Atherosclerosis & Hypertensive Vascular Disease
Pathology · CVS · lean revision notes
Atherosclerosis & Hypertensive Vascular Disease
Atherosclerosis is the disease of large and medium muscular/elastic arteries that underlies the bulk of cardiovascular mortality, while hypertensive vascular disease principally damages small arteries and arterioles. Together they form one of the most heavily tested CVS pathology areas in NEET PG, with stems built around fatty streak → plaque sequence, foam cell origin, complicated plaque events, and the onion-skin arteriole of malignant hypertension.
Arteriosclerosis: the umbrella term
"Arteriosclerosis" literally means hardening of arteries and is a generic term that includes three distinct entities. Do not confuse it with atherosclerosis, which is only one subtype.
| Entity | Vessel affected | Hallmark lesion | Clinical setting |
|---|---|---|---|
| Atherosclerosis | Large & medium elastic/muscular arteries (aorta, coronary, carotid, popliteal) | Intimal fibrofatty atheroma (plaque) | Most common, lifestyle/lipid driven |
| Mönckeberg medial sclerosis | Medium muscular arteries (radial, ulnar, thyroid, uterine) | Medial calcification (ring/pipestem), lumen spared | Age >50, usually clinically silent |
| Arteriolosclerosis | Small arteries & arterioles | Hyaline or hyperplastic wall thickening | Hypertension, diabetes |
High-yield: Mönckeberg calcification is medial, does NOT narrow the lumen, and is clinically insignificant. Atherosclerosis is intimal and narrows the lumen. This intima-vs-media distinction is a favourite single-best-answer trap.
Atherosclerosis — definition & morphologic stages
Atherosclerosis is a chronic intimal inflammatory–fibroproliferative response to endothelial injury, producing raised lesions (atheromas) composed of a lipid-rich necrotic core capped by a fibrous cap.
Stepwise evolution:
- Endothelial injury / dysfunction (chronic, repetitive) →
- Lipoprotein (LDL) entry & oxidation in intima →
- Monocyte adhesion, migration, and transformation into macrophages →
- Foam cell formation (lipid-laden macrophages) →
- Fatty streak (earliest grossly visible lesion) →
- Smooth muscle cell migration intima-ward + ECM/collagen deposition →
- Fibrous (atheromatous) plaque →
- Complicated plaque (calcification, ulceration, rupture, haemorrhage, thrombosis, aneurysm).
High-yield: The fatty streak is the earliest lesion, can appear in the aorta of infants <1 year and in virtually all children >10 years; it is not necessarily a precursor of every plaque, and its presence is universal, hence it does not predict future disease site by itself.
The fibrous cap vs necrotic core
- Fibrous cap: smooth muscle cells + dense collagen (synthesised by SMCs) — provides stability.
- Necrotic core (atheroma): cell debris, cholesterol clefts, foam cells, calcium.
- Shoulder region: junction of cap and normal intima; richest in macrophages/T cells and the weakest point → site of rupture.
High-yield: A thin fibrous cap with a large lipid core and dense macrophage infiltrate = "vulnerable plaque" → high risk of rupture and acute coronary syndrome. A thick cap with small core = stable plaque (causes stable angina via fixed stenosis). Plaque rupture, not just stenosis, triggers most MIs.
Pathogenesis — "Response-to-injury" hypothesis
The currently accepted model (Ross) views atherosclerosis as a chronic inflammatory and healing response of the arterial wall to endothelial injury.
Key molecular players (frequently asked):
- LDL oxidation: Oxidised LDL is chemotactic for monocytes, is taken up by macrophage scavenger receptors (SR-A, CD36) — uptake is not down-regulated by intracellular cholesterol, so macrophages engorge unchecked → foam cells. Ox-LDL is also cytotoxic to endothelium and stimulates cytokine release.
- Adhesion molecules: VCAM-1 (binds monocytes/T cells) up-regulated on dysfunctional endothelium.
- Cytokines/growth factors: PDGF, FGF, TGF-α drive smooth-muscle migration and proliferation; PDGF (from platelets, macrophages, endothelium) is the major SMC mitogen.
- Smooth muscle cells are central: they migrate from media → intima, switch from contractile to synthetic phenotype, and lay down collagen forming the cap. SMCs can also become foam cells.
High-yield: Foam cells derive from BOTH macrophages (monocyte-origin) and smooth muscle cells. The macrophage scavenger receptor uptake of oxidised LDL is the central event — a classic MCQ.
Sites & haemodynamics
Plaques form preferentially where there is turbulent flow / low shear stress: ostia of branch vessels, posterior wall of abdominal aorta, bifurcations. Laminar flow is atheroprotective (induces antioxidant genes, eNOS).
