Cardiovascular System Disorders Lecture Notes PDF

Disorders of Cardiovascular Function Pathophysiology Presented by Dr. Huda Atiyeh Outlines Anatomy & Physiology of the Heart Cardiac cycle Regulation of cardiac performance Disorders of Systemic Arterial Blood Flow Hypertension; primary and secondary Clinical ma...

Disorders of Cardiovascular Function Pathophysiology Presented by Dr. Huda Atiyeh Outlines Anatomy & Physiology of the Heart Cardiac cycle Regulation of cardiac performance Disorders of Systemic Arterial Blood Flow Hypertension; primary and secondary Clinical manifestations of hypertension Target-organ damage related to HTN; Heart, Kidney, Brain, and eyes Pathophysiology of Congestive Heart Failure Manifestations of Rt-and Lt-sided HF Classification of Heart Failure Compensatory mechanism; Renin–Angiotensin–Aldosterone Mechanism Diagnosis and treatment of Heart Failure  Intended Learning Outcomes At the end of this lecture, students will be able to: 1. Demonstrate the structural anatomy and Physiology of the Heart 2. Explain the cardiac cycle 3. Calculate the basic values related to cardiac performance 4. Describe ischemia as a systemic arterial blood flow disorder 5. Describe infarction as a systemic arterial blood flow disorder 6. Describe Vasculitis as a systemic arterial blood flow disorder 7. Describe Atherosclerosis as a systemic arterial blood flow disorder Describe Aneurysms as a systemic arterial blood flow disorder  Intended Learning Outcomes At the end of this lecture, students will be able to: 8. Differentiate between primary and secondary Hypertension. 9. Understand the clinical manifestations of hypertension. 10. Explain the Target-organ damage caused by HTN in relation to the heart, kidney, brain, and eyes. 11. Understand the pathophysiology of Congestive Heart Failure. 12. Describe the manifestations of Rt-and Lt-sided Heart Failure. 13. Classify the stages of Heart Failure. 14. Understand the compensatory mechanism related to heart failure; Renin– Angiotensin–Aldosterone Mechanism. 15. Identify the diagnosis and treatment of Heart Failure. Anatomy & Physiology of the Heart The heart is a four-chambered pump with two atria. The right atrium receives blood returning to the heart from the systemic circulation. The left atrium receives oxygenated blood from the lungs). The right ventricle pumps blood to the lungs. The left ventricle pumps blood into the systemic circulation. Heart valves control the direction of blood flow from the atria to the ventricles (the AV valves).  Cardiac cycle The cardiac cycle describes the rhythmic pumping action of the heart. - Systole: ventricles contraction. - Diastole: ventricles relaxation, and filling with blood  Regulation of Cardiac Performance The efficiency of the heart is measured by cardiac output (CO) or the amount of blood pumped each minute. (CO = SV × HR). Average CO in resting adults ranges from 4 to 6.0 L/minute. Cardiac reserve is the maximum percentage of increase in CO above normal resting level  Regulation of Cardiac Performance Resting CO = 4 to 6 L/min Vigorous Exercise= 21 L/min Cardiac Reserve: the difference between the maximum and resting CO If resting CO=6 L/min and after exercise increases to 21 L/min, what is the cardiac reserve?  Regulation of Cardiac Performance The heart’s ability to increase its output mainly depends on preload and afterload. Preload is the end-diastolic pressure when the ventricle has been filled. It is the load imposed on the heart prior to contraction and is the amount of blood the heart pumps per beat. It is largely determined by the venous return and accompanying stretch of cardiac muscle fibers.  Regulation of Cardiac Performance Afterload is the work post contraction required to move blood into the aorta. Systemic arterial pressure is the main source of afterload on the left heart. Pulmonary arterial pressure is the main source of afterload on the right heart. Disorders of Systemic Arterial Blood Flow  Disorders of Systemic Arterial Blood Flow The effect of impaired blood flow on the body depends on the structures involved and the extent of altered flow. Ischemia Infarction Atherosclerosis Vasculitis Aneurysms  Disorders of Systemic Arterial Blood Flow Ischemia is the reduction in arterial flow to a level that is insufficient to meet the oxygen demands of the tissues.  