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113 Cards in this Set

  • Front
  • Back
  • 3rd side (hint)
List pulmonary congenital malformations
• Tracheobronchial malformations (laryngeal web, TE fistula, tracheal stenosis/ atresia)
• Pulmonary sequestration (intra- and extra-lobar)
• Bronchogenic cysts
• Congenital lobar/ lobular emphysema
• Congenital cystic adenomatoid malformation/ aka congenital pulmonary airway malformation
• Cystic fibrosis
• Bronchopulmonary dysplasia
• Agenesis/ Hypoplasia
Tracheoesophageal fistula
Incomplete division of foregut into respiratory and digestive portions
5 types:

• Focal esophageal atresia: proximal esophagus ends as blind pouch and distal arises from trachea above bifurcation (85%).
• Both esophageal segments are blind pouches (8%)
• Both trachea and esophagus are complete, but connected at level of bifurcation (4%)
• Focal esophageal atresia: proximal esophagus connects to trachea at level of bifurcation; distal arises as blind pouch.
• Focal esophageal atresia: both proximal and distal esophageal segments communicate with the trachea.
PO- not there
Essentials- not there
Tracheal stenosis/ atresia
• Rare.
• Usually associated with some tracheoesphageal fistula
PO- not there
Essentials- not there
Laryngeal web
• Incomplete recanalization of larynx during wk 10.
• Membranous web forms at level of vocal cords, partially obstructing the airway
PO- not in pulmonary
Robbins- not in pulmonary
Essentials- not in pulmonary
Pulmonary sequestrations
• Partial or complete separation of lobe from surrounding lung; sequestered segment has no connection to main bronchial tree.
• Blood supply from aorta, not pulmonary arteries
• 20% have histology of congenital cystic adenomatoid malformation
• 2 types: extrapulmonary & intrapulmonary
Wegener's granulomatosis
• Triad of necrotizing angiitis (small - medium vessels), aseptic necrosis of upper respiratory tract and lungs, focal glomerulonephritis (necrotizing and often crescentic).
• Rule out TB and fungi w/ special stains, culture.

Pathogenesis: may be a form of hypersensitivity. ?immune mediated?

• M>F
• All ages, most common > 45.
• Sx: persistent pneumonitis w/ bilateral nodular and cavitary infiltrates, chronic sinusitis, mucosal ulcerations of the nasopharynx, renal disease
• Untreated, malignant: 80-90% die in 1 year.

• c-ANCA (+) in 90% with active generalized disease; 40% in remission; 60% with limited disease.
• Monitor disease course w/ titers.
• CXray: waxing and waning of pulmonary infiltrates and nodules
• Dx: bx of upper airway or skin showing inflammatory change

Treatment: cyclophosphamide, TMP-SMX.

Gross: well circumscribed necrotizing lesions

• Multiple bilateral nodules of liquefactive and coagulative necrosis in lung-> large geographic lesions w/ eosinophils, giant cells
• Upper respiratory tract lesions: mucosal granulomas to ulcerative lesions of nose, palate, or pharynx, rimmed by necrotizing granulomas and vasculitis
• Poorly formed granulomas: Geographic necrosis, surrounded by lymphocytes, plasma cells, macrophages, and giant cells.
• Necrotizing vasculitis of small- medium vessels.
• All surrounded by fibroblastic proliferation w/ giant cells and leukocytic infiltrate in lungs.
• Renal: early- focal necrotizing glomerulonephritis; later- crescentic glomerulonephritis.

Fulminant type: predominantly exudative changes
Fibrous scar type: abundant collagen deposition
Limited Wegener’s: involvement restricted to respiratory tract
Systemic disease of unknown origin, characterized by noncaseating granulomas.
Dx of exclusion: no specific criteria for disease; culture and use special stains

Pathogenesis: disordered immune regulation in genetically predisposed individuals exposed to certain environmental agents….i.e., ?

Organs involved:
• Lungs: either no gross lesion or 1-2 cm nodules; often in bronchial submucosa, so biopsies are helpful
• Lymph nodes: hilar or mediastinal lymph nodes involved in almost all cases, tonsils involved in 25% of cases; nodes are enlarged, may be calcified
• Liver/spleen: microscopic involvement in 75% of cases, gross disease in 20%
• Bone: Xray changes in 20%, usually small bones of hands and feet
• Skin: involved in 30-50% with erythema nodosum; also mucus membranes
• Eye: iritis or iridocyclitis in 20-50%

• Presents as perihilar node involvement, diffuse pulmonary disease, pulmonary interstitial fibrosis, localized bronchial stenosis, distal bronchiectasis and atelectasis
• Usually 20-40 years, F > M, 90% are black
• 80% w/ high serum ACE; polyclonal serum hypergammaglobulinemia common.
• 65% recover without further problems; 20% have permanent pulmonary loss; 3% die of pulmonary fibrosis+ congestive heart failure.
• Prognosis: best- hilar lymphadenopathy alone; worst- pulmonary disease without adenopathy.
• Treatment: steroids for severe symptoms, advanced disease.

• Non-caseating epithelioid granulomas with tightly packed epithelioid cells, Langhans giant cells, lymphocytes (T cells), usually in interstitium adjacent to bronchioles and around and within vessel walls, pleura, connective tissue septa.
• May also be hyalinization, diffuse interstitial fibrosis, fibrinoid necrosis and fibrosis within granulomas, intra- and extracellular inclusions.
• Schaumann bodies: laminated concretions of calcium and protein
• Asteroid bodies: stellate inclusions within giant cells, in 60% of granulomas
• Neither is specific for sarcoid (also seen in berylliosis)
Allergic granulomatosis
Churg-Strauss syndrome
Very rare

Systemic vasculitis resembling polyarteritis nodosa associated with asthma, peripheral eosinophilia, pulmonary involvement, fever

Rarely presents without pulmonary disease as fever of unknown origin

Treatment: steroids (effective, but patients may relapse)

Micro: lung and extrapulmonary sites (skin, heart, nervous system, GI) have prominent eosinophilic infiltrate, granulomatous reaction around necrotic foci with radially arranged histiocytes and pallisading giant cells near small arteries or arterioles, eosinophilic vasculitis; may have fibrin-rich edema, lymphocytes, sarcoid-like granulomas, focal fibrosis, eosinophilic microabscesses

DD: Wegener’s (also kidney involvement, no tissue or serum eosinophilia or asthma), rheumatoid nodules (no tissue or serum eosinophilia or asthma)
Necrotizing sarcoid granulomatosis
• ?? May be a form of nodular sarcoidosis, cross between sarcoid and Wegener’s or discrete entity.
• May be localized or diffuse.
• Usually women, often with mild or no symptoms.
• Excellent prognosis.
• Treatment: steroids and immunosuppressive drugs, surgery for localized lesions.
• Micro: extensive noncaseating sarcoid-like granulomas, vasculitis, and foci of parenchymal necrosis. Confluent areas of well-formed granulomas replace large areas of lung and contain irregular zones of necrosis.
Acute interstitial pneumonia
Hammon-Rich syndrome
• Aka Hammon-Rich syndrome
• Rapidly progressive disease with no identifiable cause
• Young adults with influenza-like illness followed by shortness of breath
• Death usually within 2 months
• Micro: resembles diffuse alveolar damage with brisk diffuse interstitial fibroblastic proliferation, temporally uniform
Young adults with influenza-like illness followed by shortness of breath

Micro: resembles diffuse alveolar damage with brisk interstitial fibroblastic proliferation
Bronchiolitis obliterans-organizing pneumonia (BOOP)
Common response to infectious or inflammatory injury to lungs

Also associated with drugs, collagen vascular disease, graft versus host disease in bone marrow transplant patients

Cause cannot be determined from biopsy - requires clinical history

Acute onset with cough, shortness of breath, fever and malaise

Excellent prognosis; steroid resistance may lead to death

Treatment: steroids

Micro: patchy fibroblastic plugs in bronchioles (bronchiolitis obliterans) and alveoli (organizing pneumonia); plugs formed by spindled fibroblasts in pale-staining matrix, with serpiginous or elongated shape; also foamy macrophages, rare neutrophils, thickened alveolar septa

Low power: evenly spaced nodules or plugs of organizing connective tissue and inflammation that obliterates terminal airways
Honeycomb lung
Final common pathway of various processes causing chronic interstitial fibrosis

Progressive shortness of breath, severe interstitial fibrosis, diffuse cystic changes with blebs and subsequent pneumothorax, shrunken lungs (restrictive lung disease) with elevation of diaphragm

Gross: stiff, spongy, fibrotic lungs with cystic changes

Micro: dense interstitial and peribronchial fibrosis and smooth muscle; reduced alveolar capillaries; marked medial hyperplasia of pulmonary arteries and arterioles; cystically dilated alveoli; may have mucinous metaplasia of lining epithelium with atypia
Lipoid pneumonia
aka golden pneumonia

Incidental post-mortem finding associated with debilitating disease

Gross: well-circumscribed, firm, with prominent lymphatics on lung surface in exogenous type

Micro: lipoid material (or empty spaces)- especially in foamy macrophages, inflammatory cells, young fibroblasts; reactive endarteritis, marked alveolar lining cell hyperplasia

2 types:
Endogenous (obstructive):
• Obstruction by tumor, LN, abscess
• Lipid derived from degenerating type II pneumocytes
• Cholesterol clefts, giant cells.

