Quiz Yourself - Respiratory

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					Quiz Yourself -
• The FEV1 is reduced when:
  – airway obstruction is present as with these diseases:
     • Asthma
     • Emphysema
• FEV1/FVC ratio is reduced when
  – airway obstruction is present. The normal ratio is:
     • 70-75
• The FVC is reduced with
  – restrictive lung disease
     • Pulmonary fibrosis
Lung Volumes in Disease States

      What does each of these represent?
 What is the alveolar gas equation?
• PAO2 = FIO2 x (PB – PH2O) – PaCO2/RQ

What is the standard version (room air/temp)?
• PAO2 = 150 – PaCO2/RQ       RQ = 0.8 – 1.0
What are the 2 ways to alter V/Q ratio?
Dead space
•   Regions of the lung that are ventilated but not perfused
    – Anatomic?
       • Normal. Like the trachea. About 30% of tidal volume.
    – Physiologic?
       • Includes anatomic, but in theory, when there are unperfused
         regions, as with a pulmonary embolism
•   Regions of the lung that are perfused but not ventilated!
    – V/Q mismatch = incomplete shunt. Responsive to O2 therapy
    – Shunt is refractory to O2 therapy
Key pt: regions with a high V/Q ratio cannot compensate for
   regions with a low V/Q ratio b/c the high V/Q is normal!
    What are the causes of hypoxemia and
       how do we distinguish them?
•    We distinguish between them using blood gas and A-a
•    Hypoventilation
    –   indicated by hypoxemia with a high pCO2, normal A-a.
    –   Increasing frequency of breathing while lowering tidal volume increased
        the proportion of dead space ventilation to alveolar ventilation
•    V/Q mismatch
•    Shunt
    –   indicated by hypoxemia with a HUGE A-a difference
    –   Common causes include intracardiac lesions, structural abnormalities
        of the pulmonary vasculature, filling of alveolar spaces w/ fluid or
        complete alveolar collapse
•    Low inspired O2 (Low altitude)
       What is the diffusing capacity?
– Measured by DLCO
– Impacted by diffusion barrier and aggregate surface area of
– Measured with CO (but possible errors if the hemoglobin
  levels are low)
– What does emphysema do?
   •    reduces the area  reduced DLCO
– What does fibrosis do?
   •    increases the thickness  reduced DLCO
    What are the volume patterns for the
           following diseases?
•   Obstructive diseases?
    – larger TLCs
      •   Chronic bronchitis?
          – increased RV, increased FRC
      •   Emphysema?
          – increased RV, VERY increased TLC

•   Restrictive diseases?
    – smaller TLCs
      •   Fibrosis?
          – all lung volumes decreased
      •   Obesity?
          – FRC reduced
      •   Inspiratory muscle weakness?
          – TLC reduced
      •   Expiratory muscle weakness?
          – RV is elevated
           Mechanisms of Hypoxemia
  –   Hypoventilation
  –   V/Q Mismatch
  –   Shunt
  –   Low Inspired pO2

• How do we measure lung volumes?
      •   Helium dilution
          – Used to measure absolute FRC
          – Doesn’t work if there’s lots of obstructed airways where a
      •   Plethysmography
          – The small sealed box
          – Makes measurements using Boyle’s law
         What patterns of impairment
            are associated with:
• Obstructive lung disease?
  – Diminished rates of expiratory flow (increased FEV1,
    decreased FEV1/FVC)
• Restrictive lung disease?
  – Diminished lung volumes
  – Preserved expiratory flow
• What gives a characteristic scooped appearance in
  the expiratory phase of flow-volume loops?
  – Airway obstruction like emphysema
• When is obstruction increased during inspiration?
  – When it’s an extra-thoracic variable obstruction
• When is obstruction increased during expiration?
  – When it’s an intra-thoracic variable obstruction
 What’s this?
Normal Alveoli!
Dilated bronchi

                  Muco-Purulent Debris in Dilated Bronch

• What is it?
  – A chronic dilation of bronchi or bronchioles secondary to
    inflammation or obstruction
• Pre-disposing syndromes?
  – Cystic fibrosis (CF)
  – Primary ciliary dyskinesia syndrome (Kartagener’s s.)
• Radiology?
  – Airway dilation which extends to the periphery
• Pathology?
  – Permanent dilation of bronchi
  – peri-bronchial inflammation and organization (fibrosis)
  – Can sometimes see mucopurulent debris in bronchioles

                       Charcot-Leyden crystals – eosinophil granule contents
             What disease is this?

This is ASTHMA!!!!                                 Asthma
                             Curschmann Spirals – mucus casts
• Clinical:
   –   Airway hyperresponsiveness
   –   Triggers: antigens, exercise, drugs, infections, stress
   –   Acute, usually reversible diffuse bronchial narrowing
   –   Sxs: Wheezing, dyspnea
• Radiology:
   – Alternating atelectasis and overexpansion
• Pathology:
   –   Edema
   –   smooth muscle thickening
   –   BM thickening
   –   mucous cell hyperplasia
   –   increased submucosal eosinophils
   –   thickened intralumenal mucus
   –   Curschmann spirals – mucus casts
   –   Charcot-Leyden crystals – eosinophil granule contents
            Chronic Bronchitis
       Increased numbers of mucinous glands in submucosa
• A Clinical Diagnosis!
   – Definitional: Productive cough > 3months/year x
     > 2 years
• Radiology is non-specific
• Pathology:
   – Mucous cellular and glandular hyperplasia
   – May have submucosal chronic inflammation
   – May have respiratory bronchiolitis
• Might look like this:
Centrilobular   Emphysema in COPD
• Clinical:
   – Associated with cigarette smoking (component of COPD)
   – 1-antitrypsin deficiency, esp PIZZ mutation
• Radiology:
   – Increased lucency (dark region)
      • Upper>lower lobe suggests centrilobular type
      • Lower>upper lobe suggests panlobular type
   – Possible increased AP diameter
   – Possible flattened diaphragm
• Pathology:
   – Dilation of distal airspaces with septal destruction
   – Locations:
      • Centrilobular: Cigarette smoke
      • Panlobular: A1AT deficiency or cigarette smoke
   – Increased elastase activity
   Bronchiolitis Obliterans/Organizing
         Pneumonia (BOOP)
• Clinical:
   – Acute onset cough, dyspnea, fever, and malaise
   – Multiple associations, e.g. collagen-vascular dz
   – Most patients respond to corticosteroids
• Radiology:
   – Multiple patchy airspace infiltrates
• Pathology:
   – Patchy fibromyxoid plugs in distal bronchioles – the BO
   – Fibromyxoid plugs in alveoli, +/- endogenous lipid
     pneumonia – the OP
   – Think bronchiolar and alveolar airspace fibroblasts
   Classification of Asthma
Intrinsic Asthma-                    Extrinsic Asthma-
– No allergic or (personal family)   – Strong family history of
  history                              allergies
– Usually adult onset                – Usually onset at a young age
– Often follows severe               – Other allergic manifestations in
  respiratory illness                  patients
– Symptoms usually perennial         – History of specific allergic
– More refractory to treatment,        association triggers (e.g.
  become other diseases,               pollen, animal dander)
  progress to vasculitis             – Correlation with skin and
– Eosinophils still impt               inhalation responses to specific
                                     – Type I hypersensitivity rxn
                                     – IgE mast cell and eosinophils
What does this demonstrate? What is it?
     Discoloration Around the Eye
• What are the important cells in asthma?
   – Eosinophils (in sputum)
   – B lymphocytes in mediating the asthma – more impt
• What’s the point of the methacholine challenge?
   – It demonstrates that there’s something different in the architecture of the
     asthmatic’s airways that makes them non-specifically hyperreactive
• What is a key feature of the pathophysiology of asthma that
  contributes to death?
   – Mucous plugs occluding airways
• What are Creola bodies?
   – Agglomerated bronchial epithelial cells, seen in asthma
• What happens when you administer a beta-agonist?
   – You initially decrease the O2 saturation via V/Q mismatch.
• What is AM dipping?
   – When peak flow is decreased in the morning; associated w/ more severe
• What is the late phase reaction?
   – Delayed reduction in FEV1 due to IgE and influx of inflammatory cells
• What is the cornerstone of asthma therapy?
   – Corticosteroids (effective in reducing late phase reaction)
 Findings/Diagnosing Asthma?
1.    Spirometry
     Increase lung volumes (TLC, FRC, RV)
     Decreased peak flow, FVC, FEV1, FEV1/FVC
2.    Auto peak end expiratory pressure (auto-PEEP)-with rate
      respiratory rate.
3.    DLCO
     Increased - useful in establishing dx
4.    Methacholine challenge
5.    b-agonist
     Reversible airflow obstruction when treated; albuterol
6.    Eosinophils
     Increased in blood and found in sputum
7.    ABG
     Low PO2, low PCO2
               Treatment of Asthma
• Avoid asthmatic triggers
• Use bronchodilators
  – Sympathomimetics – usually B2-AR specific to increase
     • albuterol
     • Salmeterol is a long acting B2
  – Methylxanthines – inhibits PDE  increased cAMP
  – Anticholinergics – reserved for COPD
• Use anti-inflammatory drugs
  – Corticosteroids – the cornerstone of therapy
  – Cromolyn and nedocromil – inhaled prophylactics
  – Zileuton, Zafirlukast – decreases leukotrienes
     General Strategy for Management of
• Infrequent attacks?
  – Inhaled sympathomimetics (B2)
• More frequent?
  – Add an anti-inflammatory as maintenance, usually a
• Still not good enough?
  – Regular use of inhaled B2 agonists
  – Add methylxanthines (theophylline)
• Significant attack?
  – Systemic steroids
• Status asthmaticus?
  – IV corticosteroids
  – Aggressive bronchodilators
           Classification of asthma?
•   Mild intermittent
•   Mild persistent – more than 2X/week, but <1QD
•   Moderate persistent – daily symptoms
•   Severe persistent – continual symptoms
• Common precipitating stimuli of asthma?
   – Allergen exposure – involves histamines, leukotrienes
                » Leukotrienes = why NSAIDS can precipitate asthma!

