CardiacCardiac TumorsCardiac Tumors•Rare•Usually benign and pedunculated•Three types:–Cardiac myxomas–Rhabdomyomas–Metastatic tumorsRight atrialWith stalkCardiac Myxomas•The most common primary adult tumor (35-50%)•Most arise from the left atrium (90%)•Complications:–“Ball-valve” effect may obstruct the mitral valve orifice in over half of patients with myxomasof the left atrium•Blocks diastolic filling of the ventricle, stimulating mitral valve stenosis-> may cause syncopalepisodes–One third of these patients die of embolizationof the tumor to the brain•Dx: transesophagealultrasoundStellatecells and fibroblastsAmorphous extracellular matrixHistology of Cardiac Myxomas•Loose myxoidmatrix•Abundant proteoglycanswith stellatecells within the matrixGrosslyStriated muscle (“Spider”) cellsRhabdomyomas•Most common primary cardiac tumor in infants and children –Major association with tuberous sclerosis•Forms hamartomasin the myocardium•Almost all are multiple –Involve both the left and right ventricles, and the atria in 1/3 of cases–Projects into the cardiac chamber in ½ of cases•Grossly:–Pale gray masses, up to several centimeters•Histologically:–Derived from striated muscle cells with abundant glycogenMetastatic Breast CancerMetastatic Melanoma to the HeartMetastatic Tumors to the Heart•Metastasis is more common than primary tumors–Derived from cancers of the lungs, breast, GI tract, lymphomas, leukemias, malignant melanomas•The pericardium is the most common site for metastasis–Leads to pericarditisand effusions•Metastatic cancers of the myocardium ma result in manifestations of restrictive cardiomyopathyHeart EmboliTypes of Emboli•Thromboemboli–Fragments of thrombi–Most common–Infected thrombi give rise to septic emboli•Liquid Emboli–Fat emboli–Amniotic fluid emboli•Gas Emboli–Air emboli–Decompression sickness•Solid Particle Emboli–Cholesterol crystals from atherosclerotic plaques–Tumor cells–Bone marrow emboli–BulletsClassification of Emboli•Venous emboli–Originate in veins–Typically lodge in pulmonary artery and branches -> pulmonary embolism•Arterial emboli–Originate in the heart, aorta, and major arteries–Cause infarction•Paradoxical Emboli–Venous emboli that reach the arterial circulation through an atrial septal defectSources of Venous EmboliPulmonary Embolism•Most important complication of venous emboli•Saddle emboli @entry of main pulmonary artery–Often lethal•Smaller emboli lodge in minor branches and cause wedge-shaped infarctsPulmonary Saddle EmbolusWedge-shaped pulmonary infarctArterial Emboli•Most originate from endocardium, valvular thrombi, ulcerated atherosclerotic plaques•Tend to lodge in medium-sized and smaller arteries•Lodge in:–Brain (middle cerebral artery)–Spleen–Kidneys–IntestinesSources of Arterial EmboliFat Embolism•Following fractures of long bones -> platelets adhere to fat globules -> thrombocytopenia•Fat Embolism Syndrome appears 1-3 days after injury–Respiratory symptoms: ARDS–Neurologic symptoms: mental changesAmniotic Fluid Embolism•Entry of amniotic fluid into the maternal circulation•Usually occurs @the end of labor•Histology: fetal squamous cells within pulmonary vasculature•Clinical presentation:–Sudden severe dyspnea–Cyanosis–Hypotensive shock–Seizures and coma –Pulmonary edema–DIC Fetal Epithelial SquamesBone Marrow Embolism•Usually after cardiac resuscitation •No symptomsDecompression Sickness•Form of gas embolism•Seen in scuba divers•Nitrogen gasreleased from solution during rapid ascent -> obstructing blood flow•Commonly known as the “bends”•Temporary muscle, joint painCaisson Disease•Chronic decompression sickness where vascular obstruction causes avascular necrosis of bone, primarily affecting head of the femur, tibia, and humerusHyperemia•Accumulation of blood in the peripheral circulation•Active hyperemia: dilatation of the arterioles mediated by neural signals•Passive congestive: increased venous back pressure–Consequence of CHF–Associated with pulmonary edema with L heart failure•RBC’s taken up by alveolar macrophages = hemosiderin-laden macrophages (heart failure cells)–Associated with passive liver congestion(Nutmeg liver) with R heart failureHemosiderin-Laden MacrophagesChronic Passive Congestion of the LiverHemorrhage•Cardiac–Resulting from a stab wound, or a softened heart muscle from a MI can result in ventricular rupture -> pericardial tamponade–Often fatal•Aortic–Trauma, aortic aneurysm dilation, dissection•Arterial–Penetrating wounds, fractured bones–Usually fatal•Venous–Usually traumatic; blood flows out of the body -> hypovolemia–May fill body cavities and form hematomasPetechiae, purpura, and ecchymosis•Petechiae–Small hemorrhages into skin, mucosa < 1mm in diameter•Purpura–Measure 1mm to 1cm•Ecchymoses–Larger blotchy areas under the skin due to traumaFate of the Thrombi•Small thrombi are lysed or dissolved•Larger thrombi stimulate inflammatory cells -> granulation tissue deposition (organization); inflammatory cells of granulation