Community-acquired pneumonia pathophysiology: Difference between revisions

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==Overview==
==Overview==


Since the lower [[respiratory tract]] is maintained sterile by different pulmonary defence mechanisms,<ref name="Mason-2005">{{Cite journal  | last1 = Mason | first1 = CM. | last2 = Nelson | first2 = S. | title = Pulmonary host defenses and factors predisposing to lung infection. | journal = Clin Chest Med | volume = 26 | issue = 1 | pages = 11-7 | month = Mar | year = 2005 | doi = 10.1016/j.ccm.2004.10.018 | PMID = 15802161 }}</ref> acquiring community-acquired pneumonia connotes a breach of host defence mechanisms and/or overwhelming inoculation of virulent infectious agents. Modes of transmission include macro- or micro-aspiration, from circulation, local spead, traumatic inoculation, or can be iatrogenic. Impaired immunity and inability to filter out pathogen increase the risk for developing [[pneumonia]]. Causative etiologies vary with age, immune status, geographical area, and comorbid conditions.
Because the lower [[respiratory tract]] is kept sterile by different pulmonary defense mechanisms,<ref name="Mason-2005">{{Cite journal  | last1 = Mason | first1 = CM. | last2 = Nelson | first2 = S. | title = Pulmonary host defenses and factors predisposing to lung infection. | journal = Clin Chest Med | volume = 26 | issue = 1 | pages = 11-7 | month = Mar | year = 2005 | doi = 10.1016/j.ccm.2004.10.018 | PMID = 15802161 }}</ref> community-acquired pneumonia connotes a breach of host defense mechanisms and/or overwhelming inoculation of virulent infectious agents. Modes of transmission include: macro- or micro-aspiration, circulation, local spead, traumatic inoculation, or iatrogenic. Impaired immunity and inability to filter out pathogens, as well as microbial virulence factors that impede immune clearance may increase the risk of developing community acquired [[pneumonia]].


==Pathophysiology==
==Pathophysiology==


The symptoms of CAP are the result of both the invasion of the lungs by [[microorganism]]s and the [[immune system]]'s response to the infection. The mechanisms of infection are quite different for [[virus]]es and the other microorganisms.
The symptoms of CAP are the result of both, the invasion of the lungs by [[microorganism]]s and the [[immune system]]'s response to the infection. The mechanisms of infection are quite different for [[virus]]es and the other microorganisms.


*''Viruses''
===Viruses===
:Viruses must invade cells to reproduce. Typically, a virus reaches the lungs by traveling in droplets through the [[mouth]] and [[Human nose|nose]] with [[inhalation]]. There, the virus invades the cells lining the airways and the alveoli. This invasion often leads to cell death either through direct killing by the virus or by self-destruction through [[apoptosis]]. Further lung damage occurs when the immune system responds to the infection. [[White blood cell]]s, in particular [[lymphocyte]]s, activate a variety of chemicals ([[cytokine]]s), which make fluid leak into the alveoli. The combination of cellular destruction and fluid-filled alveoli interrupts the transportation of oxygen into the bloodstream. In addition to the effects on the lungs, many viruses affect other [[Organ (anatomy)|organ]]s and can lead to illness affecting many different bodily functions. Viruses also make the body more susceptible to bacterial infection; for this reason, bacterial pneumonia often complicates viral CAP.
*Viruses must invade cells to reproduce. Typically, a virus reaches the lungs by travelling in droplets through the [[mouth]] and [[Human nose|nose]] during [[inhalation]]. There, the virus invades the cells lining the airways and the alveoli.
* This invasion often leads to cell death, either through direct killing by the virus or by self-destruction through [[apoptosis]].  
*Further lung damage occurs when the immune system responds to the infection.  
*[[White blood cell]]s, in particular [[lymphocyte]]s, activate a variety of chemicals ([[cytokine]]s), which make fluid leak into the alveoli.  
*The combination of cellular destruction and fluid-filled alveoli interrupts the transportation of oxygen into the bloodstream.  
*In addition to their affect on the lungs, many viruses affect other [[Organ (anatomy)|organ]]s; this can lead to illnesses that affect many different bodily functions.  
*Viruses also make the body more susceptible to bacterial infection; for this reason, bacterial pneumonia often complicates viral CAP.


