Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

CV > Lipid metabolism, disorders, and treatment > Flashcards

Lipid metabolism, disorders, and treatment Flashcards

1
Q

Apolipoprotein functions

A
  • stabilize lipoprotein particles
  • impart solubility to lipoproteins
  • catalyze changes in particle composition
  • facilitate entry/exit into/from cells
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Chylomicrons

A

express apo B-48 (marker of coming from intestine) and apo C-II, very large, very low density

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

VLDL

A

express apo B-100 (marker of coming from liver rather than intestine), apo E, and apo C-II. Contain mostly trigylceride, large and low density

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

IDL

A

formed by lipolysis of VLDL, also called VLDL remnant

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

HDL

A

“Good” lipoprotein and is not atherogenic- contain less cholesterol/ more protein and phospholipid. Express apo A-I and apo A-II

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

LDL

A

Most atherogenic lipoprotein, main carrier of cholesterol in body. Expresses apo B-100 (marker of coming from intestine)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Total cholesterol (TC)

A
  • concentration of cholesterol in all plasma lipoproteins

- accurately measured in lab

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

HDL cholesterol (HDL-C)

A
  • concentration of cholesterol in plasma HDL

- surrogate for number of HDL particles

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Triglycerides (TG)

A
  • concentration of triglycerides in all plasma lipoproteins

- surrogate for number of VLDL particles

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

LDL cholesterol (LDL-C)

A
  • concentration of cholesterol in plasma LDL
  • surrogate for number of LDL particles
  • not routinely measured in lab- calculated by the Friedewald equation: LDL-C = TC - HDL-C - TG/5
  • less accurate as TG levels increase since assumption that TG/5 = VLDL-C breaks down
  • includes IDL and Lp(a)
  • misleadingly low when small LDL particles are present
  • main atherogenic lipoprotein
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

The _______ of LDL particles interacting with the arterial wall drives the disease while the ______ of LDL particles modulates the risk

A

number; size

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

apo B-48

A

on chylomicrons, marker for coming from intestine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

apo E

A

recognized by remnant receptor
Defects in APOE result in familial dysbetalipoproteinemia aka type III hyperlipoproteinemia (HLP III), in which increased plasma cholesterol and triglycerides are the consequence of impaired clearance of chylomicron, VLDL and LDL remnants

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

apo C-II

A

activates lipoprotein lipase

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

apo B-100

A

Marker for coming from liver

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Endogenous pathway: basic steps

A
  • Starts in liver, production of VLDL with apo B-100, apo C-II which activates lipoprotein lipase, apo E (ligand for remnant receptor)
  • Lipolysis to IDL which is shunted to liver and taken up by remnant receptor (shunt pathway) OR IDL is converted by hepatic triglyceride lipase to form LDL
  • LDL can be deposited in extra-hepatic sites including arteries or can go back to liver, recognized by LDL receptor
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Cholesterol balance- fate of hepatic cholesterol

A
  • reintroduced into the systemic circulation as VLDL particles. VLDL is metabolized to LDL, with most being returned to the liver and some being taken up by extrahepatic tissues.
  • Most hepatic cholesterol is excreted into bile.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Cholesterol balance-
_____ of cholesterol is synthesized daily, while ______ is derived from the diet. In order to maintain cholesterol balance, the combined amount ______ must be excreted as ________

A

800 mg; 300 mg; 1100 mg; fecal sterols

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Exogenous pathway: basic steps

A
  • Begins in gut, production of chylomicrons after eating.
  • Cholesterol from the diet enters the small intestine and is absorbed by a sterol transporter
  • Cholesterol is packaged into chylomicrons in the enterocytes- chylomicrons are large spheres filled with trigylceride with surface apo B-48, apo E, and apo C-II
  • Chylomicrons are transferred to the liver via the lymphatics and venous circulation
  • Lipolysis during transport converts chylomicrons to chylomicron remnants that are cleared by liver due to recognition by remnant receptor/ apo E
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

