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Quiz Yourself - Respiratory. The FEV 1 is reduced when: airway obstruction is present as with these diseases: Asthma Emphysema FEV 1 /FVC ratio is reduced when airway obstruction is present. The normal ratio is: 70-75 The FVC is reduced with restrictive lung disease

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  • 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
Lung Volumes in Disease States

What does each of these represent?

What is the alveolar gas equation
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
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
What are the causes of hypoxemia and how do we distinguish them?

  • We distinguish between them using blood gas and A-a gradient

  • 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
What is the diffusing capacity? them?

  • Measured by DLCO

  • Impacted by diffusion barrier and aggregate surface area of alveoli

  • 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
What are the volume patterns for the following diseases? them?

  • 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
Mechanisms of Hypoxemia them?

  • 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
    What patterns of impairment them?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? them?

    Normal Alveoli!

    Dilated bronchi them?

    Muco-Purulent Debris in Dilated Bronchi


    Bronchiectasis them?

    • 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

    Eosinophil them?

    What disease is this?

    Charcot-Leyden crystals – eosinophil granule contents

    This is ASTHMA!!!!


    Curschmann Spirals – mucus casts

    Asthma them?

    • 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 them?

    Chronic Bronchitis

    • 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 them?Emphysema in COPD

    Emphysema them?

    • 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
    Bronchiolitis Obliterans/Organizing Pneumonia (BOOP) them?

    • 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 them?-

    No allergic or (personal family) history

    Usually adult onset

    Often follows severe respiratory illness

    Symptoms usually perennial

    More refractory to treatment, become other diseases, progress to vasculitis

    Eosinophils still impt

    Extrinsic Asthma-

    Strong family history of allergies

    Usually onset at a young age

    Other allergic manifestations in patients

    History of specific allergic association triggers (e.g. pollen, animal dander)

    Correlation with skin and inhalation responses to specific antigens

    Type I hypersensitivity rxn

    IgE mast cell and eosinophils

    Classification of Asthma

    Allergic shiner edema discoloration around the eye

    What does this demonstrate? What is it? them?

    ALLERGIC SHINER: Edema/ Discoloration Around the Eye

    • What are the important cells in asthma? them?

      • 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 asthma

    • 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
    Findings/Diagnosing Asthma? them?

    • Spirometry

      Increase lung volumes (TLC, FRC, RV)

      Decreased peak flow, FVC, FEV1, FEV1/FVC

    • Auto peak end expiratory pressure (auto-PEEP)-with rate respiratory rate.

    • DLCO

      Increased - useful in establishing dx

    • Methacholine challenge


    • b-agonist

      Reversible airflow obstruction when treated; albuterol

    • Eosinophils

      Increased in blood and found in sputum

    • ABG

      Low PO2, low PCO2

    Treatment of asthma
    Treatment of Asthma them?

    • Avoid asthmatic triggers

    • Use bronchodilators

      • Sympathomimetics – usually B2-AR specific to increase cAMP.

        • 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

      • Omalizumab – anti IgE antibody

    General strategy for management of asthma
    General Strategy for Management of Asthma them?

    • Infrequent attacks?

      • Inhaled sympathomimetics (B2)

    • More frequent?

      • Add an anti-inflammatory as maintenance, usually a corticosteroid

    • 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 asthma1
    Classification of asthma? them?

    • Mild intermittent

    • Mild persistent – more than 2X/week, but <1QD

    • Moderate persistent – daily symptoms

    • Severe persistent – continual symptoms

  • 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? them?

      • 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
    Mechanisms of Airflow limitation in COPD? them?

    • 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? them?

      • 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

    Treatment of copd
    Treatment of COPD COPD Pathophysiology

    • 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
    Major Points from Smoking COPD PathophysiologyCessation 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 lecture1
    Major Points from Smoking COPD PathophysiologyCessation 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
    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 smoking?

      • 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 smoking?

    Is dilated

    Giant cell


    What disease?

    Sarcoidosis smoking?

    • Clinical:

      • Multi-system granulomatous disease

      • Adults, B>W, F>M

      • Dyspnea

    • Radiology:

      • Interstitial infiltrates in bronchovascular distribution (= lympagenic distribution)

      • Usually have hilar adenopathy (picked up on routine CXR)

    • Pathology:

      • Tight, well-formed non-caseating granulomata

      • Def of granulomata: Focal accumulations of epithelioid histiocytes

    Hypersensitivity pneumonia
    Hypersensitivity Pneumonia smoking?



    Interstitial expansion



    Hypersensitivity pneumonitis extrinsic allergic alveolitis
    Hypersensitivity Pneumonitis smoking?(Extrinsic Allergic Alveolitis)

    • Clinical:

      • Organic dusts

        • Doesn’t mean carbon based

        • Means related to organic products

      • Occupational or environmental exposure

      • Acute and chronic: dyspnea, cough, fatigue

    • Radiology:

      • Bilateral interstitial linear or nodular pattern

    • Pathology:

      • Patchy peri-bronchiolar and interstitial chronic inflammation with loosely formed granulomata

    Coal dust macules smoking?

    Coal-worker’s Pneumoconiosis

    Patchy Sub-Pleural Fibrosis smoking?

    Ferruginous Body


    Fibrotic Nodules smoking?

    Late Silicosis

    Usual interstitial pneumonia uip
    Usual Interstitial Pneumonia (UIP) smoking?

    • Clinical:

      • Syn. with “Idiopathic pulmonary fibrosis (IPF)”

      • Adults, mean 51 yo; poor response to steroids, 66% mortality

    • Radiology:

      • Patchy subpleural infiltrates, DDx asbestos, rheum

    • Pathology:

      • Patchy interstitial inflammation; fibrosis alternating with normal parenchyma

      • Temporally heterogeneous = ongoing injury to lung

      • Morph overlap with rheum dzs, e.g. scleroderma

    Fibroblasts in the interstitium smoking?