   – Inhaled irritants
   – Respiratory tract infections
   – Exercise (cool air)
• When is airflow most compromised in asthmatics?
   – Expiration
• Why is FRC chronically increased in asthma?
   – Dynamic hyperinflation – can’t fully exhale all air
   – Persistent activity of inspiratory muscles
• What are the common symptoms of asthma?
   –   Cough
   –   Dyspnea
   –   Wheezing – airflow through narrowed airways
   –   Chest tightness
• What is the mechanism of low PO2, low PCO2 in asthmatics?
   – V/Q mismatch
• What are the 2 disorders under COPD? Basic defs?
  – Chronic bronchitis – diagnosis based on chronic cough and
    sputum production
  – Emphysema – diagnosis based on destruction of lung
    parenchyma and enlargement of air spaces distal to the
    terminal bronchiole
• What’s the pathogenesis of alveolar destruction?
  – Protease and protease inhibitors are in balance in lung
  – Smoking inhibits protease inhibitors
  – Neutrophils and macrophages in inflammation release
    damaging proteases
• What are the risk factors for COPD?
     •   Cigarette Smoking (also 2nd hand)
     •   Hyperresponsive Airways
     •   Occupational Factors (firemen)
     •   Alpha1-antitrypsin Deficiency – PIZZ is BAD!
              » Normally keeps elastase in check to maintain lung elastin
 Mechanisms of Airflow limitation in COPD?
        •   loss of alveolar attachments
        •   obstruction of the airway due to inflammation
        •   airway-wall fibrosis
        •   airway smooth muscle constriction
        •   luminal obstruction with mucus.
• Loss of elastic recoil in emphysema results in:
   – Decreased expiratory flow rates
        • Lower driving pressure for expiratory airflow
        • Loss of radial traction from supporting alveolar walls
• Functional abnormalities in COPD?
   –   Decreased FVC, FEV1, FEV1/FVC
   –   Increased RV, FRC, TLC
   –   Decreased DLCO in emphysema
   –   Increased Reid index in chronic bronchitis
   –   Hypoxia
   –   Hypercapnia in chronic bronchitis
• Major secondary problem with COPD? Causes?
  – Pulmonary HTN  cor pulmonale (more common in chronic
    bronchitis patients)
      •   Major Cause: Hypoxia  vasoconstriction
      •   Hypercapnia
      •   Polycythemia
      •   Destruction of the pulmonary vascular bed
• What is the protease-antiprotease hypothesis?
  – Alveolar integrity is maintained via a balancing act
  – Smoke increases the # of PMNs in the lung
  – PMNs produce elastase  degrades elastin
  – Smoke oxidants, oxidants from inflammatory cells impair
    A1AT anti-elastase activity
  – Neutrophil elastase stimulate mucus release
  – PMNs and macrophages make matrix metalloproteinases 
    shift balance towards degradation
 Clinical Distinctions Between Blue Bloater
  and Pink Puffer COPD Pathophysiology
Feature          Pink Puffer         Blue Bloater
Pathophys.       Type A              Type B
Disease          Emphysema           Chronic Bronchitis
Major Sxs        Dyspnea             Cough & sputum
Appearance       Thin, wasted        Cyantoic, obese
PO2              Decreased           Decreased
PCO2             Normal or decreased Normal or increased
Elastic recoil   Decreased           Normal
DLCO             Decreased           Normal
Hematocrit       Normal              Increased
                  Treatment of COPD
•   Bronchodilators
•   Antibiotics
•   Corticosteroids
•   Supplemental O2
•   Exercise rehab
•   Chest PT, postural drainage
•   Surgery (last resort)
    – Lung transplant
    – Lung volume reduction
• Vaccines: pneumovax, flu
• Plasma A1AT if the patient is A1AT deficient
• Mechanical ventialtion
             Major Points from Smoking
                 Cessation Lecture
• Tobacco dependence is chronic and requires
  repeated intervention
         – If at first you don’t succeed, try, try again!

• ALL pts who smoke should be offered at least ONE
  tobacco dependence treatment.
         – Pharmacotherapy CAN be helpful
         – Nicotine withdrawal can be fairly severe

• Clinicians, hospitals, etc must institute consistent ID,
  documentation, and tx of tobacco users
• Brief tobacco dependence tx is VERY effective – all
  pts should be offered at least brief tx
• Strong dose-response relation between tobacco
  dependence tx and it’s effectiveness
             Major Points from Smoking
                 Cessation Lecture
• The 3 types of counseling/behavioral therapy found to be very
  effective and should be used:
   – Social Support within treatment
   – Social Support outside treatment
   – Skills training/problem solving
• Unless contraindicated, use of effective pharmacotherapies for
  smoking cessation in all pts trying to quit should be used
• Tobacco dependence treatments are both clinically effective
  and cost-effective relative to other medical and disease
  prevention interventions
• Setting a quit date is IMPT!
• Set up follow-up dates after quit date to see your pt.
• People tend to gain weight upon quitting…
 5 first line pharmacotherapies for smoking
             abstinence that WORK
  –   Bupropion SR
  –   Nicotine gum
  –   Nicotine inhaler
  –   Nicotine nasal spray
  –   Nicotine patch
2 second line pharamcotherapies for smoking:
 - clonidine
 - nortiptyline
• What is the most successful self-help format to quit
  – Hotline “quitlines”
• Person-to-Person contact – how much helps?
  – Even <3min is (moderately) better than none!
  – 10min or more is best
• Asking your pt to quit smoking helps/doesn’t help?
  – It DOES!
• What are 3 things associated with unsuccessful
  attempts at quitting?
  – Not practicing total abstinence
  – Drinking alcohol
  – Other smokers in da’ house
               Peribronchovascular space
               Is dilated

Giant cell

                 What disease?
• Clinical:
   o   Multi-system granulomatous disease
   o   Adults, B>W, F>M
   o   Dyspnea
• Radiology:
   o   Interstitial infiltrates in bronchovascular distribution (= lympagenic
   o   Usually have hilar adenopathy (picked up on routine CXR)
• Pathology:
   o   Tight, well-formed non-caseating granulomata
   o   Def of granulomata: Focal accumulations of epithelioid histiocytes
  Hypersensitivity Pneumonia

    Interstitial expansion
              Hypersensitivity Pneumonitis
              (Extrinsic Allergic Alveolitis)
• Clinical:
   o   Organic dusts
           Doesn’t mean carbon based
           Means related to organic products
   o   Occupational or environmental exposure
   o   Acute and chronic: dyspnea, cough, fatigue
• Radiology:
   o   Bilateral interstitial linear or nodular pattern
• Pathology:
   o   Patchy peri-bronchiolar and interstitial chronic inflammation with
       loosely formed granulomata
                      Coal dust macules

Coal-worker’s Pneumoconiosis
Patchy Sub-Pleural Fibrosis

                              Ferruginous Body

     Fibrotic Nodules

Late Silicosis
UIP: Sub-pleural fibrosis adjacent to normal lung

 Usual Interstitial Pneumonia (UIP)
• Clinical:
   o   Syn. with “Idiopathic pulmonary fibrosis (IPF)”
   o   Adults, mean 51 yo; poor response to steroids, 66% mortality
• Radiology:
   o   Patchy subpleural infiltrates, DDx asbestos, rheum
• Pathology:
   o   Patchy interstitial inflammation; fibrosis alternating with
       normal parenchyma
   o   Temporally heterogeneous = ongoing injury to lung
   o   Morph overlap with rheum dzs, e.g. scleroderma
Fibroblasts in the interstitium


               Proliferative phase DAD
       Proliferative (Organizing) Phase
       Diffuse Alveolar Damage (DAD)
• Clinical:
   o   > 1-2 wks after identifiable acute lung injury (ex: MVA, septic
       shock, kidney stone, inhalation of noxious chemical)
   o   Decreased pulm compliance -> mechanical ventilation
   o   50% mortality
• Radiology:
   o   Diffuse, interstitial>alveolar pattern
• Pathology:
   o   Interstitial + intra-alveolar fibroblastic proliferation
   o   Temporally uniform
           If it’s temporally heterogeneous = UIP
   o   You HAVE to see interstitial fibroblastic proliferation
           If it’s purely intra-alveolar = BOOP
What characterizes Pulmonary function in
       Restrictive Lung Disease?
o   Characterized by reduced FVC, normal or high FEV1/FVC ratio

    Identify which is interstitial lung disease, obesity,
     and inspiratory & expiratory muscle weakness.
     Normal         ILD      Weakness          Obesity
                TLC             TLC
FRC                             FRC
                FRC              RV             FRC
RV                                                RV
• What’s the differential diagnosis for bilateral diffuse infiltrates that
  mimic diffuse parenchymal disease?
   o   Congestive heart failure
   o   Pulmonary infection
   o   Lymphangitic carcinomatosis
• What are known causes of diffuse parenchymal lung disease?
   o   Inhaled organic dusts (asbestosis, silicosis, coal workers, berylliosis
   o   Inhaled organic antigens  hypersensitivity pneumonitis
   o   Iatrogenic (drugs – amniodirone, radiation)
• What are unknown etiological diffuse parenchymal lung diseases?
   o   IPF/UIP
   o   Sarcoidosis
   o   BOOP
   o   Goodpasture’s
   o   Wegener’s
   o   And many more… (Connective tissue disease associated, Chronic eosinophilic
       pneumonia, Lymphangioleiomyomatosis, Pulmonary Langerhan’s cell
       histiocytosis, Alveolar proteinosis, Pulmonary vasculitides)
                   Pathophysiology of
               Parenchymal Lung Diseases
• Decreased lung compliance (increased stiffness)
   o   Reduced FVC, reduced FEV1, normal ratio
   o   Reduced lung volumes TLC, FRC, RV
• Diffusion impairment
   o   Destruction of alveolar-capillary interface by inflammation and
       fibrosis, reducing the surface area for gas exchange (there is a
       reduced DLCO on testing)
• Pulmonary Hypertension
   o   Hypoxemia
   o   Obliteration of small pulmonary vessels by fibrosis
               Clinical Features of
           Parenchymal Lung Diseases

