PNEUMONIA
Pneumonia is an acute infection of the lung parenchyma characterised by inflammation of the alveoli and distal airways. The defining pathological feature is alveolar filling with inflammatory exudate, which replaces air and disrupts normal gas exchange. Unlike obstructive airway diseases, pneumonia primarily affects the gas-exchanging units of the lung rather than airflow mechanics.
Pneumonia may be caused by bacteria, viruses, fungi or aspiration of gastric contents, and it can range from mild, self-limiting illness to severe, life-threatening disease. The physiological consequences of pneumonia arise from a combination of alveolar consolidation, ventilation–perfusion mismatch and systemic inflammatory responses.
What You Need to Know
Pneumonia is an acute infection of the lung parenchyma in which inflammatory processes disrupt normal alveolar function. In healthy lungs, alveoli remain air-filled and dry, allowing efficient diffusion of oxygen into the pulmonary capillaries. In pneumonia, inhaled or aspirated pathogens trigger a local immune response within the alveoli. Inflammatory mediators increase capillary permeability and recruit neutrophils into the air spaces. As a result, protein-rich fluid, immune cells, and cellular debris accumulate within the alveoli, producing consolidation and reducing the effective surface area available for gas exchange.
Although the airways themselves may remain patent, alveolar ventilation is impaired in affected regions. Blood continues to flow through these poorly ventilated alveoli, creating ventilation–perfusion mismatch. The key physiological disturbances that drive symptoms in pneumonia include:
Alveolar consolidation, where air spaces fill with inflammatory exudate rather than air
Ventilation–perfusion mismatch, due to continued perfusion of poorly ventilated lung regions
Impaired oxygen diffusion, resulting from fluid-filled alveoli and inflammatory thickening
These changes reduce arterial oxygen levels and increase the work of breathing. Hypoxaemia may develop rapidly, particularly during exertion when oxygen demand rises or in patients with limited respiratory reserve. The severity of physiological impairment varies widely and depends on the extent and distribution of lung involvement, the virulence of the infecting organism, and the host immune response. Older adults and individuals with pre-existing lung or cardiac disease are especially vulnerable because compensatory mechanisms are often limited, allowing relatively focal infection to produce significant respiratory compromise.
Beyond the Basics
Initiation of Infection and the Host Immune Response
Pneumonia develops when pathogens overcome normal airway defences and reach the alveoli. This can occur through inhalation of infectious droplets, aspiration of oropharyngeal secretions, or less commonly via haematogenous spread from another site of infection. Once within the alveoli, pathogens are detected by resident alveolar macrophages, which act as the first line of immune defence. These cells release cytokines and chemokines that signal the presence of infection and initiate a coordinated inflammatory response.
Neutrophils are rapidly recruited from the circulation and migrate across the alveolar–capillary barrier into the alveolar spaces. Their role is to phagocytose and destroy pathogens, but in doing so they release proteolytic enzymes and reactive oxygen species that damage surrounding alveolar epithelium. This collateral injury increases capillary permeability and amplifies local inflammation. While necessary for pathogen clearance, the intensity of this response largely determines the degree of alveolar dysfunction and clinical severity.
Alveolar Consolidation and Reduced Gas Exchange
As inflammation progresses, protein-rich fluid, neutrophils, fibrin, and cellular debris accumulate within the alveoli. Air-filled spaces are replaced by inflammatory exudate, a process known as consolidation. Consolidated alveoli are effectively excluded from gas exchange because oxygen cannot diffuse efficiently through fluid-filled spaces to reach capillary blood.
Blood flowing through capillaries adjacent to these alveoli remains poorly oxygenated, creating areas of intrapulmonary shunt. In shunt physiology, blood bypasses ventilated alveoli altogether, which is why hypoxaemia in pneumonia can be difficult to correct with supplemental oxygen alone, particularly when consolidation is extensive.
Ventilation–Perfusion Mismatch and Hypoxaemia
Pneumonia produces a heterogeneous pattern of lung involvement. Some alveoli are completely consolidated, others are partially filled, and surrounding regions may be affected by inflammation and oedema. This uneven distribution of ventilation relative to perfusion worsens ventilation–perfusion mismatch. Areas of lung with reduced ventilation continue to receive blood flow, lowering overall arterial oxygen levels.
Hypoxic pulmonary vasoconstriction attempts to compensate by diverting blood away from poorly ventilated regions toward healthier alveoli. However, this mechanism is often insufficient, especially in widespread pneumonia or when systemic inflammation disrupts normal vascular responses. As a result, hypoxaemia develops and may worsen rapidly during exertion or as disease progresses.
Effects on Lung Mechanics and Work of Breathing
Inflammation, alveolar filling, and interstitial oedema reduce lung compliance, making the lungs stiffer and more difficult to inflate. Greater pressure is required to achieve adequate tidal volumes, increasing the work of breathing. Patients compensate by increasing respiratory rate and adopting shallow breathing patterns to reduce the effort of each breath.
This compensatory strategy is inefficient and limits alveolar ventilation, particularly during increased metabolic demand. Persistent tachypnoea and elevated work of breathing can lead to respiratory muscle fatigue. When ventilatory effort can no longer be sustained, ventilatory failure may develop, necessitating respiratory support.
Systemic Inflammatory Response and Complications
Severe pneumonia can extend beyond the lungs and trigger a systemic inflammatory response. Circulating cytokines cause fever, tachycardia, vasodilation, and increased capillary permeability throughout the body. In some patients, this progresses to sepsis and septic shock, with impaired tissue perfusion and multiorgan dysfunction.
Within the lungs, widespread inflammatory signalling may increase alveolar–capillary permeability beyond the initially infected regions. This can lead to diffuse lung injury and, in severe cases, progression to acute respiratory distress syndrome. The transition from localized infection to systemic inflammation marks a critical escalation in disease severity and is associated with significantly higher morbidity and mortality.
Clinical Connections
Pneumonia commonly presents with cough, fever, dyspnoea, and pleuritic chest pain, reflecting inflammation of the alveoli and adjacent pleura. Auscultation may reveal crackles from air moving through fluid-filled alveoli or bronchial breath sounds over areas of consolidation where normal air-filled lung has been replaced by inflammatory exudate. Importantly, arterial oxygen levels may fall early, even when symptoms appear mild, because ventilation–perfusion mismatch and shunt physiology impair gas exchange before overt respiratory distress develops.
Several clinical features help identify physiological severity and risk of deterioration:
Hypoxaemia disproportionate to symptoms, indicating significant ventilation–perfusion mismatch
Localised bronchial breath sounds or dullness to percussion, suggesting alveolar consolidation
Systemic signs such as tachycardia, hypotension, or confusion, pointing toward evolving sepsis
Chest imaging supports diagnosis and assessment of extent, typically demonstrating focal, multilobar, or diffuse infiltrates that correspond to areas of alveolar filling. The distribution and progression of radiographic changes often parallel clinical severity. Management is directed at eradicating the infecting organism with appropriate antimicrobial therapy, supporting oxygenation, and identifying complications early. Oxygen supplementation addresses hypoxaemia, while prompt recognition and treatment of sepsis, respiratory failure, or progression to diffuse lung injury are critical to preventing escalation. Continuous reassessment of oxygen requirements, respiratory effort, and systemic signs allows timely adjustment of therapy as the inflammatory process evolves.
Concept Check
Why does pneumonia primarily impair gas exchange rather than airflow?
How does alveolar consolidation lead to intrapulmonary shunting?
Why may hypoxaemia in pneumonia be difficult to correct with oxygen alone?
How does pneumonia increase the work of breathing?
Why can severe pneumonia progress to ARDS?