Aims

1. Aims • Hypertension • Arteriosclerosis/ Atherosclerosis • Lipid metabolism/ Hyperlipidemia • Readings: • Robbins; Atherosclerosis 328-338, Hypertension 338-341.

2. Hypertension • Due to increased cardiac output (CO) and/or increased peripheral vascular resistance. • 25% of the US population is hypertensive. • Risk factors include being male, African American, and increased age. • Defined as having a blood pressure > 140/90. • Mild 140-159/90-99 • Moderate 160-179/100-109 • Severe >180/>110

3. Pathogenesis of Hypertension • 90-95% of hypertension cases have an unknown cause (__________________ or essential hypertension). • Increased Na+ resulting in increased blood volume and ultimately increased CO. • Stress results in sympathetic nervous system stimulation resulting in increased heart contraction and increased vasoconstriction. • Obesity resulting in increased blood volume resulting in increased CO.

4. Pathogenesis of Hypertension • 5-10% of hypertension cases are secondary to other organ pathologies (secondary hypertension). Robbins’ Basic Pathology Table 10-3

5. Ocular Manifestations of Hypertension • Hypertension is one of the most common causes of vascular damage to the eye (diabetes is another).

6. Ocular Manifestations of Hypertension • Hypertensive _____________________. • Narrowing of blood vessels “copper wiring”. • Flame shaped hemorrhages. • Cotton wool spots. • Focal infarcts of the retinal NFL • Optic nerve swelling. • Hypertensive choroidopathy. • Elschnig spots (Acute focal RPE lesions).

7. Treatments for Hypertension • Life style changes • Stop smoking, decrease salt and alcohol intake, lose weight , exercise. • ________________________________. • Inhibits vasoconstriction and Na+ retention. • Diuretics. • Increases Na+ and H2O loss in urine. • _____________________________. • Decreases heart rate, decrease vasoconstriction. • a-blockers. • Decreases vasoconstriction. • Calcium channel blockers. • Decreases vasoconstriction.

8. Arteriosclerosis • Literally “Hardening of the arteries” • Due to thickening and loss of elasticity of blood vessel walls. • Most frequently due to Atherosclerosis, but also due to calcium deposits as a result of Monckeberg medial calcific sclerosis and other diseases.

9. Atherosclerosis • Almost universally present in children. Robbin’s Basic Pathology 10-12

10. Fatty Streaks Can occur as early as 1 yo. Composed of: Lipid filled foam cells. Extracellular lipid. Occurs at the same anatomical sites as atheromas. -Branch points & Curvatures in the vessel. Thus, it is believed that they are atheroma precursors. Robbins’ Basic Pathology 7th Edition 10-8B

11. Atherosclerosis • Plaques develop slowly. • Symptoms begin in middle age or later. • Consequences include myocardial infarction, cerebral infarction, aortic aneurysm, peripheral vascular disease. Robbin’s Basic Pathology 10-12

12. Atherosclerotic Plaque (Atheroma) -Intimal thickening -Lipid accumulation (Cholesterol and cholesterol esters) -Fibrous cap (cells include SMC, macrophages, & lymphocytes) -Necrotic Center (Foam cells-macrophages filled with cholesterol) Robbins’ Basic Pathology 10-3

13. Atherosclerotic Plaque (Atheroma) Initially the atheroma is covered with a confluent layer of endothelial cells. -Thus, there is little clotting. Starts as a very focal disease Plaques are diffuse and complicated Sherwood’s Human Physiology 9-33 & Robbins’ Basic Pathology 10-9

14. Atherosclerotic Coronary Artery Lumen (L) is smaller. Core (C) contains cholesterol crystals. Fibrous cap (F) is thick. Inflammatory cells present Macrophages Lymphocytes Calcification Angiogenesis Robbins’ Basic Pathology 10-10

15. Aneurysm Abnormal dilation of artery due to weakened vessel wall. Robbins’ Basic Pathology 10-18

16. Response to Injury Hypothesis Atherosclerosis is a chronic inflammatory response of the arterial wall initiated by some form of injury to the endothelium.

