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Intro to Clinical Medicine Lecture (8) Heart disorders Thomas G. Forsthuber, M.D. Dr. Med. Professor of Immunology, Adjunct Professor of Microbiology & Immunology (UT Health) Office: BSE 3.250B E-mail: [email protected] Office Hours: Monday 4:30 – 5:30...

Intro to Clinical Medicine Lecture (8) Heart disorders Thomas G. Forsthuber, M.D. Dr. Med. Professor of Immunology, Adjunct Professor of Microbiology & Immunology (UT Health) Office: BSE 3.250B E-mail: [email protected] Office Hours: Monday 4:30 – 5:30 pm Major diseases affecting the heart Coronary artery disease – Stable angina pectoris – Unstable angina pectoris – Myocardial infarction Hypertensive heart disease – Cor pulmonale – Systemic hypertension Congenital heart diseases Heart valve diseases Cardiomyopathies  Basics Normal heart weight: 250 – 300 g in females, 300 – 350 g in males Wall thickness is: 0.3 – 0.5 cm for right ventricle, 1.3 to 1. 5 cm left ventricle Myocytes (heart muscle cells): 25% of the cells of the heart, but 90% of the mass of the heart Heart, gross anatomy Courtesy of Dr. E. Klatt, Webpath The four chambers of the heart Wikipedia The heart valves Bishop Miter TF, Staats Museum Munich  Heart function Ventricular systole: time period of the contraction of the ventricle (left and right). Beginning of the QRS by ECG. – Blood is ejected from the LV into the aorta, and from RV into pulmonary arteries Ventricular diastole: time period after contraction when the ventricles relax – Pressure in the ventricles drops until below pressure in the atrium – Blood flows from the left atrium into LV, and from right atrium into RV Heart function depends on conduction of electrical impulses Sinoatrial node located in the right atrium is the pacemaker of the heart SA will discharge at 70 – 80 times/minute It is innervated by vagal and sympathetic nerve fibers IF SA node fails, next lower system takes Internodal pathways over, i.e. AV node. AV node is actually a “gate keeper” to prevent too fast bundle depolarization of the (Purkinje fibers) heart!  QRS (+) ECG T P P wave: atrial depolarization (contraction) QRS complex: ventricular depolarization (contraction) T wave: repolarization of the ventricle (relaxation) Some tips for easy ECG interpretation: Normal ECG strip is 10 seconds For heart rate multiply QRS/10 sec by 6 Check if p is there, followed by QRS Check how ST waves behave HR = 54/bpm What is the HR? A - 60 B -102 C - 84 D - 96 Healio.com  Normal or not? A – Normal B – Abnormal C – Maybe? Junctional bradycardia (only AV node fires) 40 – 60 beats/min “junctional rhythm”  Heart sounds (‘lub-dub’) First heart tone (S1 or “lub”): Sound is due to vibration of the blood thrust against the closed atrial valves. Sudden pressure increase in the ventricles at the beginning of systole reverses blood flow towards atria and closes atrial valves (left: mitral valve; right: tricuspid valve). Second heart tone (S2 or “dub”): Caused by the closure of the aortic and pulmonary valves at the end of the systole. Sound is due to vibration of the blood thrust against the aortic or pulmonary valves. – S2 can sometimes be split into P2 (pulmonary valve sound) and A2 (aortic valve sound) during inspiration (inhaling of air). Heart Diastole Atrial Systole Ventricular Systole Auscultation of heart sounds Univ. Michigan  Congestive hear failure: Cyanosis Jugular vein distension Hepatomegalie Ascites Edemas Increased venous pressure Exhaustion Tiredness Heart failure (Congestive heart failure) Also called “congestive heart failure” Heart failure is the inability of the heart to pump sufficient blood through the body Heart failure can be caused by anything that impairs the pump function of the heart: MI, hypertension, arrhythmias, valve defects, pulmonary hypertension and so forth – A main cause of heart failure is volume overload = heart must pump too much blood Symptoms: – Shortness of breath on light exercise (dyspnea), or at rest (orthopnea), fatigue, pulmonary edema, peripheral edema, ascites, nocturia (urinating at night), jugular vein distension, Treatment: Resolve underlying cause, weight reduction, decrease fluid overload, sodium restriction, fluid restriction, – Drug treatment: reduce blood pressure, diuretics, beta blockers, treat arrhythmias,  General causes of heart failure Left side of the heart: Hypertensive heart disease (peripheral arterial hypertension). - Left ventricle works harder to overcome increased pressure in the aorta. Left ventricular hypertrophy Coronary heart disease Arrhythmias Right side of the heart: Cor pulmonale: hypertrophy or dilation of the right ventricle because of impaired perfusion of the lungs – Acute cor pulmonale = PE – Chronic cor pulmonale = chronic obstructive lung disease, loss of lung tissue (Tb, cancer surgery) Mechanism: right ventricle works harder to move blood through the lungs – right heart tries to compensate The heart tries to compensate until it fails Eccentric hypertrophy Concentric (dilation of the heart) = hypertrophy = volume overload pressure overload Heart can grow up to 1000 g!  