary heart field which is present in the splanchnic mesoderm gives rise to the
rest of the ventricle & the outflow tract.
• Outflow tract –
Pulmonary arteries and the Aorta
• Blood islands unite and forms a horseshoe shaped endothelial lined tube (Endocardial
Tube) that is surrounded by cardiac myoblasts.
Dorsal mesocardium
↓
Visceral Epicardium
↓
Coronary arteries
Heart is a
• 4 chambered organ ; 2 upper chambers & 2 lower chambers
• 2 septi ; Interatrial septum & Interventricular septum
• 2 inflow tracts ; SVC / IVC & Pulmonary veins
• 2 outflow tracts ; Aorta & Pulmonary infundibulum
2) Cardiac looping
Two methods.
1. By 2 actively growing tissue mass that approach each other or single mass approaching the
other end until they fuse. These tissue masses are called Endocardial cushions.
↓
At birth Left atrial pressure increases as the lung circulation begins ➔ foramen ovale closes ➔
becomes Fossa ovale
• They approach each other and fuse forming the left and the right
atrioventricular orifices.
AV Valves
Each AV orifice Is surrounded by local proliferations of mesenchymal tissue and flow of blood
hollows them out and the AV valves are formed
Membranous portion
• The two ventricles are connected by
interventricular foramen which is above
muscular portion of the ventricular septum
• The interventricular foramen is closed by fusion
of inferior endocardial cushion with muscular
part of interventricular septum
• Conus septum also helps
2 Swellings/truncus cushions appear in the Truncus arteriosus (Supported by the Neural crest
cells)
• Right superior truncal swelling grows towards left.
• Left inferior truncal swelling grows towards right.
• They twist around each other and then fuse to form aorticopulmonary septum.
• It separates truncus arteriosus into aortic channel and pulmonary channel.
1. R: dorsal
Unite each other → Unite with the Truncus septum →
Conotruncal septum → 2 Outflow tracts for two ventricles and roots
of aortic and pulmonary arteries
2. L: ventral
Neural crest cells migrate through the 3, 4, 6 Pharyngeal arches. They are important in
craniofacial development.
Therefore, heart defects and craniofacial abnormalities are associated.
Semilunar valves
SA node – Initial pacemaker lies in the caudal part of the left cardiac tube.
Then in the sinus venosus and finally in the right atrium as the sinus venosus is
incorporated into the R atrium.
4) Vascular development
• There is a Right and Left Dorsal aorta ; a DORSAL AORTA for each SIDE of the body
Arterial System
Aortic arches:
• Supply the pharyngeal arches.
• Arise from the aortic sac (distal part of the truncus arteriosus.
• 6 pairs appear.
• 5th arch either never forms or forms incompletely.
• Terminates in the Right and Left dorsal Aortae.
• R and L dorsal aortae are fused caudally to form a single vessel.
In the developed human being there are 2 parts in the venous system
• Portal venous system
• Systemic venous system
Sinus Venosus
RIGHT SINUS HORN absorbed into the RIGHT ATRIUM – Sinus Vaenarum
LEFT SINUS HORN becomes the CORONARY SINUS
VITELLINE VEINS / UMBILICAL VEINS and DUCTUS VENOSUS complex form the HEAPTIC
SINUSOIDS and the PORTAL VENOUS SYSTEM
Plexus around the Duodenum→ Portal vein and the liver sinusoids
Proximal part of the R vitelline vein forms the hepatic part of the Inferior vena cava
Umbilical veins
As the liver enlargens the liver incorporates the Left and Right umbilical veins into the liver
substance
Forming the ductus venosus and the hepatic sinusoidal system
• Right completely regress
• Proximal part of the L umbilical vein regress
• Distal part of the left vein connects the placenta to the liver
• After birth the left umbilical vein obliterates to form the ligamentum teres of the
liver
• The ductus venosus obliterates to form the ligamentum venosum
• Before birth it bypasses the live sinusoids through the ductus venosus
Before Birth:
There are 5 locations where the OXYGENATED and DEOXYGENATED BLOOD MIX
MAIN FEATURES
1) Non functioning lungs
2) Course of blood from the placenta to the heart
3) Three shunts permitting blood to bypass the liver and lungs
LV
Ascending aorta (Coronary & Common carotid arteries receive well oxygenated
blood)
Receives blood from Ductus arteriosus (Mixes with blood from the RV – As
lungs are collapsed, Blood flow in lungs are negligible)
Descending aorta
2 Umbilical arteries
Placenta
Clinicals
Dextrocardia
• Cardiac looping to left instead of right. • Related to the laterality establishment.
• Associated with - situs inversus (complete reversal of all organs)
- reversal of some organs.
Tetralogy of Fallot
Due to an unequal division of the conus and RIGHWARD DEVIATION of the CONUS SEPTUM
1. Pulmonary infundibular stenosis 3. VSD
2. Hypertrophy of the right ventricle 4. Overriding Aorta
Persistent truncus arteriosus
• The conotruncal ridges fail to fuse. • VSD is always present.
Valvular defects
• valvular stenosis • valvular atresia
Coarctation of aorta
Intercostal arteries get dilated and torturous ➔ erode lower surface of the ribs (notching of
ribs)
Right arm pressure increases & lower limb pressure decreases ➔radio-femoral delay
(porphrin)
Structure of Hb
• 4 polypeptide chains
• 2 α chains , 2 β chains
• Two identical dimers (αβ)1 & (αβ)2 – Dimers
• Each subunit has α helical structure and hydrophobic Haem binding pocket
• Interchain hydrophobic interaction between α & β subunits in dimer
• Two dimers are held together by Polar bonds – allows them to move with in respect to one
other
• Weak ionic bonds between two dimers are broken in the oxygenated state
deoxy Hb OxyHb
1 (tense state) 2018 A/L Batch Repeat
(relaxed state) Campaign
Hb
H2 CO3 HCO3- + H+
HbO2 + H+ HbH + O2
Conversely,
• Raising the pH or lowering the concentration of CO2 results in a greater affinity for O2.
• A shift to the left in the oxygen-dissociation curve.
• Stabilised oxidized form.
Under physiological conditions, HbF has a higher affinity for O2 than does HbA. Explain.
Haemoglobinopathies
α thalassaemia
glutamate
valine
Lysine
HAEM BIOSYNTHESIS
Occurs in most cells (not in RBC because Mature RBC has no Mitochondria)
Haem synthesis
Cytochrome P450
Respond to alterations in the cellular haem Matched to the rate of Globin synthesis
pool
ALA Synthase
ALAS1 ALAS2
Metal Proteins
2) Glucose – repression
3) Substrate availability – Fe2+ (in Fe2+ deficiency, Zn can be incorporated into haem)
4) Drugs – derepression (Eg- barbiturate)
5) Certain steroids induce
Porphyrias
• Inherited porphyrias are autosomal dominant with few exceptions.
• Heterogeneous group of rare inborn errors of metabolism.
• Due to defect in 7 enzymes (2nd step – 8th step)
• Accumulation and increase excretion of metabolic intermediates ; Porphyrins
• Chemicals and drugs can predispose the disease
Photosensitivity
1) Acute
2)Non-acute
Managing
Yellow Red
(Colourless)
(Brown)
(Yellow)
• Uptake by liver - Not rate limiting, facilitated transport, carrier mediated, saturable
• Conjugation - Drug inducible (Phenobarbital)
• Secretion by liver
➢ Rate limiting
➢ active transport
➢ drug inducible (Phenobarbital)
❖ Secretion of Bilirubin glucuronide into bile canaliculi is the rate limiting step.
Clinicals
1. Jaundice (Icterus)
• Definition – Yellowish discoloration of skin, sclera and nail beds due to increased levels of
conjugated or unconjugated (95% of total) bilirubin or both in blood.
• Due to deposition of pigments in tissues rich in elastin
• Clinically detectable when serum bilirubin > 2-2.5 mg/dl
Types of jaundice
Dark urine
➢ Enterohepatic circulation of urobilinogen → more enter into blood → filtered into the urine
➢ Plasma AST, ALT levels due to liver damage but no increase in ALP or slightly increased
➢ GGT increased in severe conditions
• Retention and regurgitation of bile due to bile duct obstruction (extrahepatic cholestasis).
• Due to,
• Treated with
➢ blue fluorescent light (Phototheraphy). Converts bilirubin to more polar compound
(more water soluble). Can be extracted with bile without conjugation.
➢ Administration of phenobarbital
➢ Exchange transfusion in severe cases
6. Congenital disorders
• bilirubin in plasma.
• Conjugated bilirubin level ➔ direct test (without methanol)
• Unconjugated bilirubin level ➔ indirect test (by measuring total bilirubin level using
methanol)
2) Ehrlich’s test
• bilirubin in urine
• Ehrlich’s diazo reagent + bilirubin ➔ reddish purple
• Dietary sources: Meat, fish, poultry, dark green leafy vegetables, pulses
Source % of total
body iron
Hb 66
Iron stores(Liver,Spleen,Bone 25
marrow)
Myoglobin & other H’protein 8.9
Plasma 0.1
• Iron is never found in free form (Fe2+) in cells because Fe2+ can generate oxygen free radicals.
• Always converted to Fe3+ and bound to proteins:
➢ During transport - bound to apotransferrin (to form transferrin)
➢ During storage - bound to apoferritin (to form ferritin)
NOTE: There is no specialised route for excretion of iron. Iron absorption is controlled so that the
amount absorbed is just sufficient to replace losses.
Haem oxygenase
Biliverdin + Fe2+
2) Cellular iron status is regulated at cellular level through reciprocal regulation of transferrin
receptors and ferritin expression
➢ Translation of mRNA coding for ferritin and transferrin receptors (TfRs) is reciprocally
regulated.
➢ When intracellular iron level is high, ↑ ferritin ↓ TfR
Excretion of Iron
• Iron is one-way element and very little of it is excreted. Any type of bleeding will cause loss
of iron.
• Almost no iron is excreted through urine.
• Considerable faecal loss.
• Some amount from skin.
𝑆𝐼
• Percentage of Transferrin Saturation (TS) = × 100%
𝑇𝐼𝐵𝐶
Iron overload
1. Excessive absorption → Hereditary haemochromatosis
2. Excessive intake
3. Transfusional haemosiderosis - multiple blood transfusions
4. Inappropriate administration of iron
Haemopoietic requirements
active in liver, adipose tissue, adrenal cortex, RBC, lens, corneal cells
6 phosphoglucono lactone
Glu -6- P -DH
hydrolase
Glucose-6-P 6-phosphogluconolactone 6-phosphogluconate
Reversible non-
The reversible non-oxidative steps will
Catalyzes inter conversion of 3,4,5,6, &7 carbon sugars. supplement the requirements when the
demand for nucleotide synthesis exceeds the
Ribulose-5-phosphate demand for NADPH
Glyceraldehyde-3-P
Ribulose-5-P
Fructose-6-P
NADPH
Functions of NADPH
1) Detoxification
A. Maintains the stability of the cell membrane. (esp.in RBCs)
Metabolic reactions formation of free radicals. Eg: peroxides, superoxides
H2O2 is reduced by glutathione. NADPH reduces Oxidized glutathione into its reduced form.
G-Glutamate
C-Cysteine
X linked
main regulatory enzyme in HMP
Production of NADPH in RBC is entirely dependent on HMP. (occurs in all cells, but most
severe at RBCs)
In G6PD deficiency, lack of NADPH
is.
Commonly manifests when exposed to oxidative stress
Oxidant drugs Eg: antimalarial (primaquine), herbicides
Favism (fava beans)
Infection (from oxidants produced during inflammation)
Ionizing radiation
O2 dependent mechanism
.
Respiratory burst
Reactive Oxygen species
O2- , H2O2 , OCl-, OH-
2) Reductive biosynthesis
NO synthesis
NADPH NADP+
NO synthase
Arginine Citrulline
O2
Functions of NO
Relax smooth muscle
Prevent platelet aggregation
Act as a neurotransmitter in brain
Mediate tumoricidal & Bactericidal action in macrophages
Sorbitol Pathway
Reduction of monosaccharides to polyol by Aldolase reductase an alternative mechanism for
metabolizing sugars in tissues. (Ex- lens, retina, liver, kidney, ovaries, seminal vesicles, Schwann
cells)
Sorbitol NADP+
NADH
fructose
Fructose Metabolism
Hereditary fructose intolerance
Essential Fructosuria (HFI)
Fructokinase Aldolase B
Fructose Fructose-1-P Glyceraldehyde
DHAP
ENERGY
RBC
FREE RADICALS
Production
Antioxidants
Enzymes;
Damage
• Carbonic anhydrase
These free radicals take electrons from • Peroxidase
macromolecules • Glutathione
Free radical chain reaction occur Vitamins;
Vit:C
From HMP
pathway
Glutathione reduced by glutathione reductase using NADPH. This NADPH is supplied by HMP pathway in
RBCs. (Look for HMP pathway topic for more information)
•digestion
•Mitochondrial level
•Water based fluid has high surface tension as molecules cling tighter to
each other than to air.
•The air fluid interface in lung can collapse the alveoli as the thin wall
cannot survive the force generated by the water molecules.
•surface tension needs to be removed in the lung alveoli using a
surfactant to prevent the lung from collapsing
•A Lecithin derivative (dipalmitoyl phosphatidylcholine) is an important
component of pulmonary surfactant which is secreted by type 2
pneumocytes.
1.Glutathione complex
Glutathione peroxidase
Glutathione
reductase
NADPH
G6PD
PUFA-OO° PUFA-OOH
Alpha-tocopherol Alpha-tocopherol-O°
(Reduced) (oxidized)
Vitamin C Vitamin C
(Oxidized) (reduced)
•The oxygen molecules diffuse into the cells & they finally enter to the
mitochondria.
•So the exergonic & endergonic reactions coupled together for the
continuation of the reaction.
•The energy which is released from exergonic reaction is used up in the endergonic
reaction
1. A strong reducing agents (such as NADH) donates electrons and has a negative
reduction potential,
A strong oxidizing agent (such as O2) is ready to accept electrons and has a
positive reduction potential.
• The pH and electrical gradients created by respiration are driving force for
H+ uptake.
Complex 1
Complex 2
Succinate deH
Complex 3
Cyt-b-c1 complex
Complex 4
Cytochrome oxidase
Complex 5
ATP synthase
CO Q ( ubiquinone)
Cytochrome C
• Hydrophilic
• Present in inter membranous space
• Connect complex 3 with 4
• ATP synthase
• coupled with ETC
Energy in the proton/charge gradient → kinetic energy in ATP synthase→ energy in ATP
•NADH results in more net H+ movement than FADH2 because complex I pump protons
but complex II does not.
• One NADH - 3 ATP
• One FADH -2 ATP
Uncoupling
• Uncoupling is the process which separates the ETC from ATP synthase.
•Normally, ETC and oxidative phosphorylation are tightly coupled for ATP synthesis
•Certain substances can uncouple the ETC from oxidative phosphorylation
• This causes the collapse of the electro-chemical H+ gradient
•The energy stored in the gradient is dissipated as heat
• This leads to Non-shivering thermogenesis.
1) Natural uncouplers
• Natural uncoupling protein ‘thermogenin’ (UCP1) is found in brown adipose tissue in the
newborn. Brown adipose tissue contains many mitochondria and helps maintain body
temperature. Thermogenin (UCP1) is an important factor in heat production and in lipid
turnover.
Estrogen, Norepinephrine, ANP, BNP are some examples which induce thermogenesis in
brown adipose tissue.
• Synthetic uncouplers such as 2,4-DNP and FCCP are hydrophobic and contain a
dissociable proton (i.e. they are hydrophobic weak acids). In their uncharged form, they
can pass into the mitochondrial matrix and release H+ in the matrix – dissipating the H+
gradient.
• Drugs such as aspirin (and other Salycilates) which are weak acids at high doses can act as
uncouplers.
Inhibitors
o Complex 5- oligomycin
Plasma lipids
Lipid transport
Majority
Lipoproteins
• Macromolecules
• Have week covalent bonds
• Spherical particles
• Contents : TAG, CE, PL, Cholesterol, Proteins
Lipids Proteins
Classes of LP
Density CM
Origin
CM
VLDL LDL (β lipoprotein)
LDL protein content & density VLDL (pre β
HDL Mobility
lipoprotein)
HDL
(α lipoprotein)
Apo LP LP Function
AI HDL Structural protein. Activates LCAT (PCAT). Interacts
with ABC AI transporter.
AII HDL Structural protein
B48 CM Structural protein required for synthesis and
CM remnants secretion of CM.
B100 VLDL , LDL, IDL Structural protein required for synthesis and
secretion of VLDL
Recognition and binding of LDL to LDL receptors.
( reduced due to autosomal dominant disease)
CII CM, VLDL, HDL Activates LPL.
Apo E CM, VLDL & Triggers clearance of remnants of VLDL (IDL) & CM
remnants remnants. Is recognized by remnant receptors.
Nonsense modification
Apo B gene m-RNA m-RNA R-RNA RER Apo B48 SER
(For Apo B100) (For Apo B48)
Lipids
CM Golgi Microsomal TAG
transfer protein (MTP)
CM Metabolism
• VLDLs are secreted directly in to the blood by the liver as nascent VLDL.
• Nascent VLDL contain Apo B100.
• They obtain Apo C2 & E from HDL in the blood plasma.
• Apo C2 activates LPL
• LPL hydrolyzes TAG into FFA & glycerol.
• Remnants of VLDLs, (IDL) now take part in the formation of LDLs.
• VLDL remnants return the Apo C & E to HDL but retain Apo B100.
Lipoprotein lipase
• Insulin induces synthesis and transfer of LPL to the luminal surface of capillaries
• And on the surface of capillaries (outside the tissues) or on the surface of the hepatocyte (liver
cells)
• Hydrolyzing TG to release fatty acids near the tissue. High local concentration of fatty acids
leads to their uptake by tissues.
• Apo CII activates LPL and Apo CIII inactivates LPL.
• LPL has different Km values depending on the tissue.
• Ex: Km in heart muscle cells < Km in adipose tissue
• So adipose tissue only takes up TAG when there is excessive amount.
LDL metabolism
Uptake of LDLs
• Uptake of LDL by tissue is mediated through specific cellular LDL receptors. It’s a negatively
charged glycoprotein.
• LDL binding domain of the receptor is in the N terminal end. (rich in Glu, Asp) (-)
• Cytosolic domain controls interaction with clathrin coated pits & participates in endocytosis.
• Uptake is controlled by intra cellular free cholesterol concentration.
• Produced in liver & intestine. Apo C& E synthesized in liver- transferred to intestinal form in
plasma
• Acts as a repository of Apo C & E required for CM & VLDL metabolism
• Uptake of unesterified cholesterol
• Esterifies Chol & transfer to other LPs
• Reverse transport of Chol (from tissues to liver)
HDL metabolism
1. Nascent HDL are disc shaped particles that contain PL and Apoproteins A, C and E.
2. They rapidly accumulate cholesterol via ATP binding cassette transporter-1
(ABC-A1).
3. Cholesterol is esterified within HDL by LCAT/PCAT (lecithin cholesterol acyl transferase)
4. LCAT is activated by Apo AI.
5. As the nascent HDL accumulates CE, it 1st becomes a relatively CE-poor HDL3 and eventually
CE-rich HDL2.
6. CEs are transferred to VLDLs via cholesterol ester transfer protein (CETP).
A. Free fatty acid amounts that taken up by liver can be raised due to
1. Mobilization of fat from adipose tissue
2. Hydrolysis of LP TAG by LPL in extra hepatic tissue
➢ Increase amounts of free fatty acids are taken by liver and esterified. The production of
VLDL does not keep pace with the influx of the FFA, allowing TAG to accumulate causing
fatty liver.
➢ During starvation, quantity of TAG in the liver is increased, and ability to secret VLDL is
impaired. Tis may be due to low level of insulin.
B. Due to metabolic block in the production of plasma lipoproteins, thus allowing TAG to
accumulate. lesion could be due to:
1. A block in apolipoprotein synthesis
2. A block in synthesis of lipoprotein from lipid and apolipoprotein.
3. A failure in the secretary mechanism itself.
Ethanol Acetaldehyde
Alcohol
Dehydrogenase/microsomal
ethanol oxidizing system
Composition of Plasma
• Water - 90%
• Proteins - 8%
albumin
globulin (α,β,γ - From lymphatic tissues)
fibrinogen
• Inorganic Ions - 1% (Na+, K+, HCO3-, Cl-, Mg+, Ca+)
• Others - 1% (Hormones, gases, waste products)
Medullary Extramedullary
• No organ produces plasma. it is formed from water and salts absorbed through the digestive
tract. Plasma proteins produced by distinct organs.
EPO – Erythropoietin
CFU – Colony forming unit
TPO – Thrombopoietin
SCF – Stem cell factor
TNF – Tumor Necrosis Factor
GM-CSF – Granulocyte Macrophage Colony Stimulating Factor
IL / ILs - Interleukins
G-CSF- Granulocyte Colony Stimulating Factor
M-CSF – Macrophage Colony Stimulating Factor
1. cell proliferation
2. differentiation
3. suppression of apoptosis
4. maturation
5. functional activation Growth Factors
2nd messenger
3 systems © 2018 A/L Repeat Campaign
Gene Activation
Red Blood Cells
(Hb start
Appearing)
Less
basophilic
Functions of RBC
• Transport of O2 and CO2
• Buffering action by Hb and proteins
• Contains Carbonic Anhydrase enzyme
Erythropoietin
If both kidneys are affected , non- renal production of erythropoietin (There are also non‐renal sensors)
can compensate the RBC production up to 33%-50% (1/3-1/2)
Hemoglobin
HbA2 = 2α 2δ (2.5%)
Glycated haemoglobin = HbAIC (increased in patients with Diabetes mellitus.So it used as clinical marker
for Diabetes mellitus )
oxygenation
Hb + 402 Hb (O2)4 oxyhemoglobin
2,3 BPG, pH , Temp.
Bilirubin Metabolism
(unconjugated
bilirubin)
(Jaundice GIT)
RBC Abnormalities
• Due to a defect in the membrane - Hereditary spherocytosis
• Due to a defect in hemoglobin production - Thalassemia , sickle cell disease
• Due to the deficiency of enzyme G6PD-Haemolysis
6 © 2018 A/L Repeat Campaign
Anemia
Reduction in concentration Of Hb below accepted normal range (which depends on sex, age, ethnic
group, altitude)
Features - Tachycardia, palpitations, heart murmur, dyspnea, pallor
Causes of Anaemia
↓ Production
↑ Loss ↑ Destruction
*nutritional deficiency
Hemorrhages Eg: hemolytic
anemia *↓ bone marrow erythroid cells
*renal disease
Examples of anemia
2. Megaloblastic anemia
a) Hereditary spherocytosis
Haemolyse easily
Enter a vicious cycle that may even lead to death in some cases
c) G6PD Deficiency
Hemolysis
Rh+ RBC in the fetus are attacked by Rh- antibodies from mother
f)
4. Normocytic normochromic anemia
Renal failure, Aplastic anemia , Leukemia, Acute blood loss, Erythropoietin deficiency
RBC being Hyperchromic is impossible since RBCs normally carry the maximum amount of Hb they can
carry
Polycythemia (erythrocytosis)
Polycythemia (erythrocytosis)
Primary Secondary
pathological Physiological
-cancer ↑ erythropoiesis (eg: at high
*polycythemia rubra vera attitudes)
Hypoxic
Renal disease
The proportion of blood occupied by red blood cells, usually expressed as a percentage of the total blood
volume.
Increased in Decreased in
Dengue hemorrhagic fever Pregnancy
Severe Diarrhea Anemia
Polycythemia Sickle cell Disease
High attitudes Chronic renal defect
Prolong vomiting
The rate at which red blood cells in anticoagulated whole blood descend in a standardized tube over a
period of one hour. It is a non-specific measure of inflammation. Plasma viscosity ESR
Increased in Decreased in
Severe anemia Polycythemia
Malignancies Sickle cell anemia
Pregnancy Protein abnormalities
Rheumatic fever leukemia
TB
Agglutinins: antibodies against Agglutinogens , present in plasma after birth. Type of ɣ globulin (IgM, IgG).
Produced by bone marrow/ Lymph nodes
Rh system
Antigens present only on RBC
• Unlike ABO antibodies Anti D antibodies do not develop without exposure of D- RBC to D+ RBC by
transfusion or pregnancy
• Takes 2-4 weeks to develop anti Rh agglutinins
• Several exposures lead sensitized to Rh factor
• Cross matching Donor RBC + Recipients plasma
1. Incompatibility reactions
RBC Agglutination
Clumps
IV Hemolysis
May block blood
Release Hb
vessels
Jaundice
Renal failure
2. Fever, allergic reaction, circulatory overload, Iron overload, Air embolism, diseases (ex:- malaria,
AIDS)
11 © 2018 A/L Repeat Campaign
Autologous transfusion
Autologous blood donation is the process of donating one’s own blood prior to an elective surgical
or medical procedure to avoid or reduce the need for an allogenic blood transfusion (from a
volunteer blood donor)
Advantages,
Be safer for the patient- decrease the risk of complications such as.
• mismatched blood
• Exposure to blood borne infectious agents
Save time need not to type and cross match the blood
• At first IgM antibodies which are pentamers are formed, they cannot cross placenta
• Secondly IgG antibodies which are monomeric are formed, so they can cross the placenta in
subsequent pregnancies
• Rhogam is administered within 72 hours after delivery, it consist of synthetic anti D antibodies,
prevent sensitization of mother to D antigen
Complications
o Death,
o severe anaemia
o jaundice
o oedema(hydrops fetalis)
o Kernicterus = destruction of neuronal cells due to deposition of bilirubin (as fetal blood brain barrier
is still underdeveloped and may be permeable to certain substances)
Thrombopoietin;
Glycoprotein. Produced by liver and kidneys
Regulator of platelet production
It increases the number & rate of maturation of the megakaryocytes.
Thrombocytopenia
Thrombocytosis
Thrombocytopenia
- Loss of function
Heamostasis
Haemostasis is the process of forming clots in the walls of the damaged blood vessel and preventing blood
loss while maintaining blood in fluid state within vascular system
Injury to a vessel
Anticoagulants
Bleeding
Breakdown the clot once the
damage is repaired
procoagulants
Vascular response
Platelet Response
Neutrophils
PAF (Platelet Aggregating Factor), ADP,
Monocytes
Thromboxane A2
Platelets
Platelet aggregation
21 © 2018 A/L Repeat Campaign
Platelet Plug
Aspirin
Clotting response
Clotting factors
• Plasma proteins
• Synthesized in the liver
• Responsible to regulate clotting response
• Normally in inactive state in plasma
(Not Essential)
(Platelet Phospholipids)
Xa
Common Pathway
Role of vitamin K
Thrombomodulin-thrombin complex
Heparin-Antithrombin III complex inhibits activated Factors IIa, IXa, Xa, XIa, XIIa
3. Tissue Factor pathway inhibitor (makes complex with Va, VIIa, Xa)
4. Interaction between TXA2 & Prostacyclin
5. Fibrinolytic system (Plasminogen System)
6. NO, PGI2
D dimer
Plasminogen plasmin
t-PA (Tissue plasminogen Activator), u-PA
Fibrinolytic agents
Streptokinase & Human recombinant t-PA activate human plasminogen. Activate thrombolysis. Used in
myocardial infarction (heart attack) and pulmonary embolism
Streptokinase cannot cross blood brain barrier, so recombinant t-PA is given in stroke medication
Anti-coagulants
A. In vivo
1. Low molecular weight Heparin -Facilitates binding of Antithrombin III (serine protease
inhibitor) to active forms of clotting factors II,IX, X, XI, XII and inactivate them.
Causes elevation of APPT.
* -Carboxy-glutamic acid residues increases (-) charge in the clotting factors which can then adhered to
platelet membrane phospholipids through Ca2+
Other-Dabigatran, Rivaroxaban
B. In Vitro
1. Heparin
2. Oxalate - E.g.-Na Oxalate, K Oxalate
From insoluble salts with Ca2+
Abnormalities of hemostasis
Thrombosis- Formation of clot inside blood vessels. Eg: Protein C and S deficiency
Thrombin Time
• Designed to assess fibrin formation from fibrinogen in plasma. The thrombin time is used to assess
unexplained prolongation of PT or APTT.
• reference range - 15-19 seconds
• Clotting time is the time required for a sample of blood to coagulate in vitro under standard conditions.
• for intrinsic pathway and common pathway of clotting.
• 4-10 minutes
Bleeding time
• Opsonization is done by antibodies that coating of material to be phagocyted like “making it tasty”
Neutrophils secrete
• Metalloproteinases -Facilitate the movements of other
• Elastase neutrophils by digesting collagen in the ECM
• Defensins - Antimicrobial peptide
• Thrombaxanes - Vasoconstriction
• Leukotrienes - Increases vascular permeability and attraction of other
neutrophils
• Prostaglandins - Inflammatory mediator
• PAF - platelet aggregation
• Lactoferrin -Binds to iron required for bacterial growth
• Neutrophils can only ingest 3-20 bacteria whereas macrophages can about 100.
• Macrophages have the ability to ingest large particles as RBC/malaria parasites.
• Macrophages can extrude the residual products after digesting particles and can survive for
more months whereas neutrophils cannot.
• Macrophage lysosomes have large amount of lipases which can digest the thick lipid
membranes of bacteria. (specially Tuberculosis bacillus)
Acquired
Innate
Innate Immunity
Complement system
• Plasma proteins
• Act via a cascade
• Bridge between innate and acquired immune systems
• 3 pathways to activate
o Classic pathway – activated by immune complexes
o Mannose binding lectin pathway – triggered when lectin binds to mannose groups in bacteria
o Alternative pathway – triggered by contact with virus, bacteria, fungi and tumor cells
Functions of Complements
• Glycoproteins
• Present on the surface of the cells
o MHC I – Present in all nucleated cells
o MHC II – Macrophages, dendritic cells and natural killer
cells
• Polypeptide products of digested antigens are coupled to MHC
on surface of cells.
Immunoglobulin
• Ig G = Monomer; complement activation, Long term immunity, can cross placenta
(maternal immunity)
• Ig A = localized protection in external secretion , Monomer/Dimer/Trimer, in Colostrum
• Ig M = Complement activation, Primary antibody response, can't cross placenta, Pentamer
• Ig D = Antigen recognition by B cells, Monomer
• Ig E = Binds to basophiles & mast cells, key role in allergy, Monomer
17 © 2018 A/L Repeat Campaign
Functions of Immunoglobulin
Antigen (pathogen)
Invaded by macrophages, dendritic cells, natural killer cells and other nucleated cells
Antibodies=Immunoglobin
s
Direct Actions
Agglutination
Complement
Precipitation system activation
18 (classic pathway) © 2018 A/L Repeat Campaign
Neutralization of protein toxin
Lysis by enzymes
Clonal selection & clonal expansion -stimulates division of effector cells that respond to a particular
antigen
Active Immunity - Person's own body develops either antibodies or activated T cells in
response to invasion of the body by a foreign antigen
Passive Immunity - By infusing antibodies, activated T cells or both, obtained from the blood
of someone else or from some other animal that has been actively
immunized against the antigen
Auto Immunity - The failure of an organism in recognizing its own constituent parts as self, which,
b allows an immune response against its own cells and tissues.
The collective activity of all above results in the main function of gas exchange to supply O2 and remove CO2. This task of
delivering gases between atmosphere and cells is staged into the following processes.
1. 2. 3. 4.
VENTILATION GAS EXCHANGE GAS TRANSPORT REGULATION
Mechanism of Breathing
The movement of air between the lungs &
atmosphere depends on;
1. Total pressure gradient (mass movement)
2. Partial pressure gradient of individual gases
• Pressures aiding ventilation;
Atmospheric pressure – The pressure of the outside air at sea level
Intra-alveolar pressure – The pressure inside the alveoli; Approx. to atmospheric pressure
at rest = 0mmHg
Pneumothorax
Inspiration
• Active process
• Contraction of inspiratory muscles increase thoracic
volume
• Main muscle of inspiration – diaphragm
• Other/ accessory muscles – external intercostals,
sternocleidomastoid, scaleni, serratus anterior Curve represents
• Chest wall expands, lungs begin to expand because if airway and
visceral pleura is in contact with parietal pleura, tissue resistance
expansion of lungs leads to increased elastic recoil was absent.
• Intrapulmonary volume increases
• Negative IPP transmitted to alveoli becomes -6 mmHg
• Intrapulmonary pressure drops
• Air flows into lungs
Expiration
• Passive process during rest.
• Inspiratory muscles stop contracting
(However some contraction of respiratory muscles occur in early parts of expiration to exert a
breaking action on recoil forces & slows expiration.)
• Thorax & lung come back to their original positions because the lung & chest wall are elastic.
(passive process)
• Intrathoracic volume decreases.
• Alveolar pressure becomes positive relative to the atmosphere
• Air flows out until the pressure equalize
• Negative intrapleural pressure returns to previous value (-2.5 mmHg) but does not become positive.
• Air flows by bulk flow up to the terminal bronchioles, thereafter the volume / total cross area
greatly increases causing velocity of air to rapidly decrease.
• Therefore, there is a high chance of unfiltered inhaled dust particles depositing in the respiratory zone (2µm)
• Volume of air that enters lung mainly depend on total pressure gradient
(M3)
Dilatation Constriction
Inspiration Expiration
Sympathetic Parasympathetic
• Density & viscosity of the inhaled gas (O2 mixed with He is given in hospitals)
• Direction of flow
• Nature of flow (Turbulant or Laminar )
• Large bronchi➔ Medium size bronchioles ➔ Increase resistance
Medium size bronchi➔ Small bronchioles ➔ Decrease resistance
Bronchoconstriction is precipitated (increased) by
1. Cool air
2. Exercise -> Sympathetic↑->Respir. Rate↑
Reduced warming & humidifying inflowing air
3. Irritants
4. Inflammatory agents (bacteria, virus,
allergens) Mainly
5. Cytokines happens
6. Adenosine in asthma
patients
7. Leukotrienes
8. Histamines
9. Substance P
10. Alveolar PCO2
7 11. Parasympathetic Ach-M3® ©2018 A/L Repeat Campaign
12.
Dilators
1. VIP, NO – Relaxes smooth muscles
2. Salbutamol – β2 agonist
3. Atropine – Parasympathetic antagonist
4. Xanthines-(theophiline) :inhibits breakdown of CAMP
5. Sympathetic : Epinephrine/ Norepinephrine (β2 receptors )
6. Prostaglandin E2
7. PCO2 in small airways. Draw the graph for vital capacity against time in an
asthma patient and comment on the ratio FEV1/VC
▪ Allergens of asthma
o infectious viruses, exercise, environmental and air pollution, occupational factors,
pharmacological agents
Is asthma an obstructive or restrictive lung disease?
Difficulty higher in expiration, why?
Basis of treatment
1. Dilate airways – bronchodilators. Ex: Salbutamol (2 receptor agonist)
Block bronchoconstrictors Ex: muscarinic receptor antagonist
3. Increase the pressure gradient – Mechanical ventilators & accessory muscles of inspiration
Compliance during,
▪ Supine position ▪ Pulmonary congestion(accumilation of fluids)
▪ Pneumothorax ▪ Removal of one lung (1/2 of compliance)
▪ Pulmonary oedema ▪ Rigid chest wall
▪ Old age ▪ Acute respiratory distress
Emphysema
▪ As the walls of the airways are weaker and less supported they tend to collapse when the
pressure outside increases in expiration.
“Surface tension is the force acting perpendicular on an imaginary line 1cm long on the surface of a liquid”
This occurs due to the intrinsic property of a liquid to assume the minimum surface: volume ratio (the
attractive forces between liquid molecules is greater than their attraction to other surrounding molecules.
TV 500 ml The volume of air inspired or expired with each normal breath
IRV The maximum extra volume of air that can be inspired over and above
the normal TV when the person inspires with full force
ERV The maximum extra volume of air that can be expired by forceful
expiration after the end of a normal tidal expiration
RV The volume of air remaining in the lungs after the most forceful
expiration
VC The maximum amount of air that can be expelled IRV+TV+ERV
after first filling the lungs to their maximum extent
and then expiring to the maximum extent
IC The amount of air that can be inspired, beginning at TV+IRV
the normal expiratory level and distending the lungs
to the maximum amount
FRC (relaxation The amount of air that remains in the lungs at the ERV+RV
volume) end of normal expiration
TLC The maximum volume to which the lungs can be VC+RV
expanded with the greatest possible effort
12 ©2018 A/L Repeat Campaign
• Exhalable air measured by; spirometry
• Non exhalable air by; (RV, FRC, TLC)
o He dilution method
o Total body plethysmography
o N2 washout method
FEV1 – Fraction(volume) of FVC expelled during first second of forced expiration (Normally 75% of VC)
FVC – Forced Vital Capacity
Respiratory rate – breaths per minute (12-16 per min: healthy adult)
Dead Space
The volume of gas, which occupies that region of the respiratory system, which does not take part in gas
exchange.
Calculation of Ventilation
Tidal volume = Anatomic dead space + alveolar compartment
= 150 mL + 350 mL
= 500 mL
Obstructive Restrictive
Caused by airway obstruction Caused by stiff lungs
Difficulty in expiration Difficulty in inflating lungs
FEV1 decreases FEV1 decreases
VC unchanged VC decreases
FEV1/VC ratio less than 75% FEV1/VC ratio normal or higher than 75%
Ex: Asthma, COPD, Emphysema, Bronchiactasis Ex: Lung Fibrosis, pneumothorax, pulmonary oedema
FVC
FEV1
• Peak flow is the volume of air that can be expired in a unit time in a maximum expiratory effort.
• This ranges from 400 – 750 L/min
• Peak flow meter is used
• Measurement of PEF- select best of the 3 blows, not the average.
• Peak flow is reduced in
o Restrictive diseases
▪ Fibrotic diseases
• Tuberculosis, Lung fibrosis, Silicosis
▪ Abnormal chest walls
• Kyphosis, Scoliosis
o Obstructive diseases
▪ Asthma
▪ Emphysema
Other Methods
i. Peak expiratory Flow
ii. Pulse oximetry
– measure O2 saturation
iii. ABG testing
Partial Pressure
Oxygen Cascade
PIO2 = PB%
PAO2
PaO2
40mmHg(veins)
Gas exchange occurs at blood gas interface – Made of alveolar & capillary walls + fused
basement membrane/ Alveolar capillary membrane/ Respiratory membrane
Diffusion
Factors effecting the rate of diffusion across the membrane (V/t)
• Thickness of the membrane (T)
• Surface area of the membrane (A)
• Pressure difference of the gas across the membrane (P1-P2)
• Diffusion coefficient (D) – Depend on solubility (sol) & square root of the gas’s molecular weight (MW)
𝐕 𝐀
∝ × 𝐃 × (𝐏𝟏 − 𝐏𝟐)
𝐭 𝐓 In emphysema surface area
𝐬𝐨𝐥 decreases as alveoli coalesce
𝐃∝
√𝐌𝐖
Other factors affect rate of diffusion:
o Perfusion of pulmonary capillaries
o Hb level
o Affinity of the gas for
• Volume of gas that will diffuse through the respiratory membrane each minute for a partial pressure
difference of 1 mmHg”
• It is a measure of the ability of the lung to transfer gas across the respiratory membrane. (High
surface area, adequate perfusion with haemoglobin)
Procedure
1. Inhale a gas mixture with 0.3% CO. Condition DLCO
2. Hold breath for 10s. Exercise ↑
(CO diluted by gas already present and Emphysema ↓
also taken up by Hb.) Lung Fibrosis ↓
3. Exhale 1st to wash out the dead space Lung Lobe resection ↓
4. Next exhaled alveolar sample Anaemia ↓
collected. 5.CO concentration measured. Alveolar Hematoma ↑
6. Should make corrections for Hb
concentration and lung volume.
• Diffusing capacity markedly increased in – exercise (because of capillary dilation and distension)
• Diffusing capacity decreased in – emphysema, lung fibrosis, lung lobe resection, anaemia
• Diffusing capacity CO2 >>O2 → CO2 retention is rarely a problem in patients with lung fibrosis
• O2 diffusing capacity reduction severe
Diffusion and Perfusion limitations
❖ N2O is perfusion limited. WHY?
- Rapidly crosses blood-gas barrier.
- Doesn’t bind with HB, ∴ partial pressure rises rapidly
- I.e.: it equilibrates with alveolar N2O rapidly, ∴ no gas is
thereafter transferred
-
❖ CO is diffusion limited. WHY?
- CO moves rapidly across blood brain barrier.
- Binds to Hb. ∴ large amount can be taken up by RBC
o with no ↑ in partial pressure.
- Amount of CO that diffuses into blood depends not on
amount of blood, but on properties of lung.
2 main supplies
o Bronchial arteries – oxygenated blood from aorta, supply nutrients to the pulmonary tree.
o Pulmonary arteries – deoxygenated blood from r. ventricle for gas exchange.
After exchange, oxygenated blood is carried to the heart by pulmonary veins. There it is mixed with
deoxygenated blood draining the lungs. Thus, a physiological shunt is seen here.
Shunts➔ Deoxygenated blood entering the arterial side of the circulation without undergoing gas exchange within
ventilated regions of the lung for oxygenation.
When enlarged to cause pathological Most added O2 is dissolved form, because blood that
conditions, ‘pathological is perfusing, ventilated alveoli are hardly saturated.
Mean pressure
15 mmHg
• Alveolar Pulmonary Exposed to pressure of
vessels capillaries alveoli. Compressed if
alveolar pressure >
capillary pressure
• Extra alveolar Pulmonary arteries Pulled open by radial
vessels & veins traction of surrounding
elastic lung
tissue
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©2018 A/L Repeat Campaign
Uneven Ventilation
Upright
• Lower regions ventilated better than upper
zones.
Supine
• Apical ventilation = basal ventilation.
• Lowermost (posterior) > Uppermost (anterior)
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Uneven perfusion of lungs
Effect of Gravity on Regional Blood Flow
▪ Can be explained by hydrostatic pressure difference. Nice to know -
Waterfall effect
▪ Bases are better perfused than the apex in the upright position
(Blood flow is greater in the most dependent part)
▪ Affected by exercise and change of posture (on mild exercise, regional differences become less)
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Mixed venous blood
• As V/Q ratio is altered, its gas composition
Approaches. Inspired gas
L/min V/Q
Q
V
Q
Bottom Top
Q>V V>Q
∴ V/Q is ∴ V/Q is
low high
• V/Q abnormalities
o Do not commonly lead to CO2 retention, if ventilation can be increased.
o Hypoxemia cannot be eliminated by increasing ventilation
• Different behavior of the 2 gases result from the different shapes of their dissociation curves.
• V/Q mismatch is an important & common cause of hypoxemia. It can also cause hypercapnia BUT it
does not manifest! WHY? CO2 can be excreted by increasing ventilation but not O2 diffusion. CO2 is
highly water soluble than O2
• V/Q ratio increase in emphysema, decrease in fibrosis.
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Autonomic supply – (sympathetic - ↓blood flow)
Active
- O2
Local factors (Hypoxic pulmonary vasoconstriction)
- CO2 (→ pH↓ → vasoconstriction)
- NO
Gravity
Physiological adaptations that help to keep the pulmonary interstitium relatively free
of fluid.
● The mean capillary pressure is lower and therefore hydrostatic pressure is lower
● The Interstitial pressure in the lung is slightly more negative than in the systemic
capillaries
● The colloid osmotic pressure of the pulmonary Interstitial fluid is higher than in
the systemic interstitial space.
● The pulmonary circulation has a richer lymphatic circulation and nearly all of
filtrated fluid is drained away.
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Gas Transport
O2 Transport
O2 & Hb
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❖ Systemic arterial blood - Why 97%, not 100% O2 saturation?
2. O2 saturation
𝑂2 𝑐𝑜𝑚𝑏𝑖𝑛𝑒𝑑 𝑤𝑖𝑡ℎ 𝐻𝑏
× 100%
𝑂2 𝑐𝑎𝑝𝑎𝑐𝑖𝑡𝑦
Arterial blood = 97%
Venous blood = 75 %
≈30mmHg → 50%
50mmHg → 85
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©2018 A/L Repeat Campaign
• O2 – Hb Dissociation Curve • Shape- sigmoid (due to tense-relax
- configuration)
• Steep lower part
o At low PaO2, low affinity of
Hb to bind with O2
o O2 unloading is maximum for
small change in PaO2
o Capillary PO2 > Tissue PO2,
therefore diffusion is high
• Flat upper part
o At high PaO2, high affinity of
Hb to bind with O2
o loading is not affected
o Saturation % changes very
little
o PAO2 > PaO2, therefore
diffusion is high
• Dissolved O2 has linear relationship
with PaCO2
26 P50 = the PO2 at which Hb is 50% saturated
with O2.
2) ↓ temperature ↑ temperature
4) ↓Pco2 ↑Pco2
5) ↑CO
CO2 Transport
▪ Solubility of CO2 in blood is about 20 times that of O2
▪ Mainly 3 ways. - In
o RBC
o Plasma
1. Dissolved - 7 - 10%
2. Carbamino compounds - 23 - 30% -
(bound to amino groups of Hb, plasma proteins)
3. Hydration – HCO3- - 60 -70%
Lungs
RBC
CO CO2+ H2O
2
Carbonic
H2CO3
HCO H+ HH
Band b
3
3
(AE1) Cl-
H
HbO
2
O2 O2
Neural
Effectors
Sensors Respiratory muscles
Chemoreceptors – ➢ Reciprocal innervation-
• Central excite agonists, inhibit
• Peripheral antagonists
PaCO2
PaO2
H+
Response
Change ventilation
Rate & depth
Central-medullary Peripheral
(At the floor of 4th ventricle) Carotid Bodies-IX Buffer nerves
Monitor [H+] in CSF and brain ECF Aortic bodies-X
Stimulated by –
↑ PaCO2, ↑ H+ in CSF and ECF • Has a rich blood supply for a unit mass. – because the blood
flow per unit of tissue is so enormous, the O2 needs of cells
can be met largely by dissolved O2 alone. Therefore, the
• H+ in blood cannot pass through BBB receptors are not stimulated in conditions such as Anemia or
• CO2 diffuses CO poisoning
CO2 + H2O H2CO3 H+ +HCO3- • respond to changes in dissolved O2, CO2 and pH
• Not stimulated in
o Anemia (PaO2 is normal)
o CO poisoning
Receptors for H+ • Receptors stimulated
o pH
• Main stimulation PaCO2 o PCO2(above 40mmHg)
o PO2 (below 60mmHg) Discharge rate
• When PaCO2 cerebral vasodilatation ↓
o Vascular stasis
• More CO2 diffuses to CSF and brain ECF -
o CN poisoning Respiratory center
• Stimulate respiration +
o K Infusion ↓
o Exercise Ventilation
o Nicotine & Lobeline
o Xanthine
• If peripheral chemoreceptors are denervated response to
hypoxia is abolished
• Response to H+ is affected significantly
• Morphine depresses respiration
•
Normal quiet breathing:
CO2 is the main drive- control mainly via central chemo receptors.
(Normally, O2 doesn’t affect, but important in high altitudes and disease conditions.)
• Carotid bodies are functional more important than aortic bodies.
• Removal of carotid bodies results in a loss of response to hypoxia but the response to CO2 is
only reduced.
Mechanism of peripheral chemoreceptors
During sleeping :
o Non specific afferent from ascending reticular formations control breathing
1. REM sleeping: irregular non-periodic breathing
2. NON-REM sleeping: irregular periodic breathing
Brief period of apnea occurs in normal sleeping adults due to PCO2
(absence of proprioceptive or environmental mechanisms)
PAO2
Deoxy-Hb are
weak acids
Peripheral chemo Hb is less saturated Act as a buffer.
Receptors triggered. With O2
Ventilation
More H+ binds to
Deoxy- Hb
PCO2
Respiration inhibited
Inhibit respiration
PCO2 PO2 pH
CNS Changes
• HR - ↑
• BP - ↑
Skin changes
High altitude
• At 3000m above the sea level PAO2 is about 60mmHg. And there is enough hypoxic stimulation
of chemoreceptors under normal breathing to cause hyperventilation.
▪ Cerebral oedema
▪ Increased barometric P
▪ P on the body rises
▪ Pushes N2 into blood
▪ N2 is very lipid soluble (nervous system, bone marrow, fat)
▪ If ascent rapid, PN2 ↓ abruptly, N2 ‘boils’ out of tissues→air bubbles → bends and chokes
▪ N2 narcosis is seen
▪ Similarly oxygen toxicity can be occurred leading to many neurological disturbances such as
seizures, visual problems & coma.
Responses to ageing
▪ Both anatomical and physiological dead space are increased
▪ The diffusing capacity is decreased
▪ Small increase in the lung compliance
▪ Respiratory muscle strength is diminished
▪ The FRC and The RV are increased. The VC is decreased while the TLC remains unchanged
▪ Regulatory responses to hypoxia and hypercapnoea are diminished
2. diffusion impairment
• low barometric pressure
• thickened blood gas barrier due to
o asbestosis
o fibrosis
9 ©2018 A/L Repeat Campaign
o lung oedema
3. shunts
• patent ductus arteriosus (PDA)
• ventricular septal defects (VSD)
• atrial septal defects (ASD)
4. V/Q imbalance
• COPD
• Pulmonary embolism
Cyanosis
Dusky, bluish discoloration of tissues due to increase of deoxygenated Hb concentration (above
5g/dL)
Depends on;
o Total Hb level in blood(polycythemia)
o Degree of saturation
o State of capillary circulation
Central peripheral
e.g.: - VSD, Pulmonary failure e.g.: - impaired local circulation
Conjunctiva nail beds
tongue
Management of hypoxia
• Hypoxic hypoxia – O2 therapy very valuable except in R→L shunts & V/Q imbalance
• Anaemic, stagnant, histotoxic hypoxia – O2 of limited value. Primary cause should be treated
CO2 narcosis
• If CO2 concentration exceed 7%
o Depression of CNS
o Confusion
o diminished sensorium
o coma
o respiratory depression
o Severe acidosis
o death
Unit: L/min
Normal rate: 400L/min (varies with age, gender, height and ethnicity)
Method
1. Should hold the peak flow meter horizontally.
2. Do not block the indicator with your fingers.
3. Mouthpiece and lips should be sealed.
4. Inhale deeply then blow as fast as possible.
Do this three times and take the highest reading as the result.
Nomenclature
1) Chronotropic = related to heart rate
2) Inotropic = Related to contractility of heart muscle
3) Dromotropic = Related to conductivity of AV node
Heart muscle
Pacemaker tissue/cells
No contribution from Na+ for rapid depolarization
Other features
Parasympathetic Sympathetic
Membrane hyperpolarized Slope of prepotential is
& slope of prepotential is increased
decreased By ANS+ Catecholamines
By vagi (Left-AV Right-SA)
β1 adrenaline receptor
M2 receptor-mainly in SA
present in every cell of
& AV
myocardium
Lies in atrial tissue & not in
ventricle
So Ach’s influence is to
decrease mainly
chronotropic action not
inotropic action
A
c
h
Noradrenalin
R ↓
Ach M2 muscarinic
β1 R
Other factors
Increased Decreased
- Temp. ↑ (tachycardia in fever) - Drugs – Digitalis (ve inotrope)
- Drugs (Depresses nodal tissue &exerts vagal
effects)
Mainly to AV node
ANS
Physiological Pathological
Increase During muscular exercise Fever ( 10 beats / 1
Emotional excitement deg F )
Increased action of
Decreased
High environmental temperature Haemorrhage
baroreceptors
During digestion (mild increase) Hyperthyroidism
Increased action of atrial
stretch receptors (Brain
bridge reflex)
Inspiration
Anger
Most painful stimuli
Hypoxia
Decrease Sleep (55 – 60) Hypothyroidism
Increased action of In trained athletes Increased ICP (Cushing
baroreceptors reflex)
Expiration
Fear
Grief
Stimulation of pain fibers of
trigeminal nerve
SA node
Contractile tissue
Phase
Electrocardiogram (ECG)
Body fluids are good conductors – Changes in potential that measure the
algebraic sum of action potentials can be recorded.
Record of these changes are known as an electrocardiogram.
ECG leads
-ve
Record the electrical potential differences between electrodes placed on the body.
Anterior V3, V4
Septal V1, V2
(+) (+)
LIII LII
I + III = II
ECG Paper
ECG waves are recorded on special graph paper with 1mm2 grid-like boxes
Horizontal – duration
Vertical – wave amplitude
Horizontal
Paper speed usually 25 mm/s
Each 1mm (small square) = 0.04 s (40ms)
Each 5mm (large square) = 0.2 s (200ms)
Vertical
10mm (10 small squares) = 1mV
Atrial repolarization is hidden within ventricular depolarization
T wave is positive because both vector and ion flux are opposite during repolarization
0.1 s
0.04 s
0.2 s
During inspiration
Tachycardia impulses
is seen during in theBradycardia
inspiration. vagi from isthe stretch
seen duringreceptors
expiration.inIntra-thoracic
the lungs inhibit
pressure
the cardioduring
decreases inhibitory area So
inspiration. in venous
the medulla
return oblongata. The tonicAtrial
to the atria increases. vagal discharge
stretch thatare
receptors keeps
the heart rate slow decreases, and the heart rate rises.
stimulated which results in vasodilation and hypotension. These receptors in turn signal the
medullary control centers to increase the heart rate. This is called the Bainbridge reflex.
Cardiac Axis
The direction of the largest dipole in the frontal plane is called the Cardiac axis of the heart.
The Cardiac axis has a very wide, normal range, from −30° to +90 °.
The Cardiac axis depends partly on an individual’s anatomy; the heart.
Cardiac axis are more vertical in a tall, thin person than in a short, broad-chested individual.
