CL Pathology

Question 1

What are the histological features of amyloidosis?

Answer 1

Bright pink hyaline material on microscopy

Characteristic staining with ‘Congo red’ shows apple green membranes under polarized light.

Question 2

Stages of acute inflammation

Answer 2

Haemostasis
Increased vascular permeability
Recruitment and extravasation of white cells
Phagocytosis
Resolution or chronic inflammation

Question 3

Chemical mediators involved in acute inflammation

Answer 3

Vasoactive mediators- histamine and serotonin
Bradykinin
Complement/coagulation/fibrinolytic cascade
Arachidonic acid metabolites- thromboxaneA2, leukotrienes, prostaglandins
Cytokines- TNF-a, interleukins

Question 4

What is the complement cascade?

Answer 4

Part of innate immune system
Results in formation of membrane attack complex which promotes inflammation via opsonisation and facilitation of phagocytosis
Classical pathway triggered by antigen-antibody complex
Alternative pathway triggered by cell wall of micro-organism

Question 5

Possible outcomes of acute inflammation

Answer 5

Resolution
Repair, organisation and scar formation
Chronic inflammation
Abscess formation

Question 6

What is chronic inflammation?

Answer 6

Simultaneous processes of tissue healing, inflammation and injury
Characterised by presence of macrophages and lymphocytes rather than neutrophils (as in acute inflammation)
Usually lasts longer than acute inflammation

Question 7

What is a granuloma?

Answer 7

Isolation of foreign body/infection/area of necrosis by the immune system. Surrounded by epithelioid macrophages which may converge to form Langerhans giant cells

Question 8

How can you classify granulomatous inflammation?

Answer 8

Caseating- TB

Non caseating- IBD or sarcoid

Question 9

What causes chronic inflammation?

Answer 9

Infection that cannot be eliminated by the body- TB
Persistence of insult to mucosa- eg peptic ulcer disease
Auto-immune conditions eg RA
Unknown- eg IBD

Question 10

Duke’s classification

Answer 10

Stage A: Limited to muscularis propria; nodes not involved
Stage B: Extending beyond muscularis propria; nodes not involved
Stage C: Nodes involved but highest (apical) node spared
Stage D: Distant metastatic spread

Question 11

Layers of the gastrointestinal tract

Answer 11

Mucosa (epithelium, lamina propria and muscularis mucosa) - internal
Submucosa
Muscularis propria
Adventitia/Serosa - external

Question 12

To where does colorectal cancer commonly metastasize?

Answer 12

Liver, Lung, Brain, Bone

Question 13

How would you monitor your patient for disease recurrence following a colorectal resection?

Answer 13

CT colon & CEA monitoring

Question 14

Describe constituent of malignant ascites

Answer 14

Exudate, with a protein count >30g/L (as opposed to transudate, with a low protein content)

Question 15

Causes of hepatomegaly

Answer 15

Physiological
Tumour- benign/malignant
Infective (e.g. parasitic/bacterial/viral abscesses)
Metabolic (acromegaly, alcohol)
Infiltrative (amyloid)
Vascular (right heart failure, Budd-Chiari syndrome)
Haematological- sickle cell, thalassaemia

Question 16

What is the cytological classification of thyroid nodule biopsy?

Answer 16

• Benign
• Indeterminate or suspicious
• Malignant
• Inadequate specimen

Question 17

What is the difference between primary, secondary and tertiary hyperparathyroidism?

Answer 17

• Primary hyperparathyroidism: due to excess parathyroid hormone secretion from parathyroid adenomas, hyperplasia, or carcinoma.
• Secondary hyperparathyroidism: Increase in parathyroid hormone in response to low plasma ionised calcium secondary to renal disease or malabsorption.
• Tertiary hyperparathyroidism: development of autonomous hyperplastic parathyroid glands in a patient with secondary hyperparathyroidism resulting in profound hypercalcaemia.

Question 18

Causes of hypoparathyroidism?

Answer 18

• Post-thyroidectomy
• Idiopathic (autoimmune)
• After radioactive iodine therapy for Graves

Question 19

What is the difference between primary and secondary hyperaldosteronism?

