Histo: Vascular and Cardiac Pathology Flashcards
What is atherosclerosis?
A disease characterised by atheromatous deposits and fibrosis of the inner layer (tunica intima) of arteries
List some risk factors for atherosclerosis.
- Age
- Sex
- Genetics (familial hypercholesterolaemia)
- Hyperlipidaemia
- Hypertension
- Smoking
- Diabetes mellitus
- Obesity
RFs have multiplicative effect
Outline the pathogenesis of atherosclerosis.
- Endothelial injury causes accumulation of LDL
- LDL enters intima and is trapped in sub-intimal space
- LDL is converted into modified and oxidised LDL causing inflammation
- Macrophages take up ox/modLDL via scavenger receptors and become foam cells
- Apoptosis of foam cells causes inflammation and cholesterol core of plaque
- Increase in adhesion molecules on endothelium due to inflammation results in more macrophages and T cells entering the plaque
- Vascular smooth muscle cells form the fibrous cap, segregating the thrombogenic core from the lumen
What is a fatty streak?
- Earliest change in atherosclerosis
- Lipid-filled foamy macrophages deposit in the intima
- No flow disturbance
NOTE: presence in pretty much everyone > 10 years old
What makes up an atherosclerotic plaque?
3 components:
- Cells - SMC, macrophages, other leukocytes
- ECM including collagen
- Intracellular and extracellular lipid
> > Causes local flow disturbance
What is critical stenosis?
- Point at which oxygen demand is greater than supply
- Occurs at around 70% occlusion
- Causes stable angina
List three types of acute plaque change.
- Rupture - exposes prothrombogenic plaque contents
- Erosion - exposes prothrombogenic subendothelial basement membrane
- Haemorrhage into plaque - increases size
In which patients does acute plaque change tend to happen?
Patients with mild-to-moderate atheroma (large plaques tend to be very stable)
List some features of vulnerable plaques.
- Large lipid core
- Thin fibrous cap
What is the leading cause of death worldwide for both sexes?
Ischaemic heart disease
List the possible presentations of ischaemic heart disease.
- Angina pectoris
- MI
- Chronic ischaemic heart disease with heart failure
- Sudden cardiac death
What degree of stenosis is required for:
- Chest pain precipitated by exercise
- Chest pain at rest
- 75% stenosis
- 90% stenosis
Where are the most clinically significant sites for atheromatous plaques within the coronary circulation?
- First few centimetres of the LAD and left circumflex
- Entire length of right coronary artery
What is angina pectoris?
- Transient ischaemia that does not produce myocyte necrosis
- Types: stable, unstable, prinzmetal (due to artery spasm)
What are the characteristics of stable angina?
- Precipated by exertion
- Relieved by rest
- No plaque disruption
What are the characteristics of unstable angina?
- Onset with less exertion or at rest
- Disruption of plaque
- May have superimposed thrombus
- Warning of impending infarction
What is a myocardial infarction?
Death of cardiac muscle due to prolonged ischaemia.
Outline the pathogenesis of myocardial infarction.
Coronary atherosclerosis > plaque rupture > superimposed platelet activation > thrombosis and vasospasm > occlusive intracoronary thrombus overlying disrupted plaque > ischaemia > myocardial necrosis
Outline the myocardial response to plaque rupture.
- Loss of contractility occurs within 60 seconds
- Therefore heart failure may precede myocyte death (i.e. patients could get an arrhythmia and die before any histological changes take place)
- Irreversible after 20-30 mins
Which arteries tend to be involved in myocardial infarction (in order of most to least frequent)?
- LAD - 50%
- RCA - 40%
- LCX - 10%
Describe the microscopic changes that take place in myocardial infarction.
- Under 6 hours - normal histology
- 6-24 hours - loss of nuclei + striations, homogenous cytoplasm, necrotic cell death
- 1-4 days - infiltration of PMNs then macrophages
- 5-10 days - removal of debris
- 1-2 weeks - granulation tissue, new blood vessels, myofibroblasts, collagen synthesis
- Weeks to months - strengthening and decellularising the scar
What percentage of MI are asymptomatic, and in which patient groups are these more common?
- 10-15%
- Common in elderly and diabetics
What is reperfusion injury?
- Restoring blood flow to hypoxic tissue increases supply of oxygen which leads to increased production of ROS
- Oxidative stress, calcium overload and inflammation can cause further injury
- Arrhythmias are common
- It can cause stunned myocardium - reversible cardiac failure lasting several days
What is hibernating myocardium?
