THE HEART function and its physiological pathway

THE HEART function and its physiological pathway

1. THE HEART

2. HYPERTENSION The sequence of events in cardiac hypertrophy and its progression to heart failure VALVULAR DISEASE MYOCARDIAL INFARCTION Pressure overload Pressure and/or volume overload Regional dysfunction with volume overload  Cardiac work Wall stress Cell stretch Hypertrophy and/or dilation Characterized by  heart size and mass  protein synthesis induction of immediated -early genes Induction of fetal gene program Abnormal proteins fibrosis Inadequate vasculature Cardiac dysfunction Characterized by heart failure (systolic/diastolic) arrhythmias neurohumoral stimulation

3. DILATED CARDIOMYOPATHY DILATED CARDIOMYOPATHY 30-40% genetic cause Mutations in sarcomere Mutations in cytoskeleton Mutations in nuclear envelope Mutations in mitochondria 100% genetic causes Mutations in sarcomere Defect in either force generation or transmission Defect in force generation Hypertrohpic cardiomyopathy phenotype Dilated cardiomyopathy phenotype Clinical heart failure sudden death atrial fibrillation stroke Non-genetic causes myocarditis toxic (e.g., alcohol) diopathic

4. Congestive heart failure (CHF) (IHD) Ischemic heart disease (HT) Hypertension Systolic dysfunction CHF In females Diastolic failure Contraction normal but relaxation abnormal Value failure eg . Endocarditis In “normal” heart sudden burden eg . Fluid overload

5. CVS adaptation CVS adaptation to decreased myocardial contraction increased hemodynamic burden Different pathways : Activation of neurohumoral systems Release of NE by sympathetic nervous system increased heart rate increased myocardial contraction increased vascular resistance b) Activation of renin – angiotensin aldosterone system c) Release of atrial natriuretic peptide (ANP) vasodilation Natriuresis diuresis

6. The frank starling mechanism As cardiac failure progresses increased end diastolic pressure (EDP) Increased volume of heart chamber Muscle fibres contract forcibly Increased cardiac output (CO) increased ventricle dilation Increased ventricular wall tension Increased O2 requirement of compromised myocardium Cannot propel blood oven at rest COMPENSATED HEART FAILURE DECOMPENSATED HEART FAILURE

7. Left heart failure Reduction in left ventricular output Increase left ventricular Congestion of lungs

8. Right heart failure Decrease right ventricular output Increase in right ventricular and right atrial pressure Rise in jugular venous pressure Congestive hepatomegaly Peripheral oedema ascites Venous congestion

9. Clinical features of heart failure Due to low cardiac output Features due to left heart failure Features due right heart failure Features of chronic heart disease

10. Due to low cardiac output Fatigue Poor effort tolerance Cold extremities Low BP Oliguria

11. Features due to left heart failure Dyspnoea Cough and expectoration Orthopnoea Paroxysmal nocturnal dyspnoea Inspiratory crepitations at bases of lungs 3 rd heart sound may be present Cardiac arrhythmia i.e. ventricular ectopics Cardiomegaly on chest radiograph

12. Features due right heart failure Raised JVP (jugular venous pressure) Hepatic enlargement Peripheral oedema Hydrothorax and ascites Anorexia, nausea vomiting jaundice

13. Features of chronic heart disease ( e.g ) Valvular Myocardial Congenital Defects

14. Complications of heart failure Complication Acute renal failure ( uraemia ) Hypokalaemia Hyponatraemia Impaired hepatic function (jaundice) Pathogenesis Poor renal perfusion due to diuretics therapy and low cardiac output Excretion of potassium due to diuretics or due to secondary hyperaldosteronism Loss of sodium due to diuretics, inappropriate water retention or failure of cell membrane sodium pump Poor arterial perfusion venous congestion

