BIOL 2200 Module 5 Cardiovascular Disorders PDF

Module 5: Cardiovascular Disorders Angina and Acute Coronary Syndrome Cardiac Dysrhythmias/Arrhythmias Heart Abnormalities Heart Failure Shock Vascular disorders  Atherosclerosis Definition: Fibrous fatty lesions (“plaques”) that for...

Module 5: Cardiovascular Disorders Angina and Acute Coronary Syndrome Cardiac Dysrhythmias/Arrhythmias Heart Abnormalities Heart Failure Shock Vascular disorders  Atherosclerosis Definition: Fibrous fatty lesions (“plaques”) that form in large and medium sized arteries, resulting in reduced flow rate causing ischemia to supplied organ/tissue Copyright © 2010 Pearson Education, Inc.  Atherosclerosis Principally a disease the tunica intima of arteries Fibrous fatty lesions form in large / medium sized arteries – aorta, femoral, carotid and coronary Results in: – increased wall thickness, decreased elasticity – reduced vessel radius à reduced flow rate – ischemia to supplied organ / tissue Copyright © 2010 Pearson Education, Inc.  Sites of severe atherosclerosis Copyright © 2010 Pearson Education, Inc.  Etiology Related to endothelial cell damage – Could be from hyperlipidemia, cigarette smoke, diabetes, immune mechanisms, turbulent blood flow, etc. This results in: 1. Increased endothelial permeability to plasma protein and lipids 2. Migration of monocytes and other leukocytes into sub- endothelial layers 3. Monocytes differentiate to macrophages, ingest lipid and transform into lipid filled foam cells. 4. Macrophages release growth factors that proliferate smooth muscle, as well as reactive oxygen species and other toxic substances 5. Progressive tissue damage and growth of plaque lesion Copyright © 2010 Pearson Education, Inc.  Etiology See Porth main figure 506-507 6 Copyright © 2010 Pearson Education, Inc.  Low density lipoproteins A transport form of lipids in blood LDLs are oxidized by ROS in plaques and then phagocytized by macrophages (à foam cells) There is a strong association between high levels of plasma LDLs and coronary artery disease (more atherosclerosis) Copyright © 2010 Pearson Education, Inc.  Predisposing risk factors Elevated cholesterol (may be genetic) High blood pressure > endothelial cell damage Obesity Diabetes Smoking Sedentary lifestyle  Coronary artery disease (CAD) Cause of ischemic heart disease Third of all deaths in industrialized West Nearly all elderly have some coronary impairment For health care professionals – essential to understand pathophysiology Porth p 553 Copyright © 2010 Pearson Education, Inc.  Ischemic heart disease: IHD …a disease characterized by ischemia (reduced blood supply) of the heart muscle, usually due to coronary artery disease (atherosclerosis of the coronary arteries) Since coronary artery disease is the major cause of ischemic heart disease, the two terms are often used interchangeably Copyright © 2010 Pearson Education, Inc.  Coronary arteries Left (main) and Right Both originate from aorta Main arteries on surface, deeper branches penetrate muscle Copyright © 2010 Pearson Education, Inc.  The right coronary artery The left coronary artery supplies supplies mostly the right mostly the left ventricle and ventricle and posterior regions interventricular septum of the heart 12 Copyright © 2010 Pearson Education, Inc.  Myocardial blood flow In strenuous exercise coronary blood flow é 3-4X Nervous control of myocardial blood flow operates by two mechanisms – producing vasodilation or constriction of coronary blood vessels 1. Autonomic control: – Parasympathetic via vagus nerve – Sympathetic 2. Local autoregulatory control Porth p 556 Copyright © 2010 Pearson Education, Inc.  Myocardial blood flow: autoregulation nitric oxide & adenosine Local metabolism is a major control of myocardial blood flow: vasoactive mediators produce vasodilation or constriction of coronary blood vessels to match metabolic / oxygen demands of cardiac muscle Copyright © 2010 Pearson Education, Inc.  Myocardial blood flow is highest during diastole Right Left Copyright © 2010 Pearson Education, Inc.  Myocardial blood flow When the ventricles contract (systole) the muscle compresses muscle capillaries, reducing blood flow In CAD, subendocardial regions of muscle (below the endocardium): are usually damaged first as they have most difficulty obtaining adequate blood flow Copyright © 2010 Pearson Education, Inc.  Myocardial blood flow Lifesaving value of collateral circulation – many connections called anastomoses exist between smaller coronary arteries – during acute ischemia the anastomoses dilate within seconds, providing an alternative path for blood flow Copyright © 2010 Pearson Education, Inc.  