• Aspiration of lipid material
• Right lung > left.
Essentials- not there
Robbins- not there
Loeffler’s syndrome
Acute eosinophilic pneumonia

Transient diffuse pulmonary infiltrates and serum eosinophilia

Self limited - lasts up to 1 month
Respiratory bronchiolitis
Common, almost always seen in cigarette smokers, may persist 5 years or more after quitting

May cause cough and dyspnea, which regresses after cigarette cessation

Micro: focal chronic inflammation of terminal bronchioles and alveolar ducts, with adjacent focal interstitial inflammation and fibrosis; histiocytes fill alveolar ducts and spaces, but are predominantly peribronchiolar; histiocyte cytoplasm contains brown-black-yellow granules (smoker’s granules)

DD: DIP (no pigmented macrophages)
Goodpasture’s syndrome
Autoimmune disease affecting men > women, usually ages 15-29, with simultaneous (a) sometimes massive hemorrhagic interstitial pneumonitis and (b) rapidly progressive (crescentic) glomerulonephritis

Death common due to uremia

Due to IgG antibodies to basement membrane of alveoli and glomeruli

Treatment: plasma exchange (removes antibodies and chemical mediators), immunosuppressive therapy (prevents further antibody production)

Lungs: heavy, focal necrosis of alveolar wall, fibrous thickening of septa with mild hyperplasia of alveolar lining cells, organization of blood in alveolar space, hemosiderin laden macrophages; linear deposits of immunoglobulin along basement membrane

Kidney: focal proliferative to crescentic glomerulonephritis, with linear deposits of immunoglobulin and complement along basement membrane, similar to lung

DD: mitral stenosis, periarteritis nodosa, SLE, systemic vasculitis (all cause secondary pulmonary alveolar bleeding and hemosiderosis), immune complex glomerulonephritis (granular pattern of immunofluorescence), idiopathic pulmonary hemosiderosis (no antibodies)
Granulomatous inflammation (non-infectious):

List examples
Allergic granulomatosis/ Churg-Strauss
Bronchocentric granulomatosis
Hyalinizing granuloma
Necrotizing sarcoid granulomatosis
Wegener’s granulomatosis
Limited Wegener’s
Bronchocentric granulomatosis
Granulomatous disease of lungs in which almost all granulomas are centered in bronchi or bronchioles, causing their destruction

Immunologic reaction related to chronic eosinophilic pneumonia and allergic bronchopulmonary aspergillosis

Usually adults, often with asthma history, limited to lungs, may be asymptomatic

Usually solitary lesions that appear on chest Xray as atelectasis or consolidation, not nodules

Favorable prognosis

Gross: viscous material in involved bronchi

Micro: large and medium bronchi infiltrated by neutrophils, eosinophils and necrotic debris surrounded by foreign body giant cells; fragmented elastic tissue (with elastic stain); also bronchiolitis obliterans; no fibrinoid necrosis of vessels

DD: Wegener’s (may also have bronchocentric granulomas), TB, fungi, cystic fibrosis, rheumatoid arthritis
Hyalinizing granuloma
Rare nodular lung lesion

Usually multiple, bilateral, cause unknown

Associated with sclerosing mediastinitis, retroperitoneal fibrosis, lymphoma

May be progressive but doesn’t cause death

Micro: central keloid-like collagen, arranged in whorls, surrounded by foreign body giant cells simulating nodular amyloidosis; may have plasma cells and lymphocytes between collagenous bands; usually no epithelioid granulomas, no necrosis

Negative stains: Congo red
Mesenchymal cystic hamartoma
Multifocal, bilateral cysts < 1 cm lined by normal or metaplastic respiratory epithelium resting on a cambium layer of mesenchymal cells
PO only so far
Lobar hyperinflation
congenital lobar emphysema
• 1st 6 months of life
• Sudden progressive respiratory distress.
• Perhaps due to hypoplasia of bronchial cartilage; associated with other cardiopulmonary anomalies

• Affects upper lobes or RML. May cause severe compression of other pulmonary lobes
• Micro: massive distention of alveolar spaces but no tissue destruction
Robbins- not there
Pulmonary hypoplasia
• Lung weighs less than normal with fewer alveoli than expected for gestational age.
• Bilateral disease is fatal
• Causes: space occupying lesions in the uterus, oligohydramnios (renal agenesis, fetal membrane rupture), decreased intrathoracic space (renal cystic disease, diaphragmatic hernia), reduced breathing (anencephaly, musculoskeletal disorders)
Essentials- not there
Robbins- not there
Emphysema due to alpha-1-antitrypsin deficiency
Genetic deficiency

Alpha-1-antitrypsin (AAT) inhibits proteases, particularly elastase (which digests lung tissue), which is secreted by neutrophils during inflammation

PiMM: normal phenotype; 90% of population

PiZZ: associated with AAT deficiency; 80% develop symptomatic emphysema; occurs earlier and is more severe in smokers

Neutrophils are normally present in lung and alveolar space; when stimulated, neutrophils and macrophages increase in number and release elastase and oxygen free radicals, which causes emphysema unless counteracted by antiproteases such as AAT

Smokers have more neutrophils and macrophages in alveoli, tobacco use enhances release of elastase from neutrophils, enhances elastase activity, oxidants in tobacco smoke inhibit AAT
Pulmonary- congenital bronchogenic cysts
• Abnormal detachment of a fragment of primitive foregut.
• Foregut cysts classified into bronchogenic, esophageal, or enteric.
• May occur anywhere in lung, but often hilum or middle mediastinum.
• Usually adjacent to bronchi or bronchioles.
• More often single than multiple.
• Size ranges from microscopic --> 5cm.

• Unilocular cysts with smooth muscle.
• No co,munication with tracheobronchial tree.

• Lined by bronchial-type ciliated pseudostratified epithelium
• Cavities fill with air/mucin; may become infected --> progressive squamous metaplasia of lining or total necrosis of wall, leading to lung abscess.
• Connective tissue may contain cartilage, mucous glands, smooth muscle.
• May rupture into bronchi or pleual cavity.

• Surgical resection curative.
PO- not much
Cystic fibrosis
Widespread disorder in epithelial transport affecting fluid secretion in exocrine glands and the epithelial lining of the respiratory, GI, and reproductive tracts.

• AR
• Variable penetrance
• Gene on chromosome 7 (7q22-7q31)- encodes CFTR gene, chloride transporter.
• 1/ 3200 live births in US
• Most common lethal genetic disease that affects Caucasian populations.
• 1 in 20 in (white) US are carriers
• Most common mutation is delta508 (seen in 70% with disease)
• Mutations -> defect in chloride transport -> reduced chloride ion in secretions, thicker respiratory secretions.
• Features: chronic lung disease, pancreatic insufficiency, steatorrhea, malnutrition, hepatic cirrhosis, intestinal obstruction, male infertility.
• Wide range of presentations
• Mutations also cause defective cilia and infertility
• Meconium ileus seen in 5-10% of patients; also intussusception

• Molecular analysis IDs ~90% of CF mutations
• Elevarted sweat chloride (>60mmol/L0

Gross: emphysema, bronchiectasis, abscess, fibrosis

Associated infections
• Burkholderia cepacia: unique to cystic fibrosis, seen in 20% of patients; causes rapid deterioration of pulmonary status and death; transmitted person to person, has marked social impact as those infected are excluded from social functions (camps) and ineligible for transplant; treat with Chloramphenicol, trimethoprim-sulfamethoxazole
• Pseudomonas aeruginosa: bacteria produces alginate, a capsular protein that mediates adherence; mucoid phenotype is unique to CF; bacteria is never eradicated from lung; treat with ceftazidime
• Staphylococcus aureus: infection persists despite treatment
• Stenotrophomonus maltophilia: aerobic gram negative rod, multidrug resistant, smells like onions; treat with TMP-SMX, resistant to imipenim
Robbins (in peds)
Congenital cystic adenomatoid malformation, aka
congenital pulmonary airway malformation
• aka "cystic adenomatoid transformation".
• Rare, 1 per 5,000 - 25,000 births.
• Usually neonates with respiratory distress.
• Variably sized intercommunicating cysts lined by “adenomatoid” columnar-type epithelium
• May represent a maturation defect
• May develop with and be related to other congenital or acquired lung conditions

Classification: (Types I and II most common)
• Type I (65%): large cysts (-> 10 cm), lined by pseudostratified ciliated cells interspersed with mucus cells; may appear late; good prognosis since can resect; lepidic growth within cysts and adjacent lung, resembles BAC.
• Type II: (10-15%): medium cysts (-> 2 cm), resemble dilated bronchioles separated by normal alveoli; associated with other malformations; poor prognosis.

• Type 0 (<5%): small/firm lungs; formerly called acinar dysplasia; associated with other malformations, incompatible with life.
• Type III: (5%): large # of small cysts (<1.5 cm), solid gross appearance, excess bronchiolar structures separated by small air spaces with cuboidal epithelium resembling fetal lung; poor prognosis.
• Type IV: (15%): large cysts (->10 cm), lined by flattened epithelium; good prognosis.

