LIPIDS AND DYSLIPOPROTEINEMIA

CLIN.PATHOLOGY (3rd Shifting) | (Aira Liza F. De Chavez, MD, FPSP) | (January 15, 2021)

LEGENDS • Constitute about 25% of LDL mass (lecithin: sphingomyelin ratio =

Important 2:1)
Book Powerpoint Sabi ni Clinical • Constitute about 30% of HDL mass (lecithin: sphingomyelin ratio =
for Exam
Knowledge Information Doc Importance 5:1)
(OT)
❒ ⌨ ♪ ★ ☤ NEFA (Non-Esterified Fatty Acid)
• Very important source of energy
OUTLINE • Constitute a very small fraction of total plasma lipids
I. Lipids V. Blood Sampling Storage • Transported in plasma complexed with albumin
A. Lipoprotein Structure VI. Estimation of Plasma Lipids III. PLASMA LIPOPROTEIN
B. Subheading A. Cholesterol • Four major lipoproteins:
II. Main Lipids In The Human B. Triglycerides 1. Chylomicrons
Plasma VII. NCEP 2. VLDL
III. Plasma Lipoprotein VIII. Major Risk Factors That 3. LDL
A. Lipoprotein Differentiation Modify LDL 4. HDL
B. Chylomicron IX. Testing and treatment • Basis for differentiation: Buoyant density & electrophoretic mobility
C. VLDL X. Drug therapy/hyperlipidemia
drugs A. LIPOPROTEIN DIFFERENTIATION
D. LDL
1. Ultracentrifugation
E. HDL XI. Hypertriglyceridemia
1. separates lipoprotein based on buoyant density
IV. Minor and Abnormal XII. Analysis of apoprotein levels
2. The density of a lipoprotein is determined by its protein &
Lipoprotein
triglyceride (lipid) content.
I. LIPIDS 3. The higher the lipid content, the less dense is the lipoprotein
particle & so upon centrifugation, the closer it migrates to the
• Organic substance insoluble in water but soluble in organic
top of the tube.
substance like chloroform & ether.
4. Chylomicrons (CM) & VLDL have higher triglyceride (TG) and
• Cholesterol & triglycerides are transported in plasma & ECF as part
less protein content.
of water-soluble complexes called LIPOPROTEINS.
5. HDL has high protein content & low TG content
A. LIPOPROTEIN STRUCTURE 6. LDL & IDL are denser than VLDL but less dense than HDL
• Contains cholesterol in 2 forms: 2. Electrophoresis
1. 30% free cholesterol - a polar non-esterified alcohol 1. uses agarose gel as support medium because of its speed,
2. 70% cholesterol ester – a hydrophobic form wherein sensitivity and ability to resolve the lipoprotein classes
cholesterol is linked to a fatty acid. 2. Lipoprotein are named according to their mobilities.
• It is a spherical structure arranged like a micelle. 3. CM – remain at the origin
a. Core – composed of the more hydrophobic lipids such as 4. HDL (a-lipoprotein) - migrates the fastest & moves with alpha
cholesterol esters and triglycerides. a1-globulin
5. LDL (B-lipoprotein)- migrates with the beta (B) globulins
b. Surface – is composed of the more hydrophilic lipids such as
6. VLDL (pre-B lipoprotein) migrates with the B2 globulins
free cholesterol & phospholipids arranged pointing outwards.
• Apolipoproteins are also located on the surface. Lipoproteins can also be classified based on the presence or
• Amphiphilic characteristic: absence of apo-B.
1. Hydrophobic residues interact with the hydrophobic core 1. Apo-B containing: CM, VLDL, IDL, LDL
2. Hydrophilic residues interact with the hydrophilic surface. 2. Non apo-B-containing: HDL
• Importance of apo-B:
II. MAIN LIPIDS IN THE HUMAN PLASMA 1. Only 1 apo-B molecule is present per lipoprotein and this is a
A. Cholesterol nonexchangeable apoprotein.
B. Cholesteryl esters 2. Apo-B containing lipoproteins may or may not contain additional
C. Triglycerides apoproteins such as apo-A, apo-C & apo-E. Apo-B serves as a
D. Phospholipids structural protein for these and is always associated with these
E. NEFA - non-esterified fatty acids particles.
• Apo-B are synthesized by hepatocytes and enterocytes.
Cholesterol