*''Bacteria and fungi''
===Bacteria and Fungi===
:Bacteria and fungi also typically enter the lung with inhalation, though they can reach the lung through the bloodstream if other parts of the body are infected. Often, bacteria live in parts of the [[upper respiratory tract]] and are constantly being inhaled into the alveoli. Once inside the alveoli, [[bacteria]] and [[fungus|fungi]] travel into the spaces between the cells and also between adjacent alveoli through connecting pores. This invasion triggers the [[immune system]] to respond by sending white blood cells responsible for attacking microorganisms ([[neutrophil]]s) to the lungs. The neutrophils [[phagocytosis|engulf]] and kill the offending organisms, but also release cytokines, which result in a general activation of the immune system. This causes the fever, chills, and fatigue common in CAP. The neutrophils, bacteria, and fluid leaked from surrounding blood vessels fill the alveoli and result in impaired oxygen transportation. Bacteria often travel from the lung into the blood stream and can result in serious illness such as [[septic shock]], in which there is low blood pressure leading to damage in multiple parts of the body including the [[brain]], [[kidney]], and [[heart]].
*Bacteria and fungi also typically enter the lung with inhalation, although they reach the lung through the bloodstream if other parts of the body are infected.  
*Often, bacteria live in parts of the [[upper respiratory tract]] and are constantly being inhaled into the alveoli.  
*Once inside the alveoli, [[bacteria]] and [[fungus|fungi]] travel into the spaces between the cells and also between adjacent alveoli through connecting pores.  
*This invasion triggers the [[immune system]] to respond by sending white blood cells, responsible for attacking microorganisms ([[neutrophil]]s), to the lungs.
* The neutrophils [[phagocytosis|engulf]] and kill the offending organisms, but they also release cytokines; this results in the general activation of the immune system. This causes the fever, chills, and fatigue which are common to CAP.  
*The neutrophils, bacteria, and fluid leaked from surrounding blood vessels fill the alveoli and result in impaired oxygen transportation.
* Bacteria often travel from the lungs to the blood stream; this can often result in serious illness, such as [[septic shock]], in which there is low blood pressure leading to damage to multiple parts of the body, including the [[brain]], [[kidney]], and [[heart]].


*''Parasites''
===Parasites===
:A variety of parasites can affect the lungs. In general, these parasites enter the body through the skin or by being swallowed. Once inside the body, these parasites travel to the lungs, most often through the blood. There, a similar combination of cellular destruction and immune response causes disruption of oxygen transportation.
*A variety of parasites can affect the lungs.  
*In general, parasites enter the body through the skin or by ingestion.  
*Once inside the body, these parasites travel to the lungs, most often through the blood.  
*There, a similar combination of cellular destruction and immune response causes disruption of oxygen transportation.


==Mode of Transmission==
==Mode of Transmission==


=====1. Microaspiration of Oropharyngeal Contents=====
=====1. Inhalation of Aerosolized Droplets=====
Inhalation of aerosolized droplets that are 0.5 to 1 micrometer is the most common means of acquiring [[pneumonia]]. A few bacterial and viral infections are transmitted in this fashion.  The lung can normally filter out particles that are between 0.5 to 2 micrometer in size by recruiting the alveolar macrophages.<ref name="Wunderink-2004">{{Cite journal  | last1 = Wunderink | first1 = RG. | last2 = Waterer | first2 = GW. | title = Community-acquired pneumonia: pathophysiology and host factors with focus on possible new approaches to management of lower respiratory tract infections. | journal = Infect Dis Clin North Am | volume = 18 | issue = 4 | pages = 743-59, vii | month = Dec | year = 2004 | doi = 10.1016/j.idc.2004.07.004 | PMID = 15555822 }}</ref>


Aspiration of oropharyngeal contents containing pathogenic microorganisms is one of the mechanism of acquiring [[pneumonia]].  It most commonly occurs in normal persons during sleep, in unconscious persons due to gastroesopahegeal reflux or impaired [[gag reflex]] and [[cough reflex]].<ref name="Wunderink-2004">{{Cite journal  | last1 = Wunderink | first1 = RG. | last2 = Waterer | first2 = GW. | title = Community-acquired pneumonia: pathophysiology and host factors with focus on possible new approaches to management of lower respiratory tract infections. | journal = Infect Dis Clin North Am | volume = 18 | issue = 4 | pages = 743-59, vii | month = Dec | year = 2004 | doi = 10.1016/j.idc.2004.07.004 | PMID = 15555822 }}</ref>
=====2. Microaspiration of Oropharyngeal Contents=====


