Pneumonia pathophysiology

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Hamid Qazi, MD, BSc [2], Priyamvada Singh, M.D. [3]

Overview

Bacteria and fungi typically enter the lung with inhalation. Once inside the alveoli, these microbes travel into the spaces between the cells and also between adjacent alveoli through connecting pores. This invasion triggers the immune system response by sending white blood cells responsible for attacking microorganisms (neutrophils) to the lungs resulting in manifestations of pneumonia.

Pathophysiology

Mode of Transmission

1. Inhalation of Aerosolized Droplets

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.

2. Microaspiration of Oropharyngeal Contents

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.

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. Staphylococcus aureus causes pneumonia in this way. 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.

Agent Specific Virulence Factors

Several strategies are evolved to evade host defence mechanisms and facilitate spreading before establishing an infection.

• Influenza virus possesses neuraminidases for cleavage of sialic acid residues on the cell surface and viral proteins, which prevent aggregation and facilitate propagation of viral particles.

• Chlamydophila pneumoniae induces complete abortion of cilia motions which assists colonization at the respiratory epithelium.

• Mycoplasma pneumoniae produces a virulence factor with ADP-ribosylating activity which is responsible for airway cellular damage and mucociliary dysfunction.

• Haemophilus influenzae, Streptococcus pneumoniae, and Neisseria meningitidis produce proteases that split mucosal IgA.

• Streptococcus pneumoniae possesses pneumolysin that aid the bacteria during colonization, by facilitating adherence to the host, during invasion by damaging host cells, and during infection by interfering with the host immune response.

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 LTB4.
• The neutrophils are recruited by these cells to eliminate these microorganisms.

1. Diminished Mucociliary Clearance

• The 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.

2. 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 accidents and drug overdosages is associated with an enhanced risk for aspiration pneumonia.
• Another relation to cough is genetic polymorphisms in the angiotensin-converting enzyme (ACE) gene.
• The role of cough in preventing pneumonia may be explained by a higher risk for developing pneumonia in homozygotes carrying deletion/deletion (DD) genotype who are found to have lower levels of bradykinin and tachykinins such as substance P.

3. 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 in the immune system such as complement system, cytokines, and collectins, also mediate the defense against microorganisms causing pneumonia.

Microscopic Pathology

The upper panel shows a normal lung under a microscope. The white spaces are alveoli that contain air.Lower panel shows a lung with pneumonia under a microscope. The alveoli are filled with inflammation and debris.

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.

• Chlamydophila pneumoniae induces complete paralysis of the respiratory cilia, which assists with the colonization of the respiratory epithelium.

• Mycoplasma pneumoniae produces a virulence factor with ADP-ribosylating activity that is responsible for airway cellular damage and mucociliary dysfunction.

• Haemophilus influenzae, Streptococcus pneumoniae, and Neisseria meningitidis produce proteases that cleave mucosal IgA.

• Streptococcus pneumoniae possesses pneumolysin that aid the bacteria during colonization, by facilitating adherence to the host, during invasion by damaging host cells, and during infection by interfering with the host immune response.

Aspiration Pneumonia

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Lobar Pneumonia

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Pneumocystis Pneumonia

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Pneumocystis Pneumonia

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Aspiration Pneumonia

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Aspiration Pneumonia, Infant

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Desquamative Interstitial Pneumonia

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Legionella Pneumonia

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Measles Pneumonia

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Abscess, Bronchopneumonia

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Scanning Electron Micrograph (SEM) Gallery

Produced by the National Institute of Allergy and Infectious Diseases (NIAID), this digitally-colorized scanning electron micrograph (SEM) depicts a blue-colored, human white blood cell (WBC) known specifically as a neutrophil, interacting with two pink-colored, rod-shaped, multidrug-resistant (MDR) Klebsiella pneumoniae bacteria, which are known to cause severe hospital-acquired, nosocomial pneumonia. Image obtained from CDC PHIL

Produced by the National Institute of Allergy and Infectious Diseases (NIAID), this digitally-colorized scanning electron micrograph (SEM) depicts two yellow-colored, spherical methicillin-resistant Staphylococcus aureus (MRSA) bacteria that were in the process of being phagocytized by a blue-colored human white blood cell (WBC) known specifically as a neutrophil. Image obtained from CDC PHIL

Magnified 8000X, this colorized scanning electron micrograph (SEM) depicted a grouping of Gram-negative Legionella pneumophila bacteria. Image obtained from CDC PHIL

Scanning Electron Micrograph of Streptococcus pneumoniae. Image obtained from CDC PHIL