Answer 19

• Primary hyperaldosteronism: elevated aldosterone, suppressed renin levels. Causes include aldosterone producing adenoma, adrenal hyperplasia, aldosterone producing adrenocortical carcinoma, familial hyperaldosteronism.
• Secondary hyperaldosteronism: elevated aldosterone AND renin. Causes include renal vascular disease, renin-secreting tumours, liver cirrhosis

Question 20

What are the commonest risk factors for cholangiocarcinoma?

Answer 20

The commonest cause is Primary Sclerosing Cholangitis, followed by chronic liver disease, HIV and congenital liver disease.

Question 21

What tests would you request in order to diagnose a cholangiocarcinoma?

Answer 21

Imaging: USS of the liver and biliary tree/ ERCP (for biopsy)/MRCP
If unable to obtain a biopsy via ERCP, an open biopsy should be performed

Staging: CT (full body)

Immunohistochemistry can be employed to distinguish between hepatocellular carcinoma and cholangiocarcinoma.

Question 22

Management of cholangiocarcinoma

Answer 22

Cholangiocarcinoma is incurable and rapidly lethal unless the tumour is completely resected. An open approach is usually employed.

If tumour is unresectable, adjuvant therapy, hepatectomy and liver transplantation is advisable.

Overall median survival is less than 6 months.

Question 23

How does clostridium difficile form a pseudomembrane?

Answer 23

C Diff. produces a toxin that helps it to colonize the gut. This toxin causes an inflammation of the bowel, there is production of grey-white exudate that is thin and adherent onto the bowel wall. The membrane is composed of necrotic epithelium, debris, fibrin, bacteria and neutrophils merging with the mucosa.

Question 24

What criteria must a donor meet?

Answer 24

The patient should meet the requirements for brainstem death, have consent from the next of kin or be on the organ donor register, and be ABO compatibility with the recipient. They should also be free of malignancy, HIV, hepatitis and acute infection.

Question 25

What are the criteria that must be met for brainstem death?

Answer 25

The pupils must be fixed and unresponsive to light. There must be no corneal reflex Vestibulo-ocular reflexes must be absent – ie no eye movement on injection of 50ml of ice cold water into the external auditory meatus No motor response to supraorbital pressure No gag reflex No cough in response to bronchial stimulation down the endotracheal tube No respiratory movements in response to disconnection from a ventilator, despite allowing the PaCO2 to rise to 6.65kPA on ABG Brainstem testing must be carried out by two doctors who have held registration with the GMC for more than 5 years; two sets of tests should be carried out.

Question 26

What cells mediate type 1 hypersensitivity reaction?

Answer 26

B cells, Helper T lymphocytes and mast cells mediate a type one hypersensitivity reaction The initial exposure to the antigen leads the sensitization of the T and B cells. As a result primed IgE binds to mast cells. If exposed to the antigen again, cross linking of the IgE on mast cells occurs, leading to degranulation and release of histamine.

Question 27

What causes graft-vs-host disease?

Answer 27

Graft-versus-host disease occurs when donor T cells recognizes and react against the hosts HLA antigens.

