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Cholesterol (Serum Cholesterol)

August 29, 2022Chemical pathologyLab Tests

Table of Contents

  • Serum Cholesterol
        • Sample
        • Precautions for serum cholesterol
        • Purpose of the test (Indications) for serum cholesterol
      • Pathophysiology of cholesterol
        • Sources of Cholesterol:
      • Cholesterol in the body and their calculation from LDL-cholesterol formula:
      • Cholesterol level changes in the body and its distribution along with other lipoproteins:
        • Cholesterol distribution in the lipoproteins:
      • Cholesterol absorption:
        • Cholesterol esterification: 
      • Biosynthesis of Cholesterol 
        • Cholesterol exists in two forms:
      • Cholesterol complications:
      • Cholesterol functions:
        • Normal Cholesterol level
          • Source 1 Adult
    • Cholesterol and its relation to heart disease:
        • ATP III (Adult treatment panel) recommendations for blood lipids  are:
        • Cholesterol and triglycerides risk factors for coronary artery disease (NCEP expert panel and ATP III guideline):
        • Optimal values of  lipids (ATP III guidelines):
        • Increased Cholesterol (Hypercholesterolemia):
        • Decrease Cholesterol (Hypocholesterolemia):
        • Prevention, recommendations, and treatment for the cholesterol level:
        • Risk factors  leading to heart diseases are:
        • Important:

Serum Cholesterol

Sample

  1. The best sample is after 12 hours of fasting, and that is the morning sample.
  2. The best sample is serum and separated within 2 hours of the collection.
  3. This test may be done on Serum or Plasma (EDTA) but not oxalate, citrate, or fluoride.
  4. The serum is stable at 4 °C for 5 to 7 days and 3 months at -20 °C.
  5. Avoid freezing and thawing.
  6. The result with EDTA plasma is 3% lower than serum.
  7. Sample with Cholesterol above 500 mg/dL should be diluted.

Precautions for serum cholesterol

  1. Try to separate serum or plasma from the cells within 2 hours.
  2. The best sample is after 12 to 14 hours of fasting.
  3. Pregnancy may give a high level.
  4. Drugs that may increase the level are anabolic steroids, corticosteroids, oral contraceptives, vitamin D, phenytoin, thiazide diuretics, and cyclosporin.
  5. Drugs that may decrease the level are captopril, colchicine, erythromycin, isoniazid (INH), lovastatin, neomycin, bile salt binding agents, androgens, niacin, and nitrates.

Purpose of the test (Indications) for serum cholesterol

  1. Cholesterol level is estimated to determine the coronary artery disease risk.
  2. This test may be needed to rule out hyperlipidemia.

Pathophysiology of cholesterol

  1. Total serum cholesterol comprises all of the Cholesterol found in the various lipoprotein.
  2. Cholesterol is an organic molecule, is sterol or modified steroid, a type of lipid.
  3. This is an essential part of all cell membranes.
  4. Cholesterol is the major component of LDL and a minority part of VLDL and HDL.
  5. Cholesterol is the best-known steroid because of its association with atherosclerosis.
    1. Cholesterol has biochemical significance because this is the precursor for important steroids like bile acids, adrenocortical hormones, sex hormones, Vitamin D, cardiac glycosides, sitosterol of the plant kingdom, and some alkaloids.
  6. Cholesterol is steroid alcohol with 27 carbon atoms.
      1. Cholesterol is present virtually in all cells and body fluids.
    1. Cholesterol is absorbed in the diet and synthesized in the liver and gut.
      1. It is a precursor of steroid hormones, bile acids, sex hormones, and cellular membranes.