IBAT

A

Intestinal bile acid transporter

- reabsorbs bile acids in the ileum

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

ACAT

A

acyl-CoA cholesterol acyltransferase

- esterifies cholesterol absorbed into the enterocyte

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

LPL

A

lipoprotein lipase

  • hydrolyzes lipoprotein core triglycerides into glycerol and free fatty acids
  • located on capillary endothelium
  • is activated by apo C-II
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

HMG Co-A Reductase

A

enzyme that performs the rate limiting step in cholesterol synthesis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

most common lipid abnormality in patients with premature CHD

A

Reduced HDL-C (could be alone or in combination with high LDL-C/ high TG)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

CERP

A

Cholesterol efflux regulatory protein, aka ABCA1

  • present on extra-hepatic cell surfaces
  • mediates export of cholesterol from extra-hepatic tissue into bloodstream for reverse transport back to liver
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

MTP

A

Microsomal transfer protein

  • present in enterocytes
  • packages cholesterol esters with TG, phospholipids, and the apolipoprotein (apo) B-48 into chylomicrons, which are released into the lymphatic circulation.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

LCAT

A

Lecithin cholesterol acyltransferase

- esterifies cholesterol in nascent HDL, resulting in mature HDL particle.

28
Q

CEPT

A

Cholesterol ester transfer protein, synthesized in liver and catalyzes transfer of non-polar core components of lipoproteins

  • in chylomicronemia or hypertriglyeridemia, CEPT causes transfer of cholesterol from LDL/ HDL to VLDL and transfer of triglyceride from VLDL to HDL/ LDL
  • leads to enrichment of LDL and HDL with triglyceride/ enrichment of VLDL with cholesterol
29
Q

small, dense particles

A
  • HDL and LDL that are enriched with triglycerides due to action of CEPT transferring non-polar components between LDL/ HDL and VLDL
  • are more easily oxidized and poorly metabolized
30
Q

purposes of HDL (evolutionary context)

A
  • anti-inflammatory
  • role in host defense/ immunity
  • protection from endotoxin and trypanosome infection
31
Q

Type I Dyslipidemia

A
  • lipoprotein: chylomicrons
  • dyslipidemia: LPL deficiency, apo C-II deficiency
  • secondary causes: dysglobulinemia, diabetes mellitus
32
Q

Type IIa Dyslipidemia

A
  • lipoprotein: LDL
  • dyslipidemia: pure LDL elevation as in familial hypercholesterolemia or familial combined hyperlipidemia
  • secondary causes: renal or liver disease, hypothyroidism, Cushing’s syndrome
33
Q

Type IIb Dyslipidemia

A
  • lipoprotein: LDL, VLDL
  • dyslipidemia: elevation of both LDL and VLDL as in familial combined hyperlipidemia
  • secondary causes: diabetes mellitus, nephrotic syndrome
34
Q

Type III Dyslipidemia

A
  • lipoprotein: IDL
  • dyslipidemia: excess IDL, as in familial dysbetalipoproteinemia
  • secondary causes: diabetes mellitus
35
Q

Type IV Dyslipidemia

A
  • lipoprotein: VLDL
  • dyslipidemia: excess VLDL as in familial hypertriglyceridemia or some patients with familial combined hyperlipidemia
  • secondary causes: renal diseases
36
Q

Type V Dyslipidemia

A
  • lipoprotein: chylomicrons, VLDL
  • dyslipidemia: elevated chylomicrons and elevated VLDL, as in familial hypertriglyceridemia, partial LDL deficiency and partial apo C-II deficiency
37
Q

Arcus corneus

A
  • gray hazy stripe on the inside of the iris that can be seen in dyslipidemia esp. hypertriglyceridemia
38
Q

Xanthelasmas

A
  • pale yellow fatty accumulatiosn in the medial aspects of the upper and lower eyelids
  • non-specific markers of dyslipidemia
39
Q