• An unsaturated steroid alcohol B. CHYLOMICRON
• Important component of cell membranes • Produced by the intestines
• Precursor for the synthesis of bile acids & steroid hormones • Contain 85-95% triglycerides from exogenous source (dietary)
• 60-70% transported in plasma by LDL • Poor in free cholesterol, phospholipids & proteins
• 20-35% transported in plasma by HDL • Contain 1-2 % proteins
• 5-12% transported in plasma by VLDL • Very high lipid (TG) content - less dense in water (floats without
centrifugation)
Triglycerides
• High chylomicron content in plasma results to “milky” appearance
• Long chain fatty acid esters of glycerol
upon standing (floating “cream” layer) → (standing plasma test)
• Constitute about 95% of adipose tissues
• Contains apolipoproteins: apo-B48 (intestinal origin), apo C-1, apo
• Main form of lipid storage in man
C-II, apo C-III, apo A-1, apo A-IV and apo-E
• Transported in plasma in the form of chylomicrons & VLDL
• When acted upon by lipoprotein lipase → reduced to small particles
• Present in small amounts in LDL & HDL
with less triglycerides and some surface elements → ”chylomicron
• Constitute 95% of adipose tissue by weight
remnants”
Phospholipids • Chylomicron remnants are removed from the circulation by the
• Esters of glycerol that contain 2 fatty acyl group & phosphatidic liver through the interaction of apo-E with receptors such as
acid proteoglycans, LDL receptor, and the LDL receptor-related protein
• Main plasma phospholipids are sphingomyelin, lecithin, cephalins (LRP).
C. VLDL (Very Low Density Lipoprotein)
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• Particles smaller than chylomicrons
• Rich in triglycerides (but lower than chylomicrons)
• Has lower lipid to protein ratio
• When excessive amounts are present in the plasma, it can cause
“turbidity”
• VLDL are produced by the liver
• Supply the tissues of the body with endogenous TG (from hepatic
origin) and cholesterol
• This contains apo B-100, apo C-I, apo C-II, apo C-III & apo E.
• Lipoprotein lipase (LPL) hydrolyzes VLDL and this produces VLDL
remnants (highly atherogenic particle) & IDL.
D. LDL (Low Density Lipoprotein)
• Constitute about 50% of total lipoprotein mass in human plasma
• Produced through the metabolism of VLDL in circulation
• Particles are smaller than VLDL & CM
• Does not scatter light or alter the clarity of plasma even at greatly
increased concentration
• Consists approx. 50% C, mostly esterified, 25% protein, mostly apo
B-100 with traces of apo C, 20% P & some TG
• The apo B is the largest component of protein in this particle and
this serves as the ligand for the hepatic LDL receptor.
E. HDL (High Density Lipoprotein)
• Its major apoprotein is apo A1
1. Apo A1 comprises 70% of HDL protein
• This is formed in the liver
• A small particle made up of:
a. 50% protein – Apo A-I, Apo A-II, Apo E
b. 20% esterified cholesterol
c. 30 % phospholipids
d. traces of triglycerides
• Produced by the liver & intestine
• Protective mechanism against atherosclerosis by:
1. Involved in reverse cholesterol transport wherein excess
cholesterol in the tissues are transported back to the liver,
where it is re-used or excreted in bile.
▪ Mechanism is by selective uptake of cholesterol esters from
HDL by the SR-B1 receptor in the liver.
▪ SR-B1 promotes cholesterol uptake without apolipoprotein
degradation.
▪ Cholesterol esters are removed from the internalized HDL
particles and cholesterol- depleted HDL are re-secreted.
▪ Mouse models that lack SR-B1 show increased plasma HDL,
slower HDL uptake by the liver and increased atherosclerosis
and reverse cholesterol transport is reduced.
▪ Mouse models with overproduction of SR-B1 show opposite
of the above findings.
▪ * SR-B1- scavenger receptor class B member 1
