Path Ch 15 Lungs (678-720)
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Function: exchange of gases btwn inspired air & blood
Embryology: outgrowth from ventral wall of foregut
o Midline trachea lungbuds
 Right lung bud 3 branches (lobar bronchi). More vertical, in line with trachea:

ASPIRATED MATERIALS GET STUCK ON RIGHT
 Left lung bud 2 lobar bronchi
Anatomy
o Trachea BronchiBronchioles (lack of cartilage & submucosal glands in walls) terminal bronchioles
o Acinus= lung distal to terminale bronchiole. Spherical 7mm
 Respiratory bronchioles, alveolar ducts, alveolar sacs (alveoli, GAS EXCHANGE)
o Pulmonary lobule: cluster of 3-5 terminal bronchioles w/ appended acinus
 Architecture distinguishes forms of emphysema
Histology
o Vocal chords: stratified squamous epithelium
o Respiratory tree ( larynx, trachea, bronchioles): Pseudostratified tall, columnar, ciliated epithelium
o Bronchial mucosa: neuroendocrine cells granules:
 serotonin, calcitonin, gastrin releasing peptide (bombasin)
o Trachea & bronchi: mucous secreting goblet cells+ submucosal glands
o Alveolar walls: pores of Kohn (passage of bacteria & exudate bwn alveoli)**
o Surfactant= adjacent to alveolar cell membrane
Microscopic alveolar walls (Blood Air)
o 1) Capillary endothelium: lining anastomosing capillaries
o 2) Basement membrane & interstitial tissue: separate endothelium from alveolar lining epitheliu
 Thin alveolar septum=fused epithelium & endothelium
 Thick parts separated by pulmonary interstitium (elastic fibers, collagen, fibroblasts, SM, masts)
o 3) Alveolar epithelium: continuous layer of 2 cell types
 1) Type I pneumocytes (platelike)= 95% alveolar surface,
 2) Type II pneumocyte (rounded) Surfactant synthesis in Lamellar Bodies
 give rise to Type I pneumocytes= alveolar repair**
o 4) Alveolar macrophages: loosely attached to epithelial cells or free in alveolar spaces
 derived from blood monocytes
 filled with carbon & other phagocytized material
1) CONGENITAL ANOMALIES
 PULMONARY HYPOPLASIA (small lungs):
o Defective development: diminished weight, volume, acinar number
o From abnormalities compressing lung or impeding normal expansion in utero
 Diaphragmatic hernia, oligohydraminos
 FORGUT CYSTS
o Abnormal detachment of primitive foregut (Hilum or Mid-mediastinum)
o Bronchogenic cysts, lined by bronchial type epithelium
 PULMONARY SEQUESTRATION
o Lung tissue lacking connection to airway system
o Vascular supply from Aorta or branches (not pulmonary artery)
o Extralobar sequestration
 External to lungs, anywhere in thorax or mediastinum
 Infants= mass lesions, other congenital abnormalities
o Intralobar sequestration
 Lung parenchyma, older kids as recurrent localized infection/ bronchiectasis
2) ATELECTASIS (COLLAPSE)
 Incomplete lung expansion or collapse of previously inflated lung reduced oxygenation & infection risk
 1) Resorption atelectasis: *mediastum shift TOWARD collapsed lung*
o complete airway obstruction & oxygen resorption in dependent alveoli
o causes: excessive secretions (mucus plugs), foreign body aspirate, neoplasm
 2) Compressive Atelectasis: : *mediastum shift AWAY from collapsed lung*
o pleural space expanded by fluid (cardiac failure, neoplasm, aneurysm rupture) or air
 3) Contraction Atelectasis:
o local/ generalized fibrotic changes in lung/ pleura prevent full expansion
3) PULMONART EDEMA
 Cause:
o 1. (+) Hydrostatic pressure = Hemodynamic Edema
o 2. (+) capillary permeability (endothelial/ alveolar wall injury)= Alveolar Injury Edema
o 3) High altitude, CNS trauma= Unknown origin Edema
 Lungs become heavy & wet engorged capillaries. Alveolar spaces= granular pink precipitates
 Chronic= lungs brown & firm “Brown induration”:
o interstitial fibrosis & hemosiderin laden macrophages “heart failure cells”
 Pathogenesis: impaired respiratory function & infection risk
4) ACUTE LUNG INJURY (ALI) & ACUTE RESPIRATORY DISTRESS SYNDROME (ARDS)
 ALI: abrupt hypoxemia & diffuse pulmonary infiltrates in absence of cardiac failure ARDS: severe ALI
 Inflammation-associated (+) in pulmonary vascular permeability from cell death
o “Diffuse Alveolar Damage”
 Causes in lungs or systemic: infection, trauma, toxic exposure, pancreatitis, uremia, immune rxs
o “Acute Interstitial Pneumonia”: similar changes in absence of etiology
 Morphology:
o Acute: diffusely, firm, red, boggy, heavy, edema, hyaline membranes (necrotic debris, exuded protein)
o Organizing: granulation tissue (response to hyaline membranes), Type II pneumocyte hyperplasia
o Fatal cases= bacterial infection
 Pathogenesis:
o Cause: Compromised alveolar wall vascular/air interface from damaged epithelium
o Damage: Imbalance of pro- and anti- inflammatory mediators: NF-kB inflammation
 1) Macrophage activation neutrophil recruitment (Il-8) & activate endothelium (TNF, IL-1)
 2) Activated neutrophils aggregate in vasculature ROS/ lysozyme damage
 arachidonic acid metabolites (+) neutrophil aggregation
 3) (+) vascular permeability & loss of surfactant alveoli resistant to expansion
 coag dysregulation: (+) procoagulents, (-) anticoagulents
 Clinical
o ALI: Dyspnea & tachypnea cyanosis, hypoxemia respiratory failure
o Chest xray: diffuse bilateral infiltrates
o Pathogenic regions of consolidation & atelectasis interspersed with normal tissue
o Poorly aerated regions continue perfusing ventilation/ perfusion mismatch & hypoxemia
 Therapy
o Mechanical ventilation, treat underlying cause (infection) mortality=40% (sepsis, organ failure)
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ACUTE INTERSTITIAL PNEUMONIA
o Widespread Acute Lung Injury of unknown etiology, mostly aggressive course
o Mortality= 50% in first 1-2 months survivors= reoccurrence & chronic interstitial disease
5) OBSTRUCTIVE VS RESTRICTIVE PULMONARY DISEASE
o Chronic, non-infectious, diffuse pulmonary disease
o Obstructive: (+) resistance to airflow (trachea alveoli)
o Restrictive: (-) expansion of lung parenchyma (-) lung capacity
 Chest wall disorders (neuromuscular, obesity, pleural)
 Chronic interstitial & infiltrative disease
6) OBSTRUCTIVE PULMONARY DISEASE (Emphysema, Chronic bronchitis, Asthma, Bronchiectasis)
o COPD= emphysema + chronic bronchitis (overlapping damage, from smoking), can be reversible
o Asthma= differentiated by reversible bronchospasm, but can develop irreversible components
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EMPHYSEMA
o Characteristics:
 Irreversible enlargement of airspaces distal to terminal bronchioles
 Alveolar wall destruction + fibrosis
o Anatomic classifications:
 1) Centriacinar (centrilobular)
 Destruction/ enlargement of central/close respiratory unit (acinus), sparing distal alveoli
 upper lobes, apices. Heavy smokers, associated with chronic bronchitis
 2) Panaciner (panlobular) emphysema
 uniform destruction/ enlargement of acinus lower basal zones
 associated a1-antitrypsin deficiency
 3) Distal acinar (paraseptal) emphysema
 distal acinus, near pleura & adjacent to fibrosis/ scars
 underlying lesion in spontaneous pneumothorax
 4) Airspace enlargement w/ fibrosis (Irregular Emphysema)
 irregular acinar involvement, associated with scarring
 asymptomatic, clinically insignificant
o Pathogenesis:
 Imbalanced pulmonary protease & inhibitors + oxidents vs anti-oxidentsAlveolar wall destruction
 1) Hereditary: A1- antitrypsin deficiency and other protease inhibitors
 2) Tobacco smoking
o Activates inflammatory cells. Nicotine=chemoattraction. (NF-kB ROS)
o Neutrophil release of cellular protease (elastase, proteinase 3, cathepsin G)
o Enhanced macrophage elastase activity (not inhibited by a1-antitrypsin)
o A1-antitrypsin inactivation (oxidants & ROS)
o Reduces antioxidant (superoxide dismutase, glutathione) via ROS
 3) loss of alveolar tissue (-) radial traction bronchial collapse (expiration)obstruct
 4) small airway inflammation (T & B lymphocytes) goblet cell metaplasia + mucous plug
o fibrosis brochiolar wall thickening SM hyperplasia obstruction
o Morphology
 Lungs voluminous, overlap heart
 Alveolar spaces enlarged, separated by thin septa, septal capillaries compressed & bloodless
 Alveolar wall rupture large air spaces (blebs, bullae)
o Clinical course
 3rd of pulmonary parenchyma lost: Dyspnea, wheezing, cough, severe weight loss
 barrel chested prolonged expiration (Spirometry= key diagnosis)
 over ventilation to compensate for loss of parenchyma
 well oxygenated at rest “pink puffers”
 poor prognosis: pulmonary hypertenstion + heart failure
 Death: Respiratory Acidosis, Right sided heart failure, Massive pneumothorax
o Other forms:
 1) Compensatory Hyperinflation: of remaining lung after parenchyma loss (lobectomy)
 No septal wall destruction
