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PATHOLOGY - Arteriosclerosis

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Nian Baring
Nian Baring

Arteriosclerosis is the hardening and narrowing of arteries due to plaque buildup. The three main types are arteriolosclerosis (small arteries), Monckeberg medial sclerosis (calcification of muscular arteries), and atherosclerosis (most common). Atherosclerosis features atheromas that protrude into the vessel lumen. Risk factors like age, gender, genetics, hyperlipidemia, hypertension, smoking, and diabetes accelerate atherosclerosis. Inflammation and infection also contribute to plaque formation and rupture, which can cause acute issues like heart attack or stroke.

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PATHOLOGY: Arteriosclerosis nianderthalNOTES
ARTERIOSCLEROSIS DEF: -hardening of the arteries -generic term reflecting arterial wall thickening and loss of elasticity THREE GENERAL PATTERNS: 1. Arteriolosclerosis 2. Monckeberg medial sclerosis 3. Atherosclerosis
1. Arteriolosclerosis -affects small arteries and arterioles -anatomic variants: a. hyaline b. hyperplastic
2. Monckeberg medial sclerosis -has calcific deposits in muscular arteries that may undergo metaplasia to bone -lesions do not encroach vessel lumen thus NOT CLINICALLY SIGNIFICANT
3. Atherosclerosis -most frequent and clinically important pattern -characterized by intimal lesions called ATHEROMAS that protrude into the vessel lumen -consists of a raised lesion: a. Grumuous Core – made of lipid, (cholesterol or cholesterol ester) yellow, soft b. Fibrous Cap – white
3. Atherosclerosis EPIDEMIOLOGY -Risk factors have a multiplicative effect -Constitutional Risk Factors in IHD a. Age – clinically manifests middle age or later b. Gender – premenopausal women are relatively protected due to favorable influence of estrogen -but clinical trials have failed to demonstrate any utility of hormonal therapy for vascular diseases prevention a. Genetics – MOST SIGNIFICANT INDEPENDENT RISK FACTOR
3. Atherosclerosis EPIDEMIOLOGY -Modifiable Risk Factors in IHD a. Hyperlipidemia – esp. hypercholesterolemia, increased LDL, decreased HDL, increased lipoprotein a *STATINS – a class of drugs that lower circulating cholesterol levels by inhibiting HMG-Coa reductase, the rate-limiting enzyme in hepatic cholesterol biosynthesis
3. Atherosclerosis EPIDEMIOLOGY -Modifiable Risk Factors in IHD b. Hypertension – both systolic and diastolic components are important - MOST IMPORTANT CAUSE OF LEFT VENTRICULAR HYPERTROPHY c. Cigarette smoking – prolonged smoking of one pack of cigarettes or more daily doubles the death rate from IHD
3. Atherosclerosis EPIDEMIOLOGY -Modifiable Risk Factors in IHD d. Diabetes mellitus – induces hypercholesterolemia
3. Atherosclerosis EPIDEMIOLOGY -Additional Risk Factors a. Inflammation – present during all stages of atherogenesis and is intimately linked with atherosclerotic plaque formation and rupture *C-reactive Protein (CRP) has emerged as one of the simplest and most sensitive inflammatory markers; decreased by STATINS
3. Atherosclerosis EPIDEMIOLOGY -Additional Risk Factors b. Hyperhomocysteinemia – seen in CAD, PAD, stroke and venous thrombosis -elevated homocysteine levels can be caused by low folate and Vitamin B12 intake c. Metabolic syndrome
3. Atherosclerosis EPIDEMIOLOGY -Additional Risk Factors d. Lipoprotein (a) – an altered form of LDL, associated with CAD and CVD e. Factors affecting Hemostasis f. Other Factors – lack of exercise; competitive stressful lifestyle (type A personality); obesity
