Arteriolosclerosis

1. Arteriosclerosis — framework

Arteriosclerosis = generic term for arterial wall thickening + loss of elasticity. Three patterns:

• Atherosclerosis — intimal lipid plaques of large/medium arteries.
• Mönckeberg medial sclerosis — medial calcification of muscular arteries.
• Arteriolosclerosis — small-artery/arteriole disease: hypertensive microangiopathy (hyaline + hyperplastic) and diabetic microangiopathy (= hyaline type).

2. Atherosclerosis — definition & plaque

A chronic inflammatory response of the vessel wall to endothelial injury, lipid accumulation in smooth muscle cells/macrophages, and thrombosis. The lesion is an intimal plaque protruding into the lumen:

• Lipid (necrotic) core: cholesterol crystals, ECM, cell debris, foam cells, surrounded by lymphocytes/macrophages and plasma proteins.
• Fibrous cap: endothelial cells, SMCs, collagen, with peripheral neovascularization.
• Plaque = lipid core + fibrous cap.

3. Risk factors

Risk rises exponentially with each added factor (2 factors ≈ 3×, 3 factors ≈ 7×).

Constitutional (non-modifiable)	Modifiable	Additional
Age (MI ↑ 5× ages 40–60), gender (premenopausal women protected by estrogen), genetics (familial hypercholesterolemia, HTN, DM)	Hyperlipidemia (↑ LDL “bad”, ↓ HDL “good”; Lp(a)), hypertension, cigarette smoking (1 pack/day ≈ 200×), diabetes mellitus	Inflammation (CRP), obesity, lack of exercise, stress, type A personality

4. Pathogenesis — response-to-injury

1. Chronic endothelial injury (non-denuding) from hypertension + hyperlipidemia → ↑ ROS, ↓ NO (↓ vasodilation), ↑ shear stress.
2. Lipoprotein accumulation in intima → oxidized LDL → taken up by macrophage scavenger receptors → foam cells.
3. Monocyte adhesion (adhesion molecules) → migrate into intima → macrophages → foam cells (accelerates the cycle).
4. Platelet adhesion.
5. Growth factor release (macrophages, EC, platelets) → SMC migration/proliferation + ECM → stabilizes plaque.
6. Lipid accumulation (intra- and extracellular).

5. Morphology progression

• Fatty streak: intimal lipid-laden foam cells; no flow disturbance (can appear in infant aorta).
• Atherosclerotic plaque: white-yellow raised intimal lesion = cells (SMC, foam cells, T-cells) + ECM + lipid; peripheral neovascularization.
• Complicated plaque: aneurysm (medial weakening), ulceration, thrombus (→ MI/stroke/embolism), intraplaque hemorrhage, atheroembolism, calcification.

6. Prevention

• Primary: control risk factors, childhood education (diet, exercise, no smoking).
• Secondary: statins (LDL), aspirin (antithrombotic), BP control, surgery (coronary bypass).

7. Mönckeberg arteriosclerosis

Ring-like medial calcification of medium muscular arteries (femoral, popliteal, ulnar); no inflammation, intima/adventitia intact, lumen not narrowed → no clinical significance.

8. Hypertensive microangiopathy

Hypertension (systolic > 140 / diastolic > 90 mmHg; 90–95% essential, 5–10% secondary). The kidney fixes hypertension via RAAS: arteriolosclerosis narrows renal vessels → ↓ renal perfusion → renin release → ↑ BP, perpetuating the cycle. Two arteriolar lesions:

	Hyaline arteriolosclerosis	Hyperplastic arteriolosclerosis
Associated with	Benign / essential hypertension (and diabetes)	Malignant hypertension (diastolic > 150 mmHg)
Wall change	Homogeneous pink hyaline thickening (plasma leak + ↑ ECM)	Concentric laminated “onion-skin” thickening (EC + SMC proliferation)
Extra	Ischemia → benign nephrosclerosis	Fibrinoid necrosis of wall, esp. kidney

9. Diabetic microangiopathy (hyaline type)

Same hyaline lesion but driven by hyperglycemia → endothelial dysfunction. Basement membrane thickening with PAS-positive material from non-enzymatic glycosylation (glucose + protein amino groups → Schiff base → AGEs that crosslink/trap proteins & lipoproteins). Affects kidney, retina, skin, skeletal muscle → nephrosclerosis/renal failure, retinopathy → blindness, neuropathy, coronary microangiopathy.

💡 High-yield: Arteriolosclerosis affects small vessels: hyaline (benign HTN + diabetes → onion-less pink homogeneous wall, benign nephrosclerosis) vs hyperplastic (malignant HTN → “onion-skin” + fibrinoid necrosis). Distinguish from atherosclerosis (intimal plaque = lipid core + fibrous cap, response-to-injury, foam cells) and Mönckeberg (medial calcification, no luminal narrowing, clinically silent). Diabetic microangiopathy = hyaline lesion via AGE-mediated BM thickening.