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Pneumonia

Part 1 : Symptoms and Diagnosis
Part 2 : Pathophysiology and Types of Pneumonia
Part 3 : Treatment, Complications, Prognosis & Mortality, Prevention, Epidemiology, History

Part 2

Pathophysiology

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.
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.

The symptoms of infectious pneumonia are caused by the invasion of the lungs by microorganisms and by the immune system's response to the infection. Although over one hundred strains of microorganism can cause pneumonia, only a few of them are responsible for most cases. The most common causes of pneumonia are viruses and bacteria. Less common causes of infectious pneumonia include fungi and parasites.

Viruses

Viruses must invade cells in order to reproduce. Typically, a virus reaches the lungs when airborne droplets are inhaled through the mouth and nose. Once in the lungs, the virus invades the cells lining the airways and alveoli. This invasion often leads to cell death, either when the virus directly kills the cells, or through a type of cell self-destruction called apoptosis. When the immune system responds to the viral infection, even more lung damage occurs. White blood cells, mainly lymphocytes, activate a variety of chemical cytokines which allow fluid to leak into the alveoli. This combination of cell destruction and fluid-filled alveoli interrupts the normal transportation of oxygen into the bloodstream.

In addition to damaging the lungs, many viruses affect other organs and thus can disrupt many different body functions. Viruses also can make the body more susceptible to bacterial infections; for this reason, bacterial pneumonia often complicates viral pneumonia.

Viral pneumonia is commonly caused by viruses such as influenza virus, respiratory syncytial virus (RSV), adenovirus, and metapneumovirus. Herpes simplex virus is a rare cause of pneumonia except in newborns. People with immune system problems are also at risk for pneumonia caused by cytomegalovirus (CMV).

Bacteria

Bacteria typically enter the lung when airborne droplets are inhaled, but they can also reach the lung through the bloodstream when there is an infection in another part of the body. Many bacteria live in parts of the upper respiratory tract, such as the nose, mouth and sinuses, and can easily be inhaled into the alveoli. Once inside the alveoli, bacteria may invade the spaces between cells and between alveoli through connecting pores. This invasion triggers the immune system to send neutrophils, which are a type of defensive white blood cell, to the lungs. The neutrophils engulf and kill the offending organisms, and they also release cytokines, causing a general activation of the immune system. This leads to the fever, chills, and fatigue common in bacterial and fungal pneumonia. The neutrophils, bacteria, and fluid from surrounding blood vessels fill the alveoli and interrupt normal oxygen transportation.

The bacterium Streptococcus pneumoniae, a common cause of pneumonia, photographed through an electron microscope.
The bacterium Streptococcus pneumoniae, a common cause of pneumonia, photographed through an electron microscope.

Bacteria often travel from an infected lung into the bloodstream, causing serious or even fatal illness such as septic shock, with low blood pressure and damage to multiple parts of the body including the brain, kidneys, and heart. Bacteria can also travel to the area between the lungs and the chest wall (the pleural cavity) causing a complication called an empyema.

The most common causes of bacterial pneumonia are Streptococcus pneumoniae, Gram-negative bacteria and "atypical" bacteria. The terms "Gram-positive" and "Gram-negative" refer to the bacteria's color (purple or red, respectively) when stained using a process called the Gram stain. The term "atypical" is used because atypical bacteria commonly affect healthier people, cause generally less severe pneumonia, and respond to different antibiotics than other bacteria.

The types of Gram-positive bacteria that cause pneumonia can be found in the nose or mouth of many healthy people. Streptococcus pneumoniae, often called "pneumococcus", is the most common bacterial cause of pneumonia in all age groups except newborn infants. Another important Gram-positive cause of pneumonia is Staphylococcus aureus. Gram-negative bacteria cause pneumonia less frequently than gram-positive bacteria. Some of the gram-negative bacteria that cause pneumonia include Haemophilus influenzae, Klebsiella pneumoniae, Escherichia coli, Pseudomonas aeruginosa and Moraxella catarrhalis. These bacteria often live in the stomach or intestines and may enter the lungs if vomit is inhaled. "Atypical" bacteria which cause pneumonia include Chlamydophila pneumoniae, Mycoplasma pneumoniae, and Legionella pneumophila.

Fungi

Fungal pneumonia is uncommon, but it may occur in individuals with immune system problems due to AIDS, immunosuppresive drugs, or other medical problems. The pathophysiology of pneumonia caused by fungi is similar to that of bacterial pneumonia. Fungal pneumonia is most often caused by Histoplasma capsulatum, Cryptococcus neoformans, Pneumocystis jiroveci, and Coccidioides immitis. Histoplasmosis is most common in the Mississippi River basin, and coccidioidomycosis is most common in the southwestern United States.

Parasites

A variety of parasites can affect the lungs. These parasites typically enter the body through the skin or by being swallowed. Once inside the body, they travel to the lungs, usually through the blood. There, as in other types of pneumonia, a combination of cellular destruction and immune response causes disruption of oxygen transportation. One type of white blood cell, the eosinophil, responds vigorously to parasite infection. Eosinophils in the lungs can lead to eosinophilic pneumonia, thus complicating the underlying parasitic pneumonia. The most common parasites causing pneumonia are Toxoplasma gondii, Strongyloides stercoralis, and Ascariasis.

Types of pneumonia

Pneumonias can be classified in several different ways. Pathologists classified them according to the anatomic changes that were found in the lungs during autopsies. As more became known about the microorganisms causing pneumonia, a microbiologic classification arose, and with the advent of x-rays, a radiological classification was developed. Another important classification system used for pneumonia is the combined clinical classification, which combines many factors, including age, risk factors for certain microorganisms, the presence of underlying lung disease and underlying systemic disease, and whether he or she has recently been hospitalized.

