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 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
Ranges
Reference
Borderline High
Very High
60-150
mg/dL
150-200
mg/dL
> 500
mg/dL
200-500
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 .