Myocardial Infarction Flashcards
What is a myocardial infarction?
Supply-led ischaemia caused by plaque rupture, fissure, thrombosis
How does a fatty streak develop?
Injury of blood vessel endothelium
Uptake of LDL from the blood into artery’s tunica intima
LDL oxidised - OXLDL
Monocyte migrate across endothelium & differentiate into macrophages
Macrophages take up OXLDL (scavenger receptors) and convert them to cholesterol-laden foam cells - form fatty streaks
How do fatty streaks progress to atheromatous plaques?
Various cell types release inflammatory substances that cause cell division and proliferation of smooth muscle cells and collagen deposition
How do atheromatous plaques develop into atheroma?
Lipid core (product of dead foam cells) Fibrous cap (smooth muscle + collagen) = Atheroma
How do platelets become activated in primary homeostasis?
Damage to vessel
Expose collagen and TF in sub endothelial matrix
Collagen binds to vWF + platelet glycoprotein binds
Platelet binds to collagen (integral + GPVI receptors)
Platelet activated
How does platelet activation facilitate ADP binding to platelet for further platelet activation?
Activated platelet extends pseudopodia & synthesises TXA2 - binds platelet Mediator release (5-HT, ADP, vWF, factor V Vasoconstriction + 5-HT release (indirect & direct) ADP binds to platelet & activates further platelets
What is a pseudopodia?
Temporary membrane extension)
What is TXA2?
Thromboxane 2 (aka arachidonic acid)
Where are 5-HT and ADP released from in primary haemostasis?
Dense granules
Where are factor V and vWF released from in primary homeostasis?
Alpha granules
What is the effect of ADP binding to platelet in primary homeostasis - how does it facilitate coagulation?
Activates further platelets
Increase platelet receptor expression
Expose phospholipids on platelet surface to facilitate coagulation
What occurs during the initiation phase of the coagulation cascade?
Vascular injury TF-bearing cells bind to and activate Factor VIIa Activates factor X to Xa Xa + Va (co-factor) convert II to IIa = small amount of thrombin
What is II?
Prothrombin
What is IIa?
Thrombin
What happens during the amplification phase of the coagulation cascade?
II activates platelets
Release factor V from platelet a-granules + release factor VII from vWF
Thrombin activates Factor XIa - forms complex with factor VIIIa - causing II-IIa conversion
= burst of thrombin production
What is the name of the complex formed between factor XIa and VIIIa?
Tenase
What happens during the fibrin formation phase of the coagulation cascade?
IIa cleaves fibrinogen forming fragments
Spontaneously polymerise to form fibrin
Factor VIIIa cross-links polymer to form fibrin fibre network = solid clot
What is thrombosis?
Pathological haemostasis
Thrombosis is highly unlikely in the arterial unless what? why?
Aterosclerosis or other cause of stasis
Blood flow normally laminar
What is an arterial (white) thrombus?
Mainly platelets in the fibrin mesh; forms embolus if detached that often lodges in an artery - primary treated with anti-platelets
What is a venous (red) thrombus?
red thrombus: white head, jelly-like red tail, fibrin rich
if detaches forms an embolus that usually lodges in the lung (pulmonary embolism)
White thrombi are mainly treated with?
Antiplatelets
Red thrombi are mainly treated with?
Anticoagulants
What makes up Virchow’s Triad?
Endothelial injury
Hypercoagulability
Stasis of blood flow
Ischaemia leads to?
Infarction
Infarction is?
Death of tissue
How does insufficient ATP for ATP generation cause cell death?
Increase calcium stimulating ATPase
Phospholipase - membrane image
Proteases - membrane and cytoskeleton damage
Endonuclease - DNA damage/breakdown
Mitochondrial permeability- release pro-death factors
What re symptoms & signs of an MI?
Severe central crushing pain radiating to the jaw and (esp. left) arm(s)
Similar to angina attack but more severe + not received by GTN
Associated with sweating, causes & (often) vomiting
Which ECG change is observed in the first few hours?
ST elevation
Which ECG change is observed in 1st day?
T wave inversion and Q waves
New onset LBBB
ST elevation in leads II, III and aVF is?
Inferior MI
ST elevation in leads V1-V6 is?
Anterior MI
ST elevation in leads V1-V4 is?
