Organism - University of Kentucky

Organism - University of Kentucky Pediatric Pathology Disease Cause/Risk Factors Symptoms Buzzwords Other Antigen incompatibility between fetus Anemia, Liver Failure, Hypoproteinemia and mother Hemolytic Disease of the Newborn CHF (Hydrops Fetalis) Rh (D) Antigen Incompatability doesn’t become problematic until second pregnancy Rh (treatable) Jaundice ABO (not treatable) Immature Lung, Decreased Surfactant Most Common Cause of Neonatal Respiratory Distress Syndrome Preterm Hyaline Membranes Ground Glass CXR Resuscitation at birth?Normal?Respiratory Distress in 30 min. Hyaline Membrane Disease Maternal Diabetes & C Section Difficult Respiration, Expiratory Grunt PDA Treated with corticosteroids (induce maturation) Cyanosis, Fine Rales, Ground Glass CXR Risks: PDA, Retrolental Fibroplasia, Bronchopulmonary Dysplasia Hyaline Membrane/RDS Retrolental Fibroplasia ? O2 Retinal Vessel Proliferation on return to room O2 ?Vascular Endothelial Growth Factor O2 Dependence at 28 days, Persistant Respiratory Distress at 3 months Prevented using High Frequency Ventilation, Extracorporeal Bronchopulmonary Dysplasia Very Low Birth Weight Epithelial Hyperplasia, Squamous Metaplasia membrane oxygenation, Liquid Ventilation Alveolar thickening, Interstitial Fibrosis Gut Immaturity, Oral Feeding Abdominal Distension, Tenderness, Ileus, Colonization with bacteria Necrotizing Enterocolitis Bloody Diarrhea, Pneumatosis intestinalis Mucosal Injury Mucosal Sloughing, Necrosis & Inflammation Impaired blood flow Failure to pass meconium Down’s Syndrome Abdominal Distention, Constipation Hirschsprung’s Disease Neurologic Defect Male Predominance Absence of ganglionic nerves in Abnormal Migration of neural crest submucosal/myenteric plexi ? Resorption/? Sweat NaCl Pulmonary Infections (Pseudomonas) ,F508 Cystic Fibrosis CFTR Defect (7q31-32 – ,F508) Most Common Lethal Genetic Disease in White Population Pancreatic Insufficiency; Male Infertility Elevated Sweat Chloride Cirrhosis; Malabsorption URIs, Prone Sleeping Position Unexplained Death < 1 year old Thermal Stress, Males Sudden Infant Death Syndrome Agonal Petechiae African American, Prematurity Astrogliosis of brainstem Maternal Smoking/Drug Abuse Shaken Baby: Subdural & CN II Hemorrhages, Posterior Fractures Battered Child: Bruises, Pattern Injury, Abdominal Trauma, Child Abuse/Neglect Fractures of varying ages, Lacerated Frenulum Sexual Abuse: Geniral trauma, torn hymen Caregiver simulates illness in child for secondary gain Munchausen Syndrome by Proxy Unwitnessed Events & Repeat Hospitalizations Benign Hemangioma Common in infancy, spontaneously regresses Associated with Tuberous Slcerosis & von Hippel Lindau Benign Lymphangioma Deep neck, axilla, mediastinum or retroperitoneal Usually cystic or cavernous Pediatric Pathology (contd.) Disease Cause/Risk Factors Symptoms Buzzwords Other Teratoma Teeth, hair, bone, skin Benign cystic to malignant solid Sacrococcygeal Teratoma Congenital Anomalies Teeth, hair, bone, skin 75% mature, benign; Adrenal Mudulla mass, fever, weight loss Most common malignant tumor <1 yo Encapsulated or infiltrative, cystic, hemorrhagic Homer-Wright Pseudorosettes Can become ganglioneuroma Neuroblastoma Calcified, Sheets of small blue cells Small Blue Cells Bad = Diploid, del 1p, N-myc, Stage IV = “Blueberry Muffin Baby” Homer-Wright Pseudorosettes; Peri-orbital mets Good=Stage IV-S, <1 yo, Hyperdiploid ndLarge palpable abdominal mass, Hematuria 2 most common malignant tumor Wilms Tumor Intestinal obstruction, pulmonary mets 3 cell types: Blastema (small round cells), Epithelial & Stromal WT-1 & 2 (Nephroblastoma) Nephroblastomatosis Precursor Amount of Blastema = prognosis Large, circumscribed, cystic 90% long term survival Wilms Tumor 11p13 (aniridia) Aniridia WAGR Syndrome WT-1 Genital Anomalies Retardation Gonadal Dysgenesis Denys-Drash Syndrome WT-1 Wilms Tumor Hemihypertrophy, Organomegaly, Macroglossia Other Tumors: Hepatoblastoma, Adrenocortical tumors, RMS, Beckwith-Wiedemann Syndrome WT-2 (11p15.5) Renal Medullar Cysts, Adrenal Cytomegaly Pancreatic Tumors Wilms Tumor, Other Tumors Diaphysis of long bones White male (never black) Ewing Sarcoma t11:22 Small Blue Cells Sheets of small round blue tumor, ? glycogen Metastatic in 25% of cases Extraosseous Ewing Sarcoma Neural differentiation Primitive Neuroectodermal Tumor t11:22 Rosettes (PNET) Most common soft tissue sarcoma of children Painless, proptosis, CN palsies, chronic drainage Peak 2-5 yo & again in adolescence Rhabdomyosarcoma t2:13 (Alveolar) Urinary obstruction, constipation, Hematuria Small Blue Cells Good = Embryonal: Botryoid (grapes from vagina) or Spindle Cell Small blue cell tumor Bad = Alveolar in extremities & trunk Enlarging Abdomen Hepatoblastoma Fetal or Embryonal Stem Cells Leukocoria (white papillary reflex) Retinoblastoma Rb1 on Ch 13 Assymetry, Strabismus, Painful Eye Rosettes, Calcifications Pediatric Pathology (Contd. 2) Disease Cause/Risk Factors Symptoms Buzzwords Other Solitary, esp. bone Hand-Schuller-Christian Diease Household Smoking Histiocytes & Eosinophil Infiltrate Birbeck Granules (Langerhans Cell Histiocytosis) Birbeck Granules MultifocalBone Lesions, Weight Loss, Eosinophilic Granuloma Otitis Media, Exophthalmos, Diabetes Insipidus Household Smoking Birbeck Granules (Langerhans Cell Histiocytosis) Histiocytes & Eosinophil Infiltrate Birbeck Granules Disseminated, Blood Abnormalities, Fever Letterer-Siwe Disease Seborrheic Skin Rash, Weight Loss, HSmegaly Household Smoking Birbeck Granules Often Fatal (Langerhans Cell Histiocytosis) Lymphadenopathy, Histiocytes Eosinophil Infiltrate, Birbeck Granules Partial: Primum ASD & Cleft Anterior Mitral Leaflet, Mitral Left to Right (Acyanotic), Atrioventricular Septal Defect Insufficiency, Two valve orifices Trisomy 21 (Down Syndrome) Eisenmenger Syndrome (Later) (AV Canal) Complete AVSD: Large AVSD & Common AV Valve Poorly formed AV Valves Subtypes (Rastelli A,B,C) based on bridging of anterior leaflet Narrowed or Constricted Aorta 50% bicuspid aortic valve If with PDA, manifests early, lower body cyanosis Coarctation of Aorta Monosomy X (Turner Syndrome) Systolic murmur (+ thrill) If without PDA, less severe, upper body hypertension LVH & Cardiomegaly Right to Left (Cyanotic) Truncus Arteriosus DiGeorge (del 22q11) No division into Aorta & Pulmonary Artery Early Repair to avoid late complications Single Vessel w/ vareiable # of cusps in valve Pulmonic Stenosis Noonan Syndrome (Chr 12q22) RVH, Post stenotic dilation of arteries Variable severity Supravalvular Aortic Stenosis Williams Syndrome (Chr 7 – Elastin) Left to Right (Acyanotic), Eisenmenger Syndrome (Later) Patent Ductus Arteriosus Rubella Infection Machinery Murmur Treatment: Surgery or Indomethacin (PG Inhibitor) Machinery Like Murmur Assymptomatic Right to Left (Cyanotic) Boot Shaped Heart; VSD usually large 1) VSD 2) Rt Ventricular Outflow Obstruction Tetrology of Fallot Hypercyanotic episodes due to RVOT spasm 3) Rt Ventriculare Hypertrophy Usually accompanied with Pulmonary Stenosis 4) Overriding Aorta Right to Left (Cyanotic) Abnormal Formation of Septa Requires shunt for survival (usually PDA) Transposition of Great Arteries Separation of Systemic/Pulmonary Circulation Aorta is anterior and to right of Pulmonary Artery (nl = posterior) Right Ventricular Hypertrophy TGA with Inversion of ventricles Corrected TGA Late decompensation of right ventricle due to systemic demand Aorta in parallel and to left of Pulmonary Artery Pediatric Pathology (contd. 3) Disease Cause/Risk Factors Symptoms Buzzwords Other Right to Left (Cyanotic) Requires a right to left shunt (ASD or PFO) as outlet from RA Unequal division of AV canal, large mitral orifice Tricuspid Atresia VSD allows outflow from Pulmonary Artery RV Hypoplasia High Mortality Right to Left (Cyanotic) Total Anomylous Pulmonary Requires ASD or PFO to allow pulmonary blood into the left atrium No pulmonary veins into left atrium Veinous Return RA or RV hypertrophy RA or RV hypertrophy Left to Right (Acyanotic), Secundum: Midseptal, fossa ovale, least problematic, most common Eisenmenger Syndrome (Later) Atrial Septal Defect Primum: Adjacent to AV Valves, Cleft Anterior Mitral Valve Leaflet Pulmonary Overcirculation (Flow Murmur) Sinus Venosus Defect: Near Superior Vena Cava Usually associated with other CHD Left to Right (Acyanotic), Membranous: Large, more common Ventricular Septal Defect Eisenmenger Syndrome (Later) Muscular: Multiple, smaller, well tolerated Harsh Holosystolic Murmur Infundibular: Below pulmonary valve, large Cyanotic Constriction of Pulmonary Arteries, Intimal Eisenmenger Syndrome Pulmonary Hypertension Ireeversible Lesions & Plexiform Lesions at branches Cor Pulmonale If severe, may cause Valvular Aortic Stenosis hypoplastic left heart syndrome (HLHS) HLHS: LV & arch hypolplasia; LV endocardial fibroelastosis LV Hypertrophy, Systolic murmur (+ thrill) Thickened wall of ascending aorta Supravalvular Aortic Stenosis Chr 7q (Williams Syndrome) Associated with Williams Syndrome Williams Syndrome: Facies, Cocktail Personality, MR LV Hypertrophy, Systolic murmur (+ thrill) Thickened ring below aortic cusps Usually isolated Subvalvular Aortic Stenosis May be associated with coarctation & PDA LV Hypertrophy, Systolic murmur (+ thrill) Cardiac Pathology Disease Cause/Risk Factors Symptoms Buzzwords Other Atheromas at Branch Points Medium & Large Arteries Foam Cells Located in intima Atherosclerosis ? LDL, HT, Smoking, DM, Fam Hx Foam Cells (Macrophage & Smooth Muscle) Intima Consists of a fatty core covered by a fibrous cap & endothelium Fatty Streaks? Exposed Rough Surface allows attachment of platelets and fibrin Atherothrombotic Erosion Atherosclerosis May embolize (thromboembolism) Mural Thrombosis (Atherothrombosis) Ulceration Can cause sudden occlusion Main cause of myocardial infarcts Disintegration of the fibrous cap with release into bloodstream Atherothrombotic Rupture Atherosclerosis Atheromatous Embolus May allow for formation of thrombus within the plaque Can cause sudden occlusion Crack in cap allows blood in or neovessels within plaque may burst Atherosclerotic Hemorrhage Can cause sudden occlusion May cause infarcts Atherosclerotic Calcification Brittle Arteries Hardening of arteries with time Enlarged plaque compresses media layer (pressure atrophy) Causes ballooning (aneurysm) Atherosclerotic Degeneration Aneurysm Focal area of wall = saccular aneurysm Circumferential Involvement = Fusiform aneurysm Atherosclerosis in Femoral Artery Intermittent Claudication Walking pain If thrombosis is complete it may cause necrosis of the toe or foot Atherosclerosis in Popliteal Artery Hypertension Rapidly spreading intramural hemorrhage Chest Pain Chest Pain Cystic Medial Necrosis Creates a second lumen in the media layer Acute Aortic Dissection Hypotension Tamponade Marfan’s Syndrome Initial intimal tear accompanied by a distal reentry tear Pericardial Tamponade