URTI

June 26, 2018 9:06 AM

01 Upper respiratory tract infections

NASOPHARYNX
- Necrotizing lesions of upper airways
○ Rhinocerebral mucormycosis in diabetes, immunosuppressed
○ Wegener's granulomatosis with polyangiitis
- Acute pharyngitis and tonsillitis
○ Rhinovirus, Echovirus, adenovirus, β hemolytic streptococci

Rhinosinusitis
Descript - Obstruction of sinus drainage into - Protrusion of edematous,
ion nasal cavity = inflammation, pain
over infected area
- Common Cold
• Sneezing, congestion, runny
nose
• Inflammatory infiltrate with
eosinophils
• Associated with asthma,
eczema, sinusitis
Etiology - Rhinovirus
- Allergic Rhinitis
• Type I hypersensitivity
Nasal Polyp Sinonasal Schneiderian Angiofibroma Olfactory Neuroblastoma Nasopharyngeal Carcinoma
Papilloma
- Benign tumor from - Benign tumor of nasal - Tumor from - Malignant tumor of
inflamed nasal mucosa respiratory mucosa lining mucosa neuroectodermal olfactory nasopharyngeal epithelium
nasal cavity - Made of blood vessels cells • Pleomorphic, keratin
- Adult males age 30-60 and fibrous tissue - Small round blue cell tumor positive cells in a
- Adolescent red-headed, background of
fair skinned males lymphocytes
• Enlarged cervical LN
- Repeated rhinitis - Age 15 or 50 - EBV
- Cystic fibrosis in kids • African children
- Aspirin-intolerant asthma • Young Chinese adults
• Asthma + aspirin-
induced
bronchospasms + nasal
polyps

LARYNX
Acute Epiglottitis Laryngotracheobronchitis Diphtheria Vocal Cord Nodule Laryngeal Papilloma Laryngeal Carcinoma
(Croup)

Descrip - Inflamed epiglottis
tion
Etiology - H influenza type B
• Immunized,
nonimmunized kids
Present - High fever, sore throat
ation - Drooling with dysphagia
- Muffled voice
- Inspiratory stridor
- Risk airway obstruction
- Inflamed upper airway
- Parainfluenza
- Barking cough
- Inspiratory stridor
- Corynebacterium
- Grey pseudomembrane
- Nodule on true vocal cord
- Wear and tear (singer)
- Bilateral
- Made of myxoid connective
tissue
- Hoarseness
- Resolves with rest
- Benign papillary tumor of - Squamous cell carcinoma from
vocal chord epithelial lining of vocal chord
- HPV 6, 11 (Koilocytes change) - Risk factors: alcohol, tobacco
- Single in adults - Arise from laryngeal papilloma
- Multiple in children (rare)
- Hoarseness - Hoarseness
- Cough
- Stridor

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Pulmonary Infections and TB
June 26, 2018 9:22 AM

04 Pulmonary infections - 1, Bronchiectasis, TB

05 Pulmonary infecton - 2 - Lobar, Broncho, Atypical
06 Pulmonary infection - 3 - Aspiration and Fungus

Pneumonia
- Infection of lung parenchyma
- Occurs when normal defenses impaired
○ Impaired cough
○ Damage to mucociliary escalator
○ Mucus plugging
- Fevers, chills, pleuritic chest pain, decreased breathing sounds, dullness to percussion, elevated WBC
- Sputum: productive cough
○ Yellow-green pus
○ Rusty blood
- Diagnose via chest X-Ray, sputum gram stain and culture, blood culture

Lobar Bronchopneumonia Interstitial/Atypical Aspiration - Lung Abscess

Chest X-
Ray

Lung abscess in right lower lobe

Descripti - Consolidation of entire lobe - Scattered patchy consolidation around - Diffuse interstitial infiltrates - Abscess: localized collection of pus
on bronchioles - No major consolidation • Cystic abscess: pus with fibrous wall
- Multi-focal and bilateral - Dry cough because inflammation in interstitium, - Surrounded by destroyed lung parenchyma
not alveoli - Right lung
• Location dependent on patient position
during aspiration
• Superior segment right lower lobe
• (R bronchus less acute angle than the
left)
Caused - Strep Pneumonia: middle age - Staph aureus: 2nd most common cause of - Mycoplasma: most common cause of atypical - Caused by aspiration > cancer
by adults, elderly secondary pneumonia pneumonia • Aspiration: Alcoholics, comatose
- Klebsiella: enteric flora that • Abscess, empyema • Young adults (military, dorm) patients, epileptics, elderly, bronchial
aspirate - H Influenza • Autoimmune hemolytic anemia obstruction
• Elderly, alcoholics • Secondary pneumonia • Cold agglutination
• Currant jelly sputum • Pneumonia superimposed on COPD • Can't visualize on gram stain (no cell wall) - Anaerobic bacteria in oropharynx
• Abscess - Pseudomonas: nosocomial, cystic fibrosis - Chlamydia pneumonia: 2nd most common cause - Bacteroides
patients, immunocompromised of atypical pneumonia in young adults - Fusobacterium
- Moraxella: community-acquired • Seroepidemiologic association with - Pepto coccus
• Pneumonia superimposed on COPD coronary artery disease
- Legionella: community acquired - Chlamydia psittaci: parrot fever
• Organ transplant patient - Respiratory syncytial virus: infants - Foul-smelling purulent sputum
• Pneumonia superimposed on COPD - CMV: post-implant immunosuppressive therapy - Sanguineous sputum
• Transmitted from water source • Owl Eye inclusions - (rule out carcinoma-causes in older individuals)
• Silver stain - Influenza virus: elderly, immunocompromised,
pre-existing lung disease
• Risk superimposed S aureus, H influenza
- Coxiella: Q fever
• Farmers, veterinarians
Diagnosis - Sputum culture - Sputum culture - Sputum culture - Chest-X Ray: air/fluid level
• Abscess filled with pus and air
• Cavitation
Treatme - Antibiotic - Antibiotic - Antibiotic - Clindamycin
nt - Anti-viral - Surgical removal of lung abscess

