Cardiovascular Disease Flashcards
What is this?
Atherosclerosis
What is atherosclerosis?
An arteriosclerosis characterized by atheromatous deposits in + fibrosis of the inner layer of the arteries.
What is atherosclerosis characterised by?
Intimal lesions- Atheroma (atheromatous plaques) that protrude into vessel lumen.
What is this?
Atherosclerosis
What is an atheromatous plaque?
Raised proliferation of endothelium
Soft lipid core
White fibrous cap
What are the 7 main risk factors for atherosclerosis?
Age
Sex
Genetics
Hyperlipidaemia
HTN
Smoking
Diabetes Mellitus
How do the number of risk factors affect the risk of getting atherosclerosis?
2 RFs increase risk 4-fold
3 RFs increase risk 7-fold
What is the pathogenesis of atherosclerosis according to the response to injury hypothesis?
- Endothelial injury, disrupted flow, increased permeability
- LDL accumulation
- Monocyte adhesion to endothelium
- Monocyte migration into intima -> macrophages + foam cells
- Platelet adhesion
- Factor release from activated platelets
- Induces smooth muscle cell recruitment, proliferation, ECM production + T cell recruitment
- Lipid accumulation: extra + intracellular, macrophages + smooth muscle cells
What is this?
Atherosclerosis - smooth muscle proliferation
What is a fatty streak?
Earliest lesion
Lipid filled foamy macrophages
No flow disturbance
In ~all children >10yrs
Relationship to plaques uncertain
Same sites as plaques
What characterises an atherosclerotic plaque?
Patchy: cause local flow disturbances
Only involve a portion of wall
Rarely circumferential
Appear eccentric
Composed of cells, lipid, matrix
What is this?
Atherosclerotic plaque
What are 2 consequences of atheromas?
Stenosis
Acute plaque changes
What is stenosis?
Critical stenosis: demand > supply
Occurs at ~70% occlusion (or diameter <1mm)
Causes “stable” angina
Can lead to Chronic IHD
Acute plaque rupture can occur
What is this?
Plaque disruption Type 11 eccentric ragged stenosis
What is this?
Normal coronary artery
No atherosclerosis
Widely patent lumen that carries as much blood as the myocardium requires.
What are the acute plaque changes that can occur?
Rupture: Exposes prothrombogenic plaque contents
Erosion: Exposes prothrombogenic subendothelial basement membrane
Haemorrhage into plaque: Increase size
What characterises vulnerable plaques?
Large lipid core
Thin fibrous cap
Large inflammatory infiltrate
What is the mechanism for a rupture of a vulnerable plaque?
Adrenaline increases BP + causes vasoconstriction.
Increases physical stress on plaque.
Hence emotional stress increases risk of sudden death.
Circadian periodicity to sudden death (6am-noon).
How do vulnerable plaques contribute to plaque growth?
Not all rupture causes occlusion.
Plaque disruption with platelet aggregation + thrombosis probably common.
Important mechanism for plaque growth.
What can vasoconstriction be due to?
Adrenergic agonists
Platelet contents
Reduced endothelial relaxing factors
Mediators from perivascular cells
What is this?
Coronary atherosclerotic plaque with a yellow core of lipid separated from the lumen by a fibrous cap.
Opposite core = arc of normal vessel wall
What is ischaemic heart disease?
Group of conditions resulting from myocardial ischaemia.
Imbalance of supply to demand for oxygenated blood.
Less nutrients + less waste removal.
Therefore less well tolerated than pure hypoxia.
90% myocardial ischaemia due to reduced blood flow due to atherosclerosis.
Long silent progression prior to Sx
What is this?
IHD
What is this?
IHD
List 4 presentations of IHD
Angina pectoris
Myocardial infarction
Chronic IHD with heart failure
Sudden cardiac death
What is the epidemiology of IHD?
500,000 deaths yearly USA
50% fall in death rate since 1963 (peak)
Fall due to prevention + tx
But aging population
What is the predominant pathogenesis of IHD? What is this due to?
Insufficient coronary perfusion relative to myocardial demand
Due to chronic progressive atherosclerotic narrowing of epicardial coronary arteries + variable superimposed plaque change, thrombosis + vasospasm.
