Cardiology Pathology

Cardiac

Cardiac Tumors

Cardiac Tumors • Rare • Usually benign and pedunculated • Three types: – Cardiac myxomas – Rhabdomyomas – Metastatic tumors

Right atrial

With stalk

Cardiac 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 myxomas of the left atrium • Blocks diastolic filling of the ventricle, stimulating mitral valve stenosis -> may cause syncopal episodes

– One third of these patients die of embolization of the tumor to the brain

• Dx: transesophageal ultrasound

Stellate cells and fibroblasts

Amorphous extracellular matrix

Histology of Cardiac Myxomas • Loose myxoid matrix • Abundant proteoglycans with stellate cells within the matrix

Grossly

Striated muscle (“Spider”) cells

Rhabdomyomas • Most common primary cardiac tumor in infants and children – Major association with tuberous sclerosis

• Forms hamartomas in 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 glycogen

Metastatic Breast Cancer

Metastatic Melanoma to the Heart

Metastatic 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 pericarditis and effusions

• Metastatic cancers of the myocardium ma result in manifestations of restrictive cardiomyopathy

Heart Emboli

Types 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 Bullets

Classification 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 defect Sources of Venous Emboli

Pulmonary Embolism

Pulmonary Saddle Embolus

Wedge-shaped pulmonary infarct

• 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 infarcts

Arterial Emboli • Most originate from endocardium, valvular thrombi, ulcerated atherosclerotic plaques • Tend to lodge in mediumsized and smaller arteries • Lodge in: – Brain (middle cerebral artery) – Spleen – Kidneys – Intestines Sources of Arterial Emboli

Fat 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 changes

Amniotic 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:

Fetal Epithelial Squames

– – – – – –

Sudden severe dyspnea Cyanosis Hypotensive shock Seizures and coma Pulmonary edema DIC

Bone Marrow Embolism • Usually after cardiac resuscitation • No symptoms

Decompression Sickness • Form of gas embolism • Seen in scuba divers • Nitrogen gas released from solution during rapid ascent -> obstructing blood flow • Commonly known as the “bends” • Temporary muscle, joint pain

Caisson Disease • Chronic decompression sickness where vascular obstruction causes avascular necrosis of bone, primarily affecting head of the femur, tibia, and humerus

Hyperemia

Hemosiderin-Laden Macrophages

Chronic Passive Congestion of the Liver

• 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 failure

Hemorrhage •

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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 hematomas

Petechiae, 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 trauma

Fate 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 embolize

Thrombus Classification By Location •

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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 Coagulation

Thrombus Classification Pathologically

Lines of Zahn

• 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 thrombi

Infarction • •

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Red infarct of the intestine

White infarcts of the kidney

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 obstruction involving 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 abscess

Septic emboli causing infarcts in spleen

Shock

Pathogenesis of Septic Shock

• State of hypoperfusion of 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.coli

3 Stages of Shock •

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Compilations 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 anuria

ARDS 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 adrenals

Bacterial Endocarditis

Infective Endocarditis • Infective endocarditis: Micro-organism infection of inside of heart. – – – –

Can infect Aorta, Blood vessels, prosthetic heart valves. Fungi, Rickettsia, and Chalydimdia are other rare causes. Divided into acute and subacute. Causes • Usually pt is predisposed due to: – – – – –

Artificial Valves Congenital Defects Degenerative Calcified valvular stenosis Bicuspid Aortic Valves Myxomatous Mitral Valve (mitral valve prolapse)

• Infective Endocarditis vs Rheumatic Heart disease vegetations. – Rheumatic Heart disease has sterile thrombi. – Infective Endocarditis vegetations are composed of thrombi and bacteria.

Acute Bacterial Endocarditis due to S. Aureus. Destruction of Aortic Valve.

