Pathology of Heart Failure, Hypertension, Aneurysms and Neoplasia PDF

10/2/23 Pathology of heart failure, hypertension, aneurysms and neoplasia October 2023 1 Learning Objectives 1 Revise thrombosis • Seeing Disease section 6 to revise thrombosis https://sway.office.com/kyen3WcSyrK6jWrb • Read about aneuryms Define cardiac failure – let’s make this very brief • App...

10/2/23 Pathology of heart failure, hypertension, aneurysms and neoplasia October 2023 1 Learning Objectives 1 Revise thrombosis • Seeing Disease section 6 to revise thrombosis https://sway.office.com/kyen3WcSyrK6jWrb • Read about aneuryms Define cardiac failure – let’s make this very brief • Appreciate the differences between the following pairs of terms: – acute and chronic cardiac failure; – systolic and diastolic cardiac failure; – right and left ventricular failure • Describe the causes of left and right ventricular failure – Describe the clinical effects of left and right ventricular failure 2 1 10/2/23 Learning Objectives 2 • Distinguish between pulmonary and systemic hypertension • Be aware of B-natriuretic peptide BNP • Describe the causes of systemic hypertension – Describe the end-organ effects of systemic hypertension • Describe the causes of pulmonary hypertension – Describe the end-organ effects of pulmonary hypertension • Describe what an aneurysm is • Have an idea of what neoplasms may affect the heart and that they are rare 3 Define cardiac failure • Failure of the heart to pump sufficient blood, and deliver sufficient oxygen, to satisfy metabolic demands • Results in under-perfusion which may cause fluid retention and increased blood volume 4 2 10/2/23 Acute and chronic cardiac failure • Acute heart failure – rapid onset of symptoms, often with definable cause e.g. myocardial infarction • Chronic heart failure – slow onset of symptoms, associated with, for example, ischaemic or valvular heart disease • Acute-on-chronic heart failure – chronic failure becomes decompensated by an acute event 5 Systolic and diastolic cardiac failure Systolic failure • Failure of the pump to move blood in systole • • Reduced ejection fraction Reduced ventricular contraction Causes • Myocardial ischaemia • Myocardial infarction • Myocardial scarring • • • Myocarditis Drugs eg alcohol, anti-cancer cytotoxics, cocaine Muscular disorders eg DMD Effects • Reduced cardiac output • Feedback to atria and right side of heart • • Pulmonary oedema then Peripheal oedema Treatment • Support - what else? 6 3 10/2/23 Systolic and diastolic cardiac failure Systolic failure • Failure of the pump to move blood in systole • Reduced ejection fraction • Reduced ventricular contraction Causes Diastolic failure •Failure of ventricular wall to relax •Restrictive, stiff ventricle •Reduced ventricular filling leads to reduced blood for systole •Elevated end diastolic pressure Causes •Scarring plus most causes of systolic •Infiltrative disease eg amyloid • Myocardial ischaemia • Myocardial infarction • Myocardial scarring • Myocarditis • Drugs eg alcohol, anti-cancer cytotoxics, cocaine • Muscular disorders eg DMD Effects • Reduced cardiac output • Feedback to atria and right side of heart • Pulmonary oedema then • Peripheal oedema Effects •None •Pulmonary and peripheral oedema •Response to exercise •Tachycardia and pulmonary acute oedema Treatment •Reduce AV conduction – what else? Treatment • Support 7 Right and left ventricular failure • Right Primary effects where? • Left Primary effects where? 