    Proliferative phase DAD

    Proliferative organizing phase diffuse alveolar damage dad
    Proliferative (Organizing) Phase Diffuse Alveolar Damage (DAD)

    • Clinical:

      • > 1-2 wks after identifiable acute lung injury (ex: MVA, septic shock, kidney stone, inhalation of noxious chemical)

      • Decreased pulm compliance -> mechanical ventilation

      • 50% mortality

    • Radiology:

      • Diffuse, interstitial>alveolar pattern

    • Pathology:

      • Interstitial + intra-alveolar fibroblastic proliferation

      • Temporally uniform

        • If it’s temporally heterogeneous = UIP

      • You HAVE to see interstitial fibroblastic proliferation

        • If it’s purely intra-alveolar = BOOP

    What characterizes pulmonary function in restrictive lung disease
    What characterizes Pulmonary function in Restrictive Lung Disease?

    • Characterized by reduced FVC, normal or high FEV1/FVC ratio

    Identify which is interstitial lung disease, obesity,

    and inspiratory & expiratory muscle weakness.

    Muscle Weakness
















    • What’s the differential diagnosis for bilateral diffuse infiltrates that mimic diffuse parenchymal disease?

      • Congestive heart failure

      • Pulmonary infection

      • Lymphangitic carcinomatosis

    • What are known causes of diffuse parenchymal lung disease?

      • Inhaled organic dusts (asbestosis, silicosis, coal workers, berylliosis

      • Inhaled organic antigens  hypersensitivity pneumonitis

      • Iatrogenic (drugs – amniodirone, radiation)

    • What are unknown etiological diffuse parenchymal lung diseases?

      • IPF/UIP

      • Sarcoidosis

      • BOOP

      • Goodpasture’s

      • Wegener’s

      • 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
    Pathophysiology of infiltrates that mimic diffuse parenchymal disease?Parenchymal Lung Diseases

    • Decreased lung compliance (increased stiffness)

      • Reduced FVC, reduced FEV1, normal ratio

      • Reduced lung volumes TLC, FRC, RV

    • Diffusion impairment

      • 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

      • Hypoxemia

      • Obliteration of small pulmonary vessels by fibrosis

    Clinical features of parenchymal lung diseases
    Clinical Features of infiltrates that mimic diffuse parenchymal disease?Parenchymal Lung Diseases

    • Symptoms

      • Dyspnea

      • Cough (non-productive)

    • Signs

      • Dry crackles or rales (sound like velcro)

      • Clubbing

      • Cor pulmonale

        • JVD

        • Loud P2, TR murmer

        • edema

    • What’s the major benefits of high resolution CT in diffuse parenchymal lung diseases?

      • Detects sub-radiographic disease

      • Distinguishes inflammation from fibrosis

        • Ground glass appearance suggests inflammation

    • What is thought to be the pathogenesis of sarcoidosis?

      • 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?

      • Macrophages

        • Results in increased release of TNF

      • 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 sarcoidosis?

      • Lofgrens

        • Acute onset

        • Bilateral hilar lymphadenopathy

        • Eythema nodosum

        • Fever

        • Arthralgias

        • Associated with a good prognosis

      • 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

      • Lupus pernio

        • Associated with chronic sarcoidosis

        • Usually on face, sometime butt and extremities

    • What are common abnormalities/diagnostic test results in sarcoidosis?

      • Hypergammaglobulinemia – T cells non-specifically activate B-cells  lots of Igs

      • Hypercalcemia, hypercalciuria – increased Ca2+ absorption from GI tract due to increased vitamin D formation

      • Lymphopenia – lymphocytes involved in granuloma formation

      • CD4 > CD8 in BAL – CD4 plays a greater role in granuloma formation

      • ACE elevated – due to vascular epithelial cells of granulomas

      • CXR or HRCT – parenchymal infiltrates, hilar adenopathy, sublpleural micronodules, upper lobe predominant, honeycombing, ground glass appearance

      • Gallium-67 scan – panda sign

      • Diagnosis is one of exclusion and heavily reliant on biopsy

    • How do we treat sarcoidosis? sarcoidosis?

      • Systemic corticosteroids

      • anti-TNF may be best tx (infliximab)

      • hydroxychloroquine

    • What is the staging of sarcoidosis?

      • Stage I – adenopathy

      • Stage II – parenchymal infiltrates & adenopathy

      • Stage III – just parenchymal infiltrates

      • Stave IV – fibrosis, hilar retractionm, cysts, bullae, honeycombing changes

    Uip ipf
    UIP/IPF sarcoidosis?

    • Pathogenesis?

      • Inflammatory process of the walls  fibrosis due to dyregulated response to damage of alveolar epithelial cells

      • 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?

      • Older adults, M>F

    • Signs and Symptoms?

      • Exertional dyspnea that increases over time

      • Non-productive cough

      • Possible clubbing

    • What are common abnormalities/diagnostic test results in UIP?

      • Velcro-like dry crackles

      • Peripheral edema or cor pulmonale in advanced stages

      • Hypoxemia, cyanosis, clubbing

      • CXR

        • Honeycombing

        • Diffuse reticulations

        • NO hilar enlargement

      • HRCT

        • Patchy, peripheral subpleural densities associated with small cystic spaces

    • Pathology of UIP?

      • Honeycombing

      • Fibrosis

      • Temporal heterogeneity

    What occupational exposure materials can cause inflammatory reactions in the airways
    What Occupational Exposure Materials can cause inflammatory reactions in the Airways?

    • Secretory Inflammation

      • Formaldehyde – upper airways

      • Ammonia – upper airways

      • Particulates (coal, dust, cotton) – bronchitis

      • Nitrogen dioxide – bronchiolitis

    • Hyperreactive Airways

      • Ozone, cotton dust – non-specific reactivity

      • TDI – occupational asthma

    What occupational exposure materials can cause parenchymal responses acutely chronically
    What Occupational Exposure Materials can cause Parenchymal responses Acutely? Chronically?