Sources of Cholesterol:

  1. Cholesterol sources:
    1. Exogenous sources are present in the diet, mainly from animal sources, and absorbed by the gastrointestinal tract.
    2. Endogenous sources are like the liver and other tissues.
      1. All the cells have the ability to synthesize Cholesterol, and 90% occur in the liver and intestines.
    3. Malnutrition will give low cholesterol formation.
Cholesterol sources

Cholesterol sources

Cholesterol sources and importance

Cholesterol sources and importance

Cholesterol in the body and their calculation from LDL-cholesterol formula:

  1. Three different lipoproteins carry Cholesterol in the fasting serum. So the total cholesterol sum equals the sum of these three components.
  2. Total cholesterol = HDL-cholesterol + VLDL-cholesterol + LDL-cholesterol
    1. The amount of Cholesterol in the HDL fraction can be found by precipitating from the serum.
    2. The level of Cholesterol in VLDL = Triglycerides/5
      1. This formula works in the fasting sample and when:
        1. The triglycerides are <400 mg/dL.
        2. No chylomicrons are seen.
        3. Does not work in type III dyslipidemia (β-VLDL).
  3. LDL – Cholesterol = The separation of LDL from the lipoproteins is very difficult, so the Friedewald equation is used, which is:
          1.  LDL-cholesterol = (Total cholesterol mg/dL) – (HDL-cholesterol mg/dL) – (triglycerides mg/dl)/5.
Serum Cholesterol: LDL - cholesterol calculation formula

Serum Cholesterol: LDL – cholesterol calculation formula

Cholesterol level changes in the body and its distribution along with other lipoproteins:

  1. There is day-to-day variation in the cholesterol level.
  2. This day-to-day variation may be seen in persons around 15%.
  3. An 8% difference can be found on the same day.
  4. There is a positional change in the level.
    1. The level may be decreased by as much as 15% in the recumbent position.
  5. There is a low level in the hospitalized patient.
  6. Because of these variations, two samples must be tested for heart disease risk.
  7. There is a decreased level of Cholesterol in acute MI, as much as 50% for 6 to 8 weeks.
cholesterol important facts

cholesterol important facts

cholesterol metabolism

cholesterol metabolism

Cholesterol distribution in the lipoproteins:

Type of lipoprotein Cholesterol Triglycerides Phospholipids Proteins
Chylomicron 3% to 5% 85% to 95% 5% to 10% 1% to 2%
HDL (High-density lipoprotein) 20% Very small amount 30% 50%
LDL (Low-density lipoprotein) 45% 5% to 10% 20% to 30% 15% to 25%
VLDL (Very-low-density lipoprotein) 10% to 15% 60% to 70% 10% to 15% 10%

Cholesterol absorption:

  1. The primary source of Cholesterol is diet. Another source is endogenous.
    1. Cholesterol is an important constituent in the assembly of the cell membrane.
    2. Cholesterol is the basic part of synthesizing bile acids and steroid hormones (cortisol, estrogen, androgen).
    3. In the normal biologic process, Cholesterol undergoes changes like synthesis, recycling, and degradation.
  2. Cholesterol enters the intestine from the following sources:
    1. For food like egg yolk, meat, fat-diary products, and seafood, the average amount is 400 to 700 mg/day.
      1. Plant sterols (200 to 300 mg) are ingested daily. These are poorly absorbed.
    2. Bile provides another fraction of Cholesterol.
    3. Intestinal secretions and turnover of the intestinal mucosal cells are other sources.
  3. Bile acids are detergents and are the most critical factor affecting micelles formation.
    1. In the absence of bile acids, digestion and absorption of Cholesterol and triglyceride are severely affected.
  4. Most absorption of Cholesterol takes place in the jejunum and ileum.
    1. When Cholesterol enters the intestinal cells, it is packaged with triglycerides, phospholipids, and apolipoprotein into large lipoproteins called chylomicrons.
    2. An increased amount of fat in the diet, particularly triglycerides 98%, will result in more micelles formation, allowing more Cholesterol to be solubilized and absorbed.
    3. Approximately 60% of the total Cholesterol in the male plasma is carried by LDL 22%, HDL 13%, and Chylomicrons 5%.
Cholesterol absorption