Atherosclerosis as a cause of ischemic heart disease Pathogenesis 1. Cholesterol deposited beneath endothelium of arteries 2. Deposits invaded by fibrous tissue 3. Deposits often become calcified = atherosclerotic plaques 4. Plaques protrude into vessel lumens 5. Blocks or partially blocks blood flow 6. A common site for atherosclerotic plaques is the first few cms of coronary arteries 7. A gradual hardening and narrowing of the coronary arteries can lead to angina pectoris and eventually complete occlusion (myocardial infarction) Copyright © 2010 Pearson Education, Inc.  Angina pectoris Stable angina Chest pain caused by transient myocardial ischemia not severe enough to cause necrosis Brought on through physical exertion/emotional stress Myocardial blood flow cannot respond to increased demand for blood due to narrowing of one or more coronary arteries by atherosclerotic plaque In angina pectoris (and myocardial infarction) pains radiates from the sub-sternal region of the chest to the jaw and down the arms. Copyright © 2010 Pearson Education, Inc.  Atherosclerotic plaque in angina Copyright © 2010 Pearson Education, Inc.  Angina pectoris Unstable angina The surface of a plaque experiences small disruptions, leading to the development of small thromboses, which cause periods of occlusion Very important to recognize unstable angina, as it may predict eventual myocardial infarction Requires immediate hospitalization for rest, observation and treatment: oxygen, aspirin (reduce clotting), nitrates (vasodilator), morphine Copyright © 2010 Pearson Education, Inc.  Differentiating between stable and unstable angina Stable Angina Plaque intact, partially obstructing coronary artery Pain predictably brought on by physical exertion / emotional stress Symptoms last less than 15 minutes Symptoms relieved by GTN (glycerol trinitrate) vasodilator Effects of ischemia on myocardium are temporary / no necrosis Copyright © 2010 Pearson Education, Inc.  Unstable angina Plaque movement or small thrombi formation >> temporary ischemia Chest pain is not in response to exertion or stress, but is spontaneous, sudden and unpredictable Pain generally more severe, lasting longer than 20 minutes and is not relieved by GTN Effects of ischemia on myocardium are temporary / no necrosis May lead to life threatening myocardial infarction Copyright © 2010 Pearson Education, Inc.  Acute Coronary Syndrome (ACS) ACS represents a spectrum of ischemic heart diseases: ranging from unstable angina to myocardial infarction Porth p 560 Copyright © 2010 Pearson Education, Inc.  Acute Coronary Syndrome Pain persists longer than 20 minutes Pain may increase in severity May have previous history of unstable angina as risk factor Symptoms not relieved by short acting vasodilators – e.g. glycerol trinitrate (GTN) In most cases of unstable angina there is recovery and the effects are temporary Copyright © 2010 Pearson Education, Inc.  Myocardial infarction Immediate result of complete coronary occlusion Blood flow ceases in vessels beyond occlusion except for small amount of collateral flow Produces acute ischemia in the myocardium supplied and varying degrees of ischemic injury and necrosis The area of affected myocardium is said to be infarcted The overall process is called a myocardial infarction or MI  Two important classifications of myocardial infarction Prognosis depends on the degree of muscle damage: STEMI – the clot lodges permanently in the vessel and the entire thickness of the myocardium becomes ischemic – this type of MI is associated with ST segment Elevation on ECG “STEMI” – Serious : requires immediate emergency intervention Non-STEMI – sometimes thrombus disintegrates before complete tissue necrosis: only subendocardium affected – sometimes transient ST elevation, then T wave inversion  Diagnostic features of MI 1. STEMI vs. non-STEMI 2. Serum Cardiac Biomarkers e.g. troponin T Copyright © 2010 Pearson Education, Inc.  SUMMARY Acute Coronary Syndrome Ischemia >>> myocardial damage UNSTABLE STABLE ANGINA ANGINA NON-STEMI STEMI Reversible ECG changes Duration < 15 min Duration > 20 min Pain relieved by GTN and rest Pain occurs at rest, not relieved by GTN Pain severeCardiac > increasing in biomarkers severity present Opiates usually required Copyright © 2010 Pearson Education, Inc.  General Manifestations of Acute Coronary Syndrome Abrupt onset Severe and crushing pain, usually substernal, radiating to the left arm, neck, or jaw Gastrointestinal complaints (nausea and vomiting) Complaints of fatigue and weakness Tachycardia, anxiety, restlessness, feelings of doom Pale, cool, and moist skin A “silent MI” occurs when a person doesn’t experience any symptoms or has atypical symptoms Porth p563 Copyright © 2010 Pearson Education, Inc.  Causes of Death in Myocardial Infarction 1. Decreased cardiac output 2. Fibrillation of the heart 3. Rupture of the heart Copyright © 2010 Pearson Education, Inc.  Causes of Death in Myocardial Infarction 1. Decreased cardiac output à cardiogenic shock Pumping ability reduced Maybe exacerbated by “systolic stretch”= dead muscle forced outward by pressure When cardiac output is inadequate to the needs of tissues heart failure and peripheral ischemia result This is called cardiogenic shock Copyright © 2010 Pearson Education, Inc.  