Gram Negative Bacterial Endocarditis

Acute and Chronic Infective Endocarditis • Acute Bacterial Endocarditis – – – –

High destruction of previously normal valve. Staph Aureus or Gram Negative. May perforate valve. Necrotic Valvular Lesions

• Subacute Bacterial Endocardiditis – – – –

Slower, less virulent disease St. Viridans Infection is previously abnormal heart valves Less destructive and show evidence of healing.

Subacute Bacterial endocarditis

Fischione: Infective Endocarditis Acute, Staph Aureus •

Infective Endocarditis • Infective endocarditis: Micro-organism infection of inside of heart. – – – –

Can infect Aorta, Blood vessels, prosthetic heart valves. Fungi, Rickettsia, and Chalydimdia are other rare causes. Divided into acute and subacute. Causes • Usually pt is predisposed due to: – – – – –

Artificial Valves Congenital Defects Degenerative Calcified valvular stenosis Bicuspid Aortic Valves Myxomatous Mitral Valve (mitral valve prolapse)

• Infective Endocarditis vs Rheumatic Heart disease vegetations. – Rheumatic Heart disease has sterile thrombi. – Infective Endocarditis vegetations are composed of thrombi and bacteria.

Acute Bacterial Endocarditis due to S. Aureus. Destruction of Aortic Valve.

Acute and Chronic Infective Endocarditis • Acute Bacterial Endocarditis – – – –

High destruction of previously normal valve. Staph Aureus or Gram Negative. May perforate valve. Necrotic Valvular Lesions

• Subacute Bacterial Endocardiditis – – – –

Slower, less virulent disease St. Viridans Infection is previously abnormal heart valves Less destructive and show evidence of healing.

Subacute Bacterial endocarditis

Staph on prosthetic tricuspid (top) Infected Artifical Mitral Ball Valve (bot.

Mitral Valve Prolapse

Pathogenesis 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 – EtOH abuse – Drug abuse (IV)

Subacute endocarditis St. Viridans

Pathology 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.

Candidal Endocarditis Note: Fungi produce some of the largest vegetations seen in endocarditis

Clinical 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 Endocarditis

Infective Vegetation (3) With Fibrin, Necrosis and Acute Inflammation (2)

Infective Vegetation with Pink Fibrin and Blue Staining Coccal Organisms

Signs/Symptoms of Bacterial Endocarditis “FROM JANE”: • Fever • Roth’s Spots • Osler’s nodes • Murmur (New) • Janeway lesions • Anemia • Nail-bed hemorrhage • Emboli

Janeway lesions 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 retina spot 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 (subacute bacterial 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) endocarditis is the most characteristic cardiac manifestation of the autoimmune disease systemic lupus erythematosus. Seen as mulberrylike clusters of verrucae on 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 Lupus SLE causes LSE

Rheumatic 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 pharyngitis with 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) • Aschoff bodies (Granuloma with giant cells) • Anitschkow’s cells (Activated histiocytes) • Migratory Polyarthritis • Erythema Marginatum • Sydenham chorea • Fishmouth Stenosis- Fusion of the valvular cusps

Extracardiac Findings in RHD Mnmonic: CANCER Carditis Arthritis Nodules – most common in children, overlies extensor tendons. • Chorea • ERythema Marginatum: macopapular rash 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 Sydenhams Chorea SubCuteneous Nodules Erythema Marginatum

• Minor Criteria – – – –

Hx of RF Fever Arthagias EKG + for heart damage

• Erythema marginatum: 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 rxn damages connective tissue of the heart. • Anti-strep antigen -> Antistreolysin O (ASLO or ASO) develop in all pts.

– Not all pts with ASO titers develop ARF. – Principally disease of children. Can occur in adults.

• Aschoff body: A granulomatous inflammation characteristic of acute rheumatic carditis, consisting of fibrinoid changes in connective tissue and lymphocytes.

