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Podmedics LIVE - Clinical Pathology Course
Podmedics LIVE - Clinical Pathology Course
Clinical Pathology
Course
1! © Podmedics 2009
Podmedics LIVE - Clinical Pathology Course
Welcome to our notes for the Podmedics LIVE Clinical Pathology course. The course is available to watch on
our website Podmedics.com and covers basic principles of illness and disease across all the specialties. It
would be relevant to students at all stages of their clinical training.
This course was originally designed as a revision course for the Year 5 Clinical Pathology exam at Imperial
College School of Medicine in London, and it ran at the college for two years to great acclaim. This year
however I have decided to re-record the whole course for use on the website. Do have a browse through the
notes to see what topics exactly are being covered.
These revision notes are not meant to be totally comprehensive, but include lots of space of you to fill in
while you watch the online lectures.
Podmedics.com
The course has been written by Ed Wallitt, an ex-ICSM junior doctor, who founded Podmedics.com in August
2007. For those of you who are unfamiliar with the site, Podmedics.com is a website and podcast developer
run by a group of junior doctors and medical students. All our podcasts are free, and aimed specifically at
medical students. Our ethos is to outline key medical principles and concepts that allow material
encountered in the lecture theatre and hospital to be better understood, and ultimately recalled.
There are currently well over one hundred audio and video podcasts available, either through iTunes or
direct from our website. Please do not hesitate to get in contact with me, or any of the other Podmedics, if
you have any further questions.
Ed Wallitt
(ed@podmedics.co.uk)
2! © Podmedics 2009
Podmedics LIVE - Clinical Pathology Course
Table of Contents
Haematology! 4
Anaemia! 4
Haemostatic Disorders! 7
Haematological Malignancy! 10
Chemical Pathology! 17
Fluid balance! 17
Electrolye Disorders! 19
Fluid Analysis! 25
Immunology! 29
Immunodeficiency! 29
Allergy! 33
Autoimmunity! 35
Immunology of Transplantation! 37
Therapeutics in Immunology! 38
Microbiology! 39
Anti-Microbial Therapy! 41
3! © Podmedics 2009
Podmedics LIVE - Clinical Pathology Course
Haematology
Classical Signs
Anaemia Conjunctival pallor
Koilonychia
Glossitis
Definition: “[Hb] < reference range for age, sex and gender of an individual.” Angular stomatitis
Post-cricoid webs (Plummer-
• Men < 13.5 g/dl, Women < 11.5 g/dl Vinson Syndrome)
High-flow murmur
↓ vitamin B12
↓ folate
Bone marrow
infiltration
Myelodysplasia
Anaemia of
chronic disease
4! © Podmedics 2009
Podmedics LIVE - Clinical Pathology Course
2. Increased Destruction
1. INHERITED DISORDERS
Spherocytosis
Elliptocytosis
G6PD
Sickle cell
Thalassaemia
5! © Podmedics 2009
Podmedics LIVE - Clinical Pathology Course
2. ACQUIRED DISORDERS
Target Examples
Target Examples
TTP
Valves
6! © Podmedics 2009
Podmedics LIVE - Clinical Pathology Course
Haemostatic Disorders
1. Vasoconstriction
2. Formation of a loose platelet plug
3. Stabilisation through clotting cascade
4. Fibrinolysis
Factors Investigations
Bleeding Disorders
Platelets Coagulation
Petechiae Yes No
Haemarthrosis/ No Yes
muscle
7! © Podmedics 2009
Podmedics LIVE - Clinical Pathology Course
1. Platelet Problem
Acute
Chronic
2. Clotting Problem
Haemophilia
vWD
Liver disease
Vitamin K
deficiency
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Podmedics LIVE - Clinical Pathology Course
Thrombotic Disorders
Hypercoagulability
VIRCHOWʼs
Thrombophilia Features
Factor V Leiden
Prothrombin
G20210A
Protein C deficiency
Protein S deficiency
Anti-thrombin
deficiency
ACQUIRED
9! © Podmedics 2009
Podmedics LIVE - Clinical Pathology Course
Haematological Malignancy
Basic Principles
Mechanism Examples
Translocation
Deletion
Duplication
Point mutation
Definitions:
Aetiology/Contributing factors
Examples
Viruses HTLV-1
The Leukaemias
ALL
AML
CLL
Myelodysplastic Syndromes
“Various syndromes characterised by bone marrow failure due to abnormal myeloid haematopoiesis.”
