Histopathology - Cardiac Pathology Flashcards
What is atherosclerosis?
Chronic inflammation in the tunica intima (innermost layer) of large arteries characterised by intimal thickening + lipid accumulation
What are the steps of atherogenesis?
- Endothelial injury causes accumulation of LDL
- LDL enters intima + is trapped in sub-intimal space
- LDL -> oxidised LDL, causes inflammation
- Macrophages take up oxidised LDL via scavenger receptors + become foam cells
- Apoptosis of foam cells causes inflammation + cholesterol core of plaque
- Increase in adhesion molecules on endothelium (bc of inflammation) = more macrophages + T cells enter plaque
- VSMC form fibrous cap, separating thrombogenic core from lumen
What are the principal components of an atherosclerotic plaque?
- Cells
- ECM (inc. collagen)
- Intracellular + Extracellular lipid
What are some modifiable and non-modifiable RFs of Atherosclerosis?
Modifiable:
- T2DM
- HTN
- Hypercholesterolaemia
- Smoking
Non-modifiable:
- Gender (M>F)
- Increasing age
- FHx
What is Ischaemic Heart Disease?
A group of conditions that occur when oxygen supply > demands of myocardium due to narrowed coronary vessels
What are some features of stable angina?
- ~70% vessel occlusion
- Pain on exertion
What are some features of unstable angina?
- ~90% vessel occlusion
- Pain at rest + on exertion
- High likelihood of impending infarction
What are some features of prinzmetal angina?
- Rare
- Due to coronary artery spasm (from cocaine use), not atherosclerosis
Is there muscle death in angina?
No
What is the pathogenesis of a myocardial infarction?
- Sudden change in plaque
- Platelet aggregation
- Vasospasm
- Coagulation
- Thrombus evolves
» myocardial necrosis secondary to ischaemia
What happens in severe ischaemia of a myocardial infarction?
- Lasts >20-40 mins
- Irreversible injury
- Myocyte death
What are some common atherosclerotic plaque sites?
- First few cm of LAD, LCX
- RCA
What are some complications of a myocardial infarction?
DARTH VADER
- D: Death
- A: Arrhythmias
- R: Rupture
- T: Tamponade
- H: Heart Failure
- V: Valve disease
- A: Aneurysm
- D: Dressler syndrome
- E: Embolisation
- R: Recurrence + regurgitation
What are histological findings of an MI over time?
< 6hrs: NORMAL
6-24hrs: Loss of nuclei, homogenous cytoplasm, necrotic cell death
1-4d: Infiltration of polymorphs then macrophages
5-10d: Debris removal
1-2wks: Granulation tissue, new blood vessels, myofibroblasts, collagen synthesis
Wks-mnths: Strengthening, decellularising SCAR TISSUE
What is heart failure?
Heart’s inability to pump sufficient blood to supply the demand of the body
What is preload?
An initial stretch of cardiomyocytes before contraction due to ventricular filling (increasing will increase SV)
What is afterload?
The pressure of vessels against which heart must contract to eject blood (increasing will decrease SV)
What are some causes of heart failure?
IMHC
- Ischaemic heart disease
- Myocarditis
- HTN
- Cardiomyopathy (dilated)
What are some complications of heart failure?
- Sudden death
- Systemic emboli
- Arrhythmias
What are histological complications of heart failure
- Pulmonary oedema with superimposed infection
- Hepatic cirrhosis (nutmeg liver)
What is LV heart failure?
Pooling of blood within pulmonary circulation due to high pressures in left side of heart
- Leads to decreased peripheral blood pressure and flow
What are some symptoms of LV heart failure?
- Dyspnoea
- Orthopnoea
- PND
- Wheeze
- Fatigue
- Pulmonary oedema
What is RV heart failure?
Minimal pulonary congestion but engorgement of systemic and portal venous systems
What are some causes of RV heart failure?
- Most common = secondary to LVF
- Chronic severe pulmonary HTN
What are some symptoms of RV heart failure?
- Peripheral oedema
- Ascites
- Facial engorgement
- Nutmeg liver
What is nutmeg liver?
The congestion and stasis of venous blood in the liver
What is the general histology seen in cardiomyopathy?
- Dilated heart
- Scarring + thinning of the walls
- Fibrosis + replacement of ventricular myocardium
What is dilated cardiomyopathy?
The loss of myocytes
What is hypertrophic cardiomyopathy?
A defect in β-myosin heavy chains
A/w sudden death
What is restrictive cardiomyopathy?
Impaired compliance
What is the mechanism of HF in dilated cardiomyopathy + some causes?
Systolic dysfunction
- Idiopathic
- Alcohol
- Thyroid disease
- Myocarditis
What is the mechanism of HF in hypertrophic cardiomyopathy + some causes?
Diastolic dysfunction
- Genetic
- Storage diseases
What is the mechanism of HF in restrictive HF + some causes?
Diastolic dysfunction
- Sarcoidosis
- Amyloidosis
What is the mode of inheritance of hypertrophic cardiomyopathy?
Autosomal dominant
What is seen on histology of hypertrophic cardiomyopathy?
Myocyte disarray (arrhythmogenic)
What is hypertrophic obstructive cardiomyopathy?
Septal hypertrophy resulting in an outflow tract obstruction
What is arrhythmogenic right ventricular cardiomyopathy?
Myocyte loss with fibrofatty replacement typically affecting the right ventricle
What systems does rheumatic fever affect?
- Heart: pancarditis
- Joints: arthritis + synovitis
- Skin: erythema marginatum + subcutaneous nodules
- CNS: encephalopathy + Sydenham’s chorea
When does rheumatic fever present?