• Anitschkow cell: 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 -> Cor Pulmonae -> RHF

Myocardial Infarction

Clinical Signs of MI • Crushing precordial chest pain • Constricting suffocating pain • Substernal pain 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 wk1

Diagnosis 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 Creatine Kinase and CK-MB – Absence of change in first 2 days excludes MI

• Elevated troponins in 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 wk1

Too many Big Macs may cause? Acute

Progressive Coronary Artery Disease: • Atherosclerosis of the coronaries -> myocardial ischemia • May be chronic progressive ischemia from atherosclerosis • May be acute coronary thombosis due to a sudden occlusion Results in a MI in an anatomically defined area 1/28/09

Pathology wk1

1/28/09

Pathology wk1

Distribution of MI’s: Anterior wall infarct Occlusion of the Left Anterior Descending (LAD) Artery – over 50% Lateral wall infarct Occlusion of the Left Circumflex Artery – 3040% Infarct of the right ventricle and posterior wall of the left ventricle Occlusion of the Right Coronary Artery (RCA) – 10-20%

Calcified plaque

Pathology of CAD: Coronaries -> atherosclerosis -> narrowing of the lumen due to fibrotic plaques and atheromas Plaques may be covered with fibrinous clots in an acute occlusion Granulation tissue of the plaque and thrombi in older lesions may reestablish blood flow via recanalization Wall contains calcium and cholesterol deposits 1/28/09

Pathology wk1

Myocardial Infarction: Rapid, sudden occlusion of a coronary artery • Sudden cardiac death in ~25% • Among survivors of the onset: inadequate perfusion -> multisystemic major organ failure • Cerebral ischemia most dangerous • Kidney damage most often

1/28/09

Pathology wk1

Causes: • Thrombosis of a coronary artery (80-90%) • Ulceration of an embolized atherosclerotic plaque • Prolonged vasospasm

Types of MI’s

Transmural

Subendocardial

Transmural: • Most common • All 3 layers of the heart involved • Free wall of the left ventricle and/or interventricular septum usually involved • New Q-waves develop

Subendocardial or Intramural: • Infarction usually concentric around the subendocardial layer of the left ventricle • Q waves are absent

1/28/09

Pathology wk1

Wavy, eosinophilic myocytes with contraction bands

Pink Coagulative Necrosis and PMN’s (3-4 Days Old)

1/28/09

Subacute Myocardial InfarctGranulation Tissue and Macrophages (over 1 week)

Old, Remote Infarct with White, Myocardial Fibrous Scarring

Pathology wk1

Histology of MI: Microscopic changes precede macroscopic changes • During 0-24 hours • During 1-3 days • Myocardial cell death • Eosinophilic myocytes devoid of nuclei and striations • Coagulative necrosis • Contraction bands • Predomination of PMN’s that lyse dead myocardial cells • Days 3-4 • Macrophage infiltration • End of first week • Granulation tissue invading the infarct • Macrophages phagocytize necrotic debris • Chronic MI • Necrotic myocardium replaced by white fibrous scarring

Acute with soft yellow and hemorrhagic tissue Subacute with deposition of granulation tissue

Gross Pathology of MI: First 1-2 days • Cannot be definitively identified • May be pallor of infarcted myocardium 3-5 days • Infarct becomes yellow • Hemorrhagic rim • Soft infarcted myocardium from hydrolytic enzymes released from neutrophils 1-2 weeks • Granulation tissue imparting a gray-pink, mottled appearance Chronic infarct • White-tan fibrosis 1/28/09

Pathology wk1

Complications of MI • Myocardial Rupture • Left Ventricular Aneurysm • Mural Thrombus

1/28/09

Pathology wk1

Myocardial Rupture

Myocardial Rupture: • Softened necrotic myocardium ruptures • Blood fills the pericardial sac (hemopericardium) -> cardiac tamponade (compression of the heart)

Ventricular rupture with necrosis

1/28/09

Hemopericardium due to Rupture Causing Cardiac Tamponade

Pathology wk1

Left 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

Ventricular Aneurysm W/ Mural Thrombus Ventricular Aneurysm With Infarcted Myocardial Wall 1/28/09

Pathology wk1

Mural Thrombus • Endocardium damaged/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 wk1

4 Stages of MI-Microscopic Findings 24 Hours: Myocardial cell death with wavy, eosinophilic myocytes(Pink), coagulative necrosis (Myocytes have no nucleus), and contraction bands. The nuclei are either faint or dead.