=====2. Inhalation of Aerosolized Droplets=====
Aspiration of oropharyngeal contents containing pathogenic microorganisms is one of the mechanisms for acquiring [[pneumonia]]. It most commonly occurs in in the average person during sleep, in an unconscious state, due to gastroesopahegeal reflux or impaired [[gag reflex]] and [[cough reflex]].<ref name="Wunderink-2004">{{Cite journal  | last1 = Wunderink | first1 = RG. | last2 = Waterer | first2 = GW. | title = Community-acquired pneumonia: pathophysiology and host factors with focus on possible new approaches to management of lower respiratory tract infections. | journal = Infect Dis Clin North Am | volume = 18 | issue = 4 | pages = 743-59, vii | month = Dec | year = 2004 | doi = 10.1016/j.idc.2004.07.004 | PMID = 15555822 }}</ref>
 
Inhalation of aerosolized droplets of 0.5 to 1 micrometer is the most common pathway of acquiring [[pneumonia]]. A few bacterial and viral infections are transmitted in this fashion.  The lung can normally filter out particles between 0.5 to 2 micrometer by recruiting the [[alveolar macrophages]].<ref name="Wunderink-2004">{{Cite journal  | last1 = Wunderink | first1 = RG. | last2 = Waterer | first2 = GW. | title = Community-acquired pneumonia: pathophysiology and host factors with focus on possible new approaches to management of lower respiratory tract infections. | journal = Infect Dis Clin North Am | volume = 18 | issue = 4 | pages = 743-59, vii | month = Dec | year = 2004 | doi = 10.1016/j.idc.2004.07.004 | PMID = 15555822 }}</ref>


=====3. Blood-Borne or Systemic Infection=====
=====3. Blood-Borne or Systemic Infection=====


Microbial entered through circulation may also result in pulmonary infections. Blood-borne pneumonia is seen more commonly in intravenous drug users. [[Staphylococcal aureus]] causes pneumonia in this way. [[Gram negative bacteria]] typically account for pneumonia in immunocompromised individuals.
Spread of an infection via the circulation may be a possible cause of pneumonia. Blood-borne pneumonia is seen more commonly in intravenous drug users particularly with gram-positive bacteria that may colonize the skin (i.e. ''[[Staphylococcus aureus]]''). [[Gram-negative bacteria]] typically account for pneumonia in immunocompromised individuals.


=====4. Trauma or Local Spread=====
=====4. Trauma or Local Spread=====
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Pneumonia can occur after a pulmonary procedure or a penetrating trauma to the lungs. A local spread of a [[hepatic abscess]] can also lead to pneumonia.
Pneumonia can occur after a pulmonary procedure or a penetrating trauma to the lungs. A local spread of a [[hepatic abscess]] can also lead to pneumonia.


==Pathogenesis==
==Microbial Pathogenesis==


===Virulence Factors===
===Virulence Factors===


Several strategies are evolved to evade host defence mechanisms and facilitate speading before establishing an infection.
Several mechanisms have evolved to evade host defense mechanisms and facilitate microbial spread to establish an infection.
 
* [[Influenza virus]]es possess [[neuraminidase]] that cleaves sialic acid residues on the cell surface, which prevents viral aggregation and facilitates the propagation of viral particles.
 
* ''[[Chlamydophila pneumoniae]]'' induces complete paralysis of the respiratory cilia, which assists with the colonization of the [[respiratory epithelium]].<ref name="Shemer-Avni-1995">{{Cite journal  | last1 = Shemer-Avni | first1 = Y. | last2 = Lieberman | first2 = D. | title = Chlamydia pneumoniae-induced ciliostasis in ciliated bronchial epithelial cells. | journal = J Infect Dis | volume = 171 | issue = 5 | pages = 1274-8 | month = May | year = 1995 | doi =  | PMID = 7751703 }}</ref>
 
* ''[[Mycoplasma pneumoniae]]'' produces a virulence factor with [[ADP-ribosylation|ADP-ribosylating]] activity that is responsible for airway cellular damage and mucociliary dysfunction.<ref name="Kannan-2006">{{Cite journal  | last1 = Kannan | first1 = TR. | last2 = Baseman | first2 = JB. | title = ADP-ribosylating and vacuolating cytotoxin of Mycoplasma pneumoniae represents unique virulence determinant among bacterial pathogens. | journal = Proc Natl Acad Sci U S A | volume = 103 | issue = 17 | pages = 6724-9 | month = Apr | year = 2006 | doi = 10.1073/pnas.0510644103 | PMID = 16617115 }}</ref>