Causes of Death in Myocardial Infarction 2. Fibrillation of the ventricles after MI Main cause of death in STEMI is – ventricular fibrillation (VF) – the most serious cardiac arrhythmia Normal sinus rhythm Ventricular fibrillation Cardiac output is zero Due to (erratic electrical impulses) and abnormal conduction pathways in damaged myocardium Dangerous periods for VF to occur are after first 10 minutes then after 1 hour or so Copyright © 2010 Pearson Education, Inc. Causes of Death in Myocardial Infarction 3. Rupture of the infarcted area Can occur several days after infarct as muscle fibers necrose and degenerate and the heart wall stretches thin Systolic stretch increases to the point when finally the heart ruptures One way of assessing severe MI is by cardiac imaging to monitor the degree of “systolic stretch” Copyright © 2010 Pearson Education, Inc.  ACS Management Immediate care Nitroglycerin (GTN) – fast acting vasodilator Bed rest Pain relief - morphine 12 lead ECG and ECG monitoring Oxygen therapy Beta blockers* – slow HR, lengthen diastole Anticoagulant therapy e.g. – e.g. aspirin, platelet inhibitors *beta adrenergic receptor antagonists Copyright © 2010 Pearson Education, Inc.  ACS Management The importance of (absolute body) rest: 1. Cellular death determined by – degree of ischemia due to infarct – workload on the heart – therefore ê workload = ê injury from ischemia 2. When the heart becomes highly active, coronary arteries dilate to supply healthy muscle with O2 and nutrients – this reduces the collateral circulation that may be assisting the damaged muscle during recovery Copyright © 2010 Pearson Education, Inc.  ACS Management The importance of pain relief Normally we cannot “feel” our heart – but ischemic myocardium can produce severe “crushing” pain – Experienced in central chest, down left arm, sometimes chin Believed to relate to release of lactic acid (anaerobic respiration) and mediators of inflammation e.g. histamine, kinins, etc. Pain relief in itself is important for comfort, but also because pain é stress > é cardiac output = é workload on the heart Copyright © 2010 Pearson Education, Inc. Copyright © 2010 Pearson Education, Inc.  The Electrocardiogram Electrical conduction within a normal heart Porth Chapter 25 Copyright © 2010 Pearson Education, Inc.  Normal ECG P wave: Atria depolarize QRS complex: Ventricles depolarize T wave: Ventricles recover from depolarization (repolarize) Copyright © 2010 Pearson Education, Inc.  Types of normal ECG Normal sinus rhythm Tachycardia Bradycardia Sinus arrhythmia (during respiration) Copyright © 2010 Pearson Education, Inc.  Manifestations of heart disease Dysrhythmias (arrhythmias) – Range from occasional “missed” or rapid beats to serious disturbances that impair the pumping ability of the heart – Causes: abnormal rate of impulse generation from the SA node or other pacemaker, or abnormal conduction of impulses through the heart’s conduction system Copyright © 2010 Pearson Education, Inc.  1. Atrial conduction abnormalities Most common. Ventricular filling is not totally dependent on atrial contraction, so these arrythmias may be asymptomatic: – E.g., Atrial Fibrillation – 400-600 bpm – completely disorganized and irregular atrial rhythm accompanied by irregular ventricular rhythm. Causes pooling of blood in atria (treatment most likely includes anticoagulants to prevent emboli) 2. Atrioventricular node abnormalities Heart block occurs when conduction is excessively delayed or stopped at the AV node or bundle of His (signal has trouble reaching ventricles) Partial, slower conduction (first, second degree) to total lack of conduction (third degree)– ventricles contract on their own, but cardiac output is greatly reduced Porth p613 -618 Copyright © 2010 Pearson Education, Inc.  3. Ventricular conduction abnormalities – E.g., Ventricular Fibrillation – ventricles quiver but do not contract – ineffective in ejecting blood (death within minutes if not corrected) 4. Asystole – No electrical activity in the heart / absence of a heartbeat (“flatline”) Porth p616 -617 Copyright © 2010 Pearson Education, Inc.  Some cardiac arrhythmias Atrial fibrillation Many sites within the atria are generating their own electrical impulses, leading to irregular conduction of impulses to the ventricles that generate the heartbeat Heart block Not all atrial beats getting through to the ventricles Ventricular fibrillation (VF) Disorganized electrical signals: ventricles quiver instead of contract. Patient unconscious as blood is not pumped to the brain. Immediate defibrillation is indicated. May occur in MI. Copyright © 2010 Pearson Education, Inc.  