Cholesterol absorption

Cholesterol esterification: 

  1. Cholesterol, once formed, enters the blood circulation.
  2. Cholesterol is esterified and combined with apoprotein and apolipoprotein and ultimately carried as a lipoprotein.
    1. Cholesterol esterification helps in the packing of Cholesterol into lipoproteins.
    2. Both dietary and synthesized Cholesterol are converted to cholesteryl esters, easily packed into lipoproteins.
    3. Esterification increases the lipid carrying capacity of the lipoproteins in plasma and prevents the toxicity effect of Cholesterol.
  3. 75% bound to LDL.
  4. 25% bound to HDL.
Cholesterol esterification

Cholesterol esterification

Cholesterol esterification

Cholesterol esterification

Biosynthesis of Cholesterol 

  1. 90% of cholesterol synthesis takes place in the liver and gut.
  2. Cholesterol synthesis takes place in three stages.
  3. The starting molecule is acetate.
  4. All body cells have the ability to synthesize Cholesterol from Acetyl-CoA.
Cholesterol part of lipoprotein

Cholesterol part of lipoprotein

  1. Knowing the endogenous synthesis of Cholesterol, drugs are developed that lower the cholesterol level like mevastatin, lovastatin, simvastatin, pravastatin, and atorvastatin, which will suppress the HMG-CoA reductase.
Cholesterol biosynthesis

Cholesterol biosynthesis

Cholesterol exists in two forms:

  1. Free Cholesterol.
  2. Esterified Cholesterol.
    1. 75% to 85% of the total Cholesterol is in the form of esterified Cholesterol.
  3. Cholesterol can be derived from dietary sources like meat, eggs, butter, and plants.
    1. 30 to 60% of dietary Cholesterol is absorbed.
  4. Once Cholesterol is absorbed into the mucosal cells, it becomes part of the large micelle called Chylomicron.
Cholesterol importance

Cholesterol importance

Cholesterol complications:

  • Cholesterol’s main complication is atherosclerosis which leads to heart disease and stroke.
Cholesterol complications leading to heart disease and stroke

Cholesterol complications leading to heart disease and stroke

Cholesterol  distribution in other lipids of the body:

Cholesterol found in: Cholesterol % in other lipids
Chylomicron
  • 2%
VLDL
  • 5% to 8%
LDL
  • 13%
HDL
  • 6%

Cholesterol functions:

  1. Cholesterol is a blood lipid (fat).
  2. Cholesterol is a normal part of RBC.
  3. Cholesterol, when increased, leads to atherosclerosis and is the main lipid.
  4. A total raised level of Cholesterol is associated with an increased risk of cardiovascular disease. Its subtypes LDL-C and HDL-C are more important than the total Cholesterol.
Cholesterol functions

Cholesterol functions

  1. Cholesterol is the basic unit of hormone produced by adrenal glands, ovaries, and testes.
  2. Cholesterol is needed for bile acids and cellular membranes.
  3. Cholesterol is transported in circulation by carrier proteins.
    1. Cholesterol bound to high-density lipoprotein (HDL- cholesterol) is known as good Cholesterol. HDL  will prevent atherosclerosis.
    2. Cholesterol bound to low-density protein (LDL-cholesterol) is known as bad Cholesterol and increases atherosclerosis chances.
      1. Also, the same is Cholesterol bound to very low-density lipoprotein (VLDL) is bad Cholesterol.
    3. Increased Cholesterol level is associated with atherosclerosis and coronary vessel disease.
      1. It is needed to form steroids, sex hormones, and bile acids.
      2. This is the part of cellular membranes.
      3. It gives the risk of heart disease.

