ARDS Pathogenesis

Question 1

Causes

Answer 1

=>Direct: contusions, aspiration, pneumonia, PE.
=>Indirect: Trauma, Drowning, burns, (inhalational injury), reperfusion injury, transfusion (TRALI), pancreatitis.

Question 2

Pathogenesis of ARDS

Answer 2

=>Central to the development of ARDS
Diffuse Alv. Damage due to
Noncardiogenic Pulmonary oedema sec. to:
* Damage to Alveolo- capillary barrier–>
complex alveolar Inflammatory exudate
* Surfactant dysfunction-->alveolar collapse

=>Phases of Injury

1️⃣ Exudative phase (ARDS onset)
* Pulmonary edema + alveolar flooding.
* Damage to alveolo-capillary barrier.
* Intense inflammation and surfactant dysfunction.

2️⃣ Fibrosing alveolitis
* Marked by fibroblast proliferation.
* Type III collagen deposition → fibrosis.
* Occurs early in severe cases.

Question 3

Alveolo-Capillary Barrier- what is it composed of?

Answer 3

• Separates alveolar gas from pulmonary circulation.
• Barrier to protein influx.
  *Consists of: Endothelium (capillary) + epithelium (alveolar).

Question 4

Alveolar Epithelium

Answer 4

->Controls water clearance.
->Composed of:
* Type I pneumocytes – 90 %, gas exchange.
* Type II pneumocytes – 10 %, metabolically active, surfactant secretion, progenitor for Type I.
->Alveolar lining fluid = Filterred plasma + proteins + surfactant + cells
* Cells in alveoli: macrophages (main), lymphocytes.

->In ARDS
* Damage to alveolo-capillary barrier → bidirectional leakage of fluid → protein-rich edema → impaired gas exchange.

Question 5

Damage to Epithelium and Endothelium

Answer 5

=>Epithelial Damage
* Leads to surfactant dysfunction, cytokine release, impaired reabsorption of alveolar edema.

=>Endothelium
* Plasma VWF ↑ → predictor of outcomes in ARDS.
* Microvascular thrombosis common.–>Contributes to pulmonary HTN + impaired ventilation.

=>Inflammatory Mediators
* Most important ones: IL-6, IL-8, IL-1β, TNF-α.
* IL-10 also involved in their antagonism.

Question 6

Normal BAL and BAL in ARDS

Answer 6

=>Neutrophils
* Major cell type in BAL during ARDS.
* Activated Neutrophils→ release cytokines, eicosanoids, reactive O₂ species → damage to alveolar BM + ↑ permeability.

=>Alveolar macrophages :
* Normally host defence, but in ARDS contribute to injury.
* Activation via stretch → release cytokines.

Question 7

Resolution of Alveolar oedema

Answer 7

=>Resolution of ARDS / Fibrosing Alveolitis
* Histological evidence of fibrosing alveolitis (mesenchymal cells + new vessels in alveoli) usually found after 5 days of onset.

->Clinical resolution of ARDS usually occurs if:
* Underlying cause promptly treated.
* Supportive care provided.

->Alveolar Edema Resolution
* Active transport of Na⁺ by Type II cells.
* Type II cells proliferate → re-epithelialisation → differentiation into Type I cells.

Answer 8

=>Diffuse alveolar Injury(hallmark)
=>Damage to Alveolocapillary membrane
=>Leakage of protenaceous fluid in alveoli->impaired gas exchange and ⬇️ed compliance
=>Epithelial damage->surfactant dysfunction->alveolar collapse, impaired absorption of oedema fluid
=>Endothelial injury-> ⬆️ plasma VwF, microvascular thrombosis->PHTN, inflammatory mediator release
=>Release of inflammatory mediators-IL6, IL8, TNF alfa,
=>Fibroblast proliferation->fibrosing alveolitis
=>Resolution of alveolar oedema via active transport of Na by Type II cells.
=>Re epithelisation by proliferation of Type II cells which differentiate to Type I cells