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Pathogenesis of ARDS

Syndromus respiratorius acutus arduus

For medical students2 min readUpdated 2026-10-10

Acute Respiratory Distress Syndrome (ARDS) is a severe pathological condition developing 20–40 hours after exposure to an injurious factor. Its pathogenesis involves a cascade of inflammatory responses, a sharp increase in the permeability of the blood-air barrier, pulmonary edema, and progressive respiratory failure.

TimelineInitial signs appear 20–40 hours after exposure to the precipitating factor.
Key mechanismDamage to type II alveolar cells and surfactant depletion.
Vascular changesDevelopment of pulmonary hypertension due to vasoconstriction and microthrombosis.
ABG dynamicsTransition from acute respiratory alkalosis to hypercapnia and acidosis.

Acute Injury and Exudative Phase

The triggering mechanism of the syndrome involves biologically active substances that cause massive activation of alveolar macrophages, neutrophils, and other granulocytes. These cells adhere to the microvascular endothelium and release lysosomal enzymes, cytotoxic agents, and reactive oxygen species, triggering lipid peroxidation.

Primary targets for injury include:

Such destruction leads to a sharp increase in barrier permeability to proteins, including fibrin, and blood cellular elements. As a result, interstitial and alveolar edema rapidly accumulates, gas exchange is impaired, and respiratory hypoxia develops.

Pathophysiology and Vascular Alterations

A crucial role in the development of the pathology is played by damage to type II alveolar cells, which are responsible for surfactant production. Their destruction leads to alveolar collapse, atelectasis formation, a rapid drop in lung compliance, and an increase in intrapulmonary shunting.

Pronounced vascular disorders develop in the pulmonary microcirculation, leading to pulmonary hypertension. The causes are vascular occlusion by multiple thrombi and marked vasoconstriction. Spastic reactions are sustained by mediators such as:

Morphologically, this period is characterized by infiltration of the lung tissue with macrophages and lymphocytes, as well as proliferation of cells and the extracellular matrix.

Fibrotic Stage and Systemic Manifestations

In areas of the most intense injury, the fibrotic stage develops. Excessive influx of proteins and erythrocytes into the alveoli, combined with leukocyte migration, stimulates the synthesis of collagen, argyrophilic, and elastic fibers as well as extracellular matrix components, leading to localized pulmonary fibrosis.

Systemic changes encompass multiple organs and functions:

Mnemonic

Five steps of ARDS: Cell activation $\rightarrow$ Enzymes and edema $\rightarrow$ Surfactant failure and atelectasis $\rightarrow$ Pulmonary hypertension $\rightarrow$ Fibrosis and MODS.

Frequently asked questions

What clinical phases are distinguished in the course of ARDS?

The clinical course of acute respiratory distress syndrome involves three consecutive phases.

  • Acute phase — the exudative stage lasting about a week. Characterized by impaired alveolar-capillary membrane permeability with the development of non-cardiogenic alveolar and interstitial pulmonary edema.
  • Subacute phase — the proliferative stage lasting from 4 to 10 days. During this period, edema subsides, active proliferation of type II alveolar cells and migrating fibroblasts occurs, and reparative processes are completed.
  • Chronic phase — the fibro-proliferative stage. Distinguished by marked interstitial fibrosis, membrane thickening, alveolar obliteration, and microvascular rarefaction, leading to pulmonary hypertension.
What etiologic factors (injurious factors) most commonly trigger ARDS?

Acute respiratory distress syndrome is most frequently triggered by severe infectious and non-infectious factors.

Major causes include:

  • Sepsis — precipitates the syndrome in approximately 40% of patients.
  • Multiple trauma — causes the pathology in 10–34% of cases, including fractures complicated by fat embolism.
  • Aspiration — entry of water into the respiratory tract during drowning or acidic gastric contents (leads to ARDS in 10–36% of cases).
  • Massive transfusions — transfusion of large volumes of blood, plasma, or blood substitutes.
  • Pneumonia — severe bacterial and viral pulmonary infections (including atypical pneumonia caused by SARS-CoV).
What is the triggering mechanism in the development of ARDS?

The triggering mechanism is the release of biologically active substances that activate alveolar macrophages and neutrophils, causing injury to the blood-air barrier.

Why does lung compliance decrease in ARDS?

Lung compliance decreases due to damage to type II alveolar cells, surfactant depletion, and subsequent alveolar collapse (atelectasis).

How do acid-base balance parameters change over time?

Initial stages show acute respiratory alkalosis with low partial pressures of oxygen and carbon dioxide, which later transitions into hypercapnia and acidosis.

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