01-06 Hyperlipoproteinemia Flashcards
(67 cards)
1
Q
ApoA1
—particle
—biochemistry
A
—particles: HDL
—biochemistry: activates LCAT which converts HDL to HDL2 by esterifying cholesterol in the HDL molecule
2
Q
ApoB48
—particle
—biochemistry
A
—particles: chylomicrons
—biochemistry: interacts with a B receptor
3
Q
ApoB100
—particle
—biochemistry
—clinical utility
A
—particles: VLDL, ILDL, LDL
—biochemistry: interacts with LDLR
4
Q
ApoCII
—particle
—biochemistry
A
—particles: VLDL
—biochemistry: activates LPL
5
Q
ApoE
—particle
—biochemistry
A
—particles: HDL, VLDL, chylomicrons
—biochemistry: required for receptor binding
6
Q
Apo(a)
—particle
—biochemistry
—clinical utility
A
—particles: lipoprotein (a)
—biochemistry: links to B100
7
Q
LPL
—site of synth
—MOA
—stimulus
A
—synth’d in liver
—catalyzes the hydrolysis of TG’s into phospholipids and glycerol, for entry into cells.
—insulin and contact w/ ApoCII
8
Q
HL
—acts on which particles?
—MOA?
—located where?
A
HEPATIC LIPASE
It acts on LDL and HDL borne triglycerides.
1) on the endothelium within the liver
2) functions much like LPL – but for liver cells only
—Converts HDL 2 to HDL 3
9
Q
LCAT
—location
—fxn
A
lecithin cholesterol acyl transferase
—transfers acyl groups from lecithin to cholesterol
to create cholesterol esters.
1) made in the liver
2) Interacts with with apoAI on HDL.
3) converts HDL1 to HDL 2 and HDL 2 to HDL 3
10
Q
CETP
—fxn
—site of action
A
cholesterol ester transferase protein
—converts cholesterol esters back to cholesterol for delivery to the liver
—Acts within the HDL particle
11
Q
SCAP
—fxn
—mechanism
A
SREBP Cleavage Activating Protein
1) Acts as a sensor for intracellular sterols
2) With low intracellular steroids, it binds to SREB-2 to allow S1 and S2 to cleave of SREBP-2’s N terminal segment, which is then activated
3) SCAP is therefore activated by low cholesterol diets cholesterol binding resins niacin statins
12
Q
SREBP
A
sterol responsive element binding protein
1) transcription activating factor
2) on the ER
3) released by protein cleavage
4) acts at the nucleus.
13
Q
SREBP2
A
controls genes for de novo cholesterol synthesis, such as (HMGCoA reductase) ;
activated when cytoplasmic levels of cholesterol are low
(as occurs due to treatment for high cholesterol)
14
Q
Steps in responding to low intracellular [sterol] w/ SREPB
A
1) SCAP is Modified in Golgi & binds to SREBP
2) SREPB, bound to SCAP relocates to ER; acted on by S1P and S2P (scissors) to release N terminal
3) N terminal of SREBP-2 acts as a transcription actor, increases LDLR
4) increased # of LDLRs on cell surfaces leads to incr uptake of LDL
15
Q
ABC1
—fxn
A
ATP binding casette protein 1 transfers cholesterol and phospholipids to the cell membrane for pickup by HDL particles
—In the absence of ABC1, cholesterol does not move from the cytoplasm to the outer leaflet of the cell membrane and is therefore unable to interact with the Apo1 of HDL
16
Q
LDLR
A
LDLreceptor interacts with the B100 apoplipoprotein to recognize LDL particles
17
Q
PCSK-9
A
Paraprotein Convertase Subtilisin/Kexin 9
- secreted protein Binds to LDL R
- Targets LDLR for degradation
- if you mutate/inhibit or decr the [PCSK-9] you ↑ number of LDLR on cell surface
- *novel drug target
18
Q
PPAR System
A
PPAR = peroxisome proliferation activating receptor-α
—involved in energy homeostasis
—system of PPAR-α, -∆, (catabolic) and -γ (anabolic)
PPAR-α Specifically:
—target of fibrates (e.g. gemfibrizol)
—together w/ RXR it attracts coactivators
—key determinant of VLDL synthesis: induces transcription of genes that facilitate lipid metab
19
Q
Equation for total cholesterol?
A
Total* = LDL* + VLDL + HDL*
- measured
- VLDL = TG/5
- ** calculated from these other numbers
20
Q
What is “non-HDL” cholesterol and how do we calculate it?
—Benefits?
