Session 7 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 intima and media of large and medium sized arteries.
NOTE: plaque contains other substances other than lipids
Define Arteriosclerosis
The thickening of the walls of arteries and arterioles usually as a result of hypertension or diabetes mellitus.
What are three 3 macroscopic features of an atheroma?
Fatty streak
Simple plaque
Complicated plaque
Describe the Fatty Streak of an Atheroma
Lipid deposits in the intima
Yellow, slightly raised
[Relationship to atheroma somewhat debatable (e.g.found in populations which are not prone to atheroma) but generally fatty streak is thought to be a precursor to atheroma]
Describe the Simple Plaque of an Atheroma
Raised yellow/white
Irregular outline
Widely distributed
Enlarge and coalesce (extensive atheroma)
Describe the Complicated Plaque of an Atheroma
Thrombosis
Haemorrhage into plaque
Calcification
Aneurysm formation (due to loss of elastic recoil as fibrosis occurs so as aorta expands, it remains fixed in balloon state -so wall is weaker and more prone to rupture)
What are the common sites of atheroma formation?
Aorta - especially abdominal
Coronary arteries
Carotid arteries
Cerebral arteries
Leg arteries
Describe the Normal Arterial Structure
Endothelium
Sub-endothelial connective tissue
Internal elastic lamina
Muscular media
External elastic lamina
Adventitia
How are the Microscopic Features of an Atheroma classified?
Early changes
Later changes
Describe the microscopic early changes of an Atheroma
Proliferation of smooth muscle cells
Accumulation of foam cells (containing lipid)
Extracellular lipid (within the wall of the artery)
Describe the microscopic later changes of an Atheroma
Fibrosis (include dense fibrous cap over plaque)
Necrosis
Cholesterol clefts (when cholesterol crystallises and forms deposition in the tissue, not the plaque)
+/- Inflammatory cells (very variable)
Disruption of internal elastic lamina
Ingrowth of new blood vessels (formation of new capillaries which are very leaky and therefore may contribute to haemorrhage into plaque)
Plaque fissuring (movement of blood produces shearing forces)
The effect of atheroma depends on site.
Describe the clinical effects of severe atherosclerosis in Ischaemic Heart Disease
Atheroma of the coronary arteries reduces the flow to the myocardium and coronary thrombosis commonly over atheromatous plaques.
They could lead to:
Sudden death (without any warning/ previous symptoms)
Myocardial infarction
Angina pectoris (chest pain upon exercise)
Arrhythmias (if it is ventricular fibrillation, it could lead to sudden deaths
Cardiac failure
The effect of atheroma depends on site. Describe the clinical effects of severe atherosclerosis in Cerebral Ischaemia
Transient Ischaemic Attack (‘mini-stroke’) - infarction of part of the brain.
Symptoms resolved within 24 hours - thrombus in carotid artery is dissolved by Fibrinolysis.
Cerebral infarction (stroke) Multi-infarct dementia (dementia due to multiple infarcts causing cognitive impairment)
The effect of atheroma depends on site. Describe the clinical effects of severe atherosclerosis in Mesenteric Ischaemia
Mesenteric artery can become blocked either due to atheroma or thrombus. This could lead to:
Ischaemic colitis
Malabsorption (because of impoverished blood supply)
Intestinal infarction
Aneurysm due to the high pressure, hardening and weakening.
*Black bowel due to lack of blood supply
The effect of atheroma depends on site. Describe the clinical effects of severe atherosclerosis in Peripheral Vascular Disease
Intermittent claudication (deep muscle/calf pain upon exercise - goes away after rest but may come back after walking a shorter distance progressively until there is pain at rest)
Leriche Syndrome (often associated with impotence, pain in the buttocks as the iliac artery is affected)
Ischaemic rest pain
Gangrene
Note: after an amputation, blood supply may still not be adequate for the metabolic demands of new tissue growth which results in a necessity for a second amputation.
Describe the Cellular events of Atheroma
Endothelial damage –> Platelets –> PDGF –> Smooth Muscle Proliferation
Proliferation and migration of smooth muscle takes the lipid with it.
Macrophages arrive and phagocytose the fat, becoming foam cells.
Discuss the Risk Factors for Atheroma
Age: slowly progressive throughput adult life, risk factors operate over years (although onset can seem sudden).
Gender: women protected relatively before menopause (presumed hormonal - oestrogen - basis)
Hyperlipidaemia: high plasma cholesterol associated with atheroma (LDL most significant, HDL is protective)
Cigarette smoking: powerful risk factor for IHD, risk decreases gradually after giving up, mode of action is uncertain (in the coagulation system, there is reduced PG12 which increases platelet aggregation)
Hypertension: strong link between IHD and high BP, mechanism uncertain?
Diabetes Mellitus: doubles IHD risk, protective effect in premenopausal women lost, DM also associated with high risk of cerebrovascular and peripheral vascular disease
Alcohol
Infection
Lack of exercise
Obesity
Soft water
Oral contraceptives
Stress/personality type
Explain why the mechanism linking hypertension and IHD is uncertain
Endothelial damage can be caused by raised pressure but some sites are more prone to developing atheroma than others but pressure is the same across the body, so if hypertension caused atheroma, shouldn’t atheroma have a uniform distribution?
Explain how alcohol is a risk factor for atheroma
>5 units / day associated with increased risk of IHD.
Alcohol consumption is often associated with other risk factors e.g. Smoking and high BP but still an independent risk factor.
Small amounts of alcohol may be protective (studies looked at Mediterranean diet)
What types of Infections have been linked to Atheroma?
E.g. Chalamydia pneumoniae, Helicobacter pylori, Cytomegalovirus
Note: no firm conclusive evidence - atherosclerosis is clearly multi-factorial.
Describe Lipid Metabolism
Lipid is transported around the body via lipoproteins.
Lipoproteins have a hydrophobic lipid core (cholesterol esters and TAGs) and hydrophilic coat of (phospholipids and apoproteins (A-E)).
Chylomicrons transport lipid from intestine to liver.
VLDL carry cholesterol and TAGs from liver
TAGs are removed leaving LDL. LDL is rich in cholesterol and carry cholesterol to non-liver cells.
HDL carry cholesterol from periphery back to metabolism.
Genetic variations in ApoE are associated with changes in LDL levels. Polymorphisms of the genes involved lead to at least 6 ApoE phenotypes. Polymorphisms can be used as risk markers for atheroma
Genetically determined abnormalities of lipoproteins lead to early development of atheroma (Familial Hyperlipidaemia).
What are the associated physical signs of Familial Hyperlipidaemia?
Associated physical signs include arcus (yellow ring around cornea), tendon xanthomas and xanthelasma (lipid nodules on corner of eyes or on eyelid)
Explain about the Genetic Predisposition to atheroma
Familial predisposition is well known but actual family tree/ pattern of inheritance is unclear.
Possibly due to variations in apolipoprotein metabolism or in apolipoprotein receptors - lipoprotein abnormality.
