Dyslipidemia & dyslipoproteinemia

lipoproteins and their disorders .

1. Dyslipidemia Sarah mutni almutairi . College of Medicine second year CVS block

2. -Define dyslipoproteinemia -Outline the different types of dyslipoproteinemia, -Outline common causes of dyslipidemias -List complications of dyslipoproteinemia

3. Introduction :

4. Lipoproteins: Definition : Lipoproteins are molecular complexes that consist of lipids with proteins. They are the transport vehicle for lipid in the circulation. Lipoproteins deliver the lipid components to various tissues for utilization and storage . Function : The major function of LPs is to transport TAG , Cholesterol and phospholipids around the body.

5. Structure of lipoproteins: Outer coat: - Apoproteins -Phospholipids -Cholesterol Inner core: -TG -Cholesterol ester Spherical molecules of lipids and proteins ( apoproteins )

6. Cont. Protein part: Apoproteins or apolipoproteins Abbreviations: Apo-A, B, C, D, E Functions: Structural and transport function Enzymatic function Ligands for receptors Lipid part: According to the type of lipoproteins Different lipid components in various combinations

7. Classification of lipoproteins : Atherogenic Anti- atherogenic

8. CONT.. 1- CHYLOMICRONS : Derived from intestinal absorption of triacylglycerol and other lipids. 2-VERY LOW DENSITY LIPOPROTEINS (VLDL) or pre β -lipoproteins : Derived from the liver for the export of triacylglycerol . 3- LOW DENSITY LIPOPROTEINS (LDL) or β -lipoproteins : Representing a final stage in the catabolism of VLDL . 4-HIGH DENSITY LIPOPROTEINS (HDL) or α -lipoproteins : Involved in cholesterol transport from peripheral tissue to the liver and also in VLDL & chylomicron metabolism. FOUR MAJOR GROUPS OF PLASMA LIPOPROTIEN :

9. -Atherosclerosis and hypertension. -Coronary heart diseases. - dyslipoproteinemias (hypo- and hyper- ). -Fatty liver. Lipoproteins and their Related Clinical Problems :

10. 1-Define dyslipoproteinemia. Inherited or acquired (secondary) defects in lipoprotein metabolism lead to the primary condition of either Hypo- or hyperlipoproteinemia .

11. 2- Outline the different types of dyslipoproteinemia. 1 2 Hypolipoproteinemia Hyperlipoproteinemia

12. 1-Hypolipoproteinemia : Defect Name No chylomicrons , VLDL , LDL are formed because of defect in the loading of apo B with Lipid . Abetalipoproteinemia All have low or near absence of HDL Familial alpha-lipoprotein def. Fish eye disease Apo-A-I def. Tangier disease.

13. 2-hyperlipoproteinemia (primary): مهم Defect Name Hypertriacylglycerolemia due to def. of LPL , abnormal LPL or C- ll def. causing inactive LPL . Familial lipoprotein lipase def. Type l Defective LDL receptor or mutation in ligand region of apo B-100 . Familial hypercholesterolemia Type ll a Def. in remnant clearance by the liver is due to abnormality in apo E Familial type lll hyperlipoproteinemia Overproduction of VLDL often associated with glucose intolerance and hyperinsulinemia . Familial hypertriacylglycerolemia Type lV Increase concentration of HDL . Familial hyperalphalipoproteinemia Def. of the enzyme leads to accumulation of large triacylglycerolrich HDL & VLDL remnants . Hepatic lipase def. Absence Of LCAT leads to block in reverse cholesterol transport . Familial (LCAT) def. Apo a shows structural homologies to plasminogen . Familial lipoprotein (a) excess

14. Secondary causes of hyperlipidemia :

15. 3-Outline common causes of dyslipidemias BUT FIRST , what dyslipidemia mean ? An abnormal concentration of lipids or  lipoprotein  in the blood.

16. 3-Outline common causes of dyslipidemias 1-Primary causes:  Primary causes are single or multiple gene mutations that result in either overproduction or defective clearance of TG and LDL cholesterol, or in underproduction or excessive clearance of HDL .

17. * DM : 1- ↓ insulin → ↑ lipolysis in adipose tissue → ↑ mobilization of FFA to liver → ↑acetyl COA → ↑ cholesterol. 2- ↑ FFA → ↑VLDL → ↑ TAG . * Liver disorder : Chronic liver disease → liver can not catabolizes LDL →↑ LDL * Thyroid diseases : Hypothyroidism → ↑ level of LDL Hyperthyroidism→ ↓ level of LDL * Renal disorder : Nephritic syndrome → ↑ LDL * Cushing syndrome : ↑ glucocorticoid → ↑ VLDL → converted to LDL → ↑ TAG 2- Secondary causes : acquired disorders due to other diseases That affects circulating levels of lipids in blood.

18. 4-List complications of dyslipoproteinemia .

19. Complication of hyperlipoproteinemia : 1- Xanthelasma site : (periorbital) Due to sharply demarcated deposit of yellowish fat underneath the skin. 2- Atherosclerosis . 3- Corneal Arcus site : (around the iris of the eye) Due to lipid infiltration of the corneal stroma . 4- tendon xanthomas site : ( in extensor tendons of hands , feet ,Achilles tendon & patellar tendon ) Due to deposition of yellowish cholesterol-rich material in tendons.

20. Cont.. 5- Eruptive xanthomas site : (occur in crops , particularly over the buttocks ) Due to accumulation of lipids in large foam cells within the skin . 6- Lipemia retinalis : characterized by the hyperlipidemic vascular lesions-whitish color of vessels, lipid infiltration into the retina and decrease of visual acuity 7- Thrombosis : Stroke (cerebral ) Hyperlipidemia has been linked with increased stroke risk because plaque build up due to hyperlipidemia can loosen and cause an ischemic stroke. The plaque lodges in the brain and prevent blood from flowing to the brain, resulting in cell death. An ischemic stroke is the most common type of stroke

21. Cont.. 8-Coronary heart disease . Premature Coronary Artery Disease : the vessels become so narrow that the blood cannot pump through to the heart. Early symptoms are chest pain and difficulty breathing, and eventually can cause a heart attack.

22. Complication of hypolipoproteinemia 1-Coronary atherosclerosis . Due to decrease HDL lead to accumulation of cholesterol in the intima of large artery. 2-Yellow (orange)tonsillitis ( very rare ) Due to decrease HDL cholesterol ester are accumulated in tonsils 3-Recurrent peripheral neuropathies . . accumulation of oxidized lipids in myelin, leading to peripheral neuropathy 4- Depressed tendon reflexes Decrease in HDL cholesterol ester are accumulated in TENDON

23. Summary : Dyslipoproteinemia : Inherited defects in lipoprotein metabolism Types : 1-hypolipoproteinemia 2-hyperlipoprotinemia Dyslipidemia : An abnormal concentration of lipids or lipoprotein in the blood . Causes : primary or secondary The complication of dyslipoproteinemia

24. Any Questions ?

25. References :

26. Thank you