Features
Investigations
•
•
Lymphoma
HIGH GRADE: aggressive
but potential for cure
1. Hodgkinʼs Lymphoma
LOW GRADE: indolent but
difficult to cure
• Reed-Sternberg cell
• B lymphocyte lineage with characteristic owl eye appearance.
2. Non-Hodgkinʼs Lymphoma
1. B cell (85%)
2. T cell/NK cell (15%)
Important features:
Multiple Myeloma
Important features:
• Fatigue/malaise/anorexia/weight loss
• Bone pain (vertebral collapse)
• Features of hyercalcaemia - “Bones/stones/groans/moans”
• Features of hyperviscosity - Visual loss
Diagnostic findings:
Myeloproliferative Disorders
Polycythaemia RBCs
rubra vera
Essential Platelets
thrombocythaemia
Myelofibrosis
ESR
May be influenced by:
• This measures the “sedimentation rate of blood cells.”
• Normal < 20 mm/hr [women > men] a. Red blood cells
• Severe anaemia
Porphyria
NEUROVISCERAL
CUTANEOUS
• Diagnostic findings:
• ↑ urinary ALA & PBG (urine looks like port)
• Diagnostic findings:
• ↑ urinary uroporphyrins and coporoporythins
IMMEDIATE (<24h)
Wrong blood
Febrile non-
haemolytic reaction
TRALI
Bacterial infection
Fluid overload
DELAYED (>24h)
Post transfusion
purpura
Delayed haemolytic
transfusion reaction
GVHD
Iron overload
Chemical Pathology
Fluid balance
1. CATIONS
• Intracellular = K+
• Extracellular = Na+
2. ANIONS
• Intracellular = protein and phosphate
• Extracellular = Cl- and HCO3-
Starling Forces:
CHARGED + UNCHARGED
∴ (Na++K++Cl-+HCO-) + (urea+glucose) = 2(Na++K+) + urea + glucose
The osmol gap is the difference between calculated and actual osmolalty.
INPUT OUTPUT
Lungs 0.5L
TOTAL 3L 3L
1) Water deficit/excess
2) Salt deficit/excess
TOO MUCH
FLUID
TOO LITTLE
FLUID
Electrolye Disorders
Syndrome of Inappropriate ADH secretion
i. HYPOVOLAEMIC
1. Hypokalaemia
iii. HYPERVOLAEMIC
i. Reduced intake
2. Hyperkalaemia
2. Hypernatraemia
i. Increased intake
• Common causes:
ii. Cellular loss/redistribution
• Insufficient fluid intake
• Water loss increased relative to iii. Decreased loss
sodium loss (e.g. diabetes insipidus,
osmotic diuresis, sweating)
Calcium
Causes Features Rx
HYPO-
HYPER-
a. ACID-BASE BALANCE
b. GAS EXCHANGE
BASIC EQUATION
a. The GFR
b. The urine dipstick + microscopy
THE GFR
• 60 - 120 ml/min
• Varies
"
Urine Dipstick/Microscopy
Crystals
Divide into:
• LIVER DAMAGE
• Destructive
• Obstructive
• FUNCTION
• Albumin
• Clotting
(AST/ALT)
ALP
ϒ-GT
Jaundice
Crigler-Najjar
Gilbertʼs
Dubin-Johnson
Rotor
Endocrine Investigations
Cushingʼs
syndrome
Connʼs syndrome
Addisonʼs disease
Thyroid disease
Fluid Analysis
Clinical manifestations
Blood Proteins
• REDUCED SYTHESIS
• DISTRIBUTION
• INCREASED LOSS
Cerebrospinal Fluid
CRP
α-1 anti-trypsin
Transferrin
Caeruloplasmin
Ferritin
Haptoglobin
β2-microglobulin
PSA
AFP
CA19.9
CA125
CEA
β-HCG
FAT SOLUBLE
VITAMINs
E Anaemia/neuropathy Serum
Tocopherol (e.g. abetalipoproteinaemia)
K Defective clotting PT
Phytomenadione
WATER SOLUBLE
VITAMINS
Niacin Pellagra
TRACE
ELEMENTS
“Metabolic disorder”
• “A disorder in which there is a defective gene for a crucial enzyme involved in intermediary
metabolism.”
