Classification and types of hyperlipoproteinemias
The historical classification was developed in 1967 by Fredrickson and co-authors, and later revised by WHO experts. It is based on plasma total cholesterol and triglyceride levels, as well as the distribution of lipoprotein fractions using electrophoresis and ultracentrifugation. There are 5 main types of disorders in total.
Depending on their ability to cause vascular pathologies, lipoproteins are divided into two groups:
- Atherogenic (contribute to the development of atherosclerosis): VLDL, LDL, and IDL.
- Anti-atherogenic (prevent the pathology): HDL.
The anti-atherogenic effect of HDL is provided through reverse cholesterol transport from cell membranes to the liver, as well as due to a high concentration of apoE, causing them to compete with LDL for cellular receptors.
Assessment of blood atherogenicity
To assess the risk of vascular catastrophes, the atherogenic index of plasma (AI) is used. It is calculated by the formula:
$$AI = \frac{\text{Total Cholesterol} - \text{HDL Cholesterol}}{\text{HDL Cholesterol}}$$
- Norm: values are $\le 3.0$.
- Pathology: when the indicator rises above 3.0, the risk of developing atherosclerosis increases sharply.
The course and clinical presentation of such disorders are influenced by three groups of factors: hereditary metabolic characteristics, environmental factors (diet and lifestyle), and concomitant diseases such as obesity, hypothyroidism, diabetes mellitus, or liver pathologies.
Secondary forms and hereditary pathologies
Secondary disorders develop against the background of other diseases. For example, in diabetes mellitus, lipoprotein lipase activity drops and VLDL synthesis increases, while in chronic alcoholism, a similar enzymatic inhibition and increased lipoprotein synthesis are observed.
Among hereditary combined forms, abetalipoproteinemia is distinguished, associated with a mutation in the apoB gene. In this condition, beta-lipoproteins, chylomicrons, and LDL with VLDL are completely absent in the blood. This leads to severe consequences:
- The appearance of acanthocytes — erythrocytes with spiky projections.
- Deficiency of vitamins E and A due to impaired transport.
- Steatorrhea and impaired fat absorption in the gastrointestinal tract.
- Demyelination of nervous system axons, leading to ataxia.
Briefly: answers to topical questions
What types of hyperlipoproteinemias are distinguished according to the Fredrickson classification?
According to the Fredrickson classification, 5 main types of hyperlipoproteinemias are distinguished. They differ in total cholesterol, triglycerides, and the distribution of lipoprotein fractions:
- Type I (includes variants IA and IB);
- Type II (typical of familial hypercholesterolemia);
- Type III (familial combined hyperlipidemia associated with impaired clearance of remnant lipoproteins);
- Type IV (familial hypertriacylglycerolemia);
- Type V (familial hypertriacylglycerolemia).
Hereditary defects and acquired diseases (e.g., diabetes mellitus, nephrotic syndrome) can lead to the development of various types of dyslipoproteinemias.
Which enzymes are involved in the metabolism of lipoproteins in blood plasma?
Literature on lipid metabolism indicates the following enzymes associated with lipoprotein metabolism:
- Lecithin-cholesterol acyltransferase (LCAT, LCAT);
- Hepatic lipase (HL);
- Lipoprotein lipase (LPL, including blood lipoprotein lipase).
For lipoprotein lipase, its clinical significance is noted: a decrease in its activity is observed in diabetes mellitus and chronic alcoholism as a mechanism of secondary lipid metabolism disorders. Activation of blood lipoprotein lipase is cited as an example of metabolic correction in hypercholesterolemia.
Through which receptors is LDL uptake by cells carried out?
The uptake of low-density lipoproteins by cells is carried out mainly via specialized LDL receptors.
- LDL receptors provide the main pathway for particle uptake via endocytosis. These receptors selectively recognize apolipoproteins apoB-100 and apoE, which are present on the surface of LDL particles.
Mutations in the LDL receptor protein gene impair its ability to undergo endocytosis after interacting with lipoproteins. Such structural damage to the receptor leads to the development of familial hypercholesterolemia and premature atherosclerosis.
AI = (Total cholesterol minus HDL) divided by HDL. Normal value is up to 3.0 — anything above three leads to atherosclerosis.
Class and exam questions
Which lipoproteins are considered atherogenic?
Atherogenic fractions include very low-density lipoproteins (VLDL), intermediate-density lipoproteins (IDL), and low-density lipoproteins (LDL).
What is the protective mechanism of HDL?
HDL perform reverse transport of excess cholesterol from cells to the liver for excretion with bile, and also compete with LDL for receptors due to their high apoE content.
What are the main manifestations of abetalipoproteinemia?
The pathology manifests as the absence of beta-lipoproteins and chylomicrons in the blood, the appearance of acanthocytes, steatorrhea, fat-soluble vitamin deficiency, and demyelination of nervous system axons.
What else to study on this topic
- History of the development of the Fredrickson classification and the ultracentrifugation method
- Detailed analysis of the distribution table of chylomicron remnants by HLP type
- Molecular mechanisms of Tangier disease development and foam cell accumulation
- Effect of hypothyroidism and nephrotic syndrome on lipid catabolism
- Nervous system and visual organ disorders in apoB deficiency
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