Flashcards in MoD Session 6 Deck (137):
What is atheroma?
Accumulation of intracellular and extracellular lipid in the intima and media of large and medium sized arteries
What is atherosclerosis?
Thickening and hardening of arterial walls as a consequence of atheroma
What is arteriosclerosis?
Thickening of the walls of arteries and arterioles usually from hypertension or DM
Is atherosclerosis or arteriosclerosis the same as atheroma?
What is the normal arterial structure?
Subendothelial connective tissue
Internal elastic lamina
External elastic lamina
How does the muscular media change as you move to arteries closer to the heart?
More elastin and less smooth muscle
What is the fatty streak in atheroma?
Lipid deposits in the intima which give rise to a yellow, slightly raised tissue
Why is the relationship of the fatty streak not direct to the atheroma?
Location of lesions in intima is not identical to the most severe atherosclerosis
What is the simple plaque in atheroma formation?
Individual lesions enlarge and coalesce to form widely distributed, irregularly outlined, raised yellow/white tissue
What is the complicated plaque in atheroma formation?
Haemorrhage into the thrombotic plaque by invading BV from the adventitia can cause it to rupture
Calcification of the plaque can further stiffen arterial walls
Aneurysm forms if there is a loss of elastic tissue
Where are common sites of atheroma?
Aorta - below superior mesenteric and above renal arteries
What does the severity of atheroma depend on?
What are the three early microscopic features of atheroma?
Proliferation of smooth muscle cells
Accumulation of foam cells
What are the later microscopic features of atheroma?
Cholesterol clefts from crystals
+/- inflammatory cells
Disruption of internal elastic lamina
Damage through to media
Ingrowth of BV
What leads to haemorrhage of plaque and subsequent occlusion of the artery?
Ingrowth of BV
How do cholesterol clefts appear histiologically?
As gaps as cholesterol dissolves during fixation
What is the structure of atheroma?
Smooth muscle cell
What is present in variable amounts in different atheromas?
Lipid - some hardly have any
What happens over time to an atheroma?
Matures by fibrosis
Replaces smooth muscle
What are the possible clinical effects of atheroma?
Ischaemic heart disease
Peripheral vascular disease
Abdominal aortic aneurysm
Name some consequences of ischaemic heart disease.
How is an old MI seen in the heart?
Pale tissue in heart wall
How does atheroma cause cerebral ischaemia?
Atheroma in carotid arteries causes turbulent flow --> thrombus --> embolism --> trapped in cerebral arteries
What are the sequelae of cerebral ischaemia?
Transient ischaemic attack
Multi infarct dementia
What can be a further complication of cerebral infarction?
Can haemorrhage causing extra damage to tissues which is visible
Which artery is mesenteric ischaemia particularly seen in?
What can mesenteric ischaemia cause?
Why is mesenteric ischaemia hard to recover in the elderly which is where it is most commonly seen?
Due to loss of GI function
Can the superior mesenteric artery be removed if it has become ischaemic?
Yes if BP is normal, no if BP is high
What is intermittent claudication?
Pain in calf upon exercise due to relative ischaemia which is relieved by rest but has a decreased claudication distance after
What is intermittent claudication a type of?
Peripheral vascular disease
What develops after intermittent claudication in the peripheral vascular disease pathway?
Ischaemic rest pain
What I s the final stage in the pathway of peripheral vascular disease?
What is Leriche syndrome?
Relative ischaemia in the iliac artery
What are the S/S of Leriche syndrome?
Pain in buttock
Decreased/absent femoral pulse
What happens to the collateral vessels in Leriche syndrome?
They increase in number to maintain oxygen supply
How does atheroma lead to abdominal aortic aneurysm?
Atheroma causes loss of elastic tissue --> abnormal BV wall and flow --> thrombus
When does an abdominal aortic aneurysm rupture?
When the wall stretches and is not thick enough to support the increased diameter of the aorta
What can increase the risk of atheroma formation?
Stress and personality type
Lack of exercise
Which gender has the higher risk of atheroma formation?
Male up until menopause
Which three pathogens have been linked with an increase in risk of atheroma formation?
Which lipid is most significant in the risk of atheroma formation?
What is the suggested method by which cigarette smoking increases risk of atheroma formation?
Decreases prostaglandin 2 levels
Increases platelet aggregation
Causes hypercoaguable blood
What is a powerful risk factor for IHD?
How may hypertension increase risk of atheroma formation?
Causes endothelial damage from high pressure
By how much does having DM increase the risk of IHD?
