Respiratory Pathology IBSSD 1534/1515 PDF

IBSSD 1534/1515 RESPIRATORY PATHOLOGY Luigi Strizzi, MD, PhD Department of Pathology Midwestern University LEARNING OBJECTIVES: Become familiar with nomenclature/terminology Understand the basic pathophysiologic changes of different respiratory disorders and how these r...

IBSSD 1534/1515 RESPIRATORY PATHOLOGY Luigi Strizzi, MD, PhD Department of Pathology Midwestern University LEARNING OBJECTIVES: Become familiar with nomenclature/terminology Understand the basic pathophysiologic changes of different respiratory disorders and how these result in clinical manifestations Describe the main distinguishing macroscopic and microscopic features of the different disorders discussed  Respiratory Pathology Lectures – IBSSD 1535/1516 1. Major signs and symptoms of respiratory disorders 2. Congenital pulmonary hypoplasia 3. Atelectasis 4. Pulmonary vascular disorders: pulmonary hypertension, pulmonary edema, pulmonary embolism 5. Acute respiratory distress syndrome (ARDS) & Neonatal respiratory distress syndrome (NRDS) 6. Chronic obstructive pulmonary disease (COPD): emphysema, bronchiectasis, chronic bronchitis, bronchial asthma 7. Restrictive pulmonary disease: idiopathic pulmonary fibrosis, pneumoconiosis, sarcoidosis 8. Neoplasms of the lung  Hemoptysis Cough (coughing up Dyspnea (labored breathing) - Non-productive (dry) blood) - Productive (phlegm) Tachypnea (↑ breathing rate) Digital “Clubbing” of hands & feet (hypertrophic Wheezing pulmonary osteoarthropathy) (high-pitched whistling sound 1) Major respiratory signs/symptoms usually on expiration) Stridor (loud, high-pitched grating/snoring sound usually during inspiration) Cyanosis (desaturated Hb > Acid-base 5g/dL): → peripheral vs central disturbances (see Physiology for Pain (pleuritic Changes in key spirometry relationship between Fever values (ex. FEV1/FVC) pain) Excessive CO2 and pH) weight loss Hypoxemia (↓ tissue O2 when Hb O2 saturation is < 90% 2) Congenital Anomalies - many examples…tracheoesophageal fistula, pulmonary sequestration, congenital pulmonary cysts… Congenital Pulmonary Hypoplasia: = individual is born with incomplete or defective lung development - common congenital lesion of the lung that is usually associated with other congenital anomalies…  Congenital Pulmonary Congenital Pulmonary Hypoplasia Hypoplasia Clinic: Clinic: incomplete lung development: incomplete lung development: - poor ventilation - poor ventilation - defective gas exchange - defective gas exchange → tachypnea, dyspnea, cyanosis → tachypnea, dyspnea, cyanosis - ↑risk for respiratory infections →- fever ↑risk for respiratory infections → fever diaphragmatic hernias: diaphragmatic hernias: - organ compression → GI & CV problems - organ compression → GI & CV problems renal/urinary flow defects: renal/urinary flow defects: - oligohydramnios → edema - oligohydramnios → edema Colors = definition, pathology/pathophysiology, clinical manifestations Colors = definition, pathology/pathophysiology, clinical manifestations 3) Atelectasis = a.k.a. as collapsed lung Loss of lung volume due to inadequate expansion of lung tissue/air spaces. Main types are… Compression atelectasis: Contraction atelectasis: Obstructive or absorptive atelectasis: direct physical compression → most collapse is the result of lung caused by airway obstruction. In the commonly by air (“pneumothorax”) or contraction usually caused by lung distal to the obstruction, blood fluid (ex. blood in “hemothorax” or fibrotic retraction of the ‘absorbs’ more gas than enters the abscess in “empyema”). In severe cases affected lung alveoli → lung begins to may cause shift of mediastinum away “collapse’ on itself. from the affected lung (→). →  lung air hemothorax lung Compression atelectasis of right lung caused by pneumothorax Compression