Histo: Vascular and Cardiac Pathology Flashcards
What is atherosclerosis?
A disease characterised by fatty deposits and fibrosis of the inner layer (tunica intima) of arteries
List some risk factors for atherosclerosis.
- Age (40-60)
- Gender
- Genetics
- Hyperlipidaemia
- Hypertension
- Smoking
- Diabetes mellitus
Outline the pathogenesis of atherosclerosis.
- Endothelial injury causes accumulation of LDL
- LDL enters intima and is trapped
- LDL is converted into modified and oxidised LDL causing inflammation
- Macrophages take up oxiLDL via scavenger receptors and become foam cells
- Apoptosis of foam cells causes inflammation and cholesterol core of laque
- Increase in adhesion molecules in endothelium due to inflammation results in more macrophages and T cells entering plaque as well as platelet aggregation.
- Vascular smooth muscle cells are also recruited from tunica media forming fibrous cap
What is a fatty streak?
- Earliest change in atherosclerosis
- Lipid filled foamy macrophages deposit in the intima but they do not disturb flow
NOTE: presence in pretty much everyone < 10 years old
What is critical stenosis?
When oxygen demand is greater than supply
This occurs at around 70% occlusion and causes stable angina at first
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.
- Lots of foam cells and extracellular lipids
- Thin fibrous cap
- Few smooth muscle cells
- Adrenaline increases BP and causes vasoconstriction
- Circadian rhythm (more likely to have an infarct in the morning)
List the possible presentations of ischaemic heart disease.
- Angina pectoris
- MI
- Chronic ischaemic heart disease with heart failure
- Sudden cardiac death
What are the most common 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
What is a myocardial infarction?
Death of cardiac muscle due to prolonged ischaemia.
Outline the pathogenesis of myocardial infarction.
- Coronary arthersclerosis
- Rupture of plaque resulting in platelet activation + thrombosis OR vasospasm OR emboli occluding vessel further down
- Decreased blood supply resulting in ischaemia, infarction that is irreversible past 20-40mins and results in myocardial necrosis
What is the most common cause of death in post-menopausal women?
Myocardial infarction
Outline the myocardial response to plaque rupture and subsequent ischaemia and infarction.
- Loss of contractility occurs within 60 seconds
- So, heart failure may precede myocyte death (so patients could get an arrhythmia and die before any histological changes take place)
- Irreversible after 20-40 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, homogenous cytoplasm, necrotic cell death
- 1-4 days - infiltration of polymorphs then macrophages
- 5-10 days - removal of debris
- 1-2 weeks - granulation tissue, new blood vessels, myofibroblasts, collagen synthesis
- Weeks to months - strengthening and decllularising resulting in scar tissue
What is reperfusion injury?
- Consequence of letting blood go back into the area of myocardial necrosis
- Oxidative stress, calcium ovrload and inflammation caus further injury
- Arrhythmias are common
- It can cause stunned myocardium - reversible cardiac failure lasting several days
What is hybernating 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
Dressler’s
Embolism
Recurrence
following an MI, if a patient develops ventricular anneurysm what do you expect to see on an ECG
Asymptomatic persistent ST elevation in certian leads.
What is the 1-year mortality after an MI?
30%
What is chronic ischaemic heart disease?
Progressive heart failure due to ischaemic myocardial damage
NOTE: there may be no prior infarction, usually due to atherosclerosis
What is sudden cardiac death?
Unexpected death from cardiac causes in individuals without symptomatic heart disease or early after the onset of symptoms (e.g. 1 hour)
Usually due to lethal arrhythmia (ischaemi-induced electrical instability)
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
- Congestion and statis of venous blood in liver = 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 and systolic dysfunction
List some causes of dilated cardiomyopathy.
- Idiopathic
- Infective
- Toxic (e.g. alcohol)
- Hormonal
- Genetic (e.g. haemochromatosis)
- Immunological (e.g. myocarditis)
What is hypertrophic cardiomyopathy?
- Thickening of the heart muscle
- Family history in 50% of cases
- Diastolic dysfunction
NOTE: some are associated with a specific abnormality in the beta-myosin heavy chain
What is restrictive cardiomyopathy?
- Impaired ventricular compliance
- Results in a normal sized heart with normal sized ventricles but large atria
- Diastolic dysfunction
causes of restrictive cardiomyopathy
sarcoidosis
amyloidosis
radiation induced fibrosis
Clinical features expected in Acute Rheumatic Rever
Peaks at age 5-15 years - multisystem illness affecting joints (arthritis), skin (subcutaneous nodules) and HEART (pancarditis).
Develops 2-4 weeks after strep throat infection.
What is chronic rheumatic valvular disease caused by?
Caused by immune cross-reactivity with cardiac valves in pts with rheumatic heart disease
Which valve is most commonly affected in rheumatic valvular disease?
Left-sided valves (almost always mitral)
What would you see in cardiac histology of a heart affected with rheumatic fever
Beady fibrous vegetations
Aschoff bodies (small giant cell granulomas)
Anitschkov myocytes (regenerating myocytes)
What is the most common cause of aortic stenosis?
Calcified aortic stenosis (old age)
List some causes of aortic regurgitation.
- Rigidity (rheumatic heart disease)
- Destruction (infective endocarditis)
- Disease of the aortic valve ring due to dilatation (dissecting anneurysms, Marfan’s, syphilis aortitis, ankylosing spondylitis)
Which valves are most commonly affected by endocarditis?
Left-sided valves (unless you are an IVDU)
What are the two different types of true aneurysms?
Fusiform
Saccular
Causes of pericarditis
Viral and idiopathic most common
Dressler’s syndrome (post-MI)
Granulomatous (TB)
Typical clinical features of pericarditis
Pleuritic chest pain
ST elevation in ALL limbs!