Eruptive xanthomas

A
  • small, yellowish-orange to reddish-brow pustules distributed in areas of the body that come in contact with other surfaces/ objects
  • seen in patients with chylomicronemia
40
Q

Tendon xanthomata

A
  • associated with familial hypercholesterolemia

- papules and nodules found in the tendons of the hands, feet, and achilles

41
Q

Tuberous xanthomata

A
  • associated with familial hypercholesterolemia

- characterized by xanthomas located over the joints

42
Q

Lipidemia retninalis

A
  • seen in LDL deficiency/ chylomicronemia syndrome

- white appearance of the retina, and can occur by lipid deposition

43
Q

Familial hypercholesterolemia

A

Can be caused by genetically deficient or defective LDL receptors- receptors not produced, receptors do not migrate to hepatocyte surface, do not bind LDL properly, are not internalized normally.
Autosomal dominant/ co-dominant, heterozygotes 1/500
Cholesterol values 325-450 in heterozygote adults
Tendon xanthomata, xanthelasmas, arcus corneus common

44
Q

Familial defective apo B-100

A

Leads to poor binding of LDL with receptors

Functionally and phenotypically similar to familial hypercholesterolemia.

45
Q

Polygenic hypercholesterolemia

A

Most common form of hypercholesterolemia in US
heterogeneous group of disorders
elevated cholesterol due to poor clearance of normal LDL particles
associated with apo E4 isoform

46
Q

Familial combined hyperlipidemia

A
  • group of disorders with varying patterns of LDL-C and VLDL-C elevations
  • all individuals have elevated levels of apo B-100.
  • roughly 1/3 of people also have LDL abnormality
  • LDL and VLDL have long half lives, HDL-C tends to be low
  • tend to have xantehlasmas and arcus corneus
  • commonly associated wiht hypertension, type II DM, familial obestity, may be related in part to insulin resistance
47
Q

Familial hypoalphalipoproteinemia

A
  • most common GENETIC cause of low HDL-C

- patients have cataracts and arcus corneus, high risk of CHD

48
Q

Secondary causes of hypercholesterolemia

A 
hypothyroidism
diabetes mellitus
renal disease
liver disease
obesity
use of thiazide diuretics
use of cyclosporine
pregnancy/ lactation
dysglobulinemia
Cushing's syndrome
49
Q

Secondary causes of hypertriglyceridemia

A 
alcohol abuse
diabetes mellitus
obesity
estrogen use
chronic renal disease
hypothyroidism
glucocorticoid use
use of high dose B blockers
use of high dose diuretics
use of cyclosporine
pregnancy/ lactation
Cushing's disease
dysglobulinemia
50
Q

Secondary causes of low HDL-C

A 
obesity
diabetes mellitus
chronic renal disease
use of high dose B blockers
use of anabolic steroids
use of progestins
use of retinoids
51
Q

Increased _______ adiposity is associated with insulin resistance and increased free fatty acid flux leading to hyperlipidemia, ___________, and inflammation

A

visceral; atherosclerosis

52
Q

_________, an insulin sensitive hormone, is tonically inhibited by insulin

A

Hormone sensitive lipase

53
Q

Increased concentrations of _______ containing lipoproteins, like VLDL, IDL, and LDL are atherogenic

A

apo B-100

54
Q

Adverse endocrine effects of adipose

A
  • resistin: insulin resistance, increased glucose
  • leptin: increased appetite
  • increased fatty acids: increased atherosclerosis
  • inflammatory mediators: increased TNF-a, IL-6, CRP
  • increased angiotensin –> hypertension
  • increased sympathetic activity–> hypertension
55
Q