17. Injury Endothelial Cell dysfunction Smooth muscle cell migration and macrophage activation. Macrophage and smooth muscle cell engulf lipid. Smooth muscle cell proliferation, extracellular matrix and lipid deposition. Robbins’ Basic Pathology 10-7

18. Oxidized LDL leads to Plaque Formation • Macrophages “can’t stop eat’n em” because it gets in through _______________________________ not LDL receptor. • It’s chemotactic for monocytes. • It increases the expression endothelial cell adhesion molecules ICAM and VCAM. • Stimulates cytokine and growth factor production. • Cytotoxic to endothelial cells and smooth muscle cells.

19. Injury • Results in: • Increased permeability • Increased leukocyte adhesion • Changes in gene expression (ICAM) • Caused by: • Hemodynamic Factors • Hypercholesterolemia • -LDL accumulates • -LDL is oxidized Robbins’ Basic Pathology 10-6

20. Endothelial Cell Dysfunction • Permeability to LDL • Monocytes adhere and migrate • Platelets adhere (thrombosis) Robbins’ Basic Pathology 10-6

21. Smooth Muscle Cell Migration and Macrophage Activation • Smooth muscle cells migrate from media into the intima • Macrophages are activated • -Cytokines (IL-1, TNFa) • -Chemokines (MCP-1) Robbins’ Basic Pathology 10-6

22. Macrophage and Smooth Muscle Cell Engulf Lipid ____________________ cells develop from macrophages and smooth muscle cells engulfing lipids. Robbins’ Basic Pathology 10-6

23. Smooth Muscle Cell Proliferation, Extracellular Matrix and Lipid Deposition Smooth muscle cell secretes extracellular matrix resulting in fibrosis. Robbins’ Basic Pathology 10-6

24. Ocular Manifestations of Arteriosclerosis • Opthalamic and Central Retinal artery occlusion (_________________________). • Hemorrhage. • Increased risk of glaucoma. • __________________________________. • Wet (formation of new blood vessels). • Dry (thinning of the macula with loss of RPE).

25. Treatments • Diet/exercise • Treat underlying cause (ie. Hypercholesterolemia, Hypertension, Diabetes) • Clot busters (tPA, urokinase, streptokinase).

26. Lipid Metabolism 7% of cholesterol is in blood plasma. Remember cholesterol has important functions in membrane and hormone production. Robbins & Cotran’s Pathologic Basis for Disease 6-8

27. LDL Receptor Recycling Robbins & Cotran’s Pathologic Basis for Disease 6-9

28. Hyperlipidemia • The presence of excess fat or lipids in the blood. • _____________________________. • Hypertriglyseridemia.

29. Familial Hypercholesterolemia Mutations of the LDL receptor I. No receptor made. II. No receptor makes it to the membrane. III. Poor or no binding. IV. No internalization. V. No recycling. Robbins & Cotran’s Pathologic Basis for Disease 6-10

30. Ocular Manifestations of Hyperlipidemias • Corneal arcus • Lipid deposits in the cornea stroma. • ____________________________ • Woman 4X more likely than men. • Lipid deposits in the eyelid. • Lipemia retinalis • Retinal blood vessels appear salmon to cream color. • ____________________________ • Due to retinal capillary occlusion.

31. Treatments for Hypercholesterolemia • Lifestyle change (diet/ exercise). • Bile-sequestering resins. • Colestipol • Inhibit lipid absorption. • ________________________. • Lovastatin, Lipitor, Zocor. • HMG CoA reductase inhibitors.

32. Next Time • Thrombosis • Stroke • Ischemic heart disease • Myocardial infarctions • Hypertensive heart disease • Sickle Cell Anemia • Congestive Heart Failure • Readings: Robbins; Myocardial infarctions 365-371, Hypertensive heart disease 372-374, Sickle cell anemia 400-403, Heart failure 362

33. Objectives • Describe the pathogenesis of hypertension and its ocular manifestations. • Describe the pathogenesis of arteriosclerosis. • Development of atheroma. • Response to Injury Hypothesis. • Describe the ocular manifestations of atherosclerosis. • Describe hyperlipidemias and their ocular manifestations.