Right ventricular hypertrophy: Cor pulmonale Hypertrophy of the right ventricle caused by changes in the pulmonary blood vessels. Most frequent causes: COPD: chronic obstructive pulmonary disease (chronic bronchitis/emphysema) Loss of lung tissue Leads to congestive heart failure! Coronary heart disease Also called “ischemic heart disease (IHD)” = coronary heart disease Most important cause is obstruction of coronary arteries by atherosclerosis (atheroma = lump of porridge in Greek) – Atherosclerosis is caused by deposits of cholesterol crystals between intima (endothelial cell layer) and media (muscle cell layer) and subsequent proliferation of macrophages and other cells  Progression of atherosclerosis Atheromatous plaque in coronary artery L – Lumen F – fibrous cap C – Core  Atherosclerosis Major Risk factors: – Increasing age, male gender, family history, genetic abnormalities – Hyperlipidemia (hypercholesterolemia), hypertension, smoking, diabetes – Bad cholesterol: LDL (low-density lipoproteins) Delivers cholesterol to tissues – Good cholesterol: HDL (high-density lipoproteins) Transports cholesterol from plaques to the liver for excretion Potential risk factors: – obesity, physical inactivity, stress, high carbohydrate intake, postmenopausal Cholesterol: Cholesterol Level (mg/dL) Interpretation < 200 Desirable level. Lower risk for hear disease 200 – 239 Borderline high risk >240 High risk http://www.health.harvard.edu/heart-health/making-sense-of-cholesterol-tests Total cholesterol to HDL ratio (Framingham Heart Study): Total Cholesterol/HDL Interpretation tCholesterol/HDL = 5 Average risk for heart disease tCholesterol/HDL = 3.4 Approximately half the average risk tCholesterol/HDL = 9.6 Double the average risk Mozaffarian D et al. Circulation. 2015;131:e29-e322  Coronary artery disease (CAD; ischemic heart disease) Sudden severe narrowing of the large coronary arteries Normally due to atherosclerosis Three major clinical manifestations – Stable angina pectoris – Unstable angina pectoris – Myocardial infarction (MI) Angina pectoris: ischemia leads to clinical symptoms, but not to death of heart muscle cells MI: Ischemia is so severe that it leads to clinical symptoms and death of heart muscle cells  The coronary arteries Front Back Brainkart.com Angina pectoris Sudden onset of chest discomfort: “pressure”, heaviness, burning, choking sensation, pain (discomfort) Typically radiates to left chest and arm Frequently precipitated: after heavy meals, going from warm to cold, emotional or physical stress Usually lasts for a few minutes Relieved by nitrites (vasodilators) Can radiate to abdomen = “indigestion” ECG typically normal, but stress ECG may show changes Coronary angiogram NOTE: Prinzmetal’s angina: looks like angina pectoris but is caused by vasospasm of coronary arteries Difference between stable and unstable Angina Stable Angina: – Predictable, triggered by activity, exertion, stress. – Usually resolves quickly when resting (5 – 20 minutes) – Pattern stays stable for > 1 month Unstable Angina: – Angina occurs at rest, no trigger, pattern of angina changes – May not go away – Symptoms more severe than in previous angina – Symptoms for the first time or less than a few weeks Stable angina can convert to unstable angina! Unstable angina is sometimes called “preinfarction angina” Next step for unstable angina is MI! Myocardial infarction (MI) Symptoms: – Chest pain, discomfort, nausea, vomiting, arrhythmia, loss of consciousness, possibly sudden death – Pain (sharp) radiates to left arm, jaw, back, epigastrium (stomach area) – Many patients had angina pectoris previously – Women: frequently dyspnea, weakness, fatigue – 1/3 of MI are silent! Diagnosis: ECG! = ST-elevation MI (STEMI) – Cardiac enzymes: creatine phosphokinase MB (CK-MB); Troponin I or T! Non-ST-elevation MI (NSTEMI) = ST not elevated, but cardiac enzymes elevated.  Difference between STEMI and NSTEMI STEMI: ST-elevation MI Complete occlusion of coronary artery, myocardial damage Cardiac enzymes elevated (CK-MB, I-troponin) NSTEMI: “mild heart attack” – Non-ST-elevation MI – Partial/intermittent occlusion of coronary artery, myocardial damage, – Cardiac enzymes elevated – 30% of all MI – Often STEMI MI happens hours or days later Sequence of histopathologic events after MI: Ischemia for > 20 - 40 minutes leads to myocyte death 4-12 hours: myocyte death becomes histologically visible: coagulation necrosis, edema hemorrhage 12 – 24 hours – necrosis with infiltration of neutrophils 2-3 days – necrosis with even more inflammation 5- 10 days macrophages remove dead tissue and scar formation – THIS IS THE DANGER TIME FOR MYOCARDIAL RUPTURE because the tissue is the weakest (proliferation phase of wound repair)! 