 2) Obstructive Overinflation: subtotal airway obstruction  ball valve traps air on EXPIRATION
 3) Interstitial emphysema: alveolar tears air into CT of lung, mediastinum, subcutaneous tissue
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CHRONIC BRONCHITIS
o Persistent cough w/ sputum for 3 months in at least 2 consecutive years (absence of cause)
o Pathogenesis:
 Chronic irritation of airways by inhaled substance (tobacco smoke)
 Mucous gland hypertrophy mucous hypersecretion (neutrophil proteases)
 Globlet cell metaplasia (bronchial epithelium) mucous & airway obstruction
 Bronchiolitis + Wall thickening (fibrosis), smooth muscle hyperplasia
 Secondary infections
o Morphology
 Hyperemia, mucous membrane edema
 Mucous fills airways
 Mucous gland hyperplasia= MAJOR CHANGE measure thicknessvia “Ried index”
 Inflammation, fibrosis obstruction (bronchiolitis obliterans)
 Epithelium squamous metaplasia & dysplasia
o Clinical
 Defining cough & sputum production
 Dyspnea on exertion, hypoxic, cyanotic, hypercapnic (retain CO2)= “blue bloaters”
 Death= Cor pulmnoale + heart failure, infection
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ASTHMA
o Chronic relapsing inflammatory disorder
o paroxysmal reversible bronchospasm (SM hyperactivity), (+) mucous production
o 2 types:
 1) Atopic (Allergic) asthma MOST COMMON: Type I (IgE)- mediated hypersensitivity. Family history
 2) Nonatopic Asthma: triggered by resp. infections, irritants, drugs. No Family history
 viral/chemical irritation & inflammation reduced threshold for vagal stimulation
o Inducing Drugs: NSAIDs (inhibit cyclooxygenase brochoconstrictor leukotrienes)*
o Pathogenesis:
 overproduction of TH2 IgE + eosinophils. Repeat antigen exposure:
 1) Acute phase: Antigen binds IgE mast cells 1o (leukotriene) & 2o (cytokine) mediators
o Bronchospasm, edema, mucus, leukocyte recruitment
 2) Late phase: recruited leukocytes bronchospasm, edema, infiltration, epithelial damage
 3) Repeated boats= airway remodeling* +SM & mucus gland hypertrophy/ hyperplasia
o vascularity, deposition of subepithelial collagen
o Genetics:
 Susceptibility to environmental factors
 Primary, secondary immune response, tissue remodeling, therapy reponse
 HLA, IL-13, CD14, ADAM-33 (SM & fibroblast proliferation), B2-adrenergic receptor (airway rx), IL-4
o Morphology
 Lungs overinflated: patchy atelectasis, mucus plugging
 Edema, bronchiolar infiltraes (eosinphils), fibrosis, SM & gland hypertrophy
 Whorled mucous plugs (Curschmann spirals)
 Crytalloid esosinophil granule debris (Charcot- Leyden crystals)
 Airway remodeling: Fibrosis, thickening, vascularity, gland metaplasia, SM hypertrophy
o Clinical
 Attacks last several hours: chest tightness, wheezing, dyspnea, cough
 Status asthmaticus (severe): lasts days weeks, obstruction cyanosis & death
o
BRONCHIECTASIS
o Abnormal permanent airway dilation from destructive necrotizing infection of bronchi & bronchioles
 Hereditary: Cystic fibrosis, Kartagnener syndrome, pulmonary sequestration
 Post infectious state: after necrotizing bacterial, viral, fungal pneumonia
 Bronchial obstruction: tumor, foreign body
 Chronic inflammation: RA, transplants, allergic bronchopulmonary aspergillosis
o Pathogenesis:
 Obstruction  impedes normal clearance infection & inflammation tissue destruction
o Morphology:
 Peripheral lower lobes (severe changes) airway dilation 4x
 Mild necrotizing acute & chronic inflammation + fibrosis
o Clinical: persistent, severe cough, fever, purulent sputum (from upper resp tract infection)
 Coughing associated w/ waking up & position changes. Cor pulmonale, brain abscess, amyloidosis
7) CHRONIC DIFFUSE INTERSTITIAL (RESTRICTIVE) DISEASE
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Heterogenous group with: inflammation, pulmonary interstitial tissue fibrosis of alveolar walls. Unknown causes
Clinical/functional changes= restrictive lung disease: compromised diffusing capacity, lung volumes, compliance
o No evidence of airway obstruction**
Long term: secondary pulmonary hypertension, cor pulmonale
Morphology: initially differentiated end-stage parenchymal destruction & scarring: honey-comb lung****
A) FIBROSING DISEASE
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IDIOPATHIC PULMONARY FIBROSIS
o Progressive pulmonary interstitial fibrosis. Unknown cause.
