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Lipoprotein: – Part 1 – High-Density Lipoprotein (HDL), HDL-Cholesterol (HDL-C), Lipoprotein

June 20, 2024Chemical pathologyLab Tests

Table of Contents

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  • High-Density Lipoprotein (HDL)
        • What sample is needed for High-Density Lipoprotein (HDL)?
        • What are the precautions for High-Density Lipoprotein (HDL)?
        • What are the Indications for High-Density Lipoprotein (HDL)?
        • How will you discuss the pathophysiology of Lipoproteins?
      • Chylomicron:
      • LDL:
      • VLDL:
      • HDL:
        • How will you summarize Lipoproteins?
  • High-density lipoprotein (HDL)
        • What are the Functions of High-density lipoprotein (HDL)?
        • What is the total cholesterol/HDL-cholesterol ratio?
        • What is the normal High-density lipoprotein (HDL)?
      • Abnormal values of HDL:
        • What conditions will you see increased High-Density Lipoprotein (HDL)-C?
        • What conditions will you see decreased High-Density Lipoprotein (HDL)-C?
      • How will you summarize the characteristics of the lipoproteins?
      • Questions and answers:

High-Density Lipoprotein (HDL)

What sample is needed for High-Density Lipoprotein (HDL)?

  1. This test is done on the serum.
  2. A fasting sample is preferred. Advised the patient to fast for 12 to 14 hours.
  3. This test can be done on plasma as well.
  4. Serum or plasma can be stored at 4 °C for 4 days (5 to 7 days).

What are the precautions for High-Density Lipoprotein (HDL)?

  1. Don’t use oxalate, fluoride, citrate, or heparin to collect blood.
  2. HDL values are age and sex-related.
  3. HDL value is increased in Hypothyroidism and decreased in Hyperthyroidism.
  4. Drugs that increase the value are oral contraceptives, aspirin, phenothiazine, steroids, and sulphonamides.
  5. Smoking and alcohol decrease HDL value.

What are the Indications for High-Density Lipoprotein (HDL)?

  1. Advised to evaluate coronary artery disease risk.
  2. This can be advised as part of a lipid profile.

How will you discuss the pathophysiology of Lipoproteins?

  1. Lipoproteins are insoluble and are transported in the plasma as a macromolecular complex.
  2. Lipoproteins are sphericle particles with:
    1. Nonpolar lipids are triglycerides and free cholesterol.
    2. Polar lipids are phospholipids and free cholesterol.
High-Density Lipoprotein (HDL): Lipoprotein structure

High-Density Lipoprotein (HDL): Lipoprotein structure

How will you classify Lipoprotein?

  • It is classified on  electrophoresis based on its physical and chemical structure as follows:
  1. Chylomicron:

    1. These are primarily triglycerides.
    2. These are the vehicles where lipids are absorbed from the intestine and can enter the bloodstream.
  2. LDL:

    1.  Beta-lipoprotein is the primary carrier of cholesterol.
    2. It arises primarily from the degradation of VLDL into LDL1, called intermediate-density lipoprotein (IDL).
    3. LDL-1  is short-lived, and it is converted into LDL-2.
    4. LDL-2 will remove some of the triglyceride load.
    5. LDL is a membrane protein.
    6. There are tissue receptors on the cells, which are engulfed by the cells and degraded by the lysosomal enzymes.
  3. VLDL:

    1. It is Pre-beta – lipoproteins, which are mainly triglycerides.
    2. It originates in the liver and transports triglycerides from the liver to other tissues.
  4. HDL:

    1. α–Lipoproteins are mainly proteins with a small amount of cholesterol.
    2. It arises from the liver and intestine and primarily contains apolipoproteins A-I and A-II.
    3. It is a cholesterol scavenger and removes cholesterol from the tissues.
      1. HDL will esterify cholesterol and carry it to the liver for removal.
      2. HDL converts cholesterol into bile acids and excretion into bile.
Lipoprotein electrophoresis pattern

Lipoprotein electrophoresis pattern

  1. The outer covering lipoproteins are called Apoproteins, and these are classified into:
    1. Apo-1.
    2. Apo-II.
    3. Apo- B.
    4. Apo-D.
    5. Apo-E.