tissue dissolve the thrombus & replaced with collagen•Occlusive thrombi may be recanalized•If thrombus cannot be organized or dissolved, may embolizeThrombus Classification By Location•Intramural–Attached to mural endocardium; commonly found overlying a MI–May embolize•Arterial–Attached to the arterial wall; typically cover ulcerated atheromas•Venous–Usually found in dilated veins–Long-standing are organized by granulation tissue•Microvascular–Found in arterioles, capillaries, and venules–Typical of Disseminated Intravascular CoagulationThrombus Classification Pathologically•Red Thrombi–RBC’s and fibrin–Thrombi in small vessels•Layered Thrombi–Lines of Zahn: alternating white (fibrin) and red (RBC) lines –Thrombi in larger arteries, veins, mural thrombiLines of ZahnInfarction•Classified as red or white•White infarcts–Typical or arterial occlusion in solid organs (heart, kidneys)–Paler than surrounding tissue; often rimmed by a thin red zone with extravasated blood•Red infarcts–Typical of venous obstructioninvolving intestines, or testes–Also typical of organs with a dual blood supply, i.e. liver, lungs•Septic infarcts–Infarcts caused by infected thrombi, emboli–Show signs of inflammation; may transform into an abscessRed infarct of the intestineWhite infarcts of the kidneySeptic emboli causing infarcts in spleenShock•State of hypoperfusionof tissues -> hypoxia -> multiple organ failure•Hypoxia -> shift from aerobic to anaerobic metabolism ->lactic acidosis•Three mechanisms:–Cardiogenic shock•Pump failure of the heart, often secondary to a MI–Hypovolemic shock•Loss of circulatory volume, due to hemorrhage or water loss–Septic shock•Most often due to endotoxin(LPS)-producing gram negative bacteria such as E.coliPathogenesis of Septic Shock3 Stages of Shock•Nonprogressive–Initial phase when reflex compensatory mechanisms maintain perfusion of vital organs•Progressive–Characterized by tissue hypoperfusion, and development of metabolic imbalances (acidosis)–Metabolic acidosis -> dilates arterioles -> worsens CO -> stagnation of blood in pulmonary circulation -> favors ARDS (shock lungs) –Urinary output falls due to constriction of the renal cortical vessels marking transition between reversible and irreversible stage•Irreversible–Survival is not possible–Multiple organ failure is usually present–DIC is common–Patients have marked hypotension, respiratory distress, acidosis, and anuriaCompilations of ShockARDS with hyaline membranes•In shock, alveolar capillaries in the lungs may necrotize and slough off to be covered and lined by fibrin (hyaline membranes)Waterhouse Friderichsen syndrome•Commonly associated with meningococcal (Neisseria) septic shock•Bilateral hemorrhagic infarction of the adrenalsBacterial EndocarditisInfective Endocarditis•Infective endocarditis: Micro-organism infection of inside of heart.–Can infect Aorta, Blood vessels, prosthetic heart valves.–Fungi, Rickettsia, and Chalydimdiaare other rare causes.–Divided into acute and subacute.–Causes•Usually pt is predisposed due to:–Artificial Valves–Congenital Defects–Degenerative Calcified valvularstenosis–Bicuspid Aortic Valves–MyxomatousMitral Valve (mitral valve prolapse)•Infective EndocarditisvsRheumatic Heart disease vegetations.–Rheumatic Heart disease has sterile thrombi.–Infective Endocarditisvegetations are composed of thrombi and bacteria.Acute Bacterial Endocarditisdue to S. Aureus.Destruction of Aortic Valve.Gram Negative Bacterial EndocarditisAcute and Chronic Infective Endocarditis•Acute Bacterial Endocarditis–High destruction of previously normal valve.–Staph Aureusor Gram Negative.–May perforate valve.–Necrotic ValvularLesions•SubacuteBacterial Endocardiditis–Slower, less virulent disease–St. Viridans–Infection is previously abnormal heart valves–Less destructive and show evidence of healing.SubacuteBacterial endocarditisFischione: Infective EndocarditisAcute, Staph Aureus•Infective Endocarditis•Infective endocarditis: Micro-organism infection of inside of heart.–Can infect Aorta, Blood vessels, prosthetic heart valves.–Fungi, Rickettsia, and Chalydimdiaare other rare causes.–Divided into acute and subacute.–Causes•Usually pt is predisposed due to:–Artificial Valves–Congenital Defects–Degenerative Calcified valvularstenosis–Bicuspid Aortic Valves–MyxomatousMitral Valve (mitral valve prolapse)•Infective EndocarditisvsRheumatic Heart disease vegetations.–Rheumatic Heart disease has sterile thrombi.–Infective Endocarditisvegetations are composed of thrombi and bacteria.Acute Bacterial Endocarditisdue to S. Aureus.Destruction of Aortic Valve.Acute and Chronic Infective Endocarditis•Acute Bacterial Endocarditis–High destruction of previously normal valve.–Staph Aureusor Gram Negative.–May perforate valve.