o Pathogenesis:
 repeated epithelial activation/ injury abnormal “wound healing” TGF-B1  fibrosis & apoptosis
o Morphology:
 Fibrosis pattern= usual interstitial pneumonia (UIP). Nonspecific, seen in CT disorders
 Patchy interstitial fibrosis: subpleural, interlobal septal distribution, lower lobe
 Heterogenous change: new, cellular fibroblastic foci + older fibrotic areas
 HONEY COMB LUNG**: destroyed alveolar architecture, dense fibrosis, cystic spaces
o Lined by Hypoplastic Type II pneumocytes or bronchiolar epithelium
o Arteriolar hypertensive changes
o Clinical
 Insidious onset (ages 40-70)
 Dyspnea on exertion, dry cough, progression to hypoxia, cyanosis (despite anti inflam. therapy)
 Survival= <3 yrs lung transplant= only therapy
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NONSPECIFIC INTERSTITIAL PNEUMONIA (NSIP)
o Diffusely fibrosing diease: chronic dyspnea & cough (age 50). Unknown cause
o Moderate inflammation, interstitial fibrosis w/out temporal heterogeneity in UIP. Better prognosis than UIP)
 Cellular & fibrosing patterns
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CRYPTOGENIC ORGANIZING PNEUMONIA (COP)
o AKA “BOOP” (Bronchiolitis obliterans organizing pneumonia). Unknown cause
o Presentation: cough, dyspnea, patchy subpleural/ peribronchial consolidation
o Morphology: loose fibrous tissue plugs “ MASSON BODIES”* in bronchioles, ducts, alveoli
 Same morphology from infections or inflammatory lung injury
o Clinical: spontaneous recovery or steroid therapy
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PULMONARY INVOLVEMENT IN CT DISEASE
o Ex: Systemic Lupus erythamosus, RA, scleroderma
o Patterns include: NSIP, UIP, vascular sclerosis, organizing pneumonia, bronchiolitis
o Variable prognosis, better than idiopathic UIP
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PNEUMOCONIOSES
o Non-neoplastic lung response to inhaled aerosols: mineral dust, organic dust, fumes, vapors
o Pathogenesis
 Amount of dust retained: original concentration, exposure duration, clearance
 Size, shape, particle buoyancy: small particles (1-5um) most dangerous settle in terminal alveoli
 Reactivity (toxicity) & particle solubility: highly soluble= toxic insoluble= chronic fibrosis
 Other irritants: Smoking
o Coal workers pneumoconiosis (CWP)****
 Asymptomatic anthracosis CWP (no significant dysfunction) PMF (progressive massive fibrosis)
 Progression dependent of duration, exposure, contaminants, fibrogenic cytokine production
o Morphology:
 Anthracosis: macrophages take up inhaled carbon accumulate in lymphatics & lymph tissue
 Simple CWP: 1-2mm coal macules (dust filled macrophages), larger coal nodules (collagen),
 PMF: large, blackened collagenous scars (central ischemic necrosis) replace lung portions
o Clinical:
 CWP= little functional abnormality,
 PMF (10%)= respiratory insufficiency, pulmonary hypertension
o
Silicosis
 Prolonged inhalation of silica particles chronic, progressive nodular fibrosis
 Pathogenesis: crystalline silica ingested by macrophages oxidants, cytokines, GFs, collagen
 Morphology:
 collagenous nodules in upper lung (large & diffuse as disease progresses
 lesion coalescence large dense scar
 calcification/blackening by coal dust
 hyalinized whorls of collagen + scant inflammation
 polarized light: birefringent silica particles*
 Clinical:
 Progressive massive fibrosis= dyspnea (can progress after exposure ends)
 (+) TB risk (depressed cell-mediated immunity)
o
Abestos-Related Disease
 Fibrous silicates. Occupational exposure:
 Localized pleural plaques, effusions, diffuse pleural fibrosis
 Parenchymal interstitial fibrosis (asbestosis)
 Lung cancer, malignant mesothelioma, laryngeal/ extrapulmonary neoplasm
 Pathogenesis:
 Straight, stiff amphiboles: readily reach deep lung  (+) pathology
 Curved serpentine fibers: more soluble, leached from tissue
 Morphology:
 Pleural plaques of dense collagen (rare in absence of asbestos exposure)
 Asbestosis: marked diffuse interstitial fibrosis.