atelectasis of left lung caused by massive hemothorax Clinic: dyspnea, tachypnea, cough, cyanosis, hypoxemia, chest pain 4) Pulmonary vascular disorders Pulmonary hypertension (PH) = increased pulmonary arterial pressure (PAP) > 25 mmHg - ↑PAP is the result of ↑resistance to blood flow through pulmonary circulation...if acute can lead to pulmonary edema & respiratory distress - ↑PAP → ↑strain on the RV → if chronic can lead to RV failure ( “cor pulmonale” ) → peripheral venous congestion → edema, ascites, etc. Know the flow! PH can be Precapillary or Postcapillary, i.e. upstream or downstream relative to the pulmonary capillaries (PC)… Hydrostatic pressure – the basics How would you increase water pressure ? Increase volume BP = CO x TPR Increase resistance Note, anything that increases resistance to normal blood flow in a vessel will have upstream and downstream consequences…!  PC ‘Precapillary’ causes of pulmonary hypertension (PH): RV PA PV LV - left-to-right cardiac shunt… …over time, ↑pulmonary blood V & P → ↑stress on vessel wall → thickening of pulmonary arteries → narrowing of vessel lumen → ↑ pulmonary vascular resistance (PVR) normal pulmonary artery thickened pulmonary artery causing PH ↑blood V RV volume overload → …per Frank-Starling Law → ↑ RV contractile force End result → more blood is being pumped out of the RV with greater force/unit area → ↑pulmonary arterial Pediatr Rev. 1999 pressure Long term complication of PH caused by left-to-right cardiac shunt… …over time ↑PVR & ↑contractile force of RV→ L → R shunt becomes R → L = Eisenmenger syndrome Deoxygenated venous blood from RV mixes with oxygenated blood in the LV… Clinic: - Cyanosis - Fatigue - Shortness of breath - Chest pain - Other ‘precapillary’ causes of pulmonary hypertension: …anything that can narrow the lumen of the pulmonary arteries and increase pulmonary vascular resistance original diameter of a pulmonary artery reduced by ↑fibrosis in 1ary PH - 1ary pulmonary hypertension (PH): idiopathic disorder of pulmonary arteries is most common cause…or rarely BMPR2 mutation → defective TGF-beta signaling… - result: smooth muscle hypertrophy + vessel wall fibrosis → narrowing of vessel lumen → increased PVR - Systemic disorders affecting pulmonary arteries, such as atherosclerosis, collagen vascular disease (ex. scleroderma), etc. → narrowing of vessel lumen → increased PVR original diameter of a pulmonary original diameter of a pulmonary artery reduced by atheroma artery reduced by ↑collagen deposition in scleroderma - pulmonary hypertension 2ary to disorders associated with poor ventilation (ex. COPD, restrictive pulmonary diseases, obesity, sleep apnea, etc.) Ventilation/perfusion (V/Q) matching: - intrapulmonary arteries constrict in response to alveolar hypoxia to redirect blood (“shunting”) to better-oxygenated lung segments for optimizing oxygenation of the blood and systemic oxygen delivery. blood flows to poorly “shunting” of blood ventilated area → hypoxia → reflex PA constriction → to areas that are (…V/Q mismatch) better ventilated narrowing of vessel lumen increased pulmonary vascular resistance Sleep apnea → obstruction of upper airways → poor oxygen delivery to alveoli (“…alveolar hypoxia”) → intrapulmonary arterial constriction → pulmonary hypertension obstructive sleep apnea (OSA) can also affect the eye and ocular adnexa… central serous Floppy Eye Syndrome (FES) chorioretinopathy Subretinal fluid (arrowheads) is evident on fundus photograph (a). Horizontal optical coherence tomography scan (b) shows subretinal fluid with elevated OSA → hypercapnia, hypoxemia, oxidative retina and thickened choroid stress → elastin fiber disorganization → (double head arrows) FES Ischemic Optic Neuropathy blurring of the optic disc margin in (a) compared to normal a normal-looking optic