How will you classify Apolipoprotein?

Apolipoproteins Type of lipoprotein Molecular mass in Da
  • Apo A-1
  1. HDL
  2. Chylomicron
  • 28,000
  • Apo A-II
  1. HDL
  2. Chylomicron
  • 17,000
  • Apo A-IV
It is secreted with chylomicron and transferred to HDL
  • 46,000
  • Apo B-100
  1. LDL
  2. VLDL
  3. IDL
  • 550,000
  • Apo B-48
  1. Chylomicron
  2. Remnants of chylomicron
  • 260,000
  • Apo C-I
  1. Chylomicron
  2. VLDL
  3. HDL
  • 76,000
  • Apo C-II
  1. Chylomicron
  2. VLDL
  3. HDL
  • 8,916
  • Apo C-III
  1. HDL
  2. VLDL
  3. Chylomicron
  • 8,750
  • Apo D
  • HDL (subfraction)
  • 19,300
  • Apo E
  1. Chylomicron
  2. VLDL
  3. HDL
  • 34,000
  1. Apolipoproteins are a hydrophilic component of lipoproteins.
  2. Lipids like cholesterol and triglycerides are hydrophobic and must be placed in water-soluble micellar structures (Apolipoproteins) to be transported in the plasma.
High-Density Lipoprotein (HDL): Dietary Fat absorption

High-Density Lipoprotein (HDL): Dietary Fat absorption

  1. In the case of endogenous pathways, the lipoproteins are synthesized in the liver from carbohydrates and fats.
Lipoprotein synthesis in the liver

Lipoprotein synthesis in the liver

How will you summarize Lipoproteins?

Type of lipoprotein Apoprotein contents Electrophoresis pattern The main type of lipids % of Apoprotein Origin tissue Functions
  • Chylomicron
  1. A-I, II, IV
  2. C-I, II, III
  3. B-48
  4. E-2, 3, 4
  • At the application
  1. Triglyceride = 90%
  2. Cholesterol = 5%
  3. Protein = 2%
  4. Phospholipoid = 5%
  • 1%
  • Intestine
  • Transport dietary lipids to various body tissues
  • LDL
  • B-100
  • β-lipoprotein
  1. Triglycerides = 10%
  2. Cholesterol = 45%
  3. protein = 25%
  4. Phospholipid = 20%
  • 20%
  1. The primary site is the liver
  2. Intestine
  1. It transports cholesterol to the tissue
  2. It increases atherosclerosis
  • VLDL
  1. B-100
  2. C-I, II, III
  3. E-2, 3, 4
  • Pre-β
  1. Triglyceride = 55%
  2. protein = 10%
  3. Cholesterol = 15%
  4. Phospholipids = 15%
  • 10%
  1. The primary site is the liver
  2. Intestine
  1. It transports triglyceride from the liver to fatty tissue
  2. It increases atherosclerosis
  • HDL
  1. A-1
  2. C-I, II, III
  3. D
  4. E-2, 3, 4
  • α-1
  1. Phospholipids =30%
  2. Protein = 50%
  3. Cholesterol = 15%
  4. Triglycerides = 5%
  • 50%
  • The main site of origin is the liver
  1. It carries cholesterol  from tissues to the liver
  2. It increases catabolism of chylomicron and VLDL
  3. It prevents atherosclerosis

High-density lipoprotein (HDL)

