Riassunto esame Pneumologia, prof. Centanni, libro consigliato Ards, Robbins

ARDS

• =severe Acute Lung Injury (ALI/noncardiogenic pulmonary edema)=abrupt onset of significant

hypoxemia and diffuse pulmonary infiltrates in absence of cardiac failure

• inflammation-associated increase in pulmonary vascular permeability, epithelial and endothelial cell

death.

Histologic manifestation=Diffuse Alveolar Damage (DAD); most cases associated with an underlying

etiology (sepsis); no etiologic association Acute Interstitial Pneumonia. Mainly due to a



combination of predisposing factors (shock, oxygen therapy, sepsis)

MORPHOLOGY:

♣ Acute heavy, firm, red, boggy lungs; congestion, interstitial and intra-alveolar edema,

inflammation, fibrin deposition, DAD;

♣ alveolar walls lined by waxy hyaline membranes (fibrin-rich edema fluid+cytoplasmic and lipid

remnants of necrotic epithelium)

♣ Organizing stage: type II pneumocytes proliferation granulation tissue response in alveolar walls

and spaces; resolves in most cases minimal functional impairment;

♣ sometimes fibrotic thickening of alveolar septa occurs (proliferation of interstitial cells, deposition of

collagen)

PATHOGENESIS:

• integrity of alveolar-capillary membrane (microvascular endothelium+alveolar epithelium)

compromised by endothelial/epithelial injury or both;

• endothelin and vWF (markers of endothelial injury and activation) at high levels in serum;

• swelling, vacuolization, bleb formation, necrosis;

• increased vascular permeability, alveolar flooding, loss of diffusion capacity, surfactant

abnormalities (damage to type II pneumocytes);

• microthrombiischemic injury.

Hyaline membranes=protein-rich edema fluid entrapping debris of dead alveolar epithelial cells

Lung injury mainly caused by imbalance of pro-inflammatory and anti-inflammatory mediators (probably

due to NFKB activation)

Acute insult 30 minutes: increased synthesis of IL-8, IL-1, TNF by pulmonary macrophages



endothelial activation pulmonary microvascular sequestration and activation of neutrophils (important role

of NEUTROPHILS)

Histology: increased neutrophils in vascular space, interstitium, alveoli. Neutrophils: upregulated expression

of adhesion moleculesbinding to ligands on activated endothelial cells/activated neutrophils get “stiff” and

less deformable trapped in narrow pulmonary capillary beds. Activated neutrophils: release of oxidants,

proteases, PAF, LTsdamage to alveolar epithelium

Combined damage of epithelium and endotheliumvascular leakiness, loss of surfactantalveolar unit

unable to expand

Dysregulation of coagulation system: increased levels of Tissue Factor, decreased Protein C in plasma and

BAL fluid; coagulation pathway=pro-inflammatory signal (thrombinpromotion of neutrophils adhesion to

endothelium)

RESOLUTION:

∼ Macrophagesremoval of exudates and tissue debris;

∼ epithelial cells recovered by proliferation of surviving type II pneumocytes lining basement

membranethey give rise to type I cells(=majority of alveolar epithelium);