Pathophysiology

Pathophysiology of Dyslipidaemia and Hyperlipidaemia
Dyslipidaemia is a term used to describe abnormal concentrations of blood lipids or lipoproteins. Hyperlipidaemia describes elevated blood triglyceride or cholesterol concentrations. There are several forms of dyslipidaemia and hyperlipidaemia which are dependent on the specific lipid or lipoprotein that is abnormal. Additionally, several dyslipidaemias and hyperlipidaemias have been identified as contributing to atherosclerotic disease.

Lipids are macromolecules that include fats, fatty acids, cholesterol and triglycerides. Among other things help to regulate metabolism and play a vital role in the structure of cell membranes. Lipids are not water soluble, as such they need to be transported as a lipoprotein. A lipoprotein is spherical in shape and consists of a lipid core that contains phospholipid, cholesterol and triglyceride which is surrounded by an apolipoprotein to provide water solubility.

Lipoproteins are classified into four major groups based on differing densities due to various combinations of apolipoprotein, phospholipid, cholesterol and triglyceride. Triglyceride and cholesterol move between the intestine, liver and peripheral tissue with the assistance of lipoproteins. Chylomicrons, VLDL and LDL are involved in transporting lipids from the liver to peripheral tissue. On the other hand HDL is involved in transporting lipids from peripheral tissue to the liver (reverse transport). See here for more videos
 * Chylomicrons: derived from intestinal absorption of exogenous triglyceride.
 * Very low density lipoprotein (VLDL): synthesised in the liver and is the primary transport for endogenous triglyceride.
 * Low density lipoprotein (LDL): the principle transport mechanism of cholesterol and also represents the final catabolism of VLDL
 * High density lipoprotein (HDL): responsible for the reverse transport of cholesterol.

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 * Types of Dyslipidaemia and Hyperlipidaemia**

Dyslipidaemias and hyperlipidaemias can be classified depending on which lipid or lipoprotein is abnormal**.** Dyslipidaemias and hyperlipidaemias can be categorised into four major groups; hypercholesterolaemia, hypertriglyceridaemia, hyperlipoproteinaemia and hypolipoproteinaemia**.**
 * **Hypercholesterolaemia:** Defined as blood cholesterol concentration levels >240mg/dL.
 * **﻿**Familial hypercholesterolaemia
 * Familial polygenic hypercholesterolaemia
 * Familial combined hypercholesterolaemia
 * **Hypertriglyceridaemia:** Any elevated fasting triglyceride concentrations. This may be caused by exogenous triglycerides or endogenous triglycerides synthesised in the liver.
 * Apolipoprotein E2 genotype
 * Familial lipoprotein lipase deficiency
 * Familial hypertriglyceridaemia
 * **Hyperlipoproteinaemia:** A generic term to describe any form of elevated lipoprotein concentration. This may be the result of genetics, co-morbidities or lifestyle factors.
 * Hyper-β-lipoproteinaemia
 * Hyper-α-lipoproteinaemia
 * **Hypolipoproteinaemia:** A generic term to describe any form of low lipoprotein concentration**.** As with hyperlipoproteinaemia this form of dyslipidaemia may be the result of genetics, co-morbidities or lifestyle factors.
 * A-β-lipoproteinaemia
 * Familial hypo-β-lipoproteinaemia
 * Hypo-α-lipoproteinaemia

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 * Atherosclerotic Disease**

Factors such as genetics and lifestyle affect the levels of blood lipids and lipoproteins which are positively correlated with a change in coronary heart disease (CHD) risk. Elevated LDL and to a lesser extent VLDL have been strongly correlated and atherosclerotic build up. It has been identified that LDL levels >180 mg/dL (>4.6 mmol/L) progressively increase the risk of CHD.

The atherosclerotic process begins with trauma caused to the endothelial wall of blood vessels by genetic and lifestyle factors such as elevated LDL levels. This trauma causes the endothelial wall to become more adhesive which allows LDL to attach to the endothelial wall. This is mainly seen in sites of increased blood turbulence, that includes bifurcations and curvatures of blood vessels. As LDL attaches to the walls of endothelial tissue, macrophages oxidise the LDL causing the beginning formation of foam cells. As LDL continue to migrate to the foam cells, there is a proliferation of smooth muscle cells which results in fatty streaks appearing on the endothelial wall. As this cycle of LDL accumulation in the foam cells and smooth muscle cell proliferation continues, the fatty streaks mature into a fibrous lesion. This causes a protrusion into the lumen of the artery which results in the restriction of blood flow. As this cycle continues even further, the foam cells begin to crystallise at which point they can rupture, further increasing the atherosclerosis.

Certain dyslipidaemias such as hyper-α-lipoproteinaemia (elevated HDL) seem to have a beneficial effect on CHD. As mentioned in the above section HDL is involved in the reverse transport of cholesterol from the extrahepatic tissue to the liver. Cholesterol is collected from circulating LDL and possibly the fatty streaks from endothelial walls where it is transported to the the liver for catabolism. This process of reverse transport has a beneficial effect on CHD.

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