disc (b)  PC - ‘Postcapillary’ causes of pulmonary hypertension RV PA PV LV - Left-sided cardiac disorders: stenosis (narrowing) of the mitral valve or the aortic valve or of the aorta or left ventricular (LV) heart failure → these cause obstruction or increased resistance to postcapillary blood flow from lungs → pulmonary hypertension coarctation of the aorta aortic valve …for example, in mitral valve stenosis, mitral valve the narrow mitral valve ↑ resistance to blood flow from LA. This ↑ resistance is transmitted back from the LA to pulmonary vessels causing pulmonary hypertension - Pulmonary Edema = accumulation of fluid (edema) in the lung Interstitial fluid homeostasis → balance between: 1. Hydrostatic pressure 2. Oncotic pressure 1) Cardiogenic causes of pulmonary edema: 3. Lymphatic drainage - the same causes of postcapillary pulmonary hypertension (ex. 1 mitral stenosis, left ventricular failure, etc.) - the increase in hydrostatic pressure in the pulmonary circulation eventually “pushes” fluid out into the 2 pulmonary extravascular space → edema forms 2) Non-cardiogenic causes of pulmonary edema: - decreased plasma oncotic pressure (ex. malnutrition, liver disease, nephrosis) 3 - lymphatic blockage - volume overload (ex. kidney failure; iatrogenic) - damage to respiratory membrane (ex. DAD) - high altitude → V/Q mismatch - Pulmonary Edema: - when fluid can no longer be accommodated in Pathology: the interstitium → “interstitial edema”, it spills into - eosinophilic (pink) material (edema fluid) the alveolar space → “alveolar edema” → - congestion of alveolar capillaries respiratory distress… - extravasated RBCs (common in CHF) Chest X-ray → diffuse pulmonary opacities - hemosiderin filled alveolar macrophages (“heart failure cells”) (“white out”) normal alveoli alveolar edema heart failure cells Pulmonary Embolism = sudden obstruction of a major blood vessel (artery) in the lung - blood clot (thrombotic embolus) most common→ ex. conditions associated with increased tendency to clotting (prolonged immobilization, cancer, oral contraceptive use, etc.) - can also be caused by a nonthrombotic embolus: fat, air, tumor cells, septic emboli, etc. Pulmonary Embolism 1 cm “Saddle” embolus at bifurcation of pulmonary artery Infraction is rare (~10%), when it does occur → the infracted area is typically dark brown & wedge shaped Morphology: with the occluded vessel near the apex. Varies…size, number, location of embolus(i)  “Fatal air embolism during dental implant surgery: a report of three cases.” Can J Anesth. …pulmonary embolism can occur in the “Deep vein thrombosis: A rare complication in oral and maxillofacial surgery...” dentist’s office! Contemporary Clinical Dentistry. “Septic pulmonary embolism due to periodontal disease.” Respirology. Ocular manifestations of a pulmonary embolism: pulmonary embolism → ↑ venous pressure in the eye→ edema; ↓flow in retinal or ophthalmic artery Clinic: - dilated retinal veins & edema - blurred vision or temporary vision loss (amaurosis fugax) - other signs of ↑intraocular pressure (pain, redness, etc.) 5) Acute (Adult) Respiratory Distress Syndrome (ARDS) MEDICAL EMERGENCY! Rapid onset of life-threatening respiratory distress/insufficiency, severe arterial hypoxemia, cyanosis High rate of mortality → 60% Pathogenesis: DIFFUSE ALVEOLAR DAMAGE (DAD) → injury to respiratory membrane… …thus, DAD will most often result in damage to both alveolar epithelial and endothelial cells Important causes of injury to components of the respiratory membrane (i.e. alveolar epithelial and/or endothelial cells): - Infections → pulmonary or systemic (viral, bacterial, sepsis) - Reduced tissue perfusion → shock → ischemic tissue damage → release of endothelial damaging vasoactive peptides → lung endothelial injury - Aspiration: ex. gastric