–Necrotic ValvularLesions•SubacuteBacterial Endocardiditis–Slower, less virulent disease–St. Viridans–Infection is previously abnormal heart valves–Less destructive and show evidence of healing.SubacuteBacterial endocarditisStaph on prosthetic tricuspid (top)Infected ArtificalMitral Ball Valve (bot.Mitral Valve ProlapsePathogenesis of Endocarditis•Risk Factors–Seeding of the blood with microbes due to infection in the body… Pneumonia, UTI, Dental/Surgical procedure causing a bacterima.–Neutropenia–Immunodeficiency–Diabetes–EtOHabuse–Drug abuse (IV)SubacuteendocarditisSt. ViridansPathology of Infective endocarditis•Prosthetic Valve endocarditis-> Staph Epidermis•Vegetations–Large, bulky–Contain fibrin, thrombin, inflammatory cells and bacteria.–Most commonly on Mitral #1, and Aortic #2 of non IV drug abusers.–May cause septic emboli following detachment.–Fungal vegetations tend to be larger than bacterial vegetations.–Septic Emboli most feared complication.CandidalEndocarditisNote: Fungi produce some of the largest vegetations seen in endocarditisClinical features of Endocarditis•Fever is present in all pts.•Murmur is common due to vegetations.•Acute. BE -> quick onset, chills, night sweats and weakness.•Subacute. BE ->low grade fever, fatigue and flu like symptoms.Diagnosing Endocarditis•Positive blood culture required for conformation can be obtained in 90% of cases.Gram Negative Bacterial EndocarditisInfective Vegetation (3) With Fibrin, Necrosis and Acute Inflammation (2)Infective Vegetation with Pink Fibrin and Blue Staining Coccal OrganismsSigns/Symptoms of Bacterial Endocarditis“FROM JANE”:•Fever•Roth’s Spots•Osler’s nodes•Murmur (New)•Janewaylesions•Anemia•Nail-bed hemorrhage•EmboliJanewaylesions are seen in people with acute bacterial endocarditis. They appear as flat, painless, red to bluish-red spots on the palms and soles.•Roth spots:a round white retinaspot surrounded by hemorrhage in bacterial endocarditis, and in other retinal hemorrhagic conditions. •Osler's nodes:These are small (the size of split peas), tender, transient nodules in the pads of fingers and toes and the palms and soles. They are a highly diagnostic sign of bacterial infection of the heart (subacutebacterial endocarditis). Named for the Canadian-born physician Sir William Osler (1849-1919).•Splinter hemorrhage in patients with heart murmur and unexplained fever can herald endocarditis.•Libman-Sacks(verrucous) endocarditisis the most characteristic cardiac manifestation of the autoimmune disease systemic lupus erythematosus. Seen as mulberrylikeclusters of verrucaeon the ventricular surface of the posterior mitral leaflet. The lesions typically consist of accumulations of immune complexes and mononuclear cells. Vegetations develop on both sides of valve (Mitral valve stenosis), but do not embolize. Seen in LupusSLEcauses LSERheumatic Heart Disease•Rheumatic heart disease is a complication of rheumatic fever in which the heart valves are damaged.Rheumatic fever is an inflammatory disease that begins with a strep throat. It can affect connective tissue throughout the body, especially in the heart, joints, brain and skin. Rheumatic fever develop following pharyngitiswith group A beta-hemolytic Streptococcus. Acute rheumatic fever and rheumatic heart disease are thought to result from an autoimmune response (Immune mediated not direct effect of bacteria)Rheumatic heart disease Signs/Symptoms•Valves effected: Mitral> Aortic>>Tricuspid (High pressure valves affected most)•Aschoffbodies (Granulomawith giant cells)•Anitschkow’scells (Activated histiocytes)•Migratory Polyarthritis•ErythemaMarginatum•Sydenham chorea•FishmouthStenosis-Fusion of the valvularcuspsExtracardiacFindings in RHD•Mnmonic: CANCER•Carditis•Arthritis -•Nodules –most common in children, overlies extensor tendons.•Chorea•ERythemaMarginatum: macopapularrash appearing mostly on trunk and proximal extremties.Diagnostic findings in RHD•RHD Lab Findings–RF Symptoms after strep throat infection–Pos. Titers of serum antibodies to Group A strep.–↑ESR, ↑WBC, C-Reactive Protein•Diagnosis–Jones Criteria (2 major; or 1 major + 2 minor fufilled)•Major Criteria–Pancarditis–Polyarthritis–SydenhamsChorea–SubCuteneousNodules–ErythemaMarginatum•Minor Criteria–Hxof RF–Fever–Arthagias–EKG + for heart damage•Erythemamarginatum: A condition which is characterized by reddened areas of the skin which are disk shaped with elevated edges.Acute Rheumatic Fever and Rheumatic Heart Disease•Acute Rheumatic Fever–Systemic immunologically mediated disease related to Streptococcal infection.–Occurs 2 weeks after strep throat infection.–Immune Reaction•Immune rxndamages connective tissue of the heart.•Anti-strep antigen -> AntistreolysinO(ASLO or ASO) develop in all pts.–Not all pts with ASO titers develop ARF.–Principally disease of children. Can occur in adults.•Aschoffbody: A granulomatousinflammation characteristic of acute rheumatic carditis, consisting of fibrinoidchanges in connective tissue and lymphocytes.•Anitschkowcell: large mononuclear cells with an undulating, ribbon-like formation of nuclear chromatin. These 'caterpillar cells' are found in myocardium and thought to be macrophages.Valve Changes in RHD•Insuffiency–Mitral Valve Insufficiency•Blood reflux across mitral valve.