List three medication types that primarily reduce LDL-C

A

Statins, resins, azetidiones

56
Q

List three medication types that primarily raise HDL-C and lower TG

A

Niacin, fibrates, omega-3 fatty acids

57
Q

Statins

A
  • good evidence for reduced CVD events, safety
  • major effect is 20-60% reduction in LDL-C along with modest reduction in TG and modest increase in HDL-C
  • mechanism: inhibition of HMG CoA reductase, leading to decreased cholesterol synthesis and up-regulation of LDL receptors
  • pleiotropic effects: inhibition of isoprenylation of small GTP binding proteins Rho, Ras, Rac
  • side effects: myalgia, myopathy, elevated liver function tests
58
Q

Bile acid binding resins

A
  • modest evidence for CVD reduction, long-term safety
  • reduce LDL- C by 15-30%
  • block absorption of bile salts in terminal ileum, with subsequent increase in LDL-R expression but compensatory increase in HMG CoA reductase
  • side effects: abdominal discomfort, decreased absorption of other medications and fat soluble vitamins
59
Q

Azetidinones

A

Ezetimibe, no good evidence for reduced CVD risk but well tolerated by most

  • reduced LDL-C by 14-20% with minimal increase in HDL-C and minimal decrease in TG
  • blocks absorption of cholesterol in intestine by blocking NPC1L1 protein of sterol receptor, leading to upregulation of LDL-R and compensatory increase in HMG CoA reductase
60
Q

Niacin

A
  • vitamin B3, modest evidence for use in treatment of dyslipidemia to reduce CVD events.
  • used mainly in patients with combined dyslipidemia or low HDL-C
  • Increases HDL-C by 15-30%, reduces TG by 20-50%, reduces LDL at high doses
  • mechanisms: reduces lipolysis from adipocytes leading to less fre fatty acid flux to the liver, reduction in VLDL synthesis, inhibits DGAT2, reduces apo A-1 catabolism while permitting removal of cholesterol from HDL
  • side effects: flushing, itching mediated by prostaglandin, abdominal pain, peptic ulcer disease, insulin resistance, hyperglycemia, hepatotoxicity
61
Q

Fibrates

A
  • Modest evidence for CVD reduction - best in patients with low HDL-C or high TG
  • Major effects (used if very high TGs): reduces TG by 20-50%, increases HDL-C by 10-20%, reduces LDL-C by 5-20% (or may increase LDL-C)
  • Complex mechanisms: activates PPAR-a, synthesis of apo A-I and A-II, activates LPL and reduces apo CIII (LPL inhibitor), Activates apo C-II, stimulates hepatic fatty acid uptake and catabolism by ß-oxidation, reduces TG synthesis
  • Major side-effects: abdominal pain, gall stones, increased creatinine, myalgia/myopathy, especially with statins
  • contraindications: gall stones, pregnancy, liver disease, kidney disease
62
Q

omega 3 fatty acids

A
  • reduces TG by 20-50%; modest effects on HDL-C, related to TG reduction; LDL-C may increase or not change
  • mechanisms: inhibits DGAT; reduces lipolysis stimulates hepatic fatty acid catabolism by ß-oxidation; reduces TG synthesis
  • side effects: eructation, flatulence, abdominal pain, bruising/bleeding
63
Q

Describe primary treatment goals and medication choices in a 61 year old patient with high 10 year CVD risk and TG= 190

A
  • primary goal: lower LDL-C
  • use high intensity statin to achieve 50% reduction in LDL-C and then add niacin, BAS, or ezetimibe as needed
  • encourage lifestyle changes
64
Q

Describe treatment goals and medication choices in a 59 year old patient with high 10 year CVD risk and TG=520

A
  • primary goal: lower TG
  • first and second medication will be niacin, fish oils, or fibrate.
  • consider adding statin as third drug
  • encourage lifestyle changes
65
Q

Describe treatment goals and medication choices in a 68 year old woman with moderate 10 year CVD risk and TG= 250

A
  • primary goal: lower LDL-C
  • first medication: statin or niacin
  • second medication: statin or niacin
  • third medication: add ezetimibe

CV (7 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions