Atherosclerosis & Other Vascular Pathology Flashcards
What are the basic constituents of the walls of blood vessels
Endothelial cells
Smooth muscle cells
Extracellular matrix (ECM) including elastic fibres, collagenic fibres, and glycosaminoglycans.
Arterial wall thickness gradually diminishes as the vessels become …….. (smaller, larger). The ratio of wall thickness to lumen diameter becomes ……….. (smaller, greater) with reducing size
Smaller, greater
The intima consists of …….
The intima consists of a single layer of endothelial cells with minimal underlying subendothelial connective tissue.
What is arteriosclerosis
It means hardening of arteries; group of disorder that have in common thickening & low elasticity of arterial wall
What are the three components of arteriosclerosis
Atherosclerosis is characterized by intima thickening & lipid deposition affecting elastic arteries(aorta, carotid & iliac) and muscular large & medium sizes arteries (coronary & renal arteries)
What is Monckeberg’s medial calcification sclerosis
Monckeberg’s medial calcific sclerosis:-
●characterized by ring like calcification of the media layer of muscular arteries occurring in both sexes above 50yrs. No associated inflammation.
●Vessels involved are : femoral, radius, ulnar, genital tract.
●Does not narrow the lumen
●can occur with atherosclerosis
What is arteriolosclerosis
Arteriolosclerosis is characterized by marked proliferative or hyaline thickening of the walls of small arteries and arterioles
What disease is the major cause of heart attack, CVA, and gangrene of the extremities and is responsible for about 50% of all deaths in the United State, Europe, and Japan
Atherosclerosis
What are the major RFs for atherosclerosis
Diet & hyper lipidemint hyper cholesterolemia, high TG)
Hypertension
Cigarette smoking
Diabetes Mellitus
What is the role of endothelial injury in arteriosclerosis
Increased endothelial permeability
Increased enhanced leukocyte adhesion,
Increased alterations in expression of endothelial cell gene products
What are the causes of endothelial dysfunction
cigarette smoke,
homocysteine,
viruses and other infectious agents.
hemodynamic disturbances that accompany normal circulatory function
adverse effects of hypercholesterolemia.
What is the role of inflammation in arteriosclerosis
recruitment and subsequent differentiation of macrophages is initially protective as they remove potentially harmful lipid particles,
●progressive accumulation ultimately results in lesion progression.
●Macrophages produce IL-1 and TNF, which increase adhesion of leukocytes
Several chemokines generated by macrophages, including monocytes Chemotactic protein-1 (MCP-1), may recruit more leukocytes into the plaque.
●Macrophages produce toxic oxygen species that also cause oxidation of the LDL in the lesions,
●They elaborate growth factors that may contribute to SMC proliferation.
What is the change of lipids in arteriosclerosis
Chronic hyperlipidemia, particularly hypercholesterolemia, may directly impair endothelial cell function through
Increased production of oxygen free radicals that deactivate NO, the major endothelial-relaxing factor.
With chronic hyperlipidemia, lipoproteins accumulate within the intima at sites of increased endothelial permeability.
Chemical change of lipid induced by free radicals generated in macrophages or endothelial cells in the arterial wall yields oxidized (modified) LDL
Oxidized LDL is invested by
macrophages through the scavenger receptor, distinct from the LDL receptor , thus forming foam cells
What is the role of oxidized LDL in arteriosclerosis
Increases monocytes accumulation in lesions;
Stimulates release of growth factors and cytokines; and
It is cytotoxic to endothelial cells and smooth muscle cells
What are the roles of smooth muscle cells to arteriosclerosis
Smooth muscle cells migrate from the media to the intima, where they proliferate and deposit Extra cellular matrix components, converting a fatty streak into a mature fibrofatty atheroma, and contribute to the progressive growth of atherosclerotic lesions
Several growth factors have been implicated in the proliferation of SMCs, including PDGF (released by platelets adherent to a focus of endothelial injury, and by macrophages, Endothelia Cells, and Smooth Muscle Cells), FGF, and TGF-αlpha
SMCs may also take up modified lipids, contributing to foam cell formation
Vascular SMCs synthesize extracellular matrix molecules (notably collagen) that stabilize atherosclerotic plaques.
However, activated inflammatory and immune cells in the plaque can lead to the death of intimal SMCs by apoptosis
What is the important abnormality of arteriosclerosis
The important abnormality is focal intima thickening & lipid accumulation which later forms atheromatous plaques
Affect arterial wall partially around the circumference (i.e. eccentric lesion)
What are fatty streaks
Fatty streaks
●are the precursor lesion and appear in aorta in childhood, in coronary in adolescence
●Begins as multiple yellow, flat, spots < lmm
●These coalesce - elongated streaks
Composed of lipid-filled foam cells, T- lymphocytes & Endothelial Cell lipid present in small amount, Collagen, proteoglycan & elastic fibers in variable amount
●Not all fatty streaks progress to plaques
Describe atheromatous plaques
Appear as white to whitish yellow material that impinge on the lumen of the artery
●Sizes vary from 0.3 to 1.5cm in diameter which could coalesce larger masses
●The lesions are eccentric(affect part of wall)
●Cut section-
●superficial portion – fibrous yellow cap
●Deep portion yellow or whitish yellow & soft
●In larger plaque, the center contains cellular debris
It has 3 components in varying proportion:
●(1) cells – Smooth Muscle cell, macrophages, other leukocytes
●(2) connective tissue –Extracellular material including collagen,elastic fibres, proteoglycans
[Fibrous cap is composed of (1) and (2)]
(3) Intracellular & extracellular lipid deposits- disorganized mass of lipid material, cholesterol clefts, cellular debris, plasma proteins, fibrin, thrombus in varying stages of organization. (Necrotic core )
●Progressive fibrosis of the plaque may convert the atheroma to a fibrosis scar
What are the distributions of the lesions in arteriosclerosis
Aorta-abdominal> thoracic>ostia of its major branches
Coronary arteries(first 6cm)
Popliteal A
Descending thoracic aorta
Internal carotid A
Vessels of the circle of Willis
Vessels of the upper extremeties, mesenteric and renal arteries are relatively spared except at their ostia
What are some complications of arteriosclerosis
(1) calcification
(2) focal ulceration or rupture of plaque discharge of debris into blood cholesterol emboli
(3) thrombus formation
(4) haemorrhage into the plague
(5) aneurysmal dilatation