content → chemical injury to alveolar epithelium; also, oral secretions or debris - Drugs/Toxins: via systemic route (ex. cancer chemotherapy, narcotics – heroin!) or inhaled (toxic vapors, smoke) → chemical injury to respiratory membrane  DAD → increases alveolar capillary permeability → leakage of protein-rich fluid into alveoli Acute exudative phase: 1) Cell injury → DAD If patient survives acute phase… 2) Fluid leak (Edema) → bilateral, patchy alveolar infiltrates (“white out”) on X-ray Organizing phase: 7) FIBROBLAST PROLIFERATION in interstitial space 8) Collagen deposition… 3) Two outcomes: - Complete Resolution: resorption of exudate, collagen + repair of respiratory epithelium by type II cell Or… - Fibrosis → remodeling and 3) Macrophage activation → recruit neutrophils distortion of the lung and formation 4) Recruited neutrophils release of proteolytic enzymes of cyst like spaces separated by 5) Enzymes cause further damage to alveolar wall…more fluid leaks (see 2) fibrous tissue (“honeycomb lung”) 6) Fluid ‘organizes’ → hyaline membrane formation ARDS Normal ARDS Resolving ARDS T2P AM HM Interstitial fibrosis Honeycomb lung Neonatal Respiratory Distress Syndrome (NRDS) Surfactant - Surfactant Is a mixture of phospholipoproteins (dipalmitoyl lecithin and sphinomyelin) - secreted by type II pneumocytes (T2P) - Surfactant reduces surface tension (i.e. the cohesive forces among liquid molecules) → helps keep alveoli from collapsing and sticking together, especially during expiration hydrophilic head surfactant hydrophobic tail NRDS - most common cause of death in premature/preterm infants (born before 28 – 34 wks) → immature T2P → low surfactant production (normal surfactant production begins ~ 24 - 28 wks and completed by 35 wks) - infants of diabetic mothers → abnormal fluctuations in insulin levels of diabetic mother interferes with T2P differentiation in fetus - During lung maturation T2P progressively produce more functional surfactant (i.e. containing more lecithin): [lecithin] > [sphingomyelin] → normal L/S ratio in amniotic fluid usually > 2.4 → L/S ratio < 1.5 associated with increased risk for NRDS - low surfactant → adherent alveoli → if forcibly separated → DAD - fluid leakage from DAD → ”white out”…hyaline membranes…hypoxia… dyspnea, cyanosis, tachypnea… normal NRDS Important complication in NRDS bronchopulmonary dysplasia → long term positive pressure O2 Tx → alveolar damage → inflammation → altered growth factor signaling + free radical lung damage from damage + increased ECM production → mechanical alveoli become stiff, deformed, poorly ventilation developed retrolental fibroplasia → chronic O2 Tx → disorganized vascular growth → ischemia, scarring, retinal detachment → visual impairment and/or peripheral tissue damage from excess O2 6) Chronic obstructive pulmonary disease (COPD) - COPD 4th leading cause of death in the US → ~140,000 Americans die of COPD/year… F > M - COPD includes: emphysema, bronchiectasis, chronic bronchitis, bronchial asthma Emphysema: Definition → pulmonary changes characterized by enlargement of air spaces distal to the terminal bronchiole resulting from destruction of the alveolar walls - slowly progressive clinical course…typically starts in the 50s – 60s Pathogenesis: Cigarette smoke is the most common cause Smoking induces: - direct toxic and free radical damage to respiratory epithelium - The associated inflammatory response → release of proteases from neutrophils & macrophages → enzymatic destruction of the alveolar walls  Cigarette smoke also… 1)…alters protease- antiprotease mechanism ! 