Natural History of Lobar Pneumonia

Day Findings
1. Congestion 1-2 - Congested vessels: Red-purple
- Partial consolidation of parenchyma
- Exudate mostly bacterial
2. Red Hepatization 3-4 - Red-brown, consolidated
- Exudate filled with neutrophils, fibrin, bacteria, RBC, WBC
3. Gray Hepatization 5-7 - Grey color; RBC degrade in exudate
- Exudate WBC, fibrin
4. Resolution 8+ - Enzymes digest exudate components

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4. Resolution 8+ - Enzymes digest exudate components
- Type II pneumocyte restore lining

Lung Abscess
- Lung abscess: localized accumulation of pus with destroyed lung parenchyma (alveoli, airway, blood vessel)
○ Cystic abscess: purulent exudates contained by a fibrous wall
- Caused by
○ Aspiration
○ Complication lung cancer (bronchial obstruction)
- Chest X Ray: air/fluid level = abscess filled with pus and air
○ Cavitation: formation of cavity; can be made by fluid
- Inflammation in surrounding pulmonary parenchyma
- Foul-smelling sputum may be expectorated if an abscess is connected to a bronchus

Localized collection of pus in parenchyma Chest X-Ray: air-fluid levels

TB Presentation

- Macrophages: phagocytose, release IL 12, TNF-α = recruit T cells
○ TNF-α: cachexia
○ IL 12: T cells → Th1 cells
- Th 1 cells: release INF-γ
○ INF-γ: activate macrophage to wall off bacteria
- Caseating Granuloma: calcified mass with necrotic macrophage in
center
- Size of infection = effectiveness of bacterial elimination
Description
Primary TB Pneumonia - Chronic cough with bloody mucous
- Weight loss, night sweats, hemoptysis
- Ghon complex: hilar lymphadenopathy + caseating granuloma in mid/ lower lobe
Healed latent infection - Fibrosis, calcification
- Chronic: Latent for many years
- Positive PPD test
- Nodules on X-ray
Secondary TB: - Reactivate in immunocompromised
- No TNF-α: No T-cell release INF-γ = no macrophage = uncontained TB
- Fibro caseous cavitary granuloma: apex of right upper lung (aerobic)
Miliary TB: - Disseminated TB
- Resemble millet seeds
- Meningitis: cavitary lesion, tuberculoma
- Pott's disease: TB goes to bones, spinal column
- Cement, Putty Kidney: TB goes to kidney

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Pulmonology Infections Micro Overview
July 3, 2018 8:25 PM

By Group
Gram Positive Gram Negative Atypical Bacteria Viral Fungal
- Strep pneumonia - Klebsiella - Legionella - RSV - Pneumocystosis Jirovecci
- Staph aureus - H influenza - Mycoplasma - CMV - Histoplasmosis
- Pseudomonas - TB - Influenza - Blastomycosis
- Moraxella - Chlamydia pneumonia - Coxiella - Coccidioidomycosis
- Bacteroides - Paracoccidioidomycosis
- Fusobacterium - Aspergillosis AAAA
- Peptostreptococcus - Zygomycophyta

By Age
Neonates Children Young Adults Older Adults Elderly
- Group B - RSV - Mycoplasma - Strep pneumoniae - S pneumoniae
Streptococci - Mycoplasma - Chlamydia pneumonia - H influenzae - Influenza virus
- E Coli - C Trachomatis - Staph pneumonia - Anaerobes - Anaerobes
- C pneumonia - Viruses - H influenzae
- Staph pneumonia - Mycoplasma - Gram ⊝ rods

Special Groups
Alcoholics Klebsiella, anaerobes usually due to aspiration (eg, Peptostreptococcus, Fusobacterium, Prevotella, Bacteroides)
IV Drug users S pneumoniae, S aureus
Aspiration Anaerobes
Atypical Mycoplasma, Legionella, Chlamydia
Cystic Fibrosis Pseudomonas, S aureus, S pneumoniae, Burkholderia cepacia
Immunocompromised Staph aureus, enteric gram negative rods, fungi, viruses, P jirovecii (with HIV)
Nosocomial Staph aureus, Pseudomonas, other enteric gram negative rods
Post-viral Strep pneumoniae, Staph aureus, H influenzae

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Pulmonary Infection: Fungal
July 2, 2018 11:38 AM

