1. Week 6: Cardiovascular Disease Processes

2. Outline Structure and function of blood vessels –Differences between arteries and veins Pathophysiology of atherosclerosis –Atherosclerosis and acute cardiovascular syndromes Physiology of risk factors for atherosclerosis

3. Structure of Vessel Walls Figure 21-1

4. Structure of Blood Vessels Figure 21-2

5. Arteries and Pressure Elasticity allows arteries to absorb pressure waves that come with each heartbeat

6. Vasoconstriction & Vasodilatation The contraction of arterial smooth muscle by the ANS The relaxation of arterial smooth muscle Enlarging the lumen Affect: –afterload on heart –peripheral blood pressure –capillary blood flow

7. Vascular Endothelium Regulation of own Permeability Localised Vascular Control Enzymatic Actions on Plasma Inflammation & Immune Response Angiogenesis Sensed by shear and O2 tension Releases: NO vasdodilatory, inhibits smooth muscle proliferation, leucocyte binding, platelet aggregation. Prostacyclin: vasodilator, inhibits plateley aggregation ACE Involved in white blood cell actions. Immunoglobulins: mediate leucocyte adhesion to endothelial cells

8. Atherosclerosis and Arteriosclerosis Disease Progression & Risk Factors

9. Atherosclerosis & Arteriosclerosis Atherosclerosis ‘The formation of plaques of cholesterol, platelets, fibrin, and other substances on the arterial walls.’ Arteriosclerosis Imprecise term for various disorders of arteries, particularly hardening due to fibrosis or calcium deposition, often used as a synonym for atherosclerosis.termdisorders arteriesfibrosiscalciumatherosclerosis

10. The Processes: Arterial Narrowing & Thrombus Formation

12. LDL Cholesterol accumulates in the arterial wall & undergoes chemical changes. Signals – endothelial cells to latch on to white blood cells. Triggers inflammatory response LDS- foam cells The fat-laden foam cells form a fatty streak. Plaque grows and a fibrous cap forms to ‘heal’ the plaque. If it breaks, the it can form a blood clot.

13. The fatty streak - earliest identifiable morphological change. This is pre-dated by endothelial dysfunction Characterised by accumulation of macrophage foam cells and a local chronic inflammatory infiltrate.

14. Chronic local inflammatory response.

15. The complex plaque is characterised by: smooth muscle cell migration, formation of a fibrous cap, a necrotic lipid core increasing inflammatory infiltrate.

16. Plaque rupture may occur after fibrous cap weakened by the production of: degradative enzymes reactive oxygen species by the inflammatory cellular infiltrate. Plaque rupture exposes highly prothrombotic material, that may result in the clinically recognised acute coronary syndromes.

17. Fate of a Thrombus Partial blockage in periphery: Ischaemia, Peripheral vascular disease Full blockage necrosis, gangrene Partial blockage in myocardial blood supply: Angina pectoris Full blockage MI Thrombus breaks off and moves to: Heart vessel – MI Lungs – pulmonary thrombus Cerebral vessel - stroke

18. Risk Factors Physiological Explanations

19. Lipids Low density lipoproteins (LDLs) Associated with endothelial injury Taken up by macrophages Worse when: –glycated –oxidised

20. Diabetes Impaired endothelium-related relaxation –Via advanced glycosylation end-products Increased platelet aggregation –Decreased response to a number of agonists

21. Hypertension Reduces endothelial function (via NO) Increases permeability to macromolecules Increases growth and proliferation vascular smooth muscle cells –Via Angiotensin II

22. Hypertension 2 Increases smooth muscle lipoxygenase activity –  oxidation of LDL –  inflammatory processes Pro-inflammatory response  free radical production –  NO –  leukocyte adhesions –  peripheral resistance

23. Smoking Promotes endothelial dysfunction Enhanced platelet activity Increased whole blood viscosity –Associated with secondary polycythaemia Lowers HDL, increases oxidation of LDL –Via free radical exposure

24. Obesity and Physical Inactivity Only small direct increase in atheroclerosis Effects via links with diabetes, hypertension and dyslipidaemia

25. Summary The general process of atherosclerotic plaque / thrombus formation Several physiologial risk factors for atherosclerosis

26. Hypertension The Silent Killer

27. Hypertension Primary (essential) Secondary –Tumor, kidney disorder, adrenaline gland disorder ADH, renin, aldosterone, adrenaline, ACE.

29. Effect of obesity When metabolised abdominal fat releases more triglycerides per g

31. Valvular Disorders Common Examples

32. Mitral stenosis Narrowing of mitral valve opening due to progressive scarring Rheumatic Fever Atrial remodelling –>50% AF Pulmonary Hypertension

33. Mitral Stenosis Leads to obligatory increases in pulmonary arterial pressure Reactive arteriolar constriction and structural changes in pulmonary artery (fibrosis) Sustained >70 mm/Hg pressures RV hypertrophy - increased afterload

34. Mitral Regurgitation Leaky Mitral Valve Breathlessness Heart Murmur Ultrasound Tolerated for years due to compensation

35. Causes of Mitral Regurgitation Rheumatic fever Mitral valve prolapse syndrome Hypertrophic cardiomyopathy Myocardial infarction –Damage to ventricle where the chordae are attached. –Can cause rupture of the chordae Some congenital heart problems Infection of the valve (endocarditis)

36. Cardiac Myopathy and (Congestive) Heart Failure

37. Cardiac Myopathy Disorder of the heart muscle Usually an enlargement of: –Chambers (dilated) –Muscle tissue (hypertrophic) Systolic myopathies But may be simply due to stiffening of myocardium Diastolic myopathy

40. Causes of Cardiomyopathy Mostly idiopathic Alcohol Pregnancy Viral – myocarditis MI Valvular disorders Secondary to hypertension

41. Hypertrophic or Dilated Cardiomyopathy

42. (Chronic) Heart Failure Cardiomyopathies are commonly compensatory mechanisms (C)HF is failure to meet Q-demands Outcomes: Sudden Death Pump Failure Transplantation

43. Congestive Heart Failure Left sided failure: increased pulmonary circuit pressure Pulmonary hypertension Fluid in lungs –(congestion) Common to diagnose this way

44. Signs to look out for Shortness of breath on exertion Weight gain Peripheral fluid retention Chronic ‘bronchitis’

45. Getting to Heart Failure HF occurs after an accumulation of problems that may include: –Idiopathies, Viruses, drugs More commonly in CR secondary to: –Valvular disorders –Hypertension –MI