• Symptoms
  o   Dyspnea
  o   Cough (non-productive)
• Signs
  o   Dry crackles or rales (sound like velcro)
  o   Clubbing
  o   Cor pulmonale
          JVD
          Loud P2, TR murmer
          edema
• What’s the major benefits of high resolution CT in diffuse
  parenchymal lung diseases?
   o   Detects sub-radiographic disease
   o   Distinguishes inflammation from fibrosis
           Ground glass appearance suggests inflammation
• What is thought to be the pathogenesis of sarcoidosis?
   o   A chronic systemic granulomatous idiopathic disease where there’s
       an immune response to an exogenous agent in a genetically
       predisposed individual
• What key cells are thought to be involved in sarcoidosis?
   o   Macrophages
           Results in increased release of TNF
   o   T cells (specifically CD4)
           BAL will reveal CD4>CD8
           There may be lymphopenia on peripheral blood smears
           MHC II is more impt than MHC I
           Results in increased IL-2, INF-gamma, and other cytokines
• What are the presentations/associated diseases of
   o   Lofgrens
           Acute onset
           Bilateral hilar lymphadenopathy
           Eythema nodosum
           Fever
           Arthralgias
           Associated with a good prognosis
   o   Eye manifestations
           Acute or chronic uvetitis
                 Sjorgens – destruction of exocrine glands, specifically partoid and lacrimal
                 Heerfordts – uvetis + uveoparotid fever, facial palsies, parotid swelling
           Keratoconjunctivitis sicca – decreased tear production  conjuctival and
            corneal inflammation
           Papilledema
   o   Lupus pernio
           Associated with chronic sarcoidosis
           Usually on face, sometime butt and extremities
• What are common abnormalities/diagnostic test results in
   o   Hypergammaglobulinemia – T cells non-specifically activate B-
       cells  lots of Igs
   o   Hypercalcemia, hypercalciuria – increased Ca2+ absorption from
       GI tract due to increased vitamin D formation
   o   Lymphopenia – lymphocytes involved in granuloma formation
   o   CD4 > CD8 in BAL – CD4 plays a greater role in granuloma
   o   ACE elevated – due to vascular epithelial cells of granulomas
   o   CXR or HRCT – parenchymal infiltrates, hilar adenopathy,
       sublpleural micronodules, upper lobe predominant, honeycombing,
       ground glass appearance
   o   Gallium-67 scan – panda sign
   o   Diagnosis is one of exclusion and heavily reliant on biopsy
• How do we treat sarcoidosis?
   o   Systemic corticosteroids
   o   anti-TNF may be best tx (infliximab)
   o   hydroxychloroquine
• What is the staging of sarcoidosis?
   o   Stage I – adenopathy
   o   Stage II – parenchymal infiltrates & adenopathy
   o   Stage III – just parenchymal infiltrates
   o   Stave IV – fibrosis, hilar retractionm, cysts, bullae, honeycombing
• Pathogenesis?
   o   Inflammatory process of the walls  fibrosis due to dyregulated response to
       damage of alveolar epithelial cells
   o   Factors that are dysregulated  fibrosis?
           Cytokines
           Chemokines
           Matrix metallic proteases and balance with inhibitors
           Decreased fibrinolysis
           Eicosanoid imbalance: increased luekotrienes, decreased prostaglandins
• Commonly presents in?
   o   Older adults, M>F
• Signs and Symptoms?
   o   Exertional dyspnea that increases over time
   o   Non-productive cough
   o   Possible clubbing
• What are common abnormalities/diagnostic test results in
   o   Velcro-like dry crackles
   o   Peripheral edema or cor pulmonale in advanced stages
   o   Hypoxemia, cyanosis, clubbing
   o   CXR
           Honeycombing
           Diffuse reticulations
           NO hilar enlargement
   o   HRCT
           Patchy, peripheral subpleural densities associated with small cystic spaces
• Pathology of UIP?
   o   Honeycombing
   o   Fibrosis
   o   Temporal heterogeneity
 What Occupational Exposure Materials can
cause inflammatory reactions in the Airways?
 o   Secretory Inflammation
         Formaldehyde – upper airways
         Ammonia – upper airways
         Particulates (coal, dust, cotton) – bronchitis
         Nitrogen dioxide – bronchiolitis
 o   Hyperreactive Airways
         Ozone, cotton dust – non-specific reactivity
         TDI – occupational asthma
What Occupational Exposure Materials can
 cause Parenchymal responses Acutely?
o Acutely    Chronically?
        Pulmonary Edema due to toxic reactions
            Chlorine, phosgene

            Acute silicosis

        Hypersensitivty Pneumonia
            Organic materials – farmer’s lung (mold spores in hay)

            Inorganic materials

o   Chronically
        Nodular fibrosis
            Coal – macules

            Silica – collagenous lamellated nodules

            Beryllium – Granulomata

        Diffuse Fibrosis
            Asbestosis

        Cancer
            Asbestos

            Chloromethyl Ether, Coke oven emissions
• What are the causes/common types of pneumonoconiosis?
   o   Nodular or diffuse fibrosis…
           Silicosis
           Asbestosis
           Berylliosis
           Coal Worker’s
• Important things to do to make a diagnosis in occupational
  exposure related respiratory diseases?
   o   Take a detailed history
   o   CXR to document pneumonoconoiosis
   o   Blood studies to document specific exposures
   o   Lung tissue analysis
   o   Measure peak flow throughout week
   o   Specific inhalational challenges
   o   Investigation of workplace by industrial hygienist
Respiratory Diseases due to Asbestos
I.    Non-Malignant
      A. Pleural Disease
                1. Pleural Effusion
                2. Diffuse Pleural Thickening
                3. Localized Pleural Thickening (Plaques)
      B. Diffuse Pulmonary Fibrosis (asbestosis)
II.   Malignant
      A. Malignant Mesothelioma
                - bad stuff
                - cigarette smoking is NOT related
                - latency is 30-40 years
      B. Bronchogenic Carcinoma
      C. Possibly Laryngeal Carcinoma
       Asbestosis – a restrictive Lung Dz
• Latency period?
   o   20-30days
• Pathologic features?
   o   Ferruginous bodies!
   o   Peri-bronchiolar inflammation and fibrosis
   o   May eventually honeycomb
   o   Tendency towards the lower lobes of the lungs
• Clinical Symptoms and CXR?
   o   Dyspnea on exertion
   o   Dry cough
   o   Late inspiratory crackles in bases
   o   Opacification in bases
   o   Pleural thickening
                      Occupational Asthma
• Definition?
   o   Clinically significant variable airflow obstruction due to specific workplace
       agent in lower [ ]s than should cause non-specific irritant response in normals or
       asthmatics who are not sensitized
• Risk factors?
           Potency of sensitizing material
           Level of exposure
           Accidental high exposures
           Individual patient – atopy and smoking
• Types of presentations:
   o   Typical immediate onset – w/in 30 minutes; clears hrs after leaving work. AM
       cough & sputum. Responds to bronchodilators
   o   Typical late onset – may not have wheezing; 4-8hrs afterwards with longer
       duration. Refractory to bronchodilators
   o   Dual Response
   o   Recurrent Attacks Post Exposure – at night after exposure
• Standard Treatment:
   o   Inhaled steroids and bronchodilators
   Reactive Airways Dysfunction Syndrome
• Characteristics:
   o   No preceding respiratory symptoms.
   o   Onset of symptoms after single high level exposure to an irritant.
   o   Onset of symptoms is abrupt (without 24 hours) and symptoms
       persist for at least 3 months.
   o   Symptoms of variable airway obstruction and/or
   o    Non-specific airway hyperresponsiveness present (methacholine
   o   Persistent airway inflammation but lack of eosinophils
                       Pleural Diseases
• What is pleuritic pain?
   o   Caused by inflammatory processes that intensify upon breathing
• What’s going on with a tension pneumothorax?
   o   Air escapes into pleural space  positive pressure
   o   Air can’t escape on exhalation
• How can a tension pneumothorax cause shock?
   o   By compromise of venous return
• How can ANY pneumothorax be caused?
   o   Trauma  sucking wound
   o   Iatrogenic - Overzealous use of positive pressure ventilation,
       central lines, lung biopsies
   o   Abnormal lungs  air trapping (think asthma)
   o   Spontaneous in very tall people
• What kind of pneumothorax?
   o   21 y o center for BB team
   o   Has sudden onset of R sided chest pain & mild dyspnea
   o   Patient is uncomfortable but vital signs are WNL
   o   Not Sean May hopefully!
           Pneumothorax disease
           b/c it’s a popped lung, the pneumothorax is limited and should spontaneously resolve
   o   20 y o severe asthmatic
   o   Intubated & on mechanical ventilation
   o   Suddenly becomes hypotensive & cyanotic
           This is a tension pneumothorax – must decompress the patient emergently!
• What will the CXR look like on a pneumothorax?
   o   On side of pneumothorax
           Absent vascular markings
           Appearance of a little nub near hilum (atelectic lung)
           Diaphragm depressed downwards
   o   On side opposite of pneumothorax
           Mediastinum, trachea, other structures shifted over
o   It’s a dark and stormy night… And a patient is brought into your
    ER with:
        Pleuritic chest pain
        Dyspnea
        Dullness of lungs to percussion
        Egophony at upper level
        Pleural friction rub
o   After you’re told he’s NOT possessed and isn’t just freaked out
    after watching that scary movie, you get a CXR.
o   That CXR shows:
        Blunting of the right costaphrenic angle
        Elevation or flattening of right hemi diaphragm
        And the mediastinum shifted to the left side
o   Then the scary, menacing attending asks you what does he
    have. You, being the superstar that you are, reply:
            “Why A Pleural Effusion, DUH!”
• How is normal pleural fluid made?
   o   Generated by Starling forces across a capillary bed
• Radiographic signs of pleural effusion include:
   o   Blunting of costophrenic angle on upright film
   o   Elevation or flattening of hemi diaphragm on upright film
   o   Diffuse haziness of hemi thorax on supine film
   o   If large, will cause shift of mediastinum to contra-lateral side
• How do you relieve a massive pleural effusion?
   o   Thoracentesis
           Helpful diagnostically
           Helps relieve symptoms
           Remove 1500cc or less!
                 Otherwise, you might suddenly inflate the lung.
                 Too little surfactant  pulmonary edema
       How do you relieve a massive pleural effusion?
• Thoracentesis
   o   Helpful diagnostically
   o   Helps relieve symptoms
   o   Remove 1500cc or less!
           Otherwise, you might suddenly inflate the lung.
           Too little surfactant  pulmonary edema
• How do you safely do a thoracentesis?
   o   Make sure the fluid is freely flowing and not loculated
           Use a lateral decubitus film
   o   Use ultrasound to locate effusion
   o   Be sure to draw close to the upper part of the rib directly below the
       needle you’re using, or you might hit an intercostal artery, vein,
   What are Lyte’s Criteria? Why do we use
           them in the first place?
• Helps us distinguish between an exudate and a transudate
  pleural effusion
   o   Ratio of pleural-fluid protein to serum protein > 0.5
   o   Ratio of pleural-fluid LDH > 0.6
   o   Pleural fluid LDH level > 2/3 upper limits of normal for serum
   o   Any one of these characteristics means the fluid is an exudate
• What other studies might you do on fluid from a pleural
   o   cell count & differential, glucose, cytology, Gram stain, AFB stain
       & culture, amylase, cholesterol, triglyceride level, pH, adenosine
• What if the effusion is borderline according to Lyte?
           Look at albumin gradient - If difference btw albumin in serum minus pleural
            fluid is > 1.2 than more likely a true transudate
            What are the potential causes of a
   o   CHF – due to increased pulmonary venous pressures, usually
       bilateral, usually resolves in 48 hours after diuresis
   o   Nephrosis – low oncotic pressures
   o   Cirrhosis
   o   Atelectasis – increased negative pleural pressure
   o   Ascites – can preferentially form in pleural space, hepatic-
• What are the potential causes of a massive exudate?
           Malignancy
           Trauma - hemothorax
           Empyema – bacterial infections
           Chylothorax – disruption of thoracic duct
           Rarely, TB
  o   Causes of bloody exudates?
          Cancer
          Pulmonary infarction
          Penetrating & nonpenetrating trauma
          Central line malplacement
          Chondrosarcoma
          S/P CABG
  o   Causes of turbid exudates?
          Chylothorax
          Empyema
• How do you define a hemothorax?
  o   Defined as pleural fluid hematocrit of 50% of blood hematocrit
  o   Will coagulate & may lead to loculation with complications of
      fibrothorax & possible empyema
  o   If small, may defibrinate & remain free flowing
So the good doctor said there’s a good exam
            question in here…

 o   What kind of cell count in an exudate would make
     you suspect cancer or Tb?
         >50% lymphocytes!
 o   Now what additional information on this exudate
     could help you decide that it’s probably NOT Tb?
         >5% mesothelial cells
              Remember, mesothelial cells are normally found in pleural fluid to some degree
               since they are the cells that comprise the pleura!
• Why should you distinguish between an empyema and a
  parapneumonic effusion?
   o   b/c empyemas need to be drained STAT!
• What the hell IS a parapneumonic effusion?
           Effusion secondary to a pneumonia
           Resolves with antibiotics. Course is usually very benign
• Great, so what about an empyema and why do I care?
           Implies active bacterial infection in the pleural space.
           Failure to recognize & drain can lead to unresolved sepsis & fibro thorax
• So how do I tell the difference between the two?
   o   Well if it’s an empyema, there should be:
           Gross pus
           pH < 7.1
           glucose < 40
           positive Gram stain or cultures
   o   And if it’s all borderline you need to retap that…um…lung…
Ack! It’s an Empyema! What Do I do?
o   Well a tube thoracostomy for one
o   Antibiotics to get those microbes
o   Thrombolytics if loculated or stops draining despite fluid present
    on X-ray
            Helps combat if the thing is trying to wall itself off
            Don’t let it hide – go and get it!