06 Pulmonary infection - 3

Systemic Fungus
Histoplasmosis Blastomycosis Coccidioidomycosis

Feature - Spike conidiophore on hyphae - Broad Based Budding Blastomyces BBBB - Spherules: yeast with endospores
s - Cannon ball yeast: Intracellular in macrophage
Epidemi - Ohio/Mississippi, Caribbean - Great Lakes - California, Mexico
ology - Bird, bat droppings (caves) - Decaying organic matter, rotting wood - Soil, dust: Dust storms, Earthquake
Pneumo - Granuloma - Patchy infiltrate on upper lobe - Acute pneumonia
nia - Calcification near hilum region - Large granuloma with central necrosis - X ray: nothing, cavities, nodules

Other - Calcifications in spleen - Verrucous skin lesions: painless cauliflower like - Valley Fever
Present - Erythema nodosum lesions similar to squamous cell carcinoma - Erythema nodosum
ations - Diffuse infiltrates in immunocompromised - Osteomyelitis - Skin, lung infection
- Disseminates in immunocompromised - Meningitis
Treatm - Azoles for local - Surgery - Self-limiting
ent - Amphotericin B systemic - Azoles: local - Azoles: local
- Amphotericin B: systemic - Amphotericin B: systemic

Opportunistic Fungi
Pneumocystosis Jirovecii Aspergillosis AAAA Zygomycosis, Mucormycosis

Feature - Sporocyst; honey comb appearance - Acute Angle branches - Non-septate, wide angle branches mold
s - Extracellular - Conidia fan - Conidia columnella: bulbous swelling at end, spores
Epidemi - Immunocompromised, HIV, AIDS - Hospital air, AC, shower, plant - Bread mold
ology - Immunocompromised - Immunocompromised
- Organ transplant patients with diabetes mellitus +
ketoacidosis
- Iron overload (free iron)
Pneumo - AIDS-defining!!! - Allergic Bronchopulmonary Aspergillosis: - Pulmonary mucormycosis
nia - Diffuse interstitial infiltrates • IgE → inflammation, mucus plugs • Neutropenic patients
- Death by respiratory failure - Aspergilloma: • Fungus ball formation like aspergilloma
• Lower lung, gravity
• COPD, CF patients
Other - Angio-invasive Aspergillosis → disseminate - Rhinocerebral
Present • Necrotizing pneumonia with gray • Proliferate in RBC
ations foci and hemorrhagic borders • Nasal cavity, sinus, cribriform plate, orbit,
• "target lesions" meninges, brain
• Blood vessels • Frontal cortex abscess

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 • Blood vessels • Frontal cortex abscess
Treatm - TMP + SMX - Amphotericin B - Amphotericin B
ent - Pentamidine - Voriconazole
- Surgery

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Obstructive Lung Disease
June 26, 2018 9:22 AM

02 PFTs, COPD - 1, Bronchitis, Emphysema

03 COPD - 2, Asthma
04 Pulmonary infections - 1, Bronchiectasis, TB

- Group of diseases characterized by airway obstruction

○ Lung does not empty, air is trapped =  lung volumes
- Volume of air forcefully expired decreases =  FVC
○ Especially during first second of expiration =  FEV1
○ Decreased FEV1:FVC ratio