Compressed Aortic Valve Pregnancy, Coarctation of the Aorta May compress the aortic valve & cause insufficiency Proximal Hypertension/Distal Hypotension Located opposite the ligamentum arteriosum Congenital Rib Notching Coarctation of the Aorta CHF Lower half of the body is supplied by collaterals Turner’s Syndrome Bicuspid Valve Rib notching on CXR Associated with a bicuspid valve Granulomatous Age > 50 Giant Cell Arteritis Large Arteries – Cranial Arteries Destruction of IEL Granulomatous Age < 40 & often Female Takayusu’s Arteritis Aortic Narrowing; Weak pulses Extremities Medium Sized Arteries (not lungs) Polyarteritis Nodosa No Glomerulonephritis Many organs Dilated Aneurysms Cardiac Pathology (contd) Disease Cause/Risk Factors Symptoms Buzzwords Other Large & Medium Sized Arteries Children Kawasaki Syndrome “Infantile Polyarteritis” Coronary Arteries Aneurysms Small Vessels Hypersensitivity Angitis Glomerulonephritis All organs No Immune Deposits Small Vessels Granulomas in Lungs Wegener’s Arteritis Granulomatous Vasculitis Renal Disease Medium & Small Arteries Heavy Smokers Buerger’s Arteritis Extremities Microabscesses Poor Tissue Perfusion/Venous Backup (Edema) Many Tachycardia; ? Angiotensin II Congestive Heart Failure Hemosideran Laden Macrophages Cardiogenic Shock occurs w/ loss of > 40% of left ventricle function Chronic Ischemia & Inflammation Pre-renal Azotemia; Ischemic Colitis Liver Necrosis, Muscle Wasting; Lung Edema Atherosclerosis; Arterial Spasm Assymptomatic (Diabetes) Right Coronary Artery: Posterior LV & AV Node Hypotension Arrythmias, Mitral Insufficiency Ischemic Heart Diseaes Left Anterior Descending: Anterior LV &AV Node Aortic Valve Disease: Pericardial Tamponade, Aneurysm, Thrombus Left Circumflex: Lateral LV & Papillary Muscles (Syphilis, Polyarteritis, Kawasaki) Pericarditis Exertion (Relieved by Rest) Stable Angina Pectoris Pain with exertion Reversible Ischemic Injury Stenosis Atypical Angina (Prinzmetal’s) Spasm Pain at rest (spontaneous reduction in supply) st? Troponin (1), CK (later) Subendocardial: Underperfusion ? ST ,Q Waves, Loss of R Waves, Arrhthmias Transmural: Full thickness of wall, more common Myocardial Infarction Severe atherosclerotic narrowing Leukocytosis, ? SR Troponin I & T are gold standard sensitivity (elevated for days) Pain(Squeezing), Radiation, Diaphoresis, N&V LDH>LDH after 24 hours 12 Arthritis, Rash, Nodules & Chorea Genetic? B Cell Alloantigens Rheumatic Heart Disease Pancarditis (Bread & Butter), Myocarditis, Endocarditis Group A Strep Verrucae on Vavles (Mitral Stenosis) Aschofff Bodies (no organisms) Diastolic Murmur with opening snap Rheumatic Fever (Disease) Mitral Stensosis “Fishmouth” appearance Young Females Atrial Fibrillation Marfan’s Syndrome Mitral Prolapse Late Systolic Murmur with Midsystolic click Can cause CHF, Arrhythmias, Sudden death & endocarditis Post MI LV Dilation Cardiac Pathology (contd 2) Disease Cause/Risk Factors Symptoms Buzzwords Other Diseased Valves Fever, Splinter Hemorrhages, Osler’s Nodes Staph, Pneumonia & Gonococcus are especially destructive Bacterial Endocarditis Congenital Defects Heart Failure, Hemiplegia, Changing Murmur Biggest problem is septic emboli IV Drug Use Anemia, Hematuria, + Culture Porcine: 5-10 year durability Valve Replacement Fen-Phen Mechanical: Requires anti-coagulation; concern for hemolysis Usually benign Cardiac Myxoma Polypoid, pedunculated, extends into chamber Renovascular, Chronic Renal Disease, Hyperaldosteronism, Cushings Normal <120/80; Pre <130/90; Stage I <160/100 Essential Hypertension is the majority and has no known cause Hypertension Pheochromocytoma, Coarctation Subintimal fibrosis & hyalinization Estrogens are the most common reversible cause (OCT) Estrogens, Alcohol, Amphetamines Primary: Idiopathic Dilation of all 4 chambers Secondary: Alcohol, DMD DOE/Rest, Weakness, HSmegaly Dilated Cardiomyopathy Viral (Coxsackie B3), Risk of thromboemboli/infarction Genetic?, Drugs (Adriamycin), Death within 5 years without transplant Primary: Idiopathic Secondary: Amyloidosis, Dilated Atria Restrictive Cardiomyopathy Decreased compliance (like constrictive pericarditis) Hemochromatosis (Thalessemia) Low Voltage on ECG Sarcoidosis, Glyc. Storage Disease Primary: Idiopathic Young People Decreased LV Volume/Mitral Valve Insufficiency/Obstruction Hypertrophic Cardiomyopathy Secondary: Genetic Profound IVS/LV Hypertrophy “Sub-aortic Stenosis” (IHSS) (B Myosin, Tropomyosin, Troponin) Systolic Murmur Prone to arrythmias & CHF (Myosin Binding Protein C: older pts) Q Waves Better prognosis than dilated cardiomyopathy Pulmonary Pathology Disease Cause/Risk Factors Symptoms Buzzwords Other Post-op (most common) 1)Obstructive: O2 distal to obstruction is resorbed SOB, Cough, Cyanosis, Chest Pain Tumor, Foreign Body, Mucus 2)Compressive: Pressure from outside pleura Atelectasis Prone to infection Fluid, Air, Loss of Surfactant (ARDS) 3)Patchy: Loss of surfactant Reversible Fibrotic Change 4)Contraction: Fibrotic change prevents expansion Cyanosis, SOB, Cough, Pallor Transudate in alveoli, Interstitium & Perivascular Space 1) Hemodynamic (most common) Crackles in bases 1)Hemodynamic: LV Failure, Mitral Stenosis, ? Volume, ? Protein Pulmonary Edema 2) Microvascular Injury Positive CXR 2) Microvascular: Infection, Inhaled Gas, Aspiration, Drugs, Shock 3) Undetermined Frothy Transudate, Hemosiderin Macrophages 3) Undetermined: High Altitude, Neurogenic Acute Dyspnea, Hypoxemia not responsive to O2 Adult Respiratory Hyaline Acute Phase: Exudative with Diffuse Alveolar Damage, Infection Decreased lung compliance, VQ Mismatch Distress Syndrome Injury Hyaline membranes & Type II Pneumocyte Proliferation Injury Bilateral Infiltrates on CXR (ARDS or Hyaline Membrane) Exudate Organizing Phase: Fibroblast Proliferation & Scarring Death in 60% Thromboembolus usually from DVT Embolus & Inadequate Circulation SOB, Tachypnea, Chest Pain, Cough, Hemoptysis At risk: Immobilized, Hypercoaguable, Burn, Indwelling Catheter Pulmonary Embolus Lines of Zahn Thromboembolism (most common) Saddle Embolus = Instant Death Dx: D-DImer, Doppler US, VQ Scan, Spiral CT, Arteriography Microscopic Lines of Zahn or wedge infarct at autopsy Assymptomatic until advanced Primary: Unknown Cause Unknown Dyspnea & Fatigue, Chest Pain, Cyanosis, RVH Cor Pulmonale Secondary: COPD, Heart Disease, Recurrent PEs, Drugs (Fen-Phen) Pulmonary Hypertension COPD, Heart Disease, Recurrent PEs, Plexogenic Vascular Proliferation on biopsy Plexiform Dx: Catheterization (standard), Echo (screen), Biopsy Drugs Death within 2 years in 80% (Cor Pulmonale) Plexiform Phase is irreversible Airspace enlargement without fibrosis Most Common Centriacinar Emphysema Involves upper lobes Involves Respiratory Bronchiole (Alvelolar spared) Smoking Smoking (COPD) Barrel Chested, SOB, lean forward Smoke: Stimulates M,s & PMNs & inhibits ,-1-antitripsin Slowed Forced Expiration Death from acidosis or ruptured bleb (Pneumothorax) Airspace enlargement without fibrosis Panacinar Emphysema Voluminous Lungs overlap Heart Both Respiratory & Alveolar Alpha-1-antitrypsin Deficiency Alpha-1-antitrypsin (COPD) Barrel Chested, SOB, lean forward Death from acidosis or ruptured bleb (Pneumothorax) Slowed Forced Expiration Airspace enlargement without fibrosis Young adults Distal Acinar Emphysema Spontaneous Pneumothorax Barrel Chested, SOB, lean forward Young adults Distal Acini Only (COPD) Slowed Forced Expiration Death from acidosis or ruptured bleb (Pneumothorax) Airspace enlargement without fibrosis Irregular Emphysema Any part of the acinus Previous Scarring Barrel Chested, SOB, lean forward (COPD) Death from acidosis or ruptured bleb (Pneumothorax) Slowed Forced Expiration Persistant cough w/ sputum for >3 mos in 2 years Smoking Cough, Hypercapnea & DOE (later) Chronic Bronchitis Problematic when Respiratory Bronchi get mucous plugs Pollution Hypertrophy of Bronchi (Submucosal Glands) (COPD) O2 drives breathing; Usually die from respiratory failure Infectious Agents Goblet Cell Hyperplasia of smaller airways If chronic, can cause Cor Pulomale SOB, Wheezing & Cough Environmental Allergens Chronic Inflammatory; Episoidic, Reversible Bronchoconstriction Extrinsic Asthma Thickening of Basement Membrane Workplace Chemicals Charcot-Leyden Crystals Gross plugging of airways with mucous (COPD) ? Eosinophils, Mucous Gland Size Colonizing Fungi Breakdown products of eosinophils = Charcot-Leyden Crystals Bronchial Smooth Muscle THickening Cold; Exercise SOB, Wheezing & Cough Chronic Inflammatory; Episoidic, Reversible Bronchoconstriction Intrinsic Asthma Stress Thickening of Basement Membrane Charcot-Leyden Crystals Gross plugging of airways with mucous (COPD) Viral Infections ? Eosinophils, Mucous Gland Size Breakdown products of eosinophils = Charcot-Leyden Crystals Aspirin Bronchial Smooth Muscle THickening Pulmonary Pathology (contd) Disease Cause/Risk Factors Symptoms Buzzwords Other Most common type Atopic Asthma Mast Cell Activation/Eosinophil Recruitment Most Common Type Chronic Inflammatory; Episoidic, Reversible Bronchoconstriction (An Extrinsic Type) Initial & Subsequent Exposures Edema, Mucous & Bronchoconstriction Charcot-Leyden Crystals Gross plugging of airways with mucous (COPD) Breakdown products of eosinophils = Charcot-Leyden Crystals SOB, Wheezing & Cough Nonatopic Asthma Viral Trigger lowers threshold to air pollutants Gross plugging of Thickening of Basement Membrane (An Intrinsic Type) Viral Infection Charcot-Leyden Crystals airways with mucous ? Eosinophils, Mucous Gland Size (COPD) Breakdown products of eosinophils = Charcot-Leyden Crystals Bronchial Smooth Muscle THickening SOB, Wheezing & Cough Drug Induced Aspirin blocks COX which causes an increase in leukotrienes Gross Thickening of Basement Membrane (An Intrinsic Type) Aspirin Charcot-Leyden Crystals plugging of airways with mucous ? Eosinophils, Mucous Gland Size (COPD) Breakdown products of eosinophils = Charcot-Leyden Crystals Bronchial Smooth Muscle THickening SOB, Wheezing & Cough IgE mediated Occupational Asthma Thickening of Basement Membrane Varies Charcot-Leyden Crystals Gross plugging of airways with mucous (COPD) ? Eosinophils, Mucous Gland Size Breakdown products of eosinophils = Charcot-Leyden Crystals Bronchial Smooth Muscle THickening Obstruction Cough, Fever, Copious Foul Sputum Necrotizing Infection of Bronchi & Bronchioles Bronchiectasis Tumor, Mucous Plug, Foreign Body Worse in the morning Usually located in lower airways (COPD) Cystic Fibrosis, Congenital Atelectasis of distal lung; Patent bronchi Bronchi can be followed out to pleura - Drastically dilated bronchi Kartagener’s Syndrome, Pneumonia Peribronchiolar Fibrosis Aspiration of infected material If from aspiration: in right lower lobe Pneumonia Cough, Fever, Copious Foul Sputum Lung Abscess If from sepsis: scattered throughout Septic Embolism Confirmed by CXR Must rule out cancer Cancer Ghon Complex: Parenchymal subpleural lesion at interlobar fissure Assymptomatic Primary Pulmonary Tuberculosis TB If resolved, lesion becomes calcified/fibrotic Caseating Granuloma May spread in children or immunodeficient Reactivation of old subclinical infection (only 5-10% of cases) Secondary (Reactivation) Fever & Night Sweats Lesion at apex of lungs TB Pulmonary TB Caseating Granulomas May involve regional lymph nodes Fibrocalcific scar Cavitary: Caseous Focus erodes into bronchiole Miliary: Spread by lymphohematogenous dissemination Progressive Pulmonary TB TB Caseating Granulomas Small lesions without central necrosis Bronchopneumonia: Rapid spread, tubercles may not form Necrotizing granulomas of airways Vasculitis of small-medium vessels Wegener’s Granulomatosis Immunologic? (CMI) Good response to immunosuppression; untreated 80% die within 1 yr Renal Disease (crescentic) C-ANCA Dyspnea, Cough, Chest Pain, Hemoptysis Mikulicz Syndrome Diagnosis of exclusion; Non-caseating granulomas Bilateral hilar lymphadenopathy Women Mikulicz Syndrome – salivary gland & eye involvement Sarcoidosis Infection? Lung & Spleen most often involved Non-caseating Granuloma Schaumann Bodies: Concretions of calcium & protein Skin involvement in half Schaumann & Asteroid Bodies Asteroid Bodies: Stellate inclusions in giant cells Coal Mining Assymptomatic Anthracosis Soot Innocuous Lesion (Coal Worker’s Pneumoconiosis) Smoke Carbon Pigment Ingested by Macrophages Pulmonary Pathology (contd 2) Disease Cause/Risk Factors Symptoms Buzzwords Other Coal Macules & Nodules Coal Macules: 1-2 mm lesions of carbon laden M,s Simple CWP Coal Mining More commonly in upper lobes Coal Nodules: Slightly larger lesions with collagen fibers (Coal Worker’s Pneumoconiosis) No dysfunciton Small percentage may progress to complicated type Pulmonary Hypertension & Cor Pulmonale Complicated CWP No association with cancer Larger Lesions (2-10 cm) Caplan’s Syndrome: Rheumatoid Arthritis & Pneumoconiosis (Coal Worker’s Pneumoconiosis) Simple CWP Caplan’s Syndrome Multiple black scars (Progressive Massive Fibrosis) Central necrosis with surrounding fibroblasts, M,s & collagen Dense collagen & pigment; necrotic center No association with cancer Slowly progressive nodular fibrosis Inhaled crystalline silica Most prevalent occupational lung disease Silicosis Dine nodularity of upper lobes on CXR Birefringent particles Inhaled amorphous siulica (rarely) Later lesions: hard Collagenous scars w/ central cavitation Birefringent particles with polarized light Hilar Node calcification & fibrosis Sarcoid like granulomas Inhaled Beryllium Cancer Increased incidence of lung cancer Berylliosis SOB, Cough, Weight loss, Arthralgia (More commonly chronic) Non-caseating granulomas Noncaseating granulomas in lungs and hilar nodes Variable course Asbestos SOB & Cough Asbestos Bodies: Golden-Brown Dumb bells (iron coated fibers) Asbestos Bodies Asbestosis Serpentine Fiber: more common Diffuse pulmonary interstitial fibrosis Fibrosis starts aroundrespiratory bronchioles & extends to alveoli Honeycomb Change Amphibole Fiber: more pathogenic Airspace Enlargement/Honeycomb Change Starts in lower lobes, progresses upwards Asbestos Well circumscribed plaques of dense collagen Pleural Plaques Serpentine Fiber: more common May be calcified Anterior & Posterolateral portions of parietal pleura & daphragm Amphibole Fiber: more pathogenic No Asbestos Bodies Dyspnea, Cough Idiopathic Pulmonary Fibrosis (IPF) Hypoxemia Diagnosis of exlusion Usual Interstitial Pneumonia (UIP) Idiopathic Honeycomb Change Honeycomb Change Median Survival Less than 5 years Cryptogenic Fibrosinf Alveolitis Organizing Fibrosis Intra-alveolar Macrophage Accumulation Desquamative Interstitial Smoking Slowly developing cough & dyspnea Ground Glass No real desquamationof epithelial cells Pneumonia (DIP) (Only seen in smokers) Ground Glass Infiltrates on CXR Intra-alveolar Macrophages Diffuse Accumulation of M,s with brown pigment; PAS + Good Prognosis! Bronchiolitis Obliterans Organizing Cough, SOB Polypoid plugs of loose fibrous connective tissue within alveoli Pneumonia (Idiopathic BOOP) Idiopathic History of Recent Illness (one month prior) Mild interstitial inflammation (Cryptogenic Organizing Patchy Infiltrates on CXR Improves with steroids Pneumonia) Rheumatoid Arthritis Polypoid plugs of loose fibrous connective tissue within alveoli Ongoing Infection; GVHD Cough, SOB BOOP Mild interstitial inflammation Inhaled Toxins Patchy Infiltrates on CXR Improves with steroids Drugs Ex: Farmer’s Lung, Pigeon Breeder’s Lung, Air Conditioner Lung Acute Attacks (fever, dyspnea, cough) Inhaled Organic Dusts Acute Attack Interstitial pneumonitis Hypersensitivity Pneumonitis Diffuse & nodular infiltrates on CXR Abnormal Sensitivity to Antigens Small poorly formed granulomas Small poorly formed granulomas Lymphs, few plasma eosinophils & M,s Idiopathic Hemoptysis Necrotizing Interstitial Pneumonitis / Crescentic Glomerulonephritis Young Men Virus? Consolidation on CXR Most common in young (esp men) Goodpasture’s Syndrome IgG & C3 BM deposits Dry Cleaner Solvent? Anti-basement membrane antibodies Rx: Plasma Exchange & Immunosuppression Hemosiderin Laden M,s Smoking? Hemosiderin lagen macrophages Focal necrosis of alveolar walls with intra-alveolar hemorrhage Pulmonary Pathology (contd 3) Disease Cause/Risk Factors Symptoms Buzzwords Other Idiopathic Pulmonary Cough, Hemoptysis, Anemia & Weight Loss No antiBM antibody, No renal involvement Idiopathic Hemosiderosis Diffuse Infiltrates on CXR Children & Young Adults (Similar to DIP) Elevated IL-5? If Chronic: Simple (Loffler Syndrome): Transient & Benign Pulmonary Eosinophilia Eosinophils within alveoli parasites Fever, Night Sweats & Dyspnea Tropical: Microfilariae infection Secondary: Parasite, Fungal & Bacterial Infections; Drugs Dysfunction of alveolar macrophages? No chronic fibrosis Pulmonary Alveolar Proteinosis Immunosuppression? Cough, Sputum, Fever, Dyspnea Protein within alveoli Intra-alveolar accumulation of PAS & lipid + material Malignancy? Rx: Whole lung lavage Drugs: Edema, Pneumonitis & Fibrosis Drugs Therapy Induced Lung Disease Acute XRT: fever, dyspnea, diffuse infiltrates Radiation Chronic XRT: Interstitial fibrosis & atypia Cough, Weight Loss, Pain, Dyspnea, Hemoptysis Central Location (Major Bronchus) Central/Bronchi Location More Common in Men; Local spread with late mets Squamous Cell Carcinoma Smoking 2+PTH-like Paraneoplasm (? Ca) Keratin Pearls Rx: Surgery, Chemo, Radiation Keratin Pearls; “Tadpole Cells” Radiation, Asbestos, Uranium, Nickel, Cough, Weight Loss, Pain, Dyspnea, Hemoptysis More Common in non-smokers & women Not smoking Chromates, Coal Peripheral Location Smaller lesions Adenocarcinoma Women Mustard Gas, Arsenic, Beryllium, Iron Mucin Production May be associated with pleura Peripheral Genetics, Scarring Cells try to stick together Rx: Surgery, Chemo, Radiation Radiation, Asbestos, Uranium, Nickel, A type of adenocarcinoma Cough, Weight Loss, Pain, Dyspnea, Hemoptysis Chromates, Coal Peripheral Lines alveolar septa Bronchioalveolar Carcinoma Peripheral Location Mustard Gas, Arsenic, Beryllium, Iron Confluent May be solitary, diffuse or have a pneumonia-like confluence Usually well differentiated tall columnar cells Genetics, Scarring Rx: Surgery, Chemo, Radiation Smoking, Radiation, Asbestos, Cough, Weight Loss, Pain, Dyspnea, Hemoptysis Central/Hilar Neuriendocrine Differentiated Small Cell Carcinoma Uranium, Nickel, Chromates, Coal Central/Hilar Location Aggressive Most Aggressive Type – Metastatic at Diagnosis (Oat Cell) Mustard Gas, Arsenic, Beryllium, Iron Small Cells (little cytoplasm) – Crush Artifact Crush Artifact Rx: Surgery not an option Genetics, Scarring Undifferentiated Tumor Polygonal Shaped with moderate cytoplasm Large Cell Carcinoma Smoking Features of adenocarcinoma at EM level Giant, Clear or Spindle Cells Rx: Surgery, Chemo, Radiation Radiation, Asbestos, Uranium, Nickel, Cough, Hemoptysis, Pneumonia, Bronchiectasis Rare Not smoking Chromates, Coal Emphysema, Atelectasis Neuroendocrine Differentiation Bronchial Carcinoid Younger Patients Mustard Gas, Arsenic, Beryllium, Iron Small nests & cords separated by thin bands More common in younger patients (< 40) Bleed Genetics, Scarring Bleed if biopsied Good prognosis, rarely metastasize Solitary, Round, < 4 cm Hamartoma Overgrowth of normal tissue Predominantly Cartilage Long Latent/Development Period Asbestos Diffuse lesion of pleural space, but may invade Malignant Mesothelioma Serpentine Fiber: more common Chest Pain, Dyspnea & Pleural Effusion 50% 12 month survival Amphibole Fiber: more pathogenic Epithelial, Sarcomatoid or Mixed Type Pulmonary Pathology (contd 4) Disease Cause/Risk Factors Symptoms Buzzwords Other Exudate Serofibrinous Pleuritis suppurative Inflammatory condition involving lung with extension to pleura Pus Empyema Infection seeds into pleural space Suppurative Infection in adjacent Lung Hemorrhagic Pleuritis Rickettsial Disease Bloody Inflammtory Exudate Congestion: Red & Boggy Lung Red Hepatization: Alveoli filled with RBCs & PMNs Lobar Pneumonia Strep pneumoniae Consolidation of one lobe Strep Grey Hepatization: RBCs are lysed so no red color, PMNs present Resolution: Alveolar exudate broken down Staph Multilobal Patchy Consolidation Strep Common terminal event in chronically ill patients Bronchopneumonia Frequently Bilateral Haemophilus PMN rich exudate fills bronchi Scattered 3-4 cm grey-red areas Pneumococcus Alveolar Space contains Proteinaceous fluid Mycoplasma Pneumoniae (common) No consolidation Interstitial Pneumonitis Influenza, RSV, Adenovirus, Mycoplasma Mononuclear cell infiltrate – no PMNs Chlamydia, Coxiella (Q Fever) Not dull to percussion Sudden onset of fever & chills Typical Pneumonia Pneumococci Consolidation & + CXR (Community Acquired Pneumonia) Intraalveolar exudate – productive cough Slow onset of fever & chills Atypical Pneumonia Mycoplasma Scattered Rales – No Consolidation (Community Acquired Pneumonia) Dry Cough (Interstitium) Aspirated from pneumopharynx – stimulates a brisk PMN response Pneumococcal Pneumonia Strep pneumonia (1,2,3 & 7) A Typical Pneumonia Encapsulation allows evasion (Community Acquired) (Especially Type 3) Classic pneumonia with 4 stages of congestion Laryngotracheobronchitis (fatal) Transmitted via respiratory droplets – aspirated from oropharynx Haemophilus Influenza Pneumonia Patchy consolidation to lobar Laryngotracheobronchitis H. influenza (Type B) Encapsulation allows evasion (Community Acquired) Intraalveolar PMNs Epiglottitis Most often seen in young children – a pediatric emergency Epiglottitis or Meningitis Mild URI to fatal lower respiratory infection Transmitted via respiratory droplets Mycoplasma Pneumonia Congested lungs without consolidation May progress to ARDS with hyaline membranes (Community Acquired) Fever, Headache, Myalgia, Mild dry cough Most common in young adults Cold Agglutinins An Interstitial Pneumonitits Patchy bilateral to focal