Normal Cholesterol level

Source 1
Adult
  1. The desired level to prevent coronary disease is < 200 mg/dl
  2. Moderate risk is 200-239 mg/dl
  3. High risk is > 240 mg/dl
  4. CSF <0.5 mg/dl

Source 2

Sample Male mg /dL  Female mg /dL
Cord blood 44 to 103 50 to 108
0 to 4 years 114 to 203 112 to 200
5 to 9 years 121 to 203 126 to 205
10 to 14 years 119 to 202 124 to 201
20 to 24 years 124 to 218 122 to 216
30 to 34 years 138 to 254 130 to 230
40 to 44 years 151 to 268 147 to 252
50 to 54 years 158 to 277 162 to 285
60 to 64 years 159 to 276 172 to 297
>70 years 144 to 265 173 to 280
  •  To convert into SI unit x 0.0259 = mmol/L

Cholesterol and its relation to heart disease:

  1. Desirable level is = < 170 mg/dl
  2. Moderate risk is = 170-199 mg/dl
  3. High risk is = > 200 mg/dl
  • Above 240 mg/dL   =  needs treatment.
  • Nowadays cardiology association recommends the level to be around 160 mg/dl.
Cholesterol mg/dL Risk
<160 Very low
160 to 199 low risk
200 to 239 moderate risk
240 to 279 high risk
>280 very high risk
  • According to the latest NHS research study, there is no relation between total cholesterol and heart disease risk.
    • https://www.nhs.uk/news/heart-and-lungs/study-says-theres-no-link-between-cholesterol-and-heart-disease/

ATP III (Adult treatment panel) recommendations for blood lipids  are:

Chemical substance (Lipid) Clinical effects on the people
Cholesterol
  1. Desirable level = <200 mg/dL
  2. Borderline level = 200 to 239 mg/dL
  3. High level            = >240 mg/dL
HDL
  1. Low level = <40 mg/dL
  2.  High level = >60 mg/dL
LDL
  1. Optimal level = <100 mg/dL
  2. Near-optimal =  100 to 129 mg/dL
  3. Borderline level = 130 to 159 mg/dL
  4. High level            = 160 to 189 mg/dL
  5. Very high             = >190 mg/dL

ATP  III (Adult treatment panel) LDL target level for coronary vascular disease:

Risk factors Details of risk factors The target LDL level required ( This level is mandatory)
  • Presence of coronary heart disease (CHD) or CHD-equivalent disease
CHD heart disease risk factors are:

  1. Diabetes
  2. Vascular diseases
  3. Noncoronary atherosclerosis
  4. Framingham risk of MI within 10 years of >20%
  • <100 mg/dL
  • 2 or more major risk  factors
Major risk factors including are:

  1. Smoking
  2. Hypertension >140/90 mmHg
  3. HDL <40 mg/dL
  4. Family H/O premature CHD
    1. Male first degree relatives = <55 years
    2. Female first degree relatives = <65 years
    3. Age men (>45 years), women (>55 years)
<130 mg/dL
<2 major risk factors <160 mg/dL

Framingham formula calculations (Risk score counting):