Chronic Bronchitis Emphysema Asthma Bronchiectasis

Thick mucinous glands >50%
Descript - Chronic productive cough for at least 3
ion months for 2+ years
- Hypertrophy of bronchial submucosal
glands
Etiology - Smoking
Patholo - Hypertrophy of bronchial mucinous glands - Smoking: inflammation, neutrals release
gy • Leads to increased thickness of
mucus glands relative to bronchial
wall thickness
• Reid index > 50%
- Chronic inflammation = T cells and
macrophages
Clinical - Productive cough
Feature • Due to excessive mucus production
s - Cyanosis: blue bloaters
• Mucus plug traps CO2
• ↑ PaCO2, ↓ PO2
- Risk hypoxemia → cor pulmonale
• ↑ PaCO2, hypoxic shunting
• RH pump against high pressure
Abnormally enlarged alveoli separated by thin septa
- Destruction of alveolar sacs
• Lose elastic recoil
• Airways collapse during exhalation = obstruction,
air trapping
• (alveoli's elastic recoil keeps airways open during
exhalation)
- Imbalance of protease and anti-protease
• Inflammation: neutrophils and alveolar
macrophages release protease
• α1 antitrypsin A1AT: neutralize protease
- Excessive inflammation or lack of A1AT = destroyed
alveolar sacs
• Smoking: most common cause
• A1AT deficiency: genetic
proteases/elastase
• Centriacinar emphysema
• Upper lobes
- A1AT deficiency: no anti-protease
• Pan-acinar emphysema
• Lower lobes
• Liver cirrhosis
○ Misfolded A1AT protein made and
accumulates in endoplasmic reticulum in
hepatocytes
○ Pink globules in hepatocytes PAS+
• Degree of severity based on degree of A1AT
deficiency
○ PiM: normal allele
○ PiZ: most common mutation
○ Heterozygotes: asymptomatic with less
A1AT; risk when smoke
○ Homozygotes: panacinar emphysema with
cirrhosis
- Dyspnea
- Cough with minimal sputum
- Prolonged expiration with pursed lips
• Pursed lips create backpressure to keep walls
open
• Pink puffers
- Weight loss
- Barrel chest: increased AP diameter
• Compensates for inward collapse
- Risk hypoxemia → cor pulmonale
Curschmann spirals and Charcot-Leyden Crystals
- Bronchial hyper responsive → reversible
bronchoconstriction
- Allergic stimuli: Type 1 Hypersensitivity
• Presents in childhood
• Allergic rhinitis
• Family history of atopy
- Exercise
- Viral infection
- Occupational exposures
- Cold weather
- Aspirin: aspirin intolerant asthma
• COX inhibition → leukotriene
overproduction = airway constriction
• Asthma + aspirin induced bronchospasms +
nasal polyps
- Allergens induce TH2 in CD4 T cells
- Th2 cells secrete IL4, IL5, IL10
• IL 4: class switch to IgE
• IL 5: eosinophils
• IL 10: stimulates Th2, inhibit Th1
- Re-exposure to allergen = IgE cross-link, activate
mast cells
• Early phase: Mast cells release histamine,
leukotriene C4, D4, E4 =
bronchoconstriction, inflammation, edema
○ Histamine: vasodilate at arterioles
○ Leaking fluid: post-capillary fluid,
edema
• Late phase: inflammation (MBP from
eosinophils) damage ells and perpetuate
bronchoconstriction
- Smooth muscle hypertrophy and hyperplasia;
basement membrane thickening
- Curschmann spirals: spiral-shaped mucus plugs of
shed epithelium
- Charcot-Leyden crystals: aggregates of MBP from
eosinophil breakdown
- Episodic, related to allergen exposure
- Productive cough
- Tachypnea, dyspnea, wheezing
- Hypoxemia
-  inspiratory/ expiratory ratio
- Pulsus paradoxus: when inspire, exaggerated
drop in blood pressure
• When inspire, more blood → RV
• Increased volume in RV pushes
interventricular septum to the left
• LH gets smaller, less blood enters LV
• Less blood then pumped to aorta = drop in
aortic pressure
- Status asthmaticus: severe, unrelenting attack, can
lead to death
Dilated bronchi
- Chronic necrotizing infection → permanent
dilation of bronchioles and bronchi
• Large radius = turbulent flow
• Loss of airway tone = airway trapping
-
- Due to chronic necrotizing inflammation =
permanently dilated airways
- Cystic Fibrosis: mucus plugging ↑ infection
- Kartagener syndrome: defect in dynein arm in
cilia → impaired ciliary movement
○ Sinusitis
○ Infertility
○ Chronic ear infections
○ Situs inversus: position of major organs
reversed
○ Heart sounds in wrong place
- Tumor, foreign body: block increases risk of
inflammation
- Necrotizing infection
- Allergic bronchopulmonary aspergillosis:
hypersensitivity to Aspergillus = chronic
inflammatory damage
○ Patient with asthma, cystic fibrosis
- Cough, dyspnea
- Foul smelling sputum
• Loaded with inflammatory junk, sitting
in lumen
- Hemoptysis
- Digital clubbing
- Risk hypoxemia → cor pulmonale
- Risk secondary amyloidosis
• AA released by liver

Emphysema

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 Centriacinar Panacinar

- Emphysema and normal airspaces in same acinus - All airspaces with acini evenly enlarged
and lobule
- Smokers - α1 antitrypsin deficiency

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Restrictive Lung Disease
June 26, 2018 9:22 AM

08 Restrictive lung disease -2

RESTRICTIVE LUNG DISEASE

Poor Breathing Mechanics
Features - Extrapulmonary
- Peripheral hypoventilation - Reduced diffusion capacity
- Normal Aa gradient
Examples - Poor muscle effort
• Polio
• Myasthenia gravis
- Cannot full inhale =  lung volumes • Guillain-Barre
- Increased FEV1:FVC ratio - Poor structural apparatus
○  FEV1, FVC • Scoliosis
- Patient presents with short shallow breaths • Obesity
- Most commonly caused by interstitial lung disease
○ Interstitial lung disease: Diffuse fibrosis/granulomatous inflammation
of lung parenchyma (alveolar wall, interstitium)
○ If alveoli damaged → hyaline membranes
○ Trichrome stain: stains collagen connective tissue blue
Interstitial Lung Disease
- Pulmonary
- Increased Aa gradient
- Fibrosing interstitial pneumonia
- Pneumoconiosis
- Granulomatous
• Sarcoidosis
• Hypersensitivity pneumonitis
- Pulmonary Langerhans Cell histiocytes
- Pulmonary Alveolar Proteinosis
- Wegener's granulomatosis with polyangiitis
- Drug toxicity

Fibrosing Interstitial Lung Disease

Idiopathic Pulmonary Fibrosis Non-specific Interstitial Pneumonia NIP Desquamative Interstitial pneumonia DIP Cryptogenic Organizing Pneumonia
(Usual Interstitial Pneumonia UIP) Bronchiolitis Obliterans Organizing Pneumonia
BOOP

