Cardiovascular Pathology

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Cardiovascular Pathology
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Heart Disease- the silent killer

• THE predominant cause of morbidity and mortality
  in the Western Hemisphere
• 40 of all deaths
• Vast majority of heart disease is ischemic heart
  disease (80)
• Remainder of heart disease is due to
• Hypertensive heart disease and cor pulmonale
• Congenital heart disease
• Valvular heart disease (multiple etiologies)
• Sterile and infective endocarditis
• Aortic stenosis
• Mitral valve prolapse
• Rheumatic heart disease with valvular
  derangements

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• Congestive Heart Failure
• Definition Multisystem derangement that occurs
  when the heart is no longer able to eject blood
  delivered to it by the venous system in a manner
  sufficient to meet the metabolic demands of the
  body

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Systolic vs. Diastolic Heart Failure

• Systolic Failure- heart is unable to adequately
  contract and propel blood
• Diastolic Failure- heart is unable to adequately
  relax allowing for proper filling of cardiac
  chambers

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• Types of Heart Failure
• Left Heart Failure Inability to pump blood due
  to HTN, mitral/aortic valve disease, ischemia or
  primary disease. (c/w Systolic failure)
• Right Heart Failure Inability to meet the
  demands of venous return due to left heart
  failure, pulmonary disease, valvular disease or
  left-to-right shunts

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Types of Heart Failure

• High Output Failure Elevated CO due to
  increased tissue demand which is often secondary
  to sepsis vasodilation

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• Response to Heart Failure
• Short term Increased sympathetic stimulation
  (positive inotropy chronotropy). Includes
  stimulation of renin-angiotensin system secondary
  to decrease in renal perfusion.
• Long term Heart muscle remodeling in order to
  maximize cardiac output (Frank-Starling law)
• Hypertrophy
• Dilatation

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Response to Heart Failure

• Hypertrophy
• Concentric hypertrophy due to increased pressure
  resulting in increased cell diameter (same
  chamber size with increased wall thickness)
• Eccentric hypertrophy due to increased volume
  resulting in cell lengthening (increased heart
  size and thickness)

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Response to Heart Failure

• Dilatation
• Adaptive mechanism to increase pressure and/or
  volume in an attempt to increase contractility
  (inotropy)
• Mechanism is explained by Frank-Starling curve

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AdaptiveMechanisms
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Adaptive Mechanisms
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• Clinical Findings
• Lungs Dyspnea, SOB, crackles, orthopnea, PND
• Heart Tachycardia, S3, murmurs, PMI changes,
  fibrillation
• Systemic Hepatic congestion, lower extremity
  edema, JVD, splenomegaly, pulmonary
  congestion/pleural effusions

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• Ischemic Heart Disease
• Definition Syndromes causing an imbalance
  between myocardial oxygen demand and supply
• Most common cause of death in developed world
  (1/3)
• Peak incidence between 60 to 70 y/o
• Men gt Women (until 80s)

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Ischemic Heart Disease

• Risk Factors
• HTN
• Sedentary life-style
• DM
• Smoking
• LDL
• Hypertriglyceridemia
• Family history

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• Ischemic Heart Disease Pathogenesis
• Closely associated with atherosclerosis
• Pathways
• 75 narrowing is considered critical stenosis
• Acute plaque changes which usually occur between
  50-75 stenotic range

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Ischemic Heart Disease Pathogenesis

• Sequence of acute plaque changes
• Plaque stress
• Activation of T-cells
• Secretion of ?-interferon
• Activation of macrophages
• Secretion of metalloproteinases
• Degradation of fibrous cap
• Fissuring, erosion, ulceration, hemorrhage
• Thrombotic event

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Pathogenesis of Ischemic Heart Disease
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• Results of Ischemic Heart Disease
• Angina Pectoris
• Acute Myocardial Infarction
• Sudden Cardiac Death
• Chronic Ischemic Heart Disease