3. Atherosclerosis PATHOGENESIS Hypotheses: a. Intimal Cellular Proliferation b. Repetitive Formation and Organization of Thrombi c. Response-To-Injury -views atherosclerosis as a chronic inflammatory and healing response of the arterial wall to injury -lesion progression occurs through the interaction of modified lipoproteins, monocyte-derived macrophages, and T-lymphocytes with the normal cellular constituents of the arterial wall
3. Atherosclerosis PATHOGENESIS c. Response-To-Injury -PATHOGENIC EVENTS INVOLVED: i. Endothelial Injury -increased vascular permeability -leukocyte adhesion -thrombosis ii. Accumulation of Lipoproteins in vessel wall -usually LDL and its oxidized forms iii. Monocyte adhesion to the endothelium, followed by migration into the intima and transformation into macrophages and foam cells
3. Atherosclerosis PATHOGENESIS c. Response-To-Injury -PATHOGENIC EVENTS INVOLVED: iv. Platelet adhesion v. Factor release from activated platelets, macrophages and vascular wall cells, inducing smooth muscle cell recruitment vi. Smooth muscle cell proliferation and ECM production vii. Lipid accumulation -extracellular and within cells (macropahes and smooth muscle cells)
3. Atherosclerosis PATHOGENESIS MAJOR MECHANISMS +Endothelial Cell Injury -results in intimal thickening -early human lesions begin at sites of morphologically intact endothelium, THUS, endothelial dysfunction underlies human atherosclerosis -can be caused by: -hypertension -hyperlipidemia -toxins from cigarette smoke -infectious agents -inflammatory cytokines -homocysteine
3. Atherosclerosis PATHOGENESIS MAJOR MECHANISMS +Endothelial Cell Injury 2 MOST IMPORTANT CAUSES OF ENDOTHELIAL DYSFUNCTION -hemodynamic disturbances -hypercholesterolemia
3. Atherosclerosis PATHOGENESIS +Endothelial Cell Injury *Hemodynamic Disturbances -plaques tend to occur at areas of disturbed flow patterns: a. Ostia of exiting vessels b. Branch points c. Along the Posterior wall of the abdominal aorta
3. Atherosclerosis PATHOGENESIS +Endothelial Cell Injury *Hemodynamic Disturbances -nonturbulent laminar flow in normal vasculature leads to the induction of endothelial genes whose products protect against atherosclerosis e.g. SUPEROXIDE DISMUTASE
3. Atherosclerosis PATHOGENESIS +Endothelial Cell Injury *Lipids -Lipoprotein abnormalities present in many MI survivors: -Increased LDL -Decreased HDL - Increased Lipoprotein (a) -DOMINANT LIPIDS IN ATHEROMATOUS PLAQUES ARE: -Cholesterol -Cholesterol Esters
3. Atherosclerosis PATHOGENESIS +Endothelial Cell Injury *Lipids -Lowering serum cholesterol by diet or drugs slows the rate of progression of atherosclerosis, causes regression of some plaques, and reduces the risk of cardiovascular events
3. Atherosclerosis PATHOGENESIS +Endothelial Cell Injury *Lipids -Mechanisms by which HYPERLIPIDEMIA contributes to ATHEROGENESIS: -impair endothelial cell function by increasing local oxygen free radical production -accumulate lipoproteins within the intima, which are then oxidized by oxygen free radicals
3. Atherosclerosis PATHOGENESIS +Endothelial Cell Injury *Lipids -Oxidized LDL is ingested by macrophages through a SCAVENGER RECEPTOR, distinct from LDL receptor -MACROPHAGES become FOAM CELLS after accumulation of Oxidized LDL within the phagocyte
3. Atherosclerosis PATHOGENESIS +Endothelial Cell Injury *Inflammation -dysfunctional arterial endothelial cells express adhesion molecules that encourage leukocyte adhesion -VCAM1 – binds monocytes and T cells -Monocyte recruitment and differentiation is theoretically protective because they remove harmful lipid particles, but the presence of OXIDIZED LDL AUGMENTS Macrophage activation and cytokine production