The axis also becomes more vertical during each inspiration because the descending diaphragm
tugs on the pericardium and drags down the apex
The axis depends also on the relative thickness of the right and left ventricle walls
Hypertrophy of the left ventricle (e.g. due to exercise training, hypertension or hypertrophic
cardiomyopathy) shifts the electrical axis to the left (left axis deviation)
Hypertrophy of the right ventricle (often due to pulmonary disease) produces right axis
deviation
Mechanical
events of the
cardiac cycle
1) late diastole
2) atrial systole
3) ventricular systole
a. isovolumetric ventricular contraction
b. ventricular ejection
4) early diastole→ a) Protodiastole
b) Isovolumetric relaxation
c) Rapid ventricular filling
Late diastole
Atrial systole
❖ Coincides with late ventricular diastole
❖ About 30% of ventricular filling occurs
❖ Atrial musculature contracts & propels additional blood to ventricles
❖ Orifices of SVC, IVC & pulmonary veins narrow and inertia of the
blood moving towards the heart trends to Keep blood in it
But some regurgitation occurs
Early diastole
1) Protodiastole (0.04 s)
▪ Ventricular muscle is fully contracted
▪ Already falling ventricular pressure drops more rapidly
▪ It ends when the momentum of ejected blood is
overcome and
▪ Aortic & pulmonary valves closed.
2) Isovolumetric relaxation
▪ Both AV & semilunar valves are closed
▪ Ventricular pressure continues to drop rapidly
▪ Atria in diastole are filling and atrial pressure increases
▪ Ends when ventricular pressure falls below atrial pressure
& AV valves open; permitting ventricles to fill.
𝑆𝑉
𝐸𝑗𝑒𝑐𝑡𝑖𝑜𝑛 𝐹𝑟𝑎𝑐𝑡𝑖𝑜𝑛 = = 65%
𝐸𝐷𝑉
Heart sounds
S2 Shorter - high pitched Vibrations set up by End of ventricular Loud when diastole
(Dub) closure of aortic & systole P. is elevated in
pulmonary valves aorta
Murmur
• Abnormal sound within heart
• When the velocity of blood surpasses the critical velocity, flow becomes
turbulent and creates sound
in severe anaemia cardiac output is increased, thence increased volume of blood with low viscosity flows across a
normal aortic valve, being turbulent of blood flow produces a systolic murmur
(NOTE- Systole and diastole of the cardiac cycle are named regarding to ventricles)
Pulse
Characteristics of pulse
• Rate
• Rhythm
• Character – feeling of pulse (e.g. :- thready in shock)
• Volume – normal / high / low (e.g.:- strong pulse during exercise ↑SV)
• Presence or absence of femoral pulse in relation to radial pulse (e.g. Post ductal coarctation)
• Vessel wall [e.g. Adults – vessel wall is calcified, so pulse is strong
Children – vessel wall is elastic, so pulse is weak]
Arterial pulse
• Blood forced into aorta during systole sets up a pressure wave that travels around arteries
• This pressure wave expands arterial wall which is palpable as pulse
• The pulse has no relationship with the flow of blood within the vessel.
• The speed of the pulse increases with the decrease of elasticity. (e.g. – old age, in peripheral regions)
JVP
❖ Measurement
1. Right internal jugular vein
2. Patient at 450 and head turned slightly to the left (at 450 so that jugular venous pressure is seen at
the neck. If kept supine, position where JVP is seen moves up)
3. Vertical distance between angle of Louise & highest level of jugular vein pulsation
4. Add 5cm (since R. atrium is 5cm below the angle)
Central Venous Pressure (CVP) – pressure in the SVC near the right atrium (= R. atrial P)
• Important determinant of Preload
Normal CVP=8 cm H2O (6mmHg during expiration, 2mmHg during inspiration)
➢ Venous pressure falls during inspiration as a result of the increased negative intrathoracic pressure &
rises again during expiration.
The changes in right atrial pulse pressure are transmitted to the great veins producing 3 characteristic waves
Cardiac output
The degree to which Resistance against which The intrinsic ability of heart
myocardium is stretched blood is expelled muscle to generate force and to contract
before it contracts at a given degree of stretch
( TPR)
( EDV) • independent of neurohumoral factors
but modifiable by them
Factors affecting EDV
Venous Return Ventricular filling time Ventricular filling pressure Ventricular compliance
➢ Describes the ability of the heart to change its force of contraction (& stroke volume) in response to changes
in venous return.
SV α EDV
Special.......
SV ➢ Chronotropy → Heart rate
➢ Inotropy → Force of contraction
➢ Dromotropy → Transmission in cardiac conductive tissue
Cardiac index = CO
Surface area of the body
Measuring CO
1) direct Fick method
CO = O2consumption (ml/min)
Theoretical Amount of O2 in − Amount of O2in
arterial blood (ml/L) venous blood (ml/L)
• Stroke work of LV is higher than RV (Because LV has to pump blood against a higher pressure in aorta)
• in stroke work due to an in MAP causes a greater O2 consumption than in stroke volume.
• Aortic Stenosis is considered to cause an increase in pressure work as a higher pressure must be given from
within the chamber.
• Aortic regurgitation is considered to cause an increase in volume work as some amount of blood flows back,
needing a larger volume to be pumped.
• An in afterload causes greater O2 consumption than an in preload.
Angina pectoris is more common in aortic stenosis than aortic regurgitation.
WHY?
1. In aortic stenosis pressure work increases. (O2 consumption for a given amount of pressure work is
higher than that for the same amount of volume work)
2. In stenosis ventricular hypertrophy occurs. This causes the intramyocardial blood vessels to be
compressed and occluded, increasing the pressure needed to perfuse the ventricular myocardium.
3. In aortic stenosis the pressure in the aorta is reduced, thus reducing pressure in the left coronary
artery. So the perfusion pressure of this artery is insufficient to perfuse the myocardium.
• Elastic tissue % aorta > large arteries > small arteries > arterioles
• Smooth muscle % aorta < large arteries < small arteries < arterioles
• Muscle is innervated by noradrenergic fibres (constrict)
(But in some instances, by cholinergic fibres. E.g. - Cutaneous blood vessels have muscarinic cholinergic )
• Arterioles are the major site of resistance to blood flow (dilate)
(As R 1/r4; small change in calibre causes large change in TPR)
larger elastic arteries stretch during systole and recoil during diastole(aorta)
Capillaries
P = MAP − MVP
Streamline Flow * When the vessel is obstructed flow
Parallel to long axis beyond that become turbulent.
Laminar Occurs in layers * Turbulent flow produces a noise
Flow Layer close to the wall doesn’t flow due to vibration.
Centremost layer has highest velocity * Results in bruits and murmurs
Flow is silent * This is being used as the principle of
Occurs in normal blood vessels auscultation method of BP measurement
• Laminar flow occurs up to a critical velocity
Re – Reynolds number * Higher the Re, higher the turbulence
Re = vD v – velocity
D – diameter
If Re<2000, flow is usually not
– density
turbulent
– viscosity
If Re> 3000, turbulence is almost
always present.
➢ Turbulence increases at branching points
Resistance
Poiseuille – Hagen Formula
mathematical relationship between the flow, viscosity and radius
* Flow through a vessel is
Q=P → doubled by an increase of only
Q = r4P R= 8l 19/ in its radius.
R
8l r4 * When the radius is doubled,
resistance is reduced to 1/6 of its
• Resistance to blood flow → Vascular hindrance previous value.
Radius (R 1/r4)
Determined by
Viscosity (R )
Conditions Conditions
Polycythaemia Anaemia
Temperature Pregnancy
Flow rate THINK… why can murmurs be heard
Plasma volume in pregnant women even though they
Plasma proteins (mostly immunoglobulins) do not have any disease?
Hereditary spherocytosis
➢ Increased viscosity of the blood, causing increased peripheral resistance leads to hypertension.
Shear stress
• Shear stress → force created on the endothelium parallel to the long axis of vessel
• sensed by primary cilia
changes in shear stress produce marked
changes in the expression of genes by
Shear stress = viscosity x shear rate endothelial cells (growth factors,
() () (dy/dr) interferons )
Average velocity
blood flow is driven by the difference in total energy between two points
(pressure energy is just one kind of energy that affect the flow)
• smaller the radius, lower the tension needed to balance distending pressure
Resistance Capacitance
• Principle site of peripheral resistance Have large capacity to accommodate extra
• Only 2 % of cardiac output volume of blood
is contained. e.g. 1. Veins (50% of blood)
e.g. 1. Small arteries & arterioles 2. Low pressure system
2. High pressure system
Arterial Pressure
Systolic pressure: - Peak pressure in aorta and other large arteries during cardiac cycle
Depends on CO
120 mmHg
Diastolic pressure:- Minimum pressure in aorta and other arteries during cardiac cycle
Depends on TPR
70 mmHg
Recorded as SBP/DBP = 120 mmHg
70
15 © 2018 A/L Repeat Campaign
Measurement of arterial blood pressure (Korotkoff sounds)
• laminar and turbulent flow provide physical basis for the auscultation method of blood pressure
measurement
Snapping sound onset marks SYSTOLIC phase I
Becomes soft murmur (bruit) phase II
Sounds louder clearer phase III
Muffling of sounds phase IV
Sounds disappear phase V
• 1/3 PP is taken due to the time difference and the pressure difference between the two
• Systolic pressure increases with age.
• Diastolic pressure, 1st increases then decreases.
• Therefore, pulse pressure increases.
•
Venous Pressure
Above
• Peripheral veins →
RA
Below
Thoracic pump
Venous Pressure is affected by Muscle pump
Variations in RA pressure
Shunt
• Carotid body has the highest blood flow per 100g per minute
(since neurons produce ATP almost entirely by oxidative phosphorylation with very limited
capacity for anaerobic metabolism , brain is unable to withstand ischemia)
Depends on
1. CPP - MAP, ICP
2. Viscosity
Hyperventilation causes hypocapnia, causes cerebral vasoconstriction and reduces CBF. Used
to decrease ICP in cerebral oedema especially when there is intracerebral bleeding, until
definitive management.
Lowering the head increases CBF. Practiced with immediate effect in a person who faints.
Hypercarbia causes cerebral vasodilation and increased CBF, increasing ICP, and stimulating
pain fibers.
Important in Hypertension
Coronary circulation
• 250ml/min (5% of CO)
• Supplies myocardium (no supply from blood within chambers)
• Myocardium
–High O2 consumption and high O2 extraction (70-80%)
–Requires regular uninterrupted coronary blood flow to function
• Left & right coronary arteries are end arteries.
• If need to increase O2 supply - blood supply is increased. (Flow is coupled to O2 demand)
• Considerable auto regulation present
Coronary flow to
• Left ventricle – mostly in diastole
• Other chambers – throughout cardiac cycle
• Most superficial part of LV is supplied throughout
cardiac cycle
• Subendocardium of LV is supplied exclusively in
diastole
Systolic compression
•Left ventricular wall- Generate a large force
during contraction within myocardium.
• Due to intra myocardial forces, pressure inside
becomes greater(121mmHg) than aortic
pressure(120mmHg). So coronary
vessels get collapsed increasing the coronary
vascular resistance.
• In systole, blood supply is interrupted to the area
close to the cavity (sub endocardium). Blood flows only
during diastole. (But more superficial areas of the L
ventricle get blood supply throughout the cardiac cycle.)
Coronary circulation
α β
Constriction Dilation
(Increase activity of heart)
increased work of
expelling blood against a
raised pressure (higher
afterload)
Cutaneous circulation
• Reactive hypermia
• White reaction
• Triple response
o Reddening
o Swelling
o Flare
Hypertension
Causes;
• Essential hypertension – multi factorial
• Renal disease – increased secretion of renin
• Hormonal overactivity – aldosterone, glucocorticoids,
catecholamine, GH
• Coarctation of aorta
• Drugs – oral contraceptives, cocaine
• Pregnancy induced hypertension
• Increased blood viscosity – polycythemia
• Baroreceptor resetting at a higher BP in chronic HT
• Vasodilators
• Ca2+ channel blockers
• Angiotensin Converting Enzyme Inhibitors (ACEI)
• Angiotensin II Receptor Blockers (ARB)
• α blockers
• Drugs decreasing heart rate
Hypertension
Sustained elevation of systemic blood pressure above 140/90 mmHg. ( either > 140 systolic or
> 90 diastolic BP)
If not treated leads to target organ damage
Heart – MI
Brain – strokes
Kidney – renal failure
BP determined by Cardiac output & Peripheral resistance
Hypertension usually caused by increased peripheral resistance
Peripheral resistance depends mostly on caliber of arterioles ( PR α 1/ Diameter4 )
Baroreceptor are reset at a higher BP in chronic Hypertension.
curve shifted to right to higher values.
This is one reason that it is difficult to lower the BP in chronic HT as the reset
baroreceptors identify a high BP as within the normal
Causes;
Essential hypertension – multi factorial
Renal disease – increased secretion of renin
Hormonal over activity – aldosterone, glucocorticoids,
Catecholamine, GH
Coarctation of aorta
Drugs – oral contraceptives, cocaine
Pregnancy induced hypertension
Increased blood viscosity – polycythemia
Venous Blood
HR SV volume
Calibre of
Arterial BP arteriols
The principles of management address the reduction in parameters that increase the blood
pressure. The parameters coloured are the ones which are most commonly addressed in clinical
practice
1 ©2018 A/L Repeat Campaign
Principles of management
Vasodilators (decrease systemic vascular resistance by decreasing arteriolar constriction)
venodilation also contributes by increasing the venous blood volume thereby reducing venous
return
Ca2+ channel blockers (Calcium is required for smooth muscle contraction and
blockage of calcium channels cause vascular smooth muscle relaxation)
Angiotensin Converting Enzyme Inhibitors (ACEI) – prevent AT I formation
Angiotensin II Receptor Blockers (ARB) (ii and iii inhibit the vasoconstrictor
action of angiotensin II)
alpha blockers (alpha receptor stimulation causes vasoconstriction and this
action is blocked)
beta receptor blockers (decrease heart rate and contractility)
Diuretics (reduce blood volume by increasing urine output –and thus reduce venous return,
EDV, SV and CO)
Others
Heart failure
Inability of the heart to maintain an enough cardiac output to meet tissue needs
Types
o acute or chronic
o LV (commonly), RV or both ventricles
o Systolic (deficient pumping) or diastolic ( deficient relaxing )
o High-output ( Heart pumps harder but tissue needs are greater – anemia ) or
low-output {( common) ( Heart unable to pump normal amount of blood)}
LV failure RV failure
Pathophysiology Reduced LV output Reduced RV output
Tissue perfusion Reduced (apathy, faintness) Reduced (apathy, faintness)
Management –
↓preload and afterload
Note - lowering preload is only for systolic failures
lowering afterload is for both types
Decrease venous congestion-diuretics, venodilators, aldosterone antagonist
Decrease peripheral resistance-ACE inhibitors, Angiotensin receptor blockers
Improving contractility-Digitalis, ACEI
Improving symptoms
Reducing mortality- beta blockers
f
This is the Frank – Starling curve
This curve demonstrates how Increase
in EDV decrease the ventricular
performance in heart failure
Definition -
Inadequate tissue perfusion with a relative or absolute inadequacy in cardiac output.
Classification
o Hypovolemic - Inadequate intravascular volume
Eg - Haemorrhage, trauma, severe diarrhoea
o Cardiogenic – Inadequate pumping action of heart
Eg - Myocardial infarction, heart failure, arrhythmia
o Obstructive – Obstruction of bloodflow in lungs or heart
Eg -Tension pneumothorax, cardiac tamponade, pulmonary embolism
o Distributive – Vasodilation causing increased size of vascular system despite normal
intravascular volume
Eg - Neurogenic shock (major brain or spinal injury), Anaphylaxis (triggered by
allergens), Septic shock
Cardiac tamponade - fluid collects between myocardium and pericardium. pressure within the
pericardium prevents heart chambers from expanding fully. It reduces the preload.
Pulmonary embolism – blockage of a main artery of the lung or one of its branches
Neurogenic- due to disruption of autonomic pathways in spinal cord. lack of sympathetic supply
for arterioles causes hypotension. Unopposed vagal action causes bradycardia
Anaphylactic shock- triggered by allergens, results in widespread vasodilation
Septic shock- due to an infection
In Hypovolemic shock,
o Heart rate (increases)
o Peripheral (Systemic) Vascular Resistance -(increases)
o Urine output (decreases)
o Skin (vasocontricted and increased sweating –cold,
bluish, clammy skin)
o Respiration (rate increases for increased oxygenation of
blood)
o Hormonal activation (increased catecholamines, rennin,
angiotensin, aldosterone, vasopressin --- )
( Described in detail below )
So, the venous return to the right atrium is reduced. It causes reduced preload and
stroke volume resulting in reduced cardiac output. It results in decrease in blood
pressure.
Low blood volume causes reduction of discharge rate and stimulation of volume
receptors on atrial wall at the opening of the SVC, IVC and pulmonary vessels. low blood
pressure causes reduction of discharge rate and stimulation of carotid sinus and aortic
arch baroreceptors.
This reduces the neural discharge of buffer nerves to the nucleus tractus solitarius which in turn
causes the stimulation of the vasomotor Centre and inhibition of the cardiac inhibitory Centre
resulting in an overall sympathetic stimulation and reduction of parasympathetic activity.
Furthermore, sympathetic stimulation also causes constriction of veins displacing blood towards
the heart, thus increasing venous return. Decreased vagal activity increases heart rate. Also,
sympathetic stimulation via both norepinephrine and epinephrine on β1 receptors increase
heart rate and contractility of heart muscle. Both these factors increase cardiac output and
hence blood supply to vital organs.
Increased heart rate causes rapid but thready pulse because the blood volume is
reduced.
Another part of the mechanism to maintain perfusion to vital organs is auto regulation.
This is the dilation of vessels in brain and heart due to local metabolites which maintains
a normal blood flow despite the reduction in volume.
In addition, a decrease in the stimulation of intra renal baroreceptors would cause renin to be
secreted by juxta glomerular cells which converts Angiotensinogen to Angiotensin I which is in
turn converted to Angiotensin II by ACE which is produced by the endothelium of pulmonary
vessels.
Angiotensin II causes the secretion of aldosterone and ADH which increase renal Na+
reabsorption from tubules and water reabsorption from collecting ducts respectively.
Angiotensin II constricts renal afferent and efferent arterioles; efferent arterioles are
Constricted more and angiotensin II causes constriction of mesangial cells. In both these
ways it will reduce UFR resulting in oliguria and thus increasing blood volume in turn
increases the blood pressure to supply vital organs.
Hemorrhage causes decreased blood flow through aortic and carotid body chemo
receptors resulting stagnant hypoxia which stimulate the peripheral chemoreceptors.
And due to the blood loss amount of RBC is reduced. Resulting anemia causes
Inadequate tissue perfusion.so the cells generate energy from anaerobic glycolysis. Lactic Acid is
produced. Lactic acid reduces blood pH and stimulate peripheral chemoreceptors.
The impulses from these via afferent nerves modulate the respiratory center to increase
discharge in the efferent nerves supplying respiratory muscles which would increase respiratory
rate and depth resulting in adequate O2 supply to vital organs.
In addition, the release of epinephrine as a stress reaction in shock could be having the same
effects of a sympathetic stimulation.
It is in the wake of these physiological adaptations inside the body that you would see a rapid
thready pulse, increased respiratory rate, oliguria and cold clammy hands in a person with
shock.
Echocardiography
Pulses of ultrasonic waves are emitted from a transducer
Ultrasonic waves reflected back from structures when acoustic
impedance changes
Reflected waves received by the same transducer
Used to –
o Visualize cardiac chambers, valves, vegetations (structures)
o Different axes of the heart observed
o Calculate ejection fraction
o Visualize flow in chambers (with colour Doppler )
Angiography
Medical imaging technique
Used to study the structure, lumen, and flow dynamics in blood vessels
Eg. Narrowed, blocked, enlarged, or malformed arteries or veins
Especially supplying the brain, heart, abdomen, and legs
Radio-opaque dye (radio contrast agent) inserted into the blood vessel lumen via a catheter
Path of the dye studied using a series of x-ray imaging obtaining an angiogram
Doppler Ultrasound
Measures blood flow velocity with Doppler flow meters using ultrasonic waves
The frequency of the reflected wave changes (proportionate to blood flow rate) due to Doppler
effect
Doppler studies test flow in
o Arteries
o Veins
o Heart
1) Auto Regulation
Constriction of arteriole
Decrease flow
Increase in decrease in
PCO2 PO2
T pH
K+
Lactate (Mainly in skeletal Muscles)
Histamine (Increases vascular Permeability)
Adenosine (only in cardiac muscle)
❖ In generalized/ systemic hypercapnia vasodilation takes place only in Brain and Skin.
NOS 2 – macrophages
NOS 3 – endothelium
Nitroglycerin – treatment
in angina
Vasodilators
VIP (act via NO)
Kinins (via NO)
Natriuretic hormones
ANP, BNP found in blood
CNP not found in blood (MCQ)
ANP
• Increases when atria are stretched and central venous P is increased.
• Natriuresis (increased excretion of sodium and water in urine) (MCQ)
• Vasodilation
BNP- secreted when ventricles are stretched
- Also from brain
CNP- c type natriuretic peptide
Paracrine action
From brain, kidneys, pituitary
Vasoconstrictors
Epinephrine, Norepinephrine, Vasopressin, Angiotensin II, Thromboxane A2
Receptor Baroreceptors
Centers IN Medulla
Effector
Buffer nerve – Both Vagus and glossopharyngeal nerves together known as buffer nerve. Vagus nerve carries
impulses from aortic sinus. Glossopharyngeal nerve carries impulses from carotid sinus.
Centers
Baroreceptors
Valsalva Maneuver
Take a deep breath → exhale against closed glottis → blood pressure goes up (due to the
compression of aorta at onset) → Venous return decreases (due to compression of great
veins) → CO decreases → blood pressure decreases → baroreceptor discharge decreases →
parasympathetic inactivate, sympathetic activate → HR increases, Contractility increases, CO
increase, vasoconstriction → BP increase with tachycardia → exhale → venous return come
to normal → blood pressure increases → baroreceptor discharge increases → sympathetic
inactivates parasympathetic Activates→ HR decreases, contractility decreases → still vessels
compressed → Hypertension with bradycardia
CO TPR Sympathetic
(No parasympathetic)
Afterload BP
TPR (Total peripheral resistance)
Size of ventricle • Sympathetic
Viscosity • Catecholamines
• Digitalis
• Xanthines
SV • Positive Inotropes-
Myocardial contractility → Dopamine
• Force frequency relation
• Parasympathetic
• Hypoxia
• Hypercapnia
• barbiturates, quinidine, procainamide
Frank Starling Law
• Heart failure
EDV
Adenosine----PO4-----PO4----PO4
CVS in exercise
Types of contraction
Isometric Isotonic
A prompt
increase in HR
a result of psychic stimuli on medulla oblongata. [due to a decrease in vagal tone (mainly)
+ increase in sympathetic activity]
Increased total peripheral resistance due to Net fall in PR due to vasodilation in muscles
compression of vessels (increased intra- (initially neural, then local vasodilation due to
muscular pressure due to sustained accumulation of metabolites-CO2, K+,
contraction) vasoactive substances)
Decreased or zero muscle BF (>70% of max Increased muscle blood flow
muscle tension)
Low increase in venous return (lack of muscle Marked increase in venous return
pump)
Stroke volume relatively unchanged (due to very Marked increase in stroke volume
less increase of venous return)
CO increased (CO=HR*SV; HR has ) CO markedly increased (both ,SV )
Sharp increase in systolic & diastolic pressure Moderate increase in systolic
(increased CO and PR) pressure. (increased CO)
Diastolic pressure decreased/unchanged (due
to the fall in PR)
Sympathetic
Exercise Discharge(psychic) Accounts mostly for in
CO
Contractility (of HR
(270%)
Max HR decreases
with age (Max
(Frank- Starling) HR=220-age)
EDV SV (50%) Cardiac
Output
×6
Increase due to,
(5.5→20-35) Muscle pump
Thoracic pump
Venous return
(Not the main Mobilization from viscera
cause of CO) Noradrenergic
venoconstriction
(shunting blood from
reservoirs
:skin, GUT)
Increased pressure
transmitted from
dilated arterioles to
veins.
• Therefore they can achieve a given increase in Cardiac Output by further increases in Stroke
volume without increasing their HR as much as an untrained individual does.
RS in exercise
Changes occur in:
• O2 consumption (cellular respiration)
• Pulmonary ventilation
• Diffusing capacity External and pulmonary respiration
O2 consumption:
O2 Consumption
VO2 max
Exercise intensity
❖ Above the exercise intensity corresponding to VO2 max oxygen consumption levels off.
❖ Stored 2L of O2 → Enough for 1min of heavy exercise.
❖ Rate of utilization of E stores > Rate of aerobic resynthesis of E stores
❖ Therefore, anaerobic metabolism begins Lactate is produced
O2 debt incurred
90 min
• During moderate exercise Arterial pH, PCO2 & PO2 remain constant.
• When exercise becomes more vigorous buffering of lactic acid liberates more CO2.
This further increases ventilation.
• Increases ventilation (CO2 washout) & CO2 production remain proportionate. So,
alveolar and arterial CO2 change relatively little – isocapnic buffering
• Further accumulation of lactic acid (stimulates Carotid body) causes increased ventilation
which outstrips CO2 production. Thus alveolar & arterial PCO2 fall.
• The decline in arterial PCO2 provides respiratory compensation for the metabolic acidosis
caused by lactic acid.
Diffusing capacity:
Rate at which O2 diffuses from alveoli to blood
Changes in muscle
• ↑ Muscle blood flow (×30)
×100
• ↑ O2 extraction (×3)
O2 extraction
•More O2 used by muscles muscle PO2 falls O2 gradient from blood
to muscle increased
• High Temperature/ High 2,3BPG & acidosis (due to accumulation of CO2) shift the
O2-Hb dissociation curve to right. Reduces affinity of Hb for O2
Heat (75-80%)
I
N
C
R
Myofibrils E
A
Mitochondrial Ez S
Glycogen stores E
Stored triglycerides
- Metabolic systems (aerobic + anaerobic)
Midclavicular line
Transpyloric plane
Transtubercular plane
Surface Anatomy
• T9 – Xiphoid
• L1 – Transpyloric plane {passes through tips of 9th costal cartilage (bears a distinctive step) anteriorly
and lower border of L1 posteriorly)}
*Lies halfway between the suprasternal notch & the top of the pubis /a hand’s breadth below the
xiphoid
*transpyloric plane passes through,
1. Pylorus of stomach 5. Termination of spinal cord
2. Hila of the kidneys 6. Duodenojejunal flexure
3. Fundus of gall bladder 7. Origin of superior mesenteric artery
4. Neck of pancreas 8. Tip of 9th costal cartilage
9. Splenic vein → portal vein
Mnemonic-
Please - pylorus
Feed – fundus of gall bladder
Him – hilum of the kidney
Some – origin of superior mesenteric artery
Love – lower end of spinal cord
Liver (Points)
1. Tip of right 10th rib in midaxillary line
2. Left 5th intercostal space in midclavicular line
3. Right 5th intercostal space in mid axillary line
*Not palpable in normal subjects
Kidney
Hilum-on the transpyloric plane 4 fingers’ breadth from the midline
*This plane passes through the upper part of the hilum of the right kidney & through the lower part of
the left kidney
* Two horizontal lines
1. Level of upper border of T12
2. Level of center of L3
*Right kidney is 1 inch lower than the left
*Left kidney is nearer to the median plane
Goes to corona of penis Over scrotum Over perineum Goes over the inguinal
(junction between neck and ligament and blends with
shaft of the penis fascia lata (Holden’s line)
Dartos fascia Colles’ fascia
Buck’s fascia
Line of attachment of membranous layer
o Holden’s line-a horizontal line extending laterally
from the pubic tubercle where the membranous
layer is firmly attached to the deep fascia of the
thigh
**Importance of this line- when the urethra is injured in
the perineum, it prevents extravasated urine from
descending into the thigh beyond this line
o Pubic tubercle
o Body of pubis & margins of the pubic arch
o The posterior border of the perineal membrane
❖ RECTUS SHEATH
▪ Definition–Aponeurotic sheath covering the rectus abdominis muscle
▪ 2 walls-Anterior wall- continues throughout
Adherent to the rectus muscle at tendinous intersections
- Posterior wall - free
Few para-umbilical veins accompany ligamentum teres. In portal vein obs: dilated veins cause
caput medusae at the umbilicus
▬ Lymph drainage
Above umbilicus – Axillary nodes
Below umbilicus – Superficial inguinal nodes
➢ Water-shed line – lymph and venous blood flow upwards above the plane of umbilicus &
downwards below the plane
- Innervation -lower 5 intercostal and subcostal (between internal oblique & transverse
abdominis) T7- xiphoid process, T10- umbilicus level
- Iliohypogastric L1
- Ilioingunal L1
- Subcostal and iliohypogastric supply the gluteal region as well
-between the anterior superior iliac spine & the pubic tubercle the external oblique
aponeurosis folds on itself to form the inguinal ligament
-internal oblique muscle arises from its lateral 2/3 -transversus abdominis arises from its lateral 1/3
-Conjoint tendon: fused lowest aponeurotic fibers of the internal oblique & transversus abd.
muscles. Is attached to the pubic crest
INGUINAL CANAL
▪Definition–Oblique musculo-aponeurotic passage in lower anterior abdominal wall just above the medial
half of inguinal ligament, extending from deep ring to superficial ring(4cm)
▪Rings -Superficial inguinal ring
*Is a V shaped gap in the external oblique aponeurosis, above the pubic crest
- Deep inguinal ring
*Is an opening in the fascia transversalis, situated ½ inch above the midpoint of the inguinal
ligament and immediately lateral to the stem of the inferior epigastric artery
▪Walls–
Anterior wall
• Whole extent – skin, superficial fascia, external oblique aponeurosis
• Lateral 1/3 – Internal oblique muscle fibers
Posterior wall
• Whole extent – Fascia transversalis, extraperitoneal tissue, parietal peritoneum
• Medial 2/3 – Conjoint tendon, at the medial end by the reflected part of the inguinal ligament
• Lateral 1/3 -interfoveolar ligament
Roof
• Arching fibers of internal oblique & transversus abdominis (arching in front of the cord laterally to
behind the cord medially)
Floor
• Grooved upper surface of Inguinal ligament
• Medial end by Lacunar ligament
▪Contents–Male
1. Spermatic cord (male reproductive system)
• three layers of fascia – the external spermatic, from the external oblique aponeurosis; the cremasteric,
from the internal oblique aponeurosis (containing muscle fibres termed the cremaster muscle); the
internal spermatic, from the transversalis fascia;
• three arteries – the testicular (from the aorta); the cremasteric (from the inferior epigastric artery); the
artery of the vas (from the inferior vesical artery);
• three veins – the pampiniform plexus of veins (draining the right testis into the inferior vena cava and the
left into the left renal vein), and the cremasteric vein and vein of the vas, which accompany their
corresponding arteries;
Female
1. Round ligament of 2. Ilioinguinal nerve
uterus
medial lateral
A
Surface marking of inferior epigastric artery
0.5in just above the femoral pulse (midinguinal point=halfway between pubic symphysis and anterior
superior iliac spine)
Abdominal incisions
• McBurney’s incision – for appendicectomy
(Iliohypogastric and ilioinguinal nerves should be
preserved)
• Kocher’s incision
• Midline incision
• Paramedian incision
• 2 Layers – Parietal
Visceral
• Various folds or reflections of the peritoneum connect viscera to abdominal wall or to one
another.
Some are properly called folds, others are called mesentery, omentum or ligament.
Ligamentum teres - from umbilicus to the inferior margin of Falciform lig. (remnant of
left umbilical vein) (left is left)
Median umbilical fold - containing median umbilical lig. (remnant of urachus), from apex
of bladder to umbilicus
Medial umbilical fold - containing medial umbilical lig. (remnant of umbilical artery)
Lateral umbilical fold - containing inferior epigastric vessels (only up to arcuate line)
Superior layer of coronary lig. – formed from the right leaf of the Falciform lig.
Right triangular lig. – formed where the superior & inferior layers of the Coronary lig. meet.
❖ Omentum
Contents Attachment
✓ hangs down from greater curvature of stomach
✓ Double layer of peritoneum folded on itself to form four
✓
1. Greater omentum R & L gastro epiploic vessels layers
✓
Lymph nodes & lymphatics ✓ Anterior two layers descend from greater curvature
✓ Curves back on itself & ascends
✓ Blend with – peritoneum on anterior surface of transverse
✓ colon & transverse mesocolon
✓ Bile duct
✓ Hepatic artery
✓ Portal vein
2. Lesser omentum ✓ Right gastric vessels ✓ Superior - liver (inverted L shaped attachment to porta
✓
Hepatogastric lig. ✓ Left gastric vessels hepatis & Ligamentum venosum)
✓
Hepatoduodenal lig. ✓ Lymph nodes ✓ Inferior - lesser curvature of stomach, 1st part of duodenum
(Extends from abdominal oesophagus → lesser
✓ Gastric nerves curvature → 1st part of duodenum )
2. Greater sac - Rest of the space among the serous coated organs
Epiploic foramen - a slit at the right border of lesser sac through which it communicates with greater sac
Boundaries Anterior – Right free margin of lesser omentum
Containing – Common bile duct (R)
Hepatic artery proper (L)
Portal vein (P)
Posterior – IVC, T12 vertebra, right suprarenal gland.
Inferior – 1st part of duodenum
Superior – Caudate process of liver
Pringle’s maneuver- haemorrhage during cholecystectomy is controlled by compressing the hepatic artery at the free
margin.
❖
Peritoneal compartments
1. Right sub-phrenic space (closed above by – superior layer of coronary lig.)
2. Left sub-phrenic space (closed above by – left triangular lig.)
3. Right sub-hepatic space(closed above by – inferior layer of coronary lig. & right triangular lig.)
4. Right para colic gutter (lateral to ascending colon)
5. Left para colic gutter (lateral to descending colon)
➢
Recto-vesical pouch – a peritoneal pouch between
rectum & bladder in males
➢
Recto-uterine pouch (pouch of Douglas) - a peritoneal
pouch between rectum & uterus in females -most
dependent part of the peritoneal cavity. (when sitting in
inclined position)
➢
Vesico-uterine pouch - a peritoneal pouch between uterus & bladder in females
•
Clinical
Peritonitis – Inflammation of peritoneum o Caused by
=>
Ascites – Fluid in peritoneal cavity
▪Fluid Collects in the Lesser sac => Fluid may pass through epiploic foramen to hepatorenal
pouch
1. By Posterior Gastric ulcer 2. By Pancreatitis - Pancreatic pseudocyst
Fluid Collects in the Hepatorenal pouch of Morrison’s => Subphrenic abscess (Commonest site)
✓
Most dependent part in the supine position
By spread of infection from GB, Appendix
▪Treatment =>
✓
Paracentesis – Removal of fluid in abdomen by puncturing the abdominal wall
✓
Posterior Colpotomy – Drain pus from the rectouterine pouch of Douglas through
Rectum or Posterior fornix of the vagina
✓
Pneumoperitoneum
– Air in peritoneal cavity
✓
Haemoperitoneum – Blood in peritoneum
o Inflammation of Parietal Peritoneum => localized severe pain & tenderness (pain on touch)
4. Internal Hernia –
o Through epiploic foramen into the lesser sac (Strangulated)
o Paraduodenal fossa => between the duodenojejunal flexure and the Inf. Mesenteric V.
o Intersigmoid fossa => formed by the inverted V attachment of the meso sigmoid
Pyloric
sphincter
▪Relations –
-Peritoneal,
Ventral mesogastrium (dorsal part) - lesser omentum
Dorsal mesogastrium 1.along the greater curvature- greater omentum
Along the
lesser
curvature
To the rest of
greater curvature
(Right gastroepiploic artery lies closer to the greater curvature. Therefore, during partial gastrectomy
greater omentum is divided below the right & above the left gastroepiploic arteries.)
Venous drainage :
Nerve supply
Sympathetic Greater splanchnic nerves
Vasomotor action
Contract the pyloric sphincter
Pathway for pain sensation
Parasympathetic From vagi
Increase motility & secretions
Hepatic branch
Clinical
• posterior ulceration of stomach, damaging the pancreas & splenic artery
common in lesser curvature because rugae are longitudinal (gastric canal)
• gastric carcinoma- commoner along greater curvature
• “signal nodes” (Virchow’s nodes) – left supraclavicular node is enlarged (Troisier’s sign), mostly due
to gastric carcinoma
• pyloric stenosis – causes vomiting after meals
1. Regarding stomach
a. Prepyloric vein marks the pyloric sphincter
b. Cardiac orifice lies deep to the left seventh costal cartilage
c. Part of lesser sac lies within gastrocolic ligament
d. Left supraclavicular nodes enlarges in gastric carcinoma
e. Lymph from upper part of greater curvature drains into pancreaticosplenic nodes
2. The stomach
a. Is supplied in part by arteries arising from the splenic artery
b. Is supplied by arteries which each arise from branches of the coeliac trunk
c. Has a venous drainage passing equally to the portal and systemic venous systems
d. Is lined by columnar and squamous epithelium
e. Is totally covered by serosa (peritoneum)
2) DUODENUM
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• C shaped loop around head of pancreas
• Secondarily retroperitoneal except duodenal cap. (duodenal cap - 1st half of the 1st part)
• Forms lower most boundary of epiploic foramen of Winslow.
Relations of Duodenum
• Two papillae: Major – hepatopancreatic ampulla (ampulla of Vater). 8-10cm distal to pylorus
Minor – accessory pancreatic duct opens 2cm above the major papilla
• Duodenal cap: Seen after a barium meal. 1st part of duodenum is seen as a shadow.
o Reason: absence of plicae circularis.
13 2018 A/L Batch Repeat Campaign
• Suspensory ligament of Treitz
• between DJ junction and right crus of diaphragm
• marks DJ junction
• Inferior mesenteric artery lies immediately to the left of the DJ junction.
Clinical
o peptic ulcer – common site – 1st part
o obstruction
o Annular pancreas
o Pressure by the superior mesenteric artery
o Contraction of suspensory ligament of duodenum (ligament of Treitz)
o Ulceration of gall stones into duodenum & obstruct the lower ileum-gall stone ileus
o Posterior duodenal ulcer
o Damages the gastroduodenal artery & pancreas
(Erosion of gastroduodenal artery by duodenal ulcers results in sever haemorrage)
Duodenum
a) Is almost completely covered by peritoneum
b) Lies behind the portal vein
c) Lies anterior to the hilum of the right kidney
d) Is crossed anteriorly by the superior mesenteric vessels
Jejunum Ileum
1.Wall Thicker & more vascular Thinner & less vascular
2.Lumen Wider & often empty Narrow & often loaded
3.mesentery • Less fat • More fat
• Windows present • No windows
• 1/2 arcades(few) • 3/5 arcades(numerous)
• Vasa recta long & few • Vasa recta short & numerous
4.Plicae Large & closely placed throughout Small & sparse, only in proximal part
circularis
5.Villi Large, thick & more Short, thin & few
6.Payers Present
patches Absent
7. solitary
Fewer More
lymph follicles
4. LARGE INTESTINE
▪Caecum
▪Ascending colon
▪Transverse colon
▪Descending
colon
▪Sigmoid colon
▪Appendix
●Caecum
✓ intraperitoneal (but doesn’t have a mesentry. Covered by peritoneum & mobility is high)
✓ in right iliac fossa
✓ large blind sac
✓ form commencement of large intestine
✓ width is greater than length
✓ distensible
✓ appendix opens into posteromedial wall, 2cm below ileocecal valve
Ileocecal valve :
• Lower end of ileum opens on the posteromedial aspect of caecocolic junction,
15 2018 A/L Batch Repeat Campaign
guarded by ileocaecal valve.
• Localized thickening of muscularis propria forms an intrinsic anatomical
sphincter.
• Functions- separate luminal environments of small large intestine which differ
in their composition, prevent reflux from colon, regulate forward transit of
small bowel.
1. The caecum
a) Is completely invested in peritoneum
b) Possesses a longitudinal muscle coat but no taeniae coli
c) Lies on the right psoas muscle
d) Has an ileocecal orifice opening inferiorly
e) Lies adjacent to the right femoral nerve
●Appendix
o Vermiform blind ended tube ,situated in right iliac fossa, larger in children & base is fixed
o Opens into posteromedial wall of caecum
o Tip of the appendix has no anatomy, it can be anywhere within abdominal cavity
o Position - Retrocaecal – 65%
• Pelvic – 30% Retroileal
o Base - McBurney’s point (gridiron incision)
• Junction between lateral 1/3 & medial 2/3rd of line joining the
umbilicus & the right anterior superior iliac spine
o Taeniae coli meet at the base
Clinical
Inflammation: Appendicitis
Pain initially referred to umbilicus (T10)
Later when parietal peritoneum irritates – pain in right iliac fossa
Thrombosis of appendicular artery causes gangrene as it is the sole blood supply to the appendix.
McBurney’s point- Site of maximum tenderness in appendicitis
Appendix of
• Children – larger
• Adults – obliterated
• So appendicitis occurs more in teenagers.
1. The appendix
a) Arises from the inferior aspect of the caecum
b) Has a mesentery
c) Is commonly absent
d) Usually lies retrocaecally.
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e) Is clothed in peritoneum
Colon
• Descending colon is also supplied by pelvic splanchnic nerves which arise from anterior primary
rami of S2, S3, S4 sacral nerves. This supply parasympathetic function including transmitting the
sensation of pain.
Papillary Process
Suprarenal impression
Gastric impression
Renal impression
Oesophageal
impression
Caudate Process
Ligamentum teres
hepatis
Colic
Round ligament of liver impression
Duodenal
impression
Peritoneal Attachments –
✓ enclosed in peritoneum
✓ in ventral mesogastrium
✓ except the bare area
Ventral part
i. Falciform lig. (a little right to the midline) – Attached to liver & anterior abdominal wall
In between the right & left lobes.
Inferior margin – Ligamentum teres hepatis (Remnant of L. Umbilical V.)
ii. Right & left triangular ligaments
iii. Coronary ligament – Superior & Inferior layers
Dorsal part
Lesser omentum – arise from inverted ‘L’ attachment
✓ Vertical limb – Ligamentum venosum (Remnant of Ductus Venosus)
✓
Horizontal limb - margins of porta hepatis
Anatomical Division
Functional Divisions
➢ According to distribution of Bile duct, Hepatic artery, Portal vein. Oblique plane through the GB
Fossa & IVC groove divides it into left and right halves.
➢ Each right & left functional lobe further divided into 4 segments -> 8 segments
➢ Caudate lobe -> segment 1
➢ Left lobe contains segments 1-4
➢ Right lobe contains segments 5-8
➢ Arranged in an anticlockwise manner around porta hepatis.
➢ Caudate lobe is supplied by both hepatic arteries, both portal veins, both hepatic
ducts, but it has an independent venous drainage.
➢ Stability – Ligaments, Hepatic veins, Abdominal muscle tone
Relations - 5 Surfaces
Anterior Surface
●Diaphragm
●Pleura
●Anterior Abdominal Wall
●Xiphoid Process
Right
2. Portal vein (80%)
(deoxygenated blood Left
rich in nutrients)
Left In the plane
3. Hepatic veins IVC
Middle
between
functional 2 lobes
Right
i. Gall bladder
▪ Pear shaped fibromuscular sac for storage and
concentration of bile.
▪ Lying in gall bladder fossa.
▪ Plastered onto the visceral surface of right lobe of liver, adjacent to quadrate lobe.
▪ Capacity:- 30-50 ml
▪ Relations
Neck – Superior - Attached to liver, by areolar tissue
Inferior - 1st part of duodenum
Fundus – Anterior – Anterior abdominal wall = 9th costal cartilage tip (transpyloric plane)
Posterior – Transverse colon
Blood Supply
It has a dual blood supply from:
-Cystic artery (cystic veins do not accompany the cystic artery.
-From liver bed, So gangrene is rare.
-Venous drainage is via multiple veins in gall bladder bed to Liver.
✓ Mucosa of cystic duct projects obliquely in regular succession, appearing to form a spiral valve (spiral valve
of Heister).
Clinical
Gall Stones
▪ In gall bladder-Cholelithiasis
Spasmodic pain occurs
Murphy’s sign – Tenderness during inspiration on tip of the 9th costal cartilage
▪ Hartmann’s pouch. -Posteromedial wall of the neck is dilated (Gall stones lodge here)
Inflammation of gall bladder
Referred pain -in the lower border of the scapula via sympathetics
- Stomach via vagal fibers
-Shoulder tip via phrenic nerve
4. Courvoisier’s Law
• Extrinsic obstruction (Carcinoma of head of the pancreas) – Dilation of GB
• Intrinsic obstruction (Stones) – Fibrosis, no dilation of GB
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2. Bile duct
Common hepatic duct is joined by the cystic duct at an acute angle to form the common bile duct.
(commences approximately 2.5 cm above the duodenum )
• Join main pancreatic duct of Wirsung at angle of 600 degrees, to form hepatopancreatic ampulla of Vater.
• Ampulla & the ends of the 2 ducts are each surrounded by sphincteric muscle, as a whole called ampullary
sphincter of Oddi.
• This arrangement allows for independent control of flow from bile & pancreatic ducts.
Pancreas
✓ Compound gland with a major exocrine (98%) & smaller endocrine part.
✓ Retroperitoneal (secondarily)
Surface marking
The transpyloric plane defines the level of the neck of the pancreas which overlies the vertebral Column. From
this land mark head passes downward & to the right, the body & tail pass upward & to the left
• From Coeliac trunk & Superior mesenteric artery (as it develops at the junction of foregut & midgut)
• Mainly from splenic artery –
✓ Supply neck, body & tail
✓ One large branch – arteria pancreatica magna
Inferior mesenteric vein drain into splenic vein & splenic vein joins with superior mesenteric vein behind
the neck of pancreas to form portal vein.
Lymph drainage
Coeliac
Head Neck Pancreaticosplenic nodes Pre aortic nodes
Superior mesenteric
Tail and Body Nodes along splenic artery
Clinical –
1. Carcinoma of head of the pancreas - may cause obstruction of the bile duct
2. Pancreatitis – fluid collect in the lesser sac = Pseudocyst (or by posterior gastric ulcerations)
3. Annular pancreas
4. Neoplasm of the head of pancreas – obstructive jaundice
Of the body – portal or IVC obstruction
Spleen
Surface anatomy
In Left hypochondrium
(Points) – Left side
1. Axis – 10th rib directed downwards forwards and laterally
2. Upper pole – upper border of 9th rib
3. Lower pole – lower border of 11th rib
4. Medial end – 2 inches from midline
5. Lateral end – Mid axillary line
*Must be enlarged 3 times than normal to be palpated
➢
Important Facts
1) Tetrahedral in shape
2) Lies deep to the left 9th to 11th ribs
obliquely along the long axis of 10th rib
3) 2 surfaces – diaphragmatic (smooth,
convex) and visceral.
4) Borders –
• Anterior/Superior – notched
• Posterior/Inferior
• Intermediate – separating gastric and renal impressions
5) Wedged between fundus of stomach and diaphragm
Phrenicocolic ligament
✓ runs inferior & lateral to the lower pole of spleen
✓ extends from splenic flexure of colon to diaphragm
✓ limits the upper end of left paracolic gutter
Referred Pain
Referred pain is a term used to describe the phenomenon of pain perceived at a site adjacent to / at a distance
from the site of an injury's origin.
3. Appendix - appendicitis
•Umbilical region – 1st felt => T10
•Right iliac fossa - increased inflammation =>Inflamed appendix touches the parietal peritoneum
4. Pancreas - Pancreatitis
•Epigastrium => T6 to T10
•Posterior paravertebral region =>inflamed soft tissues of retro-peritoneum
5. Kidney
• Lumbar region of back
• External genitalia of Anterior abdominal wall
=>T12 to L1 via sympathetic fibers
6. Ureter
• Renal colic – severe pain due to a ureteric stone
• Pain starts in the loin & radiates down the groin, scrotum or labium majus & inner thigh
[Pain is referred to the cutaneous areas innervated by segments, mainly T11 & L2
which also supply the ureter]
7. Uterus.
• corresponding dermatomes =>T10-L1 via sympathetic fibers
8. Ovary
• Loin & groin =>T10-T11 via Aortic plexus
Epigastrium - foregut
Common Hepatic
Gastroduodenal artery
• Pass behind the 1st part of the
duodenum
Anterior Posterior
Clinicals
✓ Foregut - Posterior gastric ulcer or cancer may erode the pancreas giving pain referred to back.
Ulceration into splenic artery (direct posterior relation to stomach) may cause torrential
hemorrhage.
posterior duodenal ulcer can erode gastroduodenal artery resulting a severe hemorrhage.
✓ Midgut - Acute infection in appendix may result in thrombosis of appendicular artery, which is
an end artery thus leading to gangrene of appendix.
Ileocolic artery
Superior branch
Inferior branch Anastomose with right colic
artery
Appendicular artery
Anterior caecal artery Posterior caecal artery
3 • Batch
2018 A/L End artery
Repeat Campaign
• 1st runs in the free margin of
the mesoappendix, then
close to appendicular wall
Ascending branch
• Cross left psoas, gonadal
Inferior mesenteric artery (L3) vessels, ureter, genitofemoral
nerve, quadratus lumborum
• Crossed anteriorly by inferior
Left colic artery mesenteric vein
Descending branch
• Anastomoses with highest
Sigmoid arteries (2-4) sigmoid artery
• Runs in the sigmoid
mesocolon
Left branch
Right branch
Clinicals
✓ Anastomotic branches near inner margin colon forms marginal artery of Drummond.
✓ Avascular window lies between middle colic and left colic arteries around the splenic flexure where
surgeons use to enter the lesser sac.
Ligamentum Teres
Portal Vein
• Runs in the free
Right Gastric Vein margin of the lesser Left Gastric vein
omentum short Gastric
Vein
Superior
Pancreaticoduodenal vein Passes behind the lower border of the body
of the pancreas in front of left renal vein and
joins splenic vein
Crosses the third
part of the
duodenum and
uncinate process
Left colic vein Sigmoid veins
of pancreas.
Psoas major
• Origin - transverse process of all lumbar vertebrae
Side of the bodies (T12-L5 )
Intervening discs (T12-L5 )
• Insertion - lesser trochanter of femur
• Action – flexion of the hip joint
❖ Roots of lumbar plexus lie within the substance of the muscle.
▪ Genitofemoral nerve - front of psoas
▪ Iliohypogastric, ilioinguinal, lateral femoral cutaneous
nerves, femoral nerve - lateral border
▪ Obturator & lumbosacral trunk - medial border
• Nerve supply - first 3 lumbar nerves
Quadratus lumborum
• Origin - transverse process of vertebra L5, the iliolumbar ligament, and the adjoining
part of the iliac crest
• Insertion - attach superiorly to the transverse processes of the first four lumbar
vertebrae and the medial half of the inferior border of rib XII.
• The surface marking of the abdominal aorta is from a point 2.5 cm above the
transpyloric plane in the midline to a point 1 to 2 cm below and to the left of a
normally situated umbilicus, level with the highest points of the iliac crest.
• Enters the abdomen behind the median arcuate ligament→ behind peritoneum
slightly inclining to left.
• The main branches of the abdominal aorta fall into 3 main categories.
• A small posterior branch, the median sacral artery leaves the aorta a little above its
bifurcation.
L1 Left
Superior mesenteric artery
• Short
• Crosses left crus & psoas behind
left renal vein
• Covered by tail of pancreas &
splenic vessels
L2 Renal arteries
(At right angle)
Right
• Long
Crossed by left renal vein
• Crosses right crus & psoas
behind IVC & right renal vein
Crossed by uncinate process
Lumbar arteries 4
(Leave the aorta opposite the
bodies of L1-L4)
Portal vein
• Formed by draining of the splenic vein into the superior mesenteric vein
• Behind the neck of the pancreas
• At the L2 vertebral level
• Relations
▪ Infraduodenal part
Anteriorly – neck of pancreas
Posteriorly – IVC
▪ Retroduodenal part
Ant. - 1st part of duodenum
Common bile duct
Pancreas
Gastroduodenal artery
Post. – IVC
▪ Supraduodenal part - between the 2 layers of the free edge of lesser omentum
Ant. – Hepatic artery
Bile duct
Post. - Epiploic foramen
• Tributaries
− Splenic vein
− Superior mesenteric vein
− Left gastric vein
− Right gastric vein
− Superior pancreaticoduodenal vein
− Paraumbilical vein (running with the ligamentum teres)
− Cystic vein (if present)
• Branches
Right – shorter & wider
Receive cystic vein & enters the right lobe of the liver
Left - longer & narrower
Receive paraumbilical vein
Ligamentum teres
Ligamentum venosum
3rd & 4th lumbar veins The 3rd and 4th lumbar veins
(1st & 2nd lumbar veins join ascending drain directly into the IVC
lumbar vein while the 1st and 2nd veins
do not.
2 Right gonadal veins→ 2 venae
commitantes unite on psoas→
Right gonadal vein
❖ Fibers pass downwards into pelvis from superior hypogastric plexus as the
hypogastric nerves to form the inferior hypogastric plexus with pelvic splanchnic
nerves.
Somatic nerves
Lumbar plexus
Formed by anterior rami of upper 4 lumbar nerves. (L1, L2, L3, L4 )
• L1 - Iliohypogastric & ilioinguinal
− Skin over the inguinal region & front of the scrotum
− Motor supply for the internal oblique & transversus abdominis (conjoint
tendon)
• L1,L2 - genitofemoral
Genital branch - Sensory to tunica vaginalis & spermatic fascia
Motor to cremaster muscle
Femoral branch – supplies an area of skin below the middle of the inguinal ligament
• L2,L3 (posterior division) - lateral femoral cutaneous
− Wholly sensory to the iliac fascia & peritoneum of the iliac fossa &
− To the lateral side of the thigh down to the knee.
