HistoPath - Cardiac pathology Flashcards
(41 cards)
Define atherosclerosis
Chronic inflammation in tunica intima (innermost layer) of large arteries characterized by intimal thickening, atheromatous deposits, and lipid accumulation
What is the process of atherogenesis
- Endothelial injury causes accumulation of LDL
- LDL enters intima and is trapped in sub-intimal space
- LDL is converted into modified and oxidized 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 → platelet adhesion → smooth muscle cell recruitment → more macrophages and T cells enter the plaque
- Vascular smooth muscle cells form the fibrous cap, segregating thrombogenic core from lumen
- Cholesterol deposition and plaque enlargement → obstruction
What are the components of atherosclerotic plaques
Cells - including SMC, macrophages and other leukocytes
Matrix (ECM) including collagen
Lipid
Only involve portion of the wall: rarely circumferential
What are the risk factors for atherosclerosis
Non-modifiable: age, post-menopausal women>men, genetics (FHx, familial hypercholesterolaemia, polymorphisms)
Modifiable: hyperlipidaemia (LDL), HTN, smoking, DM
Other: metabolic syndrome, lipoprotein a, haemostasis
Risk factors have a multiplicative effect – 2 risk factors increase the risk 4x (3 RFs = 7x increase risk)
20% of CVD events occur in absence of RFs and 75% events in healthy women occur in LDL below the risk level
Where is atherosclerosis more likely to occur
Abdominal aorta affected more than thoracic aorta.
More prominent around origins (ostia) of major branches → turbulent blood flow has low/oscillatory shear stress, which is atherogenic. High laminar flow is protective.
Plaques occur in points of disturbed flow (carotids and coronary arteries → bifurcations and curvatures)
Describe fatty streaks
Little streaks in the vessel wall
Earliest lesion
Lipid filled foamy macrophages, no flow disturbance
In virtually all children <10y/o
Relationship to plaques is uncertain but in same sites as plaques
What are the consequences of atheroma formation
Stenosis (Demand > supply) at 60% occlusion → stable angina → chronic IHD
Plaque rupture → VTE
Erosion → VTE
Haemorrhage
What are the features of vulnerable plaques
Lots of foam cells and extracellular lipid
Thin fibrous cap
Few smooth-muscle cells
Clusters of inflammatory cells
Define ischaemic heart disease
A group of conditions resulting from myocardial ischaemia (O2 supply < demand):
Angina pectoris
Unstable angina
Prinzmetal angina
MI
Chronic IHD + HF
Sudden cardiac death
Define angina and what are the types
Transient ischaemia, NOT producing myocyte necrosis
Angina pectoris: 70% vessel occlusion, pain on exertion, no plaque disruption
Unstable angina: >90% occlusion, pain at rest, plaque disruption with superimposed thrombus
Prinzmetal angina: coronary artery spasm (not atheroma)
What is the pathogenesis of myocardial infarctions
- Artery occlusion
- Sudden change of plaque (e.g. rupture) → superimposed platelet activation and aggregation
- vasospasm, coagulation and thrombosis
- Occlusive intracoronary thrombus overlying disrupted plaque - Myocardial infarction
- compromised myocardial supply → ischaemia
- Contractility loss within 60s (HF may precede)
- Necrosis, myocyte death
Ischaemia >20-40mins → irreversible injury and myocyte death
What are the histological findings of MI according to time
Under 6 hours - normal by histology (CK-MB also normal)
6–24 hrs - loss of nuclei, homogenous cytoplasm, necrotic cell death
1-4 days - infiltration of polymorphs →macrophages (clear up debris)
5-10 days - removal of debris (macrophages)
1-2 weeks - granulation tissue, new blood vessels, myofibroblasts, collagen synthesis (myofibroblasts, macrophage, angioblasts)
Weeks-months - strengthening, decellularising scar tissue.
What is the gross histology of a heart affected by MI
1-18h: none
24h: pale, oedema
3-4d: haemorrhage, necrosis, granulation
1-3w: thin, yellow
3-6w: tough white (Dense fibrosis)
What are the complications of MI
Death
Arrhythmia
Rupture (LV infarct → papillary muscle dysfunction/necrosis/rupture)
Tamponade
Heart failure (congestive, contractile dysfunction due to loss of muscle)
Valvular disease
Aneurysm of ventricle
Dressler’s syndrome (pericarditis 2/3 days after)
Embolism (Mural thrombus → embolisation (→ bowel ischaemia))
Recurrence
Reperfusion injury (oxidative stress, calcium overload, inflammation)
What is the prognosis for MI
In hospital death rate is 7%
Half of deaths occur within 1 hour of onset (most of these do not reach hospital)
Age, female, DM and previous MI = worse prognosis
Total mortality is 30% in one year but 3-4% after this due to complications
Define sudden cardiac failure
Unexpected death from cardiac causes in individuals without symptomatic heart disease or early (1 hour) after onset of symptoms”; usually due to lethal arrhythmia (from ischaemia-induced electrical instability)
What are the causes of sudden cardiac failure
BG IHD (90%)
Cocaine use
Acute myocardial ischaemia
Aortic stenosis, mitral valve prolapse, pulmonary HTN
What are the causes of chronic IHD with heart failure
Progressive HF due to ischaemic myocardial damage
Not always prior infarction
Severe obstructive coronary artery disease, enlarged/hypertrophied heart
Atherosclerosis, fibrosis
What are the most common vessels for MIs to occur in
LAD: 50%, anterior wall left ventricle, anterior septum, apex
RCA: 40%, posterior wall left ventricle, posterior septum, posterior right ventricle
LCx: 20%, lateral left ventricle, not apex
What is the histology of heart failure
Dilated heart
Scarring and thinning of the walls
Fibrosis and replacement of ventricular myocardium
What are the causes of heart failure
Ischaemic heart disease
Myocarditis
Hypertension
Cardiomyopathy (dilated)
Valve disease
Arrhythmias
What is the pathophysiology of heart failure
Cardiac damage → decreased CO → RAs activation → Salt and water retention → fluid overload
Cardiac damage → stroke volume → sympathetic nervous system activated → maintains perfusion → TPR increases → afterload increases → LVH and increased EDV → dilatation and poor contractility
What are the complications of heart faiure
Sudden death (arrhythmia)
Systemic emboli
Pulmonary oedema (LVF → pulmonary HTN → reduced peripheral BP and flow)
Hepatic cirrhosis (nutmeg liver) (LVF OR chronic severe pulmonary HTN → systemic and portal venous system engorgement)
What is the difference in presentation between Left ventricular and right ventricular failure
LVF: dyspnoea, orthopnoea, PND, wheeze, fatigue, pulmonary oedema.
RVF: peripheral oedema, ascites, facial engorgement, nutmeg liver