3. Atherosclerosis PATHOGENESIS +Endothelial Cell Injury *Infection -Microorganisms detected in atherosclerotic plaques: -Herpesvirus -Cytomegalovirus -Chlamydiae pneumoniae
3. Atherosclerosis PATHOGENESIS +Smooth Muscle Proliferation -intimal smooth muscle cell proliferation and ECM deposition convert a fatty streak into a mature atheroma *FATTY STREAK = EARLIEST LESION -Growth Factors involved: -PDGF -FGF -TGF-a
3. Atherosclerosis PATHOGENESIS +Smooth Muscle Proliferation -Smooth muscle cells synthesize ECM that stabilizes atherosclerotic plaques - Active Inflammatory cells in atheromas can cause intimal smooth muscle cell apoptosis, and increase ECM catabolism leading to unstable plaques
3. Atherosclerosis MORPHOLOGY *FATTY STREAKS -EARLIEST LESIONS IN ATHEROSCLEROSIS -begin as minute, flat yellow spots and then colaesce -not significantly raised and do not cause flow disturbance -virtually in all children older than 10 years -coronary fat streaks begin to form in adolescence, at the same anatomic sites that later tend to develop plaques
3. Atherosclerosis MORPHOLOGY *ATHEROSCLEROTIC PLAQUE -KEY PROCESSES: Intimal Thickening & Lipid Accumulation -Gross: -Color: White or Yellow (Ulcerated Plaques: Red- brown) -Size: 0.3-1.5 cm in diameter (can coalesce) -In humans, the ABDOMINAL AORTA affected MORE than THORACIC AORTA
3. Atherosclerosis MORPHOLOGY *ATHEROSCLEROTIC PLAQUE -Commonly involved Vessels (Descending Order): 1. Lower Abdominal Aorta 2. Coronary Arteries 3. Popliteal Arteries 4. Internal Carotid Arteries 5. Circle of Willis
3. Atherosclerosis MORPHOLOGY *ATHEROSCLEROTIC PLAQUE -Principal Components (CEL): 1. Cells -smooth muscle cells, macrophages, T cells 2. ECM -collagen, elastic fibers, proteoglycans 3. Lipids -intracellular and extracellular
3. Atherosclerosis MORPHOLOGY *ATHEROSCLEROTIC PLAQUE -Configuration: 1. Fibrous cap – superficial; made of smooth muscle cells, collagen 2. Shoulder – beneath and to the side of the cap; more cellular with macrophages, T cells, smooth muscle cells 3. Necrotic core – deep into cap, made of lipid primarily cholesterol and cholesterol esters, debris from dead cells, foam cells, fibrin, thrombus, other plasma proteins
3. Atherosclerosis MORPHOLOGY *ATHEROSCLEROTIC PLAQUE -The periphery of the lesions show neovascularization -Plaques enlarge due to: 1. Cell death and degenration 2. Synthesis and degradation of ECM 3. Organization of thrombus -Atheromas often undergo CALCIFICATION
3. Atherosclerosis MORPHOLOGY *ATHEROSCLEROTIC PLAQUE -Plaques are susceptible to the following CLINICAL CHANGES: 1. Rupture, ulceration, erosion 2. Hemorrhage into a plaque 3. Atheroembolism 4. Aneurysm formation
3. Atherosclerosis CONSEQUENCES OF ATHEROSCLEROTIC DISEASE -Large Elastic and Large and Medium Muscular arteries are the MAJOR TARGETS of ATHEROSCLEROSIS -Smaller vessels can become occluded, compromising distal tissue perfusion -Ruptured plaque can embolize atherosclerotic debris and cause distal vessel obstruction, or can lead to acute thrombosis -Destruction of the underlying vessel wall can lead to aneurysm formation, which can rupture and/or be a thrombi
3. Atherosclerosis CONSEQUENCES OF ATHEROSCLEROTIC DISEASE *ATHEROSCLEROTIC STENOSIS -plaques can gradually occlude vessel lumens, compromising blood flow causing ischemic injury -outward remodeling preserves lumen diameter -effects of vascular occlusion depend on arterial supply and metabolic demand of affected tissue