o ASBESTOS BODIES**: ingested fibers coated by iron protein material
 Beaded, dumbbell shaped fibers
 From attempted macrophage endocytosis
 Similar iron encrustation in other particles= Ferruginous bodies
 Clinical
 Asymptomatic plaques
 Asbestosis: dyspnea productive cough (10-20 year lag)
 Advanced: honeycombing=static or respiratory failure/ cor pulmonale
 Bad prognosis: malignancy complication
 Therapy Complications:
 1) Drug-induced: acute bronchospasm (Aspirin)pneumonitis (Amiodarone)
 fibrosis (Bleomycin)
 2) Radiation-induced (10-20%):
o Acute radiation pneumonitis & DAD (1-6 months after therapy)
o May resolve with steroid therapy
o Progression to chronic fibrosis
B) GRANULOMATOUS DISEASE
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SARCOIDOSIS
 Systemic, unknown cause. Non caseating granulomas in all tissues (90% hilar lymph nodes, lungs)
 Women, African Americans
 Pathogenesis:
 Disordered immune response to environmental agents (genetically predisposed)
o HLA-A1, HLA-B8
o Accumulated oligoclonal activated CD4+ T cells
o (+) TH1 cytokine production (IL-2, IFN-y) T cell expansion, macrophage
activation
o (+) macrophage TNF granuloma formation
o cutaneous anergy (lack of rx) to common antigens (tuberculin, candida)
o polyclonal hypergammaglobulinemia
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Morphology
 Granulomas:
o Noncaseating w/ tightly clustered epitheloid histiocytes
o Multinucleated giant cells
o Schaumann bodies (laminated, calcified protinaceous concretions)
o Asteroid bodies (stellate inclusions in giant cells) not pathogenic
 Lungs:
o diffuse, scattered granulomas (reticulonodular pattern x-ray)
o lesions heal into residual hylanized scars
 Lymph nodes:
o Always involved. Hilar & mediastinal regions, tonsils (25% cases)
 Spleen/Liver:
o Microscopically 75%. Splenomegaly, hepatomegaly= 20%
 Bone marrow: 20%. Lesions visible on x-ray. Favors phalanges
 Skin: 50%.
o Subcutaneous nodes, erythematous scaling plaques/ macules. Mucous m. lesions
 Eyes: 50%. Iritis, iridocyclitis, choroid retinitis.
o lacrimal gland inflammation, reduced lacrimation
o Salivary gland Mikulicz syndrome*
Clinical
 Variable severity, different patterns of organ involvement. possible asymptomatic
 Isolated cutaneous/ ocular lesions, peripheral lymphadenopathy, hepatosplenomegaly
 Unpredicatable course: slowly progressive, remitting, relapsing
o 70% recover, 20% permanent lung/ eye lesion, 15% die of fibrosis
 Presentation: insidious respiratory difficulty, fever, night sweats, weight loss
Diagnosis:
 Biopsy = non caseating granulomas
 Diagnosis of exclusion* rule out other diseases by culture
HYPERSENSITIVITY PNEUMONITIS
 Immunology mediated from inhaled dust/ antigens
 “Allergic alveolitis”: mainly affects alveoli
 Farmers lung: actinomycetes spores in hay
 Pigeon breeders lung: protein from bird feathers or excreta
 Humidifier/ air conditioner lung: bacteria in heated water reservoirs
 Morphology
 Interstitial pneumonitis, bronchiole fibrosis, noncaseating granulomas
 Early cessation of exposure prevents progression to chronic fibrosis & honey combing
 Clinical:
 Cough, dyspnea, fever, diffuse/nodular densities (xray), restrictive pulmonary dysfunction
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PULMONARY EOSINOPHILIA
o Diverse conditions w/ interstitial or aveolar eosinophil infiltrates:
 Acute eosinophilic pneumonia + respiratory failure: rapid onset fever, dyspnea, hypoxia
 Quick response to corticosteroids
 “Loeffler syndrome” (Simple pulmonary eosinophilia): transient infiltrates, eosinophilia (blood/lung)
 Tropical eosinophilia: microfilariae
 Secondary eosinophilia: induced by infection, hypersensitivity, asthma, allergic aspergillosis
 Idiopathic chronic esoinphilic pneumonia: focal lung consolidation, infiltration, steroid responsive