• Build-up of precursors
• Lack of product
Over 650 diseases that together account for 40% of deaths in the first year of life.
• Most common is PKU (screened for)
Amino acid disorders Autosomal recessive defect PKU (↑ phenylalanine) Failure to thrive
in metabolism of single amino Homocystinuria (↑ Seizures
acid Musty skin odour
Lysosomal storage Various defects in lysosomal Gauncher’s disease Present late (adulthood)
disorders function that lead to Niemann-Pick disease
accumulation of toxic Tay-Sachs disease
substances
Immunology
Immunodeficiency
1.
2.
3.
4.
X-linked
aggammaglobulinaemia
IgA deficiency
Wiskott-Aldrich
syndrome
CVID
T cell deficiencies
DiGeorgeʼs
Bare L syndrome
Wiskott-Aldrich syndrome
Ataxic telangiectasia
SCID
Phagocyte deficiencies
Leukocyte Adhesion
Deficiency (LAD)
Chronic
Granulomatous
Disease (CGD)
Kostmannʼs syndrome
(KS)
Cyclic neutropenia
Complement deficiencies
To understand these deficiencies you need to first remember the basic complement pathway. Draw a
diagram here
C3a, C5a
C3b
C5-9
• Total C3 & C4
Allergy
Before talking about allergy and autoimmunity it is important to understand the Gel and Coombs
classification:
Type I IgE-mediated
hypersensitivity
Allergic disease comprises a number of different conditions throughout medicine e.g. asthma, anaphylaxis,
seasonal allergies, rhinitis.
Diagnosis of Allergy
Allergic Diseases
Anaphylaxis
Food allergy
C1 inhibitor deficiency
Autoimmunity
Autoimmunity is “an immune reaction that produced tissue damage due to a reaction against self-
protein”.
SLE HLA-DR3
2. Peripheral tolerance loss
Diabetes Type I HLA-DR3/4
ORGAN-SPECIFIC:
NON-ORGAN SPECIFIC:
SLE
Drug-induced lupus
Sjogrenʼs
RA
Scleroderma
• Diffuse
• Limited/CREST
Dermatomyositis/
polymyositis
Wegnerʼs
granulomatosis
Polarteritis nodosa
Coeliac disease
Pernicious anaemia
Graveʼs disease
Hashimotoʼs thyroiditis
Diabetes Mellitus
Autoimmune hepatitis
Mixed Connective
tissue disease
Anti-phospholipid
syndrome
Immunology of Transplantation
Hyperacute rejection
Acute cellular
rejection
Acute vascular
rejection
Chronic allograft
rejection
Therapeutics in Immunology
There are essentially 3 ways that you can manipulate the immune system.
1. SUPPRESS IT
2. BOOST IT
3. DEVIATE IT
Immunosuppression is not however without complications, the most important ones are below:
• Infection
• Malignancy
• Atherogenicity
Steroids Prednisolone
Hydrocortisone
Dexamethasone
Anti- Azathioprine
proliferative
agents
Cyclophosphamide
Mycophenylate
mofetil
Tacrolimus
Anti-cytokine Infliximab
agents
Etanercept
Adalimumab
Microbiology
Bacteria
2. BACILLI
3. BRANCHING
2. BACILLI
3. COMMA-SHAPED
Spirals 1. BORRELIA
2. TREPONEMA
3. LEPTOSPIRA
Cell wall
deficient
Viruses
• DNA VIRUSES
• RNA VIRUSES
• RETROVIRUSES
Fungi
• EUKARYOTES that are classified according to their appearance (e.g. hyphae, yeasts, moulds and
dimorphics).
