2. Pneumonia: Pathophysiology and Clinical Manifestations
J. Matthew Velkey, PhD
Department of Cell Biology
Duke University School of Medicine
Andrew Alspaugh, MD
Department of Medicine
Infectious Disease Division
Duke University School of Medicine
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3. Learning Objectives
Recognize the epidemiology and morbidity of pneumonia
Define pneumonia and types of lower respiratory tract infections
Understand features involved in the pathophysiology of pneumonia
Recognize the entity known as Community Acquired Pneumonia (CAP)
Appreciate the spectrum of pneumonia clinical presentation
Identify common complications of pneumonia
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4. Pneumonia is common and serious
5.6 million cases in US in 2011(1)
2nd leading cause of hospitalization in US (1.1 million admissions in US)(1)
~20% of patients with pneumonia require hospitalization
6th leading cause of death in US in 2011 (~60,000 deaths)(1)
~10% of patients with pneumonia die
Variations in rates of disease:
Higher rates in winter months
More common in men
More common in African Americans compared to Caucasians
More common in children and older adults
(overall rate for yo is ~5 per 1000
overall rate for >65 yo is 75 per 1000 )
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(1) Anevlavis S; Bouros D (2010). Expert Opin Pharmacother 11 (3): 361–74.

5. Lower respiratory and pleural disease
Pneumonia -- infection of alveoli
(viral or bacterial)
vs. Pneumonitis -- immune-mediated
inflammation of alveoli
Empyema: purulent exudate in the pleural cavity
Bronchitis -- inflammation of bronchi, may be immune-mediated, e.g. asthma, COPD, or infectious (usually viral but can be bacterial)
Abscess: circumscribed collection of pus within the lung parenchyma
Bronchiolitis: inflammation of bronchioles (often viral but can be bacterial)
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6. PNEUMONIA: CLEARANCE vs. COLONIZATION
Microbes constantly enter airways but many factors prevent colonization:
mucous entrapment
ciliary clearance
immune surveillance
intact epithelial barrier
secreted factors such as:
secretory IgA
surfactant proteins (SP-a, SP-d)
defensins
Disrupting or overwhelming these defense mechanisms can allow microbes to colonize the lungs, resulting in PNEUMONIA
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7. Factors favoring colonization
Disruption of mucociliary clearance:
airway obstruction (CF, COPD, chronic bronchitis, neoplasm)
ciliary dysfunction (Kartagener, smoking, ciliostatic factors)
Disruption of intact epithelial barrier:
injury (e.g. pulmonary edema, intubation) or infection (e.g. viral respiratory infection such as influenza)
Increasing “inoculation” events:
altered consciousness
debility
dysphagia
intubation
bacteremia
Decreasing immune function:
immune suppression (transplant, HIV)
evading host immunity (IgA proteases, encapsulation)
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8. Effects and patterns of microbial colonization:
where and how inflammation appears can be informative
Alveolar
In alveolar lumen
Purulent exudate of RBCs and PMNs
Interstitial
Mostly in alveolar wall
Mononuclear WBCs
Fibrinous exudate
Lobar pneumonia
lobar distribution
“typical” CAP
S. pneumo, H. flu.
Bronchopneumonia
patchy distribution
aspiration, intubation, bronchiectasis
Staph, enterics, Pseudomonas
Atypical pneumonia
diffuse infiltrate w/ perihilar concentration
Mycoplasma, Chlamydophila, Legionella
Respiratory viruses, e.g. influenza
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9. Community-Acquired Pneumonia
Infection of the pulmonary parenchyma acquired from exposure in the community
Classically divided into “typical” and “atypical” syndromes:
“Typical” CAP:
presents with “typical” severe, acute infection
infectious agent (usually S. pneumo or H. flu) is culturable/ identifiable
responsive to cell-wall active antibiotics
“Atypical” CAP:
presentation is usually sub-acute
causative pathogens are difficult to culture/identify by standard methods
not responsive to penicillins
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10. Typical CAP presentation
History
Previously healthy with sudden onset of fever and shortness of breath
Physical signs and symptoms
fever
tachycardia
tachypnea
productive cough with purulent sputum and possible hemoptysis
pallor and cyanosis
localized:
dullness to percussion
decreased breath sounds
crackles , ronchi , egophony (“E” to-”A” change)
Investigations
CXR showing lobar consolidation
CBC showing leukocytosis w/ left shift
Sputum sample contains neutrophils, RBCs; Gram stain may be positive depending on organism
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11. Typical CAP presentation
History
Previously healthy with sudden onset of fever and shortness of breath
Physical signs and symptoms
fever
tachycardia
tachypnea
productive cough with purulent sputum and possible hemoptysis
pallor and cyanosis
localized:
dullness to percussion
decreased breath sounds
crackles, ronchi, egophony (“E-to-A” change)
Investigations