15. Complications of heart failure Complication Pulmonary thromoembolism (deep vein thrombosis) Arrhythmias (atrial and ventricualar ) Systemic embolism Pathogenesis Immobility Stasis of blood in veins Electrolyte disturbances i.e. hypokalaemia Underlying cardiac disease Digoxin induced Catecholamine excess Arrhythmias Left ventricular thrombus such as in mitral stenosis Left ventricular aneurysm

16. PRECIPITATING FACTORS FOR HEART FAILURE Intercurrent infections Pulmonary embolism Anaemia Pregnancy Myocardial ischaemia or infarction Thyrotoxicosis Myocarditis Arrhythmias Drugs with negative inotropic effect (beta blockers) Subacute bacterial endocarditis Hypertension Fluid retention due to high salt intake

17. Causes of heart failure Ventricular outflow obstruction Ventricular inflow obstruction Ventricular volume overload Depressed ventricular contractility

18. Ventricular outflow obstruction Left ventricular outflow obstruction (pressure overload) ( i ) Hypertension (ii) Aortic stenosis Right ventricular outflow obstruction ( i ) Pulmonary hypertension ( corpulmonale ) (ii) Pulmonary stenosis

19. Ventricular inflow obstruction Mitral stenosis (left side inflow obstruction) Tricuspid stenosis (right side inflow obstruction) Endomyocardial fibrosis

20. Ventricular volume overload Mitral regurgitation Mitral valve prolapse Aortic regurgitation Atrial septal defect Ventricular septal defect High output states (increased metabolic demand precipitates failure)

21. Depressed ventricular contractility Myocarditis Cardiomyopathy Myocardial ischaemia /infarction

22. Congenital heart disease 1% of all live births. Ductus arteriosus immediately closes after birth but if it persists after birth, then it is called patent ductus arteriosus (PDA).

23. Coronary Artery (Ischaemic Heart) Disease The involvement of heart due to coronary artery/arteries is called coronary heart disease or ischaemic heart disease. It is a condition of diverse aetiologies , all having in common a disturbance of cardiac function due to an imbalance between O2 supply and demand. INCIDENCE Commonest form of the heart disease and the single most important cause of morbidity and premature death after the age of 35.

24. Coronary artery, atherosclerosis Low power

25. Important risk factors for ischaemic heart disease Age (old age) and male sex (males ≥ 45 yrs. female ≥ 55 yrs). Family history Smoking Hypertension Mental stress Hypercholesterolemia and low HDL levels Diabetes mellitus Sedentary habits Obesity (BMI ≥ 30) Polyunsaturated fatty acid deficiencies Protein S and C deficiency Hyperfibrinogenaemia and hyperhomocysteinaemia Low levels of antioxidant vitamins (C, E, A)

26. Emerging risk factors Lipoprotein (a) Homocysteine Prothrombotic factor Impaired fasting glucose Activated protein C resistance

27. Ischemia can be caused by Reduced coronary blood flow: Common causes- coronary atherosclerosis, vasospasm, and thrombosis. Uncommon causes- reduced coronary flow include arteritis , emboli, cocaine-induced vasospasm and shock. Increased myocardial demand: e.g.,tachycardia , hypertrophy Hypoxia due to diminished oxygen transport:

28. Ischemic syndromes Four overlapping ischemic syndrome, differing in severity and rate of onset: 1) Myocardial Infarction 2) Angina Pectoris – Three patterns of angina are Stable angina: Angina symptoms reliably occur with same level of exertion & go away with rest Prinzmetal angina: due to vasospasm, angina typically occurs without fixed atherosclerotic disease. Unstable angina : due to atherosclerotic plaque disruption with variable, usually incomplete, mural thromboses; the angina therefore not clearly related to exertion.

29. 3) Chronic ischemic heart disease seen typically in elderly patients with moderate to severe multivessel coronary atherosclerosis who insidiously develop CHF it may result from post infarction cardiac decompensation or slow ischemic myocyte degeneration. 4) Sudden cardiac death is defined as unexpected cardiac death within 1 hour of symptom onset.

