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Body Composition: Salt and Water

2006; American Academy of Pediatrics; Volume: 27; Issue: 5 Linguagem: Inglês

10.1542/pir.27.5.181

1529-7233

Jennifer L. Ruth, Steven J. Wassner,

Renal function and acid-base balance

After completing this article, readers should be able to: Primitive, single-celled organisms began their ocean life continually surrounded by water and a steady supply of nutrients. As more complex organisms developed and finally left the oceans for dry land, the external sea had to be internalized. The great 19th century physiologist Claude Bernard coined the term "milieu interior" to describe that internal environment. He said that our escape from the sea was due to our ability to control our internal environment, a concept we now call homeostasis. Humans have developed sophisticated homeostatic mechanisms that control salt and water metabolism. This dynamic process changes with age and sex and in response to a variety of disturbances. In this article, we discuss fluid and electrolyte homeostasis as well as selected fluid and electrolyte problems seen within the pediatric age group.Water is the most abundant compound within the human body. It can be found within cells, around cells, within the blood vessels, and in smaller amounts within ligaments and bones. The percentage of body water changes with age and body composition. Early in gestation, almost 90% of a fetus's body weight is water. This ratio falls to 80% in severely preterm infants, 70% in term infants, 65% in young children, and approximately 60% in older children and adolescents. Body water is distributed into two main compartments: the intracellular and the extracellular. In the average adult, intracellular water makes up approximately 40% of body weight or two thirds of total body water. Water comprises approximately 80% of a cell's weight. Adipose tissue is an exception that essentially is free of intracellular water. Because obese persons have a higher ratio of adipose tissue, they have a lower percentage of total body water.In addition to the water within cells, water circulates between and around cells as well as within blood vessels. The water bathing the cells is called interstitial fluid and comprises approximately 15% to 20% of body weight; the serum, or water part of the blood, comprises another 4% to 5% of body weight. Collectively, the interstitial and intravascular fluid volumes are termed extracellular water (ECW). As a whole, ECW makes up approximately one third of total body water, or 20% to 25% of body weight (depending on age).Exchange of water between the interstitial and intravascular compartments is rapid and governed by the balance of forces known as Starling forces, named after the physiologist who first described their operation. According to the Starling formula (Fig. 1), the net movement of fluid across a capillary membrane is a function of that membrane's innate permeability as well as the difference in hydrostatic and oncotic pressures on the two sides of the membrane. Both act to maintain intravascular volume and blood pressure. As might be expected, some capillary beds are innately more permeable than others (have a higher capillary filtration coefficient). The capillary filtration coefficient takes into account, and is proportional to, the permeability of the capillary wall and the area available for filtration. For example, the glomerular capillaries have a much higher capillary filtration coefficient than other capillaries, a necessity for adults who produce more than 150 L of glomerular filtrate each day. If the capillaries in the feet were as permeable as those in the glomeruli, everyone would have pedal edema.Figure 2depicts the Starling forces acting along a typical muscle capillary. At the arteriolar end of the capillary, the net hydrostatic pressure gradient minus the net oncotic pressure gradient favors the movement of water out of the capillary and into the interstitium. As water leaves the capillary, the hydrostatic pressure falls, and the oncotic pressure begins to rise. At some point toward the venous end of the capillary, the continued decrease in hydrostatic pressure, coupled with increasing oncotic pressure, alters the balance of forces to favor fluid reabsorption into the capillary lumen. Approximately 90% of the fluid initially filtered into the interstitium at the arteriolar end of a capillary bed is reabsorbed back into the intravascular space; the other 10% is returned to the circulation by the lymphatic system. When the normal state of homeostasis has been disrupted, as in dehydration or other causes of decreased blood pressure, the net flow of fluid is from the interstitial compartment into the intravascular compartment, thus maintaining blood pressure and restoring homeostasis. Conversely, both intravascular volume overload (by increasing the capillary hydrostatic pressure) and hypoalbuminemia (by decreasing the capillary oncotic pressure) lead to the net movement of fluid out of blood vessels and into the interstitium.Unlike the movement of water within the extracellular compartment, the transfer of water between the extracellular and intracellular compartments occurs in response to osmolar gradients. Osmolality is defined as the number of milliosmoles of solute per kilogram of water. One milliosmole is equal to one millimole of solute. The