CXR showing lobar consolidation
CBC showing leukocytosis w/ left shift
Sputum sample contains neutrophils, RBCs; Gram stain may be positive depending on organism
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12. Typical CAP presentation
History
Previously healthy with sudden onset of fever and shortness of breath
Physical signs and symptoms
fever
tachycardia
tachypnea
productive cough with purulent sputum and possible hemoptysis
pallor and cyanosis
localized:
dullness to percussion
decreased breath sounds
crackles, ronchi, egophony (“E-to-A” change)
Investigations
CXR showing lobar consolidation
CBC showing leukocytosis w/ left shift
Sputum sample contains neutrophils, RBCs; Gram stain may be positive depending on organism
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13. Atypical CAP Presentation
32 YO healthy patient – one week of low grade fever, sore throat, and intractable cough
Minimal sputum production
Able to continue to work
No sick contacts, recent travel, or evidence of altered immune system
PE reveals a mildly ill-appearing patient with diffuse wheezes on lung exam
Primary care physician prescribes empiric antibiotics for CAP with complete resolution
“Walking pneumonia” syndrome
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14. Complications of pneumonia
Pleural effusion
inflammation leads to exudation of fluid into pleural space
can compromise lung function
Empyema
purulent exudate in pleural space
necrosis/breakdown of visceral pleura and/or spread of infection into pleura
Pleural adhesions, lung fibrosis
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15. Complications of pneumonia
Abscess / cavitary lesion
circumscribed focus of liquefactive necrosis within lung tissue
associated with necrotizing Staph or Strep infections or Gram-neg rods (e.g. aspiration)
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16. Credits: Pneumonia
Location of item (slide #5): "Respiratory system complete no labels" by Bibi Saint-Pol - en.wikipedia.org/wiki/File:Respiratory_system_complete_en.svg. Licensed under CC BY-SA 3.0 via Wikimedia Commons
Location of item (slide #5): "Diagram showing a build up of fluid in the lining of the lungs (pleural effusion) CRUK 054" by Cancer Research UK - Original from CRUK. Licensed under CC BY-SA 4.0 via Wikimedia Commons -
Location of item (slide #5): Bronchitis illustration: -- This work is in the public domain in the United States because it is a work prepared by an officer or employee of the United States Government as part of that person’s official duties under the terms of Title 17, Chapter 1, Section 105 of the US Code.   
Location of item (slide #6): color illustration of upper and lower airway anatomy. Blausen.com staff. "Blausen gallery 2014". Wikiversity Journal of Medicine.DOI: /wjm/  ISSN   - Own work
Location of item (slide #6): illustration of upper airway defense mechanisms. Figure 1 from Bals, R. Epithelial antimicrobial peptides in host defense against infection. Respir Res. 2000; 1: doi: /rr25
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17. Credits (continued): Pneumonia
Location of item (slide #6): illustration of alveolar defense mechanisms. Figure 1 from Wright, JR. Immunoregulatory functions of surfactant proteins. Nat Rev Immunol. 2005; 5: doi: /nri1528
Location of item (slide #7): color illustrations of alveolar and interstitial inflammation, lobar, bronchial, and interstitial patterns of pneumonia. Contributors to Quizlet.com warrant that the downloading, copying and use of the content will not infringe the proprietary rights, including but not limited to the copyright, patent, trademark or trade secret rights, of any third party.
Location of item (slide #7 and slide #12): chest x-ray of lobar pneumonia.
Location of item (slide #7): chest x-ray of bronchopneumonia.
Location of item (slide #7): chest x-ray of interstitial (atypical) pneumonia.
Location of item (slide #11): illustration of CAP patient. RWJF Pneumonia Module Springboard Video.
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18. Credits (continued): Pneumonia
Location of item (slide #11): crackles sound clip: ronchi sound clip: normal “E” lung sound: egophony lung sound (“E” to “A” change):
Location of item (slide #13): Gram Stain of a film of sputum from a case of lobar pneumonia. CDC
Location of item (slide #14 & 15): Chest X-ray of atypical pneumonia. Dr. Mike Malinzak. Duke University. Dept. of Radiology.
Location of item (slide #16): Chest X-ray of HAP. Dr. Mike Malinzak. Duke University. Dept. of Radiology.
Location of item (slide #17): "Diagram showing a build up of fluid in the lining of the lungs (pleural effusion) CRUK 054" by Cancer Research UK - Original from CRUK. Licensed under CC BY-SA 4.0 via Wikimedia Commons -
Location of item (slide #18): "CT chest in pneumonia with abscesses caverns and effusions d0" by Christaras A - Own work from anonmyized dicom image. Licensed under CC BY 2.5 via Wikimedia Commons -
Location of item (slide #18): "Abscess" by Yale Rosen - Licensed under CC BY-SA 2.0 via Wikimedia Commons -
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