Renal Physiology Osmotic Homeostasis

Alterations inwater homeostasis can disturb cell size and function. Althoughmost cells can internally regulate cell volume in response to osmolar stress, neurons are particularly at risk given a combination of complex cell function and space restriction within the calvarium. Thus, regulating water balance is fundamental to survival. Through specialized neuronal “osmoreceptors” that sense changes in plasma osmolality, vasopressin release and thirst are titrated in order to achieve water balance. Fine-tuning of water absorption occurs along the collecting duct, and depends on unique structural modifications of renal tubular epithelium that confer a wide range of water permeability. In this article, we review the mechanisms that ensure water homeostasis as well as the fundamentals of disorders of water balance. Clin J Am Soc Nephrol 10: 852–862, 2015. doi: 10.2215/CJN.10741013 Crawlingout ondry landsomemillions of years later, terrestrial forms were faced with the diametrically opposite problems, as least with respect to water. Fluid conservation, rather thanfluid elimination,was the major concern. Instead of discarding their now unnecessary pressure filters and redesigning their kidneys as efficient secretory organs, the terrestrial vertebrates modified and amplified their existing systems to salvage the precious water of the filtrate. —Robert F. Pitts (1) So wrote the great physiologist Robert F. Pitts describing the evolution of organisms from the ocean to land (1). Marine animals survive in the high tonicity of seawater (500–1000 mOsm/kg) through a variety of mechanisms. The shark maintains a high tonicity in its body fluids (2,3), whereas dolphins absorb water from foodstuffswhile producing a highly concentrated urine through complex multilobed reniculate kidneys (4). For those of us on land, however, the challenge is not only water conservation but also water elimination, in our world of coffee shops, bottled water, and “hydration for health” philosophies. Water is themost abundant component of thehuman body, constituting approximately 50%–60% of body weight. Cell membranes, which define the intracellular compartment, and the vascular endothelium, which defines the intravascular component, are both water permeable. Because the intracellular space constitutes the largest body compartment, holding approximately two thirds of body fluid, changes in water homeostasis predominantly affect cells; water excess leads to cellular swelling, and water deficit leads to cellular shrinkage. For every 1 liter of water change, approximately 666 ml affect the cellular space, with only about 110 ml affecting the vascular space. Although cells have an innate capacity to respond to changes in cell volume when extracellular osmolality changes, the body protects cells primarily by tightly regulating extracellular osmolality. The amount of body water remains remarkably stable despite a huge range of water intake and a multitude of routes for water loss, including the respiratory and gastrointestinal tract, skin, and the kidneys. In this review, we explore the mechanisms that allow our bodies to respond to a wide range of external influences, finetuning the exact amount of urinary water excretion to match the body’s immediate needs. Maintaining Brain Cell Size With a plethora of capillaries descending through the subarachnoid space into the parenchyma, the brain is remarkably vascular. Astrocytes, star-shaped neuronal cells, encapsulate the capillaries, forming a “blood-brain barrier” and controlling many important neurologic functions. Although previously thought to be impermeable (5,6), the discovery of aquaporin (AQP) channels within the astrocyte has elucidated the water permeability of this barrier (7) (Figure 1). AQP4 localizes to the perivascular and subpial aspects of astrocytes, and controls both water efflux and influx, as well as regulates potassium homeostasis, neuronal excitability, inflammation, and neuronal signaling (8). By controlling water movement from brain parenchyma into the systemic circulation, AQP4 regulates brain water content and volume (9). By controlling water influx, AQP4 plays a role in the signaling cascade that occurs in the setting of hypo-osmolar–induced cerebral edema (10). Because the amount of intracellular water affects the concentration of intracellular contents and cell size, changes in osmolality can disturb the complex signaling network that orchestrates cell function. Given the complexity of brain function, even minor changes in neuron ionic composition and size can have profound effects on the processing and transmission of neuronal signals. Consequently, the brain has developed complex osmoregulatory mechanisms to defend against changes in plasma osmolality. Within minutes Department of Medicine, Beth Israel