MoD Atheroma Flashcards
Define atherosclerosis
The thickening and hardening of arterial walls as a consequence of atheroma
Define atheroma
The accumulation of intracellular and extracellular lipid in the intimate and media of large and medium sized arteries
Define arteriosclerosis
The thickening of walls of arteries and arterioles usually as a result of hypertension or diabetes mellitus
What are the macroscopic features of an atheroma?
Fatty streak - lipid deposits in the intima, appears yellow and slightly raised
Simple plaque - raised yellow/white, irregular outline
Complex plaque - may rupture (thrombosis + haemorrhage), calcify and form an aneurysm
What are the common sites for atheroma?
Aorta - especially abdominal
Coronary arteries
Carotid and cerebral arteries
Leg arteries
What are the microscopic features of an atheroma?
Early changes: proliferation of smooth muscle cells, accumulation of foam cells and extracellular lipid
Later changes: fibrosis, necrosis and cholesterol clefts
disruption of internal elastic lamina which extends to the media, ingrowth of blood vessels and plaque fissuring
What are some of the clinical effects of atheroma?
Ischaemic heart disease - sudden death, MI, arrhythmias, cardiac failure
Cerebral ischaemia - cerebral infarction (stroke), or mini stroke
Mesenteric ischaemia - presents as rectal bleeding, intestinal infarction “black bowel”, malabsorption
Peripheral vascular disease - affects vessels supplying the legs, ischaemic rest pain, gangrene, intermittent claudication
Abdominal aortic aneurysm - fusiform bulge in aorta
What are the risk factors for athersclerosis?
Age
Gender - women protected before menopause
Hyperlipidaemia - LDL most significant, Apo E can vary genetically which changes LDL levels
Smoking
Hypertension - may cause endothelial damage
Diabetes mellitis
Alcohol
infection
How can atheroma be prevented?
Primary prevention: stop smoking, reduced fat intake, treat hypertension, reduce alcohol, weight control
Outline the stages involved in atheroma formation
There is chronic endothelial injury (due to raised LDL, toxins, hypertension)
This causes platelet adhesion, monocyte accumulation in the intima and release of cytokines and growth factors
Smooth muscle cells migrate from the media into the intimata
Smooth muscle cells and macrophages engulf lipids to become foam cells
There is collagen and matrix deposition and extracellular lipid deposition
What are the cells involved in the formation of an atheroma?
Endothelial cells - produce collagen, stimulate migration of smooth muscle cells
Platelets - PDGF stimulates proliferation and migration of smooth muscle cells
Smooth muscle cells - take up LDL to become foam cells, synthesise collagen and proteoglycans
Macrophages - oxidise LDL, take up lipids to become foam cells, stimulate smooth muscle cells
Lymphocytes - produce cytokines that stimulate proliferation and migration of smooth muscle cells
Neutrophils - secrete proteases leading to local damage and inflammation
What is the response to injury/insudation hypothesis?
Rudolf Virchow
There is endothelial injury (maybe from oxidised LDL) followed by inflammation which makes the vessel wall more permeable to plasma lipid
What is the monoclonal hypothesis?
Each plaque is monoclonal (smooth muscle cells are all derived from a single cell)
might represent abnormal growth control (benign tumour??)
What is the thrombogenic theory?
Plaques form by repeated thrombi
Lipid is derived from thrombi
