Community-acquired pneumonia pathophysiology

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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 defence mechanisms, 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, circulation, local spead, traumatic inoculation, or iatrogenic. Impaired immunity and inability to filter out pathogens increase the risk for developing pneumonia. Causative etiologies vary with age, immune status, geographical area, and comorbid conditions.

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. 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

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.

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.

Pathogenesis

Virulence Factors

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

• Influenza viruses possess neuraminidases for cleavage of sialic acid residues on the cell surface and viral proteins; neuraminidases prevent aggregation and facilitate propagation of viral particles.

• Chlamydophila pneumoniae induces complete abortion of cilia motions which assist colonization at 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 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 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.

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.

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 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.

Defective Immnue 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.