L41: Atherosclerosis And Disrupted Circulation

Question 1

What is atherosclerosis

Answer 1

Presence of fibrofatty plaque / atherosclerotic plaque within intima affecting large and medium-sized arteries

Question 2

Function of intima, media and adventitia

Answer 2

Intima: endothelial cells with anti-coagulant mechanisms to keep blood fluid

Media: smooth muscle to control diameter, produce ECM to support vessel

Adventitia: contains nerves and blood vessel to respond to neurohormonal control

Question 3

Fibrofatty plaque component

Answer 3

1. Superficial: fibrous cap
2. Central:
   - intracellular lipid (macrophage + ***SMC —> ingest lipid —> foam cells)
   - extracellular lipid (cholesterol + CE)
   - elastin
   - collagen
   - proteoglycan ground substance
   - plasma protein
   - leukocytes (lymphocytes etc.)
   - cell debris

Question 4

Precursor to fibrofatty plaque

Answer 4

Fatty streak: lipid deposits within macrophages and SMC in intima
—> elevated spots / streaks
—> normal in all children > 1

Question 5

Risk factors for atherosclerosis

Answer 5

Irreversible:

• Age
• Male (until 75-85: both sex equal)
• Family history (hyperlipidaemia, hypertension, diabetes)

Reversible:
- Smoking (damages endothelium: leukocyte adhesion + decreased ability to relax)

• Hyperlipidaemia (fluid shear: LDL enter intima —> lipid —> oxyLDL)
  —> oxyLDL stimulate intima to produce cytokine + growth factor —> stimulate monocyte to stick —> phagocytosis by macrophage + SMC —> foam cells
• Hypertension (Diastolic BP —> mechanical damage to endothelium)
• Diabetes (non-insulin dependent DM: abnormalities of lipoprotein metabolism —> ↑LDL, ↓HDL)
  —> increased glucose stick to collagen —> Amadori product (AGE) —> recognised by macrophage + platelet —> cytokine release
• Homocysteinaemia (fasting high homocysteine: renal/liver disease, lack of folate, B6, B12 to lower homocysteine)
  —> homocysteine auto-oxidise and react with ROS to damage endothelial cells —> thrombi formation
  —> homocysteine stimulate SMC to migrate into intima + produce ECM —> fibrous cap
  —> homocysteine up-regulate fatty acid synthesis

Question 6

Pathogenesis of atherosclerosis

Answer 6

Hypothesis:
Endothelial damage (initiating event)
—> Macrophage and Platelet adherence: produce growth factors (PDGF)
—> SMC proliferation + migration from media into intima

—> Endothelial cells produce own growth factors (ECGF) + IL-1
—> monocyte adhesion and migration into tissue —> macrophage

Question 7

Complications of plaque

Answer 7

1. Calcification
2. Thrombosis (erosion of endothelium, clot in vessel) —> thromboembolism
3. Ulceration —> discharge of cholesterol emboli
4. Haemorrhage

Question 8

3 factors contributing to thrombosis (clot in vessels)

Answer 8

Virchow’s triad

1. Endothelial damage (e.g. atherosclerosis)
2. Abnormal blood flow (e.g. venous stasis)
3. Hyper-coagulability (e.g. dehydration)

Question 9

Formation of fibrin

Answer 9

Factor X —> Factor V —> Factor IIa (thrombin) —> convert Factor I (fibrinogen) into Factor Ia (fibrin)

Question 10

Fates of thrombosis

Answer 10

1. Propagate
2. Recanalised
3. Incorporated into vessel wall
4. Resolved completely
5. Dislodged —> emboli —> ischaemia —> infarction (ischaemic necrosis, haemorrhagic / pale)

Question 11

Haemorrhagic infarct vs Pale infarct

Answer 11

Haemorrhagic:

• red
• lung, brain, GI
• loose tissues: RBC can diffuse into necrotic tissue —> red in colour

Pale:

• white / anaemic
• heart, kidney, spleen
• solid organs: limited RBC / haemorrhage can go into necrotic tissue

Question 13

Different types of embolism

Answer 13

1. Pulmonary thromboemboli
2. Fat
3. Marrow
4. Air
5. Amniotic fluid
6. Foreign bodies