Treatment: lobectomy
Clinical: Chronic relapsing inflammatory disorder characterized by hyperreactive airways, causing episodic, reversible bronchoconstriction

• Genetic predisposition to Type I hypersensitivity (“atopy”), acute and chronic airway inflammation, and bronchial hyper-responsiveness.
• Mediated by IgE

Typically divided into extrinsic and intrinsic:
• Extrinsic: Type I hypersensitivity; either atopic (due to allergens), occupational or due to allergic bronchopulmonary aspergillosis
• Intrinsic: nonimmune; due to aspirin ingestion, pneumonia, cold, stress, exercise

Status asthmaticus: unremitting attacks due to exposure to previously sensitized antigen; may be fatal

Gross: overdistended lungs, small areas of atelectasis, thick mucus plugs in proximal bronchi containing whorls of shed epithelium

• Curschmann spirals (from whorls of shed epithelium)
• Eosinophils and Charcot-Leyden crystals (collection of crystalloid made of eosinophil membrane protein)
• Airway remodeling: Thickened basement membrane, edema and inflammatory infiltrate in bronchial walls (lots of eosinophils and mast cells), increased# mucosal goblet cells and submucosal glands, bronchial smooth muscle hypertrophy

• Atopic
• Occupational
• Drug-induced
• Non-atopic
• Permanent dilatation of bronchi and bronchioles caused by destruction of muscle and elastic tissue, resulting from or associated with chronic necrotizing infection.
• More common in left lung and in lower lobes.
Symptoms: cough, fever, copious amounts of foul-smelling, purulent sputum

• Congenital (cystic fibrosis, intralobar sequestration of lung, immunodeficiency states, immotile cilia / Kartegeners syndrome, Young’s syndrome)
• Postinfectious conditions (necrotizing pneumonia due to MTb, staph auereus, H flu, Pseudomonas, adenovirus, influenza virus, HIV, aspergillus)
Obstruction (due to tumor, foreign body, inspissated mucus)

Pathogenesis: Obstruction and infection
• Obstruction -> normal clearing mechanisms impaired, pooling of secretions distal to obstruction, airway inflammation.
• Infection -> inflammation, often w/ necrosis, fibrosis, eventually dilatation of airways. Also, atelectasis -> increased negative intrapleural pressure, which exerts an external force on bronchial walls, causing them to dilate; usually left sided affecting lower lobes

Gross: markedly distended peripheral bronchi, usually in lower lobes, can trace to pleural surface; bronchial walls irregularly thickened

Micro: Airways dilated -> 4x. Chronic inflammation, desquamation of epithelium w/ necrotizing ulceration. Pseudostratification of columnar epithelium or squamous metaplasia. Abscess formation may occur.
Kartegeners syndrome
Autosomal recessive condition with variable penetrance, due to absent or irregular dynein arms of cilia, which causes defective bacterial clearance (bronchiectasis, sinusitis), defective cell motility during embryogenesis (situs inversus), immotile sperm (infertility)
Young’s syndrome
Infertility caused by azoospermia, but without ultrastructural ciliary abnormalities
Robbins- not there
Essentials- not there
Sinard- not there
Usual interstitial pneumonitis (UIP)
Also called chronic interstitial pneumonitis, cryptogenic fibrosing alveolitis

Most common pattern of idiopathic pulmonary fibrosis

Usually ages 50+

50% have unknown cause with insidious onset (exertional dyspnea) and chronic evolution; complications include secondary pulmonary hypertension, cor pulmonale, cardiac failure

Some cases may represent a form of immune-complex lung disease associated with collagen vascular diseases or autoimmune diseases

Most cases have circulating immune complexes; 30% have serum antinuclear antibodies (ANA)

May be associated with neurofibromatosis, pulmonary veno-occlusive disease or adenocarcinoma if atypical foci of acinar and squamous proliferation are present

May represent a common pathway for alveolar wall injury from various causes, followed by interstitial edema, alveolitis, type II pneumocyte hyperplasia, fibroblast proliferation and progressive fibrosis

Reduced diffusing capacity is mainly due to ventilation-perfusion mismatch from ventilation of lung tissue with capillary destruction and perfusion of underventilated alveoli; small component is reduced diffusion across fibrotic alveolar septa

Treatment: steroids (20% improve)

Mean survival 6 years, mortality 66%

Diagnosis: requires open lung biopsy; transbronchial biopsy specimen is inadequate

Prognostic factors: eosinophilia associated with poor response to steroids, more functional abnormalities, worse prognosis

Gross: shrunken lung with "hobnailed" pleura due to retraction by underlying fibrous scarring

Micro: marked regional variation in nature and degree of infiltrate on low power without transition (scant mononuclear infiltration, fibromyxoid connective tissue nodules, honeycomb fibrosis), fibroblast foci, architectural distortion, honeycomb change; interstitial injury is patchy, tends to be peripheral, subpleural and periseptal

Lymphoid nodules around bronchioles, bronchiolitis obliterans, fibrinous pleuritis associated with coexisting rheumatoid arthritis

Lymphoid nodules, mucinous hyperplasia, marked media thickening in pulmonary arteries associated with scleroderma

May have frequent areas of nonspecific interstitial pneumonitis or coexisting diffuse alveolar damage, BOOP

Early: firm lungs, pulmonary edema, hyaline membranes, mononuclear infiltration, type II pneumocyte hyperplasia

Later: fibrous tissue, fibrogenic foci (areas of active disease), thickened alveolar septa (solid and normal lung), hyperplastic smooth muscle, microcysts, loss of alveolar capillaries

End stage: spaces lined by cuboidal/columnar epithelium separated by fibrosis and forming honeycomb lung (particularly in the superior portion of lobes); also lymphoid hyperplasia, thickening of intima and media of pulmonary arteries

EM: fibrosis due to migration of activated mesenchymal cells through defects in epithelial lining and its basement membrane from interstitial to intraluminal compartment, replacement of alveolar type I cells by hyperplastic alveolar type II cells

DD: pneumoconiosis, hypersensitivity pneumonitis, bronchiolitis obliterans organizing pneumonia, oxygen toxicity pneumonitis, scleroderma, radiation injury, NSIP
Non-neoplastic disease due to inhalation of inorganic or organic particulates (classic ex: mineral dusts).

Development depends on:
1) Amount of dust retained in lungs [determined by dust concentration, exposure duration, effectiveness of clearance mechanisms]
2) Particulate size and shape (dangerous: 1-5 mm)
3) Particle solubility/ physicochecmical reactivity
• Small particles - >ALI
• Large particles resist dissolution and stay in lungs, - > fibrosing collagenous pneumoconiosis (silicosis)
• Some particles cause direct injury to cells, or trigger macrophages to release inflammatory mediators -> fibroblast proliferation/ collagen deposition.
4) Irritants (eg cigarette smoke- affects mucociliary apparatus)

In general, do not predispose to carcinoma (except asbestos).
Essentials- not much
Presence of carbon particles in lung

Not a pathologic condition necessarily, often due to urban living

Carbon particles are relatively inert and usually don’t elicit reactive fibrosis

May cause coal workers’ pneumoconiosis (below)
Asbestos ->
• localized fibrous plaques
• pleural effusions
• parenchymal interstitial fibrosis (asbestosis)
• bronchogenic carcinoma
• mesothelioma
• laryngeal carcinoma
• colon carcinoma?

• Serpentine/chrysotile (90%, curly, flexible) and amphibole (10%, straight, stiff, brittle).
• Most industrial asbestos industry is serpentine (i.e., serpentine is more prevalent) but amphiboles are more pathogenic, especially w/ mesothelioma.
• Chrysotiles usually are caught in upper respiratory passages, removed by mucociliary elevator; they are soluble and leached from tissue if they reach alveoli.
• Amphiboles go deeper to lungs; fibers > 8 mm and thinner than 0.5 mm are more injurious.
• Both types are fibrogenic; incidence of asbestos related disease is dose dependent; act as tumor initiator and promoter; toxic chemicals may also be adsorbed to asbestos fibers (tobacco smoke)

• Lung carcinoma w/ asbestos = 5; w/ asbesto + tobacco = 55.
• Mesothelioma w/ asbestos = 1000; same w/ + tobacco.

