Lipids Flashcards
Lipoprotein Structure
- Outer Layer - Cholesterol, phospholipid, apoliporotein
Inner Layer: (sterified) Cholesterol Ester, Triglycerides
Chylomicron
- 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
VLDL
- 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
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Interdiate (IDL)
- Carries Cholesterol and Triglycerides
- NL concentration is low
- ahtersclerosis, and risk of pancreatitis
- Apoproteins
- b100
- e (removed by liver using this)
LDL
- carries Cholesterol
- Major nl cholesterol. carrier
- Apoprotein: b100
- athersclerosis
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HDL
- 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
Lipoprotein(a)
- Carries Cholesterol
- usually low
- genetically determined
- atherogenic
- modified form of LDL
Lipoprotein X
- carries Cholesterol
- present w/biliary track obstruction
- lacks apo B
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Exogenous pathway
- ingested lipids
- Intestine > Chylo > lipoprotein lipase cleaves TG to FFA, MG > Chylo remnants > Liver LDL-R
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Endogenous Pathway
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
Frederickson phenotypes
- 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
Increased Tg
- I - Chyclomicrons
- IV - VLDL
- V - Chylomicrons & VLDL
Increased LDL
Type IIA
Increased Tg & LDL
IIB - LDL & VLDL
III - IDL & remnant LP’s
Most Common Dyslipdemias
IV - VLDL
IIA - LDL
IIB - LDL & VLDL
Type I Causes
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
Type IV Causes - Genetic
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
Type IV Causes - Acquired
- Insulin resistance
- decreased VLDL clearance: decreased activity of LPL
- Obesity, MS, prediabetes, T2DM
- Cushing, acromegaly, pheo
- steroids
Liver, Renal dz
Hypothyroidism
Type V Causes
Particles: Chylomicrons and VLDL
Any 2 causes of type IV HLP
Type IIA Causes: Genetic
- Particle: LDL
- Monogenic disorders
- Familial hypercholesterolemia
- Familial hyperapo-B-lipoproteinemia
- AR familial hypercholesteromia
- Familial combined hyperlipidemia
- PCSK9 gain-of-function mutations
- Polygenic more common
Type IIA Causes : Acquired
- Liver disease (ex: biliary tract dz)
- Renal dz (e.g. nephrosis)
- Endocrine
- Hypothyroidism
- Diabetes mellitus
- Drugs
- glucocorticoids, androgens
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- glucocorticoids, androgens
Type 2B Causes
Particles: LDL & VLDL
- Similar to HPL IIA
- except:
- familial hyperapo-B-lipoproteinemia displays only a HLP IIA phenotype (no increase in VLDL)
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- familial hyperapo-B-lipoproteinemia displays only a HLP IIA phenotype (no increase in VLDL)
Type III Causes
- 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.
abetalipoproteinemia
- 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
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