What is lost in premenopausal women with DMD?
Protective effect against atheroma formation
Why are all sizes of BV compromised in DM?
Small vessels are compromised by arteriosclerosis
Other than IHD, what else does DM increase the risk of?
Peripheral vascular disease
How many units of alcohol per day increases IHD risk?
>5 units per day
What effect can small amounts of alcohol have on the pathogenesis of atheroma formation?
May be protective
How is lipid transported in the blood?
What do lipoproteins carry?
What is the structure of a lipoprotein?
Hydrophilic outer phospholipid layer and apolipoprotein (A-E) layer
What is the function of chylomicrons?
Transport lipid from intestine to liver
What is the function of LDL?
Rich in cholesterol to carry it to non-liver cells
What is the function of VLDL?
Carry cholesterol and TAGs from liver so TAGs can be removed to leave LDL behind
What is the function of HDL?
Carry cholesterol from periphery back to liver
Genetic variations on what are associated with changes in LDL levels?
What allows there to be at least 6 Apo E phenotypes possible?
Polymorphisms of the genes involved
What can be used as risk markers for atheroma?
Polymorphisms of Apo E genes
What causes familial predisposition to atheroma?
Variations in apolipoprotein metabolism and/or receptors
What is familial hyperlipidaemia?
Genetically determined abnormalities of lipoproteins leading to early development of atheroma
How do the relative consequences for heterozygotes and homozygotes in familial hyperlipidaemia compare?
Heterozygotes are less severely affected
Homozygotes often have MI before 25 y.o.
What are visible signs of familial hyperlipidaemia?
What forms xanthomas?
Foamy macrophages sitting in the dermis, especially on tendons
What are the four possible mechanisms for atheroma formation?
Reaction to injury hypothesis
How are atheroma formed in the thrombogenic/encrustation theory?
Plaques are formed by repeated thrombi and lipid from the thrombi forms an overlying fibrous cap
How is atheroma formed by the insudation theory?
Endothelial injury causes inflammation which increases permeability of lipid through intima from plasma
What are the two mechanisms proposed by the reaction to injury hypothesis in atheroma formation?
Hypercholesteroleamia causes endothelial injury stimulating platelet adhesion and increased permeability so plaque forms whilst monocytes penetrate endothelium causing smooth muscle cells to proliferate and migrate
LDL, especially oxidised causes visually undetectable endothelial injury
What is the monoclonal hypothesis in atheroma formation?
Smooth muscle proliferation --> monoclonal tumour (plaque)
What questions can be raised about the monoclonal tumour formed in the monoclonal hypothesis of atheroma formation?
Abnormal growth control?
What processes are involved in atheroma?
Lipid accumulation in lesions
Production of abnormal ECM (fibrosis)
Interactions b/w cell types
What cells may interact at different stages of atheroma?
What do neutrophils do during atheroma?
Secrete proteases causing continued local damage and inflammation
What do lymphocytes do during atheroma?
Secrete TNF which may affect lipoprotein metabolism
Stimulate proliferation and migration of smooth muscle cells
What do macrophages do during atheroma?
Take up lipid to form foam cells
Secrete proteases which modify matrix
Stimulate proliferation and migration of smooth muscle
What do smooth muscle cells do in atheroma?
Take up LDL and other lipids to form foam cells
Synthesise collagen and proteoglycans
What do platelets do in atheroma?
PDGF stimulates proliferation and migration of smooth muscle cells
What do endothelial cells do in atheroma?
Altered permeability to lipoproteins
Stimulate proliferation and migration of smooth muscle cells
What is the unifying hypothesis for atheroma formation?
Endothelial injury leads to:
Smooth muscle cell proliferation, migration and production of matrix
Insudation of lipid by smooth muscle cells and macrophages
What are the possible causes of endothelial injury in the unifying hypothesis of atheroma formation?
High LDL levels
Toxins e.g. cigarette smoke
Haemodynamic stress which varies in different areas of circulation
What may macrophages possibly do in the unifying hypothesis of atheroma formation?
What do the cytokines secreted by foam cells in the unifying hypothesis of atheroma formation do?
Cause further smooth muscle cell stimulation
Recruit other inflammatory cells
Where do monocytes migrate to in the unifying hypothesis of atheroma formation?
What can be done to try and prevent atheroma formation?
Not too much alcohol
Lower fat intake
Control weight w/regular exercise
What interventions are used after a clinical event caused by atheroma?