    • Acutely

      • Pulmonary Edema due to toxic reactions

        • Chlorine, phosgene

        • Acute silicosis

      • Hypersensitivty Pneumonia

        • Organic materials – farmer’s lung (mold spores in hay)

        • Inorganic materials

    • 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? responses Acutely? Chronically?

      • Nodular or diffuse fibrosis…

        • Silicosis

        • Asbestosis

        • Berylliosis

        • Coal Worker’s

    • Important things to do to make a diagnosis in occupational exposure related respiratory diseases?

      • Take a detailed history

      • CXR to document pneumonoconoiosis

      • Blood studies to document specific exposures

      • Lung tissue analysis

      • Measure peak flow throughout week

      • Specific inhalational challenges

      • Investigation of workplace by industrial hygienist

    Respiratory diseases due to asbestos
    Respiratory Diseases due to Asbestos responses Acutely? Chronically?

    • Non-Malignant

      A. Pleural Disease

      1. Pleural Effusion

      2. Diffuse Pleural Thickening

      3. Localized Pleural Thickening (Plaques)

      B. Diffuse Pulmonary Fibrosis (asbestosis)

    • 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
    Asbestosis – a responses Acutely? Chronically?restrictive Lung Dz

    • Latency period?

      • 20-30days

    • Pathologic features?

      • Ferruginous bodies!

      • Peri-bronchiolar inflammation and fibrosis

      • May eventually honeycomb

      • Tendency towards the lower lobes of the lungs

    • Clinical Symptoms and CXR?

      • Dyspnea on exertion

      • Dry cough

      • Late inspiratory crackles in bases

      • Opacification in bases

      • Pleural thickening

    Occupational asthma
    Occupational Asthma responses Acutely? Chronically?

    • Definition?

      • 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:

    • Typical immediate onset – w/in 30 minutes; clears hrs after leaving work. AM cough & sputum. Responds to bronchodilators

    • Typical late onset – may not have wheezing; 4-8hrs afterwards with longer duration. Refractory to bronchodilators

    • Dual Response

    • Recurrent Attacks Post Exposure – at night after exposure

  • Standard Treatment:

    • Inhaled steroids and bronchodilators

  • Reactive airways dysfunction syndrome rads
    Reactive Airways Dysfunction Syndrome (RADS) responses Acutely? Chronically?

    • Characteristics:

      • No preceding respiratory symptoms.

      • Onset of symptoms after single high level exposure to an irritant.

      • Onset of symptoms is abrupt (without 24 hours) and symptoms persist for at least 3 months.

      • Symptoms of variable airway obstruction and/or hyperresponsiveness.

      • Non-specific airway hyperresponsiveness present (methacholine challenge).

      • Persistent airway inflammation but lack of eosinophils

    Pleural diseases
    Pleural Diseases responses Acutely? Chronically?

    • What is pleuritic pain?

      • Caused by inflammatory processes that intensify upon breathing

    • What’s going on with a tension pneumothorax?

      • Air escapes into pleural space  positive pressure

      • Air can’t escape on exhalation

    • How can a tension pneumothorax cause shock?

      • By compromise of venous return

    • How can ANY pneumothorax be caused?

      • Trauma  sucking wound

      • Iatrogenic - Overzealous use of positive pressure ventilation, central lines, lung biopsies

      • Abnormal lungs  air trapping (think asthma)

      • Spontaneous in very tall people

    • What kind of pneumothorax? responses Acutely? Chronically?

      • 21 y o center for BB team

      • Has sudden onset of R sided chest pain & mild dyspnea

      • Patient is uncomfortable but vital signs are WNL

      • Not Sean May hopefully!

        • Pneumothorax disease

        • b/c it’s a popped lung, the pneumothorax is limited and should spontaneously resolve

      • 20 y o severe asthmatic

      • Intubated & on mechanical ventilation

      • Suddenly becomes hypotensive & cyanotic

        • This is a tension pneumothorax – must decompress the patient emergently!

    • What will the CXR look like on a pneumothorax?

      • On side of pneumothorax

        • Absent vascular markings

        • Appearance of a little nub near hilum (atelectic lung)

        • Diaphragm depressed downwards

      • On side opposite of pneumothorax

        • Mediastinum, trachea, other structures shifted over

    • 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

    • After you’re told he’s NOT possessed and isn’t just freaked out after watching that scary movie, you get a CXR.

    • That CXR shows:

      • Blunting of the right costaphrenic angle

      • Elevation or flattening of right hemi diaphragm

      • And the mediastinum shifted to the left side

    • Then the scary, menacing attending asks you what does he have. You, being the superstar that you are, reply:

    Why a pleural effusion duh
    “Why A Pleural Effusion, into your ER with:DUH!”

    • How is normal pleural fluid made?

      • Generated by Starling forces across a capillary bed

    • Radiographic signs of pleural effusion include:

      • Blunting of costophrenic angle on upright film

      • Elevation or flattening of hemi diaphragm on upright film

      • Diffuse haziness of hemi thorax on supine film

      • If large, will cause shift of mediastinum to contra-lateral side

    • How do you relieve a massive pleural effusion?

      • 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
    How do you relieve a massive pleural effusion? into your ER with:

    • 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 safely do a thoracentesis?

      • Make sure the fluid is freely flowing and not loculated

        • Use a lateral decubitus film

      • Use ultrasound to locate effusion

      • 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, nerve

    What are lyte s criteria why do we use them in the first place
    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

      • Ratio of pleural-fluid protein to serum protein > 0.5

      • Ratio of pleural-fluid LDH > 0.6

      • Pleural fluid LDH level > 2/3 upper limits of normal for serum

      • Any one of these characteristics means the fluid is an exudate

    • What other studies might you do on fluid from a pleural effusion

      • cell count & differential, glucose, cytology, Gram stain, AFB stain & culture, amylase, cholesterol, triglyceride level, pH, adenosine deaminase

    • 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 transudate
    What are the potential causes of a Transudate? place?

