Secondary Dyslipidemia - Comment
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1. Secondary Dyslipidemia By : Ahmed Mohsen Ammar Yasser Heba Sadek Marwa Khalifa
2. Dyslipidemia • Definition : Dyslipidemias are disorders of lipoprotein metabolism, including lipoprotein overproduction or deficiency. These disorders may be manifested by elevation of the serum total cholesterol, low-density lipoprotein (LDL) cholesterol and triglyceride concentrations, and a decrease in the high-density lipoprotein (HDL) cholesterol concentration.
3. Classification Etiological classification 1- Primary Hyperlipidemia. 2- Secondary Hyperlipidemia.
4. Secondary hyperlipidemia Causes: • Type 2 diabetes mellitus • Cholestatic liver diseases • Nephrotic syndrome • Chronic renal failure • Hypothyroidism • Cigarette smoking • Obesity & Anorexia nervosa • Drugs : such as thiazides, β-blockers, retinoids, highly active antiretroviral agents, estrogen and progestins, and glucocorticoids.
5. Increased triglyceride level • Alcoholism • Diabetes mellitus • Hypothyroidism • Obesity • Renal insufficiency • Drugs: Beta-adrenergic blockers ,Bile acid–binding resins, Estrogens ,Ticlopidine • Acute hepatitis • Systemic lupus • Ileal bypass surgery • Monoclonal gammopathy :myeloma • Sepsis • Pregnancy
6. Decreased HDL cholesterol level • Cigarette smoking • Diabetes mellitus • Hypertriglyceridemia • Menopause • Obesity • Puberty (in males) • Uremia • Drugs: Anabolic steroids,Beta-adrenergic blockers ,Progestins
7. Increased LDL cholesterol level •Diabetes mellitus •Hypothyroidism •Nephrotic syndrome •Obstructive liver disease •Drugs: Anabolic steroids, Progestins ,Beta- adrenergic blockers ,Thiazides •Anorexia nervosa •Acute intermittent porphyria
8. Type 2 Diabetes mellitus Diabetes is an especially significant secondary cause because patients tend to have an atherogenic combination of high TGs; high small, dense LDL fractions; and low HDL (diabetic dyslipidemia) Diabetes mellitus
9. The combination may be a consequence of obesity, poor control of diabetes, or both, which may increase circulating free fatty acids (FFAs), leading to increased hepatic very-low- density lipoprotein (VLDL) production. TG-rich VLDL then transfers TG and cholesterol to LDL and HDL, promoting formation of TG-rich, small, dense LDL and clearance of TG-rich HDL.
10. Diabetic dyslipidemia is often exacerbated by the increased caloric intake and physical inactivity that characterize the lifestyles of some patients with type 2 diabetes.
11. Cholestatic Liver Disease Primary biliary cirrhosis and similar disorders may be accompanied by marked hypercholesterolemia that results from an accumulation of lipoprotein-X. Clinical stigmata include xanthomata striata palmare that may appear when the serum cholesterol concentration is 1400 mg/dL or higher.
12. Xanthomata striata palmare
13. Xanthomata appear on the extremities as well. Marked elevations in lipoprotein X has been associated with the hyperviscosity syndrome, but no clear association with coronary heart disease (CHD) has been established.
14. Nephrotic Syndrome Marked hyperlipidemia can occur in the nephrotic syndrome due primarily to high serum total and low-density lipoprotein (LDL) cholesterol concentrations. Increased hepatic production of lipoproteins, induced by part by the fall in plasma oncotic pressure is the major abnormality, but diminished lipid catabolism may play a contributory role.
15. Chronic Renal Failure Dyslipidemia is less prominent in chronic renal failure, but hypertriglyceridemia occurs in 30 to 50 percent of cases. Chronic renal failure
16. Hypothyroidism Hypothyroidism is frequently associated with and is a common cause of hyperlipidemia. This relationship was illustrated in a study of patients with primary hypothyroidism. Hypercholesterolemia was present in 56 percent, hypercholesterolemia and hypertriglyceridemia in 34 percent, and hypertriglyceridemia in 1.5 percent; only 8.5 percent had a normal lipid profile.
17. Reversal of the hypothyroidism with thyroid hormone replacement leads to correction of hyperlipidemia. Serum TSH should be measured in all patients with dyslipidemia.
18. Smoking Smoking modestly lowers the serum HDL cholesterol concentrations and may induce insulin resistance. These effects are reversible within one to two months after smoking cessation.
19. Obesity Obesity is associated with a number of deleterious changes in lipid metabolism, including high serum concentrations of total cholesterol, LDL cholesterol, VLDL cholesterol, and triglycerides, and a reduction in serum HDL cholesterol concentration of about 5 percent. Loss of body fat can reverse the hypercholesterolemia and hypertriglyceridemia.
20. Anorexia nervosa • Hypercholesterolemia has long been known to be associated with anorexia nervosa. Typically total cholesterol and LDL are elevated; HDL may be high also. With refeeding, cholesterol levels return to baseline. Other forms of malnutrition are not usually associated with high cholesterol. However, until recently the underlying mechanism has not been clearly delineated
21. Clinical Presentation • Dyslipidemia itself usually causes no symptoms but can lead to symptomatic vascular disease, including coronary artery disease (CAD) and peripheral arterial disease. • High levels of TGs (> 1000 mg/dL) can cause acute pancreatitis. • High levels of LDL can cause eyelid xanthelasmas; arcus corneae; and tendinous xanthomas at the Achilles, elbow, and knee tendons and over metacarpophalangeal joints.
22. • Patients with severe elevations of TGs can have eruptive xanthomas over the trunk, back, elbows, buttocks, knees, hands, and feet. • Extremely high lipid levels also give a lactescent (milky) appearance to blood plasma.
23. Eyelid xanthelasmas
24. Arcus corneae
25. Tendinous xanthomas
26. Tendinous xanthoma
27. • Serum lipid profile (measured total cholesterol, TG, and HDL cholesterol and calculated LDL cholesterol and VLDL) • Tests for secondary causes of dyslipidemia— including measurements of fasting glucose, liver enzymes, creatinine, thyroid-stimulating hormone (TSH), and urinary protein—should be done in most patients with newly diagnosed dyslipidemia. Diagnosis
28. Treatment • Treatment of the cause. • Lifestyle changes (eg, exercise, dietary modification) • For high LDL cholesterol, statins, sometimes bile acid sequestrants. • For high TG or low HDL cholesterol, niacin , fibrates, and sometimes other measures.
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