PBL 5 - pathology of atheroma Flashcards
what is an atheroma?
an accumulation of intracellular and extracellular lipid in the INTIMA of large and medium sized arteries
= an inflammatory condition
what are the 3 stages of the development of atheroma?
- fatty streak
- simple plaque
- complicated plaque
what is arteriosclerosis?
the thickening of the walls of arteries and arterioles usually as a result of hypertension or diabetes
(some would include atheroma as a form of arteriosclerosis)
what would a cross section of an atheromatous plaque look like?
what are blood vessels that are unsupported by surrounding cells prone to? what is the effect on the plaque?
prone to rupture and bleed into the plaque — increases the size of the plaque
how can bleeding into the plaque lead to thrombosis?
you can bleed into a plaque and rupture the surface so the extracellular lipid gets in contact with factors in the bloodstream, leading to thrombosis
what happens to the fibrous cap as it matures and what are the effects of this?
= becomes thicker and thicker as the plaque matures
- less likely to rupture
- accumulates fibrous tissue — reduces diameter of the lumen
describe a simple atheromatous plaque
- fat in intima — extracellular or within modified smooth muscle cells
- fibrous cap
- blood vessel proliferation
- inflammatory cells
why do you get blood vessel proliferation in a simple atheromatous plaque?
- in response to low oxygen environment
- because initially there is no blood supply
describe a complicated atheromatous plaque
- calcification
- plaque disruption = rupture of surface
- haemorrhage into plaque — small blood vessels bleed into plaque structure
- thrombosis
- aneurysm formation
how do you get calcification in a complicated atheromatous plaque?
- breakdown of fat — WBCs come along to deal with it
- release fatty acids from triglycerides
- fatty acids bind to circulating calcium = calcification
how can an aneurysm form in a complicated atheromatous plaque?
inflammation causes weakening of elastic tissue in wall — can lead to blood clot formation
what is the typical site of an aneurysm caused by atheroma?
lower end of the abdominal aorta, immediately above the bifurcation into the common iliac arteries
what happens to a bulging aneurysm?
wall gets thinner and thinner until it ruptures
name some common sites of atheroma
- aorta — especially abdominal
- coronary arteries
- carotid arteries
- cerebral arteries
- leg arteries
name some risk factors for atheroma
- smoking
- male sex
- menopause
- diet (high in fat)
- alcohol
- obesity
- familial hyperlipidaemia (can cause atheromas in early adult life)
- acquired hyperlipidaemia
- diabetes mellitus
- lack of exercise
- type A personality
- stress
- infection
- oral contraceptives
why do some people say red wine can be protective?
contains salicylates — prevent platelet aggregation so considered protective — however don’t actually drink enough for it to be protective
name 5 hypotheses/mechanisms of atheroma
- encrustation of platelets
- insulation of lipid from blood
- monoclonal proliferation of smooth muscle cells (lysonisation = suggests proliferation from a patch of cells that themselves have a single cell ancestor)
- response to injury (endothelial damage)
- infection with Ag-Ab complexes deposition
what is ischaemia?
reduced delivery of blood to an organ, or part of an organ, sufficient to compromise function
what is infarction?
reduced delivery of blood to an organ, or part of an organ, sufficient to lead to its death
what are some major consequences of atheroma around the body?
- brain — cerebral infarct, vascular dementia
- gut — small bowel infarction
- kidney — chronic renal failure
- limbs — peripheral vascular disease - largely the legs - number of failures in the function of the muscles of the limbs
- heart — IHD (ischaemic heart disease)
what is a small bowel infarction dye to obstruction of? what can it cause?
- superior mesenteric artery
- can cause sufficient mucosal defect
what is ischaemic colitis and why does it gradually appear?
- ischaemia in the large intestine
- less common consequence of atheroma than small bowel infarction but is also disasterous
- creeps up gradually because if the blood supply to the colon is poor, it can be bypassed to a degree because of the anastomotic connections between the branches of the superior mesenteric and inferior mesenteric arteries
what is intermittent claudication?