–Aortic Insufficiency•Blood reflux back from aorta to LV -> left ventricular hypertrophy and dilation.•Stenosis–Mitral Stenosis•Stagnation of blood in left atrium -> RHF–Aortic Stenosis•Impedes blood flow from LV into Aorta -> LV hypertrophy -> CorPulmonae-> RHFMyocardial InfarctionClinical Signs of MI•Crushing precordialchest pain•Constricting suffocating pain•Substernalpain that may radiate to the left arm, neck, jaw•Loss of consciousness/fainting•Nausea/vomiting•Fatigue/weakness•Tachycardia, anxiety, restlessness•Pale, cool, moist skin•Pain prolonged, not relieved by nitro 1/28/09 Pathology wk1Diagnosis of MI•ECG changes in acute MI:–Prolonged Q wave –Elevated ST segment–Inverted T wave•Increased lactic acid production -> metabolic acidosis–Ischemic myocardial cells revert to anaerobic metabolism•Hyperkalemia-> arrythmias–Potassium released into the ECF, affecting membrane potentials of functioning myocardial cells•Elevated CreatineKinaseand CK-MB –Absence of change in first 2 days excludes MI•Elevated troponinsin the serum–Remain elevated for 7-10 days –Gold standard for diagnosis of acute MI because more specific for myocardial tissue•Not pathognomonic•Lactate dehydrogenase(LDH) flip–Normally LDH2 is higher than LDH1•In acute MI, LDH1 is released, causing the “flip”–Better markers now, not used much 1/28/09 Pathology wk1Too many Big Macs may cause?Acute 1/28/09 Pathology wk1 ProgressiveCoronary Artery Disease:•Atherosclerosis of the coronaries -> myocardial ischemia •May be chronic progressive ischemia from atherosclerosis •May be acute coronary thombosisdue to a sudden occlusionResults in a MI in an anatomically defined area1/28/09 Pathology wk1 Distribution of MI’s:Anterior wall infarctOcclusion of the Left Anterior Descending (LAD) Artery –over 50%Lateral wall infarctOcclusion of the Left Circumflex Artery –30-40%Infarct of the right ventricle and posterior wall of the left ventricleOcclusion of the Right Coronary Artery (RCA) –10-20%1/28/09 Pathology wk1 Calcified plaquePathology of CAD:Coronaries -> atherosclerosis -> narrowing of the lumen due to fibrotic plaques and atheromasPlaques may be covered with fibrinousclots in an acute occlusionGranulation tissue of the plaque and thrombi in older lesions may reestablish blood flow via recanalizationWall contains calciumand cholesteroldeposits1/28/09 Pathology wk1 Myocardial Infarction:Rapid, sudden occlusion of a coronary artery•Sudden cardiac death in ~25%•Among survivors of the onset: inadequate perfusion -> multisystemicmajor organ failure•Cerebral ischemia most dangerous•Kidney damage most often Causes:•Thrombosis of a coronary artery (80-90%)•Ulceration of an embolizedatherosclerotic plaque•Prolonged vasospasmTypes of MI’sTransmural:•Most common•All 3 layers of the heart involved•Free wall of the left ventricle and/or interventricularseptum usually involved•New Q-waves develop 1/28/09 Pathology wk1 Subendocardialor Intramural:•Infarction usually concentric around the subendocardiallayer of the left ventricle•Q waves are absentTransmuralSubendocardial1/28/09 Pathology wk1 Histology of MI:Microscopic changes precede macroscopic changes•During 0-24 hours•During 1-3 days•Myocardial cell death•Eosinophilicmyocytesdevoid of nuclei and striations•Coagulativenecrosis•Contraction bands•Predomination of PMN’sthat lysedead myocardial cells•Days 3-4•Macrophage infiltration•End of first week•Granulation tissue invading the infarct•Macrophages phagocytizenecrotic debris•Chronic MI•Necrotic myocardium replaced by white fibrous scarringWavy, eosinophilicmyocyteswith contraction bandsPink CoagulativeNecrosis and PMN’s (3-4 Days Old)SubacuteMyocardial Infarct-Granulation Tissue and Macrophages (over 1 week)Old, Remote Infarct with White, Myocardial Fibrous ScarringAcute with soft yellow and hemorrhagic tissueSubacutewith deposition of granulation tissue 1/28/09 Pathology wk1 Gross Pathology of MI:First 1-2 days•Cannot be definitively identified•May be pallor of infarctedmyocardium3-5 days •Infarct becomes yellow•Hemorrhagic rim•Soft infarctedmyocardium from hydrolytic enzymes released from neutrophils1-2 weeks•Granulation tissue imparting a gray-pink, mottled appearanceChronic infarct•White-tan fibrosisComplications of MI•Myocardial Rupture•Left Ventricular Aneurysm•Mural Thrombus 1/28/09 Pathology wk1Ventricular rupture with necrosisHemopericardiumdue to Rupture Causing Cardiac Tamponade 1/28/09 Pathology wk1 Myocardial Rupture:•Softened necrotic myocardium ruptures•Blood fills the pericardial sac (hemopericardium) -> cardiac tamponade(compression of the heart)Myocardial RuptureLeft Ventricular Aneurysm•MI’s of the left ventricle -> granulation and fibrous tissue replacement -> bulge under pressure -> ventricular aneurysm•Fibrous tissue does not contract -> heart dilated and contracts irregularly 1/28/09 Pathology wk1 Ventricular AneurysmW/Mural