o   Decortication if unable to achieve drainage & lung is trapped in
    fibrinous peel
              Yeah – RIP off that clot and scar tissue that I wish you saw…
o   So what if I don’t and say I did?
        Untreated you might get empyema necessitans (where it attempts to drain
         through the chest wall b/c you were too lazy to drain it)
        Or you might get a bronchopleural fistula causing overwhelming sepsis
            Cartilage in excess and disarray


o   It’s BENIGN!!!!
o   Clin:
        Adolescence  adulthood
        None in newborns - not congenital
o   Rad:
        Solitary nodule +/- popcorn calcification
        Peripheral > central
o   Path:
        Gross: solitary, lobulated, cartilagenous
        Micro: normal tissues in excess/disarray
               If it’s calcified, it’s comforting b/c it tends to be non-
     What are the Malignant epithelial
       neoplasms (Carcinomas)?
o   Squamous cell carcinoma
o   Adenocarcinoma
o   Large cell undifferentiated carcinoma
o   Small cell undifferentiated carcinoma

     One of these things is not like the others.
     One of these things just doesn’t belong…

     Small cell is treated differently and has a much
      more severe progression!


 Squamous Cell Carcinoma
            Squamous cell carcinoma
• Clin:
   o   Smokers association?
           YES
   o   Prevalence?
           20-30% of common carcinomas
   o   May secrete PTH-like compound
• Radiology:
   o   central > > peripheral
• Path:
   o   Bronchi > Larynx > Trachea
   o      +/- Desmosomes (intercellular bridges)
          +/- Keratin production, e.g. keratin pearls

          Gland formation

                                      Pleural effusion
                Mucin production (red on PASd stain)
• Clin:
   o   30-40% of common carcinomas
   o   Smoking association?
           Most common carcinoma in non-smokers, but 80% of adenoCAs
            occur in smokers
• Rad:
   o   peripheral > central
• Path:
   o +/- glands

   o +/- mucin
   o   Bronchiolo-alveolar carcinoma subset
Bronchiolo-alveolar carcinoma
- Note the mucin in the alveoli. Gas exchange is gonna suck in this patient!
           Bronchioloalveolar carcinoma
• Subset of?
  o   Adenocarcinoma
• Incidence?
  o   Rising incidence (presently 20-25%)
  o   Associated w/ smoking?
          Not associated with cigarette smoking
• Rad:
  o   Peripheral, can be multifocal and bilateral
• Path:
  o   Lepidic (butterfly-like) growth pattern
  o   Mucinous or non-mucinous
  o   Unifocal or multifocal
Large cell undifferentiated carcinoma
Large cell undifferentiated carcinoma
o   Clin:
      10% of common carcinomas

o   Rad:
      non-specific

o   Path:
      H&E: Undifferentiated

      cDNA microarrays: distinct disease

         Basically,   it’s a carcinoma with no distinguishing features

         Viable carcinoma
Normal lymphocytes

  At diagnosis              Response to therapy

  Small Cell Carcinoma
                     Small cell carcinoma
• Clin:
   o   Smokers?
           YES
   o   20 % of common carcinomas
   o   Paraneoplastic Syndromes:
           Ectopic ACTH, ADH, Eaton-Lambert, carcinoid s.
   o   Commonly high stage at presentation
   o   Responsive to chemo/RT, but low 5 yr survival
• Rad:
   o   Central in >90%
   o   Frequent metastases to LNs and distant sites
• Path:
   o   Malignant cytology; high N:C ratio
   o   No nucleoli; punctate salt and pepper nucleoli
   o   High mitotic activity and tumor cell necrosis
   o   Think small round blue cells!
                                Thin delicate microvilli

      Associated w/ ferruginous bodies          Visible

       Mesothelioma         Angle
               Loss of C-P Normal thickness pleura
Thickened pleura
               = Pleural effusion or mass
Most Common Metastatic carcinomas in the

    Breast adenoCA
    GI adenoCA

    Renal adenoCA

    Head/neck squamous cell CA
                    Lung Cancer - Basics
• What are the 2 most impt risk factors for lung cancer?
   o   Genetics
   o   Smoking (15% smokers will get lung cancer; 85% CA in smokers)
• What types of molecules are the predominant carcinogens in
   o   Polycyclic hydrocarbons
• What sex is more susceptible to lung CA? Theories why?
   o   WOMEN
   o   Differences in metabolism, CYP450
   o   Hormonal effects in lungs
• What are some mutations that have been implicated?
   o   3p – NSCLC
   o   Ras – adenocarcinoma
   o   Myc – small cell
   o   NSCLC – p53
   o   Rb – small cell
   o   Random breaks in 1, 3, 5, 7, 15, 17
              More Lung Cancer Basics
• Most common sites of metastases:
   o   Liver
   o   Bone
   o   Brain
   o   Adrenals
• What are the paraneoplastic syndromes associated w/
   o   Clubbing, Hypertrophic orthropathy (adeno), Hypercalcemia
• What are the paraneoplastic syndromes associated w/
   o   SIADH (hyponatremia), Cushings, Lambert-Eatons, peripheral
       neuropathy, cerebellar degeneration
                  Diagnostic Tools for Lung CA
• The Basics
   o   Detailed hx and physical (esp lungs and supraclavicular nodes)
   o   CXR
   o   Chest CT
   o   Lab tests: CBC, liver fxn, alkaline phosphatase, serum Ca2+
• The Good, Special Stuff
   o   For central, endobronchial lesions
           Sputum cytology (3+ specimens for 90% yield)
           Bronchoscopy
                 Can also do transtracheal needle aspirate of nodes near trachea and
   o   For peripheral lesions
           Transthoracic needle biopsy (CT guided)
           Thoracentesis (effusions)
                 Malignant (w/ CA cells in exudate) or paramalignant
                            Staging Lung CA
  o   What’s Useful?
     Limited stage disease vs. extensive stage disease
        Limited stage - confined to hemithorax; within a radiation port

        Extensive - Tumor beyond a radiation port, includes malignant pleural

         effusion; what most pts present with
  o   What’s not so useful?
          TNM system (which is used in NSCLC)
               T – location, size
               N – nodes
                                                                                  IIIA, IIIB = locally
               M – metastases                                                    advanced
                  -   Stage I – no nodes involved                                 IIIB, IV =
                  -   Stage II – nodes on the same side/hilum of CA               advanced, effusion
                  -   Stage III – nodes/mediastinum
                  -   Stage IV – another organ involved or a second lesion in the lung
• Tricks to help us stage NSCLC?
   o   Intrathoracic
           Chest CT
           FDG PET Scan
           Mediastinoscopy
   o   Extrathoracic
           Bone scan
           CT/MRI of brain
           Abdominal CT (liver, adrenals)
           Biopsies of extrathoracic lesions
• Treating NSCLC
   o   Early – surgical resection + chemo
   o   Locally Advanced – chemo + surgery or radiation
   o   Advanced – chemo
           Can help improve sxs, cost effective, increases 1yr survival
• Treating SCLC
   o   Limited – chemo + radio
   o   Extensive – chemo, w/ palliative radio as needed
 Adenocarcinoma
     Most common NSCLC in US
     Smokers and non-smokers
     Peripheral (in the lung parenchyma)
     May arise in area of previous scarring
     More likely to spread to lymph nodes and outside of the chest
     Hypotrophic orthopathy or clubbing alone may be present
 Bronchioloalveolar carcinoma
     Subtype of adenocarcinoma
     More common in women
     More common in non-smokers than smokers for poorly defined
     Cough and bronchorrhea (frothy sputum production)
     Variable radiographic presentation: solitary nodule, multiple
      nodules, infiltrate/consolidation with air-bronchograms
 Squamous cell carcinoma
      Exclusively in smokers
      Generally arise in proximal airways
      May cause obstruction of the airway with distal atelectasis, post obstructive
      May cavitate
      Hypercalcemia due to PTH like substance (weakness, dehydration, mental
       status changes), clubbing
 Small Cell Lung Cancer
      15-20% of all lung CAs (decreasing)
      The least common lung CA
      Exclusively in smokers
      Generally originate within bronchial wall
      Bulky central tumor with extensive mediastinal lymph node involvement
      Rapid grown and early distant metastases
      Paraneoplastic syndromes especially SIADH (low sodium or hyponatremia
       associated with mental status changes)
         Got Your Sound On?

      Time to Take a
      Study Break!!!
    Is it close to midnight?
And that exam is lurking in the morn
Types of inflammatory responses/cells in
  infections and likely disease process
  Neutrophils
     Acute pneumonia (usually bacterial)
     Usually in alveoli
  Lymphocytes
     Usually viral or atypical pneumonia
     Usually in interstitium
  Granulomatous inflammation (epitheloid
   histiocytes, lymphocytes, giant cells)
     Usually mycobacterial or fungal
Neutrophils filling alveolar space in acute pneumonia
Interstitial lymphocytes in viral pneumonia
                                Giant Celll

Histiocytes and multinucleated giant cells (granulomatous inflammation)
in mycobacterial pneumonia
     Common bacterial pneumonia microbes
• Community acquired
   normal flora, common agents
      Pneumococcal (streptococcus pneumoniae)
      Klebsiella
      Hemophilus, Staph aureus, other strep

• Nosocomial (hospital acquired)
   Pseudomonas aeruginosa
        especially in cystic fibrosis patients
   Methicillin resistant staphylococcus aureus (MRSA)
• Types of pneumonia patterns on CXR
   Lobar (entire lobe
   Bronchopneumonia (patchy in more than one lobe
    surrounding a bronchus
            What is the agent of Pneumococcal
           pneumonia? How do you get it? Sxs?
    Streptococcus pneumoniae is the prototype of bacterial
      Encapsulated gram + cocci (diplococcus)
      Normal resident of the nasopharynx
      Often preceded by a viral infection  sets you up for
       bacterial pneumonia
      Clinical: fever, chills, chest pain, purulent or bloody
       sputum, opacified chest X ray
      Pathology
              Early: pulmonary edema and proliferation of bacteria, intra-
               alveolar accumulation of neutrophils and erythrocytes (―red
              Later: serum and fibrinous exudates, intra-alveolar organization,
               macrophages (―gray hepatization‖)
   What are the sxs of Legionella pneumonia?
• ―Legionnaires’ disease‖
    Acute onset of malaise, fever, pneumonia, myalgias,
     abdominal pain, diarrhea
• Type of bact? Gram stain? How do you see it?
    Small gram negative bacillus
    Need special stains to visualize
• What does CXR look like?
    Pathology: bronchopneumonia with multiple lobes
     involved, alveoli filled with fibrin and inflammation
    X ray is frequently more worrisome than clinical
     symptoms would suggest
     What patients are susceptible to pneumonias
           caused by anaerobic bacteria?
   Anesthetized patients
   Alcoholics
   Seizure disorder
• What are characteristics of anaerobic
   Normal inhabitants of oral cavity
   Streptococci, fusobacteria, bacteroides
   Often cause necrosis
   Foul smelling sputum
   May develop abscess formation
            What are common complications of
                 bacterial pneumonias?
• Lung abscesses
   Walled off area of infection with destruction of pulmonary
    parenchyma  destruction of all normal architecture
   Clinical: fever, cough, foul smelling sputum, mortality 5-10%
• Pyothorax/empyema
   Infection of pleural fluid with purulent material within the pleural
   May become loculated (fibrous walls around the inflammation),
    which requires drainage as well as antibiotics to treat.
                A clinical problem b/c it doesn’t have normal blood flow for tx
                 with antibiotics AND it doesn’t drain normally w/ a chest tube