    • CHF – due to increased pulmonary venous pressures, usually bilateral, usually resolves in 48 hours after diuresis

    • Nephrosis – low oncotic pressures

    • Cirrhosis

    • Atelectasis – increased negative pleural pressure

    • Ascites – can preferentially form in pleural space, hepatic-hydrothorax

  • What are the potential causes of a massive exudate?

    • Malignancy

    • Trauma - hemothorax

    • Empyema – bacterial infections

    • Chylothorax – disruption of thoracic duct

    • Rarely, TB

    • Causes of bloody exudates? place?

      • Cancer

      • Pulmonary infarction

      • Penetrating & nonpenetrating trauma

      • Central line malplacement

      • Chondrosarcoma

      • S/P CABG

    • Causes of turbid exudates?

      • Chylothorax

      • Empyema

  • How do you define a hemothorax?

    • Defined as pleural fluid hematocrit of 50% of blood hematocrit

    • Will coagulate & may lead to loculation with complications of fibrothorax & possible empyema

    • If small, may defibrinate & remain free flowing

  • So the good doctor said there s a good exam question in here
    So the good doctor said there’s a good exam question in here…

    • What kind of cell count in an exudate would make you suspect cancer or Tb?

      • >50% lymphocytes!

    • Now what additional information on this exudate could help you decide that it’s probably NOTTb?

      • >5% mesothelial cells

        • Remember, mesothelial cells are normally found in pleural fluid to some degree since they are the cells that comprise the pleura!

    Empyemas here…

    • Why should you distinguish between an empyema and a parapneumonic effusion?

      • 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?

    • Well if it’s an empyema, there should be:

      • Gross pus

      • pH < 7.1

      • glucose < 40

      • positive Gram stain or cultures

    • And if it’s all borderline you need to retap that…um…lung…

  • Ack it s an empyema what do i do
    Ack! It’s an Empyema! What Do I do? here…

    • Well a tube thoracostomy for one

    • Antibiotics to get those microbes

    • 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!

  • 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…

  • 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 here…






    Hamartoma here…

    • It’s BENIGN!!!!

    • Clin:

      • Adolescence  adulthood

      • None in newborns - not congenital

    • Rad:

      • Solitary nodule +/- popcorn calcification

      • Peripheral > central

    • 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-malignant!

    What are the malignant epithelial neoplasms carcinomas
    What are the Malignant epithelial neoplasms (Carcinomas)? here…

    • Squamous cell carcinoma

    • Adenocarcinoma

    • Large cell undifferentiated carcinoma

    • 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!

    Desmosomes here…


    Squamous Cell Carcinoma


    Squamous cell carcinoma
    Squamous cell carcinoma here…

    • Clin:

      • Smokers association?

        • YES

      • Prevalence?

        • 20-30% of common carcinomas

      • May secrete PTH-like compound

    • Radiology:

      • central > > peripheral

    • Path:

      • Bronchi > Larynx > TracheaKEY CHARACTERISTICS?

      • +/- Desmosomes (intercellular bridges) +/- Keratin production, e.g. keratin pearls

    Primary here…

    Gland formation

    Pleural effusion

    Mucin production (red on PASd stain)


    Adenocarcinoma here…

    • Clin:

      • 30-40% of common carcinomas

      • Smoking association?

        • Most common carcinoma in non-smokers, but 80% of adenoCAs occur in smokers

    • Rad:

      • peripheral > central

    • Path:

      • +/- glands

      • +/- mucin

      • Bronchiolo-alveolar carcinoma subset

    Bronchiolo-alveolar carcinoma here…

    - Note the mucin in the alveoli. Gas exchange is gonna suck in this patient!

    Bronchioloalveolar carcinoma bac
    Bronchioloalveolar carcinoma (BAC) here…

    • Subset of?

      • Adenocarcinoma

    • Incidence?

      • Rising incidence (presently 20-25%)

      • Associated w/ smoking?

        • Not associated with cigarette smoking

    • Rad:

      • Peripheral, can be multifocal and bilateral

    • Path:

      • Lepidic (butterfly-like) growth pattern

      • Mucinous or non-mucinous

      • Unifocal or multifocal

    Large cell undifferentiated carcinoma
    Large cell undifferentiated carcinoma here…

    • Clin:

      • 10% of common carcinomas

    • Rad:

      • non-specific

    • Path:

      • H&E: Undifferentiated

      • cDNA microarrays: distinct disease

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

    Necrotic here…


    Viable carcinoma

    Normal lymphocytes

    Response to therapy

    At diagnosis

    Small Cell Carcinoma

    Small cell carcinoma
    Small cell carcinoma here…

    • Clin:

      • Smokers?

        • YES

      • 20 % of common carcinomas

      • Paraneoplastic Syndromes:

        • Ectopic ACTH, ADH, Eaton-Lambert, carcinoid s.

      • Commonly high stage at presentation

      • Responsive to chemo/RT, but low 5 yr survival

    • Rad:

      • Central in >90%

      • Frequent metastases to LNs and distant sites

    • Path:

      • Malignant cytology; high N:C ratio

      • No nucleoli; punctate salt and pepper nucleoli

      • High mitotic activity and tumor cell necrosis

      • Think small round blue cells!

    Visible here…



    Loss of C-P Angle

    = Pleural effusion or mass

    Normal thickness pleura

    Thickened pleura

    Thin delicate microvilli

    Associated w/ ferruginous bodies


    Most common metastatic carcinomas in the lung
    Most Common Metastatic carcinomas in the Lung? here…

    • Breast adenoCA

    • GI adenoCA

    • Renal adenoCA

    • Head/neck squamous cell CA

    Lung cancer basics
    Lung Cancer - Basics here…

    • What are the 2 most impt risk factors for lung cancer?

