Lipids

Question 1

Lipoprotein Structure

Answer 1

• Outer Layer - Cholesterol, phospholipid, apoliporotein

Inner Layer: (sterified) Cholesterol Ester, Triglycerides

Question 2

Chylomicron

Answer 2

• Post prandial Tg carrier
• absent from fasting plasma
• high levels can cause pancreatitis
  
  • plasma has clear infranatant overnight at 4 C
• Apoproteins:
  
  • B48, CII, E
  • sheds CII through interaction with LPL

Question 3

VLDL

Answer 3

• transports Tg
• Major normal Tg carrier
• high levels leads to atherosclerosis and pancreatitis
  
  • in plasma specimen overnight at 4 C →turbidity supernate
• Apoproteins:
  
  • b100
  • cII (sheds this to HDL)
  • E
    *

Question 4

Interdiate (IDL)

Answer 4

• Carries Cholesterol and Triglycerides
• NL concentration is low
• ahtersclerosis, and risk of pancreatitis
• Apoproteins
  
  • b100
  • e (removed by liver using this)

Question 5

LDL

Answer 5

• carries Cholesterol
• Major nl cholesterol. carrier
• Apoprotein: b100
• athersclerosis
  *

Question 6

HDL

Answer 6

• carries Cholesterol
• Reverse cholesterol transport (from tissue to liver)
• high HDL is good
• higher is active people and pregnancy
• low level increases risk of athersclerosis

Question 7

Lipoprotein(a)

Answer 7

• Carries Cholesterol
• usually low
• genetically determined
• atherogenic
• modified form of LDL

Question 8

Lipoprotein X

Answer 8

• carries Cholesterol
• present w/biliary track obstruction
• lacks apo B
  *

Question 9

Exogenous pathway

Answer 9

• ingested lipids
• Intestine > Chylo > lipoprotein lipase cleaves TG to FFA, MG > Chylo remnants > Liver LDL-R
  *

Question 10

Endogenous Pathway

Answer 10

Liver > VLDL > LPL cleaves FFA, MG for tissues > IDL > Liver LDL-R

IDL can be converted to LDL (hepatic lipase activity)

Some LDL is returned to livers, some is used to by tissues

Question 11

Frederickson phenotypes

Answer 11

• One way is to remember these is to classify as to the major lipid abnormality:
• Types 1, IIA, IIB, III, IV, and V
• Increased Tg - I, IV, V
• Increased LDL - IIA
• Increased Tg and LDL - IIB, III

Question 12

Increased Tg

Answer 12

• I - Chyclomicrons
• IV - VLDL
• V - Chylomicrons & VLDL

Question 13

Increased LDL

Answer 13

Type IIA

Question 14

Increased Tg & LDL

Answer 14

IIB - LDL & VLDL

III - IDL & remnant LP’s

Question 15

Most Common Dyslipdemias

Answer 15

IV - VLDL

IIA - LDL

IIB - LDL & VLDL

Question 16

Type I Causes

Answer 16

Particle: Chylomicrons

• LPL deficiency
  
  • AR, 1 in 10^6
  • Onset: infancy
• Apo CII deficiency
  
  • ligand for LPL
  • AR, 1 in 10^6
  • Onset: childhood
• SLE
  
  • Acquired
  • Autoab to LPL

Question 17

Type IV Causes - Genetic

Answer 17

Particle: VLDL

• Insulin resistance (rare)
  
  • Insulin receptor mutation
  • Lipodystrophy (fat deposition problems)
• Familial hypertriglyceridemia - AD
• Familial combined hyperlipidemia - AD
• Inborn erros of metabolism
  
  • e.g. Glycogen storage disease

Question 18

Type IV Causes - Acquired

Answer 18

• Insulin resistance
• decreased VLDL clearance: decreased activity of LPL
• Obesity, MS, prediabetes, T2DM
• Cushing, acromegaly, pheo
• steroids

Liver, Renal dz

Hypothyroidism

Question 19

Type V Causes

Answer 19

Particles: Chylomicrons and VLDL

Any 2 causes of type IV HLP

Question 20

Type IIA Causes: Genetic

Answer 20

• Particle: LDL
• Monogenic disorders
  
  • Familial hypercholesterolemia
  • Familial hyperapo-B-lipoproteinemia
  • AR familial hypercholesteromia
  • Familial combined hyperlipidemia
  • PCSK9 gain-of-function mutations
• Polygenic more common

Question 21

Type IIA Causes : Acquired

Answer 21

• Liver disease (ex: biliary tract dz)
• Renal dz (e.g. nephrosis)
• Endocrine
  
  • Hypothyroidism
  • Diabetes mellitus
• Drugs
  
  • glucocorticoids, androgens
    *

Question 22

Type 2B Causes

Answer 22

Particles: LDL & VLDL

• Similar to HPL IIA
• except:
  
  • familial hyperapo-B-lipoproteinemia displays only a HLP IIA phenotype (no increase in VLDL)
    *

Question 23

Type III Causes

Answer 23

• Particles: IDL & rem. LP’s
• Apo E2/E2 plus and environmental trigger:
• Environment
  
  • Etohism
  • DM
  • Renal Dz
  • Liver Dz
• ** APO E4 is present in about 25-30% of population and about 40% of all people with late-onset Alzheimer’s DZ.

Question 24

abetalipoproteinemia

Answer 24

• only genetic cause of hypolipidemia to care about
• hematology and neuropath
• AR (autosomal recessive)
• failure of production of apo B
  
  • very low Tg & chol
  • very low: VLDL & LDL
• HLD: preserved (lacks apo B)
• Clinical
  
  • Acanthocytes
  • Developmental failure in infancy/childhood
  • fat malabsorption
    *