* [[Influenza virus]] possesses [[neuraminidase]]s for cleavage of sialic acid residues on the cell surface and viral proteins, which prevent aggregation and facilitate propagation of viral particles.
* ''[[Haemophilus influenzae]]'', ''[[Streptococcus pneumoniae]]'', and ''[[Neisseria meningitidis]]'' produce [[protease]]s that cleave mucosal [[immunoglobulin A|IgA]].


* ''[[Chlamydophila pneumoniae]]'' induces complete abortion of cilia motions which assists colonization at the [[respiratory epithelium]].<ref name="Shemer-Avni-1995">{{Cite journal | last1 = Shemer-Avni | first1 = Y. | last2 = Lieberman | first2 = D. | title = Chlamydia pneumoniae-induced ciliostasis in ciliated bronchial epithelial cells. | journal = J Infect Dis | volume = 171 | issue = 5 | pages = 1274-8 | month = May | year = 1995 | doi = | PMID = 7751703 }}</ref>
* ''[[Streptococcus pneumoniae]]'' possesses [[pneumolysin]] that aid the bacteria during colonization, by facilitating adherence to the host,<ref>{{cite journal|last=Rubins|first=JB|coauthors=Paddock, AH, Charboneau, D, Berry, AM, Paton, JC, Janoff, EN|title=Pneumolysin in pneumococcal adherence and colonization.|journal=Microbial pathogenesis|date=December 1998|volume=25|issue=6|pages=337–42|pmid=9895272|doi=10.1006/mpat.1998.0239}}</ref> during invasion by damaging host cells,<ref>{{cite journal|last=Rubins|first=JB|coauthors=Janoff, EN|title=Pneumolysin: a multifunctional pneumococcal virulence factor.|journal=The Journal of laboratory and clinical medicine|date=January 1998|volume=131|issue=1|pages=21–7|pmid=9452123}}</ref> and during infection by interfering with the host immune response.<ref>{{cite journal|last=Cockeran|first=R|coauthors=Anderson, R, Feldman, C|title=The role of pneumolysin in the pathogenesis of Streptococcus pneumoniae infection.|journal=Current Opinion in Infectious Diseases|date=June 2002|volume=15|issue=3|pages=235–9|pmid=12015456}}</ref>


===Host Factors===
==Host Factors==


The lungs can normally filter out large droplets of aerosols. Smaller droplets of the size of 0.5 to 2 micrometer are deposited on the [[alveoli]] and then engulfed by alevolar macrophages. These [[macrophages]] release [[cytokines]] and [[chemokines]], which also includes [[tumor necrosis factor-alpha]], [[interleukin]]-8 and [[leukotriene|LTB4]]. The [[neutrophils]] are recruited by these cells to eliminate these microorganisms.<ref name="Strieter-2003">{{Cite journal  | last1 = Strieter | first1 = RM. | last2 = Belperio | first2 = JA. | last3 = Keane | first3 = MP. | title = Host innate defenses in the lung: the role of cytokines. | journal = Curr Opin Infect Dis | volume = 16 | issue = 3 | pages = 193-8 | month = Jun | year = 2003 | doi = 10.1097/01.qco.0000073766.11390.0e | PMID = 12821807 }}</ref><ref name="Mason-2005">{{Cite journal  | last1 = Mason | first1 = CM. | last2 = Nelson | first2 = S. | title = Pulmonary host defenses and factors predisposing to lung infection. | journal = Clin Chest Med | volume = 26 | issue = 1 | pages = 11-7 | month = Mar | year = 2005 | doi = 10.1016/j.ccm.2004.10.018 | PMID = 15802161 }}</ref>
The lungs can normally filter out large droplets of aerosols. Smaller droplets 0.5 to 2 micrometer in size are deposited in the terminal [[alveoli]] and then engulfed by alevolar macrophages. These [[macrophages]] release [[cytokines]] and [[chemokines]] such as [[tumor necrosis factor-alpha]], [[interleukin]]-8 and [[leukotriene|LTB4]]. This leads to accelerated recruitment of [[neutrophils]] to the involved area.<ref name="Strieter-2003">{{Cite journal  | last1 = Strieter | first1 = RM. | last2 = Belperio | first2 = JA. | last3 = Keane | first3 = MP. | title = Host innate defenses in the lung: the role of cytokines. | journal = Curr Opin Infect Dis | volume = 16 | issue = 3 | pages = 193-8 | month = Jun | year = 2003 | doi = 10.1097/01.qco.0000073766.11390.0e | PMID = 12821807 }}</ref><ref name="Mason-2005">{{Cite journal  | last1 = Mason | first1 = CM. | last2 = Nelson | first2 = S. | title = Pulmonary host defenses and factors predisposing to lung infection. | journal = Clin Chest Med | volume = 26 | issue = 1 | pages = 11-7 | month = Mar | year = 2005 | doi = 10.1016/j.ccm.2004.10.018 | PMID = 15802161 }}</ref>