= the pain in the muscles caused by exercise in the context where the blood supply is insufficient and causes an individual to stop walking
- pain walking a sufficient distance
what can intermittent claudication (peripheral vascualar disease) lead to when obstruction gets worse?
ischaemic rest pain and gangrene (deaths of body tissue due to lack of blood flow)
what is the cause of 99% of IHD?
coronary artery atheroma
what are some other causes of IHD?
- a few rare diseases eg. Kawasaki disease
- stimulant misuse (eg. cocaine — causes accelerated atheroma in coronary arteries. also damages cardiac muscle)
what are some possible clinical consequences of IHD?
- nothing
- cardiac arrhythmia
- acute coronary syndromes — angina pectoris, acute MI
- acute LV failure
- chronic heart failure
- sudden unexpected death
name 3 cardiac arrhythmias possible from IHD
- atrial fibrillation — common and treatable if detected
- heart block
- ventricular fibrillation
what is heart block?
a disruption in the flow of electrical impulse that causes systolic contraction
what is ventricular fibrillation?
causes ventricles to pump in sufficiently with lots of little contractions (several hundred a minute)
what is angina pectoris?
- chest pain induced by exercise and relieved by rest
- pain emanating from ischaemia in the heart because it has been pushed to the limit because it doesn’t have enough O2 to function in response to exercise — can only walk a particular distance, stop to relieve pain, then repeat
- major forms = stable and unstable
describe stable angina
- symptoms stereotypic
- lowish risk of infarct
describe unstable angina
- pain at rest
- increasing severity of attack — each attack lasts longer than the last
- pain lasting over 15 minutes
- medical emergency
- very high risk of infarct
how is acute myocardial infarction classified according to its distribution?
- REGIONAL (occupying only a proportion of the diameter of the LV) or CIRCUMFERENTIAL (more likely to be clinically silent or difficult to diagnose as ECG changes are less prominent)
- TRANSMURAL (endocardium to epicardium) or SUBENDOCARDIAL (typically limited to 1/3 of the myocardium of the LV)
- regional are usually transmural
- circumferential are usually subendocardial
what are transmural MIs typically associated with?
coronary artery thrombosis
what are subendocardial MIs typically associated with?
increased demand on the heart eg. tachycardia, AF — circumferential subendocardial
is there always an infarction in STEMI and NSTEMI?
no
which is more serious: STEMI or NSTEMI?
STEMI
STEMI vs NSTEMI on an ECG
STEMI has ST elevation
why would an infarct be not fully transmural?
oxygen diffuses in from adjacent structures, sparing often in subendocardial zone
where is it more dangerous to have an infarct than in the free wall of the heart and why?
septum — where conducting tissue runs
complications of an acute MI
- cardiac arrhythmia
- cardiac failure — acute or chronic
- cardiac rupture — free wall or septum
- sudden unexpected death
what causes cardiac tamponade?
- rupture in free wall of heart
- blood fills pericardium
- pericardium doesn’t stretch therefore get cardiac tamponade
describe acute LV failure
- pump failure of LV
- increases pressure in pulmonary capillaries
- rapid fluid accumulation in alveolar walls, and then air spaces — pulmonary oedema
- symptoms come on suddenly
describe chronic heart failure + symptoms
- more gradual onset than acute LV failure
- pump failure on both ventricles
- inadequate systemic blood supply
- tiredness, ankle swelling, minor liver dysfunction
why do you get ankle swelling in chronic HF and what may it be indicative of?
- may be indicative of elevated central venous pressures
- due to increased pressure in the tiny capillaries in the lower part of the body
why do you get minor liver dysfunction in chronic HF?
liver gets congested with blood so can’t get rid of toxic substances
describe sudden unexpected death
- IHD is the most common cause of sudden unexpected death
- a few are acute MI
- moire are acute LV failure
- most are (probably) cardiac arrhythmia
describe how a plaque forms due to hyperlipidaemia (from pharmacology lecture)
- excess LDL in circulation enters the intima of a blood vessel
- monocytes migrate to the intima and transform into macrophages
- macrophages take up oxidised LDL and transform into foam cells
- foam cells attach to the endothelium and form the fatty streak
- foam cells release cytokines and other growth factors that recruit smooth muscle cells
- migrating smooth muscle cells thicken the streak into a stable plaque
