Histo: Vascular and Cardiac Pathology Flashcards
What is atherosclerosis?
A disease characterised by atheromatous deposits in and fibrosis of the inner layer (tunica intima) of arteries
List some risk factors for atherosclerosis.
- Age
- Gender
- Genetics
- Hyperlipidaemia
- Hypertension
- Smoking
- Diabetes mellitus
Outline the pathogenesis of atherosclerosis.
- Endothelium gets injured and *LDLs accumulate in the tunica intima
- LDLs oxidised causing inflammation
- Macrophages consuming fat to become foam cells
- Apoptosis of foam cells causes inflammation and cholesterol core of plaque
- Platelet adhesion makes the issue worse, smooth muscle cells are accumulated and form the fibrous cap
- Lipid accumulates and the plaque grows
plaque has three principle components:
- Cells (smooth muscle, macrophages and leukocytes)
- ECM including collagen
- intracellular and extracellular lipid
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
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.
- Sudden change in plaque
- Platelet aggregation
- Vasospasm
- Coagulation
- Thrombus evolves
What is the most common cause of death in post-menopausal women?
Myocardial infarction
Outline the myocardial response to plaque rupture.
- 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 20-30 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, 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 the scar
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 hypernating 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 (chest pain, fever, pericarditis, pleural effusion - weeks/months after MI)
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
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
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
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
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 big atria
What is chronic rheumatic valvular disease caused by?
Caused by immune cross-reactivity with cardiac valves
Which valve is most commonly affected in rheumatic valvular disease?
Left-sided valves (almost always mitral)
What is the most common cause of aortic stenosis?
Calcified aortic stenosis
List some causes of aortic regurgitation.
- Rigidity (rheumatic, degenerative)
- Destruction (endocarditis)
- Disease of the aortic valve ring (dilatation, dissectin, Marfan’s, syphilis, 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
What is Dressler’s syndrome?
It consists of fever, pleuritic pain, pericarditis and/or pericardial effusion.
Happens weeks-months following MI
Compensatory mechanisms for heart failure?
Activation of RAS to increase BP
Activation of sympathetic nervous system to increase TPR
Symptoms of LV failure
Lung problem
causes of RV failure
symptoms of RV failure
commonly due to LV failure but can be from chronic severe pulmonary hypertension
nutmeg liver
peripheral oedema
ascites
Ix for heart failure
BNP/NT-proBNP
CXR
ECG
Echo
Inheritance of HCM + gene
Autosomal domiant
Beta myosin gene
What is acute rheumatic fever
Untreated strep throat/scarlet fever/impetigo
Develops 2-4w after the strep throat infection
Occurs at 5-15y, affecting:
- heart (pancarditis - endocarditis, myocarditis, pericarditis)
- joints (arthritis, synovitis)
- skin (erythema marginatum)
- CNS (encephalopathy)
Explain the criteria for rheumatic fever
Jones’ Major Criteria
Diagnosis: Group A strep + 2 majors
or 1 major + 2 minors
MAJOR CRITERIA- CASES
Carditis
Arthritis
Sydenham’s chorea
Erythema Marginatum
Subcutaneous nodules
MINOR CRITERIA
Fever
Raised ESR/CRP
Migratory Arthralgia
Prolonged PR
Previous rheumatic fever
Malaise
Tachycardia
EVIDENCE OF GAS INFECTION
Positive throat culture
Elevated ASO titre
Which valves do rheumatic fever affect?
What about in IVDU?
Mitral valve only (70%)
Mitral and aortic (25%)
Then right sided valves (tricuspid and pulmonary)
What is the main pathogen for rheumatic fever valve vegetation? And what is the pathophysiology
Lancefield group A strep
Antigenic mimicry - cross reaction of anti-strep antibodies with heart tissue
Histology of rheumatic fever valve vegetation?
Beady fibrous vegetation (verrucae), Aschoff Bodies (small giant-cell granulomas), Anitschkov myocytes
Treatment for rheumatic fever?
Benzylpenicillin
or erythromycin if pericillin-allergic
Pathogens for acute and subacute infective endocarditis?
Acute - staph aures (30-45%) or strep pyogenes
Subacute - strep viridans, staph epidermis
Immune vs thromboembolic phenomenon of infective endocarditis?
Immune
- roth spots
- oslers nodes
- haematuria due to glomerulonephritis
Thromboembolic
- Janeway lesions
- Septic abscess
- splinter haemorrhages
- splenomegaly
What is the diagnosis - nonspecific FLAWS symptoms and haematuria
infective endocarditis
What criteria for infective endocarditis and explain it
Duke’s criteria, diagnosis by:
- 2 major
- 1 minor + 3 major
- 5 minor
MAJORS
- positive blood culture growing typical IE organisms or 2 positive cultures for something >12hrs apart
- evidence of vegetation/abscess on echo or new regurigtant murmur
MINORS
- risk factor for it
- fever >38
- Thromboembolic phenomenon
- Immune phenomena
- +ve blood cultures but not meeting major criteria
order the valves in order of most likely to be affected by chronic rheumatic fever
Mitral > aortic > tricuspid > pul
What is beck’s triad and what does it indicate
Pericardial effusion
Muffled heart sounds, raised JVP, hypotension
Causes of pericarditis
Viral and idiopathic (90%)
