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

January 3, 2023Chemical pathologyLab Tests

Table of Contents

  • High-Density Lipoprotein (HDL)
      • Sample for High-Density Lipoprotein (HDL)
      • Precautions for High-Density Lipoprotein (HDL)
      • Purpose of the test (Indications) for High-Density Lipoprotein (HDL)
    • Pathophysiology of Lipoproteins 
      • Summary of the lipoproteins:
  • High-density lipoprotein (HDL):
      • Functions of High-density lipoprotein (HDL) function:
      • The total cholesterol/HDL-cholesterol ratio:
      • Normal High-density lipoprotein (HDL):
      • Abnormal values of HDL:
      • Increased High-Density Lipoprotein (HDL)-C value is seen in:
      • Decreased High-Density Lipoprotein (HDL)-C values are seen in:
      • Table showing the summary of characteristics of the lipoproteins:
      • Questions and answers:

High-Density Lipoprotein (HDL)

Sample 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. Can store serum or plasma at 4 °C for 4 days (can keep for 5 to 7 days).

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.

Purpose of the test (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.

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

  1. Lipoprotein is classified by 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, are the primary carrier of cholesterol.
      2. It arises primarily from the degradation of VLDL into LDL1, and it is 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 carries 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.
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. While lipids like cholesterol and triglycerides are hydrophobic and need to 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

Summary of the 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
  • Triglyceride = 90%
  • 1%
  • Intestine
  • Transport dietary lipids to various body tissues
LDL
  • B-100
  • β
  • Cholesteryl- ester = 45%
  • 20%
  1. The primary site is 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
  • Triglyceride = 55%
  • 10%
  1. The primary site is 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
  • Phospholipids =30%
  • 50%
  • The main site of origin is 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 is composed of 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%), and it is 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 where it is excreted in the bile.
    1. HDL transports cholesterol to the liver, where cholesterol serves as 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 through the mechanism of LDL moving cholesterol into the arteries and HDL removing it from the arteries.
    3. HDL-C is good cholesterol and is proportional to coronary artery disease (CAD) risk.
High density lipoprotein (HDL) function

High-density lipoprotein (HDL) function

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

Functions of High-density lipoprotein (HDL) function:

  1. HDL is the carrier of cholesterol from the peripheral tissue.
  2. From peripheral tissue, HDL carries cholesterol to the liver for excretion in the bile, 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.

Table showing HDL and its relationship with 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

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.

 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.

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 454 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

Increased High-Density Lipoprotein (HDL)-C value is seen in:

  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.

Decreased High-Density Lipoprotein (HDL)-C values are seen in:

  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.

Table showing the summary of 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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