======Diminished Mucociliary Clearance======
======Diminished Mucociliary Clearance======


The [[Respiratory epithelium#Ciliary Escalator|cilia]] lining the [[respiratory epithelium]] serve to move secreted [[mucus]] containing trapped foreign particles including pathogens towards the [[oropharynx]] for either expectoration or swallowing. Elevated incidence of [[pneumonia]] in patients with genetic defects affecting [[mucociliary clearance]] such as [[primary ciliary dyskinesia]] suggests its role in the pathogenesis of community-acquired pneumonia.
The [[Respiratory epithelium#Ciliary Escalator|ciliary]] lining of the [[respiratory epithelium]] serves to move secreted [[mucus]] containing trapped foreign particles, including pathogens, towards the [[oropharynx]] for either expectoration or swallowing. The elevated incidence of [[pneumonia]] among patients with genetic defects affecting [[mucociliary clearance]], such as [[primary ciliary dyskinesia]], suggests the important role of ciliary clearance in preventing community-acquired pneumonia.


======Impaired Cough Reflex======
======Impaired Cough Reflex======


[[Cough]], together with [[mucociliary clearance]], prevent pathogens from entering the lower [[respiratory tract]]. Cough suppression or [[cough reflex]] inhibition seen in patients with [[cerebrovascular accident]]s and [[overdose|drug overdosage]]s is associated with an enhanced risk for [[aspiration pneumonia]].  Another relation to [[cough]] is [[genetic polymorphism]]s in the [[angiotensin-converting enzyme|angiotensin-converting enzyme (ACE)]] gene. The role of [[cough]] in preventing [[pneumonia]] may be explained by a higher risk for developing [[pneumonia]] in [[homozygote]]s carrying [[deletion|deletion/deletion (DD)]] [[genotype]] who are found to have lower levels of [[bradykinin]] and [[tachykinins]] such as [[substance P]].<ref name="Morimoto-2002">{{Cite journal  | last1 = Morimoto | first1 = S. | last2 = Okaishi | first2 = K. | last3 = Onishi | first3 = M. | last4 = Katsuya | first4 = T. | last5 = Yang | first5 = J. | last6 = Okuro | first6 = M. | last7 = Sakurai | first7 = S. | last8 = Onishi | first8 = T. | last9 = Ogihara | first9 = T. | title = Deletion allele of the angiotensin-converting enzyme gene as a risk factor for pneumonia in elderly patients. | journal = Am J Med | volume = 112 | issue = 2 | pages = 89-94 | month = Feb | year = 2002 | doi =  | PMID = 11835945 }}</ref><ref>{{Cite journal  | last1 = Rigat | first1 = B. | last2 = Hubert | first2 = C. | last3 = Alhenc-Gelas | first3 = F. | last4 = Cambien | first4 = F. | last5 = Corvol | first5 = P. | last6 = Soubrier | first6 = F. | title = An insertion/deletion polymorphism in the angiotensin I-converting enzyme gene accounting for half the variance of serum enzyme levels. | journal = J Clin Invest | volume = 86 | issue = 4 | pages = 1343-6 | month = Oct | year = 1990 | doi = 10.1172/JCI114844 | PMID = 1976655 }}</ref>
[[Cough]], together with [[mucociliary clearance]], prevents pathogens from entering the lower [[respiratory tract]]. Cough suppression or [[cough reflex]] inhibition seen in patients with [[cerebrovascular accident]]s and [[overdose|drug overdose]]s is associated with an increased risk for [[aspiration pneumonia]]. The role of [[cough]] in preventing infection of the lower respiratory tract is demonstrated by a higher risk of [[pneumonia]] among patients with lower levels of [[bradykinin]] and [[tachykinins]], such as [[substance P]]. These patients have a diminished cough reflex. <ref name="Morimoto-2002">{{Cite journal  | last1 = Morimoto | first1 = S. | last2 = Okaishi | first2 = K. | last3 = Onishi | first3 = M. | last4 = Katsuya | first4 = T. | last5 = Yang | first5 = J. | last6 = Okuro | first6 = M. | last7 = Sakurai | first7 = S. | last8 = Onishi | first8 = T. | last9 = Ogihara | first9 = T. | title = Deletion allele of the angiotensin-converting enzyme gene as a risk factor for pneumonia in elderly patients. | journal = Am J Med | volume = 112 | issue = 2 | pages = 89-94 | month = Feb | year = 2002 | doi =  | PMID = 11835945 }}</ref><ref>{{Cite journal  | last1 = Rigat | first1 = B. | last2 = Hubert | first2 = C. | last3 = Alhenc-Gelas | first3 = F. | last4 = Cambien | first4 = F. | last5 = Corvol | first5 = P. | last6 = Soubrier | first6 = F. | title = An insertion/deletion polymorphism in the angiotensin I-converting enzyme gene accounting for half the variance of serum enzyme levels. | journal = J Clin Invest | volume = 86 | issue = 4 | pages = 1343-6 | month = Oct | year = 1990 | doi = 10.1172/JCI114844 | PMID = 1976655 }}</ref>