- Chronic sublethal ischaemia leads to lower metabolism in myocytes which can be reversed with vascularisation
List some complications of MI.
DARTH VADER
- Death
- Arrythmia
- Rupture
- Tamponade
- Heart failure
- Valve disease
- Aneurysm (ventricular)
- Dressler’s syndrome
- Embolism
- Recurrence
What is the 1-year mortality after an MI?
30%
What is chronic ischaemic heart disease?
- Progressive heart failure due to ischaemic myocardial damage
- Leads to hypertrophied, dilated LV
- Usually due to long-standing atherosclerosis
- Microscopic fibrosis
NOTE: there may be no prior infarction
What is sudden cardiac death?
- Unexpected death from cardiac causes in individuals without symptomatic heart disease or early (1hr) after the onset of symptoms
- Usually due to lethal arrhythmia
What are some underlying conditions that can cause sudden cardiac death?
IHD (90%)
- Acute myocardial ischaemia the usual trigger
- Leads to electrical instability of the conduction system
- This usually occurs at sites of old MI scars
Non-atherosclerotic cause (10%) - e.g. long QT
List some causes of heart failure.
- Ischaemic heart disease
- Valve disease
- Hypertension
- Myocarditis
- Cardiomyopathy
List some complications of heart failure.
- Sudden death
- Arrhythmias
- Systemic emboli
- Pulmonary oedema with superimposed infection
- Hepatic cirrhosis (nutmeg liver)
Outline the histology of heart failure.
- Dilated heart
- Scarring and thinning of the walls
- Fibrosis and replacement of ventricular myocardium
What are cardiomyopathies?
Intrinsic problems of the heart muscle
What is dilated cardiomyopathy?
Caused by progressive loss of myocytes leading to a dilated heart
Systolic dysfunction
List some causes of dilated cardiomyopathy.
- Idiopathic
- Genetic: familial, haemochromatosis
- Infection: post-viral myocarditis
- Toxins: alcohol, drugs (cocaine, doxorubicin)
What is hypertrophic cardiomyopathy?
- Thickening of the heart muscle
- Family history in 50% of cases
- Leads to ventricular outflow obstruction and arrhythmia
Diastolic dysfunction
NOTE: some are associated with a specific abnormality in the beta-myosin heavy chain
What is restrictive cardiomyopathy?
Impaired ventricular compliance - diastolic dysfunction, near-normal systolic function
Causes:
- Amyloidosis
- Sarcoidosis
- Haemochromatosis
What is chronic rheumatic heart disease caused by?
Antigenic mimicry
Caused by immune cross-reactivity of group A streptococcal antigens and cardiac valves
Which valve is most commonly affected in rheumatic heart disease?
Mitral valve
What is the most common cause of aortic stenosis?
Aortic valve sclerosis - calcification (age-related)
List some causes of aortic regurgitation.
Valvular defect
- Congential bicuspid valve
- Age-related degeneration
- RHD
- Endocarditis
Aortic dilatation
- Dissection
- Chronic hypertension
- Connective tissue diease e.g. Marfan’s
- Aortitis e.g. syphilis
Which valves are most commonly affected by endocarditis?
- Left-sided valves (mitral > aortic)
- If IVDU, then tricuspid
What are the two different types of true aneurysms?
- Saccular
- Fusiform
Describe the histology of rheumatic heart disease
- Beady fibrous vegetations (verrucae)
- Aschoff bodies (small giant-cell granulomas)
- Anitschkov myocytes (regenerating myocytes)
Acute vs subacute endocarditis?
Causative organism:
- Acute = staph aureus, strep pyogenes
- Subacute = strep viridans
Virulence:
- Acute = high
- Subacute = low
Vegetation morphology:
- Acute = larger and more localised
- Subacute = friable, soft thrombi, few mm in size
Spread:
- Acute = aorta
- Subacute = chordae
Treatment for infective endocarditis?
Acute:
- MSSA - fluclox
- MRSA - rifampicin + vancomycin + gentamicin
Subacute:
- Benzylpenicillin + gentamicin, or vancomycin for 4wks
What is the most common cause of constrictive pericarditis?
TB
What is the most common cause of myocarditis?
Viral infection
What is the most common primary tumour in the heart?
Myxoma
What type of necrosis occurs in MI?
Coagulative necrosis
What is the most common cause of mitral valve stenosis?
Rheumatic heart disease