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SMOKING RELATED INTERSTITIAL DISEASE
o Desquamative interstitial pneumonia (DIP)
 Presentation: Insidious dyspnea, dry cough, emphysema (improved with steroids)
 Morphology: intra-alveolar dusty brown (smokers) macrophages + mild inflammation and fibrosis
o
Respiratory Bronchiolitis-Associated Interstitial Lung Disease
 Presentation: Gradual, mild dyspnea & cough
 Morphology: patchy bronchiolar accumulations of smokers macrophages
 peribronchiolar inflammation +fibrosis (improves with smoking cessation)
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PULMONARY ALVEOLAR PROTEINOSIS (PAP) rare
o Surfactant accumulation in alveoli, bronchioles. 3 types, similar histology, different pathogenesis:
 1) Acquired (90%): autoantibodies against GM-CSF (macrophages)impaired surfactant clearance
 2) Congenital: newborns, fatal. GM-CSF mutations in production/ signaling. Or surfactant mutations
 3) Secondary PAP: exposure to irritating dust/ chemicals. Or immunucompromised
o Clinical: respiratory difficulty, cough, abundant sputum= chunks of gelatinous material
 Risk of secondary infection*
o Morphology: dense, amorphous, periodic acid-schiff (PAS) positive, lipid -protein exudates (alveolar space)
DISEASE OF VASCULAR ORIGIN
o PULMONARY EMBOLISM, HEMMORHAGE, INFARCT
o Occlusions mostly EMBOLIC* . Thrombosis rare: pulm. Hypertension, atherosclerosis, heart failure.)
o DVT= 95% of pulmonary emboli. Prevalence of PE correlates w/ leg thrombosis predisposition
o Outcome depends on: obstruction, vessel size, # emboli, heart status, release of vasoactive factors (platelets)
o Pathogenesis:
 1) Respiratory compromise: lack of perfusion of ventilated lung
 2) Hemodynamic compromise: (+) pulmonary arterial resistance
o Clinical:
 1) Large emboli block major pulmonary arteries
 Saddle embolus*= block pulmonary artery bifurcation sudden death from:
o electromechanical dissociation (no blood in pulm. Circulation)
o cor pulmonale (right sided heart failure)
 2) Multiple small/medium emboli= clinically silent, transient chest pain, hemoptysis from hemmg.
 3) Multiple small PE= uncommon pulmonary hypertension, vascular sclerosis, cor pulmonale
 Only 10% PE= infarct: in pts w/ cardiac failure. Peripheral wedge shaped hemorrhagic necrosis*
o
PULMONARY HYPERTENSION
o Pulmonary pressure= 25% of systemic levels. Causes:
 Chronic obstructive/ interstitial lung disease
 Congenital/acquired heart disease + left sided heart failure
 Recurrent PE, CT disease
 Obstructive sleep apnea, idiopathic/ familial (rare)
o Pathogenesis:
 1) Familial: mutations in BMPR2SM hyperplasia & (+) vascular resistance
 influenced by environmental triggers & modifier genes that affect vascular tone
 2) Secondary forms: endothelial dysfunction (+) vascular tone, thrombosis, cytokine production
o Morphology:
 Atherosclerosis in pulmonary artery & branches
 Medial Artery hypertrophy ( muscular/ elastic )
 Right Ventricular hypertrophy
 Plexiform lesions (tufts in capillary channels)= severe disease**
 Primary Pulm. Hypertension & congenital cardiovascular abnormalities
 Numerous organized thrombi= Recurrent pulmonary thromboembolism
o Clinical
 Symptoms only in advanced disease*
 Idiopathic forms= women age 20-40: progresses to resp. insufficiency, decompensated cor
pulmonale, death in 2-5 yrs
o Therapy: vasodilators & lung transplant
o
DIFFUSE PULMONARY HEMORRHAGE SYNDROMES
o Goodpasture Syndrome
 Pathogenesis:
 1) Autoantibodies against collagen IV a3 chain
 2) Basement membrane destruction (renal glomeruli, pulmonary alveoli)
 3) Glomerulonephritis & necrotizing hemorrhagic interstitial pneumonitis
 Morphology:
 focal alveolar wall necrosis, intra-alveolar hemorrhage, hemosiderin laden macrophages
 immunofluorescence: linear immunoglobulin deposition (septal BM)
 Clinical: Hemoptysis*, symptoms of glomerulonephritis. Uremia=death. Male smokers, adolescents