osmolality of both the intracellular and extracellular spaces reflects the amounts and different types of solutes within each compartment. The kidney regulates solute and water homeostasis in the extracellular space, but the concentration of these solutes within cells is carefully controlled by a variety of cellular transport mechanisms. Because cells are bounded by semipermeable membranes, water flows across these membranes to equalize extracellular and intracellular osmolalities. The major extracellular osmoles are sodium and its accompanying anion, chloride. Other physiologic osmoles within the ECW are glucose and urea nitrogen (BUN). Serum osmolality can be estimated by the following equation: \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \[2{\ast}\mathrm{Na}\ (\mathrm{mEq}/\mathrm{L}){+}{[}\mathrm{BUN}\ (\mathrm{mg}/\mathrm{dL})/2.8{]}{+}{[}\mathrm{Glucose}\ (\mathrm{mg}/\mathrm{dL})/18{]}\] \end{document} Multiplying sodium concentration by 2 reflects the presence of the anions (predominantly chloride) that accompany each sodium ion. Dividing the BUN by 2.8 and glucose by 18 converts their units from mg/dL to mmol (mOsm)/L. By convention, potassium usually is ignored in the calculation of plasma osmolality because its contribution is negligible. As can be seen from the equation, hypernatremia always is synonymous with hyperosmolality, but hyponatremia does not necessarily imply hypo-osmolality because urea (as in acute or chronic renal failure), glucose (as in diabetes mellitus), or even other unmeasured osmoles (such as lactate, ethanol, or methanol) also can contribute to total osmolality.Total and effective osmolality should be distinguished. Compounds such as ethanol or methanol rapidly diffuse across cell membranes, so although they contribute to the total osmolality, their presence does not lead to the movement of fluid across cell membranes. Urea diffuses more slowly, and the acute administration of urea has been used to increase extracellular osmolality and decrease cerebral swelling. However, when serum urea concentrations are chronically elevated, intracellular and extracellular concentrations are equivalent, and urea does not contribute to effective osmolality.Glucose, unlike the previous compounds, diffuses poorly across cell membranes. High serum glucose concentrations always lead to the development of an osmotic gradient and the movement of fluid from the intracellular to the extracellular compartment. This condition is seen commonly in the hyperglycemia of uncontrolled diabetes mellitus. The movement of water from within cells to the extracellular space leads to a lower serum sodium concentration (hyponatremia), which some authors have incorrectly called "factitious hyponatremia." In truth, this is an example of true hyponatremia because the ECW content is increased for the amount of sodium present. Lowering blood glucose concentrations by the administration of insulin decreases ECW osmolality, which leads to diffusion of water back into the intracellular space and an increase in serum sodium concentration.Rapid changes in ECW osmolality always are associated with compensatory changes within the intracellular compartment. Cell function depends on a stable volume to keep the intracellular concentration of enzymes, cofactors, and ions at appropriate levels. Therefore, the movement of water and the resultant cellular swelling (or contraction) can lead to cellular dysfunction. The brain has limited tolerance for either cellular swelling or contraction, which explains why disturbances in plasma osmolality can be accompanied by central nervous system dysfunction, including lethargy, seizures, and coma. As noted previously, the hyperosmolality of uncontrolled diabetes mellitus leads to a shift of water out of cells and into the extracellular fluid space. In contrast, decreased plasma osmolality (as sometimes occurs with vomiting, diarrhea, or the administration of hypotonic intravenous fluids) is associated with movement of water into cells and the development of cellular swelling. This swelling is of most concern within the brain, where the ability of brain cells to expand is limited by the bony skull. As a result, acute hypo-osmolality (hyponatremia) can be associated with the development of intracellular cerebral edema, seizures, and death.In addition to its presence within a skull of defined volume, the brain is tethered to the skull by membranes that contain blood vessels. Conditions that induce hyperosmolality may cause brain cell volume to decrease acutely by as much as 10% to 15%. To reverse this shrinkage, the brain has the unique ability to maintain intracellular volume by producing organic compounds such as taurine, glycine, glutamine, sorbitol, and inositol. Collectively, these compounds are known as idiogenic osmoles. An increase in the concentration of the idiogenic osmoles has been detected as early as 4 hours after the onset of hypernatremia, but does not become significant until after 24 hours. If hyperosmolality develops acutely, the brain may not be able to respond quickly enough to preserve cell volume. The resultant cellular contraction can lead to structural changes, tearing of the membrane-bound blood vessels, and development of intracranial hemorrhage. This combination of changes helps explain the relatively high incidence of permanent neurologic damage associated with