Statins to decrease lipid levels
Is atherosclerosis seen in veins?
What percentage of lumen occlusion is required to significantly affect flow through an artery?
Which three diseases cause decrease in arterial elasticity thus causing arteriosclerosis?
Which arteries does atherosclerosis affect?
Medium and large sized
How does atherosclerosis progress?
Begins in intima producing plaques filled with necrotic gruel-like material
What is arteriolosclerosis?
Hardening of the arterioles affecting the small arteries
Describe the connection b/w arteriolosclerosis and atherosclerosis.
Little or none
What is arteriolosclerosis usually secondary to?
Which arterioles does arteriolosclerosis particularly affect?
Those of the kidney
What is Monkeberg's disease?
Uncommon calcification of the media of large arteries
What is the approximate diameter of the basic lesion (plaque) seen in atherosclerosis?
What causes the endothelium to bulge in the pathogenesis of atherosclerosis?
Crowded foam cells
What happens in the final stage in the pathogenesis of atherosclerosis?
Necrosis in the plaque followed by development of cholesterol crystals, calcification and vascularisation from the adventitia
What is the key event in the pathogenesis of atherosclerosis?
Focal accumulation of look and cells beneath the endothelium forming a raised, flat plaque 1-2 mm thick
Where can plaque formation in atherosclerosis be a major obstacle to flow?
How long does the process of plaque formation in atherosclerosis in humans take?
What favours lipid deposition and plaque formation?
Areas of disturbed flow
How can a plaque in atheroma formation become ulcerated?
Fibrous cap eroded from underneath exposing core
What can cause spasm at the site of a plaque?
Thrombi releasing vasoconstrictors
What can happen if the exposed atheroma in a plaque complication breaks up?
It can shed atheromatous emboli
What can develop in and around a plaque making the artery even stiffer?
What plaque complication is seen in cerebral arteries and is especially associated with hypertension?
Rupture of the atherosclerotic artery and bleeding secondary to weakening of the medial layer
What are dilatations in veins called?
What is a saccular aneurysm?
Weakening of an artery wall shaped like a sac
What can prevent the bursting of a saccular aneurysm?
Lining/filling by thrombus
What diameter can saccular aneurysms reach in the aorta?
What are fusiform anuerysms?
Aneurysms shaped like a spindle
How do dissecting aneurysms occur?
Inner layer of arterial wall tears open --> blood enters tear --> media separates into two layers --> blood sometimes reenters lumen through second tear
Where do dissecting aneurysms occur?
Virtually only in aorta and its major branches
What is the survival of dissecting anuerysms like?
At what point does atherosclerosis stop being a totally silent disease?
Symptoms secondary to plaque comic actions arise
How do macrophages cause oxidation of LDL?
Produce toxic oxygen species
What stage of the morphological appearance of atheroma is seen in children?
In which type of arteries are atherosclerotic plaques seen?
Medium and large sized muscular
What range of diameter do atheromatous plaques occupy?
Where do symptoms of severe atherosclerosis usually occur?
How do statins reduce risk of atheroma formation?
Inhibit HMG CoA reductase which is required for cholesterol biosynthesis in the liver
Why is premature vascular disease seen in homocystinuria?
Due to high levels of circulating homocysteine
Why can low folate or vitamin B intake cause premature vascular disease?
Causes raised levels of homocysteine
How can geography be linked to atheroma development?
Ubiquitous among developed nations
Lower incidence in South America, Africa and Asia
Migrants who immigrate to high risk locations and adopt new lifestyles and diet have same risk as the new location
How can genetic variations causing higher levels of angiotensin converting enzyme be a risk marker for atheroma formation?
Higher levels result in hypertension
What is the difference between primary and secondary prevention in atherosclerosis?
Primary = in people who have never had complications
Secondary = in people who have had events
What interventions can be used in atherosclerosis?
Lipid lowering drugs
Control of arrhythmias
What level of anti-oxidant intake should be avoided to decrease risk of atherosclerosis?
What is found in vegetable and seed oils, soya beans, saffron, sunflower, cereal and nuts which has a possible protective role?
Vitamin E (antioxidant)
What oils should be used for cooking to decrease the risk of a high atherosclerosis-risk patient?
Monounsaturated (olive) and polyunsaturated (sunflower, soya)
Which foods can be avoided to reduce dietary cholesterol?
What type of sugar should be consumed to reduce atherosclerosis risk?
Unrefined not simple
Which foods high in soluble fibre reduce circulating lipid?