(M) Lec 4: Lipids and Lipoproteins (Part 2) Flashcards by Kchianna Lauren Coronel

TAGs (TESTING)

What sample is used: Plasma or Serum?

Both

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TAGs (TESTING)

How long is the fasting period for TAG analysis?

12-14 hours

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TAGs (TESTING)

TOF: Postural changes increase TAGs

False (decrease)

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TAGs (TESTING)

Chemical Methods:
1. A fluorimetric method that produces a pink colored reaction
2. A colorimetric method that produces a blue colored reaction

A. Van Handel and Zilversmith
B. Hantzsch Condensation

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TAGs (TESTING)

What is the enzymatic method called that is also known as the Bucolo and David Method?

Glycerol Kinase Method

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TAGs (TESTING)

What is the CDC Reference Method for TAG analysis?

MODIFIED VAN HANDEL and ZILVERSMITH Method

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TAGs (TESTING)

Modified Van Handel and Zilversmith Reference Method:

Alkaline Hydrolysis
Solvent Extraction
Adsorption
Colorimetry
End Product

A. Formaldehyde
B. Alcoholic KOH
C. Silisic Acid
D. Chromotropic Acid
E. Chloroform

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TAGs (TESTING)

Silisilic Acid Chromatography isolates what?

TAGs

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TAGs (TESTING)

Reference Values:
1. >500 mg/dL
2. 150-199 mg/dL
3. < 150 mg/dL
4. 499 mg/dL

A. Normal
B. Borderline High
C. High TAG
D. Very High TAG

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TAGs (TESTING)

What is the conversion factor?

0.011 mmol/L

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TAGs (TESTING)

Increased or Decreased?
- Hyperlipoproteinemia Type I, IIb, III, IV, V
- Alcoholism
- Nephrotic syndrome
- Hypothyroidism
- Pancreatitis

Increased

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TAGs (TESTING)

Increased or Decreased?
- Malabsorption syndrome
- Hyperthyroidism
- Malnutrition burns
- Brain infarction

Decreased

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Lipoproteins (TESTING)

What sample is used: Plasma or Serum?

Both

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Lipoproteins (TESTING)

What 2 anticoagulants can be used for lipoprotein fractions?

SST and EDTA

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Lipoproteins (TESTING)

What 2 parameters can be measured using a NON-FASTING sample?

HDL and TC

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Lipoproteins (TESTING)

This method:
- is the reference method to quantify lipoproteins
- isolates the protein and TAG content of lipoproteins
- separation is based on density and weight
- reagent used is: potassium bromide with a 1.063 density

Utracentrifugation

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Lipoproteins (TESTING)

Ultracentrifugation results using a potassium bromide reagent is expressed as what unit?

Svegberg Unit

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Lipoproteins (TESTING)

This method:
- has a supporting medium of agarose gel (alam na)
- has the ff. staining dyes: Oil Red O, Fat Red 7B, and Sudan Black B
- moves from the most anodal to the least anodal portion of the media

Electrophoresis

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Lipoproteins (TESTING)

The electrophoretic pattern of lipoproteins moves from most anodal to least anodal, order the ff. analytes in that manner:

LDL
VLDL
Chylomicrons
HDL

HDL (most anodal), VLDL, LDL, and Chylomicrons (least anodal)

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Lipoproteins (TESTING)

This method:
- is an apolipoprotein assay that uses an antibody complex
- lipoprotein (a) is measured by a immunoturbidimetric assay

Immunoassay or Immunonephelometry

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Lipoproteins (TESTING)

In chromatographic methods, what 2 types of chromatography is done?

Gel Chromatography or Affinity Chromatography

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Lipoproteins (TESTING)

This method has the ff. principle:
The nuclei (sample) of atoms with characteristic spins when immersed in a static magnetic field and second oscillating magnetic field produce resonance or chemical shift that is measured and recorded.

Nuclear Magnetic Resonance Spectroscopy (NMRS)

Note: It measures HDL and LDL

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Lipoproteins (TESTING)

What samples can be used in Nuclear Magnetic Resonance Spectroscopy (NMRS)? (3 answers)

Serum
EDTA Plasma
Heparinized Plasma

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Lipoproteins (TESTING)

What is the main disadvantage of Nuclear Magnetic Resonance Spectroscopy (NMRS)?

Requires a large volume of sample

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# Lipoproteins (TESTING) This test is for the detection of increased chylomicrons and VLDL; the patient plasma stands overnight undisturbed in a refrigerator (@ 4ºC)

Standing Plasma Test/ Ref. Test/ Overnight Standing Test

# Lipoproteins (TESTING) Standing Plasma Test: If (+) for chylomicrons, what is found on the top of the sample?

Milky/creamy layer

# Lipoproteins (TESTING) Standing Plasma Test: If (+) for VLDL, what can be said about the turbidity of the sample?

Uniform/Homogenous

# Lipoproteins (TESTING) Standing Plasma Test: If (+) for both Chylomicrons and VLDL, what can be said about the appearance of the sample?