  1. HDL cholesterol is synthesized and secreted into the liver and intestine.
  2. This can be separated by electrophoresis and ultracentrifugation.
  3. HDL comprises phospholipids and apolipoprotein (Apo A-1 and Apo – A-II), almost 90% of the total protein.
  4. The ratio of Apo- A-1 to Apo- A-11 is ∼ 3:1 by weight.
    1. HDL from the intestine does not contain Apo-C or Apo-E and only contains Apo-A.
  5. The dominant Apoprotein is Apo-A I (67%), followed by A-II, C, and E.
  6. This may be responsible for the transport of dietary cholesterol.
  7. HDL plays a role in transporting cholesterol to the liver from the tissue excreted in the bile.
    1. HDL transports cholesterol to the liver, where cholesterol is the precursor of the bile acids or part of the VLDL component.
    2. While lipoproteins transport cholesterol, triglycerides, and other insoluble fats.
  8. HDL (Composition) consists of the following:
    1. Cholesterol = 6%.
    2. Cholesterol ester = 13%.
    3. Triglycerides = 3%.
    4. Phospholipids = 28%.
    5. Protein  = 50%.
      1. HDL has very few triglycerides.
      2. There is a high percentage of proteins, phospholipids, and cholesterol.
  9. Another source says:
    1. Triglycerides = 5%
    2. Cholesterol = 15%
    3. Phospholipids = 30%
    4. Proteins = 50%
High-density lipoprotein (HDL)

High-density lipoprotein (HDL)

  1. The ratio of esterified and free cholesterol is 3:1.
  2. The decreased level of HDL is atherogenic.
    1. HDL Raised level protects against atherosclerosis by removing the cholesterol from the arteries and taking it to the liver.
    2. HDL and LDL may combine to maintain cellular Cholesterol balance by moving cholesterol into the arteries and HDL removing it from the arteries.
    3. HDL-C is good cholesterol proportional to coronary artery disease (CAD) risk.
High density lipoprotein (HDL) function

High-density lipoprotein (HDL) function

  1. The treatment is not indicated when a high HDL with a high cholesterol level exists.

What are the Functions of High-density lipoprotein (HDL)?

  1. HDL is the carrier of cholesterol from the peripheral tissue.
  2. HDL carries cholesterol from peripheral tissue to the liver for excretion in the bile, a process known as reverse cholesterol transport.
  3. HDL has a protective role by preventing cellular uptake of cholesterol and lipids.
  4. HDL protects against cardiovascular diseases.

What is the relationship between HDL and coronary heart disease?

Risk of heart disease Male Female
  • Low
  • 60 mg/dL HDL
  • 70 mg/dL HDL
  • Moderate
  • 45 mg/dL HDL
  • 55 mg/dL HDL
  • High
  • 25 mg/dL HDL
  • 35 mg/dL HDL

What is the total cholesterol/HDL-cholesterol ratio?

  1. The ratio is very important to know the risk of coronary heart disease.
  2. A high ratio is associated with increased risk.
  3. The normal ratio should be at least 5:1, and the best is 3:1.

 What is the relationship between Total cholesterol/HDL-cholesterol Ratio Risk for Coronary disease?

Risk  Women  Men
  • Below average
  • 3.3
  • 3.4
  • Average
  • 4.4
  • 5.0
  • Above-average x 2 times
  • 7.0
  • 9.6
  • Above-average x 3 times
  • 11.0
  • 23.4
  • HDL-cholesterol level of 70 mg/dl or greater is associated with longevity of life.

What is the normal High-density lipoprotein (HDL)?

Source 1

HDL-Cholesterol

 Age  Male mg/dL  Female mg/dL
 Cord blood 6 to 53 13 to 56
 5 to 9 year 38 to 75  36 to 73
 10 to 14 year 37 to 74 37 to 70
 15 to 19 year 30 to 63 35 to 74
 20 to 24 year 30 to 63 33 to 79
 25 to 29 year  31 to 63 37 to 83
30 to 34 year 28 to 63 36 to 77
35 to 39 year 29 to 62 34 to 82
40 to 44 year 27 to 67 34 to 88
45 to 49 year 30 to 64 34 to 87
50 to 54 year 28 to 63 37 to 92
55 to 59 year 28 to 71 37 to 91
60 to 64 year 30 to 74 38 to 92
65 to 69 year 30 to 75 35 to 96
>70 year 31 to 75 33 to 92
  • To convert into SI unit x 0.0259 = mmol/L

Source 2

HDL

  • Male = >50 mg/dL
  • Female = >55 mg/dL

Another source

HDL

  • Men= 36 to 65 mg/dl or > 45 mg/dl (>0.75 mmol/L).
  • Women= 35 to 80 mg/dl or > 55 mg/dl (>0.91 mmol/L).