Order of vessel involvement (most → least, classically tested): Lower abdominal aorta > coronary arteries > popliteal > internal carotid > circle of Willis.
Risk factors
| Non-modifiable | Modifiable (major) |
|---|---|
| Age | Hyperlipidaemia (↑LDL, ↓HDL) |
| Male sex (pre-menopause protection in women) | Hypertension |
| Family history / genetics | Cigarette smoking |
| Genetic (e.g., familial hypercholesterolaemia – LDL receptor defect) | Diabetes mellitus |
Emerging / additional: ↑CRP (inflammation marker, strong independent predictor), hyperhomocysteinaemia, lipoprotein(a), metabolic syndrome, inadequate physical activity.
High-yield: The single most important modifiable risk factor overall is hyperlipidaemia; hs-CRP is the best-validated inflammatory biomarker predicting risk. Familial hypercholesterolaemia (autosomal dominant LDL-receptor mutation) is the classic monogenic cause and a recurrent exam theme.
Complications of atheroma (complicated plaque)
Mnemonic — "RACH-T" for what a plaque does badly:
- Rupture / fissuring / ulceration → exposes thrombogenic core
- Aneurysm formation (medial atrophy/pressure) → e.g., abdominal aortic aneurysm
- Calcification (dystrophic)
- Haemorrhage into plaque (from neovessels) → rapid expansion
- Thrombosis / embolisation (cholesterol emboli, atheroemboli)
Downstream consequences: myocardial infarction, ischaemic stroke, peripheral artery disease/gangrene, mesenteric ischaemia, renal artery stenosis, aortic aneurysm with rupture.
High-yield: Cholesterol (atheroembolic) emboli show needle-shaped cholesterol clefts in small downstream vessels (e.g., kidney, skin → blue toe syndrome) — a recognisable histology stem.
Hypertensive Vascular Disease
Hypertension damages small vessels through two patterns of arteriolosclerosis and produces characteristic cardiac and renal changes.
Hyaline vs Hyperplastic arteriolosclerosis
| Feature | Hyaline arteriolosclerosis | Hyperplastic arteriolosclerosis |
|---|---|---|
| Associated with | Benign (essential) hypertension, diabetes mellitus, ageing | Malignant / accelerated hypertension (diastolic often >120 mmHg) |
| Wall change | Homogeneous pink hyaline thickening (plasma protein leak + ↑ECM) | Concentric laminated "onion-skin" SMC + reduplicated basement membrane |
| Lumen | Narrowed | Markedly narrowed |
| Severe form | — | Necrotising arteriolitis (fibrinoid necrosis) ± acute haemorrhage |
| Classic organ | Kidney → benign nephrosclerosis ("granular leathery" small kidneys) | Kidney → malignant nephrosclerosis ("flea-bitten" kidney – petechiae) |
High-yield: Onion-skin concentric proliferation = malignant hypertension; hyaline thickening = benign HTN and diabetes. The diabetic hyaline change also affects the efferent + afferent arterioles (contributing to glomerular hyperfiltration/Kimmelstiel–Wilson nodules in the glomerulus).
Pathophysiology of hypertension (essentials)
- BP = Cardiac Output × Peripheral Resistance. Chronic elevation reflects ↑ peripheral resistance and/or ↑ blood volume.
- RAAS (renin → angiotensin II → vasoconstriction + aldosterone-driven Na⁺/water retention) and sympathetic tone are central regulators.
- Primary (essential) HTN = ~90–95% (multifactorial; genetic + Na intake + stress).
- Secondary HTN = renal (renovascular, parenchymal — most common secondary cause), endocrine (Conn, Cushing, phaeochromocytoma), coarctation, drugs.
- Malignant HTN: severe BP (e.g., diastolic >120) + papilloedema/retinal haemorrhages + renal failure; histology shows fibrinoid necrosis + hyperplastic arteriolosclerosis.
Hypertensive Heart Disease (HHD)
Left-sided (systemic) HHD criteria (need both, with no other cause):
- Concentric LV hypertrophy (LV wall thickening WITHOUT dilatation initially) — pressure-overload pattern; heart weight often >500 g, wall >2 cm.
- History/pathologic evidence of hypertension.
Progression: compensated concentric LVH → diastolic dysfunction → eventual dilatation, systolic failure, and ↑ risk of MI, arrhythmia (AF), sudden cardiac death.
Right-sided HHD = Cor pulmonale — RV hypertrophy/dilatation secondary to pulmonary hypertension (lung disease, recurrent PE). Acute cor pulmonale = sudden RV dilatation after massive PE.