• Bacteremia
   Bacteria within the bloodstream
   May seed distant sites
   Endocarditis, meningitis, pericarditis
What does this

                      Center of pulmonary abscess showing acute
                            inflammation with destruction of
                    Normal pulmonary architecture (no alveolar walls)

 Alcoholics on the right
                                          An abscess.
 lung b/c that’s where
    aspiration goes!                      Who’s likely to get it and
necrotizing granulomatous inflammation

                                                 Peripheral focus of granulo
                                                 Inflammation (Ghon focus)

 Granulomatous inflammation
 In hilar lymph node

           Beaded look to the bact
       Positive AFB

   Initial tuberculous infection: Ghon complex
   (Ghon focus + involved hilar nodes)
• Primary tuberculosis
    Inhalation of aerosolized droplets  settle in periphery of lower lobes
    Ghon complex: Peripheral focus of infection (granuloma, Ghon focus,
     often in a lower lobe) and the infected hilar/ mediastinal lymph node
    Pathology: caseous (cheese like) necrotizing granulomatous
    90% of primary infections are asymptomatic; 10% progressive primary
     Tb (enlarged lesion >6cm, spread to other parts of the lung, children or
     immunosuppressed patients)
• Secondary tuberculosis
    Reactivation of primary Tb OR a new infection in previously sensitized pt
    Clinical: fever, fatigue, weight loss, sweats, cough, hemoptysis
    Numerous caseating granulomas most common in the apical and
     posterior segments of upper lobes (highest aeration)
    These may heal and calcify, but some may erode into a bronchus,
     leading to tuberculosis cavity
        Usually 3-10 cm, often in apex of lung
        Communication with bronchus allows dissemination of organisms
         throughout lung
                 Complications of tuberculosis
• Miliary Tb
    Multiple small (millet seed size) granulomas in many organs
    Results from hematogenous dissemination
    Kidneys, adrenals, bone marrow, spleen, liver lymph nodes are
     common sites
• Hemoptysis
    Erosion of inflammatory response/Tb granuloma into a
     pulmonary artery
• Bronchopleural fistula
    Erosion of inflammatory response/granuloma into the pleural
     space, resulting in Tb empyema
• Unusual complications – you cough up Tb and swallow it, and it’s
  happy to colonize somewhere else
          Tuberculous laryngitis
          Intestinal tuberculosis
           Other mycobacterial diseases
• Mycobacterium avium-intracellulare
   Found in soil, water, food
   Causes disease in immunocompromised patients,
    particularly HIV+ (HIV Tb)
• Mycobacterium kansasii
   Associated with Hairy cell leukemia
• Mycobacterium bovis
   Infection from ingested milk (the bow Tb)
• Found in:
    in infected dust, bird droppings
• Appearance:
    dimorphic fungus with tiny yeast forms
• Common location:
    Endemic in midwest and southeast US, particularly Mississippi and
     Ohio valleys
• Clinical and pathologic findings
    Similar to Tb
    Yeast phagocytosed by macrophages and PMNs
    result in focal infections with parenchyma and hilar lymph nodes
    granulomas and caseating necrosis
    Old granulomas frequently calcify
    Immunosuppressed patients may have disseminated disease involving
     lungs, liver, adrenals, intestines
• Appearance:
    dimorphic fungi with large thick walled sporangia 30-60
     microns filled with endospores 1-5 microns
• Geography/location:
    Endemic in southwestern US, particularly San Joaquin
• Clinical and pathologic findings
    Similar to Tb and histoplasmosis,
    Immunocompromised patients may have release of
     endospores into lung causing with fulminant disease with
     purulent response
    Meningeal and MSK involvement possible
• Appearance?
    yeast 4-9 microns with mucinous capsule
• Found in?
    pigeon droppings
• Clinical and pathological presentation?
    Clinical disease almost exclusively in immunocompromised
    Lung is the portal of entry
    CNS is the most common symptomatic site (especially
     cryptococcal meningitis)
    Organism may be demonstrated in CSF, lung
     washings/BAL and biopsy with special stains (India Ink,
     mucin stains). Cryptococcus is one of the few fungi with
     mucicarmine positive capsule.

                         Cryptococcus: mucicarmine positive capsule
Cryptococcus on GMS stain showing narrow based budding
• Appearance:
   a large dimorphic fungus with broad based budding.
• Geography/location:
   In US in Mississipi and Ohio River valleys and Great
    Lakes regions
• Pathology:
   Disease usually confined to lungs, causes mixed
    granulomatous and suppurative inflammation

Blastomycosis: Large yeast with broad based budding
• Appearance:
    septate hyphae with acute angle branching, found in soil and
     decaying plant material
• Diseases/Presentation
    Aspergilloma (Mycetoma, ―fungus ball‖)
         Grows with preexisting cavity, often Tb cavity
         Tangled mat of hyphae within cavity, X-ray may
          show mass and air within cavity
    Allergic-Bronchopulmonary aspergillosis (ABPA)
         Asthmatics develop immunological reaction to
          Aspergillus, w/ infiltrates on CXR, eosinophilia of
          blood/sputum, wheezing, cough and sputum
         Treatment with steroids to control immune
         It’s not the fungus that hurts you, it’s your body’s
Aspergilloma showing non-invasive fungus within granulation tissue line
    Aspergilloma (fungus ball) within pre-existing cavity
Aspergillus: septate hyphae with 45 degree branching
                       Aspergillus within
                       blood vessel wall

Invasive aspergillus
           Mucormycosis (Zygomycosis)
• Caused by inhalation of spores of several fungi
  (Mucor, Rhizopus, Absidia) ubiquitous in soil,
  food, decaying vegetable material
• Appearance?
   grow as non-septate hyphae
• Common patients?
   patients with underlying illness, particularly diabetics
• Common presentation?
   rhinocerebral (nasal sinuses and brain) and
    pulmonary. Causes vascular invasion, septic
    infaction, hemorrhage
                  Pneumocystis carinii

• What is it?
   A common pulmonary pathogen causing pneumonia in
    immunosuppressed patients, especially HIV
• What do you see?
   Trophozoites and cysts, latter identifiable with GMS
    stain, fills alveolar spaces with organisms and
    proteinaceous fluid, preventing gas exchange
• Bronchoalveolar lavage useful for diagnosis
• Causes dyspnea and CXR with infiltrates
• Dx by cytology
Pneumocystis on GMS stain: cup shaped organisms within alveolar spaces
                      Viral pneumonias
• Cytomegalovirus – most common viral infxn
    Interstitial pneumonia in infants and immunocompromised
     patients, especially organ transplant patients, now we screen
     (donor & recipient)
    Large cell, big nucleus w/ large, single basophilic intranuclear
• Measles
    Multinucleated giant cells with nuclear inclusions
• Varicella (chicken pox and herpes zoster) are usually
    Interstitial mononuclear cell pneumonia, may produce
     focal necrosis
    Nuclear eosinophilic viral inclusions, may be
• Herpes simplex
    necrotizing tracheobronchitis and diffuse alveolar damage
• Other viruses (especially in children)
    Adenovirus
    Respiratory syncytial virus
Measles pneumonia: multinucleated giant cells with viral inclusions
Cytomegalovirus pneumonia
                                Viral inclusion
Herpes virus on cytology specimen
Mycoplasm pneumonia: sparse lymphocytic interstitial inflammation
• Small free-living prokaryote, common cause of acute self-
  limited pneumonia and tracheobronchitis,
• milder than usual bacterial pneumonia (―walking
• Highly transmissible through airborne droplets
• Cause of 15-20% of pneumonias in developed countries
• Pathology: patchy consolidation, mononuclear
  infiltrate, usually of a lower lobe
• Very common but not very bad
• You’ll see something on CXR but not lots of sxs
       Really common at college/in dorms
           What are common host defenses to
                 respiratory infection?
     Upper Airway (nose)
     Epiglottis/Larynx
     Epithelial Tight Junctions
     Mucociliary and Cough Clearance
     “Innate” (lysozyme; lactoferrin; “defensins”)
     Immune Response
           Secretory IgA (nasal/bronchial)
           Humoral Antibody
           Cellular
     Alveolar Macrophages (AM)
     Inflammatory Response (PMNs, etc.)
• What defenses are protecting the proximal airways and
    Primary Components: cilia, liquid/mucus, submucosal gland
    Mucociliary clearance – respond to neurohormonal and
     mechanical stimuli
    Secretions of the submucosal glands – what’s in this?
     IgA – neutralizing; secreted as a dimer
     IgG – opsonizing
• What are the defenses in the alveoli/distal airways?
    No cilia or mucus
    Macrophages – they can seek and phagocytose pathogens, as well
     as coordinated the cellular response via chemotactic factors and
    IgG
• Secondary defense mechanisms thoughout the lung?
    Neutrophils and other inflammatory cells
                Lung Defense Failures
• Common:
   viral infection - after influenza, other infxns can occur
   cigarette smoking
   COPD
   patients w/ underlying lung disease
• Severe failures of lung defense include:
   AIDS
   Medications (corticosteroids like prednisone, other
    immunosuppressives, chemotherapy
   Malignancies (leukemia, lymphoma) – can lower cell
    and antibody mediated immunity
   Endotracheal tubes – HAP
           Routes of Infection of Lung
• Aspiration
   Microaspiration of pathogens colonizing the
    oropharynx (your upper away)
   Gross aspiration of mouth/GI tract contents into
• Inhalation
   Ambient droplets/particles entrained (e.g. TB,
• Hematogenous
   e.g. Staph. aureus with IVDA, endocarditis, or a
         Typical vs Atypical Pneumonia
Typical Pneumonia                 Atypical Pneumonia
• Rapid onset                     • Indolent onset (7-10days)
• Ill appearing                   • Less ill appearing
• High fever, rigors (shaking     • Low-grade fever, malaise,
  chills), chest pain, purulent     headache, dry cough

• Consolidation, rales on exam    • Rales without consolidation
• Leukocytosis (15-20K)           • Mild/no leukocytosis;
                                    negative cultures

• Airspace filling/lobar          • Patchy/interstitial infiltrates
  infiltrate on CXR with air        on CXR
• Meant to describe: S.           • Meant to describe:
  pneumo, S. aureus, GN bacilli     Mycoplasma, or Chlamydia
  like Klebsiella

        This is the most important test that
    needs to be done in diagnosing pneumonia?
• Chest Radiography
   May distinguish pneumonia from other problems (bronchitis,
    CHF, TB, PE, cancer)
   Assesses severity/distribution (multilobar) of disease and
    identifies complications (pleural effusion, abscess, empyema)
   Many patterns observed
        Airspace filling processes (lobar; patchy
        Interstitial patterns
        Location, cavitation, adenopathy…
  But CXR won’t tell you what the
   responsible pathogen is
 Since CXR and clinical presentation only tells you
 the patient has pneumonia, do you even care what
              the causative microbe is?
   The pathogen determines how you treat it (and in my case, how
    much I freak out)
• Great, so how do I figure out WHAT the pathogen is
   Sputum Gram’s stain and culture: used but utility debated
    due to high false+ and false- rates
   Blood cultures: for hospitalized patients (specific, but not
    sensitive); much better.
                Strep pneumoniae causes the most + blood cultures
   Ancillary testing for specific organisms
        Legionella: Urinary antigen immunoassay
         (serotype 1) DFA, selective media
        Chlamydia, Mycoplasma: serologies, but these are
         relatively unhelpful in the acute setting
        TB: AFB smear/culture
        Fungus: KOH/culture
   So when is this sputum Gram stain & Culture
      going to be worth me missing sleep?