3. Atherosclerosis CONSEQUENCES OF ATHEROSCLEROTIC DISEASE *ACUTE PLAQUE CHANGE -plaque erosion or rupture is typically promptly followed by partial or complete vascular thrombosis resulting in acute tissue infarction -THREE CATEGORIES OF PLAQUE CHANGES: 1. Rupture/Fissuring – exposing thrombogenic constituents 2. Erosion/Ulceration – exposing subendothelial basement membrane to blood 3. Hemorrhage into the atheroma
3. Atherosclerosis CONSEQUENCES OF ATHEROSCLEROTIC DISEASE *ACUTE PLAQUE CHANGE -the precipitating lesion in patients who develop MI or other coronary syndromes is NOT NECESSARILY a severely stenotic and hemodynamically significant lesion BEFORE ITS ACUTE CHANGE
3. Atherosclerosis CONSEQUENCES OF ATHEROSCLEROTIC DISEASE *ACUTE PLAQUE CHANGE INTRINSIC and EXTRINSIC FACTORS THAT INFLUENCE RISK OF PLAQUE RUPTURE: INTRINSIC EXTRINSIC Plaque Structure Blood Pressure Plaque Composition Platelet Reactivity Adrenergic stimulation
3. Atherosclerosis CONSEQUENCES OF ATHEROSCLEROTIC DISEASE *ACUTE PLAQUE CHANGE VULNERABLE Plaques: -contain large areas of foam cells and extracellular lipids -with thin fibrous caps *collagen represents the major structural component of the fibrous cap and accounts for its mechanical strength and stability -contain few smooth muscle cells -have clusters of inflammatory cells *STATINS stabilize plaques by reducing plaque inflammation
3. Atherosclerosis CONSEQUENCES OF ATHEROSCLEROTIC DISEASE *ACUTE PLAQUE CHANGE -Peak time of onset of acute myocardial infarction is between 6 AM and 12 NOON
3. Atherosclerosis CONSEQUENCES OF ATHEROSCLEROTIC DISEASE *THROMBOSIS *VASOCONSTRICTION -compromises lumen size and by increasing local mechanical forces can potentiate plaque disruption -stimulated by: 1. Adrenergic agonists 2. Local platelet contents 3. impaired secretion of cell relaxing factors 4. mediators released from perivascular inflammtory cells

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PATHOLOGY - Arteriosclerosis

  • 2. ARTERIOSCLEROSIS DEF: -hardening of the arteries -generic term reflecting arterial wall thickening and loss of elasticity THREE GENERAL PATTERNS: 1. Arteriolosclerosis 2. Monckeberg medial sclerosis 3. Atherosclerosis
  • 3. 1. Arteriolosclerosis -affects small arteries and arterioles -anatomic variants: a. hyaline b. hyperplastic
  • 4. 2. Monckeberg medial sclerosis -has calcific deposits in muscular arteries that may undergo metaplasia to bone -lesions do not encroach vessel lumen thus NOT CLINICALLY SIGNIFICANT
  • 5. 3. Atherosclerosis -most frequent and clinically important pattern -characterized by intimal lesions called ATHEROMAS that protrude into the vessel lumen -consists of a raised lesion: a. Grumuous Core – made of lipid, (cholesterol or cholesterol ester) yellow, soft b. Fibrous Cap – white
  • 6. 3. Atherosclerosis EPIDEMIOLOGY -Risk factors have a multiplicative effect -Constitutional Risk Factors in IHD a. Age – clinically manifests middle age or later b. Gender – premenopausal women are relatively protected due to favorable influence of estrogen -but clinical trials have failed to demonstrate any utility of hormonal therapy for vascular diseases prevention a. Genetics – MOST SIGNIFICANT INDEPENDENT RISK FACTOR
  • 7. 3. Atherosclerosis EPIDEMIOLOGY -Modifiable Risk Factors in IHD a. Hyperlipidemia – esp. hypercholesterolemia, increased LDL, decreased HDL, increased lipoprotein a *STATINS – a class of drugs that lower circulating cholesterol levels by inhibiting HMG-Coa reductase, the rate-limiting enzyme in hepatic cholesterol biosynthesis