Note: asbestos related tumors have no special histologic features
• Initial injury at bifurcations of small airways and ducts; macrophages ingest fibers, release chemotactic factors and fibrogenic mediators -> diffuse interstitial fibrosis
• Begins as fibrosis around respiratory bronchioles and alveolar ducts, extends distally; eventually -> honeycomb lungs
• Begins in lower lobes and subpleurally (in contrast to CWP and silicosis), progresses to middle and upper lobes

• Pleural plaques: well circumscribed plaques of dense collagen, often with calcium; on parietal pleura and dome of diaphragm; do not contain asbestos bodies, but rare if no asbestos history; may induce pleural effusions, usually no symptoms

Micro: Similar to other diffuse interstitial fibroses except for presence of asbestos bodies.
• Early: interstitial pneumonia with desquamative features, hyperplastic alveolar cells with intracytoplasmic Mallory’s hyaline tissue;
• Later: diffuse interstitial fibrosis with honeycombing (silicosis is nodular), asbestos bodies (golden brown, fusiform or beaded rods with translucent center; asbestos fibers coated with iron-containing proteinaceous material); iron from phagocyte ferritin.
• Asbestos fibers may have oxalate crystal deposition,
• Ferruginous bodies: inorganic particulates coated with phagocyte ferritin

Asbestos fiber detection: H&E, incineration, EM

Symptoms usually begin after 10 years of exposure, initially dyspnea with exertion, later at rest; may progress to heart failure
Due to heavy exposure to dusts or fumes of beryllium, more common in nuclear and aerospace industries

Acute disease has disappeared due to exposure standards

Low-dose exposure may cause granulomatous lesions that mimic sarcoidosis

Chronic berylliosis due to cell-mediated immunity; 2% of those exposed develop disease; delayed hypersensitivity leads to noncaseating granulomas in lungs, hilar nodes, become progressively fibrotic; no symptoms until late

Heavy beryllium exposure is linked to lung cancer
Coal workers’ pneumoconiosis (CWP)
Incidence declining due to dust reduction measures.

Wide spectrum of diseases:
• Anthracosis
• Simple coal worker’s pneumoconiosis (CWP)
• Complicated CWP, aka progressive massive pulmonary fibrosis (PMF).

• Relatively innocuous, in all urban dwellers.
• Carbon pigment is engulfed by macrophages, accumulates in connective tissue along lymphatics

Simple CWP:
• Patients have coal macules (1-2 mm collections of carbon-laden macrophages + network of collagen fibers) and coal nodules (coal macules and fibrosis) throughout lung, upper lobe and upper zone of lower lobe> others, near respiratory bronchioles.
• Usually minimal symptoms but 10% -> PMF.

Progressive massive fibrosis:
• Develops on background of simple CWP—requires years.
• Multiple, intensely blackened scars > 2 cm, containing dense collagen and pigment; center of lesion may be necrotic due to ischemia

• PMF associated w/ pulmonary hypertension and cor pulmonale. May progress even if dust exposure ceases.
• Pattern of lung injury may be due to any pneumoconiosis, but most common in CWP and silicosis.
• Increased incidence of Tb, chronic bronchitis and emphysema, independent of smoking
• Does not appear to increase the risk of lung cancer

Caplan syndrome: RA and pneumoconiosis -> rapidly developing nodular pulmonary lesions, composed of central necrosis surrounded by collagen, fibroblasts and macrophages (similar to rheumatoid nodules); associated with exposure to coal, asbestosis, silica dust
Extrinsic allergic alveolitis
hypersensitivity pneumonitis
• Spectrum of immunologically mediated, interstitial lung disorders caused by intense, often prolonged exposure to inhaled (extrinsic) organic dusts and occupational antigens.
• Combination of type III (immune complex) and type IV (cell-mediated) reactions.
• Individuals have abnormal sensitivity or heightened reactivity to these antigens.
• Similar to asthma, but involves alveoli, not bronchi.
• Acute: 4-6 hours after inhalation; diffuse/nodular pulmonary infiltrates on CXR; severe dyspnea, cough, fever; self-limited, resolves in 12-18 hours.
• Chronic exposure: -> dyspnea, respiratory failure, cyanosis, decreased total lung capacity and compliance.
• Good prognosis,
• Tx: steroids and withdrawal of offending antigen

Causes: spores of thermophilic bacteria, fungi, animal proteins, bacteria from hay, grain, sugar cane, bark, cheese, cork, animal feces.


• Air conditioner lung: due to thermophilic bacteria.
• Byssinosis: in textile workers due to fibers from cotton, linen, hemp; resembles asthma clinically; may not be immune mediated.
• Farmer’s lung: from moldy hay containing spores of thermophilic actinomycetes.
• Maple bark stripper’s lung: fungal spores.
• Pigeon breeder’s lung: also called bird fancier’s disease: proteins from serum, feathers, excreta.

• Patchy chronic interstitial bronchiolocentric pneumonitis- lymphocytes, plasma cells, macrophages, temporally synchronized, uninvolved lung in between;
• Necrotizing granulomas (2/3);
• Interstitial fibrosis and obliterative bronchiolitis (>1/2);
• Intra-alveolar infiltrate.
• Chronic form resembles other chronic interstitial diseases, not the acute form.
List subtypes
Air conditioner lung: due to thermophilic bacteria

Byssinosis: in textile workers due to fibers from cotton, linen, hemp; resembles asthma clinically; may not be immune mediated

Farmer’s lung: from moldy hay containing spores of thermophilic actinomycetes

Maple bark stripper’s lung: fungal spores

Pigeon breeder’s lung: also called bird fancier’s disease: proteins from serum, feathers, excreta
Acute Respiratory Distress Syndrome (ARDS)/ Diffuse alveolar damage (DAD)
Correlates of each other
• ARDS= clinical
• DAD = histopathological

• Presentation: Rapid onset of severe, life-threatening respiratory insufficiency, cyanosis, severe arterial hypoxemia refractory to oxygen therapy, usually severe pulmonary edema, with diffuse alveolar infiltration on Xray
• Mortality 60%; 150,000 cases and 90,000 deaths per year in US
• Causes are many: sepsis, aspiration, diffuse pulmonary infections (viral, mycoplasma, Pneumocystis, tuberculosis), mechanical trauma, surfactant deficiency in newborns, near drowning; also other injury, inhaled irritants, chemical injury, radiation, amiodarone, chemotherapy, acute pancreatitis, burns, uremia
• Treatment: nitric oxide (vasodilator) decreases pulmonary vascular resistance and reduces ventilation-perfusion mismatch

• Final common pathway of diffuse damage to alveolar capillary walls in both lungs.
• -> increased vascular permeability, alveolar flooding, loss of diffusion capacity, damage to type II pneumocytes -> surfactant abnormalities

Gross: heavy, firm, red, boggy lung

Early exudative stage (1st week post injury; Xray normal):
• Edema (interstitial and intraalveolar), hemorrhage
• Fibrin deposition and thrombi and small vessels/ capillaries
• Hyaline membrane formation (3-7d)
• Sloughing of alveolar cells, denudation of basement membrane

Later proliferative stage (2nd week plus); Xray shows diffuse bilateral infiltrates):
• Increasing interstitial inflammation
• Fibroblast proliferation and interstitial fibrosis
• Organization and phagocytosis of hyaline membranes
• Proliferation of type II pneumocytes, hobnailing
• Bronchiolar damage with atypical squamous metaplasia
Obstructive vs Restrictive pulmonary diseases
Obstructive airway disease: increase in resistance to airflow due to obstruction at any level; includes emphysema, chronic bronchitis, bronchiectasis, asthma, tumor, foreign body; reduced maximal airflow rates (FEV1)

Restrictive airway disease: reduced expansion of lung parenchyma with decrease in total lung capacity; normal FEV1; due to chest wall disorders (polio, obesity, pleural disease, kyphoscoliosis), interstitial / infiltrative diseases (ARDS, dust diseases, interstitial fibrosis)
List pulmonary vascular disorders
* Pulmonary congestion/ edema
* Pulmonary embolism/ infarct
* Pulmonary hypertension
* Lymphangiomyomatosis
List infectious pulmonary granulomatous inflammations
* Histoplasmosis
* Coccidiomycosis
* Blastomycosis
* Mycobacterium tuberculosis
* Dirofilariasis
List collagen vascular diseases affecting lungs
* RA
* Scleroderma

List them
* Silicosis
* Asbestosis
* Coal worker's pneumoconiosis
* Mixed dust fibrosis
* Siderosis
* Berylliosis
List the interstitial pneumonias
(keep going....)
Extrapulmonary sequestration
• External to lung.
• Covered with separate pleural lining.
• May be anywhere in thorax or mediastinum.
• Usually infants.
• Abnormal masses.
• 90% on left side.
• 20% have other congenital anomalies.
• Associated with polyhydramnios and edema.
• Systemic anomalous arterial supply, usually small.
• Venous drainage is azygous veins.
Intralobar sequestrations
• M:F= 1:1
• Within the lung
• Usually lower lobe
• 60% on left
• Not invested with its own pleura
• Segment is supplied by a large artery from thoracic aorta or below diaphragm.
• Venous drainage is pulmonary veins.
• Associated with infections, bronchiectasis, chronic inflammation, fibrosis.
• May be congenital or due to repeated infections.
• Caused by inhalation of crystalline silicon dioxide (silica).
• Most prevalent chronic occupational disease worldwide due to foundry work, sandblasting, stone cutting, coal mining.

• Usually progressive, nodular, fibrosing pneumoconiosis after decades of exposure.
• Less often, heavy exposure over short time -> acute silicosis: similar to alveolar proteinosis with generalized accumulation of lipoproteinaceous material within alveoli
• Presentation: routine CXR w/ fine nodularity in upper lobes, normal pulmonary function; no symptoms until PMF, then disease progresses even if exposure ceases.
• Not associated with lung cancer (controversial).
• Increased susceptibility to Tb.

