Intracellular and subcellular oedema and dehydration.
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).
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001834:Body Water / Q000378:metabolism*; D002199:Capillary Permeability; D002463:Cell Membrane Permeability; D003681:Dehydration / Q000378:metabolism; D005089:Exocytosis; D005966:Glucuronidase / Q000378:metabolism; D066298:In Vitro Techniques; D007424:Intracellular Fluid / Q000378:metabolism; D007773:Lactates / Q000378:metabolism; D008264:Macrophages / Q000201:enzymology; D008928:Mitochondria / Q000378:metabolism; D009997:Osmotic Pressure; D010101:Oxygen Consumption; D011650:Pulmonary Alveoli / Q000098:blood supply / Q000378:metabolism; D011654:Pulmonary Edema / Q000378:metabolism* / Q000503:physiopathology; D011817:Rabbits; D012964:Sodium / Q000378:metabolism
D007773:Lactates; D000255:Adenosine Triphosphate; D012964:Sodium; D005966:Glucuronidase