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CardiacBy The Dark Horse
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
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.
• 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) 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)
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
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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
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Too many Big Macs may cause?Acute
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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
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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%
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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
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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
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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
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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
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Ventricular rupture with necrosisHemopericardium due to Rupture Causing Cardiac Tamponade
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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
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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
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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
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 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), 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 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
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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)
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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
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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 Pericarditisetiologies:
• 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 (Bread & Butter) Pericarditis
Hemorrhagic PericarditisHemorrhagic Pericarditis etiologies:TBMalignancy (Melanoma)
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
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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
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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
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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 130LG4.5 & 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
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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 132LG4.5 & 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 133LG4.5 & 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 134LG4.5 & 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 135LG4.5 & 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 136LG4.5 & 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 137LG4.5 & 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 138LG4.5 & 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 139LG4.5 & 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 140LG4.5 & 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 141LG4.5 & 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 142LG4.5 & LG4.7 Pathology
Clinical Findings of Thromboangiitis obliterans
• Claudication
• Painful ulceration of the digits
Necrosis of finger tips
2/17/2009 143LG4.5 & 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 144LG4.5 & 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.
Dilated Cardiomyopathy
– 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
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.
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; 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.
Congo Stain for Amyloid; Yellow-Green birefringent under polarized light
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
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
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
Congestive Heart Failure
•Failure of the heart as a pump
•Characterized by forward failure, backward failure, or both
Compensatory Mechanisms to Prevent CHF (but eventually become a burden)
• Increased sympathetic stimulation– Norepi ↑HR, contractility– Leads to myocardial ischemia,
angina in severe CHF• Fluid retention
– ↓CO activates the Renin-Angiotensin-AldosteroneSystem -> ↑VR -> ↑preload -> ↑contractility
– Leads to edema as failure progresses
• Cardiac muscle hypertrophy– Volume overload (↑preload)
causes dilation and hypertrophy– Usually will have a combination
of both dilation and hypertrophyLeft ventricular hypertrophy as a
compensatory mechanism
Left Heart Failure• Etiology:
– Ischemic heart disease– HTN– Aortic and mitral valve disease– Non-ischemic myocardial disease
• Pathology:– LVH with dilation -> secondary enlargement
of the left atrium -> atrial fibrillation -> blood stasis -> thromboemboli
– Lungs due to backward failure:• Pulmonary congestion and edema• **Hemosiderin-laden macrophages (“heart-
failure cells”)** : macrophages phagocytizeRBC’s in alveolar sacs
– Kidneys due to forward failure:• ↓CO -> activation of the RAS -> fluid retention
-> pulmonary edema– Brain due to forward failure:
• Hypoxia -> hypoxic encephalopathy -> stupor, loss of consciousness, restlessness, coma
• Clinical:– Dyspnea– Orthopnea– Cough– Fatigue– Limb weakness
Lung Hemosiderin-laden macrophages
Pulmonary edema
Right Heart Failure• Etiology:
– Most common cause is left heart failure
– If isolated: cor pulmonale• Pathology:
– Backward failure -> congestion of the venous system
– Hepatomegaly: chronic passive congestion of the liver(“Nutmeg liver”)
– Splenomegaly– Ascites (fluid within the
abdomen)– Peripheral edema
• Ankle• Sacrum
– JVD– Pleural effusions
Centrilobular passive congestion of the liver (Nutmeg liver)
Pitting ankle (petal) edema
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