Acute MI With Wavy, Eosinophilic Myocytes with Contraction Bands

4 Stages of MI-Microscopic Findings • Days 1-3: The appearance of PMN’s which will predominate for the next three days.

Pink (eosinophilic) Coagulative Necrosis and PMN’s

Note: PMN’s Have segmented Nuclei, they are granulomas (Innate immunity)

4 Stages of MI-Microscopic Findings • Days 3-7: The infarcted area becomes infiltrated with macrophages, which persist in the lesion for about a week that phagocytize and 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), myofibroblasts and fibroblasts depositing collagenous matrix. Macrophages replace the PMN’s and phagocytized the necrotic debris. (these are subacute findings 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 Scarring

4 Stages of MI-Gross Findings The infarcted area cannot be definitively identified during the first 1-2 days. There may be some pallor of the infarcted area. 1-7 days : After the occlusion, the infarct becomes yellow.

Acute Myocardial Infarct-Soft Yellow and Hemorrhagic Tissue

4 Stages of MI-Gross Findings • 7-28 days :After the occlusion, the infarct becomes pallor and is surrounded by a hemorrhagic rim, and the infarcted myocardium is soft as a result of action of hydrolytic enzymes released from the neutrophils.

Acute Myocardial InfarctionGranulation Tissue (Pallor surrounded by Red rim)

• Months: White-tan fibrosis predominates within an older or chronic infarct.

Old Myocardial Infarct

Pericarditis

Pericarditis • Inflammation of the visceral or parietal pericardial layers • Most often associated with myocarditis, tuberculosis Causes 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 wk1

Pathology of Pericarditis Exudation of fluid into the pericardial sac – Clear yellow with serous pericarditis (viral infections) – Purulent with bacterial infections – Serofibrinous exudate associated with more severe damage (Rheumatic fever)

Bacterial (Suppurative)

1/28/09

Serous

Pathology wk1

Fibrinous Pericarditis • Does not resolve as easily as a serous exudate • Fibrin bridges the space between the two layers of the pericardial sac – When separated the epicardium and 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 wk1

Pericarditis 3 types: Serous Fibrinous Hemorrhagic ECG findings: Diffuse ST Elevation Pulsus Paradoxus: an exaggeration of the normal variation in the pulse during the inspiratory phase 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 pain Friction Rub Distant Heart Sounds

Serous Pericarditis • • • • •

Serous Pericarditis etiologies: SLE (Lupus) Rheumatoid Arthritis Infection Uremia

(Serous) Rheumatoid Pericarditis

Fibrinous Pericarditis • Fibrinous Pericarditis etiologies: • Uremia • MI ( Dressler’s syndrome) - The syndrome consists of a persistent low-grade fever, chest pain (usually pleuritic in 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 Uremia

Fibrinous (Bread & Butter) Pericarditis

Hemorrhagic Pericarditis • Hemorrhagic Pericarditis etiologies: • TB • Malignancy (Melanoma)

Hemorrhagic Pericarditis

Pericarditis • Viral Infections: The fluid is clear yellow in serous pericarditis. • Bacterial Infections: Purulent exudate is 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) Pericarditis

Bacterial (Purulent) Pericarditis

Constrictive Pericarditis

Myocarditis

Myocarditis Clinical Presentation: • Mild fever • Shortness of breath • Malaise • Signs of heart failure if severe and chronic – Tachycardia – Peripheral cyanosis – Pulmonary edema