Parasites
• Unicellular EUKARYOTES:
Anti-Microbial Therapy
Anti-virals
HIV “HAART”
2 NRTI + NNRTI/PI
Target Examples
Aciclovir
• A nucleoside analogue that inhibits viral DNA polymerase (activated by viral thymidine kinase).
- Myelosuppression -
Ganciclovir
Pregnancy Myelosuppression -
Antibiotics
Glycopeptides Vancomycin
Teicoplanin
Carbapenems Imipenem
Monobactams Aztreonam
Tetracycline Tetracycline
Doxycycline
Macrolides Erythromycin
Clarithromycin
Others Chormapheicol
Fusidic acid
Others Metronidazole
Trimethoprim
Rifampicin
Sulphonamides
1. Penicillins
• Very useful against Gram +ve (some have additional Gram -ve cover).
• 4 major types
4. Anti-pseudomonal penicillins
• Pipericillin + Tazobactam = Tazocin
Anaphylaxis
Nausea/vomiting
2. Cephalosporins
There are 3 generations whose Gram -ve activity becomes greater as you ascend...
Ceftazidime Anti-psudomonal
Adverse reactions
Bleeding
Thrombophlebitis
3. Glycopeptides
! e.g. vancomycin (IE/MRSA/C. difficile), teicoplanin (bad gram +ve infections)
• These agents are generally active against aerobic and anerobic Gram +ve
Thrombophlebitis
4. Carbapenems
" e.g. imipenem, meropenem
• These agents have a very wide broad specture against Gram +ve and Gram -ve
• Best single choice for nosocomial infection
Nausea/vomiting
Seizures
Aminoglycosides
! e.g. gentamicin (topicals, 2nd line in severe Gram -ve infection), streptomycin (resistant TB)
• These are agents that inhibit protein synthesis through binding to the 30S ribosome.
• They are inactive orally.
Thrombophlebitis
Tetracycline
! e.g. tetracycline (acne), doxycycline (chlamydia, lyme disease, anthrax)
• These are relatively broad specturm agents that have particular action against intracellular organisms
Macrolides
# e.g. erythromycin (good respiratory antibiotics, useful in penicillin-allergic), clarithromycin (more
potent)
Quinolones
# e.g. ciprofloxacin, ofloxacin
• These drugs are active against many Gram -ve and Gram +ve organisms (bowel infections,
pseudomonas, cystic fibrosis lung infections, gonorrhoea)
Metronidazole
• This agents is very active against anaerobes and protozoal infections (entamoeba histolytics, giardia
lamblia, trichomonas)
• It is a well tolerated drug
Hepatotoxicity
In this section we shall review important infections by organ system. You really need to know the following
about each system.
• WHAT ORGANISM
• MANIFESTATIONS
• DEFINITIVE INVESTIGATION
• BROAD/DEFINITIVE TREATMENT
Cerebral Infections
Cerebral
abscess
Encephalitis
Meningitis
CAP
HAP
AP
TB
GI Infections
Throat
infection
Upset
tummy
Hepatitis A
Hepatitis B
Hepatitis C
Sexual Infections
• DISCHARGE
• E.g. Gonorrhoea, chlamydia, NGU
• ULCERATION
• E.g. Syphilis, LGV, chancroid + viruses
• HIV
Chlamydia
Gonorrhoea
NSU
Syphilis
LGV
HSV
HPV
Simple
cystitis
Pyelonephritis
Skin Infections
Cellulitis
Infected eczema
Dermatophytosis
Malaria
Leptospirosis
Lyme Disease
Schistosomiasis
Trypanosomiasis
Leishmaniasis
Atherosclerosis
NON-MODIFIABLE MODIFIABLE
There are 4 key stages:
•
•
•
•
Hypertension
" Defintion:
Primary
Secondary
1.
2.
3.
4.
5.
6.
Cardiac Failure
• Final COMMON PATHWAY of most cardiac disease. “Inability of heart to meet demands of the
body.”