• L2,L3,L4 (posterior division) - femoral
• L2,L3,L4 (anterior division) - obturator
Left hilum
Transpyloric plane
Right hilum
✓ Side differences –
o R. kidney little lower => Liver superiorly located
o R. kidney little away from the mid-line => IVC medially located
o R. kidney lies anterior to 12th rib, while L. kidney lies anterior to 11th& 12th ribs
Relations
-Posterior – similar to both kidneys
✓ Diaphragm & quadratus lumborum muscles
✓ Behind the diaphragm – costodiaphragmatic recess
✓ Medially overlaps (hilum) – Psoas major
✓ Laterally overlaps – Transversus abdominis
✓ Upper pole – Medial & lateral arcuate ligaments
✓ Emerging beneath the lateral arcuate ligament – Subcostal vein, artery and
nerve
✓ Emerging from the lateral border of psoas major – Iliohypogastric & ilioinguinal nerves
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- Anterior
Right Left
Medial
Above the hilum - Suprarenal glands
Below the hilum - Ureter
Lateral
Right kidney Left kidney
Right lobe of the Liver Spleen
Hepatic flexure of the colon Descending colon
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Coverings (inside to outside)
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Coverings (inside to outside)
1. Fibrous/true capsule- easily stripped off in normal, but becomes adherent in disease conditions
4. Paranephric fat
Variable amount of fat lying outside the renal fascia
Fills up the paravertebral gutter, forming a cushion for the kidney
▪Structure
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▪ Blood supply
Supply each vascular segment
Venous drainage Arterial supply [END ARTERIES]
But their corresponding veins
IVC Aorta communicate with each other
RENAL
INTERLOBAR
Arches over pyramid bases
ARCUATE At right angles to interlobar A
At corticomedullary junction
INTERLOBULAR
EFFERENT ARTERIOLES
PERITUBULAR CAPILLARIES
• Renal artery
Apical segment
Upper segment
Anterior division
Middle segment
Lower segments
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Lymphatic Drainage
Into para aortic nodes- L2 level
Nerve Supply
• Sympathetic – from T12 to L1
• Pain may be referred to back and lumbar region which may radiate to anterior abdominal wall and down to
the external genitalia
▪Clinical
2. Renal angle – Angle between 12th rib-lower border & erector spinae-outer border
▪Enlarged kidney – Lower pole bimanually palpated, on deep inspiration
4. In Renal Failure –
o Kidney Transplantation – In recipient’s pelvis
o Peritoneal dialysis or hemodialysis
6. Nephroptosis
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Ureter
➢ Extraperitoneal throughout
➢ 25cm
➢ Whitish non pulsatile cord which shows peristaltic
activity when gently pinched with forceps.
Constrictions
1. Pelvi-ureteric junction
2. Pelvic brim
3. Point of crossing of the ureters by the
ductus deferens/ ligamentum teres.
4. Passage through the bladder wall
5. At its opening at the latera angle of
the trigone.
▪ Course
1) Abdominal part
• Begins within renal sinus=renal pelvis
• Renal pelvis lies along medial border of kidney behind it
• At lower pole it becomes ureter proper
• Lies on psoas major, underneath the peritoneum
• Crosses in front of the genitofemoral nerve
• It descends in front of tips of transverse processes of L2-L5
Crossed By [Anteriorly]
Right Both Sides Left
3rd part of Duodenum Gonadal vessels Left colic
Right colic Genitofemoral N. [Posteriorly]
Ileocolic
Root of the mesentery of small intestine
2) Pelvic part
• Passes anterior to the bifurcation of the common Iliac A.
o At pelvic brim + In front of Sacroiliac jnt. + Level of lumbosacral disk
o Left side – In the Intersigmoid recess [Under the apex of sigmoid mesocolon]
• Goes along the curvature of greater sciatic notch & anterior to internal Iliac A.
• Reaches ischial spine & turns forwards & medially
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MALE FEMALE
Crossed By - [Superiorly from lateral to medial]
Ductus deferens Uterine artery
Lies - [Superior to]
Seminal vesicles Lateral fornix of vagina
o Posterior –
▪ Sacroiliac joint
▪ Lumbosacral trunk
▪ Internal iliac vessels
o Lateral –
▪ Obturator internus and fascia
▪ Obturator nerves and vessels
▪ Superior vesical arteries
▪ Inferior vesical veins
▪ Posterior border of ovarian fossa
3) Intravesical part
• Enters the bladder at an acute angle
• Obliquity of the course produces a sphincteric function
4) Nerve supply
- Sympathetic => T10 to L1 Parasympathetic => S2 to S4 (pelvic splanchnic)
5) Blood Supply
• Segmental blood supply
• Upper end – ureteric branch of renal artery
• Middle – abdominal aorta, gonadal, common iliac, internal iliac
• Lower end – superior and inferior vesical, uterine artery
6) Lymph drainage
• Abdominal part → para – aortic nodes
• Pelvic part → internal iliac nodes & common iliac nodes
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Clinical
1. Ureteric Stones [Calculus]
- Lodge in constricted sites of ureter
- Renal [Ureteric] Colic => Due to spasm of the ureter
Severe spasmodic pain – radiates from loin to groin, inner aspect of thigh &
referred to testis
- In X-rays =>
❖ Postero-Anterior View - Ureteric stones – At the tip of transverse processes of lumbar vertebra
❖ Lateral view - Ureteric + Kidney stones – On the body of vertebra
GB stones – Anterior to the body of vertebra
Two parts
- Cortex -- mesodermal origin
- Medulla (1/10 of gland)-- neural crest origin
➢ Right supra renal gland apex related to bare area of liver. It is overlapped medially by the inferior vena cava.
➢ Blood supply
o Arterial supply
▪ Superior suprarenal artery– from inferior phrenic artery
▪ Middle suprarenal artery – abdominal aorta
▪ Inferior suprarenal artery- renal artery
o Venous drainage
▪ Right suprarenal vein– to IVC
▪ Left suprarenal vein – left renal vein
➢ Lymph Drainage
To para aortic lymph nodes
➢ Nerve Supply
Preganglionic sympathetic fibers from splanchnic nerves via coeliac plexus
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PELVIS
1. Bony Pelvis(pelvic girdle) formed by 4 bones united by 4 joints
• 2 hip bones anteriorly by pubic symphysis (2ry cartilaginous joint)
• Sacrum & coccyx by sacrococcygeal joint (fibrocartilaginous joint)
• Sacrum & 2 hip bones each side by 2 sacroiliac joints(synovial joints)
2. Bony pelvis is divided into true pelvis & false pelvis by,
Pelvic brim (pubic crest, pectinate line of pubis, arcuate line of ilium, ala & promontory of sacrum)
Linea terminalis
3. The plane of the pelvic brim is oblique, lying at 600 with the horizontal plane (the vagina lies in the same plane)
4. Pelvic floor slopes downwards and faces forwards (so that the anterior superior iliac spine (ASIS) and the upper
border of the pubic symphysis lies in the same coronal plane)
1. Transverse diameter of the outlet- distance between the ischial tuberosities along a plane of the anus
2. Anteroposterior outlet diameter-distance from the pubis to the sacrococcygeal joint.
3. Diagonal conjugate—from the lower border of the pubic symphysis to the promontory of the sacrum.
4. Finger of the examiner should not reach sacral promontory in vaginal examination
Clinical
Caudal anesthesia
The sacral hiatus, between the last piece of sacrum and coccyx - entered by a needle which pierces skin, fascia
and the tough posterior sacrococcygeal ligament to enter the sacral canal.
Pelvic fascia
Pelvic muscles
Piriformis
• Origin – front of the middle 3 pieces of its own half of the sacrum
• Sacral plexus and sacral nerves lie on the muscle
• Pelvic surface of the muscle and sacral plexus are covered by pelvic fascia.
Obturator Internus
• Origin – from the whole Obturator membrane and from the bony margins of the foramen
• Leaves the pelvis through the lesser sciatic foramen; makes a 90° bend around the ischium between the
ischial spine and ischial tuberosity.
Pelvic diaphragm
Levator ani
• Nerve supply from the S4 sacral nerve & inferior rectal nerve
• Arises from the posterior aspect of the body of the pubic bone, the fascia of the side wall of the pelvis
(thickening of obturator internus fascia/white line) and the spine of the ischium.
• Contain 2 parts
1. Pubococcygeus
➢ Levator prostate/Sphincter vaginae
o Anterior fibers
o form a sling around the prostate/vagina
o In both sexes, fibers also attach to the perineal body
➢ Puborectalis
o Middle fibers
o form a sling around the rectum and also insert into deep part of the longitudinal muscle
coat of the anal sphincter at the anorectal ring
➢ Pubococcygeus proper
o Posterior fibers
o Attached to the sides of the coccyx and to the median fibrous raphe, which stretches
between the apex of the coccyx and the anorectal junction.
2. Iliococcygeus
o posterior half of the white line & ischial spine
Actions
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1. Acts as the principal support of the pelvic floor
2. Has a sphincter action on the rectum and vagina.
3. Assists in increasing intra-abdominal pressure during defecation, micturition and parturition.
Obturator artery
• Periosteum of back of pelvis
• Accessory/abnormal obturator artery can arise from the
inferior epigastric artery*
• Crossed by ureter (in the ovarian fossa in females)
Uterine artery
• Uterus, cervix, uterine tube
Anterior • Crossed by ureter 1cm lateral to supra vaginal fornix
Uterine
division
Vaginal
• Upper part of vagina
Inferior vesical
• Trigone, lower bladder, vas deferens
Internal pudendal
• Leaves the pelvis through the greater sciatic foramen below the piriformis
• Anal region, external genitalia
Inferior gluteal
• Leaves the pelvis first through S1 & S2 ventral rami & then
through the greater sciatic foramen below the piriformis
Anterior (lateral)
• Psoas, Quadratus lumborum
Lumber branch (5th
lumbar segmental
artery) Posterior
• Erector spinae
Iliac branch
• Iliac fossa, iliacus, iliac
bone
Posterior Anastomosis
Lateral sacral around ASIS
division
• Piriformis
Spinal branches
Superior gluteal
7 • Leaves the pelvis first through lumbosacral trunk ©2018 A/L Repeat Campaign
& S1 ventral rami & then through the greater
sciatic foramen above the piriformis
Bladder
• Pelvic organ; as the bladder fills, it
domes into the abdominal cavity.
• Trigone of the bladder
o Least mobile part of the bladder
o Mucous layer tightly adhered
Relations
• Empty bladder is tetrahedral (three
sided pyramid) in shape.
• Has an apex, base, neck, superior
surface and 2 inferolateral surfaces.
o Neck
▪ In the male; lies against the upper surface or the base of the prostate
▪ In the female; lies above the urethra in the connective tissue of the anterior abdominal wall
1. Anteriorly - the pubic symphysis, puboprostatic & pubovesical ligaments in the retropubic space
2. Superiorly - the bladder is covered by peritoneum with coils of small intestine and sigmoid colon In the
rectovesical pouch in male. In the female; the body of the uterus flops against its posterosuperior aspect forming
the vesicouterine pouch.
3. Posteriorly - in the male; the rectum, the termination of the vas deferens and the seminal vesicles; separated
from the rectum by denonvilliers’ fascia
in the female; the vagina and the supravaginal part of the cervix (with no peritoneum
intervening)
4. Laterally - the levator ani and obturator internus
• Blood supply; mainly by superior and inferior vesical arteries. Veins do not follow the arteries; instead forms
the vesicoprostatic plexus in the groove between the bladder and prostate, which drain into internal iliac
vein.
• Lymph drainage is mainly into external iliac nodes.
• Nerve supply;
o Sympathetic (vasomotor & inhibitory to Detrusor muscle) – superior and inferior hypogastric plexus
(L1,L2)
o Parasympathetic (motor and sensory) – Pelvic splanchnic nerves
o Trigone is supplied exclusively by sympathetic nerves
Clinical
Scrotum is supplied by widely separated dermatomes (L1 & S3)
So whole scrotum is difficult to anesthetize at once.
Anterior 1/3- L1
Posterior 2/3- S3
• Tunica Vasculosa- Innermost vascular coat of the testis, lines the lobules
Spermatic chord
M L
Ju Ju
st st
sl sl
o o
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w w
d d
The glandular part of the testis consists of lobules which contains seminiferous tubules.
Seminiferous tubules Rete testis Efferent ductules Epididymis
Arterial supply - testicular artery
venous drainage - pampiniform plexus of veins
Clinical
1. Referred pain: - loin (region between ribs and hips)/ sympathetic supply by the T10 segment- motor
(testicular artery smooth muscle) and sensory (explains referred pain in loin region)
4. Ectopic testis
• Testis remain in a site other than its normal course
• Abdomen
• Perineum
• Upper thigh
• Femoral canal
• Penis
• The testis is fully developed. Usually accompanied by indirect inguinal hernia
5. Hydrocele
• Condition where fluid accumulates in the processus vaginalis of peritoneum
▪ Root
Made up of 3 masses of erectile tissue:
• two crura – covered by ischiocavernosus muscle
• bulb - covered by bulbospongiosus muscle. The deep surface is pierced by the urethra.
▪ Body
Composed of three elongated masses of erectile tissue;
• Right and left corpora cavernosa- Forward continuation of the crura. They terminate
under the cover of the glans penis.
• Corpus spongiosum- This is the forward continuation of the bulb of the penis. Its terminal part
enlarges to form the glans penis. Traversed by the urethra throughout the whole length.
Supports of penis
(3 pairs of arteries)
vein
(Veins are unpaired unlike
arteries)
Ischiopubic ramus
Ischial tuberosity
Anal aperture
Sacrotuberous ligament,
covered by inferior border
Anal triangle of gluteus maximus
Anal triangle
Ischio-anal fossa (Ischio-rectal fossa)
wedge shaped space filled with fat either side of anal canal Below the pelvic diaphragm.
Clinical
1. Abscesses can be ruptured internally or externally into the anal canal or to the surface of perineum –
anorectal fistula.
2. Ischiorectal fossa acts as a cushion giving support to rectum & anal canal.
3. Anteriorly infection of one space can't communicate across the midline, but posteriorly communicates
through horseshoe shaped path
Pudendal canal
connective tissue tunnel on the lower lateral wall of the ischioanal fossa
Attachments: -
• external anal sphincter – unpaired
• pubovaginalis / puboprostaticus of levator Ani
• Bulbospongiosus Paired
• Superficial transverse perineal muscle
• deep transverse perineal muscle
action: -
stabilizing influence for pelvic and perineal structures
Weakness causes prolapse of the vagina and uterus.
Perineal Membrane
bulbous scrotal expansion (dartos fascia) cylindrical penile expansion (buck’s fascia)
Anterior
Transverse Posterior
margin of
scrotal artery Glans penis
perineal artery perineal
membrane
Helicine arteries
Skin, fascia of penis
Supply cavernous
o Prostatic sinus- shallow depressions on either side of the crest/ openings of prostatic
glands
Clinical
1. Catheterization – catheter should be introduced into the urethra beak downwards???
Roof of navicular fossa bears a mucosal fold/ pit like recess called lacuna magna. It is directed forwards
and can catch the tip of catheter.
2. Urethral rupture in a fall astride injury - In damage to spongy part/ bulbar of urethra, urine does not
extravasate into;
a) Thigh
b) Ischiorectal fossa
Urine passes into;
a) Scrotum
b) Penis
Internal genitalia
1. Epididymis
• Organ made of a highly coiled tube
• Three parts
o Head
o Body
o Tail (inferiorly)
• Lies on the lateral part of posterior border of testis
• Supplied by branches of the testicular artery
2. Ductus deferens
▪ 45cm long thick-walled muscular tube
▪ Originates from the tail of epididymis
▪ Testis - Ascends along posterior border of testis medial to epididymis
▪ Spermatic chord - Enters the spermatic cord.
▪ Traverses the inguinal canal within spermatic cord
4. Prostate gland
• Pyramidal shape fibromuscular gland
• Apex lies inferiorly
• Fibro muscular stroma of gland- anterior – non glandular, posterior- glandular
• Five lobed (as described earlier)/ glandular tissue divided into three lobes (median and 2
lateral)
• The prostatic urethra emerges just in front of the apex. Base directed upwards and fused
with the neck of the bladder.
• Structures within the prostate- Prostatic urethra- traverses the gland vertically at the
junction b/w anterior 1/3 and posterior 2/3(travels more anteriorly), prostatic utricle-
blind ending sac directed upwards and backwards, ejaculatory ducts on either side.
• Relations
• Superiorly- neck of bladder
• Inferior – apex rests on urogenital diaphragm
• Anterior – pubic symphysis separated by retropubic fat
Prostatic venous plexus
Puboprostatic ligament
• Posterior – Rectum (Separated by Denonvillier’s fascia- obliterated rectovesical
pouch)
• Lateral – Levator ani
• Capsules
• TRUE capsule :- condensation of peripheral part of gland
• FALSE capsule: - lies outside the true capsule/ derived from endopelvic fascia/
anteriorly continuous with puboprostatic ligaments
o Prostatic venous plexus lies between two capsules
• Zones (McNeal’s classification)
- Peripheral zone - 70% of glandular tissue. Located behind the central zone. / cancer
vulnerable
- Central Zone – 20% glandular tissue. Forms the base of the gland. Surrounds the ejaculatory
ducts. / not involved in disease
- Transitional zone - 5% of glandular tissue. Lies around the distal part of the pre- prostatic
urethra. / benign prostatic hyperplasia
• Blood supply:
Supplied by the branches of the inferior vesicle, middle rectal and inf. Pudendal arteries.
Venous drainage is to the venous plexus situated between the false and the true capsules.
Venous plexus> vesical plexus> sup. Vesicle, inf. Vesicle veins> int. pudendal vein.
Clinical
1. Pathological capsule
Benign prostatic hypertrophy
Normal peripheral part of the gland become compressed into the capsule. / distortion of
urethra> acute retention of urine
3. Denonvillier’s fascia
In excising rectum, the plane passes through this without damaging prostate &
urethra and acts as a barrier to prevent spread of carcinoma of prostate into
the rectum and vice versa.
Penis (skin)
Superficial Inguinal nodes
Scrotum
1. Uterus
▪ Peritoneal attachments
1. Anterior ligament or uterovesical fold
2. Posterior ligament or rectovaginal fold
3. Two broad ligaments
Mesovarium-ovary to posterior layer
Mesosalpinx - part between ovarian ligament & uterine tube
Mesometrium- part below ovarian ligament
4. Suspensory ligament of ovary
1. Broad ligament
Primary Secondary 2. Uterovesical fold
3. Rectovaginal fold
Fibromuscular Muscular
1. Pelvic
1. Uterine axis diaphragm
2. Perineal
2. Pubocervical body
ligament
3. Distal
Cervixurethral
to pubissphincter
mechanism
3. Round ligament of uterus
4. Transverse cervical ligament
Cervix to lateral
pelvic wall
Structure
• Muscular organ responsible for the protection & nourishment of fertilized ovum so
that it can develop into a full-term fetus.
• Pear shaped
• Possess 3 parts
FUNDUS
Posterior surface
• Directed upwards
• Related to coils of terminal ileum & sigmoid colon
• Covered with peritoneum & forms rectouterine pouch posterior to it
Lateral borders
• Provide attachment of uterus to the side walls of the pelvis
• Uterine tubes open into the uterus at the upper end of this border
• Anteroinferior to the opening of uterine tubes is the round ligaments
• Posteroinferior to the opening is the ligament of the ovary
• Uterine cavity occupies the body & is triangular shaped
• Apex is directed downwards & is continuous with the cervical canal via the internal
os.
CERVIX
• Lower cylindrical part of the uterus
• Projects into the vault of the vagina
• Contains two parts
1. Supravaginal part
➢ Related anterior to bladder
➢ Posteriorly to rectouterine pouch
➢ Lateral to it are the ureters
➢ Uterine artery between layers of the broad ligament
2. Vaginal part
➢ Projects into vagina
➢ A deep sulcus is formed around (fornices of the vagina)
➢ Cervical canal opens to the vagina through the external os
Ureter runs forwards slightly above the lateral fornix of vagina and is 2cm lateral to
supravaginal part of cervix
Uterine artery crosses ureter superiorly at right angles from lateral to medial
▪ Clinical
- In hysterectomy ureter can be divided in the process of clamping uterine artery
- The only site where a ureteric stone can be palpated is where the ureter relates to
supravaginal cervix
2. Ovaries
• Situated in ovarian fossa of lateral pelvic wall
• Has 2 poles; upper and lower.
• Has 2 borders; anterior or mesovarian border and posterior border.
• Has 2 surfaces; medial and lateral.
3. Uterine tubes
- form a connection between abdominal & uterine cavities
Infundibulum – mouth is fimbriated
Ampulla (lateral 2/3rd) – widest
Isthmus (medial 1/3rd)
Intrauterine/ Interstitial part – narrowest
➢ Only the lower pole and the lateral surface of the ovary are not related to the
uterine tube. The remaining 2 borders, upper pole and medial surface are related
to the tube.
- Clinical
Blockage of uterine tubes – commonest cause for female sterility
Rubin’s test
Hysterosalpingography
4. Vagina
• Fibromuscular tube
• Extends from vaginal orifice within vestibule
• Upward & backwards towards uterus
• Passes through pubovaginalis, deep perineal pouch & the perineal membrane
• Expanded upper end has uterine cervix projected into it
• Circular groove in the vagina around uterine cervix is fornices
• 4 fornices
• Anterior –shallowest, posterior-deepest & 2 lateral
• Below the cervix anterior & posterior walls of vagina lie within contact with each
other to form a H shaped slit
• Lower end of vagina is covered by a thin fold called hymen in virgins, in married
women replaced by tags called hymen caruncles
▪Relations
Ant 1. Base of bladder (upper half)
2. Urethra embedded in anterior wall (lower half)
Post (above downwards)
▪ant wall of vagina >1.Pouch
pos wallof Douglas (in upper 1/4th)
th
▪ ant wall of vagina >2.pos
Rectum
wal (in middle 2/4 )
3. Anal canal (in lower 1/4th) [separated by perineal body]
Lat 1. Transverse cervical ligament (upper 1/3rd)
2. pubovaginalis muscle (middle 1/3rd)
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3. Bulb of vestibule, bulbospongiosus & ducts of greater vestibular
gland (lower 1/3rd – after piercing perineal membrane)
▪ per vaginal examination
1. Anterior & posterior relations are palpable
2. Ureteric stones
3. Ovary, uterine tubes, side of pelvis is felt laterally
4. Collection of fluid, prolapsed uterine tubes, ovaries & distended bowel in pouch of Douglas
Arterial Supply
1. Ovarian Artery
• Arises from the abdominal aorta, just below the renal artery.
• Descends over the posterior abdominal wall & enters the suspensory
ligament of the ovary.
• Supplies the ovary through the mesovarium & continues medially through
the broad ligament to anastomose with the ovarian artery.
• Also supplies the lateral 1/3rd of the uterine tube, the side of the uterus &
ureter.
2. Uterine artery
• Branch of the anterior division of the internal iliac artery.
• First passes medially across the pelvic floor in the base of the broad
ligament to reach the cervix.
• Crosses the ureter above the lateral fornix of the vagina, 2cm lateral to the
fornix.
• Ascends along the side of the uterus, with a tortuous course.
• Runs laterally towards the ovary & ends by anastomosing with the ovarian
artery.
• Also supplies the medial 2/3rd of the uterine tube, vagina, ovary, ureter &
structures in the broad ligament.
➢ The vagina is supplied mainly by the vaginal branch of the internal iliac artery. In
addition,
• Upper part - Uterine artery
• Lower part - Middle rectal & uterine artery
Nerve Supply
• Lower 1/3rd of the vagina is pain sensitive & supplied by the pudendal nerve
through the inferior rectal & posterior labial branches of the perineal nerve.
• The rest has a sympathetic & parasympathetic supply
• Parasympathetic supply for the ovaries, medial half of the uterine tubes, uterine
tubes and vagina is by the nerve rots S2 – S4
• Lateral halves of the uterine tubes are supplied by the vagus nerve.
1. Ovary
• Supplied by the ovarian plexus
• Sympathetic supply is by T10/ T11
2. Uterine tubes
• Supplied by the hypogastric plexuses
• Sympathetic supply is by T10 – L2
3. Uterus
• Supplied by the inferior hypogastric plexus & the ovarian plexus.
• Sympathetic supply is by T12 – L1
Lymph Drainage
• The lateral 2/3rd of the uterine tubes drain into the lateral & preaortic nodes.
• The medial 1/3rd of the uterine tubes drain into the superficial inguinal nodes
following the course of the round ligament.
Vagina
• Upper 1/3rd - External iliac nodes
• Middle 1/3rd - Internal iliac nodes
• Lower 1/3rd - Superficial inguinal nodes
Layers of GI tract
1. Mucosa ➔epithelium
Lamina propria ( supporting)
Muscularis mucosa ( thin smooth muscle layer)
( produce local movements & folding of mucosa)
2. Submucosa ➔ supportive tissue collagenous fibres
Blood vessels, lymphatics & nerves
3. Muscularis propria ➔ smooth muscle (Inner circular and outer longitudinal)
(oblique layer present innermost in stomach)
4. Adventitia ➔ The outer layer of loose supporting tissue conducts major vessels nerves &
contains variable adipose tissue.
Where the gut lies within the abdominal cavity( peritoneal cavity), the adventitia
is referred to as the serosa( visceral peritoneum)
It is lined by a simple squamous epithelium (mesothelium)
Elsewhere, the adventitial layer merges with retroperitoneal tissues.
Oral Cavity
Adapted to mastication, Good healing properties
Mucosa: Transverse folds Accessory salivary glands
• Epithelium
– Stratified squamous non-keratinizing
– Stratified squamous keratinizing (palate)
• LP – dense collagen, blood vessels, lymph vessels
• SM:
Loose CT – so_ palate & floor of mouth Dense CT – hard palate & tooth bearing ridges
Tongue
Epithelium: Stratified squamous non-keratinizing Taste receptors
LP: dense collagen à binds epithelium to muscle
Skeletal muscle
Accessory salivary glands
• Anterior 2/3 - Mucosa form papillae
• Posterior 1/3 - Underlying lymphoid tissue
(Lingual tonsil)
– Lymphoid follicles Part of Waldeyer’s ring Guard the entrance to the GIT
Taste buds
• Within the papillae - Ovoid shape
• Cells – pale, columnar
– sensory cells, support cells
– microvilli (surface) sense the contents of the oral cavity
• Underlying lymphoid tissue (Lingual tonsil) – Lymphoid follicles Part of Waldeyer’s ring Guard the
entrance to the GIT
Fundus/body pylorus
Glands- straight tubular Glands- Branched coiled tubular
Occupies ¼ of thickness of gastric Occupies half the thickness of the
mucosa mucosa
(Compound tubular)
Plicae circularis -
Submucosa and mucosal folds
❖ The villi tend to be longest in the duodenum & become shorter towards the ileum
❖ Lymphoid tissue become more prominent in the ileum & is fairly inconspicuous in the
duodenum.
❖ Plicae circular are most prominent & numerous in the jejunum & proximal ileum & generally
absent in proximal duodenum & distal ileum.
Junctions of GI tract
1. Gastro-oesophageal junction –
• Contains a physiological sphincter
• Transition from stratified squamous epithelium (SE) to
simple columnar epithelium & tightly packed secretory
glandular mucosa (GM)
Clinicals-Barrett’s oesophagus
3. Ileocecal junction -
• There is an abrupt transition in the lining of the valve from
the small intestinal villi form pattern (S) to the glandular form
in the large intestine (L)
• No change in the type of epithelium
• Contains a valve formed by thickening of muscularis propria
4. Anorectal junction –
• The rectal mucosa (RM) is the same as the rest of the large bowel
except they it has even more numerous goblet cells.
• At the anorectal junction(J), it undergoes an abrupt transition to
become stratified squamous epithelium (SS) in the anal canal.
• Branched tubular circumanal glands open at the anorectal
junction into small pits at the distal ends of the columns of
morgangi.
Stomach
Oesophagus
Small intestine
Duodenum
Colon
➢ Hepatic acinus
• Functional unit of liver
• Ellipsoid mass of hepatocytes
• Lies between 2 or more terminal hepatic
venules
• Centered on a portal tract
• Divided into 3 zones
Zone 1 – closer to portal tract,
receive more oxygenated blood
Zone 2 – intermediate in oxygen
supply
Zone 3 – receive less oxygen, more
prone to ischaemic injury
Pancreas
❖• Exocrine component-
secretory branched acinar glands and duct system
• Individual acini consist of pyramidal cells which secrete digestive enzyme
• Acinar cells have abundant RER, secretory zymogen granules
• Ducts system eventually drain to large interlobular ducts lined by tall cuboidal/ columnar
epithelium
❖ Endocrine component –
• islets of Langerhans - most humorous in tail
• Highly vascularized
β-cells-insulin ( most abundant) α-cells-glucagon δ-cells-somatostatin
• Acinar cells –> intercalated ducts –> intralobar ducts –> interlobular duct (small ducts- cuboidal,
large ducts - stratified cuboidal) ➔pancreatic duct
Nephron
• Structural and functional unit of kidney
• Nephron = renal corpuscle + renal tubule (from Bowman’s capsule to collecting
ducts)
• Renal corpuscle = Bowman’s capsule + glomerulus
- Tall microvilli form a brush border to increase the surface area of reabsorption
- Contain a large number of mitochondria (but less than in PCT) for active
reabsorption and secretion
- There are no micro villi in DCT.
➢ Collecting ducts – contain 2 types of cells
- Principle cells involved in Na reabsorption
PCT DCT
Lumen
Cell size
Nuclei
Brush border
Juxtaglomerular apparatus
• Specialization of glomerular afferent arteriole and DCT of the same nephron
• Situated near the glomerular vascular pole
• Function – regulation of blood pressure
3. Extraglomerular mesangial cells / Lacis cells - flat elongated cells with fine
cytoplasmic processes
▪Inner longitudinal
▪Outer circular
• Tunica vaginalis
• Tunica albuginea(capsule)
- Lymphatics
Seminiferous tubules
• Tubules within testicular lobules
• Tightly packed, highly convoluted
• Each lobule has 1-4 seminiferous tubules
• Production of spermatozoa
• Tubules lining cells(stratified)
Rete Testis
• Surrounded by highly vascular collagenous supporting tissue containing myoid cells.
• The rete testis is lined by a single layer of cuboidal epithelial cells with surface microvilli and a single
cilium.
• Myoid cell contraction helps to mix the spermatozoa and move them towards the epididymis.
• The lining epithelium reabsorbs protein and potassium from the seminal fluid.
Ductuli efferentes
• The rete testis drains into the head of the epididymis via some 15-20 convoluted ducts, the ductuli
efferentes.
• The ductuli are lined by a single layer of epithelial cells,
-tall columnar and ciliated
- short and non-ciliated
• Ciliary action in the ductuli propels the still non-motile spermatozoa towards the epididymis.
• A thin band of circularly arranged smooth muscle surrounds each ductulus and aids propulsion of the
spermatozoa towards the epididymis
• The none ciliated cells reabsorb some of the fluid produced by the testis.
Ductus deferens
• The ductus (or vas) deferens, conducts spermatozoa from the epididymis to the ejaculatory ducts.
• It is a thick-walled muscular tube consisting of inner and outer longitudinal layers and a thick
intermediate circular layer.
• Like the distal part of the epididymis, the ductus deferens is innervated by the sympathetic nervous
system, producing strong peristaltic contractions to expel its contents into the urethra during
ejaculation.
• The ductus deferens is lined by a pseudostratified columnar epithelium.
• Epithelium and lamina propria are highly folded
• The dilated distal portion of each ductus deferens, known as the ampulla, receives a short duct
draining the seminal vesicle, thus forming the short ejaculatory duct; the ejaculatory ducts from each
side converge to join the urethra as it passes through the prostate gland
Seminal vesicle
• Each seminal vesicle is a complex glandular diverticulum of the associated ductus deferens.
• Between them the seminal vesicles secrete up to 50 - 70% of the total volume of seminal
fluid, most of the rest being secreted by the prostate gland.
• The epithelial lining is usually of a pseudostratified tall columnar type.
• The prominent muscular wall is arranged into inner circular and outer longitudinal layers
and is supplied by the sympathetic nervous system; during ejaculation, muscle contraction
forces secretions from the seminal vesicles into the urethra via the ampullae
• Irregular, honeycomb shaped lumen at low magnification.
- Corpora cavernosa
- Corpus spongiosum
• The vascular sinuses of cavernous bodies of the penis are supplied by numerous
anastomosis thick walled arteries & arterioles called helicine arteries.
Follicular Maturation
1. Primordial follicle
• Contains the primary oocyte (large nucleus, small cytoplasm)
• Surrounded by a single layer of flattened follicular cells
2. Primary follicle
• Primary oocyte enlarges
• Follicular cells proliferate to form cuboidal shaped granulosa cells (zona granulosa)
• Zona pellucida – glycoprotein and proteoglycan rich acellular layer between granulosa
cells and primary oocyte
• Surrounding stromal cells (fibroblasts) organize to form a cellular layer around zona
granulosa called theca folliculi
4. Graffian follicle
• Initially contains the primary follicle
• Just before ovulation, primary oocyte completes the 1st meiotic
division and forms the secondary oocyte
• Follicular antrum enlarges
• Zona granulosa forms an even layer around the periphery of the
follicle (cumulus oophorus diminish)
• Corona radiata – a thick cellular layer around zona granulosa, attach
to ZG by thin bridges of cells
• During ovulation, secondary oocyte, zona pellucida, corona radiate
are released from the ovary
5. Corpus luteum
• Contains granulosa and theca lutein cells
• Granulosa cell are large polygonal cells with round nuclei and
abundant cytoplasm, SER, mitochondria, lipid droplets and lipofuscin
(yellow colour)
• Theca externa – dark staining
• Theca interna – pale staining due to the presence of lipid droplets
Fallopian tube
• Mucosa contains branched longitudinal folds which is most prominent in ampulla, the usual site of
fertilization.
• The muscular wall has 2 layers, an inner circular & an outer longitudinal.
• Epithelium - single layer of tall columnar epithelial cells.
Uterus
Basic organization - perimetrium, myometrium, endometrium
(1) Endometrium - Epithelium lining tall, columnar cells with microvilli or cilia
Form numerous simple tubular glands supported by endometrial stroma
Histological layers
1. Stratum compactum stratum functionalis – undergo cyclical changes
2. Stratum spongiosum functional layers are shed off during menstrual phase
3. Stratum basalis ➔ No shedding during menstrual cycle
-columnar cells (cilia or microvilli) Tall columnar cells Functional layers shed
-glands-initially simples tubular, straight, sparse Coiled tubular glands off due to the absence
But proliferation is started (saw tooth appearance) of implantation
Lined by tall columnar cells Tall columnar cells Stratum functionalis
undergo ischaemia
due to spasm of spiral
arteries
-gradually stroma become thicker, very cellular Stroma reaches to the
maximum thickness, highly
vascular
-Blood vessels less More blood vessels
When taking endometrial curetti ngs/biopsies the first day of last menstrual cycle is very important
Uterine cervix
• The function of the cervix is to admit spermatozoa to the genital
tract at the same time when fertilization is possible.
Endocervix –lined by simple columnar epithelium
Ectocervix – lined stratified squamous epithelium
• The cells of ectocervix o\en have clear cytoplasm due to their high glycogen content.
• The junction between the ecto & endo cervical epithelium is quite abrupt & is normally located
at the external is, the point where the endo cervical canal opens into the vagina.
• Endocervix contents endo cervical glands which are lined by the columnar mucus secreting
cells.
• During menstrual cycle, the endo cervical epithelium undergo cyclical changes in secretory
activity.
Cervical canal
• Lined by tall columnar mucous secreting cells
• Leukocytes are more between junction of endocervix and ectocervix (external os) - at squamocolumnar
junction
Cervical cytology
Cervical smear /pap test
anaerobic
Glycogen respiration lactic acid (inhibit growth of microorganisms)
(2) Lamina propria -no glands, contain elastin fibres, has rich plexus of veins.
(3) smooth muscle layer – inner circular and outer longitudinal muscle layers ( ill defined)
(4) Adventitia – fuse with that of rectum posterior and bladder anteriorly.
Junction bet.
proximal 2/3 &
distal 1/3
endoderm
MESENTERY
1. Ventral Mesogastrium – Derived from the Septum Transversum
Foregut (only) => divided by the liver
Ventral part – Falciform, Coronary, Triangular lig.
Dorsal part – Lesser omentum
2. Dorsal Mesogastrium – Divided by the spleen
Ventral part – Gastrosplenic lig.
Dorsal part – Lienorenal lig.
Duodenum => Dorsal mesoduodenum
Midgut => Mesentery proper
Hindgut => Dorsal mesocolon
FOREGUT
• Derivatives – Lung, Liver, Gall bladder & Pancreas
• Supplied by – Celiac artery
1. Oesophagus
Tracheo-oesophageal septum separates – Dorsal oesophagus from the ventral trachea
At first it is short. It elongates with the descent of heart and lungs.
Endoderm - mucosa and glands
Surrounding splanchnic mesoderm - muscular coating (muscularis propria), Lamina Propria,
Submucosa and Adventitia.
Mesenchyme of branchial arches - Striated muscles of upper 1/3rd
Abnormalities
I. Oesophageal atresia and/or Tracheo-oesophageal fistula
Due to - Posterior deviation of tracheo-oesophageal septum
Dorsal wall of foregut pushed anteriorly
Milk in lung (pneumonia) as well as air in stomach (respiratiory distress) can occur.
II. Oesophageal stenosis (usually in lower 1/3rd) – Failure to Recanalize
1 © 2018 A/L Repeat campaign
2
III. Short oesophagus - due to failure of elongation. Associated with thoracic stomach.
2. Stomach
Endoderm - mucosa and glands
Splanchnic mesoderm - Submucosa, musculosa & serosa.
Growth Difference
Posterior wall > Anterior wall
- Greater curvature => to the left
- Lesser curvature => to the right
Abnormalities
I. Hour-glass stomach: Constriction of stomach dividing it into 2 dilated parts with a narrowing in-between.
II. Thoracic stomach: Protrusion of upper part of stomach through diaphragm due to short oesophagus.
(partial or complete)
III. Transposition of stomach: Right sided stomach.(situs inversus)
IV. Pyloric stenosis: Hypertrophy of the circular/ longitudinal musculature of pylorus.
Projectile vomiting can be seen. Treatment:- Surgical excision of thickened sphincter.
V. Gastric volvulus/ Volvulus of stomach: Twisting of all/part of stomach by >180 o
Variable loss of blood supply and possible tissue death.
-
• Spleen (mesodermal origin), in the 5th week grows in the left leaf of dorsal mesogastrium with the rotation
of stomach around longitudinal axis, dorsal mesogastrium rotates to the left. Mesogastrium between spleen
and dorsal midline of the body fuses with the peritoneum over the posterior abdominal wall and disappears
and connect to the body wall in left kidney.
3. Duodenum
Formed by – both foregut &midgut (Therefore blood supply by both coeliac and superior mesenteric
arteries)
- Due to rotation of the stomach, it becomes ‘C’ shaped & rotates to the right.
- Right surface of the dorsal mesoduodenum presses against the posterior abdominal wall and disappears.
- Become retroperitoneal [secondarily]
- Duodenal cap – intraperitoneal
- Solidification => recanalization
Failure of recanalization leads to narrowing of the lumen (stenosis) Can affect any part of GIT but
usually affects duodenum.
- Liver bud appears as an outgrowth of endodermal epithelium, at the distal end of foregut (3rd to 4th week)
- Hepatic cells of the liver bud proliferate & penetrate septum transversum
- Mesoderm of septum transversum forms hematopoeitic cells, kupffer cells, connective tissue
- Invasion by liver cells into the septum transversum forms
Lesser omentum – between liver & foregut
Falciform, coronary, triangular lig. – between liver & body wall
- Cranial surface of the liver remains in contact with the original septum transversum & forms the bare area
of the liver
- Connection between the liver bud & the foregut form the bile duct
-Bile duct moves dorsally due to rotation of duodenum
- Ventral out growth from the bile duct gives rise to the gall bladder & cystic duct
Abnormalities
I. Extrahepatic biliary atresia.
II. Annular pancreas
- Ventral pancreatic bud usually consists of right & left parts which fuse & rotates around the
duodenum
- If they fail to fuse, left part migrates in the opposite direction
- But the right part goes in the normal direction
- Duodenum surrounded by the pancreatic tissue =>
Obstruction
III. Accessory pancreatic tissue
-It may show all characteristics of pancreas
Frequently found in => Mucosa of the stomach
Meckel’s diverticulum
-Can be found anywhere from distal end of oesophagus to
tip of primary intestinal loop
MIDGUT
• Supplied by – superior mesenteric artery
• Elongation of the gut & mesentery proper => Primary intestinal loop
• At the apex, communicates with the yolk sac via the vitelline duct
Rotation
When viewed from the front -
Counterclockwise around an axis formed by the superior mesenteric artery
th
6 week I. While herniating - 900 [6th week]
II. While retracting - 1800 [10th week]
10th week
Retraction
-During 10th week due to decreased growth of liver and adequate expansion of abdominal cavity and
regression of mesonephric kidney
- Herniated intestinal loops return to the abdominal cavity
- Cecal bud => Conical dilation of the primary intestinal loop
Last part of the gut to reenter the abdominal cavity
Then lies below the right lobe of the liver, which descends into the right iliac fossa
Distal end of the cecal bud => Appendix
-first to reenter abdominal cavity ➔ proximal part of jejunum
• Mesentery of ascending & descending colon press against posterior abdominal wall =>
to become retroperitoneal
Abnormalities
Mesentery defects
I. Mobile caecum – Persistence of mesentery of ascending colon, without fusing
HINDGUT
Derivatives – Distal 1/3rd of transverse colon, descending colon, sigmoid colon, rectum, anal
canal(upper part)
(Endoderm of Hindgut also forms internal lining of bladder and urethra)
• Supplied by – Inferior mesenteric artery
• Terminal part of hindgut enters the posterior part of cloaca.
• Allantois enters the anterior part of cloaca.
• Urorectal septum (a layer of mesoderm) separates anterior Allantois & posterior hindgut. Those which
enter the cloaca, grows caudally with the caudal folding of embryo. Tip of urorectal septum comes close to
cloacal membrane.
• Cloacal membrane ruptures
o Anterior opening – for the urogenital sinus
o Posterior anal opening – for the hindgut
In between urorectal septum forms perineal body.
• Anal canal
-Upper 2/3rd – From endoderm of hindgut. Supplied by Superior rectal artery (branch of inferior
mesenteric)
- Lower 1/3rd – From ectoderm around proctodeum. Supplied by inferior rectal artery (branch of internal
pudendal)
Junction is marked by pectinate line just below anal columns (Epithelium => Columnar to Stratified Squamous)
Abnormalities
I. Imperforated anus – Failure to breakdown the anal membrane. So noncotinuity of the 2 parts.
II. Congenital megacolon (Hirschsprung Disease)–Defect in neural crest cell migration. Absence of
parasympathetic ganglia in the bowel wall. No peristalsis. Dilation/distention of colon.
III. Rectourethral/Rectovaginal fistula
- When the urorectal septum does not extend far enough caudally
- When the cloaca is too small, causing the opening of the hindgut to shift anteriorly
IV. Rectoanal atresia
Urinary system
Kidney system
• Three slightly overlapping kidney systems formed In cranial to caudal sequence (in nephrogenic ridge)
➢ Pronephros
➢ Mesonephros
➢ Metanephros
1. Pronephros 2. Mesonephros
Appear at the beginning of the 4th week and completely Appear during the regression of the pronephros (4th week) and
regress at the end of the 4th week. regresses at 2nd month.
In cervical region In thoracic & upper lumbar (L3)
Non functional Functional in intrauterine life
No duct system Duct system – mesonephric duct
Completely disappears – Not associated to form any Important to produce genital organs. Not associated to form the
urogenital structure definitive kidney
Duct System
Clinicals
• Congenital polycystic kidney disease –(Autosomal recessive) – cysts form from collecting ducts
o Kidney- very large. Renal failure occurs in childhood
• Adult polycystic kidney disease- (Autosomal dominant) – Cysts form from all segments of the nephron
o Usually renal failure occurs in adulthood
• Duplication of ureter – early splitting of ureteric bud (partial or complete)
• One ureter may be ectopic. In such cases it may open into,
o Vagina
o Urethra
o Vestibule
• Abnormal locations of kidneys
o Pelvic kidney - Remain in the pelvis close to the common iliac artery.
o Horseshoe kidney - Lower poles fuse due to fusion of two metanephric masses in the midline. So
ascent is blocked by inferior mesenteric artery. Ureters pass anterior to the isthmus.
• Renal dysplasia & agenesis
o Severe malformation of kidney
Bilateral • Anuria
Potter • Flattened face (potter facles)
renal • Oligohydramnios
sequence - Beak ulce nose & clubfeet
agenesis • Hypoplastic lungs
• Cloaca is divided into Urogenital sinus (anteriorly) and anal canal (posteriorly) by the Urorectal septum
• Tip of the urorectal septum forms the perineal body
• Urogenital sinus
o Upper part - Urinary bladder
Allantois (continuous with the upper part of the urogenital sinus) Urachus
median Umbilical ligament
o Pelvic part prostatic urethra & membranous urethra
o Definitive urogenital sinus ( phallic part) associate to form external genitalia/penile urethra
Trigone of bladder
• During differentiation of the cloaca, the caudal portions of the mesonephric ducts are absorbed into the wall
of the urinary bladder.
• Consequently, the ureters, initially outgrowths from mesonephric ducts, enter the bladder separately.
• As a result of ascent of the kidneys, the orifices of the ureters move farther cranially.
• Mesonephric ducts move close together to enter the prostatic urethra and become ejaculatory ducts
• Mesonephric ducts and ureter originates from mesoderm. Mucosa of the bladder formed by incorporation of
the mesonephric duct (so trigone is also mesodermal)
• With the time, mesodermal lining of the trigone is replaced by endodermal epithelium
(Finally, inside the bladder is completely endodermal)
• Urethra
o Epithelium is formed by the endoderm
o Smooth muscles – by the splanchnic mesoderm
o In males; epithelium of the prostatic urethra proliferate to form the Prostatic gland
o In females; cranial part of Urethra give rise to urethral and para-urethral glands
(3rd week)
Development of Ovary
Genital ducts
1. Mesonephric duct (Wolffian duct) - Duct system of Mesonephros
2. Paramesonephric duct (Mullerian duct)
o Connects the peritoneal cavity with cloaca
o Crosses the mesonephric duct (lateral to medial)
➢ Genital ducts in males (mainly - mesonephric duct)
o Efferent ductules – remaining parts of the excretory tubules of mesonephric mesoderm
o Vas difference
Ejaculatory duct mesonephric/wolfian duct
Epididymis
Vagina
• Fornix + upper part –uterine canal (paramesonephric duct)
• Lower part –urogenital sinus (sinovaginal bulb vaginal plate)
• First appear as solid canals & then recanalize.
Clinicals – Defects of vagina and uterus
External genitalia
• Indifferent stage
o Cloacal folds – Slightly elevated
folds around the cloacal
membrane
o Genital tubercle – Fused cranial
part of cloacal folds
• th
In 6 week – Urogenital membrane
Cloacal membrane
Anal membrane
Urethral folds
Cloacal folds
Anal folds
• Genital swellings- Pair of elevations on each side of urethral folds
Clinical
• Cryptorchidism – undescended testicle
• Hydrocele
Mucous
Salivary secretion
● Parietal cells secrete HCl which has a pH of 0.8(extremely acidic) required for the
activation of pepsinogen to pepsin(optimum ph is 1.8-3.5)
● Together with the contents of the stomach and the other secretions the net pH is
around 2.0 – 3.0.
● C02 and OH from water produces HC03- and H+.
● The H+ is pumped out and K+ is pumped in via energy requiring H+-K+ ATPase
maintaining electrolyte balance.
● On the basolateral side,HC03- ions are taken into venous blood (therefore gastric
venous blood is alkaline when stomach secretes acid )in exchange for Cl-ions
creating a Cl- ion gradient to secreate Cl- into canaliculi
● Na -K ATPase on the ECF side ensures a low sodium inside the cell so that sodium is
reabsorbed into the cell from the lumen.
● In the lumen, both Na+and K+ ( (+)ve ions), H+ ions can be secreted into the lumen.
● Water moves by osmosis ,thus ensures that a very concentrated hydrochloric acid is
secreted into the lumen.
As the upper part of the duodenum is exposed to acid chyme from the stomach, Brunner’s
glands secrete alkaline mucous to protect the duodenal cells.
Pancreas
Secretion of sodium
bicarbonate by
pancreas (Guyton
and Hall)
Small intestine
● Alkaline pH innactivates pepsin and stimulates duodenal enzymes which are optimal
at a pH of 7.0 to 8.0( pH of NaHCO3 secretion is around 8.0)
The gallbladder concentrates the bile produced in the liver, and bile contains the salts of
bile acids. Secreation into duodenum has a pH of 7.5 to 8
Large intestine
● Bacterial action on the faeces produces acids but the wall is protected by the
alkalinity, pH 8.0, due to mucus and HCO3-.
● Na+ and Cl- are efficiently absorbed HCO3- is secreted. The osmotic gradient due to
Na+ and Cl- movement allows water absorption.
The pH varies in the different segments and provides the optimum pH for each enzyme
that is found in a given location.
Carbohydrate structure
Monosaccharides are the building blocks, can be join to form disaccharides, oligosaccharides,
and polysaccharides.
Disaccharides Polysaccharides
Lactose - glucose + galactose Glycogen (animal source)
Carbohydrates digestion
Breakdown of complex carbohydrates to simple sugars
• Pancreatic amylase: When the acidic stomach contents reach the small intestine, they are
neutralized by bicarbonate secreted by the pancreas, and pancreatic α
amylase continues the process of starch digestion.
The digest resulting from its action contains a mixture of short, branched and un branched
oligosaccharides known as dextrins.
Disaccharides are resistant to amylase and will also continue in to the small intestine where
they will be finally broken down to monosaccharides before absorption.
Digestion of disaccharides
Primarily at the mucosal lining of the duodenum and upper jejunum
Several disaccharidases
These enzymes are transmembrane proteins of the brush border on the luminal surface
of the intestinal mucosal cells.
Lactase (β-galactosidase) cleaves the β(1→4) bond in lactose → galactose and glucose.
Lactose intolerance
Due to deficiency in the activity of Lactase
2. Secondary active transport (an active process which on the ion-gradient, which is
established through the hydrolysis of ATP, known as primary active transport).
Transport of glucose and other hexoses by GLUT transporters and the variation
in affinity for the hexoses
• GLUT –Glucose Transporters
• 14 glucose transporters
• The 14 human GLUT proteins possess various substrate specificities and are involved in the
transport of several hexoses
• GLUT-1, GLUT-3, and GLUT-4 : involved in glucose uptake from the blood.
• GLUT-2: liver and kidney; transport glucose into these cells when blood glucose levels are high
or transport glucose from these cells when blood glucose levels are low
• Have a high affinity low km for glucose and uptake from the bloodstream is constant
GLUT2
• Located in the plasma membrane of hepatocytes and pancreatic beta cells
GLUT4
• Insulin sensitive, moderate affinity & km
• Found in muscle (cardiac, skeletal) and adipose tissue and brain (recent finding) • As muscle is
a principal storage site for glucose and adipose tissue for triglyceride (into which glucose can be
converted for storage)
• The drug metformin phosphorylates GLUT4, thereby increasing its sensitivity to insulin.
GLUT 5
• Hence transport of glucose is dependent upon the existing sodium gradient which is
generated through the active functioning of the Na+/K+ ATPase.
• As the cotransport of glucose with sodium from the lumen does not directly require ATP
hydrolysis but depends upon the action of the ATPase, this is described as secondary
active transport.
Insulin independent
Glucose absorption
Insulin independent
Glucose retention
Stomach
o Pepsin is an endopeptidase.
o Optimum pH for pepsin = 2
Pancreas
Small Intestine
Lipid Digestion
• Begins in stomach, completed in SI
• What is needed?
1. Bile Salts – made in liver, stored in gall bladder
2. Lipases- lingual, gastric, pancreatic- hydrolyse ester bonds
3. Cholesterol esterase
4. Phospholipase A2
5. Colipase – binds to lipase at 1:1, anchors the lipase at lipid
aqueous interface.
Digestion in the Stomach
• By lingual and gastric lipases
• Act mainly on short or medium chain length(<12
carbons) FA
• Important in individuals with pancreatic insufficiency
Emulsification in Small Intestine
• This increases the surface area of lipid droplets so that digestive
enzymes can act effectively.
• Emulsification is done by 2 complementary mechanisms,
1. Use of detergent properties of bile salts
2. Mechanical mixing due to peristalsis
• Emulsifying agents stabilize the broken small lipid droplets.
Absorption of Lipids
• Formation of HMG-CoA
• Formation of 5 carbon intermediates(Isoprenoids)
• Formation of squalene by 6 isoprenoids
• Formation of cholesterol by squalene and O2
*Formation of HMG-CoA
CO2
*Formation of cholesterol
Cholesterol Catabolism
Excess cholesterol excreted via bile in unesterified form as ‘bile acids’
7 α hydroxylase
Cholesterol Bile acids
Shortening of cholesterol molecule, Reduction of double bonds, Oxidation of side chains occur.
• This is the 1 and principal regulatory step and rate limiting step
• 1st Cholesterol is converted into 7α hydroxy cholesterol in the SER
• Then 7α hydroxy cholesterol forms primary bile acids in the liver.
SCAP- SREBP
cleavage activating Transcription
protein SREBP2-SCAP
[-] inactive (integral
protein of SER
Cholesterol membrane)
Translation
Functions of saliva
Keeps the mouth moist
Facilitates swallowing
Digestive function
Solvent for molecules that stimulate taste buds
Aids speech by facilitating movements of lips and tongue
Keep the mouth and teeth clean
Has antibacterial action / defense
Neutralizes gastric acid and relieves heart burn
Absorptive function –drugs, glucose
Salivary secretion
+ -
K , HCO3 NaCl
Iso/hypertonic
reabsorption is
e e e e e e e a v
1. Acini produces the primary secretion
2. The composition of the saliva is then modified as it flows from the acini out into ducts that eventually
coalesce and deliver the saliva into the mouth.
3. Na+ and Cl- are extracted and K+ and bicarbonate are added. Because the ducts are relatively
impermeable to water, the loss of NaCl renders the saliva hypotonic, particularly at low secretion
rates.
4. As the rate of secretion increases, there is less time for NaCl to be extracted and the tonicity of the
saliva rises, but it always stays somewhat hypotonic with respect to plasma.