consolidation Chlamydial Pneumonia Interstitial collections of lymphocytes Aerosol Transmission? Chlamydia pneumoniae (Community Acquired) Pharyngitis progresses to pneumonia Produces a patchy atypical pneumonia Fever, cough & crackles Pulmonary Pathology (contd 5) Disease Cause/Risk Factors Symptoms Buzzwords Other Influenza A & B (winter) Patchy or diffuse congestion Viral Pneumonia RSV (winter in children) Transmitted via respiratory droplets No consolidation (Community Acquired) Adenovirus (all year) Influenza damages ciliary elevator – prone to superinfection (fatal) Dry Cough Rubeola & Varicella Patchy consolidation – involves entire lobes Legionaires’ Disease Intraalveolar infiltrate Transmitted via respiratory droplets Legionella (Community Acquired) Higher mononuclear/PMN ratio Pontiac Fever = mild case (no pneumonia) Focal areas of necrosis with silver stain Bacteroides + Strep viridans Bronchopneumonia to lobar pattern (rare) Anaerobic Pneumonia Alcoholics Frequently combined with oral aerobes (S. viridans) Fusobacteria Abscesses (Community Acquired) Abscesses Seen in patients with periodontal disease prone to aspiration Actinomycetes Lots of PMNs Bronchopneumonia to lobar pattern Very Common Pseudomonas Pneumonia Pseudomonas aeruginosa Necrotizing Fleur-de-Lis Fleur-de-Lis Aspirated from oropharynx (Hospital-Acquired) PMN rich exudate filling bronchi & alveoli Produces elastase & phospholipase Klebsiella Bronchopneumonia to lobar pattern (like strep) Enteric Pneumonia Aspirated from oropharynx Serratia Ocassional abscesses Low Body Temp (Hospital-Acquired) Klebsiella has an antiphagocytic capsule Enterobacter High or Low Body Temp with productive cough Focal Abscesses Staphylococcal Pneumonia Staph aureus Bronchopneumonia to lobar pattern Abscesses Aspirated from oropharynx or from bacteremia (Hospital-Acquired) Drug Use, IV, Wounds, Endocarditis PMN rich exudate Insidious: Fever, Tachycardia, ? Resp Rate Patchy or diffuse Pneumocystis cariniii Pneumocystis Pneumonia Beefy Red Airless Lungs Often a coexistant infection is seen (CMV) AIDS (Immunocompromised Pneumonia) Foamy Alveolar Space (filled with debris & bugs) Most common cause of death in HIV patients Children with protein malnutrition Hyaline Membranes & Interstitial Infiltrate Patchy or Diffuse Infiltrate CMV CMV Pneumonia Intranuclear Inclusions Immunosuppressd Usually coexists with PCP in AIDS patients, but not BM Transplant (Immunocompromised Pneumonia) Minimal Interstitial Inflammation Neonates Hyaline Membranes & Proteinaceous Fluid Granulomatous or Airless (If Compromised) Histoplasmosis Pneumonia Inhalation of organism from contaminated soil (bird droppings) Histoplasma capsulatum Show up on silver stain (Immunocompromised Pneumonia) Attaches to integrin receptors on macrophages Fever, Weight Loss, Night Sweats Blood Pathology Disease Cause/Risk Factors Symptoms Buzzwords Other Variation in size Anisocytosis Sideroblastic Anemia Increased RDW Small Cells Iron Deficiency Anemia Microcytosis Low MCV Thalassemia Hypochromic Folate & B12 Deficiencies Alcoholism Large Cells Macrocytosis Hypothyroidism High MCV Post Chemotherapy Decreased hemoglobin Iron Deficiency Anemia Hypochromia Increased zone of central pallor Thalassemia Usually microcytic Increased Hemoglobin Hyperchromasia Spehrocytosis Increased MCHC Henolysis Blue Reticulocytes (Wright’s Stain) Polychromasia Blood Loss Basophilic stippling in reticulocytes Ovalocyte Normal (< 10% of blood) Variation in shape = oval (Poikilocytosis) B12 & Folate Deficiency Normal (< 10% of blood) Elliptoocyte Heriditary Elliptocytosis Variation in shape = elliptical (Poikilocytosis) Iron Deficiency, Thalassemia Hemoglobinopathies Thalassemia Hemoglobinopathies Target Cells Iron Deficiency Liver Disease causes lipid metabolism abnormalities Obstructive Liver Disease Splenectomy Heriditary Spherocytosis Lack biconcave shape & central pallor Spherocytes Defect in internal support proteins in hereditary condition Warm antibody immune hemolysis Increased MCHC Fibrin Strand Damage Heart Valve Replacements Schistocytes Cell fragments AKA Helmet Cells Microangiopathic Hemolytic Anemia DIC, Burns Hyperosomolarity Irregular Margin Echinocytes Renal Failure Bumpy surface Blood Pathology (contd) Disease Cause/Risk Factors Symptoms Buzzwords Other Liver Disease Acanthocytes Abetalipoproteinemia Spicules with bulbous ends Post-SPlenectomy Myeloproliferative Disease Dacrocytes Megaloblastic Anemia Teardrop shape (Teardrop cells) Thalassemia Drepanocytes Hemoglobin S (Sickle Cells) Decreased O2 or pH Splenectomy Megaloblastic Anemia Remnants of nuclear chromatin Howell-Jolly Bodies Abnormal Erythropoeisis Single Marginal Clump Hemolytic Anemia G6PD Deficiency Fragments of denatured hemoglobin Heinz Bodies Toxin Damage Single Marginal Clump Lead Poisoning Basophilic Stippling Thalassemia Excess Iron Pappenheimer Bodies Splenectomy Sideroblastic Anemias Erythroblastosis Fatalis Normoblasts Normal in newborn Space Occupying Marrow Lesions Rouleaux Formation Multiple Myeloma Increased Plasma Protein Blackfan Diamond Syndrome Pure Red Cell Aplasia Bleeding Tendency Bernard-Soulier Syndrome Genetic (AD) Deficiency of GP Ib Receptors Large platelets with thrombocytopenia Absence of platelet aggregation Glanzmann’s Thrombasthenia Genetic (AD) Deficiency of GP IIb/IIIa Receptors Minimal Bruising to Severe Hemorrhage Blood Pathology (contd 2) Disease Cause/Risk Factors Symptoms Buzzwords Other Mild to moderate bleeding diathesis