Pneumonia and Pulmonary Edema

Pathophysiology of Pneumonia

Noah Stewart

Learning Objectives

By the end of this section, you will be able to:

  • Explain why certain individuals may be more predisposed to developing pneumonia than others
  • Outline the different inflammatory patterns present in pneumonia
  • Describe how inflammation in the lungs contributes to the symptomology of pneumonia
  • Describe the role of pulmonary edema in pneumonia

Who Gets Pneumonia?

As discussed in the previous chapter, pneumonia is an infection of one or both lungs that is characterized by inflammation of the alveoli and interstitial tissue. The many pathogens that may cause pneumonia do not express explicit related features to infect the lower respiratory tract. Instead, pneumonia is largely considered to be the result of failure in the host response to pathogens, although the individual properties of microorganisms do contribute to their ability to cause pneumonia. For this reason, pneumonia most commonly affects children <5 years of age, adults >70 years of age, and patients with ongoing health problems – those whose defenses against infection are either not fully developed or may be weakened. Nevertheless, anybody may develop pneumonia. Pneumonia may be a primary condition, where there are no apparent pre-existing conditions that may predispose a patient to developing pneumonia, or a secondary condition where the patient has another condition that may predispose them to developing pneumonia, such as COPD, cystic fibrosis, or aspiration pneumonia.

Initial Infection and Colonization of the Lower Respiratory Tract

The first step in the pathophysiology of pneumonia is exposure to the pathogen. Owing to the variety of pathogens that can cause pneumonia, the ways in which they can first infect a person can vary. Most commonly the pathogens that cause pneumonia are spread when an infected individual coughs or sneezes and releases oropharyngeal secretions in the form of droplets into the air, which contain the pathogen. These droplets are suspended in the air and can be breathed in by others. Rarely, pathogens may spread to the lungs through the blood following an initial infection at another site of the body.

Failure of pulmonary protective mechanisms, in addition to features of the pathogen that help it infect the airways, can lead to penetration and proliferation of the pathogen in the lower respiratory tract. For example, in comatose patients whose cough reflex is impaired, or in chronic cigarette smokers whose mucociliary clearance is impaired, the ability to prevent infection in the lower respiratory tract is diminished. The fine balance between the healthy and tolerated endogenous bacteria of the lower respiratory tract and the local and systemic defense mechanisms of the host is disrupted, thus leading to inflammation of the functional tissue of the lung (pneumonia).

Examples of Impaired Pulmonary Protective Mechanisms Seen in Pneumonia

Defense mechanism Possible cause
Impaired cough reflex Comatose patient, certain substances of abuse
Impaired mucociliary clearance Cigarette smoking, Kartergerner syndrome
Accumulation of secretions Cystic fibrosis, bronchial obstruction
Impaired systemic defense mechanisms Cigarette smoking (suppressed neutrophil function), chemotherapy, HIV


The Immune Response to Infection

Following penetration and proliferation of the pathogen in the lower airways and alveoli, the immune system responds to eliminate the pathogens. The body’s response to infection is what causes the clinical and histopathological findings of pneumonia, which will be discussed in more detail in  later chapters. Infection and tissue damage spurs a systemic inflammatory response when chemical messengers called cytokines are released, although the exact inflammatory response depends on the type of pathogen. Cytokines are released when cells are damaged or when they recognize pathogens. Lung epithelial cells, when activated, release antimicrobial proteins and cytokines into the surrounding tissue to recruit neutrophils to the site of infection. Macrophages present in the alveoli play a large role in the innate immune response to infection. Alveolar macrophages are able to ingest (phagocytose) and kill pathogens, promote local inflammation, and release cytokines to attract other immune cells to the site of inflammation. To make it easier for immune cells to find and enter the site of infection from the bloodstream, the released cytokines cause dilation of nearby blood vessels leading to increased blood flow and leaky capillaries. This inflammatory response aims to destroy invading pathogens and infected cells, but also causes damage to the healthy lung tissue. The systemic cytokine release during pneumonia also acts on the hypothalamus in the brain and disrupts normal thermoregulation, causing fever and chills.

Patterns of Inflammation

There are three main inflammatory patterns depending on the cause of pneumonia and the areas that are affected: lobar pneumonia, bronchopneumonia, and interstitial pneumonia. Lobar pneumonia affects an entire lobe of the lung, and the inflammatory response causes the accumulation of cells, protein, and fluids leaking out of nearby capillaries in the lungs and into the alveoli of the affected lobe. The buildup of fluid and debris, known as plasma exudate, in alveoli prevents gas exchange from taking place, leading to less oxygen making it to the blood and a compensatory increase in respiratory rate and difficulty breathing. The fluid buildup also leads to irritation and attempted clearance of the airway by coughing, which leads to the production of phlegm. This is known as a productive cough.