Forms: crystalline (quartz, crystobalite, tridymite) and amorphous
• Crystalline more fibrogenic than amorphous forms;
• Quartz is particularly fibrogenic, although quartz plus other minerals is less fibrogenic
• Silica causes macrophages to release mediators -> stimulate fibroblasts, including TNF
• Talc, vermiculite and mica: noncrystalline silicates that less commonly cause pneumoconiosis

• Early: tiny, discrete pale to black nodules in upper lung zones -> Collagenous scars; more fibrotic than CWP.
• Nodules have stellate shape at edges
• May cavitate due to tuberculosis or ischemia;
• Fibrosis present in hilar nodes and pleura; LN may show eggshell calcification on Xray.

• Early lesions: small nodules of fibroblasts and histiocytes with abundant silica, -> less cellular/ more hyalinized with time;
• With PMF: concentric layers of hyalinized and condensed collagen, needle-like spicules w/ pointed ends, <5 microns, birefringent with polarization, intra- or extracellular
Smoking-related diseases of lung
Obstructive: emphysema and chronic bronchitis

Restrictive/ interstitial: DIP, RBILD
Desquamative Interstitial Pneumonia (DIP)
• Presents in 4th – 5th decade w/ insidious onset of shortness of breath, -> respiratory insufficiency; also cough, cyanosis, clubbing
• Cause unknown
• Mean survival 12 years, mortality 28%
• 90% are current or past cigarette smokers
• Associated with collagen vascular disease, positive ANA (similar to UIP)
• Rx: Good prognosis w/ excellent response to steroid therapy and smoking cessation (better than UIP).
• Xray: bilateral, lower lobe, ground glass infiltrates

• Diffuse collections of intra-alveolar macrophages containing lipid and PAS+ granules (originally thought to be desquamated pneumocytes)
• Type II pneumocyte hyperplasia
• Acute and chronic inflammatory cells thickening alveolar septa
• May be focal interstitial fibrosis
• No necrosis, no hyaline membranes, no fibrin

EM: type II pneumocytes contain lamellar bodies (surfactant), may be phagocytosed by macrophages
PO- done
Robbins- done
Respiratory Bronchioloitis-Associated Interstitial Lung Disease (RBILD)
• Common, almost always seen in cigarette smokers, with average 30 pack year exposure.
• Patients typically current smokers in 4th to 5th decade of life, with 2M:1F.
• Symptomes are mild and of gradual onset, and consist of cough and dyspnea.
• Cigarette cessation -> improvement of symptome.

• Pigmented intraluminal macrophages in 1st and 2nd order respiratory bronchioles;
• Changes are patchy and histiocytes fill alveolar ducts and spaces, but are predominantly peribronchiolar;
• histiocyte cytoplasm contains brown-black-yellow granules (smoker’s granules).
• Patchy submucosal and peribronchiolar infiltrate od lymphocytes and histiocytes.
• Mild peribronchiolar fibrosis.
PO- done
Robbins- done
Triad of asthma, allergic rhinitis, articaria, eczema...

Asthma, atopic
• Begins in childhood, triggered by environmental allergens (dander, dust, pollen, food), often positive family history
• Skin test causes wheel and flare reaction (classic example of Type I IgE mediated hypersensitivity reaction)
• Initial sensitization -> Th2 cells release IL-4/5, which promote IgE release by B cells, mast cells and eosinophils
• Re-exposure to allergen -> IgE crosslinking on sensitized mast cells on mucosa-> mediator release -> open mucosal tight junctions and enhance penetration of antigen to submucosal mast cells
• Acute/immediate response is bronchoconstriction, edema, mucus secretion, hypotension
• Late phase reaction, due to influx of other inflammatory cells, is release of major basic protein of eosinophils ->epithelial damage and airway constriction
• Putative mediators: leukotrienes C4, D4, E4 and acetylcholine; minor mediators: histamine, prostaglandin D2
• Associated with serum eosinophilia, sputum eosinophils
Sinard- not there
Essentials- not there
Asthma, occupational
• Due to repeated exposure to fumes, dusts, gases, chemicals, often in minute quantities
Sinard- not there
Essentials- not there
Asthma, drug induced
• Associated with aspirin use
• Rare, associated with recurrent rhinitis and nasal polyps
• Patients are sensitive to small doses of aspirin, get urticaria and asthma
• May be due to direct effects of aspirin on cyclooxygenase pathway
Sinard- not there
Essentials- not there
Asthma, nonatopic
• Due to respiratory viral infection (rhinovirus, parainfluenza virus); usually not familial
• Normal serum IgE, negative skin tests
• Viral induced inflammation may lower threshold of subepithelial vagal receptors to irritants
Sinard- not there
Essentials- not there
Primary ciliary dyskinesia
Primary ciliary dyskinesis

AR with variable penetrance
1 per 15,000 – 40,000 births
Poorly functioning cilia -> retention of secretions, recurrent infections
Absence or shortening of dynein arms
½ have Kartegener’s
• defective bacterial clearance (bronchiectasis, sinusitis)
• defective cell motility during embryogenesis (situs inversus)
• immotile sperm (infertility)
Essentials- not there
Allergic bronchopulmonary aspergillosis (ABPA)
• Condition resulting from hypersensitivity reaction to Aspergillus fumigatus.
• Complication of asthma and CF.
• Intense airwar inflammation with eosinophils and mucus plugs.
• Exacerbations and remissions -> proximal bronchiectasis, fibrotic lung disease.
• Bronchocentric granulomatosis
• May see the fungal hyphae within plugs and later in bronchial walls.
Pulmonary hypertension
• Defined as > 25% of systemic pressure (normal= 10% of systemic, due to low resistance of pulmonary vasculature).
• Usually due to structural diseases causing increased pulmonary blood flow or pressure, increased pulmonary vascular resistance or left heart resistance.
• Pulmonary atherosclerosis implies pulmonary hypertension.

• Emphysema (hypoxia and alveolar destruction reduce the number of capillaries, -> increased arterial resistance, -> hypertension),
• Congenital and acquired heart disease such as mitral valve stenosis (elevated left atrial pressure, pulmonary venous and arterial pressure)
• Recurrent thromboemboli (reduced cross sectional area of pulmonary vascular bed causes increased vascular resistance),
• Idiopathic (rare),
• Vasospasm,
• Endothelial cell dysfunction,
• Ingestion of bush tea (Crotalaria spectabilis),
• Aminorex (appetite suppressant),
• Adulterated olive oil,
• Fenfluramine / phenterimine,
• Interstitial fibrosis,
• Chronic liver disease,
• Pulmonary veno-occlusive disease

• ? due to decreased production of NO & prostacyclin and increased levels of endothelin, -> to endothelial cell activation & thrombogenesis.
• Usually women ages 20-40.
• Asymptomatic until late, then shortness of breath, fatigue, angina, progressing to right ventricular hypertrophy, cor pulmonale, pulmonary emboli, pneumonia.

Treatment: vasodilators, calcium channel blockers, nitric oxide, antithrombotic medications
• Disease reversible if arterial lesions restricted to medial hypertrophy, intimal thickening of longitudinal smooth muscle or cellular intimal proliferation
• Irreversible if moderate/severe concentric laminar intimal fibrosis, fibrinoid necrosis, plexiform lesions

Micro: organizing thrombi (suggests recurrent pulmonary emboli); interstitial fibrosis if hypoxia; changes in major vessels / branches are similar to systemic atherosclerosis; small vessels have medial hypertrophy and intimal fibrosis which may narrow lumina to pinpoint; plexogenic arteriopathy: tuft of capillaries spanning lumina of arteries
Primary plexogenic hypertension
• Young women with progressive shortness of breath, angina, syncope and possibly sudden death
• Associated with collagen vascular disease and positive ANA
• Death usually within a few years; 5 year survival is only 35%

• Grade I (early) - muscularization and media hypertrophy (>7% of lumen) of pulmonary arteries
• Grade II - intimal hyperplasia causing attenuation of vascular lumen
• Grade III - subintimal fibrosis with onion-ring appearance; marked reduplication of internal elastic membrane; arteries and arterioles resemble pipes
• Grade IV to V - dilation and plexiform lesions, aneurysmal dilation of small pulmonary arteries, plexiform and glomeruloid nodules; fibrin thrombi within plexiform lesion, old/new hemorrhage present
• Grade VI - uncommon, acute necrotizing arteritis with fibrinoid necrosis and acute inflammation of vessel wall, similar to polyarteritis nodosa; associated with extreme pulmonary hypertension
Infections associated with cystic fibrosis
Associated infections
• Burkholderia cepacia: unique to cystic fibrosis, seen in 20% of patients; causes rapid deterioration of pulmonary status and death; transmitted person to person, has marked social impact as those infected are excluded from social functions (camps) and ineligible for transplant; treat with Chloramphenicol, trimethoprim-sulfamethoxazole
• Pseudomonas aeruginosa: bacteria produces alginate, a capsular protein that mediates adherence; mucoid phenotype is unique to CF; bacteria is never eradicated from lung; treat with ceftazidime
• Staphylococcus aureus: infection persists despite treatment
• Stenotrophomonus maltophilia: aerobic gram negative rod, multidrug resistant, smells like onions; treat with TMP-SMX, resistant to imipenim
Bronchopulmonary dysplasia
• Complication of prematurity
• Respiratory distress continues for months
• Patients have limited pulmonary reserve, develop repeated infections, often have pulmonary hypertension and develop cor pulmonale
• Micro: bronchiolar and interstitial fibrosis, compensatory emphysema of less damaged acini, inadequate alveolar development causes fewer but larger alveoli
Spectrum of diseases that includes
• chronic bronchitis,
• emphysema,
• asthma,
• bronchiectasis

