Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0034063 (pulmonary edema)
 10,665 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Changes in intracellular water content appear to be common abnormalities induced by a wide variety of pathogenic mechanisms. Such changes in cell water produce changes in the water in various subcellular organelles bound by semipermeable membranes. Cell and subcell functions then alter in their turn. In isolated alveolar macrophages (rabbit), intracellular and intramitochondrial oedema reduces mitochondrial O2 utilization. Metabolic control is maintained because lactate production reverses (Pasteur effect). On reconstitution, O2 utilization and lactate production return towards normal, indicating reversibility. Cellular and intramitochondrial dehydration also reduces mitochondrial O2 utilization but metabolic control is lost because lactate production also decreases. Osmotic reconstitution does not reverse the abnormality. Exposure to hypotonic media leads to release of lysosomal enzymes (beta-glucuronidase, EC 3.2.1.31) to the extracellular phase of isolated alveolar macrophages. Some of this release is caused by exocytosis although, at low osmotic concentrations, intralysosomal oedema ultimately ruptures lysosomes, with extensive discharge of enzyme. In turn, lysosomal enzymes may injure more normal cells. Impairment of energy metabolism caused by hypoxia leads to intracellular oedema, because Na+ accumulates in the cells when ATP is no longer available for the sodium pump. Continued studies of the disorders in cell physiology caused by changes in cell and subcell water should provide important new insights into a wide variety of disease states (including pulmonary oedema).
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PMID:Intracellular and subcellular oedema and dehydration. 104 40

A major function of the alveolar epithelium is to keep the airspace free of fluid and preserve gas exchange. Since Na-K-ATPase is believed to be important in this process, we hypothesized that Na-K-ATPase in the rat lung would increase in response to acute lung injury with pulmonary edema. Na-K-ATPase localization, mRNA expression, and protein levels were determined in hyperoxic lung injury. Adult male rats were exposed to greater than 97% oxygen for 60 h followed by recovery in room air. At 60 h of hyperoxia, the wet-to-dry lung weights increased, consistent with edema. Within the alveolar capillary region, the sodium pump remained localized to the type II cell basolateral membrane by immunocytochemistry. By Northern blot analysis, the level of total lung mRNA expression of the alpha 1- and beta-subunits of Na-K-ATPase increased three- to fourfold during hyperoxia compared with unexposed rats. Total lung Na-K-ATPase membrane protein, visualized with a Western blot technique, appeared to increase by 24 h of hyperoxic insult when compared with levels in unexposed animals. The increase in sodium pump gene expression that occurs during hyperoxic insult, followed by an increase in sodium pump membrane protein, suggests that type II cells increase their Na-K-ATPase synthesis as an early response to pulmonary edema and/or hyperoxia.
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PMID:Upregulation of rat lung Na-K-ATPase during hyperoxic injury. 165 77

Pulmonary oedema is a life-threatening condition that frequently leads to acute respiratory failure. From a physiological perspective, pulmonary oedema develops either because of an increase in lung vascular hydrostatic pressure or an increase in lung vascular permeability. Resolution of alveolar oedema depends on the active removal of salt and water from the distal air spaces of the lung across the distal lung epithelial barrier. Much has been learned about the molecular and cellular basis for oedema fluid reabsorption, including the role of apical ion transporters for sodium (epithelial sodium channel) and chloride (cystic fibrosis transmembrane conductance regulator), as well as the central importance of the sodium pump. The rate of fluid clearance can be upregulated by both catecholamine-dependent and -independent mechanisms. Injury to the alveolar epithelium can disrupt the integrity of the alveolar barrier or downregulate ion transport pathways, thus, reducing net alveolar fluid reabsorption and enhancing the extent of alveolar oedema. Endogenous catecholamines upregulate alveolar fluid clearance in several experimental models of acute lung injury, but this upregulation may be short term and insufficient to counterbalance alveolar flooding. There is new evidence, however, that pharmacological treatment with beta2-adrenergic agonists and/or epithelial growth factors may influence a more sustained stimulation of alveolar fluid reabsorption and in turn facilitate recovery from experimental pulmonary oedema. Similar results have been achieved experimentally by gene transfer to enhance the abundance of sodium transporters in the alveolar epithelium. Clinical studies show that impaired alveolar fluid transport mechanisms contribute to the development, severity and outcome of pulmonary oedema in humans. Very recent data suggest that mechanisms that augment transepithelial sodium transport and enhance the clearance of alveolar oedema may lead to more effective prevention or treatment for some types of pulmonary oedema.
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PMID:Alveolar epithelial fluid transport in acute lung injury: new insights. 1244 88