2) As a result of antiprotease defect, proteases (e.g. elastases) are free to affected patients lyse elastin & other structural are usually proteins → loss of alveolar elastic younger, 20s – tissue + loss of septal tissue 40s…& often have signs of liver disease like jaundice  Histopathology of emphysema normal lung Emphysema = destruction of alveolar walls → abnormally enlarged airspaces Emphysema IHC shows staining for elastin (brown) in walls of normal arteriole, bronchiole & alveoli - In emphysema → destruction of elastin in alveolar wall → reduced lung elasticity → expiration difficulty → air gets trapped in the lung → lung hyperinflation In emphysema, chest X-ray shows hyperinflated lungs (i.e., lung fields are darker because of increased air content) & diaphragmatic flattening Emphysema Complications: Clinical manifestations: 1) continued destruction of alveolar walls → ↓surface cough, dyspnea, hyperventilation (helps maintain area for gas exchange → worsening hypoxia adequate gas exchange…at least initially!) & weight loss 2) alveolar capillaries are destroyed → network for blood flow → increased resistance PA blood flow → “pursed lip breathing” pulmonary hypertension → RV failure (cor pulmonale) “pink puffers” 3) air filled blebs or bubbles form on lung surface (bullous emphysema) can rupture → air leakage into pleural space → pneumothorax Bronchiectasis Definition → Damage to walls of bronchi and bronchioles that leads to permanent dilation of these structures Pathogenesis: 3 1. obstruction (different causes*…mucous 4 secretions most common) 2. microbial proliferation (usually S. aureus, K. pneumoniae) 5 3. inflammation → leukocytic infiltration → release 2 of proteases 4. Damage to epithelia → impair mucociliary clearance 1* 5. Stagnation of cellular debris, proteases, etc. → continued erosive inflammatory process → destruction of muscle and elastic tissue of bronchi/bronchiole wall → vicious cycle → * a) “ciliary dyskinesia” → defective ciliary structure → impaired mucous flow impaired mucociliary clearance -> mucous b) “cystic fibrosis” → defective flow of Cl-, Na+ and H2O → viscous mucous obstruction….infection…etc. c) other causes that can obstruct mucous flow (ex. foreign body, etc.) Bronchiectasis Morphology: - Abnormally dilated airways (tubular/cylindrical or varicose aspect) - Lack of normal bronchial tapering i.e. normal airways can be usually traced up to 2-3 cm away from pleura → in bronchiectasis dilated bronchi can be traced close to pleura Bronchiectasis Clinical features: airway obstruction: - ventilation defects - chronic hypoxia → cyanosis, digital clubbing, etc. - V/Q mismatch → pulmonary htn - obstructive/absorptive atelectasis - irritation → chronic cough → productive, mucopurulent cough excess mucous: - air/fluid levels - infections (S. aureus, K. pneumoniae) - fever - foul smelling secretions - Inflammation - thickened lung markings - erosion of bronchial wall → lose of elasticity → poor ventilation - erosion of bronchial blood X-ray → thickened lung markings, “doughnut holes”, “tram vessels → hemoptysis tracks”, air/fluid levels Chronic Bronchitis Definition → Persistent, productive cough for at least three months per year during a period of two consecutive years. Pathogenesis inhaled irritants -> smoking, air pollutants Leads to… goblet cell hyperplasia Bronchial submucosal glandular hyperplasia wall mucus hypersecretion thickening mucus plugging bacterial infection -> acute inflammation/exudate -> alveolar and/or bronchial wall destruction -> emphysema and/or bronchiectasis bronchial squamous metaplasia Chest X-ray: increased broncovascular markings (especially of the proximal bronchial branches) consistent with bronchial wall thickening in chronic bronchitis Chronic Bronchitis chronic bronchitis normal bronchial histology  Chronic bronchitis -hypercapnia, hypoxemia, cyanosis → elevated Hb -mucus hypersecretion → recurrent infections → destruction of Clinical course alveolar septa/bronchial wall → emphysema & bronchiectasis - inflammation + glandular