2. HDL also possess anti-inflammatory, antioxidant, antithrombotic
and nitric oxide-inducing mechanisms believed to add to its
protective effect.
▪ Such protection may come from HDL function rather than
from its increased plasma levels.
• Has 2 subclasses: HDL 2 & HDL 3
1. HDL 2 is more cardioprotective than HDL 3
• Sub-fractionation of HDL into:
1. Particles that contain Apo A-I but not Apo A-II
2. Particles that contain both Apo A-I & Apo A-II
• Significance:
1. Apo A-I is present in all HDL particles and makes up 70% of the
protein content
2. Apo A-II is present on about 2/3 of HDL particles in humans. It
makes up 20% of the HDL lipoprotein.
3. Apo A –II plays an important role in maintaining levels of HDL in
plasma.
4. Apo A-I & II are required for normal HDL biosynthesis &
metabolism.
• A high percentage of HDL2 particles falls into the Apo A-I only
category.
IV. MINOR AND ABNORMAL LIPOPROTEIN
1. Lipoprotein (a) – Lp(a)
1. Similar to LDL in density and overall composition
2. It is believed to be an LDL particle to which an apo(a) is added,
linked to apo B-100 by disulfide bond
PATHO Lipids and Dyslipoproteinemia
3. Electrophoretic activity is usually pre-B
4. Increased levels are related to genetic disorder (autosomal
dominant inheritance) & associated with increased risk of CHD.
5. Atherogenic properties are not yet well understood. Lp(a) might
interfere with normal thrombolysis by virtue of its similarity to
plasminogen.
2. LpX lipoprotein
1. Seen in patients with obstructive biliary disease and those with
LCAT (lecithin/cholesterol acytransferase) deficiency
2. 90% of its weight is lipids (phospholipids, unesterified &
esterified cholesterol)
3. Apo C & albumin constitute less than 10% of its weight.
3. B-VLDL (Floating B Lipoprotein)
1. An abnormal lipoprotein that accumulates in type 3
hyperlipoproteinemia
2. Richer in cholesterol than VLDL & apparently results from
defective catabolism of VLDL.
3. Found in the VLDL density range but migrates
electrophoretically with or near LDL.
♪NOTE! Read the chapter on Lipids & Dyslipoproteinemia.
Pay particular attention to all the Tables presented in this chapter.
V. BLOOD SAMPLING & STORAGE
A. Fasting
1. 10-12 hours (because chylomicrons are cleared within 9 hours of
fasting)
2. Presence of chylomicrons after 12 hours of fasting is abnormal
3. Chylomicrons can markedly increase triglyceride concentration
4. Fasting has little effect on plasma total cholesterol level & HDL-
C.
B. Position upon blood extraction:
1. Standing patient who reclines- about 10% decrease in the value of
total cholesterol, LDL, HDL, apo-B, Apo A-I after 20 mins of
recumbence (due to transfer of extravascular water to the
vascular system- dilution effect); for TG, the decreased is 50%
greater.
2. Standing to sitting position- wait for 5 minutes before extracting.
• Therefore: patient position should be standardized.
• Prolonged venous occlusion can lead to hemoconcentration which
can cause 10-15% increase in cholesterol.
• Therefore, tourniquets should not be applied longer than a minute
or two.
3. Sample to be used – either serum or plasma
4. If plasma is to be used, EDTA anticoagulant is the best
5. Blood samples could be frozen ( -70 degrees centigrade)
VI. ESTIMATION OF PLASMA LIPIDS
A. CHOLESTEROL
1. Colorimetric – not very accurate because of interfering substances
like increased bilirubin, high hemoglobin, very high triglycerides
2. Enzymatic – commonly used because it can give more precise
results; easier to use and can be done rapidly
B. TRIGLYCERIDES
1. Chemical method
2. Enzymatic method
1. more specific, rapid & easy to use
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 2. not affected by interfering substances like phospholipids &
glucose