Disorders of the Heart 1. Pericarditis (p550) – Acute inflammation of the pericardium: pain, fever – Various causes (idiopathic, infection, surgery, etc.) – Treated by relieving symptoms, anti-inflammatory drugs 2. Cardiomyopathy (p571-576) – Diverse group of diseases that primarily affect the myocardium, itself – Many cases are idiopathic, some genetic, some acquired (e.g., result of inflammation) Copyright © 2010 Pearson Education, Inc.  – E.g., Dilated cardiomyopathy: increased ventricular volume, which causes impairment of systolic function Causes: 1/3 cases are inherited; infections, chemotherapy or idiopathic Typical clinical manifestations: dyspnea, orthopnea, reduced exercise capacity Common cause of heart failure, transplantation - E.g., Hypertrophic cardiomyopathy: thickening of septum, which decreases left ventricular size and obstructs blood outflow One of most common types of cardiomyopathies - an inherited disease. Mostly asymptomatic, but symptoms can include angina, dyspnea, reduced exercise capacity Copyright © 2010 Pearson Education, Inc.  Disorders of the Heart 3. Valvular dysfunction Can be congenital or acquired – One of the most common acquired causes is rheumatic heart disease (after infection Streptococcus pyogenes) Most commonly affects aortic and mitral valves Two types of disruptions can occur: – Stenosis: narrowing of valve opening, causing turbulent flow and enlargement of emptying chamber – Incompetent (regurgitant) valve: permits backward flow Sounds made by abnormal flow = “murmurs” Porth p 580-586 Copyright © 2010 Pearson Education, Inc. Copyright © 2010 Pearson Education, Inc.  Heart Failure (HF) Heart is unable to generate an adequate cardiac output (= stroke volume x heart rate) – Stroke volume depends upon preload, afterload and myocardial contractility HF may cause inadequate perfusion of tissues, or increased pulmonary capillary pressures, or both, depending upon which side of the heart is affected Common causes: coronary artery disease, valvular disease and cardiomyopathies Most common reason for admission to hospital for those over 65 yrs of age Porth p 625-626 Copyright © 2010 Pearson Education, Inc.  Risk factors for heart failure Include: Ischemic heart disease Older age Hypertension Lack of exercise Diabetes mellitus type 2 Smoking Obesity Copyright © 2010 Pearson Education, Inc.  Terms affecting stroke volume: a) Preload Volume of blood in the ventricle at the end of diastole Determined by: – Amount of blood entering ventricle during diastole – Blood left in ventricle after systole (depends upon strength of the contraction and resistance to ventricular emptying) – Frank-Starling law of the heart: the more stretched the ventricle wall, the greater the force of the contraction (up to a maximum value). i.e. the more blood in the ventricles, the stronger the contraction (= greater stroke volume) Copyright © 2010 Pearson Education, Inc.  * The Frank-Starling ventricular function curve in a normal heart *LVED= left ventricular end diastolic) Porth p481 Copyright © 2010 Pearson Education, Inc.  b) Afterload Resistance to ejection of blood from the left ventricle Peripheral vascular resistance is usually a good indicator of afterload Copyright © 2010 Pearson Education, Inc. Porth p481  c) Inotropy (contractility) Contractility (force of contraction) of muscle The ability of the actin and myosin of the heart muscle to interact and shorten against a load Increases cardiac output, independent of preload and afterload Other effects on inotropy: – Ventricular hypertrophy increases contractility – Myocardial infarction decreases contractility Copyright © 2010 Pearson Education, Inc. Porth p481  Systolic heart failure Myocardial contractility is impaired leading to a decrease in ejection fraction (normal = 65%; dysfunction = 40%) -> decreased cardiac output Causes: – Decreased contractility (e.g., due to MI, cardiomyopathy) – Volume overload (e.g., valvular incompetence) – Pressure overload (e.g., hypertension) More blood remains in the ventricle after contraction, thus increasing pre-load à leads to pulmonary or peripheral edema (depending on side of heart affected) Copyright © 2010 Pearson Education, Inc. Porth p628-629  https://courses.lumenlearning.com/suny-ap2/chapter/capillary-exchange/ Copyright © 2010 Pearson Education, Inc.  Diastolic heart failure Occurs on left side This is caused by decreased diastolic relaxation so that less blood enters the ventricle (= definition) -> decreased cardiac output Can be caused by conditions that: – Decrease expansion of the ventricle (e.g., pericardial effusion) – Increase wall thickness and reduce chamber size (hypertrophic cardiomyopathy) – Delay diastolic relaxation (myocardial ischemia; decreased energy for calcium pumps) This results in pulmonary edema, as blood backs up into pulmonary circulation from LV, thus increasing pulmonary pressure Can occur alone, or with systolic heart failure Causes 35-55% of cases of left heart failure Copyright © 2010 Pearson Education, Inc. Porth p 629 Copyright © 2010 Pearson Education, Inc.  