2 – 4 weeks – granulation tissue  MI Treatment: MI is an emergency Rest, half-sitting Upon recognition of MI: immediately 325 mg Aspirin MONA – Morphine, oxygen, nitroglycerin, Thrombolysis (recombinant tPA, streptokinase, urokinase) Cardiac catheter, angioplasty Door to balloon time = 90 minutes until opening of the artery! – 2005 – 2010 nationwide gone from median 96 minutes to 64 minutes (Krumholz et al, 2011). – Under 90 min: from 44.2% to 91.4% – Under 75 min: from 27.3% to 70.4% Acute MI TTC stain (triphenyltetrazolium chloride staining)  Shock Three most frequent types of shock: – Cardiogenic shock – failure of the heart to pump blood (MI, arrythmias, PE, heart tamponade – Hypovolemic shock – loss of blood volume (bleeding, burns, trauma) – Septic shock – systemic infection (mostly gram negative organisms – endotoxic shock) Peripheral vasodilation, endothelial injury, disseminated intravascular coagulation, cytokine release (TNF, IL-1, IL-6) Multi-organ system failure – Other types of shock: anaphylactic shock, neurogenic shock after spinal cord injury Clinical symptoms of shock Anxiety, restlessness, disorientation Hypotension Rapid pulse (tachycardia) Cool, clammy, mottled skin, Decreased urine production (oliguria) Rapid breathing (hyperventilation) Other symptoms of shock depend on the type of shock, i.e. cardiogenic shock, septic shock, hypovolemic shock Intro to Clinical Medicine Lecture (8) Heart disorders Part II Thomas G. Forsthuber, M.D. Dr. Med. Professor of Immunology, Adjunct Professor of Microbiology & Immunology (UT Health) Office: BSE 3.250B E-mail: [email protected] Office Hours: Monday 4:30 – 5:30 pm Congenital heart disease Congenital heart diseases are defects of the heart from birth These diseases are grouped into: – Left-to-Right shunts Ventricular septal defect Atrial septal defect Patent ductus arteriosus – Right-to-Left shunts Tetralogy of Fallot Transposition of the great arteries Truncus arteriosus Tricuspid atresia – Obstructive congenital anomalies Aortic coarctation Pulmonary stenosis and atresia Aortic stenosis and atresia  Most frequent congenital heart diseases Ventricular septal defect (VSD) 4/1000 = 42% Atrial septal defect (ASD) = 10% Pulmonary stenosis = 8% Patent ductus arteriosus = 7% Tetralogy of Fallot = 5% ~ 70% Causes of congenital heart diseases Congenital heart disease is caused by developmental malformations – Genetic defects – Chromosomal abnormalities lead to congenital heart disease: Trisomies 21, 13, 15, 18 – Environmental factors: Infection (Rubella!), drugs, chemicals, alcohol – DiGeorge Syndrome (thymic aplasia)  Left-to-right shunts = NO cyanosis ASD & VSD Ventricular septal defect (VSD) VSD is a defect in the ventricular septum Leads to a shunt of blood from left ventricle to right ventricle Most frequent congenital birth defect (2-3 per 1000 life births, 42%) Frequently associated with other congenital disorders, such as Down syndrome (Trisomy 21) Can also form after MI Medium to large VSD leads to hypertrophy of the right ventricle and ultimately to heart failure and death VSD is detected by auscultation = holosystolic murmur (during whole systole) Left-right shunt on ultrasound Treated surgically by closing the defect  Problem is the large VSD! Large VSD will lead to hypertrophy of right heart and eventually to reversal of shunt Oxygen poor blood will flow from right to left and cause cyanosis = Eisenmenger’s syndrome Prognosis very poor if this occurs Blood circulation before and after birth Prior to birth blood is oxygenated via placenta and not lungs In the fetus blood is bypassing the lungs via the foramen ovale between RA and LA. Shortly before and after birth, this “hole” closes. Blood from pulmonary artery takes “short cut” via ductus arteriosus to Aorta From: lecturio.com  Atrial septal defect (ASD) Left-right shunt develops if: – Septum wall does not form properly (ASD) Consequences are usually not as severe as VSD = no symptoms before age 30 Eventually, right heart hypertrophy will develop Systolic murmur! Note: Paradoxical embolus: – If foramen ovale does not close it is called “patent foramen ovale” (PFO). Thrombus can go from right heart to left heart and cause stroke Patent ductus arteriosus (PDA) In the fetus blood from the right heart does not go through the lungs, but via shortcuts (foramen ovale & ductus arteriosus) directly into the aorta. After birth, the lungs unfold, and the blood is now going through the lungs. The ductus arteriosus closes by 15 hours after birth. If the duct does not close, blood will move from the aorta (which has a much higher blood pressure after birth), into the lungs This will increase the flow of blood through the lungs and decrease oxygenated blood in the aorta. Heart has to work much harder. Clinically: machine-like sound over the heart!  