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The Acute Respiratory Distress Syndrome

Claude A. Piantadosi, MD; and David A. Schwartz, MD, MPH
[+] Article, Author, and Disclosure Information

From Duke University Medical Center, Durham, North Carolina.

Grant Support: By the National Heart, Lung, and Blood Institute, National Institutes of Health (PO1 HL 31992-18).

Potential Financial Conflicts of Interest: None disclosed.

Requests for Single Reprints: Claude A. Piantadosi, MD, Division of Pulmonary and Critical Care Medicine, Box 3315, Duke University Medical Center, Durham, NC 27710; e-mail, piant001@mc.duke.edu.

Current Author Addresses: Dr. Piantadosi: Division of Pulmonary and Critical Care Medicine, Box 3315, Duke University Medical Center, Durham, NC 27710.

Dr. Schwartz: Division of Pulmonary and Critical Care Medicine, Box 2629, Duke University Medical Center, Durham, NC 27710.

Ann Intern Med. 2004;141(6):460-470. doi:10.7326/0003-4819-141-6-200409210-00012
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The lung's alveolar–capillary structure normally provides a large surface for gas exchange and a tight barrier between alveolar gas and pulmonary capillary blood. Diffuse damage to the alveolar region occurs in the acute or exudative phase of acute lung injury and ARDS (Figure 2). This damage involves both the endothelial and epithelial surfaces and disrupts the lung's barrier function, flooding alveolar spaces with fluid, inactivating surfactant, causing inflammation, and producing severe gas exchange abnormalities and loss of lung compliance. These events are reflected in the presence of bilateral infiltrates, which are indistinguishable by conventional radiology from cardiogenic pulmonary edema (11). Computed tomography of the chest often demonstrates heterogeneous areas of consolidation and atelectasis, predominantly in the dependent lung (1213), although areas of apparent sparing may still show inflammation. Pathologic findings consist of diffuse alveolar damage, including capillary injury, and areas of exposed alveolar epithelial basement membrane (1416). The alveolar spaces are lined with hyaline membranes and are filled with protein-rich edema fluid and inflammatory cells. The interstitial spaces, alveolar ducts, small vessels, and capillaries also contain macrophages, neutrophils, and erythrocytes.

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Figure 1.
Relationships between extravascular lung water and development of hypoxemia in the acute respiratory distress syndrome.

The graph illustrates the decrease in Pao2 as a function of the increases in lung water and mean pulmonary artery pressure (PAP ).

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Figure 2.
Cellular and molecular events that interfere with gas exchange in the acute respiratory distress syndrome.

These events include endothelial activation, recruitment of inflammatory cells, activation of coagulation, and inhibition of fibrinolysis. See text for explanation.

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Figure 3.
Capillary fluid filtration described by the Starling equation.

Pulmonary capillaries filter fluid (Jv) in proportion to the net capillary filtration pressure minus the net osmotic pressure across the vessel wall. The hydraulic conductance (Kf,c) is the capacity to filter fluid as filtration pressure increases relative to number and size of endothelial openings per unit surface area. The osmotic reflection coefficient (σ ) determines osmotic permeability to specific proteins (0 is permeable and 1 is impermeable). Capillary damage in the acute respiratory distress syndrome may increase Kf,c and decrease σ , increasing capillary fluid flux at constant hydrostatic pressure. P = mean capillary hydrostatic pressure; P = mean interstitial hydrostatic pressure; π = interstitial protein osmotic pressure; π = plasma protein osmotic pressure.

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Figure 4.
The lung's edema safety factor in the acute respiratory distress syndrome.

The safety factor prevents airspace flooding during increases in filtration (hydrostatic) pressure (arrow). The safety factor has 3 components arranged in a series (squares 1, 2, and 3). As filtration pressure increases, dilute fluid is forced into the interstitial space, which increases the absorption force (arrowhead) opposing it (square 1). The increase in interstitial fluid volume causes perivascular swelling (square 2), and interstitial fluid is removed at a greater rate (square 3) by lung lymphatics (Ly). A breech of the alveolar epithelium allows plasma and interstitial fluid to leak into the airspaces faster than salt and water can be pumped back into the interstitial space. ENaC = epithelial sodium channel.

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Figure 5.
Pulmonary edema formation in congestive heart failure (CHF) and the acute respiratory distress syndrome (ARDS).

In CHF, the edema safety factor prevents pulmonary edema fluid accumulation until pulmonary capillary pressure is elevated to approximately 22 mm Hg. In ARDS, an increase in capillary permeability produces edema at normal capillary pressures and greatly increases the rate of edema formation at elevated capillary pressures.

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Figure 6.
The effects of alveolar–capillary leak and positive end-expiratory pressure (PEEP) on pulmonary gas exchange.

The left half of the diagram shows how alveolar flooding occurs when the capillary leak rate exceeds the safety factor. Flooded alveoli are noncompliant and become hypoxic because of poor or absent ventilation. Pulmonary arterial (PA) blood entering such units cannot be oxygenated and decreases the oxygen saturation of blood returning to the left atrium (LA ). Local hypoxic pulmonary vasoconstriction diverts PA blood flow to better ventilated alveoli, which improves ventilation–perfusion matching. If hypoxic pulmonary vasoconstriction is absent or large areas of lung are flooded, pulmonary venous oxygen saturation decreases and hypoxemia occurs. The right half of the diagram illustrates the effect of PEEP, which stabilizes alveoli that are then better able to exchange gas because they have more surface area. When pulmonary venous oxygen saturation increases, hypoxic pulmonary vasoconstriction is relieved, allowing more uniform distribution of blood flow. However, PEEP may overdistend healthy alveoli, thereby damaging functional gas exchange units and redirecting blood flow toward damaged alveoli, worsening the capillary leak rate. ARDS = acute respiratory distress syndrome.

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