• When you’ve got…
   Large numbers of bacteria with a single morphology
    observed in setting of many PMN’s and few/no
    squamous epithelial cells (i.e. lower airway specimen)
   Obtained before antibiotics
   Detection of a non-colonizer (mycobacteria, endemic
    fungi, Legionella, PCP)
      That’s when I go:

               (yes I know I’m a dork, but you’re laughing – admit it.
                     And I have to entertain myself SOMEHOW!)
This is a sputum sample and it tells us?

                              That it was probably an incompetent
                              med student who this specimen, b/c
                              it SUCKS. Look at all the squamous
                              epithelial cells and where are the
                              inflammatory cells?!?!?
So after you fix that previous
person’s mistake, you see
this. What are you thinking?

                                 Besides thinking “damn, I’m good
                                 you should be thinking STREP!!!
 When Do I give up on the whole idea of a bacterial
   pneumonia and consider TB/fungal agents?

• CXR:
   Upper lobe cavitary infiltrate: TB!!
• Clinical course:
   Indolent course x weeks/months
   Non-resolving on treatment
• Exposure history:
   Outdoorsman (Blastomycosis)
   Desert southwest (Coccidioidomycosis)
   TB contacts or from endemic area
  The patient asks you to predict how bad the infxn is.
    You’ll assess the severity looking at what? And
                what’ll make you panic?
    Age >60 years,
    comorbidities (cancer, ―organ failures‖, immunosuppressed
     conditions, CHF)
• Clinical findings:
    altered mental status
    severe vital sign abnormalities
      (RR>30; SBP < 90; T>40 or <35; HR >125)
• Lab data:
    WBC >30k or <4k;
    hypoxemia;
    acidosis
• CXR:
    multilobar involvement,
    fulminant progression
                 or you could just use a magic eight ball…
 Pathogens ~ Modifying Risk Factors
• Aerobic GN bacilli             Alcoholism, nursing home, cariopulmonary disease
    like Klebsiella

• Anaerobes                      Loss of consciousness (alcohol, seizure), swallowing
                                 dysfunction, poor dental hygiene, airway obstruction

• H. influenzae                  COPD, smoker

• S. aureus                      Nursing home, post-influenza, IVDA, bronchiectasis

• P. aeruginosa                  Structural lung disease (bronchiectasis, CF), recent
                                 broad spectrum antibiotics therapy, malnutrition,
                                 chronic steroids

• DRSP                           Age > 65; b-lactam therapy within 3 months; exposure
  drug resistant S. pneumoniae   to child in daycare; underlying medical co-morbidities
             What are your basic Treatment
               Groups for Pneumonia?

         Outpatient                        Inpatient
1.   No underlying. disease or   3.  Inpatients not needing ICU
     modifying factors               care
                                    a. No comorbidities
2.   Underlying comorbidities       b. Underlying comorbidities
     or modifying factors        4. Severe pneumonia requiring
     (COPD, CHF,                     ICU care
     alcoholism,…)                  a. Low risk for
                                    b. Risk for pseudomonas
             How do you treat each group?
Outpatient: No cardiopulmonary   Advanced generation macrolide
 disease or modifying factors              (azithromycin, clarithromycin)
                                 Antipneumococcal fluoroquinolone
                                 (levofloxacin, moxifloxacin)
Outpatient: With                 Antipneumococcal fluoroquinolone
Cardiopulmonary                                       OR
Disease/Modifying Risk Factors   2nd/3rd generation cephalosporin +
Inpatient: Not needing ICU       IV 3rd generation cephalosporin + macrolide
                                 IV antipneumococcal fluoroquinolone
Inpatients: ICU requiring        IV 3rd generation cephalosporin + macrolide
                                 IV antipneumococcal fluoroquinolone
                                 Consider Vancomycin (MRSA and PRSP)
                                 If there is a Pseudomonas risk, add these:
                                      Anti-pseudomonal B-lactam + cipro
            HAP Pathogens and Treatment
• Treatment based upon the local hospital flora
                  Commonly available along w/ the drug resistances!

• Common pathogens:
      P. aeruginosa,
      Enterobacter,
      E. coli,
      Klebsiella,
      Proteus,
      Serratia,
      S. aureus,
      Acinetobacter,
      anaerobes
• HAP more likely to be polymicrobial
• Resistant GN’s and S. aureus (MRSA) more common,
  and may spread rapidly to at risk patients
      So in the Immunocompromised Host, what is
        reflective of the specific immune deficit?
• Risk for pathogens reflect specific immune
   Neutropenia:
       bacteria,
       aspergillus,
       candida
   Splenectomy:
       encapsulated organisms
   T-cell number (HIV) or function
       fungi,
       mycobacteria,
       viruses (CMV, EBV),
       bacteria
         HIV lung infections reflect what?
• Risk for infection proportional to CD4 count:
   >500: lower risk (M. tuberculosis, bacterial pneumonia)
   <200: Pneumocystis carinii
   <50: disseminated M. avium complex
• Higher frequency of bacterial pneumonia, esp. S.
  pneumoniae and H. influenzae, and tuberculosis
  at all CD4 counts
• How do you avoid PCP in HIV+ patients?
   Prophylactic therapy in compliant patients quite
      trimethoprim/sulfa – also used to treat
      Dapsone
      inhaled pentamidine – also used to treat
           AIDS and Pneumocystis carinii
• Clinical Presentation
   Dyspnea, dry cough, fever – insidious onset
   Diffuse infiltrates typical (normal in 5%; atypical with
    inhaled pentamidine)
   Hypoxemia prominent feature
• Diagnosis
   Visualization (DFA, silver stain) of organisms in lower
    resp. secretions (induced sputum; bronchoalveolar
    lavage 85-95% sensitive in HIV)
• Treatment:
   Trimethoprim-Sulfamethoxazole (Bactrim)
   IV pentamidine
   Corticosteroids: for pO2 < 70 mmHg or A-a grad >35
    mmHg (reduces risk of resp. failure and death)
       AIDS and Non-TB mycobacteria

• Primary species are within M. avium complex
• Risk when CD4 count < 50 (prophylaxis with
• Primarily cause disseminated disease, rather
  than pulmonary disease
   Fever, weight loss, anemia/leukopenia, diarrhea,
    hepatitis, adenopathy
   MAC cultured from blood, bone marrow, stool
• Treated with Clarithromycin + ethambutol
         AIDS and Fungal Pneumonia

• Cryptococcus neoformans:
   Common cause of meningitis, usually without
   May cause local or diffuse pulmonary disease;
• Histoplasmosis, Coccidiodomycosis:
   Usually disseminated disease in HIV
• Invasive Aspergillosis:
   End-stage (CD4 < 50) disease, concomitant
    neutropenia (e.g. meds…) are risk factors
AIDS and Non-infectious Lung Diseases

• Kaposi’s sarcoma: infiltrates, nodules, pleural
  effusions, adenopathy, and airway lesions all
  possible (Gallium scan negative)
    human herpesvirus-8
• Lymphocytic interstitial pneumonitis (LIP)
    especially children with HIV
• Non-specific interstitial pneumonitis (NSIP)
• Pulmonary Hypertension
    Pathology identical to primary pulmonary
             What is bronchiectasis? 2 modes of
              pathogenesis? Its vicious cycle?
“Irreversible dilation of airways caused by inflammatory
   destruction of airway walls”
    Infection/Inflammation
         bacterial pneumonia, tuberculosis, measles,
    Airway obstruction
       Cystic Fibrosis (CF)
       Primary Ciliary Dyskinesia (PCD; Kartagener’s
       Hypogammaglobulinemia
 • Airway obstruction/Infection (total; IgG2/IgG4; IgA)
     Airway wall damage/dilation
        Impairment of mucus clearance
            Promotion of Airway Infection
        Other Etiologies of Bronchiectasis
   ―Traction bronchiectasis‖ - ILD
   Airway obstruction (e.g. foreign body)
   ABPA (Allergic bronchopulmonary aspergillosis)
   1-antitrypsin deficiency
   COPD
   Rheumatologic diseases (Sjogren’s syndrome, RA)
   Young’s syndrome (bronchiectasis, obstructive
    azoospermia, sinusitis; normal sweat Cl- and CFTR
• What happens to the bronchial arteries in
  bronchiectasis and why?
   Marked hypertrophy of bronchial arteries due to
    chronic inflammatory stimuli
        Clinical features of bronchiectasis
• Chronic cough
• copious purulent sputum production
   ~10% with ―dry bronchiectasis‖
• Periodic hemoptysis
   May be massive, as source is hypertrophied bronchial
    arteries, which are at system blood pressure
• Abnormal lung sounds and clubbing variably
What is suggestive history of bronchiectasis?
How do we diagnose bronchiectasis?
  HRCT – procedure of choice to demonstrate presence,
   location, and extent of disease
               So you have a pt and the HRCT shows
                   bronchiectasis. Now what?
• Figure out what the cause is!
    CF:
         Sweat chloride or CFTR genotyping
    Immunoglobulin deficiency:
         IgG/subclasses, IgA
    PCD:
         nasal scrape for cilia structure; exhaled NO level
    1-antitrypsin
    ABPA:
      immediate aspergillus skin test; IgE
• Treatment?
    Antibiotics aimed at airway flora
    Airway clearance
         Chest percussion (manual, devices), exercise
    b-agonists
         Reduces reversible airway obstruction and promotes
          mucociliary clearance
    Surgery
                        Cystic Fibrosis
• What are the major defects?
    Production of thick, tenacious secretions from exocrine glands
    Elevated concentrations of Na2+, K+, and Cl- in sweat
• What are the major clinical problems from CF?
    Pancreatic insufficiency
    Recurrent episodes of tracheobronchial infections
    Bronchiectasis
• What is the genetic basis of CF?
    Most common lethal genetic disease in Caucasian population
         Affects 1 : 3,300 Caucasian births
    Monogenetic, autosomal recessive
    Affected gene is called ―Cystic Fibrosis Transmembrane
     Conductance Regulator‖, or CFTR.
    >1000 individual CFTR mutations identified, but DF508 mutation
     accounts for 2/3 of CF alleles worldwide
      What is the Cascade to Lung Disease in CF?
CFTR Gene Mutation

  Altered Ion Transport

    Abnormal airway surface liquid (volume depletion)

       Impaired airway defenses (reduced mucociliary clearance)

           Chronic airway infection/inflammation

               Progressive bronchiectasis

       Sodium is reabsorbed WAY too much from the airways. Water follow
       inwards. This leads to the collapse of mucociliary clearance.
                          How do you diagnose CF?

