Hyperlipidemia PDF - Mansoura National University

Hyperlipidemia By Dr. Maamon Eisa Lecturer of Medical Biochemistry [email protected] 24/09/2024 Mansoura National University 2  Contents Lipid Profile. Hyperlipoproteinemias....

Hyperlipidemia By Dr. Maamon Eisa Lecturer of Medical Biochemistry [email protected] 24/09/2024 Mansoura National University 2  Contents Lipid Profile. Hyperlipoproteinemias. Fatty Liver. Lipotropic factors. 24/09/2024 Mansoura National University 3  Learning Outcomes (LOs) At the end of this session, the students should be able to: Define Lipid profile. Recognize normal values and components of lipid profile. Recognize types of hyperlipoproteinemia. Recognize definition and causes of fatty liver. Define Lipotropic factors. Correlate the knowledge to clinical settings and diseases. 24/09/2024 Mansoura National University 4  Lipid profile Definition: group of blood tests to determine the pattern of lipids in the blood. Usually includes the levels of: 1.Total Cholesterol, 2.Triglycerides, 3.high-density lipoprotein (HDL) cholesterol (good cholesterol), 4.Low density lipoprotein ( LDL) cholesterol (bad cholesterol). Using these values, may also calculate: Very low-density lipoprotein and LDL:HDL ratio?? 24/09/2024 Mansoura National University 4  1.Total Cholesterol: Measures all cholesterol (good and bad) carried by lipoproteins. Level (mg/dl) Interpretation 240 High Risk 24/09/2024 Mansoura National University 5  2. LDL-Cholesterol: It’s called "bad" cholesterol. High levels reflect a high risk of heart disease. Too much LDL cholesterol builds up in the walls of the arteries forming plaque (Atherosclerosis) Level (mg/dl) Interpretation 160 High Risk 24/09/2024 Mansoura National University 6  3. HDL-Cholesterol: HDL cholesterol is known as "good" cholesterol because a high HDL level seems to protect against heart attack. Level (mg/dl) Interpretation 60 High HDL level, optimal condition considered protective against heart disease 24/09/2024 Mansoura National University 7  4. Triglycerides: The storage form for fat in adipose tissue. Some triglycerides circulate in the blood to provide fuel for muscles to work. Extra triglycerides are found in blood after eating a meal, fat is being sent from the gut to adipose tissue for storage. Level (mg/dl) Interpretation 200 High risk 24/09/2024 Mansoura National University 8  Lipoproteins and Related Clinical Problems Atherosclerosis and hypertension Coronary heart diseases Lipoproteinemias (hypo-and hyper-) Fatty liver 24/09/2024 Mansoura National University 9  Lipoproteins and Atherosclerosis Atherosclerosis is hardening of the arteries due to the deposition of atheroma. caused by the deposition of cholesterol esters on the walls of arteries, blockages can form. LDL (bad cholesterol): Risk factor for atherosclerosis HDL (good cholesterol): Protective factor for atherosclerosis Atherogenic index (LDL/HDL cholesterol ratio): > 4/1 predispose to atherosclerosis & coronary heart disease. 24/09/2024 Mansoura National University 10  Hyperlipidemia Is the condition of abnormally elevated levels of any or all lipids and/or lipoproteins in the blood. 24/09/2024 Mansoura National University 11  Clinical disorders of lipoproteins (Dyslipoproteinemias) o Defects in lipoprotein metabolism lead to: Hyperlipoproteinemia Or Hypolipoproteinemia 24/09/2024 Mansoura National University 37  Hyperlipoproteinemias A group of disorders characterized by increased plasma lipoproteins. May be congenital or acquired. There are 5 types of primary hyperlipoproteinemias. 24/09/2024 Mansoura National University 38  Hyperlipoproteinemias Types Cause Increased Plasma Risk for Acquired types lipoproteins as in Type I Chylomicrons, ↑TG Deficiency of lipoprotein VLDL Turbid lipase enzyme Type II LDL ↑cholesterol -Atherosclerosis -Familial Defect of LDL receptors and coronary heart -Hypothyroidism disease. hypercholesterolemia (FH) Type III IDL, ↑TG -Atherosclerosis -Dysbetalipoproteinemia Defective apoE Chylomicron ↑cholesterol (impaired hepatic remenants uptake of chylomicron remnants and IDL) Type IV Overproduction of TG VLDL ↑TG -Hyperprebeta (and VLDL) from Some ↑ in -Type II DM carbohydrates cholesterol -Obesity lipoproteinemia -Alcoholism -Hypertriacylglycerolemia Type V Chylomicrons, ↑TG -It is usually -Comlined Unknown, but may be VLDL ↑cholesterol associated with due to increase obesity.. hyperlipidemia formation of apoB 24/09/2024 Mansoura National University 35 24/09/2024 Mansoura National University 39  Types Cause Increased Plasma Risk for Acquired lipoproteins types as in Type I Deficiency of Chylomicron ↑TG lipoprotein s, Turbid lipase enzyme VLDL Type II Defect of LDL LDL ↑cholester - Hypo- Familial receptors ol Atherosclerosi thyroidism hypercholest- s and coronary heart disease. erolemia (FH) Type III Defective apoE IDL, ↑TG - Dysbetalipo- (impaired Chylomicron ↑cholester Atherosclerosi hepatic uptake remenants ol s proteinemia of chylomicron remnants and 24/09/2024 IDL) Mansoura National University 15 Type IV Overproduction ↑TG *Type II DM Hyperprebeta- of TG (and VLDL) VLDL Some ↑ in *Obesity from cholesterol lipoproteinemia carbohydrates *Alcoholism Hypertriacyl- glycerolemia Type V Unknown, but Chylomicrons, ↑TG -It is usually Combined may be due to VLDL ↑cholesterol associated with increase obesity. hyperlipidemia formation of apoB Type VI: → ↑ HDL Estrogen Hyper alpha- ↑ cholesterol therapy lipoproteinemia 24/09/2024 Mansoura National University 16 Type Cause Type I: Hyperchylomicronemia ↓ lipoprotien lipase (familial) Type II: Hyperbetalipoproteinemia 1- Familial: ↓ LDL receptors (↑LDL) 2- Acquired: hypothyroidism Type III: Dysbetalipoproteinaemia ↓ apo E (important for uptake of chylomicron remnant & VLDL remenant (IDL) Type IV: Hyperpre beta- 1- Familial: ↑ lipogenesis form lipoproteinemia CHO 2- Acquired: type II DM, obesity - alcoholism Type V: Hyperchylomicronemia & unknown may be due to increase Hyper prebeta-lipoproteinemia apo B synthesis Type VI: → Hyper alpha- Estrogen therapy 24/09/2024 Mansoura National University 17 lipoproteinemia  Hypolipoproteinemias 1- Abetalipoproteinemia: - Defect in lipid transport to apoB. - ↓ or absent chylomicrons, VLDL and LDL. - ↓ plasma lipids. - Accumulation of TG in the intestine → Steatorrhea, and liver → fatty liver. 2-Hypobetalipoproteinemia: - Gene mutation → ↓ formation of apoB. -↓ chylomicrons, VLDL and LDL. -↓ plasma lipids. 24/09/2024 Mansoura National University 40  Hypolipoproteinemias 3-Familial α-lipoprotein deficiency (Tangiers disease): - Gene mutation affects the efflux of cholesterol from the cells. - ↓ or absent HDL and apoA. - Accumulation of CE in tissues. 4-Familial LCAT deficiency: - Genetic mutation in LCAT → absent enzyme. - ↓↓ HDL (remains nascent). - Accumulation of free cholesterol in tissues. 24/09/2024 Mansoura National University 41  Fatty liver Abnormal condition characterized by ↑ deposition of fat (mainly TG) in liver. 24/09/2024 Mansoura National University 20   Normal fat content of liver 5% (mainly phospholipids)  In fatty liver →↑ up to 25-30% (mainly TG) Effects: chronic accumulation→ fibrosis→ cirrhosis & impaired function. 24/09/2024 Mansoura National University 21  Causes 1. ↑ Fat in diet→ ↑ uptake by liver if uptake > mobilization by VLDL ↑ Fatty liver 2. ↑ CHO diet → First CHO → stored as glycogen If excess → lipogenesis If lipogenesis > VLDL synthesis → fatty liver 3. ↓ FA oxidation → direct FA → TG 24/09/2024 Mansoura National University 22 4. ↑ Mobilization of Fat from adipose tissue to liver as in 1-↓ CHO diet 2- DM 3- Starvation 5. ↓ Mobilization of fat from liver to adipose tissues due to ↓ apo B100 →↓ VLDL → Accumulation of TG in liver due to impaired lipid transport form liver. 6. Liver poisons: chloroform, Puromycin, CCL4→↓ Apo proteins 24/09/2024 Mansoura National University 23  Lipotropic factors substances which facilitate mobilization of fat from liver = prevent fatty liver Mechanism : Fat to be mobilized from liver must be in the from of phospholipid So lipotropic factors help phospholipids synthesis 24/09/2024 Mansoura National University 24  Examples 1. Choline → lecithin, plasmalogen, sphingomyelin 2. Methionine → choline synthesis (-CH3) 3. Folic acid & Vit B12 : transfer -CH3 gp → choline 4. Insoitol → Phosphatidyl inositol 24/09/2024 Mansoura National University 25 5. Essential FA → FA No 2 in phospholipids 6. Glycine → choline 7. Betaine → choline 8. Vit E & selenium → ↓ FA peroxidation 9. Adequate diet → proteins– vitamins 24/09/2024 Mansoura National University 26 24/09/2024 Mansoura National University 27