Disorders of Systemic Arterial Blood Flow Infarction refers to an area of ischemic necrosis in an organ produced by occlusion of its arterial blood supply or venous drainage  Disorders of Systemic Arterial Blood Flow Atherosclerosis is a progressive disease characterized by the formation of fibro-fatty plaques in the intima of large- and medium- sized vessels  Disorders of Systemic Arterial Blood Flow Vasculitis is an inflammation of the blood vessel wall, resulting in tissue injury and necrosis. Arteries, capillaries, and veins may be affected.  Disorders of Systemic Arterial Blood Flow Aneurysms are abnormal localized dilatation of an artery because of a weakness in the vessel wall. Hypertension  Hypertension Hypertension is a sustained elevation of blood pressure within the arterial circuit. It is a primary risk factor for cardiovascular disease and a leading cause of morbidity and mortality worldwide. Primary hypertension: refers to the clinical presence of hypertension without evidence of a specific causative clinical condition. Secondary Hypertension: elevation in blood pressure because of another disease condition Classification of BP –American Heart Association  What leads to Primary HTN? A. Nonmodifiable Risk Factors of Primary Hypertension: Age: increase with age. Gender: More among Males. Family history, and genetics B. Modifiable Risk Factors of Primary Hypertension: Uncontrolled glucose levels in diabetes Lipid disorders (elevated low-density lipoprotein- cholesterol [LDL-C] and triglycerides Overweight- obesity Hyperuricemia Metabolic syndrome Unhealthy lifestyle habits (e.g. smoking, high alcohol intake, sedentary lifestyle). 27  Secondary HTN: Causes 1. Drugs: Cocaine and amphetamines. 2. Medications: sympathomimetic agents (decongestants, anorectics), erythropoietin, and licorice (including some chewing tobacco with licorice as an ingredient). 3. Kidney disease (i.e., renovascular hypertension, Renal parenchymal disease, Renal artery stenosis): largest single cause of secondary hypertension. 4. Disorders of adrenal cortical hormone (Primary hyperaldosteronism, Cushing syndrome) 28  Secondary HTN: Causes 1. Pheochromocytoma: the tumor releases hormones that may cause high blood pressure, headache, sweating, and symptoms of a panic attack. Increased plasma levels of Metanephrines secreted by Adrenal Medulla. Metanephrines are made when the body breaks down hormones called catecholamines 2. Coarctation of the aorta: Higher blood pressure in upper than lower extremities Delayed or absent femoral pulses; with coarctation of the aorta, the left ventricle works harder to pump blood through the narrowed aorta. As a result, blood pressure rises in the left ventricle. The wall of the left ventricle may become thick (hypertrophy). 3. Thyroid disease. 4. Obstructive sleep apnea (OSA); OSA episodes produce surges in systolic and diastolic pressure that keep mean blood pressure levels elevated at night. In many patients, blood pressure remains elevated during the daytime, when breathing is normal. 5. Use of oral contraceptive agents.  Clinical Manifestations of Hypertension Primary hypertension is typically an asymptomatic disorder. When symptoms do occur, they are often related to long-term effects of hypertension on target-organ systems, such as the kidneys, heart, eyes, and blood vessels. Target-organ damage varies markedly among people with similar levels of hypertension  Target-Organ Damage Increased perfusion pressure can damage target organs, and increased intravascular pressure can damage vascular endothelial cells, which increases the risk for the development of atherosclerotic vascular disease Target-organ damage particularly affects organs that are highly vascular or dependent on adequate blood supply for appropriate function. Hypertension is a leading cause of ischemic heart and brain disease, end-stage renal disease, and visual impairment or blindness caused by retinopathy  Heart and HTN Elevated blood pressure increases the workload of the left ventricle. Over time, the left ventricular wall remodels and hypertrophies to compensate for the increased pressure work. This is a major risk factor for coronary heart disease, cardiac dysrhythmias, sudden death, and congestive heart failure because it cannot pump efficiently.  