30. Myocardial infarction Two interrelated types: 1) Transmural Infarct - involve the full thickness of ventricular wall - caused by severe coronary atherosclerosis, with acute plaque rupture & superimposed occlusive thrombosis. 2) Subendocardial Infarct - limited to inner one third of the ventricular wall - caused by increased cardiac demand in the setting of limiting supply due to fixed atherosclerotic disease.

31. The wavefront of myocardial necrosis - Schematic

32. Pathogenesis Transmural infarcts: are largely a consequence of coronary atherosclerosis & one disrupted plaques. the initial event in most transmural MIs erosion, ulceration, fissuring, rupture, hemorrhagic expansion of an atherosclerotic plaque. Plaques involved in coronary events typically have a large lipid pool, a thin fibrous cap, and macrophage-rich inflammation; plaque with such features are considered susceptible to rupture ,and are termed Vulnerable . Patients at risk of cardiovascular events may have multiple vulnerable plaques. Transient changes in blood pressure and platelet reactivity (both occur upon morning awakening),affected by exercise and smoking (both are associated with catecholamine release),and may increase the risk of plaque rupture and thrombosis. High levels of serum markers of inflammation (C –reactive protein(CRP) and hypercoagulability ( e.g protein C or S deficiency, factor V Leiden) also affect a patient’s risk of acute cardiovascular events.

33. Heart, myocardial rupture - Very low power

34. Heart, acute myocardial infarction - Medium power

35. Thrombosis follows the acute plaque change and occludes flow to distal tissues. The time interval between onset of complete myocardial ischemia and the initiation of irreversible injury is 20 to 40 minutes. If the patient survives, thrombi may either lyse spontaneously or after fibrinolysis ; alternatively, vasospasm may relax. In both cases, flow is reestablished and some myocardium is spared from necrosis. Reflow to (reperfusion of )precariously injured cells may restore viability but leave the cells poorly contractile (stunned) for 1 to 2 days. Nearly all transmural MIs affect the left ventricle; 15% simultaneously involve the right ventricle, particularly in posterior – inferior left ventricle infarcts. Isolated right ventricle infarction occurs in 1% to 3% of cases.

36. Subendocardial infarcts Diffuse coronary atherosclerosis and global borderline perfusion made transiently critical by increased demand, vasospasm, or hypotension but without superimposed thrombosis. Plaque disruption with overlying thrombus that spontaneously lyses (or is removed by therapeutic intervention), thereby limiting the extent of myocardial injury. Myocardial injury is usually less than in a transmural infarct and often multifocal.

37. Gross changes Before 6 to 12 hours, MIs are usually inapparent . Early 3 to 6 hours after injury can be highlighted by histochemical techniques- e.g., Triphenyltetrazolium chloride is a substrate for lactate dehydrogenase . By 18 to24 hours, infarcted tissue is generally readily apparent as discrete pale to cyanotic areas. In the first week, lesions progressively more defined, yellow & softened Hyperemic granulation tissue appears by 7 to 10 days at the infarct White fibrous scar is usually well established by 6 weeks.

38. Heart, acute myocardial infarct Gross, cut surface

39. Heart, post myocardial infarction rupture of left ventricular free wall - Gross, cut surface

40. Microscopic changes Within 1 hour of an MI, there is intercellular edema, & myocytes at the edge of the infarct become wavy & buckled. From 12 to 72 hours after MI, dead myocytes become hypereosinophilic with loss of nuclei ( coagulative necrosis). From 3 to 7 days after injury, dead myocytes are digested by invading macrophages. After 7 to 10 days, granulation tissue progressively replaces necrotic tissue, ultimately generating a dense fibrous scar.

41. Heart, contraction band necrosis - High power

42. Clinical features Diagnosis of MI based on a) symptoms – chest pain, nausea, diaphoresis, dyspnea . b) Electrocardiographic changes c) Elevation in the serum of cardiomyocyte -specific proteins released from dead cells e.g., creatine kinase MB isoform or various troponins About 25% of patients experience sudden death after infarction Of those surviving, the risk of death within 1 month after MI is 7% to 10%, & 80% to 90% will develop complications Early restoration of flow through occluded vessels responsible for the infarction yields a better prognosis.