Sleep
Fatigue
vasoconstriction
Dehydration
Fear
Reflex Arc
Stimulus- Food in the mouth
Receptor- Taste receptors
Afferents- CN 7 9
Central integrating area- Superior and Inferior salivatory nuclei
Efferents- CN 7 9
Effector- Salivary glands
Effect- Salivation
Swallowing
Is a reflex
Centre NTS/ NA
th th th
Mechanism of Swallowing
Efferent V , VII , IXth, Xth, XII cranial
1. Collection of food on tongue & pushing it back on the
nerves. Effectors Pharyngeal muscles, tongue. pharynx by pressure of tongue
2. Soft palate is pulled upward to close posterior nares
Effect Swallowing 3.Palatopharyngeal folds on each side of pharynx are pulled
medially to approximate each other
4.Vocal cords are strongly approximated
Anti-reflux mechanism 5.Epiglottis swings backward over the opening of larynx.
Tonic constriction of LES. 6.Pharyngoesophageal sphincter becomes relaxed
Lower end of oesophagus has a 7.A fast peristaltic wave initiated by the nervous system of the
higher pressure than stomach. pharynx forces the bolus of food into the upper oesophagus
Flap valve is formed by oblique 8. Conducts food rapidly from the pharynx to the stomach
angle of LES. (Assisted by peristalsis)
Fold of the mucus barrier.
Act of swallowing – Initiated voluntary & continued involuntarily
Voluntary collection of food on the tongue and pushing them back into the pharynx
Relaxation of UES
Peristalsis
Relaxation of LES
myenteric plexus
Secondary peristalsis
Peristalsis wave stimulated by distention of oesophagus by retained food
Continues in waves till the oesophagus is cleared
Gastric secretion
Gastric secretions – 2.5 L/day
HCl
Chief cells Pepsinogen 1 & 2 Pepsin
Gastric lipase
TAG FA + Glycerol
Ileal receptors
Absorbed by endocytosis
Alkaline urine
1. Cephalic Gastrin
synergistic
Acid secretion
The three agonists of the parietal cell—gastrin, histamine, and acetylcholine —each bind to distinct
receptors on the basolateral membrane. Gastrin and acetylcholine promote secretion by elevating
cytosolic free calcium concentrations, whereas histamine increases intracellular cyclic adenosine
3′,5′monophosphate (cAMP)
1. Protons are generated in the cytoplasm via the action of carbonic anhydrase II.
2. Bicarbonate ions are exported from the basolateral pole of the cell either by vesicular fusion or via a
chloride/bicarbonate exchanger
3. The cells are packed with mitochondria that supply energy to drive the apical H+ , K+ -ATPase, or proton
pump, that moves H+ ions out of the parietal cell against a concentration gradient of more than a million-
fold.
4. At rest, the proton pumps are sequestered within the parietal cell in a series of membrane compartments
known as tubulovesicles.
5. On stimulation tubulovesicular structures with H+ /K + ATPase move to apical membrane and fuse with it,
increasing surface area available for H+ /K+ exchange
6. The apical membrane also contains potassium channels, which supply the K+ ions to be exchanged for H+
The presence of the meal also buffers gastric acidity. Acidity otherwise would serve as a feedback
inhibitory signal to shut off secretion, secondary to the release of somatostatin, which inhibits both G and
ECL cells as well as secretion by parietal cells themselves
3.Intestinal
Others - Stimulants
Hypoglycemia – acts via brain and vagal afferents
Alcohol – acts directly on the mucosa
Caffeine – Stimulate CCK / gastrin
Mucus
Forms a flexible gel coating the mucosa. Secretion stimulated by prostaglandins
Made up of glycoproteins(mucins). Function – “Gastric mucosal barrier”
Secreted by neck and surface mucosal
Cells.
Disrupted by,
-ethanol NSAIDS Inhibits cyclooxygenase
-Vinegar
-Bile salts Prostaglandin secretion is inhibited
-NSAIDS e.g.-Aspirin
-Helicobacter pylori infections Mucus secretion Acid secretion
Bile
Haem Globin
2+
Porphyrin Fe
Prehepatic
Biliverdin
Circulation Bilirubin reductase
Bilirubin + Albumin Bilirubin
uptake
Active
EHC Liver Post
Urobilinogen Hepatic
Stercobilinogen Stercobilin Fecal excretion
Unconjugated bilirubin (Indirect) Conjugated bilirubin (Direct)
Poor water solubility More water soluble
Not excreted in urine Excreted in Urine
High lipid affinity Low lipid affinity
High albumin binding Low albumin binding
JAUNDICE(Icterus)
When total plasma bilirubin (free and conjugated bilirubin) level is greater than 2 mg/dL or 34 µmol/L it is known
as Jaundice.
Yellowish tint to the body tissues (skin, sclera, deep tissues)
Classification of Jaundice
Prehepatic Hepatocellular Post-hepatic
excess production of bilirubin decreased uptake of bilirubin into hepatic cells extrahepatic bile duct obstruction
disturbed intracellularprotein binding or conjugation
disturbed secretion of conjugated bilirubin intobile
canaliculi.
intrahepatic bile duct obstruction.
unconjugated bilirubin conjugated or unconjugated bilirubin conjugated bilirubin
Prothrombine time normal PT – abnormal. Isn’t corrected with Vit K. PT – abnormal. Corrected with Vit K.
Cholesterol HEPATOCYTE
↓
Iry bile acids (0.2 g/d)
↓conj: with glycine and
taurine Glycocholic/Taurocholic acid
↓ Na+/K+
+ +
Na ,K salts of glycocholate and
Taurocholate/Bile salts (3.5 g/d)
+
At the terminal ileum > 95% reabsorbed by Na
- bile salt cotransporter via enterohepatic
Excreted in bile circulation
ry
Secondary bile salts are produced by action of bacteria on I bile salts in the colon.
Gall stones
Calcium bilirubinate stones
1. 2 types
Cholesterol stones
2. Causes: -
Enteropeptidase
Procarboxypeptidase Carboxypeptidase
In acute pancreatitis, intra pancreatic activation of pancreatic enzymes like trypsin and auto digestion of
pancreatic issue.
Acute pancreatitis
Phospholipase A2 is activated prematurely in the pancreatic ducts, with the formation of lyso-PC from
the PC that is a normal constituent of bile. This causes disruption of pancreatic tissue and necrosis of
surrounding fat.
Cystic fibrosis
Small Intestine
Carbohydrate absorption
Luminal Enterocyte Basolateral
+
3Na
+
2Na
+
SGLT 1 & 2
2K
Glucose(&Galactose)
GLUT 2
GLUT 5
Glucose
Fructose
+
[Independent of Na
facilitated diffusion] Some fructose is converted to glucose in
the mucosal cell.
Pentose
Simple Diffusion
Finally emulsified in SI
(Detergent action of bile salts, lecithin, monoglycerides)
Take up lipids
Enter Enterocyte
FA > 10 - 12 C & Re-esterified Tri Glycerides Chylomicrons
Cholesterol
Fat & cholesterol
Lacteals
SCFA (FA < 10 - 12 C)
Lymph
Actively transported in to capillaries
Steatorrhoea Fatty
Bulky
Clay coloured
Stools Pale
Foul smelling
Greasy
Hard to flush
Pancreatic Lipase
deficiency Chronic liver ↓ Alkaline secreon from
disease pancreas
Acidity
Fat ↑ Gastric Acid
Bile duct
Malabsorption
obstruction
Cystic fibrosis (CF) is caused by mutations in the gene encoding the CF transmembrane conductance
regulator (CFTR)
CFTR is expressed on the apical membrane of epithelial cells in the small pancreatic ducts and
facilitates the transport of chloride and bicarbonate that produces alkaline fluid in ducts.
Pancreatic exocrine functions are severely compromised due to altered composition in the pancreatic
secretions and mucous plugging causing obstruction
Pancreatic enzymes are essential for lipid, carbohydrate and protein digestion. Maldigestion leads to
malabsorption of essential nutrients.
This causes malnutrition.
Fe3+ Fe2+
2+
Fe via DMT1 in duodenum
Almost all the iron absorption occurs in the duodenum.
2+
Heme is transported into the Transport of Fe into the
enterocyte by a separate enterocytes occurs via DMT1
heme transporter.
(heme carrier protein)
Water - mainly (98%) in small intestine. Jejunum > Ileum > Colon
Vitamin B12
Binds to Intrinsic Factor in the small intestine
The complex is absorbed predominantly in the Ileum
Na+ Absorption
NaCl enters across the apical membrane via the coupled activity of a a a
+ + - -
a Na /H exchanger (NHE) and a Cl /HCO3 exchanger.
+ - -
K /Cl cotransporter (KCCl) in the basolateral membrane provides for Cl
+ + +
exit, whereas Na is extruded by the Na /K ATPase.
Cholera ;
Vibrio cholera releases A-B exotoxin.
Causes activation of a G protein coupled receptor and production of cAMP.
Sodium flows out to negate the charge difference and water follows producing
diarrhea.
Protective function
Mucus
Solitary
Protection Lymph
Aggregated (Peyer’s patches)
Defensins Paneth cells
Large Intestine
+ -
Functions K , HCO 3
1. Absorption of water (1 – 2 L) and electrolytes
K+ - component of mucus,
+ -
Na , Cl , • Contain crypts of leiberkuhn
H2O but no villi.
along an electrochemical gradient
• No digestive enzymes but
HCO3 - to neutralize the acidic substances
-
secretes mucus.
Produced by microbial activation. • Mucus secretion increased by
Na+ - active transport(ENaC) Desquamated mucosal parasympathetic stimulation.
Cl in exchange for HCO3
- -
cells/mucus • Mucus secretion increased in
irritation of the colon (bacterial
2. Formation and excretion of faeces infections) causing diarrhoea)
Cellulose
Cellulose
Inorganic material
2+
mostly Ca , PO43-, fat
and fat derivatives.
Non-dietary in origin (unaffected by diet & starvation – Even in prolonged starvation)
Prebiotics are compounds in food that induce the growth or activity of beneficial microorganisms like bacteria and fungi.
Probiotics are the beneficial microorganisms that naturally live in the body.
3. Microbial activity
Effects of intestinal bacteria
4. Conversion of AA NH3
o Harmful in liver disease
o Associated with hepatic
encephalopathy
Vit ADEK ↓
Overgrowth of bacteria Steatorrhoea 2+
Ca ↓
Unconjugated
E.g. blind loop
bile salts PT ↑
syndrome Irritates
Colon Diarrhoea
When the bacterial overgrowth happens in the upper small intestine the bile salts will
get deconjugated decreasing the emulsification process of lipids. Which will lead to
lipid and lipid soluble vitamin malabsorption.
Gastroileal reflex
Food leaving stomach Relaxation of caecum Passage of chyme through ileocecal valve
Ileocecal valve
Usually closed. Opens when ileal pressure ↑ & closes when colonic pressure ↑
Movements of colon
Peristalsis
Segmentation contraction
Mass action contraction
o Only in colon. Simultaneous contraction of smooth muscle over a large confluent area.
Defecation
Spinal reflex ( S2-S4 spinal cord segment) which can be modified voluntarily.
In infants no voluntary control
Resting,
Rectum empty reflex evacuation of the rectum can occur
External anal sphincter in a state of tonic contraction even in the setting of spinal injury.
Internal anal sphincter tone - ↑ by sympathetic stimulation
↓ by parasympathetic stimulation
Urge to defecate
Inappropriate Appropriate
Puborectalis relaxed
Defecation
Reverse peristalsis
(Upper part of SI to stomach)
Glottis closure
Reverse peristalsis
Ejecting gastric content
Stimulation of vomiting
Motility of GIT
1. Peristalsis Oesophagus to rectum A reflex response to stretch
2. BER All part of the GIT except Spontaneous rhythmic fluctuations in RMP
oesophagus and proximal of GIT smooth muscles
part of the stomach
3. MMC Stomach to distal ileum Cycles of motor activity during fasting
period
4. Segmentation Small intestine Ring like contractions appear at regular
contraction Large intestine intervals, then disappear and are replaced
by another between the previous two
5. Tonic Small intestine Prolonged contraction of isolated
contractions segments at a time
6. Mass action Large intestine Simultaneous contraction of smooth
contractions muscles
over a large confluent area
Patterns of GI motility
Spontaneous rhythmic fluctuations in the membrane potential of GI smooth muscle.( (-45) - (-65) mV )
All parts except esophagus & the proximal part of the stomach.
This BER is initiated by the interstitial cells of Cajal.
BER rarely cause muscle contractions.
If the membrane potential drifts up to the threshold, spike potentials appear.
Spike Potentials excite muscle contraction.
The function of the BER is to coordinate
The depolarizing peristaltic and other motor activity, such as
portion of each spike is setting the rhythm of segmentation;
2+
due to Ca influx, and contractions can occur only during the
the repolarizing portion depolarizing part of the waves. After vagotomy
+
is due to K efflux or transection of the stomach wall, for
example, peristalsis in the stomach becomes
irregular and chaotic.
Associate with increase in gut secretions and helps to clean the left overs (Housekeeping Waves)
In the stomach and SI up to distal ileum.
During periods of fasting and abolished by eating.
Each cycle
Phase I - Quiescent period (resting/ inactive)
Phase II – irregular electrical and mechanical activity.
Phase III – burst of regular activity.
Mediated by motilin which increases in blood of intervals of 90- 120 min between meals.
Causes gastric secretion, bile flow, pancreatic secretion.
Clear the stomach & small intestine to avoid bacterial growth.
Segmentation
A segment of bowel contracts at both ends followed by a contraction in the middle of the segment
and forces chyme backwards and forwards.
Slows down movement of intestinal contents along intestine allowing time for digestion &
absorption.
Carried out by enteric nervous system.
GI regulatory mechanisms
Hormonal act in paracrine fashion, also enters blood stream
Neural Extrinsic
Intrinsic (enteric nervous system)
Neural regulation
Hormonal regulation
Blood supply to the LOH by Network of peritubular capillaries Vasa recta capillary loops
Kidney Functions
Excretory:
• excretion of metabolic waste products - creatinine, urea, uric acid, bilirubin & various
hormones
• foreign substances - drugs and metabolites of drugs, food additives & ingested
pesticides.
Regulatory:
Endocrine:
• production of erythropoietin
• 1, 25-DHCC
• renin
• prostaglandins & kinins
Role of Erythropoietin
1) Glomerular Filtration
I. Filtration Membrane (contains negatively charged heparin sulphate. Therefore, repels albumin
preventing filtration)
These are stellate cells located
Afferent between the basal lamina and the
arteriole endothelium
Efferent arteriole
Capillary
endothelium
Mesangial
cells
Basal lamina
Epithelium
of capsule Podocytes
Filtration slit
II. Filtrate
• Isotonic to plasma
• Contain plasma except – plasma proteins (albumin)/ fat/ blood cells/protein bound
calcium ion
• Contains,
➢ Water
➢ Low molecular weight organic substances: ex. glucose, AA
➢ Waste products: ex. creatinine, urea, urobilinogen etc.
➢ Inorganic substances (electrolytes): ex. Na+, K+, Ca2+, Cl-, HCO3-
➢ Smaller proteins (many of the peptide hormones ex. Insulin, ADH) – their
amounts in the filtrate are negligible compared to amounts of larger proteins in
blood
• Glomerular filtrate contains very minute quantities of albumin (about 0.02% of the concentration of albumin
in plasma) and some smaller proteins.
• But filtrate is considered as “nearly protein-free”
(no proteins)
Capillary length
➢ GFR may vary due to changes in the above quantities
Efferent arteriolar constriction has a biphasic effect on GFR. At moderate levels of constriction, there is
a slight increase in GFR, but with severe constriction, there is a decrease in GFR.
• Glomerular capillaries have high concentrated plasma proteins as plasma filters through the membrane.
𝐺𝐹𝑅
𝐹𝑖𝑙𝑡𝑟𝑎𝑡𝑖𝑜𝑛 𝐹𝑟𝑎𝑐𝑡𝑖𝑜𝑛 = = 0.16 − 0.20
𝑅𝑒𝑛𝑎𝑙 𝑃𝑙𝑎𝑠𝑚𝑎 𝐹𝑙𝑜𝑤
(Note: When blood pressure drops GFR and Renal Plasma Flow both reduced. But Renal Plasma Flow reduced
more than GFR. So filtration fraction increases.)
Arterial pressure
(mmHg)
90 220
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Renal Blood flow to cortex & medulla and Oxygen consumption
Renal clearance
The volume of plasma that is completely cleared or removed of substance by the kidneys in unit time.
Renal Clearance
Complete
Zero Partial
Eg:- PAH (para amino hippuric
Eg:- glucose acid) Eg:- creatinine
All substances filtered is Almost completely removed By filtration & tubular secretion
completely absorbed (90%)in a single circulation, by Inuline
filtration and tubular secretion
Only by filtration.
Advantages Disadvantages
Plasma[y] mg/ml × Plasma volume filtered ml/min = Urine[y] mg/ml × Urine volume excreted ml/min
GFR = Volume of plasma cleared of substance ‘y’ by the kidneys per minute
V – Urine volume
eGFR (mL/min/1.73m2) = 186 X (Scr)-1.154 X (Age)-203 X constant (0.742 if female) x (1.210 if black African)
CCr (mL/min)
0 60
• Serum Urea
• influenced by many factors. not constant.
• 95% of urea excretion is by the kidneys.
Physiological control of
GFR & RBF
Mesangial cells
Mechanism
• Increased Na+ reabsorption via Na+/K+/2Cl- co-transporter
• Na+ and Cl- in DCT sensed by macula densa
• Increased Na+/K+ ATPase activity
• More adenosine formed by ATP hydrolysis
• Act on receptors of macula densa cells
• Release of Ca2+
Endothelin flow
Collecting Tubule
PCT
Collecting Duct
• PCT is the main site except for K+ (main site is PCT & CD)
• Control blood pH
• The fluid which filter from glomerular membrane remain isotonic when passing through PCT.
02.Thin Limb of LOH
• Water is reabsorbed mainly along the osmotic gradient which is produced by medullary
hyperosmolality.
• K+, H+ Secretion
Intercalated Cells
Principal cells
• In late part of DCT, Principal cells involve in water reabsorption by the actions of ADH &
Aldosterone. Intercalated cells involve in Acid Base Balance.
• Collecting tubules act same as late part of DCT.
Urea Reabsorption
• Required to maintain the medullary hyper osmolality
• Reabsorption is increased by vasopressin
• Urea reabsorption increases after a high protein diet as urea excretion increases.
02.Na+
7% cotransporter
99% reabsorbed
Na+/ Cl-
3%
65% mainly at PCT
The ability to eliminate unwanted K+ is less dependent on GFR than urea and creatinine
04.Ca2+
Diabetes Insipidus
Humans have the concentrating ability of urine according to the needs of the body. Osmolality of urine
varies in a vast range according to the body water need. (30-1400 mOsm/kg)
Depends on
Produced by Maintained by
• Solutes recirculate in medulla while water get absorbed to the vasa recta.
• This maintain the medullary hyperosmolality
• Vasa recta do not create the medullary hyperosmolarity, but they do prevent it from
being dissipated.
Role of Urea
• About 20 - 50% of filtered urea is excreted
• Rate of urea excretion depends on
➢ [urea] in plasma
➢ GFR
➢ Renal tubular urea reabsorption
• About 40 – 50% urea is reabsorbed passively by PCT
• Thick LOH, DCT and cortical CD are relatively impermeable to urea
Isotonic
Hypotonic
Isotonic Cortex
Isotonic
Medulla
Hypertonic
9 © 2018 A/L Repeat Campaign
Regulation of renal functions
Regulation of blood pressure and volume
Renin-Angiotensin-Aldosterone mechanism
• Renin is a glycoprotein
• Secreted by juxtaglomerular cells in the juxtaglomerular apparatus
• Converts angiotensin to angiotensin I
• Lead to formation of Angiotensin II from angiotensin I by ACE
• ACE found in vascular endothelium
• Specially lungs
Diuretics
Cirrhosis
Intra renal baroreceptor mechanism – Renin is secreted when the blood pressure falls.
Stimulate aldosterone
secretion (indirect effect)
)
Increase the number & activity of Increases the activity of
Na+/K+ ATPase pumps of DCT & CD Na+/K+ exchanger
*Angiotensin II stimulate aldosterone secretion but main stimulus for Aldosterone secretion is
increasing the Plasma K+ concentration.
Natriuretic peptides
Receptors
• Osmoreceptors – In hypothalamus
• Baroreceptors – In blood vessels
Vasopressin
• Cause vasoconstriction.
• Increase water reabsorption. How??
pressure. pressure.
• After a haemorrhage, plasma ADH levels do not change appreciably until blood volume
is reduced by about 10%.
NTS
Vasopressin
Increased plasma
osmolality
Low pressure baroreceptors
V2 Receptors in Principle
cells Decreased blood
volume
Baroreceptors
Osmoreceptors in
hypothalamus Angiotensin II
Hypothalamus
Dryness in
pharyngeal mucosa Thirst
Drinking
vasopressin hypothalamus
GFR is increased
Converted by Renin
Angiotensin I Angiotensinogen
Reabsorption of Cl-
Limiting pH of urine-4.5
Intracellular pH 6.8
If pH is more than normal - alkalemia.
If pH is lower than normal - acidemia ECF survival range 6.8-7.7
Defense mechanisms
1. Buffer systems in body fluid (Act immediately)
2. Respiratory system (within minutes)
3. Renal system (hours, days) – Most effective
H+ in ECF H+ in ECF
<7.4 >7.4
↓ ↓
Acidemia Alkalemia
Mechanisms of H+ secretion
1. Na+/H+ exchange – PCT, Thick ascending limb of LOH and early DCT
2. ATP-driven proton pump – Intercalated cells in late DCT
and CD (Increased by aldosterone)
3. H+/K+ ATPase – In DCT and CD
HCO3- buffer
Rapidly removes H+ from urine. But no excretion of H+ in urine.
Prevents decrease in pH of filtrate
For each HCO3- absorbed from filtrate one HCO3- is added to blood – “Reclaiming HCO3- “
Metabolism of proteins
↓
Non-volatile acids
-
H+ secretion HCO3
H+ secretion
• Independent of Na+ reabsorption
• Secreted by ATPase driven proton pump – I cells of CD
• Iry active transport
• Aldosterone increases its activity.
• In acidosis many tubulo-vesicular structures are inserted to the apical membrane to
increase H+ secretion.
• Limiting pH is achieved. (4.5pH)
• For each H+ secreted, HCO3- enters the interstitial fluid
• Secreted H+ buffered by
o Phosphate buffer in the filtrate
o NH3 made in the cells
• Mainly in I cell
• Amino acid metabolism ➔ Glutamine (in liver )
• Glutamine glutamate + NH4+
Glutaminase
-KG + 2 H+ 2HCO3-
➢ NH3 lipid soluble ➔ diffuses across cell membranes
Most of the acid is excreted in PCT. In the PCT pH drops slowly as secreted H+
binds with HCO3- and form H2CO3 and then
- But only little as × 4 increase in urine [H+]
CO2 and H2O. The apical membrane is
- Lower limit pH 6.7 permeable to CO2 and it is removed from
Only 5% of the acid secreted in DCT the tubular cells by Carbonic Anhydrase.
- But as × 900 increase in [H+] But,
In DCT, secreted H+ is buffered by many
- Lower pH limit 4.5
HPO4- or NH3
Increase Decrease
• PCO2 ↑
• H+ ↑ , HCO3- ↓
• ECF volume ↓ Opposite
• angiotensin II ↑
• aldosterone ↑
• Hypokalemia
In diabetes mellitus
Water Diuresis –
Begins 15 mins. After drinking water (40 mins maximum)
Small decrease in vasopressin secretion even before water is absorbed from the gut.
• Ethanol → inhibit vasopressin secretion
• Antagonists of V2 receptors → inhibit action of vasopressin on CD
Osmotic Diuresis –
Increase in urine volume due to presence of large quantities of unabsorbed solutes in the renal tubules
❖ In diabetes mellitus filtered glucose is not completely reabsorbed. Remaining glucose cause
osmotic diuresis leading to polyuria and polydipsia
Process
1. ↑concentration of osmotically active particles in PCT lumen hold water in the tubules, not allowing
reabsorption
2. ↑water volume in lumen → ↓[Na⁺] concentration in spite of high Na⁺ amount→ limiting concentration
gradient reached (at DCT) → Na⁺ reabsorption down the concentration gradient prevented→↑Na⁺
reducing further water reabsorption
Kidney diseases
AKD / ARF CRF / CKD
• Snake bites, toxins • Progressive loss of function of more and more
• Kidney abruptly stops working, entirely or nephrons.
almost entirely. • Gradually decreases overall kidney function.
• May eventually recover nearly normal
function.
Micturition
Is the process by which the urinary bladder empties when it becomes filled.
• Step1: progressively fill till threshold is reached.(filling phase)
• Step 2: Initiation of micturition reflex, conscious desire to urinate.(voiding phase)
Micturition reflex: an autonomic spinal cord reflex, facilitated and inhibited by higher brain centers in the
cerebral cortex or brain stem.
v Self – regenerative reflex – initial contraction of bladder activates stretch receptors in the bladder and
posterior urethra which causes a further increase in reflex contraction of the bladder.
Then the reflex fatigue and regenerative reflex cycle ceases & bladder relaxes
\ Cycle
1. progressive & rapid↑ of pressure
2. sustained pressure
3. return to basal tone
Urine is made in the kidneys and comes down to the bladder for storage.
Oblique passage through the bladder wall keeps the ureters closed except during peristaltic waves which bring in
urine.
\ During contraction of detrusor muscle, reflux of urine from the bladder to the ureter is prevented.
Abnormally short oblique passage, valve malfunctions results in Vesicoureteral reflux (back flow of urine from
bladder to ureter – if reflux is severe it can increase pressure in renal calyces & renal medullary structures.)
Once micturition reflex has occurred but not emptied, nervous elements of the reflex usually remain inhibited for a
few minutes to 1 hour till the next reflex
As the bladder progressively fills, reflexes occur more frequently and powerfully
Once the micturition reflex is powerful enough it induces another reflex that inhibits contraction of external
sphincter.
Innervations
- Pelvic nerves (S2, S3, S4) - Sensory → detect degree of stretch of bladder wall
Preganglionic parasympathetic Motor → (parasympathetic) postganglionic fibres to
detrusor muscle
- Pudendal nerve (S2, S3, S4) – skeletal motor fibers to external sphincter
- Hypogastric nerves - sympathetic innervations (No part in micturition)
Sphincters – Internal muscle bundles on either side of urethra prevent reflux of semen in to the
bladder during ejaculation (sympathetic innervations, no parasympathetic innervation)
External ring of skeletal muscles, voluntary control of micturition
Pressure of the bladder is investigated using cystometrogram.
1 © 2018 A/L Repeat Campaign
Micturition reflex
Stimulus - stretch in the posterior urethra at the back of the bladder
Afferent - pelvic nerves (sensory – parasympathetic)
Coordinating center - sacral portion of the spinal cord
Higher center inputs - facilitatory center in the pons (PMC), posterior hypothalamus, inhibitory area in midbrain,
cortex
Efferents - pelvic nerve (motor – parasympathetic)
Effector – Detrusor
Effect – micturition
Micturition reflex is the basic cause of micturition, but higher centres exert its final control:
1. Maintain reflex partially inhibited unless when desired
2. Prevent micturition even if reflex occurs by tonic contraction of EUS until it’s appropriate.
3. When appropriate, Cortical centers facilitate sacral micturition centers to initiate a micturition reflex while
simultaneously inhibiting EUS contraction.
Voluntary micturition – voluntary contraction of abdominal muscles
Initiate micturition before reflex is naturally initiated
↑ Pressure in bladder → stretch receptors stimulated →Micturition reflex excited → ext. sphincter inhibited →
voiding of urine
During micturition – Perineal muscles are relaxed
Lowering of pelvic floor
External urethral sphincter relaxed
Detrusor muscles contract
After urination - Female - urethra empties by gravity
Male- expelled by several contractions of bulbocavernosus muscle
Voiding can be initiated without straining even when the bladder is nearly empty by the effect of higher centres
• Plot of intravesicular pressure vs. volume
of urine in bladder as it fills.
Cystometrogram has 3 phases
Ia. Initial slight rise – Due to increase in
urine volume (till 50mL)
Ib. Long flat segment – Law of Laplace
(Till 400mL)
II. Sharp rapid rise (over 400ml)
Flat segment is a manifestation of the law of Laplace
P=2T\R
As T rises so does R
\P remains constant
v When the bladder is filled, volume increases. So, the R of viscus increases. This causes a decrease in
intramural pressure (P). P is maintained by increasing muscular tension (T) of the bladder wall. So, P returns
to basal level.
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Abnormalities in micturition
1. Deafferentiation
• Sacral dorsal roots are damaged or tabes dorsalis (Tabetic bladder)
• All reflex contractions of the bladder are abolished. But intrinsic myogenic contractions to stretch
can happen,
• Results in atonic neurogenic bladder– distended, thin walled and hypotonic & Overflow
incontinence (non-periodically emptying- dribbles a bit when filled to capacity)
Eg: crush injury to sacral region of spinal cord.
2. Denervation
• Both afferent and efferent nerves are destroyed. By damage to cauda equina.
• Results in autonomous bladder. Bladder becomes shrunken and hypertrophic, dribbling urine
present under denervation hypersensitivity
3. Spinal cord transection
• During spinal shock, bladder is flaccid and unresponsive
• Results in overflow incontinence
After spinal shock, voiding reflex returns gradually with denervation hypersensitivity resulting in spastic
neurogenic automatic bladder. no voluntary control and no inhibition or facilitation from higher centers
• Voiding can be initiated in such patients by mild mass reflex
4. Nocturnal micturition (enuresis) – normal until 3 to 7 years
Male Female
SEXUAL DIFFERENTIATION
Embryonic
ovary does
not produce
or excrete any
hormone in
considerable
amounts
hCG
AND
X
(From 8th -
13th week)
• Hormonal treatment of the mother has no effect on gonadal differentiation. But affects internal and
external genitalia development
• At the 13th week development of genitalia is complete. So exposure to hormones after this period will not
affect development of any genitalia.
• Both DHT and testosterone bind with the same receptors. But DHT has higher affinity to the receptor.
MIS Levels
• In females, MIS is secreted in very low (undetectable) amounts by granulosa cells in the fetal and pre
pubertal stage.
• Levels increase at puberty and acquire a constant value.
• After puberty plasma MIS level is equal in both male and female. (2ng/mL)
Chromosomal Hormonal
Results in Pseudohermaphroditism
Cholesterol
3 HSD
21 Hydroxylase
11 Hydroxylase
• Puberty is the period when endocrine and gametogenic functions of the gonads have first developed to
the point where reproduction is possible.
• Adolescence – A time of transition during which young people are no longer children but have not
assumed responsibilities of adults.
• Age of onset
o Girls: 8 – 13 years A burst of testosterone secretion occurs in
o Boys: 9 – 14 years male foetuses before birth. In the neonatal
period there is another burst. But there
after Leydig cells become quiescent until
the commencement of puberty.
BOTH SEXES
1. Increased physical growth
t
Pubertal growth spurt
ga 15.2
in
(c Pubertal growth spurt
10.2 occurs earlier in females
Girls
Boys
5.1
2 4 6 8 10 12 14 16 18 18
Age in years
Though both DHT and Testosterone play huge roles in the changes which occur in males at puberty, these 2
hormones also have functions which are exclusive to each of them
1. Dihydrotestosterone (DHT)
• Enlargement of the prostate
• Enlargement of the penis
• Temporal recession of the hair line
• Facial hair
• Acne
2. Testosterone
• Increase in muscle mass
• Increase in male sex drive and libido
Boys Girls
• Axillary and Pubic hair • Axillary and Pubic hair
• Growth and enlargement of internal • Growth and enlargement of internal
and external genitalia and external genitalia
• Increased facial + body hair • Breast development
• Decreased scalp hair (hair line goes • Subcutaneous fat deposition
above) • Menarche
• Increased muscle mass
• Low pitched voice
4. Adrenarche
✓ Increase in adrenal androgenswithout a simultaneous increase in ACTH.
✓ Due to increased activity of enzymes in androgen producing pathway
✓ Principal adrenal androgen – DHEA (Dehydroepiandrosterone)
✓ Promotes;
▪ physical growth,
▪ axillary and pubic hair growth,
▪ sebaceous gland development,
▪ body odour and acne.
Note; Growth of pubic and axillary hair in both sexes is due to androgens, rather than oestrogen
Chronological order
GIRLS
Breast budding (Thelarche)
1. Thelarche
Pubic hair begins (Pubarche)
✓ Development of breast followed by development of pubic and axillary hair
✓ Ovarian oestrogen stimulates growth of lactiferous ducts Peak height spurt
✓ Progesterone – Alveolar lobule development
Menarche
Onset of PUBERTY
Precocious puberty
True-precocious Pseudo-precocious
- Maturation of H-P-G axis - H-P-G axis is immature
- GnRH, FSH, LH increased - GnRH, FSH, LH levels are low
- True gametogenesis - No gametogenesis
- Early, but normal pubertal pattern of - Excess oestrogen in girls and Androgens
pituitary gonadotrophin secretion. in boys
Delayed puberty
Boys Girls
- No genital growth by 20 years - No menarche by 17 years (primary
amenorrhoea)
Causes Causes
- Klinefelter Syndrome - Turner’s Syndrome
- Anorexia Nervosa
Transport of Hormones
• Begins during Puberty
• Requires
v FSH
ü Acts on Sertoli cells to facilitate late stage of spermatid development.
ü Stimulate secretion of Inhibin
ü Stimulate androgen-binding protein production.
ü With testosterone, promote spermatogenesis.
v Testosterone
v LH indirectly
ü Acts on G-Protein Coupling receptors on Leydig cells to stimulate testosterone synthesis.
ü Trophic effects on Leydig cells.
ü Locally produced oestrogen.
v Low Temperature 34°C
Temperature is maintained by counter-current mechanism.
• Takes about 74 days.
• 1 spermatogonium gives rise to 512 spermatids.
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Further Maturation of Sperm
• Acquire progressive motility (the ability to move forward) by activating CatSper proteins in principal piece
of the sperm within epididymis.
• The CatSper protein forms an alkaline sensitive Ca2+ channel that becomes more active when the sperm
travels from the acidic vagina to the more basic cervical mucus.
• At rete testes, fluid is absorbed, and spermatozoa are concentrated.
• This is carried out by the activity of oestrogen on receptors in this region.
• Failure of this process leads to infertility.
• Spermatozoa contain olfactory receptors required for chemotaxis
Capacitation–
Ø Functional changes which make sperms able to fertilize.
Ø Occurs in isthmus of uterine tubes
ü Increase motility
ü Preparation for acrosome reaction
Ø Capacitation is facilitatory, not obligatory, because fertilization can be produced in vitro without it.
Acrosome Reaction
Breakdown of acrosome and release of enzymes- proteases (e.g. Acrosin)
Proteolytic enzymes help in penetrating zona pellucida but isn’t essential
Acrosomal reaction can occur in many sperms. But only one acrosome reacted sperm fuses with the oocyte.
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Seminal Fluid
Testicular products Products of accessory glands
Sperms Fluid of e.g. – ● Seminal vesicles (60% of seminal volume)
epididymis Seminal vesicle fluid contains Fructose, Ascorbic
acid & prostaglandins.
● Prostate
Citric acid, cholesterol, fibrinolysin, acid
phosphatases, Zn
“Fertile” Seminal Fluid
Chemical disrupters of Reproductive
Sperm count - 60-100million/ml
function
Volume - 2.5 to 3.5 ml/ ejaculate
pH – 7.35-7.5 • Alcohol
Sperm motility - >40% actively motile • Smoking
Sperm morphology - <20% abnormal • Narcotics
Liquefication time - 5 to 30 mins • Pesticides/ Weedicides
Azoospermia – absence of sperms
Oligospermia – count <20 million
Asthenospermia – active motility <40%
Varicocele causes male infertility
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Neuroendocrine regulation of male reproductive system
Hypothalamus
GnRH
Stimulation
Negative feedback
Anterior pituitary
LH FSH Male gonadotrophin secretion is
noncyclical
Leydig cells Sertoli cells
In both sexes main regulator of FSH is
inhibin
Testosterone Inhibin B
Estrogen Estrogen
• Castration causes increased levels of FSH & LH.
• Administered testosterone decreases sperm count due to negative feed back of FSH and LH.
• Testosterone doesn’t inhibit FSH at physiological concentrations but may do so in large doses.
• Inhibin is used as a male contraceptive. (Testosterone can also be used)
• Inhibins are produced in Sertoli cells in males and granulose cells in females.
• Testosterone mainly bound to GBG/SHBG.
• Androstenedione, estradiol and progesterone bound to albumin.
• Late spermatids & spermatozoa contain a germinal Angiotensin-converting enzyme.
Inhibin
• Two types are present
o Inhibin A - Has both α and βA subunits bound covalently by disulfide bonds
o Inhibin B - Has α and βB subunits
FSH regulating inhibin in adult men and women
• Found not only in gonads but also in other tissues
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Female Reproductive System
Menstruation
Periodic vaginal bleeding with shedding of uterine mucosa, from menarche to menopause which is absent during
pregnancy & sometimes during lactation. Most common cause for secondary amenorrhoea is pregnancy.
• Menorrhagia is excess bleeding during menstruation.
• Dysmenorrhoea is painful menstruation.
Note; Oogenesis begins during fetal life. No new ova formed after birth.
• Formation of an antrum around the oocyte causes the development of several antral
follicles
Development of
Recruitment of dominant follicle Formation & maintenance
follicles (1-5 d) Rest – become atretic. of corpus luteum
1 6 14 24 28
Dominant follicle; has the highest Ovulation Corpus luteum
capacity to secrete estragon regression begins
Ovarian Changes
➢ FSH levels high in early follicular phase to stimulate granulosa cells to produce estragon. Decrease in
follicular phase and luteal phase due to negative feedback.
➢ LH levels initially low due to negative feedback. Peak happens at mid-cycle due to positive feedback from
high levels of oestrogen.
➢ LH surge occurs 9 hours before ovulation.
➢ Just before ovulation, the first meiotic division is completed.
➢ Corpus luteum secretes oestrogen and progesterone in luteal phase and maintains FSH and LH at low
levels.
➢ Inhibin levels reach the peak at mid luteal phase. Then decrease allowing FSH levels to rise.
➢ Progesterone and oestrogen levels then decrease in late luteal phase due to formation of corpus albicans.
Endometrium is shed because high levels of oestrogen and progesterone are needed to maintain it in
secretory phase.
➢ Ovum lives for 72 hours after ovulation but fertilizable for 24 hours.
➢ Oestrogen levels show 2 peaks. Just before ovulation mid luteal phase.
2 © 2018 A/L Repeat Campaign
Pattern of secretion of reproductive hormones during the normal menstrual cycle
•primary oocyte
•granulosa cells
Secondary
(Pre-Antral) •theca cells (interna + externa)
follicles •Theca interna- Andogen producing Theca externa-Protective capsule
Menstruation
•due to regression of Corpus Proliferative phase
luteum (5th - 14th day)
•endometrium - becomes thinner •rapid increase in
•spasm & degeneration of walls of thickness. (proliferation)
arteries due to locally produced •Straight uterine glands
prostaglandins --> ischemia and lengthen
necrosis of superficial layers -->
spotty haemorrhages --> •Maintained by estrogen
confluence --> menstrual flow
Secretory phase
•highly vascularised
•stroma oedematous
•coiled glands
About 14 days •spiraling of the arteries
increased
Length of the secretory •secretes clear fluid
phase is more constant than •changes in cell adhesion
the length of the proliferative molecules etc Note Menstrual blood is
•later --> Prolactin mainly arterial and does
phase.
production
not clot due to the
•Maintained by estrogen
& progesterone presence of fibrinolysin
Cervical mucus
Effects on breast
• Estrogen & progesterone act on the breast during the luteal phase.
• Swelling, tenderness, and pain during the 10 days preceding menstruation due to distension
of ducts and hyperaemia.
Anovular menstruation
• Can occur during the,
a. 1st 12 – 18 months after menarche
b. Before the onset of menopause
• Duration of the cycle is variable, but is always less than 28 days.
Estrogen synthesized
Endometrium develops absence of progesterone
Follicular atresia
Estrogen endometrium breaks
LH FSH
C Cholesterol
i
r Cholesterol Androstenedione
c A
u n
Androstenedione aromatase
l t
a r
Estrone Estrone Estradiol
t u
i Estradiol Granulosa m
Theca interna
o cells/theca lutein
cells/theca lutein
n in corpus luteum
in corpus luteum
Note;
❖ Both LH and FSH act by increasing cAMP levels
❖ Granulosa cells produce inhibin too
❖ LH also stimulate mature granulosa cells
❖ FSH is responsible for the early maturation of the ovarian follicles and FSH and
LH together are responsible for their final maturation.
Hypothalamus Stimulate
GnRH
Negative
feedback
Anterior Pituitary
LH and FSH LH stimulate progesterone
production. FSH and LH both
Corpus Luteum stimulate estrogen
production.
Oestrogen Inhibin
Progesterone
Transport of Hormones
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Detection of ovulation
Menstrual history – regularity, Dysmenorrhoea (pain in menstruation),
Mid cycle pain (indicate the ovulation)
During second half of cycle – Serum hormones (progesterone day 21 to 24)
Changes in cervical mucus (watery change to viscid)
Rise in basal body temperature (1-2 days after ovulation)
Secretory endometrium
Visualization by ultrasound and laparoscopy (corpus luteum or Graafian follicle)
Oestrogen Progesterone
3 forms, ✓ Thermogenic
✓ Regulation of hypothalamus and
• 17β estradiol-Normal menstrual cycle
• Estrone-After menopause pituitary
• Estriol-Pregnancy ✓ Breast-lobular, alveolar growth
Menopause
Q. Why FSH, LH found in the urine of women after menopause in considerable amounts?
• Decrease of oestrogen & progesterone levels will reduce their negative feedback on FSH &
LH.
• No significant change in the progesterone levels as
it is produced by the corpus luteum.
Transitional period (4th decade) -
↓Reduction in gonadotrophin- ↓Estradiol ↑FSH (Progesterone and LH no
responsive follicles Inhibin significant change)
After menopause -
↓Absent gonadotrophin- ↓Estradiol ↑ FSH, LH (Excreted in urine)
responsive follicles Inhibin
Progesterone
Estrogen deficiency
• Hot flushes
• Atrophy of breast & reproductive tract
• Reduced vaginal acidity (reduced glycogen in cells – prone to infections)
• Dyspareunia (pain during sexual intercourse)
• Prone to IHD. Why? LDL, TAG ↑; HDL ↓
• Behavioural & emotional changes
• Osteoporosis
Hot flashes (flushes)
• Set point of the central thermostat lowered
• Heat dissipating mechanisms are activated
• Wave of heat passing over the chest & spreading to neck, face, upper arms followed by
sweating
• Marked vasodilatation followed by vasoconstriction
• Oestrogen therapy brings relief
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HUMAN SEXUAL RESPONSE
Sexual dysfunction
Desire disorders Sexual Arousal disorders
Orgasm disorders disorders Pain disorders
Physical causes
Diabetes mellitus, neurological disorders, obesity, endocrine disorders, alcoholism, drug abuse,
side effects of some medication.
Psychological causes
Stress, anxiety, marital and relationship issues, depression.
Males Females
1.Erectile dysfunction 1. Inability to achieve orgasm.
Inability to achieve or maintain an erection 2. Inadequate vaginal lubrication (before and
suitable for intercourse. during intercourse)
2. Premature ejaculation 3. Vaginismus
Inability to control the timing of ejaculation Inability to relax the vaginal muscles enough
leading to early ejaculation. to allow penetration of penis.
3. Retarded ejaculation
Absent or delayed ejaculation despite adequate
sexual stimulation
Males Females
Erection takes a long time Excitement takes a longer time
Weak erection (physiological impotence) ↓ vaginal secretions leading to dyspareunia
Extended plateau phase
Shortened orgasmic phase
Ejaculation may not happen on all occasions
↓ seminal fluid volume and expulsive phase of
ejaculation
↑ refractory period
• Somatogenic or Psychogenic
• Stimuli are classified according to the sense involved
Visual – nude photographs, porn films
Olfactory – certain scents, pheromones (odorless chemicals that act as hormones
Auditory – certain music, special person’s voice
Somatosensory – touch of an erogenous zones (regions of high concentration of nerve
endings)
• Environment – romantic
• Stimuli for sexual arousal vary from person to person and from one time to another
Males Females
Stimulus is more physical/somatogenic (naked Stimulus is more psychological (intimacy, privacy,
photos) feeling valued)
Erotic stimuli
↓
Excitement
↓
Plateau
↓
(If conditions are satisfactory, coitus/masturbation)
Orgasm
↓
Resolution
During the sexual response cycle certain physiological changes are evident through out the entire body.
• Extra genital reactions
• Genital reactions
Males Females
Testes Clitoris
Cowper’s gland
secretes clear fluid
Prostate enlarges
Coordinated activity
Sympathetic
Parasympathetic
Somatic
Erection
The process in which the flaccid penis becomes engorged, enlarged and widened and longer and harder.
A spinal reflex
Stimulus – Rubbing of the penis (masturbation or thrusting the penis into the vagina)
Effector organ – The smooth muscle cells of the matrix of the corpora cavernosa
Effect – erection
Sildenafil (Viagra) inhibits the action of phosphodiesterase which breaks down cGMP into 5-GMP and
thus is used to treat erectile dysfunction.
Ejaculation
A sympathetic response, integrated in the upper lumbar segments of the spinal cord (T10 – L3)
Afferents from touch receptors of glans penis (via internal pudendal nerve)
↓
Activation of spinal cord integrating centers
↓
Efferent sympathetic output via hypogastric nerve
↓
Contraction of the internal urethral sphincter (prevents reflux of semen into the bladder when
urethral pressure increases)
↓
Contraction of ampulla of vas deference, seminal vesicles, smooth muscles of prostate
↓
Deposition of the seminal fluid in the prostatic urethra
True ejaculation
This part of the reflex is mediated in lower lumbar and upper sacral segments of the spinal cord.
Motor pathway traverse 1st to 3rd sacral roots and the internal pudendal nerves.
One sperm fuse with ovum, mediated by fertilin in sperm head, nucleus released, and fusion of
nuclei
➢ Sperms move up due to their own motility and due to propulsion of uterus and oviducts,
produced by oxytocin.
➢ Sperms fertile up to 72 hours in female genital tract (Highly fertile 12-24 hours)
➢ Ovum fertilizable up to 24 hours after ovulation (8-12 hours maximum fertile period)
➢ Most fertile period is 48 hours before ovulation
Blastocysts
Tropoblast
Inner cell mass Outer cell mass
Forms placenta
Placenta
Oestrogen synthesis during pregnancy 37th week of gestation is called the Term
Source - Corpus luteum of pregnancy-2/3months
Feto placental unit
Main type-estriol
Functions- Enlargement of uterus, genitalia
Enlargement & ductal proliferation of breast
Relaxation of pelvic ligaments
Cholesterol
Pregnenolone
Pregnenolone DHEAS 16OHDHEAS
Estriol 16OHDHEAS
(Principal)
hCS
• Polypeptide
• Found in prostate gland in men (involved in sperm motility & penetration)
• Found in the secretory phase, not proliferative phase
• Secreted by
▪ Corpus luteum ▪ Uterus
▪ Placenta ▪ Mammary gland
Actions
▪ Relaxes pubic symphysis & other pelvic joints
▪ Softens and dilates uterine cervix
▪ Inhibits uterine contraction
o hCG and relaxin – peak in first trimester
o oestrogen, progesterone, hCS – peak at term
Amniotic fluid
▪ Amniotic sac grows and begins to fill, approximately 2/52 after fertilization
▪ Contains water, proteins, carbohydrates, lipids, phospholipids, urea, electrolytes, alpha-feto
protein
▪ Maternal and foetal origin
▪ Volume increases as the fetus grows till 34/52(800 mL)
▪ Foetus ‘swallows’, ‘inhales’ and ‘exhales’ amniotic fluid
▪ Amnion ruptures at term during labour
Diagnosis of pregnancy
Clinical: Amenorrhoea Foetal heart sounds
Uterine enlargement Breast, skin changes
Nausea, vomiting Frequency of micturition
Period of gestation-280days from the 1st day of the last regular period (Period of
amenorrhea)
37thweek→term
conception
12 28 40 weeks
Metabolic changes
o ↑Fat mobilization and tendency of ↑ketoacidosis
Endocrine glands
o Ovaries / thyroid enlarge
o ↑ Secretion by most of the endocrine organs
Parturition
Endometrium
Oxytocin release
Increase of ACTH
Increase of Cortisol
Maturation of Respiratory
system
Oxytocin
o Neuropeptide
o Secreted mainly by the hypothalamus
o Stored in the posterior pituitary
o Acts primarily on breasts and uterus
o G protein coupled serpentine receptor in myometrium, mammary tissue and gonads
Functions
o Contract myoepithelial cells on ducts of breast to cause milk ejection
o Contracts smooth muscles of uterus
▪ Labour
▪ Assist in sperm transport
o Luteolysis
o Others,
Sexual function, love, bonding, social behaviour
Painful uterine contractions aided by voluntary contractions of, maternal abdominal muscles for
expulsion of uterine contents
Increasing frequency and force of uterine contractions
↓
Cervical dilation
↓
Bearing down (spinal reflexes and voluntary contraction of abdominal muscles)
↓
Expulsion of fetus
↓
Expulsion of placenta
However, delivery can occur without bearing down and without a reflex increase in secretion of
oxytocin from the posterior pituitary gland, since paraplegic women can go into labour and deliver.
Puerperium
Changes in pregnancy revert approximately to the non-pregnant state during the 6 weeks from
child birth
Lactation is established.
Systems come to non-pregnant levels
Lactation
➢ During puberty
Oestrogen Progesterone
➢ During pregnancy
• [Oestrogen]&[ progesterone] are high
• Prolactin levels increase steadily in term → Full lobulo-alveolar development of breast
• Milk secretion is inhibited by oestrogens.
➢ Ejection of milk (Oxytocin)
• Expulsion of placenta initiates lactation.
Hypothalamus
Oxytocin ↓Dopamine
Contraction of myoepithelial cells ↑ Prolactin
Milk ejection/ let down ↑Milk production
(↑mRNA of milk proteins-
Lactalbumin, casein
↑mRNA of UDP-galactosyltransferase
Oestrogen – prevents lactation
Binding of PRL to receptors
Milk volume
Progesterone – prevents initiation
No effect once established
Prolactin
From anterior pituitary
Is also secreted by the endometrium and by the placenta.
Secretion inhibited/regulated by dopamine (prolactin inhibiting hormone)
A peptide, structurally similar to GH &hCS.
Receptors resemble GH receptors
1) Inhibits GnRH secretion and action of it on pituitary
2) Antagonizes the gonadotrophins' actions in ovary
3) Prevents Ovulation
4) Excess prolactin secretion in males causes erectile dysfunction.
So, women who nurse regularly have amenorrhea for 25 – 30 weeks (who do not - up to 6 weeks)
Hypothalamus
GnRH
-
Prevent
↑ Breast ↑ Prolactin - Anterior
pituitary
menstruation
feeding & ovulation
- FSH/LH
Contraceptive
Ovary effect
Oestrogen& Progesterone
Barrier
Ryhthm/calander method Condoms Hormonal IUCD Vasectomy LRT
Methods
Subdermal
Cervical Mucus method Condoms OCP DMPA
Implants
Symto-thermal Method Diaphragm COC
Spermicidal
POP
Creams
Emergency CP
1 © 2018 A/L Repeat Campaign
Natural methods
Contraceptive Mechanism of action Advantages Disadvantages
Periodic abstinence
safe period - 5 days before and 2 days after ovulation
*calendar method
Record the length of at least six menstrual cycles
Ø Subtract 18 from the shortest cycle (Gives the probable 1st day of fertile
period)
Ø Subtract 10 from the shortest cycle (Gives the probable last day of fertile
period)
Avoid sexual intercourse during fertile period
Emergency contraceptives
• Not recommended for regular use
• Following unprotected intercourse to prevent unplanned pregnancies
• Can prevent pregnancies but unable to interrupt an established pregnancy
• Effective only if administered in the first few days following intercourse
• Levonorgestrel (Progesterone only method) & Copper bearing intra uterine
contraceptive devices Cu-IUCD) are commonly used
Note; Though 4 low dose COC pill within first 72 hours and then another 4 COC pills after 12
hours can be taken Instead of Prostinor , they are intolerance due to severe side effects
Cu-IUCDs Copper prevents Should be inserted ü If a woman is pregnant
fertilization by within 5 days (120 should not be used
causing a hours) of unprotected ü Most effective form of
chemical change intercourse emergency
that damages Most efficient contraception available
ovum & sperm emergency ü Safe method-Risk of
contraceptive method infections, expulsion, &
available perforations are less
• External occipital protuberance – junction of head & neck, most prominent point – INION
• Superior nuchal line – junction of head & neck – pass from the protuberance
• Highest nuchal line – begin from upper part of the protuberance
• Occipital point – above inion farthest from glabella
• Occasionally interparietal bone present
Lateral view
(temporal view)
• Zygomatic arch – temporal process of zygomatic bone + zygomatic process of temporal bone
• Jugular point – anterior end of zygomatic arch
• PTERION: point where frontal, parietal, temporal, sphenoid bones meet
- Deeply lies middle meningeal vein, anterior of middle meningeal artery & stem of the lateral sulcus of
the brain (7.17 C) grants
- 4cm above zygoma, 2.5cm behind frontozygomatic suture
*attachments
⎯ Pharyngeal tubercle: raphe of superior constrictor
⎯ Medial pterygoid: pharyngobasilar fascia, superior constrictor, pterygomandibular raphe
⎯ Lateral pterygoid plate: lateral pterygoid and medial pterygoid
⎯ Foramen magnum: anterior, posterior Atlanto-occipital membrane, alar ligament
⎯ External occipital protuberance: ligamentum nuchae
4. Norma frontalis
Inferior view
Incisive foramen – nasopalatine nerve, greater palatine vessels
Greater palatine foramen – greater palatine nerve
Lesser palatine foramen – lesser palatine nerve
Pterygoid canal – pterygoid nerve and vessels
Foramen ovale – Mandibular nerve
Accessory meningeal artery
Lesser petrosal nerve
Emissary vein
Foramen spinosum – middle meningeal artery, meningeal branch of mandibular nerve
Foramen lacerum – filled with cartilage
Foramen magnum – continuation of brain and spinal cord, vertebral arteries and nerve plexus
Anterior spinal artery
Posterior spinal arteries
Roots of accessory nerve
Meninges
Carotid canal – internal carotid artery and nerve plexus
Condylar canal – emissary veins
Hypoglossal canal – hypoglossal nerve (XII) and vessels
Jugular foramen – Internal jugular vein
Glossopharyngeal nerve (IX)
Inferior petrosal sinus
Vagus nerve (XII)
Accessory nerve (XI)
Stylomastoid foramen – Facial nerve (VII)
INTERNAL FORAMINA
Anterior cranial fossa
Foramen cecum – emissary veins to nasal cavity
Olfactory foramen in cribriform plate – olfactory nerve (I)
Clinicals
Anterior cranial fossa fracture:
bleeding or CSF leakage through nose-CSF rhinorrhoea
Black eye
Middle cranial fossa
fracture: - commonly
fractured
Bleeding & leakage of CSF through ear
Bleeding through nose & mouth
Vertigo
Damage to the VII & VIII nerves
Posterior fossa fracture: Bruise extends over mastoid region to sternocleidomastoid
1. Falx cerebri
Separate the right and left cerebral hemispheres and contains the superior and inferior sagittal sinus(posterior 2/3rd).
