MLAB 2401: Clinical Chemistry Keri Brophy-Martinez Lipids and Lipoprotein Disorders

Dyslipidemias Disease associated with abnormal lipid concentrations Subdivided into two major categories Hyperlipoproteinemias Hypolipoproteinemias Usually due to Congestive Heart Disease (CHD) or arteriosclerosis Acquired – Environmental/lifestyle imbalance Congenital – Genetic abnormalities Secondary – Due to other diseases

Arteriosclerosis Effects both men and women; however, women present later in life Disease stems from the deposition of lipids in artery walls.

Plaque Formation Lipid deposition leads to fatty streaks in the subendothelial space. As time goes on, these streaks can develop into plaques Plaques are formed from the repeated cycle of cell injury and repair. LDL plays a central role in plaque formation The vessel continues to narrow due to this cycle, which increases the pressure within the vessel Once the plaque ruptures, the thrombus formed blocks blood flow and causes a myocardial infarction

Hyperlipoproteinemia Result of malfunctions in the synthesis, transport or catabolism of lipoproteins Elevated lipoprotein levels Divisions – Hypercholesterolemia – Hypertriglyceridemia – Combined hyperlipidemia: elevation of cholesterol and triglyceride

Hypercholesterolemia Linked to heart disease Familial hypercholesterolemia (FH) – Genetic abnormality that predisposes people to high cholesterol levels, specifically LDL cholesterol – Make cholesterol normally but lack or are deficient in active LDL receptors, so LDL builds up in the circulation – Without the LDL receptors, LDL can not be bound and cholesterol can not be transferred into the cell

Hypercholesterolemia Clinical signs and Symptoms – Heart attacks occur at an early age (teenage years) – Patient exhibit xanthomas, which are cholesterol deposits under the skin – Cholesterol can range from mg/dL

Hypertriglyceridemia Imbalance between synthesis and clearance of VLDL in circulation Deficiency of LDL or apo-C ( co-factor for LPL activity) – Chylomicrons can not be cleared and triglycerides remain high – Normal function is for LDL to hydrolyze triglycerides carried in the chylomicrons and VLDL to give cells energy

Hypertriglyceridemia Causes of: – Genetic Abnormalities Familial hypertriglyceridemia – Secondary causes Hormonal abnormalities in pancreas, adrenals, pituitary and of diabetes mellitis

Hypertriglyceridemia Influenced by many hormones – Insulin, glucagon, pituitary growth hormone, adrenocorticotropic hormone (ACTH), thyrotropin, epinephrine, norepinephrine – Hormones trigger lipase Can cause acute and recurrent pancreatitis

Hypertriglyceridemia According to the National Cholesterol Education Program( NCEP) Triglyceride ReferenceBorderlineHighVery High Ranges mg/dL mg/dL mg/dL > 500 mg/dL

Combined Hyperlipoproteinemia Presence of elevated levels of serum cholesterol and triglycerides Results from accumulation of cholesterol-rich VLDL and chylomicron remnants from defective catabolism Risk factor for CHD Primarily congenital

Hypolipoproteinemia Low levels of lipoproteins Two forms – Hypoalphalipoproteinemia Decrease in circulating HDL (< 40 mg/dL) Lack of hypertriglyceridemia Due to a genetic defect – Tangier Disease – Hypobetalipoproteinemia Low levels of LDL cholesterol

Abetalipoproteinemia Absence of lipoproteins containing Apo-b – Includes: LDL and VLDL Hallmarks – Difficulty in weight gain and growth – Fat absorption problems – RBC membrane defects – Usually effects infants

References Bishop, M., Fody, E., & Schoeff, l. (2010). Clinical Chemistry: Techniques, principles, Correlations. Baltimore: Wolters Kluwer Lippincott Williams & Wilkins. Sunheimer, R., & Graves, L. (2010). Clinical Laboratory Chemistry. Upper Saddle River: Pearson.