hypernatremic dehydration. The brain's production of idiogenic osmoles increases its intracellular osmolality and re-expands brain cell volume. In experimental rat studies, when hypernatremia was maintained for 1 week, the brain was able to regain approximately 98% of its water content. Once idiogenic osmoles are present, they dissipate slowly. Therefore, the treatment of hyperosmolality must proceed cautiously. If ECW osmolality is corrected too rapidly, the presence of the idiogenic osmols within the brain can lead to cerebral swelling during the recovery phase.As noted previously, sodium is the major extracellular osmole and, in large part, regulates the volume of the ECW. Given the importance of sodium in the control of both body fluid volume and osmolality, the human body has developed complex mechanisms to regulate both serum sodium concentration and total body salt content. Of particular importance to children is that sodium also is required for growth, and any increase in body size requires a positive sodium balance. This need is particularly apparent during the first postnatal year, when growth is rapid. During the first 6 months after birth, infants gain approximately 4 kg (or 2.6 L of water). To maintain their serum sodium concentrations at 140 mEq/L (140 mmol/L), infants also must retain approximately 360 mEq (360 mmol) of sodium or 2 mEq/d (2 mmol/d). During this time, breastfed infants ingest about 1 mEq (1 mmol)/100 kcal per day, and formula-fed infants consume 1 to 3 mEq (1 to 3 mmol)/100 kcal per day, so they are easily able to achieve adequate sodium intake. For infants and children requiring intravenous therapy, 2 to 3 mEq (2 to 3 mmol)/100 kcal per day is appropriate. One exception to this rule is that preterm infants may require two to three times this amount due to the immaturity of their renal function and initial rapid growth. Once a child begins to eat table foods, sodium intake greatly exceeds recommended amounts, with the largest contribution of ingested sodium coming from the salt added during processing and manufacturing. For healthy infants and children of any age, 1 to 3 mEq (1 to 3 mmol)/100 kcal of sodium is sufficient.The human body is very effective at keeping total body sodium content constant, and with allowances for growth, salt intake is balanced exquisitely by salt excretion. The kidney performs this function through the filtration and reabsorption of large amounts of glomerular filtrate. Each day, the kidney filters a volume approximately three times as large as the individual's total body water; the tubules reabsorb 99% of the filtered sodium and equivalent amounts of water. Throughout the nephron, a variety of local factors and hormones control and modulate salt and water reabsorption, with the most important hormones being angiotensin II, aldosterone (sodium), and antidiuretic hormone (water). Although other hormones are important, a full discussion of their roles is beyond the scope of this article.The excretion of free water (ie, water unaccompanied by solute) is under the control of the posterior pituitary hormone, antidiuretic hormone (ADH). The release of ADH is regulated primarily by highly sensitive osmoreceptors within the hypothalamus. Experimental studies have demonstrated that these osmoreceptors can respond to changes in osmolality as small as 1% to 2%. At plasma osmolalities below 280 mosm/kg H2O, the secretion of ADH is suppressed; above this level, ADH concentration rises sharply. An increase in osmolality also stimulates osmolar thirst receptors within the brain. The release of ADH is not equally sensitive to all solutes. For example, the release mechanism is maximally sensitive to sodium, but minimally sensitive to urea and glucose. ADH secretion also is regulated by a less sensitive volume receptor system. Animal studies have shown that a loss of approximately 5% of body water is necessary to stimulate the release of ADH.The sensitivity of the osmoreceptor system underlies the importance that the body places on maintaining normal serum osmolality. For example, in situations where excess sodium is retained, serum osmolality increases transiently, causing increased thirst and ADH secretion. Water is conserved to restore serum sodium concentration (and osmolality) to normal. Until the excess sodium is excreted, affected individuals have a normal serum sodium concentration and an expanded extracellular fluid volume. Conversely, until the patient loses approximately 5% of total body weight, losses in serum sodium are accompanied by proportional losses in water to preserve serum sodium concentration. Although less sensitive, the volume regulation system is more powerful than the osmoregulatory system. In the face of significant dehydration, ADH secretion increases, free water is retained, and the serum sodium concentration decreases. In essence, the body chooses to maintain blood volume and tissue perfusion over serum sodium concentration.In the middle of the summer, you are called to the emergency department to examine a previously healthy 6-year-old boy who has hypotonic dehydration. He has no history of vomiting or diarrhea, and his mother notes that he always has been drawn to salty foods and uses the saltshaker liberally. Examination of an old chart reveals that this is the child's second episode of hypotonic dehydration in the past 2 years, the previous one being last