Attaches to the crista galli.
2. Falx cerebelli
Separate the right and left cerebellar hemispheres. Contains the occipital sinus.
3. Tentorium cerebelli
Separate the cerebrum and cerebellum. It divides the cranial cavity into the supratentorial and infratenotorial
compartment. It contains the straight,tranverse and petrosal sinuses.
3. Straight sinus
Commence continuation of inferior sagittal sinus with receiving the great cerebral vein of Galen
Ends turning into the transverse sinus generally to the left at the internal occipital protuberance
Course slopes down steeply in the attachment of the falx cerebri into the tentorium cerebelli
Drains from inferior sagittal sinus, great cerebral vein, adjacent occipital lobes, upper surface of cerebellum
4. Transverse sinus
Commence at the internal occipital protuberance
Drains from Right sup sagittal sinus Left inf sagittal sinus
Nearby surfaces of cerebral and cerebellar hemispheres
• One sinus is larger – which receives the sup sagittal sinus (right)
• Communicate with each other at confluence of sinuses
5. Sigmoid Sinus
Commence as the termination of transverse sinus
Ends expands into the superior jugular bulb of the internal jugular vein
Course Deeply grooving the inner surface of the mastoid part of the petrous bone
Curves downwards and forwards to the post margin of the jugular foramen through which it passes
Drains from transverse sinus at superior end - sup petrosal sinus
Inferior end – occipital sinus
Cerebellar veins
Veins from mastoid air cells
Drains into internal jugular vein
• Mastoid emissary vein sigmoid sinus with post auricular vein (mastoid foramen)
• Emissary vein through post condylar foramen sigmoid sinus with suboccipital plexus of veins
• Communicates with the internal vertebral plexus (veins outside the spinal dura) at the foramen magnum
7. Basilar plexus
• On the clivus
• Connects the two inferior petrosal sinuses
• Drains from the lower part of medulla and pons
• No veins accompany the vertebral and basilar arteries
• Vertebral vein itself commences outside the skull below the occipital bone.
8. Cavernous sinus
Commence medial end of the superior orbital fissure (apex of the orbit)
Ends apex of the petrous bone
Course alongside the body of the sphenoid bone in the middle cranial fossa
• Structures in the center and lateral wall of sinus are separated from blood by the endothelial lining.
Communications (valve-less)
Extradural hemorrhage
• Fractures of the side of the skull may rupture the middle meningeal artery (especially the frontal
branch)
• Hematoma between the bone of the skull and the dura
• In x-rays, it has a lens shaped whitish area as it is attached to the sutures.
Subdural hemorrhage
• Venous blood escapes into the (potential) space between the dura and arachnoid
• Venous blood is involved (so it is slower to develop and less severe)
• In x-rays, they are shown in a crescent shape (falx cerebri)
Subarachnoid hemorrhage
• Rupture of arteries that lie within the space, such as aneurysms of arterial circle at the base of
brain.
• Causes blood to contaminate CSF
Appear in whitish (accumulation of blood in fissure)
• Blood accumulates along fissures
Major endocrine gland. Pea sized oval structure suspended by the pituitary stalk(infundibulum) from the brain. It
lies in the pituitary/hypophyseal fossa of sella turcica(Turkish saddle) in the skull.
Relations
Anteriorly - tuberculum sellae
Anteriorinferiorly - sphenoid sinus
Posteiroly - posterior intercavernous sinus, dorsum
sellae(posterior wall of sellae turcica), basilar artery,
pons
Superiorly - diaphragma sellae(dural reflection pierced
by the stalk), optic chiasma
Laterally - cavernous sinus
Embryology
Infundibulum-downward growth of forebrain,becomes the pituitary stalk and posterior pituitary gland.
Development begins at week 3 of gestation. Rathkes pouch appears and extends upwards towards the
infundibulum. By week 8 it has detached from the oral cavity and lies tightly against the infundibulum forming
the pituitary gland.
Clinical
Pituitary adenomas can compress nearby structures, especially the optic chiasma. It can gained access by the
sphenoid sinus and nasal cavity due to its relation. This procedure is called trans sphenoidal surgery.
Scalp
➢ Extent
• Anteriorly - supraorbital margin
• On each side - superior temporal line
• Posteriorly - superior nuchal line, external occipital protuberance
➢ 5 layers
• S - Skin
• C - Connective tissue
(superficial fascia)
• A – Aponeurosis
(Epicranial aponeurosis /galea
aponeurotica)
• L - Loose connective tissue
• P - Pericranium
• The 1st 3 layers are called the
surgical layers of the scalp / scalp proper.
➢ Skin
• Thick (thickest in occipital region)
• High concentration of sebaceous glands
• Skin is adherent to epicardial aponeurosis
Through dense superficial fascia.
➢ Aponeurosis
• Epicranial aponeurosis is movable on
Pericranium with skin, superficial fascia
• on each side attached to superior temporal
line – blends with temporoparietal fascia
• (expansion of aponeurosis passes over the
temporal fascia)
• Occipitofrontalis
▪ Occipitalis arises from the lateral 2/3rd
of superior nuchal line
▪ Occipital muscle bellies are separated across the midline by the aponeurosis
▪ Occipitalis is innervated by posterior auricular branch of facial nerve
▪ Frontalis arises from the front of the aponeurosis/skin of forehead and is inserted to the upper part of
orbicularis oculi and overlying skin of the eyebrow. (Frontalis part has no attachment to the skull).
▪ The sub aponeurotic space extends down beneath the orbicularis oculi into the eyelids.
▪ Bleeding anywhere beneath the aponeurosis may appear as a ‘black eye’ due to the blood tracking through
the space.
▪ Frontalis muscle bellies are partially united in the midline and innervated by the temporal branch of the
facial nerve
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▪ Function of the frontalis muscle is to raise eyebrows & cause horizontal wrinkles in the forehead.
➢ Pericranium
• Loosely attached to surface of the bones but adherent to the sutures
• Therefore, a collection of fluid deep to the pericranium (cephalohematoma) takes the shape of the bone
concerned.
➢ Blood Supply
• External carotid – occipital, posterior auricular, superficial temporal
• Internal carotid – supraorbital and supratrochlear (first two branches of ophthalmic artery)
• There is an external and internal carotid anastomosis around the vertex over the temple.
• Veins receive diploic veins from vault bones and emissary veins from intra cranial sinuses.
▪ Superficial temporal vein retromandibular vein
▪ Posterior auricular vein external jugular vein
▪ Occipital vein vertebral vein
▪ Supratrochlear & supraorbital veins angular vein facial vein
➢ Lymph drainage
• Anterior – pre-auricular(parotid)
• Posterior – mastoid (post auricular)
• Ultimately drain into deep cervical chain
• No lymph nodes within the scalp.
➢ Nerve supply
• Occipital region – greater occipital & 3rd occipital nerves
• Skin behind the ear – lesser occipital
• Temple – auriculotemporal & zygomaticotemporal
• Forehead & front of head – supratrochlear & supraorbital
Scalping – evulsion of the layers of the scalp above the loose areolar tissue that doesn't cause necrosis of
underlying bones
Face
➢ Extends from adolescence position of hairline (superiorly) base of mandible (inferiorly) & auricles (on either side)
➢ Forehead common both to face & scalp
• Skin – very vascular (wounds heal rapidly)
• rich in sebaceous & sweat glands
• Laxity of greater part of skin . [facilitates rapid spread of oedema]
• Boils in nose & ear causes pain because of fixity of skin to cartilage
• Superficial fascia
▪ facial muscle inserted into skin[thus , muscles are subcutaneous ] – injuries tend to gape
▪ Fat absent in eyelids but well developed in cheeks [buccal fat pad ]
• Deep fascia – absent except over parotid gland [parotid fascia] & buccinator muscle [buccopharyngeal fascia]
Orbicularis oculi
• 2 parts
▪ palpebral part (close eye lids gently)
▪ Orbital part (both parts – close eye lids forcibly)
• Nerve supply – temporal & zygomatic branches of facial nerve
Orbicularis oris
• Bulk is formed by buccinator
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• Nerve supply – buccal and marginal mandibular branches of facial nerve
Buccinator
• Origin – alveolar processes of maxilla & mandible, pterygomaxillary ligament, pterygomandibular raphe
• Insertion – orbicularis oris (fibers from the raphe decussate; maxillary & mandibular fibers do not
decussate)
• Nerve supply – buccal branch of facial nerve
• Action – prevent distention of cheeks when intraoral pressure rises
• Pierced by the parotid duct opposite the 3rd upper molar teeth.
➢ Arterial Supply
1. Facial artery [mainly] given off in carotid triangle External carotid artery
2. Transverse facial artery – superior temporal
3. Supraorbital and supratrochlear – from ophthalmic artery – Internal carotid
Venous drainage
• Entirely superficial
• Forehead – supraorbital & supratrochlear veins unite at medial canthus to form the angular vein
• Angular vein – continues as facial vein (straight)
• Facial vein – just below the lower border of mandible pierces the deep fascia and joins retromandibular
vein;
Posterior
Anterior division Posterior division
auricular
vein
Common External
facial vein jugular vein
Internal
jugular vein
PAROTID
GLAND
PAROTID
GLAND
LOCATION
Parotid capsule
[true capsule: condensation of fibrous stroma]
• investing layer of deep cervical fascia splits to form the false capsule (between angle of mandible and mastoid
process)
• superficial lamina thick & adherent to gland S
• attached to zygomatic arch superiorly
• deep lamina thin & attached to styloid process & angle of mandible
• part of the deep lamina forms stylomandibular ligament which separates the gland from the submandibular
gland
• thickened anteroinferiorly
Surface marking
1. upper border of the head of the mandible
2. center of the masseter muscle
3. posteroinferior to the angle of the mandible
4. upper part of the anterior border of the mastoid process
Relations
➢ pyramid shaped: base, superficial surface, anteromedial & posteromedial surfaces
• Apex
a) Overlaps posterior belly of digastric
b) Cervical branch of facial nerve & 2 divisions of retromandibular vein
• Base
a) Cartilaginous part of external acoustic meatus
b) Posterior part of TM joint
c) Superficial temporal vessels
d) Auriculotemporal nerve
e) Temporal branch of facial nerve
• Superficial surface
a) Skin
b) Parotid fascia
c) Lymph nodes
d) Anterior branch of great auricular nerve
• Anteromedial surface
a) Grooved by ramus of mandible
b) Masseter
c) Lateral part of TM joint
d) Medial pterygoid
e) Emerging branches of facial nerve
f) Maxillary artery emerges
• Posteromedial surface
a) External carotid artery enters through
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this surface
b) Mastoid process
c) Styloid process & structures related to it
d) Medial to this surface> styloid process, in between ICA
and IJV last 4 cranial nerves
Structures within the gland
Superficial to deep : facial nerve> Retromandibular vein>external
carotid artery
1) External carotid artery, maxillary artery, superficial temporal
artery , transverse facial artery
2) Retromandibular vein formed by union of superficial temporal
& maxillary vein
3) Facial nerve
4) Parotid lymph nodes
Blood supply
• Arterial supply - external carotid artery
• Venous drainage – Retromandibular vein
Nerve supply:
Lymphatic drainage
• Parotid nodes upper deep cervical nodes
➢ Facial Nerve
• Extra-cranial course
▪ Crosses the lateral side of the styloid process after emerging through stylomastoid foramen
▪ Enters the posteromedial surface of the parotid gland
▪ Crosses the retromandibular & external carotid artery
▪ Behind the neck of mandible divides into terminal branches
c) Chorda tympani
• Vertical part of facial nerve, arises 6mm above the Stylomastoid Foramen
• Closely related to tympanic membrane
• Leaves middle ear through petrotympanic fissure
• Medial to the spine of sphenoid
• Joins the lingual nerve
• Carries,
1. Preganglionic secretomotor fibers to submandibular & sublingual glands
2. Taste fibers from tongue
b) Digastric
c) Stylohyoid
C. Terminal branches
• The branches leave the gland through its anteromedial surface & appear on the surface at the
anterior border.
a) Temporal
1. auricularis anterior & superior
2. Intrinsic muscles on lateral side of ear
3. Frontalis
4. Orbicularis oculi
5. Corrugator supercili
b) Zygomatic
1. orbicularis oculi
c) Buccal
1. Orbicularis oris
2. Buccinator
3. Muscles of nostrils & upper lip
d) Marginal mandibular
1. Platysma
2. Muscles of lower lip & chin
e) Cervical
1. platysma
• Joint capsule
• Stability
▪ Most stable when teeth in occlusion.
▪ Forward displacement is more common.
• Relations
Superiorly – glenoid fossa, middle cranial fossa, middle meningeal artery
Medially- maxillary artery & proximal branches (middle meningeal), auriculotemporal nerve
• Movements
1. Depression and elevation
a. Lower compartment – hinge movement
b. Upper compartment – gliding movement
c. Axis – horizontal
2. Side to side movements – Medial and lateral pterygoids of the same side contract together.
[chewing from right side involves left lateral and left medial pterygoid, right temporalis ,right
masseter]
3. Protraction – All 4 pterygoids contract.
Retraction – Elastic recoil (Temporalis, Masseter)
Depression – mainly by lateral pterygoid[digastric, mylohyoid, geniohyoid]
Elevation – masseter, medial pterygoid, temporalis
• Nerve Supply
▪ Auriculotemporal Nerve
▪ Nerve to Masseter
Contents
1. temporalis muscle
2. Deep temporal arteries
3. Deep temporal branches of mandibular nerve
4. Middle temporal artery – a branch of superficial temporal artery
Masseter Lower border of Angle and Lateral Masseteric branch Elevation and
Zygomatic Arch surface of Ramus of of Anterior division protrusion
3 layers the Mandible of mandibular
nerve
Buccal and maxillary artery pass between the 2 heads of the muscle
Deep- Deep head of medial pterygoid, sphenomandibular ligament, middle meningeal artery, mandibular nerve
Greater palatine
Pharyngeal
• Relations
▪ In infratemporal fossa
▪ In middle cranial fossa – Middle meningeal veins are closer to the bone than artery
Clinical
Pterygoid plexus
• Lie around and within the lateral pterygoid muscle
• Plexus is valved, and acts as a peripheral heart
• Receives inferior ophthalmic vein, deep facial vein
• Drains into Short Maxillary Vein
• Connect with cavernous sinus via emissary veins through Foramen Ovale and Foramen Lacerum
enters fossa through Foramen Rotundum and runs through inferior orbital fissure into Infraorbital Canal as
Infraorbital Nerve.
Completely sensory Branches From main trunk – meningeal, zygomatic, superior alveolar nerves
(anterior, middle and
posterior), infraorbital nerve
▪ Midline Structures
• Symphysis menti
• Hyoid bone – C3
• Notch of thyroid cartilage (Laryngeal Prominence)
• Cricothyroid ligament (important - cricothyroid puncture :-
Access Upper airway)
• Lower border of Cricoid cartilage - C6
• Tracheal rings
• Isthmus of thyroid gland – 2-4 tracheal rings (sometimes
palpable)
• Suprasternal notch
▪ Sternocleidomastoid
Also, at the lower border of the cricoid cartilage (C6) lies the,
1. junction of larynx with trachea
2. junction of pharynx with oesophagus
3. inferior thyroid artery enters & middle thyroid vein leaves the thyroid gland
4. vertebral artery enters foramen transversarium of C6 vertebra
5. superior belly of omohyoid crosses carotid sheath
6. middle cervical sympathetic ganglion
7. carotid artery can be compressed against anterior tubercle of the transverse process (carotid tubercle) of 6th
cervical vertebra
❖ Cutaneous innervation
• C2, C3, C4
• anterolateral part – anterior primary rami through
▪ lesser occipital
▪ great auricular Cutaneous branches of cervical plexus
▪ Transverse cervical
▪ supraclavicular
• posterior part – posterior primary rami
*C1 – no cutaneous innervation
C4 – through supraclavicular nerves supply pectoral region
❖ SUPERFICIAL FASCIA
− platysma 1. thin sheet of muscle 2. covers the external & anterior jugular vein
− cervical branch of facial nerve
− lymph nodes & vessels.
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➢ external jugular vein
• deep to platysma
• posterior auricular + posterior division of
retromandibular vein
Clinical:
Division of the external Jugular vein in the supraclavicular space may cause air embolism and death because the cut
ends of the vein are prevented from retraction and closure by the fascia, attached firmly to the vein.
1. investing layer
• surrounds the neck like a collar
• Forms the roof of anterior & posterior
triangle.
• attachments
A) superiorly – external occipital
protuberance,
Superior nuchal line,
Mastoid,
Lower border of mandible
➢ between angle of mandible &
mastoid process, the fascia
splits to enclose the parotid gland
➢ superficial lamina is thick – attached to zygomatic arch
➢ deep lamina is thin – attached to styloid process, mandible,
tympanic plate
o deep lamina forms stylomandibular ligament – separates parotid & submandibular glands
o pierced by external carotid artery
B) inferiorly – spine of scapula
Acromion process, Clavicle, Manubrium
C) posteriorly – ligamentum nuchae, Spine of C7
D) anteriorly – hyoid bone, covers the infrahyoid muscles.
• encloses 2 muscles, salivary gland, 2 spaces
supraclavicular space
• external jugular vein
• supraclavicular nerves
• lymphatics
Clinical:
Thyroid gland and all thyroid swellings move with deglutition because the thyroid is attached to
cartilage of the larynx by the suspensory ligament of Berry.
Swellings due to lymph node enlargement do not move with deglutition.
3. Prevertebral layer
• in front of prevertebral muscles
• cylindrical layer
• forms floor of posterior triangle
• attachments
− superiorly – base of skull
− inferiorly – anterior longitudinal ligament & body of T4
− anteriorly – separated from pharynx & buccopharyngeal fascia by retropharyngeal space (areolar tissue)
anterior surfaces of transverse processes and bodies of vertebrae C1 – C3
− Laterally – thins out deep to trapezius
• cervical & brachial plexuses lie behind the fascia
• forms the axillary sheath – does not contain axillary vein
− Posteriorly – ligamentum nuchae
• covers the cervical nerve roots, subclavian artery
• superficially – accessory nerve and LN.
4. Carotid sheath
• condensation of fibroareolar tissue around vessels of neck
• contains - M-CCA , ICA, L- IJV, Pos.- Vagus nerve
− − cranial nerves
• Attachments
− Superiorly – base of the skull
− Inferiorly – adventitia of the arch of the aorta
• anteriorly embedded in the carotid sheath lies the ansa cervicalis
• posteriorly between the carotid sheath and the prevertebral fascia
lies the sympathetic chain
• fuses with pretracheal and investing layers of deep fascia
5. Buccopharyngeal layer
covers superior constrictor externally & extends on to the
superficial surface of buccinator.
So that parotid duct has to pierce it
6. Pharyngobasilar layer
Thick between upper border of superior constrictor & base of skull
Clinicals
• parotid swellings are painful due to the unyielding nature of parotid fascia
• while excising submandibular gland external carotid artery should be secured
• thyroid gland & all swellings move with deglutition due to fascial attachments
• pus due to tuberculosis of vertebrae may pass forward forming a chronic retropharyngeal abscess in
the median plane
o it may extend laterally through axillary sheath; it may descend as far as superior
mediastinum
• pus collected from neck infections
In front of prevertebral fascia extend in a paramedian position as far as the posterior
mediastinum
• neck infections
4 In front of pretracheal fascia extend into the anterior mediastinum © 2018 A/L Repeat Campaign
❖ Muscles of the neck
Muscles of the Neck
Sternocleidomastoid Suprahyoid Infrahyoid (strap muscles)
STERNOCLEIDOMASTOID MUSCLE
• origin
- sternal head – (tendinous) manubrium sterni
- clavicular head – (musculotendinous) medial 1/3rd of superior surface of clavicle *deep to the interval between the 2
heads lie the internal jugular vein
• insertion
- mastoid process
- lateral half of superior nuchal line
• crossed superficially by great auricular, ex. jugular, transverse cervical
• nerve supply
motor – spinal accessory nerve proprioceptive – ventral rami of C2
• blood supply
occipital artery (2 branches), superior thyroid & suprascapular arteries
• actions
contraction of 1 muscle – 1. Turns chin to opposite side
2. Tilts head towards shoulder
contraction of both muscles – 1. Draw head forwards
2. Flex neck against resistance
3. Forced inspiration
• relations
superficial
▪ skin
▪ superficial fascia
▪ platysma
▪ external jugular vein
▪ superficial layer of investing fascia
▪ lymph nodes
▪ parotid gland
▪ great auricular, transverse cutaneous, medial supraclavicular
nerves
(The muscle is crossed superficially form above downwards by the great auricular nerve, external jugular vein and the
transverse cervical nerve)
deep
• bones & joints – mastoid process, sternoclavicular joint
• carotid sheath
• muscles – sternohyoid, sternothyroid, omohyoid, 3 scaleni. Levator scapulae, longissimus capitis,
posterior belly of digastric
• arteries – common, internal & external carotids, arteries to muscles, occipital, subclavian,
suprascapular, transverse cervical
• veins – internal jugular, anterior jugular, facial & lingual
• nerves – X, XI, cervical plexus, upper part of brachial plexus, phrenic, ansa cervicalis
• lymph nodes deep cervical.
CLINICALS
− most common cause for swelling in the posterior triangle is due to – enlargement of supraclavicular lymph nodes
5 − left supraclavicular nodes – signal nodes (malignancies in stomach & testis) © 2018 A/L Repeat Campaign
− wry neck – head bends to 1 side & chin points to other side: spasm of muscles supplied by spinal accessory nerve
Muscle Innervation Action
Suprahyoid muscles
1. Digastric Posterior belly – Facial nerve
Anterior belly – Nerve to mylohyoid
2. Stylohyoid Facial nerve
3. Mylohyoid Own nerve from inferior alveolar
4. Geniohyoid Branch from hypoglossal nerve
Infrahyoid muscles
1. Sternohyoid Ansa cervicalis
2. Omohyoid Superior belly – superior root of
ansa cervicalis
All depressors of larynx
Inferior belly – ansa cervicalis
3. Thyrohyoid Branch from hypoglossal nerve
4. Sternothyroid Ansa cervicalis
It’s a space on the side of the neck situated behind the sternocleidomastoid muscle
Boundaries
o anteriorly – posterior border of sternocleidomastoid
o posteriorly – anterior border of trapezius
o base – middle 1/3rd of clavicle
o apex – superior nuchal line where the 2 muscles meet
o roof – investing layer of deep cervical fascia
o floor – prevertebral layer of deep cervical fascia covering splenius capitis, levator scapulae, scalenus medius
Divisions – divided by inferior belly of omohyoid into larger upper part (occipital triangle) & smaller lower
part (subclavian triangle)
Borders Contents
submental lymph nodes
submental on each side - anterior belly of digastric formation of anterior jugular vein
triangle base – body of hyoid bone apex – chin
floor – mylohyoid muscle
The triangle crosses the midline
Submandibular salivary gland and lymph nodes
digastric Anteroinferiorly-anterior belly of digastrics Facial, submental and mylohyoid vessels
triangle Posteroinferiorly-posterior belly of digastrics Hypoglossal and mylohyoid nerves
Base-the lower border of the mandible and
line joining the angle of mandible to mastoid
process
Roof – skin, superficial fascia, deep fascia
Floor – anteriorly – mylohyoid: posteriorly –
hyoglossus
• Arteries
carotid Antero-superiorly – posterior belly of Common, internal & external carotid
triangle digastric Carotid sinus & body
Antero-inferiorly – superior belly of All branches of external carotid except posterior auricular
omohyoid • Veins
Posteriorly – sternocleidomastoid Internal jugular
Roof – skin, superficial fascia, deep fascia Common facial
Floor – thyrohyoid, hyoglossus, middle & Lingual
inferior constrictors Pharyngeal
• Nerves
Vagus
Superior laryngeal
Spinal accessory
Hypoglossal
Sympathetic chain
Cervical plexus
Formed by ventral rami of upper four cervical nerves. (C1 gives no cutaneous branches)
Branches:
Superficial branches-
1. Lesser Occipital (C2)
2. Great auricular (C2, C3)
3. Transverse cutaneous nerve of the neck (C2, C3)
4. Supraclavicular (C3, C4)
Deep branches –
Muscular branches to:
1. Rectus capitis anterior (C1)
2. Rectus capitis lateralis (C1, C2)
3. Longus capitis (C1-C3)
4. Lower root of Ansa cervicalis
Communication branches:
1. Grey rami from the superior cervical ganglion to C1-C4 nerves.
2. Branch from C1 joins the hypoglossal nerve
3. Branch from C2 to sternocleidomastoid & branches from C3 & C4 to the Trapezius
communicate with accessory nerve.
Ansa Cervicalis
− This is a thin nerve loop that lies embedded in the anterior wall of carotid sheath over the lower part of larynx.
− It supplies the infrahyoid muscles.
− Formed by a superior and inferior root.
− Superior root (anterior to ICA/CCA) is the continuation of the descending branch of the hypoglossal nerve derived from
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C1.
− Inferior root (on the int. jugular vein) derived from C2, C3. This root winds around the internal jugular vein and
continues anteroinferiorly to join the superior root in front of the common carotid artery.
Distribution:
− superior root to the superior belly of omohyoid
− Ansa cervicalis to the sternohyoid, the sternothyroid and the inferior belly of omohyoid
− Thyrohyoid and geniohyoid are supplied by separate branches from the first cervical nerve through the hypoglossal
nerve.
2) Prevertebral fascia
a) encloses the thyroid gland
b) extends laterally into the upper limb as the axillary sheath
c) has the cervical sympathetic chain embedded in it
d) blends inferiorly with anterior longitudinal ligament infront of body of C6 vertebra
e) splits around the hyoid bone
• At the junction between head and neck there is a circular arrangement of lymph nodes.
• Submental nodes – submental triangle Drain superficial tissues
• Submandibular nodes – digastric triangle of head & neck
• Preauricular(parotid) nodes – within the gland / deep or superficial to capsule
• Mastoid nodes – on the mastoid process
• Occipital nodes – apex of posterior triangle of the neck
• Mandibular and buccal nodes
Retropharyngeal nodes – behind the pharynx – back of nose, pharynx, auditory tube
All lymph from horizontal and vertical groups drain into deep cervical nodes.
o Stylomandibular ligament
o Stylohyoid ligament
o Sphenomandibular ligament
o Pterygomandibular raphe
o Pterygomaxillary ligament
o Petrosphenoid ligament
• Is bounded by the
1. T1 vertebra
2. 1st pair of ribs & costal cartilages
3. Manubrium of the sternum
➢ Scalenus Anterior
• Origin – Anterior tubercles of the transverse processes of typical vertebrae (C3-C6)
• Insertion – Scalene tubercle & adjacent ridge on 1st rib
• Nerve supply – Anterior rami of C4-C6
Anterior relations
1) The Phrenic Nerve,
▪ passes vertically down across the obliquity of the muscle. (plastered to the prevertebral fascia).
▪ The nerve leaves the medial border of the muscle low down.
▪ Crosses in front of the Subclavian Artery and its internal thoracic branch, behind the Subclavian Vein.
▪ Lying on the supra pleural membrane it passes medial to the apex of the lung, in front of the Vagus Nerve,
to enter the superior mediastinum.
Medial relations
• Pyramidal Space,
▪ The medial edge of scalenus anterior muscle makes a pyramidal space/ ∆ with the lateral border of the lower
part of longus colli.
▪ There’s no fascial roof across the pyramidal space between the muscles.
o Base - is formed by the subclavian artery lying on the suprapleural membrane.
o Apex - is the Carotid (Chassaignac's) Tubercle on the transverse process of C6 vertebra. (Common carotid
artery can be compressed against it.)
Posterior relations
▪ 2nd part of the Subclavian artery.
▪ Scalenus Medius
Lateral relations
▪ 3rd part of the Subclavian artery.
Cervical pleura:
• Covers the apex of the lung.
• It rises into the root of the neck.
• The pleural dome is strengthened on its outer surface by the supra pleural membrane (Sibson’s Fascia) so that
the root of the neck is not puffed up and down during respiration.
1) Glands
Thyroid Gland
Introduction
• Butterfly shaped/ shield like endocrine gland.
• The gland has 2 conical lobes each joined by an isthmus in its lower part.
• An inconstant pyramidal lobe may project upwards form the isthmus.(Left sided)
Arterial supply
- 2nd most vascular organ
2. Superior Thyroid Artery
▪ The 1st anterior branch of external carotid artery
▪ Close relation to external laryngeal nerve away from gland.
▪ At the upper pole divides into anterior and posterior branches.
▪ Divides into branches after piercing false capsule
▪ External laryngeal nerve deviates at the apex of a lobe of the gland. Therefore, during thyroidectomy superior
thyroid artery is ligated near the gland
▪ Anterior branch anastomoses with the same branch of opposite side.
4. Additional supply
▪ Thyroidea ima artery (brachiocephalic or arch of aorta)
▪ Oesophageal and tracheal branches.
• Superior thyroid artery reaches the upper pole of the gland and anastomosis with the opposite artery along
the upper border of the isthmus.
• Inferior thyroid artery reaches the lower pole.
Venous drainage
• Superior thyroid vein emerges from the upper pole of the gland drains into internal jugular vein.
• Middle thyroid vein also drains into internal jugular vein.
• Inferior thyroid vein emerges from the lower border of the isthmus, to be eventually drained into the left
brachiocephalic vein.
• Dense capillary plexus present deep to the true capsule.
Lymphatic drainage
• Lymph from the upper part of the gland drains into upper deep cervical lymph nodes.
Nerve supply
• Sympathetic fibres are mainly derived from the middle cervical ganglia / cervical sympathetic trunk.
(Vasoconstrictor)
Relations
• Superficially/Anterolateral
▪ skin, superficial fascia and investing deep fascia
▪ strap muscle of the neck (sternohyoid, sternothyroid, superior belly of omohyoid) overlapped by
sternocleidomastoid.
▪ Anterior jugular vein courses over the isthmus.
(These layers have to be cut in thyroidectomy)
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• Medially
▪ On the deep aspect lie the larynx (Cricothyroid) and trachea, pharynx (Inferior constrictor) and
oesophagus
▪ Recurrent laryngeal nerve coursing on the tracheoesophageal groove is closely related to the inferior
thyroid artery.
▪ External laryngeal nerve is closely related to the superior thyroid artery.
• Behind/Posterolaterally
▪ The carotid sheath (common carotid artery, internal jugular vein, vagus nerve) lies on either side.
▪ Cervical sympathetic ganglion
• Posterior
▪ Parathyroid gland
▪ Trachea
Clinical Anatomy
1. Swellings (goitre) move with deglutition (gland is adhered to the trachea)
2. Flex head when palpating
3. Cancer recurrent laryngeal nerve damage hoarseness of voice/stridor
4. In thyroidectomy Superior thyroid ligated near gland to save the external laryngeal nerve. Inferior thyroid
ligated away from gland to spare the recurrent laryngeal nerve
Parathyroid gland
• 2 pairs Superior and inferior. (1 pair on each lateral lobe).
• Lies on the posterior surface of the thyroid gland, within the false capsule
• Size of split pea
• Brownish yellow colour
• Lie close to anastomosis between superior & inferior thyroid arteries (middle of the posterior border of the lobe of
the thyroid gland)
• Superior parathyroid more constant in position
• Inferior parathyroid inconsistent position
▪ Within capsule
▪ Outside capsule
▪ Within substance of lobe
▪ Within thymus (due to the same embryological origin )
▪ Behind trachea
▪ Behind great vessels
• Blood supply – mainly from Inferior Thyroid Artery (both inferior & superior glands)
• Easily subject to subscapular haematoma formation on handling
Relations
3rd PART
Costocervical trunk Axillary artery
• Passes back across the suprapleural membrane
towards the neck of the 1st rib & divides into. Dorsal scapular
1. Superior/Supreme intercostal (runs downwards) – • Runs laterally through the brachial
into the thorax. plexus in front of scalenus medius &
2. Deep cervical (runs upwards) – Passes backwards then deep to the levator scapulae to
between the transverse process of C7 & the neck take part in the scapular
of the 1st rib and then ascends. anastomosis.
Relations
3) Veins
Subclavian Vein
• Continuation of the axillary vein at
the outer border of 1st rib. Joins
internal jugular vein to form
brachiocephalic vein.
• Receives External jugular vein.
• Receives the thoracic duct (left) or
right lymphatic duct (right) at its
confluence with the internal jugular
vein.
• Relations
▪ Anterior - Clavicle
▪ Posterior - Subclavian artery,
Scalenus anterior & Phrenic nerve
▪ Inferior - Upper surface of 1st rib
• Tributaries are:
▪ External Jugular vein
▪ Dorsal scapular vein
Brachiocephalic vein
• The left is longer than the right.
• Formed behind the Sternoclavicular
Joint
▪ Right – Vertical
▪ Left – Oblique
• The two unite at lower border of right 1st coastal cartilage to form SVC
• Tributaries
▪ Branches of 1st part of subclavian artery
▪ 1st posterior intercostal vein
Clinical Anatomy
1. Cardiac failure - Internal jugular vein dilated.
2. Closely associated lymph nodes mean that the vein should also be resected in removing malignancy.
4) Nerves
Phrenic nerve
• Origin - C3, C4 (main), C5
• Mixed nerve
▪ The sole motor supply of diaphragm.
▪ Sensory to Central Tendon of Diaphragm, Pleura, Pericardium & part of Peritoneum.
• Formed at lateral border of scalenus anterior at the level of upper border of Thyroid Cartilage.
• Runs vertically downwards on Scalenus Anterior from lateral to medial.
• Leaves scalenus anterior & runs downwards on cervical pleura & enters thorax behind 1st costal cartilage.
• Descends anterior to the lung root & then on the surface of the pericardium.
• In the left side, the nerve leaves the medial margin of the Scalenus Anterior at a higher level and crosses in
front of the first part of the Subclavian Artery.
Spinal segments
Spinal meninges
• 3 coverings
o Dura mater, Arachnoid mater, Pia mater
• Between the dura mater and bony vertebral canal – Extra dural/ Epidural space
- contain fat and veins
1.Dura mater
• Dense, strong, outermost, fibrous membrane
• Continues with the cranial dura mater at foramen magnum
• Inferiorly extends up to S2 vertebral level
• Extends along spinal nerves
• Attaches to epineurium of nerve
2.Arachnoid mater
• Delicate and impermeable
• Extends along spinal nerves
• Subarachnoid space extends along spinal nerves up to intervertebral foramen
• Ends on filum terminale at S2 level
3.Pia mater
• Vascular membrane
• Extends laterally to form tooth like extensions which attach to inner surface of
dura mater – “Ligamenta denticulata” 22 pairs, hold spinal cord in position
Spinal nerves
Clinicals-
➢ Lumbar Puncture
• To obtain CSF
• Spinal cord ends at lower border of L1
• Subarachnoid space extends to the lower border of S2
• Below 1st lumbar vertebrae can be used to do a lumbar puncture. Usually done between
Nucleus dorsalis
Rami communicans
◼ Fibres that pass from the spinal cord to the sympathetic ganglion (contain myelinated fibres hence
white colour) are called white rami communicans
◼ Another set of fibres that pass from the sympathetic ganglion to the spinal nerves (contain
unmyelinated fibres hence are grey in colour) are called grey rami communicans
1) Longitudinal vessels
• Two for each spinal segment in embryonic stage (one from each side)
• Derived from various parent vessels depending on level
➢ Vertebral
➢ Costocervical
➢ Posterior intercostal
➢ Lumbar
➢ Lateral sacral
• In adult many segmental arteries are absent and the remaining ones
form anastomoses with ASA &PSA
• Variable in number & position
➢ Eg: Lower cervical
➢ Lower thoracic
➢ Upper lumbar
➢ Arteria radicularis magna of Adamkiewicz - largest, arise from lower intercostal or
upper lumbar aortic branch on left side, unilateral, major supply to lower 2/3
◼ Upper / lower thoracic region – anterior spinal aa. can be small → T4 and L1 prone to
ischaemia
• Anastomotic connection deep to pia mater between ASA, PSA and radicular arteries are capable
of supplying peripheral areas of the spinal cord, hence the sparing of sacral regions of
anterolateral tracts and lateral corticospinal tracts in ASA interference.
Anterior & Posterior midline longitudinal veins and pair of longitudinal veins behind anterior and
posterior nerve roots
Basivertebral veins
Segmental veins
➢ Tract – Group of fibers in CNS that have common origin, course and termination
➢ Nucleus – Group of nerve cells that have common cellular features and giving rise to fibers
that have common path, termination and function
➢ Decussation – Fibers from right cross to left side and fibers from left cross to right
➢ Ipsilateral – Fibers that enter spinal cord pass on the same side
➢ Contralateral – Those who cross to opposite side
o Mainly, 3 neurons
- First order neuron – sense organ -> posterior grey horn
- Second order neuron – Posterior grey horn ->Thalamus
- Third order neuron Thalamus -> sensory cortex
Dorsal columns
Has 2 large ascending tracts
o Fasciculus gracilis
− Throughout cord (lumbar-Sacral)
o Fasciculus cuneatus
− Only from midportion
Discriminative touch, proprioception and vibration sensation,
Stereognosis, graphesthesia
High portion of myelinated fibers
Descending Tracts
General arrangement
First order neuron (UMN) – Has cell body in the cerebral cortex. Axon descends to spinal
cord.
Second order neuron – Internuncial neuron situated in anterior gray column.
Third order neuron (LMN) - In anterior gray column. Innervates skeletal muscles.
- Originate primarily in the cerebral cortex and numerous sites within the brain
stem
- Control of the movements, muscle tone, posture, modulation of spinal reflexes
➢ Lateral column
o Lateral corticospinal tract
o Rubrospinal tract
➢ Ventral column
o Anterior corticospinal tract
o Vestibulospinal tract
o Tectospinal tract
o Reticulospinal tract
o Olivospinal tract
• Most corticospinal fibers synapse with internuncial neurons, which, in turn, synapse with α
motor neurons and some γ motor neurons
• Only the largest corticospinal fibers synapse directly with the motor neurons.
• Branches to cerebral cortex, caudate and lentiform nucleus , red nucleus, olivary nucleus and
to reticular formation .
UMN lesion
Types of paralysis
➢ Hemiplegia- paralysis of one side of the body
➢ Monoplegia- paralysis of one limb
➢ Diplegia- paralysis of 2 corresponding limbs
➢ Paraplegia- paralysis of both legs
➢ Quadriplegia- paralysis of all 4 limbs
Mid CN 3
brain CN 4 Mesencephalic
Pons CN 6
CN 7 Motor
CN 5
Main sensory
Medulla CN 8
CN 9
Spinal nucleus
CN 10 (NA, NTS, DNV)
CN 11
CN 12
Medulla oblongata
Gross appearance
Levels of olives
• Section through the inferior part of 4th ventricle
• Increased amount of gray matter is present at this level
• Olivary nuclei complex
• Nuclei of vestibulocochlear, glossopharyngeal, vagus, accessory, and hypoglossal nerves and the arcuate
nuclei
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Olivary nuclei complex
• Largest nucleus – inferior olivary nucleus
• Smaller dorsal and medial accessory olivary nuclei also are present
• Afferent fibers to inferior olivary nucleus from spinal cord (spino-olivary tract) and from the cerebrum and
cerebral cortex
• Inferior olivary nucleus sends fibers to cerebellum through inferior cerebellar peduncle
• Function – associated with voluntary muscle movements
Vestibulocochlear nuclei
• 4 vestibular nuclei
o Medial vestibular nucleus o Lateral vestibular nucleus
o Inferior vestibular nucleus o Superior vestibular nucleus
• 2 cochlear nuclei
o Anterior cochlear nucleus
o Posterior cochlear nucleus
Nucleus ambiguus
Clinicals
• Vascular disorders
Blood supply
• Posterior inferior cerebellar artery (from vertebral artery)
• Medullary artery (from vertebral artery)
• Anterior inferior cerebellar artery (from basilar artery)
Pons
Gross appearance
• Connects the medulla oblongata and midbrain
• Anterior to cerebrum
• Pons – “bridge” that connect right and left hemispheres
• The anterior surface is convex from side to side
• Shows many transverse fibers that converge on each side to form the middle cerebral peduncle
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• Shallow groove in midline – basilar groove, basilar artery is lodged there
• Trigeminal nerve emerges from the anterolateral surface of pons
• In the groove between medulla and pons the abducent, facial and vestibulocochlear nerves emerge
• Posterior surface is covered from cerebellum
• It forms the upper half of the floor of the fourth ventricle and is triangular in shape
• The posterior surface is limited laterally by the superior cerebellar peduncles and is divided into symmetrical
halves by a median sulcus
Internal structure
Transverse section through the caudal part, passing through the facial colliculus
Transverse section through the cranial part, passing through the trigeminal nuclei
Pontine hemorrhage
The pons is supplied by the basilar artery and the anterior, inferior, and superior cerebellar arteries
2. paralysis of the limbs on the opposite side corticospinal fibers as they pass through the pons
3. paralysis of conjugate ocular deviation the abducent nerve nucleus and the medial
longitudinal fasciculus
1. the pupils may be “pinpoint” ocular sympathetic fibers
2. bilateral paralysis of the face and the limbs corticospinal fibers and facial nerve nucleus
Bilateral
Midbrain
Gross appearance
• Connect the pons and the cerebellum with the forebrain
• The midbrain is traversed by a narrow channel, the cerebral aqueduct
• On the posterior surface are four colliculi, rounded eminences that are divided into superior and inferior pairs
by a vertical and a transverse groove
o Superior colliculus - centers for visual reflexes
o Inferior colliculus - lower auditory centers
• The trochlear nerves emerge from the posterior surface of midbrain, below the inferior colliculi
• The superior brachium passes from the superior colliculus to the lateral geniculate body and the optic tract
• The inferior brachium connects the inferior colliculus to the medial geniculate body
• Interpeduncular fossa - deep depression in the midline
• It is bounded on either side by the crus cerebri
• Many small blood vessels perforate the floor of the interpeduncular fossa - the posterior perforated substance
• The oculomotor nerve emerges from a groove on the medial side of the crus cerebri
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Internal structure
Midbrain
Vascular lesions of midbrain
Weber syndrome
• Cause: Occlusion of a branch of a posterior cerebral artery
• There is ipsilateral ophthalmoplegia – damaged medal
longitudinal fasciculus
• Contralateral paralysis of the lower part of the face, the
tongue, and the arm and leg
• The eyeball is deviated laterally
• There is drooping (ptosis) of the upper lid and the pupil is
dilated and fixed to light and accommodation.
Benedikt’s syndrome
• Similar to Weber syndrome
• But the necrosis involves the medial lemniscus and red
nucleus
• Contralateral hemianesthesia and involuntary movements
of the limbs of the opposite side
Lateral lemniscus • superior olivary & trapezoid body →medial geniculate body
Note
Medial longitudinal fasciculus→ connect CN 3, 4, 6, 8
Applied neuroanatomy
Brainstem lesions
• ipsilateral cranial nerve damage
• contralateral hemiparesis
• contralateral sensory loss in the body
Brainstem lesions
2. Sixty-year-old hypertensive female patient complains of imbalance& difficulty in speaking. She also complains of
nausea & vertigo. On examination she was found to have right sided palatal paralysis, loss of pain & temperature
sensation over the right side of the face. There were also positive cerebellar signs on the right side.
a) Where is the most possible site of the lesion?
b) What is the most possible cause?
c) Explain the above signs & symptoms
d) What other clinical features would you expect to find in this patient?
3. Draw & label a cross section at the trigeminal level of the pons to show the position of the ascending &
descending tracts (50 marks)
Give the commencement & the termination of these tracts (50 marks)
4. Draw a labeled diagram of the transverse section through the pons at the level of the facial nucleus (40)
On what anatomical basis would you differentiate between UMN lesion & LMN lesion of the facial nerve (20)
5. Draw & label a diagram of the midbrain at the level of inferior colliculus (30)
Describe the trochlear nerve from its origin to its termination (70)
T/F
1. Facial colliculus is formed by facial nucleus.
2. Facial nerve curves over the 6th cranial nerve to form facial colliculus.
3. Spinal lemnisci are most posterior in the lower part of the mid brain.
4. Trochlear nerve leaves the brainstem on its dorsal aspect.
5. Hypoglossal nerve leaves the brainstem between olives & inferior cerebellar peduncles.
Diencephalon
• Extent – from interventricular foramen of Monro to commencement of cerebral aqueduct.
• Inferior surface – anterior to posterior – optic chiasma, infundibulum with tuber cinereum, mammillary
bodies
• Superior wall – roof of 3rd ventricle
• Lateral wall – internal capsule
• Medial wall – thalamus, hypothalamus (lateral wall of 3rd ventricle)
Relations
● Anterior - Interventricular foramen of Monroe
● Posterior - Forms pulvinar which overhangs superior colliculus
telachoroidea, fornix
choroid plexus of lateral ventricle
● Superior -
body of the caudate nucleus (thalamus forms part of the floor of the body of lateral
ventricle)
Hypothalamus
● Inferior - tegmentum of mid brain
3rd ventricle
● Medial - interthalamic connection (gray matter)
internal capsule
● Lateral - lentiform nucleus
● Poster superiorly - Epithalamus (pineal gland + 2 habenular nuclei)
3rd ventricle
• Slit like cleft between 2 thalami
• Anterior wall – lamina terminalis with anterior commissure
• Posterior wall – opening of cerebral aqueduct,
posterior commissure
pineal recess
habenular commissure
• Roof – ependymal + telachoroidea,
Choroid plexus of 3rd ventricle,
More above - fornix & corpus callosum
• Floor – optic chiasma,
Tuber cinereum
infundibulum
mammillary bodies
cerebral peduncles
tegmentum
• Lateral wall – thalamus
hypothalamus
• Communicate,
o Anteriorly – lateral ventricle (via interventricular foramen)
o Posteriorly – 4th ventricle (via cerebral aqueduct)
Regarding the thalamus
Relations
● Anterior - optic chiasma
lamina terminalis
anterior commissure
● Posterior - tegmentum of the mid brain
● Superior - thalamus
● Inferior - optic chiasma
tuber cinereum & infundibulum
mammillary bodies
● Medial - 3rd ventricle
Hypothalamo - hypophyseal tract
• Supraoptic nucleus - Vasopressin
• Paraventricular nucleus - oxytocin
Clinical syndromes of hypothalamus
• Carried by axons to the pituitary
• Obesity/wasting
Hypophyseal portal system • Sexual disorders
• Carries releasing & release inhibitory hormones to the pituitary • Sleep disorders
(GnRH, GHRH, GHIH)
• Hyperthermia/hypothermia
• Formed by the superior hypophyseal artery of the internal carotid
• Diabetes insipidus
Epithalamus
• consists of the habenular nuclei and the pineal gland
Subthalamus
• Lies inferior to the thalamus
• Superior to the tegmentum of the mid brain
• Frontal lobe
o Precentral area
• Primary motor area (4) -
carry out the individual
movements of different
parts of the body
• Premotor area, secondary
motor area - store
programs of motor activity
assembled as the result of
past experience
o Frontal eye field - control
voluntary scanning
movements of the eye and
is independent of visual
stimuli
o Motor speech area of Broca
- formation of words by its
connections with the
adjacent primary motor
areas
o Prefrontal cortex - the
makeup of the individual's
personality
• Parietal lobe
o Primary somatic sensory
cortex (SI)
o Secondary somesthetic area
(SII)
o Somesthetic association
area–stereognosis
• Occipital lobe
o Primary visual area (17) -
afferent from LGB
o Secondary visual area (18) -
relate the visual information
received by the primary visual area to past visual experiences, thus enabling the individual to recognize and
appreciate what he or she is seeing
o Occipital eye field - reflex and associated with movements of the eye when it is following an object
• Temporal lobe
o Primary auditory area (41, 42)
o Secondary auditory area (22) – interpretation of sounds and for the association of the auditory input with
other sensory information
o Sensory speech area of Wernicke - permits the understanding of the written and spoken language and
enables a person to read a sentence, understand it, and say it out loud.
1. Caudate nucleus
Separated almost entirely by the internal capsule
2. Lentiform nucleus
I. Globus pallidus
II. Putamen
3. Amygdaloid nucleus
4. Claustrum
Lentiform nucleus
Corpus Striatum
Caudate nucleus
Caudate nucleus
▪ C shaped
▪ Closely related to lateral ventricle
▪ Lateral to thalamus
▪ Laterally internal capsule
Lentiform nucleus
▪ wedge shaped
▪ Medially – internal capsule –
separates it from caudate nucleus
and thalamus
▪ Laterally – external capsule –
separates it from claustrum
Parkinson’s disease
1. Resting tremor (pill rolling tremor)
2. Lead pipe rigidity (cogwheel, plastic)
3. Bradykinesia (slurred speech,
expressionless face, can’t initiate
movements)
4. Postural instability (Shuffling gait)
Commissural fibers
1. Corpus callosum- At the
bottom of the longitudinal
cerebral fissure
2. Anterior commissure-
Rostrum (continuous with
the lamina terminalis)
3. Posterior commissure
4. Hippocampal
commissure - Genu, body,
splenium
5. Fornix – from
hippocampus to
mammillary bodies
Blood supply
1. Middle cerebral artery- medial & lateral striate central branches
2. Anterior cerebral artery- central branches
3. anterior choroidal artery
• Anterior limb: middle cerebral artery (superior half) & anterior cerebral artery (inferior half)
• Genu: middle cerebral artery
• Posterior limb: middle cerebral artery (superior half) & anterior choroidal artery of the internal carotid artery
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(inferior half)
Lesions
• Cause: high blood pressure
• Even a small lesion causes severe damage
• contralateral hemiparesis or hemiplegia
Lateral ventricle
3rd ventricle
• Slit like cleft between the 2 thalami
• The interthalamic adhesion runs through the ventricle
• Communicate with the lateral ventricles anteriorly by the interventricular foramen (of Monroe)
• Communicate with the 4th ventricle posteriorly by the cerebral aqueduct of Silvius
Cerebral aqueduct
• Narrow channel which connects the 3rd ventricle with the 4th ventricle
• No choroidal plexus
FORMATION
• From choroid plexus of the
ventricles
• Which is a vascular fold composed
of pia mater covered with
ependymal cells lining the
ventricular cavity
• CSF is actively secreted
• Production is not pressure
dependent
• Continuous even if the reabsorption
is obstructed
CLINICAL NOTES
1. Papilledema
• Intracranial subarachnoid spaces extend forward around the optic nerve
• High CSF pressure compress the retinal wall → bulging forward of the optic disk causes edema of
the disk
2. Hydrocephalus - abnormal increase in the volume of CSF within the skull
• Communicating hydrocephalus – due to obstruction of interventricular foramen or cerebral
aqueduct by tumors
• Non-communicating hydrocephalus – due to increased formation or decreased absorption of CSF
➢ Supplied by the
▪ 2 internal carotid arteries
▪ 2 vertebral arteries
Ophthalmic Artery
Middle Cerebral Artery
• Largest branch
• Supplies;
Internal Carotid ▪ Entire lateral surface of hemisphere
(except the part supplied by anterior
cerebral artery)
▪ All the parts of the Internal capsule
via lateral & medial striate arteries
▪ Lentiform and Caudate nuclei
➢ Vertebral Artery
• Vertebral arteries are major arteries of the neck
• branch of 1st part of the subclavian artery
• Ascends through foramen transversarium of upper 6 cervical vertebrae (not through C7)
• Grooves the superior surface of posterior arch of atlas
• Enters the skull through Foramen Magnum
• Pierces dura and arachnoid maters to enter the sub arachnoid space (cerebellomedullary
cistern)
• 2 vertebral arteries join up to form the Basilar Artery at the lower border of Pons.
Pontine Arteries
• Supplies;
Basilar Artery ▪ Pons
Labyrinthine Artery
• Accompany Facial & Vestibulo-Cochlear
nerves to Internal Acoustic Meatus
• Supplies;
▪ Inner ear
Medulla Pons
▪ Vertebral artery ▪ Basilar artery
▪ Ant. and post. spinal arteries ▪ Anterior inferior cerebellar
▪ Posterior inferior cerebellar artery artery
▪ Basilar artery ▪ Superior cerebellar artery
Cerebellum
Mid brain ▪ Anterior inferior cerebellar
▪ Basilar artery Circle of Willis artery
▪ Superior cerebellar artery (Regions supplied) ▪ Posterior inferior cerebellar
▪ Posterior cerebral artery artery
▪ Superior cerebellar artery
• Anterior cerebral artery occlusion – Contralateral Hemiparesis & hemi-sensory loss involving leg
& foot.
• Middle cerebral artery occlusion – Contralateral Hemiparesis & hemi-sensory loss involving face
& arm (+ Aphasia if left-sided lesion) (legs are spared)
• Posterior cerebral artery occlusion – Contralateral Homonymous Hemianopia with macula
sparing due to collateral supply from middle cerebral artery.
