Hyperlipidemia Flashcards
Hyperlipidemia
Abnormal elevated levels of lipids/lipoproteins in blood
Chronic disease - ongoing medication
Lead to atherosclerosis
Exogenous lipid metabolism pathway
1) dietary lipids into chylomicrons in the intestine
2) chylomicrons enter circulation to peripheral tissues. Lipoprotein lipase release free FA - metabolised by muscle/adipose tissue = chylomicron remnants
3) chylomicron remanants are taken up by the liver in the formation of HDL
Endogenous lipid metabolism pathway
1) VLDL formed in the liver from triglycerides and cholestrol esters
2) triglycerides carried in VLDL are metabolised in muscle and adipose tissue by lipoprotein lipase releasing free FA = IDL formed
3) IDL is futher metabolised to LDL. Taken up by LDL receptors in tissues - liver = bile acids + secreted to intestines
Atherosclerosis primary causes
gene mutations in defective clearanve of triglycerides and LDL or excessive clearance of HDL
Atherosclerosis secondary causes
Sedentary lifestyle - high calorie diet Diabetes Kidney Disease Hypothyrodism Obesity Obstructive Liver Disease Alcohol/Smoking
Hypercholesterolemia
Increase in cholestrol only
Hypertriglyceridemia
Increase in triglycerides only
Combined hyperlipidemia
Increase in both cholestrol and triglycerides
Type 2a - familal hypercholestrolemia
Defect = reduction in LDL receptor
Serum abnormality = increased LDL - clear
Clinical features = Xanthelasma + Arcus senilis + Tendon Xanthomas
Treatment = statins/niacin/cholestyramine or cholestipol
Type 2b - familal combined hypercholestrolemia
Defect = reduction in LDL receptors & increased Apo B
Serum abnormality = Increased LDL and VLDL - clear
Treatment = statins/niacin/fibrate
Xanthomas
yellow deposists of cholestrol rich material - skin lesions anywhere in body.
accumulation of lipids as large foam cells
High levels of LDL - Hypercholesterolemia symptoms
arcus cornea
xanthomas at achillies/elbow/knee tendons
xathelasma
High levels of TG - hypertriglycerliemia symptoms
xathomas
acute pancreatitis
Xanthelasma
Yellow plaques of cholestrol deposits that occur on/ around eyelids
Can also occur in primary biliary cirrhosis and normal lipid levels
Type 2a familial hypercholesterolaemia
Serum lipid profile
total cholestrol
TG
HDL
LDL
Diagnosis - primary
Serum total cholestrol > 240mg/dL
Onset of premature CVD (<60)
Family history of CVD
Diagnosis - secondary
Fasting glucose Liver enzymes Creatinine TSH Urinary protein
Familial Hypercholesterolemia
Genetic disorder
High levels of LDL from birth = early CVD
Mutations in the LDLR - normally removes LDL from circulation or ApoB - part of LDL that binds with the receptor
Heterozygous for LDLR gene = premature CVD
Homozygous = severe CVD in childhood
Class 1
no LDLR synthesis
Class II
no LDLR transport = not properly transported from ER to golgi for expression on cell surface
Class III
no LDL or LDLR binding = LDLR does not bind LDL properly on cell surface - defect in apolipoprotein
Class IV
no LDLR- LDL internalisation - LDLR bound to LDL doesn’t cluster for receptor mediated endocytosis
Class V
no LDLR recycling back to cell surface
Mutations in PCSK9 gene
gain in fuction of gene
enhanced activity causes LDL receptors to be broken down more quickly - reduction in number of receptors on liver cell surface. LDL not removed from blood = high blood cholestrol levels
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Hypertriglyceridemic Pancreatitis
fasting serum trigkyceride level of >150mg/dL
amylase and lipase falsely normally
causes = poorly controlled diabetes/alcohol/pancreatitis/pregnancy/ FH
Auto digestion pancreatic injury
chylomicrons = large enough to occlude pancreatic capillaries -> ischemia + release of pancreatic lipase
Hyperlipidemia treatment
Lifestyle changes
High LDL = statins/bile acid sequestrant + PCSK9 inhibitors
High TG = niacin/fibrates + omega 3 FA