======Defective Immnue System======
======Defective Immune System======


[[Pathogen-associated molecular pattern|Pathogen-associated molecular patterns (PAMPs)]] are initially recognized by [[Toll-like receptor|Toll-like receptors (TLRs)]] and other [[pattern recognition receptor|pattern-recognition receptors (PRRs)]] of the [[innate immune system]]. Effectors in the [[acquired immunity|acquired immune system]] are involved in elimination of microorganisms and generation of immunological memory. Other components in the immune system such as [[complement system]], [[cytokine]]s, and [[collectin]]s, also mediate the defense against microorganisms causing pneumonia.
[[Pathogen-associated molecular pattern|Pathogen-associated molecular patterns (PAMPs)]] are initially recognized by [[Toll-like receptor|Toll-like receptors (TLRs)]] and other [[pattern recognition receptor|pattern-recognition receptors (PRRs)]] of the [[innate immune system]]. Effectors in the [[acquired immunity|acquired immune system]] are involved in elimination of microorganisms and generation of immunological memory. Other components of the immune system, such as [[complement system]], [[cytokine]]s, and [[collectin]]s, also mediate the defense against microorganisms that cause pneumonia. Any defects in the this immune pathway can cause and increased risk of infections, namely pneumonia.


==References==
==References==
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[[Category:Disease]]
[[Category:Disease]]
[[Category:Pulmonology]]
[[Category:Pulmonology]]
[[Category:Infectious disease]]
[[Category:Pneumonia|Pneumonia]]
[[Category:Pneumonia|Pneumonia]]
[[Category:Emergency medicine]]
[[Category:Emergency medicine]]
[[Category:primary care]]

Latest revision as of 21:02, 29 July 2020

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Chetan Lokhande, M.B.B.S [2]

Overview

Because the lower respiratory tract is kept sterile by different pulmonary defense mechanisms,[1] community-acquired pneumonia connotes a breach of host defense mechanisms and/or overwhelming inoculation of virulent infectious agents. Modes of transmission include: macro- or micro-aspiration, circulation, local spead, traumatic inoculation, or iatrogenic. Impaired immunity and inability to filter out pathogens, as well as microbial virulence factors that impede immune clearance may increase the risk of developing community acquired pneumonia.

Pathophysiology

The symptoms of CAP are the result of both, the invasion of the lungs by microorganisms and the immune system's response to the infection. The mechanisms of infection are quite different for viruses and the other microorganisms.