Left heart failure (LHF) Commonly called congestive heart failure Can be systolic, diastolic, or both Decreased cardiac output to systemic circulation (from left ventricle) When decreased cardiac output to the systemic circulation occurs, blood accumulates in the left side -> then in the pulmonary circulation, causing increased pulmonary venous pressure. If this exceeds osmotic pressure in capillaries, fluid enters the lung tissue = pulmonary edema Most common causes: hypertension, acute MI, cardiomyopathy Copyright © 2010 Pearson Education, Inc. Porth p 629-630 https://digitalcommons.otterbein.edu/cgi/viewcontent.cgi?article=1156&context=stu_msn Copyright © 2010 Pearson Education, Inc.  Right heart failure (RHF) Inability of right ventricle to move deoxygenated blood from systemic circulation into the pulmonary circulation Pressure then rises in systemic venous circulation, leading to peripheral edema – usually seen in lower limbs, due to gravity – congestion of the viscera (hepatomegaly, ascites) – in severe cases, can visualize the external jugular veins even in someone standing, as the veins become distended due to increased venous pressure Copyright © 2010 Pearson Education, Inc. Porth p 629 -30  Right heart failure (RHF) - causes 1. Most commonly caused by left heart failure: – Left heart failure creates increased pulmonary pressure – This backs up into the right ventricle, which is poorly equipped to compensate, so will dilate and fail 2. Cor pulmonale - when RHF occurs in response to pulmonary disease not LHF § E.g., COPD, cystic fibrosis, ARDS all increase pulmonary pressure 3. Can occur in response to right heart issues which affect right heart contractility § E.g., MI, cardiomyopathies, and valvular disease Copyright © 2010 Pearson Education, Inc. Copyright © 2010 Pearson Education, Inc.  Compensatory mechanisms – try to help, but sometimes make things worse … 1. Sympathetic Nervous System activation to increase blood pressure and cardiac output However, the increase in heart rate and contractility actually put more strain on the already weakened heart Porth p631-632 Copyright © 2010 Pearson Education, Inc.  Compensatory mechanisms in HF - cont’d 2. RAAS activation –decreased cardiac output decreases renal blood flow, which leads to activation of the Renin-Angiotensin Aldosterone System (RAAS) -> which also leads to release of ADH The vasoconstriction that results increases afterload, and the increase in blood volume increases pre-load; both of which put more strain on the heart 3. Hypertrophy– depending upon the stimulus, this can lead to a disproportionate thickening of the ventricle walls (caused by increasing fiber width), which may increase ischemia or thinning of the ventricular walls (caused by increasing fiber length), leading to dilation and impairment of contraction Copyright © 2010 Pearson Education, Inc.  Progressive decompensated heart failure Untreated, cardiac output progresses from compensated (B) until death is imminent (D) Frank-Starling curves Normal Compensated Decompensated – heart failure worsening Severe cardiogenic shock Preload Copyright © 2010 Pearson Education, Inc.  Heart failure Symptoms: (for each, think about why) dyspnea - shortness of breath orthopnea – sitting-up helps relieve dyspnea (RHF) fatigue and tires easily decreased urine output edema – especially in lower extremities (weight gain) Treatment: concentrates on decreasing preload and afterload – salt restriction and diuretics, weight management Digitalis (improves stroke volume), beta blockers, O2 therapy Copyright © 2010 Pearson Education, Inc.  Circulatory Failure: Shock An acute failure of the circulatory system to supply the body with an adequate blood supply, resulting in cellular hypoxia Many causes and various clinical manifestations Ultimately proceeds to organ failure and death unless corrected Porth p640-651 Copyright © 2010 Pearson Education, Inc.  Clinical manifestations of Shock Depends upon the type of shock – Symptoms can be conflicting in nature Individual may report being sick, weak, cold, hot, dizzy, confused, afraid, thirsty, short of breath One consistent sign is hypotension with mean arterial pressure (MAP= average pressure in the arteries throughout the cardiac cycle) below 60 mm Hg – Normal MAP = 70-110 mm Hg Respiratory rate is usually increased Copyright © 2010 Pearson Education, Inc.  Cellular effects of shock Without sufficient oxygen delivery, cell switches to anaerobic respiration, which produces far less ATP Without sufficient ATP, the cell’s sodium/potassium pump operates poorly – The intra/extra cellular ion concentrations of Na, K, and Ca are not maintained, interfering with nervous and muscular systems Several positive feedback mechanisms can occur, increasing the severity of the condition: Porth p642 Copyright © 2010 Pearson Education, Inc.  