Quiz Yourself - Respiratory

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Quiz Yourself - Respiratory
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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

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(No Transcript)
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Lung Volumes in Disease States
What does each of these represent?
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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

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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
• Shunt
• 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!

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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)

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What is the diffusing capacity?

• 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

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What are the volume patterns for the following
diseases?

• Obstructive diseases?
• larger TLCs
• Chronic bronchitis?
• increased RV, increased FRC
• Emphysema?
• increased RV, VERY increased TLC
• Restrictive diseases?
• smaller TLCs
• Fibrosis?
• all lung volumes decreased
• Obesity?
• FRC reduced
• Inspiratory muscle weakness?
• TLC reduced
• Expiratory muscle weakness?
• RV is elevated

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Mechanisms of Hypoxemia

• Hypoventilation
• V/Q Mismatch
• Shunt
• Low Inspired pO2
• How do we measure lung volumes?
• Helium dilution
• Used to measure absolute FRC
• Doesnt work if theres lots of obstructed
  airways where a
• Plethysmography
• The small sealed box
• Makes measurements using Boyles law

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What patterns of impairment are associated with

• Obstructive lung disease?
• Diminished rates of expiratory flow (increased
  FEV1, decreased FEV1/FVC)
• Restrictive lung disease?
• Diminished lung volumes
• Preserved expiratory flow
• What gives a characteristic scooped appearance in
  the expiratory phase of flow-volume loops?
• Airway obstruction like emphysema
• When is obstruction increased during inspiration?
• When its an extra-thoracic variable obstruction
• When is obstruction increased during expiration?
• When its an intra-thoracic variable obstruction

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Whats this?
Normal Alveoli!
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Bronchiectasis
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Bronchiectasis

• 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 (Kartageners
  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

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Eosinophil
What disease is this?
Charcot-Leyden crystals eosinophil granule
contents
This is ASTHMA!!!!
Asthma
Curschmann Spirals mucus casts
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Asthma

• 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

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Chronic Bronchitis

• A Clinical Diagnosis!
• Definitional Productive cough gt 3months/year x
  gt 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

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Centrilobular Emphysema in COPD
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Emphysema

• Clinical
• Associated with cigarette smoking (component of
  COPD)
• ?1-antitrypsin deficiency, esp PIZZ mutation
• Radiology
• Increased lucency (dark region)
• Uppergtlower lobe suggests centrilobular type
• Lowergtupper 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

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Bronchiolitis Obliterans/Organizing Pneumonia
(BOOP)

• Clinical
• Acute onset cough, dyspnea, fever, and malaise
• Multiple associations, e.g. collagen-vascular dz
• Most patients respond to corticosteroids
• Radiology
• Multiple patchy airspace infiltrates
• Pathology
• Patchy fibromyxoid plugs in distal bronchioles
  the BO
• Fibromyxoid plugs in alveoli, /- endogenous
  lipid pneumonia the OP
• Think bronchiolar and alveolar airspace
  fibroblasts

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Classification of Asthma

• Intrinsic Asthma-
• 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

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ALLERGIC SHINER Edema/ Discoloration Around the
Eye
What does this demonstrate? What is it?
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• What are the important cells in asthma?
• Eosinophils (in sputum)
• B lymphocytes in mediating the asthma more impt
• Whats the point of the methacholine challenge?
• It demonstrates that theres something different
  in the architecture of the asthmatics 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)

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Findings/Diagnosing Asthma?

• 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
• Hyper-responsive
• b-agonist
• Reversible airflow obstruction when treated
  albuterol
• Eosinophils
• Increased in blood and found in sputum
• ABG
• Low PO2, low PCO2

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Treatment of Asthma

• 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

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General Strategy for Management of Asthma

• 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

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Classification of asthma?

• Mild intermittent
• Mild persistent more than 2X/week, but lt1QD
• Moderate persistent daily symptoms
• Severe persistent continual symptoms

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• Common precipitating stimuli of asthma?
• Allergen exposure involves histamines,
  leukotrienes
• Leukotrienes why NSAIDS can precipitate asthma!
• Inhaled irritants
• Respiratory tract infections
• Exercise (cool air)
• When is airflow most compromised in asthmatics?
• Expiration
• Why is FRC chronically increased in asthma?
• Dynamic hyperinflation cant 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

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• What are the 2 disorders under COPD? Basic defs?
• Chronic bronchitis diagnosis based on chronic
  cough and sputum production
• Emphysema diagnosis based on destruction of
  lung parenchyma and enlargement of air spaces
  distal to the terminal bronchiole
• Whats 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

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Mechanisms of Airflow limitation in COPD?

