Atheroma Flashcards
What is the difference between a fatty streak, simple plaque, and complicated plaque?
Fatty streak: lipid deposits in intima (yellow, slightly raised)
Simple plaque: raised yellow-white plaque with an irregular outline, widely distributed; tend to enlarge and coalesce
Complicated plaque: simple plaque + thrombosis, haemorrhage, calcification, or aneurysm
Define atheroma, atherosclerosis, and arteriosclerosis.
ATHEROMA = accumulation of intracellular and extracellular lipid in the intima and media of large and medium-sized arteries
ATHEROSCLEROSIS = thickening and hardening of arterial walls as a consequence of atheroma
ARTERIOSCLEROSIS = thickening of the walls of arteries and arterioles usually as a result of hypertension or diabetes mellitus (NOT DUE TO ATHEROMA)
Outline the formation of atheroma.
Early: proliferation of smooth muscle cells (tunica media), accumulation of foam cells and extracellular lipid
Later: fibrosis, necrosis, formation of cholesterol-clefts (needle-shaped cholesterol crystals which dissolve to leave small clefts), +/- inflammatory cells
Laterer: disruption of internal elastic lamina, damage extends into media, ingrowth of blood vessels, plaque fissuring
What are some of the different outcomes of ischaemic heart disease?
Sudden death
Myocardial infarction
Angina pectoris
Arrhythmias
Cardiac failure
Cerebral:
- transient ischaemic attack (“mini-stroke”): carotid artery occluded but symptoms resolve after 24hrs
- cerebral infarction (stroke)
- multi-infarct dementia: series of small strokes which affect cognitive impairment
Mesenteric:
- ischaemic colitis: inflammation of colon due to ischaemia
- malabsorption (due to restricted bloodflow)
- intestinal infarction (“black bowel”): caused by hernia, adhesions, emboli
Peripheral vasculature:
- intermittent claudication
- Leriche syndrome: occluded iliac arteries - claudication pain in buttocks with associated impotence
- ischaemic rest pain: burning pain in arch/distal foot whilst recumbent (lying down)
- gangrene
Abdominal aortic aneurysm/aortic dissection
What is an aneurysm? What can an abdominal aortic aneurysm progress to?
ANEURYSM: abnormal balloon-like swelling in the wall of an artery (localised, permanent, abnormal dilatation of a blood vessel)
- rupture of abdominal aortic aneurysm -> retroperitoneal haemorrhage (5cm< wide - likely to rupture)
- leg claudication (distal occlusion of vessels)
- aortic dissection
- aorta presses against bowel wall -> friction -> inflammation -> fibrosis -> aorta and bowel stick together -> fistula -> haemorrhage into bowel cavity
What is an aortic dissection?
Tunica media degeneration
Intima & adventitia rub against each other
Tear
Blood forced through tear
Can lead to an aneurysm which can lead to a hameopericardium
What are some of the risk factors for atheroma?
- Age: slowly progressive throughout life
- Gender: women protected before menopause (?oestrogen), but post-menopausal same risk as men the same age
- Hyperlipidaemia: see familial hypercholesterolaemia/ApoE polymorphisms
- Smoking: affects coagulation system, reduces prostaglandins, increases platelet aggregation
- Hypertension: possibly damages endothelium
- Diabetes: related to hypertension and hyperlipidaemia
- Alcohol: small amount is protective (increased HDLs) but >5units/day affects liver’s ability to metabolise fat (increased fat in liver increases fat deposition elsewhere)
- Infection: possible link to Chlamydia, Heliobacter, Cytomegalovirus
- Obesity
- Stress
- Genetics: variation in apoprotein receptors/metabolism
- ?soft water, ?oral contraceptives
Outline the interaction of cell types during atheroma formation.
ENDOTHELIAL CELLS: alters permeability to lipoproteins, secretion of collagen, increased proliferation and migration of smooth muscle cells (PDGF)
PLATELETS: haemostasis and proliferation and migration of smooth muscle cells (PDGF)
LYMPHOCYTES: TNF may affect lipoprotein metabolism and proliferation and migration of smooth muscle cells (PDGF)
MACROPHAGES: take up LDL to become foam cells, oxidise LDL, secrete proteases which modify the matrix, and proliferation and migration of smooth muscle cells (PDGF)
SMOOTH MUSCLE CELLS: take up LDL to become foam cells and synthesise collagen and proteoglycans
NEUTROPHILS: secrete proteases causing local damage and inflammation
How does endothelial injury cause atheroma to form? What can cause endothelial injury?
Endothelial injury: raised LDLs, “toxins” (smoking), hypertension, haemodynamic stress
- platelet adhesion, PDGF release -> smooth muscle proliferation and migration
- insudation of lipid, LDL oxidation, uptake of lipids by smooth muscle cells and macrophages
- migration of monocytes into intima
What is the ideal cholesterol level?
Below 5mmol/l
How do people with occluded iliac arteries present?
Leriche syndrome = claudication in buttocks/thighs, impotence, weakness/absence of femoral pulses
Buerger’s syndrome = recurrent inflammation and thrombosis of medium arteries and veins in hands and feet (caused by smoking -> peripheral vascular disease) -> claudication, weakness/absence of peripheral pulses, cyanosis, ulcerations, gangrene
How does the endothelium prevent thrombosis?
Produces prostacyclin (prevents adhesion and aggregation of platelets to endothelium), thrombomodulin (binds to thrombin and activates protein C), and prothrombin