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Angina Pectoris
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• Angina Pectoris
• Stable (or classic) angina
• Unstable (or preinfarction) angina
• Prinzmetal (or variant) angina

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Angina Pectoris

• Stable Angina
• Intermittent substernal chest pain
• Represents reversible myocardial ischemia
• 75 fixed coronary lesion
• Treat with nitroglycerin causing vasodilation and
  decreased cardiac work

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Angina Pectoris

• Unstable Angina
• Crescendo chest angina increasing in frequency
  with progressively less work
• Due to acute plaque changes
• Associated with thrombosis, embolism and/or
  vasospasm

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Angina Pectoris

• Prinzmetal Angina
• Substernal chest pain occurring at rest
• Due to vasospasm with or without a fixed
  atherosclerotic lesion
• Pathogenesis is unknown
• Treated with calcium channel blockers resulting
  in vasodilatation

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• Myocardial Infarction
• Necrosis due to local ischemia which is primarily
  caused by thrombi
• Can lead to vasospasm and/or emboli
• Site, size and effect of an MI depends on
  location of event
• Location
• Left Anterior Descending (40 to 50)
• Right Coronary Artery (30 to 40)
• Left Coronary Artery (15 to 20)

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Myocardial Infarction

• Vascular obstruction leads to myocardial ischemia
• Within 30 min the subendocardium becomes
  infarcted
• Within 3 to 6 hours the lesion becomes transmural
  and reaches its full size
• Treatment within 3 hours reduces morbidity and
  mortality dramatically

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MyocardialInfarction
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Diagnosis of AMI

• HP
• EKG
• Labs
• Myoglobin- earliest rise
• CK-MB- 2 to 4 hours after MI (not specific)
• TROPONIN-I- highly sensitive and specific Show
  around 4 hrs after MI- peak at 48 hrs
• C-reactive protein

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Pathological Changes

• Gross
• 0-12 hrs No changes or slight mottling
• 18-24 hrs Dark mottling
• 24-72 hrs Dark mottling with pallor
• 4-7 days Well defined w/ hyperemic borders,
  central tan necrosis
• 7-9 weeks Gray-white scar (outside?in)
• gt 2 months Scarring complete w/ fibrosis

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Pathological Changes

• Histologically
• 0-30 min No change
• 1-2 hrs Wavy fibers at margin
• 4-12 hrs Early necrosis neurophils
• 18-24 hrs Contraction band necrosis
• 24-72 hrs Complete necrosis
• 4-7 days Macrophages
• 10 days Granulation tissue
• 7-8 wks Fibrosis
• gt 2 months Dense collagenous scar

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PathologicChanges
Triphenyltetrazolium chloride
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Complications of an AMI

• Contractile dysfunction (pump failure)
• -In 10- 15 of patients
• -70 mortality with cardiogenic shock
• Arrythmias- major cause of sudden death in MI
• -Type of arrythmia is secondary to location and
  size of infarct
• Mural thrombus- due to lack of motility of
  ventricular wall and thrombogenic nature of
  damaged myocytes

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• Complications of an AMI
• Papillary muscle dysfunction/rupture
• Mitral valve regurgitation
• Rupture around day three s/p AMI
• 50 mortality rate with rupture
• Ventricular rupture
• Occurs around day 4 to 7 s/p AMI
• Results in cardiac tamponade
• 1 to 3 involve septum resulting in a left to
  right shunt

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Complications of an AMI

• Fibrinous pericarditis
• Occurs on day 2 to 4
• Associated with transmural neutrophilic
  infiltrate
• Leads to restrictive pathology
• Ventricular aneurysm
• Late complication of large transmural infarcts
• Results in bulging during systole
• Often contains mural thrombi
• Can disrupt conduction pathways

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Complications
Papillary Muscle Rupture
Anterior Myocardial Rupture
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Complications
Fibrinous Pericarditis
Fibrinous Pericarditis
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Complications
Ventricular Aneurysms
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• Sudden Cardiac Death
• Definition Death within 24 hours of initial
  symptomatology
• -Most deaths occur within 1 hour
• Most commonly related with ischemic heart disease
• 50 of all patients with ischemic heart disease
  suffer this fate
• Ultimate cause of death is usually arrhythmia-
  electrical irritability of myocardium