 Therapy: plasmapheresis, immunosuppresion
o
Idiopathic Pulmonary Hemosiderosis
 Rare childhood disease: cough & hemoptysis*
 Intermittent diffuse alveolar hemorrhage. Immune case (immunosuppression helps)
o
Wegener Granulomatosis
 Autoimmune disease presents with hemoptysis
 Capillaritis & scattered, poorly formed granulomata
PULMONARY INFECTIONS
 Impaired lung/ systemic defense: nasal, bronchial, alveolar filter, neutralize, clearance of inhaled particles
o (-) cough reflex aspiration (coma, anesthesia, neuromuscular disorder)
o injury of mucocilia (smoking, viral infection, genetic defect)
o Secretion accumulation (cystic fibrosis, chronic bronchitis)
o (-) phagocytic/ bactericidal function of alveolar macrophages (smoke, oxygen toxicity)
o Edema, congestion (CHF)
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“PNEUMONIA”= any infection of lung parenchyma
o 1 type (viral) leads to 2nd type (bacterial) due to compromised body
o most begin in respiratory tract spread in blood
o common in pts with terminal illnesses when hospitalized (Nosocomial infections)
 antibiotic resistance, invasive procedure, contamination, exposure
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COMMUNITY-AQUIRED ACUTE PNEUMONIA
o Risks: age, chronic disease, immune deficiency, lack of splenic function
o Bacterial or viral :
 1) Strep pneumonia** (pneumococcus): MOST COMMON CAUSE
 2) H. Influenzae:
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pleomorphic gram (-), encapsulated & uncapsulaed, colonizes pharynx
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life threatening lower resp. tract infection, meningitis (kids), adults with COPD
 Type b serotype= most common encapsulated severe invasive disease
 Virulence: adhesive pili (prevents ciliary beating), protease that degrades IgA
 3) Moraxella catarrhalis:
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bacterial pneumonia (elderly)
 exacerbates COPD, common cause of pediatric Otis media*
 4) Staph Aureus:
 complicates viral illness, risk of abscess formation, empyema*
 IV drug users= endocarditis risk
 5) Klebsiella pneumonia:
 MOST COMMON CAUSE GRAM (-) PNEUMONIA*
 Chronic alcoholics at risk
 6) Pseudomonas aeruginosa:
 nosocomial infections: cystic fibrosis, Neutropenic pts
 invades blood vessels spread systemically
 7) Legionella pneumonophilia (Legionnaires’ disease, Pontiac fever)
 artificial aquatic environments (water-cooling towers)
 Aerosolization spread
 Severe pneumonia in immunocompromised
o Morphology:
 Bronchopneumonia: (patchy exudative consolidation of lung parenchyma)
 Focal palpable consolidation
 Acute suppurative exudation fills bronchi, bronchioles, alveoli (resolves)
 Pleuritis fibrous thickening + adhesions. Empyema (infection in pleural space)

Lobar pneumonia (entire lobe)
 1) Initial congestion (vascular engorgement, alveolar transudates)
 2) Red hepatization (massive neutrophilic exudation + hemorrhage looks like liver)
 3) Gray hepatization (RBC disintegration, fibrinopurulent exudate)
 4) Resolution (enzymatic digestion of exudates, macrophages eat debris, fibroblast ingrowth
o restores normal lung structure/function + fibrous scars
o
Clinical
 High fever, rigors, productive cough, hemoptysis
 Pleural involvement= Friction rub, pleuritic chest pain
 Complications: abscess, systemic dissemination endocarditis, meningitis, suppurative arthritis

COMMUNITY-AQUIRED ATYPICAL (VIRAL & MYCOPLASMAL) PNEUMONIAS
o Range form mild upper tract (cold) severe (lower trac)
 Mycoplasma Pneumonia, C. pneumonia/pisttaci/ trachomatis, Coxiella burnetti (Q fever)
o Pathogenesis:
 Attachment to epithelial cells necrosis & inflammation
 Alveoli fluid transudation
 Upper airways: loss of mucociliary clearance secondary bacterial infection
o Morphology:
 Patchy, lobar congestion WITHOUT consolidation like bacterial pneumonias (hence, ATYPICAL)
