A2 atherosclerosis Flashcards
Role of endothelial cells
Single layer of cells lining lumen of blood vessels
- physical barrier to blood cells (e.g. inflammatory cells). Without barrier, blood cells would be activated and clot (thrombus)
- Release bioactive substances to prevent inadvertent thrombus formation
- Release mediators that inhibit platelet activation
- Cause relaxation/contraction of underlying smooth muscle
Earliest stage of atherosclerosis development
fatty streak develops
describe stage one atherosclerosis
Insult to vascular endothelium (smoking, high shear stress, infection)
Increased adhesion and migration of leukocytes.
Increased permeability to lipids (LDL’s – bad cholesterol)
Build up of fatty streak and focus of inflammation
describe stage two atherosclerosis
(site of foam inflammation allows) Platelet adhesion & release of PDGF leads to migration of smooth muscle (from blood vessel) cells to form a fibrous cap over the foam cell layer
describe stage three atherosclerosis
Lesions become stiff, bulky and calcified
Plaques become very brittle and may rupture
Plaque rupture exposes underlying tissue & leads to thrombus formation. If large enough can cut off blood supply in coronary artery myocardial infraction (M.I.)
advanced stage atherosclerosis what is happening in coronary artery
Severe Stenosis Calcification Recent thrombosis Cholesterol Crystals Can lead to stroke, MI, heart failure
name the 3 main consequences of Atherosclerosis
- Reduced vessel lumen diameter (decreased blood flow at rest)
- Impaired relaxant function of smooth muscle: inability to increase flow in response to demand (angina – chest pain)
- Impaired antithrombotic function of endothelium
propensity to thrombosis (myocardial infarction)
Risk Factors for Plaque Formation
Hypertension High plasma cholesterol-LDL with low HDL Smoking Disease Lifestyle factors Infections?
Angina occurs as a result of
ischemia/ coronary artery disease
name 3 types of angina
- Angina of effort (Stable angina) - by exercise. result of permanent narrowing of Coronary artery by atheroma. attacks 2-3mins
- Variant (Prinzmetal’s) angina - occurs at rest. result of coronary artery spasm
- unstable angina
Sudden alteration in pattern of angina pain (may imply impending acute coronary occlusion) dangerous with high mortality
Symptoms/signs of angina
pain breathlessness elevated left ventricular end-diastolic pressure reduced coronary blood flow metabolic changes Changes in ECG
How long does it take for Myocardium to become ischemic
- what happens next
10sec from coronary occlusion
(Working cells remain viable for up to 20 minutes)
- Anaerobic mechanisms kick in: Lactic acid
Free radical damage, esp after reperfusion
Treatment for Stable Angina
Drugs: Nitrates, Beta blockers, Ca Channel Blockers
Surgery: Bypass,
PCI (PTCA, Stent)
how can nitrates be administered
and name interactions
Sublingual (works in 1–3 mins/ lasts an hour), Translingual spray, Topical Ointment, Transdermal patch, PO Sustained release capsules higher doses d/t first pass effect (isosorbide mononitrate, dinitrate), IV infusion
Interactions
Other hypotensive drugs, Beta blockers, verapamil, diltiazem, Sildenafil (Viagra)
what does Nitroglycerine do
has Vasodilating actions
Primarily acts on veins and large arteries
Uptake by VSM cells and converts to active form: NO
Therapeutic uses: Stable Angina
Decreases preload -> decreases contraction -> oxygen demand