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Sudden Cardiac Death
Seen in 300,000 to 400,000/yr Causes Coronary
Artery Diseases Coronary Atherosclerosis Devel
opmental Disorders Coronary Artery
Embolism Myocardial Diseases Cardiomyopathies
Myocarditis Right Ventricular
dysplasia Valvular Diseases Mitral Valve
Prolapse Left Ventricular Outflow
Obstruction Endocarditis Conduction
Abnormalities
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• Hypertensive Heart Disease
• Results in LV hypertrophy in patients with poorly
  controlled HTN
• Differentiated from LV hypertrophy secondary to
  aortic stenosis or primary hypertrophic
  cardiomopathy
• Some regression possible with adequate treatment
• Leads to heart failure due to decreased
  efficiency

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• Cor Pulmonale
• Definition Right-sided heart failure secondary
  to pulmonary hypertension
• Causes of pulmonary hypertension are diverse and
  extensive

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Cor Pulmonale
Causes Intrinsic Lung Diseases Chronic
Obstructive Lung Disease Diffuse Pulmonary
Interstitial Fibrosis Cystic Fibrosis Diseases
of the Pulmonary Vasculature Pulmonary
Embolism Primary Pulmonary Vascular
Sclerosis Extensive Pulmonary Arteritis (e.g.
Wegeners Granulomatosis) Drug-, Toxin-,
Radiation- induced vascular sclerosis
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Cor Pulmonale
Causes (Cont.) Disorders Affecting Chest
Movement Kyphoscoliosis Marked Obesity
(Pickwickian Syndrome) Neuromuscular
Diseases Disorders inducing Pulmonary Arteriolar
Constriction Metabolic Acidosis Hypoxemia C
hronic Altitude Sickness Obstruction to Major
Airways Idiopathic Alveolar Hypoventilation
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• Cardiac Valves
• Valves help each heart chamber perform its work
  without being affected by adjacent chambers
• Valves perform their responsibilities passively
  or passively and actively
• Pathologies include regurgitation and stenosis
• Acquired stenosis (2/3) of valve disease

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Rheumatic Heart Disease
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• Rheumatic Heart Disease
• Immune mediated disorder secondary to pharyngitis
  caused by GAßHS (Strep. pyogenes)
• Presents 2-3 weeks following infection
• Possibly due to cross reactivity of anti-M
  capsular Abs

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Rheumatic Heart Disease

• Slight familial predisposition
• 3 of infections progress to RF
• 70 have mitral valve involvement
• 25 have combined mitral aortic valve
  involvement
• Mitral valve involvement gt women
• Aortic valve involvement gt men
• Stenosis gt regurgitation
• Incidence on decline- abxtx, socioeconomics,
  decreased virulence

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Rheumatic Heart Disease
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Rheumatic Heart Disease

• Immune complex deposition
• Mixed inflammatory infiltrate of all heart layers
  with fibrinoid necrosis
• Possible fibrinous pericarditis
• Aschoff bodies, ring of mixed inflammatory cells
  with central necrosis and large macrophages
  (Anitschkow cells)
• Line of closure vegetations and leaflet/chordae
  tendineae fusion

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Rheumatic Heart Disease
Friable Vegetations at Line of Closure
Mitral Stenosis with Diffuse Thickening
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Rheumatic Heart Disease
Aschoff Body
Line of Closure Vegetations
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Diagnosis of Rheumatic Fever

• Jones criteria- 2 major manifestations or 1 major
  and 2 minor manifestations
• Major manifestations (1) migratory polyarthritis
  (2) carditis (3) subcutaneous nodules (4)
  erythema marginatum (5) Sydenham chorea
• Minor- non-specific
• 1 mortality rate