Kidney and HTN One way hypertension causes damage to the kidneys is through glomerular hypoperfusion, which causes glomerulosclerosis and tubulointerstitial fibrosis. Other ways include endothelial dysfunction resulting from high glomerular pressures. Also plays an important role in accelerating the course of other types of kidney disease, particularly diabetic nephropathy.  Brain and HTN Narrowing and sclerosis of small penetrating arteries in the subcortical contribute to hypoperfusion, loss of autoregulation of blood flow, and impairment of the blood–brain barrier, ultimately leading to subcortical white matter demyelination  Eyes and HTN The eye will initially have increased vasomotor tone, which causes generalized arteriolar narrowing. As hypertension persists, arteriosclerotic changes include media wall hyperplasia, intimal thickening, and hyaline degeneration. These long-term changes can cause more severe Retinal arteriovenous (Retinal AV) nicking and may cause blindness. Acute increases in blood pressure can lead to hemorrhages, microaneurysms, and hard exudates. Congestive Heart Failure  General terms Ejection fraction; normally about 55% to 70%. Ejection fraction (EF) is a measurement, expressed as a percentage, of how much blood the left ventricle pumps out with each contraction. An ejection fraction of 60 % means that 60 % of the total amount of blood in the left ventricle is pushed out with each heartbeat.  Heart failure is a complex syndrome resulting from any functional or structural disorder of the heart that results in or increases the risk of developing manifestations of low cardiac output and/or pulmonary or systemic congestion.  Pathophysiolgy of Heart Failure The heart has the capacity to adjust CO to meet the varying needs of the body. The ability to increase CO during increased activity is the cardiac reserve. During exercise, CO can increase up to five to six times resting Level. People with heart failure often use their cardiac reserve at rest, and mild activity may cause shortness of breath because of exceeding their cardiac reserve.  Congestive Heart Failure Causes: - CAD. - Hypertension. - Dilated cardiomyopathy. - Valvular heart disease.  Classification of CHF The American College of Cardiology /American Heart Association guidelines have incorporated a classification system of heart failure that includes four stages: - Stage A—High risk for developing heart failure, but no identified structural abnormalities and no signs of heart failure. - Stage B—The presence of structural heart disease, but no history of signs and symptoms of heart failure. - Stage C—Current or prior symptoms of heart failure with structural heart disease. - Stage D—Advanced structural heart disease and symptoms of heart failure at rest on maximum medical therapy.  Classification of HF Systolic versus Diastolic Dysfunction: Left ventricular (LV) failure can be divided into systolic and diastolic dysfunction. Systolic dysfunction is characterized by a reduced ejection fraction (under 40% ) , and an enlarged LV chamber. It is clinically associated with left ventricular failure in the presence of marked cardiomegaly.. Diastolic dysfunction is characterized by increased resistance to filling with increased filling pressures. It is accompanied by pulmonary congestion together with a normal or only slightly enlarged ventricle.  Right versus Left Ventricular Dysfunction Right Ventricular Dysfunction When the right ventricle fails, there is reduced deoxygenated blood moving into the pulmonary circulation and a reduction in LV CO. If the right ventricle does not move the blood forward, there is congestion of blood into the systemic venous system. This increases right ventricular end-diastolic, right atrial, and systemic venous pressures. A major effect of right-sided heart failure is peripheral edema.  Right versus Left Ventricular Dysfunction Right-sided heart failure also produces congestion of the viscera. As venous distention progresses, blood backs up in the hepatic veins that drain into the inferior vena cava, and the liver becomes engorged (hepatomegaly) and right upper quadrant pain. Portal circulation congestion may also lead to spleen engorgement and the development of ascites. GI tract congestion may interfere with digestion and absorption of nutrients, causing anorexia and abdominal discomfort. In severe right-sided heart failure, the external jugular veins become distended and can be seen when sitting up or standing.  