- Develops 2-4wks post-strep throat infection
Peak age of onset = 5-15 years
What is the diagnostic criteria for rheumatic fever?
Group A strep infection + 2 major criteria, or 1 major + 2 minor criteria - Jones’ criteria
Major (CASES):
- C: Carditis
- A: Arthritis
- S: Sydenham’s chora
- E: Erythema marginatum
- S: Subcutaneous nodules
Minor criteria:
- Fever
- Raised ESR/CRP
- Migratory arthralgia
- Prolonged PR interval
- Prev. Rh Fever
- Malaise
- Tachycardia
Which valves are affected in rheumatic fever?
- 70% mitral valve only
- 25% affects mitral + aortic valves
What is the main pathogen causing rheumatic fever?
Lancefield group A strep
What is seen on histology of rheumatic fever?
- Beady, fibrous vegetations
- Aschoff bodies
- Anitschkov myocytes
What is the treatment for rheumatic fever?
Benzylpenicillin
(erythromycin if allergic)
What is infective endocarditis?
The colonisation of the endothelium
What can cause bacteraemia in infective endocarditis?
- Poor dental hygiene
- IVDU
- Soft tissue infection
- Dental treatments
- Cannulae/lines
- Cardiac surgery/pacemakers
What are the acute causative organisms in infective endocarditis and where do they spread?
- Staphylococcus. aureus
- Strep. pyogenes
- Aorta
What are the subacute causative organisms in infective endocarditis and where do they spread?
Strep. viridians
- Staphylococcus epidermidis
- HACEK
- Coxiella
- Mycoplasma
- Candida
- Chordae
What are the HACEK bacteria causing endocarditis?
Unusual bacteria
- H: Haemophilus
- A: Aggregatibacter
- C: Cardiobactam
- E: Eikenella
- K: Kingella
What is antigenic mimicry?
Cell-mediated immunity and antibodies. to streptococcal antigen cross-react with myocardial antigens
What is the pathology of rheumatic heart disease + some characteristics of its vegetations?
- Antigenic mimicry
- Verrucae (small, warty vegetations on closure line of valve leaflet)
What is the pathology of infective endocarditis + some characteristics of its vegetations?
- Colonisation or invasion of heart valves or mural endocardium by microbe
- Large, irregular masses on valve cusps, extends into chordae
What is the pathology of non-bacterial thrombotic endocarditis (Marantic) + some characteristics of its vegetations?
- DIC/hypercoagulable state
- Small, bland vegetations on closure lines - formed of thrombi
What is the pathology of Libman-Sacks endocarditis + some characteristics of its vegetations?
- Unknown (a/w SLE + APLS)
- <2mm warty vegetations, sterile + platelet rich
What are some clinical features of infective endocarditis?
- Constitutional = fever, malaise, rigors, anaemia
- Cardiac = new murmur (MR/AR)
- Immune phenomena = ROTH SPOTS, Osler’s nodes, HAEMATURIA (secondary to glomerulonephritis)
- Thromboembolic phenomena = janeway lesions, septic abscesses, microemboli, SPLINTER HAEMORRHAGES, SPLENOMEGALY
Which valves are usually involved in infective endocarditis?
Mitral/aortic valve UNLESS IVDU when right-sided valves are involved
What criteria is used to diagnose infective endocarditis?
Duke criteria
Require for diagnosis:
- 2 major
- 1 major + 3 minor
- 5 minor
What is the Duke criteria?
Major:
- +ve blood culture growing typical IE organisms or 2 +ve cultures >12hrs apart
- Evidence of vegetation/abscess on echo/new regurge murmur
Minor:
- RF
- Fever >38C
- Thromboembolic phenomena
- Immune phenomena
- +ve blood cultures not meeting major criteria
What is the treatment for infective endocarditis?
- Broad spectrum Abx once cultures taken
- Subacute: benzylpenicllin + gentamicin / vancomycin
Acute: flucloxacillin (MSSA) / rifampicin + vancomycin + gentamicin (MRSA)
What is the pathophysiology and some causes of aortic stenosis?
- Narrowed aortic valve, high velocity, high pressure
- Calcification (old age), congenital bicuspid valve
What is the pathophysiology + some causes of aortic regurgitation?
- Incompetent aortic valve blood flows back into LV after systole
- Infective endocarditis, diessecting aortic aneurysm, LV dilation, connective tissue disease
What is the pathophysiology + some causes of mitral stenosis?
- Narrowed mitral valve high velocity, high pressure flow
- Back pressure in left atrium dilatation
- Rheumatic fever
What is the pathophysiology + some causes of mitral regurgitation?
- Incompetent mitral valve blood flows back into left atrium during systole
- Infective endocarditis, connective tissue disease, post-MI, rheumatic fever, left ventricular dilation
What is chronic rheumatic valve disease?
Thickening of the valve leaflet, especially along closure/fusion lines. Thickening, shortening + fusino of chordae tendinae
- Predominantly left-sided
- Mitral > Aortic > Tricuspid > Pulmonic
What is the clinical presentation of mitral valve prolapse?
- Middle aged woman
- SOB + chest pains
- Mid-systolic click + late systolic murmur
What is pericarditis?
Inflammation of the pericardium
What are the types + some causes of pericarditis?
- Fibrinous (MI, uraemia)
- Purulent (staphylococcus)
- Granulomatous (TB)
- Haemorrhagic (tumour, TB, uraemia)
- Fibrous/constrictive (any of the above)
What is a pericardial effusion and it’s usual cause?
Serous fluid in the pericardial sac
- Exudative fluids occur secondary to infection/inflammation/malignancy/autoimmune processes in pericardium
- Chronic heart failure
What is a haemopericardium?
Myocardial rupture from myocardial infarction or trauma