Patchy dense fibrosis with focal microscopic Loose fibrous tissue in alveoli and bronchioles
honeycomb fibrosis
Descripti - Pulmonary fibrosis - Pulmonary fibrosis - Pulmonary fibrosis (minimal) - Inflamed bronchioles and surrounding tissue
on - Unknown cause → Cyclical lung injury - Secondary to infection, collagen vascular - Seen in smokers, related to respiratory - Non-infectious pneumonia
• Injured pneumocytes release TGF-β disease, hypersensitivity pneumonitis, fibrosing bronchiolitis - Unknown etiology (diagnosis of exclusion)
• TGF β induce fibrosis changes • Inflammation by chronic disease
- 60 year old non-smoker • Rheumatoid arthritis
• Medication side effect: Amiodarone
Pathologi - Aggressive temporal heterogeneity fibrosis - Diffuse, temporarily uniform proliferative and - Minimal fibrosis; alveolar structure - No interstitial fibrosis
cal - Honey-comb lung: scarring fibrosis begins fibrosing changes preserved - Masson bodies: polypoid plugs of loose fibrous
Findings in subpleural → entire lung - Ground glass appearance tissue in alveoli and bronchioles
- Not really desquamation of alveolar
epithelium
• Alveoli are pigment-laden
macrophages
Presentat - Gradual deterioration in pulmonary status - Best prognosis - No sputum, blood culture; no response to
ion despite treatment - Stop smoking antibiotics
- Worst prognosis - May recover spontaneously
- Treat with lung transplantation - May need steroids

Pneumoconiosis
- Interstitial fibrosis due to chronic occupational exposure
- Alveolar macrophages engulf small foreign particles, induce fibrosis to wall off
- Risk cor pulmonale, cancer, Caplan syndrome
- Caplan syndrome: rheumatoid arthritis and any pneumoconiosis with intrapulmonary nodules
○ Rheumatoid nodules: granuloma with central necrosis and outer fibrosis

Asbestosis Berylliosis Coal Worker Silicosis

Asbestos bodies Non-caseating granuloma (sarcoidosis) but Carbon-laden macrophages Fibrotic nodules
with history of beryllium exposure
Exposure - Construction workers, plumbers - Beryllium miners - Carbon dust - Sandblasters

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Exposure - Construction workers, plumbers - Beryllium miners - Carbon dust - Sandblasters
- Shipyard workers - Aerospace industry - Seen in coal miners - Silica miners
Location Lower lobes Upper lobes Upper lobes Upper lobes
Pathological - Ivory white calcified plaques - Non-caseating granuloma in lung, - Mild exposure (pollution) → Anthracosis: - Silica impairs phagolysosome formation in
Findings • Supradiaphragmatic hilar LN, systemic organs collection of carbon-laden macrophage macrophages
• Pleural • Similar to sarcoidosis but • Not clinically significant - Fibrotic nodules in upper lobes
- Asbestos bodies: Long golden brown fibers caused by beryllium - Black lung: macrophages filled with • Chest X-ray: eggshell calcification of hilar
made of iron carbon → inflammation, fibrosis LN
• Stain Prussian blue
Notes Risk cancer of lung > pleura - Risk lung cancer - Risk for TB: impaired macrophages
• Mesothelioma: cancer of pleura

Granulomatous Interstitial Lung Disease

Sarcoidosis Hypersensitivity Pneumonitis

Non-caseating granuloma with asteroid bodies Potato nodes: bilateral hilar LN

Descript - Non-caseating granulomas in multiple organs - Allergic non-caseating granulomatous reaction to inhaled organic antigens
ion • Bilateral lung hilar LN → restrictive lung disease • Type 3, Type 4 Hypersensitivity
• Eye → uveitis ○ Farmer's lung: actinomycetes
• Skin nodules, erythema nodosum ○ Pigeon breeder's lung
• Lupus pernio ○ Byssinosis: textile, cotton, linen with Monday Morning blues
• Salivary, lacrimal glands (mimic Sjogren syndrome) - Extrinsic allergic alveolitis: prolonged exposure to organic antigen
• Potato nodules • No IgE, no eosinophils
- Systemic disease - Chronic exposure → interstitial fibrosis
- African American females
Patholo - Asteroid bodies: stellate inclusions seen in giant cells of granuloma in lung - Intra-alveolar infiltrate
gical - Schumann bodies: laminated concentration of Ca and proteins - Interstitial pneumonitis and fibrosis
Findings • Eosinophils rare
Note - Elevated serum ↑ ACE
- Hypercalcemia ↑ Ca
• Granulomas have 1 α hydroxylase activity = activate vitamin D
- Hypergammaglobulinemia
- T-cell anergy: Negative response to PPD test
- Treat with steroids
- Resolves spontaneously without treatment

Other Causes of Interstitial Lung Disease

Pulmonary Langerhans Cell Histiocytosis Pulmonary Alveolar Proteinosis Lymphocytic Interstitial Pneumonitis LIP
"Eosinophilic Granuloma"

Description - Tumor of Langerhans histocytes - Surfactant accumulates in intra-alveolar and - Diffuse lymphocyte and plasma
• Do NOT form granulomas bronchiolar spaces infiltration in interstitium and alveolar
- Langerhans cells with eosinophils - Caused by spaces
• Birbeck granules: tennis racket granules in • Defect GM-CSF
Langerhans cells, seen on EM • Pulmonary macrophage dysfunction
- Nodular infiltrates lung, bony sites (ribs) - Heavy lung
- Cough, sputum contain gelatinous material
- PAS +
- Treat with whole lung lavage, GM-CSF therapy
Epid - Young adult smokers - Child: indicates AIDS
- Adult: female predilection
• Sjogren syndrome
• Autoimmune disease

