Lipoprotein Clinical

Question 1

describe Tangier Disease

Answer 1

• patients have defective cholesterol ABC-transporter in the PM
  
  • this leads to less substrate for LCAT and to early degradation of the lipid-poor apo A-1 which results in very low HDL levels
• symptoms:
  
  • orange colored tonsils

Question 2

describe abetalipoproteinemia

Answer 2

• MTP deficiency which leads to reduced release of VLDL and CMs
  
  • CM release into lymph requires MTP
• blood TAG levels <19 (normal = 150)
• total cholesterol levels <50 (normal = 200)
• symptoms:
  
  • fat malabsorption; steatorrhea
  • TAG accumulation in liver and intestine
  • retinitis pigmentosa, progressive blindless, peripheral neuropathy

Question 3

describe the Friedewald equation

Answer 3

• Total cholesterol, HDL-C and VLDL-TAGs are measured directly
• LDL-C is calculated indirectly
• LDL-C = total C - (HDL-C + TAG:5)

Question 4

describe type I

Answer 4

• familial hyperchylomicronemia
• high CM levels after an overnight fast
  
  • patient’s blood in vial shows lipemic plasma (milky) which is characterized by a creamy layer on top
• signs:
  
  • xanthomas over the trunk, buttock or extremities
  • increased risk of pancreatitis

Question 5

describe type IIa

Answer 5

• high LDL levels and normal VLDL levels
• defective LDL-receptor
  
  • can be treated with statin drugs
• signs:
  
  • xanthomas over tendon and xanthelasma (over eyes)

Question 6

describe type IIb

Answer 6

• familial combined hyperlipidemia
• high LDL and high VLDL levels
  
  • overproduction of apoB100
  • overproduction of VLDL
  • defective clearance of LDL
• clinical features similar to type IIa

Question 7

describe type III

Answer 7

• dysbetalipoproteinemia
• high CM and IDL remnant levels
  
  • apo E deficiency
• signs:
  
  • palmar xanthomas
  • xanthomas over the elbows and knees

Question 8

describe type IV

Answer 8

• familial hyperprebetalipoproteinemia
• high VLDL
  
  • caused by LPL deficiency or overproduction of VLDL
• high serum TAGs increases risk of pancreatitis

Question 9

describe type V

Answer 9

• familial mixed hypertriacylglycerolemia
• high CM levels and high VLDL levels
• caused by similar factors leading to type I or type IV
• patient’s blood in vial shows lipemic plasmia and turbid lower part due to high VLDL

Question 10

name the 3 potential treatments to reduce hypercholesterolemia

Answer 10

when hepatic free cytosolic cholesterol is reduced then more LDL-receptors are synthesized; this reduces LDL levels since LDLs are taken into the liver. Reduction of free cholesterol by:

1. inhibition of hepatic cholesterol synthesis by statin drugs
2. reduction of dietary uptake of cholesterol (stanols, Ezetimibe)
3. bile acid binding drugs leads to excretion of more bile acids, so the liver uses cholesterol to synthesize bile acids

Question 11

what is used to reduce VLDL in serum?

Answer 11

• Niacin reduces levels of TAGs and LDL-cholesterol and raises level of HDL
  
  • niacin reduces hepatic TAG synthesis which is needed to fill VLDL
• Fibrates lower VLDL in blood by decreasing VLDL synthesis and increasing LPL activity
  
  • fibrates increase HDL levels via stimulated apo A-1 synthesis in hepatocytes

Question 12

describe LDL-B

Answer 12

• LDL-B considered risk for for coronary heart disease
• LDL-B penetrates the endothelium easily, is retained by the ECM and can be oxidized to oxLDL
• pattern B could result from:
  
  • saturated FAs
  • trans-FAs
  • continued cleavage of TAGs in LDL-A by hepatic lipase

Question 13

describe lipoprotein a (Lp(a))

Answer 13

• Apo(a) is a glycoprotein covalently linked to apoB100 via a disulfide bond and is a structrual analog to plasminogen and may compete for the binding to fibrin
  
  • Lp(a) may reduce the removal of blood clots