ThrombusVentricular Aneurysm With InfarctedMyocardial WallMural Thrombus•Endocardiumdamaged/disrupted•Blood coagulates in contact with the necrotic endocardium/exposed myocardium -> thrombus attached to the wall •Complications:–Impede blood flow–Weakens ventricular contractions–May detach giving rise to emboli -> cerebral Infarcts 1/28/09 Pathology wk14 Stages of MI-Microscopic Findings24 Hours: Myocardial cell death with wavy, eosinophilicmyocytes(Pink), coagulativenecrosis (Myocyteshave no nucleus), and contraction bands. The nuclei are either faint or dead. Acute MI With Wavy, Eosinophilic Myocytes with Contraction Bands4 Stages of MI-Microscopic Findings•Days 1-3: The appearance of PMN’swhich will predominate for the next three days.Pink (eosinophilic) CoagulativeNecrosis and PMN’sNote: PMN’s Have segmented Nuclei, they are granulomas (Innate immunity)4 Stages of MI-Microscopic Findings•Days 3-7: The infarctedarea becomes infiltrated with macrophages, which persist in the lesion for about a week that phagocytizeand remove necrotic debris and myocytes.Subacute Myocardial Infarct-Granulation Tissue and Macrophages (over 1 week)4 Stages of MI-Microscopic Findings•Days 7-28 : Toward the end of the first week, the infarct is invaded with granulation tissue composed of small blood vessels (angiogenesis), myofibroblastsand fibroblasts depositing collagenousmatrix. Macrophages replace the PMN’s and phagocytizedthe necrotic debris. (these are subacutefindings in an MI)Subacute Myocardial Infarct with Collagen and Angiogenesis (Granulation Tissue)4 Stages of MI-Microscopic Findings•Months: Ultimately, the necrotic myocardium is replaced by white fibrous scarring between islands of myocytes.Old, Remote Infarct with White, Myocardial Fibrous Scarring4 Stages of MI-Gross FindingsThe infarctedarea cannot be definitively identified during the first 1-2 days. There may be some pallor of the infarctedarea.1-7 days : After the occlusion, the infarct becomes yellow. Acute Myocardial Infarct-Soft Yellow and Hemorrhagic Tissue4 Stages of MI-Gross Findings•7-28 days :After the occlusion, the infarct becomes pallor and is surrounded by a hemorrhagic rim, and the infarctedmyocardium is soft as a result of action of hydrolytic enzymes released from the neutrophils.Acute Myocardial Infarction-Granulation Tissue (Pallor surrounded by Red rim)•Months: White-tan fibrosis predominates within an older or chronic infarct.Old Myocardial InfarctPericarditisPericarditis•Inflammation of the visceral or parietal pericardial layers•Most often associated with myocarditis, tuberculosisCauses of Pericarditis:•Bacteria, viruses, fungi (rarely)•Severe autoimmune diseases (SLE)•Rheumatic Heart Disease•Chronic renal failure -> metabolic waste products in the blood (uremia)•Trauma, radiation injury, and open-heart surgery 1/28/09 Pathology wk1Pathology of PericarditisExudation of fluid into the pericardial sac–Clear yellow with serous pericarditis(viral infections)–Purulent with bacterial infections–Serofibrinousexudateassociated with more severe damage (Rheumatic fever) 1/28/09 Pathology wk1 Bacterial(Suppurative)SerousFibrinousPericarditis•Does not resolve as easily as a serous exudate•Fibrin bridges the space between the two layers of the pericardial sac–When separated the epicardiumand pericardium resemble bread and butter taken apart•Macrophages invade exudate-> stimulate fibroblasts -> further fibrous adhesion = adhesive pericarditis•Blood vessels invade exudate-> organization= blood vessels fill space occupied by fibrin and obliterate it•Fibrous scarring may prevent expansion in diastole = constrictive pericarditis 1/28/09 Pathology wk1Pericarditis3 types:SerousFibrinousHemorrhagicECG findings: Diffuse ST ElevationPulsusParadoxus: an exaggeration of the normal variation in the pulse during the inspiratoryphase of respiration, in which the pulse becomes weaker as one inhales and stronger as one exhales. It is a sign that is indicative of several conditions including cardiac tamponade, pericarditis.Pericardial painFriction RubDistant Heart SoundsSerous Pericarditis•Serous Pericarditisetiologies: •SLE (Lupus)•Rheumatoid Arthritis•Infection•Uremia(Serous) Rheumatoid PericarditisFibrinousPericarditis•FibrinousPericarditisetiologies:•Uremia•MI ( Dressler’s syndrome)-The syndrome consists of a persistent low-grade fever, chest pain (usually pleuriticin nature), a pericardial friction rub, and /or a pericardial effusion. The symptoms tend to occur after a few weeks or even months after infarction and tend to subside in a few days. An elevated ESR is an objective laboratory finding.•Rheumatic fever Fibrinous Pericarditis Due to UremiaFibrinous (Bread & Butter) PericarditisHemorrhagic Pericarditis•Hemorrhagic Pericarditisetiologies:•TB•Malignancy (Melanoma)Hemorrhagic PericarditisPericarditis•Viral Infections: The fluid is clear yellow in serous pericarditis.