1 Myocardial Infarction Flashcards
Define an MI
Ischaemic necrosis of the myocardium as a result of acute occlusion of a coronary artery
What is included in the clinical definition of MI?
- Symptoms - characteristic of myocardial pain
- ECG changes - characteristic of myocardial infarct/ischaemia
- Cardiac enzymes - evidence for cardiac myocyte necrosis (without enzymes → Acute Coronary Syndrome)
What is unstable angina and how should it be treated?
Change in character, duration, frequency, severity of chest pain
Treat as acute coronary syndrome
Name some common causes of MI
Atheroma,
Hypercoagulability,
Aortic dissection - flap occlusion,
Coronary artery dissection/aneurysm
What are the major symptoms of MI?
Chest pain - ususally sudden onset, crushing, >20 mins, may radiate
Sweating
Pallor
Nausea
What are the signs of MI?
Excess sympathetic tone - Tachycardia, Hypertension
or Excess parasympathetic tone - Bradycardia and Hypotension
Impaired left ventricle function → hypotension, lung crackles, murmur
What are the stages of ECG changes in MI?
ST depression - not always there - ischaemia + partial occlusion
T wave peaking - ischaemia (or hyperkalaemia)
ST elevation - ischaemia + total artery occlusion
T wave inversion - ST segment slowly → baseline
Q wave development
What is indicative of a LBBB?
Wide QRS
Broad +/- notched R wave - prolonged upstroke in V5, V6 (and 1, AVL)
Left axis deviation may/may not be present
What are the major cardiac enzymes implicated in MI?
Troponin (T or I)
Released within 4-6 hours, raised up 2 weeks after Infarction (but also rises in PE, septicaemia, renal failure, cardiac trauma)
Other enzymes: MB creatinine kinase, Lactate dehydrogenase-1
What is the immediate treatment of MI?
AMONAC
Antiemetic, Morphine, O2, Nitrate, Aspirin, Clopidogrel
Cyclizine, Morphine/Diamorphine, GTN, Aspirin, Clopidogrel
What is the treatment for STEMIs?
Reperfusion therapy <12 hours
Immediate Percutaneous Coronary Intervention (PCI) - most effective <90 mins
or
Thrombolysis
What does Percutaneous Coronary Intervention involve?
Balloon Angioplasty +/- stenting, with drugs:
Glycoprotein IIb/IIIa Inhibitors (Abciximab, Eptifibatide) - Antiplatelet - reduce risk of immediate vascular obstruction
Unfractioned Heparin
What does thrombolysis involve?
Recombinant tissue plasminogen activator: Plasminogen → Plasmin → Break down fibrin
Telecteplase
Given with LMWH
What is the treatment and management for an NSTEMI?
LMWH, or unfractioned Heparin
Take troponin 12 hours after onset
GRACE system >3% CV event risk → Coronary angiography +/- PCI (within 96 hours)
<3% → non-invasive ischaemia testing
For confirmed MI, what drugs should be given?
MI5 (AABCS)
Aspirin - Antiplatelet
ACE inhibitor - Decrease BP and cardiac workload
Beta blocker - Bisoprolol - Slow HR and contractility
Clopidogrel - Antiplatelet
Statin - Lower cholesterol
Also warfarin/fondaparinux (anticoagulants) and Insulin if required
Where are atheromas distributed?
Patchily in elastic arteries and large/medium muscular arteries
What are the layers of the arterial wall structure?
Intima - Endothelium (simple squamous), basal lamina, subendothelial connective tissue
Media - thickest, smooth muscle, elastic and collagen fibres
Adventitia - thin outer layer to prevent overstretch - contains vasa vasorum, nervi vascularis
What is the structure of a plaque?
- Fibrous cap - made of smooth muscle, with collagen and elastin
- Shoulder regions - accumulation of foam cells and T lymphocytes
- Lipid core - oxidised LDL and cholesterol, cell debris and some foam cells
- Weak vessel wall under plaque due to degeneration of vessel media
What are the stages of plaque development?
- LDLs damage and enter the endothelium
- Monocytes attracted
- Foam cells die
- Cytokines encourage smooth muscle to form fibrous cap
- Continued growth and development of nectrotic core
- Deterioration of plaque
How do LDLs damage and enter the endothelium?
Monocytes release free radicals → oxidise LDLs
oxLDL → damages endothelium at points of high shear stress and bind to basement membrane proteoglycans
How are monocytes attracted in plaque development?