• Males > females Diagnosis & Treatment: • Diagnosis: – Endomyocardial biopsy

• Treatment: – Supportive measures 1/28/09

Pathology wk1

Myocarditis • 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 – Aschoff bodies: granulomas in the myocardium – Bacteria are a rare cause • Epimyocardial microabscesses – Other causes: • Radiation • Hypersensitivity • Sarcoidosis 1/28/09

Pathology wk1

Toxoplasma Myocarditis cyst

Myocardial Aschoff Bodies in Rheumatic Heart Disease

Viral Myocarditis • Viruses damage organelles > cell death • Myocardium invaded by Tlymphocytes -> secrete interleukins, TNF -> destroy virus-infected myocardial cells • Pathology:

Viral (interstitial) myocarditis

– 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 Myocarditis

Acute Viral Myocarditis • Histology: – Patchy, diffuse infiltrate of T-cells and macrophages surrounding individual myocytes – Focal or patchy acute myocyte necrosis

1/28/09

Pathology wk1

Vasculitides

Vasculitis • Inflammation/necrosi s 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

LG4.5 & LG4.7 Pathology

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Pathogenesis of Vasculitis May be associated with a viral infection Small vessel vasculitides – i.e. Wegener granulomatosis and Polyarteritis Nodosa – associated with ANCA (anti-neutrophil cytoplasmic antibodies)

C-ANCA’s seen in Wegener’s

• Common patterns are:

P-ANCA’s seen in Polyarteritis Nodosa 2/17/2009

LG4.5 & LG4.7 Pathology

– perinuclear immunoflouresnce (PANCA) – cytoplasmic immunoflourescence (CANCA) 133

Polyarteritis Nodosa • • • • • • • • • •

•

Acute systemic necrotizing vasculitis that affects medium and smaller-sized muscular arteries Associated with Hepatitis B Primarily in whites Men > women Patchy lesions with area of fibrinoid necrosis 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, cyclophosphamide 2/17/2009

LG4.5 & LG4.7 Pathology

Destruction of arterial wall with fibrinoid necrosis

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Complications of Polyarteritis Nodosa

Healing Polyarteritis Nodosa with transmural fibrosis & inflammation 2/17/2009

• 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 laminae LG4.5 & LG4.7 Pathology

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Temporal (Giant Cell) Arteritis • • • • •

Most common form of vasculitis Focal chronic granulomatous inflammation 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

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Gross pathology: – Cord-like, nodular thickening of vessel; lumen reduced

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Clinical presentation: – Throbbing, pain over temporal artery with swelling, tenderness, redness – Associated with Polymyalgia Rheumatica: generalized muscular aching, stiffness in the shoulders or hips – Visual symptoms – Malaise, fever, weight loss

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Diagnosis: – Temporal artery biopsy

• 2/17/2009

Treatment:

LG4.5 & LG4.7 Pathology –

Corticosteroids

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Microscopic Pathology of Temporal Arteritis • Granulomatous inflammation of the media and intima • Presence of Giant Cells • Foci of necrosis in the elastic lamina with fragmentation • Thrombosis may obliterate the lumen

2/17/2009

LG4.5 & LG4.7 Pathology

137 Fragmentation of Internal Elastic Lamina

3 year old presents w/ a high fever for the past week. Physical exam reveals:

Rash

Mucocutaneous lesions

Peeling of the fingertips

2/17/2009

Desquamation of the sole of foot LG4.5 & LG4.7 Pathology

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Kawasaki Disease • AKA mucocutaneous lymph node syndrome • Acute necrotizing vasculitis of infancy and early childhood • Symptoms: Coronary artery with aneurysmal formations

– – – –

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 B19 Large coronary artery aneurysmLG4.5 & LG4.7 Pathology

2/17/2009

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Takayasu Arteritis 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, claudication of the arms/legs – Asymmetrical BP – Pulse in one extremity may be absent – Majority eventually manifest CHF and visual defects • Gross pathology: – Aorta thickened; intima exhibits focal, raised plaques – Branches of aorta exhibit stenosis/occlusion = “Pulseless Disease” when subclavians affected – Thoracic/abdominal aorta commonly show aneurysms • Treatment: Aortic angiogram: narrowing of great vessels – Steroids for early disease – Surgery 2/17/2009 LG4.5 & LG4.7 Pathology 140 •