Risk factors Points for the calculation for women Points for the calculation for men
  1. Age  20 to 34 years
    1. Age 35 to 39 years
    2. Age 40 to 44 years
    3. Age 45 to 49 years
    4. Age 50 to 54 years
    5. Age 55 to 59 years
    6. Age 60 to 64 years
    7. Age 65 to 69 years
    8. Age 70 to 74 years
    9. Age 75 to 79 years
  1.  -7 points
  2. -3 points
  3. 0 point
  4. 3 points
  5. 6 points
  6. 8 points
  7. 10 points
  8. 12 points
  9. 14 points
  10. 16 point
  1. -9 points
  2. -4 points
  3. 0 points
  4. 3 points
  5. 6 points
  6. 8 points
  7. 10 points
  8. 11 points
  9. 12 points
  10. 13 points
  1. Total cholesterol: age 20 to 39 years  cholesterol level is <160 mg/dL
    1. 160 to 199 mg/dL
    2.  200 to 239 mg/dL
    3.  240 to 279 mg/dL
    4.  28o or higher mg/dL
  2. Total cholesterol Age 40 to 49 years = <160 mg/dL
    1.  160 to 199 mg/dL
    2.  200 to 239 mg/dL
    3.  240 to 279 mg/dL
    4. 280 or higher mg/dL
  3. Total cholesterol Age 50 to 59 years  cholesterol < 160 mg/dL
    1. 160 to 199 mg/dL
    2. 200 to 239 mg/dL
    3. 240 to 279 mg/dL
    4. 280 or higher or mg/dL
  4. Total cholesterol Age 60 to 69 years cholesterol < 160 mg/dL
    1. 160 to 199 mg/dL
    2. 200 to 239 mg/dL
    3. 240 to 279 mg/dL
    4. 280 or higher mg/dL
  5. Total cholesterol Age 70 to 79 years cholesterol < 160mg/dL
    1. 160 to 199 mg/dL
    2. 200 to 239 mg/dL
    3. 240 to 279 mg/dL
    4. 280 or higher mg/dL
  1. 0 point
    1. 4 points
    2. 8 points
    3. 11 points
    4. 13 points
  2. 0 point
    1. 3 points
    2. 6 points
    3. 8 points
    4. 10 points
  3. 0 point
    1. 2 points
    2. 4 points
    3. 5 points
    4. 7 points
  4. 0 point
    1. 1 point
    2. 2 point
    3. 3 points
    4. 4 points
  5. 0 point
    1. 1 point
    2. 1 point
    3. 2 points
    4. 2 points
  1. 0 point
    1. 4 points
    2. 7 points
    3. 9 points
    4. 11 points
  2. 0 point
    1. 3 points
    2. 5 points
    3. 6 points
    4. 8 points
  3. 0 point
    1. 2 points
    2. 3 points
    3. 4 points
    4. 5 points
  4. 0 points
    1. 1 point
    2. 1 point
    3. 2 points
    4. 3 points
  5. 0 point
    1. 0 point
    2. 0 point
    3. 1 point
    4. 1 point
  1. Cigarette smoking  age: 20 to 39 years
    1. Age 40 to 49 years
    2. Age 50 to 59 years
    3. Age 60 to 69 years
    4. Age 70 to 79 years
  1. 9 points
  2. 7 points
  3. 4 points
  4. 2 points
  5. 1 point
  1. 8 points
  2. 5 points
  3. 3 points
  4. 1 point
  5. 1 point
All non-smokers 0 point 0  point
  1. HDL  cholesterol  = 60 mg/dL or higher level
    1. 50 to 59 mg/dL
    2. 40 to 49 mg/dL
    3. <40 mg/dL
  1. -1 point
  2. 0  point
  3. 1 point
  4. 2 points
  1. -1 point
  2. 0 point
  3. 1 point
  4. 2 points
  1. Systolic blood pressure untreated under 120 mmHg
    1. 120 to 129 mmHg
    2. 130 to 139 mmHg
    3. 140 to 159 mmHg
    4. 160 or higher mmHg
  2. Treated cases of blood pressure  under 120 mmHg
    1. 120 to 139 mmHg
    2. 130 to 139 mmHg
    3. 140 to 159 mmHg
    4. 160 or higher mmHg
  1. 0 point
    1. 1 point
    2. 2 points
    3. 3 points
    4. 4 points
  2. o point
    1. 3 points
    2. 4 points
    3. 5 points
    4. 6 points
  1. 0 point
    1. 0 point
    2. 1 point
    3. 1 point
    4. 2 point
  2. 0 point
    1. 1 point
    2. 2 point
    3. 2 point
    4. 3 point

10 years risk for cardiovascular diseases according to Framingham risks in %:

Total points %  Framingham score (risk) 
0 point <1%
1 to 4 points 1%
2 points 5% to 6%
7 points 3%
8 points 4%
9 points 5%
10 points 6%
11 points 8%
12 points 10%
13 points 12%
14 points 16%
15 points 20%
16 points 25%
17 points >30%