Where do plaques usually occur in IHD?
1st few cm of LAD or LCX
Entire length RCA
What is the pathogenesis of acute coronary syndrome?
Stable plaque becomes unstable.
Due to rupture, erosion, haemorrhage
Generally leads to superimposed thrombus which increases occlusion.
What is angina pectoris?
Transient ischaemia not producing myocyte necrosis.
What are the different types of angina?
Stable, Prinzmetal, Unstable
Stable comes on with exertion, relieved by rest, no plaque disruption.
Prinzmetal: Uncommon, due to artery spasm
What is unstable angina pectoris?
Unstable more frequent, longer onset with less exertion/ at rest.
Disruption of plaque.
Superimposed thrombus.
Possible embolisation or vasospasm.
Warning of impending infarction.
What is a myocardial infarction? What is the incidence?
Death of cardiac muscle due to prolonged ischaemia.
5/1000 yearly UK (STEMI).
IHD most common cause death postmenopausal women.
What is the pathogenesis of artery occlusion in MI?
Sudden change to plaque
Platelet aggregation
Vasospasm
Coagulation
Thrombus evolves
What is the myocardial response to an MI?
Myocardial blood supply compromised leading to ischaemia
Loss of contractility within 60s
Therefore HF can precede myocyte death
Potentially reversible
Irreversible after 20-30m
What are common sites of occlusion in an MI?
LAD: 50%, ant wall LV, ant septum, apex
RCA: 40%, post wall LV, post septum, post RV
LCx: 20%, lat LV not apex
What is the evolution of changes after an MI?
< 6h: Normal histology + CK-MB
6–24h: Loss of nuclei, homogenous cytoplasm, necrotic cell death.
1-4d: Infiltration of polymorphs then macrophages (clear up debris).
5-10d: Removal of debris.
1-2w: Granulation tissue, new blood vessels, myofibroblasts, collagen synthesis.
Weeks-months: Strengthening, decellularising scar.
What is this?
MI, 3–7 days
What is this? What can be seen?
MI 1-3 days.
Coagulation necrosis
Loss nuclei + striations
Neutrophils +++
What is this? What can be seen?
MI 10-14 days
Granulation tissue
Macrophages.
What is this? At what time point?
MI
>2 months old
Lots of fibrosis + scar formation
What are clinical features of an MI?
Common in elderly + diabetes mellitus
10 – 15% asymptomatic
Cardiac enzymes (High CK, Troponin)
Subendocardial infarct may not cause usual ST changes.
What is a reperfusion injury?
Clinical importance uncertain
Due to oxidative stress, Ca overload, inflammation
Arrhythmias common
Biochemical abnormalities last days -> weeks
Thought to cause “stunned myocardium” – reversible cardiac failure lasting several days.
What are 7 short term complications of MI?
Contractile dysfunction → Cardiogenic shock
Arrhythmia: conduction disturbance- bradycardia, SVT
Myocardial rupture: LV free wall most common at ~4-5d
Pericarditis (Dressler syndrome): 2-3d after MI
RV infarction
Infarct extension: new necrosis adjacent to old
Infarct expansion: necrotic muscle stretches → mural thrombus
What is this?
Dressler syndrome
What is the mortality associated with an MI?
Total mortality = 30% in 1 year.
3-4% mortality per year after
What is chronic ischaemic heart disease?
Progressive heart failure due to ischaemic myocardial damage.
May not be have had prior infarction.
Can arise with severe obstructive coronary artery disease.
Enlarged heavy heart, hypertrophied, dilated LV.
Atherosclerosis
Maybe mural thrombi
Fibrosis
What is sudden cardiac death?
Unexpected death from cardiac causes in individuals without symptomatic heart disease or early (1hr) after onset of Sx.
Usually due to lethal arrhythmia
Usually on background of IHD (90%)
Which conditions are associated with sudden cardiac death?
Acute myocardial ischaemia is usual trigger.
Usually causes electrical instability at sites distant from conduction system often near scars from old MIs.
Other conditions also associated e.g. Aortic stenosis, mitral valve prolapse, pulmonary HTN.
What is cardiac failure?
What are the two types of cardiac failure?
End point of many conditions.
Congestive Heart Failure (L+R).