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Drugs that Cause Interstitial Fibrosis
- Amiodarone
- Bleomycin, busulfan
- Cyclophosphamide
- Methotrexate
- Nitrosurea

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ARDS
July 1, 2018 8:24 PM

07 Restrictive lung disease - 1, ARDS

Hyaline Membrane

RESPIRATORY DISTRESS SYNDROME

Acute Respiratory Distress Syndrome ARDS Neonatal Respiratory Distress Syndrome

(Diffuse Alveolar Damage) Hyaline Membrane Disease

Diffuse white out Diffuse granularity, ground-glass appearance

Descrip - Diffuse alveolar damage
tion - Diagnosis of exclusion
- Patient with normal lungs develop respiratory failure within 1
week alveolar insult, bilateral lung opacities, hypoxemia
Risk - Secondary to diseases
Factors • Sepsis, infection, shock, aspiration, pancreatitis,
hypersensitivity reactions, drugs, near drowning
Patholo - Neutrophils induce protease + ROS damage type I and type III - Surfactant: made by type II pneumocytes
gy pneumocytes
• Endothelial damage = ↑ alveolar capillary permeability
• Protein-rich fluid leak into alveoli = edema
• Edema + necrotic epithelial cells = hyaline membrane - No surfactant → atelectasis: lungs collapse, hypoxemia
- Alveolar macrophage digest hyaline membrane
- Loose fibrosis thickens alveolar septa
- Get restructure pulmonary parenchyma + cyst
Clinical - Hypoxemia and cyanosis with respiratory distress
Feature • Thick diffusion barrier
s • Hyaline membrane high surface tension, inward pull =
collapse air sacs
- Chest X Ray: diffuse white out
- Respiratory distress due to inadequate surfactant levels
- Prematurity:
• Synthesis begins at week 26, complete at week 35
• Screen L:S ratio in amniotic fluid to assess lung development
○ Lecithin levels increase as surfactant produced
○ Sphingomyelin remains constant
○ Ratio >2 is adequate
- C-section: lack of stress-induced steroids
• Steroids increase surfactant synthesis
- Maternal diabetes: baby's insulin decreases surfactant production
○ Made of lecithin (phosphatidylcholine)
○ Reduces surface tension in lung = prevent alveolar air sac collapse
after expiration
○ CO2 retention → acidosis → pulmonary vasoconstriction and
hypoperfusion
○ Endothelial and epithelial damage → hyaline membrane
- Increased respiratory effect after birth
• Tachypnea
• Accessory muscles
• Grunting
- Hypoxemia with cyanosis
• Risk PDA

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 • Risk PDA
• Risk necrotizing enterocolitis
- Chest X-Ray: diffuse granularity of lung (ground-glass)
Treatm - Address underlying cause - Supplemental oxygen
ent - Ventilation with positive end-expiratory pressure PEEP • Risk free radial injury
• Leave pressure in lung to prevent collapse when expire ○ Injure retina = blindness
- Recovery may be complicated by interstitial fibrosis ○ Injure heart = intraventricular hemorrhage
• No type II pneumocytes ○ Injure lung = impair development
• Get repair (fibrosis) but no regeneration

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Pulmonary Vascular Disorders
June 26, 2018 9:22 AM

09 Pulmonary edema, hypertension

10 Pulmonary embolism, pleural disorders

Pulmonary Edema Pulmonary HTN Pulmonary Embolism

Cardiogenic edema: bilateral infiltrate in lung bases with Kerley B lines

Non-cardiogenic edema: bilaterally patchy infiltrates throughout lungs

Westermark's sign: Pulmonary arteries cut off; focal sign of oligemia in one lobe
Smooth muscle hypertrophy with plexiform lesions Hampton's hump: peripheral wedge shape density over diaphragm

Descript - Leakage of interstitial fluid into alveolar space = heavy wet - Normal pulmonary pressure: 10 mmHg - Embolism blocks pulmonary artery
ion lungs - Pulmonary hypertension: 25+ mmHg • Increased Aa gradient
○ Pulmonary trunk atherosclerosis - Saddle embolus: embolus blocks main branches of pulmonary artery
○ Pulmonary artery smooth muscle hypertrophy → sudden death
○ Intimal fibrosis
○ Plexiform lesions in severe, long-standing disease
▪ Capillaries group together
Etiology - Cardiogenic pulmonary edema - Primary pulmonary HTN - DVT → embolize
• LH failure = increases hydrostatic pressure • Young, adult females - Risk factors: Virchow's triad
• Heart failure cells: macrophage with hemosiderin • Mutate BMPR2: proliferate vascular smooth muscle • Stasis
○ RBC extravasate in alveoli - LH disease: systolic/diastolic dysfunction and valve disease • Hypercoagulability
○ Macrophages eat RBC - Lung disease, hypoxia: COPD, lung inflammation/fibrosis, • Endothelial injury
• Jugular venous distention hypoxemic vasoconstriction
• S3 in dilated cardiomyopathy - Recurrent pulmonary embolism
• Chest X-ray: fluid accumulates in basal lobes •  cross sectional area of pulmonary vascular bed
• Heart failure cells:
- Alveolar wall injury: direct or blood-transfusion related
- High altitude
Present - Heavy, wet lungs = coughing - Exertional dyspnea - Sudden onset dyspnea and tachypnea
ation - Leads to RV hypertrophy → cor pulmonale - Fever
- Pleuritic chest pain, friction rub
- Expiratory wheezing
Diagnos - Chest X-Ray: normal chest X-Ray
is • Westermark's sign: Pulmonary arteries cut off
• Hampton's hump: wedge shape infiltrate in costodiaphragmatic
corner
- Spiral CT angiography (gold standard)
- Pulmonary angiogram (gold standard to confirm)
- ECG: S1QT3