Viruses

  • Viruses must invade cells to reproduce. Typically, a virus reaches the lungs by travelling in droplets through the mouth and nose during inhalation. There, the virus invades the cells lining the airways and the alveoli.
  • This invasion often leads to cell death, either through direct killing by the virus or by self-destruction through apoptosis.
  • Further lung damage occurs when the immune system responds to the infection.
  • White blood cells, in particular lymphocytes, activate a variety of chemicals (cytokines), which make fluid leak into the alveoli.
  • The combination of cellular destruction and fluid-filled alveoli interrupts the transportation of oxygen into the bloodstream.
  • In addition to their affect on the lungs, many viruses affect other organs; this can lead to illnesses that affect many different bodily functions.
  • Viruses also make the body more susceptible to bacterial infection; for this reason, bacterial pneumonia often complicates viral CAP.

Bacteria and Fungi

  • Bacteria and fungi also typically enter the lung with inhalation, although they reach the lung through the bloodstream if other parts of the body are infected.
  • Often, bacteria live in parts of the upper respiratory tract and are constantly being inhaled into the alveoli.
  • Once inside the alveoli, bacteria and fungi travel into the spaces between the cells and also between adjacent alveoli through connecting pores.
  • This invasion triggers the immune system to respond by sending white blood cells, responsible for attacking microorganisms (neutrophils), to the lungs.
  • The neutrophils engulf and kill the offending organisms, but they also release cytokines; this results in the general activation of the immune system. This causes the fever, chills, and fatigue which are common to CAP.
  • The neutrophils, bacteria, and fluid leaked from surrounding blood vessels fill the alveoli and result in impaired oxygen transportation.
  • Bacteria often travel from the lungs to the blood stream; this can often result in serious illness, such as septic shock, in which there is low blood pressure leading to damage to multiple parts of the body, including the brain, kidney, and heart.

Parasites

  • A variety of parasites can affect the lungs.
  • In general, parasites enter the body through the skin or by ingestion.
  • Once inside the body, these parasites travel to the lungs, most often through the blood.
  • There, a similar combination of cellular destruction and immune response causes disruption of oxygen transportation.

Mode of Transmission

1. Inhalation of Aerosolized Droplets

Inhalation of aerosolized droplets that are 0.5 to 1 micrometer is the most common means of acquiring pneumonia. A few bacterial and viral infections are transmitted in this fashion. The lung can normally filter out particles that are between 0.5 to 2 micrometer in size by recruiting the alveolar macrophages.[2]

2. Microaspiration of Oropharyngeal Contents

Aspiration of oropharyngeal contents containing pathogenic microorganisms is one of the mechanisms for acquiring pneumonia. It most commonly occurs in in the average person during sleep, in an unconscious state, due to gastroesopahegeal reflux or impaired gag reflex and cough reflex.[2]

3. Blood-Borne or Systemic Infection

Spread of an infection via the circulation may be a possible cause of pneumonia. Blood-borne pneumonia is seen more commonly in intravenous drug users particularly with gram-positive bacteria that may colonize the skin (i.e. Staphylococcus aureus). Gram-negative bacteria typically account for pneumonia in immunocompromised individuals.

4. Trauma or Local Spread

Pneumonia can occur after a pulmonary procedure or a penetrating trauma to the lungs. A local spread of a hepatic abscess can also lead to pneumonia.

Microbial Pathogenesis

Virulence Factors

Several mechanisms have evolved to evade host defense mechanisms and facilitate microbial spread to establish an infection.

  • Influenza viruses possess neuraminidase that cleaves sialic acid residues on the cell surface, which prevents viral aggregation and facilitates the propagation of viral particles.
  • Streptococcus pneumoniae possesses pneumolysin that aid the bacteria during colonization, by facilitating adherence to the host,[5] during invasion by damaging host cells,[6] and during infection by interfering with the host immune response.[7]

Host Factors

The lungs can normally filter out large droplets of aerosols. Smaller droplets 0.5 to 2 micrometer in size are deposited in the terminal alveoli and then engulfed by alevolar macrophages. These macrophages release cytokines and chemokines such as tumor necrosis factor-alpha, interleukin-8 and LTB4. This leads to accelerated recruitment of neutrophils to the involved area.[8][1]

Diminished Mucociliary Clearance

The ciliary lining of the respiratory epithelium serves to move secreted mucus containing trapped foreign particles, including pathogens, towards the oropharynx for either expectoration or swallowing. The elevated incidence of pneumonia among patients with genetic defects affecting mucociliary clearance, such as primary ciliary dyskinesia, suggests the important role of ciliary clearance in preventing community-acquired pneumonia.