A
“non-HDL” = total - HDL
—includes: LDL, IDL (known atherogens), VLDL (possible atherogen), ApoB and lipoproteins
—no need to fast before blood draw
—maybe be better at predicting risk in DM2 or FCH
21
Q
Why do you need to fast before lipid panel?
A
Triglycerides —> VLDL estimate & LDL_calc
22
Q
Interpreting the chilled tube test
A
White on top = chylos —should be absent w/ fasting sample —otherwise = excess chylos Fluid in middle = serum —should be translucent —if cloudy = excess VLDL GEL RBCs
23
Q
1° Causes of chylomicron excess + presentation
A
LPL deficiency & apoCII deficiency
—both very rare, recessive conditions
—both cause: TGs 1000-2000mg/dL, pancreatitis, eruptive xanthomas
24
Q
1° Causes of VLDL excess + presentation
A
Familial hypertriglyceridemia
—common (1%) dominant inheritance
—TGs 250-1000 & pancreatitis
FCH: see separate card
25
FCH
Causes both VLDL & LDL excess
—dom. inher
—thought to be due to excessive VLDL synth
—↑ chol, TGs, VLDL and LDL
—variable presentation: eruptive and tuberous xanthomas, ASCVD,
26
1° Causes of ILDL excess + presentation
remnant removal dz (familial dysbetalipoproteinemia, Hyperbetalipoproteinemia)
—super rare, recessive condition
—must have ApoE2
—cholesterol is = to TG which is abnl (usu TGs < chol when fasting)
—palmar and tuberous xanthomas; ASCVD
27
1° Causes of LDL excess + presentation
```
1. Familial Hypercholesterolemia
—defect in LDL-R
—0.2% and dominant inher
—homozygotes die before 20
—heteros: chol = 350-550; ASCVD; tendon xanthomas
```
2. Familial Defective Apo B100
—0.2% also, but recessive (vs. FH)
—same presentation as hetero FH: chol = 350-550; ASCVD; tendon xanthomas
3. FCH (see card)
4. Polygenic Hypercholesterolemia
—diet induced?
—ASCVD
28
Tendon xanthomas occur on which tendons?
extensors
| —don't know why
29
xanthelasma
periorbital lipid deposits
30
Tangier's Dz
```
1° cause of HYPERlipidemia
—very rare
—mutation in ACB1 (bring chol outer leaflet of cell)
—low HDL
—ASCVD
```
31
Lp(a) Excess
LDL w/ a side chain
—atherogenic
—High Lp(a), ASCVD
32
2° Causes of Chylomicron Excess
—Lipid Panel Results?
—DDx?
—↑ TGs
| —CRF (chronic renal failure?)
33
2° Causes of VLDL Excess
—Lipid Panel Results?
—DDx?
```
—Labs: ↑ TGs and Chol
—DDx:
Alcohol
Carbohydrate inducible
CRF
Uncontrolled DM
HAART
Nephrotic syndrome (highest chol you'll see!)
Estrogens
```
34
2° Causes of LDL Excess
—Lipid Panel Results?
—DDx?
```
—Labs ↑ Chol
—DDx:
Hypothyroidism
Nephrotic syndrome
Obstructive liver disease (chol = 2000-4000!)
```
35
Health hazard of ↑ chylos?
| —Tx?
pancreatitis
Tx:
—diet restriction of sat fat & EtOH
—fish oil
36
Health hazard of ↑ VLDL?
| —Tx?
```
pancreatitis and fatty liver
—restrict sat fat, carbs, EtOH
—PPARα agonists (fibrates)
—Niacin
—These drugs slow release of VLDL from liver
```
37
Health hazard of ↑ ILDL?
| —Tx?
```
atherosclerosis and fatty liver
TREAT LIKE ↑ VLDL:
—restrict sat fat, carbs, EtOH
—PPARα agonists (fibrates)
—Niacin
```
38
Health hazard of ↑ LDL?
athero
Tx:
—Diet: ↓chol & sat fat (↓7-15%)
—Bile acid sequestrants: cholestyramine, Welchol
—HMG CoA reductase inhib: statins (↓30-65%)
—Chol transport inhib: eztemibe (↓20%)
—Red Rice Yeast (↓10-25%)
39
Health hazard of ↓ HDL?
