MoD 6 Atheroma Flashcards
Describe the macroscopic features of atherosclerosis.
Fatty streaks - lipid deposits in the tunica intima, often yellow in color, and slightly raised.
Simple plaque - yellow/white in color and widely distributed. Irregular outline and widely dispersed. They often eventually coalesce and then enlarge.
Complicated plaque - thrombosis, haemorrhage into the plaque as well as calcification - calcified aorta often visible on X-ray. Aneurysms can also form.
Describe the microscopic features of atherosclerosis.
Early - proliferation of smooth muscle cells, accumulation of foam cells as well as extracellular lipid deposition.
Late - fibrosis/necrosis, cholesterol clefts, growth of blood vessels into the plaque (liable to rupture as they are leaky) with damage to elastic Lamina.
Describe the effects of severe atherosclerosis in the following:
IHD Cerebral ischaemia Mesenteric ischaemia Peripheral vascular disease Abdominal aortic aneurysm
IHD
- death (often when asymptomatic of atherosclerosis, and then it presents and the person dies)
Angina pectoris - subsides when the person stops exerting themselves
MI
Arrythmias
Cerebral ischaemia
- TIA - loss of blood flow but without the infarct (tissue death)
- cerebral infarct - brain tissue dies
- multi infarct dementia - a vascular problem NOT neurological
Mesenteric ischaemia
- malabsorption
- ischaemic colitis
- intestinal infarct
AAA
- usually proximal to the Ileac bifurcation
- build of thrombosis in the media and intima until it cannot stretch anymore and then it ruptures catastrophically.
PVD
- intermittent claudication
- leriches syndrome
- gangrene
Describe the risk factors for coronary heart disease
Age Gender Hyperlipidaemia - apoE etc. Genetics Smoking Hypertension Diabetes Obesity/lack of exercise
Describe the insulation theory of atherogenesis
Endothelial injury causes an inflammatory response, which increases the permeability to lipids. These can then aggregate within the walls of the vessel
—> Virchows triad.
Describe the response to injury hypothesis for atherogenesis.
Endothelial injury occurs and lipids and LDL accumulate beneath the endothelium. Leukocytes and monocytes then aggregate, and monocytes become activated to become macrophages in the presence of oxidised LDL. These then accumulate in the tunica intima and take up the LDL - forming foamy macrophages (and a fatty streak). This continues to occur until a fibrous plaque forms.
Define Atherosclerosis, atheroma and arteriosclerosis.
Atherosclerosis - thickening and hardening of arterial walls due to atheromas.
Atheroma - the accumulation of intra and extra cellular lipids in the tunica media and intima of medium to large arteries.
Arteriosclerosis - thickening of the walls of arteries and arterioles due to hypertension and diabetes.
Describe the cellular events leading to the formation of atherosclerotic lesions
Thrombosis
Lipid accumulation
Interaction between cells
Production of intercellular matrix.
Name and briefly describe the types of cells involved in the process of atherogenesis.
Platelets - stimulate the migration and proliferation of smooth muscle cells via PDGF.
Macrophages - accumulate lipid to become foamy macrophages. Secrete proteases that modify matrix. Stimulate the proliferation of the smooth muscle cells.
Smooth muscle cells - migrate from the media to intima and also become foam cells.
Neutrophils - secrete proteases that lead to local damage and inflammation
Lymphocytes- affect lipoprotein metabolism and stimulate SMC.
Endothelial cells - altered permeability to lipids, secretion of collagen and proliferation and migration of the SMCs.
What is the unifying hypothesis ?
Endothelial damage is caused by toxins, hypertension, raised LDL and haemodynamic stress, amongst others.
Endothelial damage causes:
- Platelet adhesion and release of PDGF which stimulates SMC.
- lipid insudation (increased permeability to lipids) foam cells produced
- migration of monocytes into the tunica intima
- foam cells secrete cytokines which further stimulate SMC and other inflammatory cells.
