Pneumonia: Its Pathogenesis and Histopathology

Abstract

Pneumonia is a condition defined primarily as a lung infection, typically caused by pathogenic microorganisms such as bacteria, viruses and fungi. It is characterised by the inflammation of the alveoli in one or both lungs situated in the thoracic cavity where the aforementioned air sacs may fill with purulent material such as pus or fluid. This article aims to provide a comprehensive overview of the pathogenesis of pneumonia; it will offer an explanation of the different stages from the entry of the pathogen to the resolution. Moreover, it seeks to articulate the histopathology for the infection.

Introduction 

Pneumonia is a condition defined primarily as a lung infection, typically caused by pathogenic microorganisms such as bacteria, viruses and fungi. It is characterised by the inflammation of the alveoli in one or both lungs situated in the thoracic cavity where the aforementioned air sacs may fill with purulent material such as pus or fluid, consequently resulting in symptomatic features such as fever, chills, phlegm and difficulty breathing being experienced by the patient[1].

The incidence of pneumonia, including that due to respiratory viruses, is markedly more prevalent in children less than 5 years old and older adults over the age of 50 years. Viruses are the pathogenic microorganisms more commonly detected. However, it is to be noted that there is difficulty in distinguishing between viral and bacterial pneumonia for most patients at presentation as the symptoms are overlapping – further clarification is provided with diagnostic tests[3]. 

According to the World Health Organisation (WHO), pneumonia resulted in the deaths of 808000+ children under 5 years old in 2017; this figure encompasses 15% of all deaths of children at that age[2]. Other sources report that globally, the number of children under the age of 5 years succumbing to pneumonia annually was 900,000 in other years. It has been a leading cause of hospitalisation and death among adults within the United States and such precedent has led to the country pouring in more than $10 billion into combatting the disease[3].

Pathogenesis 

Pathogenesis encompasses the study of how a pathogen enters a host, establishes an infection and causes the development of a disease. In other words, it is the process by which a condition arises and consequently proceeds, from the interaction of the host with the pathogen to the biological and molecular processes carried out as the infectious agent engages with the body cells . Pathogenesis also encompasses how the infection progresses and whether it ultimately leads to recovery, death or chronic illness[4].

The bacterial culprits responsible for community acquired pneumonia include Pneumococcus, Haemophilus influenzae, Moraxella catarrhalis and other anaerobic or aerobic gram-negative organisms. In the United States specifically, the list includes Streptococcus pneumoniae, Mycoplasma pneumoniae and gram-negative enteric bacilli. Scientists can still not say with absolute certainty that viral species are a primary cause or whether they contribute by secondary bacterial causes to the pathogenesis as this is still being investigated. Nevertheless, viral agents such as influenza virus, respiratory syncytial virus, parainfluenza virus and adenoviruses are the most frequent ones responsible for community acquired pneumonia[5]. 

The lower respiratory tract typically sustains a delicate balance between host defense mechanisms which can be innate or adaptive and the resident organisms despite being continually exposed to environmental pathogenic microorganisms. When this balance is disrupted, it can subsequently lead to an inflammation of the lung parenchyma. This henceforth, can be characterised as bacterial pneumonia developing in the body[6][7]. 

There are a plethora of host defences, ranging from mechanical ones to chemical ones which protect the body against the invasion of disease causing pathogens. Key defences in this particular circumstance include mechanical barriers such as nasal hair and mucociliary clearances. Chemical defenses like surfactant proteins D and A play an important role and the immune responses include alveolar macrophages and neutrophils[7]. These defences become compromised through different conditions: 

• Mucociliary dysfunction in smokers or Kartagener syndrome

• Impaired cough reflex in comatose patients 

• Accumulation of secretions in cystic fibrosis 

• Immunodeficiencies like CVID and X-linked agammaglobulinemia[6]

When bacteria evade these defences by employing virulence factors like adhesion proteins in the case of M.pneumoniae, they colonise the alveoli[7]. 

Alveolar macrophages then proceed to engulf the bacteria and release cytokines, an example of which is IL-8. This triggers a cascade of inflammatory events and the response recruits neutrophils. This development enhances mucin production via the likes of IL-9 and IL-13 and consequently activates both cellular and humoral immunity[7]. The resultant inflammation increases alveolar-capillary permeability; this leads to exudative congestion, reduced gas exchange, fibrosis and dyspnea. While the macrophages aim to eliminate pathogens, their inflammatory response is central to the pathogenesis of pneumonia and its symptomatic and clinical features[6].

Histopathology

Histopathology can be evaluated as two separate topics: lobar pneumonia and bronchopneumonia[6].

1. Lobar Pneumonia 

This can be categorised under four stages. The first stage is congestion which occurs typically within 24 hours of infection. The number of bacteria that have successfully invaded the lungs by bypassing the mechanical barriers are far greater than the number of white blood cells. Blood flow increases to fight against the infection which is why the lungs may appear to be red and the lung tissue swells up[6]. The second stage is defined as Red Hepatization. This occurs 48 hours to 72 hours post infection and can persist for up to 4 days. The lungs become dry, airless and granular as a result of the infection and red blood cells, white blood cells, bacteria and cellular debris clogging the lung airways. It has been said that the lungs possess a consistency resembling the liver during this stage[8]. 

The third stage is Grey Hapitzation. The lungs appear grey or yellow in colour during the 4 to 8 days this stage occurs. Fibrin, hemosiderin and red blood cells disintegrate and break down, subsequently leading to a more fluid-like exudate. Macrophage production begins. The fourth and final stage is the resolution. The time period is typically between days 8 to 10 post infection[8]. Fluids and collateral damage from cell destruction are reabsorbed, the macrophages assist in clearing neutrophils and debris[6]. The alveoli are then able to return to normal lung function and recovery is achieved[8].

2. Bronchopneumonia 

Bronchopneumonia includes the suppurative inflammation localised in patches around the bronchi which do not necessarily have to be localised to a singular lobe of the lung. Severe versions of pneumonia can result in the formation of abscess in the lungs and puss-filled pockets in the focal areas as well as a breakdown of tissue, though it is extremely rare[6].

Conclusion 

Pneumonia is a condition defined primarily as a lung infection, typically caused by pathogenic microorganisms such as bacteria, viruses and fungi. It is characterised by the inflammation of the alveoli in one or both lungs situated in the thoracic cavity where the aforementioned air sacs may fill with purulent material such as pus or fluid, consequently resulting in symptomatic features such as fever, chills, phlegm and difficulty breathing being experienced by the patient. Bacterial agents are largely responsible for it and result in inflammation when they evade the host’s mechanical and chemical defence barriers. The body however is able to combat it and recovery does occur. Histopathology can be evaluated as two separate topics: lobar pneumonia and bronchopneumonia.

Resources:

1. Pneumonia - an article published on the official website for Mayo Clinic - https://www.mayoclinic.org/diseases-conditions/pneumonia/symptoms-causes/syc-20354204#:~:text=Pneumonia%20is%20an%20infection%20that,and%20fungi%2C%20can%20cause%20pneumonia.

2. World Health Organisation’s website - Pneumonia- https://www.who.int/health-topics/pneumonia#tab=tab_1 

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6. Jain V, Vashisht R, Yilmaz G, et al. Pneumonia Pathology. [Updated 2023 Jul 31]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK526116/ 

7. Sattar SBA, Nguyen AD, Sharma S. Bacterial Pneumonia. [Updated 2024 Feb 26]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK513321/ 

8. What are the 4 Stages of Pneumonia? Medically reviewed by Leigh Ann Anderson, PharmD. - https://www.drugs.com/medical-answers/4-stages-pneumonia-3558984/