Right-to-left shunts = cyanosis Tetralogy of Fallot (ToF) RIGHT-TO-LEFT SHUNT! Classically four components: 1 - Pulmonary stenosis 2 - Large VSD 3 - Overriding aorta (large aortic valve arises from both left and right ventricle) 4 - Right ventricular hypertrophy 1 3 Most common cyanotic heart defect = blue baby syndrome (5% of congenital hear dis.) Cyanosis manifests days to weeks after birth Diagnosis: cyanosis, failure to thrive, difficulty 2 breathing, typical posture, clubbing of fingers and toes, protrusion of sternum 4 Squatting makes symptoms better Blalock-Taussig (Thomas) shunt (connecting subclavian artery to pulmonary artery) was first surgery for congenital heart disease Surgery now repairs pulmonary stenosis and VSD Right-to-left shunt = cyanosis  Right-to-left shunt = cyanosis Vivien Thomas Blalock-Taussig (Thomas) shunt Blood is re-routed from vertebral, carotid, and internal mammary artery to arm  The heart valves Heart valve disease Heart valve disease is more frequent for the valves of the left heart because of the higher pressures in the LV – Aortic valve & Mitral valve Stenosis is the failure to open completely = outflow impaired Insufficiency is the failure to close completely = reflux of blood Abnormal heart sound is called “murmur” Rheumatic heart disease (rheumatic fever) is a major cause of heart valve disease in underdeveloped countries Other causes: Damage to valves after MI, infections, heart dilation, Mitral valve prolapse, senile calcific aortic stenosis, i.v. drug abuse, genetic (Marfan syndrome, Ehlers-Danlos syndrome), drugs Most important heart valve defects: 1. Mitral valve insufficiency (regurgitation) 2. Mitral valve stenosis 3. Aortic valve insufficiency 4. Aortic valve stenosis 5. Mitral valve prolapse  Rheumatic fever Has become less frequent in developed countries because of treatment of strep throat with antibiotics Still very important in underdeveloped countries Usually affects children 6 to 15 years of age after strep throat or scarlet fever with Group A beta hemolytic Streptococcus pyogenes RF symptoms occur several weeks (2 – 4 wks) after the actual strep infection Rheumatic fever can involve joints, heart, skin, brain Rheumatic fever is an autoimmune reaction caused by antibodies formed against the Strep A that also bind to tissue in joints and the heart (cell wall antigen of group A strep “M antigen” is similar to cardiac myosin) Can be prevented by antibiotic treatment of people with group A strep People who had RF frequently have relapses after infection with Strep Some notable Facts: Children age 5 – 15 yrs are most affected Rare under 3 yrs and over 21 years Girls more often than boys More frequent during fall and winter months Incidence is up to 3 % in children with untreated strep pharyngitis  Diagnosis of RF (Jones criteria) Major Criteria – Carditis (congestive heart failure, murmur, pericarditis, dyspnea) – Migratory polyarthritis (very painful inflammation of large joints moving from joint to joint) – Sydenham’s chorea (rapid uncontrolled movement of hands and arms; occurs late in disease) – Erythema marginatum (long lasting rash that starts as macules, then form rings) – Subcutaneous nodules (Aschoff bodies, painless granulomas with a necrotic center surrounded by inflammatory cells) Minor criteria – Fever, – Arthralgia = joint pain without swelling – Laboratory abnormalities (enhanced ESR, leukocytosis – ECG abnormalities (prolonged PR interval) – Evidence for Group A Strep infection Note: 2 major or 1 major + 2 minor = RF diagnosis Most important heart valve defects: 1. Mitral valve insufficiency (regurgitation) 2. Mitral valve stenosis 3. Aortic valve insufficiency 4. Aortic valve stenosis 5. Mitral valve prolapse  Heart murmurs Wikipedia Mitral valve insufficiency Also called mitral regurgitation Bad prognosis due to late detection and rapid enlargement of LA & LV Most frequently caused by mitral prolapse. Other causes: rheumatic fever, ischemic heart disease, bacterial endocarditis, Fen-Phen (Fenfluramine), MARFAN!, No symptoms for years, sudden decompensation and heart failure Treatment: urgent replacement of mitral valve Systolic murmur  Mitral valve stenosis Narrowing of the mitral valve Early symptoms Shortness of breath, pulmonary edema, “mitral face” with cyanosis of the lips LA hypertrophy, pulmonary hypertension, coughing tinged with blood Arrhythmia of the left atrium Thrombosis! Bad prognosis Mid diastolic murmur (low rumbling) Aortic valve insufficiency “Aortic regurgitation” Dilation of the aortic root, valve disease Aortic valve does not completely close Combined concentric and eccentric LV hypertrophy Typically asymptomatic for a long time Elevated blood pressure = head bobs with the heart beat Early diastolic murmur, decreasing  Aortic valve stenosis Narrowing of the aortic valve Mid-systolic murmur Mild to moderate stenosis may not show symptoms More sever stenosis shows shortness of breath, angina pectoris, syncope, chest pain, left