      • Genetics

      • Smoking (15% smokers will get lung cancer; 85% CA in smokers)

    • What types of molecules are the predominant carcinogens in cigarettes?

      • Polycyclic hydrocarbons

    • What sex is more susceptible to lung CA? Theories why?

      • WOMEN

      • Differences in metabolism, CYP450

      • Hormonal effects in lungs

    • What are some mutations that have been implicated?

      • 3p – NSCLC

      • Ras – adenocarcinoma

      • Myc – small cell

      • NSCLC – p53

      • Rb – small cell

      • Random breaks in 1, 3, 5, 7, 15, 17

    More lung cancer basics
    More Lung Cancer Basics here…

    • Most common sites of metastases:

      • Liver

      • Bone

      • Brain

      • Adrenals

    • What are the paraneoplastic syndromes associated w/ NSCLC?

      • Clubbing, Hypertrophic orthropathy (adeno), Hypercalcemia (squamous)

    • What are the paraneoplastic syndromes associated w/ SCLC?

      • SIADH (hyponatremia), Cushings, Lambert-Eatons, peripheral neuropathy, cerebellar degeneration

    Diagnostic tools for lung ca
    Diagnostic Tools for Lung CA here…

    • The Basics

      • Detailed hx and physical (esp lungs and supraclavicular nodes)

      • CXR

      • Chest CT

      • Lab tests: CBC, liver fxn, alkaline phosphatase, serum Ca2+

    • The Good, Special Stuff

      • For central, endobronchial lesions

        • Sputum cytology (3+ specimens for 90% yield)

        • Bronchoscopy

          • Can also do transtracheal needle aspirate of nodes near trachea and bronchi

      • For peripheral lesions

        • Transthoracic needle biopsy (CT guided)

        • Thoracentesis (effusions)

          • Malignant (w/ CA cells in exudate) or paramalignant

    Staging lung ca
    Staging Lung CA here…

    • SCLC

      • 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

      • What’s not so useful?

        • TNM system (which is used in NSCLC)

          • T – location, size

          • N – nodes

          • M – metastases

            • Stage I – no nodes involved

            • Stage II – nodes on the same side/hilum of CA

            • Stage III – nodes/mediastinum

            • Stage IV – another organ involved or a second lesion in the lung

    IIIA, IIIB = locally advanced

    IIIB, IV = advanced, effusion


    • Tricks to help us stage NSCLC? here…

      • Intrathoracic

        • Chest CT

        • FDG PET Scan

        • Mediastinoscopy

      • Extrathoracic

        • Bone scan

        • CT/MRI of brain

        • Abdominal CT (liver, adrenals)

        • Biopsies of extrathoracic lesions

    • Treating NSCLC

      • Early – surgical resection + chemo

      • Locally Advanced – chemo + surgery or radiation

      • Advanced – chemo

        • Can help improve sxs, cost effective, increases 1yr survival

    • Treating SCLC

      • Limited – chemo + radio

      • Extensive – chemo, w/ palliative radio as needed

    • Adenocarcinoma here…

      • 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 reasons

      • Cough and bronchorrhea (frothy sputum production)

      • Variable radiographic presentation: solitary nodule, multiple nodules, infiltrate/consolidation with air-bronchograms

    • Squamous cell carcinoma here…

      • Exclusively in smokers

      • Generally arise in proximal airways

      • May cause obstruction of the airway with distal atelectasis, post obstructive pneumonia

      • 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)

    Time to take a study break

    Got Your Sound On? here…

    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
    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 pneumonia

    Interstitial likely disease process lymphocytes in viral pneumonia

    Giant Celll likely disease process

    Histiocytes and multinucleated giant cells (granulomatous inflammation)

    in mycobacterial pneumonia

    Common bacterial pneumonia microbes
    Common bacterial pneumonia microbes likely disease process

    • 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 pathology
    What is the agent of Pneumococcal pneumonia? How do you get it? Sxs? Pathology?

    • Streptococcus pneumoniae is the prototype of bacterial pneumonia

      • 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 hepatization”)

        • Later: serum and fibrinous exudates, intra-alveolar organization, macrophages (“gray hepatization”)

    What are the sxs of legionella pneumonia
    What are the sxs of Legionella pneumonia? it? Sxs? Pathology?

    • “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
    What patients are susceptible to pneumonias it? Sxs? Pathology?caused by anaerobic bacteria?

    • Anesthetized patients

    • Alcoholics

    • Seizure disorder

  • What are characteristics of anaerobic pneumonias?

    • 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
    What are common complications of it? Sxs? Pathology?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 space.

      • 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 it? Sxs? Pathology?


    Center of pulmonary abscess showing acute

    inflammation with destruction of

    Normal pulmonary architecture (no alveolar walls)

    Alcoholics on the right

    lung b/c that’s where

    aspiration goes!

    An abscess.

    Who’s likely to get it and where?

    necrotizing granulomatous inflammation it? Sxs? Pathology?

    Peripheral focus of granulomatous

    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)

    Tuberculosis it? Sxs? Pathology?

    • 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 inflammation

      • 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
    Complications of tuberculosis it? Sxs? Pathology?

    • 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
    Other mycobacterial diseases it? Sxs? Pathology?

    • 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)

    Histoplasmosis it? Sxs? Pathology?

    • 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

    Coccidioidomysis it? Sxs? Pathology?

    • 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 valley.

    • 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

    Cryptococcosis it? Sxs? Pathology?

    • Appearance?

      • yeast 4-9 microns with mucinous capsule

    • Found in?

      • pigeon droppings

    • Clinical and pathological presentation?

      • Clinical disease almost exclusively in immunocompromised patients

      • 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

    Blastomycosis it? Sxs? Pathology?

    • 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

    Aspergillosis it? Sxs? Pathology?

