Sodium

Sodium is essential in maintaining extracellular fluid balance and, thus, volume status. The kidney is capable of effecting large changes in sodium excretion in a variety of normal and pathologic states.

There are 4 main sites of sodium transport. Approximately 60% of sodium is absorbed in the proximal tubule by coupled transport with glucose or amino acids, 25% in the ascending loop of Henle (mediated by NKCC2, the bumetanide-sensitive sodium-potassium 2 chloride transporter), and 15% in the distal tubule (mediated by NCCT, the thiazide-sensitive sodium chloride cotransporter) and collecting tubule (mediating by EnaC, the epithelial sodium channel).

The urinary excretion of sodium normally approximates the sodium intake of 2-6 mEq/kg/24 hr for a child consuming a typical American diet, minus 1-2 mEq/kg/24 hr required for normal metabolic processes. However, in states of volume depletion (dehydration, blood loss) or decreased effective circulating blood volume (septic shock, hypoalbuminemic states, heart failure), there may be a dramatic decrease in urinary sodium excretion to as low as 1 mEq/L. Changes in volume status are detected by baroreceptors in the atria, afferent arteriole, and the carotid sinus and by the macula densa, which detects changes in chloride delivery.

The major hormonal mechanisms mediating sodium balance include the renin-angiotensin-aldosterone axis, atrial natriuretic factor, and norepinephrine. Angiotensin II and aldosterone increase sodium reabsorption in the proximal tubule and distal tubules, respectively. Norepinephrine, released in response to volume depletion, does not directly act on tubular transport mechanisms but affects sodium balance by decreasing renal blood flow and thus decreasing the filtered load of sodium as well as stimulating renin release. With more-severe volume depletion, antidiuretic hormone is also released (Chapter 524). Sodium excretion is promoted by atrial natriuretic factor and suppression of renin.

Potassium

Extracellular potassium homeostasis is regulated because small changes in plasma potassium concentrations have dramatic effects on cardiac, neural, and neuromuscular function (Chapter 52.4). Essentially all filtered potassium is fully reabsorbed in the proximal tubule. Therefore, urinary excretion of potassium is completely dependent on tubular secretion by potassium channels present in the principal cells of the collecting tubule. Factors that promote potassium secretion include aldosterone, increased sodium delivery to the distal nephron, and increased urine flow rate.

Calcium

A significant portion of filtered calcium (70%) is reabsorbed in the proximal tubule. Additional calcium is reabsorbed in the ascending loop of Henle (20%) and the distal tubule and collecting duct (5-10%). Calcium is reabsorbed by passive movement between cells (paracellular absorption) in a process driven by sodium chloride reabsorption and potassium recycling into the lumen. In addition, calcium uptake is actively regulated by calcium receptors, specific transporters, and calcium channels. Factors that promote calcium reabsorption include parathyroid hormone (released in response to hypocalcemia), calcitonin, vitamin D, thiazide diuretics, and volume depletion (Chapter 564). Factors that promote calcium excretion include volume expansion, increased sodium intake, and diuretics such as mannitol and furosemide.

Phosphate

The majority of filtered phosphate is reabsorbed in the proximal tubule by active transport. Reabsorption is increased by dietary phosphorus restriction, volume contraction, and growth hormone. Parathyroid hormone and volume expansion increase phosphate excretion.

Magnesium

About 25% of filtered magnesium is reabsorbed in the proximal tubule. Modulation of renal magnesium excretion occurs primarily in the ascending loop of Henle, with some contribution of the distal convoluted tubule. Although specific magnesium transporters have been identified, the precise mechanisms by which they are regulated remain unclear.

Acidification and Concentrating Mechanisms

Acidification and concentration are addressed in the sections on renal tubular acidosis and nephrogenic diabetes insipidus, respectively (Chapters 523 and 524).

Developmental Considerations

Tubular transport capabilities of neonates (especially premature infants) and young infants are less than those of adults. Although nephrogenesis (the formation of new glomerular/tubular units) is complete by about 36 wk of gestation, significant tubular maturation occurs during infancy. Renal tubular immaturity, reduced glomerular filtration rate, decreased concentrating gradient, and diminished responsiveness to antidiuretic hormone are characteristic of young infants. These factors can contribute to impaired regulation of water, solute, and electrolyte and acid-base homeostasis, particularly during times of acute illness.