hyperplasia + mucus hypersecretion → lumen narrowing -with progression → pulmonary hypertension → cor pulmonale → air flow obstruction… → RV failure → peripheral edema “blue bloater” Bronchial asthma (Asthma) = Bronchial obstruction caused by airway hypersensitivity associated with inflammation, bronchial smooth muscle contraction and increased mucous production Two Types: 1) Intrinsic or Non-atopic asthma and 2) Extrinsic or Atopic (allergic) asthma 1) Intrinsic asthma or Non-allergic usually involve Agents that can cause irritation & hyper-reactivity of airways ASA inhibits COX but not LOX so more bronchoconstrictive direct chemical irritation leukotrienes are produced viral respiratory infection lowers threshold of sub-epithelial vagal receptors to irritants cold air, exercise → dry airways → irritation → hyper-reactivity psychological stress; emotions (anger, laughter) → stimulates vagus → bronchoconstriction chemicals in food: ex. food coloring 2) Extrinsic or Allergic (atopic) asthma → Positive family history is common (i.e. can run in the family!!) Initial immune sensitization: APC present airway allergen/Ag to naïve T cells → differentiate into TH2 cells that produce interleukins: - IL-4 -> stimulate B cell → produce IgE that localize on mast cells - IL-3, IL-5 -> eosinophil activation Subsequent allergic response: - Immediate phase Ag binds to and cross-links IgE on mast cells -> within minutes mast cells release mediators (ex. bradykinin, histamine, IL-13, ECF) that: - stimulate subepithelial vagal receptors -> bronchoconstriction - increase vascular permeability -> edema - increase mucous production - recruitment of more eosinophils - Late phase response - the accumulation of eosinophils amplify and sustain inflammatory response via release of ECF, MBP & eosinophil IL-5 receptor antagonists peroxidase (damage airway epithelial cells), cysteinyl (ex. reslizumab, leukotrienes (induce bronchoconstriction) mepolizumab) for eosinophilc asthma  Chest x-ray in patient with asthma Asthma Clinical Course Acute attack with dyspnea (“…somebody is sitting on my chest”), wheezing, patient tends to remain motionless during attack can last several hours → cyanosis may asthma develop FEV1/FVC < 0.7 response to bronchodilator (ex. 2-agonists) in most cases status asthmaticus → can last days or weeks → does not respond well to therapy → life threatening Over time… ↑ air trapping → chronic hyperinflation excess mucous production can predispose to bacterial infection → bronchitis or pneumonia → can lead to emphysema hyperinflation compromised gas exchange → altered pulmonary diaphragmatic flattening hemodynamics (V/Q mismatch, etc.) → Cor Increased bronchial cuffing & bronchovascular marking pulmonale/heart failure +/- mucous plugs Asthma Morphology Areas of distended lungs + areas of atelectasis Mucous casts Mucus plugs/casts occlude bronchi Bronchial wall thickening epithelial cell debris Curshman spirals = from eosinophil granules Charcot-Leyden crystals Hyperinflation + areas of atelectasis mucous plug obstructing a bronchial bifurcation  Asthma Histopathology 1) Inflammatory infiltration (eosinophils !!) 2) Reduced airway lumen caliber/thickening of mucosa 3) Increased size of submucosal glands & thickening of basement membrane 4) Smooth muscle hyperplasia airway remodeling in asthma normal 7) Restrictive pulmonary disease - Reduced expansion/elastic recoil of lung parenchyma → rigid/non elastic lungs asthma - reduced lung expansion means less total air in the lungs…↓FVC - reduced elastic recoil means “it takes longer to blow out air”… ↓FEV1 restrictive pulmonary disease - ↓FEV1…but also ↓FVC…so FEV1/FVC ratio may show little to no change Major causes Chest wall disorders (with normal lung parenchyma) Acute or Chronic interstitial (lung parenchyma) diseases - severe obesity - acute → example: ARDS - diseases of the pleura - chronic → examples: idiopathic pulmonary - neuromuscular disorders affecting respiratory muscles interstitial fibrosis → interstitial fibrosis 2ary to fibroblastic proliferation; pneumoconiosis → caused by inhalation of certain dust particles; infiltrative granulomatous diseases like sarcoidosis) Clinic: dyspnea, tightness of the chest, productive cough - Pneumoconiosis = Lung disease caused by CHRONIC inhalation of mineral dust particles - nomenclature according to the substance inhaled: anthracosis = coal silicosis = silica or quartz asbestosis = asbestos dust dust fibers chronic exposure & particle size are Small particles that can reach alveoli are most important… dangerous… - stimulate release of fibrogenic factors in alveoli & - large particles >10 microns get trapped on interstitium causing fibrosis mucous covered bronchi and bronchioles and - from interstitium → lymphatics → LNs or pleural subsequently removed by mucociliary transport. space (asbestos!) → pleuritis, effusion, fibrosis…  silicosis asbestosis anthracosis Anthracotic deposits In “black lung” disease a.k.a. coal workers’ lung Scarring and formation of silicotic Peripheral lung and pleural scarring from nodules build up of asbestos fibers (‘ferruginous bodies’). These may be found in the expectorate/sputum. - Sarcoidosis Mikulicz syndrome = sarcoidosis of the salivary - Multisystem, chronic granulomatous disease of unknown glands → xerostomia → increased risk for caries etiology affecting skin, bone, CNS, spleen, liver, bone, salivary glands, eyes and lungs… Ocular Sarcoidosis → keratoconjunctivitis sicca, uveitis, optic neuropathy → blurred vision → vision loss Sarcoidosis - lung sarcoidosis -> restrictive lung disease - on chest X-ray -> bilateral lymphadenopathy Clinic: -young adults (< 40 yrs) common; certain Scandinavian populations - in US: African-Americans 10X > than US Caucasians - Higher prevalence in non-smokers - association with HLA-A1 and HLA-BB common - increased ACE levels, hypercalcemia, polyclonal hypergammaglobulinemia Sarcoidosi s Pathology: exaggerated interstitial and intra-alveolar CD4+ Th1 response to unknown antigen → macrophage activation and noncaseating granuloma formation noncaseating granuloma “lymphangitic” distribution of granulomas that compress & distort lung tissue → activated macrophages “restricts” pulmonary fuse → multinucleated expansion. Can also giant cells characteristic compress pulmonary of granulomas vessels → pulmonary hypertension 8) Neoplasms of the lung Benign lesions : - adenomas, - papillomas - hamartomas on imaging appear as well circumscribed circular masses → “coin lesions” Histopathology: mixture of adipose, cartilage, fibrous tissue & blood vessels Malignant lesions : - Primary Lung Cancer - #1 cause of cancer related deaths in the industrialized world - #1 cause of cancer related deaths in men & women in the U.S. Causes: - Cigarette smoking!! → squamous cell carcinoma! - heavy smokers 60X increased risk vs non-smokers; exposure to passive smoke 2X increased risk vs non-smokers; women more susceptible to cigarette induced damage vs men - Environmental pollution and industrial toxins (radioactive ore (radon), arsenic, chromium, nickel, vinyl chloride, asbestos, etc.) - 1ary Lung Cancer 95% of 1ary lung cancers originate from the bronchial epithelium (bronchogenic carcinoma) 5% miscellaneous group: neuroendocrine tumors (carcinoids) – secrete active neuroendocrine molecules serotonin, calcitonin, etc.; mesenchymal tumors (ex. fibrosarcomas, leiomyomas); lymphomas Clinic: coughing +/- hemoptysis, dyspnea, chest pain, weight loss, fatigue, infections Major Histologic types of lung cancer: - squamous cell - non-small cell lung carcinoma (NSCLC)carcinoma surgery - adenocarcinoma - large cell