    • 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 production

        • Treatment with steroids to control immune response

        • It’s not the fungus that hurts you, it’s your body’s response

      • Invasive aspergillosis – usually fatal

        • Almost exclusively in immunocompromised hosts

        • Invasion of pulmonary blood vessels with organismcausing infaction, thrombosis, exsanguination

    Aspergilloma showing non-invasive fungus within granulation tissue lined


    Aspergilloma (fungus ball) within pre-existing cavity

    Aspergillus within tissue lined

    blood vessel wall

    Invasive aspergillus

    Mucormycosis zygomycosis
    Mucormycosis (Zygomycosis) tissue lined

    • 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

    Mucomycosis tissue lined

    Pneumocystis carinii
    Pneumocystis carinii tissue lined

    • 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

    Viral pneumonias
    Viral pneumonias alveolar spaces

    • 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 inclusion

    • Measles

      • Multinucleated giant cells with nuclear inclusions

    • Varicella (chicken pox and herpes zoster) are usually asymptomatic

      • Interstitial mononuclear cell pneumonia, may produce focal necrosis

      • Nuclear eosinophilic viral inclusions, may be mutlinucleated

    • Herpes simplex

      • necrotizing tracheobronchitis and diffuse alveolar damage

    • Other viruses (especially in children)

      • Adenovirus

      • Respiratory syncytial virus

    Viral inclusion inclusions

    Herpes virus on cytology specimen

    Mycoplasma inflammation

    • Small free-living prokaryote, common cause of acute self-limited pneumonia and tracheobronchitis,

    • milder than usual bacterial pneumonia (“walking pneumonia”)

    • 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
    What are common host defenses to inflammationrespiratory infection?


      • Upper Airway (nose)

      • Epiglottis/Larynx

      • Epithelial Tight Junctions


      • Mucociliary and Cough Clearance

    • IMMUNE

      • “Innate” (lysozyme; lactoferrin; “defensins”)

      • Immune Response

        • Secretory IgA (nasal/bronchial)

        • Humoral Antibody

        • Cellular


      • Alveolar Macrophages (AM)

      • Inflammatory Response (PMNs, etc.)

      • Anti-Proteases

    • What defenses are protecting the proximal airways and nose? inflammation

      • Primary Components: cilia, liquid/mucus, submucosal gland secretions

      • Mucociliary clearance – respond to neurohormonal and mechanical stimuli

      • Secretions of the submucosal glands – what’s in this?

        • Lysozymes

        • 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 cytokines

      • IgG

    • Secondary defense mechanisms thoughout the lung?

      • Neutrophils and other inflammatory cells

    Lung defense failures
    Lung Defense Failures inflammation

    • 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
    Routes of Infection of Lung inflammation

    • Aspiration

      • Microaspiration of pathogens colonizing the oropharynx (your upper away)

      • Gross aspiration of mouth/GI tract contents into lungs

    • Inhalation

      • Ambient droplets/particles entrained (e.g. TB, fungi)

    • Hematogenous

      • e.g. Staph. aureus with IVDA, endocarditis, or a catherter

    Typical vs atypical pneumonia

    Typical Pneumonia inflammation

    Rapid onset

    Ill appearing

    High fever, rigors (shaking chills), chest pain, purulent sputum

    Consolidation, rales on exam

    Leukocytosis (15-20K)

    Airspace filling/lobar infiltrate on CXR with air bronchograms

    Meant to describe: S. pneumo, S. aureus, GN bacilli like Klebsiella

    Atypical Pneumonia

    Indolent onset (7-10days)

    Less ill appearing

    Low-grade fever, malaise, headache, dry cough

    Rales without consolidation

    Mild/no leukocytosis; negative cultures

    Patchy/interstitial infiltrates on CXR

    Meant to describe: Mycoplasma, or Chlamydia

    Typical vs Atypical Pneumonia


    This is the most important test that needs to be done in diagnosing pneumonia
    This is the most important test that inflammationneeds 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 “bronchopneumonia”)

        • 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?

    • YES

      • 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 then?

      • 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
    So when is this sputum Gram stain & Culture patient has pneumonia, do you even care what the causative microbe is?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? patient has pneumonia, do you even care what the causative microbe is?

    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
    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 You’ll assess the severity looking at what? And

    • 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
    What are your basic Treatment You’ll assess the severity looking at what? And Groups for Pneumonia?


    No underlying. disease or modifying factors

    Underlying comorbidities or modifying factors (COPD, CHF, alcoholism,…)


    Inpatients not needing ICU care

    No comorbidities

    Underlying comorbidities

    Severe pneumonia requiring ICU care

    Low risk for pseudomonas

    Risk for pseudomonas

    How do you treat each group
    How do you treat each group? You’ll assess the severity looking at what? And

    Hap pathogens and treatment
    HAP Pathogens and Treatment You’ll assess the severity looking at what? And

    • 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
    So in the Immunocompromised Host, what is reflective of the specific immune deficit?

    • Risk for pathogens reflect specific immune deficit

      • Neutropenia:

        • bacteria,

        • aspergillus,

        • candida

      • Splenectomy:

        • encapsulated organisms

      • T-cell number (HIV) or function (immunosuppressives):

        • fungi,

        • mycobacteria,

        • viruses (CMV, EBV),

        • bacteria

    Hiv lung infections reflect what
    HIV lung infections reflect what? specific immune deficit?

    • 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 tuberculosisat all CD4 counts

    • How do you avoid PCP in HIV+ patients?

      • Prophylactic therapy in compliant patients quite effective

        • trimethoprim/sulfa – also used to treat

        • Dapsone

        • inhaled pentamidine – also used to treat

    Aids and pneumocystis carinii
    AIDS and specific immune deficit?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
    AIDS and Non-TB mycobacteria specific immune deficit?

    • Primary species are within M. avium complex

    • Risk when CD4 count < 50 (prophylaxis with clarithromycin)

    • 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
    AIDS and Fungal Pneumonia specific immune deficit?

