Pneumonia pathophysiology

Pneumonia Microchapters
Home
Patient Information
Overview
Historical Perspective
Classification
Pathophysiology
Causes
Differentiating Pneumonia from other Diseases
Epidemiology and Demographics
Risk Factors
Screening
Natural History, Complications and Prognosis
Diagnosis
Diagnostic Criteria
Diagnostic Algorithm
History and Symptoms
Physical Examination
Laboratory Findings
Chest X Ray
CT
Other Imaging Findings
Treatment
Medical Therapy
Prevention
Cost-Effectiveness of Therapy
Future or Investigational Therapies
Case Studies
Case #1
Pneumonia pathophysiology On the Web
Most recent articles
Most cited articles
Review articles
CME Programs
Powerpoint slides
Images
American Roentgen Ray Society Images of Pneumonia pathophysiology All Images X-rays Echo & Ultrasound CT Images MRI
Ongoing Trials at Clinical Trials.gov
US National Guidelines Clearinghouse
NICE Guidance
FDA on Pneumonia pathophysiology
CDC onPneumonia pathophysiology
Pneumonia pathophysiology in the news
Blogs on Pneumonia pathophysiology
Directions to Hospitals Treating Pneumonia
Risk calculators and risk factors for Pneumonia pathophysiology

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.

Community Acquired Pneumonia

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. 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.

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.

• 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.

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.

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.

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.

Aspiration Pneumonia

{{#ev:youtube|bTqgAfQv0p4}}

Lobar Pneumonia

{{#ev:youtube|dxXrxYIXbL8}}

Pneumocystis Pneumonia

{{#ev:youtube|KfF_pPUjR8o}}

Pneumocystis Pneumonia

{{#ev:youtube|zSdK_yWe_S4}}

Aspiration Pneumonia

{{#ev:youtube|bTqgAfQv0p4}}

Aspiration Pneumonia, Infant

{{#ev:youtube|RXnnEuEZ0BY}}

Desquamative Interstitial Pneumonia

{{#ev:youtube|G0TFmAAYjWU}}

Legionella Pneumonia

{{#ev:youtube|BDWEnPilfIQ}}

Measles Pneumonia

{{#ev:youtube|v80kA_dt6EE}}

Abscess, Bronchopneumonia

{{#ev:youtube|wO2x7O2KEZY}}

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