Pathophysiology of Lobar Pneumonia created by Sarah Perkins under a CC BY NC ND license

Pulmonary Edema in Pneumonia

The abnormal buildup of fluid inside the lungs is called pulmonary edema. The most common cause of pulmonary edema is pressure-induced, where the circulatory system is unable to remove enough blood from the pulmonary circulation and thus causes it to leak into the lungs. This has been discussed in the chapter on Heart Failure. Pneumonia instead may cause pulmonary edema through inflammatory mechanisms by increasing the permeability of blood vessels in response to infection and tissue damage in the lungs, causing fluid to leak into the lungs.



On the other hand, certain pathogens cause what is known as interstitial pneumonia. Interstitial pneumonia affects the walls between alveoli, in contrast to lobar pneumonia which is caused by the buildup of inflammatory cells, fluid, and proteins inside of the alveolar spaces. Similar to lobar pneumonia, interstitial pneumonia results in the impairment of gas exchange and difficulty breathing. However, in the case of interstitial pneumonia, impairment of gas exchange is caused by the thickening of the alveolar walls which makes it difficult for gases to diffuse due to the increased distance between the blood vessels and the alveolar air space. Thickening of the alveolar walls is caused by the buildup of immune cells and cellular debris in the space between the alveoli and the blood vessels. The inflammatory response in the alveolar walls cause irritation and also trigger the cough reflex. In lobar pneumonia, coughing led to the production of phlegm via the fluid trapped inside the alveoli. Because there is no fluid buildup inside the alveolar airspace in interstitial pneumonia, a dry cough is produced.

Pathophysiology of Interstitial Pneumonia created by Sarah Pinault under a CC BY NC ND license

Bronchopneumonia, as the name suggests, is caused by the inflammation of the bronchi and nearby alveoli. Bronchopneumonia is similar to lobar pneumonia in its features, and often transforms into lobar pneumonia as the infection progresses. Bronchopneumia is hallmarked by the accumulation of inflammatory cells, debris, and fluid in the bronchi and/or bronchioles and adjacent alveoli in inflamed patches around the lung. This contrasts with lobar pneumonia, where the entire lobe of a lung and its alveoli are affected.


There are many ways to classify pneumonias. Classification by the pattern of involvement, as is presented above, is relevant histologically when lung tissue is viewed under the microscope (as will be discussed in the next chapter) as well as when looking at certain lab findings, such as chest X-rays. Other ways pneumonia can be classified are by the type of pathogen, how/where it is spread, and by how the patient presents.

Section Review

  • Pneumonia is the result of pathogens overcoming the protective mechanisms of the body and penetrating into the lower respiratory tract
  • Patients who have reduced functioning of these barriers are at a greater risk for developing pneumonia
  • The clinical manifestations of pneumonia are the result of the body’s inflammatory immune response to the invading pathogen
  • The pattern of inflammation can vary depending on the invading pathogen, but all may lead to the characteristic symptoms of fever/chills, fatigue, and dyspnea
  • Gas exchange can be impaired in pneumonia by the accumulation of fluid in the alveoli (pulmonary edema) or by the thickening of the space between alveoli and capillaries

Review Questions


Jain, V., Vashisht, R., Yilmaz, G., & Bhardwaj, A. (2022). Pneumonia Pathology. In StatPearls. StatPearls Publishing.


Kumar V. (2020). Pulmonary Innate Immune Response Determines the Outcome of Inflammation During Pneumonia and Sepsis-Associated Acute Lung Injury. Frontiers in immunology11, 1722.

Laura Byford-Richardson. (2016). Adult Pneumonia: Pathogenesis and Clinical Findings. In The Calgary Guide. The Calgary Guide to Understanding Disease.


Lyczak, J. B., Cannon, C. L., & Pier, G. B. (2002). Lung infections associated with cystic fibrosis. Clinical microbiology reviews15(2), 194–222.

Torres, A., Cilloniz, C., Niederman, M. S., Menéndez, R., Chalmers, J. D., Wunderink, R. G., & van der Poll, T. (2021). Pneumonia. Nature reviews. Disease primers7(1), 25.


Icon for the Creative Commons Attribution-NonCommercial 4.0 International License

Pathology Copyright © 2022 by Noah Stewart is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License, except where otherwise noted.

Share This Book