Hypercholesterolemia high blood cholesterol

The measurement of serum cholesterol is one of the most common tests performed in the clinical laboratory. Hypercholesterolemia (high blood cholesterol levels) can be the result of a variety of medical conditions. Among the conditions implicated are diabetes mellitus, atherosclerosis, and diseases of the endocrine system, liver, or kidney. High blood cholesterol levels do not point to a specific disease determination of cholesterol is used in conjunction with other clinical measurements mainly for confirmation of a particular diseased condition, rather than for diagnosis of a specific ailment. 

Drugs that inhibit HMG-CoA reductase have been developed for the treatment of hypercholesterolemia (high blood cholesterol). These drugs are based on a class of fungus-derived molecules called statins. One such chemical stmcture is shown in Fig. 12-12 note how part of the molecule is similar in shape to HMG-CoA, and it is via this moiety that it binds to HMG-CoA reductase. 

A proper balance of cholesterol in the bloodstream requires having an adequate balance of receptors to process the amount of cholesterol in the blood. Receptors are continually regenerated, produced, and disappear in the cell in response to blood biochemistry. The liver contains the greatest concentration of receptors. Too few receptors or excess dietary cholesterol intake can lead to elevated blood cholesterol. A genetic disorder called familial hypercholesterolemia results when a person inherits a defective gene from one parent resulting in the inability to produce sufficient receptors. A diet with too much cholesterol represses the production of LDL receptors and leads to high blood cholesterol and Apo B. 

Hypercholesterolemia—Hereditary olemia—high blood cholesterol levels-to the development of gallstones. 

The answer is D. This patient s tests indicate that he has severe hypercholesterolemia and high blood pressure in conjunction with atherosclerosis. The deaths of several of his family members due to heart disease before age 60 suggest a genetic component, ie, familial hypercholesterolemia. This disease results from mutations that reduce production or interfere with functions of the LDL receptor, which is responsible for uptake of LDL-cholesterol by liver cells. The LDL receptor binds and internalizes LDL-choles-terol, delivers it to early endosomes and then recycles back to the plasma membrane to pick up more ligand. Reduced synthesis of apoproteins needed for LDL assembly would tend to decrease LDL levels in the bloodstream, as would impairment of HMG CoA reductase levels, the rate-limiting step of cholesterol biosynthesis. Reduced uptake of bile salts will also decrease cholesterol levels in the blood. 

HMG CoA reductase can be inhibited therapeutically by administering the drug lovastatin, based on the fungal products mevinolin and compactin, which competitively inhibit the enzyme and hence decrease the rate of cholesterol biosynthesis. Therefore, these compounds are routinely used for the treatment of hypercholesterolemia (high levels of blood cholesterol) (see Topic K6). 

The NCEP/Expert Panel on Blood Cholesterol Levels in Children and Adoiescents and the American Academy of Pediatrics defined high cholesterol as concentrations more than the 95th percentile for total and LDL cholesterol in children and adolescents from families with hypercholesterolemia or premature vascular disease (see Table 26-18). Borderline total and LDL cholesterol concentrations are defined as values between the 75th and 95th percentiles. The NCEP panel referred to total and LDL cholesterol values below the 75th percentile as "desirable. Low HDL cholesterol was also defined as a concentration below 35 mg/dL. Children tend to have higher HDL cholesterol concentra-... 

In addition to diabetes mellitus, Mr. Applebod has a hyperlipidemia (high blood lipid level—elevated cholesterol and triacylglycerols), another risk factor for cardiovascular disease. A genetic basis for Mr. Applebod s disorder is inferred from a positive family history of hypercholesterolemia and premature coronary artery disease in a brother. 

The causal relationship between low bile acid production and high serum cholesterol in familial hypercholesterolemia remains unknown. It can be postulated that they are not associated initially, particularly because augmented conversion of cholesterol to bile acids is not able to normalize the serum cholesterol level. On the other hand, it can be speculated that cholestyramine treatment, for instance, stimulates cholesterol production by hepatocytes so that subnormal amounts of newly synthesized cholesterol are utilized for bile acid synthesis, a relatively large amount being released as lipoproteins into the bloodstream so that blood cholesterol still remains high. 

Diet, genetic inheritance, or both may cause hypercholesterolemia (high cholesterol). Familial hypercholesterolemia is caused by mutations in several genes. These mutations cause a decrease in the number of low-density lipoprotein receptors (LDLR), the main carrier of cholesterol in the blood. The condition is more prevalent in Afrikaner, Finnish, French Canadian, and Lebanese populations. However, the majority of hypercholesterolemia is caused by lifestyle choices—diet, exercise, and smoking. (USNLM, 2007). 

Because elevated blood cholesterol concentrations, which cause heart attacks in the victims, are directly related to high LDL levels, the removal of LDL-cholesterol in the extracorporeal shimt effects considerable relief from hypercholesterolemia. After saturation, the immimosorbent anti-LDL column is removed from the extracorporeal shunt and regenerated by elution of the LDL with glycine-HCl buffer at pH 3.0 (see Fig. 3). 

Hypercholesterolemia Metabolic disease in which the patient has increased levels of blood cholesterol (>200-240 mg/dL). The high levels of cholesterol increase the risk of atherosclerosis and cardiovascular diseases due to the formation of plaques in the walls of arteries. These diseases worsen when the levels of LDL are increased. 

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