43. Complications Depend on size & location of injury as well as functional myocardial reserves. Arrhythmias CHF Cardiogenic shock Ventricular rupture Papillary muscle infarction with or without rupture Fibrinous pericarditis is common 2 to 3 days after MI Mural thrombosis Ventricular aneurysm Repetitive infarction

44. HYPERTENSIVE HEART DISEASE SYSTEMIC (Left-Sided) Hypertensive Heart Disease Diagnosis Pathogenesis Morphology Clinical Features Pulmonary (Right-Sided) Heart Disease (Cor Pulmonale) Morphology Clinical Features

45. SYSTEMIC (Left-Sided) Hypertensive Heart Disease Diagnosis: A history or extracardiac anatomic evidence of hypertension Left ventricular hypertrophy, typically concentric Absence of other lesions that induce cardiac hypertrophy (e.g., aortic valve stenosis, aortic coarctation) Pathogenesis: Thickened myocardium reduces left ventricle compliance impairing diastolic filling increase oxygen demand Individual myocyte hypertrophy increase the distance for oxygen & nutrient diffusion

46. SYSTEMIC (Left-Sided) Hypertensive Heart Disease c ) Morphology: The left ventricular wall is thickened (>2 cm) Heart weight is increased (>500 gm) Myocytes and nuclei are enlarged Long-term, diffuse interstitial fibrosis and focal myocyte atrophy Degeneration may develop, with resulting left ventricle chamber dilation & wall thinning. d) Clinical Features: CHF Sudden cardiac death Renal disease Stroke or unrelated causes

47. Pulmonary (Right-Sided) Heart Disease (Cor Pulmonale) Cor pulmonale is the right-sided counterpart to systemic hypertensive heart disease; basically, pulmonary hypertension (caused by disorders affecting lung structure or function) causes right ventricular hypertrophy or dilation. Right ventricular enlargement due to congenital heart disease or left ventricular pathology is excluded. Acute cor pulmonale refers to right ventricular dilation after massive pulmonary embolization. Chronic cor pulmonale results from chronic right ventricular pressure overload. Hypoxemia and acidosis (e.g., in the setting of pneumonia or pulmonary emboli) cause vasoconstriction in the pulmonary vasculature that exacerbates any baseline pulmonary hypertension.

48. Pulmonary (Right-Sided) Heart Disease (Cor Pulmonale) Morphology : Right ventricular hypertrophy (often ≥1 cm), dilation, or both are present Right ventricular dilation can cause tricuspid regurgitation. b) Clinical Features : Chronic obstructive pulmonary disease

49. VALVULAR HEART DISEASE Valvular heart disease in adults is typically caused by: degeneration (e.g., calcific aortic stenosis, mitral annular calcification, mitral valve prolapse) immunologic inflammatory processes (e.g., rheumatic heart disease) infection (e.g., infective endocarditis)

50. VALVULAR HEART DISEASE Degenerative Calcific Aortic Valve Stenosis Morphology Clinical Features Mitral Annular Calcification Mitral Valve Myxomatous Degeneration (Mitral Valve Prolapse) Morphology Clinical Features 4) Rheumatic Fever and Rheumatic Heart Disease Morphology Clinical Features

51. Degenerative Calcific Aortic Valve Stenosis Is a common age related lesion that typically becomes clinically important over the age of 70. Morphology : Nodular, rigid calcific sub endothelial masses on the outflow surface of the valve cause cuspal thickening and immobility, thus impeding aortic outflow. Clinical Features : Angina Syncope CHE Urgent surgical valve replacement should be done.

