Patients with lipid disorders have problems maintaining normal body fat (cholesterol) levels. The most common lipid disorders; It is excess cholesterol, excess triglyceride, or low protective cholesterol (HDL Cholesterol). High levels of this fat are associated with heart (coronary) disease, stroke, and peripheral vascular disease (circulatory problems in the legs). Endocrinologists are trained to detect hypothyroidism (low thyroid hormone), medication use (such as cortisone), genetic or metabolic conditions that may be associated with lipid disorders. Lipid disorders may coexist with conditions such as diabetes, metabolic syndrome, polycystic ovarian syndrome (PCOS) and obesity that require special management. Special diets, exercise and medications can be applied to treat hyperlipidemia and other lipid disorders.
Lipids are fats absorbed from foods or synthesized by the liver. Although all lipids are physiologically important, high triglyceride (TG) and cholesterol levels cause diseases. The primary function of triglycerides is to store energy in adipocytes and muscle cells. If it is cholesterol. It is a common component of cell membranes, steroids, bile acids and signaling molecules. All lipids are hydrophobic and mostly insoluble in blood. Therefore, they must be transported in hydrophilic and spherical structures called lipoproteins; Lipoproteins also have surface proteins (apoproteins) that are cofactors and ligands for lipid processing enzymes. Lipoproteins are classified according to their size and density (density is determined according to the ratio of lipid to protein) and are important because high levels of low-density lipoproteins (LDL) and low values of high-density lipoproteins (HDL) are the main risk factors in atherosclerotic heart diseases.
xogen. (dietary) lipid metabolism: more than 95% of dietary lipids are triglycerides; the rest are phospholipids, free fatty acids FFA), cholesterol (found in foods as esterified cholesterol) and fat-soluble vitamins. Dietary triglycerides are digested as monoglycerides (MG) and free fatty acids (FFAs) in the stomach and duodenum, thanks to gastric and pancreatic lipases and peristalsis of the stomach. Cholesterol esters in the diet are also released by the same mechanism. It is also esterified to cholesterol. Following this process, monoglycerides (MG), free fatty acids (FFAs) and free cholesterol become soluble in the intestine thanks to bile acid micelles, which transport them to the intestinal villi for absorption. When absorbed from enterocytes, they are restructured as triglycerides and packaged with cholesterol into chylomicrons, the largest lipoprotein.
Chylomicrons transport dietary triglycerides and cholesterol from enterocytes through the lymphatics into the circulation. Apoprotein C-II (apo C-Il) on the chylonicron in the capillaries of adipose and muscle tissues. It activates endotellipoprotein lipase (LPL), which converts 90% of chylomicronTG into fatty acids and glycerol. Fatty acids and glycerol are retained by adipocytes and muscle cells for energy use and storage. Cholesterol-rich chylomicron residues then return to the liver, where they are cleared through a process dependent on apoprotein E (apo E).
Endogenous lipid metabolism: Lipoproteins synthesized by the liver, endogenous TG and cholesterol they carry. Lipoproteins continue to circulate in the blood until the TG they contain are taken up by surrounding tissues or are cleared in the liver. As they lose TG, they become more saturated with cholesterol, so factors that trigger hepatic lipoprotein synthesis lead to elevated plasma cholesterol.
Very-low-density lipoproteins (VLDL) contain apoprotein B-100 (apo B), are synthesized in the liver and They transport TG and cholesterol to surrounding tissues. VLDL is the liver's way of exporting excess TG obtained from plasma FFA and chylomicron residues. VLDL synthesis also increases when intrahepatic FFA increases, as in high-fat diets, and when excess adipose tissue puts FFA directly into the circulation (such as obesity, uncontrolled diabetes). Apo C-II on the surface of VLDL activates endothelial LPL to split TGs into FFA and glycerol, which are absorbed by cells.
Intermediate-density lipoproteins (IDL) are the products of LPL processing of VLDL and chylomicrons. IDLs are cholesterol-rich VLDL and chylomicron residues, which are either cleared by the liver or metabolized by hepaticlipase to LDL, which retains apo B.
Drop� High-density lipoproteins (LDL), VLDL and IDL are products of metabolism and have the richest cholesterol values of all lipoproteins. Approximately 40% of LDLs are cleared by the liver through a process initiated by Apo B and hepatic LDL receptors. The rest is retained by hepatic LDL or non-hepatic non-LDL (scavenger) receptors. Hepatic LDL receptors are reduced by the transfer of cholesterol to the liver by chylomicrons and high saturated fats in the diet; They may also increase with low dietary fats and cholesterol. Nonhepatic scavenger receptors, located most prominently on macrophages, take up excess oxidized circulating LDLs that are not processed by hepatic receptors. Oxidized-LDL-rich macrophages then migrate to the endothelium in response to endothelial inflammation or another stimulus and form foam cells in atherosclerotic plaques. There are two forms of LDL: large floating LDL and small dense LDL. Small, dense LDLs are rich in cholesterol esters and are linked to metabolic disorders such as hypertriglyceridemia, insulin resistance, and are particularly atherogenic. The high atherogenicity of small, dense LDLs is due to their less effective binding to hepatic LDL receptors, leading to longer retention in the circulation and increased oxidation by the endothelium.