athero
40
Case 03
A 28 year old woman presents because she is ‘worried about my heart”. Her brother had a heart attack at 36 and her sister had a heart attack at 40. There is a family history of heart attacks before the age of 50 going back at least 2 generations, and nobody on her fathers side seems to live past 60. Her blood pressure is 110/60 and she does not smoke. She is eating a lowfat diet and exercises regularly. She is using an oral contraceptive. On exam, she has thickened achilles tendons
```
Fasting lipids:
Chol 360
TG 85
HDL 40
LDL 303
```
** the lab calls – the tube was chilled in transit . There was no layering and the serum was clear
1. What particle, if any, is in abnormal amounts?
2. What is DDx?
3. What is health risk?
4. What are tx options?
1. What particle, if any, is in excess?
Normal TG, markedly elevated cholesterol, normal HDL Excess LDL
2. What is the differential diagnosis
If primary: FCH, familial hypercholesterolemia
If secondary: high cholesterol diet, hypothyroidism nephrosis, biliary disease
3. What is the health risk?
Early atherosclerotic disease: MI, CVA, PVD
4. What are the treatment options?
Medications: diet + statins +/- ezetimbe
41
Trigs and athero?
some epidemological associations but Weak to no correlation w/ multi-variate analysis
42
Atherosclorotic lipids?
```
LDL (esp oxidized)
ILDL
Small Dense VLDL
Lipoprotein B particles
NOT: chylos, usual VLDL or ?TGs
```
43
Case 01
40 year old man presents with abdominal pain, sometimes severe and disabling, over the last 6 months. It is occasionally associated with vomitting. There is a family history of pancreatitis. He is on no medications
He eats three meals a day and usually purchases lunch out- typically a burger and fries or a pizza. He drinks 2-4 beers in the evening.
```
Fasting lipids:
Chol 190
TG 3500
HDL 20
LDL (not calc)
```
** the lab calls – the tube was chilled in transit and showed up with a thick white layer occupying the top; the serum was clear
1. What particle, if any, is in abnormal amounts?
2. What is DDx?
3. What is health risk?
4. What are tx options?
No LDL calc b/c chylos so high
1. What particle, if any, is in abnormal amounts?
Markedly elevated TG, relatively normal cholesterol Excess Chylomicrons, low HDL
2. What is the differential diagnosis
If 1°: LPL or C-II deficiency If 2°: ? Renal failure
3. What is the health risk ?
Pancreatitis
4. What are the treatment options?
Dietary: low fat diet, alcohol avoidance
44
Case 02
A 35 year old woman presents to your office. She has been referred because she has very high serum lipids. Her grandmother died of a heart attack at 95 years of age. She is in otherwise good health. She eats three meals a day and is following a very lowfat diet because “it is healthier”. She is 10 lbs over ideal body weight. She takes a multivitamin each day and a birth control pill.
```
Fasting lipids:
Chol 240
TG 800
HDL 30
LDL (not calc)
```
** the lab calls – the tube was chilled in transit . There was no layering but the serum was cloudy
1. What particle, if any, is in abnormal amounts?
2. What is DDx?
3. What is health risk?
4. What are tx options?
1. What particle, if any, is in excess?
Markedly elevated TG, elevated cholesterol, low HDL Excess VLDL , low HDL
2. What is the differential diagnosis?
If 1°: FCH, familial hyperTG, If 2°: high carb diet (from her low fat diet!), estrogens
3. What is the health risk?
Pancreatitis, possibly increased atherosclerosis
4. What are the treatment options?
Stop estrogens, balance diet, consider niacin or fibrates
45
Case 03
A 28 year old woman presents because she is ‘worried about my heart”. Her brother had a heart attack at 36 and her sister had a heart attack at 40. There is a family history of heart attacks before the age of 50 going back at least 2 generations, and nobody on her fathers side seems to live past 60. Her blood pressure is 110/60 and she does not smoke. She is eating a lowfat diet and exercises regularly. She is using an oral contraceptive. On exam, she has thickened achilles tendons
```
Fasting lipids:
Chol 360
TG 85
HDL 40
LDL 303
```
** the lab calls – the tube was chilled in transit . There was no layering and the serum was clear
1. What particle, if any, is in abnormal amounts?
2. What is DDx?
3. What is health risk?
4. What are tx options?
1. What particle, if any, is in excess?
Normal TG, markedly elevated cholesterol, normal HDL Excess LDL
2. What is the differential diagnosis
If primary: FCH, familial hypercholesterolemia
If secondary: high cholesterol diet, hypothyroidism nephrosis, biliary disease
3. What is the health risk?
Early atherosclerotic disease: MI, CVA, PVD
4. What are the treatment options?
Medications: diet + statins +/- ezetimbe
46
Health hazard of ↑ chylos?
| —Tx?
pancreatitis
Tx:
—diet restriction of sat fat & EtOH
—fish oil
47
Health hazard of ↑ VLDL?
| —Tx?