Positive feedback loop #1 With more sodium entering cell, water follows. Interstitial fluids then pull water out of the vascular system, which results in a drop in blood pressure. Decreased volume in the vascular system intensifies the decrease in perfusion of tissues. Positive feedback loop #2 Lysosomal enzymes that damage tissues are released by: disruption of the cell membrane (due to low ATP and swelling of cell) àdamage to surrounding tissue by these enzymes activates the inflammatory response, resulting in further damage to the tissues, and further impairment of cellular metabolism (including ATP production) Copyright © 2010 Pearson Education, Inc.  Positive feedback loop #3 The acidic conditions also affect hemoglobin, decreasing its affinity with oxygen, thus decreasing the oxygen carrying capacity of the blood, which further increases the tissue hypoxia Once enough cells of vital organs have damage to membranes, leakage of lysosomal enzymes and ATP depletion, shock can be irreversible. Copyright © 2010 Pearson Education, Inc.  Types of shock Copyright © 2010 Pearson Education, Inc.  Types of shock Cardiogenic Shock Enough blood volume, but decreased cardiac output due to decreased contractility, increased preload and/or increased afterload Decrease in blood pressure causes compensation: – increase in epinephrine release and RAAS system increased oxygen/nutrient demand of the heart ->puts further strain on the heart -> resulting in it becoming incapable of pumping an adequate volume Usually follows MI, but can have other causes, as well Often unresponsive to treatment (mortality rate of 70%) Porth p643 Copyright © 2010 Pearson Education, Inc.  Hypovolemic Shock Not enough blood volume Causes: significant loss of whole blood (hemorrhage), plasma (burns) or interstitial fluid (diarrhea or diuresis) Begins to develop when intravascular volume has decreased by about 20% Compensatory mechanisms can initially help: – HR and vasoconstriction increase – Interstitial fluid moves into blood – Liver and spleen add to blood volume – RAAS and ADH activated However, if loss continues, these mechanisms will ultimately fail Treatment begins with rapid fluid replacement Porth p644 Copyright © 2010 Pearson Education, Inc.  Distributive Shock Result of massive vasodilation Blood volume has not changed but the amount of space containing the blood has increased – causing decrease in BP below that required to drive nutrients across capillary membranes to cells Three shock states share this mechanism: a) Neurogenic b) Anaphylactic c) Septic Copyright © 2010 Pearson Education, Inc.  a) Neurogenic Shock Result of massive vasodilation resulting from overstimulation of the parasympathetic NS and under-stimulation of the sympathetic NS Causes: trauma to the spinal cord or medulla, anesthetic agents, severe pain Rare and usually transient Porth p647 Copyright © 2010 Pearson Education, Inc. b) Anaphylactic Shock Results from widespread Type I hypersensitivity reaction, known as anaphylaxis – Release of histamine and other compounds by mast cells results in vasodilation and vascular permeability to the point of peripheral pooling and tissue edema – Smooth muscle constriction can result in laryngospasm, bronchospasm and diarrhea Onset is usually very sudden and progression to death can occur within minutes Treatment: intramuscular administration of epinephrine – causes vasoconstriction and reverses airway constriction Copyright © 2010 Pearson Education, Inc. Porth p647  c) Septic shock Most common type of vasodilatory shock Severe infection with a microorganism – microorganism releases toxins that stimulate an overwhelming inflammatory response – and/or there is an overwhelming inflammatory response to the microorganism, itself Common cause of death in intensive care units Manifestation differs from other types of shock: skin is warm and flushed (widespread vasodilation) – other types of shock constrict blood vessels, thus decreasing blood flow to skin, Porth p648 Copyright © 2010 Pearson Education, Inc.  Obstructive shock – Results from mechanical obstruction of the blood flow through the central circulation (great veins, heart or lungs) – Most common cause is pulmonary embolism (other causes include cardiac tamponade, pneumothorax, etc.) – Elevated right heart pressure occurs – Significant decrease in cardiac output – Often classified under cardiogenic shock Copyright © 2010 Pearson Education, Inc.  Treatment of shock must remove underlying cause IV fluid to expand blood volume vasopressors (drugs that increase vasoconstriction) supplemental oxygen once positive feedback loops have been established, intervention is very difficult Copyright © 2010 Pearson Education, Inc.  