CSIM 1.61: Cardiovascular Disease 1

Question 1

What are the stages of atheroma?

Answer 1

Type 1) Initial lesion
• Isolated macrophage foam cells in the form of HISTIOCYTES

Type 2) Fatty streak lesion
• Intracellular lipid accumulation

Type 3) Intermediate lesion
• Type 2 + small extracellular lipid pools

Type 4) Atheroma lesion
• Type 2 + large core of extracellular lipid

Type 5) Fibroatheroma lesion
• Lipid core and fibrotic layer
• Lipid present in histiocytes and freely
• Smooth muscle cells migrade from the media and proliferate

Type 6) Complicated lesion
• Surface defect (thrombus, rupture)
• Calcification present (visible on x-ray)

IMG 152

Question 2

Describe how a plaque becomes complicated (type 6)

Answer 2

• Ulceration and fissure reveal the fibrous plaque contents, triggering thrombosis
  
  • Inflammation associated with the plaque weakens it

Question 3

Which arteries can be affected by atherosclerosis?

Answer 3

Those larger than 1mm in diameter
• Not brachial arteries
• Not renal arteries

Question 4

What are the consequences of atheroma?

Answer 4

• Narrowing leading to ischaemia
  
  • Occlusion leading to infarction
  • Embolism
  • Aneurysms due to weakened wall

Question 5

What is the most common site for aneurysm?

Answer 5

Infrarenal abdominal aorta (triple a)
• Aorta dilates
• This space is filled with lamellated thrombus
• Eventually this aorta ruptures

Question 6

How does someone with a ruptured abdominal aortic aneurysm present?

Answer 6

• Severe abdominal or back pain

* Shock due to hypovolemia

Question 7

Which organs are most commonly affected by occlusion, embolism and narrowing?

Answer 7

• Heart
  
  • Brain
  • Legs
  • Gut
  • Kidneys

Question 8

What does narrowing and occlusion of coronary arteries lead to?

Answer 8

Narrowing: angina
Occlusion: MI

Question 9

What is pain in the calves when walking indicative of?

What does occlusion of the femoral artery lead to? What else can cause this?

Answer 9

Claudication - caused by atheroma of the femoral artery

Gangrene - also caused when CO decreases in the case of severe stenosis of the femoral artery

Question 10

What causes gut infarctions?

Answer 10

Thrombosis over an atherosclerotic plaque in the mesenteric arteries

Question 11

In which patients is the renal artery not spared from atherosclerosis? What does this cause

Answer 11

Diabetic patients

• Atherosclerosis in the renal arteries causes atrophy of the kidney due to chronic ischaemia .
• The underperfused kidney releases renin, activating the angiotensin pathway causing renal hypertension

Question 12

Describe the pathogenesis of atherosclerosis

Answer 12

• Initial damage to the endothelium results in an inflammatory response.
  
  • Monocytes enter the artery wall from the bloodstream, with platelets adhering to the area of insult.
  • The monocytes differentiate into macrophages, which ingest oxidised LDL, slowly turning into large “foam cells” (due to many internal vesicles filled with fat)
  • Under the microscope, the lesion now appears as a fatty streak.
  • Cholesterol is delivered into the vessel wall by cholesterol-containing low-density lipoprotein (LDL) particles.
  • Smooth muscle cells, which in turn ingest lipids, become replaced by collagen and transform into foam cells themselves.
  • Fibrous and fatty tissue results

Question 13

List pro-atherogenic conditions with regard to blood contents

Answer 13

• Increased LDL
  
  • Increassed inflammatory adhesion molecules ICAM-1
  • Reduced NO
  • Reduced TGF-β
  • Reduced IL-10

Question 14

List the atheroprotective conditions with regard to blood contents

Answer 14

• Increased HDL
  
  • Increased Treg cells
  • Increased B1 cells secreting natural antibodies which suppress inflammation

Question 15

What are the two prevailing theories for pathogenesis of atherosclerosis?

Answer 15

Lipid hypothesis
• Initial accumulation of plasma-derived lipoproteins

Response-to-injury hypothesis
• Chronic endothelial injury leading to damage