• 1+ typical phenotypic features and evidence of CFTR malfunction
    CFTR malfxn:
       Sweat Chloride Test – gold standard; > 60 mmol/L
       CFTR Mutation Analysis – genotyping; 2 mutations required
       Nasal Potential Difference (PD) testing – demonstrates ion transport
    Phenotypic features:
       Chronic Sinopulmonary Disease:
                Persistent infection with P. aeruginosa, S. aureus
                Chronic cough/sputum
                PFTs (obstruction)
                Radiographs: bronchiectasis (upper lobe)
                Nasal Polyps, sinusitis
                Digital Clubbing
          GI:
                Meconium ileus, rectal prolapse, Distal Intestinal Obstruction Syndrome (DIOS)
                Pancreatic insufficiency
                Malnutrition
                Fat soluble vitamin deficiency
                Focal biliary cirrhosis
          Others:
                Salt loss syndromes: acute salt depletion, chronic metabolic alkalosis
                Obstructive azoospermia (CBAVD)
      How do you get pseudomonas in CF?
   Impaired mucociliary clearance
   Static, hypoxic mucus layer
   Pseudomonas growth in biofilms by altering
    metabolism from aerobic  anaerobic
   Intense inflammation with resolution of infection
• What are serious complications of CF?
   Pneumothorax
   Massive hemoptysis due to dilation of bronchial
   Respiratory insufficiency
   Cor pulmonale
            What is the standard maintenance therapy for
• Airway obstruction from thick secretions
      Airway clearance
      DNase, mucolytics
      Hypertonic saline – speeds up clearance of mucus
      Bronchodilators
• Infection
    Inhaled and oral antibiotics
• Inflammation
    Ibuprofen
    Corticosteroids
    Azithromycin – also an antibiotic! Shown to slow disease
• Nutritional Support
    High fat/calorie diet
    Pancreatic enzyme supplementation
    Fat soluble vitamin supplementation (A,D,E,K)
• Screening for other complications
    CF-related diabetes
    Liver disease
    Bone disease
Occluded artery

             Parenchymal infarct
             with hemorrhage

 Pulmonary Thromboembolism
     Pulmonary Thromboemboli (pulmonary
                embolism, PE)

• Clinical:
   Dyspnea, hemoptysis
   Commonly due to lower extremity thrombi
• Radiology:
   Decreased flow, V/Q mismatch  abnormal V/Q
• Pathology:
   Pulmonary arterial thromboemboli
   Survivors may have peripheral wedge-shaped
Medial and intimal hypertrophy
                                 Plexiform lesion
             Pulmonary Artery Hypertension

• Clinical:
    Sporadic Primary PH: Idiopathic; young adults; 5%
    Familial Primary PH: Autosomal dominant; 5%
    Secondary PH: Identifiable cause of increased pulmonary blood
     flow and/or increased resistance; 90%
• Radiology:
    Non-specific
• Pathology:
      Medial hypertrophy
      intimal proliferation
      intimal fibrosis
      plexiform vascular lesions
Necrotizing   Granulomatous    Vasculitis
 Elastica disruption = vascular injury
  Hemosiderin-laden macrophages = prior hemorrhage

                     Wegener’s Granulomatosis
What are the 2 Mechanisms That are Used when
there’s increased blood flow through the lungs?
               What’s going on with the
    pulmonary vasculature resistance as you inhale?
• Total pulmonary vasculature resistance
  increases as you inhale/increase lung volumes
   Alveolar components increase with inspiration
   Extra-alveolar components decrease w/ inspiration
• How do you define pulmonary hypertension?
   Defined as mean pulmonary artery pressure >25 mm
    Hg at rest or 30 mm Hg during exercise
• What is the general progression of disease w/
  increased pulmonary vasculature resistance?
   Pulmonary vascular obstruction  increased
    pulmonary vascular resistance  pulmonary HTN 
    increased RV work  cor pulmonale
         What is the vicious cycle of
             pulmonary HTN?

                   Pulmonary HTN

Decreased Cross-
 Sectional Area          Vascular Changes
                           Intimal proliferation
                            Medial hypertrophy
                        Angiomatoid transformation
                            Fibrinoid necrosis
       What are the Mechanisms of
        Pulmonary Hypertension
• Passive:
   increased left atrial pressure, e.g. mitral
    stenosis, mitral regurgitation, LV failure
• Hyperkinetic:
   high flow states: VSD, ASD
• Occlusive:
   Chronic PE
• Obliterative:
   emphysema, interstitial lung disease, vasculitis,
• Vasoconstrictive:
   hypoxia, scleroderma
                    What is the basis of
              Primary Pulmonary Hypertension
• Potential etiologies
        PGIS,
       endothelin,
       Kv-channels,
       eNOS,
       mutant BMPR2,
       ANP
•   Mean age at diagnosis is 36
•   More common in females than males
•   No racial predilection
•   Familial Disease accounts for ~10% of cases
•   Disease progresses to cor pulmonale and premature
    death if not treated with median survival of 2.5-3
                     Symptoms of PPH
   Progressive exertional dyspnea—virtually 100%
          Patient may faint upon exercise
     Fatigue
     Chest pain—due to right ventricular
     Ischemia
     Exercise syncope or near syncope
     Hemoptysis
     Hoarseness
     Peripheral edema
• Physical Exam Findings
   Jugular venous distention
   Accentuated second heart sound (P2)
   Right ventricular heave @ left sternal border
   Right sided gallops (S3, S4) @ sternal border
   Tricuspid regurgitation murmur (systolic) or pulmonic (diastolic)
   Peripheral edema due to RHF
     Therapy of Pulmonary Hypertension
 Anticoagulation– improves survival
 Oxygen – in hypoxemic patients
 Ca2+ channel blockers – may improve exercise
  tolerance and hemodynamics in patients (~25%) with
  mild-moderate disease
 Prostacyclin—intravenous/subcutaneous
  administration improves hemodynamics, exercise
  tolerance, and prolongs survival in severe PPH
 Bosentan—endothelin receptor antagonist that
  improves exercise tolerance.
 Transplantation – the last resort
               What are the Pathophysiological
            Consequences of Pulmonary Embolism
• Pulmonary consequences
     Increased alveolar deadspace
     Pneumoconstriction—described in animals
     Hypoxemia—shunt, V/Q mismatch
     Hyperventilation
     Depletion of alveolar surfactant—takes ~24 hr
     Pulmonary infarction
• Hemodynamic consequences
   Decrease in x-section area of pulmonary vascular bed:
          50-60% reduction  significant pulmonary
           HTN, RHF, hypotension
   Humoral reflex mechanisms—hypoxic vasoconstriction,
    mediator release (like 5HT)
             Diagnostic Tests for DVT

•   Venography
•   Impedance Plethysmography
•   Duplex Scanning
•   Dopper flow velocity
•   MRI scans
                 Diagnosis of Acute Pulmonary Embolism
•   Symptoms
        Dyspnea
        Pleuritic pain
        Apprehension
        Cough
        Hemoptysis
        Syncope
•   Signs
        Tachycardia
        Increased P2
        Thrombophlebitis – in lower extremeties
        S3,S4 gallop
        Diaphoresis
        Edema
        Murmur
        Cyanosis
•   Laboratory Studies
        ECG- non-specific, sign of Right heart strain S1Q3 pattern in precordial leads
        CXR
        Blood Gases
        D-Dimers – more useful to r/o
•   Ventilation Perfusion Scanning – w/ good sxs, it’s fairly reliable
•   Spiral or helical CT scanning
•   Pulmonary Angiography
         Contraindications to Heparin Therapy

• Absolute:
   Recent (w/in two weeks) hemorrhagic CVA.
   Recent neurosurgery, ocular or spinal surgery
• Relative:
    Recent major surgery
    Major trauma
    Intracranial neoplasm
    Recent gastrointestinal bleeding
    Concurrent guaiac positive stool
    Mild to moderate hemostatic defects
    Severe uncontrolled hypertension >200mm Hg
     Systolic or >110mm Hg diastolic
    Hematuria
• In these situations, you would use an IVC!
       So you’ve got edema in the distal airways
   and alveolar epithelium. What cell helps you deal?
• TYPE II pneumocytes (main cell)
   By increasing Na-K ATPase on basolateral surface, you
    can increase influx of Na+ from the airspaces via ENaC
   Water follow Na+
      Na-K ATPase is inhibited by oubain
      ENaC is inhibited by amiloride
      This process is accelerated by beta-agonists
      Can upregulate in at risk infants w/ corticosteroids
       to mom and infant  more type II cells  more
       surfactant and more efflux
      Dexamethasone also helps increase expression of
• How can you measure the efficacy of alveolar
  fluid clearance in the lung?
   Inject a mix of regular and radioactive albumin
Fibrin-rich “hyaline membranes”

 Alveolar filling pattern
 with air bronchograms
      Exudative (Acute) Phase Diffuse
         Alveolar Damage (DAD)

• Clinical:
   Adult respiratory distress syndrome (ARDS)
   Identifiable lung injury 0-2 wks before
   Acute dyspnea, hypoxemia, decreased
• Radiology:
   Diffuse alveolar filling pattern
• Pathology:
   Endo- or epithelial injury, Type II cell
   First 2 wks after injury: edema  fibrin
      Respiratory distress syndrome of
• Clinical:
   Prematurity
   Tachypnea, intercostal muscle retraction,
• Radiology:
   Diffuse alveolar filling pattern with air
• Pathology:
   Insufficient surfactant production by type II cells
   Atelectasis  hypoxia/acidosis  epith necrosis
   Diffuse intra-alveolar hyaline membrane formation
    (exudative DAD)
RBCs filling
alveolar spaces

                  Alveolar Hemorrhage Syndrome
               Causes of
    Alveolar Hemorrhage Syndrome

• Goodpasture’s syndrome
• Acute lupus pneumonitis
• Wegener’s granulomatosis
         Goodpasture’s syndrome

• Clinical:
   Young adults, M>F
• Radiology:
   Diffuse alveolar pattern
• Pathology:
   Anti-basement membrane IgG antibodies
    damage pulmonary and renal basement
   Linear IgG and C’ deposition by
    ImmunoFluorescence and Electron microscopy
   Anti-GBM IgG is detectable in serum
              Acute lupus pneumonitis
• Clinical:
   Component of systemic lupus erythematosus (SLE)
   Children & adults, F>M
• Radiology:
   Diffuse alveolar pattern
• Pathology:
   Necrotizing capillaritis due to immune complexes
   Granular IgG/C’ deposition by IF and EM
   ANA or anti-dsDNA Ab detectable in serum