```
pancreatitis and fatty liver
—restrict sat fat, carbs, EtOH
—PPARα agonists (fibrates)
—Niacin
—These drugs slow release of VLDL from liver
```
48
Health hazard of ↑ ILDL?
| —Tx?
```
atherosclerosis and fatty liver
TREAT LIKE ↑ VLDL:
—restrict sat fat, carbs, EtOH
—PPARα agonists (fibrates)
—Niacin
```
49
Health hazard of ↑ LDL?
athero
Tx:
—Diet: ↓chol & sat fat (↓7-15%)
—Bile acid sequestrants: cholestyramine, Welchol
—HMG CoA reductase inhib: statins (↓30-65%)
—Chol transport inhib: eztemibe (↓20%)
—Red Rice Yeast (↓10-25%)
50
Health hazard of ↓ HDL?
athero
51
Health hazard of ↑ Lipo(a)?
athero
52
Trigs and athero?
some epidemological associations but Weak to no correlation w/ multi-variate analysis
53
Atherosclorotic lipids?
```
LDL (esp oxidized)
ILDL
Small Dense VLDL
Lipoprotein B particles
NOT: chylos, usual VLDL or ?TGs
```
54
Case 01
40 year old man presents with abdominal pain, sometimes severe and disabling, over the last 6 months. It is occasionally associated with vomitting. There is a family history of pancreatitis. He is on no medications
He eats three meals a day and usually purchases lunch out- typically a burger and fries or a pizza. He drinks 2-4 beers in the evening.
```
Fasting lipids:
Chol 190
TG 3500
HDL 20
LDL (not calc)
```
** the lab calls – the tube was chilled in transit and showed up with a thick white layer occupying the top; the serum was clear
1. What particle, if any, is in abnormal amounts?
2. What is DDx?
3. What is health risk?
4. What are tx options?
No LDL calc b/c chylos so high
1. What particle, if any, is in abnormal amounts?
Markedly elevated TG, relatively normal cholesterol Excess Chylomicrons, low HDL
2. What is the differential diagnosis
If 1°: LPL or C-II deficiency If 2°: ? Renal failure
3. What is the health risk ?
Pancreatitis
4. What are the treatment options?
Dietary: low fat diet, alcohol avoidance
55
Case 02
A 35 year old woman presents to your office. She has been referred because she has very high serum lipids. Her grandmother died of a heart attack at 95 years of age. She is in otherwise good health. She eats three meals a day and is following a very lowfat diet because “it is healthier”. She is 10 lbs over ideal body weight. She takes a multivitamin each day and a birth control pill.
```
Fasting lipids:
Chol 240
TG 800
HDL 30
LDL (not calc)
```
** the lab calls – the tube was chilled in transit . There was no layering but the serum was cloudy
1. What particle, if any, is in abnormal amounts?
2. What is DDx?
3. What is health risk?
4. What are tx options?
1. What particle, if any, is in excess?
Markedly elevated TG, elevated cholesterol, low HDL Excess VLDL , low HDL
2. What is the differential diagnosis?
If 1°: FCH, familial hyperTG, If 2°: high carb diet (from her low fat diet!), estrogens
3. What is the health risk?
Pancreatitis, possibly increased atherosclerosis
4. What are the treatment options?
Stop estrogens, balance diet, consider niacin or fibrates
56
Case 03
A 28 year old woman presents because she is ‘worried about my heart”. Her brother had a heart attack at 36 and her sister had a heart attack at 40. There is a family history of heart attacks before the age of 50 going back at least 2 generations, and nobody on her fathers side seems to live past 60. Her blood pressure is 110/60 and she does not smoke. She is eating a lowfat diet and exercises regularly. She is using an oral contraceptive. On exam, she has thickened achilles tendons
```
Fasting lipids:
Chol 360
TG 85
HDL 40
LDL 303
```
** the lab calls – the tube was chilled in transit . There was no layering and the serum was clear
1. What particle, if any, is in abnormal amounts?
2. What is DDx?
3. What is health risk?
4. What are tx options?
1. What particle, if any, is in excess?
Normal TG, markedly elevated cholesterol, normal HDL Excess LDL
2. What is the differential diagnosis
If primary: FCH, familial hypercholesterolemia
If secondary: high cholesterol diet, hypothyroidism nephrosis, biliary disease
3. What is the health risk?
Early atherosclerotic disease: MI, CVA, PVD
4. What are the treatment options?
Medications: diet + statins +/- ezetimbe
57
Health hazard of ↑ chylos?
| —Tx?