    • Cryptococcus neoformans:

      • Common cause of meningitis, usually without pneumonia

      • May cause local or diffuse pulmonary disease; disseminate

    • 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
    AIDS and Non-infectious Lung Diseases specific immune deficit?

    • 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 hypertension

    What is bronchiectasis 2 modes of pathogenesis its vicious cycle
    What is bronchiectasis? 2 modes of specific immune deficit?pathogenesis? Its vicious cycle?

    “Irreversible dilation of airways caused by inflammatory destruction of airway walls”


    • Infection/Inflammation

      • bacterial pneumonia, tuberculosis, measles, pertussis

    • Airway obstruction

      • Cystic Fibrosis (CF)

      • Primary Ciliary Dyskinesia (PCD; Kartagener’s Syndrome)

      • Hypogammaglobulinemia (total; IgG2/IgG4; IgA)

    • Airway obstruction/Infection

      • Airway wall damage/dilation

        • Impairment of mucus clearance

          • Promotion of Airway Infection

    Other etiologies of bronchiectasis
    Other Etiologies of Bronchiectasis specific immune deficit?

    • “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 genotype)

  • What happens to the bronchial arteries in bronchiectasis and why?

    • Marked hypertrophy of bronchial arteries due to chronic inflammatory stimuli

  • Clinical features of bronchiectasis
    Clinical features of bronchiectasis specific immune deficit?

    • 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 present

      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
    So you have a pt and the HRCT shows specific immune deficit?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

      • -agonists

        • Reduces reversible airway obstruction and promotes mucociliary clearance

      • Surgery

        • For refractory symptoms/hemoptysis from localized disease

    Cystic fibrosis
    Cystic Fibrosis specific immune deficit?

    • 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? specific immune deficit?

    CFTR Gene Mutation

    Altered Ion Transport

    Abnormal airway surface liquid (volume depletion)

    Impaired airway defenses (reduced mucociliary clearance)

    Chronic airway infection/inflammation



    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
    How do you diagnose CF? specific immune deficit?

    • 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 abnormalities

      • 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
    How do you get pseudomonas in CF? specific immune deficit?

    • 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 arteries

    • Respiratory insufficiency

    • Cor pulmonale

  • What is the standard maintenance therapy for cf
    What is the standard maintenance therapy for CF? specific immune deficit?

    • 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 specific immune deficit?

    Parenchymal infarct

    with hemorrhage

    Pulmonary Thromboembolism

    Pulmonary thromboemboli pulmonary embolism pe
    Pulmonary Thromboemboli (pulmonary embolism, PE) specific immune deficit?

    • Clinical:

      • Dyspnea, hemoptysis

      • Commonly due to lower extremity thrombi

    • Radiology:

      • Decreased flow, V/Q mismatch  abnormal V/Q scan

    • Pathology:

      • Pulmonary arterial thromboemboli

      • Survivors may have peripheral wedge-shaped infarction

    Plexiform lesion specific immune deficit?

    Medial and intimal hypertrophy

    Pulmonary artery hypertension
    Pulmonary Artery Hypertension specific immune deficit?

    • 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 specific immune deficit?



    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 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
    What’s going on with the increased blood flow through the lungs?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
    What is the vicious cycle of increased blood flow through the lungs?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
    What are the Mechanisms of increased blood flow through the lungs?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, sarcoidosis

    • Vasoconstrictive:

      • hypoxia, scleroderma

    What is the basis of primary pulmonary hypertension
    What is the basis of increased blood flow through the lungs?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 years

    Symptoms of pph
    Symptoms of PPH increased blood flow through the lungs?

    • 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) murmur

    • Peripheral edema due to RHF

  • Therapy of pulmonary hypertension
    Therapy of Pulmonary Hypertension increased blood flow through the lungs?

    • 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
    What are the Pathophysiological increased blood flow through the lungs?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
    Diagnostic Tests for DVT increased blood flow through the lungs?

    • Venography

    • Impedance Plethysmography

    • Duplex Scanning

    • Dopper flow velocity

    • MRI scans

    Diagnosis of acute pulmonary embolism
    Diagnosis of Acute Pulmonary Embolism increased blood flow through the lungs?

    • 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
    Contraindications to Heparin Therapy increased blood flow through the lungs?

    • 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
    So you’ve got edema in the distal airways increased blood flow through the lungs?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 ENaC

    • 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” increased blood flow through the lungs?

    Alveolar filling pattern

    with air bronchograms

    Exudative acute phase diffuse alveolar damage dad
    Exudative (Acute) Phase Diffuse Alveolar Damage (DAD) increased blood flow through the lungs?

    • Clinical:

      • Adult respiratory distress syndrome (ARDS)

      • Identifiable lung injury 0-2 wks before

      • Acute dyspnea, hypoxemia, decreased compliance

    • Radiology:

      • Diffuse alveolar filling pattern

    • Pathology:

      • Endo- or epithelial injury, Type II cell hyperplasia

      • First 2 wks after injury: edema  fibrin

    Respiratory distress syndrome of newborns
    Respiratory distress syndrome of newborns increased blood flow through the lungs?

    • Clinical:

      • Prematurity

      • Tachypnea, intercostal muscle retraction, hypoxemia

    • Radiology:

      • Diffuse alveolar filling pattern with air bronchograms

    • Pathology:

      • Insufficient surfactant production by type II cells

      • Atelectasis  hypoxia/acidosis  epith necrosis

      • Diffuse intra-alveolar hyaline membrane formation (exudative DAD)

    RBCs filling increased blood flow through the lungs?

    alveolar spaces

    Alveolar Hemorrhage Syndrome

    Causes of alveolar hemorrhage syndrome
    Causes of increased blood flow through the lungs?Alveolar Hemorrhage Syndrome

    • Goodpasture’s syndrome

    • Acute lupus pneumonitis

    • Wegener’s granulomatosis

    Goodpasture s syndrome
    Goodpasture’s syndrome increased blood flow through the lungs?