It has both a creamy layer on top and uniform turbidity

# Lipoproteins (TESTING) This test uses the ff. reagents. - heparin sulfates - dextran sulfates - phosphotungstate - (+) divalent cations: Ca, Mg, and Mn

Polyanion precipitation

# Lipoproteins (TESTING) What is the most widely used reagent in the Polyanion Precipitation method?

Heparin Sulfate + Mn | Note: Mn removes interferences

# Lipoproteins (TESTING) The ff. parameters are the bases for what event in Polyanion Precipitation? - Reagent conc. - pH - Ionic strength - Lipid/Protein ratio

Separation

# Lipoproteins (HDL TESTING) This method of measuring HDLs: - precipitates all Apo-B (100 and 48) containing lipoproteins such as chylomicrons, VLDL, LDL, and IDL - liberated/remaining HDL is measured using a Chole reagent (used for cholesterol as well)

Polyanion Precipitation followed by Measurement of Supernatant Cholesterol

# Lipoproteins (HDL TESTING) This method of measuring HDLs: - gets no prior treatment and separation procedures - uses 2 reagents which: (1) prevents HDL from reacting [block non-HDL] and (2) releases HDL before measuring it enzymatically, respectively

Homogenous Assays

# Lipoproteins (HDL TESTING) What is the CDC's reference 3-Step Method for HDL Testing?

1. Ultracentrifugation 2. Heparin Manganese Precipitation 3. Abell-Kendall Assay

# Lipoproteins (HDL TESTING) What is the alternative to CDC's reference method for HDL Testing?

Modified Dextran Sulfate Method (w/o ultracentrifugation)

# Lipoproteins (LDL TESTING) This method is for cholesterol measurement (you subtract HDL, VLDL, and cholesterol to get LDL)

Selective Chemical Precipitation

# Lipoproteins (LDL TESTING) This method combines ultracentrifugation and chemical precipitation using plasma

Beta Quantification

# Lipoproteins (LDL TESTING) This method is aka the "homogenous method" which uses 2 reagents that block non-LDL substances and release LDL for enzymatic measurement

Direct LDL Measurement

# Lipoproteins (LDL TESTING) What is the formula for LDL-Cholesterol?

Total Cholesterol = Cholesterol Ester + Free Cholesterol (basis for derivation) LDL = TC - HDL - VLDL (indirect formula) ## Footnote Note: VLDL and LDL are not given in the machine; VLDL is [(value of TAG)/factor]

# Lipoproteins (LDL TESTING) Computing for VLDL: What method uses the ff. factors? - 2.175 mmol/L - 5.0 mg/dL

Friedewald Method (Indirect) | Note: Cannot be used on a NON-FASTING SAMPLE

# Lipoproteins (LDL TESTING) Computing for VLDL: What method uses the ff. factors? - 2.825 mmol/L - 6.5 mg/dL

De Long Method (Indirect Method)

# Lipoproteins (LDL TESTING) This LDL formula has good applicability, showing superiority in relation well to the Friedewald formula, especially for LDL-C values < 100mg/dL, diabetes, and, hypertriglyceridemia

Martin-Hopkins Formula LDL-C

# Lipoproteins (LDL TESTING) What is the formula for Martin-Hopkins?

[TC - HDL - TAG]/ Adjustable Factor | Adjustable factor: Depends on the non-DL value and TAG value ## Footnote Unit is mg/dL

# Disorders Associated with Lipids and Lipoprotein These disorders are collectively known as what?

Dyslipidemias

# Disorders Associated with Lipids and Lipoprotein - refers to the thickening and hardening of the walls of the arteries - there is deposition of lipids in the form of esterified cholesterol in the artery walls - fatty streaks eventually develop into plaques - is associated with increased LDL or decreased HDL

Atherosclerosis ## Footnote Is different from arteriosclerosis, that is a type of atherosclerosis (shrinking diameter of the vessel)

# Disorders Associated with Lipids and Lipoprotein Plaque develops in the arteries of the arms or legs

Peripheral Vascular Disease

# Disorders Associated with Lipids and Lipoprotein - plaque develops in the heart - is associated with angina and myocardial infarction