Impaired Cough Reflex

Cough, together with mucociliary clearance, prevents pathogens from entering the lower respiratory tract. Cough suppression or cough reflex inhibition seen in patients with cerebrovascular accidents and drug overdoses is associated with an increased risk for aspiration pneumonia. The role of cough in preventing infection of the lower respiratory tract is demonstrated by a higher risk of pneumonia among patients with lower levels of bradykinin and tachykinins, such as substance P. These patients have a diminished cough reflex. [9][10]

Defective Immune System

Pathogen-associated molecular patterns (PAMPs) are initially recognized by Toll-like receptors (TLRs) and other pattern-recognition receptors (PRRs) of the innate immune system. Effectors in the acquired immune system are involved in elimination of microorganisms and generation of immunological memory. Other components of the immune system, such as complement system, cytokines, and collectins, also mediate the defense against microorganisms that cause pneumonia. Any defects in the this immune pathway can cause and increased risk of infections, namely pneumonia.

References

  1. ↑ 1.0 1.1 Mason, CM.; Nelson, S. (2005). "Pulmonary host defenses and factors predisposing to lung infection". Clin Chest Med. 26 (1): 11–7. doi:10.1016/j.ccm.2004.10.018. PMID 15802161. Unknown parameter |month= ignored (help)
  2. ↑ 2.0 2.1 Wunderink, RG.; Waterer, GW. (2004). "Community-acquired pneumonia: pathophysiology and host factors with focus on possible new approaches to management of lower respiratory tract infections". Infect Dis Clin North Am. 18 (4): 743–59, vii. doi:10.1016/j.idc.2004.07.004. PMID 15555822. Unknown parameter |month= ignored (help)
  3. ↑ Shemer-Avni, Y.; Lieberman, D. (1995). "Chlamydia pneumoniae-induced ciliostasis in ciliated bronchial epithelial cells". J Infect Dis. 171 (5): 1274–8. PMID 7751703. Unknown parameter |month= ignored (help)
  4. ↑ Kannan, TR.; Baseman, JB. (2006). "ADP-ribosylating and vacuolating cytotoxin of Mycoplasma pneumoniae represents unique virulence determinant among bacterial pathogens". Proc Natl Acad Sci U S A. 103 (17): 6724–9. doi:10.1073/pnas.0510644103. PMID 16617115. Unknown parameter |month= ignored (help)
  5. ↑ Rubins, JB (December 1998). "Pneumolysin in pneumococcal adherence and colonization". Microbial pathogenesis. 25 (6): 337–42. doi:10.1006/mpat.1998.0239. PMID 9895272. Unknown parameter |coauthors= ignored (help)
  6. ↑ Rubins, JB (January 1998). "Pneumolysin: a multifunctional pneumococcal virulence factor". The Journal of laboratory and clinical medicine. 131 (1): 21–7. PMID 9452123. Unknown parameter |coauthors= ignored (help)
  7. ↑ Cockeran, R (June 2002). "The role of pneumolysin in the pathogenesis of Streptococcus pneumoniae infection". Current Opinion in Infectious Diseases. 15 (3): 235–9. PMID 12015456. Unknown parameter |coauthors= ignored (help)
  8. ↑ Strieter, RM.; Belperio, JA.; Keane, MP. (2003). "Host innate defenses in the lung: the role of cytokines". Curr Opin Infect Dis. 16 (3): 193–8. doi:10.1097/01.qco.0000073766.11390.0e. PMID 12821807. Unknown parameter |month= ignored (help)
  9. ↑ Morimoto, S.; Okaishi, K.; Onishi, M.; Katsuya, T.; Yang, J.; Okuro, M.; Sakurai, S.; Onishi, T.; Ogihara, T. (2002). "Deletion allele of the angiotensin-converting enzyme gene as a risk factor for pneumonia in elderly patients". Am J Med. 112 (2): 89–94. PMID 11835945. Unknown parameter |month= ignored (help)
  10. ↑ Rigat, B.; Hubert, C.; Alhenc-Gelas, F.; Cambien, F.; Corvol, P.; Soubrier, F. (1990). "An insertion/deletion polymorphism in the angiotensin I-converting enzyme gene accounting for half the variance of serum enzyme levels". J Clin Invest. 86 (4): 1343–6. doi:10.1172/JCI114844. PMID 1976655. Unknown parameter |month= ignored (help)
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