Lipids & Lipid Disorders Flashcards
What are the causes of Secondary Hyperlipidemia? (The 4 Ds)
- Drugs:
- Anti-hypertensives: beta blockers, high dose thiazide diuretics
- Steroids: corticosteroids, anabolic steroids, estrogen & progestins
- Others: protease inhibitors for HIV, anti-psychotics, retinoids, some immunosuppressants, bile acid-binding resins - Dietary (lifestyle): obesity, alcohol, smoking, anorexia
- Dysmetabolism: Hypothyroidism, Diabetes, Pregnancy
- Diseases: Chronic Renal Failure, Nephrotic Syndrome, Liver disease (PBC, Hepatitis, CLD), some autoimmune diseases (SLE)
What drugs can cause hyperlipidemia?
Anti-hypertensives: beta blockers, high dose thiazide diuretics
Steroids: corticosteroids, anabolic steroids, estrogen and progestins
Others: protease inhibitors for HIV, anti-psychotics, retinoids, some immune suppressants, bile acid-binding resins
What basic lab tests would you do when presented with a patient with hyperlipidemia?
Fasting glucose HbA1C TSH Urinalysis and Creatinine ALP, ALT, GGT
What is a major acute complication of ++++TGs?
Pancreatitis
What is the consequence of ++++cholesterol?
Atherosclerosis
What does the microsomal triglyceride transfer protein (MP) do? If there is a deficiency what results?
MTP is an enzyme that facilitates the packaging of lipids with apoB48 to from nascent CMs. If there is a deficiency the body is unable to transfer TGs to CMs (essentially you can’t get fat into the body and you die). This is called ABETALIPOPROTEINEMIA.
What do LPL and apoCII do? If there is a deficiency what is the result?
LPL frees FAs for peripheral tissue (energy and storage) and requires apoCII to do so. The product is CM remnants. If there is a deficiency of either LPL or apoCII the result is +++TGs because CMs cannot be metabolized and build up in the circulation.
What does apoE do? If there is a mutation what is the result?
apoE clears CM remnants. If there is a mutation in apoE the result is an increase in TGs and total cholesterol due to a build up of remnant particles. This condition is called DYSBETALIPOPROTEINEMIA.
What happens if there is a mutation in the LDL receptor?
The LDL receptor allows for uptake of LDL. If there is a mutation in the receptor then there result is an increase in cholesterol (from LDL). This condition is FAMILIAL HYPERCHOLESTEROLEMIA.
What are the 3 main functions of HDL?
HDL Functions:
- reverse cholesterol transport (remove cholesterol from the body)
- transfers apoC to nascent CMs and VLDL (apoC is required for TGs to be broken down into FAs)
- delivers cholesterol to adrenals and gonads for steroidogenesis (LDL does this too)
Why/How does hypothyroidism raise total cholesterol?
Hypothyroidism raises total cholesterol by:
- Decreasing LDL receptor expression and therefore decreasing LDL clearance
- Decreasing hepatic lipase activity therefore decreasing IDL metabolism
- Decreasing bile acid synthesis and therefore decreasing the elimination of cholesterol
It also increases TGs due to decreased LPL activity.
Chylomiconemia Syndrome
Severe hypertrigylceridemia that results in shortness of breath, confusion, memory loss, abdominal pain, and pancreatitis.
LPL or apoCII deficiency results in what primary lipid abnormality?
Severe Hypertriglyceridemia. LPL and apoCII are involved in the metabolism of chylomicrons so if there is a deficiency you get a build up of chylomicrons.
What is dysbetalipoproteinemia?
This disease has a combined hyperlipidemia and the classical feature is palmar crease xanthomas.
When considering a patient with eruptive xanthomas, which lipoprotein is most likely to be elevated?
a. chylomicrons
b. beta VLDL (IDL)
c. LDL
d. HDL
a. chylomicrons - Chylomicrons are very TG rich. You can also get eruptive xanthomas with a high VLDL but IDL is a remnant of VLDL and will not cause eruptive xanthomas.
Eruptive xanthomas - small yellowish papule surrounded by a reddish macular area, TG rich skin macrophages, found on the extensor surfaces of the limbs, on the back and buttocks
A patient with lipemic serum, is likely to present with which physical finding?
a. eruptive xanthomas
b. palmar xanthomas
c. tendon xanthomas
d. xanthelasma
e. lipemic retinalis
a. and e. = eruptive xanthomas and lipemia retinalis
Considering a patient with lipemic serum, all of the aberrations might cause that finding EXCEPT:
a. LPL deficiency
b. poorly controlled DM
c. ApoCII mutation
d. ApoE mutation
e. PCSK9 mutation
e. PCSK9 is involved in the elimination of LDL and not related to hypertriglyceridemia in this case.
What are some lifestyle choices/conditions that inhibit LPL function?
LPL inhibitors:
- Insulin deficiency
- EtOH use
- Excess glucocorticoids
- Obesity
- Sedentary lifestyle
- Pregnancy
- ApoCII deficiency
What is the pharmacological treatment for a patient with lipemic serum/milky plasma?
a. statin
b. fibrate
c. ezitimibe
d. bile acid sequestrate
e. niacin
b. fibrate
When considering a patient with tendon xanthomas; which lipoprotein is most likely to be elevated?
a. chylomicrons
b. beta VLDL (IDL)
c. LDL
d. HDL
c. LDL
FH results in +++LDL and deposits are most obvious on the achilles tendon and knuckles.
In your work up of a patient with tendon xanthomas, what is the best pharmacological treatment?
a. statin
b. fibrate
c. exitimibe
d. bile acid sequestrate
e. niacin
a. statin
A 37 year old man presents for his yearly physical exam and is found to have an HDL of 0.6 (normal is greater than 1). He is concerned and asks you what factors have caused this low HDL cholesterol. What would you tell him is the single most important determinant of HDL?
a. lack of exercise
b. excess body weight
c. genetics
d. high-fat, high cholesterol diet
e. alcohol ingestion
c. genetics
All of these things contribute to HDL but genetics is the most important factor.
Which of the following is the LEAST effective medicine for treating LDL levels?
a. cholestyramine
b. niacin
c. gemfibrozil
d. pravastatin
Gemfibrozil (fibrate)