8 4 10/2/23 Describe the causes of left and right ventricular failure • Coronary heart disease • Hypertension • Cardiomyopathies-Familial/genetic or non-familial/non-genetic (including acquired, e.g. Myocarditis) Hypertrophic (HCM), dilated (DCM), restrictive (RCM), arrhythmogenic right ventricular (ARVC), unclassified • Drugs-beta-Blockers, calcium antagonists, antiarrhythmics, cytotoxic agents • Toxins Alcohol, medication, cocaine, trace elements (mercury, cobalt, arsenic) • Endocrine Diabetes mellitus, hypo/hyperthyroidism, Cushing syndrome, adrenal insufficiency, excessive growth hormone, phaeochromocytoma • Nutritional Deficiency of thiamine, selenium, carnitine. Obesity, cachexia • Infiltrative Sarcoidosis, amyloidosis, haemochromatosis, connective tissue disease • Others Chagas’ disease, HIV infection, peripartum cardiomyopathy, endstage renal failure 9 Describe the causes of left and right ventricular failure • Coronary heart disease • Hypertension • Cardiomyopathies-Familial/genetic or non-familial/non-genetic (including acquired, e.g. Myocarditis) Hypertrophic (HCM), dilated (DCM), restrictive (RCM), arrhythmogenic right ventricular (ARVC), unclassified • Drugs-beta-Blockers, calcium antagonists, antiarrhythmics, cytotoxic agents • Toxins Alcohol, medication, cocaine, trace elements (mercury, cobalt, arsenic) • Endocrine Diabetes mellitus, hypo/hyperthyroidism, Cushing syndrome, adrenal insufficiency, excessive growth hormone, phaeochromocytoma • Nutritional Deficiency of thiamine, selenium, carnitine. Obesity, cachexia • Infiltrative Sarcoidosis, amyloidosis, haemochromatosis, connective tissue disease • Others Chagas’ disease, HIV infection, peripartum cardiomyopathy, endstage renal failure 10 5 10/2/23 Describe the causes of left and right ventricular failure • Coronary heart disease • Hypertension • Cardiomyopathies-Familial/genetic or non-familial/non-genetic (including acquired, e.g. Myocarditis) Hypertrophic (HCM), dilated (DCM), restrictive (RCM), arrhythmogenic right ventricular (ARVC), unclassified • Drugs-beta-Blockers, calcium antagonists, antiarrhythmics, cytotoxic agents • Toxins Alcohol, medication, cocaine, trace elements (mercury, cobalt, arsenic) • Endocrine Diabetes mellitus, hypo/hyperthyroidism, Cushing syndrome, adrenal insufficiency, excessive growth hormone, phaeochromocytoma • Nutritional Deficiency of thiamine, selenium, carnitine. Obesity, cachexia • Infiltrative Sarcoidosis, amyloidosis, haemochromatosis, connective tissue disease • Others Chagas’ disease, HIV infection, peripartum cardiomyopathy, endstage renal failure 11 Describe the causes of left and right ventricular failure • Coronary heart disease • Hypertension • Cardiomyopathies-Familial/genetic or non-familial/non-genetic (including acquired, e.g. Myocarditis) Hypertrophic (HCM), dilated (DCM), restrictive (RCM), arrhythmogenic right ventricular (ARVC), unclassified • Drugs-beta-Blockers, calcium antagonists, antiarrhythmics, cytotoxic agents • Toxins Alcohol, medication, cocaine, trace elements (mercury, cobalt, arsenic) • Endocrine Diabetes mellitus, hypo/hyperthyroidism, Cushing syndrome, adrenal insufficiency, excessive growth hormone, phaeochromocytoma • Nutritional Deficiency of thiamine, selenium, carnitine. Obesity, cachexia • Infiltrative Sarcoidosis, amyloidosis, haemochromatosis, connective tissue disease • Others Chagas’ disease, HIV infection, peripartum cardiomyopathy, endstage renal failure 12 6 10/2/23 Describe the causes of left and right ventricular failure • Coronary heart disease • Hypertension • Cardiomyopathies-Familial/genetic or non-familial/non-genetic (including acquired, e.g. Myocarditis) Hypertrophic (HCM), dilated (DCM), restrictive (RCM), arrhythmogenic right ventricular (ARVC), unclassified • Drugs-beta-Blockers, calcium antagonists, antiarrhythmics, cytotoxic agents • Toxins