Microscopic Findings of Takayasu Arteritis Panarteritis with granulomatous inflammation – Infiltrates of neuts, lymphs, and giant cells

Inflammatory destruction of media 2/17/2009

LG4.5 & LG4.7 Pathology

141

Wegener Granulomatosis • Systemic necrotizing vasculitis with granulomatous lesions in the upper respiratory tract, and the kidneys • Men > women usually in 5th-6th decades • 90% exhibit C-ANCA in the blood Necrotizing granulomatous inflammation of the lung • Microscopic pathology: – Parenchymal necrosis – Acute inflammation, granulomatous inflammation and fibrinoid necrosis leading to medial thickening, intimal proliferation, and narrowing of the lumen 2/17/2009

Vasculitis of small artery

LG4.5 & LG4.7 Pathology

142

Clinical Presentation of Wegener granulomatosis • Respiratory tract symptoms: pneumonia, sinusitis – Most prominent pulmonary feature: persistent bilateral pneumonia with nodular infiltrates that undergo cavitation

• Hematuria and proteinuria Necrotizing segmental glomerulonephritis

– Most prominent kidney features: focal necrotizing glomerulonephritis which progresses to crescentic glomerulonephritis (rapidly progressive glomerulonephritis)

• Rashes, muscular pains, joint involvement, neurologic symptoms • Treatment: 2/17/2009

Rash

– Cyclophosphamide

LG4.5 & LG4.7 Pathology

143

Churg-Strauss Syndrome

Granulomatous foci around blood vessels

• AKA allergic granulomatosis and angiitis • Systemic vasculitis in young people with asthma • Both C-ANCA and PANCA are demonstrated in 2/3 of patients • Microscopic findings: – Granulomas with intense eosinophilic infiltrate -> fibrinoid necrosis & thombosis

2/17/2009

LG4.5 & LG4.7 Pathology

Intense eosinophilic infiltrates

144

Thromboangiitis obliterans

Thrombosis with *microabscesses* (specific)

• AKA Buerger disease • Occlusive, inflammatory disease of medium/small arteries in distal arms/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 mediumsized and small arteries with PMN infiltrates

• Complications: – Thrombosis and obliteration of the lumen – Microabscesses with neutrophils and giant cells – Gangrene of the extremities

2/17/2009

LG4.5 & LG4.7 Pathology

Obliteration of lumen by thrombus and abscess

145

Clinical Findings of Thromboangiitis obliterans

• Claudication • Painful ulceration of the digits

Necrosis of finger tips

2/17/2009

LG4.5 & LG4.7 Pathology

146

Varicose Veins • Etiology: – Incompetence of venous valves – Pooling of blood, i.e. from back pressure from a failing heart -> veins remain dilated/tortuous

Stasis Dermatitis

2/17/2009

• 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 form LG4.5 & LG4.7 Pathology 147

Cardiomyopathies

Cardiomyopathies • 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 fibrosis

Banana Septum Indicative of What?

Myocyte Disarray (Trichrome Stain)

Hypertrophic Cardiomyopathy • Gross Findings – Asymmetrical thickening of ventricular septum. – Banana-Shaped Septum – Endocardial thickening with mural plaque formation of outflow tract.

• Histology – Extensive Myocyte Hypertrophy w/ “Myocyte Dissarray” – Primary cause unknown typically affects young males. Genetic- AD.

Amyloid causes what type of cardiomyopathy?