High-density lipoproteins (HDL) are synthesized in the enterocytes and liver and They are lipoproteins that initially do not contain cholesterol. HDL metabolism is complex, but the most important role of HDL is to collect cholesterol from surrounding tissues and deliver it to areas where it is needed most, such as the liver, for clearance by other cells, other lipoproteins (using cholesteryl ester transfer proteins [CETP|). Its most important effect is that it is anti-atherogenic. The removal of free cholesterol from cells is ensured by the ATP-binding cassette transporter A 1 (ABCA1), which combines with apo A-I to produce “new” HDL. The free cholesterol in new HDL is esterified by the enzyme lecithin-cholesterol acyltransferase (LCAT) and produces mature HDL. HDL values in the blood may not fully reflect reverse cholesterol transport.
Lipoprotein(a) ILp(a)] contains apolipoprotein(a) and contains 5 cysteine-rich enzymes called kringle. It is defined by the gin region. One of these regions is homogeneous with plasminogen and is thought to competitively inhibit fibrinolysis and predispose to thrombus. Lp(a) can also directly stimulate atherosclerosis. The metabolic pathways of Lp(a) production and clearance are not well defined, but values are increased in diabetic nephtopathy patients.
What is Dyslipidemia (Hyperlipidemia)?
Dyslipidemia is elevation of plasma cholesterol and/or TGs or low HDL values that contribute to the development of atherosclerosis. Causes can be primary (genetic) or secondary. Diagnosis is made by calculating plasma values of total cholesterol, TG and lipoproteins. Treatment includes dietary changes, exercise and lipid-lowering medications.
There is probably a linear relationship between lipid values and cardiovascular risk. The strongest evidence of success in the treatment of hyperlipidemia is that the treatment reduces high LDL values. Treatment is less effective in reducing high TG values and increasing low HDL values; high TG and low HDL values are more obvious indicators of cardiovascular risk in women than in men.
The primary causes are overproduction and deficiency of TG and LDL cholesterol. These are single or multiple genetic mutations that cause HDL to be cleared or to under-produce and over-clear HDL (see the table below). Primary lipid disorders are suspected when a patient has physical signs of dyslipidemia, early onset of atherosclerotic disease (< 60 years of age), a family history of atherosclerotic disease, or serum cholesterol > 240 mg/dl (>6.2mmol/L). Although primary disorders are the most common causes of dyslipidemia in children, they are less common in adults.
Secondary causes are seen in many cases of dyslipidemia in adults. The most important secondary cause in developed countries is the intense intake of saturated fat, cholesterol and trans-fatty acids (TFA) into the body through diet and a sedentary lifestyle. TFAs are formed by adding hydrogen atoms to polyunsaturated fatty acids; They are commonly found in many processed foods and, as saturated fats, are atherogenic. Other common secondary causes: diabetes mellitus, high alcohol use, chronic renal failure, hypothyroidism, primary biliary cirrhosis, and other cholestatic liver diseases and medications (thiazides, beta blockers, retinoid, estrogen, progestin and glucocorticoids). Patients with high TG; Diabetes is a particularly important secondary cause as they tend to have atherogenic combinations such as high, small, dense LDL fractions and low HDL. Especially Type 2 diabetic patients are in the risk group. Diabetic dyslipidemia is often exacerbated by the high calorie consumption and physical inactivity that define the lifestyle of some type 2 diabetic patients.
Symptoms and Signs
Dyslipidemia on its own can cause symptoms. but may cause symptomatic vascular diseases, including coronary artery and peripheral artery diseases. High TG (> 1000 mg/dl) can cause acute pancreatitis. High levels of LDL cause eyelid xanthelasma: tendinous xanthomas located on the corneal arch and Achilles, elbow and knee tendons, and metacarpophalangeal joints. Patients with the homozygous form of familial hypercholesterolemia may have planar or cutaneous xanthomas in addition to the above findings. In patients with severely high TG, “eruptive” xanthomas may be seen on the trunk, back, elbows, back, knees, hands and feet. Rare dysbetaliproteincmia patients may have palmar and tuberous xanthomas.
Severe hypertriglyceridemia (>200 mg/dL [22.6mmol/LJ) may give a creamy white appearance to the retinal arteries and veins (lipemiaretinalis). Excessively high lipid levels can give the blood plasma a milky appearance.
Diagnosis and Screening
Although dyslipidemia can be suspected in patients with characteristic physical findings. Diagnosis is made by measuring serum lipids. Routine measurements (lipidprofile) total cholesterol (TK), TG. Includes HDL and LDL measurements.
TK, TG and HDL are calculated directly; TC and TG values cholesterol and chylomicron, VLDL. IDL reflects the cholesterol and TGs in all circulating lipoproteins, including LDL and HDL. Testing should be postponed until after recovery from an acute illness, because TG increases and cholesterol levels decrease in inflammatory conditions.
Fasting lipid profile (TK, TG, HDL, and measured LDL) should be obtained from all adults aged twenty years and over.
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