Atherosclerosis Flashcards
definition: Arteriosclerosis
“Hardening of the arteries” – a group of disorders that have in common thickening and loss of elasticity of arterial walls. Three distinctive
morphological variants are recognised
Atherosclerosis
progressive disease affecting the intima of elastic and
muscular arteries characterised by focal atheromas (fibrofatty plaques) consisting
of a lipid core covered by a fibrous cap. Atherosclerosis overwhelmingly accounts
for more death and serious morbidity in the Western world than any other
disorder.
Monckeberg’s medial sclerosis
characterised by calcification of the media of
muscular arteries.
Arteriolosclerosis
Characterised by the proliferative or hyaline thickening of the walls of small arteries and arterioles
Major predisposing factors for atherosclerosis
Diet and hyperlipidaemias (hypercholesterolaemia, hypertriglyceridaemia)
Hypertension – both systolic and diastolic hypertension
Cigarette smoking – esp. responsible for increasing heart disease in women
Diabetes mellitus – 2x risk of myocardial infarct, 8x-150x risk of gangrene of the extremities
Minor predisposing factors for atherosclerosis
Obesity Physical inactivity Male gender Increasing age Family history Stress (“type A” personality – competitive, stressful lifestyle) - controversial Oral contraceptives - controversial High carbohydrate intake - controversial
AHA stages of atherosclerosis
Type I – Lipid is present in macrophages in the intima
Type II – Lipid is present in both macrophages and smooth muscle cells
Type III – Fibrous plaque
Type IV – Complex plaque (fibrous cap overlying a lipid core)
Pathogenesis of atherosclerosis
The lesions of atherosclerosis are initiated as a response to some form of injury to arterial endothelium.
There are roles for endothelial injury, macrophages
and other inflammatory and immunological mechanisms, smooth muscle cell proliferation, hyperlipidaemia and thrombosis.
Endothelial injury: role
Endothelial damage is a major risk factor in atherogenesis (well shown in experimental animals) but early lesions in humans develop at sites of intact
endothelium.
Endothelial damage is a major risk factor in atherogenesis (well
shown in experimental animals) but early lesions in humans develop at sites of intact
endothelium.
Monocytes migrate into the intima and then accumulate low-density lipoprotein (LDL) to produce foam cells.
Monocytes/macrophages express the LDL receptor and a specific receptor
(scavenger receptor) for oxidised LDL (oxidised by EC, platelet or white blood cell enzymes).
T cells (CD4+ and CD8+) are found in plaques – role uncertain.
Smooth muscle proliferation
With lipid accumulation, smooth muscle cell
proliferation and extracellular matrix deposition in the intima are the major processes
for the progressive growth of plaques.
Hyperlipidemia
Hyperlipoproteinaemia is the abnormality common to most syndromes of premature atherosclerosis.
Can be primary (due to a genetic defect) or
secondary to some other disorder (e.g. nephrotic syndrome, alcoholism, hypothyroidism, and diabetes mellitus). Increases in the plasma level of LDL may
increase the level of lipid penetration in the arterial wall.
Hyperlipoproteinaemia may also directly alter EC function.
Infaction definition
An infarct is an area of ischaemic necrosis within a tissue or organ,
produced by occlusion of either its arterial supply or its venous drainage.
Infarcts usually result from acute arterial occlusion
White infarcts occur
(1) with arterial occlusion and (2) in solid tissues e.g. heart,
spleen, kidneys.
Red infarcts occur
(1) with venous occlusions, (2) in loose tissues e.g. lung, (3) in
tissues with a double circulation e.g. liver and (4) in tissues that are previously
congested.
Transmural infarct (MI)
(commonest) – the ischaemic necrosis involves the full or
nearly full thickness of the ventricular wall in the distribution of a single coronary
artery. Usually associated with coronary atherosclerosis, plaque rupture and superimposed
thrombosis.
Subendocardial Myocardial infarct
(= Acute coronary syndrome) – this constitutes an area of ischaemic necrosis limited to the inner one-third, or at most one-half, of the
ventricular wall. There is diffuse stenosing coronary atherosclerosis and global
reduction of coronary flow (e.g. due to shock) but no plaque rupture and no
thrombosis.
Infarction
Areas of damage undergo a progressive sequence of changes that consists of:
typical ischaemic coagulative necrosis, followed by inflammation and repair.