Diseases of the Arteries 1. Atherosclerosis, continued Leading cause of coronary artery and cerebrovascular disease Clinical Manifestations: Depends upon where the atherosclerosis is: – In large vessels ( e.g. aorta) mainly thrombus formation (could lead emboli), and weakening of the vessel wall (could lead to aneurysm) Copyright © 2010 Pearson Education, Inc. Porth 502-506  Clinical Manifestations of atherosclerosis cont’d – In medium-sized arteries (e.g. coronary, cerebral): mainly ischemia and infarction due to vessel occlusion (coronary= heart attack, cerebral= stroke) CAD (coronary artery disease) caused by atherosclerosis is the major cause of myocardial ischemia Peripheral artery disease (PAD): obstruction of peripheral arteries can cause significant pain and disability (prevalent in diabetics) Copyright © 2010 Pearson Education, Inc.  Atherosclerosis management: Reduction of risk factors and prevention of plaque progression (in diseases where artery obstruction has not become acute) – Exercise, quit smoking, control of hypertension, reducing LDL reduction with diet or drugs Copyright © 2010 Pearson Education, Inc.  Diseases of the Arteries 2. Hypertension A consistent elevation of systemic arterial blood pressure – a sustained systolic BP >140 mmHg or a diastolic pressure >90 mmHg Increased risk for myocardial infarction, kidney disease, stroke 2 categories: primary (idiopathic) or secondary (resulting from another disorder) Porth p530-539 Copyright © 2010 Pearson Education, Inc.  Primary hypertension Most cases (95%) due to a combination of genetics and the environment Factors that can lead to primary hypertension include: – family history, age, gender, race, high dietary sodium intake, insulin resistance, cigarette smoking, obesity Determined by several BP measurements at different times, and tests to exclude secondary hypertension – E.g., complete blood count (CBC), urinalysis, blood chemistry, ECG, assess target-organ damage Copyright © 2010 Pearson Education, Inc.  Increased blood pressure is due to 1) increase in circulating blood volume 2) increased peripheral resistance, or both Due to an interaction of several factors, including: 1. Sympathetic nervous system – increases heart rate and vasoconstriction 2. Overactivity of renin-angiotensin-aldosterone system (RAAS) – increases vasoconstriction and blood volume and pressure (by retaining sodium and water in kidneys) 3. Chronic inflammation results in smooth muscle contraction Copyright © 2010 Pearson Education, Inc.  Clinical manifestations of hypertension Early stages have no symptoms/signs, other than elevated blood pressure (= “silent disease”) Some people never develop signs, symptoms or complications, others become very ill and die Most clinical manifestations become evident when damage to other organs/systems occur, and are specific to the affected organ/system: – coronary heart disease, kidney disease, CNS dysfunction (stroke, dementia), impaired vision, etc. can all be caused by sustained hypertension Copyright © 2010 Pearson Education, Inc.  Treatment of hypertension Includes lifestyle modification: – exercise, lose weight, stop smoking and alcohol use Medications – diuretics and other anti-hypertensives e.g., ACE inhibitors Copyright © 2010 Pearson Education, Inc.  Hypertension during pregnancy Can be classified as: 1. Pre-existing: present before pregnancy, or appears before 20 weeks of pregnancy 2. Gestational: occurs at or after 20 weeks of pregnancy Porth 539-541 Copyright © 2010 Pearson Education, Inc.  Why would hypertension develop during pregnancy? Unknown Possibly due to a decrease in placental blood flow -> leading to release of toxic compounds (cytokines, reactive oxygen products, etc.) that cause changes in blood vessel walls throughout the body = Risk for development of many pathological effects including – Preeclampsia, liver failure, kidney failure, heart disease, respiratory distress, DIC, generalized edema, etc. Copyright © 2010 Pearson Education, Inc.  What is preeclampsia? A woman would be diagnosed if she presented with: 1. Hypertension (either gestational or pre-existing) 2. Proteinuria 3. Adverse conditions: e.g., persistent or new headache, visual disturbances, persistent abdominal pain, elevated liver enzymes, etc.. Copyright © 2010 Pearson Education, Inc.  Preeclampsia may lead to eclampsia – the occurrence of convulsions and possible coma, due to development of blood clots in cerebral vessels Decrease in placental blood flow in gestational hypertension also affects the fetus – frequently resulting in infants who are small for gestational age requiring early delivery Definitive cure for preeclampsia: birth of baby and accompanying delivery of placenta Copyright © 2010 Pearson Education, Inc.  Diseases of the arteries 3. Orthostatic (Postural) Hypotension Specific decrease in blood pressure within 3 min of moving to a standing position, causing dizziness, fainting More frequently observed in elderly Normal mechanisms to maintain BP when standing up do not function - e.g? Common cause: use of certain medications (e.g., antihypertensives), ageing, dehydration Treatment: alleviating the cause (e.g., changing antihypertensive). If not possible, can be managed by learning ways to cope (e.g., sitting up gradually, the use of elastic support hose, etc.) Porth 505-508 Copyright © 2010 Pearson Education, Inc.  