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• Calcific Aortic Stenosis
• Degenerative valvular changes with age (repeated
  mechanical stress) and/or atherosclerosis
• Common with congenitally unicuspid (rare) or
  bicuspid valves (1)
• Frequently asymptomatic
• Sclerotic with calcifications at line of closure
• Left heart failure and crescendo-decrescendo
  systolic murmur
• Stenosis causes increased pressures across valve
  and increase in proximal chamber

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Calcific Aortic Stenosis
Degenerative Changes w/o Fusion of Commissures
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• Mitral Valve Prolapse
• Floppy valve syndrome
• 3 to 5 of the population with 97 being
  asymptomatic
• Presents between 20 to 40 y/o
• More common in women
• Associated with Marfans Syndrome or ruptured
  papillary m./chordae tendinae
• Intercordal hooding with thick, rubbery valves
• Concomitant involvement of tricuspid (20-40)
• Harsh holosystolic murmur with possible infective
  endocarditis, arrhythmias, or thrombi
• Unknown cause

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Mitral Valve Prolapse
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• Nonbacterial Thrombotic Endocarditis
• Also known as marantic endocarditis
• Sterile deposition of fibrin, platelets, and
  blood components
• Associated with debilitated patients
• Line of closure vegetations
• Often resolve spontaneously (Lamble excrescenes)
• Commonly affects mitral valve (50)
• Unknown etiology, possible due to subtle
  endothelial abnormalities
• Embolic events are main concern

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Nonbacterial Thrombotic Endocarditis
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• Libman-Sacks Endocarditis
• Sterile vegetations associated with SLE
• Found on undersurface of tricuspid and mitral
  valves, cords, or endocardium
• Fibrinoid necrosis
• Decreased incidence with steroid therapy
• Embolic events and valve fibrosis are of concern

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Libman-Sacks Endocarditis
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• Infective Endocarditis
• Heart valve infection commonly due to bacteria
• Commonly affects aortic and mitral valves
• Bulky friable, necrotizing vegetations
• Types
• Acute Organisms of high virulence,
  destructive, 50 mortality even with tx (i.e.
  Staph. aureus)
• Subacute Organisms of low virulence with
  previous valvular damage, less destructive (i.e.
  Strep. viridans)

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Infective Endocarditis

• Diagnosis by culture and/or histology
• Treatment requires six months of antibiotics
• Organism (native valves)
• Strep. viridans (50 to 60)
• Staph. aureus (20), most common in IV drug
  users
• HACEK (Haemophilus, Actinobacillus,
  Cardiobacterium, Eikenella, Kingella)
• S. epidermidis (prosthetic valves)

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Infective Endocarditis

• Variable clinical signs and symptoms
• Acute- rapid onset, fever, chills, weakness,
  lassitude
• Sub-acute- highly variable, with FEVER, fatigue,
  flu like symptoms
• New murmurs are consistently found
• Vegetations on echocardiogram, () blood
  cultures- major criteria
• Predisposing heart lesion, IV drug use, fever,
  emboli, soft blood culture or echocardiogram
  findings
• Preventative antibiotic therapy is crucial in
  patients with hx of valve replacement

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InfectiveEndocarditis
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• Valvular Replacement
• Types
• Biological prosthetic
• Artificial prosthetic
• Complications
• Mechanical deterioration
• Thrombus formation
• Infective endocarditis
• Paravalvular leak
• Mechanical hemolysis

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ReplacementValves
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Myocarditis
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• Myocarditis
• Mononuclear inflammation/infiltration of the
  myocardium
• Causes are idiopathic to infectious to autoimmune
  in nature
• Most commonly associated with viral agents
  (parasitic most common in 3rd world)
• PCR can be used to determine organism
• Pts. can be asymptomatic. Many have fever,
  fatigue, chest discomfort, SOB, palpatations
• Acute sequelae- arrythmia, dilated cardiomyopathy
  (chronic also) , mitral regurgitation

