Hyperlipidemias: Types, Causes, Manifestations - PDF

**HYPERLIPIDEMIAS** The most widely accepted Frederickson\'s classification is shown in Table 25.4. In all cases of hyperlipidemias, the elevated lipid fraction is either cholesterol or TAG or both. Hence from a clinical and therapeutic point of view, hyer-lipidemias are classified into, hyperchole...

**HYPERLIPIDEMIAS** The most widely accepted Frederickson\'s classification is shown in Table 25.4. In all cases of hyperlipidemias, the elevated lipid fraction is either cholesterol or TAG or both. Hence from a clinical and therapeutic point of view, hyer-lipidemias are classified into, hypercholesterolemia (Type IIa), hypertriglyceridemia (Type I, IV and V) and combined hyperlipidemia (Type IIb and Type III). The elevation of lipids in plasma leads to the deposition of cholesterol on the arterial walls, leading to atherosclerosis (see under Coronary Artery Diseases). The coronary and cerebral vessels are more commonly affected. Thromboembolic episodes in these vessels lead to ischemic heart disease and cerebrovascular accidents. The deposition of lipids in subcutaneous tissue leads to xanthomas. The type of xanthoma depends on the nature of lipid deposited. Eruptive xanthomata are small yellow nodules associated with deposition of triglycerides. They disappear when the lipid level falls. Tuberous xanthomata are yellow plaques containing triglycerides and cholesterol, found mainly over the elbows and knees. Xanthelasma are lipid deposits under the periorbital skin and contain mainly cholesterol. Tendinous xanthomata are found over the tendons. Deposits of lipids in cornea lead to corneal arcus; indicating hyper cholesterolemia. Hyperlipidemias, in the order of highest to lowest incidence, are described below. **Type II A** **(Primary familial hypercholesterolemia)** There is elevation of LDL. Patients seldom survive the second decade of life due to ischemic heart disease (Table 25.4). The cause is LDL receptor defect. Receptor deficiency in liver and peripheral tissues will result in the elevation of LDL levels in plasma, leading to hypercholesterolemia. The LDL receptor defect may be due to the following reasons: 1\. LDL receptor deficiency. 2\. Defective binding of B-100 to the receptor. A substitution of glutamine for arginine at 3500^th^ amino acid results in poor binding to LDL receptors. This defect is known as B-3500 or familial defective apo-B. 3\. Receptor-LDL complex is not internalised. Secondary type II hyperlipoproteinemia is seen in hypothyroidism, diabetes mellitus, nephrotic syndrome and cholestasis (Table 25.5). **Type II B hyperlipoproteinemia** There is elevation of both cholesterol and triglycerides with excessive production of apo-B. Therefore, LDL and VLDL are elevated. The abnormalities are manifested only by the third decade of life. Type IV (familial endogenous type) This is due to overproduction of triglycerides by liver. The VLDL level in plasma is elevated. Cardiac manifestations are seen in the 4th decade of life. It may be associated with diabetes mellitus, obesity and impaired glucose tolerance. **Type I** It is rare. It is due to lipoprotein lipase deficiency. It usually manifests in young age. A chylomicron band in fasting plasma is the characteristic finding. Hepatomegaly, eruptive xanthoma and abdominal pain are seen (Table 25.4). **Type III** It is very rare. It is due to increased levels of LDL and IDL. Beta lipoprotein floats on ultra centrifugation and a broad beta band is observed on electrophoresis (see Table 25.4). Palmar xanthomas and vascular disease are noticed. **Type V** Chylomicrons and VLDL are increased. Hypertriglyceridemia, usually secondary to other disorders like obesity, excessive alcohol intake, renal failure, pancreatitis, etc. are common (see Table 25.5). Other causes of hyperlipoproteinemias include hepatic lipase defect, LCAT defect and Lp(a) excess and Wolman\'s disease (Table 25.6).