heart failure. Wikipedia Mitral valve prolapse Mitral prolapse is the most common valve disorder in the industrialized world 3% of the population Usually not significant finding and discovered by chance Cause is unknown – more frequent with Marfan Syndrome Degenerative disorder of the mitral valve Usually found by ultrasound Sometimes heart sound Good prognosis Antibiotic coverage for tooth extractions Can lead to Mitral valve insufficiency  Patent ductus arteriosus Pericardial friction rub (after pericarditis) VSD Bacterial Endocarditis Colonization of heart valves by bacteria Leads to development of thrombi mixed with bacteria = “vegetations” Are very friable and easily dislodge Mostly bacteria, but also fungi, rickettsia, chlamydia Subacute and acute forms Acute bacterial endocarditis quickly destroys heart valve and endocard and may lead to death in days and weeks Clinically: – Spiking fever, no clear cause – Bacteremia (Streptococci, Staphylococcus aureus, Enterococci) – Septic emboli – Petechiae – Heart murmur – Splinter hemorrhages Treat with high dose antibiotics  Cardiomyopathy (“heart muscle disease”) “Extrinsic” cardiomyopathies = etiology outside of the heart muscle “Intrinsic” cardiomyopathies = etiology within the heart muscle Most CM are extrinsic (ischemia = coronary artery disease). INTRINSIC CARDIOMYOPATHIES: Patients with signs of heart disease and enlargement in the absence of coronary disease, valvular disease, or hypertension! Three forms: Dilated cardiomyopathy (90%) Hypertrophic cardiomyopathy Restrictive cardiomyopathy Symptoms: shortness of breath, easy tiring, sometimes during or after infectious disease, sudden death! Noteworthy: 70% of people die within 5 years of diagnosis, males live only half as long as women, African Americans live half as long as whites Intrinsic Cardiomyopathies Type of CMP Findings All four chambers are dilated, and there is also hypertrophy. The most common Dilated (Congestive) cause is chronic alcoholism, though some 90%!!!!! may be the end-stage of remote viral myocarditis. The most common form, idiopathic hypertrophic subaortic stenosis (IHSS) Hypertrophic results from asymmetric interventricular septal hypertrophy, resulting in left ventricular outflow obstruction. The myocardium is infiltrated with a material that results in impaired Restrictive ventricular filling. The most common causes are amyloidosis and hemochromatosis. E. Klatt  Etiology of intrinsic cardiomyopathy (90% DCM) Idiopathic = unknown = frequently genetic, familial Toxins/Drugs – Alcohol!! – Chemotherapeutic agents (Cyclophosphamide, Doxorubicin) Infection – Viral (Coxsackie B) – Fungi – Bacteria – Parasites (Chagas disease =Trypanosoma cruzi, Trichinosis (Trichinella spiralis, roundworm) Immunologic (autoimmune myocarditis, graft rejection after transplantation, amyloidosis Metabolic – Starvation, vitamin deficiency (thiamine), diabetes, hypothyroidism, acromegaly, hemochromatosis Storage disorders – glycogen storage disease Neuromuscular Intro to Clinical Medicine Diseases of Blood Vessels and Circulatory System Thomas G. Forsthuber, M.D. Dr. Med. Professor of Immunology, Adjunct Professor of Microbiology & Immunology (UT Health) Office: BSE 3.250B E-mail: [email protected] Office Hours: Monday 4:30 – 5:30 pm You are encountering the following situations: 1) You are seeing a 75-year-old female patient in your office. She complains about painless swelling of her legs, shortness of breath going up a flight of stairs in her house, and overall tiredness. What would be your working diagnosis? 2) While you are dealing with the above patients, you receive an urgent call from relatives of a 67-year-old female patient. The relatives are worried about their grandmother having sudden onset of dizziness, shortness of breath, and nausea. What do you do? 3) You have worked tirelessly in the hospital ER since 5 am this morning and decided that it is time for a lunch break. On the way to the elevator, you pass a child that was hit with a football in the head during a flag football game at school and which is on the way to admissions. You hear that the child complains about headaches and increasing dizziness. Can this wait until after lunch?  