Physical Address
304 North Cardinal St.
Dorchester Center, MA 02124
Lung-Kidney Cross-Talk
Objectives
This chapter will:
- 1.
Review the pathophysiology of acute lung injury.
- 2.
Summarize the emerging understanding of lung-kidney cross-talk in the critically ill patient.
- 3.
Identify the mechanisms by which acute kidney injury may potentiate acute lung injury.
Growing evidence points to harmful interactions between lung and kidney dysfunctions, which suggests a partial explanation for the natural history of multiorgan failure. This is important because typically the cause of death in patients with acute respiratory failure is sepsis and/or multiorgan failure rather than refractory hypoxemia. Critically ill patients with acute respiratory failure have an estimated incidence of acute kidney injury (AKI) of 35% and face a mortality rate as high as 80% when their illness is combined with AKI, with the rate rising with AKI severity. Observational data indicate that 75% of all patients with respiratory failure require some form of renal replacement therapy.
Alveolar-Capillary Barrier as a Functional Unit
The alveolus represents the actual site of gas exchange with a total surface area of approximately 50 to 100 m 2 . An extensive capillary network occupies most of the area surrounding the alveoli, which makes the thin alveolar-capillary membrane (0.5–2 µm) highly efficient but also susceptible to injury. Under resting conditions, 25% to 33% of the diffusion area is sufficient to ensure gas exchange, and the high diffusion reserve is used only under conditions of increased cardiac output and/or impaired diffusion (e.g., prolonged diffusion abnormality in pulmonary edema or pneumonia, and capillary rarefaction in emphysema or lung fibrosis). Because the diffusion coefficient for CO 2 is 20 times higher than that for oxygen, any disturbance in alveolar diffusion primarily manifests as hypoxemia without influencing CO 2 elimination. This is in contrast to hypercapnia, which is mainly a result of alveolar hypoventilation (e.g., respiratory muscle weakness and hyperinflation).
To ensure adequate function of the alveolar-capillary barrier, it is important that the alveoli and interstitium remain not overloaded with fluid. This is maintained by a complex interplay of alveolar hydrostatic and capillary protein osmotic pressures, which leads to passive fluid transport to the capillary bed and lymphatic drainage of fluid accumulated in the interstitium. Importantly, type 1 and 2 pneumocytes express apical sodium channels (ENaCs) and basolateral sodium-potassium transporting adenosine-5′-triphosphatases (Na + -K + -ATPases) that actively pump sodium into the interstitium with secondary chloride adsorption via apical cystic fibrosis transmembrane conductance regulators (CFTRs). This promotes passive fluid clearance across the alveolar epithelium, which potentially is facilitated by aquaporin 5 water channels ( Fig. 121.1 ). Notably, the lung and the kidney appear to have similar electrolyte and water channels, and this issue is addressed below. In the setting of an imbalance in any of these components (e.g., increasing capillary hydrostatic pressure in pulmonary congestion resulting from left heart failure or fluid overload), interstitial pulmonary edema can be the consequence, followed by alveolar pulmonary edema.
Acute Lung Injury
Acute lung injury (ALI) describes the classic response to different inciting inflammatory insults, which result in diffuse pulmonary epithelial and endothelial cellular damage, leading to increased alveolar-capillary permeability and the development of protein-rich inflammatory pulmonary edema. The primary molecular and cellular determinants of ALI are poorly understood and are likely to be heterogeneous. There is considerable evidence that an increase in lung vascular permeability occurs primarily at the level of the lung microcirculation and leads to interstitial and alveolar fluid accumulation. This fluid is characterized by high concentrations of proteins and cytokines (e.g., interleukin-1, interleukin-6, and tumor necrosis factor-alpha), which activate secondary neutrophil- and platelet-dependent pathways that augment lung injury and vascular thrombi.
Acute respiratory distress syndrome (ARDS) is the clinical manifestation of ALI with an incidence of 10.4% of intensive care unit admissions. Among the most common clinical disorders associated with ARDS development are pneumonia and extrapulmonary sepsis (40% to 50%), aspiration, and noncardiogenic shock. Recently, a new consensus definition of ARDS, the Berlin definition, was published. This definition introduces three levels of severity, according to the PaO 2 /FiO 2 ratio and a minimum positive end-expiratory pressure, that should reflect the underlying lung injury. Because hydrostatic edema as a result of left ventricular failure and/or fluid overload may superimpose ARDS, the Berlin definition has removed the pulmonary artery wedge pressure criterion for ARDS diagnosis. Patients would have ARDS if they meet the following diagnostic criteria: (1) acute hypoxemic respiratory failure; (2) onset within 1 week of a known clinical insult, or new worsening respiratory symptoms; (3) bilateral airspace disease on chest x-ray or computed tomography not fully explained by effusions, lobar or lung collapse, or nodules; and (4) cardiac failure not the primary cause. The term ALI as a clinical categorization no longer exists. Under the Berlin definition, patients with a PaO 2 /FiO 2 ratio of 200 to 300 mmHg will now be diagnosed with “mild ARDS.”
Conceptually, ARDS requires increased lung fluid in the absence of underlying heart failure (noncardiogenic pulmonary edema) , which leads to noncompliant and nonaerated lungs with the consistency of a “wet heavy sponge” and an increase in extravascular lung fluid from 5 mL/kg to 15 mL/kg ( Fig. 121.2 ). The increased lung weight can produce compression atelectasis with further impairment of lung mechanics and gas exchange. Additional microvascular thrombi promote ventilation/perfusion mismatching and the development of pulmonary hypertension (PH), all of which result in severe hypoxemia and hypercapnia resulting from increased alveolar dead space.
In cardiogenic pulmonary edema, alveolar fluid theoretically can be absorbed across the intact alveolar epithelium and lead to edema resolution once the elevated pulmonary microvascular pressure normalizes. This is in contrast to ARDS, in which the impaired alveolar fluid clearance is a result of (1) an injury to the alveolar-capillary barrier and (2) inflammation/oxidant-mediated injury and/or downregulation of the epithelial active ion transport system. Experimental studies have attempted to restore and/or potentiate electrolyte movement across the alveolar epithelial barrier. They have found that the activation of various transcriptional and translational pathways, and hormonal (e.g., dopamine, corticosteroids, and thyroid hormone) and cAMP-induced stimulation of sodium conductance can reduce bronchoalveolar lavage protein levels and improve alveolar fluid clearance and respiratory mechanics. However, no pharmacologic treatment addressing impaired vectorial fluid transport across the alveolar epithelium has as yet resulted in an improvement in survival, most likely because of the lack of functional alveolar epithelium and microvascular endothelium.
In summary, ARDS is characterized by the disruption of the endothelial-epithelial barrier and alveolar damage that lead to acute, diffuse, noncardiogenic, inflammatory, and protein-rich pulmonary edema with increased lung weight, loss of lung aeration, and respiratory failure. Airspace infiltration with neutrophils amplifies and sustains the lung injury. Impaired alveolar fluid clearance is mediated by several mechanisms, including dysfunction of the transepithelial ion transport system.
You're Reading a Preview
Become a Clinical Tree membership for Full access and enjoy Unlimited articles
If you are a member. Log in here