Pathophysiology

• Atherosclerosis

  Endothelial dysfunction → increased permeability → high conc of LDLs → deposit into tunica intima (TI) → endothelial cells release ROS & MMPs → oxidise LDLs (cannot leave TI) → activate endothelial cells → expression of adhesion molecules → WBCs adhere to endothelium → monocytes & T cells to enter TI → monocytes to macrophages → macrophages phagocytose oxidised LDLs → macrophages to foam cells → FCs release chemokines → more monocytes & migration of smooth muscle cells from tunica media to TI → smooth muscle proliferation → increase collagen synthesis → hardens plaque
• Atherosclerosis (progression).

  Foam cells die & release their contents → further increases inflammation → further growth of plaque

  Plaque grows → increase pressure (risk of rupture)

  Plaque can rupture → thrombosis
• What is atherosclerosis?

  Complex inflammatory process

  Characterised by accumulation of lipid, macrophages & smooth muscle cells in intimal plaques
• What is the physiology of cardiogenic shock?

  CO falls -> right atrial pressure rises -> fall in BP -> baroreceptor & other responses -> sympathetic system activation -> increased venous return & stimulation of heart -> reduced renal blood flow, urine output & increased fluid retention -> danger of reduced BP -> poor myocardial perfusion (esp through disease coronary circulation) = cycle of further damage
• What is coronary artery disease?

  When coronary blood flow to a region of the myocardium may be reduced by mechanical obstruction due to:

  • atheroma
  • thrombosis
  • spasm
  • embolus
  • coronary ostial stenosis
  • coronary arteritis

  Decreased in flow of O2 blood to myocardium
• When does myocardial ischaemia most commonly arise?

  Coronary artery disease (from coronary atherosclerosis)
• What is myocardial ischaemia due to?

  Imbalance between supply of O2 to cardiac muscle & myocardial demand
• What is the most common cause of myocardial ischaemia?

  Coronary artery atheroma
• How does angina occur?

  Due to reduced blood flow to myocardium -> due to narrowing of coronary arteries (usually due to atherosclerotic plaque)

  Coronary blood flow only occurs during diastole

  If increased cardiac work -> decreased perfusion (due to less time in diastole)

  Increased sympathetic activity -> increase HR -> decreased time in diastole (this is why beta blockers are used in angina)
• What is stable angina?

  Chest pain brought on by emotional or physical stress

  Goes away with rest or GTN spray
• Fill in the blanks

  A) stable angina

  B) unstable angina

  C) NSTEMI

  D) STEMI

  
• Fill in the blanks

  A) Aorta

  B) Pulmonary artery

  C) Left coronary artery

  D) Circumflex

  E) Left anterior descending

  F) Left circumflex marginal artery

  G) Diagonal

  H) Marginal

  I) Left circumflex

  J) Right coronary artery

  K) Posterior descending artery

  
• What is the function of the collateral vessels in angina?

  Alternative route

  Only a small amount of blood can get past the atheromatous plaque

  Collateral vessels allows blood to reach tissue distal to the plaque

  
• What is the progression of atheromatous plaques?

  Atheromatous deposits

  Plaques

  Atherosclerosis
• What is 3rd degree heart block?

  Electrical signal from the atria to ventricles is completely blocked

  -> ventricles beat on their own, out of rhythm from atria

  Irregular
• What is the progression from angina to MI?

  Stable angina

  Unstable angina

  Thrombosis/MI
• Path - MI (atherosclerosis)

  Vulnerable plaque ruptures → activates TF → coagulation → superimposed clot → blocks coronary artery (atherothrombosis) → hypoxia & ischaemia → pain signals to brain → activates sympathetic NS → adrenaline release → tachycardia → more hypoxia (less diastole) → myocytes switch to anaerobic resp → myocytes unable to make own ATP → decreased contractility & Na+/K+ pump fails → accumulation of waste (e.g. lactate) → myocytes leak troponin → loss of myocytes (necrosis) → less contraction → MI
• What is the effect of an MI of the heart's ability to contract?

  MI → hypoxia & ischaemia → cells switch from aerobic respiration to anaerobic → cells unable to to generate own ATP → contractility of area rapidly decreases & Na+/K+ pump fails → accumulation of waste products (e.g. lactic acid) → necrosis of myocytes → less contraction of cardiac myocytes
• What can activate platelets?

  Collagen

  Thrombin

  ADP

  Thromboxane A2

  Platelet activating factor (PAF)

  Adrenaline

  Serotonin
• What happens when platelets are activated?

  Platelet aggregation

  Activation of platelets -> change in affinity of aIIbB3 (from low to high) → fibrinogen can bind to aIIbB3 → fibrinogen crosslinks activated platelets (binds to another aIIbB3 on another platelet) → more platelets recruited → large aggregate (or thrombus)