VII. NCEP (NATIONAL CHOLESTEROL EDUCATION PROGRAM

INTERPRETATION (NCEP- national cholesterol education program

& ATP III - adult treatment plan III) (mg/dl)
Total Cholesterol <200 – desirable
200-239 – borderline high
>240 - high
Triglycerides <150 – normal
150-199 – borderline high
VIII. MAJOR RISK FACTORS THAT MODIFY LDL GOALS
200-499 – high
1. Cigarette smoking
>500 – very high
2. Hypertension (BP >/= 140/90 or on antihypertensive meds)
LDL-C <100 – optimal 3. Low HDL–C (<40mg/dl)
100-129 – near optimal /above optimal 4. Family history of premature CHD
130-159 – borderline high a. CHD in a male 1st degree relative <55
160-189 – high b. CHD in a female 1st degree relative <65
>190 – very high 5. Age
HDL-C <40 – low a. Men = >/= 45 yrs old
>60 - high b. Women = >/= 55 years old
INTERPRETATION 6. Diabetes mellitus
Borderline high LDL cholesterol – 130-159 mg/dl 7. Pre-existing CHD
Total cholesterol – 150-199 mg/dl

Borderline high risk Total cholesterol = 5.195 – 6.202 mmol/L

(risk is 2x greater) or 200 – 239 mg/dl

LDL cholesterol = 3.377 – 4.130 mmol/L or

130 – 159 mg/dl

High risk Total cholesterol = greater or equal to

(risk is 3x-4x 6.234 mmol/L or 240 mg/dl
greater)
LDL cholesterol = greater or equal to
4.156 mmol/L or 160 mg/dl
A. HDL
• A very strong independent correlate of CHD
CUTPOINTS FOR PLASMA CHOLESTEROL (NCEP)
• Low levels of HDL (< 40 mg/dl) may be associated with increased
• Detection, evaluation & treatment of high blood cholesterol in
cardiovascular heart disease even if the cholesterol & LDL levels
Adults:
are within normal limits.
1. Total cholesterol level is the basis for initial patient
• Increased HDL may be solely responsible for the increased
classification
hypercholesterolemia in 5% of adults and in 20% of children and not
2. All blood cholesterol levels above 5.195 mmol/L (200 mg/dl)
connote cardiovascular disease risk.
should be confirmed by repeat measurements and the average
• Some factors which may be associated with low levels of HDL:
value is used to guide clinical decisions
1. Male gender
3. With borderline high cholesterol levels, consider other risk
2. Progesterone
factors for coronary heart disease in selecting follow-up
3. Obesity
measures.
4. Increased carbohydrate intake
4. All patients with levels 6.234 mmol/L (240 mg/dl) or above, do
5. Sedentary lifestyle
lipoprotein analysis.
6. DM type 2
5. Individuals in whom lipoprotein analysis are performed are
7. Hypertriglyceridemia
subsequently treated according to their LDL-Cholesterol levels.
8. Cigarette smoking
♪NOTE! LDL-cholesterol level is the basis for decision about • Some factors which are associated with high levels of HDL:
initiating dietary or drug therapy: 1. Female gender
• Patients with LDL-cholesterol levels of 4.156 mmol/L (160 mg/dl) 2. Estrogens
or greater are considered as high risks for CHD. They should be 3. Exercise
given cholesterol-lowering treatment. 4. Moderate intake of alcohol
• Patients with LDL-cholesterol levels of 3.377 to 4.130 mmol/L 5. Intake of nicotinic acid
(130 mg/dl-159 mg/dl) should also be treated to lower their • LDL & HDL are independent risk factors
cholesterol if they have definite CHD or two other CHD risk • The less cholesterol carried in LDL and the more in HDL, the lower
factors is the risk of cardiovascular disease.
• There is an inverse relationship between HDL & TG, such that
elevated TG tend to be associated with decreased HDL levels.
• Elevated TG is an independent risk factor for CHD.
• The protective effect of high HDL level is mediated primarily by the
HDL2 component.
• Exercise and moderate alcohol consumption can increase HDL2
levels.
B. LDL

