Pneumonia:

Pathophysiology and Clinical Manifestati ons

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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 Learning Objecti ves
• 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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 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 children and older adults
• More common in men (overall rate for 18-49 yo is ~5 per 1000
• More common in African Americans overall rate for >65 yo is 75 per 1000 )
compared to Caucasians

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(1)
Anevlavis S; Bouros D (2010). Expert Opin Pharmacother 11 (3): 361–74.
 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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 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 6
 Factors favoring colonizati on
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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 Eff ects and patt erns of microbial colonizati on:
w he re an d h ow i nfl a m mati o n a pp e a rs ca n b e info r mati ve
Alveolar Interstitial
• In alveolar lumen • Mostly in alveolar wall
• Purulent exudate of • Mononuclear WBCs
RBCs and PMNs • Fibrinous exudate

Lobar pneumonia
• lobar distribution
• “typical” CAP
• S. pneumo, H. flu.

Bronchopneumonia Atypical pneumonia

• patchy distribution • diffuse infiltrate w/ perihilar concentration
• aspiration, intubation, • Mycoplasma, Chlamydophila, Legionella
bronchiectasis • Respiratory viruses, e.g. influenza
• Staph, enterics,
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Pseudomonas
 Community-Acquired Pneumonia
• Infection of the pulmonary parenchyma acquired from
exposure in the community
• Classically divided into “typical” and “atypical” syndromes:
I. “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
II. “Atypical” CAP:
• presentation is usually sub-acute
• causative pathogens are difficult to culture/identify by standard methods
• not responsive to penicillins 9
 Typical CAP presentati on
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 10
 Typical CAP presentati on
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 11
 Typical CAP presentati on
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 12
 Atypical CAP Presentati on

• 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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 Complicati ons 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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 Complicati ons 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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C r e d i t s : 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
http://commons.wikimedia.org/wiki/File:Respiratory_system_complete_no_labels.svg#/media/File:Respiratory_system_comp
lete_no_labels.svg
 
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 email from CRUK. Licensed under CC BY-SA 4.0 via Wikimedia Commons -
http://commons.wikimedia.org/wiki/File:Diagram_showing_a_build_up_of_fluid_in_the_lining_of_the_lungs_(pleural_effusi
on)_CRUK_054.svg#/media/File:Diagram_showing_a_build_up_of_fluid_in_the_lining_of_the_lungs_(pleural_effusion)_CRU
K_054.svg

Location of item (slide #5): Bronchitis illustration: http://commons.wikimedia.org/wiki/File:Bronchitis.jpg -- 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:10.15347/wjm/2014.010. ISSN 20018762. - Own work

Location of item (slide #6): illustration of upper airway defense mechanisms. http://
openi.nlm.nih.gov/detailedresult.php?img=59560_rr25-1&req=4. Figure 1 from Bals, R.
Epithelial antimicrobial peptides in host defense against infection. Respir Res. 2000; 1: 141-50. doi:10.1186/rr25
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C r e d i t s ( c o n t i n u e d ) : Pneumonia
Location of item (slide #6): illustration of alveolar defense mechanisms.
http://www.nature.com/nri/journal/v5/n1/fig_tab/nri1528_F1.html. Figure 1 from Wright, JR. Immunoregulatory
functions of surfactant proteins. Nat Rev Immunol. 2005; 5: 58-68. doi:10.1038/nri1528

Location of item (slide #7): color illustrations of alveolar and interstitial inflammation, lobar, bronchial, and interstitial
patterns of pneumonia. http://quizlet.com/27416956/pulmonary-pathology-and-pathophysiology-flash-cards/.
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.
http://biomarker.cdc.go.kr/biomarker/diseaseimg/pneumonia-Community_acquired.jpg

Location of item (slide #7): chest x-ray of bronchopneumonia.

http://www.ebmedicine.net/topics.php?paction=showTopicSeg&topic_id=118&seg_id=2306

Location of item (slide #7): chest x-ray of interstitial (atypical) pneumonia.

http://www.ebmedicine.net/topics.php?paction=showTopicSeg&topic_id=118&seg_id=2306

Location of item (slide #11): illustration of CAP patient. RWJF Pneumonia Module Springboard Video.

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C r e d i t s ( c o n t i n u e d ) : Pneumonia
Location of item (slide #11): crackles sound clip: http://en.wikipedia.org/wiki/File:Crackles_pneumoniaO.ogg; ronchi sound clip:
http://www.easyauscultation.com/cases?coursecaseorder=5&courseid=201; normal “E” lung sound:
http://www.easyauscultation.com/cases?coursecaseorder=4&courseid=202; egophony lung sound (“E” to “A” change):
http://www.easyauscultation.com/cases.aspx?coursecaseorder=5&courseid=202

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 email from CRUK. Licensed under CC BY-SA 4.0 via Wikimedia Commons -
http://commons.wikimedia.org/wiki/File:Diagram_showing_a_build_up_of_fluid_in_the_lining_of_the_lungs_(pleural_effusion)_CRU
K_054.svg#/media/File:Diagram_showing_a_build_up_of_fluid_in_the_lining_of_the_lungs_(pleural_effusion)_
CRUK_054.svg

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 -
http://commons.wikimedia.org/wiki/File:CT_chest_in_pneumonia_with_abscesses_caverns_and_effusions_d0.jpg#/media/File:CT_ch
est_in_pneumonia_with_abscesses_caverns_and_effusions_d0.jpg

 
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Location of item (slide #18): "Abscess" by Yale Rosen - http://www.flickr.com/photos/pulmonary_pathology/3679097009/. Licensed