Dyslipidemia Flashcards
What are the causes of dyslipidemia?
PRIMARY
- single of multiple gene mutation
- over production or defective clearance of triglycerides & LDL, underproduction or excessive clearance of HDL
SECONDARY
- sedentary life style
- Diet: excessive intake of saturated fat, alcohol consumption
- Drugs: thiazides, retinoids, antiretroviral agents, cyclosporin, tacrolimus, estrogen & progestins, & glucocorticoids
- Disease: diabetes, hypothyroidism, obesity, chronic liver disease, primary biliary cirrhosis, chronic renal failure
Where are triglycerides stored?
in adipocytes & muscle cells
store unused calories
What is the physiology of lipid digestion?
1- dietary triglycerides are digested in the stomach & duodenum by gastric lipase, stomach peristalsis, & pancreatic lipase INTO monoglycerides & FFAs
2- monoglycerides, FFA, & free cholesterol are solubilized in the intestine by bile acid -> absorbed into intestinal villi
3- in enterocytes they are reassembled into TGs & packaged with cholesterol into chylomicrons
4- chylomicrons transport dietary TGs & cholesterol into the circulation
5- Apolipoprotein C-II (apo C-II) on chylomicron activates endothelial lipoprotein lipase (LPL)
6- LPL converts the TGs in chylomicron to fatty acids & glycerol
7- fatty acids & glycerol are taken up by adipocytes & muscle cells for energy use or storage
8- cholesterol rich chylomicron remnants circulate back to the liver to be cleared by apolipoprotein E (apo E)
What is the largest lipoprotein?
Chylomicrons
What leads to elevated plasma cholesterol & TG levels?
stimulation of hepatic lipoprotein synthesis
What is the function of VLDL?
- contains apolipoprotein B-100
- synthesized in the liver & transports TGs & cholesterol to peripheral tissue
- its synthesis increases with increased intrahepatic FFA (to export excess TG out of the liver)
- apoprotein C-II -> activates LPL
What is the function of IDL?
- product of LPL processing of VLDV & chylomicrons
- either cleared by the liver or metabolized by hepatic lipase into LDL (retains apo B)
What is the function of LDL?
- the MOST CHOLESTEROL RICH of all lipoproteins
- product of VLDL & IDL metabolism
- 40 - 60% of all LDL are cleared by the liver by apo B & hepatic LDL receptors
- hepatic LDL receptors are down-regulated by increased dietary saturated fat intake & chylomicrons
- hepatic LDL receptors are up-regulated by decreased dietary fat & cholesterol
What is the function of HDL?
- synthesized in enterocytes & liver
- obtains cholesterol from peripheral tissues & other lipoproteins & transport it to the liver for clearance
- ANTI-ATHEROGENIC EFFECT
What is lipoprotein a?
- an LDL that contains apoprotein a
- inhibits fibrinolysis -> promotes thrombus formation
- directly promotes atherosclerosis
What is the function of PCSK9?
- regulates levels of LDL receptors
- binds to LDL receptors -> stops LDL from being removed from the blood -> increased LDL levels
- gain of function mutations -> reduce LDL receptors in the liver -> high levels of plasma LDL -> increased susceptibility to coronary heart disease
- loss of function mutations -> higher levels of LDL receptors -> lower plasma LDL -> protection from coronary heart disease
What is the genetic classification of dyslipidemias?
TYPE I - chylomicronemia syndrome
- LPL or ApoCII genetic defect
- Triglyceride levels -> 1000 - 10 000
- eruptive xanthomas & pancreatitis
TYPE IIa - increased LDL
- polygenic hypercholesterolemia: LDL-C > 130
- > increased risk of ASCVD
- heterogenous familial hypercholesterolemia: LDL-C > 190
- homogenous familial hypercholesterolemia: LDL-C > 350
- > increased risk of premature ASCVD
- > tendon xanthoma
TYPE IV - increased triglycerides & VLDL
- familial hypertriglyceridemia
- TG > 150
What levels of triglyceride could lead to acute pancreatitis?
> 500mg/dL (>5.65 mmol/L)
What are the signs & symptoms of high LDL levels?
- corneal arcus
- xanthelasma
- tendon xanthomas -> at achilles, elbow, knee tendons, & over metacarpophalageal joints
- tuberous xanthomas -> painless, firm nodules located over extensor surfaces of joints
- eruptive xanthomas -> over the trunk, back, elbows, buttocks, knees, hands, & feet
- severe elevations of TGs can give a lactescent (milky) appearance to blood plasma
What should be done to diagnose dyslipidemia?
- serum lipid profile (total cholesterol, TG, HDL & calculated LDL) -> measured while fasting for 12 hours for maximum accuracy
- non-HDL cholesterol (TC - HDL cholesterol) can be measured without fasting -> predictive of CAD risk (N < 130)
- TC/HDL ratio -> predicts risk of ischemic heart disease (N < 5)
- Lp(a) is checked in patients with premature atherosclerotic cardiovascular disease but normal or near normal lipid levels