Coronary Artery Disease

# Disorders Associated with Lipids and Lipoprotein - plaque develops in the vessel of the brain - associated with stroke

Cerebrovascular Disease

# Drugs for Dyslipidemia An emulsifying agent that absorbs lipids

Bile Acid Sequestrants

# Drugs for Dyslipidemia This blocks cholesterol synthesis by blocking/removing HMG-CoA

HMG-CoA Reductase Drug Inhibitors

# Drugs for Dyslipidemia This is most effective in raising HDL levels

Niacin or Nicotinic acid

# Drugs for Dyslipidemia This inhibits the absorption of cholesterol by inhibiting the Niemann Pick C1-licke 1 (NPC1-L1) transporter in the intestine without impacting the absorption of fat-soluble nutrients (+ uses statin to lower LDL)

Ezetimibe | Note: For greater reduction of HDL

# Drugs for Dyslipidemia This reduces cardiovascular disease as it contains omega 3 fatty acids

Fish Oil

# Guidelines for the Laboratory Assessment of CAD 1. Desirable: < 150mg/dL 2. Desirable: < 200mg/dL 3. Desirable: < 130mg/dL 4. Desirable: < 55mg/dL A. Total Cholesterol B. LDL-C C. HDL-C D. TAG

1. D 2. A 3. B 4. C

# Guidelines for the Laboratory Assessment of CAD 1. Borderline: 250-500mg/dL 2. Borderline: 200-249mg/dL 3. Borderline: 130-159mg/dL 4. Borderline: 25-54mg/dL A. Total Cholesterol B. LDL-C C. HDL-C D. TAG

1. D 2. A 3. B 4. C

# Disorders Associated with Lipids and Lipoprotein This type of hyperlipoproteinemia: - has defects in Apo B, LDL Receptor, and PCK9 LDL Adaptor Proteins

Hypercholesterolemia

# Disorders Associated with Lipids and Lipoprotein This type of hypercholesterolemia can manifest as stroke in as early as one's teenage years

Homozygous Hypercholesterolemia

# Disorders Associated with Lipids and Lipoprotein This type of hypercholesterolemia can manifest as stroke at the age of 50 and above

Heterozygous Hypercholesterolemia

# Disorders Associated with Lipids and Lipoprotein This type of hyperlipoproteinemia: - has an imbalance between synthesis and clearance of VLDL in the circulation (genetic abnormalities) - there is severe or recurrent pancreatitis

Hypertriglyceridemia

# Disorders Associated with Lipids and Lipoprotein Refers to elevated levels of cholesterol and TAG with increased risk of CHD development

Combined Hyperlipidemia

# Disorders Associated with Lipids and Lipoprotein An excessive hepatic synthesis of apoprotein B- , increased VLDL secretion and production of LDL

Familial Combined Hyperlipidemia

# Disorders Associated with Lipids and Lipoprotein The accumulation of cholesterol rich VLDL and chylomicron remnants

Familial Dysbetalipoproteinemia

# Disorders Associated with Lipids and Lipoprotein Refers to low lipoprotein levels

Hypolipoproteinemia

# Disorders Associated with Lipids and Lipoprotein What kind of hypolipoproteinemia and syndrome are these symptoms correspondent to? - Defective Apo-B synthesis - VLDL, LDL, and Chylomicrons are absent - Chole and TAG are low - There is a deficiency of microsomal TAG transfer protein used in the synthesis and secretion of VLDL - Defects in the absorption of fat-soluble vitamins A, E, and K

Abetalipoproteinemia: Basses-Kornzweig Syndrome ## Footnote Note: Vit. D does not depend on chylomicrons for absorption and Vit. K is the least impacted as it has its own independent transport system

# Disorders Associated with Lipids and Lipoprotein This type of hypolipoproteinemia manifests as: - Apo-B deficiency - Decreased Total Cholesterol and LDL - Normal/ Decreased TAG and VLDL

Hypobetalipoproteinemia

# Disorders Associated with Lipids and Lipoprotein Accumulations of sphingomyelin in the BM, spleen and lymph nodes (a lipid storage disorder)

Niemann-Pick Disease

# Disorders Associated with Lipids and Lipoprotein - Deficiency of HDL due to a mutation in the ABCA 1 gene (excess cholesterol is not returned to the liver) - Orange to yellow discoloration of tonsils and pharynx

Tangier’s Disease

# Disorders Associated with Lipids and Lipoprotein - A mutation in the LCAT gene which leads to cholesterol not being able to be esterified - aka "Fish Eye Disease"

LCAT Deficiency

# Disorders Associated with Lipids and Lipoprotein - Deficiency of the enzyme Hexominidase A - Accumulation of sphingolipids in the brain (neurodegenerative disorder)

Tay-Sachs Disease

# Disorders Associated with Lipids and Lipoprotein - the inability to clear chylomicron particles - aka "Classic Type 1 Chylomicronemia Syndrome" (TAG = 10,000 mg/dL) - manifests as abdominal pain and pancreatitis - Is essential for hydrolysis of TAG and conversion of chylomicron remnants