Storage Pool Deficiency Genetic Deficiency of Dense Granules (ADP & Serotonin) Impaired aggregation More Common Type Hemophilia A Favtor VIII Deficiency (X-Linked) Intrinsic Pathway Deficiency – Abnormal APTT APTT of 50-65 sec = moderate (Classical Hemophilia) Mutation (30%) 20% develop IgG4 antibodies Rx: 1 unit of VIII = 2% increase for 11 hours (minimal = 30%) Can also use Desmopressin, E-Aminocaproic and Tranexamic Acid Hemophilia B Favtor IX Deficiency (X-Linked) Intrinsic Pathway Deficiency – Abnormal APTT Rx: 1 unit of IX = 1% increase for 22 hours (minimal = 30%) (Christmas Disease) Mutation (30%) 20% develop IgG4 antibodies Muco-cutaneous bleeding Type 1 Von Willebrand Disease Genetic (AD – low penetrance) ? VWF activity & antigen ? Factor VIII No HMW VWF Moderate ? Factor VIII & VWF Antigen Type 2a Von Willebrand Disease Genetic (AD) Impaired polymerization & cytoplasmic retention or ? degradation Severe ? VWF Activity Bleeding from defect in 1º Hemostasis No HMW VWF Increased affinity of HMW VWF to GP1b receptors & clearance Type 2b Von Willebrand Disease Genetic (AD) Grossly abnormal PFA-100 test Increased affinity of platelets for ristocetin (VEF:RCof) Moderate ? VWF Activity & Antigen Normal VWF lefels Type 2M Von Willebrand Disease Decreased platelet directed function of VWF Normal level of Factor VIII Mimics Mild Hemophilia A Decreased affinity of VWF for Factor VIII Type 2N Von Willebrand Disease Genetic (AR) Facotr VIII levels of ~10% Inability of VWF to bind and stabilize Factor VIII Normal levels of VWF Abnormal PFA-100 Prolonged APTT due to ? VIII Type 3 Von Willebrand Disease Genetic (AR) Absent VWF synthesis in megakaryocytes & endothelium Bleeding from mucous membranes Bleeding into muscles & joints Variable Factor XI Deficiency Ashkenazi Jews Prophylactic transfusions with antifibrinolytic therapy for surgery Assymptomatic to Transfusions Required Severe Bleeding Early in life Treat with plasma or cryo Factor XIII Deficiency Normal coagulation tests t of Factor XIII is ~ 8 days & prevents bleeding at 1% notmal 1/2 Intermittant Hemorrhage Afibrinogenemia Genetic (AR) Rx: Cryo PT, APTT, TCT all prolonged Blood Pathology (contd 3) Disease Cause/Risk Factors Symptoms Buzzwords Other Majority are assymptomatic Dysfibrinogenemia Genetic (AD) Abnormally functioning fibrinogen Fibrinogen doesn’t convert to fibrin Coagulation tests prolonged Antibodies to Factor VIII Aquired Hemophilia Autoimmune Rx: Immunosuppression Similar to Hemophilia A Rapid Clearance of VWF Aquired Type 3 VWD Autoimmune Antibodies to VWF Rx: Desmopressin (release of VEF from stores) 1) Stasis May cause Edema & congestion, Outcomes: Propagation, Embolization, Dissolution, Venous Thrombosis 2) Endothelial Damage Infarction or Embolization Organization, Recanalization 3) Hypercoaguable State Solid Tissue: Heart, Kidney, Spleen, etc Tissue is so dense that hemorrhage is minimal White Infarct Wedge Shaped Result from arterial occlusion Hemorrhagic Red Infarct Tissues where bleeding is profuse Wedge Shaped Septic Infarcts Abscess Formation Usually bacterial and embolic from valve vegetations Obstetric Complications (most) Microangiopathic Hemolytic Anemia Activation of coagulation casecade with microthrombi Disseminated Intravascular Infection Low platelets & coagulative factors (?PT & PTT) Ooozing Consumptive Coagulopathy Coagulation (DIC) Neoplasia Infarction Activation of fibrolytic pathway (? D DImers) Massive Tissue Injury Petichiae, Ecchymoses & Oozing Type 1: Absence of protein synthesis Genetic (AD) Thromboembolism (Types 1,2 & Homozygous 3) Type 2: Defect in enzyme binding domain Heriditary Deficiency of AT Pregnancy, Surgery, Juvenile onset with thrombosis in unusual sites Type 3: Defect in heparin binding domain Trauma, Infection Rx: Oral Anticoagulants Protein C is normally activated by Thrombomodulin/Thrombin Neonatal Purpura Fulminans APC normally cleaves VIIIa & Va Heriditary Deficiency of Protein C Genetic (AR) DIC Heterozygous patients at no increased risk Rx: Recombinant Protein C Two Types: 1) Free & Bound Reduced 2) Free Reduced Heriditary Deficiency of Protein S Genetic (AD) Thrombosis Carriers at risk Carriers at risk Decreased Sensitivity of Factor V to APC Factor V Leiden Mutation Genetic (AD) Replacement of Arginine by Glutamine Thrombosis Blood Pathology (contd 4) Disease Cause/Risk Factors Symptoms Buzzwords Other Prothrombin-Gene Mutation Increased level of prothrombin activity Guanine to Adenine mutation in 3’ UTR of Prothrombin gene (Prothrombin G20210A) Risk for venous thromboembolism Anemia, Hyperbilirubinemia, Siderosis Genetic (AR) Reticulocytosis, HSmegaly, PE, Priapism Sickle Cell Disease HbSS Homozygous Hemoglobin S Fever, Pain “Spiky head” XRay Benign Genetic (AR) Sickle Cell Trait Hematuria HbAS Heterozygous Hemoglobin S Crisis with extreme hypoxia Mild Hemolytic Anemia Homozygous Hemoglobin C Genetic (AR) Abdominal Pain HbCC Splenomegaly & Jaundice Benign & Assymptomatic Heterozygous Hemoglobin C HBAC Slight HbA2 & HbF elevations Hemoglobin SC Disease Similar to Sickle Cell Disease (less severe) Severe anemia in infancy Splenic Enlargement, Iron Overload, Early Death Thalassemia Major Requires lifelong blood transfusions Anisocytosis, Poikilocytosis, Microcytosis, Hypochromia, Target Cells & Polychromatophilia Moderate anemia Thalassemia Intermedia Thalassemic morphology No anemia or mild anemia Thalassemia Minor Thalassemic morphology Normal Thalassemia Minima Detected only by family studies