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• Serum cholesterol is composed mainly of LDL
• LDL is difficult to measure, so cholesterol is used as a substitute for
the initial screening for lipid disorders
• LDL cholesterol is estimated using the Friedewald formula:
Computations:
• LDL cholesterol = total cholesterol – HDL - TG/5)
1. used when values are in mg/dl
• LDL cholesterol = total cholesterol – HDL - TG /2.2)
1. used when the values are in mmol/L
• TG/5 or TG/2.2 = VLDL cholesterol
• Cannot be used when the TG value is 10.39 mmol/L or 400 mg/dl
or higher
IX. TESTING AND TREATMENT
• Cholesterol goals:
1. ATP III recommends a complete lipoprotein profile (TC, LDL, HDL
& TG) as initial test for evaluating blood cholesterol.
2. Testing should be done in all adults 20 years & older and should
be repeated at least once every 5 years.
▪ If nonfasting state – TG & HDL only
▪ If TC is 200 mg/dl or HDL is <40 mg/dl, perform follow-up lipid
profile
3. LDL is used as the primary target for cholesterol–lowering
therapy
▪ TLC – therapeutic lifestyle change (1st line of therapy)
a. Dietary change
b. Physical activity
c. Regular follow-up
▪ Drug therapy
X. DRUG THERAPY/HYPERLIPIDEMIA DRUGS
1. Statins:
2. primary effect – lower LDL-C (20-60%)
3. Secondary effect – small decreases in elevated TG & modest
increases in HDL
4. MOA: inhibit HMG-COA reductase
5. Side effects- GI disturbance (rare); liver problems;
rhabdomyolysis
6. Ex. Lovastatin, Simvastatin, Pravastatin, Atrovastatin
2. Fibric acid derivatives (TG-lowering drug)
1. primary effect – lower TG (20-50%)
2. Secondary effect- small increases in HDL (10- 15%)
3. MOA: not clearly defined; may decrease catabolism of HDL;
increase the activity of LPL; inhibit hepatic synthesis of VLDL
4. Side effects – GI disturbances, increased incidence of cholesterol
gallstones, increased effects of warfarin, tendency of statins to
cause rhabdomyolysis
5. Ex. Gemfibrozil, Fenofibrate
3. Bile acid resins
1. Primary effect- lower LDL (10-20%)
2. Secondary effect- bind bile acids in intestine leading to
secretion
3. MOA: cholestyramine (bile acid sequestrant)
4. Side effects – GI disturbance
5. Ex. Colestipol, Colesevelam
4. Niacin /Nicotinic acid (TG-lowering drug)
1. Primary effect – lowers TG (20-50%)
2. Secondary effect – raises HDL (15-35%)
3. MOA:
1. Decreased VLDL production in the liver by inhibition of
mobilization of FA in adipocytes via C-protein-coupled
receptor HM74A
2. reduce LDL (10-20%)
1. Side effects- GI disturbance, flushing, chills, pruritus, gout,
elevated blood sugar
XI. HYPERTRIGLYCERIDEMIA
• ATP III identifies elevated TG as an independent risk factor for CHD
• Factors associated with high TG
a. Obesity
b. Physical inactivity
c. Cigarette smoking
d. Excess alcohol intake
e. High carbohydrate diet (>60% of energy intake)
PATHO Lipids and Dyslipoproteinemia
f. Some diseases – DM type 2, CRF, nephritic syndrome
g. Some drugs- corticosteroids, estrogens, retinoids, higher doses
of B-adrenergic blocking agents
h. genetic diseases- familial combined hyperlipidemia, familial
hypertriglyceridemia, familial dysbetalipoproteinemia