Alcohol, medication, cocaine, trace elements (mercury, cobalt, arsenic) • Endocrine Diabetes mellitus, hypo/hyperthyroidism, Cushing syndrome, adrenal insufficiency, excessive growth hormone, phaeochromocytoma • Nutritional Deficiency of thiamine, selenium, carnitine. Obesity, cachexia • Infiltrative Sarcoidosis, amyloidosis, haemochromatosis, connective tissue disease • Others Chagas’ disease, HIV infection, peripartum cardiomyopathy, endstage renal failure 13 Describe the causes of left and right ventricular failure • Coronary heart disease • Hypertension • Cardiomyopathies-Familial/genetic or non-familial/non-genetic (including acquired, e.g. Myocarditis) Hypertrophic (HCM), dilated (DCM), restrictive (RCM), arrhythmogenic right ventricular (ARVC), unclassified • Drugs-beta-Blockers, calcium antagonists, antiarrhythmics, cytotoxic agents • Toxins Alcohol, medication, cocaine, trace elements (mercury, cobalt, arsenic) • Endocrine Diabetes mellitus, hypo/hyperthyroidism, Cushing syndrome, adrenal insufficiency, excessive growth hormone, phaeochromocytoma • Nutritional Deficiency of thiamine, selenium, carnitine. Obesity, cachexia • Infiltrative Sarcoidosis, amyloidosis, haemochromatosis, connective tissue disease • Others Chagas’ disease, HIV infection, peripartum cardiomyopathy, endstage renal failure 14 7 10/2/23 Describe the causes of left and right ventricular failure • Coronary heart disease • Hypertension • Cardiomyopathies-Familial/genetic or non-familial/non-genetic (including acquired, e.g. Myocarditis) Hypertrophic (HCM), dilated (DCM), restrictive (RCM), arrhythmogenic right ventricular (ARVC), unclassified • Drugs-beta-Blockers, calcium antagonists, antiarrhythmics, cytotoxic agents • Toxins Alcohol, medication, cocaine, trace elements (mercury, cobalt, arsenic) • Endocrine Diabetes mellitus, hypo/hyperthyroidism, Cushing syndrome, adrenal insufficiency, excessive growth hormone, phaeochromocytoma • Nutritional Deficiency of thiamine, selenium, carnitine. Obesity, cachexia • Infiltrative Sarcoidosis, amyloidosis, haemochromatosis, connective tissue disease • Others Chagas’ disease, HIV infection, peripartum cardiomyopathy, endstage renal failure 15 Describe the causes of left and right ventricular failure • Coronary heart disease • Hypertension • Cardiomyopathies-Familial/genetic or non-familial/non-genetic (including acquired, e.g. Myocarditis) Hypertrophic (HCM), dilated (DCM), restrictive (RCM), arrhythmogenic right ventricular (ARVC), unclassified • Drugs-beta-Blockers, calcium antagonists, antiarrhythmics, cytotoxic agents • Toxins Alcohol, medication, cocaine, trace elements (mercury, cobalt, arsenic) • Endocrine Diabetes mellitus, hypo/hyperthyroidism, Cushing syndrome, adrenal insufficiency, excessive growth hormone, phaeochromocytoma • Nutritional Deficiency of thiamine, selenium, carnitine. Obesity, cachexia • Infiltrative Sarcoidosis, amyloidosis, haemochromatosis, connective tissue disease • Others Chagas’ disease, HIV infection, peripartum cardiomyopathy, endstage renal failure 16 8 10/2/23 Describe the causes of left and right ventricular failure • Coronary heart disease • Hypertension • Cardiomyopathies-Familial/genetic or non-familial/non-genetic (including acquired, e.g. Myocarditis) Hypertrophic (HCM), dilated (DCM), restrictive (RCM), arrhythmogenic right ventricular (ARVC), unclassified • Drugs-beta-Blockers, calcium antagonists, anti-arrhythmics, cytotoxic agents • Toxins Alcohol, medication, cocaine, trace elements (mercury, cobalt, arsenic) • Endocrine Diabetes mellitus, hypo/hyperthyroidism, Cushing syndrome, adrenal insufficiency, excessive growth hormone, phaeochromocytoma • Nutritional Deficiency of thiamine, selenium, carnitine. Obesity, cachexia • Infiltrative Sarcoidosis, amyloidosis, haemochromatosis, connective tissue disease • Others Chagas’ disease, HIV infection, peripartum cardiomyopathy, endstage renal failure 17 Describe the clinical effects of left and right ventricular failure Left or right failure? 