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Pulm II - Tumors, Obstructive, Restrictive Dzs, Lung Pathology Chronic Obstructive Pulm Dz -airway dz->limited FEV1 -dyspnea -many overlapping features EMPHYSEMA Abnl enlargement distal to term bronchiole -destruction of walls, but not fibrosis Centriacinar-95%-proximal acini parts -heavy smokers (also resembles CWP) -upper zones Panacinar-LOWER zones; Alpha-1-AT def -PiZZ phenotype (80%) (PiMM NL) -voluminous lungs Paraseptal-distal acinar; fib, scar at pleura -atalectasis; all worse at upper lung Irregular-ass’d w/ scarring-male smokers -bullae, blebs common Compensatory(hyperinflate post-lobectomy), Senile (larger ducts, smaller alvi), Obstructive overinflation, Bullous, Interstitial PATHOGENESIS -protease-antiprotease mech – destruction Alpha-1 AT vs elastase(PMNs) ->elastase dmg w/ def -Smokers w/ more PMNs, macs in alvi -via inc. IL-8, nicotine -oxidants in cig smoke inhibit a1-AT MORPH-destroy septal walls, alvi fuse->bleb ->distort blood, air flow CLINICAL-at 1/3 incapacitation -Dysp, cough, wheezing, wt loss, barrel chest, prolonged, forced expiration, hunched over, pursed lips ABGs pretty NL – PINK PUFFERS Death via resp acidosis, Rt HF, pneumothorax, Lung Pathology Lung Tumors Paraneoplastic Syndromes (1-10% CA) SCC-ADH->hyponatremia SCC-ACTH->Cushing Syndrome SqCC-PTH, sim peptides, PGE->hyperCa Calcitonin->hypocalcemia Gonadotropins->gynecomastia Serotonin->carcinoid syndrome Lambert-Eaton Myasthenic Syndrome -AI ABs to neuron Ca channel Periph Neuropathy (sensory) Acanthosis Nigrans, leukemoid rxns Apical CAs (Pancoast)-> -invade sup structures ->Horner syn, BRONCHIAL ASTHMA Hyperreactive airways ->episodic, reversible bronchoconstriction -due to atopy-making more IgE -can->chronic bronchitis or cor pulmonale Extrinsic-type I HS rxn to extrinsic Ag-types: -atopic (allergic), occup, allergic bronchopulm aspergillosis Intrinsic (idiosyncratic)-nonimmune causes -aspirin, pulm infx (viral esp), cold, irritants, stress, exercise, emboli MORPH-overdistended, overinflated lungs -small ateletatic areas, thick bsmt memb -mucous plugs in bronch,’ioles -Curschmann Spirals-shed epith from plugs -Eos, Charcot-Leyden crystals (crystalloids) -Creola bodies-shed epith in clumps -edema, bigger glands (Reid), wall mm. ->emphysema, bronchitis (w/ infx) poss CLINICAL-attack-several hrs->coughing ->cough up resp secretions -can persist at low level OR Status Asthmaticus-days-wks->cyanosis/death -find Curschmann, C-L crystals, elev Eos Severe-hyperinf->emphysema Infx->chronic bronchitis, BE, pneumonia ->poss Cor pulmonale, heart failure Pathogenesis Chronic inflam, bronchial hyperresponsiveness ATOPIC-most common, begins in childhood -triggered by any Ag – usual FHx of atopy Ag inhalation->Th2->IL-4(mast), IL-5(IgE) -subsequent->acute response, late-phase rxn Acute->bronchoconstrict(subepith vagal receps) -edema, mucus secretion, hypotension, WBCs Late-stage-4-8 hrs-24hrs – from mast, PMNs, lymphos extravasated from acute phase -and from air epith (eotaxin), endoth cells ->Eos MajorBP->epith dmg, airway constrict Mediators: 1. Leukotrienes C4, D4, E4->bronchoconstrict ACh->airway sm. mm. constriction 2. Minor role: Histamine, PGD2, PAF 3. Unknown role: IL-1, TNF, IL-6, chemokines, neuropeptides, NO, bradykinin, endothelins NONATOPIC-triggered by resp tract infx-viruses esp (rhino, parainflu), Lung Pathology Lung Tumors METASTATIC TUMORS Frequent site carc and sarcomas -from anywhere via blood/lymph Direct: esoph CA, MS lymphoma -mult nodules scattered in PERIPH -“Cannonball Lesions” Or peribronchiolar, perivasc (lymph) -in septa, CT – gray-white Tumor emboli can->pulm HTN, Lung Pathology Lung Tumors MISC TUMORS Lung hamartoma relatively common -incidental opacity (coin lesion) -‘popcorn calcifications’ -mostly mature hyaline cartilage-push lung -can have resp epith in cart. clefts -or fat, fibrous, vessels Mediastinal (MS)-invade, compress lung -lymphoma, thymoma, thyroid, para, Lung Pathology Chronic Obstructive Pulm Dz -airway dz->limited FEV1 -dyspnea -many overlapping features Inhalation of foreign object, Lung Pathology Lung Tumors NEUROENDOCRINE TUMORS មyo, M & F, no smoking relation Tumorlets-benign small hyperplastic cells -in chronic inflam or scarring Bronchial Carcinoid-1-5% lung tumors -locally invasive or ->mets -like Kulchitsky cells, intes. CA -salt/pepper nuc, slow mitoses -no p53 mutation (typical carcinoid) -rarely hormonally active, can resect MORPH: polypoid; ‘collar-button’ ->obstruct bronch, bleed->cough, hemop ->emphy, BE, atalectasis, bac infx -cells in carcinoid nests, sep by fibrous -black neurosec granules Spread to LNs w/ little effect Few argentaffinoma-like lesions->lil carc syn, Lung Pathology Chronic Obstructive Pulm Dz -airway dz->limited FEV1 -dyspnea -many overlapping features BRONCHIAL ASTHMA Hyperreactive airways ->episodic, reversible bronchoconstriction -due to atopy-making more IgE -can->chronic bronchitis or cor pulmonale Extrinsic-type I HS rxn to extrinsic Ag-types: -atopic (allergic), occup, allergic bronchopulm aspergillosis Intrinsic (idiosyncratic)-nonimmune causes -aspirin, pulm infx (viral esp), cold, irritants, stress, exercise, emboli MORPH-overdistended, overinflated lungs -small ateletatic areas, thick bsmt memb -mucous plugs in bronch,’ioles -Curschmann Spirals-shed epith from plugs -Eos, Charcot-Leyden crystals (crystalloids) -Creola bodies-shed epith in clumps -edema, bigger glands (Reid), wall mm. ->emphysema, bronchitis (w/ infx) poss CLINICAL-attack-several hrs->coughing ->cough up resp secretions -can persist at low level OR Status Asthmaticus-days-wks->cyanosis/death -find Curschmann, C-L crystals, elev Eos Severe-hyperinf->emphysema Infx->chronic bronchitis, BE, pneumonia ->poss Cor pulmonale, heart failure, Lung Pathology Lung Tumors BRONCHIOLOALVEOLAR CA 1-9% CA – in Pulm parenchyma MORPH-periph lung -single, or mult diffuse nodules -grayish-confused w/ pneumonia Histo: tall, col-cub epith cells in alv as Branching papillary formations-glandular -lots of mucus, preserve septa architect -Bronchiolar, Clara, or type II cells CLINICAL: 20+ yo, M or F Sx-sim to BG CA-cough, hemop, pain -not bronchi->no atalectasis, emphysema -can have diffuse interstitial pneumonitis -METS eventual in 25%, but late, small Tx-surgery –high 5 yr survival, overall 25%, Lung Pathology Chronic Obstructive Pulm Dz -airway dz->limited FEV1 -dyspnea -many overlapping features CYSTIC FIBROSIS ABNLly viscid secretions->obstruct organ ducts AUTOSOMAL RECESSIVE-whites -Chromosome 7->CFTR (Cl channel) -most w/ deletion of codon: Phe-position 508 ->ABNL folding (-)Sx to Classic CF presentation: BE, Pancreatic insuff (steatorrhea), male infertility, hepatic fibrosis Infants w/ meconium ileus Sweat glands-decreased Cl reabsorption Airway-reduced Cl secretions into airway ->more Na into cell->more H2O absorbed ->thicker secretions, defective mucocilia ->obstruction, can’t clear bac: S. aureus P. aeruginosa secrete more ALGINATE-mucoid ->host immune->more dmg, not clearing MORPH-Lung and panc involvement (85%) -mild: dilation of exocrine glands -later: plugged glands-> exocrine panc atrophy -malabsorption (fat, vit A) -biliary cirrhosis, salivary duct dilation -PULM most important changes