Atherosclerosis Flashcards
What dietary advice would you give to a patient at risk of atherosclerosis?
Lose weight if needed
Lipid lowering diet (decrease dairy and meat, increase fish and poultry, remove fat and skin from meat, bake and grill, avoid pastry and cake etc)
Use monounsaturated oils
Reduce dietary cholesterol
Eat refined carbohydrates which are absorbed slowly
Increase fibre intake which reduces circulating lipid
Avoid excess alcohol which can cause secondary hyperlipidaemia
What dietary factors may influence the development of atherosclerosis?
Hypertriglyceridaemia and hypercholesterolaemia caused by diets high in fats
Alcohol - moderate consumption appears protective as it increases HDL cholesterol levels
Avoidance of obesity
Good glycaemic control in diabetes
Possible protective role of vitamin E
Define arteriosclerosis and name the conditions that fall under it
Hardening of the arteries.
includes atherosclerosis, arteriolosclerosis, Monkeberg’s disease
Describe atherosclerosis
Disease of the large and medium sized arteries, begins in the intima.
Produces atheromatous plaques filled with a necrotic, gruel-like material. Atheromas contain cholesterol, lipoid material and lipophages are formed within the intima and inner media of large and medium-sized arteries
Describe arteriolosclerosis
Hardening of the arterioles. Little or no connection to atherosclerosis usually secondary to severe hypertension.
Affects arterioles throughout the body but especially those in the kidney.
Describe Monkeburg’s disease
Calcification of the media of large arteries
Uncommon
Describe the pathogenesis of atherosclerosis
Transendothelial passage of lipid droplets which become oxidised, monocytes pick up and become foam cells (endothelium intact)
Crowded foam cells cause endothelium to bulge, smooth muscle cells arise from the media. Lesion is called a fatty streak.
Growth of plaque by an increase in number of foam cells and smooth muscle cells. Some smc take up lipid. Platelets adhere where there are gaps between endothelial cells. Some smc form a roof which is reinforced by collagen, elastin and other matrix proteins (fibrous cap)
Necrosis in the plaque followed by development of cholesterol crystals, calcification, few inflammatory cells and vascularisation of the adventitia (weak and leaky - haemorrhage and thrombosis)
What size arteries does high blood cholesterol affect?
Large and medium (and only parts of these)
Where does atherosclerosis begin?
The intima (often where flow is disturbed, such as around the opening of a branch)
What is atheroma?
The necrotic core of the plaque consisting of dead cells, debris and cholestrol clefts
Where does lipid in an atheromatous plaque generally come from?
LDLs which carry cholesterol
Describe how ulceration of an atheromatous plaque can cause problems.
The core is exposed as the fibrous cap is eroded from underneath. This leads to immediate blood clotting and triggers a cascade which leads to clot enlargement, which can quickly obstruct blood flow
How can thrombus formation cause an atheroma to break up, and what problem would this cause?
It releases vasoconstrictors which causes spasms at the site of the plaque.
This can cause it to shed emboli.
What is the consequence of calcification in and around the plaque?
Arteries become stiffer
How can atherosclerosis cause an aneurysm?
Local weakening of the wall as the plaque invades the media and disrupts the elastic fibres, which causes local dilatation
Describe an aneurysm.
Local dilatations of an artery due to weakening of the arterial wall.
Describe the difference between a saccular and fusiform aneurysm.
Saccular - shaped like a sac. can be 10-15cm in the aorta. Lined and/or filled with a thrombus.
Fusiform - shaped like a spindle.
Where do dissecting aneurysms tend to occur?
In the aorta and it’s major branches
Describe what causes an aneurysm to dissect.
A tear in the intima allows blood to enter and separate the media. It can sometimes re-enter the lumen through a second tear
Why is prevention important in atherosclerosis?
The course of atherosclerosis is mostly silent until secondary symptoms appear. By this time it can be too late.
Give the cellular events that can lead to atherosclerotic lesions.
Chronic endothelial damage
Endothelial dysfunction allowing monocyte and platelet adhesion, and emigration of T-lymphocyte. Growth factors and cytokines are released which are cytotoxic to endothelial and smooth muscle cells.
Platelets release factors causing migration of smooth muscle cells from the media to intima.
Smooth muscle emigrates, macrophage activation
Macrophages and smooth muscle cells engulf lipid.
Macrophages produce toxic oxygen species which oxidise LDLs which are then engulfed by macrophages to form foam cells
Smooth muscle proliferation causes collagen and other ECM deposition, extracellular lipid and neovascularisation.
PDGF causes proliferation of smooth muscle cells.
What is platelet-derived growth factor (PDGF) produced by?
Platelets
Macrophages
Endothelial cells
Smooth muscle cells
Describe the morphological appearance of fatty streaks.
Flat and yellow, no disturbance to blood flow.
Seen in children
Contains some T-lymphocytes and extracellular lipid.
Describe the morphological appearance of atherosclerotic plaques.
White/yellow and impinge on the lumen
Raised lesion initiating within the intima with a soft, yellow core of lipid covered by a firm, fibrous cap.
Tend to be partly circumferential and occur more in the abdominal than thoracic aorta.