Diseases of the blood vessels and heart Leading cause of morbidity and mortality. Account for more than 40% of death after birth Diseases of blood vessels and heart impair the circulation of blood and delivery of oxygen and nutrients (glucose) to tissues/organs Decreases the function of cells and organs. Impaired perfusion: due to obstruction of blood vessels, rupture of blood vessels, or failure of the heart to pump blood Particularly important for: brain, heart, kidneys The term “cardiovascular disease” is an umbrella term used for: Atherosclerotic diseases of heart or blood vessels (arteries) Myocardial infarct Stroke Atherosclerosis is the most common cause of cardiovascular disease But there are also other, less frequent causes for cardiovascular diseases (e.g. hypertension, diabetes, drugs such as cocaine) Important disease conditions of blood vessels and heart: Atherosclerosis Coronary heart diseases/myocardial infarct Thrombosis Embolism Aneurysms Congenital heart diseases Cardiomyopathy Congestive heart failure Hypertension  Functional anatomy of the circulatory system Arteries: blood vessels that carry blood away from the heart towards the peripheral tissues Arteries normally carry oxygen-rich blood Veins: blood vessels that carry blood towards the heart Veins normally carry oxygen- poor (deoxygenated) blood EXCEPTIONS: - Pulmonary arteries carry oxygen-poor blood - Pulmonary veins carry oxygen-rich blood wiki Blood vessels have 3 layers:  Anatomy of the circulatory system Major veins Major arteries ar.inspiredpencil.com Heart and aorta The ABC’s of the aortic vessels: A = Aorta B= Brachiocephalic trunc splits into right carotid artery and right subclavian artery C = Carotid artery (left) S = Subclavian artery (left) Wikipedia And that’s how it looks in reality The coronary arteries Front Back Brainkart.com  Heart, gross anatomy Courtesy of Dr. E. Klatt, Webpath The major disturbances in blood flow EDEMA: Increased fluid in interstitial tissue HEMORRHAGE: Bleeding THROMBOSIS: Occlusion of blood vessels by local blood clot – Venous thrombosis (Deep venous thrombosis = DVT) – Arterial thrombosis (Stroke, MI) EMBOLISM: Blockage of a blood vessel by circulating blood clot. – Can also be due to: fat embolism, air embolism, amniotic fluid – Venous thrombus (right side of the heart) will end up in the lungs (pulmonary arteries) and lead to pulmonary embolism – Arterial thrombus (left side of the heart) can result in arterial thrombosis anywhere in the body (e.g. stroke) INFARCTION: Tissue necrosis due to occlusion of arterial blood supply leading to tissue ischemia. – Myocardial infarction, stroke, gangrene SHOCK: Dramatic drop in blood pressure leading to hypoperfusion of vital tissues.  EDEMA EDEMA: Accumulation of fluid in interstitial tissues or body cavities – For example, edema of arms, legs, lung edema, – Edema in body cavities has special names: Hydrothorax Ascites (abdomen) Hydropericardium Many factors can lead to edema – Increased hydrostatic pressure: Impaired venous return, heart failure, venous obstruction/insufficiency, – Reduced plasma oncotic pressure (hypoproteinemia = decrease in blood proteins) Kidney diseases with protein loss Liver cirrhosis Malnutrition – Lymphatic obstruction (lymphatic vessels drain tissue fluid) – Salt retention (Sodium retention) – Inflammation Edema “Pitting” edema is present when a depression remains upon pressure Edema does not show the cardinal signs of inflammation Lymphedema Lymphedema is often “non-pitting”  75% of blood flowing through liver comes from portal vein HEMORRHAGE (bleeding) Hemorrhage is an undesired loss of blood Hemorrhage can be acute or chronic Hemorrhage is usually due to the rupture or injury of a blood vessel (artery or vein) Hemorrhage less than 20% can usually be tolerated in adults, but not in smaller children Hemorrhage may be external, internal, or into tissues (hematoma) – Hematomas or hemorrhage can be clinically important depending on the size and location (e.g. inside the scull = epidural hematoma = medical emergency, 20% death!!!)  HEMORRHAGE (bleeding) The size of a hemorrhage gives clues as to its cause: – Petechiae: very small, 1 – 2 mm hemorrhage in skin, mucous surface Low platelet counts (thrombocytopenia), platelet defects, some milder clotting factor deficiencies, increased blood pressure – Purpura: >3mm, same cause as petechiae, vascular inflammation (vasculitis), increased fragility of vessels Thrombocytopenic purpura, vascular disorders, vasculitis, Henoch-Schonlein purpura (IgA vasculitis) – Ecchymosis (bruise): > 1cm, bleeding into tissues (subcutaneous), after injury, bleeding disorders, – Bleedings in body cavities: hemothorax (chest cavity), hemopericardium (pericard), hemoperitoneum (abdomen), hemarthrosis (bleeding into joints): injury, bleeding disorders Difference between ecchymosis and hematoma: Hematoma: Pocket of blood in tissues Hematoma can be felt when touched Hematoma can be external or internal Often pain or tenderness Ecchymosis: Non-blanching purple or red discoloration of skin due to leakage of RBCs from small ruptured blood vessels. Cannot be felt Usually not painful or tender  Hemostasis & Thrombosis Hemostasis is the normal mechanism of how a bleeding is terminated. – Primary hemostasis: platelets bind to damaged/inflamed vessel wall and form a platelet plug (occurs in seconds) – Secondary hemostasis: coagulation cascade forms a fibrin clot that stabilizes (“cements”) the platelet plug (may take minutes) Thrombosis is the undesired activation of the coagulation system that leads to the occlusion of vessels and hypoperfusion Blood coagulation The most important factors that contribute to blood coagulation are: a) Blood vessels b) The coagulation system c) Blood platelets Sequence of events: After injury arteries initially constrict The injury to blood vessels exposes extracellular matrix and tissue factors that activate blood coagulation Platelets adhere to site of injury and become activated and release granules that activate even more platelets Fibrin is produced by the coagulation cascade and stabilizes the platelet thrombus.  