summer. His urinary sodium concentration is less than 5 mEq/L (5 mmol/L). Because there is no history of gastrointestinal losses, you suspect that sodium loss may be occurring through his skin. After rehydration, you refer him for genetic testing, which reveals a mild variant of cystic fibrosis.The most common salt-losing states in children are associated with vomiting and diarrhea. Other causes include cystic fibrosis, diuretic use, salt-losing renal disease, and the common forms of congenital adrenal hyperplasia. Salt-losing states always are associated with a loss of ECW, and affected children present with evidence of volume depletion and weight loss. Individuals who have chronic forms of volume depletion, such as with chronic diuretic use, may be reasonably well adapted to their volume-depleted states and may not show overt signs of volume depletion.When salt loss occurs, the body has two coordinated response pathways: a protective response to maintain blood pressure and a restorative response to replenish the ECW volume (Fig. 3). As mentioned, salt loss always is associated with ECW loss. Acutely, the kidneys sense this salt loss as a lowered perfusion pressure and respond by secreting renin. Once in the bloodstream, renin cleaves the protein angiotensinogen into angiotensin I. Angiotensin I is biologically inactive and must be cleaved by angiotensin-converting enzyme into angiotensin II (Ang II). Ang II is one of the most potent vasoconstrictors known, acting directly on vascular smooth muscle to produce arteriolar constriction and increase systemic blood pressure. Ang II also facilitates the release of norepinephrine, another potent vasoconstrictor. During this cascade, ADH is stimulated, which conserves water by concentrating the urine.Although the acute response preserves blood pressure and perfusion to vital organs, it is the restorative response that replaces the salt and water losses. In addition to producing arteriolar constriction, Ang II stimulates salt reabsorption by two mechanisms. First, it acts directly in the proximal tubule to induce sodium reabsorption. Ang II also stimulates the release of the potent mineralocorticoid aldosterone from the adrenal cortex. Aldosterone acts on the cortical collecting tubules of the kidney to increase sodium reabsorption. As renal sodium reabsorption is increased, water reabsorption follows, and as long as the inciting event ceases, ECW volume is restored to its baseline state.A 2-year-old boy presents with a 2-week history of eyelid swelling and weight gain. He was seen 1 week ago, believed to have an allergic reaction, and treated with an over-the-counter antihistamine. Physical examination today demonstrates a weight gain of 3 kg, normal vital signs, bilateral eyelid edema, a nontender abdomen with obvious ascites, and pitting edema from his ankles to his knees. Nephrotic syndrome is confirmed by laboratory studies, which reveal a urine specific gravity of 1.030, no blood, no glucose, and 4+ protein. Serum electrolytes, BUN, and creatinine levels are normal, but the albumin concentration is 1.7 g/dL (17 g/L). The measured urine sodium concentration is only 5 mEq/L (5 mmol/L). In spite of the normal blood pressure and pulse, this child's kidneys are avidly retaining sodium and water. The amount of salt retained over the past 2 weeks can be calculated, noting that the child has gained 3 kg of weight or about 3 L of water. Because his serum sodium concentration remains normal, his kidneys have had to retain 140 mEq (140 mmol) of sodium for each liter of water retained, for a total of 420 mEq (420 mmol) of sodium or about 3 tsp of salt. Retaining 3 tsp of salt, therefore, led to his 3-kg weight gain.When total body sodium concentrations are low, salt retention is the appropriate response. There are numerous conditions, however, in which salt is retained in the face of normal or increased total body sodium content. When plasma oncotic pressure is low (as in liver disease, cirrhosis, or severe malnutrition) or when tissue is damaged and membrane permeability is increased, examination of the Starling forces predicts the movement of fluid from the intravascular to the extravascular compartment. Such movement of fluid out of the intravascular compartment is termed "third spacing." The kidney senses this situation as a reduction in perfusion pressure and acts to increase salt and water retention, even though there is no net loss of salt or water from the body.Another situation in which salt is retained is congestive heart failure. Clinically, affected patients present with increased body weight (due to retained water) and a relatively normal serum sodium concentration. Depending on the degree of sodium retention, edema commonly is present. The primary abnormality is abnormal salt retention, with water being conserved to maintain serum osmolality within the normal range.A third category of disorders, primary salt retention, is relatively uncommon in pediatrics. In these situations, salt is retained due to primary mineralocorticoid excess (Cushing syndrome, primary hyperaldosteronism, the less common forms of congenital adrenal hyperplasia), administration of exogenous steroids, or rare genetic syndromes of increased renal salt retention. Affected patients also present with increased body weight and a serum sodium concentration within the normal range. A clinical distinction is