• Primary aim of therapy – achieve target level for LDL-C.
1. Higher levels of LDL- weight reduction, exercise, medications
(nicotinic or fibrate)
2. Borderline high levels- weight reduction, exercise
A. NEW CONCEPTS FOR EVALUATION OF HYPERLIPIDEMIA
• Diabetes mellitus is now considered a risk equivalent because it
confers a high risk of new CHD within 10 years.
1. It means that DM patients with elevated cholesterol are treated
like patients who already have CHD.
• Metabolic syndrome
1. a physiologic syndrome, with risk factors like:
a. abdominal obesity
b. atherogenic dyslipidemia (increased TG, LDL & decreased
HDL)
c. increased BP
d. Insulin resistance (with or without glucose intolerance
e. Prothrombotic states
f. Pro-inflammatory states
*** LDL is the main target of therapy.
***Treatment of underlying causes like obesity and other risk factors.
DISEASE STATES
A. Single Gene Disorder:
1. Familial hypercholesterolemia
▪ decreased activity of LDL receptors → Increased LDL
cholesterol in the plasma
▪ Autosomal dominant
▪ Premature coronary atherosclerosis, xanthomas in skin &
tendons, arcus cornea
▪ (Type II hyperlipoproteinemia)
2. Familial Hypertriglyceridemia
▪ Increased VLDL in the blood accompanied by the triad of
obesity, hyperglycemia, & hyperinsulinemia (glucose
intolerance)
▪ Xanthomas are not characteristic of this disease
▪ Autosomal dominant
▪ (Type IV hyperlipoproteinemia)
▪ There’s a block in the conversion of VLDL to IDL and LDL .
3. Familial dyslipoproteinemia or broad beta disease
▪ A rare disorder
▪ Elevated both triglycerides & cholesterol
▪ Electrophoresis show “floating B” lipoprotein
▪ Impaired uptake & metabolism of VLDL in the liver
▪ (Type III hyperlipoproteinemia)
4. Multiple-lipoprotein-type hyperlipidemia or familial combined
hyperlipidemia
▪ Autosomal dominant
▪ Increase triglycerides & or cholesterol
▪ Increased hepatic secretion of VLDL
▪ Premature atherosclerosis but no xanthomas
B. MULTIFACTORIAL DISORDERS:
1. Polygenic hypercholesterolemia
▪ Elevated LDL cholesterol in the blood
▪ The cholesterol levels are sensitive to different
environmental factors like drugs, diet, alcohol intake, obesity
& concurrent disease/s.
2. Sporadic hypertriglyceridemia
▪ Elevated levels of endogenous triglycerides with or without
elevated levels of chylomicrons
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 ▪ Etiology is not genetics but as a result of outside factors ▪ Hepatic lipase deficiency
▪ Cholesterol 7-alpha-hydroxylase deficiency
• Low Total C & TG
→ uncommon disorder
→ due to defective apo B synthesis or metabolism leading to low
or non-existent apo B lipoproteins (CM, VLDL, &LDL)
→ Fat soluble vitamin deficiencies are common
→ Therapy: low fat or diet therapy are required
a. Abetalipoproteinemia
b. Hypobetalipoproteinemia (Bazen-Kornzweig syndrome)
c. Chylomicron retention disease – Anderson’s disease
• Isolated low HDL
→ associated with CHD
a. Familial hypoalphalipoproteinemia
b. apoA-1 def & apo C-III def
c. apoA-1 variants
d. Tangier disease- rare autosomal recessive disorder;
complete absence of HDL
e. LCAT def.

