Water metabolism

Thirst.

Thirst, the neurally induced motivation to find and consume water, is vital for defending against hypovolemia. Hypovolemic thirst is triggered when body water levels decrease by ~2%–3%. Hypertonic thirst occurs when osmolality increases to >290 mOsm/kg. Hypotension and hemorrhage also stimulate thirst. Peripheral and central mechanisms detect and react to these physiologic perturbations, leading organisms to seek and ingest appropriate fluids and fluid volumes. Drinking stimulates oral and pharyngeal receptors, thereby providing hypothalamic input to end the thirst sensation. Thirst ends even before plasma tonicity is reduced, likely preventing water overingestion. Thirst sensation is so powerful that normal subjects do not become hypernatremic if they have access to water. The inability to find, detect, react, request, or drink water adequately can cause severe illness and even death. The inability to self-regulate water intake—for example, during anesthesia and critical illness—makes patients totally dependent on caregivers to prevent and treat water disorders.

In the elderly, decreased kidney function, physical and cognitive problems, blunted thirst, and polypharmacy increase dehydration risk. There is also reduced renal sodium conservation (altered renal tubular function, greater peripheral atrial natriuretic peptide [ANP] concentrations but with reduced renal effects, lower renin–angiotensin–aldosterone secretion), decreased renal water excretion (lower renal blood flow, glomerular filtration rate, and distal renal tubular diluting capacity; greater renal passive water reabsorption and antidiuretic hormone [ADH] secretion), and reduced solute delivery caused by poor nutrition, limiting free water excretion. However, during dehydration, ADH secretion is often reduced, causing increased urinary output, and thus worsening the dehydration. A water-loss dehydration prevalence of up to 30% is observed in the elderly with concomitant morbidity. A positron emission tomography study revealed age-associated changes in central nervous system (CNS) satiation patterns in response to hyperosmolarity, which were associated with inadequate hydration. Paradoxically, elderly patients with worsening heart failure have increased thirst.

Metabolic water production.

Water is the principal end product of nutrient oxidation ( Table 97.1 ). Although more water molecules are produced per mole of fat than per mole of glucose (129 vs. 36) per kilocalorie, overall, aerobically oxidized carbohydrates contribute to ~15% more water molecules than lipids. An increased metabolic rate increases metabolic water production.

Renal function.

Renal function, the major mechanism defending against disordered water balance, protects blood osmolarity within a narrow range by altering urine osmolarity over a wide range (50–1200 mOsm/L). Concentrated urine is formed by creating an osmotic gradient that progressively increases from the corticomedullary border to the tip of the inner medulla. When the body must rid itself of excess water, urine can be diluted to as low as 50 mOsm/L.

Aging reduces the maximum urine-concentrating ability. Compared with younger individuals, those aged 60–79 years had a ~20% reduction in maximum urine osmolality, a ~50% decrease in the ability to conserve solute, and a 100% increase in minimum urine flow rate.

Insensible losses.

Insensible losses include transepidermal diffusion and evaporation of solute-free water plus evaporative water loss from the respiratory tract. Total insensible losses, ~800 mL/day in unstressed adults, are equally divided between skin and respiratory tract losses. Activity increases respiratory water losses so that active adults can lose up to 50 mL/h. Age reduces transepidermal water losses. In febrile patients, insensible losses can increase by fourfold to sixfold.

Respiratory water losses are affected by many factors (see Table 97.1 ). In normal subjects, mouth breathing resulted in 42% greater water loss compared with nose breathing. Cold exposure increases the need to humidify and warm inspired gases, thus increasing water losses. Using heat-and-moisture-retaining face masks during sleep reduced these losses. In critically ill patients, rapid spontaneous respiratory rates increase respiratory water losses, whereas endotracheal tubes bypass the natural warming and humidifying mechanisms, requiring inspiratory gases to be artificially humidified and warmed.

Sweating.

Sweating is mainly a mechanism of thermoregulation, although it also occurs in response to psychologic stress (see Table 97.1 ). Sweating involves the secretion of water-rich liquid by the eccrine glands located throughout the body surface and secretion of protein-, lipid-, and steroid-containing sweat by the apocrine glands found in the axilla, mammary, perineal, and genital areas. Thermoregulatory sweating mainly involves eccrine secretion occurring in response to intrinsic (fever, exercise) and extrinsic stimuli (elevated environmental temperatures). Maximum adult sweat rates can be 2–4 L/h during intense exercise.

Antidiuretic hormone (ADH)/arginine vasopressin (AVP).

ADH is a peptide produced by the neurons of the hypothalamic paraventricular and supraoptic nuclei as a prohormone, prepropressophysin (pre-provasopressin), comprising ADH, neurophysin II, and copeptin. Neurons containing osmoreceptors have excitatory synapses with prohormone neurosecretory cells. ADH, bound to the carrier protein neurophysin II, then travels down the pituitary stalk (infundibulum) axons to the posterior pituitary, where it is stored and secreted into the circulation. Plasma osmolarity and plasma ADH concentration have a linear relationship above the osmoregulatory threshold for ADH secretion. This threshold determines when decreased intravascular volume and blood pressure effect ADH release. The threshold is more permissive during hypovolemia. As the hypovolemia worsens, nonosmotically regulated ADH release can persist despite significant hyponatremia.

ADH production and secretion are also stimulated by angiotensin II and decreased blood volume detected by atrial stretch-sensitive low-pressure/vascular volume baroreceptors. A 5%–10% blood volume decrease is necessary for substantial ADH release. ADH is also secreted when carotid sinus and aortic arch baroreceptors detect a 10% blood pressure drop. Copeptin, the C-terminal fragment of the prohormone, is more stable than ADH. Copeptin plasma concentrations are often used as an ADH surrogate.

ADH levels increase the water permeability of distal renal tubules and collecting ducts, thus increasing water reabsorption and resulting in greater urine osmolarity and reduced renal water excretion. ADH binds to vasopressin-2 receptors on renal epithelial cells. These G-protein–coupled receptors activate adenylyl cyclase, converting adenosine triphosphate (ATP) to cyclic adenosine monophosphate (cAMP). Increased cAMP increases the transcription of the aquaporin-2 gene (Aqp2), increasing aquaporin-2 in collecting duct cells and triggering the fusion of aquaporin-2 water channels to the apical membranes of distal tubule and collecting duct epithelial cells, allowing water to move down an osmotic gradient into the nephron. Aquaporin-3, located on the opposite side of the nephron, permits water leaving the nephron to be reabsorbed into the blood. ADH also upregulates aquaporin-3.

cAMP also activates protein kinase A, leading to protein phosphorylation (aquaporin-2 and thiazide-sensitive sodium chloride cotransporter) and upregulating expression of urea transporters, thereby increasing urea permeability of the collecting duct. There is also greater sodium absorption across the ascending loop of Henle. These two effects further increase distal tubular and collecting duct water reabsorption, resulting in concentrated/hyperosmotic urine, which facilitates body water conservation.