20-40 min post MI
Ultrastructural changes of irreversible damage
2-3h post MI
Staining defect with tetrazolium dye (detects dehydrogenase enzymes)
4-12 h post MI
Classic histological features of necrosis
12-24 h post MI
Gross alterations visible with the naked eye (pallor or red-blue hue)
2-3 days post MI
Acute inflammation most prominent
5-10 days post MI
Macrophages remove necrotic cardiac muscle cells
2-4 weeks post MI
Granulation tissue most prominent
6 weeks post MI
scarring well advanced
how can you distinguish the age of a well healed old infarct?
Once an infarct is well healed, it is impossible to distinguish its age (i.e. an 8-wek-old
and a 10-year-old infarct can look similar.
embolisation definition
Embolism is the transfer of abnormal material by the bloodstream and its impaction in a vessel.
The impacted material = the embolus.
how many presentations of CHEST PAIN a year?
600,000
patients
per
year
how many have NSTEMI/UA a year?
150,000 have UA/NSTEMI (1 in 4)
How many have STEMI a year?
60 000 (1 in 10)
how many dead after stemi in 6 months?
12% dead at 6 months!
coronary occlusion can result from:
- Atherosclerotic plaque rupture and subsequent thrombus formation
- Coronary dissection
- Coronary Spasm
- Coronary artery embolism
other causes of ST elevation
- Acute pericarditis/myocarditis
- Massive PE (VI‐V2 occasionally)
- Brugada (V1‐V3 with RBBB morphology)
- Takotsubo Stress Induced Cardiomyopathy
- Hyperkalaemia (V1‐V2)
- Hypothermia
- Hypercalcaemia
secondary prevention after PCI
- Aspirin 75mg
- Clopidogrel 75mg
- Bisoprolol
- Ramipril
- High dose Statin
- Cardiac rehab and follow up
- DVLA: no driving for 1 week post PCI
prostaglandin pathway
membrane phospholipids (phospholipase A)»_space;> arachidonic acid (COX)»> PG2 (COX)»_space;> PH2»_space; specific enzymes:
1) TXA2 -plt aggregation, vasoconstriction
2) PGI2 aka prostacyclin - vasodilatation, inhibits aggregation, inhibits gastric acid production
3) PGE2 - natriuresis, vasodilatation, inhibits gastric acid production
ASPIRIN STUDIES
300mg loading dose in AMI
Significant reduction in cardiovascular mortality
(ISIS-2), non-fatal MI and decreased reocclusion
rates following AMI
Reduction in progression from unstable angina
to MI in 40% (RISC)
Secondary prevention: 75mg/day with a
reduction in events
Thienopyridines
Clopidogrel & Prasugrel
Inhibit ADP-mediated stimulation of the P2Y12 receptor
resulting in inhibition of platelet activation and aggregation
Reduce major cardiac events, thrombosis and restenosis rate
ACS &DES: 12 months clopidogrel; BMS: 1 month
Ex-vivo testing: 34% clopidogrel non-responders
effects of nitrates
1) Decrease myocardial O2 demand: Low dose: venodilatation Larger dose: arterial vasodilatation 2) Improve coronary blood flow: Dilate coronary arteries Improve coronary collateral flow Reverse coronary artery spasm
cardiac rupture post MI
CARDIAC RUPTURE (1-5 % of cases). Results from the mechanical weakening that occurs in necrotic and inflamed myocardium. Commonest at 4-7 days post-infarct. Most commonly involves ventricular free wall >>haemopericardium and cardiac tamponade. Rupture of interventricular septum >> left-to-right shunt. Rupture of papillary muscle -> severe acute mitral incompetence.
pericarditis post-mi
Usually develops about the 2nd or 3rd day. It is
fibrinous or fibrinohaemorrhagic and is usually localised to the region overlying the necrotic area.
mural thrombosis post MI
(15-40 % of cases). The combination of a
local myocardial abnormality in contractility (causing stasis) and endocardial damage (causing a thrombogenic surface) leads to mural thrombosis and thromboembolism.
ventricualr aneurysm
A late complication that most
commonly results from a large anteroseptal, transmural infarct that heals into a large area of thin scar tissue that paradoxically bulges during systole.
