Porth's Essentials of Pathophysiology, 4e

593

Disorders of Ventilation and Gas Exchange

C h a p t e r 2 3

The pathogenesis of ALI/ARDS is unclear, although both local and systemic inflammatory responses occur. It is thought that dysregulated inflammation, accumulation of neutrophils, uncontrolled activation of coagulation pathways, and altered permeability of the endothelial and epithelial barriers all play a role. 67 Initially, a direct or indirect pulmonary insult is believed to promote the accumulation of neutrophils in the microcirculation. These neutrophils activate and migrate in large numbers across the alveolar epithelial surfaces, releasing prote- ases, cytokines, and reactive oxygen species that lead to increased permeability in the alveolar epithelial cells and damage to type I and type II alveolar cells. This in turn leads to pulmonary edema, hyaline membrane for- mation, and loss of surfactant that decrease pulmonary compliance and make air exchange difficult. Clinical Features Clinically, ALI/ARDS is marked by a rapid onset, usually within 12 to 18 hours of the initiating event, of respira- tory distress, an increase in respiratory rate, and signs of respiratory failure. Chest radiography shows dif- fuse bilateral infiltrates of the lung tissue in the absence of cardiac dysfunction (non-cardiogenic pulmonary edema). Marked hypoxemia occurs that is refractory to treatment with supplemental oxygen therapy. Many per- sons with ARDS have a systemic response that results in multiple organ failure, particularly of the renal, gastro- intestinal, cardiovascular, and central nervous systems. The treatment goals in ARDS are to supply oxy- gen to vital organs and provide supportive care until the condition causing the pathologic process has been reversed and the lungs have had a chance to heal. Assisted ventilation using high concentrations of oxy- gen may be required to correct the hypoxemia. Positive end-expiratory pressure breathing, which increases the

CHART 23-2   Conditions inWhich ARDS Can Develop* Aspiration Near-drowning Aspiration of gastric contents Drugs, Toxins, Therapeutic Agents Free-base cocaine smoking Heroin Inhaled gases (e.g., smoke, ammonia) Breathing high concentrations of oxygen Radiation

Infections Septicemia Trauma and Shock Burns

Fat embolism Chest trauma Disseminated Intravascular Coagulation Multiple BloodTransfusions

*This list is not intended to be inclusive.

As the disease progresses, the work of breathing becomes greatly increased as the lung stiffens and becomes more difficult to inflate. There is increased intrapulmonary shunting of blood, impaired gas exchange, and hypox- emia despite high supplemental oxygen therapy. Gas exchange is further compromised by alveolar collapse resulting from abnormalities in surfactant production. When injury to the alveolar epithelium is severe, disorga- nized epithelial repair may lead to fibrosis.

Protein-rich edematous fluid

Alveolus

Platelets

Sloughing type I alveolar cells

Hyaline membrane

Type II alveolar cell

Alveolar macrophage

Fibrin

Cellular debris

FIGURE 23-15. Mechanism of lung changes in acute respiratory distress syndrome. Injury and increased permeability of the alveolar capillary membrane allow fluid, protein, cellular debris, platelets, and blood cells to move out of the vascular compartment and enter the interstitium and alveoli. Activated neutrophils release a variety of products that damage the alveolar cells and lead to edema, surfactant inactivation, and formation of a hyaline membrane. PAF, platelet activating factor.

Injured endothelial cells

Inactivated surfactant

Leukotrienes Oxidants PAF Proteases

Edematous interstitium

Capillary

Neutrophil

Red blood cells

Plasma proteins