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 Melanoma to the
Metastatic Breast Cancer 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
Pulmonary Saddle Embolus artery
– Often lethal
• Smaller emboli lodge in
minor branches and
cause wedge-shaped
infarcts

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
Fetal Epithelial Squames – 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
• 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
Hemosiderin-Laden Macrophages
• RBC’s taken up by alveolar
macrophages =
hemosiderin-laden
macrophages (heart failure
cells)
– Associated with passive liver
congestion (Nutmeg liver) with
R heart failure

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
Lines of Zahn thrombi
 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 abscess
Red 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
Pathogenesis of Septic Shock E.coli
 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
Compilations of Shock 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
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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

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 infarct
Occlusion 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 occlusion
Granulation 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
embolized
atherosclerotic plaque
• Prolonged vasospasm
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 Types of MI’s

Transmural Subendocardial
Transmural:
Subendocardial or Intramural:
• Most common
• Infarction usually concentric
• All 3 layers of the heart involved
around the subendocardial
• Free wall of the left ventricle and/or
interventricular septum usually
layer of the left ventricle
involved • Q waves are absent
• New Q-waves develop
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Wavy, eosinophilic myocytes
with contraction bands
Subacute Myocardial Infarct-
Granulation Tissue and
Macrophages (over 1 week)
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
Pink Coagulative Necrosis Old, Remote Infarct with White,
that lyse dead myocardial
and PMN’s (3-4 Days Old) Myocardial Fibrous Scarring 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
1/28/09 Pathology wk1 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
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 Complications of MI

• Myocardial Rupture
• Left Ventricular Aneurysm
• Mural Thrombus

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

Hemopericardium due to Rupture

Ventricular rupture with necrosis Causing Cardiac Tamponade

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 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
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Ventricular Aneurysm With Infarcted
Myocardial Wall
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

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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 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 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) Serous

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 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:
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
Toxoplasma Myocarditis cyst
– Aschoff bodies:
granulomas in the myocardium
– Bacteria are a rare cause
• Epimyocardial microabscesses
– Other causes:
• Radiation
• Hypersensitivity
• Sarcoidosis
Myocardial Aschoff Bodies in
1/28/09 Pathology wk1 Rheumatic Heart Disease
 Viral Myocarditis
• Viruses damage organelles -
> cell death
• Myocardium invaded by T-
lymphocytes -> secrete
interleukins, TNF -> destroy
virus-infected myocardial
cells Viral (interstitial) myocarditis
• Pathology:
– Tiger Effect
• Pale, congested areas
with mild hypertrophy
• Biventricular dilatation
• Generalized hypokinesis
• Flabby, dilated heart

Tiger Effect from Acute Viral Myocarditis

1/28/09 Pathology wk1
 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 132
 Pathogenesis of Vasculitis
May be associated with a
viral infection

Small vessel vasculitides

C-ANCA’s seen in Wegener’s
P-ANCA’s seen in Polyarteritis Nodosa
2/17/2009
– i.e. Wegener
granulomatosis and
Polyarteritis Nodosa
– associated with ANCA
(anti-neutrophil
cytoplasmic antibodies)
• Common patterns are:
– perinuclear
immunoflouresnce (P-
ANCA)
– cytoplasmic
immunoflourescence (C-
ANCA)
LG4.5 & LG4.7 Pathology 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 Destruction of arterial wall
necrosis with fibrinoid 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 134
 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 135
 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:
2/17/2009 LG4.5 & LG4.7 Pathology
– Corticosteroids 136
 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:

Mucocutaneous lesions Rash

Peeling of the fingertips Desquamation of the sole of foot

2/17/2009 LG4.5 & LG4.7 Pathology 138
 Kawasaki Disease
• AKA mucocutaneous lymph
node syndrome
• Acute necrotizing vasculitis
of infancy and early
childhood
• Symptoms:
– High fever, rash
– Conjunctival, oral lesions
Coronary artery with aneurysmal formations – 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 139
 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
2/17/2009 – Surgery
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 LG4.5 & LG4.7 Pathology 142
Vasculitis of small artery
 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
• AKA allergic
granulomatosis and
angiitis
• Systemic vasculitis in
young people with
asthma
• Both C-ANCA and P-
Granulomatous foci around blood vessels ANCA 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 144

Intense eosinophilic infiltrates
 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:
Thrombosis with *microabscesses* (specific) – 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

2/17/2009 LG4.5 & LG4.7 Pathology 145

Obliteration of lumen by thrombus and abscess
 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
• Predisposed to clotting
• More likely to occur with family
histories of connective tissue
disease, in professions requiring
long hours of standing, and during
Stasis Dermatitis 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
2/17/2009
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