    • Clinical:

      • Young adults, M>F

    • Radiology:

      • Diffuse alveolar pattern

    • Pathology:

      • Anti-basement membrane IgG antibodies damage pulmonary and renal basement membranes

      • Linear IgG and C’ deposition by ImmunoFluorescence and Electron microscopy

      • Anti-GBM IgG is detectable in serum

    Acute lupus pneumonitis
    Acute lupus pneumonitis increased blood flow through the lungs?

    • 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

    Lipid increased blood flow through the lungs?

    Aspiration of cooked fat

    Aspiration increased blood flow through the lungs?

    • 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
    Endogenous lipoid pneumonia increased blood flow through the lungs?(“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

    Foamy increased blood flow through the lungs?


    Endogenous (Post-Obstructive) Lipid Pneumonia

    Transudate in interstitium and alveolar airspaces increased blood flow through the lungs?

    Capillary congestion

    Severe Pulmonary Edema

    Pulmonary edema
    Pulmonary Edema increased blood flow through the lungs?

    • Clinical:

      • Cardiogenic: LV pump failure, mitral valve stenosis

    • Radiology:

      • Incr. vascular markings, reticular +/- nodular

      • Think Kerley B lines

    • Pathology:

      • Venous and capillary congestion

      • Incr. free water in the interstitium +/- alveoli

    Define ards
    Define ARDS increased blood flow through the lungs?

    • Acute Respiratory Distress Syndrome

      • A clinical definition

      • Acute onset

      • Bilateral infiltrates on CXR

      • Pulmonary Artery wedge pressure <18 or no evidence of left atrial hypertension

        • PaO2/FIO2 < 300: Acute Lung Injury

        • PaO2/FIO2 < 200: ARDS

    • Common Causes? Most Common Cause?

    Indirect Lung Injury


    Multiple Trauma

    Other Shock

    Acute Pancreatitis

    Multiple Transfusions

    Drug Toxicity

    Direct Lung Injury



    Pulmonary Contusion

    Fat Emboli

    Inhalational Injury

    Near Drowning

    Septic shock
    Septic Shock increased blood flow through the lungs?

    Inflammatory Cytokines

    Nitric Oxide from Vasc. Endothelium

    Low Systemic Vascular Resistance

    High Cardiac Output Hypotension

    Wide pulse pressure ex: (90/30)

    Brisk capillary refill


    Decreased urine output

    Decreased mental status

    Lactic Acidosis –

    b/c all these tissues are underperfused

    Continuum and definitions of septic shock
    Continuum and Definitions of increased blood flow through the lungs?Septic Shock

    • Infection

      • 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
    Acute or Exudative Phase of ARDS increased blood flow through the lungs?

    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
    Proliferative or Fibrotic Phase of ARDS increased blood flow through the lungs?

    • 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 increased blood flow through the lungs?

    Respiratory Failure

    Hypoxemic - inadequate O2 delivery

    Hypercapnic - respiratory acidosis (high PCO2)

    secondary to failure to adequately ventilate

    Hypoxemic Failure increased blood flow through the lungs?

    Physiological Causes

    • Decreased PIO2

    • Decreased VA

    • C. Ventilation/Perfusion [V/Q] Mismatch

    • D. RL Shunt

    • E. Diffusion Limitation only problematic during exercise

    Physiologic causes of hypoxemic failure
    Physiologic Causes of Hypoxemic Failure increased blood flow through the lungs?

    • 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 failure
    Physiologic Causes of Hypercapnic Failure increased blood flow through the lungs?

    • 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 increased blood flow through the lungs?

    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 increased blood flow through the lungs?

    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? increased blood flow through the lungs?

    • A. Diagnose and treat underlying cause

    • Consider respiratory stimulants

      • 1. Naloxone (opioid antagonist)

      • 2. Controlled hypoxemia (in proper clinical settings)

      • 3. Chemicals (rarely effective; xanthines, progesterone)

    • 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.

    • 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 patterns
    Damage to these parts of the brain are associated with what types of breathing patterns?

    • 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
    What is Sleep Apnea? types of breathing patterns?

    • 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
    Who needs evaluated for OSA ? types of breathing patterns?

    • 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 Pediatric).

    Osa treatment
    OSA Treatment types of breathing patterns?

    • Continuous Positive Airway Pressure (CPAP, BiPAP)

    • Surgery – 50-50 chance of success

    • Dental Device

    • Weight Loss

    • Medication

    • Avoidance of alcohol

    • Sleep on side

    Respiratory failure
    Respiratory Failure types of breathing patterns?

    Lung Failure

    Ventilation Failure

    Gas Exchange Failure



    Low Inspired O2

    Diffusion Limit

    CNS Depression


    Muscular Fatigue

    Poor VA

    Mechanical Failure

    VQ Mismatch

    Causes of hypercapnic failure
    Causes of Hypercapnic Failure types of breathing patterns?

    • Normal Ventilation

      • Increased Production of CO2 (fever, tramua)

    • 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 acidosis
    What’s the Poor Mans Rule of Thumb for Acute versus Chronic Respiratory Acidosis?

    • 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
    What are the causes of dyspnea? Chronic Respiratory Acidosis?

    • 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 Chronic Respiratory Acidosis?

    should you be thinking about?

    If given these findings in the physical exam, Chronic Respiratory Acidosis?

    what diseases should you be thinking about?

    If given these findings in the physical exam, Chronic Respiratory Acidosis?

    what diseases should you be thinking about?

    If given these findings in the physical exam, Chronic Respiratory Acidosis?

    what diseases should you be thinking about?

    If given these diagnostic results, Chronic Respiratory Acidosis?

    what diseases should you be thinking about?

    What are these diagnostic tests useful for Chronic Respiratory Acidosis?

    in making diagnoses?

    Congrats you re done

    Congrats! Chronic Respiratory Acidosis?You’re Done!

    Good luck on the exam