Early classification schemes

Initial descriptions of pneumonia focused on the anatomic or pathologic appearance of the lung, either by direct inspection at autopsy or by its appearance under a microscope. A lobar pneumonia is an infection that only involves a single lobe, or section, of a lung. Lobar pneumonia is often due to Streptococcus pneumoniae. Multilobar pneumonia involves more than one lobe, and it often is a more severe illness than lobar pneumonia. Interstitial pneumonia involves the areas in between the alveoli, and it may be called "interstitial pneumonitis." Interstitial pneumonia is more likely to be caused by viruses or by atypical bacteria.

The discovery of x-rays made it possible to determine the anatomic type of pneumonia without direct examination of the lungs at autopsy and led to the development of a radiological classification. Early investigators distinguished between typical lobar pneumonia and atypical (e.g. Chlamydophila) or viral pneumonia using the location, distribution, and appearance of the opacities they saw on chest x-rays. Certain x-ray findings can be used to help predict the course of illness, although it is not possible to clearly determine the microbiologic cause of a pneumonia based on x-rays alone.

With the advent of modern microbiology, classification based upon the causative microorganism became possible. Determining which microorganism is causing an individual's pneumonia is an important step in deciding treatment type and length. Sputum cultures, blood cultures, tests on respiratory secretions, and specific blood tests are used to determine the microbiologic classification. Because such laboratory testing typically takes several days, microbiologic classification is usually not possible at the time of initial diagnosis.

Combined clinical classification

Traditionally, clinicians have classified pneumonia by clinical characteristics, dividing them into "acute" (less than three weeks duration) and "chronic" pneumonias. This is useful because chronic pneumonias tend to be either non-infectious, or mycobacterial, fungal, or mixed bacterial infections caused by airway obstruction. Acute pneumonias are further divided into the classic bacterial bronchopneumonias (such as Streptococcus pneumoniae), the atypical pneumonias (such as the interstitial pneumonitis of Mycoplasma pneumoniae or Chlamydia pneumoniae), and the aspiration pneumonia syndromes.

The combined clinical classification, now the most commonly used classification scheme, attempts to identify a person's risk factors when he or she first comes to medical attention. The advantage of this classification scheme over previous systems is that it can help guide the selection of appropriate initial treatments even before the microbiologic cause of the pneumonia is known. There are two broad categories of pneumonia in this scheme: Community-acquired pneumonia and hospital-acquired pneumonia.

Community-acquired pneumonia

Community-acquired pneumonia (CAP) is infectious pneumonia in a person who has not recently been hospitalized. CAP is the most common type of pneumonia. The most common causes of CAP differ depending on a person's age, but they include Streptococcus pneumoniae, viruses, the atypical bacteria, and Haemophilus influenzae. Overall, Streptococcus pneumoniae is the most common cause of community-acquired pneumonia worldwide. Gram-negative bacteria cause CAP in certain at-risk populations. CAP is the fourth most common cause of death in the United Kingdom and the sixth in the United States. An outdated term, walking pneumonia, has been used to describe a type of community-acquired pneumonia of less severity (hence the fact that the patient can continue to "walk" rather than require hospitalization). Walking pneumonia is usually caused by a virus or by atypical bacteria.

Hospital-acquired- pneumonia

Hospital-acquired pneumonia, also called nosocomial pneumonia, is pneumonia acquired during or after hospitalization for another illness or procedure. The causes, microbiology, treatment and prognosis are different from those of community-acquired pneumonia. Up to 5% of patients admitted to a hospital for other causes subsequently develop pneumonia. Hospitalized patients may have many risk factors for pneumonia, including mechanical ventilation, prolonged malnutrition, underlying heart and lung diseases, decreased amounts of stomach acid, and immune disturbances. Additionally, the microorganisms a person is exposed to in a hospital are often different from those at home. Hospital-acquired microorganisms may include resistant bacteria such as MRSA, Pseudomonas, Enterobacter, and Serratia. Because individuals with hospital-acquired pneumonia usually have underlying illnesses and are exposed to more dangerous bacteria, it tends to be more deadly than community-acquired pneumonia. Ventilator-associated pneumonia (VAP) is a subset of hospital-acquired pneumonia. VAP is pneumonia which occurs after at least 48 hours of intubation and mechanical ventilation.

Other types of pneumonia

  • Severe acute respiratory syndrome (SARS)
SARS is a highly contagious and deadly type of pneumonia which first occurred in 2002 after initial outbreaks in China. SARS is caused by the SARS coronavirus, a previously unknown pathogen. New cases of SARS have not been seen since June 2003.
  • Bronchiolitis obliterans organizing pneumonia (BOOP)
BOOP is caused by inflammation of the small airways of the lungs. It is also known as cryptogenic organizing pneumonitis (COP).
  • Eosinophilic pneumonia
Eosinophilic pneumonia is invasion of the lung by eosinophils, a particular kind of white blood cell. Eosinophilic pneumonia often occurs in response to infection with a parasite or after exposure to certain types of environmental factors.
  • Chemical pneumonia
Chemical pneumonia (usually called chemical pneumonitis) is caused by chemical toxins such as pesticides, which may enter the body by inhalation or by skin contact. When the toxic substance is an oil, the pneumonia may be called lipoid pneumonia.
  • Aspiration pneumonia
Aspiration pneumonia (or aspiration pneumonitis) is caused by aspirating foreign objects which are usually oral or gastric contents, either while eating, or after reflux or vomiting which results in bronchopneumonia. The resulting lung inflammation is not an infection but can contribute to one, since the material aspirated may contain anaerobic bacteria or other unusual causes of pneumonia. Aspiration is a leading cause of death among hospital and nursing home patients, since they often cannot adequately protect their airways and may have otherwise impaired defenses.

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