Infective Endocarditis
A 28-year-old intravenous drug user presents with high fever, new-onset murmur, and septic emboli to the lungs. Which organism is most likely, and why does this form of endocarditis often affect previously normal valves?
Staphylococcus aureus (high-virulence organism). Acute bacterial endocarditis caused by highly virulent organisms can destroy normal valves and has high mortality if not treated rapidly.
A 55-year-old man develops central crushing chest pain at rest that radiates to the left arm and is not relieved by rest or nitrates. Explain the most common pathogenetic sequence leading to this presentation.
Atherosclerotic plaque undergoes acute change (intraplaque haemorrhage, rupture/ulceration) → exposure of subendothelial collagen and necrotic core → platelet activation + coagulation cascade → occlusive thrombus (≈90% of cases)
A 60-year-old hypertensive smoker has an infrarenal abdominal aortic aneurysm measuring 5.8 cm. Explain the two major mechanisms by which atherosclerosis contributes to aneurysm formation.
(1) Ischaemic injury to medial smooth-muscle cells (plaque impairs nutrient diffusion) leading to loss of medial cells and fibrosis; (2) imbalance of matrix metalloproteinases versus TIMPs → excessive degradation of collagen and elastin, weakening the wall.
A 45-year-old patient has sustained BP of 150/95 mmHg with no identifiable secondary cause. Outline the interplay of genetic and environmental factors that produce the elevated peripheral resistance and volume expansion characteristic of primary hypertension.
Genetic polymorphisms affecting RAAS, renal sodium handling, and sympathetic tone interact with environmental factors (high sodium intake, obesity, stress, smoking) → defects in sodium excretion, increased vasoconstriction, endothelial dysfunction, and vascular remodelling → sustained rise in CO ×
Q1. A patient with long-standing mitral stenosis develops progressive dyspnoea and right-ventricular hypertrophy. Classify the type of pulmonary hypertension and explain the pressure-transmission mechanism.
Answer: Passive (venous) pulmonary hypertension. Elevated left-atrial pressure is transmitted retrograde through valveless pulmonary veins to the capillary bed; when LA pressure exceeds ≈18 mmHg, reflex pulmonary arteriolar vasoconstriction further elevates pressure.
A patient with known rheumatic heart disease develops low-grade fever and fatigue over several months. Blood cultures grow Streptococcus viridans. Explain why this organism typically requires pre-existing valve damage and contrast the clinical course with acute bacterial endocarditis.
Low-virulence organisms such as Strep. viridans need damaged valves (e.g., rheumatic valvulitis) to establish infection. Subacute bacterial endocarditis has a protracted course (months), better antibiotic response, and lower mortality compared with the highly destructive acute form.
Why is the subendocardial region particularly vulnerable to ischaemia when global coronary perfusion is reduced (e.g., shock or severe triple-vessel disease)?
It is a watershed zone farthest from the epicardial arteries, experiences higher intramural pressure, and relies more on diastolic perfusion from the ventricular lumen; therefore it suffers first when overall flow falls.
Distinguish a stable from a vulnerable atherosclerotic plaque in terms of composition and clinical risk.
Stable: small lipid core, thick fibrous cap, low inflammation → gradual stenosis (stable angina). Vulnerable: large necrotic lipid core, thin fibrous cap, abundant macrophages/T-cells releasing MMPs → high risk of rupture and thrombosis (acute coronary syndrome).
A patient presents with BP 220/130 mmHg, papilloedema, and acute renal failure. What pathologic changes are expected in the renal arterioles, and why is this a medical emergency?
Answer: Fibrinoid necrosis of arterioles + hyperplastic (“onion-skin”) arteriolosclerosis → severe luminal narrowing, ischaemia, and pinpoint haemorrhages/infarcts. Rapid target-organ damage (brain, kidney, heart, retina) constitutes a hypertensive emergency.
Why do pre-tricuspid left-to-right shunts (e.g., ASD) usually take decades to produce significant pulmonary hypertension, whereas large post-tricuspid shunts (e.g., VSD) produce it much earlier?
Answer: Pulmonary vasculature is highly distensible and can accommodate a three-fold increase in flow without raised resistance (pre-tricuspid). Post-tricuspid shunts transmit systemic pressure directly into the pulmonary circuit, causing earlier and more severe vascular remodelling (risk of Eisenmenger syndrome).
At autopsy, large friable vegetations are found along the lines of valve closure of the mitral valve, with evidence of embolization and papillary muscle rupture. What pathologic features of the vegetations make embolization and local destruction common?
Vegetations are large (>5 mm), friable (due to bacterial enzymes and neutrophils), and composed of fibrin, proliferating bacteria, and acute inflammation; they readily fragment and embolize and can cause abscesses or chordae/papillary rupture.
At autopsy of a patient who died 5 days after the onset of chest pain, the myocardium shows a yellow centre with a red hyperaemic rim. What is the expected microscopic finding at this stage, and why is this a high-risk period for certain complications?
