Cardiovascular System and Diseases PDF

Components of the circulatory system ◼ A pump - the heart ◼ A distributary system - aorta, arteries, arterioles (different in size) ◼ An oxygenation system – pulmonary vessels/lungs ◼ A system for exchange - the capillaries ◼ A collecting system - veins, vena cava Heart Four valves: To maintain unid...

Components of the circulatory system ◼ A pump - the heart ◼ A distributary system - aorta, arteries, arterioles (different in size) ◼ An oxygenation system – pulmonary vessels/lungs ◼ A system for exchange - the capillaries ◼ A collecting system - veins, vena cava Heart Four valves: To maintain unidirectional blood flow through the heart- incomplete valve function can cause hypoxia Heart Myocardium: The cardiac muscle composed primarily of a collection of specialized muscle cells called cardiac myocytes Ventricular myocytes are arranged circumferentially in a spiral orientation and contract during systole and relax during diastole Heart blood supply To meet energy need, cardiac muscles rely almost exclusively on constant supply of oxygenated blood via the coronary arteries Three major epicardial coronary arteries 1.Left anterior descending (LAD) artery, most commonly effect by plaque 2.Left circumflex (LCX) artery 3.Right Coronary artery Most coronary arterial blood flow to the myocardium occurs during ventricular diastole, when the microcirculation is not compressed by cardiac contraction Cardiac conduction system Regulates the heart rate and rhythm Excitable tissue: can for action potentials with electrical signal cardiac muscle, nervous system Sensory system Skeletal muscle ◼ ◼ ◼ ◼ Why is the SA node tissue a pacemaker and not other tissues? The node can go very fast, cardio myocytes can beat 40 times a minute so SA node is the control The sinoatrial (SA) pacemaker of the heart, the SA node, located near the junction of the right atrial appendage and the superior vena cava The AV node, located in the right atrium along the atrial septum; The bundle of His, which courses from the right atrium to the summit of the ventricular septum; and its major divisions The right and left bundle branches, which further arborize in the respective ventricles through the anteriorsuperior and posterior-inferior divisions of the left bundle and the Purkinje network http://www.slideshare.net/Firedemon13/cardiac-conduction-system The electrocardiogram tracing Disorders of cardiac conduction Conduction defects (arrhythmias) due to uncoordinated generation of impulses lead to non- uniform and inefficient contraction of the heart Ventricular fibrillation- the heart cannot contract properly and pump Blood out, will probably have a cardiac arrest (stop beating) Compensatory mechanisms The Frank-Starling mechanism: Increased filling volumes dilate the heart and thereby increase functional cross-bridge formation within the sarcomeres → contractility Myocardial adaptations, including hypertrophy (athletes coping with high demand)with or without cardiac chamber dilation Activation of neurohumoral systems: 1) Release of noradrenaline by adrenergic cardiac nerves of the autonomic nervous system (↑heart rate, myocardial contractility, vascular resistance) 2) Activation of the renin-angiotensin-aldosterone system, final product will constrict muscle and will retain sodium and water in increase heart output 3) Release of atrial natriuretic peptide, does opposite to 2, reduces water and sodium to counteract the system above The latter two factors act to adjust filling volumes and pressures Structure and function of blood vessels Vascular arterial muscles have smooth muscle = contract, blood pressure/ resistance is determined by arterioles (proportional to diameter), needs to be looked at when seeing hypertension Extracellular matrix (ECM): elastin, collagen, and glycosoaminoglycans Blood pressure Blood pressure is a function of cardiac output and peripheral vascular resistance ▪ Systemic and local tissue blood pressures must be maintained within a narrow range ▪ Hypotension (low pressures) results in inadequate organ perfusion and can lead to dysfunction or tissue death ▪ Hypertension (high pressures) can cause vessel and end-organ damage Hypertension WHO data 2013 ◼ Globally cardiovascular disease accounts for approximately 17 million deaths a year, nearly one third of the total. Of these, complications of hypertension account for 9.4 million deaths worldwide every year. ◼ Hypertension is responsible for at least 45% of deaths due to heart disease (total ischemic heart disease mortality) ◼ It is responsible for 51% of deaths due to stroke Hypertension Clinically significant hypertension: According to the National Heart, Lung, and Blood Institute of the U.S.A. ◼ ◼ ◼ a sustained diastolic pressure greater than 89 mm Hg or a sustained systolic pressure in excess of 139 mm Hg associated with a measurably increased risk of atherosclerosis Risk factors Major factors that determine blood pressure variation within and between population: Stress Hypertension classification ◼ ◼ Essential (idiopathic) hypertension: do not know the full reason, not genetic ~90-95% cases A complex, multi-factorial disorder Genetic factors play an important role Secondary hypertension, from a disease, for example diabetes Blood pressure regulation