4th leading cause of morbidity and mortality in US
Associated with cigarette smoking
• Abnormal permanent enlargement of air spaces distal to terminal bronchiole with wall destruction but without fibrosis
• Usually due to tobacco

Pathogenesis: Alteration in balance between proteases and antiproteases

• Often overlaps with COPD
• No symptoms until 1/3 of functional capacity is lost
• Symptoms: dyspnea, coughing, wheezing, weight loss; barrel chest; breath through pursed lips (pink-puffer) -> slowing of forced expiration
• May cause secondary pulmonary vascular hypertension, cor pulmonale, congestive heart failure
• Death due to respiratory acidosis and coma, pneumothorax

Based on anatomic distribution
• Centriacinar
• Panacinor (panlobular)
• Paraseptal
• Irregular
Other types, called “emphysema” but term is less stringent
• Bullous
• Interstitial
• Compensatory
• Senile
Centroacinar emphysema
• 95% of emphysema cases
• Causes significant airflow obstruction
• Affects central part of acini, sparing distal alveoli
• Worse in upper lobes, particularly apices
• Walls are anthracotic with parabronchial inflammation
• Seen in heavy smokers, coal worker pneumoconiosis
• Clinically significant at age 40+ in smokers, ventilatory deficits earlier
Panacinar (panlobular) emphysema
• 5% of cases
• Causes significant airflow obstruction
• Acini uniformly enlarged from respiratory bronchiole to terminal alveoli; usually lower lungs
• Associated with alpha-1-antitrypsin deficiency
• Lungs usually voluminous
Paraseptal (distal acinar) emphysema
• Minor clinically
• Only distal acini affected, emphysema is next to pleura, near areas of fibrosis, scarring or atelectasis
• Multiple continuous airspaces (.5 -> 2.0 cm) are affected, form cystic spaces
• May be source of spontaneous pneumothorax in young adults
Irregular emphysema
• Minor clinically
• Invariably associated with scarring,
• Irregular involvement of acini
Compensatory emphysema
• Response to loss of lung elsewhere, such as post-lobectomy
Senile emphysema
• Due to age-related alterations in internal geometry of alveoli leading to larger alveolar ducts, smaller alveoli, but no loss of elastic tissue or destruction of lung substance
Obstructive emphysema
• Due to tumor, foreign body or congenital lobar overinflation (infants, perhaps due to hypoplasia of bronchial cartilage; associated with other cardiopulmonary anomalies);
• Due to ball-valve effect with inhalation via collaterals (pores of Kohn, canals of Lambert);
• May compress normal lung, may be life-threatening
Bullous emphysema
• Any form that produces blebs > 1 cm;
• Often subpleural, near apex, associated with tuberculosis scarring
• May rupture and cause pneumothorax, hemorrhage
• Called placental transmogrification if it resembles chorionic villi
Interstitial emphysema
• Air into connective tissue stroma of lung, mediastinum or subcutaneous tissue;
• Due to alveolar tears, chest wounds, coughing, whooping cough
Chronic Bronchitis
• Diagnosis: persistent cough with sputum for 3 months in 2 consecutive years
• Often overlaps with emphysema.
• More infections, purulent sputum, hypercapnia, hypoxia than emphysema; clinically called “blue bloaters”
• May cause secondary pulmonary vascular hypertension, cor pulmonale, congestive heart failure; death due to respiratory acidosis and coma, congestive heart failure, pneumothorax

Simple chronic bronchitis: cough but no physiologic evidence of airway obstruction
Chronic asthmatic bronchitis: hyperreactive airways with intermittent bronchospasm and wheezing
Obstructive bronchitis: often have associated emphysema

Causes: 4-10x more common in smokers, also chronic irritation, infections maintain but do not initiate chronic bronchitis

Reid index: ratio of thickness of mucus gland layer to thickness of wall between epithelium and cartilage; normal is 0.4, increased in chronic bronchitis

• early-hypersecretion of mucus in large airways with hypertrophy of submucosal glands in tracheobronchial tree
• later-increase in goblet cells in small airways causes excessive mucus production and airway obstruction; increased Reid index

Gross: boggy mucosa with excessive mucinous secretions, pus

• Chronic inflammation of airways (mostly lymphocytes)
• Enlargement of mucous secreting glands of trachea and bronchi (assessed w/ Reid Index)
• Bronchial epithelium w/ squamous metaplasia and dysplasia
• Bronchioles may be markedly narrowed or show bronchiolitis obliterans
Pulmonary edema
Due to hemodynamic disturbances (cardiogenic) or local microvascular injury

Hemodynamic disturbances:
• Due to increased hydrostatic pressure from CHF.
• Lungs are wet and heavy.
• Fluid initially at base of lower lobes because hydrostatic pressure is greater here.
• Micro: engorged alveolar capillaries and intra-alveolar pink precipitate, edema (initially interstitial, then alveolar), hemosiderin laden macrophages (heart failure cells); later fibrosis and thickening of alveolar walls (brown induration of lung)

Local microvascular injury:
• Injury to vascular endothelium, or to alveolar epithelial cells with secondary endothelial damage -> leakage of fluids and proteins into interstitial space, eventually into alveoli.
• When diffuse, may -> ARDS.
Types of acute lung injury
• Pulmonary edema
• AIP/ Hamman-Rich
Per Robbins


aka lymphangioleiomyomatosis

• Rare, unknown etiology
• Almost always white women of reproductive age.
• Associated with TS, renal AML
• No smoking history.
• May involve mediastinal or periaortic LN.
• Symptoms: dyspnea with pneumothorax or emphysema, chylous pleural effusions, recurrent pnumothorax.
• Disease is progressive, prognosis poor, death due to respiratory failure or cor pulmonale.
• Disease worsened by pregnancy or menstruation, improved post-menopause
• Treatment: oophorectomy, hormone manipulation (progesterone or antiestrogens), lung transplantation (but may recur in lung allografts).

Derived from perivascular epithelioid cells

Gross: emphysematous-like changes/ widespread cystic spaces separated by thick, gray-white septa

• Haphazard proliferation of smooth muscle around airways, lymphatics, blood vessels; expands lung parenchyma; resembles renal AML in that smooth muscle appears to spin off muscle coats of these structures, extending towards adjacent alveoli.
• Muscle cells have optically clear cytoplasm, intracytoplasmic glycogen;
• Hemosiderin pigment is common

IHC: (+) for HMB45, ER, PR
Robbins- not there
Pulmonary Alveolar Proteinosis (PAP)
Rare disease characterized by (radiology) bilateral, patchy asymmetric pulmonary opacification and (histology) accumulation of acellular surfactant in intra-alveolar and bronchiolar spaces.

3 types:
• Acquired (90%): unknown etiology, probably autoimmune with GM-CSF as autoantigen
• Congenital- rare
• Secondary- rare. Due to lysinuric protein, acute silicosis, inhalational syndromes, immunodefieicny disorders, malignancies, hematopoietic disorders.

Homogeneous granular precipitate w/ in alveoli -> focal to confluent consolidation of large areas of lungs with minimal inflammatory reaction, variable fibrosis. Precipitate is PAS (+) and contains cholesterol clefts

• Insidious onset of cough and abundant sputum that contains chunks of gelatinous material.
• Associated with secondary infection by Nocardia, Mycobacteria, Aspergillus
• Course varies.
• Treatment: whole lung lavage
• Fatal, immediately apparent.
• Full terms w/ progressive RDS.
• Die by 3-6 mo.
Eosinophilic granuloma

• Aka eosinophilic granuloma, Langerhans cell granulomatosis, histiocytosis X (“H-X”), Hand-Schuller-Christian disease, Letterer-Siwe disease.
• Usually ages 20-39 years; almost all are smokers; 4M:1F
• 20% with multicentric disease (bone, skin, lymph nodes, spleen, pituitary) have lung involvement.
• 50% of cases only involve lung.
• Often associated with pneumothorax, Pneumocystis carinii pneumonia.
• Usually lung disease resolves or stabilizes, but 10-20% may progress to respiratory failure.
• Clonal process; possibly reactive rather than neoplastic

Gross: lesion of upper lobes, local or diffuse, with nodules and cavitary lesions and late honeycombing

• Interstitial scarring with nodular aggregates of Langerhans cells with a bronchiolocentric distribution;
• Prominent eosinophils and mesothelial cells;
• Langerhans cells have abundant eosinophilic cytoplasm and grooved nuclei with indented nuclear membranes;
• Frequent hemosiderin, necrosis, alveolar lining cell hyperplasia, pigmented alveolar macrophages;
• Variable vasculitis;
• Older lesions have fewer eosinophils and more interstitial fibrosis;

IHC: (+) CD1a, S100, HLA-DR
EM: Birbeck’s granules (pentilaminar intracytoplasmic structures, tennis racket shaped)
check Robbins and Sinard
Pulmonary infections (general)
Due to impaired host defense mechanism:
• Loss/ suppression of cough reflex (drugs, virus)
• Injury to mucociliary apparatus (smoking, virus, Kartegener’s)
• Interference with phagocytic/ bactericisal action of alveolar macrophages (tobacco, EtOH, anoxia)
• Pulmonary congestion/ edema
• Accumulation of secretions (CF)

Types (by clinical setting):
• Community acquired acute
• Community acquired atypical
• Nosocomial
• Aspiration
• Chronic
• Lung abscess
• Pneumonia in immunocompromised host.