18 9 10/2/23 Describe the clinical effects of right ventricular failure Pitting oedema Congested “nutmeg” liver 19 Left ventricular failure • Particularly resulting from hypertensive and ischaemic heart failure • Causes pulmonary oedema, with associated • symptoms • Leads to pulmonary hypertension and, eventually, right ventricular failure • Combined left and right ventricular failure often called ‘congestive’ cardiac failure 20 10 10/2/23 Right ventricular failure Common causes • Secondary to left ventricular failure • Related to intrinsic lung disease • ‘Cor pulmonale’ due to pulmonary hypertension • Primary pulmonary hypertension 21 Key features of the clinical examination inpatients with heart failure • Appearance -alertness, nutritional status, weight • Pulse rate -rhythm, and character • Blood pressure -systolic, diastolic, pulse pressure • Fluid overload -jugular venous pressure • Peripheral oedema -(ankles and sacrum), hepatomegaly, ascites • Respiratory rate, crackles, effusion (transudate) • Apex displacement, gallop rhythm, third heart sound, flow murmurs suggesting valvular dysfunction 22 11 10/2/23 Clinical features sometimes referred to as: • “Forward” failure – Reduced perfusion of tissues – Tends to be more associated with advanced failure • “Backward” failure – Due to increased venous pressures – Dominated by fluid retention and tissue congestion 23 24 12 10/2/23 25 B-natriuretic protein BNP is one of of the natriuretic peptide hormone family, produced by ventricular muscle. It is a stress response protein that increases in heart failure. Acts on the ANP receptor but with relatively lower affinity but longer half life than other natriuretic proteins. Part of a family: ANP produced in atrial muscle, CNP from large blood vessels, DNP present in blood probably originates from heart • Vessel dilatation • • • • • • Reduced load on heart Changes in glomerular filtration Inhibits renin secretion Decrease aldosterone Natriuresis Reduction in blood pressure 26 13 10/2/23 Distinguish between pulmonary and systemic hypertension 27 Systemic hypertension • Common • Classification – Primary vs secondary (based on cause) – Essential vs accelerated (based on clinical presentation) – (be aware of the previous use of the misnomer “benign” hypertension) • Definition – Persistent raised blood pressure above 140/90 mmHg (Framingham, Multiple Risk Factor Intervention Trial –both suggest systolic pressure more important in determining cardiovascular risk) • Remember it is a global health problem – https://www.who.int/news-room/fact-sheets/detail/hypertension 28 14 10/2/23 Why is it important? • Hypertension is a major risk factor for: – Cardiovascular disease – Ischaemic heart disease – Accelerated atherosclerosis – Alzheimer type dementia • Important preventable cause of premature disease and death in developed and developing countries. 