Cholesterol

DESCRIPTION: Cholesterol has a steroid structure and is a cyclic alcohol (5-cholesten-3-ol). The -OH group (position 3), double bonds in positions 5 and 6 and carbon in position 7 are responsible for cholesterol reactions. A part of cholesterol is taken into the body through food (100-500 mg per day) – this is the so-called exogenous cholesterol. This cholesterol is resorbed in the small intestine in the form of fatty acid esters and as such enters the composition of chylomicrons (1-3%). Cholesterol is found in the blood in a relatively high concentration (3.8 – 7.6 mmol/L) as free cholesterol (about 25%) and as cholesterol ester (about 75%). Most of the cholesterol is bound to beta-lipoproteins. In addition, cholesterol is created in the body. Cholesterol biosynthesis takes place in the liver (mostly – 1.5 g per day) and in extrahepatic tissues (about 0.5 g per day). In the liver, and mostly in the circulation, cholesterol is esterified. Cholesterol esterification is catalyzed by the enzyme acyl-cholesterol-acyltransferase (ACAT) in liver cells, adrenal cortex and artery walls, and by lecithin-cholesterol-acyltransferase (LCAT) in plasma. Cholesterol esters are broken down by lysosomal cholesterol-esterase. If lysosomal cholesterol-esterase is missing, there is an accumulation of cholesterol esters (Cholesterol ester storage disease). About 1/3 of cholesterol from the circulation is removed by the liver, where it is hydroxylated and converted into bile acids. Steroid hormones are also produced from cholesterol in the body. 60-80% of cholesterol esters are found in the circulation. In the blood, cholesterol is bound in lipoproteins – mostly in beta-lipoproteins. DETERMINATION: Colorimetric method for determination of cholesterol with cholesterol oxidase (CHOD-PAP) according to IFCC. Sample: Serum or plasma (heparin or EDTA) Sample stability is 7 days at 2°C – 8°C, several months at -20°C. CLINICAL SIGNIFICANCE: 1) Physiological variations of cholesterol in the serum The concentration of cholesterol in the serum depends on many factors. Estrogen hormones increase the synthesis of cholesterol, but they act even more in terms of excretion, so that they lower the concentration of cholesterol in the serum. This is why women have a lower cholesterol concentration until menopause. Serum cholesterol concentration depends on age and sex. A) After a meal (100 mg of cholesterol in food increases the concentration of cholesterol in the serum by 0.3 mmol/L (12 mg/dl). B) Starvation (cholesterol synthesis is reduced) C) Age D) Free cholesterol increases during pregnancy. Around the 30th. during the first week of pregnancy, cholesterol reaches its maximum value (20-25% above normal) E) A vegetable diet rich in unsaturated fats (e.g. sunflower oil) can lead to a decrease in serum cholesterol concentration (increased excretion of cholic acid into the bile) F) Foods rich in animal fats or foods rich in vegetable saturated fatty acids can cause an increase in serum cholesterol 2) Pathological changes in serum cholesterol concentration A) Increased cholesterol concentration values in: Acute tonsillitis / Amyloidosis / Atherosclerosis / Peripheral artery diseases / Diabetes mellitus / Familial hyper-alpha-lipoproteinemias / Forbes diseases / Gout / Hypercholesterolemia (Cholesterol 7.89 +/- 0.94 mmol/L) / Hyperlipoproteinemia type I, IIa, IIb, III, IV and V / Idiopathic hypercholesterolemia / Xanthomatosis / Multiple myeloma / Postmenopause / Secondary hyperlipoproteinemia Liver diseases: Acute and subacute necrosis of the liver / Biliary cirrhosis / Extrahepatic obstructions / Infectious hepatitis (mild form) / Laennec’s or alcoholic cirrhosis of the liver / Mild portal cirrhosis / Malignant neoplasms of the intrahepatic bile ducts / Obstructive jaundice / Primary biliary cirrhosis / von Gierk’s disease Kidney diseases: Glomerulonephritis (minimal changes) / IgA nephropathy / Nephritis in the nephrotic stage / Nephrotic syndrome Pancreatic diseases: Diabetes mellitus / Chronic pancreatitis (some cases) / After pancreatectomy Thyroid diseases: Hyperthyroidism / Hypothyroidism (in patients with TSH values >20 mU/L) / Myxedema. Heart diseases: Acute myocardial infarction / Atherosclerosis / Coronary artery diseases / Essential hypertension / Ischemic heart disease / Malignant hypertension. B) Lowered values of cholesterol concentration in: A-beta-lipoproteinemia (Bassen-Kornzweig syndrome) / Bacterial pneumonia / Patients with severe mental retardation / Cerebral infarction / Familial acyl-transferase deficiency / Nausea / Hemophilia / Hyperparathyroidism / Hyperthyroidism / Infectious mononucleosis / Malabsorption / Nicotinic acid in large doses / Rheumatoid arthritis / Acquired immunodeficiency syndrome (AIDS, AIDS) / Steatorrhea / Tangier disease (A-alpha-lipoproteinemia) / Estrogen therapies / Clofibrate and androsterone therapies / Cortisone and ACTH therapies / L-asparaginase therapies / Triparanol therapies (inhibits cholesterol synthesis) / Terminal stage uremia / Severe sepsis / Viral pneumonia Liver diseases (all severe liver damage): Acute and subacute liver necrosis / Infections associated with liver damage (e.g. viral hepatitis, yellow fever, etc.) / Congestive cardiac decompensation with severe liver congestion / Liver damage by zincophene, chloroform, carbon tetrachloride and phosphorus / Terminal portal cirrhosis. Anemia: Folic acid deficiency / Hemolytic anemia / Hypocholesterolemia (associated with a drop in hematocrit) / Pernicious anemia / Severe hypochromic anemia RISK FACTORS: Decreased values: – 4-methylaminoantipyrine (greater or = 120 mg/L) – Ascorbic acid (greater or = 50 mg/L) – Time of year: summer – Hospitalization – Methyldopa (greater or = 50 mg/L) – Stress – Physical exertion Increased values: – Alcoholism – Age – Starvation ) – Caucasians – Smoking – Sex – Pregnancy EFFECT OF DRUGS: Decreased values: acetylsalicylic acid, allopurinol, amikacin, aminoantipyrine, ampicillin, ascorbic acid, bromides, citrates, dipyrone, DTNB, fluorides, iodides, methylaminoantipyrine, methyldopa, nitrites, novaminsulfone, penicillamine, rifampin, sulfpyride, thiouracil Increased values: amphotericin, cefotaxime, dextran, digitonin, phenytoin, fluosol, iodates, chlorpromazine, corticosteroids, lipochrome, methotrexate, tetracyclines, vitamin D, vitomycin RESULT: The reference interval depends on sex, age and method of determination. The reference interval is displayed on each validated result.

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