RVF LVF
Hypertrophic
Dilated
Restrictive
ARVD
Valve Disease
• Try to appy some general causes to all the different valve problems:
• CONGENITAL
• Bicuspid valve
• ACQUIRED
• Rheumatic fever
• Endocarditis
• Functional e.g. annulus stretched, papillary muscle damage
• Degeneration
Rheumatic
fever
Infective
endocarditis
1. Pulmonary embolism
2. Pulmonary hypertension
The Airways
Asthma COPD
Emphysema
2 types:
1. PANLOBULAR/PANACINAR
2. CENTRILOBULAR/PARASEPTAL
PATHOGENESIS:
Bronchiectasis
The Interstitium
Pulmonary fibrosis
Idiopathic
Extrinsic allergic
alveolitis
Pneumonconioses
Autoimmune
Drugs
Radiation
Lung Tumours
• NON-SMALL CELL
• Sqaumous cell carcinoma
• Adenocarcinoma
• Large cell undifferentiated
• SMALL CELL
• LOCAL
• Bronchial obstruction
• Impaired mucus clearance
• Invasion
• Extension through pleura/pericardium/lymphaticx
• DISTANT
• Peptide production
• ACTH
• ADH
• PTH-like peptide
• Paraneoplastic syndrome
• Metastases
The Pleura
Pneumothorax
TENSION SIMPLE
Pleural Effusions
Pleural Effusions
• Manifestations
1. PLEURAL PLAQUES
2. ASBESTOSIS
3. ADENOCARCINOMA
4. MESOTHELIOMA
You need to review the basic structure of the liver and the most basic
cell types:
Cirrhosis
1.NODULE SIZE
PATHOGENESIS (draw a diagram) 2. AETIOLOGY
1.
2.
3.
4.
Alcohol
Steatohepatitis
Wilsonʼs disease
Haemochromatosis
Alpha-1 anti-trypsin
deficiency
Autoimmune
Hepatic Neoplasia
2. Cholangiocarcinoma - < 5%
• Aetiology unknown
• Gross appearance: pale + firm
• Presentation: Man in sixties with all features of pancreatic tumour (jaundice, weight loss, pruritus and
abdominal pain).
• Very poor prognosis
Gallstone Disease
Basic Principles
• 2 main functions
• ENDOCRINE (5%) - glucagon, insulin, somatostatin, VIP
• EXOCRINE (95%) - proteases, lipasess
Congenital Disorders
Pancreatitis
Acute Chronic
Cystic Tumours
Congential cysts Anomalous development of pancreatic ducts e.g. congenital polycystic disease (kidney
and liver also affected)
Cystic tumours < 5% of all pancreatic neoplasms (many types e.g. serous cystadenoma, mucinous)
Painless and slow-growing
Solid Neoplasms
• Clinical features
• Weight loss + pain
• Jaundice if head is affected
• Trousseau syndrome - “migratory thrombophlebitis.”
OESOPHAGUS
Motor Disorders
Hiatus hernia “Failure of the gastro-oesophageal spincter with herniation of the stomach.”
2 types: SLIDING (95%), ROLLING (5%)
Common. Associated with REFLUX
Reflux Oesophagitis/GORD
Pathological sequelae
•
•
•
Types Associations
STOMACH
Causes Features
Infection
Autoimmunity
Drugs
Alcohol
Gastric Tumours
Types Associations
Adenocarcinoma
LEIMYOMAS/LEIOMYOSARCOMAS
Coeliac Disease
• “Inflammatory disease of the small intestine due to intolerance of gliadin dietary gluten”
• Pathology:
• T cell driven chronic inflammation of small bowel --> loss of absorptive surface --> malabsorption
(iron, folate, NOT B12)
• Lymphocyte enteritis + subtotal villous atrophy
Diagnosis
• Clinical features
Colo-rectal adenocarcinoma
ADENOMA CARCINOMAA
Size
Histological Type
Dysplasia
Staging systems:
• Dukes: A-D
• TNM:
Renal Pathology
• Kindey function – waste excretion, maintenance of ECF, acid-base, hormones (erythropoietin, rennin,
calcitriol)
• 1 million nephrons: each has glomerulus and associated tubular system
• Urine drains to collecting ducts, open onto surface on renal papillae then into calyces.