Question 28

Complications of steroids

Answer 28

``` General Cushingoid features: Central obesity Muscle wasting in limbs Thin skin Bruising Buffalo hump Striae Hirsutism ``` Cardiovascular system: Hypertension Fluid retention GI system: Fatty liver Pancreatitis Neurological system: Depression Psychosis Insomnia Locomotor system: Osteoporosis Avascular necrosis Proximal myopathy Immune system: Immunosuppression Endocrine system: Diabetes mellitus

Question 29

What is H Pylori?

Answer 29

Gram-negative, microaerophilic spiral bacterium found in the stomach

Question 30

How does H Pylori colonise the stomach?

Answer 30

H pylori is able to detect pH and uses its flagella to swim away from the acidic contents of the lumen and adheres to the more neutral epithelial lining of the stomach.

Question 31

How does H Pylori survive the acidic conditions in the stomach?

Answer 31

H. pylori produces the enzyme urease. This converts urea to carbon dioxide and ammonia. The ammonia then binds with H+ to form ammonium which neutralizes gastric acid.

Question 32

How is H Pylori diagnosed?

Answer 32

Via the CLO campylobacter-like organism) test which is dependent on urease production by H Pylori A gastric mucosal biopsy is taken during gastroscopy and is placed into a medium consisting of urea and an indicator such as phenol red. Urease produced by H Pylori converts urea to ammonia which increases the pH changing the colour from yellow to red, hence a positive test.

Question 33

Eradication therapy for H Pylori?

Answer 33

7-day twice-daily course of treatment consisting of a: Full-dose PPI + amoxicillin/clarithromycin AND metronidazole 80% of patients infected with H pylori are asymptomatic

Question 34

Other tests for H Pylori other than mucosal biopsy?

Answer 34

Urease breath test: By having the patient drink radiolabelled urea, the carbon dioxide produced will also be labelled and can be collected and measured. Stool antigen test Serum antibody test

Question 35

How is hydrochloric acid produced in the stomach?

Answer 35

There is nervous stimulation via the cephalic phase (thinking about food) and gastric phase (having food in the stomach). G cells in the stomach are stimulated to produce gastrin. Gastrin travels in the circulation to stimulate enterochromaffin-like cells to produce histamine. The histamine and gastrin both stimulate parietal cells to produce hydrochloric acid.

Question 36

What are hypersensitivity reactions?

Answer 36

Exaggerated response of host’s immune system to stimulus | Undesirable tissue damage follows the humeral (mediated by antibodies) or cell-mediated immunity.

Question 37

What is the pathophysiology behind a type 2 hypersensitivity reaction and can you give some examples?

Answer 37

Antibodies vs antigens on surface of cells | Eg transfusion reactions and autoimmune haemolytic anaemia

Question 38

What is the pathophysiology behind a type 3 hypersensitivity reaction and can you give some examples?

Answer 38

The formation of antibody-antigen complexes (immune complex mediated) Eg SLE

Question 39

What is the pathophysiology behind a type 4 hypersensitivity reaction and can you give some examples?

Answer 39

Delayed hypersensitivity reaction mediated by T-lymphocytes. Takes 48-72 hours to see the effects. Eg contact dermatitis

Question 40

What is the pathophysiology behind a type 5 hypersensitivity reaction and can you give some examples?

Answer 40

Formation of stimulatory autoantibodies in autoimmune conditions Eg Graves’ disease and myasthenia gravis.

Question 41

What is actinic keratosis?

Answer 41

Premalignant skin condition provoked by UV light. It can progress to squamous cell carcinoma

Question 42

What histological feature characterizes a squamous cell carcinoma?

Answer 42

Proliferation of atypical keratinocytes, invasion of the dermis and keratin pearls

Question 43

Signs of systemic toxicity of local anaesthetic?

Answer 43

Perioral tingling and parasthesia progressing to drowsiness, seizures, coma, apnoea, paralysis, arrhythmias and shock (LAs are negative inotropes and vasodilators).

Question 44

Organisms causing rheumatic fever

Answer 44

Group A beta haemolytic strep

Question 45

Diagnostic criteria name for rheumatic fever

Answer 45

Jones Criteria

Question 46

How to diagnose rheumatic fever with Jones criteria

Answer 46

Evidence of infection 3 major or 1 major 2 minor

Question 47

Describe the Jones criteria

Answer 47

``` Evidence: +ve blood culture/antigen/ASOT Major: -Arthritis (migratory), -Bulky elbows (subcutaneous nodules), -Carditis, -Dancing (Sydenham's chorea), -Erythema marginatum ``` Minor: - Arthralgia - Block (heart block) - CRP elevated - Temperature

Question 48

What is the diagnostic criteria for infective endocarditis?

Answer 48

Modified Duke criteria

Question 49

How do you diagnose infective endocarditis with modified Duke criteria?

Answer 49

2 major 1 major 3 minor 5 minor

Question 50

Describe the modified Duke criteria

Answer 50

BETI MVP Major: -Blood cultures (2 separate, IE known organisms, >24h apart), -Endocarditis on echo Minor: - Temperature, - Immune phenomena (Oslers nodes, glomerulonephritis, roth spots) - Microbiology not meeting major criteria (non diagnostic/non IE organisms) - Vascular phenomena (aneurysms, septic emboli, splinter haemorrhages, Janeway lesions) - Predisposing factors (artificial valve, IVDU)