• Aneurysms in posterior communicating artery can compress oculomotor nerve (surgical
oculomotor nerve palsy)
• Occlusion of the posterior inferior cerebellar artery (PICA) or vertebral artery causes Lateral
Medullary Syndrome (of Wallenberg)
• Occlusion of the medullary branch of vertebral artery (or anterior spinal artery) causes Medial
Medullary Syndrome
▪ Affect the Hypoglossal nerve, Medullary Pyramids and Medial Lemniscus
• Occlusion of a branch of the posterior cerebral artery that supplies the midbrain causes Weber
syndrome
▪ Ipsilateral occulomotor nerve palsy
▪ Contralateral hemiparesis
~Spinal(SVE) Trapezius,
sternocleidomastoid
XII Hypoglossal(GSE) - Tongue muscles - Hypoglossal canal
Corticonuclear tract
Pyramidal cells (precentral gyrus) corona radiata genu of the internal capsule CN nucleus
Bilateral connections are present for all the motor nuclei except,
1. Part of the facial nucleus that supply the muscles of the lower part of the face
2. Part of the hypoglossal nerve that supply the genioglossus muscle
Therefore, unilateral corticonuclear lesions will not produce symptoms except in the above nerves.
Second order neuron – Cells and axons of the cranial nerve nucleus
Axons cross the midline and synapse with the thalamus/nuclei of termination/another sensory nuclei
Central processes of olfactory hair cells in the olfactory mucosa pass through the cribriform
plate to synapse with mitral cells in olfactory bulb.
Axons of mitral cells pass as olfactory tract to uncus (1ry olfactory cortex)
Fibers do NOT relay in thalamus
Bilateral anosmia – due to fracture of anterior cranial fossa associated with CSF rhinorrhea.
CN 2 - OPTIC NERVE
• Fibers=axons of the ganglionic cells
• Leave the eye at the optic disc (medial to the center- blind spot)
• Fibers are myelinated. BUT by oligodendrocytes (comparable to CNS- a tract not a nerve)
Course
Intraneural
Courses anteriorly Through red nucleus
Exit from Anterior surface of mid brain
Intracranial
Exit between the 2 cerebral peduncles in the Inter peduncular fossa,
Between superior cerebellar & posterior cerebral arteries
Crossed by posterior communicating artery
Runs along the free edge of tentorium cerebelli
Enters the Middle cranial fossa
Runs in the Lateral wall of the cavernous sinus (above CN 4)
Divides into superior & inferior divisions
Enters the Orbit through middle part of the superior orbital fissure (SONIA)
Distribution
• Motor –superior division (+sympathetic)
1. superior rectus
2.levator palpebrae superioris
Superior cervical ganglion → Postganglionic sympathetic fibers → Internal carotid cavernous plexus →
Superior division of oculomotor nerve → Smooth muscle part of the LPS (Muller muscle)
Parasympathetic fibers
motor fibers
➢ Main sensory-
-posterior part of pons
-lateral to the motor nucleus
-continues with spinal nucleus
touch & pressure
➢ Spinal-
-continues -superiorly with main sensory nucleus
-inferiorly with substantia gelatinosa of the spinal cord
-extent: whole length of medulla oblongata and inferiorly to the C2 segment of spinal cord
-pain & temperature
➢ Mesencephalic—
midbrain –proprioception from
1)Muscles of mastication
2) Facial muscles
3) Extraocular muscles
These fibres bypass trigeminal nucleus (They are dendrites of unipolar cells)
➢ Motor-
-pons, medial to main sensory
nucleus -Supply: - muscles of
mastication
-anterior belly of Digastric
-mylohyoid
-tensor veli palatini & tensor tympani
Course-
Leaves the anterior aspect of the pons as a small motor root & a large sensory root
Trigeminal ganglion
Lateral wall of cavernous sinus, inferior to Trochlear nerve & superior to maxillary nerve
post.ethmoidal
infratrochlear ant.ethmoidal
foramen rotundum
zygomaticotemporal
infraorbital foramen
face
sensory root to
pterygopalatine ganglion
Fuse to form main trunk which lies in infratemporal fossa on the tensor veli palatini,
Sensory to deep to lateral pterygoid
buccinator Meningeal (nervus spinosus) medial pterygoid
(only sensory branch)
nerve to medial pterygoid Tensor veli
Buccal
otic ganglion palatine &
Tensor tympani
masseteric
CLINICALS
Motor div. –by asking the patient to clench his teeth & feeling for the contracting masseter.
& asking the patient to move the jaw from side to side
TRIGEMINAL NEURALGIA
Sensory root is divided preserving fibres of the ophthalmic div. to avoid damage to the cornea.
Lingual nerve can be damaged in extracting the malplaced wisdom tooth as the nerve lies in
contact with the medial surface of the 3rd molar tooth.
Intracranial
1. Longest intracranial course
2. Ascend on the clivus in the pontine cistern
3. Sharp bend over the superior surface of the petrous temporal bone(crosses apex of petrous
temporal bone
4. Runs anteriorly Through cavernous sinus (inferolateral to internal
carotid artery)
Extracranial
1. Orbit →middle part of the superior orbital fissure (inferolateral to CN 3 & nasociliary) (SONIA)
2. Enter the ocular surface of the lateral rectus muscle
Clinical
Complete paralysis
1. Medial (convergent) squint
2. Diplopia
False localizing sign in raised intra cranial pressure
Due to
1. long course
2. Sharp bend over petrous temporal bone
-Downward shift of brainstem due to raised intracranial pressure
Accommodation reflex
When eyes are directed from a distant to near objects
1. Medial recti contract -Occular axis converge
2. Ciliary muscle contract -Lens thickens & refractive power increases
-direct light waves to the thickest central part of the lens
3.Pupils constrict 1. Optic nerve
2. Optic chiasma
3. Optic tract
4. Lateral geniculate body
5. Optic radiation
6. Visual cortex
7. Eye field of the frontal cortex
● CN 3 nucleus →medial recti
● Edinger-Westphal nucleus of both sides
CN 3
Ciliary ganglion
Short cilliary nerves
Constrictor pupillae & ciliary muscle
Corneal reflex
Light touching of cornea results in blinking of the eye (V1→MLF→VII)
Trochlear nerve
nuclei-
3. Main motor
lacrimatory
2. Parasympathetic in pons
sup. Salivatory
3. Sensory - NTS
Main motor
–lower part of the pons (at the level of facial colliculus)
•Part of nucleus that controls the muscles of lower half of the face receive corticonuclear fibres only
from contralateral cerebral hemisphere.
•Upper part from both cerebral hemispheres.
Lesion 1
Lesion 2
Parasympathetic--
same level
-fibers from hypothalamus
Sensory-
Taste- anterior 2/3 of tongue
Floor of mouth
Palate
• Taste sensation travels through axons of cells situated in geniculate ganglion. (1st order)
• Central processes synapse on cell bodies of NTS.
• Efferents (2nd order neurons) from NTS cross the medial plane and ascend to VPM nucleus to
thalamus.
• From the thalamus fibers (3rd order neurons) pass through internal capsule, corona radiata
14 © 2018 A/L Repeat Campaign
to taste area of cortex.
NTS VPM of
Lingual Chorda Facial thalamus
nerve tympani nerve
Tongue nerve Geniculate cortex
Course- ganglion
Intracranial-
-Consists of motor & sensory root
-motor fibers travel posteriorly around the medial side of the abducent nucleus. (facial colliculus)
-sensory root + parasympathetic root-Nervus intermedius
Emerges through Ponto medullary junction (CP angle)
below the canal for lateral semicircular canal Crosses the neck of the
malleus & pars flaccida of
bend downwards at the posterior wall of tympanic cavity tympanic membrane in the
middle ear
vertically downwards medial to aditus
nerve to stapedius Corda tympani(6mm above
exit from the stylomastoid foramen styomastoid foramen)
posterior auricular, occipitalis
temporofacial cervicofacial
Clinical notes
SYMPTOMS SITE OF LESION
Internal strabismus Pons
Hearing loss IAM
Loss of lacrimation Facial canal before geniculate ganglion
Hyperacusis Facial canal before giving nerve to stapedius
Loss of taste in ant. 2/3 of tongue + lack of salivation Facial canal before giving corda tympani
Paralysis of muscles of facial expression extracranial
VESTIBULAR
MLF
COCHLEAR
CP angle
Parotid gland
Between the internal jugular vein & the internal carotid artery carotid branch (carotid sinus)
Between internal & external carotid arteries pharyngeal branches pharyngeal plexus
Clinicals
Clinical testing
• gag reflex - on tickling the posterior wall of the pharynx there is reflex contraction of
pharyngeal muscles
• testing the taste sensibility of the posterior 1/3 of the tongue
Course
• Between olives & inferior cerebellar peduncles
• Through the middle part of the jugular
foramen anterior to C.N 11
• Joined by the cranial part of accessory
Nuclei
1. Nucleus ambiguus
2. Spinal nucleus (lateral part of the anterior grey column-C1-C5)
Cranial root
• B/w olives & inf cerebellar peduncle (posterolateral sulcus)
• Unite with the spinal root
• Middle part of the jugular foramen
• Separate from the spinal root
• Fuse with Vagus below inferior ganglion
• Distributed through its branches to palate, pharynx, larynx
Spinal root
• B/w ventral & dorsal roots of spinal cord up to C5
• Enters the cranium through foramen magnum
• Unite with the cranial root
• Middle part of the jugular foramen
• Separate from the cranial root
• Descend b/w internal jugular vein & internal carotid artery
• Deep to styloid process
• Deep to sternocleidomastoid
• Pierce the posterior border of it near its middle
• Enter the posterior triangle
• Pass deep to ant border of trapezius 5cm above clavicle
• Supply sternocleidomastoid & trapezius
Clinical
Ask the patient to shrug the shoulders against resistance
Ask the patient to turn the chin to opposite side against resistance
Location
Situated in the posterior cranial fossa.
Relations
Anterior - 4th ventricle
Brain stem(Pons and medulla)
Choroid plexus of 4th ventricle
Superior and inferior colliculus
External Features
2 cerebellar hemispheres and median vermis.
2 surfaces- superior and inferior
2 lobes in each hemisphere- anterior, posterior, flocculonodular
3 fissures -
Primary-between anterior and posterior lobes
Horizontal- in posterior lobe(no importance)
Uvulonodular-seperates posterior and flocculonodular lobes
Microscopic structure
Cortex
• 3 layers- Molecular, Purkinje, Granular (My Personnel Guard )
• 5 cell types-
Molecular - Outer stellate & Inner basket cells
Purkinje - Purkinje cells & Golgi type 1 cells
Granular - Granular cells and Golgi cells
Functional Divisions
01. Vestibulocerebellum- Flocculonodular lobe
02. Spinocerebellum- Vermis & Intermediate zone
03. Cerebrocerebellum- Lateral part.
1. Vestibulo-cerebellum
2. Spino-cerebellum
• Intrinsic
– Do not leave the cerebellum
– Interconnect folia of the cerebellar cortex and vermis of thesame side
or connect the two cerebellar hemispheres
• Afferent
– Input fibers
– Enter cerebellum through inferior and middle cerebellar
peduncles
• Efferent
– Output fibers
– Commence as the axons of Purkinje cells – cerebellar nuclei
– superior and inferior cerebellar peduncles
Intracerebellar nuclei (Deep nuclei)
1. Dentate
2. Emboliform Outflow runs through sup. peduncle
3. Globose
4. Fastigial- outflow runs through inf. Peduncle
(Don’t Eat Greasy Food)- from lateral to medial
Sympathetic Parasympathetic
Autonomic ganglia
Basic structure
I. greater splanchnic (5-9 II. lesser splanchnic (9-11 III. least splanchnic
thoracic ganglions) thoracic ganglions) nerves (12th thoracic
It descends and pierces the crus It descends with the greater ganglion)
of the diaphragm to synapse with splanchnic nerve and pierces the The least splanchnic nerve (when
the ganglia of the diaphragm to join with the ganglia present) pierces the diaphragm,
i. celiac plexus in the lower part of the celiac and synapses with the ganglia of
ii. renal plexus plexus. the renal plexus
iii. suprarenal medulla.
Ganglion impar
Afferent →Without synapsing in ganglion via white rami communicans → Posterior root ganglion
(myelinated)
afferent component of local reflex arc Central axons
Supra-renal medulla
A few preganglionic fibers, traveling in the greater splanchnic nerve, end directly on the cells of the
suprarenal medulla. These medullary cells, which may be regarded as modified sympathetic excitor
neurons, are responsible for the secretion of epinephrine and norepinephrine.
• The sympathetic chain continues upwards from thorax by crossing the neck of the first rib
• Then ascends embedded in the posterior wall of the carotid sheath to the base of the skull
• No white rami communicans from cervical part of sympathetic chain
• Preganglionic fibres origin from lateral grey horn of T1-T4 & ascend to the cervical ganglia.
• 3 ganglia –Superior, Middle, Inferior
Superior cervical ganglion (fusion of C1-C4 ganglia)
• Largest
• Lies opposite C2 and C3 vertebrae
• Sends grey rami communicans to C1-4 spinal nerves
SYMPATHETIC PARASYMPATHETIC
Action Prepares body for emergency Conserves & restores energy
Outflow T1 - L2(3) Cranial nerves III, VII, IX, & X;
S2,3 & 4
Preganglionic fibres Myelinated B Myelinated B
Ganglia Paravertebral (sympathetic trunks), Small ganglia close to viscera
prevertebral (ex: celiac, superior (eg: otic, ciliary) or ganglion cells
mesenteric, inferior mesenteric) in plexuses
(eg: cardiac, pulmonary)
Neurotransmitter within ganglia Acetylcholine Acetylcholine
Postganglionic fibres Long non-myelinated C Short non-myelinated C
Characteristic activity Wide spread due to many post-ganglionic Discrete action with few post
fibres & liberation of epinephrine & ganglionic fibres
norepinephrine from supra renal medulla.
Neurotransmitter at postganglionic Norepinephrine at most endings & Acetylcholine at all endings
endings acetylcholine at few endings (sweat glands)
Higher control Hypothalamus Hypothalamus
Large collections of sympathetic and parasympathetic efferent nerve fibers and their
associated ganglia, together with visceral afferent fibers, form autonomic nerve plexuses.
Thorax
1. Cardiac plexus
Sympathetic – cardiac nerves, fibers from upper thoracic ganglia
2. Pulmonary plexus
Parasympathetic – vagal fibers
3. Esophageal plexus
Abdomen
1. Coeliac plexus Sympathetic – Greater, lesser, least splanchnic nerves, upper two
2. Superior mesenteric plexus lumbar splanchnic nerves
3. Inferior mesenteric plexus Parasympathetic – vagal fibers (coeliac branch of posterior gastric
nerve)
The postganglionic fibers arise from the peripheral plexuses and are distributed to the
smooth muscle and glands of the viscera.
Submucous/Meissner plexus between mucous membrane and control of the glands of the
circular muscle layer mucous membrane
Due to interruption of the sympathetic nerve supply to the head and neck.
Causes
- Lesion in the brain stem or cervical part of the spinal cord- damage to the descending tracts from
hypothalamus (Reticulospinal tract)
3. Frey’s syndrome
– Nerves will supply the sweat glands instead of the salivary tissue (sweating at the time of salivation)
– Nerves will supply the lacrimal gland instead of submandibular and sublingual (tearing with salivation)
called crocodile tears
4. Hirschsprung’s disease
– Aganglionic segment in the colon
– No peristalsis
– Proximal colon distended
5. Vagotomy
– Delayed gastric emptying
– Diarrhoea
In all the following ganglia only the parasympathetic fibers are relayed.
1. CILIARY GANGLION
• Location: - Near the apex of the orbit. Between the optic nerve & the tendon of the lateral rectus
• Topographically - related to optic nerve
• Functionally - related to oculomotor nerve
Parasym. root
Sensory root Sympathetic root
Edinger Westphal
nucleus Trigeminal nerve Sup. cervical
ganglion
Oculomotor nerve
Inferior division
Ciliary
Ganglion
Short ciliary
nerves
Dilator pupillae&
Sphincter blood vessels
pupillae & eyeball (vasomotor)
Ciliaris
Parasympathetic root
Inferior Salivatory
nucleus
Tympanic plexus
Mandibular nerve External carotid plexus (middle meningeal artery)
Lesser petrosal
nerve
Auriculotemporal
nerve Nerve to Medial
Pterygoid
(Middle Cranial
cavity) Tensor veli
palatini &
Tensor tympani
Auriculotemporal
Parotid gland
Nervus Intermedius
Maxillary nerve Nasal branches
{ Medial posterior superior
Facial nerve nasal nerves ( largest one
Sensory roots called nasopalatine nerve ) and
Lateral posterior superior
nasal nerves }
Geniculate ganglion
Nerve of
pterygoid canal Pharyngeal branches
Zygomaticotemporal
Postganglionic fibres
nerve
Superior cervical
ganglion Lacrimal nerve Lacrimal gland
Sympathetic root
5
© 2018 A/L Repeat Campaign
4. SUBMANDIBULAR GANGLION
● Topographically related to Lingual nerve
● Functional component of Facial nerve (Chorda tympani branch)
● Location :- Lies on the Hyoglossus muscle,
Chorda tympani
Lingual nerve External carotid plexus
(facial artery)
Lingual nerve
Submandibular gland
a) Supplies the sphincter pupillae muscle through its zygomatico temporal fibres
b) Supplies secretomotorfibres for the lacrimal gland
c) Gives passage to sympathetic fibres
d) Distributes secretomotorfibres to the glands of the nose, palate and nasopharynx
e) Receive fibres from the maxillary nerve
➢ Clinicals
1. In blow out fracture, orbital floor or medial wall (most likely lamina papyracea=paper like thin lamina =
orbital lamina of ethmoid bone & lacrimal bone) may be damaged because those walls are thin and the
maxillary sinus and ethmoid sinus are located adjacent to them.
2. Fracture of floor causes herniation of orbital fat into maxillary sinus
3. Entrapment of an extra-ocular muscle causing diplopia
4. Injury to infra-orbital nerve
➢ Openings
• Supra orbital notch/foramen - supraorbital nerve & vessels
• Infraorbital groove - infraorbital nerve & vessels. Lodges the orbitalis muscle
• Nasolacrimal canal - nasolacrimal duct
• Inferior orbital fissure - maxillary & zygomatic nerves, inferior ophthalmic vein, sympathetics
(gap between lateral wall and floor)
• Superior orbital fissure - L, F, T - S, O, N, I, A
(gap between lateral wall and roof)
• Optic canal - optic nerve & ophthalmic artery
• Anterior & posterior ethmoidal foramina – at the junction of roof and medial wall. Transmits the anterior &
posterior ethmoidal nerves & vessels
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Leftenant protects the girl Sonia
L - Lacrimal nerve (smallest branch of V1)
F - Frontal nerve (Largest branch of V1)
T - Trochlear nerve (CN IV)
S - Superior division of Oculomotor nerve (CN III)
O-
N - Nasociliary Nerve (branch of V1)
I - Inf. division of oculomotor nerve
A - Abducent nerve (VI)
Orbital Fascia
• Periosteum of orbital skeleton
• Posteriorly continuous with dural sheath for optic nerve
• Anteriorly continuous with periosteum lining the bones of the orbital margin
• Gap in the I.O.F. bridged by Orbitalis - sympathetic supply Exophthalmus
• Extensions:-
- Orbital septum = Palpebral fascia
- Attaches to the Trochlea (Fibrous pulley of tendon of superior oblique)
- Lacrimal fascia
➢ Clinicals
• Horner's syndrome or lesions of sympatheic supply - Muller muscle paralysed - Partial ptosis
• Oculomotor nerve lesion - voluntary part of LPS paralyzed - Complete ptosis
• Meibomian cysts/ Chalazion – distention & inflammation of the meibomian glands due to obstruction of
tarsal / Meibomian gland ducts which causes swelling.
• Stye (Hordeolum) – external hordeolum - infection of sebaceous (of Zeis) & sweat glands (of Moll)
Internal hordeolum - infection of Meibomian glands
Conjunctiva
• Delicate mucous membrane lining the inner surface of lids
• Attached to sclera at the margins of cornea (Corneoscleral junction).
• Reflected to inner surfaces of eye lids.
o Over the eye lids – palpebral conjunctiva/thicker and highly vascular
o Over the sclera – bulbar conjunctiva/thinner
o Over the cornea – reduced to a single layer
• Superior conjunctival fornix receives opening of lacrimal glands
Conjunctival fornix – line of reflection from lid to the sclera
Orbital septum
➢ Attached to margins of orbit forming palpebral fissure between eye lids.
➢ Above and below the fissure form superior and inferior Tarsal plates.
➢ At the medial end – medial palpebral ligament
➢ At the lateral end – lateral palpebral ligament
➢ Levator palpebral superioris is attached to superior tarsal plate.
➢ Tarsal/meibomian glands embedded within tarsal plates
Lacrimal apparatus
• Concerned with secretion & drainage of tear fluid/Lacrimal fluid.
• Components - 1.lacrimal gland & ducts, 2.conjunctival sac, 3.lacrimal puncta & canaliculi, 4. lacrimal sac,
5.nasolacrimal duct
Lacrimal gland
• A serous gland situated in the lacrimal fossa (in the ant.
upper lateral part of the orbit & partly on the upper
eyelid)
• J shaped
• Indented by the tendon of levator palpebrae superioris
• Has orbital part & palpebral part
• Orbital part - large & deeper
• Palpebral part - smaller & superficial (all the ducts open
through this part, so removal is functionally equivalent to
the removal of the entire gland)
• 8-12 small ducts drain the gland
• Ducts pierce the conjunctiva of upper eye lid & open into
the conjunctival sac near the superior Conjunctival fornix
3 ©2018 A/L Repeat Campaign
• secretions spread over the surface of the eye
• lacrimal canaliculi drain tears to the lacrimal sac via lacrimal papillae
• Lacrimal sac lies in lacrimal groove formed by the maxilla and lacrimal bone.
• Nasolacrimal duct begins at lower end of lacrimal sac
• Naso-lacrimal duct opens into inferior Meatus of nose.
• Small accessory lacrimal glands are found in the conjunctival fornices
• Supplied by lacrimal branch of ophthalmic artery & lacrimal nerve (both sensory & secretomotor)
secretomotor fibres from superior salivary nucleus which travel in greater petrosal nerve
pterygopalatine ganglion
Lacrimal nerve
>Closest to Corneoscleral
junction - Medial Rectus
>Furthest -
Superior Rectus
➢ II – optic nerve
• Nerve of sight
• Made up of axons of ganglionic layer of retina
• Passes through optic canal to enter the middle cranial fossa
• Enclosed in 3 meningeal sheaths
• Relations:
1. At the apex of the orbit closely surrounded by the recti muscles
2. Ciliary ganglion is between optic nerve & lateral rectus
3. Pierced by central artery of retina, inferomedially
4. Crossed inferiorly by the nerve to medial rectus
5. Crossed superiorly by ophthalmic artery, nasociliary nerve & superior ophthalmic vein
➢ VI – abducent nerve
• Arises from between pons & medulla
• Passes forwards to enter cavernous sinus
• Lies inferolaterally to internal carotid artery
• Enters superior orbital fissure through the annulus of Zinn lying inferolateral to the oculomotor &
Nasociliary nerves.
• Supply Lateral rectus (LR6)
➢ V – Trigeminal nerve
Trigeminal nerve
Zygomatic
Maxillary division
Infra-orbital
➢ Ophthalmic artery
• Branch of internal carotid artery (cerebral part)
• Runs through optic canal inferolaterally to optic nerve within its Dural sheath.
• In orbit the artery pierces the dura mater, ascends over the lateral side & crosses above the optic nerve
from lateral to medial along with nasociliary nerve anterior to it.
• Runs forwards along the medial wall of the orbit & terminates by dividing into supratrochlear & dorsal
nasal branches
• Branches
▪ Central artery of retina (end artery, given off within the dural sheath) - supply optic nerve and retina
(Posterior ciliary capillaries supply the choroid coat of eye, they also supply outer layers of retina but
there is no anastomosis bet central artery and them)
▪ Lacrimal artery (gives off after piercing the dural sheath) runs along lat. wall.
▪ from main trunk which runs in the medial wall of the orbit (branches accompany all the branches of
nasocilliary, lacrimal and frontal nerves)
i. Ciliary branches (long & short)
ii. Supraorbital & supratrochlear
iii. Anterior & posterior ethmoidal
iv. Medial palpebral branches
v. Dorsal nasal
Establish connections between external and internal carotid systems.
➢ Ophthalmic veins
Superior ophthalmic vein (Connects cavernous sinus & the facial vein)
• Commences above the med palpebral ligament
• Passes back above optic nerve, accompanies the ophthalmic artery. Passes through S.O.F.
• Drain to cavernous sinus via superior orbital fissure
• Communicate with supraorbital & angular vein at its commencement.
Sclera - 5/6
• is tough / dense fibrous tissue
• outer surface is covered by Tenon’s capsule
• deep part of limbus contains canal of Schlemm
▪ maintains shape of eyeball
▪ receives insertion of extraocular muscles
▪ posteriorly pierced by optic nerve
▪ dural sheath continues
Cornea - 1/6
• avascular
• 5 layers
1. Corneal Epithelium (stratified)
2. Basement/Bowman’s membrane
3. Connective tissue stroma/substantia propria
4. Descemet’s membrane basement membrane of endothelium.
5. Corneal Endothelium - Hexoganal shaped cells, single layer. don’t undergo mitosis
• Cornea is supplied by
▪ Short ciliary nerves
▪ Long ciliary nerves
(rich pain sensation)
(Trigeminal -> Ophthalmic division
->Nasociliary branch Long Ciliary nerves
Ciliary ganglion
Short Ciliary nerves
Choroid
• thin
• pigmented
• highly vascular
• pierced by optic nerve
• lines the inner surface of the sclera
• anteriorly ends at ora serrata iris by joining ciliary body
Ciliary Body
• Thickened part of uveal tract behind the corneal limbus.
-near scleral surface → Ciliary muscle
-near vitreous surface → posteriorly - pars plana - smooth
→ anteriorly - pars plicata - ridged to form ciliary processes - zonular fibers =
suspensory ligament attached to the grooves (zonule)
• ciliary ring & ciliary process continuous with iris and choroid
• ciliary muscle changes convexity of lens (accommodation)
- ring of smooth muscle → contraction → diameter → relaxes suspensory ligaments →Lens become
- supplied by parasympathetic fibers convex for near vision.
3. Neural coat
Retina → Thin, delicate, inner layer
• outer pigmented
• Inner neural
• Continuous with optic nerve
• anterior pole is called ora serrata
• posterior pole is called macula lutea
Blood supply
→Central artery of retina-ganglion & bipolar cells
→rods & cones- diffusion from capillaries
in the choroid
macula lutea fovea centralis 3mm nasally Optic disc = Blind spot Optic Cup
(site of central vision) (only cones, no vessels) (no rods or cones)
Central artery
Temporal Temporal
Upper Lower
Nasal Nasal
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• no blood vessels over fovea
• maximum visual acuity is in fovea centralis (fovea centralis is the thinnest part of the retina)
• Outer Receptor Layer (Outer segment shape gives the name)
▪ The rods and cones, synapse with bipolar cells
▪ bipolar cells synapse with ganglion cells.
▪ Horizontal cells connect photoreceptor cells to the other photoreceptor cells in the outer plexiform
layer.
▪ Amacrine cells connect ganglion cells to one another in the inner plexiform layer via processes of
varying length and patterns.
obliteration of iridocorneal angle
1st order neurons- bipolar cells
2nd order neurons- ganglion cells impaired reabsorption
3rd order neurons- LGB to cortex
increased intra-ocular tension
Lens
• Biconvex, placed between ant. & post. segments. GLUCOMA
• Contributes to about 15D refraction(Cornea 45D)
• Enveloped by lens capsule; an elastic membrane
• between vitreous body & aqueous humor
• more curved posteriorly
• Anterior surface is kept flattened by the tension of suspensory ligament
• No blood supply, no nerve supply.
Aqueous Humor
• Anterior segment→ Cornea to lens
• filtered plasma
• secreted into posterior chamber from ciliary processes. • Post. segment → Vitreous & Retina
• aquous humor passes between iris & lens, then through
pupil into the ant. chamber. ❖ Ant. Chamber-Between
• Then drains through trabecular meshwork into canal of Schlemm Cornea & Iris Aqueous
• Then it drains into the episcleral venous plexus.
❖ Post. Chamber-Bet. Iris & Lens Humor
❖ Vitreous chamber/ Postremal chamber -
Vitreous Humor Bet. Lens & Retina → Vitreous humor
• thin transparent gel within hyaloid membrane
• pierced by lymph filled hyaloid canal
• occupies the posterior 4/5th of the eye ball
Clinicals
➢ Oculomotor nerve paralysis
• Ptosis – paralysis of levator palpebrae superioris
• When the lid manually lifted up, eye is looking down and out - unopposed action of lateral rectus and
superior oblique
• Diplopia (double vision)
• When looking out diplopia disappears - lateral rectus intact
• Pupil is dilated and doesn’t react to direct light reflex or accommodation - interruption of
parasympathetic fibres
• Consensual light reflex of opposite eye works.
➢ Abducens nerve paralysis
• Can’t look outwards - paralysis of lateral rectus
• diplopia
➢ Trochlear nerve paralysis
• Can’t look downwards - superior oblique paralysis (patient complain of diplopia when reading or
difficulty in going downstairs
• Extortion effect due to inferior oblique (to compensate extortion, patient tilts the head towards the
opposite shoulder)
❖ Oral cavity can be divided into oral cavity proper (Inner larger)
and vestibule (outer smaller )
PALATE
Separates the oral cavity from the nasal cavity
1.Hard palate:
Palatine plate of maxilla- anterior 2/3
Horizontal plate of palatine bone- posterior 1/3
2.Soft palate:
Divide naso & oro pharynx
Anterior surface marked by median
raphe uvula at posterior edge
* Muscles
• tensor veli palatini (tenses soft palate) Framework by the aponeurosis
• levator palatine (elevation)
• palatoglossus
• palatopharyngeus inserted to the aponeurosis
• muscular uvulae
* Lymph drainage
• tip bilaterally submental nodes
• remaining anterior 2/3 unilateral Submandibular Jugulo-omohyoid
• posterior 1/3 bilateral jugulo-digastric
Sensory Supply
Extent
In the anterior midline of neck, between large vessels of the neck.
From root of tongue to trachea.
In adult male C3 – C6
Structure
Musculofibrous structure with a cartilaginous framework.
Overview of Constitutions
Epiglottis
Cuneiform. Elastic fibrocartilages
Corniculate
Cricoid
Signet-ring shaped.
Vertical ridge for
Composed of cricoid arch anteriorly, and quadrilateral Oesopagus
cricoid lamina.
Only complete cartilaginous ring in the whole air
passage.
Facets on superolateral surface of the lamina
articulates with the base of arytenoid cartilages
forming a synovial joint.
In the posterior surface, esophagus is attached to a
vertical ridge.
Depression on either side are for attachment of
posterior cricoarytenoid muscles.
Clinicals
Cricoid pressure/Sellick maneuver- Pressure
applied on cricoid arch to occlude underlying
oesophagus.
Reduces the risk of aspiration during
endotracheal intubation.
Cricoarytenoid muscles
Arytenoid
Three sided-Pyramidal shaped.
Apex articulates with corniculate cartilages.
Base articulates with upper border of cricoid lamina.
Prolonged anteriorly to form vocal process& laterally
to form muscular process.
Epiglottis
Corniculate
Elastic fibrocartilage.
Articulate with the apex of the arytenoid cartilage.
Lie in the posterior part of aryepiglottic fold.
Cuneiform
Lie in aryepiglottic fold, anteriorly to corniculate.
Epiglottis
leaf-shaped elastic fibrocartilage with a stalk.
Placed in anterior wall of laryngopharynx.
Attached to posterior surface of thyroid cartilage at
angle via Thyroepiglottic ligament.
Folds and ligaments attached to it,
Aryepiglottic fold
Hyoepiglottic ligament
Glossoepiglottic fold
Lingual surface - non-keratinized strat. squamous.
Laryngeal surface – ciliated respiratory epithelium.
Histology
Thyroid, cricoid & arytenoids(basal part) – hyaline
Others – elastic
Cricoarytenoid joint
Synovial joint.
Between facets of cricoid cart. & the base of the
arytenoids.
Rocking(increase Rima Glottidis) &
Gliding(adduction/abduction of vocal folds).
Gliding Rocking
Cricotracheal ligament
From lower border of the cricoid to upper border
of 1st tracheal ring.
Mucous membrane
Anterior surface & upper half of posterior surface of
epiglottis, the upper part of epiglottic folds & vocal
folds – stratified squamous.
Other areas – ciliated columnar respiratoy.
Mucous glands absent over vocal folds.
Vocalis
Thyroarytenoid
Cricothyroid
Laryngeal cysts
Nerve supply
Blood supply
Outer surface- Deep auricular branch of maxillary artery
Inner surface – anterior tympanic branch of maxillary artery
posterior tympanic branch of maxillary artery
stylomastoid branch of posterior auricular artery
Middle ear/tympanic cavity
• Narrow, air filled space located in the petrous temporal bone
• Cube shaped with six walls
• Roof/tegmental wall – formed by tegmen tympani, separates middle ear from middle cranial
fossa and temporal lobe of the brain
• Floor/jugular wall – formed by a part of temporal bone, separates middle ear from the superior
bulb of the internal jugular vein
Tympanic canaliculus transmit tympanic branch of glossopharyngeal nerve
• Anterior/carotid wall –
i. superior part has the opening of the canal for tensor tympani muscle
ii. Middle part has the opening for the auditory tube
• Posterior/mastoid wall –
i. has an opening through which middle ear communicate with mastoid/tympanic antrum
and mastoid air cells,
ii. posterior canaliculus for chorda tympani through which the nerve enter middle ear
iii. Has an opening for passage of the tendon of stapedius muscle.
iv. Has a canal for facial nerve
• Lateral/membranous wall –
i. Separates middle ear from external acoustic meatus
ii. Formed mainly by tympanic membrane and partly by squamous temporal bone
iii. Petrotympanic fissure lodge anterior process of malleus and transmit tympanic branch
of maxillary artery
iv. Contain anterior canaliculus for chorda tympani nerve
• Medial/labyrinthine wall –
i. Separates middle ear from internal ear
ii. Presents – promontory : formed by first turn of cochlea, fenestra cochleae (round
window), fenestra vestibule (oval of lateral window), prominence of facial canal &
prominance of
lateral semicircular canal
• Lateral wall of the middle ear cavity is formed by the tympanic membrane mainly and a part above it
is formed by the squamous temporal bone.
• The part of the middle ear cavity above tympanic membrane is known as epitympanic recess.
• It contains head of malleus and incus.
Mastoid Antrum
CLINICAL ANATOMY
Otitis media (middle ear infection)
• Throat infections commonly spread through auditory tube to the middle ear and cause otitis
media.
• Pus from the middle ear can take one of the following courses.
01. May discharge into external ear following rupture of tympanic membrane.
02. May erode the roof and spread upwards causing meningitis and brain abscess.
03. May erode the floor and spread downwards causing thrombosis of sigmoid sinus and internal
jugular vein.
Tympanic04. May spread
nervous plexusbackwards causing mastoid abscess.
• Membranous labyrinth –
i. Epithelium is specialized to form receptors for
sound(organ of corti), receptors for static
balance (maculae), receptors for kinetic balance
(cristae)
ii. Contains 3 parts
a. organ of corti (anteriorly)
b. Utricle and saccule with maculae (within vestibule)
c. Semicircular ducts with cristae (posteriorly)
• Blood supply – Mainly from labyrinthine branch of basilar artery and partly from stylomastoid
branch of posterior auricular artery.
Bony part –
i. Forms posterior 1/3 of the tube, 12mm long.
ii. Lie in petrous temporal bone near tympanic plate.
iii. Lateral end open on the anterior wall of middle ear and the medial end is narrow and jagged.
iv. Relations – superior: canal for tensor tympani, medial: carotid canal, lateral: chorda tympani,
auriculotemporal nerve, spine of sphenoid and temporomandibular joint.
Cartilaginous part –
i. Forms anteromedial 2/3 of the tube and 25mm long
ii. Lies in sulcus tubae (a groove between greater wing of sphenoid and apex of petrous temporal)
iii. Made up of a triangular plate of cartilage which forms the superior and medial walls. Lateral wall
and floor are completed by a fibrous membrane.
• Blood supply – Arterial supply by ascending pharyngeal artery, middle meningeal artery and
artery of pterygoid canal.
• Veins drain into pharyngeal and pterygoid plexuses of veins.
• Nerve supply –
− at the ostium : by pharyngeal branch of pterygopalatine
ganglion
− cartilaginous part: by nervus spinosus branch of mandibular
nerve,
− bony part: by tympanic plexus.
Glossopharyngeal nerve
Cervical spine lesions, Tongue –
other neck lesions and posterior 1/3 lesions
geniculate herpes.
• After chickenpox clears, the virus lies dormant in the nerves. If they reactivate and effect the facial nerve.
• A painful red rash (fluid filled blisters) in, on and around the ear.
• Facial weakness/ paralysis on same side
Nose
Consists of external nose and nasal cavity, Skin is abundant in
sebaceous glands Dorsum
External nose − bony & cartilage framework
Bones
• 2 nasal bones
• frontal process of maxilla Tip
Cartilages
• lateral Processes of septal cartilages
Base
• major alar cartilages
• minor alar cartilages
• Ala→solely of fatty tissue at its free lower border
Lateral wall
• frontal process of maxilla (mainly)
• perpendicular plate of the palatine bone
• medial pterygoid plate
• ethmoid labyrinth with superior and middle conchae
• inferior nasal conchae
• nasal bone
• lacrimal bone
• Cartilaginous part
Meatus
− Passages beneath the
overhanging conchae
− Paranasal sinuses
open into meatus
1. Superior meatus→ posterior ethmoidal air cells
2. Middle meatus→ ● Ethmoidal bulla middle ethmoidal air cells
• hiatus semilunaris (A deep semicircular sulcus below bulla)→Frontal sinus (anteriorly)
Anterior ethmoidal air cells (middle)
Maxillary air sinus (posteriorly)
1 2018 A/L Batch Repeat Campaign
3. Inferior meatus→ nasolacrimal duct
❖ Spheno-ethmoidal recess (just above the superior conchae) → sphenoidal air cells
* Roof
− horizontal – made by cribriform plate
− anteriorly – frontal bone
− posteriorly – sphenoid bone
* Floor
Hard palate = Palatine process of maxilla + horizontal plate of palatine bone
Soft palate
Mucous membrane
• Olfactory epithelium - thin
− confined to superior conchae and adjacent upper part of septum
• Respiratory epithelium - thick (mucous secretions)
Little’s area
Anterior inferior part of the septum
Has rich arterial supply
Anastomoses between
− Superior labial branch of facial artery
− Greater palatine artery
− Branch of sphenopalatine artery
Forms the Kiseselbach’s plexus
A common site for nosebleed
(epistaxis)
Blood supply of the nasal cavity
• Include vessels that originate from both
the internal and external carotid arteries
✓ Vessels that originate from branches of
external carotid artery
• Sphenopalatine(major blood
supply),greater palatine, superior labial
and lateral nasal arteries
Clinicals
symptoms in carcinoma of maxillary sinus
1) Medial – epistaxis, obstruction of nares
epiphorea (blocked nasolacrimal duct)
2) Orbit - diplopia + exophthalmos
infraorbital nerve facial pain, anesthesia of skin over the maxilla
3) Floor – bulging/ulceration in the palatal roof
4) Lateral - swelling of face
5) Posterior - palatine nerves referred severe pain to teeth of upper jaw
2. Infections of the maxillary sinus
▪ From nasal cavity
▪ From caries of upper molar teeth
3. Ethmoidal sinus
• Numerous, small, intercommunicating spaces (8-10)
• Lie within the labyrinth of ethmoid bone
• Divided in to anterior, middle and posterior groups
Clinicals
• related to frontal lobe - frontal lobe abscess
• C.S.F rhinorrhea
4. Sphenoid sinus
• Either side of midline, in body of sphenoid
• Drain above superior conchae (spheno-ethmoidal recess)
4 2018 A/L Batch Repeat Campaign
Clinicals
In pituitary tumor, Pituitary gland may be excised through fibre-optic trans-nasal trans-sphenoidal approach
(endoscopically)
ENDOCRINE SYSTEM -HISTOLOGY
- Groups of secretory cells, surrounded by highly vascular delicate layer of collagenous tissue.
- Fenestrated capillaries.
1. Thyroid gland
Microscopic structure
• Fenestrated capillaries
Thyroid follicle
• Small • Large
Endocrine cells
Follicular cells
• Secrete T3/T4
• Rest on a BM
-Exocytosis (thyroglobulin→lumen)
EM structure
- Mitochondria-with rER
• Secrete calcitonin
CLINICALS
2.Hypothalamus
• Blood vessels
01.Adenohypophysis/Anterior pituitary
Anterior pituitary
• Surrounded by BM
-Somatotrophs (50%)
-Lactotrophs (20%)
-Corticotrophs (20%)
-Thyrotrophs (5%)
-Chromophobes
• EM:
Pars intermedia
• Acini
- lumen-colloid
Pars tuberalis
• Pale basophilic
• Nonmyelinated axons(mainly)
• Function-neurosecretory activity
• Pituicytes
- Supportive function
Infundibulum ,plexus -----Long & short portal blood vessels------>Capillary plexuses of anterior lobe
of arteries
Hypothalamus-hypophyseal tract
Hypothalamus-Hypothalamic nuclei
-Supraoptic nucleus (ADH) ----Nerve axonal fibres----> Posterior pituitary- dailated ends of axons
CLINICALS
• During pregnancy, in anterior lobe cells increase in number to increase FSH, LH & Prolactin production.
• If heavy bleeding occurs at the time of the birth, cells undergo necrosis, hormone deficiency can
occur-Sheehan syndrome
4.Adrenal gland
- mineralocorticoids (ex:-aldosterone)
• Vasculature-subcapsular plexus →short and long cortical arteries→ sinusoids →Venules→ central vein
- Secrete aldosterone.
- Secrete cortisol.
- Cells contain catecholamine granules – oxidized to brown colour with chromium salts
(chromaffin cells).
- No stored lipids.
5.Parathyroid gland
• Usually 2 pairs
• Within thyroid capsule, embedded in thyroid parenchyma
• Rich vascular network
Microscopic anatomy
CLINICALS
6.Pineal gland
• Pinealocytes
Pineal sand
•Islets of Langerhans
Mesenchyme Structure
Pharyngeal Arches
❖ All the muscular components of each pharyngeal arch has its own nerve and arterial
supply
• 4 pairs
• 5th is rudimentary
• Epithelial endodermal lining give rise to several structures
❖ Thymus migrates in caudal and medial direction pulling inferior parathyroid with it &
then fuses with the counterpart from opposite side. (Final position – Anterior part of
thorax)
Pharyngeal clefts
Clinical
Birth defects
1) Ectopic thymic and parathyroid tissue
• Accessory glands remain in the migration pathway
• May found in the neck
• Inferior parathyroids may found at the bifurcation of the common carotid
artery
3) Cervical cysts
• Remnants of cervical sinus
• Found anywhere along ant. border of SCM, frequently just below the angle of
jaw
• Become evident in child head
Tongue
Thyroid Gland
• Epithelial outgrowth from floor of the tongue - Foreman cecum (between tuberculum
impar and copula)
• Connected to the tongue by thyroglossal duct
• Descends in front of pharyngeal gut in midline
• Descend in front of hyoid bone, thyroid & cricoid cartilages
• Positioned in front of trachea in 7th week - with an isthmus & two lobes
• Ultimobranchial body (4th pouch) – incorporated into the gland – give rise to C cells
• Starts function at the end of 3rd month
o Follicular cells ➔ thyroxine & triiodothyronine
o Parafollicular cells( C cells) ➔ Calcitonin
Clinical
• Thyroglossal Cyst
o Always in the midline
o Cystic remnant of thyroglossal duct
o 50% under hyoid bone
• Thyroglossal fistula
o Thyroglossal cyst connected to the outside by canal
o May be present at birth
• Aberrant thyroid tissue
o Remnants of tissue along the migratory pathway
Development of face
Nasolacrimal groove
• Between maxillary & lateral nasal prominence
• Floor forms a solid epithelial cord
• By canalization forms nasolacrimal duct with lacrimal sac
Development of palate
Primary palate
o Formed by intermaxillary segment
Secondary palate
o Formed by palatine shelves of maxillary bones
Palatine shelves
• Two shelf like outgrowths
• Forms main part of palate
• At 6th week directed obliquely by sides of the tongue
• Later ascends and fuse with each other and nasal septum
• Anteriorly fuse with primary palate
• Incisive foramen is the landmark between primary and secondary palates
Clinical
1.Facial clefts
• Two types- anterior and posterior cleft deformities
• Incisive foramen is the landmark
Anterior Posterior
Lateral cleft lip Secondary cleft lip
Cleft uvula
Cleft upper jaw
Nasal cavities
• 6th week – nasal pits deepen
• Oronasal membrane which separates it from nasal cavity disappears
• Primitive choanae formed
• Secondary palate develops
• Definitive choanae formed
MCQ
1. In the development of the face
A. Mandibular process is derived from the second pharyngeal arch
B. Maxillary process is developed from the first pharyngeal arch
C. Nasolacrimal canal develops along the line of fusion of the frontonasal and
maxillary processes
D. Part of the upper jaw bearing the incisor teeth develops from the frontonasal
process
E. Forehead is formed from the maxillary processes
2. Regarding the pharyngeal and branchial arches
A. Cartilage of the first arch is called Reichet’s cartilage
B. Mesoderm of the 2nd arch gives rise to muscle supplied by the maxillary
division of the third cranial nerve
C. Palatine tonsils are derived from the endoderm of the second pharyngeal
pouch
D. Branchial cyst form the persistence of the epicardial ridge
E. Only blood vessels remaining from the 5th aortic arch on the right side is the
proximal part of the subclavian artery
3. In the development of the pharyngeal arches
A. Nerve of the 4th arch is the superior laryngeal
B. External acoustic meatus is derived from the 2nd pharyngeal cleft
C. Sphenomandibular ligament is a remnant of the 2nd pharyngeal arch cartilage
D. Greater and lesser horns of the hyoid bone have the same origin
E. Larynx is derived from cartilage of the 4th and 6th arches
4. First pharyngeal arch
A. Gives rise to the malleus and the incus
B. Is innervated by the trigeminal nerve
C. Gives rise to the palatine tonsil
D. Gives rise to the muscles of facial expressions
E. Gives rise to the external auditory meatus
Answers
1-FTFTF
2-FFTFF
3-TFFFT
4-TTFFT
5-FFFTT
Central nervous system appears at the beginning of the 3rd week as neural placodes.
Lateral edges elevate and form neural folds
Neural folds fuse forming neural tube
Closure of cranial neuropore 25th day
Closure of caudal neuropore 28th day
Clinicals
Ossification defects in bones of skull
Hormonal communication
▪ Hormones behave very similar to enzymes, they have some features in common
Enzymes Hormones
Similarities Body catalysts Body catalysts
Only small quantities needed Only small quantities needed
for action for action
Not used up during reaction Not used up during reaction
Differences Synthesised in cells Synthesised in an organ
themselves. different from their site of
action transport via blood
Always proteins Always not proteins. Can be
steroid/ eicosanoids
Free T4 (fT4) and free T3 (fT3) → methodological problems if binding proteins grossly altered (plasma
total T3 and T4 affected by binding proteins)
TSH - increased in hypothyroidism.
TRH test - TSH measured before and after IV administration of TRH
Thyroid antibodies - Thyroperoxidase antibodies, thyroglobulin antibodies Thyroid imaging
Uptake tests
cellular
response
degradation
of hormone
↓
The binding of the G protein to the receptor causes the replacement of GDP by GTP
↓
α subunit dissociate from the others.
↓
α subunit bind to adenylate cyclase
↓
Activation of adenylate cyclase
↓
ATP is converted to cAMP→ cAMP activates protein kinases (phosphorylation)
↓
Inherent GTPase activity in the α subunit
↓
GTP hydrolyzes to GDP
↓
α subunit re-associate with the other two subunits
Ex:
• β adrenergic receptors Epinephrine
Norepinephrine
• Glucagon
• TSH, FSH, LH, ACTH
• PTH
• ADH
• Calcitonin
Transduction via phosphodiesterase Gi (inhibition)
Eg: - Angiotensin
↓
GTP hydrolyzes to GDP
↓
α subunit dissociate from the others.
↓
α subunit bind to phospholipase C
↓
Activation of phospholipase C
↓
Phosphatidylinositol bisphosphate hydrolyze into Diacylglycerol (DAG) and inositol triphosphate
(IP3)
↓
IP3 release stored Ca+2 from ER
DAG opens Ca+2 ion channels and increase Ca+2 influx (via protein kinase C)
↓
Increased Ca+2 levels inside the cell
↓
Calmodulin binds with Ca+2
↓
Activate PKs
↓
Activation of enzymes
Importance
Transporters of glucose
Occurs in cytosol - Glucose is polar – can’t cross membranes – need transporters (tissue specific)
1. Passive transporters (Na+ and ATP independent uniporter - Facilitated diffusion) - along conc. gradient
GLUT transporters – exist in 2 conformation states
ATP
production
1. Phosphorylation of glucose (commits glucose for further metabolism in the cell, by trapping
glucose)
Phosphorylated glucose molecules don’t penetrate cell membranes as they don’t have specific
membrane transporters.
They are too polar and can’t cross the cell membrane.
Hexokinase/glucokinase
Glucose Glucose - 6-P
-
ATP (adequate energy)
Citrate (TCA cycle saturated)
PFK 2
F-6-P F-2,6- BP
FBP 2
Adenylate
cyclase
Glucagon cAMP Active protein kinase A phosphorylates the bifunctional enzyme
Pyruvate kinase
PEP Pyruvate
+ Feed forward regulation
F-1,6-BP
When blood glucose level is low, HEPATIC pyruvate kinase is phosphorylated (via cAMP) and thereby
inactivated inhibiting glycolysis and driving gluconeogenesis.
Pyruvate
Aerobic Anaerobic
CO2 /H2O/ATP/
NADH/FADH
• Under anerobic conditions , pyruvate is converted to lactate and NADH produced during glycolysis is
oxidized to NAD+ .
• So glycolysis provide ATP even in the absence of oxygen and allow the tissues to survive in anoxic
conditions.
Lactic Acidosis
Causes:
1. Low O2 concentration as a result of collapse of circulatory system due to
• MI
• Pulmonary embolism
• Severe haemorrhage
• Shock
Lactate in muscle
RBCs entirely depend on glycolysis for ATP production as they lack mitochondria. In the deficiency of
the enzyme ATP production by glycolysis is reduced. Premature lysis of RBCs occurs due to inability of
maintaining ion pumps in the cell membrane. Hemolytic anemia results. (prickle cells, jaundice and
splenomegaly)
Action of Arsenate
Conversion of Glyceraldehyde-3-P to 1,3-BPG catalyzed by glyceraldehyde-3-P dehydrogenase is the first
oxidation reduction reaction in glycolysis. It produces 2 NADH per glucose molecule. Arsenate (a
structural analog of phosphate) does not inhibit the pathway but can prevent the net ATP and NADH
production by competing with phosphate for Glyceraldehyde-3-P dehydrogenase forming a complex that
spontaneously hydrolyzes to 3PG without forming NADH.
Fluoride ions in the presence of phosphite ions inhibit the glycolysis enzyme Enolase by forming a
fluorophosphate complex with Mg which is the co-factor of the enzyme.
Role of 2,3-BPG in RBCs made from 1,3-bisphosphoglycerate in response to chronic hypoxia. (high
altitudes, chronic hypoxia in COPD/ emphysema etc.) Binds with beta chain of hemoglobin and reduces
its affinity for oxygen. More oxygen is released in the tissues.
Isomers
Same chemical formula but structures differ ( eg: C6H12O6 )
Epimers
Isomers that differ at only ONE carbon (eg: Glucose and Galactose – C4 epimers)
Aldehyde
Group( aldose)
Glycosidic Bonds
Eg: lactose formed by C1 of β- galactose and C4 (OH) of glucose. Bond is β (1→4) glycosidic bond
Fructose Metabolism
Fructokinase Aldolase B
Fructose Fructose-1-P Glyceraldehyde
DHAP
• Fructose metabolism is very rapid because it bypasses the major rate limiting step in
glycolysis.
UDP Galactose
4 Epimerase
Galactosemia
• Genetic defect causing inability to metabolize galactose.
• Caused by deficiency in Galactokinase or GALT.
• This leads to accumulation of Galactose and Galactose-1-P.
• The accumulated galactose is shunted to produce Galactitol.
• Irreversible reaction, which occurs in mitochondrial matrix. (but not a part of TCA cycle)
• Pyruvate needs to enter the mitochondrial matrix, so a specific transporter helps
to cross the inner mitochondrial membrane -H+ symport by pyruvate translocase
(H+/Pyruvate Symporter).
• Needs aerobic conditions (O2) - (to regenerate NAD+ and FAD+ via ETC)
• Catalyzes by Pyruvate Dehydrogenase enzyme (PDH), which is a multi-enzyme complex
(multiple copies of three enzymes) in the mitochondrial matrix
Decarboxylation
cAMP insensitive.
Dehydrogenation
• PDH requires 5 co-enzymes Trans acetylation
➢ CoA (vitamin B5) PHD kinase and
➢ NAD (vitamin B3) PDH phosphatase
➢ Lipoic acid
➢ FAD (vitamin B2)
➢ TPP (vitamin B1)
(mnemonic – CFL Nethi Torch)
CoA CO2
1. Covalent Modification
• Acetyl CoA
• NADH
Impaired activity of PDH Accumulation of Pyruvate Excessive lactate production Lactic Acidosis
Treatment - give a Ketogenic diet (rich in lipids and low in carbohydrates)
ATP ADP
LCFACoA
Succinyl CoA
• Formation of citrate from acetyl CoA and oxaloacetate is thermodynamically favourable
exergonic and favours the products.
• Therefore it is the committed step and likely to be controlled.