Normal blood coagulation TF vWF collagen Overview: coagulation cascade (most important: Factor Xa) (Factor II) (Factor I)  The coagulation cascade (11 factors, I-XIII; not VI) Two main coagulation pathways: tissue factor (coagulation factor III) pathway TRIGGERS coagulation, contact activation pathway SUSTAINS COAGULATION Coagulation factors are enzymes (serine proteases) that catalyze the next reaction of coagulation until fibrin is formed Most important steps: Conversion of prothrombin to thrombin, which then converts fibrinogen to fibrin Thrombus formation is a constant battle of factors that promote thrombus formation against factors that inhibit thrombus formation Contact activation pathway Tissue factor pathway Activated by Thrombin! - - “Jump starts” coagulation Also: contact with negative charged surface (bacteria, damaged RBC) - Primary job is to activates this pathway. generate “thrombin burst” Tested by the PTT (aPTT)= Activated partial thromboplastin time Tested by the PT test = (only phospholipids added) prothrombin time (add TF + PTT PT Can be used to measure Heparin phospholipids). effects (Heparin activates It is now reported as INR antithrombin III) value for the dosing of Warfarin (Coumadin) Note: Coumadin inhibits Hemophilia A is deficiency of vitamin K dependent factors (II, factor VIII (90% of VII, IX, X) hemophilias!) Hemophilia B: factor IX Hemophilia lab tests: aPTT prolonged PT normal Platelets normal Bleeding time normal Factor VIII or IX reduced  Direct-acting oral anticoagulants (DOACs) (or Novel oral anticoagulants (NOACs) Came on the market first in 2010 incl. dabigatran (Pradaxa, Boehringer), rivaroxaban (Xarelto, 2011), apixaban (Eliquis, 2012). Target thrombin (dabigatran, Pradaxa) or factor Xa (rivaroxaban, Xarelto) As effective as warfarin (Coumadin, Vit. K dependent inhibition of II, VII, IX, X) Much more predictable effects Much faster No need for routine anticoagulation monitoring Problem was lack of antidotes First antidote became available May 2018 Concerns: – DOACs are 5 to 15-fold more expensive – Initially no Antidotes (until now) – Once-a-day dosing may be inefficient and not work for all – Bleeding risk Pathologic thrombus formation An intravascular blood clot is called a thrombus; the condition is called thrombosis. Thrombus = blot clot. Thrombi (plural) may form in veins, arteries, or the heart If a thrombus becomes dislodged, it can move with the blood stream until it does not fit through anymore and forms an embolus. Three main factors contribute to thrombus formation (“Virchow’s Triad”): – Stasis of the blood flow (creates turbulence) Platelets are forced against vessel walls and in contact with endothelium which may activate them Anti-clotting factors are diluted and endothelial cells activated – Endothelial injury (atherosclerosis, inflammation, smoking/nicotine) More important for thrombus in the arterial system Exposure of extracellular matrix activates platelets and clotting system – Blood hypercoagulability (genetic or acquired; elevated prothrombin)  Important risk factors for thrombosis/embolism 350,000 to 900,000 cases of DVT per year! Prolonged bed rest or immobility Underlying conditions (age + smoking + sitting in the same position) Atrial fibrillation MI Prosthetic heart valves Status after surgery, fracture, burns Tumors Most important clinical situations Deep vein thrombosis (DVT) Pulmonary embolism (PE) Arterial thrombosis  Clinically: DVT – Swelling, pain, redness Diagnosis: – Ultrasound – Elevated D-dimers levels (> 300 ng/ml) – D-dimers are fibrin breakdown products created by plasmin digesting blood clots. – Negative D-dimers basically rule out thrombosis – Intravenous venography Therapy: Anticoagulation – Short term: heparin (PTT test!) – Long term: warfarin (Coumadin – PT test) – Thrombolysis in extreme situations – Inferior vena cava filter (Greenfield filter) in recurrent DVT – Prevent by mobilizing patients DVT with venous insufficiency Recently reported: not only DVT but also: Superficial vein thrombosis is not harmless! 2 – 13% severe PE.  