1. Chest Pain and Atheroma Flashcards
What are the 3 clinical syndromes of ischaemic heart disease?
What are the 3 main aetiologies (causes) of IHD?
List some risk factors for IHD (non-modifiable and modifiable).
Angina (stable/unstable - chest pain at rest), MI, sudden cardiac death.
Atheroma of coronary arteries (95%), coronary artery vasculitis, coronary artery vasospasm.
Non-modifiable: Sex (M), age, family history, hyperlipidaemia, hypertension.
Modifiable: diabetes mellitus (except T1), smoking, obesity, stress, lack of exercise.
What is this pathology?
Coronary artery atheroma (yellow).
What are 4 pathogenesis theories for IHD/atheroma development?
What are some complications of vessel atherosclerosis?
- *1. Encrustation (Rokitansky):** platelet thrombi over injured endothelium
- *2. Imbibition (Virchow):** low grade inflammation leads to increased plasma filtration
- *3. Reaction to injury (Ross and Glomset):** endo injury with increased permeability and macro/smooth muscle accumulation
- *4. Monoclonal hypothesis (SM cells):** unknown factor such as virus may induce atherosclerosis by altering growth control in SM cells
Ulceration, fissuring, haemorrhage, thrombosis, aneurysm.
Describe the stages of atherosclerosis.
STAGE 1: Endothelial damage
Sheer stress (e.g. eddies in blood flow, HT) toxic damage (e.g.smoking), high lipid levels or infection causes endothelial damage -> vasoconstriction and activated endothelial cells (loose platelets stick to them). Partly loosened injured endothelium at sites of platelet reactions -> release PDGF -> low grade inflammation + oedema, ruptures of internal elastic membrane
STAGE 2: Uptake of modified LDL, adhesion and macrophage infiltration
LDL modifaction (from oxidation and glycation) stimulates expression of inflammatory mediators inc. adhesion molecules for monocytes, which bind to endothelium, cross it and become macrophages. They accumulate large lipid droplets to become foam cells -> fatty streak. NB. nomally macrophages recognise LDL via LDL receptors recognising apolipoprotein B100 on LDL and -ve fb (downreg LDL receptor numbers) but modified LDL not recognised. SM cells also take up fat and store (droplets) but becomes overloaded and burst, releasing fat droplets for macrophages to phagocytose.
STAGE 3: SM proliferation and formation of fibrous cap
Endothelial cells and macrophages release growth factors esp PDGF, which converts contractile SM to proliferating, which secretes collagen, starts to break down internal elastic lamina. Cytokines secreted by endothelium and macrophages stimulates migration of SM cells. Plaque bulges in lumen (=angina/claudication). Centre becomes necrotic and calcified, then gruel-like with cholesterol crystals. Vessels from vasa vasorum grow into intima. Collagen forms fragile fibrous cap. Fragility increased by calcification -> rigid artery. Cap rupture exposes collagen to blood and triggers thrombus formation, can occlude vessel.
NB: 2 main cell types: SM cell, macrophage. Both recruit circulating LDL into plaque.
Describe the 2 main types of acute myocardial infarction.
What vessels can be occluded in a myocardial infarct? What kind of MI will they give?
1. Transmural: involves the whole thickness of the ventricular wall. Underlying lesion is an atheromatous plaque that has undergone fissuring and occlusive thrombosis.
2. Subendocardial: confined to the inner third or half of the myocaardium, results from generalised underperfusion of the myocardium.
Main L coronary artery -> massive anterolateral MI
- *L anterior decending** -> anteroseptal MI
- *L circumflex** -> lateral MI
- *R coronary** artery -> posterior (inferior) MI
What does A show and what might it lead to?
How does the macroscopic appearance and histology of a MI change over time?
a) 0-12 hrs
b) 12-24 hrs
c) 24-72 hrs
d) 3-10 days
e) weeks - months
Occluded coronary artery (by thrombus). May lead to MI.
a) No changes
b) MA: pale with blotchy discolouration. Histology: bright eosinophilia of muscle fibres reflecting onset of coagulation necrosis; intracellular oedema
c) MA: soft, pale and yellow. Histology: coagulative necrosis with loss of nuclei and striations; beginning of acute inflammatory response with heavy interstitial neutrophil infiltrate
d) MA: soft, yellow-brown with hyperaemic border. Histology: replacement of infected area by granulation tissue
e) MA: white, fibrous scar. (pic) Histology: collagenous scar tissue. May not beat properly -> thrombus may develop.
What can you see in this histology, and hence how old is this MI?
What are some short term complications of MI?
Muscle fibre necrosis, heavy neutrophil infiltrate. 24-72 hours (3 days).
L ventricular failure, cardiac dysrhythmias, rupture of ventricular wall, papillary muscle infarction, mural thrombus, fibrinous pericarditis, DVT. Further MI.
What short term complication of an MI is the arrow indicating?
What are some long term complications of MI?
Ruptured myocardium. Ventricular wall v thin and haemorrhagic.
Intractable L ventricular failure, ventricular aneurysm, Dressler’s syndrome (type of pericarditis +/or pericardial effusion), recurrent MI.
What short term complication of an MI is the arrow indicating?
What do the effects of a pulmonary embolus depend on?
How could a large pulmonary embolus affect circulation?
Does a medium PE have the same effect?
Ventricular aneurysm. Thrombus may form in it due to static blood.
Size of occluded vessel, number of emboli, adequacy of the bronchial blood supply.
Coil within one major pulmonary artery OR ‘saddle’ embolus blocks both pulmonary arteries = circulatory collapse. (L pic)
No - dual blood supply protects lungs from effects of pulmonary artery obstruction (R pic)
NB. Multiple emboli combined with poor bronchial blood supply -> pulmonary infarction. May need IVC filter mesh to trap any small emboli blocking lungs.
Mr C is a 55 yr old diabetic smoker who has had well controlled angina for the past 12 years. Once evening while watching TV, he develops severe central chest pain which is not relieved by his usual GTN. He remembers that his GP told him to call for an ambulance if he has prolonged symptoms and within 1 hour of the onset of his symptoms he is in A and E. He is diagnosed with a large anterior MI. Treatment is instituted, a stent is inserted and he is transferred to CCU. He is discharged home on day 5 with numerous medicaitons.
What condition did Mr C have that caused his symptoms?
He becomes depressed at the situation, loses his job and becomes increasingly inactive. One day he notices that his left calf is swollen and tender. His GP is called and sends him to A and E. By now he is breathless and has right-sided chest pain.
What condition does Mr C have now?
Ischaemic heart disease.
DVT - pulmonary embolus
What are the arrows pointing to, and what does the histology show?
Pulmonary emboli.
(Top L - saddle embolus between R and L pulmonary arteries. Top R - smaller pulmonary artery with embolus, can see clot on the R (diff colour). Bottom - can see inflammatory cell infiltrate.)
What is the arrow pointing to?
Cholesterol crystals floating in liquid centre of plaque.
