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 CancerMetastatic 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

• 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

Pulmonary Saddle Embolus

Wedge-shaped pulmonary infarct

Arterial 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– 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:

– Sudden severe dyspnea– Cyanosis– Hypotensive shock– Seizures and coma – Pulmonary edema– DIC Fetal Epithelial Squames

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• 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

Hemosiderin-Laden Macrophages

Chronic Passive Congestion of the Liver

Hemorrhage• 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

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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• 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

• 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 Zahn

Infarction• 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 abscessRed infarct of the intestine

White infarcts of the kidney Septic emboli causing infarcts in spleen

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.coliPathogenesis of Septic Shock

3 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 Shock

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 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 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 endocarditisSt. 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 EndocarditisNote: 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.

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• 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).

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• 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 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)

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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


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


Distribution of MI’s:Anterior wall infarct

Occlusion 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 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 occlusionGranulation tissue of the plaque and thrombi in older lesions may reestablish blood flow via recanalization

Wall contains calcium and cholesterol deposits


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

Causes:• Thrombosis of a coronary

artery (80-90%)• Ulceration of an

embolizedatherosclerotic plaque

• Prolonged vasospasm

Types of MI’s

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 develop1/28/09 Pathology wk1

Subendocardial or Intramural:• Infarction usually concentric

around the subendocardiallayer of the left ventricle

• Q waves are absent

Transmural Subendocardial


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

Wavy, eosinophilic myocyteswith contraction bands

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

Subacute Myocardial Infarct-Granulation Tissue and Macrophages (over 1 week)

Old, Remote Infarct with White, Myocardial 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

Complications of MI

• Myocardial Rupture

• Left Ventricular Aneurysm

• Mural Thrombus


Ventricular rupture with necrosisHemopericardium due to Rupture Causing Cardiac Tamponade


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

the heart)

Myocardial Rupture

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 ThrombusVentricular Aneurysm With Infarcted

Myocardial Wall

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


4 Stages of MI-Microscopic Findings

24 Hours: Myocardial cell death with wavy, eosinophilic myocytes(Pink), coagulativenecrosis (Myocytes have no nucleus), and contraction bands. The nuclei are either faint or dead.

Acute MI With Wavy, Eosinophilic Myocytes with Contraction Bands


• 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)


• Days 3-7: The infarcted area 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)


• 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)


• 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 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 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


Pathology of PericarditisExudation 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) Serous

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


Pericarditis

3 types:SerousFibrinousHemorrhagicECG findings: Diffuse ST ElevationPulsus 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 painFriction RubDistant 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

MyocarditisClinical 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 measures1/28/09 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


Toxoplasma Myocarditis cyst

Myocardial Aschoff Bodies in Rheumatic Heart Disease

Viral 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 wk1Tiger Effect from Acute Viral Myocarditis

Viral (interstitial) myocarditis

Acute Viral Myocarditis• Histology:

– Patchy, diffuse infiltrate of T-cells and macrophages surrounding individual myocytes

– Focal or patchy acute myocyte necrosis


Vasculitides

Vasculitis

• 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 132LG4.5 & LG4.7 Pathology

Pathogenesis of VasculitisMay be associated with a

viral infection

Small vessel vasculitides– i.e. Wegener

granulomatosis and Polyarteritis Nodosa

– associated with ANCA(anti-neutrophilcytoplasmic antibodies)

• Common patterns are:– perinuclear

immunoflouresnce (P-ANCA)

– cytoplasmicimmunoflourescence (C-ANCA)

C-ANCA’s seen in Wegener’s

P-ANCA’s seen in Polyarteritis Nodosa2/17/2009 133LG4.5 & LG4.7 Pathology

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

Destruction of arterial wallwith fibrinoid necrosis

2/17/2009 134LG4.5 & LG4.7 Pathology

Complications of Polyarteritis Nodosa

• 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 Polyarteritis Nodosa with

transmural fibrosis & inflammation

2/17/2009 135LG4.5 & LG4.7 Pathology

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

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

lumen reduced • 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

• Diagnosis:– Temporal artery biopsy

• Treatment:– Corticosteroids2/17/2009 136LG4.5 & LG4.7 Pathology

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

Fragmentation of Internal Elastic Lamina2/17/2009 137LG4.5 & LG4.7 Pathology

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

Mucocutaneous lesions Rash

Peeling of the fingertips Desquamation of the sole of foot2/17/2009 138LG4.5 & LG4.7 Pathology

Kawasaki Disease• AKA mucocutaneous lymph

node syndrome• Acute necrotizing vasculitis

of 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 B19

Large coronary artery aneurysm

Coronary artery with aneurysmal formations

2/17/2009 139LG4.5 & LG4.7 Pathology

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:– Steroids for early disease– Surgery

Aortic angiogram: narrowing of great vessels2/17/2009 140LG4.5 & LG4.7 Pathology

Microscopic Findings of Takayasu Arteritis

Panarteritis with granulomatousinflammation – Infiltrates of neuts,

lymphs, and giant cells

Inflammatory destruction of media

2/17/2009 141LG4.5 & LG4.7 Pathology

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

• Microscopic pathology:– Parenchymal necrosis– Acute inflammation,

granulomatousinflammation and fibrinoidnecrosis leading to medial thickening, intimalproliferation, and narrowing of the lumen

Necrotizing granulomatous inflammation of the lung

Vasculitis of small artery2/17/2009 142LG4.5 & LG4.7 Pathology

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– Most prominent kidney features:

focal necrotizing glomerulonephritis which progresses to crescenticglomerulonephritis (rapidly progressive glomerulonephritis)

• Rashes, muscular pains, joint involvement, neurologic symptoms

• Treatment:– CyclophosphamideRash

Necrotizing segmental glomerulonephritis

2/17/2009 143LG4.5 & LG4.7 Pathology

Churg-Strauss Syndrome• AKA allergic

granulomatosis and angiitis

• Systemic vasculitis in young people with asthma

• Both C-ANCA and P-ANCA are demonstrated in 2/3 of patients

• Microscopic findings:– Granulomas with

intense eosinophilicinfiltrate -> fibrinoidnecrosis & thombosis

Granulomatous foci around blood vessels

Intense eosinophilic infiltrates2/17/2009 144LG4.5 & LG4.7 Pathology

Thromboangiitis obliterans• 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 medium-

sized and small arteries with PMN infiltrates

• Complications:– Thrombosis and obliteration of

the lumen– Microabscesses with neutrophils

and giant cells– Gangrene of the extremities

Thrombosis with *microabscesses* (specific)

Obliteration of lumen by thrombus and abscess2/17/2009 145LG4.5 & LG4.7 Pathology

Clinical Findings of Thromboangiitis obliterans

• Claudication

• Painful ulceration of the digits

Necrosis of finger tips

2/17/2009 146LG4.5 & LG4.7 Pathology

Varicose 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 form

Stasis Dermatitis

2/17/2009 147LG4.5 & LG4.7 Pathology

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 DefectL > 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

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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 DefectsL > 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

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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 DuctusVenosus

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Cardiology Pathology