Congo Red Staining For Amyloid

Restrictive 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; Amyloid Sarcodosis, 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 10th week. – CHD form before this time. – Rubella Virus infection in mother best known cause of CHD. • Ventricular Septal Defect • Patent Ductus Arteriosus • Tetralogy of Fallot

– Chromosomal Abnormalities • • • •

Down syndrome 21 (VSD, ASD) Edward 18 Patau 13 Turner XO -> coarctation of the aorta

Tetralogy of Fallot • Early R -> L Shunt *Cyanosis* – – – –

10% of CHD Heart is enlarged and boot-shaped due to RVH. Most common form of cyanotic CHD. 4 Features Mmnonic: PROV • Pulmonary Artery Stenosis – If mild then ToF shunt is left to right.

• Right Ventricular Hypertrophy • Overriding Aorta (overrides the VSD) • Ventricular Septal Defect

• 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% mortality

Transposition 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 Ovale or PDA -> unstable shunt; needs surgery before closure. – “corrected transposition” surgery entails switching of great vessels as well as coronary arteries.

Ventricular Septal Defect L > 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 death

Patent Ductus Arteriosus • Cause: – Low O2 tension cause relaxing effect on the ductus maintain its patency. RSD -> prolonged patency of ductus.

• Presentation – – – – –

10% associated with VSD and Coarctation of the Aorta Machine Like Murmur No Cyanosis initially Eventual pulmonary HTN and RVH with reversal of flow. Ductus empties into aorta distal to origin of left subclavian. Cyanosis of L.E and toes but not fingers.

• Treatment – Closed early as possible. – Indocin suppresses PgE synthesis. -> closes patent ductus

Atrial Septal Defects L>R • • • • • •

Most common CHD that is asymptomatic until adulthood. Murmor Present due to excessive flow through pulmonic valve. More common in males Eventual reversal of flow with RVH Treatment: Surgical Closure Secundum Type: – 90% of all ASD – Defect in area of foramen ovale – Fenestrated or deficient septum.

• Primum Type “Endocardial Cushion Defect”: – 10% of all ASD – Adjacent to AV valves – Foramen ovale is closed

Secunum Type ASD

Coarctation of the Aorta • Infantile Form: – coarctation proximal to a PDA. – symptomatic in early children.

• Adult Form: – discrete infolding of the aorta distal to a ligamentum arteriosus. asymptomatic until well into adult life. – Presents with hypertension in U.E, weak pulses and low BP in L.E. – Claudication – Enlarged intercostal and internal thoracic arteries. – Notching of the ribs on X-ray – Significant coarctation -> LVH and Murmors – Tx: Surgery excellent results

Rib Notching

Heart Formation (1) • Heart formation begins at 4th week. – Mesoderm -> pericardial cavity and heart forming region. – HFR remodels into a heart tube with 3 layers at the midline. – Five Dilations become apparent. • • • • •

Truncus Arteriosus -> ascending aorta and pulmonary trunk. Bulbus Cordis -> smooth parts of LV and RV (outflow tract) Primitive Ventricle -> trabeculated parts of LV and RV Primitive Atrium -> trabculated LA and RA. Sinus Venosus -> Coronary Sinus, smooth part RA

Heart Formation (2) • Partitoning of Primitive Atrium – 1. Foramen primum narrows as septum primum grows toward endocardial cushion. – 2.Perforation in septum primum form foramen secundum. – 3. Foramen secundum maintains right to left shunt as septum secundum begins to grow. – 4.septum secundum contains permanent opening (Foramen Ovale). – 5.Foramen secundum enlarges and upper part of septum priumum degenerates. – 6. Remaining portion of septum primum forms 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 Ductus Venosus which connects with IVC. – Blood in IVC is not well oxygenated. • UE -> good O2 conc. • LE -> 50% sat

Fetal Changes After Birth • Lungs, GI, Liver become functional. • Pulmonary Resistance drops -> pulm. Blood flow increases • LA > RA pressure foramen ovale closes. • Ductus Arteriosus -> Ligamentum Arteriosum • Ductus Venosus -> Ligamentum Venosum • Umbilical Arteries -> Medial Umblical Ligaments -> Ligamentum Teres (remains patent for some time).

Umbilical Vein Connecting Ductus Venosus