Left-sided heart failure Left-sided heart failure Impairs the movement of blood from the low-pressure pulmonary circulation into the high-pressure arterial side of the systemic circulation. Impairment of left heart function decreases CO to the systemic circulation. Blood accumulates in LV, left atrium, and pulmonary circulation, which causes an elevation in pulmonary venous pressure. When the pressure in the pulmonary capillaries (10 mm Hg) exceeds capillary osmotic pressure (25 mm Hg), there is a shift of intravascular fluid into the interstitium of the lung, resulting in pulmonary edema. Manifestations of Rt-and Lt-sided HF Compensatory mechanisms in heart failure  Compensatory Mechanism Sympathetic Nervous System Activity: Stimulation of the sympathetic nervous system plays an important role in the compensatory response to decreased CO and SV. Cardiac sympathetic tone and catecholamine levels are elevated during the late stages of most heart failure. By direct stimulation of HR and cardiac contractility, regulation of vascular tone, and enhancement of renal sodium and water retention, the sympathetic nervous system initially helps maintain perfusion of the body organs. An increase in sympathetic activity by stimulation of β-adrenergic receptors leads to tachycardia, vasoconstriction, and cardiac arrhythmias. Sympathetic& Parasympathetic Nervous System Activity  Renin–Angiotensin–Aldosterone Mechanism: Renin–Angiotensin–Aldosterone Mechanism: One of the most important effects of lowered CO in heart failure is reduction in renal blood flow and glomerular filtration rate, which leads to sodium and water retention. Decreased renal blood flow, there is a progressive increase in renin secretion by the kidneys and increases in circulating levels of angiotensin II.  Renin–Angiotensin–Aldosterone Mechanism Angiotensin II provides a powerful stimulus for aldosterone production. Aldosterone increases tubular reabsorption of sodium and water. Angiotensin II also increases antidiuretic hormone (ADH). Angiotensin II and aldosterone stimulate inflammatory cytokine production, attract inflammatory cells, activate macrophages at sites of injury and repair, and stimulate growth of fibroblasts and synthesis of collagen fibers. Fibroblast and collagen deposition results in ventricular hypertrophy and myocardial wall fibrosis, which decreases compliance, causing heart remodeling and progression of both systolic and diastolic ventricular dysfunction. Renin–Angiotensin–Aldosterone Mechanism  Myocardial Hypertrophy and Remodeling: Cardiac muscle cells respond to stimuli from stress on the ventricular wall by initiating several different processes that lead to hypertrophy. These include stimuli that produce symmetric hypertrophy with a proportionate increase in muscle length and width, as occurs in athletes; concentric hypertrophy with an increase in wall thickness, as occurs in hypertension; and eccentric hypertrophy with a disproportionate increase in muscle length, as in Dilated cardiomyopathy (DCM); is characterized by dilatation of the ventricles, impairs diastolic filling, and systolic dysfunction. PO= Pressure Overload VO=Volume Overload  Diagnosis and Treatment The diagnostic methods in heart failure are directed toward establishing the cause and extent of the disorder. Treatment is directed toward correcting the cause whenever possible, improving cardiac function, maintaining the fluid volume within a compensatory range, and developing an activity pattern consistent with individual limitations in cardiac reserve.  Diagnosis and Treatment Among the medications used in the treatment of heart failure are diuretics, Angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blocking agents, β-adrenergic receptor blockers, digoxin, and vasodilators. Mechanical support devices, including ventricular assist devices(VADs), sustain life in people with severe heart failure. Heart transplantation remains the treatment of choice for many people with end-stage heart failure.  References  Carol, Mattson Porth, and Grossman Sheila (2018). "Porth’s Pathophysiology: Concepts of Altered Health States 10th edition."  Judy Craft, Christopher Gordon, Sue Huether, Kathryn, McCance, Valentina Brashers (2018).Understanding Pathophysiology, 3rd edition, Elsevier. The End