J. Matthew Velkey, PhD Department of Cell Biology - PowerPoint Presentation

Slide1

J. Matthew Velkey, PhD

Department of Cell BiologyDuke University School of Medicine

Andrew Alspaugh, MDDepartment of MedicineInfectious Disease DivisionDuke University School of Medicine

Pneumonia:Pathophysiology and Clinical Manifestations

2

Learning Objectives

Recognize the epidemiology and morbidity of pneumoniaDefine pneumonia and types of lower respiratory tract infectionsUnderstand features involved in the pathophysiology of pneumoniaRecognize the entity known as Community Acquired Pneumonia (CAP) Appreciate the spectrum of pneumonia clinical presentationIdentify common complications of pneumonia

3

Pneumonia is common and serious

4

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 hospitalization6th leading cause of death in US in 2011 (~60,000 deaths)(1)~10% of patients with pneumonia dieVariations in rates of disease:

(1)

Anevlavis S; Bouros D (2010). Expert Opin Pharmacother 11 (3): 361–74.

More common in children and older adults (overall rate for 18-49 yo is ~5 per 1000 overall rate for >65 yo is 75 per 1000 )

Higher

rates in winter months

More common in men

More common in African Americans compared to

Caucasians

Lower respiratory and pleural disease

5

Pneumonia

-- infection of alveoli

(viral or bacterial)vs. Pneumonitis -- immune-mediated inflammation of alveoli

Bronchitis

-- inflammation of bronchi, may be

immune-mediated

, e.g. asthma, COPD, or infectious (usually viral but can be bacterial)

Empyema:

purulent exudate in the pleural cavity

Abscess

: circumscribed collection of pus within the lung parenchyma

Bronchiolitis

: inflammation of bronchioles (often viral but can be bacterial)

PNEUMONIA:

CLEARANCE

vs. COLONIZATION

Microbes constantly enter airways but many factors prevent colonization:mucous entrapmentciliary clearanceimmune surveillanceintact epithelial barriersecreted factors such as:secretory IgAsurfactant proteins (SP-a, SP-d)defensins

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Disrupting or overwhelming these defense mechanisms can allow microbes to colonize the lungs, resulting in

PNEUMONIA

Factors favoring colonization

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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 consciousnessdebilitydysphagiaintubationbacteremiaDecreasing immune function:immune suppression (transplant, HIV)evading host immunity (IgA proteases, encapsulation)

Effects and patterns of microbial colonization:where and how inflammation appears can be informative

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Alveolar

In alveolar

lumenPurulent exudate of RBCs and PMNs

Interstitial

Mostly in alveolar wallMononuclear WBCsFibrinous 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

Community-Acquired Pneumonia

Infection of the pulmonary parenchyma acquired from exposure in the communityClassically divided into “typical” and “atypical” syndromes:“Typical” CAP:presents with “typical” severe, acute infectioninfectious agent (usually S. pneumo or H. flu) is culturable/ identifiableresponsive to cell-wall active antibiotics“Atypical” CAP:presentation is usually sub-acutecausative pathogens are difficult to culture/identify by standard methodsnot responsive to penicillins

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Typical CAP presentation

History

Previously healthy with sudden onset of fever and shortness of breathPhysical signs and symptomsfevertachycardiatachypneaproductive cough with purulent sputum and possible hemoptysispallor and cyanosislocalized:dullness to percussiondecreased breath soundscrackles , ronchi , egophony (“E” -to-”A” change)InvestigationsCXR showing lobar consolidationCBC showing leukocytosis w/ left shiftSputum sample contains neutrophils, RBCs; Gram stain may be positive depending on organism

10

Typical CAP presentation

History

Previously healthy with sudden onset of fever and shortness of breathPhysical signs and symptomsfevertachycardiatachypneaproductive cough with purulent sputum and possible hemoptysispallor and cyanosislocalized:dullness to percussiondecreased breath soundscrackles, ronchi, egophony (“E-to-A” change)InvestigationsCXR showing lobar consolidationCBC showing leukocytosis w/ left shiftSputum sample contains neutrophils, RBCs; Gram stain may be positive depending on organism

11

Typical CAP presentation

History

Previously healthy with sudden onset of fever and shortness of breathPhysical signs and symptomsfevertachycardiatachypneaproductive cough with purulent sputum and possible hemoptysispallor and cyanosislocalized:dullness to percussiondecreased breath soundscrackles, ronchi, egophony (“E-to-A” change)InvestigationsCXR showing lobar consolidationCBC showing leukocytosis w/ left shiftSputum sample contains neutrophils, RBCs; Gram stain may be positive depending on organism

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Atypical CAP Presentation

32 YO healthy patient – one week of low grade fever, sore throat, and intractable cough

Minimal sputum productionAble to continue to workNo sick contacts, recent travel, or evidence of altered immune systemPE reveals a mildly ill-appearing patient with diffuse wheezes on lung examPrimary care physician prescribes empiric antibiotics for CAP with complete resolution“Walking pneumonia” syndrome

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Pleural effusion

inflammation leads to exudation of fluid into pleural spacecan compromise lung functionEmpyemapurulent exudate in pleural spacenecrosis/breakdown of visceral pleura and/or spread of infection into pleuraPleural adhesions, lung fibrosis

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Complications of pneumonia

Abscess /

cavitary lesioncircumscribed focus of liquefactive necrosis within lung tissueassociated with necrotizing Staph or Strep infections or Gram-neg rods (e.g. aspiration)

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Complications of pneumonia

Credits:

Pneumonia

16

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_complete_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_effusion)_CRUK_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

#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

Credits (continued):

Pneumonia

17

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

M

odule Springboard Video.

Credits (continued):

Pneumonia

18

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)_CRUK_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_chest_in_pneumonia_with_abscesses_caverns_and_effusions_d0.jpg

Location of item (slide #

18):

"

Abscess

" by Yale

Rosen -

http

://www.flickr.com/photos/pulmonary_pathology/3679097009

/

. Licensed

under CC BY-SA 2.0 via Wikimedia Commons -

http://commons.wikimedia.org/wiki/File:Abscess.jpg#/media/File:Abscess.jpg