the frequent prominent physical finding of hypertension and rarity of edema.As discussed previously, changes in total body salt content are associated with concomitant changes in total body water, with salt-retaining states leading to weight gain and salt-losing states associated with weight loss. In both of these situations, serum sodium concentrations generally are maintained within the normal range, which leads to the somewhat counterintuitive statement that "disorders of sodium metabolism present as changes in total body weight (body water)."In addition to the movement of water and sodium within the kidney, in a number of conditions, water loss or retention occurs independently of sodium movement. When water is lost in excess of sodium, the result is volume depletion and hypernatremia. Conversely, the retention of water in excess of sodium intake leads to hyponatremia. Because these statements refer to sodium and water relative to each other, hyper- and hyponatremia can be present with a total body water content that is decreased, normal, or even increased and leads to another seemingly counterintuitive statement that "disorders of water metabolism present as changes in serum sodium concentration." These changes are most obvious when caused by primary disorders of water metabolism (diabetes insipidus, syndrome of inappropriate secretion of antidiuretic hormone [SIADH]). A full discussion of these complex disorders is beyond the scope of this article.A 6-month-old infant presents with his second episode of diarrhea and hypernatremic dehydration (serum sodium 173 mEq/L [173 mmol/L]). His mother notes that he is always hungry and that she feeds him at least 32 oz/d of a commercially prepared ready-to-feed formula. He has at least 15 "soaked" diapers each day and except for the two episodes of diarrhea, he generally is constipated. Family history reveals that the mother had a brother who died in infancy of unknown causes. Intravenous rehydration is difficult and requires large amounts of fluid over several days before the serum electrolyte values return to normal. Throughout this period, the infant has copious urine output, and the urine specific gravity is always less than 1.005. Because recurrent hypernatremic dehydration is uncommon, you search for a possible underlying cause. The infant's BUN, creatinine, and renal ultrasonography findings are normal, ruling out chronic kidney disease. Given the presence of normal renal function and the suspicious family history, you suspect that the infant is unable to concentrate his urine because of X-linked diabetes insipidus.Hypernatremia can result from two primary mechanisms: an increase in sodium intake by a patient who has no access to "free water" and the loss of water in excess of salt. The activation of osmoreceptors within the brain stimulates both the release of ADH and the sensation of thirst. Because the desire to drink is so intense, most patients who present with hypernatremia are very old, very young, or physically unable to get to water. For example, as soon as children who have diabetes insipidus can access water independently, they are able to maintain normal serum tonicity and, in the absence of intercurrent illness, do not develop hypernatremia.You note that one of the hospitalized patients you are covering, a 6-year-old boy (status-postappendectomy) has significant electrolyte abnormalities. His serum sodium level is 126 mEq/L (126 mmol/L), potassium is 3.7 mEq/L (3.7 mmol/L), chloride is 111 mEq/L (111 mmol/L), and bicarbonate is 25 mEq/L (25 mmol/L). His BUN is 5 mg/dL (1.8 mmol/L) and creatinine is 0.3 mg/dL (26.5 mcmol/L). He has received several doses of morphine for pain. He has taken nothing orally since the operation, receiving D5 1/4 normal saline as his maintenance intravenous (IV) fluid. Over the past 11/2 days, he has had approximately 2 L of IV intake and has urinated only 500 mL. You tentatively diagnose SIADH due to both the pain and morphine. Because he is asymptomatic, you limit his free water intake and put his IV on "Keep open" status. The child recovers without incident.Acute hyponatremia most often is a consequence of acute dehydration, which results from two mechanisms. First, infants who have diarrhea frequently are given hypotonic solutions and second, the decreased volume stimulus for ADH release causes the kidney to reabsorb water and maintain blood pressure even at the expense of hyponatremia. Other causes of acute hyponatremia are related to the administration of water in excess of the kidney's ability to excrete it. Such water excess can occur in both acute and chronic renal failure as well as in neonates, the elderly, and postoperative patients who inadvertently receive excess fluid. Mild hyponatremia often is present in cases in which there is a chronic decrease in "perceived" intravascular volume, most commonly chronic diuretic use or congestive heart failure. In both cases, the mild hyponatremia is due to increased ADH secretion, released appropriately by the pituitary to preserve intravascular volume. Chronic, severe hyponatremia is due most likely to a hormonal disorder that affects the kidney's ability to excrete water. In addition to ADH, two other hormones, thyroid hormone and cortisol, are required for the kidney to excrete a water load. Thus, patients having either hypothyroidism or Addison disease may develop hyponatremia.