• loss of alveolar attachments
• obstruction of the airway due to inflammation
• airway-wall fibrosis
• airway smooth muscle constriction
• luminal obstruction with mucus.
• Loss of elastic recoil in emphysema results in
• Decreased expiratory flow rates
• Lower driving pressure for expiratory airflow
• Loss of radial traction from supporting alveolar
  walls
• Functional abnormalities in COPD?
• Decreased FVC, FEV1, FEV1/FVC
• Increased RV, FRC, TLC
• Decreased DLCO in emphysema
• Increased Reid index in chronic bronchitis
• Hypoxia
• Hypercapnia in chronic bronchitis

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• Major secondary problem with COPD? Causes?
• Pulmonary HTN ? cor pulmonale (more common in
  chronic bronchitis patients)
• Major Cause Hypoxia ? vasoconstriction
• Hypercapnia
• Polycythemia
• Destruction of the pulmonary vascular bed
• What is the protease-antiprotease hypothesis?
• Alveolar integrity is maintained via a balancing
  act
• Smoke increases the of PMNs in the lung
• PMNs produce elastase ? degrades elastin
• Smoke oxidants, oxidants from inflammatory cells
  impair A1AT anti-elastase activity
• Neutrophil elastase stimulate mucus release
• PMNs and macrophages make matrix
  metalloproteinases ? shift balance towards
  degradation

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Clinical Distinctions Between Blue Bloater and
Pink Puffer COPD Pathophysiology
Feature Pink Puffer Blue Bloater
Pathophys. Type A Type B
Disease Association Emphysema Chronic Bronchitis
Major Sxs Dyspnea Cough sputum
Appearance Thin, wasted Cyantoic, obese
PO2 Decreased Decreased
PCO2 Normal or decreased Normal or increased
Elastic recoil Decreased Normal
DLCO Decreased Normal
Hematocrit Normal Increased
Cor pulmonale Infrequent Common
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Treatment of COPD

• Bronchodilators
• Antibiotics
• Corticosteroids
• Supplemental O2
• Exercise rehab
• Chest PT, postural drainage
• Surgery (last resort)
• Lung transplant
• Lung volume reduction
• Vaccines pneumovax, flu
• Plasma A1AT if the patient is A1AT deficient
• Mechanical ventialtion

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Major Points from SmokingCessation Lecture

• Tobacco dependence is chronic and requires
  repeated intervention
• If at first you dont 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 its effectiveness

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Major Points from SmokingCessation 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

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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

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• What is the most successful self-help format to
  quit smoking?
• Hotline quitlines
• Person-to-Person contact how much helps?
• Even lt3min is (moderately) better than none!
• 10min or more is best
• Asking your pt to quit smoking helps/doesnt
  help?
• It DOES!
• What are 3 things associated with unsuccessful
  attempts at quitting?
• Not practicing total abstinence
• Drinking alcohol
• Other smokers in da house

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Peribronchovascular space Is dilated
Giant cell
Sarcoidosis
What disease?
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Sarcoidosis

• Clinical
• Multi-system granulomatous disease
• Adults, BgtW, FgtM
• 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

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Hypersensitivity Pneumonia
Loose Granulomas
Interstitial expansion
Peri-Bronchiolar Expansion
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Hypersensitivity Pneumonitis(Extrinsic Allergic
Alveolitis)

• Clinical
• Organic dusts
• Doesnt 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

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Coal dust macules
Coal-workers Pneumoconiosis
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Patchy Sub-Pleural Fibrosis
Ferruginous Body
Asbestosis
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Fibrotic Nodules
Late Silicosis
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UIP
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Usual Interstitial Pneumonia (UIP)

• 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

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Proliferative phase DAD
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Proliferative (Organizing) Phase Diffuse Alveolar
Damage (DAD)