carcinoma - small cell lung carcinoma (SCLC) chemotherapy Squamous cell carcinoma (SCC) of the lung – most common in cigarette smokers; usually originates as a central, perihilar mass …like ‘squamous’ epithelium of the skin SCC of the lung: layers of polygonal, squamous or ‘scale- …like reptile ‘scales’ like’ cancer cells -concentric layers of keratinized cells (a.k.a. ‘keratin pearls’) can be found within the layers of malignant squamous epithelium (arrow) keratin pearls & keratinized cells in BAL or sputum cytology from SCC of the lung Adenocarcinoma of the lung – most common in women and non-smokers; Usually manifests as a peripheral mass composed of malignant epithelium arranged in glandular-like structures (arrows) LCLC – can arise anywhere in the SCLC usually arise centrally and lung; composed of large quickly spreads through lung undifferentiated cells with abundant cytoplasm Sheets of highly malignant, anaplastic, “small, dark blue cells” with scarce cytoplasm resembling lymphocytes... a.k.a. “oat cell” carcinomas… - SCLC often associated with paraneoplastic syndromes (ectopic ACTH syndrome; syndrome of inappropriate ADH). Pancoast tumor (a.k.a. cancer of the lung apex) Vagus nerve Sympathetic Brachialtrunk plexus Recurrent nerve Subclavian artery & vein Associated with: - Compression of subclavian -> swelling of face, head and neck veins - Brachial plexus compression -> shoulder & arm pain - Compression of recurrent laryngeal nerve -> hoarseness of the voice - Compression of cervical sympathetic plexus -> Horner syndrome (miosis, enophthalmos, ptosis, anhidrosis) - 1ary Lung Cancer: classifying the extent of tumor growth → “Where is it? How big is it? Has it spread?” → TNM/Staging system http://cancerstaging.org/references-tools/quickreferences/documents/lungmedium.pdf  - Secondary Lung Cancer Common Primaries that metastasize to the lungs bladder cancer breast cancer colon cancer “popcorn-like” appearance of multiple foci of cancer metastasis to the lung kidney cancer neuroblastoma prostate cancer soft tissue sarcoma The End  Match items in column A with items in column B Column A Column B 1. adenocarcinoma of the lung 1. ventilation/perfusion mismatch causing shunting of pulmonary blood flow 2. ARDS 2. can cause pulmonary hypoplasia 3. asthma 3. Th2 immune response and airway remodeling 4. atelectasis 4. squamous cell carcinoma 5. bronchiectasis 5. diffuse alveolar damage and hyaline membrane formation 6. oligohydramnios 6. hemosiderin filled macrophages 7. Charcot-Leyden crystals 7. pulmonary arterial pressure >25mmHg 8. chronic bronchitis 8. alveolar wall digestion by proteases from inflammatory cells 9. popcorn aspect 9. can cause postcapillary pulmonary hypertension 10. emphysema 10. permanent airway dilatation due to erosive inflammatory process 11. ferruginous bodies 11. oat cell cancer 12. heart failure cells 12. most common type in nonsmokers 13. hypertrophic osteoarthropathy 13. loss of lung volume due to inadequate expansion of air spaces 14. Floppy eye syndrome 14. ventilation/perfusion mismatch causing increased dead space 15. paraneoplastic syndromes 15. found in mucous from asthma patients 16. keratin pearls 16. digital clubbing 17. mitral valve stenosis 17. multiple metastatic foci in the lung 18. Pancoast tumor 18. can cause neonatal respiratory distress syndrome (NRDS) 19. pneumoconiosis 19. caused by inhalation of certain types of mineral dust particles 20. pulmonary embolism 20. multisystemic granulomas that can affect lacrimal and salivary glands 21. pulmonary hypertension 21. asbestosis 22. surfactant defect 22. blue bloater 23. sarcoidosis 23. Can result from hypoxemia related elastin fiber disorganization 24. sleep apnea 24. cancer of the lung apex 25. small cell lung cancer 25. associated with production of hormone-like substances