Why can a coronary artery narrowed by only about half cause a fatal myocardial infarction, while one narrowed far more causes only exertional angina? ANSWER: because acute events are caused by PLAQUE RUPTURE, not by the degree of narrowing. 1. A plaque has a LIPID CORE covered by a FIBROUS CAP. 2. The core is intensely thrombogenic. 3. When the cap TEARS, blood meets the core directly and thrombosis follows within minutes — occluding the vessel regardless of how narrow it was before. SO: MODEST plaque with a THIN cap → silent, then sudden and fatal SEVERE plaque with a THICK cap → predictable exertional angina, detectable on testing TWO CONSEQUENCES: - A reassuring exercise test does not promise safety. - Treatment aims at STABILISING plaques, which is why lipid-lowering reduces events out of proportion to any change in narrowing.

A post-operative patient with cancer develops a deep vein thrombosis. Explain the risk using Virchow's triad. ANSWER: all three arms are present. STASIS Post-operative IMMOBILITY — blood in the leg veins is not moving. ENDOTHELIAL INJURY SURGICAL trauma to vessels; any indwelling cannula. HYPERCOAGULABILITY MALIGNANCY produces a prothrombotic state. THE VALUE OF THE TRIAD: you can DERIVE a risk assessment rather than recall a list. Given any risk factor, name which arm it belongs to. EXAM POINT: PREGNANCY and MAJOR SURGERY are the two states that hit ALL THREE arms simultaneously — which is exactly why both carry high thromboembolic risk and why prophylaxis is routine in both.

Why does atrial fibrillation cause STROKE, while a deep vein thrombosis causes PULMONARY EMBOLISM? ANSWER: because an embolus travels DOWNSTREAM from where it formed, and the two sites drain into different circulations. DEEP LEG VEIN → venous return → RIGHT heart → PULMONARY arteries So a leg clot lodges in the LUNG. Deep vein thrombosis and pulmonary embolism are ONE disease in two places. LEFT ATRIUM (fibrillating, so blood stagnates) → left ventricle → AORTA → systemic arteries So the clot can reach the BRAIN, gut or a limb. NOT ALL EMBOLI ARE CLOT: fat after a long bone fracture, air from a line, amniotic fluid in labour — but the same principle applies. The material lodges where the vessels first become too small.

Classify these adaptations: the thickened left ventricle in hypertension, and the enlarged prostate. ANSWER: THICKENED VENTRICLE = HYPERTROPHY — BIGGER cells. Cardiac muscle cannot divide, so when more work is demanded it makes larger cells rather than more of them. ENLARGED PROSTATE = HYPERPLASIA — MORE cells. Prostatic tissue can still divide. THE OTHER TWO: ATROPHY smaller or fewer cells when demand, blood supply or innervation is withdrawn — the limb in a cast, muscle after nerve injury METAPLASIA one cell type replaced by another better able to survive the insult THE UNIFYING POINT: all four are REVERSIBLE if the stimulus is removed. They are RESPONSES, not diseases — which distinguishes them from DYSPLASIA, which is disordered growth and genuinely premalignant.

Describe the sequence from chronic acid reflux to oesophageal carcinoma, and say which step matters most. ANSWER: 1. Chronic REFLUX irritates the lower oesophagus. 2. METAPLASIA — squamous epithelium is replaced by a columnar type better able to withstand acid. This is BARRETT'S OESOPHAGUS, and it is reversible in principle if the irritation stops. 3. Persisting irritation → DYSPLASIA. Disordered growth. PREMALIGNANT, and what surveillance is looking for. 4. → CARCINOMA IN SITU → INVASIVE CARCINOMA. THE STEP THAT MATTERS MOST: INVASION THROUGH THE BASEMENT MEMBRANE. Until that happens, the abnormal cells cannot reach blood vessels or lymphatics, and therefore CANNOT METASTASISE. Everything before that point is potentially curable by local treatment.

Why is cervical screening effective, and what does this tell you about which cancers can be screened for? ANSWER: because there is a LONG, DETECTABLE and TREATABLE premalignant phase. 1. Persistent HPV infection causes metaplasia, then DYSPLASIA. 2. Dysplasia persists for YEARS before becoming invasive. 3. It can be detected by sampling cells. 4. It can be treated locally, preventing the cancer entirely. WHAT THIS IMPLIES GENERALLY: a cancer that progresses from normal to invasive QUICKLY, or that has no detectable premalignant phase, CANNOT be screened for in the same way — however desirable that would be. So the NATURAL HISTORY of a disease determines whether screening is possible at all, which is the principle the epidemiology chapter sets out from the other direction.

Why do the kidney and spleen infarct completely when their artery occludes, while the liver and lung tolerate it better? ANSWER: because of how the blood supply is designed. END ARTERY supply (kidney, spleen) A single artery supplies a territory with NO collateral. Occlusion → complete infarction of that territory. DUAL supply (liver, lung) The liver receives both the hepatic artery and the portal vein. The lung receives both pulmonary and bronchial arteries. Occlusion of one leaves an alternative, so infarction is less likely and less complete. THE SAME ANATOMICAL LOGIC appears elsewhere: it is why adrenaline is traditionally avoided in tissues supplied by end arteries — fingers, toes, nose, ears — as the anaesthesia chapter explains.