Aspiration of cooked fat
• Clinical:
   Children - foreign bodies
   Adults - gastric acid, food
      Lipids, e.g. mineral oil laxatives or nasal
       drops (―exogenous lipid pneumonia‖)
• Radiology:
   Focal alveolar pattern
   typically RLL
• Pathology:
   Gastric acid  DAD
   Foreign material  foreign body giant cell
    reaction with exogenous material
         Endogenous lipoid pneumonia
         (“post-obstructive”, “golden” pneumonia)

• Clinical:
   Central major airway obstruction
• Radiology:
   Peripheral infiltrates +/- central mass
• Pathology:
   Increased numbers of foamy alveolar macrophages
    distal to an airway obstruction, +/- cholesterol clefts,
    without foreign material

Endogenous (Post-Obstructive) Lipid Pneumonia
Transudate in interstitium and alveolar airspaces

Capillary congestion

                 Severe Pulmonary Edema
                Pulmonary Edema

• Clinical:
   Cardiogenic: LV pump failure, mitral valve
• Radiology:
   Incr. vascular markings, reticular +/- nodular
   Think Kerley B lines
• Pathology:
   Venous and capillary congestion
   Incr. free water in the interstitium +/- alveoli
                        Define ARDS
• Acute Respiratory Distress Syndrome
   – A clinical definition
   – Acute onset
   – Bilateral infiltrates on CXR
   – Pulmonary Artery wedge pressure <18 or no evidence of left atrial
       • PaO2/FIO2 < 300: Acute Lung Injury
       • PaO2/FIO2 < 200: ARDS
• Common Causes? Most Common Cause?
       Direct Lung Injury                Indirect Lung Injury
          Pneumonia                         Sepsis
          Aspiration                        Multiple Trauma
          Pulmonary Contusion               Other Shock
          Fat Emboli                        Acute Pancreatitis
          Inhalational Injury               Multiple Transfusions
          Near Drowning                     Drug Toxicity
                   Septic Shock

                     Inflammatory Cytokines

           Nitric Oxide from Vasc. Endothelium

            Low Systemic Vascular Resistance

             High Cardiac Output Hypotension

Wide pulse pressure ex: (90/30)    Decreased urine output
Brisk capillary refill             Decreased mental status
Hyperdynamic                       Lactic Acidosis –
                                   b/c all these tissues are underperfused
            Continuum and Definitions of
•   Infection
                   Septic Shock
    – Inflammatory response to microorganisms, or
    – Invasion of normally sterile tissues
•   Systemic Inflammatory Response Syndrome (SIRS)
    – Systemic response to a variety of processes
        •    Fever,
        •    tachypnea,
        •    tachycardia,
        •    Leukocytosis
    – Be careful; there are some infections that resemble sepsis but AREN’T despite the
      overlap with SIRS
    – It all comes down to is it multiorgan?!?!
•   Sepsis
    – Infection plus
    – 2 SIRS criteria
•   Severe Sepsis
    – Sepsis
    – Organ dysfunction (ex: hypotension, hypoxemia)
•   Septic shock
    – Sepsis
    – Hypotension despite fluid resuscitation
•   Multiple Organ Dysfunction Syndrome (MODS)
    – Altered organ function in an acutely ill patient
    – Homeostasis cannot be maintained without intervention
Acute or Exudative Phase of ARDS
             Exposure to a Risk Factor

 Alveolar Capillary Injury         Epithelial Cell Injury

       Leak of Protein Rich Fluid into Interstitium
                      and Alveolus

     Arterial hypoxemia refractory to oxygen = SHUNT!
                  Bilateral patchy infiltrates
        VERY Decreased lung compliance (need PEEP)
                Rapid onset respiratory failure
       Proliferative or Fibrotic Phase of ARDS

• Fibrosing Alveolitis
   – Procollagen III peptide present day 1 or 2
   – Histologic changes day 5-7
• Clinical Evidence Day 5-10
   –   Persistent hypoxemia
   –   Increased alveolar dead space
   –   Further decrease in compliance
   –   Pulmonary hypertension - Obliteration of pulmonary capillary bed
• Steroids are helpful in this stage (but not in the
  acute/exudative phase)
• When ventilating a patient, make sure you don’t overdo it
   – You don’t want to injure the healthy parts of the lung
   – Use a low tidal volume at a higher frequency (despite the inability
     to get rid of CO2)
      2 General Classes of
      Respiratory Failure

Hypoxemic - inadequate O2 delivery

Hypercapnic - respiratory acidosis (high PCO2)
              secondary to failure to adequately ventilate
               Hypoxemic Failure
              Physiological Causes
A. Decreased PIO2
B. Decreased VA
C. Ventilation/Perfusion [V/Q] Mismatch
D. RL Shunt
E. Diffusion Limitation only problematic during exercise
   Physiologic Causes of Hypoxemic
• Decreased PIO2
  – As with high altitude
• Decreased VA
  – Hypoxia (PAO2) secondary from hypercapnia (PACO2)
• V/Q Mismatch
  – Can be corrected by supplemental O2
• RL Shunt
  – Refractory to O2 treatment
• Diffusion Limitation
  – Only a problem under exercise stress due to
    increased CO (common in pulmonary fibrosis)
    Physiologic Causes of Hypercapnic
•   Increased VE 2o  VCO2
    –   fever, trauma
•   Increased VE 2o  VD/VT
    –   pulmonary embolism, emphysema
•   Decreased VA
    –   Many, many causes
•   Causes of Decreased Minute Ventilation
        1. Respiratory drive
              (e.g., narcotic overdose)
        2. Nerve conduction
              (e.g., cervical cord trauma, Guillain-Barre syndrome)
        3. Neuromuscular (e.g., myasthenia gravis, muscle atrophy)
        4. Chest wall (e.g., flail chest,  kyphoscoliosis)
        5. Lung disease (e.g., asthma, COPD)
        6. Upper airway obstruction
Arterial blood gases and diagnosis
pH     pCO2 HCO3-

7.40   40   24      Normal

7.30   55   26      Acute Failure

7.37   55   31      Compensated Failure

7.25   85   36      Acute and Chronic Failure
    Clinical signs of
    respiratory muscle weakness
   1. Tachypnea
   2. Decreasing Vital Capacity
   3. Decreasing Maximum Inspiratory Force
   4. Ineffective cough
Note: Hypercapnea is a late sign of respiratory failure
      due to neuromuscular limitations.
Support ventilation prior to Resp. Failure
How do you TREAT Hypercapnic Failure?
A. Diagnose and treat underlying cause
B. Consider respiratory stimulants
             1. Naloxone (opioid antagonist)
             2. Controlled hypoxemia (in proper clinical settings)
             3. Chemicals (rarely effective; xanthines, progesterone)
C. Assist devices
  1. Negative pressure - Iron lung, Cuirass ventilator
  2. Nasal/Face Mask CPAP - Continuous Positive Airway Pressure
  3. Cycled CPAP (BiPAP) - Bilevel Positive Airway Pressure
D. Threshold for tracheal intubation and positive pressure ventilation -
   usually low pH.
E. Mechanical ventilation techniques
             1. Breath initiation/Respiratory Rate
             2. Tidal volume
             3. Patient regulation of VE
                         -Spontaneous breaths
                         - Tidal volume
             4. PEEP = Positive End Expiratory Pressure
    Damage to these parts of the brain are
   associated with what types of breathing
• Forebrain
  – Post hyperventilation apnea
  – Cheyne Stokes Respiraton:
     • crescendo-decrescendo
     • Due to problems w/ CNS or HF
• Hypothalamus
  – Central reflex hypernea
• Pons
  – Apneustic breathing – pause btw inspiration and expiration
  – Cluster breathing
  – Ataxic breathing
• Medullary
  – Ondine’s Curse – no involuntary control of breathing
  – Ataxic breathing
                   What is Sleep Apnea?
•   Repetitive episodes of diminished air flow associated with oxygen desaturation
    or arousal
•   Patients may have hundreds of events per night
•   Two types:
     – Obstructive
         • You try to breath, but the airway is closed
         • Relaxation of upper airway muscles
     – Central
         • There is no stimulus to breath
         • Relaxation of lower airway muscles
•   Associated w/:
     – Snoring
     – Obesity (can still occur in normal body habitus)
     – Mixed w/ Cheyne-Stokes or hypoventilation
     – HTN
     – Tachycardia
     – Narrow airway, edema, large neck
     – Risk factors: smoking, alcohol, GERD, brain disease, heart disease, ADHD (any kid
       who snores, evaluate!)
     – IS a risk factor for: HTN, MI, Stroke, RHF, pulmonary HTN, Diabetes, Motor vehicle
       accidents, HA, Depression, Shorter life span by 7-10yrs
 Who needs evaluated for OSA ?
• Snoring associated with HTN, obesity, DM, or any
  vascular disease.
• Snoring in individuals with unrefreshing sleep,
  excessive sleepiness or insomnia.
• All children who snore (American Academy
           OSA Treatment
• Continuous Positive Airway Pressure (CPAP,
• Surgery – 50-50 chance of success
• Dental Device
• Weight Loss
• Medication
• Avoidance of alcohol
• Sleep on side
            Respiratory Failure
 Lung Failure           Ventilation Failure

Gas Exchange Failure

 Low Inspired O2
 Diffusion Limit         CNS Depression
 Shunt                   Muscular Fatigue
 Poor VA
                         Mechanical Failure
 VQ Mismatch
Causes of Hypercapnic Failure
 • Normal Ventilation
   – Increased Production of CO2 (fever,
 • Normal Ventilation with Increased
   Deadspace (VQ Mismatch)
   – Pulmonary Embolus
   – Emphysema
 • Decreased Ventilation (lots of causes)
   – Breath Holding
   – Obesity
   – Drugs
What’s the Poor Mans Rule of Thumb for
  Acute versus Chronic Respiratory

 • Acute Respiratory Acidosis
   -HCO3 rise by 1 mEq/L for each 10 mmHg PCO2
 • Chronic Respiratory Acidosis
   -HCO3 rise by 4 mEq/L for each 10 mmHg PCO2
        – The body has had time to renally/metabolically compensate for the
          respiratory acidosis by increasing HCO3- amts to counteract the
          drop in pH.
  What are the causes of dyspnea?
• Abnormal gas exchange or acidosis
  – Hypercapnia – sensed in medulla, carotid bodies
  – Hypoxemia – sensed in carotid bodies
  – Low pH - sensed in medulla, carotid bodies
• Increased neuromuscular stimuli
  – Chest wall muscle receptors
  – Parenchymal and airway receptors
• Abnormal perception/psychogenic
If given these Sxs in the history, what diseases
          should you be thinking about?
If given these findings in the physical exam,
what diseases should you be thinking about?
If given these findings in the physical exam,
what diseases should you be thinking about?
If given these findings in the physical exam,
what diseases should you be thinking about?
      If given these diagnostic results,
what diseases should you be thinking about?
What are these diagnostic tests useful for
          in making diagnoses?
You’re Done!
   Good luck on the exam