29 Epidemiology • An estimated 1.28 billion adults aged 30–79 years worldwide have hypertension, most (two-thirds) living in low- and middleincome countries • An estimated 46% of adults with hypertension are unaware that they have the condition • Less than half of adults (42%) with hypertension are diagnosed and treated • Approximately 1 in 5 adults (21%) with hypertension have it under control • Hypertension is a major cause of premature death worldwide • One of the global targets for noncommunicable diseases is to reduce the prevalence of hypertension by 33% between 2010 and 2030 Source – WHO Fact Sheet on hypertension 30 15 10/2/23 Is it helpful to categorise? • Optimal 120/80 mm Hg ideal blood pressure is usually considered to be between 90/60mmHg and 120/80mmHg • Hypertension high blood pressure is considered to be 140/90mmHg or higher (or 150/90mmHg or higher if you're over the age of 80) • Isolated systolic hypertension >130/<80 mm Hg – commonest in >65 year old 31 Systemic hypertension • 90% Primary (sometimes still referred to as essential or idiopathic) • 10% Secondary 32 16 10/2/23 Causes of secondary hypertension • • • • Renal disease – 75% are from intrinsic renal disease: e.g. glomerulonephritis, polyarteritis nodosa, systemic sclerosis, chronic pyelonephritis or polycystic kidneys. – Approximately 25% are due to reno-vascular disease -most frequently atheromatous (e.g. elderly cigarette smokers with peripheral vascular disease Endocrine disease – Cushings disease, – Conns disease, – Phaeochromocytoma, – Acromegaly, – Hyperparathyroidism Others – coarctation, – pre-eclampsia and hypertension in pregnancy Drugs and toxins, – alcohol, – cocaine, – ciclosporin, tacrolimus, – erythropoietin, – adrenergic medications, – decongestants containing ephedrine – herbal remedies – liquorice 33 Describe the end-organ effects of systemic hypertension Primary • Slow changes in vessels and heart with chronic end-organ dysfunction Accelerated • Rapid changes in vessels with acute endorgan dysfunction End organs Brain, heart, kidneys, arteries, eyes 34 17 10/2/23 Kidney • Nephrosclerosis – Drop-out’ of nephrons due to vascular narrowing – Proteinuria – Haematuria • Chronic renal failure • Acute renal failure can be associated with accelerated and severe hypertension 35 • Acceleration of atherosclerosis • Intimal proliferation and hyalinisation of arteries and arterioles • Accelerated and severe hypertension – fibrinoid necrosis 36 18 10/2/23 Brain Atherosclerosis Ischaemia and TIA Infarct Haemorrhage 37 Eyes 38 19 10/2/23 Describe the causes of pulmonary hypertension • Increased pulmonary vascular resistance • Diffuse lung disease, for example COPD • Elevated left atrial pressure e.g. left ventricular failure, mitral valve stenosis • Recurrent pulmonary emboli • Primary pulmonary hypertension (unknown cause) - genetics • Left-right shunts e.g. ASD, VSD 39 Describe the end-organ effects of pulmonary hypertension • Pulmonary arteries • Heart • Treat underlying cause, give symptomatic relief, transplant 40 20 10/2/23 Aneurysms - bulging, swollen blood vessel • Aortic and other arteries – Atherosclerosis – Hypertension • Berry aneurysm – Congenital • Dissecting aneurysm – Thoracic aorta, Marfan’s • Mycotic aneurysm – Infective endocarditis Local and systemic effects Screening Prevention Treatment 41 Neoplasia and the heart Rare - most often metastatic eg melanoma or small cell undifferentiated lung cancer Primary benign – atrial myxoma Primary malignant – angiosarcoma, rhabdomyosarcoma……. 42 21 10/2/23 Learning Objectives Revise thrombosis • Seeing Disease section 6 to revise thrombosis https://sway.office.com/kyen3WcSyrK6jWrb • Read about aneurysms Think about cardiac failure • Distinguish between pulmonary and systemic hypertension • Be aware of B-natriuretic peptide BNP Hypertension is a global problem • Describe the causes of systemic hypertension – Describe the end-organ effects of systemic hypertension • Describe the causes of pulmonary hypertension – Describe the end-organ effects of pulmonary hypertension Describe what an aneurysm is Have an idea of what neoplasms may affect the heart 43 22