Anteroseptal MI
ST elevation in leads I, aVL, V1-V6 is?
Anterolateral MI
Creatinine kinase peaks within?
24 hours
Troponin I and T are highly specific to?
Cardiac necrosis
What are complications post-MI?
Cardiac rupture Dressler's syndrome VSD Mitral valve regurgitation Left ventricular aneurysm formation Mural thrombosis +/- septum emboli Inflammation Acute pericarditis
What is Dressler’s Syndrome?
Type of pericarditis that occurs many (6) weeks after an MI
What is the pathophysiology behind Dressler’s syndrome?
Damaged heart releases previously un-encountered material stimulating an immune response
What are non-pharmacological guidelines to secondary preventative measures?
No smoking
Healthy diet
Regular aerobic exercise
What should be the aimed cholesterol level?
<4 mmol/L
What is the aimed BP?
<140/86
In organ damage diabetes, renal disease and/or organ damage; target BP is?
135/80
What drug regimen is recommended post-MI?
Consider warfarin for 3 months if large anterior MI Aspirin Beta-blocker ACEI Statin ?Clopidogrel
What is the mechanism of warfarin?
Blocks clotting factors II, VII, IX and X
Prevent new thrombosis by binding to hepatic vitamin K reductase preventing conversion of epoxide to active hydroquinone
How is warfarin administered?
PO
What is warfarin’s onset of action?
2-3 days
Why does warfarin take a while to take actionß
Inactive factors replace active gamma-carboylated factors that are slowly cleared from plasma
What may be added to warfarin for rapid anticoagulatory effect?
Heparin
Warfarin has a low therapeutic index. Patients need to be monitored using the?
INR
What are side effects of warfarin?
Haemmorhage
What potentiates the risk of haemorrhage with warfarin treatment?
Liver disease
Increased metabolic rate
Drug interaction (aspirin/NSAIDs)
Reduction of vitamin K
Why do NSAIDs potentiate warfarin haemorrhage risk?
Inhibit platelet function
What do you give a patient if they overdose on warfarin?
Vitamin K
What is the mechanism of aspirin?
Irreversibly blocks cyclo-oxygenase (COX) in platelets and anti-thrombotic prostaglandin I2 in endothelial cells
Endothelial cells can produce new COX; platelets can’t resulting in anti-thrombotic dominance
Giving aspirin inhibits TXA2 synthesis for 7-10 days. Why?
Irreversible blockage of COX - all platelets need to be replaced; takes 7-10 days
What is an example of a beta-blocker used?
Bisoprolol
What is an example of a statin?
Simvastatin
A statin aims to..?
Reduce total and LDL cholesterol
Reduce triglycerides
Slightly increase HDL
Decrease inflammation, reverse endothelial dysfunction, decrease thrombosis, stabilise atherosclerotic plaques
What is the mechanism of a statin?
Competitive inhibitor of HMG-CoA reductase - rate limiting step in cholesterol synthesis
How do you administer a statin?
PO
What are the side effects of a statin?
Myositis
Rarely rnhabdomylosis
A statin shouldn’t be prescribed in?
Pregnancy
What is the mechanism of clopidogrel?
Forms disulphide bond to P24-12 receptor
Irreversible inhibitor
Prevents ADP activating platelets
How do you administer clopidogrel?
PO
Clopidogrel has a synergistic effect with?
Aspirin
What are the side effects of clopidogrel?
Dyspepsia, abdo pain, diarrhoea, bleeding disorders
What is the pathogenesis of atheroma?
Endothelial injury causes trans-endothelia migration
Macrophages stimulate lipid uptake which along with smooth muscle proliferation and collagen and fibrin acccumulation forms a fibro-fatty plaque
What are the risk factors for atheroma
Smoking Hypertension Hyperlipidaemia Diabetes Old age Male sex Genetics (rare)
What are complications of atheroma?
Stenosis Thrombosis Aneurysm Dissection Embolism
What is used to reopen occluded arteries in an acute MI or stroke? (rarely used)
Fibrinolytics
What is an example of a fibrinolytic that decreases mortality in acute MI?
Streptokinase (admin IV)
How can overdose of streptokinase be controlled?
Oral Tranexamic acid (inhibits plasminogen activation)
Streptokinase should not be given if the patient has had a recent ______ infection
Strep