High-yield: Concentric hypertrophy (↑ wall thickness, ↓ chamber radius) = pressure overload (HTN, aortic stenosis). Eccentric hypertrophy (chamber dilatation, sarcomeres in series) = volume overload (regurgitation). This pattern question is a perennial favourite.
Diagnosis & investigations
Atherosclerosis is largely a pathologic/clinical diagnosis; investigations target its consequences:
- Lipid profile (LDL, HDL, TG, total cholesterol) — risk stratification.
- hs-CRP — inflammatory risk marker.
- Coronary angiography — gold standard to demonstrate luminal stenosis; CT coronary angiography / coronary calcium (Agatston) score for non-invasive burden.
- Carotid Doppler / ABI (ankle-brachial index <0.9 = PAD).
- For hypertension workup: confirm BP on repeated readings, fundoscopy (Keith-Wagener-Barker grading), ECG/Echo for LVH, urea/creatinine, urinalysis, fasting glucose, and screen for secondary causes if young or refractory.
Management / drug of choice (pathology-level)
- Atherosclerosis risk reduction: lifestyle + statins (HMG-CoA reductase inhibitors) are the drug of choice for LDL lowering and plaque stabilisation (pleiotropic anti-inflammatory effect); add antiplatelets (aspirin) for established disease; control BP, glucose, stop smoking.
- Hypertension: stepwise per stage — thiazides, ACE inhibitors/ARBs, CCBs. ACEi/ARB favoured in diabetic nephropathy. Malignant/emergency HTN: IV agents (labetalol, nitroprusside, nicardipine) with controlled BP reduction to avoid hypoperfusion.
Key differentials & look-alikes
- Atherosclerosis vs Mönckeberg — intimal narrowing vs medial calcification (lumen patent).
- Hyaline vs hyperplastic arteriolosclerosis — benign HTN/diabetes vs malignant HTN.
- Atherosclerosis vs vasculitis (e.g., Takayasu, giant cell) — inflammatory infiltrate of the wall, granulomas, younger or specific demographics.
- Concentric (pressure) vs eccentric (volume) hypertrophy.
- Fibrinoid necrosis (malignant HTN, vasculitis) vs hyaline change.
Recently asked / exam angle
- Identify the earliest lesion of atherosclerosis → fatty streak (foam cells in intima).
- Foam cell origin → macrophage (monocyte) and smooth muscle cell, via scavenger-receptor uptake of oxidised LDL.
- Onion-skin appearance of arteriole → malignant hypertension (hyperplastic arteriolosclerosis), kidney = flea-bitten.
- Hyaline arteriolosclerosis → associations: benign HTN + diabetes mellitus + ageing.
- Most common vessel first/most severely involved by atherosclerosis → lower abdominal aorta.
- Vulnerable plaque features → thin cap, large lipid core, many macrophages → rupture → ACS.
- Cell responsible for fibrous cap collagen → smooth muscle cell (synthetic phenotype).
- Best inflammatory biomarker for CV risk → hs-CRP.
- Mönckeberg sclerosis → medial calcification, lumen spared, clinically silent.
- Major growth factor for SMC proliferation → PDGF.
- Cardiac response to chronic HTN → concentric LV hypertrophy.
Rapid revision
- Atherosclerosis = intimal disease of large/medium arteries; arteriolosclerosis = small vessels in HTN/DM; Mönckeberg = medial calcification.
- Fatty streak = earliest lesion; foam cells = lipid-laden macrophages and SMCs.
- Oxidised LDL is chemotactic, cytotoxic, and taken up unregulated via scavenger receptors → foam cells.
- PDGF drives smooth-muscle migration; SMCs build the collagen fibrous cap.
- Vulnerable plaque = thin cap + large necrotic core + macrophages → rupture → thrombosis → MI/stroke.
- Order of involvement: abdominal aorta > coronary > popliteal > internal carotid > circle of Willis.
- Plaque complications = rupture, haemorrhage, calcification, aneurysm, thrombus/embolus (cholesterol clefts in atheroemboli).
- Hyaline arteriolosclerosis = benign HTN + diabetes; hyperplastic "onion-skin" = malignant HTN ± fibrinoid necrosis.
- Malignant nephrosclerosis = "flea-bitten" kidney (petechiae); benign = granular, contracted kidneys.
- Hypertensive heart disease = concentric LV hypertrophy (pressure overload); cor pulmonale = RV due to pulmonary HTN.
- Best CV inflammatory marker = hs-CRP; drug of choice for LDL/plaque stabilisation = statin.
- Familial hypercholesterolaemia = AD LDL-receptor defect → premature, severe atherosclerosis.