Varicose Veins (chronic venous insufficiency =CVI) Insufficiency of the venous valves. Increases risk for DVT ~ 4-fold. 2-fold increase in PE risk. Potential outcomes of DVT  Pulmonary embolus – clinical picture Blot clot from DVT dislodges and ends up in the lungs Major artery in the lungs is occluded: pulmonary trunk, pulmonary arteries, Clinically: – SUDDEN ONSET of shortness of breath (dyspnea), – rapid breathing (tachypnea), – chest pain, – cyanosis (blue skin tint), – tachycardia, – dizziness, risk factors! Diagnosis: – Pulse oximetry, chest X-ray (to exclude other conditions) – CT scan, CT scan with radiocontrast, pulmonary angiography (contrast X-ray), ventilation-perfusion scan (V/Q scan), ECG, Echocardiography, blood tests (D-dimer, clotting status) Treatment: Thrombolysis (tPA = tissue plasminogen activator; Streptokinase), oxygen, analgesia, anticoagulation, surgical removal of embolus Untreated PE has > 25% mortality!!!!! Smaller PE’s can be survived Courtesy of Dr. E. Klatt, Webpath  Anatomy of a Thrombus Thrombus “Lines of Zahn” Alternating bands of pale pink platelets and fibrin (light) with red bands of RBCs (dark) Lines of Zahn mostly form in arteries (fast flowing blood), less often in veins Only form when patient is alive (not post-mortem) Arterial thrombus/embolus MOST IMPORTANT CAUSE FOR THROMBUS FORMATION IS ATHEROSCLEROSIS OF ARTERIAL BLOOD VESSELS However: Thrombi frequently form in the heart (atrial fibrillation), heart valve disease If dislodged thrombus will enter the arterial system Frequently located to: – Brain – Kidneys – Skin Clinical symptoms according to location! Thrombus on abdominal aortic aneurysm Splinter hemorrhage  Infarction Ischemic necrosis caused by occlusion of arterial supply (>95%) or venous drainage of an organ – Hemorrhagic (red) infarcts: tissue is infarcted and then blood flows back in from another artery that supplies this tissue. Occurs in lungs, tissues perfused from several sources (lungs, GI), after rupture of a vessel, after re-perfusion, venous infarcts – Anemic (white) infarct: arterial occlusion of organs that have only one arterial supply (heart, spleen, kidney) Causes: thrombosis, embolus, twisting of vessels, entrapment of a vessel (e.g. in a hernia sac) Symptoms depend on the tissue and its blood supply: How much oxygen does it need; does it have another blood supply. – Myocardial infarct – Cerebral infarct/stroke. Note: Hemorrhagic stroke or ischemic stroke – Bowel infarction – Gangrene of a limb This is a main cause of infarction: Thrombus formation on atherosclerotic vessels E. Klatt, FSU  Atherosclerosis is a form of arteriosclerosis! Arteriosclerosis = hardening of arteries THREE MAIN TYPES OF ARTERIOSCLEROSIS: 1) ATHEROSCLEROSIS: Most frequent form or arteriosclerosis. - Atherosclerosis is hardening of arteries specifically due to atheromatous plaques = inflammation caused by deposition of lipoproteins (cholesterol from LDL) and inflammation. 2) Mönckeberg’s medial calcific sclerosis (calcium deposits in muscular arteries 3) Arteriolosclerosis: affects small arteries; thickening of the walls found in diabetes and hypertension “Other” embolisms Fat embolism – Microscopic emboli of fat droplets after fracture of large bones – Fat obstructs/inflames blood vessels, veins, arteries, capillaries – Clinically pulmonary insufficiency, neurologic symptoms, anemia, thrombocytopenia, petechiae in 20 – 50 %! – Triad: Confusion, dyspnea, petechiae Air embolism – During surgical procedures, chest wall injury, – Arteries or veins – Decompression injury after diving = nitrogen bubbles in the blood! Amniotic fluid embolism – Complication of labor and immediate postpartum – Sudden onset of severe dyspnea, cyanosis, shock, seizures, coma, after/during birth – 80% maternal mortality!!!!!! – Cause is entering of amniotic fluid or fetal tissue into maternal blood circulation due to rupture of uterine veins or tear in placental membranes  Epidural hematoma Remember: Epidural hematoma: “Lucid interval”! Clinical presentation of epidural hematoma: Preceding trauma Initial loss of consciousness > lucid interval > followed by decline in mental status! HOWEVER: presentation may be variable!!!!! Headache Nausea/vomiting Seizures Focal neurologic deficits: visual dropouts, aphasia, weakness, numbness Do you know now how to proceed in these cases? 1) You are seeing a 75-year-old female patient in your office. She complains about painless swelling of her legs, shortness of breath going up a flight of stairs in her house, and overall tiredness. What would be your working diagnosis? 2) While you are dealing with the above patients, you receive an urgent call from relatives of a 67-year-old female patient. The relatives are worried about their grandmother having sudden onset of dizziness, shortness of breath, and nausea. What do you do? 3) You have worked tirelessly in the hospital ER since 5 am this morning and decided that it is time for a lunch break. On the way to the elevator you pass a child that was hit with a football in the head during a flag football game at school and which is on the way to admissions. You hear that the child complains about headaches and increasing dizziness. This can wait until after lunch, right?