Atherosclerosis & Vascular Pathology
From the first foam cell to the ruptured aorta: the whole vascular-pathology map
Pathogenesis of atherosclerosis
Terminology. Arteriosclerosis is the umbrella term for arterial thickening and hardening. Atherosclerosis is its intimal, plaque-forming subtype, affecting large elastic arteries (aorta) and medium muscular arteries (coronary, carotid, popliteal); arteriolosclerosis and Monckeberg medial sclerosis are the other forms.
Response to injury. Endothelial dysfunction — from hypertension, smoking, hyperlipidemia, hyperglycemia, or turbulent flow — raises permeability and adhesiveness. LDL enters the intima, is oxidized, and drives a chronic inflammatory response.
- Endothelial injuryHypertension, smoking, LDL, hyperglycemia, and turbulent flow damage the lining.
- LDL entry and oxidationOxidized LDL in the intima recruits monocytes.
- Foam cells and fatty streakMonocytes become macrophages that engulf oxidized LDL via scavenger receptors.
- Smooth muscle and fibrous capPDGF and FGF draw smooth muscle cells from the media into the intima to proliferate and lay down matrix.
- Atheromatous plaqueFibrous cap over a necrotic lipid core; may calcify, ulcerate, or rupture.
Fatty streak. Aggregated foam cells form the fatty streak, the earliest lesion, seen even in children and teenagers and still reversible. Scavenger receptors, unlike the LDL receptor, are not down-regulated as cholesterol accumulates, so macrophages keep ingesting lipid until engorged.
Fibrous cap. Smooth muscle cells, not macrophages, synthesize the collagen-rich matrix of the cap. The mature atheroma is a fibrous cap over a necrotic core of lipid, cholesterol crystals, foam cells, and debris.
Risk factors, distribution, and plaque behavior
Risk factors. Modifiable: high LDL and low HDL, smoking, hypertension, diabetes, and hyperhomocysteinemia. Non-modifiable: age, male sex, and family history. Hyperlipidemia and smoking are among the strongest.
Distribution. From most to least affected: abdominal aorta (the infrarenal segment is the classic worst site) → coronary arteries (especially the LAD) → popliteal artery → internal carotid → circle of Willis. Plaques favor branch points, and the order roughly tracks turbulent flow.
| Feature | Stable plaque | Vulnerable plaque |
|---|---|---|
| Fibrous cap | Thick | Thin (macrophage proteases degrade collagen) |
| Lipid core | Small | Large |
| Inflammation | Little | Prominent |
| Clinical result | Fixed stenosis → stable angina, claudication | Rupture → thrombosis → acute MI or stroke |
Other sequelae. Aneurysm, embolism, ischemic bowel, and PAD. Atheroembolism of cholesterol crystals, often after arterial catheterization, produces blue toes, livedo reticularis, acute kidney injury, and eosinophilia.
Aortic aneurysms
Abdominal aortic aneurysm (AAA). Sits below the renal arteries and is associated with atherosclerosis; inflammation and matrix metalloproteinases degrade medial elastin and collagen, so the wall thins and dilates. Smoking is the strongest risk factor, followed by male sex, age over 65, and hypertension. It may be found as a pulsatile abdominal mass. Rupture presents with hypotension, back or flank pain, and a pulsatile mass.
Thoracic aortic aneurysm. Linked to hypertension and to cystic medial degeneration — loss of elastic fibers and smooth muscle with mucoid pools in the media — in Marfan syndrome (fibrillin-1), Ehlers-Danlos syndrome, and bicuspid aortic valve. Tertiary syphilis is the classic infectious cause.
Syphilitic aortitis. Obliterative endarteritis of the vasa vasorum starves the media, which scars and weakens, giving a wrinkled tree-bark intima, dilation of the ascending aorta and root, and aortic regurgitation. Syphilis favors the ascending aorta and root; atherosclerosis favors the abdominal aorta.
| Feature | AAA | Cystic medial degeneration | Syphilitic |
|---|---|---|---|
| Usual site | Infrarenal abdominal aorta | Aortic root, ascending aorta | Ascending aorta and root |
| Mechanism | Atherosclerosis-associated medial degradation | Weak connective tissue of the media | Vasa vasorum endarteritis → medial ischemia |
| Key associations | Smoking, male sex, age over 65, hypertension | Hypertension, Marfan, Ehlers-Danlos, bicuspid valve | Tertiary syphilis |
| Classic sequel | Rupture | Dissection, aortic regurgitation | Tree-bark intima, aortic regurgitation |
Aortic dissection
Mechanism. An intimal tear lets blood track into the media, creating a false lumen. Hypertension is the main risk factor; others are Marfan and Ehlers-Danlos syndromes, bicuspid aortic valve, cocaine, and pregnancy.
Presentation. Sudden, severe tearing chest pain radiating to the back, with unequal pulses or arm blood pressures and a widened mediastinum on chest X-ray.
Stanford classification. Type A involves the ascending aorta and needs emergency surgery. Type B is confined to the descending aorta and is managed medically, starting with β-blockers to lower heart rate and pressure.
A proximal dissection can rupture into the pericardium (tamponade), dilate the root (acute aortic regurgitation), or occlude a coronary ostium (MI).
Arteriolosclerosis and medial calcific sclerosis
Hyaline arteriolosclerosis. Homogeneous pink (hyaline) thickening of arteriolar walls from leaked plasma proteins and basement-membrane material narrows the lumen. It is caused by benign hypertension and diabetes mellitus and produces glomerular scarring (nephrosclerosis).
Hyperplastic arteriolosclerosis. Concentric onion-skin thickening from smooth-muscle proliferation and reduplicated basement membrane, sometimes with fibrinoid necrosis, in malignant hypertension (over 180/120). It causes acute kidney injury and a flea-bitten kidney with petechial hemorrhages.
Monckeberg medial calcific sclerosis. Ring-like calcification of the media of medium muscular arteries (radial, ulnar) in patients over 50. X-rays show pipestem arteries, but the lumen is spared, so it is usually incidental and does not cause ischemia; the stiff, noncompressible vessels can falsely raise cuff pressures.
| Type | Layer and vessels | Appearance | Cause or setting | Consequence |
|---|---|---|---|---|
| Atherosclerosis | Intima; large and medium arteries | Fibrofatty plaque | LDL, smoking, hypertension, diabetes | Stenosis, rupture, aneurysm |
| Hyaline | Arterioles | Pink homogeneous wall | Benign hypertension, diabetes | Nephrosclerosis |
| Hyperplastic | Arterioles | Onion-skin ± fibrinoid necrosis | Malignant hypertension | AKI, flea-bitten kidney |
| Monckeberg | Media; medium arteries | Ring-like calcification | Age over 50 | Usually none; lumen spared |
Peripheral artery disease
Presentation. Lower-limb atherosclerosis causes intermittent claudication — calf pain on walking, relieved by rest — with diminished pulses, hair loss, cool shiny skin, and ulcers. Rest pain, nonhealing ulcers, or gangrene mark critical limb ischemia.
Ankle-brachial index. ABI = ankle systolic pressure ÷ brachial systolic pressure. A value under 0.9 is diagnostic of PAD; a value above about 1.4 suggests calcified, noncompressible arteries (as in diabetes or CKD) and is unreliable.
Leriche syndrome. Aortoiliac occlusion gives claudication of the buttocks and thighs, impotence, and absent femoral pulses.
Beyond smoking cessation, exercise, statins, and antiplatelet therapy, cilostazol (a PDE-3 inhibitor, contraindicated in heart failure) lengthens pain-free walking distance.