MLAB 2401: Clinical ChemistryKeri 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 300-1000 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

Reference Borderline High Very High

Ranges 60-150 mg/dL

150-200 mg/dL

200-500 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.

• http://www.nlm.nih.gov/medlineplus/ency/imagepages/1554.htm

• Sunheimer, R., & Graves, L. (2010). Clinical Laboratory Chemistry. Upper Saddle River: Pearson .