  • 8. 3. Atherosclerosis EPIDEMIOLOGY -Modifiable Risk Factors in IHD b. Hypertension – both systolic and diastolic components are important - MOST IMPORTANT CAUSE OF LEFT VENTRICULAR HYPERTROPHY c. Cigarette smoking – prolonged smoking of one pack of cigarettes or more daily doubles the death rate from IHD
  • 9. 3. Atherosclerosis EPIDEMIOLOGY -Modifiable Risk Factors in IHD d. Diabetes mellitus – induces hypercholesterolemia
  • 10. 3. Atherosclerosis EPIDEMIOLOGY -Additional Risk Factors a. Inflammation – present during all stages of atherogenesis and is intimately linked with atherosclerotic plaque formation and rupture *C-reactive Protein (CRP) has emerged as one of the simplest and most sensitive inflammatory markers; decreased by STATINS
  • 11. 3. Atherosclerosis EPIDEMIOLOGY -Additional Risk Factors b. Hyperhomocysteinemia – seen in CAD, PAD, stroke and venous thrombosis -elevated homocysteine levels can be caused by low folate and Vitamin B12 intake c. Metabolic syndrome
  • 12. 3. Atherosclerosis EPIDEMIOLOGY -Additional Risk Factors d. Lipoprotein (a) – an altered form of LDL, associated with CAD and CVD e. Factors affecting Hemostasis f. Other Factors – lack of exercise; competitive stressful lifestyle (type A personality); obesity
  • 13. 3. Atherosclerosis PATHOGENESIS Hypotheses: a. Intimal Cellular Proliferation b. Repetitive Formation and Organization of Thrombi c. Response-To-Injury -views atherosclerosis as a chronic inflammatory and healing response of the arterial wall to injury -lesion progression occurs through the interaction of modified lipoproteins, monocyte-derived macrophages, and T-lymphocytes with the normal cellular constituents of the arterial wall
  • 14. 3. Atherosclerosis PATHOGENESIS c. Response-To-Injury -PATHOGENIC EVENTS INVOLVED: i. Endothelial Injury -increased vascular permeability -leukocyte adhesion -thrombosis ii. Accumulation of Lipoproteins in vessel wall -usually LDL and its oxidized forms iii. Monocyte adhesion to the endothelium, followed by migration into the intima and transformation into macrophages and foam cells
  • 15. 3. Atherosclerosis PATHOGENESIS c. Response-To-Injury -PATHOGENIC EVENTS INVOLVED: iv. Platelet adhesion v. Factor release from activated platelets, macrophages and vascular wall cells, inducing smooth muscle cell recruitment vi. Smooth muscle cell proliferation and ECM production vii. Lipid accumulation -extracellular and within cells (macropahes and smooth muscle cells)
  • 16. 3. Atherosclerosis PATHOGENESIS MAJOR MECHANISMS +Endothelial Cell Injury -results in intimal thickening -early human lesions begin at sites of morphologically intact endothelium, THUS, endothelial dysfunction underlies human atherosclerosis -can be caused by: -hypertension -hyperlipidemia -toxins from cigarette smoke -infectious agents -inflammatory cytokines -homocysteine
  • 17. 3. Atherosclerosis PATHOGENESIS MAJOR MECHANISMS +Endothelial Cell Injury 2 MOST IMPORTANT CAUSES OF ENDOTHELIAL DYSFUNCTION -hemodynamic disturbances -hypercholesterolemia
  • 18. 3. Atherosclerosis PATHOGENESIS +Endothelial Cell Injury *Hemodynamic Disturbances -plaques tend to occur at areas of disturbed flow patterns: a. Ostia of exiting vessels b. Branch points c. Along the Posterior wall of the abdominal aorta
  • 19. 3. Atherosclerosis PATHOGENESIS +Endothelial Cell Injury *Hemodynamic Disturbances -nonturbulent laminar flow in normal vasculature leads to the induction of endothelial genes whose products protect against atherosclerosis e.g. SUPEROXIDE DISMUTASE