•Bacterial Infections: Purulent exudateis a hallmark of bacterial infections and is caused by pus-forming bacteria, such as Staph or Strept.•Constrictive Pericarditis: The fibrous scarring of the pericardial sac may completely encase the heart and prevent its expansion in diastole.Serous (Viral) PericarditisBacterial (Purulent) PericarditisConstrictive Pericarditis MyocarditisMyocarditisClinical Presentation:•Mild fever•Shortness of breath•Malaise•Signs of heart failure if severe and chronic–Tachycardia–Peripheral cyanosis–Pulmonary edema•Males > femalesDiagnosis & Treatment:•Diagnosis:–Endomyocardialbiopsy•Treatment:–Supportive measures 1/28/09 Pathology wk1Myocarditis•Acute inflammation of the myocardium–Most often due to viral infections•Coxsackie B virus–Also can be caused by parasites•Toxoplasmosis–Can be due to a secondary disorder•Rheumatic fever–Aschoffbodies: granulomasin the myocardium–Bacteria are a rare cause•Epimyocardialmicroabscesses–Other causes:•Radiation•Hypersensitivity•Sarcoidosis 1/28/09 Pathology wk1 ToxoplasmaMyocarditiscystMyocardial Aschoff Bodies in Rheumatic Heart DiseaseViral Myocarditis•Viruses damage organelles -> cell death•Myocardium invaded by T-lymphocytes -> secrete interleukins, TNF -> destroy virus-infected myocardial cells•Pathology:–Tiger Effect•Pale, congested areas with mild hypertrophy•Biventricular dilatation•Generalized hypokinesis•Flabby, dilated heart 1/28/09 Pathology wk1 Tiger Effect from Acute Viral MyocarditisViral (interstitial) myocarditisAcute Viral Myocarditis•Histology:–Patchy, diffuse infiltrate of T-cells and macrophages surrounding individual myocytes–Focal or patchy acute myocytenecrosis 1/28/09 Pathology wk1VasculitidesVasculitis•Inflammation/necrosis of blood vessels•Pathogenesis thought to involve immune mechanisms:–Deposition of Immune complexes–Direct attack on vessels by antibodies–Cell-mediated immunity 2/17/2009 132 LG4.5 & LG4.7 PathologyPathogenesis of VasculitisMay be associated with a viral infectionSmall vessel vasculitides–i.e. Wegener granulomatosisand PolyarteritisNodosa–associated with ANCA(anti-neutrophilcytoplasmicantibodies)•Common patterns are:–perinuclearimmunoflouresnce(P-ANCA)–cytoplasmicimmunoflourescence(C-ANCA)C-ANCA’s seen in Wegener’sP-ANCA’s seen in PolyarteritisNodosa 2/17/2009 133 LG4.5 & LG4.7 PathologyPolyarteritisNodosa•Acute systemicnecrotizing vasculitisthat affects medium and smaller-sized muscular arteries•Associated with Hepatitis B•Primarily in whites•Men > women•Patchy lesions with area of fibrinoidnecrosis •Obliteration of the tunica media and intima•Acute inflammatory response surrounds area of necrosis•Heals with fibrosis that obstructs the lumen•Associated with P-ANCA•Clinical Presentation:–Fever, weight loss–Kidney, heart, skeletal muscle, skin, mesentery involvement–Fatal without treatment•Treatment:–Corticosteroids, cyclophosphamideDestruction of arterial wallwith fibrinoidnecrosis 2/17/2009 134 LG4.5 & LG4.7 PathologyComplications of PolyarteritisNodosa•Thrombosis of smaller arteries with infarcts in involved organs•Formation of small aneurysms in larger arteries -> may cause hemorrhage•Healing with fibrosis of the media leaving gaps in the elastic laminaeHealing PolyarteritisNodosawith transmuralfibrosis & inflammation 2/17/2009 135 LG4.5 & LG4.7 PathologyTemporal (Giant Cell) Arteritis•Most common form of vasculitis•Focal chronic granulomatousinflammation of the temporal arterities•Average age of onset: 70•Women > men•Etiology:–Obscure, perhaps genetic, or immunological due to presence of activated CD4+ T-cells•Gross pathology:–Cord-like, nodular thickening of vessel; lumen reduced •Clinical presentation:–Throbbing, pain over temporal artery with swelling, tenderness, redness–Associated with PolymyalgiaRheumatica: generalized muscular aching, stiffness in the shoulders or hips–Visual symptoms–Malaise, fever, weight loss•Diagnosis:–Temporal artery biopsy•Treatment:–Corticosteroids 2/17/2009 136 LG4.5 & LG4.7 PathologyMicroscopic Pathology of Temporal Arteritis•Granulomatousinflammation of the media and intima•Presence of Giant Cells•Foci of necrosis in the elastic lamina with fragmentation•Thrombosis may obliterate the lumenFragmentation of Internal Elastic Lamina 2/17/2009 137 LG4.5 & LG4.7 Pathology3 year old presents w/a high fever for the past week. Physical exam reveals:MucocutaneouslesionsRashPeeling of the fingertipsDesquamation of the sole of foot 2/17/2009 138 LG4.5 & LG4.7 PathologyKawasaki Disease•AKA mucocutaneouslymph node syndrome•Acute necrotizing vasculitisof infancy and early childhood•Symptoms:–High fever, rash–Conjunctival, oral lesions–Lymphadenitis–Desquamation of the fingertips, soles and palms•In 70%: affects coronary arteries -> *coronary artery aneurysms*•Possible association with Parvovirus B19Large coronary artery aneurysmCoronary artery with aneurysmalformations 2/17/2009 139 LG4.5 & LG4.7 PathologyTakayasuArteritis•Inflammatory disease of large arteries, especially the aortic arch and its major branches•Primarily