Sudden Progressive
1. Blood vessels
Hypertension
Atherosclerotic
disease
2. Glomerulus
PROLIFERATIVE
STRUCURAL
NECROTISING
3. Tubules
ATN
Toxic ATB
Renal tubular
disorders
4. Interstitium
Acute Dramatic inflammatory infiltration of interstium (usually Type I hypersensitivity) --> ARF
5. Outflow Tract
Bacterial infection
Obstruction
• Kidneys full of multiple fluid-filled cysts, progressive enlargement destroys renal parenchyma (50% ->
CRF)
• Aetiology – PKD1 mutation coding for polycystin-1
Urogenital Pathology
Stones
1. Increased solute
concentration
2. Increased urine
concentration
3. Stasis
Manifestations:
•
•
Tumours
Types Associations
Renal cell
carcinoma
Testicular Pathology
Testicular Tumours
Lymphomas
Secondary tumours
Cerebrovascular Disease
• THROMBOTIC/EMBOLIC
• Sites: Intracerebral arterial, internal carotid artery
• Embolism: post-MU mural thrombus, endocarditis
• HAEMORRHAGIC
• Usuually hypertension related
• BERRY ANEURYSMS: congental weakness in arterieal wall (1% population)
• 80% internal carotid, 20% vertebro-basilar
• Other congenital malformations
• AV MALFORMATIONS
• CAPILLARY TELANGECTASES
• VENOUS ANGIOMAS
• CAVERNOUS ANGIOMAS
Extra-dural Outside the dura Disruption of arteries from the LOC---lucid period— CT (lens shaped
mater middle meningeal artery deterioration (coning)---death haematoma)
Neurosurgical drainage
Sub-dural Between arachnoid Rupture of bridging vein Insidious onset (alcoholics/ Inv: CT
and dura elderly)
Rx: Surgical evacuation
Headache, sensory/ motor of haematoma
S/S
Subarachnoid Under arachnoid Trauma or ruptured Berry Sudden onset headache Inv: CT, cerebral
aneurysm angiography
Meningism Rx: Conservate/Surgery
(clipping/embolisation)
Intra-cerebral Within brain tissue Damage to brain Compressive and localising Surgical drainage
substance signs
1. CONCUSSION
2. DIFFUSE AXONAL INJURY
3. CONTUSION
4. TRAUMATIC INTRACEREBRAL HAEMORRHAGE
Mechanisms
• Acute: Cytotoxicity
• Chronic - Vasogenic activity
Generalised Localised
4 important complications
• VASCULAR DAMAGE
• HERNIATION
• OBSTRUCTION TO CSF FLOW
• INTRACRANIAL NERVE DAMAGE
Brain Tumours
1. Astrocytomas
2. Medulloblastomas
3. Ependymomas
4. Oligodendromas
Lymphoma B cell
T cell
Neuroepithelial Medullablastoma
Retinoblastoma
Neuroblastoma
Ganglioblastoma
Alzheimerʼs disease
Multi-infarct dementia
Pickʼs disease
Huntingdonʼs
Variant cJD
Others
Parkinsonism
Multiple sclerosis
MND
The Pituitary
Anterior
Posterior
• HYPERPITUITARISM
• HYPOPITUITARISM
Pituitary adenomas
Type Pathology/Features
Prolactinomas
Growth hormone
adenomas
Corticotroph
adenomas
The Thyroid
HYPO-
HYPER-
Goitres
1. Lingual thyroids
• Residual tissues at the base of the tongue
2. Thyroglossal cysts
• Remnant thyroid tissue
• Midline, smooth and cystic mass that moves upwards on swallowing
Smooth Nodular
Acute suppurative
DeQuervain’s
Inflammatory
Riedel’s
Hashimoto’s
Thyroid Neoplasms
May be:
"
Adrenal Disease
• CORTEX
• Zona gloemulosa --> aldosterone
• Zona fasciculata --> glucocosrticoids
• Zona reticularis --> androgens/corticosteroids
• MEDULLA --> adrenaline/noradrenaline
1. Adrenal excess
2. Adrenal Deficiency
This may be PRIMARY or SECONDARY (reduced ACTH e.g. large pituitary adenomas/other brain
neoplasms)
Acute
Chronic
Phaechromacytoma
Type Features
MEN 1
MEN 2a
MEN 2b