  • 20. 3. Atherosclerosis PATHOGENESIS +Endothelial Cell Injury *Lipids -Lipoprotein abnormalities present in many MI survivors: -Increased LDL -Decreased HDL - Increased Lipoprotein (a) -DOMINANT LIPIDS IN ATHEROMATOUS PLAQUES ARE: -Cholesterol -Cholesterol Esters
  • 21. 3. Atherosclerosis PATHOGENESIS +Endothelial Cell Injury *Lipids -Lowering serum cholesterol by diet or drugs slows the rate of progression of atherosclerosis, causes regression of some plaques, and reduces the risk of cardiovascular events
  • 22. 3. Atherosclerosis PATHOGENESIS +Endothelial Cell Injury *Lipids -Mechanisms by which HYPERLIPIDEMIA contributes to ATHEROGENESIS: -impair endothelial cell function by increasing local oxygen free radical production -accumulate lipoproteins within the intima, which are then oxidized by oxygen free radicals
  • 23. 3. Atherosclerosis PATHOGENESIS +Endothelial Cell Injury *Lipids -Oxidized LDL is ingested by macrophages through a SCAVENGER RECEPTOR, distinct from LDL receptor -MACROPHAGES become FOAM CELLS after accumulation of Oxidized LDL within the phagocyte
  • 24. 3. Atherosclerosis PATHOGENESIS +Endothelial Cell Injury *Inflammation -dysfunctional arterial endothelial cells express adhesion molecules that encourage leukocyte adhesion -VCAM1 – binds monocytes and T cells -Monocyte recruitment and differentiation is theoretically protective because they remove harmful lipid particles, but the presence of OXIDIZED LDL AUGMENTS Macrophage activation and cytokine production
  • 25. 3. Atherosclerosis PATHOGENESIS +Endothelial Cell Injury *Infection -Microorganisms detected in atherosclerotic plaques: -Herpesvirus -Cytomegalovirus -Chlamydiae pneumoniae
  • 26. 3. Atherosclerosis PATHOGENESIS +Smooth Muscle Proliferation -intimal smooth muscle cell proliferation and ECM deposition convert a fatty streak into a mature atheroma *FATTY STREAK = EARLIEST LESION -Growth Factors involved: -PDGF -FGF -TGF-a
  • 27. 3. Atherosclerosis PATHOGENESIS +Smooth Muscle Proliferation -Smooth muscle cells synthesize ECM that stabilizes atherosclerotic plaques - Active Inflammatory cells in atheromas can cause intimal smooth muscle cell apoptosis, and increase ECM catabolism leading to unstable plaques
  • 28. 3. Atherosclerosis MORPHOLOGY *FATTY STREAKS -EARLIEST LESIONS IN ATHEROSCLEROSIS -begin as minute, flat yellow spots and then colaesce -not significantly raised and do not cause flow disturbance -virtually in all children older than 10 years -coronary fat streaks begin to form in adolescence, at the same anatomic sites that later tend to develop plaques
  • 29. 3. Atherosclerosis MORPHOLOGY *ATHEROSCLEROTIC PLAQUE -KEY PROCESSES: Intimal Thickening & Lipid Accumulation -Gross: -Color: White or Yellow (Ulcerated Plaques: Red- brown) -Size: 0.3-1.5 cm in diameter (can coalesce) -In humans, the ABDOMINAL AORTA affected MORE than THORACIC AORTA
  • 30. 3. Atherosclerosis MORPHOLOGY *ATHEROSCLEROTIC PLAQUE -Commonly involved Vessels (Descending Order): 1. Lower Abdominal Aorta 2. Coronary Arteries 3. Popliteal Arteries 4. Internal Carotid Arteries 5. Circle of Willis
  • 31. 3. Atherosclerosis MORPHOLOGY *ATHEROSCLEROTIC PLAQUE -Principal Components (CEL): 1. Cells -smooth muscle cells, macrophages, T cells 2. ECM -collagen, elastic fibers, proteoglycans 3. Lipids -intracellular and extracellular