• Clinical
• gt 1-2 wks after identifiable acute lung injury
  (ex MVA, septic shock, kidney stone, inhalation
  of noxious chemical)
• Decreased pulm compliance -gt mechanical
  ventilation
• 50 mortality
• Radiology
• Diffuse, interstitialgtalveolar pattern
• Pathology
• Interstitial intra-alveolar fibroblastic
  proliferation
• Temporally uniform
• If its temporally heterogeneous UIP
• You HAVE to see interstitial fibroblastic
  proliferation
• If its purely intra-alveolar BOOP

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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
Obesity
ILD
Normal
TLC
TLC
TLC
TLC
FRC
FRC
RV
FRC
FRC
RV
RV
RV
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• Whats 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
• Goodpastures
• Wegeners
• And many more (Connective tissue disease
  associated, Chronic eosinophilic pneumonia,
  Lymphangioleiomyomatosis, Pulmonary Langerhans
  cell histiocytosis, Alveolar proteinosis,
  Pulmonary vasculitides)

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Pathophysiology of 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

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Clinical Features ofParenchymal Lung Diseases

• Symptoms
• Dyspnea
• Cough (non-productive)
• Signs
• Dry crackles or rales (sound like velcro)
• Clubbing
• Cor pulmonale
• JVD
• Loud P2, TR murmer
• edema

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• Whats 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 theres 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 CD4gtCD8
• 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

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• 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

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• 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 gt 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

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• How do we treat 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

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UIP/IPF

• 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, MgtF
• Signs and Symptoms?
• Exertional dyspnea that increases over time
• Non-productive cough
• Possible clubbing

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• 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

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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

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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 farmers 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

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• What are the causes/common types of
  pneumonoconiosis?
• Nodular or diffuse fibrosis
• Silicosis
• Asbestosis
• Berylliosis
• Coal Workers
• 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

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Respiratory Diseases due to Asbestos

• 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

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Asbestosis a 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

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Occupational Asthma

• 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

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Reactive Airways Dysfunction Syndrome (RADS)

• 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

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Pleural Diseases

• What is pleuritic pain?
• Caused by inflammatory processes that intensify
  upon breathing
• Whats going on with a tension pneumothorax?
• Air escapes into pleural space ? positive
  pressure
• Air cant 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

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• What kind of pneumothorax?
• 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 its 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

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• Its 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 youre told hes NOT possessed and isnt
  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

69
Why A Pleural Effusion, 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

70
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 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 youre using, or
  you might hit an intercostal artery, vein, nerve

71
What are Lytes 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 gt
  0.5
• Ratio of pleural-fluid LDH gt 0.6
• Pleural fluid LDH level gt 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 gt 1.2
  than more likely a true transudate

72
What are the potential causes of a Transudate?

• 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

73

• Causes of bloody exudates?
• 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

74
So the good doctor said theres a good exam
question in here

• What kind of cell count in an exudate would make
  you suspect cancer or Tb?
• gt50 lymphocytes!
• Now what additional information on this exudate
  could help you decide that its probably NOT Tb?
• gt5 mesothelial cells
• Remember, mesothelial cells are normally found in
  pleural fluid to some degree since they are the
  cells that comprise the pleura!

75
Empyemas

• 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 its an empyema, there should be
• Gross pus
• pH lt 7.1
• glucose lt 40
• positive Gram stain or cultures
• And if its all borderline you need to retap
  thatumlung

76
Ack! Its an Empyema! What Do I do?

• 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
• Dont 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 dont 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

77
STOP!
Hamartoma!
78
Hamartoma

• Its BENIGN!!!!
• Clin
• Adolescence ? adulthood
• None in newborns - not congenital
• Rad
• Solitary nodule /- popcorn calcification
• Peripheral gt central
• Path
• Gross solitary, lobulated, cartilagenous
• Micro normal tissues in excess/disarray
• If its calcified, its comforting b/c it tends
  to be non-malignant!