DIFFUSE PULMONARY HEMORRHAGE SYNDROMES

Goodpasture Syndrome Wegner Granulomatosis with Idiopathic Pulmonary Hemosiderosis
Polyangiitis

Descripti - Autoimmune disease: Anti-GBM bind to pulmonary - Necrotizing granulomatous vasculitis - Intermittent, diffuse alveolar hemorrhage
on alveolar capillary basement membrane hemorrhage with • Lungs
renal failure • Kidney
• Lung • Nasopharynx
• Kidney
- Anti-GBM: circulating auto-antibodies against non-
collagenous domain of α3 chain of collagen type IV
Epidemio - Active smokers - Middle age man with associated organ - Children
logy symptoms
Histology - Lung: focal necrosis of alveolar walls with intra-alveolar
hemorrhages
• Hemosiderin-laden macrophages
- Kidney: crescentic glomerulonephritis
Clinical - Lung: hemoptysis, focal pulmonary consolidation - Lungs: pneumonia, nodular lesions - Insidious onset of cough, hemoptysis, anemia
Features - Kidney: glomerulonephritis, rapidly progressive renal - Kidney: renal disease - focal with diffuse pulmonary infiltrations

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Features - Kidney: glomerulonephritis, rapidly progressive renal - Kidney: renal disease - focal with diffuse pulmonary infiltrations
failure → hematuria necrotizing/crescentic
glomerulonephritis
- Nasopharynx: sinusitis, ulcers
- Saddle nose
Lab - Anti-GBM - C-ANCA
- Immunofluorescence: linear IF - Immunofluorescence: pauci-immune

- Lung Transplant: for non-neoplastic terminal lung disease

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Pleural Disorders
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10 Pulmonary embolism, pleural disorders

13 Lung cancer - 3, mesothelioma

PLEURAL DISORDERS
- Pleuritis: inflammation of pleura
- Pleural Effusion: fluid accumulates in pleura
- Pneumothorax: air accumulates in pleura
- Mesothelioma: cancer of the pleura

Pleural Effusion
- Accumulation of fluid in pleural space
○ Increased Hydrostatic pressure: CHF
○ Increased Vascular permeability: pneumonia
○ Increased intrapleural negative pressure: atelectasis
○ Decreased Osmotic pressure: nephrotic syndrome
○ Decreased Lymphatic drainage: mediastinal carcinomatosis
- Restrict lung expansion during inspiration
- Effusion:
○ Transudate: clear; due to systemic factors
○ Exudate: cloudy, high in proteins and LDH; due to local factors
▪ Must be drained to avoid infection
- Decreased breath sounds
- Mediastinal shift to opposite side
- Thoracentesis: remove, reduce fluid

Hydrothorax Empyema Hemothorax Malignant Effusion Chylothorax

Fluid Transudate Pus Blood Blood, lymph Lymph, chyle

Associations - Nephrotic syndrome - Bacterial infection - Trauma - lung > breast > lymphoma and - Thoracic duct leak
- Meig's syndrome: ascites, ovarian - Ruptured aortic aneurysm leukemia - Left sided
fibroma, R sided hydrothorax - TAG

Pneumothorax
- Air inside pleural cavity
○ Normally, intrapleural pressure lower than atmospheric pressure = lungs expand, fill with air
○ If air inside pleural cavity, no normal lung expansion
○ Atelectasis: collapsed lung
- Dyspnea, uneven chest expansion
- Symptoms on affected side: chest pain, ↓ tactile fremitus, hyperresonance, diminished breath sounds
○ Pain may radiate to shoulder or back
- Chest X ray: collapsed lung, and can't see vascular markings on that side
Primary Spontaneous Secondary Spontaneous Traumatic Pneumothorax Tension Pneumothorax
Pneumothorax Pneumothorax
- Rupture of apical subpleural bleb - Due to diseased lung - Open: chest wall penetrated, - Air enters pleural space but cannot exit
or cyst (emphysema, infection) outside air enters pleura - Air accumulates inside pleura,
- Tall, thin, young males - Barotrauma: due to mechanical • Air enters through wound, compress lung down
- Collapse portion of lung ventilation with high pressure equalizes pressure - Intrapleural pressure increases >
- Trachea shift towards collapse - Closed: chest wall intact (ex. intrathoracic pressure
Fractured rib) - Trachea shift opposite injury side
- Medical emergency
○ Can put pressure on heart, vital
structures
○ SVC = jugular distention
○ ↑ intrathoracic pressure = ↓ VR,
CO = hypotension
○ Treat with chest tube

Mesothelioma
Solitary Fibrous Tumor Mesothelioma

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Description - Small tumor attached to pleura by pedicle - Malignant neoplasm of mesothelial cells
- Big, bulky tumours = pleural thickening, encase lung
- Presents with recurrent pleural effusions, dyspnea, chest pain