Blood volume Na Mineralocorticoids Atriopeptin Humoral factors Constrictors Angiotensin II Catecholamines Endothelin Dilators Prostaglandins Kinins NO Cardiac Peripheral BP = X output resistance Cardiac factors Heart rate Contractility Local factors pH hypoxia Neural factors Constrictors α-adrenergic Dilators β-adrenergic Pathogenesis of secondary hypertension Renal- decrease lumen= increase resistance Endocrine Cardiovascularnarrowing of aorta Neurologicaldepression, stress Symptoms of hypertension Persistent headache Blurred or double vision Nosebleeds Shortness of breath Treatment: Antihypertensive drugs ◼ ◼ ◼ ◼ ACE inhibitors or angiotensin receptor antagonistscounteracts the constriction of vessel Beta-blockers- reduces adrenaline, heart beats less, reduces hypertension Calcium channel blockers- smooth muscle contraction= calcium channels, so blocking this will relax vessels Diuretics- removes excess urine, which reduces water and reduce blood volume= reduced blood volume and pressure Hypertensive heart diseases Hypertension causes pressure-overload and ventricular hypertrophy ◼ Systemic hypertension causes left heart hypertrophy (most common) ◼ Pulmonary hypertension causes right heart hypertrophy Morphology of hypertensive left ventricular hypertrophy: ◼ Left ventricular wall thickening ◼ Increased heart weight ◼ Ventricular wall stiffness impairs diastolic filling causing left atrial enlargement Hypertensive heart diseases Compensated stage may be asymptomatic, and can be diagnosed by electrocardiogram or echocardiography Progress to heart failure or ischemic heart disease In lecture question and discussion Which of the following is a compensatory mechanism for cardiac dysfunction? a) Cardiac hypertrophy b) Release of noradrenaline c) Activation of renin-angiotensin-aldosterone system d) Release of atrial natriuretic peptide e) All of the above Atherosclerosis ◼ Atherosclerosis ("hardening of the arteries") is a generic term for thickening and loss of elasticity of arterial walls ◼ Characterized by intimal lesions (atheromatous or fibrofatty plaques) which protrude into and obstruct vascular lumens ◼ Atherosclerotic plaques develop primarily in elastic arteries (e.g., aorta, carotid) and large and medium sized muscular arteries (e.g., coronary arteries) ◼ Associated with increased LDL-cholesterol and reduced HDL-cholesterol ◼ Causes of atherosclerosis are still unclear Risk Factors – non-modifiable For example, age cannot be changed, we can pay more attention to these people Age ◼ Gender M>F ◼ Positive family history ◼ Genetic abnormality (eg, ACE gene) ◼ Risk Factors – modifiable ◼ ◼ ◼ ◼ ◼ ◼ Hyperlipidemia – eat less fatty food Hypertension – reduce blood pressure, can cause AS via endothelial damage as lipids and macrophages can get in Smoking- causes oxidative stress Diabetes- causes direct damage to vessel Obesity Physical inactivity Pathological feature - Atherosclerotic plaques ◼ Characterized by intimal lesions - atheromas (atheromatous or atherosclerotic plaques) ◼ The plaques protrude into vessel lumens ◼ The plaque consists of a raised lesion with a soft, yellow, grumous core of lipid (mainly cholesterol and cholesterol esters) covered by a white fibrous cap Structure of atherosclerotic plaques ◼ A superficial fibrous cap – SM cells, relatively dense collagen ◼ Beneath and to the side of the cap ("shoulder") - a more cellular area containing macrophages, T cells, SM cells ◼ Necrotic core (deep to the fibrous cap, containing lipid, debris from dead cells, foam cells (lipid inside), fibrin, variably organized thrombus, and other plasma proteins) ◼ The cholesterol, frequently present as crystalline aggregates or "clefts” ◼ Neovascularization (due to chronic inflammation) at the periphery of the lesions Fibrous cap pushes lumen to make it smaller and apply pressure Nature Reviews Cardiology 2015 3 principal components: 1. Cells: SMCs, macrophages, and other leukocytes 2. Extracellular matrices: collagen, elastin, proteoglycans 3. Intracellular and extracellular lipid Morphology of the Lesions ◼ Earliest aortic atherosclerosis ◼ fatty streaks (slow process) lipid-filled foamy macrophages  begin as multiple minute flat yellow spots  ◼ Advanced complicated atherosclerosis in abdominal aorta many of the lesions have ruptured ◼ become thrombosed (thrombosis) ◼ Pathogenesis Key pathogenic events ◼ Endothelial injury: increases vascular permeability, leukocyte adhesion (adhesion proteins will be expressed), and thrombosis ◼ Accumulation of lipoproteins: (mainly LDL) in the vessel wall ◼ Monocyte adhesion to the endothelium, followed by migration into the intima and transformation into macrophages and foam cells ◼ Platelet adhesion- start of clotting, they attract clotting factors --> thrombosis ◼ Factor release from activated platelets, macrophages, and vascular wall cells --> SMC recruitment and further accumulation of macrophages ◼ SMC proliferation and ECM production- makes blood vessels narrow ◼ Lipid accumulation: both extracellularly and within cells (macrophages and SMCs) Consequences of atherosclerotic plaques ◼ Rupture, ulceration, or erosion of the intimal surface → highly thrombogenic substances → thrombosis ◼ Haemorrhage into a plaque. Rupture of the fibrous cap → intra-plaque haemorrhage → plaque rupture ◼ Atheroembolism. Plaque rupture → atherosclerotic debris into bloodstream → microemboli ◼ Aneurysm formation. Atherosclerosis-induced pressure, ischemic atrophy, loss of elastic tissue → weakness → aneurysmal dilation and potential rupture Stages of atherosclerotic pathogenesis and complications Rupture gets bigger and bigger= lumen gets smaller and smaller Clinical outcomes of atherosclerotic diseases The principal outcomes depend on    Size of the involved vessels, coronary artery= effect the heart, brain artery= stroke Relative stability of the plaque itself, want to increase stability of plaque Degree of degeneration (underlying arterial wall ) Major consequences: ◼ Myocardial infarction (heart attack) ◼ Cerebral infarction (stroke) ◼ Aortic aneurysms ◼ Peripheral vascular disease (gangrene of the legs), can stay in patient for a long time Ischemic heart disease Ischemic heart disease (IHD) is the leading cause of death worldwide for both men and women In more than 90% of cases, the cause of myocardial ischemia is reduced blood flow due to obstructive atherosclerotic lesions in the coronary arteries (blockage) Clinical manifestations: ◼ Angina pectoris, chest pain ◼ Myocardial infarction, the most important form of IHD ◼ Heart failure ◼ Sudden cardiac death Angina pectoris (chest pain) ◼ ◼ ◼ ◼ Characterized by paroxysmal and usually recurrent attacks substernal or precordial chest discomfort variously described as constricting, squeezing, choking, or knifelike caused by transient (not permanent, not yet caused cell death), (15 seconds to 15 minutes) myocardial ischemia, more than 1 hour, patient has serious Patterns of angina pectoris Three overlapping patterns: WARNING!! 1) Stable or typical angina, can be caused by stress/ vigourous exersize 2) Variant (Prinzmetal, vasospastic) angina, smooth muscle spasm, Rare 3) Unstable (crescendo) angina, can happen with no cause, somewhat common ST depression Not all ischemic events are perceived by patients (silent ischemia) Myocardial Infarction (MI) Known as "heart attack," is the death of cardiac muscle due to prolonged severe ischemia Pathogenesis: Coronary arterial occlusion, due to plaque overgrowth or plaque blockage Causes of coronary arterial occlusion ◼ Coronary atherosclerosis (90%) ◼ Vasospasm with or without coronary atherosclerosis ◼ Emboli from the left atrium in association with atrial fibrillation ◼ Others Clinical Features ◼ The most frequent symptom of acute myocardial infarction is severe chest pain ◼ This often develops suddenly but may build up gradually, and generally lasts for several hours ◼ Pain is usually accompanied by profuse sweating, nausea and vomiting ◼ Many patients give a previous history of angina or non-specific chest pain in the weeks before the acute event ◼ In at least 10% of patients, myocardial infarction is painless or 'silent'; this is particularly true in the elderly ECG changes of MI Q wave can diagnose myocardial infarction, it will not return back to normal Before Minutes afterwards Hours afterwards Days afterwards Weeks afterwards Progression of IHD Ischemic heart disease at any time can cause sudden death, directly or Heart failure Heart failure is a complex syndrome that can result from any structural or functional cardiac disorder that impairs the ability of the heart to function as a pump to support a physiological circulation. It is often called congestive heart failure (CHF), is a common, usually progressive condition with a poor prognosis. CHF occurs when the heart 1. Is unable to pump blood at a rate sufficient to meet the metabolic demands of the tissues or 2. Can do so only at an elevated filling pressure Different forms of heart failure ▪ Acute heart failure ▪ Myocardial infarction ▪ Chronic heart failure ▪ Valvular defects ▪ Left heart failure ▪ Hypertension, ischemic heart disease ▪ Right heart failure ▪ Severe pulmonary hypertension; secondary to left heart failure Left-sided heart failure Most common causes: due to failed left ventricular chamber, so pulmonary blood cannot be pumped back, all the tissue in the left- hand side on the hear tis compromised ▪ Ischemic heart disease ▪ Hypertension ▪ Aortic and mitral valvular diseases ▪ Myocardial disease The morphological and clinical effects of left-sided CHF primarily result from 1) congestion of the pulmonary circulation 2) stasis of blood in the left-sided chambers 3) hypoperfusion of tissues leading to organ dysfunction Morphology of left heart failure Heart: Left ventricle hypertrophy and dilation Left atrium dilation Lungs: Pulmonary congestion and oedema Perivascular and interstitial oedema Interlobular septa Alveolar septa Alveolar oedema Right-sided heart failure Most commonly a secondary consequence of left-sided heart failure due to increase in pressure in the pulmonary circulation Morphology: ◼ Heart: Hypertrophy and dilation of the right atrium and ventricle ◼ Liver: Congestive hepatomegaly, because blood from here and the spleen needs to be taken back to the vena cava ◼ Spleen: Congestive splenomegaly ◼ Lung: Pulmonary oedema ◼ Accumulation of fluid in pleural, pericardial, or peritoneal spaces (effusions) ◼ Oedema of the peripheral: Ankle (pedal) and pretibial oedema is a hallmark of right-sided heart failure, clinically, you can differentiate between the two