Damaged endothelium expresses cell surface adhesion molecules for monocytes
Macrophages migrate to subendothelium and take up oxLDL → Foam Cells
What happens when foam cells die?
They cannot process LDL, the debris realases further free radicals and attracts more monocytes/T cells
How is the fibrous cap formed?
Cytokines cause SMCs to migrate → intima
- Secrete collagen and elastin → forms cap
- Encourage angiogenesis into plaque
- Encourage further SMC migration into plaque/cap
How is the necrotic core formed?
Foam cells death → toxic free radicals and cytokines → induction of apoptosis
How does the plaque deteriorate?
Macrophage/Foam cells produce factors → SMC death and fibrous cap breakdown
Erosion: Cytokine-induced apoptosis and enzymes cutting basement membrane → endothelium erosion
How does thrombosis form?
Erosion/ rupture of the fibrous cap
How does rupture occur?
Unstable plaque development:
- Thin fibrous cap with few SMCs
- Increased inflammatory cell concentration (especially active macrophages instead of foam)
- Eroded epithelium
How does NO play a role in plaque formation?
Undersecretion
When is NO normally secreted? and what are its actions?
In response to shear stress
Vasodilation
Antiatherogenic - inhibits: SMC proliferation, monocyte attraction, LDL oxidation; and antiplatelet effects
Damaged endothelium less likely to be able to produce NO
What are the sources of cholesterol?
Diet and synthesised by liver from Acety CoA
How is cholesterol excreted?
Bile acids
How is cholesterol regulated in the body?
Negative feedback - inhibits further synthesis of itself by inhibiting HMG-CoA reductase
Insulin/glucagon control - insulin → increases synthesis; glucagon → decreases synthesis
Long term control - inhibition of HMG-CoA reductase → decrease cholesterol
also: reduced cellular uptake by inhibition of cholesterol receptor expression
What is the basic lipoprotein structure?
Non-polar lipid core - mostly TAGs and cholesterol esters
Polar (hydrophilic) outer coat
What are the sources of cholesterol?
Diet and synthesised by liver from Acety CoA
How is cholesterol excreted?
Bile acids
How is cholesterol regulated in the body?
Negative feedback - inhibits further synthesis of itself by inhibiting HMG-CoA reductase
Insulin/glucagon control - insulin → increases synthesis; glucagon → decreases synthesis
Long term control - inhibition of HMG-CoA reductase → decrease cholesterol
also: reduced cellular uptake by inhibition of cholesterol receptor expression
What is the basic lipoprotein structure?
Non-polar lipid core - mostly TAGs and cholesterol esters
Polar (hydrophilic) outer coat
What is a chylomicron?
Takes TAGs from small intestine → tissues
What do VLDLs do?
Take TAGs from liver → tissues
What is IDL?
Remnant of VLDL and can form LDLs
Diagram for major groups of lipoproteins and their actions
What are LDLs?
Take cholesterol esters from IDL → tissues
What is HDL?
Free cholesterol scavenger in periphery → liver
How are long chain FAs transported from the intestine?
Converted to TAGs, packaged into chylomicrons → secreted into lacteals
(Exogenous pathway)
Diagram for major groups of lipoproteins and their actions
how are short and medium chain FAs transported from the intestine?
Secreted into bloodstream as FFAs
Increase in FFAs in blood → insulin secretion → encourage uptake by liver/muscle/tissue
Decrease FFAs in blood between meals → adipocyte release of FFAs
What is a chylomicron?
Takes TAGs from small intestine → tissues
What does the exogenous lipid transport pathway include?
Takes lipids from small intestine → tissues via chylomicrons
- Chylomicrons secreted into lymph system by intestinal mucosal cells
- Chylomicrons acquire apolipoproteins from HDL circulating in blood (apoC and apoE)
- CMs and TAGs broken down → FFAs by lipoprotein lipase (apoC) for the tissues to absorb
- Remnants taken up by liver (apoE)
What is involved in the endogenous pathway?
Takes TAGs and Cholesterol to tissues via VLDL → IDL → LDL
- VLDL synthesised in the liver (TAGs + apolipoproteins/cholesterol)
- TAGs removed by lipoprotein lipase in capillaries → IDL
- Majority IDL donates apolipoproteins to HDL → becomes LDL
- LDL taken up by peripheral tissues (provide cholesterol)
What does reverse cholesterol transport invovle?