Note: Viral predisposes to bacterial
Complications: abscess, empyema, organization, sepsis, meningitis
Consolidation: exudative solidification of lung
Symptoms: dyspnea, fever, productive cough, malaise, friction rub (if fibrinous pleuritis)
Essentials- not much
Morphologic patterns of bacterial pneumonia
• Widespread fibrinopurulent consolidation
• Rare now b/c of antibiotics
• 95% caused by pneumococci
• Also: Klebsiella, Staphylococcus, Streptococcus, H. flu
4 stages:
1: Congestion- vascular engorgement, intraalveolar fluid, numerous bacteria, few PMN
2: Red hepatization: extravasated RBCs, fibrin, more PMNs
3: Gray hepatization: much more fibrin and PMN, disintegrating RBCs
4: Resolution: organization


Patchy consolidation of lung w/ foci of acute suppurative inflammation, grossly poorly defined.
Can be extensive and merge to involve entire lobe.
Essentials- not much
Community acquired acute pneumonia
Usually bacterial, often following viral.
Lungs fill with inflammatory exudate (consolidation).
Symptoms: abrupt onset high fever, shking, chills, cough productive of mucopurulent sputum.
Rx: antibiotics
ID of organism and its antibiotic sensitivity are key to appropriate therapy.

• Streptococcus pneumonia
• Haemophilus influenzae
• Moraxella catarrhalis
• Staphylococcus aureus
• Legionella pneumonia
• Enterobacteriaceae (Klebsiella) and Pseudomonae
Sinard- NO
Essentials- NO
Community acquired atypical pneumonia
All symptoms milder than “typical”: moderate amount of sputum, no physical findings of consolidation, moderately elevated WBC.
Clinical course is varied.

Patchy or lobar involvement.
• Interstitial inflammatory infiltrate.
• Alveolar septae widened: edematous and with mononuclear infiltrate.
• May show intra-alveolar proteinaceous material, cellular exudate, and pink hyaline membranes—alveolar damage similar to ARDS.
• May have superimposed bacterial infection.

• Mycoplasma pneumonia- most common
• Chlamydia spp (pneumoniae, psittaci, trachomatis)
• Coxiella burnetti (Q fever)
• Virues: RSV, parainfluenza virus, Influensa A&B, adenovirus, SARS
Sinard- NO
Essentials- NO
Nosocomial pneumonia
Hospital acquired
Usually in patients with severe underlying disease, immunosuppression, prolonged antibiotic therapy, invasive access devices, mechanical ventilation.
Often life-threatening

• G(-) rods of Enterobacteriaceae (Klebsiella spp, Serratia marcescens, E coli) & Pseudomonas spp
• Staphylococcus aureus
Sinard- NO
Essentials- NO
Aspiration pneumonia
In very debilitated patients, usually with abnormal gag and swallowing reflexes.
Pneumonia is part chemical and part bacterial.
Usually polymicrobial, aerobic > anaerobic.
Often necrotizing, fulminant, and cause of death.
Common complication: abscess


• Anaerobic oral flora (Bacteroides, Prevotella, Fusobacterium, Peptostreptococcus) admixed with aerobic bacteria (S. pneumo, S. aureus, H. influenza, P. aeruginosa)
Sinard- NO
Essentials- NO
Pulmonary abscess
• Local suppurative process with necrosis of lung tissue.
• Any organism but most commonly due to streptococci, Staphylococcus aureus, and G(-)s.
• Via aspiration, antecedent primary bacterial infection, septic embolism, and neoplasia (postobstructive pneumonia).

• Micro: suppurative destruction of lung parenchyma w/in central area of cavitation. Cavity may or may not contain suppurative debris. Chronic cases: fibroblastic proliferation  fibrous wall.

• Symptoms: cough, fever, copious foul-smelling sputum.
• Most resolve with antibiotics.
• Complications: infection of pleural cavity/ empyema, brain abscesses/ meningitis from septic emboli
• 10% of cases are associated with underlying carcinoma
• May extend into pleural cavity, create septic emboli causing meningitis or brain abscess, serve as nidus for fungal overgrowth (Mucor, Aspergillus), spread elsewhere in lung
• Treatment: lobectomy
Sinard- NO
Essentials- NO
Chronic pneumonia
Often localized lesion in immunocompetent host, +/- regional LN involvement.

• Nocardia
• Actinomyces
• Granulomatous: MTb and atypical mycobacteria, Histoplasma capsulatum, Coccidioides immitis, Blastomyces dermatitidis
Sinard- NO
Essentials- NO
Pneumonia in immunocompromised host: organisms
• Invasive aspergillosis
• Invasive candidiasis
• “Usual” bacteria, viral, and fungal organisms listed elsewhere
Sinard- NO
Essentials- NO
AIDS related pneumonia
Leading cause of morbidity and mortality in AIDS patients.
May be of “usual” type as well as “opportunistic”.
CD4+ T cell count defines risk of infection:
• >200: bacterial and Tb more likely
• <200: PCP
• <50: CMV, MAI

Diagnose with BAL, transbronchial biopsy or open lung biopsy
Nonspecific features resemble DIP or lymphocytic interstitial pneumonia
Patients often have multiple infections
Open lung biopsies should routinely be stained for Pneumocystis, fungi, mycobacteria
Cavitary lesions: Staphylococcus, fungi (Candida, Aspergillus, Cryptococcus, Histoplasma, Blastomyces), MTb, MAI, Rhodococcus equi
Patients also have infections from CMV, Pneumocystis carinii, toxoplasma, microsporidia
Associated with Kaposi’s sarcoma.
Sinard- NO
Essentials- NO
Streptococcus pneumoniae pneumonia
Most common cause of community acquired pneumonia.
• Gram stained sputum w/ numerous PMN w/ G(+) lancet-shaped diplococci (but part of endogenoud flora in 20% adults).
• BCX: more specific, less sensitive.
• Rx: penicillin, if not resistant.
Sinard- NO
Essentials- NO
Haemophilus influenza pneumonia
Pleomorphic G(-).
Young children: Major cause of life-threatening acute lower respiratory tract infections and meningitis.
Adults: very common cause of community-acquired pneumonia.
Colonizes pharynx in encapsulated (5%) and unencapsulated forms (95%).
Traditionally, encapsulated was dominant form, w/ 6 serotypes (b most frequent).
With vaccine, incidence w/ b serotype decreasing, nonencapsulated increasing.
Virulence factors:
• Pili: mediate adherence of respiratory epithelium
• Secreted factor: degrades IgA.
• Capsule: Prevents opsonization

Pediatric H influenza pneumonia: emergency w/ high mortality rate.
Descending laryngotracheobronchitis -> airway obstruction w/ smaller bronchi plugged by fibrin-rich exudate of PMN
Sinard- NO
Essentials- NO
Staphylococcus Aureus pneumonia
Often cause of secondary pneumonia (following virus).
High incidence of complications.
IV drug users have high risk of developing SA pneumonia in association w/ endocarditis.
Important cause of nosocomial pneumonia.
Sinard- NO
Essentials- NO
Klebsiella Pneumoniae pneumonia
Most frequent cause of G(-) bacterial pneumonia.
Commonly affects debilitated and malnourished people, especially chronic alcoholics.
Thick gelatinous sputum.
Sinard- NO
Essentials- NO
Pseudomonas aeruginosa
G(-) bacillus
Seen in infants (below), patients w/ burns or on ventilators, immunocompromised, critically ill.
Immunocompromised patients: rapidly progressive course, paucicellular pattern. Immunocompetent: more protracted course, cellular pattern.