52. Mitral Annular Calcification These degenerative, non-inflammatory calcific deposits are found within the mitral annulus, usually in the elderly. Regurgitation can occur from inadequate systolic contraction of the mitral valve ring. Stenosis can occur because leaflets are unable to open over bulky deposits. Nodular calcific deposits can impinge on conduction pathways, causing arrhythmias. Rarely, these deposits become a focus for infective endocarditis.

53. Mitral Valve Myxomatous Degeneration (Mitral Valve Prolapse) One or both mitral valve leaflets are enlarged, myxomatous, and floppy; they balloon back (prolapse) into the left atrium during systole, causing midsystolic clicks and regurgitation. Morphology Gross: redundancy and ballooning of the mitral valve leaflets is seen with elongated, attenuated, or occasionally ruptured chordae tendineae. Microscope: the fibrosa layer (on which the strength of the leaflet depends) shows thinning and degeneration with myxomatous expansion of the spongiosa. Similar changes occur in the chordae.

54. Secondary changes: Fibrous thickening of valve leaflets, especially at points at points of contact. Thickened ventricular endocardium at sites of contact with prolapsing leaflets or chordae Atrial thrombosis behind the balloning cusps,a potential source of emboli. Mitral annular calcification Clinical Features : Asymptomatic Atypical chest pain Infective endocarditis Gradual mitral valvular insufficiency to produce CHF Arrhythmias Sudden death

55. Rheumatic Fever and Rheumatic Heart Disease Rheumatic fever is an acute inflammatory disease classically occurring in children (5-15 years old) within 5 weeks following group A streptococcal infection (usually pharyngitis). It is attributed to host antistreptococcal antibodies that cross-react with cardiac antigens. Diagnosis is based on clinical history, and two of five major (Jones) criteria (minor criteria include fever, arthralgia, and leukocytosis).

56. Erythema marginatum : Macular skin lesions with erythematous rims and central clearing, typically in a bathing suit distribution. Sydenham chorea : A neurologic disorder with rapid, involuntary, purposeless movements. Carditis : 50% to 75% of children and 35% of adults; can involve myocardium, endocardium, or pericardium Subcutaneous nodules Migratory large joint polyarthritis: 90% of adults; less common in children Myocarditis and arthritis are transient and resolve without complications Valvular involvement can deform and scar the valve causing permanent dysfunction (chronic rheumatic heart disease) and subsequent CHF. Chronic rheumatic heart disease is most likely when the first attack is in early childhood or is particularly severe, or with recurrent attacks.

57. Morphology : Characteristic features in the acute phase : Aschoff bodies are pathognomonic ; these are foci of fibrinoid necrosis typically found in the myocardium. Initially surrounded by lymphocytes, macrophages, and plasma cells, they are slowly replaced by scar. Transient fibrinous pericarditis may contain Aschoff bodies. Inflammatory valvulitis is characterized by beady fibrinous vegetations ( verrucae ) that can contain Aschoff bodies. Characteristic features in the chronic phase : Fibrous thickening of leaflets Bridging fibrosis across valve commissures ( commissural fusion ), generating fishmouth or buttonhole stenoses Thickened, fused, and shortened chordae Calcification occurring deep in the fibrous leaflets Subendocardial collections of Aschoff nodules, usually in the left atrium, forming thickened MacCallum plaques ) Solitary mitral involvement occurs in 65% to 70% of cases, with combined aortic and mitral involvement in 20% to 25%; tricuspid and pulmonary valves are less frequently affected .

58. Clinical Features Changes secondary to mitral stenosis (the most frequent chronic result): Left atrial hypertrophy and enlargement, occasionally with mural thrombi Atrial fibrillation secondary to atrial dilation CHF with chronic pulmonary congestive changes Right ventricular hypertrophy Increased risk of infective endocarditis

59. Diagnostic Criteria for Infective Endocarditis Pathologic Criteria Clinical Criteria Major Minor

60. Pathologic Criteria Microorganisms, demonstrated by culture or histologic examination, in a vegetation, embolus from a vegetation, or intracardiac abscess. Histologic confirmation of active endocarditis in vegetation or intracardiac abscess.