Transports free/used cholesterol back to the liver
HDL scavengers: free cholesterol in peripheries → liver
Provides apolipoproteins to CMs, VLDL, IDL
What is xanthelasma?
Yellow flat plaques on upper/lower eyelids - lipid-containing macrophages condensing around the socket
Usually due to high cholesterol/atheromatous disease
What is corneal arcus?
Grey opaque line surrounding margin of cornea
Common in Type II Diabetes
What is the pathophysiology of Familial Hypercholesterolaemia?
Genetic disorder - autosomal dominant, though varying effect with homo/heterozygous
Causes LDL Receptor dysfunction - prevents proper uptake of LDL by cells
What investigations can be used for diagnosis of Familial Hypercholesterolaemia?
Bloods
Total cholesterol >7.5mmol/l
LDL >4.9mmol/l
Plus tendon xanthoma → diagnosis
What is the treatment for Familial Hypercholesterolaemia?
Diet/lifestyle
Treatment of associated conditions
Statins - decrease cholesterol synthesis and increase LDL uptake; increase atherosclerotic plaque stability
Fibrates - decrease hepatic secretion + increase peripheral uptake → decrease serum triglyceride
Increase gallstone risk by increasing choleseterol content of bile
What is the clinical definition of familial hypercholesterolaemia?
Increased total cholesterol or LDL
+ Tendon Xanthoma in patient or close relative
how are short and medium chain FAs transported from the intestine?
Secreted into bloodstream as FFAs
Increase in FFAs in blood → insulin secretion → encourage uptake by liver/muscle/tissue
Decrease FFAs in blood between meals → adipocyte release of FFAs
What is the treatment for Familial Hypercholesterolaemia?
Diet/lifestyle
Treatment of associated conditions
Statins - decrease cholesterol synthesis and increase LDL uptake; increase atherosclerotic plaque stability
Fibrates - decrease hepatic secretion + increase peripheral uptake → decrease serum triglyceride
Increase gallstone risk by increasing choleseterol content of bile
What investigations can be used for diagnosis of Familial Hypercholesterolaemia?
Bloods
Total cholesterol >7.5mmol/l
LDL >4.9mmol/l
Plus tendon xanthoma → diagnosis
What is the pathophysiology of Familial Hypercholesterolaemia?
Genetic disorder - autosomal dominant, though varying effect with homo/heterozygous
Causes LDL Receptor dysfunction - prevents proper uptake of LDL by cells
What is corneal arcus?
Grey opaque line surrounding margin of cornea
Common in Type II Diabetes
What is xanthelasma?
Yellow flat plaques on upper/lower eyelids - lipid-containing macrophages condensing around the socket
Usually due to high cholesterol/atheromatous disease
What is the clinical definition of familial hypercholesterolaemia?
Increased total cholesterol or LDL
+ Tendon Xanthoma in patient or close relative
What does reverse cholesterol transport invovle?
Transports free/used cholesterol back to the liver
HDL scavengers: free cholesterol in peripheries → liver
Provides apolipoproteins to CMs, VLDL, IDL
What is involved in the endogenous pathway?
Takes TAGs and Cholesterol to tissues via VLDL → IDL → LDL
- VLDL synthesised in the liver (TAGs + apolipoproteins/cholesterol)
- TAGs removed by lipoprotein lipase in capillaries → IDL
- Majority IDL donates apolipoproteins to HDL → becomes LDL
- LDL taken up by peripheral tissues (provide cholesterol)
What does the exogenous lipid transport pathway include?
Takes lipids from small intestine → tissues via chylomicrons
- Chylomicrons secreted into lymph system by intestinal mucosal cells
- Chylomicrons acquire apolipoproteins from HDL circulating in blood (apoC and apoE)
- CMs and TAGs broken down → FFAs by lipoprotein lipase (apoC) for the tissues to absorb
- Remnants taken up by liver (apoE)
How are long chain FAs transported from the intestine?
Converted to TAGs, packaged into chylomicrons → secreted into lacteals
(Exogenous pathway)
What is HDL?
Free cholesterol scavenger in periphery → liver
What are LDLs?
Take cholesterol esters from IDL → tissues
What is IDL?
Remnant of VLDL and can form LDLs
What do VLDLs do?
Take TAGs from liver → tissues
