MT2_1_Dyslipidemia_Pathophysiology

Question 1

Explain how cholesterol synthesis occurs.

Answer 1

• Acetyl-CoA
• HMG-CoA Synthase to make HMG-CoA
• HMG-CoA Reductase to make mevalonate
• turns into cholesterol, which is important in the formation of bile acids, steroid hormones, and components of cell membranes

Question 2

What are the functions of phospholipids and TGs?

Answer 2

Phospholipids: cellular function and lipid transport

TG: store energy in adipose tissue

Question 3

Explain how lipids are transported?

Answer 3

Cholesterol in the gut after a fatty meal is taken up by bile acids, which are then formed in chylomicrons to be delivered in the blood or liver.

Question 4

What are the functions of lipoproteins? What serve as ligands for receptors?

Answer 4

transport lipids (that are water insoluble) which are formed in hepatocytes and enterocytes

• Apolipoproteins serve as ligands

Question 5

What are the different types of lipoproteins? (include TG and Cholesterol content)

Answer 5

Chylomicrons (high TGs)
VLDL, IDL, LDL (less TGs, more cholesterol)
HDL: good cholesterol

Question 6

Explain the lipid transport pathway.

Answer 6

• Liver makes chylomicrons by making VLDL molecules rich in TG
• As VLDL goes through the bloodstream, APOLIPO protein signals the tissues to uptake VLDL
• As VLDL continues to deposit, it turns into IDL then LDL (more cholesterol rich)
• LDL will bind to receptors in the liver, but when there is too much it will deposit in the vasculature of bodies, causing pathogenesis

Question 7

What are the functions of apolipoproteins?

What are the key ones?
CII, CIII, B100, A1

Answer 7

• structure, activate enzyme systems, and ligand for cell wall receptors
• CII: activates lipoprotein lipase
• CIII: down regulates LPL activity
• B100: binds to LDL receptor on cell membrane
• A1: promotes cholesterol extraction from tissue

Question 8

How is the LDL receptor recycled?

Answer 8

As the receptor ages, the nucleus releases PCSK9 into the blood to bind to the LDL receptor, signaling it to be broken down to prevent future use.

Question 9

Describe the pathogenesis of atherosclerosis.

1. Accumulation of ___
2. Retained lipoproteins are __
3. Endothelial cells release __
4. Recruited monocytes are converted to __
5. Macrophages phagocytose __
6. ____accumulate in the endothelium, forming ___ that ___
7. Foam cells create a ___
8. Secretion of ___and__ ___the lesion
9. Chronic lesions lead to ____while younger lesions lead to ____.

Answer 9

1. lipoproteins in sub endothelium
2. oxidized
3. monocyte adhesion molecules
4. macrophages
5. oxidized lipoproteins
6. cholesterol-laden macrophages…foam cells that damage endothelium
7. fatty streak
8. chemoattractants and growth factors, stabilize
9. progressive stenosis__susceptible to rupture

Question 10

What are the main complications of artherosclerosis?

Answer 10

• cerebral infarction
• acute coronary heart syndromes (MI)
• renal dysfunction, HTN
• limb ischemia