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Causes of Myocarditis
Infections Viruses (e.g. Coxsackievirus,
Echovirus, Influenza virus, HIV,
Cytomegalovirus) Chlamydia (e.g. C.
psittaci) Rickettsia (e.g. R. typhi) Bacteria
(e.g. Corynebacterium diphtheria, Neisseria
meningitides, Borrelia burgdorferi) Fungus
(e.g. Candida sp.) Protozoa (e.g. Trypansoma
cruzi, Toxoplasmosis) Helminths (e.g.
Trichinosis)
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Causes of Myocarditis
Immune-Mediated Reactions Post viral Post
streptococcal (Rheumatic Fever) Systemic Lupus
Erythematosus Drug hypersensitivity (e.g.
methyldopa, sulfonamides) Transplant
Rejection Unknown Sarcoidosis Giant Cell
Myocarditis (poor prognosis)
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• Cardiomyopathies
• Definition Primary myocardial abnormalities
  (intrinsic disease)
• Types
• Dilated (i.e. Flabby)
• Progressive hypertrophy, dilation, and
  contractile dysfunction due to cytoskeletal
  protein dysfunction
• Most common cardiomyopathy (90)
• Four chamber dilatation with mild hypertrophy
• Causes include viral, Etoh, toxins,
  pregnancy, inherited (muscular dystrophies)

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Cardiomyopathies

• Types (Cont.)
• Hypertrophic
• Marked septal hypertrophy
• Intermittent outflow obstruction
• Interventricular septum is diproportionately
  thickened
• Abnormal sarcomeric proteins with haphazard
  myocyte arrangement
• Restrictive
• Decreased compliance due to idiopathic
  fibrosis, Lofflers syndrome, etc
• See Table 12-10 in Robbins

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Cardiomyopathies
Dilated Cardiomyopathy
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Hypertrophic Cardiomyopathy
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• Left to Right Shunts
• Late Cyanosis
• Ventricular Septal Defect (1)
• Size/location determine significance
• Associated with Downs Syndrome
• Atrial Septal Defect (2)
• Found in 1/3 of the population
• Types
• Ostium Primum (15)
• Ostium Secundum (75)

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Left to Right Shunts

• Late Cyanosis (Cont.)
• Patent Ductus Arteriosus
• Closes on day 1 to 2 postpartum due to increase
  oxygen and decreased prostaglandin E2
• Sequelea
• EISENMENGERS SYNDROME

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Congenital Left to Right Shunts
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Congenital Left to Right Shunts
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• Right to Left Shunts
• Early Cyanosis
• Tetralogy of Fallot
• Associate with VSD, subpulmonary stenosis,
  overriding aorta, and RV hypertrophy
• Transposition of Great Vessels
• Truncus Arteriosis

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Congenital Right to Left Shunts
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• Coarctation of the Aorta
• Pre-Ductus Arteriosis
• Systemic circulation via right ventricle
• Post-Ductus Arteriosis
• Systemic circulation via aorta and
  collateralization (intercostal, phrenic and
  epigastric arteries)
• Upper extremity HTN
• Lower extremity hypotension

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Congenital Obstructive Lesions
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• Pericarditis
• Inflammation of the pericardium most commonly due
  by viral agents
• Types
• Acute -- Fibrinous exudate which resolves or
  progresses to chronic form
• Chronic Varies from delicate fibrous adhesions
  to fibrotic scarring
• Sequelea Constrictive pericarditis

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PericardialDisease
Acute Suppurative Pericarditis
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• Pericardial Effusions
• Serous Due to decreased protein (cirrhosis) or
  increased pressure (CHF)
• Serosanguinous Due to decreased protein with
  blood (trauma or cancer)
• Chylous Due to lymphatic obstruction (cancer)
• Sanguinous Due to trauma or acute events
  (dissections or rupture)

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• Heart Tumors
• Types
• Metastatic (1 overall)
• Myxomas
• Lipomas
• Rhabdomyomas (1 in children)
• Angiosarcomas
• Rhabdomyosarcomas

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Heart Tumors