B. SECONDARY HYPERLIPOPROTEINEMIAS • Isolated High HDL

• Third trimester of pregnancy or those taking contraceptives a. Cholesteryl ester transfer protein defects
→ Elevated levels of VLDL XII. ANALYSIS OF APOPROTEIN LEVELS
→ Due to an estrogen-induced increase in hepatic secretion of • Not routinely done in clinical setting
VLDL • Strong predictors of Coronary heart disease:
• Patients taking thiazide diuretics – hyperlipidemia 1. Low Apoprotein A1 (a major component of HDL)
• Nephrotic syndrome 2. High Apoprotein B
→ elevated TG & cholesterol 3. Apoprotein A1 to Apoprotein B ratio
→ Due to a defect in the clearance of VLDL & LDL from the
peripheral tissues ★ KEYPOINTS:
→ Or due to an overproduction of lipoproteins in the liver in 1. TG & Cholesterol, the major lipids of the blood, are
response to hypoalbuminemia transported in lipoproteins.
• Cushing’s syndrome ▪ VLDL & LDL are primarily responsible for the delivery of
→ associated with increased levels of TG and cholesterol TG and cholesterol, respectively to peripheral tissues.
→ Due to increased hepatic secretions of VLDL → LDL ▪ HDL is involved in the return transport of cholesterol to
• Extrahepatic biliary obstruction & Primary biliary cirrhosis the liver for reuse/secretion to bile.
→ increased cholesterol levels 2. Hyperlipidemia may result from primary & secondary
→ Due to impairment in the biliary excretion & the enterohepatic disorders of lipoproteins.
circulation of cholesterol ▪ Primary hyperlipoproteinemias may reflect single gene
• Hypothyroidism defects or multifactorial disorders.
→ associated with increased levels of cholesterol ▪ Secondary hyperlipoproteinemias are associated with a
→ Due to decreased metabolism of LDL wide variety of conditions.
DISORDERS 3. Evaluation of a suspected lipid disorder is based on
• High C with high LDL: measurements of total cholesterol and TG in blood.
→ Polygenic (nonfamilial) hypercholesterolemia ▪ HDL can also be easily measured.
→ Familial hypercholesterolemia ▪ The amount of LDL cholesterol is then estimated by the
→ Familial defective apo-B Friedewald formula.
→ Sitosterolemia 4. In general, the more cholesterol is carried in LDL and the
▪ plant sterols (phytosterols/are absorbed & accumulated in less carried in HDL the greater the risk of cardiovascular
plasma & peripheral tissues) disease; conversely, the less cholesterol carried in LDL and
→ Autosomal dominant & autosomal recessive the more carried in HDL, the lower the risk.
hypercholesterolemia
5. The National Cholesterol Education Program (NCEP)
• High TG with normal C recommends screening for risk of cardiovascular disease
→ related to elevations of TG-rich particles (CM or VLDL) using total serum cholesterol; decisions regarding therapy
→ due to hyperbetalipoproteinemia (VLDL) and may be due to should be made on the basis of calculated LDL cholesterol
secondary causes like excess alcohol intake or high levels.
carbohydrate diet. ▪ The NCEP’s categories for total cholesterol are: desirable,
→ Fredrickson types 1 & 4 borderline-high, and high.
a. Diabetic dyslipidemia
b. Familial hypertriglyceridemia ★ SUMMARY:
c. Lipoprotein lipase deficiency (hyperlipoproteinemia type I or • All lipoproteins contain TG, cholesterol, phospholipids and
hyperchylomicronemia) proteins in proportions characteristic for each type.
d. Apo C-II deficiency – activating co-factor for LPL • It also contains apoproteins or apolipoproteins which bind
e. Apo C-III excess – interferes with action of LPL selectively to different cell receptors thus initiating cellular
f. Apo A-V deficiency metabolism
• High C with High TG • Lipoproteins are separated by:
→ associated with increased cardiac risk; most common primary 1. Ultracentrifugation – HDL, LDL, VLDL, Chylomicrons
hyperlipoproteinemia 2. Electrophoresis – alpha, beta, pre-beta, chylomicrons (do not
→ Fredrickson types 2B & 3 migrate)
▪ Familial combined hyperlipidemia (type 2B) • VLDL is responsible for the delivery of TG to the peripheral
▪ Acquired combined hyperlipidemia tissues
▪ Dysbetalipoproteinemia (type 3)

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 • LDL is responsible for the delivery of cholesterol to peripheral
tissues
• HDL is involved in the return transport of cholesterol to the liver
for excretion (good cholesterol)
• HYPERLIPIDEMIA – increase in blood lipids. i.e TG or Cholesterol
or Both.
• HYPERLIPOPROTEINEMIA – increase in one or more lipoproteins
& is almost always accompanied by hyperlipidemia.
• Although ultracentrifugation and electrophoresis are of
historical significance, most useful lipid & lipoprotein testing
methods are now enzymatic.
• LDL can be measured directly but it is usually calculated using
Friedewald formula. Calculated values require evaluation of
fasting samples.
• LDL is currently considered the MOST important value in
assessing cardiac risk & directing therapy.
• The profile currently recommended for initial screening in adults,
age 20 or older includes TC, LDL, HDL & TG. Testing should be
repeated at least once every 5 years.
• Other tests including apolipoprotein level and lipoprotein
subclasses, may prove valuable in fine-tuning risk assessment
& evaluating response to therapy.
• New guidelines elevate the perceived atherosclerotic risk of DM
& support aggressive intervention in diabetic patients and
patients with metabolic syndrome.

V. REFERENCES
• Dr. De Chavez’s PPT
EFERENCES

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