Histology - Whorls of reticulin - Keratin +

- CD34 + - Epithelial type: calretinin +
- Mesenchymal, sarcamatoid type: spindle cell sarcoma
- Psammoma bodies
Epidemiology - Associated with asbestos exposure
• Lung cancer > mesothelial
• Asbestos bodies stain Prussian blue

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Lung Cancer
June 26, 2018 9:22 AM

11 Lung cancer -1
12 Lung cancer - 2
13 Lung cancer - 3, mesothelioma

LUNG CANCER
- Most common cause of cancer mortality in US
- Onset age 60+
- Risk factors
○ Cigarette smoke:
▪ 60+ carcinogens: Polycyclic aromatic hydrocarbons, arsenic
▪ Cancer risk related to pack years
○ Radon:
▪ Radon formed by radioactive decay of uranium present in soil
▪ Accumulates in closed spaces, basements
▪ Responsible for most of the public exposure to ionizing radiation
▪ Second most common cause of lung cancer in US
○ Asbestos: lung cancer > mesothelioma
- Non-specific symptoms: cough, hemoptysis, dyspnea, weight loss, post -obstructive pneumonia
- Single Coin lesion on Chest X Ray, noncalcified nodule on CT
- Multiple cannon ball lesions: metastasis from breast, colon; more common than primary lesions

Single Coin Lesions

- Young patients
- Granuloma: TB, histoplasma
- Bronchial harmatoma: benign tumor of lung tissue + cartilage, calcifies in lung
○ Harmatoma: mass of tissue that belongs in that region but is unorganized
○ Popcorn pattern of calcification in lung

Carcinomas
- Arise from single cell type
- Non-small cell carcinoma: surgically resect
- Small cell carcinoma: can't be surgically resected; when present are usually in advanced stage
○ Manage with chemotherapy ± radiation

Small Cell Carcinoma Adenocarcinoma Bronchioalveolar Adenocarcinoma Squamous Cell Carcinoma Large Cell Carcinoma Bronchial Carcinoid Tumor

Histo - Poorly differentiated small cells
- Arise from Kulchitsky cell
(neuroendocrine origin)
- Chromogranin +
- Neuron-specific enolase +
Etiology - Male smokers
• Strongest association
Locatio - Central
n
Notes - Rapid growth and early
metastasis
- Myc oncogenes
- Paraneoplastic syndrome:
• ADHSIADH
• ACTH Cushing Syndrome
• Antibodies against pre-
synaptic Ca channel →
Eaton-Lambert Syndrome
- If cancer starts with S, it will be associated with smoking, central, and associated with paraneoplastic syndromes
- Glands or mucin
- Keratin +
- Non-smokers (most common)
- Female smokers (most common)
- Peripheral
- KRAS, EGFR, ALK
- Associated with pleural fibrosis,
subpleural scars
- May appear irregular until replace
entire lobe
- Associated with hypertrophic
osteoarthropathy: clubbing
- Columnar cells that grow along
pre-existing bronchioles and
alveoli
- Arise form Clara cells
- Not related to smoking
- Peripheral
- Pneumonia-like hazy consolidation - Hilar mass from bronchus
on imaging
- Excellent prognosis
- Keratin pearls and
- Intercellular bridges
• Desmosomes connection
between squamous cells
- Male smokers (most common)
- Central
- Cavitation
- Paraneoplastic syndrome
• PTHrP: Hypercalcemia
(stones, groans, thrones,
psychiatric overtones)
- Poorly differentiated large - Well-differentiated
cells neuroendocrine cells
- No keratin pearls, bridges, • Grow in nests
glands or mucin - Chromogranin +
- Diagnosis of exclusion
- Smoking - Not related to smoking
- Peripheral - Polyp-like mass in bronchus
- Poor prognosis - Low grade malignancy
- Rarely causes carcinoid syndrome
- Symptoms due to mass effect or
carcinoid syndrome (flushing,
diarrhea, wheezing)

TNM Staging and Complications

T - Size and local extent of tumor
- Block SVC → SVC Syndrome: distended head and neck veins with edema, blue arms and face
- Recurrent laryngeal nerve (of vagus) → hoarseness
- Phrenic nerve → diaphragm paralysis
- Pancoast tumor: apical tumor
N - Regional LN
- Hilar, mediastinal LN
M - May spread to may spread to adrenal gland
- 5 year survival: 15%

Complications
Pancoast Tumor SVC Syndrome

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Description - Carcinoma in apex of lung, invades cervical
sympathetic chain
Presentation - Symptoms due to tumor compressing on local
structures
- Recurrent laryngeal nerve = hoarseness
- Horner syndrome: ptosis, pinpoint pupil,
anhidrosis
- Brachial plexus: shoulder pain, hand weakness
- SVC syndrome
- Brachiocephalic vein syndrome:
- Obstruction SVC impairs blood drainage from upper body
- Caused by malignancy, mediastinal mass, thrombosis from
indwelling catheters
- Upper body edema:
• Blanching after finger-tip pressing
• Face plethora
- Distended jugular vein
- May increase ICP → headache, dizzy, risk aneurysm,
rupture intracranial arteries

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