Isocitrate DH
Isocitrate α ketoglutarate +NADH +CO2
- +
ATP ADP
NADH Ca2+
3 2018 A/L Batch Repeat Campaign
PDH and αKGDH
• Structurally similar
➢ 3 distinct enzymes are identical (αKGDH, Transsucinylase, dihydrolipoyl dehydrogenase)
➢ Coenzymes are similar
➢ αKGDH is not subjected to regulation by phosphorylation & dephosphorylation.
• αKGDH is inhibited by
a) Succynyl CoA
b) NADH
c) ATP, GTP (high energy)
d) Arsenite
• Activated by
a) Ca2+
Succinate dehydrogenase
• Embedded in inner Mitochondrial membrane (complex II in ETC)
• Inhibited by OAA, Malonate
• Reducing power of Succinate Dehydrogenase is not sufficient to reduce NAD+.
Aconitase
• Inhibited by Fluoro-acetate (use as pesticide)
• Citrate Isocitrate
Malate Dehydrogenase
• Endergonic reaction.
• But driven by the highly exergonic Citrate synthase reaction.
• NADH formation
Isocitrate DH
Isocitrate αKG
NAD+ NADH + H+
α KGDH
αKG Succinyl CoA
NAD + NADH + H+
NAD+ NADH + H+
succinate thiokinase
Succinyl CoA succinate
GDP GTP
• FADH2 formation
Succinate DH
Succinate Fumarate
FAD+ FADH2
Summary of production,
Refilling is
needed for
continuity.
Advantages
➢ Than glucose,
➢ Insoluble
➢ low osmotic activity
➢ no influx of water into cell
➢ Than Fats,
➢ Can provide energy under anaerobic conditions by glycolysis
(FAs can’t net produce glucose) ?
➢ Formation of glu-1-PO43- no ATP is needed to channel glucose into glycolysis
Importance
Liver glycogen : - Maintain blood glucose level between meals- lasts 24h in fasting
Glucose activation
GLUCOSE -6-P < PHOSPHOGLUCOMUTASE Glucose-1-P
UDP-Glucose pyrophosphorylase
Glucose-1-P + UTP UDP-Glucose + PPi (Pyrophosphate)
(Activated form)
PPi + H2O 2Pi
➢ Therefore, all reactions producing PPi are shifted to right & almost irreversible
Glycogenesis requires formation of (UDP- Glucose)
Initiation of glycogen synthesis
Chain elongation
Glycogen synthase
(Glycogen)n + UDP-Glucose (Glycogen)n+1 +UDP
• Glucose is added to non-reducing ends. → α-1-4-glycosidic bonds
• Branching enzyme cuts a string of glycogen (8-10 glycosyl units) from the growing end and
grafts onto the 6th C atom of a non-terminal glucosyl residue in the chain. →α-1-6-glycosidic
bonds
• Further elongation by glycogen synthase.
Phosphoglucomutase Brain
Glucose-1-P Glucose-6-P Glycolysis directly
Liver
Muscle Use to HMP pathway
Glucose 6-phosphatase s
Allosteric
Two types
Covalent Hormonal
(phosp
Hormonal regulation
(Phosphorylation /dephosphorylating)
• Synthesis increases in:
Glucose – 6- P
• Degradative Pathway
Liver
ATP
G–6–P Glycogen phosphorylase
Glucose b
6
(Inactive) 2018 A/L Batch Repeat Campaign
LIVER MUSCLE
Glycogen acts as a glucose reserve. Glycogen acts as an energy reserve.
Maintains blood glucose level – buffers glucose Provide ATP for muscle action.
End product is glucose. End product is Glucose-6-phosphate.
Glucose-6-phosphatase enzyme is present. Glucose-6-phosphatase enzyme is absent.
Hormonally regulated by glucagon, insulin, Insulin, epinephrine. (no glucagon influences.)
epinephrine.
Receptors: insulin, glucagon, adrenergic (α,β) Insulin, β adrenergic.
2nd messengers: 2nd messengers:
cAMP, Ca2+, IP3, DAG cAMP, Ca2+
Ca2+ released from SER due to epinephrine via α1 Ca2+ released from SER during muscle
receptors activates phosphorylase kinase contraction activates phosphorylase kinase
without phosphorylation (partially without phosphorylation (partially
active)→activates glycogen phosphorylase active)→activates glycogen phosphorylase
AMP has no role in regulating glycogen AMP directly activates glycogen phosphorylase
phosphorylase without phosphorylation.
Glucose allosterically inhibits glycogen Glucose has no action in regulation of glycogen
phosphorylase. phosphorylase.
Glycogen stores: Glycogen stores:
Increased- during well-fed state. Increased- during resting state
Depleted- during fasting. Depleted-during muscle contraction.
FFA
Translocation Steps
Outer Membrane
Inner Membrane
• to 3–Ketoacyl CoA
• by L-3-hydroxyacyl CoA dehydrogenase
to produce Acetyl–CoA
Questions to discuss
– Isomerization
– Reduction
– In final round of degradation the products are acetyl CoA and propionyl CoA
– In peroxisomes
• Very long chain fatty acids (VLCFA) are degraded only in peroxisomes
• ß oxidation in peroxisomes shortens the side chains of cholesterol in bile acid synthesis
• Peroxisomes contain several oxidases in the process forming hydrogen peroxide (H2O2), which is then
degraded by catalase. Oxidation of fatty acids by peroxisomes
• First fatty acids must be transported into the peroxisome from cytosol
• Peroxisomal β oxidation is a slightly modified form than in the mitochondria and generates
acetyl-CoA and H2O2
• Initial step is catalyzed by flavoprotein linked dehydrogenase
• ß oxidation in peroxisomes ends at octanoyl-CoA
• Octanol and acetyl groups are then transported to mitochondria and further oxidized in
mitochondria (via TCA)
• The acetyl group are also transported into the cytosol for synthesis of cholesterol and other
metabolites
– Beta oxidation of fatty acyl CoA to acetyl CoA and subsequent oxidation of acetyl CoA in the TCA
cycle, move via the ETC to O2, coupled to ATP synthesis
Questions to discuss
Impaired oxidation of fatty acids give rise to diseases often associated with hypoglycemia.
– Mitochondrial acetyl-CoA produced by; oxidation of pyruvate, degradation of FA, KB & certain AA
– In the cytosol it is cleaved back to cytosolic OAA & acetyl-CoA by ATP-citrate lyase
Since synthesis occurs in cytosol acetyl CoA must be transported from mitochondria
– carried by citrate
• needs biotin
Mammalian FAS is a homodimer with each chain containing three domains joined by flexible regions
• 8 molecules
• 6 molecules
Control of ACC,
• Insulin activates
• Glucagon and epinephrine inactivate
Eg:-
o Acetoacetate
o ß hydroxybutrate
o Acetone (volatile)
Steps
• Two molecules of Acetyl CoA, catalyzed by Thiolase,
condense to form acetoacetyl CoA
• Acetoacetyl-CoA combines with another molecule of acetyl-
CoA, catalyzed by rate determining enzyme HMG CoA Synthase,
to produce HMG CoA.
• HMG CoA lyase subsequently breaks down HMG CoA into
acetoacetate and acetyl CoA.
• Acetoacetate can then be reduced to β hydroxybutrate or
undergo spontaneous decarboxylation to form acetone.
• Soluble in water
• Can be used in brain
• ………………..
• ………………..
• ………………..
Protein turnover
Body Proteins
(400g)
Synthesis of
Dietary Proteins
non-essential
A.A (Varies) (100g)
AA
Pool
(100g)
Catabolism Synthesis of other
of A.A N containing
(Varies 14%) compounds (30g)
Body proteins
(400g)
Clinical
Redistribution HB level
Dietary AA pool Degradation
to meet Reduce
Protein of HB
reduce essential resulting
Reduce
needs anaemia
Degradation of Proteins
Protein Degradation
Cytosol Lysosome
• Selectively degrade • Non selectively degrade
• Proteins tagged with ubiquitin • Using acid hydrolases
• Recognized by proteasome • Extracellular, membrane associated,
• It unfolds, deubiquinate and cut the glycoproteins and long lived
protein into AA by proteases intracellular proteins are degraded.
• Degradation of regulatory proteins with
short half-life or misfolded proteins.
• Target intracellular proteins
1) Ubiquitination
2) Oxidation of amino acid residues
3) PEST sequence
4) N terminal amino acid residues
1) Ubiquitination
➢ Ubiquitin is recycled.
2) Oxidation of amino acid residues
3) PEST sequence
➢ Repeated sequence of P E S T
➢ Pro, Glu, Ser, Thr, are known as pest sequences
➢ Usually half-life less than 2 hours
➢ Target proteins for rapid degradation.
➢ Hydrolyze by ubiquitin-proteasome system
➢ Proteins with and amino terminal of Phe, Leu, Tyr, Trp, Lys, Arg
➢ Have short metabolic half life
Nitrogen balance
States of balance
3. Negative N Balance
➢ Intake < output (loss)
➢ Starvation / Fasting
➢ Trauma (protein malnutrition, diet low in essential amino acids)
➢ Wasting
➢ Poorly controlled diabetes - because amino acids degraded to gluconeogenesis.
Transamination
❖ Thr & Lys do NOT take part in transamination reactions. They lose their alpha amino group by
deamination.
❖ Proline and hydroxyl proline also doesn’t take part
❖ Vit. B6 requirements increase with protein intake
Pyruvate glutamate
ALT
Alanine α KG
OAA glutamate
AST
Asp α KG
➢ ALT & AST Important in diagnosis of liver and heart damage, because they are normally
intracellular enzymes.
Oxidative Deamination
NAD(P)+ NAD(P)H + H+
Glu α KG
GDH NH4 +
NAD(P)+ NAD(P)H + H+
Glu α KG
(+) Glutamate Dehydrogenase
Some AAs (-) NH4+
(+) (-) (-)
LOW
Energy GTP High ATP NADH
High Energy
( ADP , NAD+)
Urea
Urea
cycle
(Transaminati (Oxidative
deamination)
❖ α Keto acids are metabolized and can be used to replenish the TCA cycle.
AMP deamination
Adenosine is a
coronary vasodilator.
Production of Ammonia
Toxicity of NH3
1) Depletion of α KG
Glutaminase Glutamate
Glutamine isozyme
Glutamate
NH3
GABA
• +
NH4 inhibits Glutaminase
• Therefore [glutamate]↓ [Glutamine]↑
• Glutamate is an excitatory neurotransmitter
• Low neurotransmitter levels synaptic transmission impaired
• Glutamate is required for GABA synthesis
• Glutamine is osmotically active.
• Accumulation leads to brain oedema. (brain swelling and cell death)
NH4+ NH3 + H+
Transport of NH3
Glutamine
ATP ADP
Glutamate Glutamine
Glutamine Synthatase
NH3
H2O
• Glutamine serves as a fuel for gut, kidney and cells of immune system.
• It removes ammonia in brain by producing glutamine.
Formation of Alanine by the transmission of pyruvate produced from aerobic glycolysis etc. (in
skeletal muscles)
• Irreversible.
• 1st two reactions occur in mitochondria and others in cytosol.
• Occurs in liver and transported to the kidney.
• 3 ATP used (needs energy)
• 1st N from ammonia and 2nd N from Aspatrtate. (Asp is an immediate precursor of Glutamate)
• C from CO2 / HCO3-
• Arginase is present only in liver.
• Dietary ornithine is requiring for continued activity of urea cycle but not dietary aspartate
• Act as both ammonium and bicarbonate disposal.
• From all the excretion products 80% is disposed as urea.
• Urea diffuses from liver transport to kidney and excreted in urine.
• Portion of urea diffuse from blood to intestine.
Bacteria Urase
Urea CO2 + NH3
Bridge between
gluconeogenesis
TCA
cycle
Malate
OAA
Glucose
Skeletal muscle
• Uptake of amino acids for protein synthesis
• Major site for amino acid pool
• Release of amino acids during starvation mainly alanine
and glutamine (During starvation,
• Acetyl Co A↑ from FA oxidation → Inhibit PDH → ↑ Pyruvate → Alanine (from
Transamination)
Kidney
• Major site of production of Ser
• Uptake of Gln NH4+ production for acid base regulation
• Also produce the Ala.
Brain
• Uptake of Branched Chain Amino Acids (Val, Leu, Ile)
• Val as an energy source
MS MTHFR
(-) Cystathionine
Vitamin B6
CGL
Cysteine
❖ Deficiency of vitamins required for the conversion to methionine (Vit. B12, Folate)
➢ hyperhomocystenemia (increased level of total HC in urine and plasma.)
➢ homocystenemia
❖ Metabolism of Homocysteine involve Folate, Vit B12, Vit B6 and Riboflavin (B2).
Alkaptonuria
Homogentisic oxidase
Homogentisic acid Maleyactoacetic acid
Phenylketonuria
Phenyl acetate
Phenyl pyruvate
Phenyl lactate
Tetra-hydrobiopterine
Phenylalanin
Dihydropteridine e
Reductase Phenylalanine hydroxylase
Tissue proteins Melanin
Tyrosine
Catecholamine
Fumarate Acetoacetate
Di-hydrobiopterine
• Autosomal recessive
• Deficiency of phenylalanine hydroxylase & dihydropteridine reductase.
• Accumulation of phenylalanine
• Deficiency of tyrosine
• ↑[Phe] tissues, plasma, urine
• ↑Phenyl lactate, Phenyl acetate, Phenyl pyruvate
• Cause;
➢ mental retardation
➢ Failure to talk and walk
➢ Seizers hyperactivity tremor
➢ Microcephaly
➢ Hypopigmentation because high [Phe] competitively inhibit hydroxylation of Tryosine by
tryosinase.
• Treatment- low [Phe] diet. Supply Tyr in diet.
Purines
1) De Novo Synthesis - base can’t be synthesised separately always built upon a PRPP
2) Salvage Pathway
3) Catabolism - no breakage in purine ring just a conversion
Pyrimidine
1) De Novo Synthesis - primary base (orotate) is synthesised separately & attach to a
PRPP
2) Salvage pathway
3) Catabolism- ring is broken
PURINE METABOLISM
➢ Adenine, Guanine
• Double ringed structures
• Cannot be opened in human cell
• Purine ring primarily constructed in liver
1) De Novo Synthesis
➢ Energy consuming
process Which
requires;
• Aspartate
• Glycine (only for the
purine synthesis)
• Glutamine
• N10 Formyl - THF
• CO2
APRT
Adenine + PRPP AMP + PPi
HGPRT
Guanine + PRPP GMP + PPi
HGPRT
Hypoxanthine + PRPP IMP + PPi
HGPRT Deficiency
• Xanthine is the point of convergence for the catabolism of purine bases, & it’s
converted to Uric acid by Xanthine Oxidase.
Nucleotide → Nucleoside → Base → Xanthene → Uric acid
AMP Deaminase
AMP IMP XMP GMP
5’nucleotidase
NH3
Adenosine Inosine Xanthosine Guanosine
Adenosine
Deaminase
Hypoxanthine Guanine
Xanthine oxidase
Xanthine
Xanthine oxidase
[-]
[-]
further modification
Allopurinol
[Purine analog] Uric acid urine
Doesn’t occur in primates
including humans.
Hyperuricemia
PRPP amidotransferase
PRPP Phosphoribosyl amine
Glutamine Glutamate
These two are glutamine antagonists
Mercaptopurine The reaction cannot go ahead without glutamine
Azaserine (diazo acetyl – L – serine) So purine synthesis is blocked at PRPP.
PRPP accumulates
R, subunit contains
➢ Active sites
➢ Substrate specific sites
➢ SH groups from cysteine.
❖ Precursors,
• HCO3-
• Aspartate Amino acids
• Glutamate
❖ Thymine, Cytosine
De Novo Synthesis
CAD
Carbamoyl Phosphate (multi-
+ ATP functional
Aspartate Aspartate Transcarbomoylase Polypeptide)
- CTP
Carbamoyl aspartate
Prokaryotic cells
Dihydroorotase
Dihydroorotate
Orotate
Orotate
PRPP
Orotate phosphoribosyl transferase
irreversible
2Pi PPi OMP
H2O
OMP decarboxylase ← - UMP, CMP (competitive
CO2 Inhibitors)
UDP dUDP
Ribonucleotide reductase
UTP
dUMP
CTP Synthase
(add amino group from glutamine)
CTP
Methylene H4 folate
[Permanently
bind to enzyme]
[-] 5-FdUMP
Thymidylate
Tetrahydrofolate
synthase
Fluoro deoxy
[-] Methotrexate
uridine mono
Dihydrofolate phosphate
NADPH + H+ reductase
Dihydrofolate
dTMP
NADP+
5 florouracil
[Thymine analogue
- suicide inhibitor]
2) Salvage of pyrimidines
• Few are salvaged in humans
• Pyrimidine nucleosides nucleoside kinases (user ATP)
• Basis for using uridine/cytidine for treatment of orotic aciduria
Orotic aciduria
• Absence of orotate phosphoribosyl transferase or OMP decarboxylase or both
• Retarded growth, anaemia(megaloblastic)
• Can also occur due to Ornithine transcarbomylase deficiency
• Give uridine, cystidine as treatment
• Then they Converted to UTP, CTP by salvage pathway & inhibit pyrimidine synthesis
process
OTC
Ornithine Citrulline
Carbamoyl phosphate
HMP pathway
3) Pyrimidine Catabolism
• Easily opened and degraded to soluble liver β -alanine and β -amino isobutyrate
Cytosine Thymine
NADP+
β-Alanine
Glucogenic substrates
• Lactate: The Cori cycle- from exercising skeletal muscle, mitochondria less cells (RBC)
• Amino acids: Except leucine & lysine (which are ketogenic) all other A.A are glucogenic.
Eg: glucose- alanine cycle
Alanine, Glutamine are the major sources of Glucose during fasting
Amino Acid α KG OAA
• Glycerol: glucagon activates HS lipase hydrolyses TAG in Adipocytes→ glycerol & Fatty acids
Glycerol → transports to liver → forms DHAP (glycerol Kinase is not present in
adipocytes)glycerol --GK---------glycerol 3 p-G-3p dehydrogenase----------DHAP
Fatty Acid → Acetyl Co A → no net production of glucose (not glucogenic)
Odd chain F.A → propionyl Co A → glucogenic
Glycolysis Gluconeogenesis
Hexokinase Glucose 6 Phosphatase
PFK1 FBP 1
Pyruvate Kinase Pyruvate Carboxylase and PEP Carboxykinase
Sources of pyruvate
Regulation of gluconeogenesis
OAA cannot cross the mitochondrial membrane. It’s done via following shuttles.
OAA PEP
GTP GDP
F6P
+F26BP -F26BP
+AMP -AMP
PFK1 F1,6BPase
-ATP +ATP
-Citrate +Citrate
-H+
F1,6BP
Dephosphorylation of G6P
G6P Glucose
G6Pase
2) Energy state
↑ATP / AMP
PK inhibited. PEP guided to form glucose
PFK 1 is inhibited
F 1,6 Bisphosphates activated
↓ATP/AMP
PK activated
PFK 1 activated Gluconeogenesis Inhibited
F-1,6- bisphosphates inhibited
↑ADP
Pyruvate Carboxylase and PEP Carboxykinase inhibited
3) Allosteric regulation
Acetyl CoA activates PC
AMP & F-2,6 BP inhibit fructose-1,6-bisphosphatase
Citrate & ATP activates Fructose 1,6 Bisphosphates
4) Covalent Modification
• Allosteric regulation
Lowers F2,6BP level so activates F1,6BP and inhibits PFK
• Covalent modification
Elevation of Cyclic AMP increase cyclic AMP dependent PK activity
PK phosphorylated PK is inactivated
Alcohol DH AldehydeDH
CH3CH2OH CH3CHO CH3COONAD+
• Pyruvate & OAA and DHAP for gluconeogenesis decrease & hence the rate of GNG decreases
• which leads to (Fasting) Hypoglycemia & (Hyperuricemia)
• NADH accumulates. Prevents Lactate Pyruvate. (Lactic acidosis.) Uric acid excretion ↓
Alcohol DH
CH3CH2OH CH3CHO
MEOS
Food is digested –end product [Monosaccharides, Amino acid, lipid is packed in to CM]
Send to tissues to be use as energy or storage as glycogen (mainly liver and Skel muscles)
• Facilitated diffusion via GLUT 2 ( very active when blood glucose concentration is high)
• Glucose movement can occur both way
• GLUT 2 HAS LOW AFFINITY , HIGH Km
• Gradient is maintained by rapid phosphorylating glucose by GK
GK
Glucose ---------------------------------------→Glucose 6 p
GK →1 maintain low intracellular glucose concentration (favoring its facilitated diffusion into the cell)
2 Cannot diffuse out of the cell (glucose 6 P negatively charge & no transporter for phosphorylated
sugar in plasma membrane.
GK
GK has high Km, low affinity.[ Km for glucose is higher than value of fasting blood glucose]
Therefore glucose is produced through gluconeogenesis and glycogenolysis. Release glucose maintains
blood glucose level.
• In living systems numerous metabolic pathways are operating simultaneously, and also they are
connected with each other.
• So, each pathway needs to be able to “sense” the status of the other pathways.
• Metabolism attempts to fulfill 3 needs of the organism,
➢ ATP
➢ Reducing power (NADPH, NADH)
➢ Building blocks for biosynthesis
➢ Glucagon plays a role in lipolysis in adipose tissue but the major activators of HSL, are the
Catecholamines.
➢ Both Insulin & Glucagon affects the gene transcription of related enzymes.
❖ Metabolic Pathways
➢ Glycolysis ➢ Gluconeogenesis
➢ Glycogen Synthesis ➢ Glycogen Breakdown
➢ FA & Cholesterol synthesis ➢ FA β oxidation
➢ TCA Cycle ➢ HM Pathway
➢ Urea Cycle ➢ AA metabolism
❖ Major Intermediates
1) Pyruvate
NAG
synthesis
(Urea cycle)
AA
(degradat TCA Cycle
ion)
KB FA
(ketolysis) synthesis
Acetyl
CoA
FA (beta KB
oxidatio) synthesis
Pyruvate Cholesterol
(PDH) synthesis
Aerobic
Glycolysis
Ethanol
Oxidation
ETC
NADH
Beta
Oxidation
Pyruvate
to lactate
PDH
Reaction TCA Cycle
3 © 2018 A/L Repeat Campaign
Regulation Of Metabolic Pathways
Compartmentalization
• Metabolic fate of certain molecules depends on their location, which is regulated by location of
their relevant transporters & enzymes.
• Portal blood is rich in absorbed nutrients and insulin secreted from pancreas.
➢ Carbohydrate
G6P ↑
G6PD Activated
↑ HMP Pathway
NADP/NADPH ↓
LCFA ↑
Glucose 6
phosphate ↑
↑ Glycolysis FA Synthesis
FAT
a) Increased FA synthesis
↑ HMP ↑ NADPH
b) Increased TAG synthesis
➢ Metabolism of all amino acids except Branched Chain Amino Acids (Val, Leu, Ile)
➢ Liver AA catabolizing enzymes with high Km
➢ Therefore, only excess AA are catabolized
➢ Liver t-RNA charging enzymes low Km
➢ Ensures metabolism of AA for hepatic protein synthesis
a) ↑ Protein synthesis
• Only a transient increase in synthesis of hepatic proteins resulting in replacement of any
proteins that may have been degraded during fasting period.
b) ↑ AA degradation(excess)
• More AAs are present than the amount that the liver can use in the synthesis of proteins
• Excess is not stored but either released to blood or deaminated.
• Resulting C skeletons
Carbohydrate
Fat
Carbohydrate
➢ Skeletal muscle is unique in being able to respond to substantial changes in the demand for
ATP that accompanies muscle contraction.
➢ ↑ glucose uptake by GLUT 4
➢ ↑ Glycolysis - to provide energy needs.
➢ ↑ Glycogen synthesis (Particularly if glycogen stores have been depleted as a result of
exercise.)
Lipids
➢ ↑ Protein synthesis
➢ ↑ uptake of branched chain AAs (principle site for degradation of the BCAA)
Brain
Carbohydrate
➢ Brain uses glucose exclusively as a fuel (GLUT 1)-astrocytes and endothelium of BBB), GLUT3-
neuron cells
➢ No significant stores of glycogen.
➢ Therefore, completely dependent on the availability of blood glucose.
Lipids
Intestines
• Two priorities: -
1. Need to maintain adequate plasma levels of glucose to sustain energy by metabolism of
brain, RBC & other glucose requiring tissues.
2. Need to mobilize FAs from adipose tissue & the synthesis & releasing of ketone bodies from
the liver to supply energy to all other tissues.
❖ FASTING STATES
1. Post absorptive-hepatic glycogen (4-16 h) is main energy source
Gluconeogenesis beginning, Cori and glucose alanine cycle become important
Carbohydrate
• ↑ glycogen degradation
➢ Glycogen phosphorylase - activated
(↑ Glucagon and epinephrine levels→ phosphorylates glycogen phosphorylase)
➢ Glycogen is nearly exhausted after 10-18 hours of fasting
➢ Hepatic glycogenosis is a transient response to early fasting
• ↑ gluconeogenesis
➢ Substrate
✓ Proteins → Gluconeogenic AA
✓ TAG → Glycerol
✓ Muscle → Lactate
a) ↑ FA oxidation
❖ Liver cannot utilize ketone bodies - liver lacks thiophorase, an enzyme needed for its
degradation.
Adipose tissue
Carbohydrate
Lipids
Carbohydrate
➢ ↓ Uptake
Lipids
Proteins
➢ During the first few days, there is some breakdown of protein → AAs → gluconeogenesis
• Mostly Alanine & Glutamine
• Catabolism of branched chain AAs
➢ By several weeks’ rate of proteolysis decreases
➢ After several weeks of starvation, when ketone bodies also reduce, proteolysis begins
Carbohydrate
Kidney
✓ Renal medulla is mainly glucose utilization.
✓ Renal cortex is responsible for gluconeogenesis.
✓ RENAL GLUCONEOGENESIS IS MORE SENSITIVE TO CATECHOAMINES WHEREAS GLUCOGON
HAS LITTLE TO NO EFFECT
Carbohydrate-Late fasting 50% of gluconeogenesis occurs in kidney
Compensate for acidosis resulting from increased production of ketone bodies.
Glutaminase
& GDH
BCAA breakdown (Muscle) → Glutamine α-KG + NH3
Diabetes Mellitus
❖ 2 types: -
1) Type 1 diabetes
2) Type 2 diabetes
1. Hyperglycaemia
Hyperglycaemia
Accelerated hepatic
gluconeogenesis using amino acids
obtained from peripheral tissues
2. Hypertriacylglycerolemia
Insulin resistance
➢ Decreased ability of the target tissues (liver, adipose and muscles) to respond to
normal circulating concentrations of insulin.
➢ Caused by weight gain and obesity.
➢ Insulin resistance itself does not cause type 2 DM. Initially with insulin resistance,
insulin secretion by β cells increase causing hyperinsulinemia.
➢ However, with time β cells dysfunction and insulin secretion decreases leading to type
2 DM.
1. Hyperglycaemia
Hyperglycaemia
Accelerated hepatic
gluconeogenesis using amino acids
obtained from peripheral tissues
• chemical substances
• relay, amplify and modulate signals
• between neuron and another cell
Transmitters in brain – more than 50 types – amino acids, amines, peptides and some gases
Transmitters in PNS – Ach and nor-adrenaline
1. Amino acids or amino acid derivatives (glutamic acid, aspartic acid, glycine, GABA) 2.
2. Monoamines (dopamine, norepinephrine, serotonin)
3. Acetylcholine
4. peptides (neuropeptides)
5. nitric oxide (NO)
Glutamate
• inhibitory neurotransmitter
• by causing neuronal membrane hyperpolarization
• (alter transmembrane potential difference)
• binds the post-synaptic GABA receptor complexes.
• formed by decarboxylation of L-glutamate,
o catalyzed by L-glutamate decarboxylase
o pyridoxal phosphate (vitamin B6) as the coenzyme.
Tyrosine
(Rate limiting step)
Tyrosine hydroxylase*
DOPA - Dihydroxyphenylalanine
DOPA
Noradrenaline Catecolamines
Adrenaline
• inactivated by
o oxidative deamination catalyzed by monoamine oxidase (MAO)
o O-methylation catalyzed by catechol-O-methyl transferase (COMT).
• products excreted in urine as
o vanillylmandelic acid (VMA) from epinephrine and norepinephrine
o homovanillic acid (HVA) from dopamine.
Epinephrine Nor-epinephrine
MAO Dopamine
MAO COMT
MAO
COMT Dihydroxymandelic acid COMT
Dihydroxyphenylacetic 3-methoxytyramine
metanephrine COMT acid
Nor -metanephrine
COMT MAO
MAO MAO
vanillylmandelic acid Homovanillic
acid
Cllinical applications
Phaeochromocytoma – VMA in urine and epinephrine and/or norepinephrine in plasma increased –
for diagnosis of Phaeochromocytoma (cancer in adreal medulla)
Parkinson disease – neurodegenerative disorder – insufficient dopamine
but treatment cannot use dopamine for transmission – don’t cross BBB – L-DOPA instead
MOA inhibitors – inhibit catecholamine degradation – accumulation of epinephrine in synapses –
improve neurotransmission – antidepressant action
Acetylcholine
• acts at
o neuromuscular junctions
o synapses in the ganglia of the visceral motor system
o different sites in the central nervous system.
• synthesised from choline and acetyl CoA
o catalysed by choline acetyltransferase.
▪ Found predominantly in RBC and nervous tissue
o Acetyl - derived from pyruvate generated by glycolysis
o choline - transported into the terminals via a Na+ -dependent transporter.
• After released into the synapse, ACh rapidly metabolized by acetylcholinesterase
o choline is transported back to the nerve terminal.
o Ach esterase concentrated in the synaptic cleft
ensure rapid decrease in acetyl choline
concentration in the synaptic cleft.
Organophosphates –
o inhibit Ach esterase
↓
o accumulation of acetyl choline at
cholinergic synapses
↓
pronounced cholinergic response
↓
neuromuscular paralysis
Synthesis of NO
• Substrates:
o Arginine
o O2,
o NADPH
• Enzyme:
o cytosolic NO
synthase (NOS).
• Coenzymes:
o Flavin mononucleotide (FMN)
o FAD
o Haem
o tetrahydrobiopterin
• Products:
o NO
o citrulline
Stored in vesicles in the terminus of the neuron Neither stored in synaptic vesicles nor released by
exocytosis
Released from this neuron into the synapse by
exocytosis Simply diffuses from nerve terminals
Act on postsynaptic cell Diffusion is not restricted to a synapse
can diffuse in any direction across the extracellular
space.
Structures in the vicinity of the NO producing cell,
both neuronal and nonneuronal, are influenced
following release of NO.
• Chemical transmitters
• Shows ductless secretion into blood/interstitial fluid
• Act on target organs distant or nearby
• Has specific receptors
• Regulate cellular activities in multiple places simultaneously
• Maintains homeostasis
Hormones
Most hormones in the body Gonadal hormones Thyroid, adrenal medullary hormones
Anterior & Posterior pituitary Adrenocortical hormones Epinephrine, NE
Hormones, Insulin, Glucagon
PTH
Synthesis
RER Golgi Packed to from cholesterol By SER Derivatives of tyrosine
vesicles Exocytosis Regulated by stAR(Steroidogenic
Acute Regulatory Protein)
(Pregnenolone-First intermediate in synthetic pathway)
Storage
As prohormone in the Are not stored Thyroid-Bound to thyroglobulin in
secretory granules Cholesterol is stored and follicles
synthesized rapidly when needed Catecholamine-in the secretory
granules
Secretion
Exocytosis diffuse through the Thyroid- first pinocytosis then
(Ca2+/cAMP dependent) membrane diffuse through membrane
Catecholamine-Exocytosis
Transport
Dissolved in plasma Bound to plasma protein Thyroid - Bound to plasma
(Biologically active) (Biologically inactive, TBG (biologically inactive)
Only free form is active) Catecholamine - Dissolved in
plasma (Biologically active)
Ion-channel
linked
G-protein
Cell membrane receptors
linked
Peptide Hormones
Enzyme
Receptors linked
Within Steroid
cytoplasm Hormones
Intracellular receptors
Within Thyroid
nucleus Hormones
Influx of ions
α subunit dissociates
JAK2 phosphorylation also activates several other enzyme systems leading to more rapid effects of leptin
First messenger- extracellular ligand (ligand is a substance that forms a complex with a biomolecule to serve a
biological purpose)
Second messenger- intracellular mediator that brings about the biological response
Cellular response
Receptor molecules
inactivated
Inactivation / Clearance
1. Metabolic destruction by the tissues
2. Binding with the tissues
3. Excretion by liver (Bile) or kidney (urine)
Ultradian rhythm –
Episodic/ pulsatile secretion in repeated cycles within 24 hrs. e.g. – Growth hormone
Circadian rhythm –
Secretion following day & night cycles (responding primarily to light & darkness) e.g. – Cortisol, melatonin
Infradian rhythm –
Periods longer than 24 hr cycles. E.g. – FSH, LH, Estrogen
1. Radioimmunoassay (RIA)
A known quantity of antibody specific to the above antigen is added to the assay
Antigens present in the sample is bound with the antibodies in the assay
It displaces radiolabeled antigens from the antibodies, making them 'free' antigens
The 'free' antigens are separated from the assay and measured
A substrate is added to be converted by the enzyme into a color or fluorescent or electrochemical signal.
The absorbance or fluorescence or electrochemical signal (e.g., current) of the plate wells is measured to
determine the presence and quantity of antigen.
Specific Antibody
Hormone deficiency:-
1)Absolute
• Destruction of glandular structures that secrete the hormone, defects in the process of synthesis
• Eg:- Type I diabetes-autoimmune destruction of insulin secreting cells of the pancreas, iodine deficiency leading to
hypothyroidism
• Measured hormone level in the blood is low
Hormone excess:-
• Can be due to excessive secretion of a hormone or overstimulation of receptors
• Can occur
• in the presence of tumors in endocrine glands- GH secreting adenomas in pituitary gland
• Stimulation of receptors by antibodies-graves’ thyrotoxicosis ( TSH stimulating antibodies)
Pituitary Gland
Anterior pituitary
• Regulated by chemical substances secreted by the hypothalamus- “Hypophysiotropic hormones”
• Synthesized by hypothalamic neurons, Carried to anterior pituitary in portal hypophysial vessels
• TSH, ACTH, LH, FSH, GH – Tropic hormones ‘Tropic’- Stimulates secretion of hormones from other endocrine glands
and in the case of GH, IGF1 from liver
• *Prolactin- acts on breasts
Growth Hormone
• Bound to a protein in plasma
• This protein is a large fragment of the extracellular domain of the GH receptor
• Produced by cleavage of receptor
• Is an index of number of GH receptors in the tissues
• 50% of GH is bound- provides a reservoir
• GH activates many intracellular enzyme cascades JAK2 – STAT pathway
• JAK2- member of Janus family of cytoplasmic tyrosine kinases
• STATs (signal transducers and activators of transcription)- are a family of inactive cytoplasmic transcription factors
• GH activates JAK2 phosphorylates STATs migrate to nucleus to activate various genes
8 ©2018 A/L Repeat Campaign
Effects of GH:-
1)On growth:-
❖ Stimulates chondrogenesis
• Cartilagenous epiphysial plates widen → increases stature
• when epiphyseal plates are not fused, prolonged exposure to GH cause gigantism
❖ Stimulates growth of soft tissue and viscera
• Size of viscera increased
• Protein content/ fat content ratio increases
GH secretion
• Pulsatile secretion- very low during most of the day
• Exhibits a diurnal rhythm- two thirds of daily secretion at night at onset of slow wave sleep
• Marked rapid and spontaneous fluctuations in children and young adults
• Decreased in old age
1)Increased secretion
• Actual or at -risk situations of reduced substrate for energy production
( hypoglycaemia) -exercise, fasting
• Certain AA are increased in plasma (arginine, protein meal)
• Stressful situations- hypovolaemia, sepsis
• Chronic malnutrition • Going to sleep • Thyroid hormones
2)Decreased secretion
• REM sleep
• Glucose
• Cortisol
• FFA
• Obesity
Abnormal GH secretion:-
❖ Childhood GH deficiency:-Dwarfism
• Associated with GH, GRH or IGF 1 deficiency
• Deficiency occurs in childhood before epiphyseal closure
Posterior pituitary
• ADH (Vasopressin) • Oxytocin
• Synthesised in cell bodies of neurons in Supraoptic and Paraventricular nuclei in hypothalamus
• Transported down their axons to posterior pituitary
Aquaporins
• Are stored in endosomes • ADH causes their rapid translocation to luminal membranes
ADH insufficiency
• Diabetes Insipidus (DI)
• Passage of copious amounts of dilute urine and polydipsia
• Cranial DI • Nephrogenic DI
Endocrine Pancreas
• Both exocrine and endocrine functions
• Endocrine portion – islets of Langerhans
• Scattered but more in the tail
• Four types of cells – A,B,D,F
A – glucagon B – insulin
Insulin
• Polypeptide • Two chains
• A & B chains are attached by C peptide
• 90% - 97% insulin is released with equimolar amounts of C peptide.
• Can be measured
• Is an index of B cell function
• Presence of C peptide in plasma helps to diagnose the cause when a person presents hypoglycaemia
Insulin secretion
1) Glucose enter B cells of pancreas (GLUT 2)
2) Glucose is metabolized in the B cells
3) ATP is produced in mitochondria
4) ATP enters cytoplasm
5) Inhibition of ATP- sensitive K+ channels and reduced K+ efflux
6) B cell depolarised with resultant Ca++ influx
7) Exocytosis of insulin containing secretory granules (initial rapid rise)
• Intracellular glutamate act on a second pool of granules
(prolonged second phase of secretion)
Insulin receptor
• Cell membrane receptor • Found on many cells
• Tetramer • 4 sub units- 2α, 2β
• α units are outside cell membrane and β units span it
• Intracellular portions of β subunits have tyrosine kinase activity
2)Skeletal muscles:-
• Exercise increases GLUT 4 on skeletal muscle cell membrane
• Independent of insulin • Exercise lowers blood glucose
1)Timing
a) Rapid effects:- •Increased entry of glucose, amino acids and K+ in to insulin sensitive cells
b) Intermediate effects:- •Stimulation of protein synthesis •Inhibition of protein breakdown
• Activation of glycolytic enzymes and glycogen synthase •Inhibition of gluconeogenesis
c) Delayed effects:- •Increased lipogenesis
2)Site of Action:-
Insulin
Net effect
•Increased cell growth •storage of carbohydrates, protein and fat
“ Anabolic hormone”
Insulin Excess
•Leads to hypoglycaemia
Insulin Deficiency
•Leads to Diabetes mellitus
2)Somatostatin
• Clinical relevance
⃝Portal hypertension
Insulin Deficiency:-
Other pancreatic hormones ⃝GH hypersecretion
•Leads to Diabetes mellitus
1)Glucagon
• Polypeptide found in pancreatic A cells
• Gluconeogenic • Glycogenolytic
• Lipolytic • Ketogenic
• Large doses – increases myocardial contractility
Stimulates secretion of GH, insulin and
pancreatic somatostatin
3) Pancreatic polypeptide
• Slower absorption of food – smoothes out the process
• 21- b hydroxylase – common – production of Cortisol, Aldosterone are reduced – increased ACTH-more androgens
• 11- b hydroxylase - Less cortisol, retained mineralocorticoid effects
(Cholesterol desmolase, 3b – hydroxysteroid dehydrogenase , 17 – a hydroxylase , 17, 20 lyase read about these deficiencies in
ganong)
Cortisol
CBG - synthesized in the liver - secretion in pregnancy - secretion in liver diseases and low protein states –
-Nephrosis, Multiple myeloma
Glucocorticoids
• Direct effects by binding to receptor – Hormonereceptor complex promoting or suppressing the synthesis
of proteins
• Permissive effect via activating or facilitating the effects of other hormones – e.g. Glucagon and
catecholamines
Effects – Intermediary metabolism
- Immunity
- CNS, CVS, Bones
Stress response- Provision of energy substrates, Glucose production, Provision of substrates for glucose production,
conserving glucose for essential organs
Maintain blood glucose levels during fasting (HOW? - High levels / Increased secretion following stress- diabetogenic
Anti insulin hormone’ - ↑ Blood glucose)
• Gluconeogenesis - Increased activity of glucose 6 phosphatase , Decreases the activity of the breakdown
pathway of glucose 6 phosphate to pyruvate- increased production of glucose
• Lipolyitic
Direct effects
Decreased peripheral glucose uptake except for brain and heart- Decreasing insulin sensitivity, reduction of number
GLUT (transporters) At pancreatic Beta cells - Decreased secretion of insulin
• Inhibit protein synthesis and enhances protein catabolism - Activating proteases in muscles and tissues
• protein stores in body cells (except in liver)
• blocks amino acid uptake in peripheral tissues
Sustained elevation of blood glucose leading to DM occur with steroid therapy due to the
- increased activity of glucagon
- increased synthesis due to enhanced enzyme activity and availability of substrates
- decreased peripheral utilization.
Water homeostasis
Gastrointestinal actions
• Bone
– Inhibit osteoblast function , promotes osteoclasts
• Plasma Ca2+ - negative calcium balance
– intestinal absorption of Ca2+
– ↑ renal calcium excretion
– ↑ PTH (leading to ↑ bone resorption)
Prolonged high doses of glucocorticoids as corticosteroids reduce bone mineral density and weaken the
microarchitecture of bones causing osteoporosis by
-suppression of bone formation via the action on osteoblasts and decreasing the availability of calcium
and phosphate
- induction of apoptosis of mature bone cells
- enhancing bone resorption via PTH and osteoclasts.
• Mechanisms –
- Inhibition of protein synthesis
- Growth hormone secretion, decrease IGF1
Fetal life – High doses affect growth. Towards term-levels increases to stimulate maturation and to prepare for
delivery-lung maturation through the synthesis of surfactant
Mineralocorticoids (Aldosterone)
In Excess?
• Increased Na+ and Water – expansion of ECF
volume, excretion of K+
• Hypertension
• Hypokaleamia
Escape mechanism • Oedema?
When expansion of ECF volume exceeds a certain point
→ Na+ and water excretion in spite of continuous
Mineralocorticoid activity
(? mediated through ANP )
usually no oedema in mineralocorticoid excess
Adrenal androgens
• Plasma free epinephrine level - 30pg/mL(0.16nmol/L) – Fall to zero after bilateral adrenalectomy.
Low levels appear later.
• Plasma Dopamine level - 0.13nmol/L
• PNMT (Phenylethanolamine – N –
methyltransferase) found in significant amounts
only in adrenal medulla and brain. Therefore
Epinephrine is not formed in postganglionic
sympathetic nerve endings.
• Adrenal medullary PNMT is induced by
glucocorticoids.
• Development of adrenal medulla is dependent
on glucocorticoids.
• In 21β-hydroxylase deficiency glucocorticoid
secretion is reduced during fetal life and the
adrenal medulla is dysplastic. (common cause
congenital adrenal hyperplasia)
©2018 A/L Repeat Campaign
SECRETION OF ADRENAL MEDULLARY HORMONES
• Release of epinephrine and norepinephrine occur in response to stress. (Cholinergic and beta
adrenergic stimulation)
• Secretion of catecholamine stored in granules is initiated by acetylcholine released by sympathetic
preganglionic neurons.
• Acetylcholine activates Ca2+ influx which triggers exocytosis.
• Secretion is inhibited by ⍺ adrenergic response
CATECHOLAMINES IN CIRCULATION
Effects on BP
Effect on Heart & Blood Vessels • Norepinephrine – Increases systolic &
• Increase the force and rate of diastolic BP
contraction of the isolated heart. (β 1). • Epinephrine – Increases Systolic Blood
[(+)ve Ionotropic & (+)ve chronotropic]
Pressure (SBP), No significant effect on
• Increase myocardial excitability
[(+)ve dromotrophic-can cause extra systoles Diastolic Blood Pressure (DBP), Widening of
or cardiac arrhythmias] pulse pressure (PP)
• Norepinephrine –
Vasoconstriction in most organs (α1) &
increases TPR Effects on CNS
• Epinephrine – vasodilation in • Increase alertness and induce anxiety and fear.
skeletal muscle & liver (β2) & (Epinephrine usually evokes more anxiety and fear.)
vasoconstriction elsewhere (α1) • Fight or Flight Reaction to Stress
effects of dilatation > constriction
Net effect: TPR decreases
Effects of Dopamine
• Physiological function of the dopamine in
the circulation is unknown.
• Dopamine causes renal and mesenteric
vasodilation.
• Other sites vasoconstriction by releasing
norepinephrine.
• Positive inotropic action on the heart
through beta 1 adrenergic receptors.
• Net effect is rise in SBP with no rise in
DBP.
• Moderate dose of dopamine is used in
cardiogenic shock
• About 50% of secreted catecholamine appear in urine as free or conjugated metanephrine and
normetanephrine.
• 35% of secreted catecholamine appear as VMA
• Measurement of urinary metabolites used as an index of the rate of Secretion of catecholamines.
• Useful screening to exclude pheochromocytoma (in patients with episodic or sustained hypertension)
– The thyroid gland has a rich vascular supply. The capillaries are of the fenestrated type.
Thyroid Hormones
❖ The primary hormone secreted by the thyroid is thyroxine (T4), along with much lesser amounts
of triiodothyronine (T3)
❖ T 3 has much greater biological activity than T 4
❖ T 3 specifically generated at its site of action in peripheral tissues
by deiodination of T 4
❖ Both hormones contain iodine
❖ Small amounts of reverse triiodothyronine (3, 3′, 5′-
triiodothyronine, RT 3) and other compounds are also found in
thyroid venous blood.
❖ RT 3 is not biologically active.
Iodine homeostasis
❖ Iodine is an essential raw material for thyroid hormone synthesis.
❖ Dietary iodide is absorbed by the intestine and enters the circulation
❖ Minimum daily iodine intake for normal thyroid function is 150 μg in adults.
❖ Supplementation of table salt leads to an average dietary intake of approximately 500 μg/d.
❖ The principal organs that take up circulating I– are
the thyroid, which uses it to make thyroid hormones
The kidneys, which excrete it in the urine
This diagram shows the process of synthesis, The numbers indicated in blue refer to important steps of
synthesis.
2. Iodide is then pumped into the colloid through an ion transporter called pendrin, which exchanges
iodide for chloride, since they are both negatively charged. This process of concentrating the iodide
in the cell is called iodide trapping.
3. Once iodide is in the colloid, it undergoes oxidation with the enzyme peroxidase and hydrogen
peroxide, which changes it into an iodine atom.
4. It is then attached to tyrosine amino acid residues which are found throughout thyroglobulin. This
process is called iodination. Some tyrosine residues are bound by only one iodine, whereas others
are bound by two iodine atoms. Incorporation of iodine into the carbon 3 position of tyrosine
residues yields Monoiodotyrosine or MIT, and MIT is next iodinated on the carbon 5 position to
form Diiodotyrosine or DIT.
5. These molecules are then linked together by thyroperoxidase, a process known as coupling. Two
DIT molecules then combine to form T4. Combination of MIT with DIT forms T3. The thyroid
hormones that are produced remain as part of the thyroglobulin molecule until needed. As such,
colloid represents a reservoir of thyroid hormones Humans can ingest a diet completely devoid of
iodide for up to 2 months before a decline in circulating thyroid hormone levels is seen. T4 is created
in greater amounts than T3. A small amount of R3 (reverse tri-idothyronine) is also produced.
6. When there is a need for thyroid hormone secretion, colloid is internalized by the thyrocytes by
endocytosis (pinocytosis) and directed toward lysosomal degradation.
7. Most of the thyroglobulin is not released into the circulating blood; instead, T4 and T3 are cleaved
from the thyroglobulin molecule, and then these free hormones are released.
8. During the digestion of the thyroglobulin molecule to cause release of T4 and T3, iodinated tyrosines
also are freed from the thyroglobulin molecules. However, they are not secreted into the blood.
Instead, their iodine is cleaved from them by an iodotyrosine deiodinase enzyme that the iodine
available again for recycling. In the congenital absence of this deiodinase enzyme, many persons
become iodine deficient because of failure of this recycling process.
• Most of the thyroid hormones secreted are in the form of T4, whereas derivatives T3 and RT3 are
mostly formed by deiodination at the sites of action.
• RT3 is reverse tri-iodothyronine, an inactive form of T3.
• These deiodination reactions catabolize the hormones, but also provide a local supply specifically of
T3, which is the primary mediator of the physiologic effects of thyroid secretion.
• Many factors affect the activity of deiodinases.
o Starvation (Reduction in T3 & rise in RT3)
o Overfeeding (Rise in R3 & reduction in RT3)
o Se deficiency (Same as starvation)
o Non thyroidal illness -
(Burns,Trauma,Cancer,Cirrhosis,Chronic
kidney diseases,Miocardial infarctions) –
reduction in T3.
Fluctuations in binding
❖ When a sudden, sustained increase in the concentration of thyroid-binding proteins in the plasma takes place,
the concentration of free thyroid hormones falls.
– Change is temporary
3) Graves Disease
• Autoimmune disease which produce antibodies which stimulate TSH receptors in thyroid & produce
marked increase in T3/T4 secretion & enlargement of thyroid gland (Goitre)
9
Ca-binding proteins
• Troponin – Involved in contraction
of skeletal muscle
• Calmodulin – Involved in
contraction of smooth muscle
• Calbindin – Controls I/C
concentration of Ca2+ (Endogenous
Ca2+ buffer)
❖ Mechanism of Action
• Actions on Bones
o Short-term Ca2+ buffering action results
from osteocyte activation
o Increases bone resorption increases Ca2+
and PO4 3- (Bone remodeling) resorption
from the bones (By osteoclasts via
activation of osteoblasts)
• Actions on Kidneys
o Promotes conversion of 25-
hydroxycholecalciferol to 1,25- DHCC in
the kidney
o Increases Ca2+ reabsorption in the distal renal tubules
o Increases phosphate excretion in urine (Phosphaturic action)
• Actions on Intestine
o Increases intestinal absorption of Ca2+ and PO4 3- indirectly via 1, 25 – DHCC
• PTH increase plasma calcium and decrease plasma phosphate levels
❖ Regulation of PTH secretion
o Ionized calcium level in the circulation – action via
Ca2+ receptors (CaR or CaSR)
o Direct action of 1, 25 – DHCC to decrease
preproPTH mRNA
o Increased plasma phosphate stimulates PTH
secretion
o Increased plasma phosphate inhibits 1,25-DHCC
formation
o Mg is necessary for normal PTH secretion (Mg
deficiency leads to hypocalcaemia)
2. Vitamin D
❖ Actions of 1,25-DHCC
o Actions on Intestine
▪ Increases Ca2+ absorption from the intestine by increasing the production of Ca2+
Binding Proteins (CaBP), Ca2+-ATPase
▪ Increases phosphate absorption from the intestine
o Actions on KIdneys
▪ Increases Ca2+ reabsorption by the distal renal tubules
o Actions on Bones
▪ Increases synthetic activity of osteoblasts
▪ Stimulation of osteoblasts, increases the activity of osteoclasts
o Increase plasma Ca2+ & PO43- levels.
Bone Resorption
• Osteobalsts are responsible for the formation of bone.
• Osteoclasts are responsible for bone resorption. Osteoclasts are a member of the
monocyte family.
• Receptors (RANK and receptors for Macrophage colony stimulating factor-M-CSF) are
expressed on preosteoclasts.
• PTH stimulates osteoclast activity and thereby bone resorption through the activation of
osteoblasts.
3. Calcitonin
5. Glucocorticoids
o Lower plasma Ca2+ levels by
- inhibiting formation and action of osteoclasts
o Over long periods contribute to osteoporosis by
- increasing bone resorption
- decreasing bone formation (inhibit protein synthesis in osteoblasts)
- decreasing intestinal absorption of Ca2+ and PO43-
- increasing renal excretion of these ions
9. Estrogens
o Prevent osteoporosis
- by inhibiting secretion of certain cytokines which facilitates development of
osteoclastic activity
- by stimulating production of a specific cytokines which increases apoptosis of
osteoclasts
Hypercalcaemia
Hypocalcaemia
• Depression of the Nervous system
• Hypocalcaemic tetany
• Sluggish reflex activities of the CNS
o Trousseau sign
• Decrease in QT interval of the heart
o Chvostek sign
• Lack of appetite
• Laryngospasm
• Constipation - may be due to
o when severe - Airway
depressed contractility of the muscle
gets obstructed &
walls of the GIT
fatal asphyxia results
• Precipitation of Ca phosphate crystals
Sensory Receptor
• Specialized dendritic endings of afferent nerve fibers which convert various forms of energy into
action potentials in sensory neurons.
Sensory Organ
• Sensory receptors and associated non-neural cells that surround them
Adequate stimulus
• The particular form of energy to which a receptor is most sensitive
• Almost not sensitive to the normal intensities of other forms of energy.
Eg – rod and cones are stimulated by light, not heat
Chemo R
Nociceptors
Thermal R
(Pain-Temp)
Mechano R
Polymodal R
(combination
of above 3)
b) Adequate stimulus
• Is the type of energy that a receptor is most sensitive?