Abnormal values of HDL:

HDL value Risk for coronary disease (CAD)
  • <25 mg/dL
  • CAD risk is 2 times and is a dangerous level
  • 26 to 35 mg/dL
  • CAD risk is 1.5 times. This is a high-risk group
  • 36 to 45 mg/dL
  • CAD risk is 1.2 times. This moderate-risk group
  • 45 to 59 mg/dL
  • This is an average-risk group
  • >60 mg/dL
  • Below-average risk group
Critical values
  • Male
  • <35 mg/dL
  • Female
  • <40 mg/dL

What conditions will you see increased High-Density Lipoprotein (HDL)-C?

  1. When it is >60 mg/dL.
  2. Chronic liver diseases like cirrhosis, hepatitis, and alcoholism.
  3. Long-term vigorous exercises.
  4. Familial hyper-alpha-lipoproteinemia.
  5. The increased level may be due to some drugs.
    1. Estrogen therapy.
    2. Moderate intake of alcohol.
    3. Insulin therapy.
  6. Hypobetalipoproteinemia.

What conditions will you see decreased High-Density Lipoprotein (HDL)-C?

  1. When it is <40 mg/dL.
  2. Poorly controlled diabetes
  3. Cholestasis.
  4. Chronic renal failure, uremia, and nephrotic syndrome.
  5. Hypertriglyceridemia.
  6. Familial hypo-alpha-lipoproteinemia.
  7. Alpha and beta – lipoproteinemia.
  8. The decreased level may also be seen in some of the drugs.
    1. Steroids.
    2. Antihypertensive drugs.
    3. Diuretics.
    4. Beta-blockers.
    5. Thiazide.
  9. The secondary causes are:
    1. Stress and recent illnesses like AMI, stroke, and surgery.
    2. Starvation and a nonfasting sample are 5% to 10% lower.
    3. Diabetes mellitus.
    4. Hypothyroidism.
    5. Liver diseases.
    6. Uremia and nephrosis.

How will you summarize the characteristics of the lipoproteins?

Characteristics Chylomicron HDL LDL VLDL
Plasma appearance Creamy layer, slightly turbid Clear Clear or yellow-orange tint Turbid to opaque
Size (diameter nm) >70.0 4 to 10 19.6 to 22.7 25 to 70
Electrophoretic mobility Origin α – region β – region Pre-β-region
Molecular weight 0.4 to 30 x 109 3.6 x 109 2.75 x 109 5 to 10 x 109
Synthesized in (Tissue of origin) Intestine Intestine and liver Intravascular Liver and intestine
Composition by weight in %
                     Cholesterol esterified 5 38 49 11 to 14
                    Cholesterol unesterified 2 10 13 5 to 8
                    Triglycerides 84 9 11 44 to 60
                    Phospholipids 7 22 27 20 to 23
                    Proteins 2 21 23 4 to 11
Triglycerides Markedly raised Normal Normal/ Raised Moderately to Markedly raised
Clinical significance of Pancreatitis and acute abdomen Decreased risk of CAD Increased risk of CAD Increased risk of CAD
Functions Transport dietary lipids to tissue Carry cholesterol from tissue to liver Carries cholesterol to tissue Transport endogenous TG from the liver to adipose tissue

Questions and answers:

Question 1: What is the role of HDL.
Show answer
It prevents atherosclerosis.
Question 2: What is the role of LDL.
Show answer
It increases atherosclerosis and coronary artery disease.

Possible References Used
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