  • 32. 3. Atherosclerosis MORPHOLOGY *ATHEROSCLEROTIC PLAQUE -Configuration: 1. Fibrous cap – superficial; made of smooth muscle cells, collagen 2. Shoulder – beneath and to the side of the cap; more cellular with macrophages, T cells, smooth muscle cells 3. Necrotic core – deep into cap, made of lipid primarily cholesterol and cholesterol esters, debris from dead cells, foam cells, fibrin, thrombus, other plasma proteins
  • 33. 3. Atherosclerosis MORPHOLOGY *ATHEROSCLEROTIC PLAQUE -The periphery of the lesions show neovascularization -Plaques enlarge due to: 1. Cell death and degenration 2. Synthesis and degradation of ECM 3. Organization of thrombus -Atheromas often undergo CALCIFICATION
  • 34. 3. Atherosclerosis MORPHOLOGY *ATHEROSCLEROTIC PLAQUE -Plaques are susceptible to the following CLINICAL CHANGES: 1. Rupture, ulceration, erosion 2. Hemorrhage into a plaque 3. Atheroembolism 4. Aneurysm formation
  • 35. 3. Atherosclerosis CONSEQUENCES OF ATHEROSCLEROTIC DISEASE -Large Elastic and Large and Medium Muscular arteries are the MAJOR TARGETS of ATHEROSCLEROSIS -Smaller vessels can become occluded, compromising distal tissue perfusion -Ruptured plaque can embolize atherosclerotic debris and cause distal vessel obstruction, or can lead to acute thrombosis -Destruction of the underlying vessel wall can lead to aneurysm formation, which can rupture and/or be a thrombi
  • 36. 3. Atherosclerosis CONSEQUENCES OF ATHEROSCLEROTIC DISEASE *ATHEROSCLEROTIC STENOSIS -plaques can gradually occlude vessel lumens, compromising blood flow causing ischemic injury -outward remodeling preserves lumen diameter -effects of vascular occlusion depend on arterial supply and metabolic demand of affected tissue
  • 37. 3. Atherosclerosis CONSEQUENCES OF ATHEROSCLEROTIC DISEASE *ACUTE PLAQUE CHANGE -plaque erosion or rupture is typically promptly followed by partial or complete vascular thrombosis resulting in acute tissue infarction -THREE CATEGORIES OF PLAQUE CHANGES: 1. Rupture/Fissuring – exposing thrombogenic constituents 2. Erosion/Ulceration – exposing subendothelial basement membrane to blood 3. Hemorrhage into the atheroma
  • 38. 3. Atherosclerosis CONSEQUENCES OF ATHEROSCLEROTIC DISEASE *ACUTE PLAQUE CHANGE -the precipitating lesion in patients who develop MI or other coronary syndromes is NOT NECESSARILY a severely stenotic and hemodynamically significant lesion BEFORE ITS ACUTE CHANGE
  • 39. 3. Atherosclerosis CONSEQUENCES OF ATHEROSCLEROTIC DISEASE *ACUTE PLAQUE CHANGE INTRINSIC and EXTRINSIC FACTORS THAT INFLUENCE RISK OF PLAQUE RUPTURE: INTRINSIC EXTRINSIC Plaque Structure Blood Pressure Plaque Composition Platelet Reactivity Adrenergic stimulation
  • 40. 3. Atherosclerosis CONSEQUENCES OF ATHEROSCLEROTIC DISEASE *ACUTE PLAQUE CHANGE VULNERABLE Plaques: -contain large areas of foam cells and extracellular lipids -with thin fibrous caps *collagen represents the major structural component of the fibrous cap and accounts for its mechanical strength and stability -contain few smooth muscle cells -have clusters of inflammatory cells *STATINS stabilize plaques by reducing plaque inflammation
  • 41. 3. Atherosclerosis CONSEQUENCES OF ATHEROSCLEROTIC DISEASE *ACUTE PLAQUE CHANGE -Peak time of onset of acute myocardial infarction is between 6 AM and 12 NOON
  • 42. 3. Atherosclerosis CONSEQUENCES OF ATHEROSCLEROTIC DISEASE *THROMBOSIS *VASOCONSTRICTION -compromises lumen size and by increasing local mechanical forces can potentiate plaque disruption -stimulated by: 1. Adrenergic agonists 2. Local platelet contents 3. impaired secretion of cell relaxing factors 4. mediators released from perivascular inflammtory cells