- Left sided: SOB, pulmonary oedema
- Right sided: Peripheral oedema
What is this?
Pulmonary oedema due to left sided heart failure.
What are causes of heart failure?
Ischaemic heart disease
Valve disease
HTN
Myocarditis
Cardiomyopathy
Left sided heart failure (Right)
What are complications associated with heart failure?
Sudden Death
Arrhythmias
Systemic emboli
Pulmonary oedema with superimposed infection
What is the histopathology of heart failure?
Dilated heart, Scarring + thinning of the walls.
Microscopy: Fibrosis + replacement of ventricular myocardium.
What are the types of cardiomyopathy?
Dilated
Hypertrophic
Restrictive
(Too thin, too thick, too stiff)
What is dilated cardiomyopathy?
Progressive loss of myocytes.
Dilated heart.
What are causes of dilated cardiomyopathy?
Idiopathic
Infective: Viral myocarditis
Toxic: Alcohol, chemotherapy (adriamycin, daunorubicin), cobalt, iron
Hormonal: Hyper-, hypo- thyroid, diabetes, peri-partum (?).
Genetic: Haemochromatosis, Fabry’s, McArdle’s.
Immunological: Myocarditis incl. Viral (hypersensitivity component)
What is hypertrophic cardiomyopathy?
LV hypertrophy
Familial in 50% (AD, variable penetrance)
Beta-myosin heavy chain
Thickening of septum narrows left ventricular outflow tract.
What is restrictive cardiomyopathy?
Impaired ventricular compliance
Idiopathic or secondary to myocardial disease eg amyloid, sarcoidosis
Normal size heart, big atria
What is chronic rheumatic valvular disease?
Sequelae of rheumatic fever. Predominantly left-sided valves (almost always mitral).
- Mitral > Aortic > Tricuspid > Pulmonary
- Mitral alone 48%, Mitral + aortic 42%
Thickening of valve leaflet, especially along lines of closure.
Fusion of commissures.
Thickening, shortening + fusion of chordae tendineae.
What is calcific aortic stenosis?
Commonest cause aortic stenosis
Occurs in 70-80s.
Calcium deposits outflow side cusp impairs opening.
Orifice compromised.
Outflow tract obstruction.
What are causes of aortic regurgitation?
Rigidity: Rheumatic, degenerative
Destruction: Microbial endocarditis
Disease of aortic valve ring: Results in dilitation. Valve insufficient to cover increased area.
What are 4 conditions associated with aortic regurgitation?
Marfan’s Syndrome
Dissecting aneurysm
Syphilitic aortitis
Ankylosing spondylitis
What are the two main categories of aneurysms?
True: All layers wall
False: Extravascular haematoma
What are 4 causes of aneurysms?
Weak wall
Congenital e.g. Marfans
Atherosclerosis
Hypertension
Which lipids are good and which are bad?
LDL = BAD
HDL = GOOD
What 7 less obvious risk factors contribute to atherosclerosis?
Inflammation: pro inflammatory state
Metabolic syndrome: HTN, hyperlipidaemia
Lipoprotein a: RF for Cerebrovascular + cardiovascular disease
Haemostasis: procoagulation
Lack of exercise
Stress
Obesity: HTN, DM, low HDL
What is the response to injury hypothesis?
Chronic inflammatory + healing response of arterial wall to endothelial injury.
Why are there many asymptomatic potential victims in atherosclerosis?
Majority of plaques show only mild-moderate luminal stenosis prior to acute change
How does vasoconstriction contribute to risk of disruption of a vulnerable plaque?
Reduced luminal size increases local mechanical forces
How does vasoconstriction contribute to risk of disruption of a vulnerable plaque?
Reduced luminal size increases local mechanical forces
Describe the impact of IHD worldwide
Leading cause of death worldwide for M+F (7million/year).
In general, what amount of stenosis is required to cause symptoms?
75% = Sx precipitated by exercise
Vasodilation cannot compensate above this
90% = pain at rest
List 3 long term complications of MI
Ventricular aneurysm → thrombus, HF, arrhythmia
Papillary muscle rupture
Chronic IHD: progressive late HF
What is this? How common is it?
Ventricular aneurysm
Very rare
What is this?
Papillary muscle rupture