Perivascular bacterial infiltration is somewhat specific for pseudomonas.
Micro: necrotizing pneumonia with 2 patterns –
• paucicellular coagulative confluent bronchopneumonia with perivascular bacillary infiltration or
• cellular pneumonia without evidence of perivascular organisms

• Rare (0.3% of neonatal ICU admissions); usually low birth weight (1.2% of low birth weight admissions)
• Mortality 32-87% with death within 1-2 days
• Diagnosis made by culture
Sinard- NO
Essentials- NO
Legionnaires’ disease
• Legionella pneumophila
• Initial awareness after epidemic in Philadelphia convention of American Legion.
• Retrospective review disclosed sporadic cases since early 1900’s.
• Seen in pts w/ predisposing conditions, especially organ transplant.
• Caused by short, G(-) bacillus.
• Causes: artificial aquatic environments.
• Transmission: inhalation of aerosolized organisms or aspiration of contaminated drinking water.
• Micro: extensive bronchopneumonia with intra-alveolar neutrophils, macrophages, fibrin, often with leukocytoclastic neutrophilic infiltrate, small vessel vasculitis and necrosis.
• Positive stains: Dieterle silver stain
• Dx: Cx is gold standard. Rapid: Legionella antigens in urine or by (+) fluorescent antibody test on sputum samples.
• Treatment: erythromycin, other antibiotics, although high mortality in immunocompromised.
Sinard- NO
Mycoplasma pneumoniae pneumonia
• Associated with immunosuppression, chronic obstructive lung disease, prior TB, pneumoconiosis, bronchiectasis, lung carcinoma.
• Causes interstitial pneumonia > bronchopneumonia.
• Cold agglutinins present in 50% of cases.
• Gross: red-blue, congested, patchy lungs, usually no pleuritis
• Micro: bronchiolitis, interstitial and minimal intra-alveolar involvement with widened alveolar septa due to lymphoplasmacytic inflammatory cells; intra-alveolar proteinaceous material; neutrophilic infiltrate in bronchioles, bronchiolar metaplasia, lymphoplasmacytic infiltrate in bronchial wall, pneumocyte hyperplasia.
• Culture required for diagnosis.
• Positive stains: acid fast (bacilli are longer [20 microns], more coarsely beaded and more bent than MTb)
Sinard- NO
SARS (Severe Acute Respiratory Syndrome)
Caused by SARS-associated coronavirus, a new member of Coronaviridae
Outbreaks worldwide in 2002.
First transmitted to humans through contact w/ wild masked palm civets eaten in China, then person to person.
Dx: PCR for virus, or by antibodes
Micro: DAD varying w/ duration of illness;
< 10 days - acute phase DAD, airspace edema, bronchiolar fibrin, small airway injury.
> 11 days - organizing phase DAD, type II pneumocyte hyperplasia and marked reactive atypia, squamous metaplasia, multinucleated giant cells, acute bronchopneumonia.
Sinard- NO
Essentials- NO
Histoplasmosis pneumonia
• Histoplasma capsulatum: intracellular parasite of histiocytes
• Thermally dimorphic fungus.
• Ovoid, 1-5 mm.
• In soil, Ohio and Mississippi valleys.
• Via inhalation.
• Necrotizing granulomas w/ cores of multiple concentric lamellae, often calcified, surrounded by palisading histiocytes and active inflammation, surrounded by zone of acellular collagen.
• ID: Cx, histo (silver stain shows organisms in necrotic cores), serology for antibodies and antigen.
• Fulminant disseminated histo: variant in immunocompromised ots: focal accumulations of mononuclear phagocytes filled w/ fungal yeasts throughout tissues and organs of body.
Coccidiodes pneumonia
• Coccidioides immitis
• Thermally dimorphic fungus.
• In Southwest US, Mexico, Central America and San Joaquin Valley (California) in soil.
• Everyone who inhales spores becomes infected.
• Most primary infections are asymptomatic.
• 10% have San Joaquin Valley fever complex: lung lesions, fever, cough, pleuritic pains.
• Numerous small (2-5 microns) endospores in thick-walled spherules (30-60 microns).
• Necrotizing granuloma w/ prominent eosinophilic infiltrate in surrounding tissue w/ organisms throughout necrotic and viable zones.
Cryptococcal pneumonia
• Cryptococcus neoformans
• From soil, pigeon droppings
• 2-15 microns, but pleomorphic and of varying dimensions.
• Intracellular collections in histiocytes -> look bubbly
• Mucicarmine stains capsule bright red.
• Varying dimensions
• Usually necrotizing granulomas; some non-necrotizing.
Blastomycosis pneumonia
• Blastomyces dermatitidis
• Thermally dimorphic fungus.
• Central and SE US.
• 8-15 microns; round; thick double-countoured cell wall, multinucleated.
• Initially acute inflammation followed by suppurative granulomas with centers containing necrotic neutrophils.
• Numerous round, refractile organisms; stain strongly w/ mucicarmine.
• 3 clinical forms: pulmonary, disseminated, primary cutaneous.
Mycobacterium tuberculosis pneumonia
• Aka Koch bacillus
• Used to be most common in children, young adults; now in 5-60 yr olds.
• Histology: caseating granulomas (soft tubercle); may have cellular center (hard tubercle)

Primary Tb: exogenous, usually clinically silent and self-limiting.
• Ghon focus: 1-1.5 cm gray-white inflammatory consolidation at periphery of upper part of lower lobe or lower part of upper lobe (greatest volume of airflow) -> becomes granulomatous then centrally nexrotic.
• Ghon complex: combination of primary lung lesion and ipsilateral LN involvement.
• Rarely primary focus rapidly enlarges and erodes into bronchi –> satellite lesions. May seed bloodstream -> miliary dissemination or meningitis.

Secondary Tb
• From reactivation of old primary lesions; presents as apical or posterior segment lesions (tuberculomas), may be bilateral. Can scar down or progress -> tuberculous empyema, intestinal Tb, or miliary seeding.
• Produces more damage than primary TB
• Isolated distal organ involvement:cervical LN, meninges, kidneys, adrenals, bones, FT, epididymis.
• Usually symptomatic.
Dirofilariasis pneumonia
• Dirofilaria immitis: canine heartworm; may infect humans as secondary end-stage host, in US: southern coastal states.
• Most patients asymptomatic.
• CXR: Well-circumscribed coin lesion.
• Adult worms die in right ventricle, embolize in pulmonary arterial circulation -> necrotizing granulomatous response with vasculitis in lung tissue.
• Central infarct with surrounding coagulative necrosis and granulomatous inflammation
• Rarely see dead worms, but: organisms in lumen of necrotic artery: 200 micron diameter w/ thick, multi-layered cuticle w/ transverse striations. May calcify w/ time.
• Usually self limited in humans, but may cause lung infarct.
Pneumocystis jiroveci (carinii) pneumonia
• Immunocompromised host; most common pneumonia in AIDS patients, who are at high risk if CD4 < 200 or if protein-calorie malnutrition
• Diffuse/ patchy pneumonia;
• Micro: alveolar spaces filled with pink, foamy, amorphous material composed of proliferating fungi and cell debris; fungi are 4-6 microns w/ single or paired intracystic bodies (1-2 microns), cup/boat shaped cysts- ID w/ silver stain; also mild inflammatory reaction with fibrin exudate, hyaline membranes.
CMV pneumonia
• Immunocompromised host.
• May be multifocal, miliary, or diffuse.
• Predominantly mononuclear inflammation w/ edema and alveolar epithelial hyperplasia.
• Foci of hemorrhagic necrosis can be seen.
• Cytoplasmic and nuclear viral inclusions seen.
Adenovirus pneumonia
• Bronchocentric; transmural bronchiolitis w/ marked destructive inflammation; bronchiolitis obliterans
• Smudge cells
• Cold agglutinins present in 20%
Aspergillus pneumonia
Second most common infective fungus, especially in hospitals.
45 degree angle branching septate hyphae.
3 types of infection:
• Allergic bronchopulmonary aspergillosis: inhalation of large # of spores -> hypersensitivity rxn in bronchi or alveoli.
• Colonizing (secondary): growth of organisms in pulmonary cavity forming a mass (aspergilloma) w/o invasion.
• Invasive (primary): opportunistic infection involving primarily lung, also heart valves, brain, kidneys. Targetoid lesions w/ necrotizing center and hemorrhagic border. Angioinvasive hyphal forms.
Malakoplakia pneumonia
Very rare, usually in immunocompromised patients
70% due to Rhodococcus equi, an animal pathogen causing opportunistic infections
Treatment: antibiotics
Gross: nodular masses or infiltrates with cavitation
Micro: intraalveolar histiocytes with pink or foamy cytoplasm that fill and destroy alveoli, not interstitium; histiocytes contain PAS+ bacteria, also Michaelis-Gutmann bodies [round/oval structures, 5-20 microns, with laminated or targetoid appearance that stain deeply with H&E, iron and calcium stains]; also lymphocytes, plasma cells, neutrophils
Robbins- NO
Sinard- NO
Mucormycosis pneumonia
Fungi common in patients with diabetes
Micro: large, non-septa hyphae with 90 degree angle branching and non-parallel walls.
Robbins- NO
Sinard- NO
Mycobacterium avium-intracellulare pneumonia
More common in AIDS patients with low CD4 counts or other immunosuppressed individuals.
Micro: marked intraalveolar and parenchymal infiltration by foamy histiocytes or proteinaceous reaction
Positive stains: acid fast (high numbers of intracellular bacteria)
Sinard- NO
Nocardia pneumonia
Opportunistic lung infection associated with transplantation, chemotherapy, immunosuppression, steroids
Gram stain: slender, slightly beaded, branching, filamentous bacilli
Micro: focal bronchopneumonia with microabscesses, ill-defined granulomas
Positive stains: acid fast- modified Fite stain.
Robbins- NO
Sinard- NO
Toxoplasma gondii pneumonia
Associated with AIDS, immunosuppression
Intracellular parasite that causes focal parenchymal necrosis, diffuse interstitial pneumonia
Micro: organisms present in histiocytes, alveolar lining cells, endothelial cells
Positive stains: GMS, Giemsa, Gram-Weigert
Robbins- NO
Sinard- NO