pancreatitis
Tx:
—diet restriction of sat fat & EtOH
—fish oil
57
Case 03
A 28 year old woman presents because she is ‘worried about my heart”. Her brother had a heart attack at 36 and her sister had a heart attack at 40. There is a family history of heart attacks before the age of 50 going back at least 2 generations, and nobody on her fathers side seems to live past 60. Her blood pressure is 110/60 and she does not smoke. She is eating a lowfat diet and exercises regularly. She is using an oral contraceptive. On exam, she has thickened achilles tendons
```
Fasting lipids:
Chol 360
TG 85
HDL 40
LDL 303
```
** the lab calls – the tube was chilled in transit . There was no layering and the serum was clear
1. What particle, if any, is in abnormal amounts?
2. What is DDx?
3. What is health risk?
4. What are tx options?
1. What particle, if any, is in excess?
Normal TG, markedly elevated cholesterol, normal HDL Excess LDL
2. What is the differential diagnosis
If primary: FCH, familial hypercholesterolemia
If secondary: high cholesterol diet, hypothyroidism nephrosis, biliary disease
3. What is the health risk?
Early atherosclerotic disease: MI, CVA, PVD
4. What are the treatment options?
Medications: diet + statins +/- ezetimbe
57
Health hazard of ↑ VLDL?
| —Tx?
```
pancreatitis and fatty liver
—restrict sat fat, carbs, EtOH
—PPARα agonists (fibrates)
—Niacin
—These drugs slow release of VLDL from liver
```
57
Health hazard of ↑ ILDL?
| —Tx?
```
atherosclerosis and fatty liver
TREAT LIKE ↑ VLDL:
—restrict sat fat, carbs, EtOH
—PPARα agonists (fibrates)
—Niacin
```
57
Health hazard of ↑ LDL?
athero
Tx:
—Diet: ↓chol & sat fat (↓7-15%)
—Bile acid sequestrants: cholestyramine, Welchol
—HMG CoA reductase inhib: statins (↓30-65%)
—Chol transport inhib: eztemibe (↓20%)
—Red Rice Yeast (↓10-25%)
57
Health hazard of ↓ HDL?
athero
57
Health hazard of ↑ Lipo(a)?
athero
57
Trigs and athero?
some epidemological associations but Weak to no correlation w/ multi-variate analysis
57
Atherosclorotic lipids?
```
LDL (esp oxidized)
ILDL
Small Dense VLDL
Lipoprotein B particles
NOT: chylos, usual VLDL or ?TGs
```
57
Case 01
40 year old man presents with abdominal pain, sometimes severe and disabling, over the last 6 months. It is occasionally associated with vomitting. There is a family history of pancreatitis. He is on no medications
He eats three meals a day and usually purchases lunch out- typically a burger and fries or a pizza. He drinks 2-4 beers in the evening.
```
Fasting lipids:
Chol 190
TG 3500
HDL 20
LDL (not calc)
```
** the lab calls – the tube was chilled in transit and showed up with a thick white layer occupying the top; the serum was clear
1. What particle, if any, is in abnormal amounts?
2. What is DDx?
3. What is health risk?
4. What are tx options?
No LDL calc b/c chylos so high
1. What particle, if any, is in abnormal amounts?
Markedly elevated TG, relatively normal cholesterol Excess Chylomicrons, low HDL
2. What is the differential diagnosis
If 1°: LPL or C-II deficiency If 2°: ? Renal failure
3. What is the health risk ?
Pancreatitis
4. What are the treatment options?
Dietary: low fat diet, alcohol avoidance
57
Case 02
A 35 year old woman presents to your office. She has been referred because she has very high serum lipids. Her grandmother died of a heart attack at 95 years of age. She is in otherwise good health. She eats three meals a day and is following a very lowfat diet because “it is healthier”. She is 10 lbs over ideal body weight. She takes a multivitamin each day and a birth control pill.
```
Fasting lipids:
Chol 240
TG 800
HDL 30
LDL (not calc)
```
** the lab calls – the tube was chilled in transit . There was no layering but the serum was cloudy
1. What particle, if any, is in abnormal amounts?
2. What is DDx?
3. What is health risk?
4. What are tx options?
1. What particle, if any, is in excess?
Markedly elevated TG, elevated cholesterol, low HDL Excess VLDL , low HDL
2. What is the differential diagnosis?
If 1°: FCH, familial hyperTG, If 2°: high carb diet (from her low fat diet!), estrogens
3. What is the health risk?
Pancreatitis, possibly increased atherosclerosis
4. What are the treatment options?
Stop estrogens, balance diet, consider niacin or fibrates