Total Cholesterol relation to coronary artery disease:

  1. Another source:
  2. Desirable level = <200 mg/dL
  3. Borderline level = 200 to 239 mg/dL
  4. High Risk level = >240 mg/dL

Cholesterol and triglycerides risk factors for coronary artery disease (NCEP expert panel and ATP III guideline):

Risk factors grades Total cholesterol Total triglycerides Total cholesterol/HDL-C ratio LDL/HDL ratio
Normal or low risk <200 mg/dL <150 mg/dL 3.3 to 4.4

0.5 to 3.0

 

Average risk (>optical risk) 150 to 190 mg/dL 4.4 to 7.1
Moderate or borderline risk 200 to 239 mg/dL 200 to 499 mg/dL 7.1 to 11.0 3.0 to 6.0
High-risk group >240 mg/dL >500 mg/dL >11.0 >6.0

Optimal values of  lipids (ATP III guidelines):

Risk level LDL cholesterol Total cholesterol Triglycerides HDL cholesterol
Optimal fasting values <1000 mg/L <2000 mg/L <150o mg/L >400 mg/L
Near-optimal fasting level 1000 to 1290 mg/L
Borderline high fasting level 1300 to 1590 mg/L
High fasting level 1600 to 1890 mg/L
Very high fasting level >1900 mg/L

Increased Cholesterol (Hypercholesterolemia):

  1. Familial combined hyperlipidemia.
  2. Hyperlipoproteinemia type, 1V, V.
  3. Intra- and extrahepatic cholestasis.
  4. Glomerulonephritis.
  5. Nephrotic syndrome and chronic renal failure.
  6. Malignant neoplasm of pancreas and prostate.
  7. Hypothyroidism.
  8. Gout.
  9. Diabetes mellitus.
  10. Alcoholism.
  11. Glycogen storage disease type 1 (Von Gierke disease).
  12. Stress.
  13. Biliary cirrhosis.

Decrease Cholesterol (Hypocholesterolemia):

  1. alpha-Lipoprotein deficiency.
  2. Hepatocellular necrosis.
  3. Malignant neoplasm of the liver.
  4. Hyperthyroidism.
  5. Malabsorption and malnutrition (starvation).
  6. Severe acute illness.
  7. Extensive burns.
  8. Rheumatoid arthritis.
  9. Cholesterol-lowering medications.

Prevention, recommendations, and treatment for the cholesterol level:

Total cholesterol <200 mg/dL
  • Check after 5 years
Total cholesterol 200 to 239 mg/dL
  1. 0 to 1 risk factor and no coronary disease.
  2. Needs diet control and repeat the test after one year.
Total cholesterol >240 mg/dL
  • Diet control and drugs intervention

Risk factors  leading to heart diseases are:

  1. Cigarette smoking.
  2. Cerebrovascular disease.
  3. Diabetes mellitus.
  4. Hypertension.
  5. The family history of coronary heart disease.
  6. Sex as in male.
  7. Overweight >30%
  8. peripheral occlusive vascular disease.

Important:

    • There is variation in the level of Cholesterol so take at least two samples.
    • Critical value = >500 mg/dL.
      Chemical substance Panic value (critical value)
      Cholesterol >240 mg/dL (>500 mg/dL)
      HDL-cholesterol <40 mg/dL
      LDL- cholesterol >160 mg/dL
      Triglycerides >500 mg/dL

Possible References Used
Go Back to Chemical pathology

Comments

Roland Freiler Reply
September 22, 2020

I agree with you

Dr. Riaz Reply
September 22, 2020

Thanks

Lipids Total, Lipids Role in Our Body – Labpedia.net Prof. Riaz Reply
December 9, 2021

[…] the liver, cholesterol, and triglycerides are packed into another type of lipoprotein called  Very low-density […]

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