affects young women < 30•Clinical Findings:–Dizziness, visual disturbances–As disease progresses -> Cardiac symptoms, claudicationof the arms/legs–Asymmetrical BP–Pulse in one extremity may be absent–Majority eventually manifest CHF and visual defects•Gross pathology:–Aorta thickened; intimaexhibits focal, raised plaques–Branches of aorta exhibit stenosis/occlusion = “PulselessDisease” when subclaviansaffected–Thoracic/abdominal aorta commonly show aneurysms•Treatment:–Steroids for early disease–SurgeryAortic angiogram: narrowing of great vessels 2/17/2009 140 LG4.5 & LG4.7 PathologyMicroscopic Findings of TakayasuArteritisPanarteritiswith granulomatousinflammation –Infiltrates of neuts, lymphs, and giant cellsInflammatory destruction of media 2/17/2009 141 LG4.5 & LG4.7 PathologyWegener Granulomatosis•Systemicnecrotizing vasculitiswith granulomatouslesions in the upper respiratory tract, and the kidneys•Men > women usually in 5th-6thdecades•90% exhibit C-ANCAin the blood•Microscopic pathology:–Parenchymalnecrosis–Acute inflammation, granulomatousinflammation and fibrinoidnecrosis leading to medial thickening, intimalproliferation, and narrowing of the lumenNecrotizing granulomatousinflammation of the lungVasculitisof small artery 2/17/2009 142 LG4.5 & LG4.7 PathologyClinical Presentation of Wegener granulomatosis•Respiratory tract symptoms: pneumonia, sinusitis–Most prominent pulmonary feature: persistent bilateral pneumonia with nodular infiltrates that undergo cavitation•Hematuriaand proteinuria–Most prominent kidney features: focal necrotizing glomerulonephritiswhich progresses to crescenticglomerulonephritis(rapidly progressive glomerulonephritis)•Rashes, muscular pains, joint involvement, neurologic symptoms•Treatment:–CyclophosphamideRashNecrotizing segmental glomerulonephritis 2/17/2009 143 LG4.5 & LG4.7 PathologyChurg-Strauss Syndrome•AKA allergicgranulomatosisand angiitis•Systemicvasculitisin young people with asthma•Both C-ANCA and P-ANCAare demonstrated in 2/3 of patients•Microscopic findings:–Granulomaswith intense eosinophilicinfiltrate -> fibrinoidnecrosis & thombosisGranulomatousfoci around blood vesselsIntense eosinophilicinfiltrates 2/17/2009 144 LG4.5 & LG4.7 PathologyThromboangiitisobliterans•AKA Buergerdisease•Occlusive, inflammatory disease of medium/small arteries in distalarms/legs in middle-aged heavy smokers•Cessation of smoking can be followed by remission•Etiology: tobacco byproducts elicit antibodies -> inflammation•Microscopic pathology:–Acute inflammation of medium-sized and small arteries with PMN infiltrates•Complications:–Thrombosis and obliteration of the lumen–Microabscesseswith neutrophilsand giant cells–Gangrene of the extremitiesThrombosis with *microabscesses* (specific)Obliteration of lumen by thrombus and abscess 2/17/2009 145 LG4.5 & LG4.7 PathologyClinical Findings of Thromboangiitisobliterans•Claudication•Painful ulceration of the digitsNecrosis of finger tips 2/17/2009 146 LG4.5 & LG4.7 PathologyVaricose Veins•Etiology:–Incompetence of venous valves –Pooling of blood, i.e. from back pressure from a failing heart -> veins remain dilated/tortuous•Predisposed to clotting•More likely to occur with family histories of connective tissue disease, in professions requiring long hours of standing, and during pregnancy•Complications:–Clotting, thrombosis -> may embolize–Leakage of blood into tissues -> brownish discoloration, “stasis dermatitis”(small pinpoint hemorrhages from ruptured capillaries)–Ischemia -> skin may necrotize and stasis ulcers may formStasis Dermatitis 2/17/2009 147 LG4.5 & LG4.7 PathologyCardiomyopathiesCardiomyopathies•Cardiomyopathy: heart disease resulting form abnormality in myocardium.Dilated Cardiomyopathy•Progressive chamber dilation and systolic dysfunction.–Results in EF < 25%–Most common type of Cardiomyopathy.–Causes:•Toxic (Alcohol, Adriamycin, Cytoxin, Cocaine, Cobalt)•Viral Myocarditis•Pregnancy•High Catecholamines(pheochromocytoma)•Primary (genetic) -> mostly AD but can be AR and sex linked recessive.–Gross and Microscopic Findings:•Thin Wall partially replaced by fibrous tissue.•Heart Size 2-3x normal.•Impaired Contractility•Eventual CHF•Normal Coronary Arteries•Muscle cells are hypertrophied w/enlarged nuclei and interstitial fibrosisBanana Septum Indicative of What?MyocyteDisarray(TrichromeStain)Hypertrophic Cardiomyopathy•Gross Findings–Asymmetrical thickening of ventricular septum.–Banana-Shaped Septum–Endocardialthickening with mural plaque formation of outflow tract.•Histology–Extensive MyocyteHypertrophy w/“MyocyteDissarray”–Primary cause unknown typically affects young males. Genetic-AD.Amyloidcauses what type of cardiomyopathy?Congo Red Staining For AmyloidRestrictive Cardiomyopathy•Decrease in ventricular compliance–Impaired ventricular filling during diastole normal systole function.–Heart cannot expand to receive inflowing blood.–Idiopathic or associated with abnormal infiltrate. IE; AmyloidSarcodosis, metastatic tumor, radiation fibrosis.