Coagulative necrosis with heavy neutrophil infiltrate (and beginning macrophage activity). Softening of the necrotic tissue makes free-wall rupture (cardiac tamponade), septal rupture, or papillary-muscle rupture more likely.
A 70-year-old man is found to have ring-like calcifications of medium-sized muscular arteries on plain radiographs, yet he has no symptoms of ischaemia. What form of arteriosclerosis is this, and why is the lumen usually preserved?
Mönckeberg medial calcific sclerosis – calcification is confined to the tunica media; the intima and lumen remain largely unaffected, so flow is not obstructed.
A young woman develops hypertension and is found to have an adrenal cortical adenoma producing excess aldosterone. Explain the mechanism of hypertension and how it differs from the mechanism in phaeochromocytoma.
Answer: Conn syndrome → excess aldosterone → sodium/water retention and volume expansion. Phaeochromocytoma (medullary tumour) → excess catecholamines → acute vasoconstriction, tachycardia, and increased cardiac output.
A patient with severe emphysema develops pulmonary hypertension. List the three contributing mechanisms.
Answer: (1) Capillary destruction (obliterative); (2) hypoxic pulmonary vasoconstriction; (3) secondary polycythaemia increasing blood viscosity.
A patient on long-term haemodialysis develops infective endocarditis. List two host or procedural factors that increase risk and one intracardiac factor that further predisposes.
Host/procedural: long-term haemodialysis (repeated vascular access, potential bacteraemia) and immunodeficiency or neutropaenia. Intracardiac: prosthetic valves, indwelling catheters, or pre-existing valvular disease.
. A patient presents with sudden pulmonary oedema and a new holosystolic murmur 4 days after an inferior MI. Which structural complication is most likely, and what is the haemodynamic consequence?
Papillary-muscle rupture → acute severe mitral regurgitation → acute left-sided volume overload and pulmonary oedema.
List the vessels most frequently affected by atherosclerosis in descending order and give one clinical consequence for each of the top three.
Abdominal aorta (aneurysm/rupture), coronary arteries (IHD/MI), popliteal arteries (critical limb ischaemia/gangrene).
Why does renal-artery stenosis cause secondary hypertension, and what is the key effector pathway?
Answer: Reduced renal perfusion is sensed as hypovolaemia → continuous activation of the renin–angiotensin–aldosterone system → systemic vasoconstriction (angiotensin II) and sodium retention (aldosterone).
Q4. At what approximate mean pulmonary-artery pressure ranges do medial hypertrophy, intimal fibrosis, and irreversible plexiform lesions appear, and what is the clinical implication of plexiform change?
Answer: ≈40–70 mmHg → medial hypertrophy (still reversible); higher pressures → intimal fibrosis; plexiform lesions and fibrinoid necrosis are irreversible and indicate advanced, fixed pulmonary vascular disease.
How would you distinguish the vegetations of acute bacterial endocarditis from those of non-bacterial thrombotic endocarditis in terms of composition and clinical behaviour?
Acute bacterial vegetations contain proliferating bacteria + neutrophils + fibrin and are highly destructive/embolic; non-bacterial thrombotic vegetations are sterile fibrin-platelet thrombi that embolize but do not destroy valves or produce suppuration.
How does the macroscopic appearance of an infarct change between 4–24 hours and 2–8 weeks, and how can special staining (TTC) help confirm early infarction?
4–24 h: dark mottling; 2–8 weeks: white fibrous scar. TTC stains viable myocardium red (binds dehydrogenase); necrotic areas remain yellow/unstained because the enzyme has leaked out.
A young patient with Marfan syndrome develops a thoracic aortic aneurysm. How does the underlying connective-tissue defect predispose to aneurysm formation, and how does this differ from the pathogenesis of a typical atherosclerotic abdominal aortic aneurysm?
Defective fibrillin-1 → abnormal elastic fibres and weakened media. Atherosclerotic AAA is driven by chronic inflammation, medial ischaemia, and matrix degradation rather than a primary genetic defect of elastic tissue.
Q5. List three major target-organ complications of long-standing hypertension and the vascular lesion that accelerates each.
Answer: (1) Stroke – accelerated atherosclerosis + Charcot-Bouchard micro-aneurysms; (2) ischaemic heart disease/heart failure – accelerated coronary atherosclerosis + left-ventricular hypertrophy; (3) chronic kidney disease – hyaline/hyperplastic arteriolosclerosis (benign/malignant nephrosclerosis).
Q5. A young woman presents with progressive dyspnoea and is diagnosed with idiopathic pulmonary arterial hypertension. Contrast the histologic end-stage lesions with those seen in passive pulmonary hypertension secondary to left-heart disease.
Answer: Idiopathic PAH shows plexiform lesions, concentric intimal fibrosis, and fibrinoid necrosis of small arteries. Passive (venous) hypertension shows venous sclerosis, arterial medial hypertrophy, interstitial fibrosis, and haemosiderin-laden macrophages (“heart-failure cells”) without plexiform lesions.