Lipoprotein Lipase Deficiency

# Disorders Associated with Lipids and Lipoprotein Apo B-48 deficiency (decreased chylomicrons)

Anderson’s disease

# Disorders Associated with Lipids and Lipoprotein - plant sterols are absorbed and will accumulate in plasma and peripheral tissue - a mutation in ABCG8/ABCG5 - high cholesterol and xanthomas (skin lesions containing fats)

Sisterolemia

# Disorders Associated with Lipids and Lipoprotein - increases the risk for CHD and CVD - a variant of LDL with an extra apolipoprotein which has a high degree of homology with plasminogen

Lipoprotein (a) elevation

# Disorders Associated with Lipids and Lipoprotein If Lipoprotein (a) has the same binding site (fibrin binding site) with plasminogen (dissolves clot-like crystals), there will be what?

Buildup (plaque formation)

# Friedrickson Classification of Disease "INC for TAG and Chylomicrons" A. Type 1: Familial LPP Lipase Deficiency B. Type 2A: Familial Hypercholesterolemia C. Type 2B: Familial Combined Hyperlipidemia D. Type 3: Familial Dysbetalipoproteinemia E. Type 4: Familial Hypertriglyceridemia F. Type 5: Familial Hyperlipoproteinemia

# Friedrickson Classification of Disease "INC for Cholesterol and LDL" A. Type 1: Familial LPP Lipase Deficiency B. Type 2A: Familial Hypercholesterolemia C. Type 2B: Familial Combined Hyperlipidemia D. Type 3: Familial Dysbetalipoproteinemia E. Type 4: Familial Hypertriglyceridemia F. Type 5: Familial Hyperlipoproteinemia

# Friedrickson Classification of Disease "INC for TAG, Cholesterol, LDL, and VLDL" A. Type 1: Familial LPP Lipase Deficiency B. Type 2A: Familial Hypercholesterolemia C. Type 2B: Familial Combined Hyperlipidemia D. Type 3: Familial Dysbetalipoproteinemia E. Type 4: Familial Hypertriglyceridemia F. Type 5: Familial Hyperlipoproteinemia

# Friedrickson Classification of Disease "INC for TAG, Cholesterol, and VLDL" A. Type 1: Familial LPP Lipase Deficiency B. Type 2A: Familial Hypercholesterolemia C. Type 2B: Familial Combined Hyperlipidemia D. Type 3: Familial Dysbetalipoproteinemia E. Type 4: Familial Hypertriglyceridemia F. Type 5: Familial Hyperlipoproteinemia

# Friedrickson Classification of Disease "INC for TAG and VLDL" A. Type 1: Familial LPP Lipase Deficiency B. Type 2A: Familial Hypercholesterolemia C. Type 2B: Familial Combined Hyperlipidemia D. Type 3: Familial Dysbetalipoproteinemia E. Type 4: Familial Hypertriglyceridemia F. Type 5: Familial Hyperlipoproteinemia

# Friedrickson Classification of Disease "INC for TAG, Cholesterol, VLDL, and Chylomicrons" A. Type 1: Familial LPP Lipase Deficiency B. Type 2A: Familial Hypercholesterolemia C. Type 2B: Familial Combined Hyperlipidemia D. Type 3: Familial Dysbetalipoproteinemia E. Type 4: Familial Hypertriglyceridemia F. Type 5: Familial Hyperlipoproteinemia

# Familial Diseases * Problem involving the chylomicrons * Manifested as hypertriglyceridemia (high TAGs and Chylomicrons)

Type 1: Familial Chylomicronemia

# Familial Diseases - Problem involving LDL metabolism & a defective Apo B (LDL receptors cannot recognize Apo-B) - Inability to clear LDL = High TC and LDL - Clinical findings: Xanthelasma & Planar xanthomas

Type 2A: Familial Hypercholesterolemia

# Familial Diseases * Problem involving VLDL and LDL * Increased TAG and Cholesterol

Type 2B: Familial Combined Hyperlipidemia

# Familial Diseases - Presence of floating B-VLDL (accumulation of IDL) - Abnormality in Apo-E2 content (rare form) - aka "Broad Beta Disease"; electrophoretic pattern

Type 3: Familial Dysbetalipoproteinemia

# Familial Diseases - A problem involving VLDL (it cannot be converted) with high TAG but normal LDL

Type 4: Familial Hypertriglyceridemia

# Familial Diseases * Problem involving VLDL and Chylomicrons * Manifested as hypertriglyceridemia

Type 5: Mixed Hyperlipidemia

(M) Lec 4: Lipids and Lipoproteins (Part 2) Flashcards

(86 cards)