•Gross and Microscopic Findings–Slightly enlarged ventricles, firm mycocardium–Patchy or diffuse interstitial fibrosis.•Diagnosis–Slightly enlarged ventricles, firm mycocardium–Patchy or diffuse interstitial fibrosis.Congenital Heart Defects (CHD)Congenital Heart Defects (CHD)•Heart is formed by 10thweek.–CHD form before this time.–Rubella Virus infection in mother best known cause of CHD.•Ventricular SeptalDefect•Patent DuctusArteriosus•Tetralogyof Fallot–Chromosomal Abnormalities•Down syndrome 21 (VSD, ASD)•Edward 18•Patau13•Turner XO -> coarctationof the aortaTetralogyof Fallot•Early R -> L Shunt *Cyanosis*–10% of CHD–Heart is enlarged and boot-shapeddue to RVH.–Most common form of cyanotic CHD.–4 Features Mmnonic: PROV•Pulmonary Artery Stenosis–If mild then ToFshunt is left to right.•Right Ventricular Hypertrophy•Overriding Aorta (overrides the VSD)•Ventricular SeptalDefect•Infant Clinical Presentation–Cyanosis after birth (blue babies)–RHF is rare due to pulmonary stenosis•Treatment and Prognosis–Without surgery dismal outlook–Open Heart Surgery total correction possible. <10% mortalityTransposition of the Great Vessels•Aorta arises from right ventricle; Pulmonary artery arises from left ventricle.–Children of diabetic moms–Cyanosis at Birth–4% of CHD•Death without a shunt–VSD allows life. -> stable shunt–Patent Foramen Ovaleor PDA -> unstable shunt; needs surgery before closure.–“corrected transposition” surgery entails switching of great vessels as well as coronary arteries.Ventricular SeptalDefectL > R Shunt•Most common congenital heart defect–Incomplete closure of ventricular septum.–Usually size of aortic valve orifice.–90% below pulmonary valve in membranous septum. 10% lie within muscular septum.–50% of small muscular VSDS close spontaneously.•Clinical Presentation–RVH and Pulmonary Hypertension–Overtime shunt reversal; Cyanosis, Clubbing, Polycythemia, and deathPatent DuctusArteriosus•Cause:–Low O2 tension cause relaxing effect on the ductusmaintain its patency. RSD -> prolonged patency of ductus.•Presentation–10% associated with VSD and Coarctationof the Aorta–Machine Like Murmur–No Cyanosis initially–Eventual pulmonary HTN and RVH with reversal of flow.–Ductusempties into aorta distal to origin of left subclavian. Cyanosis of L.E and toes but not fingers.•Treatment–Closed early as possible.–Indocinsuppresses PgEsynthesis. -> closes patent ductusAtrialSeptalDefectsL > R•Most common CHD that is asymptomatic until adulthood.•MurmorPresent due to excessive flow through pulmonicvalve.•More common in males•Eventual reversal of flow with RVH•Treatment: Surgical Closure•SecundumType:–90% of all ASD–Defect in area of foramen ovale–Fenestrated or deficient septum.•PrimumType “EndocardialCushion Defect”:–10% of all ASD–Adjacent to AV valves–Foramen ovaleis closedSecunumType ASDCoarctationof the Aorta•Infantile Form: –coarctationproximal to a PDA. –symptomatic in early children.•Adult Form: –discrete infoldingof the aorta distal to a ligamentumarteriosus. asymptomatic until well into adult life.–Presents with hypertension in U.E, weak pulses and low BP in L.E. –Claudication–Enlarged intercostaland internal thoracic arteries.–Notching of the ribs on X-ray–Significant coarctation-> LVH and Murmors–Tx: Surgery excellent resultsRib NotchingHeart Formation (1)•Heart formation begins at 4thweek.–Mesoderm -> pericardial cavity and heart forming region.–HFR remodels into a heart tube with 3 layers at the midline.–Five Dilations become apparent.•TruncusArteriosus-> ascending aorta and pulmonary trunk.•BulbusCordis-> smooth parts of LV and RV (outflow tract)•Primitive Ventricle -> trabeculatedparts of LV and RV•Primitive Atrium -> trabculatedLA and RA.•Sinus Venosus-> Coronary Sinus, smooth part RAHeart Formation (2)•Partitoningof Primitive Atrium–1. Foramen primumnarrows as septum primumgrows toward endocardialcushion.–2.Perforation in septum primumform foramen secundum.–3. Foramen secundummaintains right to left shunt as septum secundumbegins to grow.–4.septum secundumcontains permanent opening (Foramen Ovale).–5.Foramen secundumenlarges and upper part of septum priumumdegenerates.–6. Remaining portion of septum primumforms valve of foramen ovale.Fetal Circulation•Fetal lungs, kidneys, liver, digestive tract need very little O2.–Oxygenated blood enter into umbilical vein and ascends to the fetal liver.–Small portion of blood passes portal sinuses–Most blood bypasses liver by entering DuctusVenosuswhich connects with IVC.–Blood in IVC is not well oxygenated.•UE -> good O2 conc.•LE -> 50% satFetal Changes After Birth•Lungs, GI, Liver become functional.•Pulmonary Resistance drops -> pulm. Blood flow increases•LA > RA pressure foramen ovalecloses.•DuctusArteriosus-> LigamentumArteriosum•DuctusVenosus-> LigamentumVenosum•Umbilical Arteries -> Medial UmblicalLigaments -> LigamentumTeres(remains patent for some time).Umbilical Vein Connecting DuctusVenosus