• Receptors has a very high threshold for other modalities while lowest threshold is
for the adequate stimulus
2. Identifying the location of a stimulus Sensory unit: - single sensory axon with all its
o Law of projection peripheral branches which is sensitive to one
o Lateral inhibition type of sensation (modality)
o Sensory unit & receptive field The area supplied by one sensory unit usually
overlaps an interdigitates with the areas supplied
a) Law of projection by others
• The sensory pathway extends from Receptive field:-the area of the sensory unit that
the receptor to the cortex produces a response
• If we stimulate anywhere along
this pathway
• The conscious sensation produced is always referred to the location of the receptor
4. Identifying Duration
• As long as the AP come to the brain
• Adaptation represses AP & decreases duration
Cortical plasticity
• When a stimulus of constant strength is applied to a receptor, the frequency of action potential
generation decreases over time
Degree of adaptation
Pain: Unpleasant
Emotional
Withdrawal
Treatable
Potential tissue damage
Pain Afferents:
▪ Aδ (small myelinated) & C (unmyelinated)
Lateral spinothalamic tract SI localization of pain
S11
Cingulated gyrus, Cerebellum, Insular cortex, Amygdala, PAG,
Reticular formation
Pain types
Fast pain Slow pain
• First pain • Second pain
• Sharp, pricking pain • Aching, burning pain
• Well localize • Diffuse
• Aδ fibers • C fibers
• Glutamate at dorsal horn
• Substance P at dorsal horn
Pain perception alone doesn’t require cortex (thalamus can sense pain)
Cortex – meaningful interpretation of pain and associated emotional component
5 ©2018 A/L Repeat Campaign
Site of pain Cause of pain
Somatic pain Ischemic pain
Deep pain inflammatory pain
Bad pain(chronic)
Muscle pain Neuropathic pain
visceral pain Psychogenic pain
Physiological pains- Good pain (acute)
Cause of pain :
1. Ischemic pain/muscle pain
• Decreased blood supply results muscle ischemia
• Causes accumulation of P factor (K+?) → RMP more positive → Excitability ↑
• Stimulates pain fibers
• No pain when the blood supply is restored. (chemicals washed out or metabolites)
Ex: Angina pectoris,
intermittent claudication
2. Inflammatory pain
• Due to tissue damage
• Chemical mediators like bradykinin, cytokines, and prostaglandins are released
• They act on pain receptors and dorsal horn, producing
Mechanism of hyperalgesia and allodynia :- significantly increased sensitivity of nociceptive afferant fibers
Chemicals released at the site of injury such as K+ directly deporlarize nerve terminals, making nociceptors more responsive.
. (sensitization)
3. Neuropathic pain (Resistant Pain)
• Due to damage or inflammation of nerves (Toxins, diabetes, DDHF, CGRP, Glutamate, Sub P)
• Hyperalgesia and allodynia - abnormal connections by sprouting Aα and Aβ in dorsal horn
• Occurs in various forms
• Hard to treat
E.g.:
• Pain in the phantom limb
• Causalgia – burning pain long after a trivial injury
• Reflex Sympathetic Dystrophy – after damage to a peripheral nerve trunk, noradrenergic
sympathetic fiber may over grow to the dorsal root ganglia. Sympathetic discharge gives
pain.
2. Visceral pain
• Due to distension, spasms, ischemia, inflammation in visceral organs
• Relative deficiency of Aδ nerve fibers in deep structures
• Pain is poorly localized (carried out by C fibers)
• Afferents come via sympathetic and parasympathetic fibers
• Associate with autonomic symptoms
• Causes reflex spasms in nearby skeletal muscles - guarding
• Radiates or referred to other area
• Radiation of pain – pain felt in the viscus spreads to another somatic area
• No proprioceptors in viscera, Temperature and touch receptors are less in number
REFERRED PAIN
• Irritation of a viscus or a deep somatic structure produces pain perception in another distant
somatic area
Eg.: -
O Myocardial pain is referred to the arm and neck (T1-T4) Radiation of pain – when pain is felt in the
O Pain in the knee joint is referred to the hip joint viscous as well as in the reffered somatic
O Subdiaphragmatic → tip of shoulder (C3-C5) area
O Ureter → testis
O Appendix/ SI → Paraumbilical (T10)
3. Also, visceral pain may facilitate the firing of the somatic nerve ending
which in turn stimulate the 2nd order neurons.
Thus, brain identifies it as coming from the somatic fibers.
Pain modulation
1. Physical (Dorsal horn gate)
2. Chemicals
• Inflammatory mediators – hyperlagesia and allodynia
• Endogenous opiods – endorphins and enkephalins
3. Psychological methods
4.other
Gate control theory of pain
• Decending pathways from the brain close the gate by inhibiting the projector neurons and diminishing pain projection.
• Stimulation of periaqueductal grey matter (PAG) (by higher centers and by pain conducting C fibers via
Hypothalamus) in mid brain activates Enkephalin releasing neurons that project to,
Serotonin Catecholaminergic/noradrenergic
E.g.:-
O Rubbing on the site of pain
O Acupuncture
O Psychological factors
O Transcutaneous electrical nerve stimulation (TENS)
O Applying irritable substances to a painful area (counter irritation)
Release of opioids
• Opioids are peptides
• Endogenous opioids are
enkephalin and endorphin
• Exogenous opioids are morphine,
pethidine… etc.
• They bind to opioid receptors
• Opioid receptors are produced in
dorsal root ganglia cells
• And transported centrally and
peripherally along their nerve
fibers
• Morphine→ Descending tr.→ IN
• → Opioids
• Morphine / opioids cause addiction,
tolerance, dependence
Psychological methods
• Distraction, over emphasis, depression, bordem
• Stress analgesia : soldiers don’t feel pain in their wounds until the battle is over
✓ Reduce sensitivity during stressful events
✓ Release of norepinephrine – amygdela
✓ Release of endogenous cannabinoids such as 2-arachidonyl glycerol (2AG) and Anantamide
Other
• Aspirin (NSAIDs) and paracetamol
• Cannabinoids
• NMDA antagonists
• TRPV1 receptor antagonists
• TENS
SPECIAL SENSATIONS
Itch (Pruritus)
• Due to repeated local mechanical stimulation
• Chemicals involved are kinins, histamines (antihistamines reduce pruritus)
• Specific receptors are present
• Pathway – spinothalamic tract, thalamus and cortex
• Has an emotional component - annoying
• Itching ↑ - CKD, Atopic dermis HIV, Hepatic diseases.
• Simple scratching reduce itching
• Activates large fast conducting afferents that gate transmission in the dorsal horn.
• Anti histamines (Piriton) – reduce pruritus associated with allergic reaction
Tickle
✓ Due to repeated light touch
Synthetic Sensations
Vibration
• Stimuli – A pattern of rhythmic pressure stimuli
• Pacinian corpuscles – fast vibration Meissner’s corpuscles – slow vibration
• Pathway – dorsal column, thalamus, cortex
10 ©2018 A/L Repeat Campaign
• Tested by using 128 Hz tuning fork to the skin of fingertip, tip of toe or a bony prominence
• Loss of vibration (associated with proprioception) is an early sign of degeneration of dorsal
columns. (Buzzing sensation)
• Ability to feel vibration; Pallesthesia
• E.g.:- DM, Pernicious anemia (vit B12)
Two-point discrimination
• Ability to distinguish simultaneous two touch stimuli as coming from two different areas
• Has both cortical and receptor component
• Depend on the size of the receptive fields of sensory units & receptor density
• 2-point threshold – minimum distance by which 2 touch stimuli must be separated, to be
perceived as separate
• Sensory units and lateral inhibition are important in two-point discrimination
• Magnitude of two-point discrimination threshold varies from place to place in the body
Eg: Back 6mm, finger tip 2mm
Stereognosis
• Ability to identify objects by handling without looking at them
• Touch, pressure and large cortical component
• Affected when dorsal column or parietal cortex is damaged
Sensory cortex
Primary sensory Cortex (SI) – Post central gyrus
Secondary sensory cortex (SII) – Walls of sylvian
fissure SI projects to SII
Sensory homunculus
• Thalamic projections are arranged representing body parts
• Legs on the top and head at the foot of the gyrus
• Size of the cortical area proportional to the number of receptors in the part (large area for
hand)
• Face bilaterally represented
• Cells are arranged in vertical columns responding to specific sensory modality from a
particular region
• Information mainly from opposite side of the body
Making motor plan (Frontal cortex, All motor areas, Posterior Parietal
cortex, Lateral cerebellum, Basal ganglia)
Premotor cortex
- Located in front of motor cortex in the lateral surface of the brain
- Sets posture at the start of a movement (mainly proximal muscles)
- Organized somatotopically
- Projects into brain stem, motor cortex, descending motor pathways
Damage to small area of the motor cortex results in taking over the function of that area by the
adjacent undamaged cortex with return of function due to divergence and convergence of nerve
fibers.
Descending Tracts
Motor Unit
− Components - each single motor neuron and all the muscle fibers innervated by it
− The number of muscle fibers in a motor unit varies (muscles concerned with
fine movements - lesser number of fibers for each motor neuron and vice
versa
Pyramidal tracts
• All pyramidal fibers converge from the surface of the brain like a fan - corona radiata
• These come down and join together to form the internal capsule at the level of the thalamus
• Some fibers are densely packed in the internal capsule, lesions in this region produce dense
weakness (paresis) of the contralateral side than a small lesion in the motor cortex.
• Pyramidal tracts start crossing to the opposite side at the level of medulla
Reticular
• Reticularspinal Ipsilaterl skeletal muscles of trunk and proximal
Motor cortex
Reflex: an automatic response to a stimulus occurring by a relatively simple neuronal network. (Reflex arc)
Reflexes
A) Monosynaptic reflexes B) Polysynaptic reflexes
• Reaction time – time between the application of the stimulus and response. (20-24ms)
• Central delay – Time taken for the reflex activity to transverse the spinal cord. (0.6-0.9ms)
Monosynaptic reflexes
Intrafusal
fibers
Nuclear chain
Nuclear bag
(static)
2-3 per 5 per spindle
spindle
thinner, shorter
Dynamic Static
Dynamic Static
β efferents – larger diameter, supply both interfusal and extra fusal fibers
• Dynamic response: very sensitive for velocity, speed information, quick connective movements.
6 ©2018 A/L Repeat Campaign
• Static response: steady, state length information.
Feedback mechanism in maintaining muscle length
Shortening of muscle
Relaxation of muscle
Antagonist relaxes
Increase in sensitivity of
Collaterals of α-γ linkage
muscle spindle
Spontaneous γ discharge
discharge keeps (help to maintain muscle contraction)
the muscle tone
• Increased by
o Anxiety – hyperactive tendon reflexes
in anxious patients
o Stimulation of skin by noxious agents
o Jendrassik’s maneuver
o Descending fibers from
▪ Reticular facilitatory area
(Pons)
▪ Vestibular nuclei
• Decreased by
o Descending fibers from
▪ Motor cortex
▪ Basal ganglia
▪ Cerebellum
- co-activation
Descending tracts from higher centers will stimulate both α and ϒ motor neurons
simultaneously.
• To keep the muscle spindle sensitive throughout the contraction. (to transmit
sensory information)
α-γ linkage/servo-assisstance
Stimulated alpha fibers send collaterals to gamma fibres and activate them to maintain the
sensitivity of the muscle spindle.
Stimulation of γ efferents
Net effects
Muscle tone
After discharge
Continuation of reflex withdrawal even after cessation of sensory receptor firing.
This is due to
1. Presence of short and long pathways
2. Presence of reverberating pathways
Posture
• Alignment and orientation of the body in relation to the environment
• Way of stand/walk/sit
• Postural reflexes; produced, maintained, restored by a series of coordinated reflexes.
• Cortex, brain stem, basal ganglia, cerebellum
• Stimulus → gravity, visual, stretch, pressure on the body
• Sense organs → muscle spindle, proprioceptors, eyes, ears
Stance reflex
Postural reflexes Static
(Spinal cord Righting reflex
Brain stem)
Stretch Other
(Most important postural reflex) Placing reaction
Phasic
(cortex)
Hopping reaction
Gait
• A series of rhythmical, alternating movements of the trunk and limbs which results in forwards propagation
of center of gravity.
• 2 types of gait modifications
o Automatic
▪ Adjustment of postural muscle tone, rhythmic limb movements
▪ Information processing in Basal ganglia, cerebellum, brain stem, and spinal cord
o Intentional
▪ Require motor programming
Gate cycle
period of time from one heal strike to the nxet heal strike of the same limb
1. Stance phase 2. Swing phase
Clonus
1. The stretch reflex and inverse stretch reflex of the same muscle (alternates).
• Initially due to stretch (along with increased γ efferent discharge), the muscle strongly
contracts.
• The ankle will plantar flex.
• But this contraction will increase the tension in the tendon of the same muscle.
• Impulses from the Golgi tendon organ will cause relaxation of the muscle.
• Since the force on the ankle is maintained, the ankle will return to its dorsiflexed state.
• This cycle repeats.
3. It can also occur as a result of repetitive sequential contraction of flexors and extensors.
• Due to damage to the descending cortical tracts that activate the Renshaw cells
(which inhibits the extensor)
1. Hemisection transection
➢ Common features depending on the site of injury
o At the level of LMN – ipsilateral
o Below UMN – ipsilateral
o Medial pathway – loss of gross movements and postural relexes
Spinal shock
• Paralysis of skeletal/ smooth muscles below the level of lesion
• Loss of tone in skeletal muscles
• Loss of bladder, bowel function – due to interruption of descending autonomic pathways
• Loss of sensation below the level of lesion
• Loss of tendon reflexes
• No excitatory inputs from descending pathways. Activation of inhibitory interneurons
Reason;
➢ Cessation of excitatory inputs on stretch reflex by descending pathways Duration of
spinal shock depends on the degree of encephalization of motor functions (human
normally 2 weeks)
Mass reflex
• Stroking any part of the limb or perineum cause evacuation of bladder and bowel.
• Due to afferent stimuli irradiating to the autonomic centers of bladder and bowel function
• Intentional mass reflex
• Could be lethal
• Can even cause retinal detachment due to excess autonomic activation and increased pressure
Bulbar palsy
✓ Is a similar disorder as pseudobulbar palsy, but is caused by LMN lesion
✓ It consists of LMN signs in region innervated by VII, IX, X, XII cranial nerves.
Inhibition of cerebral cortex/ corticospinal tract, basal ganglia, rubrospinal tract on discharge
motor discharge due to the hyperactivity of the medial tracts (vestibular nuclei and
reticular facilitatory area)
Destruction of dorsal horns – theses hyperactivity of the extensors is gone. Also there is a direct
activation of α motor neurons independent of γ loop
Decerebrate rigidity seen in uncal herniation (uncus of the temporal lobe herniates into subtentorial
region of midbrain and compresses midbrain)
Uncal Herniation
Before;
− Decreased consciousness
− Lethargy
− Poor pupil reactivity
− Hyperactive reflex
− Bilateral Babinski
After;
− Pupil fixation
− Waxing & Waning respiration with apnoea
4 − Medullary function loss and breathing ceases ©2018 A/L Repeat
Campaign
Decorticate rigidity
Flexion of the upper extremities – Facilitation of flexors in upper limb by rubrospinal pathway Extension
of the lower limb – Facilitation of extensors in lower limb by reticulospinal and vestibulospinal pathway
Reticulospinal facilitatory and inhibitory tracts are intact ascending sensory fibers activate the
reticulospinal facilitatory tract.
Autonomic Dysreflexia
Widespread vasoconstriction
Relayed via IX & X to Detected by baroreceptors (mostly in Splanchnic
brain vasculature)
Doperminergic neurones,
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Treatment
o No treatment, Symptoms relief only
o Dopamine does not cross blood brain barrier
o Therefore, L-dopa is used as it crosses the blood brain barrier
o Use of anticholinergic drugs
Huntington disease
• Autosomal dominant disorder
• Loss of intra-striatal cholinergic and GABAergic neurons.
• Releasing of inhibition
• Hyperkinetic features- chorea, athetosis, hemiballismas
• Abnormal repetitive sequence leading to abnormal production of protein huntingtin
Wilson disease (Hepatolenticular Disease)
• Wilson's disease is a genetic disorder in which copper builds up in the body.
• Copper accumulates in the liver tissue;
• When the amount of copper in the liver increases it causes oxidative damage
• This damage eventually leads to chronic active hepatitis
• This free copper precipitates throughout the body but particularly in the kidneys,
eyes, and basal ganglia, particularly in the putamen and globus pallidus
• This causes basal ganglia disorders.
Tardive Dyskinesia
Due to long term use of drugs that cause biochemical abnormalities in the striatum or affect
Doperminergic transmission.
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Cerebellum
Has two lateral cerebellar hemispheres joined by a medial vermis. Anatomically divided in to
• Anterior lobe
• Posterior lobe
• Flocculonodular lobe
Organization of the cerebellum
Cerebellum has,
§ an external cortex-gray matter
§ four deep cerebellar nuclei in the internal white matter
Control of voluntary movements Learning new skilled voluntary movements
• Compare motor plan with proprioceptives • From inferior olivary nucleus
• Error calculated • Climbing fibres into cerebellum
• Correct errors via output signals by • Complex spike – cause burst of spikes in Purkinje cells
• Motor cortex via thalamus • Long term modification of mossy fibres
• Corticospinal tracts • ↑ Climbing fibre input with learning
Cerebellar Cortex
3 layers
• Outer molecular layer
• Middle Purkinje cell layer
• Inner granular layer
5 types of cells
• Stellate cells
• Basket cells
• Purkinje cells
• Granular cells - Has parallel fibres in molecular layer
• Golgi cells
Purkinje cells are the only output from the cerebellar cortex
They send excitatory impulses which is then followed by an inhibitory impulse to deep cerebellar
nuclei.
signal will be sent from the relevant muscle areas of In this test the damping action will make
sure that finger will reach the target and
the cerebral motor cortex of the person, to the motor not provide overshoot or past pointing.
pathways activating those muscles. However, when the cerebellum is damaged
this damping action won't occur properly
when provides an overshoot or past
The same motor plan is conveyed to the cerebellum
pointing.
which greatly increases deep nuclear cell excitation.
This overshoot will prevail as long as the
individual try to reach the target.
There will be a rapid excitatory signal from the deep This back-and-forth overshoot until
nuclei to the motor pathway to initially enhance the reaching the target is known as intention
tremor or oscillation (Differs from the
motor movement. tremor seen in Parkinson’s disease and
Almost immediately, inhibitory signals from the hyperthyroidism)
motor pathway.
This is like a negative feedback after a small delay,
and is referred to as damping of the movement.
• Ataxia
§ Incoordination of the movements
§ Lateral lobe lesions produce - ataxia of the limbs
§ Midline lesions in vermis produce - truncal ataxia\ Not made worse by closing the
eyes
• Disturbances of posture and gait
§ Head tilted to the side of the lesion; patient tends to fall to the side of
the lesion- ‘drunken gait’
• Dysarthria/ scanning speech (slurred speech) - defects of skilled movements
• Dysmetria
§ inability to predict the extent of a movement
§ also called past pointing
§ when attempting to touch an object with the finger overshooting to one side
• Intention tremor
• Rebound phenomenon
§ inability to stop the movements suddenly
• Dysdiadochokinesia
§ inability to perform rapid alternating opposite movements
• Nystagmus
• Involuntary movements of the eyeballs
• Muscle hypotonia
• Pendular knee jerk
• Loss on influence on stretch reflexes movement continuous as a series of flexion & extension
movements at the knee joint.
• Decomposition of the movements
• Inability to perform movements involving more than one joint.
Posture
• Way of stand/walk/sit
• Postural reflexes; produced, maintained, restored by a series of coordinated reflexes.
• Cortex, brain stem, basal ganglia, cerebellum
• Stimulus - gravity, visual, stretch, pressure on the body
• Sense organs-muscle spindle, proprioceptors, eyes, ears
• Muscle tone
• Postural reflexes
Retinochiasmatic fibres
Suprachiasmatic nucleus(SCN)
GABA
Paraventricular nucleus
Pineal gland
Melatonin
Cyclical phenomenon
Thirst mechanism
Thirst
11) Regulation of food intake – to maintain the body weight in a given set point
➢ Orexigenic stimuli→ stimulate food intake, circulating levels during fasting
• NPY- neuropeptide Y
• Cortisol
• MCH- melanin concentrating hormone
• AGRP
• Orexin A & B
• Ghrelin (release from stomach when it is empty)
➢ Anorexigenic stimuli→ inhibit food intake
• α- MSH- melanin stimulating hormone
• CART- cocaine & amphetamine regulating transcript
• CRH- corticotrophin releasing hormone
• PYY- peptide YY
• CCK
• GLP-Glucagon like peptide
• Leptin
• Insulin
• Serotonin
• norepinephrine
Inputs to regulate food intake
Neural signals
-GIT (via vagus) regarding stomach filling
-cerebral cortex (smell, sight, taste)
Hormonal signals
GIT – CCK, PYY, Insulin
Adipose tissue - Leptin
2) Satiety center
- Ventromedial nuclei, paraventricular nucleus
- Stimuli sense of satisfaction
- Destruction- Hyperphagia - hypothalamic obesity
2) Lipostatic hypothesis
Food in gut
4) Thermostatic hypothesis
↑Secretion of polypeptides
↓Body temp→stimulate appetite
Inhibit feeding center
↑Body temp→inhibit appetite
Inhibit food intake
glucose
Hormones of hypothalamus
➢ Both Oxytocin and Vasopressin are secreted from the posterior pituitary (neurohypophysis).
Core temperature (36.3 – 37.1 0c) is closely represented by rectal temperature – varies least with
environmental changes
Surface (skin)
Temperature
(29.5 – 33.9
Rectal temperature
°C)
Scrotal Temperature
32 °C
Pathological Hyperthyroidism ↑
Lesion to brain (Ant ↑
Hypothalamus)
Infection ↑
Hypothyroidism ↓
hypothermia
Lesion to hypothalamus ↓
(Post)
The normal human core temperature undergoes a regular circadian fluctuation of 0.5 – 0.7 0C
Balance between heat production and heat loss determines Body temperature
Heat loss
𝐸𝑣𝑎𝑝𝑜𝑟𝑎𝑡𝑖𝑜𝑛
∝ 𝐸𝑛𝑣 𝑇𝑒𝑚𝑝𝑒𝑟𝑎𝑡𝑢𝑟𝑒
𝑅𝑎𝑑𝑖𝑎𝑡𝑖𝑜𝑛
Cutaneous vasodilation37 0C
Increase Heat
Sweating 370C
loss
Increased respiration
Temperature set point – 37.1 0 C
Skin temperature determines the set point level at which shivering or sweating begins.
Fever/Pyrexia
“As if thermostat is reset” - to a new point above normal body temperature
Protective response which inhibits pathogen growth and increase antibody production
Inflammation
Endotoxins from bacteria (exogenous pyrogens)
Pyrogens released from degenerative tissues
Fever
Hypothermia
Fat cells contain several small droplets of fat Fat cells contain only a single large droplet
of fat
Fat cells as well as blood vessels have an
extensive sympathetic innervation Principal sympathetic innervation is solely
on blood vessels
Fat cells contain many mitochondria
1 method of oxidation which generates ATP
2 methods of oxidation
Oxidative phosphorylation which
generates ATP
Uncoupled oxidative phosphorylation
which doesn’t generate ATP, but
produce HEAT
Heat stroke – Body temperature higher than 41.10c. Neurological dysfunction occur. Sudden
severe fatigue, nausea, dizziness, disorientation, flue like symptoms.
Complete spinal cord transection at neck above sympathetic outflow impairs internal body
temperature regulation
Explicit memory initially required for a task can become implicit when a task is
learnt.
Eg: riding a bicycle
• Implicit memory / skill memory – motor activity
*Post tetanic potentiation, Habituation, Sensitization, LTP,LTD – enhance or suppress signal conduction
Consolidation of memory
• STM to LTM
• Results from chemical, physical and anatomical changes in the synapse (protein synthesis)
• Require time (5-10 min to 1 hour or more)
• Rehearsal / repetition enhances consolidation
• Interruption of the process by electrical shock or by anesthesia will prevent memory
development . eg – retrograde amnesia in TBI/seizure
Memory disorders
Amnesia (Retrograde & anterograde)
Dementia - Alzheimer’s
- Senile dementia
Syvian fissure
• Language involves in understanding of the spoken and printed words and expressing ideas in speech and writing
• Human language function depend more on categorical hemisphere / dominant hemisphere
Cerebral dominance
Neocortical function
Categorical/dominant hemisphere-categorization and symbolization
(language function, mathematical problem solving)
Representational hemisphere- spatiotemporal relations (recognizing objects,
places, faces, music etc.)
Hemispheric specialization is related to the handedness
Cerebral dominance of Left handed people,
70% -left, 15% -right, 15% -no clear lateralization
Right handed people,
96% -left, 4% -right
Features of lesions
Categorical hemisphere Representational hemisphere
Language disorders Astereognosis – Inability to identify
Fluent, non fluent and anomic aphasia objects by feeling
Acalcuia Agnosia - Inability to identify objects by
difficulty in mathematics particular sensory modelity
Patients are disturbed and often depressed Unilateral inattention and neglect
about their disability prosopagnosia
Patient are unconcerned and euphoric about their
disability
Hippocampus
• Extensive ability to undergo plasticity
• Can become hyperexcitable /
epileptogenic
δ θ α β Υ
<4 4-7 8-13 13-30 30-80
Alpha (α) Beta (β) Gamma (γ) Theta (ϑ) Delta (δ)
Awake but rest with Mentally alert Focused attention Large amplitude Large slow waves
mind wandering Marked in frontal aroused slow waves
Eyes closed region Involved in high Deep sleep in adults
marked in parieto- mental activity Seen in children & (3rd and 4th stages
occipital area Seen in infants • Perception in early sleep of N-REM Sleep)
• Problem
Gradually appears solving Often found over Early childhood
during adolescence • Fear & the parietal and (infancy)
consciousness Temporal areas. Abnormal if in
a Block / adults in awareness
desynchronization - (raised ICP)/Brain
by opening eyes. disease -tumor,
(Replace α waves haematoma,
with fast irregular encephalopathy
waves of low
voltage- β waves) In overbreathing
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Flat tracing- seen during death
Waves seen in childhood (without sleeping)
• β Rhythm Waves during
• θ Rhythm Sleep – Low frequency, high amplitude
• δ Rhythm Awake – high frequency, low amplitude
factors affecting waveform
1. age
2. sleep/awake status
3. level of consciousness –
metabolic abnormalities, head
trauma, sleep onset latency
4. Epilepsy
α frequency
Low blood glucose
Low body temperature
↑ PaCO2
↓cortisol. Opposite
Anesthesia /analgesia
Forced over-breathing
Alcohol, barbiturates and antipsychotics
- Hyperventilation brings out hidden EEG abnormalities
Arousal Sleep
• Sensory system stimulation * stimulation of sleep zones
- Up to midbrain level - slow wave sleep
• Activation of MB reticular area * pontine reticular area
• Mid-thalamic neurons are partially depolarized * Mid-thalamic neurons are hyperpolarized.
(Electrical state of the thalamo-cortical neurons influences the sleep-wake cycle)
• Evoked potentials
• Brain electrical response to a stimulus
1. Motor Eps (MEPs)
2. Sensory Eps:
- Auditory(AEPs). – Visual (VEPs) - somatosensory(SSEPs)
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Features of CSF in Meningitis
Features Normal Pyogenic Tuberculosis Viral Meningitis
Meningitis Meningitis
Colour Clear Yellow turbid Turbid + fibrin web Clear
Cells No neutrophils High (as acute) Very low Very low
Lymphocyte Less High High
<5/mm3
Glucose 66% of plasma Low (consumed by Low
glucose bacteria)
Plasma proteins 0.4g/L High High Not very high
(virus disrupts
permeability microcirculation)
Absorption: -
• Through arachnoid villi è into cerebral venous sinuses
• Smaller villi è into spinal veins
• Through the cribriform plate è into cervical lymphatics
* Rate of absorption depends on intra- ventricular pressure
* Absorption is unidirectional (bulk flow)
* When CSF pressure is elevated
o Possibly increased expression of aquaporin channels in choroid plexus and cerebral micro
vessels.
o More and more arachnoid villi open up
* Below 68 mmH2O absorption stops
CSF pressure
• Lumbar CSF pressure 70 – 180 mmH2O (Average normal – 112 mmH2O)
• CSF pressure can go up by laughing, sneezing, coughing & straining
Head injuries
Cerebral damage results with blows to the skull
Mild/ moderate moderate/severe
CSF protects brain by cushioning effect
coup injury contrecoup injury
damage to the damage to the opposite
same side of the brain side of the brain
ü A "traumatic tap" occurs if the needle inadvertently has entered an epidural vein during
insertion.
ü Xanthochromia is the yellow discoloration indicating the presence of bilirubin in the
cerebrospinal fluid.
ü Xanthochromia is usually caused by red blood cell degeneration in the CSF as would be
seen in subarachnoid hemorrhage (SAH).
Taste Bud
Specialized sense organ for taste. Respond to taste stimuli. ( tastant )
Adults - 3000-10,000 taste buds (child >> elderly)
Found on Tongue – Circumvallate, fungiform, foliate papillae
Pharynx, Palate, epiglottis, proximal esophagus, Tonsillar pillars
Von Ebner’s glands secrete saliva into the cleft around papillae
o Cleanse the papillae and prepare for the next tastant
Composed of gustatory receptors and sustentacular cells.
Filiform papillae are the most numerous. But they don’t have taste buds
Taste Bud
Types of cells - Taste cells & other supporting cells
Outer tips of cells at taste pore
Microvilli called ‘taste hair’ project into taste pore
Stimulation of taste
afferent fibres
Taste chemicalgrdually washed away from the
taste villus by saliva (stimulus removed)
o Cortical centers are anterior insula and the overlying Frontal Operculum.
o Lies close to the area of tactile sensation from tongue
o Lesions produce Unilateral loss of taste
Taste Reflexes
Ascending taste signals produce reflex secretion of saliva
Integrated in brain stem
Connection of NTS with superior and inferior salivatory nuclei
Efferents via CN VII and VIII
Stimulate secretion of saliva from parotid, sublingual and submandibular glands
Adaptation
Adaptation to taste occurs rapidly
About half of adaptation occurs in taste buds
The rest occurs in CNS –mechanism not well understood
Taste threshold
Different substances have different thresholds
Intensity discrimination is crude – needs ~ 30% change in concentration in order to detect a
change
Flavour
Mainly synthesized from 5 tastes combined with other sensations such as smell, pain,
temperature, Consistency & texture ( hot chillie sauce, crunchy chips, ice cream, hot tea)
Olfactory pathway
Inhibition
Periglomerular cells
& Granular cells
cAMP
Phospholipase C
products of phosphatidyl inositol hydrolysis
Depolarization of membrane
Olfactory Bulb
Lies over the cribriform plate
Contain discrete synapses – Olfactory glomeruli
o Each glomeruli respond to specific smell
o Consist of Axons of Bipolar cells & Dendrites of mitral & tufted cells
o Each bipolar cell project axons in to 1 or 2 glomeruli
o Axons of mitral and tufted cells transmit signals to higher levels of CNS
Peri-glomerular cells – inhibitory interneurons connecting glomeruli
o Stimulated by mitral or tufted cell ( glutamate)
o Reciprocally inhibits mitral or tufted cell ( GABA )
Granule cells – make reciprocal connections between mitral & tufted cells
Lateral inhibition by Peri-glomerular cells & Granule cells ‘sharpen’ & focus olfactory signals
Olfactory cortex
Piriform cortex – 1ry olfactory cortex
Lateral & frontal orbitofrontal gyri – Olfactory discrimination
Amygdala – emotional responses to stress
Entorhinal cortex – Olfactory memories
Olfactory threshold
Increase with age
Methyl mercaptan can be smelled when concentration reaches 1/25 trillion g/ml
Poor ability to detect change in intensity of odorants
30% change in concentration needed before difference detected ( vision – 1% change in
intensity detected )
Concerned with detecting qualitative ( presence / absence ) aspects rather than
quantitative aspects of smell
Occurs at,
Receptor level – Calmodulin binds to receptor and inactivates
Central level – Efferents from CNS stimulate granule cells – feedback inhibition
Vomeronasal organ –
Signal transduction
Complex odor discrimination Perception of odors
About 10-20 million odorant receptors that act as
One type of olfactory receptors project into one pheromones.
Olfactory glomerulus Closely related with
Each olfactory neuron carries only one odor. sexual function
Lateral inhibition by periglomerular & granule cells.
Poorly developed in
Abnormalities human
Smell more in women
Taste
Ageusia – absence of Smell
taste sensation Anosmia – inability to smell
Hypogeusia – diminished Hyposmia / Hyper-osmia –diminished / enhanced olfactory
taste sensitivity sensation
Dysgeusia – unpleasant Dysosmia –distorted sensation of smell
perception of taste / Many olfactory genes for different receptors
altered taste sensitivity - Absence of genes – Odor blindness for single substance
T/F
a) Monosodium glutamate is used as an artificial sweetener
b) Receptors for bitter taste are localized to the posterior aspect of the tongue
c) Taste fibers relay in the nucleus of tractus solitarius
d) Taste perception has a high intensity of discrimination
e) Vagus carries afferent from taste receptors
3 chambers
– Anterior
– Posterior
Functional anatomy – Vitreous
Separated by 2 groups
– Iris
– Zonule and lens
2 types of fluids
Aqueous humour
Vitreous humour
Aqueous humour
Ganglion cells are the only output of retina, and their To Optic
Nerve
axons form the optic nerve Light
Optic Cup
Rhodopsin
α
β Transducin
Opsin Retinal ( in the center ) GDP γ
Regenerate Rhodopsin
Dark adaptation
Moving from brightly lit area to a dimly lit area / Red goggles
In sudden darkness, o Wavelenght of red light,
Difficult to see until rhodopsin is increased & the o Allow cones to work well
sensitivity of retina is increased o So provide good vision in
Retina slowly becomes more sensitive to light. bright light
Threshold sensitivity of rods is decreased o But don’t stimulate rods
This decline in visual threshold is called Dark significantly Thus, time for
adaptation dark adaptation is reduced.
Takes time Night blindness
Sensitivity is nearly maximal after 20 min. o Caused by decreased vit. A
Light adaptation level
When suddenly moving from dark to bright light, o Inadequate reforming of
light seems to be to bright ( as in cinema) rhodopsin from retinal
Improves in about 5 min when pigments o Difficult to see at night
breakdown and sensitivity of retina is decreased o But during daytime cones can
Due to disappearance of dark adaptation. still be excited preserving
Visual threshold rises daytime vision
Occurs over 5 mins.
Reaches cortex
Refraction
Optic chiasma
o Light rays from objects > 6m away are considered to be parallel
Optic tract
Optic radiation
Visual cortex
Strabismus (squint)
Visual images do not fall on corresponding retinal points. (Misalignment of eyes)
Chronic –
one visual image If not corrected before age 6 Permanent loss of vision in one eye
is suppressed (In children)
(Cortical effect) So vision remains only in one eye
Amblyopia
Refractive error in image is blurred Decreased vision in affected eye
one eye & distorted (permanent) & person starts seeing
with the other eye
Short cilliary
nerve
Right
D
B
Left
A
Heteronymus
B Hemianopia
(can be left or right)
A
Homonymus
C Hemianopia (can be
binasal or bitemporal)
Quadrantic defects
D ( can involve any of 4
quadrants )
Scotoma
A-Total blindness of right eye – damage to right optic nerve
F
B-Bitemporal hemianopia – damage to optic chiasma
C-Left Homonymous hemianopia – damage to right optic tract
D- Left upper quadrant hemianopia / left upper quadrontopia
( Spots of blindness )
E- Left homonymous hemianopia with macular sparing
Damage to Result
Right optic nerve total blindness of Right eye
Optic chiasma Bitemporal heteronymous hemianopia
Right optic tract Left homonymous hemianopia
Right geniculo-calcarine tract Left homonymous hemianopia
Right Visual cortex Left homonymous hemianopia with macular
sparing
Cortical areas
Primary visual cortex ( Occipital cortex / V1 ) –
o Point for point representation of retina & LGB
o Segregate information about colour, form & movement
o Combines information from 2 eyes
But there are other areas
Secondary visual cortex ( V2 )
Tertiary visual cortex ( V3 & V4 )
They involved in –
o Motion, Control of movement, Recognition of large objects, Colour vision etc.
Red
Primary colours Green
Blue
Young-Helmholtz theory
3 kinds of cones with 3 pigments
Each have a different photo pigment maximally sensitive to one of the primary colours.
Colour perception determined by relative frequency of impulses from different cones.
colour vision depend on colour of other objects in visual field
Human eye can see any colour due to combination of red, green, blue in different
propotions
Colour blindness
Blind site –residual response to visual stimuli after bilateral destruction of occipital cortex
Visual acuity
Charity / sharpness of vision
The degree to which details and colours of objects are perceived
Definition - Shortest distance by which two lines can be separate & still be perceived as two
lines.
Visual acuity assessmet is done by using Snellen chart
Mechanism of Hyperpolarization
Cells get depolarized Stereocilia are pushed toward the opposite
direction of the kinocilium
Depolarizes afferent neurons Tension of tip links reduce
(Glutamate maybe the neurotransmitter released by hair Cation influx reduces
cells) Cells get hyperpolarized
Glutamate discharge is reduced
Sound conduction
1. Ossicular conduction – transmission of sound via tympanic membrane, ossicles to cochlea via oval window
(most efficient) – Main pathway
2. Bone conduction – transmission of sound via bone to inner ear
3. Air conduction – by vibrating secondary tympanic membrane of round window ( Not important for normal
hearing)
Middle ear
● Pressure of Sound is multiplied by 22 times. ( 1.3 × 17 )
1. Lever action of ossicles (by 1.3 times) – amplitude of incus movement > amplitude of stapes mov.
2. Surface area difference of tympanic membrane and oval window ( by 17 times )
● Middle ear muscles
1. Tensor tympani – Attached to handle of malleus
Pulls malleus medially / pulls tympanic membrane medially - vibration of tym.
2. Stapedius – Attached to stapes membrane
Pulls stapes laterally out of oval window
Both are skeletal muscles
When these contract, ossicles become rigid & vibration.
Tympanic reflex
Cochlea
Perilymph Endolymph
↑[Na+] ↓[K+] ↓[Na+] ↑[K+]
Basilar
Bony labyrinth communicate with CSF space via membrane
cochlear & vestibular ducts.
Basilar membrane
Basilar membrane has Tonotopic arrangement.
- Spatial arrangement where sound of similar frequencies
are represented in neighbouring regions.
Basilar membrane contain basilar fibers.
- Length - from base to apex of cochlear
- Diameter - from base to apex of cochlear
Organ of Corti o Reticular lamina –
Lying on entire length of basilar membrane Solid surface at the top of the hair cells
So the top of the hair cells are in endolymph &
Inner / Internal hair cells –
bottom of the hair cells are in perilymph
● Single row of cells. Less numerous.
Hair fixed in rigid reticular lamina
● Primary receptor cells
● Majority of afferents of the VIIIth Nerve 1. Perilymph - 0 mV
● Tips are not embedded in the 2. ICF - (-) 70 mV relative to perilymph
tectorial membrane. 3. Endolymph - + 80 mV relative to
Bent by fluid movement perilymph
4. ICF at (-) 150 mV relative to endolymph
External / Outer hair cells – ( Cochlear amplifier ) 5. Therefore high potential diference
● 3 – 4 rows of cells between haircell apex & endolymph
● Majority ( 90% ) of efferents from the VIII th Cranial Nerve 6. Results in sensitivity of hair cells
(From Olivo - cochlear bundle)
● Efferent impulses modulate sensitivity of the hair cells. + 80 mV
● Help in increasing amplitude
Apex
● Increases clarity of sound
● Tips are embedded in the Tectorial membrane ICF - (-)70 mV
- Depolarization - cell length moves tectorial Base
- Hyperpolarization - cell length membrane 0 mV
Hair cell
Hearing deficits
Hearing deficits
Hearing tests
o In Rinne test Positive means
normal ( only here )
Auditory reflexes
Involuntary responses to sound that are mediated by branches from the
main auditory pathway
Auditory palpebral reflex - blink / eye closure in response to sudden loud noise
Auditory occulogyric reflex - eye deviation towards sound
Cochleopupillary reflex - pupillary dilation or contraction followed by dilation in
response to a loud noise
Useful in assessing hearing in children, those with altered mental status
or those who are malingering
Linear Acceleration
CaCO 3 crystals ( Otoliths / Statoconia / Ear dust )
embedded in gelatinous layer
Otoliths are denser than endolymph
When linear acceleration occurs in one
direction, the otolith displaces to the
opposite direction of acceleration due to
greater inertia.
This bends the processes of the hair cells
and generates action potentials.
These are recognized by brain.
Rotational Acceleration
Mechanism of Action
If rotating in opposite direction - Cupula pushed towards the opposite direction than what it used to before -
Hair cells hyperpolarize.
Central connections
1. Vestibular nerve fibers ( VIII th nerve ) – most terminate in medial & lateral vestibular nuclei at the junction between
medulla & pons
2. 2nd Order fibers pass to Medial Vestubulospinal – down to mid thoracic
● Vestibulocerebellar –Balance level ( neck & shoulder muscles )
● Vestibulospinal*– Send impulses to α & γ motor neurons & Lateral Vestibulospinal – Throughout the cord
facilitates tone of ( extensors ) antigravity muscles
● Vestibulothalamocortical –Conscious awareness of position & movement of head
● Vestibulo-ocular pathway – medial longitudinal fasciculus – Co-ordinate eye & head movements
● Reticular nuclei in brain stem
● Cerebral cortex – parietal lobe ( deep in sylvian fissure )
Vestibulo-ocular reflex
Stimulation of vestibular receptors evokes eye
movements of equal magnitude in the direction
opposite to movement of head to maintain the visual
field.
( keep retina focused on same visual field )
Mediated by the coordination of VIII th , VI th and III rd
Cranial nerves through the medial longitudinal
fasciculus
Equilibrium – Other inputs
Vestibular system – movement & position of the
head
Information needed from other areas of body
Proprioception ( esp.neck ) – informs if head moving independently / together with rest of the body
Vision
Cutaneous exteroceptors – touch / pressure ( esp.foot pads, pressure on front of body
Cerebellum
Physiological Nystagmus
Nystagmus is a reflex that maintains visual fixation on a stationary point when head rotates.
It can be divided into a slow and fast component
SLOW COMPONENT
When head rotation starts the eyes move together slowly in a direction opposite to that of head rotation
maintaining a visual fixation. ( Vestibulo-Ocular reflex ) – by vestibular labyrinths
FAST COMPONENT
When the limit of this movement is reached, the eyes quickly snap back / rapid adjustment to a new fixation
point – by brainstem nuclei
By convention, the direction of Nystagmus is considered to be the direction of the fast component.
Observed transiently as soon as rotation of head stops ( normal phenomenon )
Pathological Nystagmus
Pathological nystagmus is when nystagmus occurs when the head is not rotating.
Occurs due to abnormalities in the vestibular system
Caused by persistent stimulation of hair cells
Seen in damage to Vestibular system & cerebellum
Can be elicited by caloric testing
Caloric Test
- C O - Cold water induces nystagmus to the opposite direction than the ear to
which water was instilled. / away from the stimulus
- W S - Warm water induces nystagmus to the same direction / toward the stimulus
In unilateral vestibular damage - Nystagmus reduced / absent on affected side
When irrigating the ear – water at body temperature must be used to avoid
Nystagmus & Vertigo
Vertigo
Sensation of rotation in the absence of rotation due excessive stimulation of the vestibular system.
Eg – Labyrinthitis
Bening paroxisomal positional vertigo – thought to be due to displacement of otoliths
Motion sickness
Due to prolonged and excessive stimulation of the vestibular system.
During motion & when conflicting information is fed into vestibular & other sensory systems
• Ring electrodes are placed on index finger which receives sensory fibres from median nerve
𝐷𝑖𝑠𝑡𝑎𝑛𝑐𝑒 𝑏𝑒𝑡𝑤𝑒𝑒𝑛 stimulating 𝑎𝑛𝑑 recording 𝑒𝑙𝑒𝑐𝑡𝑟𝑜𝑑𝑒𝑠
Conduction velocity =
Latency
Electromyography
Identification Increased in
Neutrophil Nucleus with 3-5 lobes, granulated Bacterial infection (Acute)
(decreased – viral infection, TB)
Eosinophil Nucleus with 2 lobes, reddish orange Chronic hypersensitivity – asthma,
staining with granules parasitic infections
Basophil Highly dense granules, deep blue or purple Immediate hypersensitivity – allergy
granules, small marginal cytoplasm Viral infection
Malignant disease
Monocyte Kidney shaped nucleus, non-granulated Bacterial infection (chronic)
cytoplasm Malignant disease
Lymphocyte Large round nucleus, thin non-granulated Viral infection, chronic lymphocytic
cytoplasm leukaemia
(decreased: AIDS, lymphocytopenia)
Eosinophil
RBC
Platelets Neutrophil
Lymphocyte
Basophil
Monocyte
➢ Macrohaematocrit method
• Items needed – Wintrobe tube, Anticoagulant (1.5%
EDTA), Centrifuge
• Blood: EDTA ratio = 10:1
• Reading – Fraction or Percentage of the volume of
the red cell column out of the total blood volume
• Reading is expressed as a percentage. (%- no unit)
• when taking the reading buffy coat should be excluded
• Precautions
✓
Haematocrit should be determined ideally within 6 hours
of collection of blood.
✓
Blood sample should not be haemolysed as it will yield
falsely low results.
✓
Anticoagulant volume should not affect the total blood
volume.
✓
Air bubbles should not be included in the tube
Wintrobe tube
➢ Microhaematocrit method
• Items needed – capillary haematocrit tube (heparinised), micro haematocrit reader, micro
haematocrit centrifuge, anticoagulant Heparin
• Precautions
• When aligning the height of the plasma column, get the lower margin of the meniscus of the
plasma column.
• Exclude the buffy coat when aligning the height of the red blood cell column.
1.Newborn : 0 - 2 mm/hour
2. Children : 3 -13 mm/hour
3. Women
range for ages 18 to 50 years : 0 - 20 mm/hour
range for ages > 50 years : 0 - 30 mm/hour
Normal maximum = (Age in years+10)/2 mm/hour
4. Men
range for ages 18 to 50 years : 0 - 15 mm/hour
range for ages > 50 years : 0 - 20 mm/hour
Normal maximum = (Age in years)/2 mm/hour
• ESR increase with age, females > males, pregnancy (due to increase in fibrinogen concentration)
• Increased in – severe anaemia, tuberculosis, rheumatic fever, malignancies, osteomyelitis, Renal
diseases (e.g. end stage renal failure, nephrosis), Gastrointestinal diseases (e.g. Cholecystitis,
peritonitis, acute pancreatitis)
• Decreased in – polycythaemia, red blood cell abnormalities e.g. spherocytosis & sickle cell
anaemia, protein abnormalities, severe leucocytosis
• Heparin should not be used as an anticoagulant as it alters the zeta potential of RBCs.
• The tube should not be kept in direct sunlight or path of draughts, surface on which the stand is
kept should be flat, horizontal and should not vibrate.
• Advantages
✓ Inexpensive and easy to perform
• Disadvantages
✓ Fresh blood samples are required.
✓ Low sensitivity and specificity.
• Slide method;
❖ Clumping of RBC observed after adding antisera
❖ Anti A- Blue Anti B- Yellow Anti D – colourless
Centrifuge Centrifuge
Observe Observe
Tube method
Items needed – Haemocytometer (counting chamber), microscope, cover slip, mouthpiece, lancet,
cotton wool, surgical spirit
• For RBC counting – RBC pipette (red colour ball inside) is filled with blood and RBC counting fluid.
This fluid lyses WBC. (1:200 dilution)
• For WBC counting – WBC pipette is filled with blood and WBC counting fluid. (this fluid lyses RBCs).
(1:20 dilution)
RBC pipette
WBC pipette
• Bleeding time is the time taken to stop bleeding from small subcutaneous vessels which have
been severed by a standard lancet.
• Tests vascular response (vasoconstriction) and platelet response (platelet plug formation)
• Items needed – circular filter paper, stopwatch, standard sterile blood lancet
• Reading – I min + (no. of gaps x 30s)
• Normal range – 1 – 5 minutes
• Increased in
✓ Thrombocytopenia - reduction in platelet
count E.g. Dengue fever, bone marrow
malignancies
✓ Thrombasthenia - abnormality of platelet
function.
3. Spirometry
o Is a method of studying pulmonary ventilation by recording the movement of air
in and out of the lungs.
• VC-Begins with full inspiration but the patient is asked to exhale fully but slowly.
• FVC- Same except the patient has to exhale as fast as and hard as he/she can.
• In healthy individuals, there is no/little difference in volume vise.
Voluntary hyperventilation
• After hyperventilation
Period of apnoea shallow breathing Period of apnoea shallow
breathing
This happens periodically until PACO2 level becomes normal.
1. Electrocardiogram (ECG)
ECG waveforms
Pulse
• Rate
• Rhythm
• Volume
• Character
• Radio-femoral delay coarctation of aorta
• Arterial Pulse
Central pulse – recorded in arteries close to the aorta.
Eg: Carotid, Femoral
Peripheral Pulse – recorded from distal arteries
Eg: Radial, Dorsalis pedis
• <60/min – bradycardia
• >100/min - tachycardia
1. The patient should either be seated or lying comfortably. He should have rested for
at least 3 minutes prior to blood pressure measurement.
2. The sphygmomanometer is placed at the same level of the cuff on the patient’s arm
and the observer’s eye level.
3. The arm should be horizontal and at the heart level.
4. The center of the bladder should be positioned over the line of the artery.
5. Feel the patient’s brachial (or radial) pulse and inflate the cuff to a pressure above
which pulse can no longer be felt.
The point of disappearance of pulse represents the systolic pressure.
6. Place the stethoscope gently over the brachial artery.
7. Inflate the cuff further to raise the pressure to 30 mmHg above the systolic blood
pressure as estimated by palpation.
8. Deflate the cuff at 2-3mmHg per second, listening carefully to the appearance of
Korotkoff sounds.
• Phase 1
Appearance of tapping sound
Indicates systolic pressure
• Phase 2 and 3
Sounds get louder as more blood enters brachial artery
• Phase 4
Sounds become muffled
• JVP is the pressure exerted on internal jugular vein during cardiac cycle.
• Assessed from visible wave form of the internal jugular vein.
• Only seen, not felt.
•
• JVP is an indirect measure of central venous pressure (CVP) which is the pressure
in the great veins at their entrance to the right atrium.
Important,
• Volunteer lies on a bed with the head end raised to 450 angel.
• Measure the vertical height between the highest level of internal jugular vein
pulsations and sternal angel. This value in cm H2O is JVP.
• To obtain CVP, add 5cm to the measurement since right atrium lies 5cm below
the sternal angle.
• Items required:
1. Bicycle ergometer (To perform the isotonic exercise)
2. Hand dynamometer (To perform the isometric exercise)
3. Stop watch
4. Mercury thermometer
5. Measuring tape
6. Stethoscope
7. Sphygmomanometer
Hand dynamometer
Bicycle ergometer
•
• Results in isometric exercise
Respiratory 14 20 15
rate(breaths/min)
1. Pulse rate: heart rate increases in both types of exercises from the beginning by decreasing
parasympathetic stimulation on SA node.
2. Blood pressure:
In isotonic exercises- systolic blood pressure increases as CO increases. But vasoactive
metabolites cause vasodilatation resulting decreased diastolic blood pressure.
After exercise BP may fall transiently (persistent vasodilation by metabolites while the CO
has decreased).
In Isometric exercises systolic and diastolic blood pressure sharply increased. Compression
of vessels leads to increased diastolic blood pressure.
4. Oral temperature: Total heat production of the body exceeds increased total body heat
dissipation. So, core temperature will increase in both exercises.
5. Calf circumference:
• Fluid transudation to interstitial fluid increases. Despite of increased lymph
flow, calf circumference still increases in both types of exercises
• Dilation of blood vessels.
20
30
40
50
Refractometer
• Digital machine
• Can display the osmolality of an unknown sample when calibrated by a known sample.
• Urine osmolality can be varied from 50 mOsm/kg – 1400 mOsm/kg.
Urine analysis
1. Macroscopic examination
This includes assessment of
• Quantity - volume or amount of the urine
• Colour - normal urine ranges from colourless, pale yellow to amber
• Appearance - normal urine is clear or slightly cloudy
2. Microscopic examination
• Take a urine sample a. Types of casts
• Then centrifuge it. ▪ Hyaline, red cell, white cell, epithelial
• Discard the fluid at the top cell casts
• Examine the drops of fluid remaining b. Types of crystals
in the bottom under microscope ▪ Calcium oxalate, triple phosphate urate
• Cells, crystals and casts are observed crystals
and reported as number observed c. Types of cells
per low power field (LPF) or high- ▪ RBCs, WBCs, epithelial cells
power field (HPF).
1. Examination of muscles
• Inspection
Inspect the muscles for
Wasting
Fasciculations
Abnormal movements
And Skin for scars
Tremors
• Upper Limb
Biceps jerk (C6)
Tendon hammer
Triceps jerk (C7)
Brachioradialis jerk (C5, C6)
• Lower limb
Knee reflex (L3)
Ankle reflex (S1)
Plantar response
Planter response
4. Examination of gait
Observe for posture, base, length of strides and speed arm swing, symmetry, balance and any
abnormality
4. Facial nerve
• Inspect for facial asymmetry
• Motor examination
• Test for weaknesses in
Raising eyebrows and observe for loss of
wrinkling
Sensory areas which are checked
Closing eyes tightly
when examining the divisions of
Blowing cheeks out trigeminal nerve
Showing teeth
6. Accessory nerve
• Ask patient to shrug the shoulders against resistance (Trapezius)
• Ask patient to turn the head to the side against resistance (sternocleidomastoid)
7. Hypoglossal nerve
• Ask the patient to protrude the tongue
• Inspect for tongue atrophy, fasciculations or asymmetry in movement.
o Damage to lower motor neuron
Atrophy, fasciculations
Deviation of tongue to affected side o Damage to upper motor
neuron
Deviation of tongue away from the affected side
Vision
1. Visual acuity
a. Visual acuity is the shortest distance by which two lines can be separated
and still perceived as two lines.
1. Confrontation method
2. Perimetry
Perimetry is mapping the peripheral visual fields using a perimeter that flashes lights
randomly at various points in the visual field.
Important: During the test, bring the light to the front of patient’s eye from the side to
avoid discomfort.
1 Both direct and consensual reflexes Both direct and consensual light reflexes
are lost. are present.
3 Both direct and consensual reflexes Both direct and consensual light reflexes
are present. are present.
1. Accommodation
2. Convergence of visual axes
3. Pupillary constriction
2. Sensorineural deafness
Ex: i. Damage to hair cells, cochlear nerve or/and organ of Corti.
ii. Acoustic neuroma
iii. Hereditary defects
iv. Infections, Inflammations (mumps, meningitis)
v. Transverse facture of the petrous temporal bone
Hearing tests