Diseases of the arteries 4. Aneurysm Local outpouching of vessel or heart chamber wall, usually in the abdominal aorta, Most commonly caused by atherosclerosis and hypertension Manifestations depend upon where the aneurysm is, and involve the production of pressure on local structures E.g. edema of the face due to pressure on the superior vena cava cough due to pressure on the trachea may also be asymptomatic until they rupture; rupture causes extreme pain and hypotension Copyright © 2010 Pearson Education, Inc. Porth 512-515 Copyright © 2010 Pearson Education, Inc.  5. Thrombus – Caused by any condition that promotes activation of coagulation (surgery, infection, low BP, inflammation, etc.) – Can occlude the artery/vein, or can break off to form an embolus 6. Embolism – Obstruction of a vessel by an embolus (air bubble, fat, dislodged thrombus, clump of cells). No matter how tiny, it will eventually lodge in a vessel – Arterial emboli arise from the left heart and are associated with thrombi that occur after heart trauma (e.g., heart attack (MI)) – Pulmonary emboli arise from the venous side (e.g.,DVT or in the right heart – Damage depends upon where the embolus lodges: brain artery = stroke, heart artery = MI Copyright © 2010 Pearson Education, Inc.  Diseases of the Veins 1. Varicose veins Definition: Veins in which blood has pooled, producing distended, tortuous, and palpable vessels Why do they occur in the legs? – There are no valves in the inferior vena cava or the common iliac veins, making the veins in the legs (external iliac, femoral) responsible for supporting the blood in these vessels – If pressure increases in the abdomen (pregnancy, repeated heavy lifting) this increases the strain on these valves – Standing for long periods of time also puts extra strain on these valves, as the leg muscles are not being used to pump blood back to the heart Copyright © 2010 Pearson Education, Inc. Porth p516-517  Development of varicose veins 1. If a valve in a vein is damaged, a section of the vein is subjected to the pressure of a larger volume of blood under the influence of gravity 2. The vein swells and edema develops in the surrounding tissue 3. This can damage the remaining upstream valves in the vein, making them unable to maintain normal venous pressure 4. Tends to happen in the external veins, as the deep veins are supported by muscle, bone and connective tissue (external veins have only the subcutaneous fat and connective tissue) Copyright © 2010 Pearson Education, Inc.  Risk factors for varicose veins: standing long periods, crossing legs at the knee, age, female gender, family history, obesity, pregnancy, deep venous thrombosis and previous leg injury Treatment for varicose veins: wearing compression stockings, physical exercise, surgical ligation, vein stripping Copyright © 2010 Pearson Education, Inc.  Possible complication of varicose veins: Chronic Venous Insufficiency (CVI) = inadequate venous return over a long period of time, which impairs blood flow to the area Especially in obese individuals Can lead to, impaired nutrition, edema and venous hypertension, causing inflammation in the vessels and tissue Symptoms include darkening of the skin of the feet and ankles Circulation may become so poor that any trauma or pressure can lower the delivery of oxygen to the tissues to the point of causing necrosis (stasis ulcer) and infection (poor circulation can’t deliver sufficient immune response) Porth p517 Copyright © 2010 Pearson Education, Inc.  Diseases of the Veins 2. Deep Venous Thrombosis (DVT) The development of a thrombus in deep vein - occurs primarily in lower extremity Risk factors include: Venous stasis - due to immobility; allows pooling of clotting factors – E.g. after hip fracture, joint replacement, spinal cord injury Impaired cardiac function – acute myocardial infarction, congestive heart failure Venous endothelial damage – intravenous drug use/groin injection Hypercoagulable states – inherited disorders, pregnancy Porth p 518 Copyright © 2010 Pearson Education, Inc.  Development of DVT: 1. Clotting factors and platelets accumulate (often near a valve) and form a thrombus 2. Inflammation around the thrombus promotes further platelet aggregation and the thrombus grows 3. Because the vein is deep in the leg, it is usually asymptomatic (may get edema if vessel is obstructed significantly) – Most thrombi will eventually dissolve, however, are associated with higher risk of pulmonary embolism – Hard to detect (often asymptomatic), so prevention is important early ambulation after pregnancy or surgery, the use of support stockings, prophylaxis with anticoagulants Copyright © 2010 Pearson Education, Inc.