Some Pathophysiology

The normal function of lipoproteins is to distribute and recycle cholesterol. The pathways of lipid metabolism and transport and their primary (inherited) disorders appear in Figure 25.1 and can be summarised thus:

• Cholesterol is absorbed from the intestine and transported to the liver by chylomicron remnants, which are taken up by the low-density lipoprotein (LDL)-receptor-related protein (LRP).

• Cholesterol is then transported to peripheral tissues where, for example, it is converted to steroid hormones or used to form cell walls and membranes. Hepatic cholesterol enters the circulation as very-low-density lipoprotein (VLDL) and is metabolised to remnant lipoproteins after lipoprotein lipase removes triglyceride. The remnant lipoproteins are removed by the liver through apolipoprotein E-receptors or LDL-receptors (LDL-R) or further metabolised to LDL and then removed by peripheral tissues or the liver by LDL-R.

• The quantity of cholesterol transported from the liver to peripheral tissues greatly exceeds its catabolism there and mechanisms exist to return cholesterol to the liver. Through this 'reverse transport', cholesterol is carried by high-density lipoprotein (HDL) from peripheral cells to the liver where it is taken up by a process involving hepatic lipase. Cholesterol in the plasma is also recycled to LDL and VLDL by cholesterol-ester transport protein (CETP).

• Cholesterol in the liver is reassembled into lipoproteins, or secreted in bile then recycled by absorption at the terminal ileum or excreted in the faeces.

Disorders of lipid metabolism are manifest by elevation of the plasma concentrations of the various lipid and lipoprotein fractions (total and LDL cholesterol, VLDL, triglycerides, chylomicrons) and they result, predominantly, in cardiovascular disease.

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