79
What are the Malignant epithelial neoplasms
(Carcinomas)?

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

80
Squamous Cell Carcinoma
Normal
81
Squamous cell carcinoma

• Clin
• Smokers association?
• YES
• Prevalence?
• 20-30 of common carcinomas
• May secrete PTH-like compound
• Radiology
• central gt gt peripheral
• Path
• Bronchi gt Larynx gt TracheaKEY CHARACTERISTICS?
• /- Desmosomes (intercellular bridges)
  /- Keratin production, e.g. keratin pearls

82
Adenocarcinoma
83
Adenocarcinoma

• Clin
• 30-40 of common carcinomas
• Smoking association?
• Most common carcinoma in non-smokers, but 80 of
  adenoCAs occur in smokers
• Rad
• peripheral gt central
• Path
• /- glands
• /- mucin
• Bronchiolo-alveolar carcinoma subset

84
Bronchiolo-alveolar carcinoma - Note the mucin in
the alveoli. Gas exchange is gonna suck in this
patient!
85
Bronchioloalveolar carcinoma (BAC)

• 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

86
Large cell undifferentiated carcinoma
87
Large cell undifferentiated carcinoma

• Clin
• 10 of common carcinomas
• Rad
• non-specific
• Path
• HE Undifferentiated
• cDNA microarrays distinct disease
• Basically, its a carcinoma with no
  distinguishing features

88
Normal lymphocytes
Response to therapy
At diagnosis
Small Cell Carcinoma
89
Small cell carcinoma

• 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 gt90
• Frequent metastases to LNs and distant sites
• Path
• Malignant cytology high NC ratio
• No nucleoli punctate salt and pepper nucleoli
• High mitotic activity and tumor cell necrosis
• Think small round blue cells!

90
Thin delicate microvilli
Associated w/ ferruginous bodies
Mesothelioma
91
Most Common Metastatic carcinomas in the Lung?

• Breast adenoCA
• GI adenoCA
• Renal adenoCA
• Head/neck squamous cell CA

92
Lung Cancer - Basics

• 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

93
More Lung Cancer Basics

• 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

94
Diagnostic Tools for Lung CA

• 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

95
Staging Lung CA

• SCLC
• Whats 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
• Whats 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
EARLY
96

• Tricks to help us stage NSCLC?
• 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

97

• Adenocarcinoma
• Most common NSCLC in US
• Smokers and non-smokers
• Peripheral (in the lung parenchyma)
• May arise in area of previous scarring
• More likely to spread to lymph nodes and outside
  of the chest
• Hypotrophic orthopathy or clubbing alone may be
  present
• Bronchioloalveolar carcinoma
• Subtype of adenocarcinoma
• More common in women
• More common in non-smokers than smokers for
  poorly defined reasons
• Cough and bronchorrhea (frothy sputum production)
• Variable radiographic presentation solitary
  nodule, multiple nodules, infiltrate/consolidation
  with air-bronchograms

98

• Squamous cell carcinoma
• 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)

99
Time to Take a Study Break!!!
Got Your Sound On?
Is it close to midnight?
And that exam is lurking in the morn
100
(No Transcript)
101
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

102
Neutrophils filling alveolar space in acute
pneumonia
103
Interstitial lymphocytes in viral pneumonia
104
Giant Celll
Histiocytes and multinucleated giant cells
(granulomatous inflammation) in mycobacterial
pneumonia
105
Common bacterial pneumonia microbes

• Community acquired
• normal flora, common agents
• Pneumococcal (streptococcus pneumoniae)
• Klebsiella
• Hemophilus, Staph aureus, other strep
• Nosocomial (hospital acquired)
• Pseudomonas aeruginosa
• especially in cystic fibrosis patients
• Methicillin resistant staphylococcus aureus
  (MRSA)
• Types of pneumonia patterns on CXR
• Lobar (entire lobe
• Bronchopneumonia (patchy in more than one lobe
  surrounding a bronchus

106
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)

107
What are the sxs of Legionella pneumonia?

• Legionnaires disease
• Acute onset of malaise, fever, pneumonia,
  myalgias, abdominal pain, diarrhea
• Type of bact? Gram stain? How do you see it?
• Small gram negative bacillus
• Need special stains to visualize
• What does CXR look like?
• Pathology bronchopneumonia with multiple lobes
  involved, alveoli filled with fibrin and
  inflammation
• X ray is frequently more worrisome than clinical
  symptoms would suggest

108
What patients are susceptible to pneumonias
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

109
What are common complications ofbacterial
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 doesnt have normal
  blood flow for tx with antibiotics AND it doesnt
  drain normally w/ a chest tube
• Bacteremia
• Bacteria within the bloodstream
• May seed distant sites
• Endocarditis, meningitis, pericarditis

110
What does this demonstrate?
Center of pulmonary abscess showing acute
inflamm