 Interstitial pneumonitis : widened, edematous alveolar walls + inflammation
 Hyaline membranes= DAD

INFLUENZA INFECTIONS
o SINGLE STRANDED RNA: 8 strands bound by nucleoprotein determines type: A,B,C
 Type A: major epidemic thru viral mutation
 Type B & C: don’t mutate. Childhood infections= lifelong protection
o Surface: lipid bilayer + hemagglutinin (H1, H2, H3) or neuraminidase (N1, N2)= subtype
 Antibodies to N subtype prevent future infection**
o Pathogenesis:
 “Antigenic drift”: mutations in hemoagglutinin or neuraminidase
 pandemics= both antigens replaced + RNA recombination
 avian H5N1: cannot be confined to lung** activated by many tissue types
 other viruses cleaved only in lung
o Host defense: cytotoxic T cells, innate immune response (Mx1= macrophage anti-influenza protein)

HUMAN METAPNEUMOVIRUS (MPV)
o Paramoxyovirus 2001 bronchiolitis, pneumonia in very young, very old, immunocompromised
o 20% peds outpatient visits for acute respiratory tract infection

SEVERE ACUTE RESPIRATORY SYNDROME (SARS)
o Coronavirus 30% upper respiratory tract infections. SARS differs: infects lower tree systemic
o Transmission= respiratory secretions
o Presentation: dry cough, malaise, myalgias, fever
o Clinical: 1/3 recover, rest progress, 10% die (DAD + multinucleated giant cells)

ASPIRATION PNEUMONIA
o Debilitated/ unconscious patients chemical (gastric acid) + bacterial (oral flora)
o Necrotizing fulminant course, lung abscess common

LUNG ABSCESS
o Localized suppurative lung necrosis
o Pathogenesis:
 Mixed infections common: Staph, strep, gram (-) species, aenerobes. Abscesses:
 Aspiration of infective material: most common in R lung (vertical)
 Antecedent primary bacterial infection
 Septic emboli from infected thrombi or right-sided endocarditits
 Obstructive tumors (15%)
 Direct traumatic puntures, Spread from adjacent organs
o Morphology
 Single/ multiple , microscopic large cavities
 Pus + air depending on drainage
 Chronic abscesses surrounded by reactive fibrous wall
o Clinical:
 Extension into pleural cavity, hemorrhage, septic embolization, secondary amyloidosis

CHRONIC PNEUMONIA
o Localized granulomatous inflammation in immunocompromised (possible lymph node involvement)
o Cause: TB, fungal infections
o Clinical: Asymptomatic limited disease, Risk of dissemination fulminant (immunocomp)
o Fungal infections:
 Histoplasmosis (Histoplasma Capsulatum) Ohio, Mississippi Rivers, Caribbean basin
 Intracellular macrophage parasite
 Morphology: Granulomas + coagulative necrosis fibrosis + concentric calcification
 Diagnosis: Silver stain 3-5 um THIN* walled fungal cysts
 Blastomycosis (Blastomyces dermatidis) central, southeast US, Canada, mexico
 Pulmonary, disseminated, cutaneous (rare) suppurative granulomas
 Diagnosis: 5-15um THICK*-walled yeast, divides by budding
 Coccidioidomycosis (Coccidioides immitis) Southwest, Western US and Mexico
 80% regional population= delayed type hypersensitivity
 pyogenic granulomatous
 diagnosis: 20-60 um THICK walled SPHERULE w/ small ENDOSPORE

PNEUMONIA IN IMMUNOCOMPROMISED
o Opportunistic infections= lifethreatening. More than one agent involved
o bacteria: Pseudomoas, mycobacteria, legionella, listeria
o viral: CMV, herpesvirus
o fungi: Pneumocystis, Candida, Aspergillus

PULMONARY DISEASE IN HIV
o More than one cause, atypical symptoms
o Absolute CD4+ T cell count defines infection risk with specific organisms:
 200+:
Bacteria, TB
 50- 200: Pneumocystis
 <50:
CMV, mycobacterium avian (MAC)
o pulmonary disease from Kaposi sarcoma, lymphoma, lung cancer

LUNG TRANSPLANT
o Indications: Emphysema, idiopathic pulmonary fibrosis, cystic fibrosis, primary pulmonary hypertension
o Complications: infection (immunosuppression), acute rejection (infiltrates),
chronic rejection + fibrotic occlusion (bronchiolitis obliterans)
o Survival: 1 yr= 78%, 5 yrs= 50%, 10 yrs= 26%