The glomerular filtrate initially enters the proximal tubule of the nephron where an estimated two-thirds of it is isosmotically reabsorbed, coupled with the active transport of sodium. Proximal sodium reabsoption is chiefly an active process, relying on Na +,K+-ATPase pumps. The primary anions of the extracellular fluid, choride and bicarbonate, accompany sodium reabsorption via a Na+/H+ countertransport exchange system in order to maintain electrical neutrality. Bicarbonate, glucose, and amino acids (cotransported with sodium) are almost complete reabsorbed in the proximal tubule. This nephron segment, displaying a high permeability to water, also links volume and solute reabsorption. The rate of ionic and water proximal tubule reabsorption is invariably subject to the kidney's interpretation and regulation of the body's physiological requirements. Finally, the proximal tubule is a major site of creatinine and organic acid (uric acid) secretion. Physical factors modulating proximal tubule reabsorption include hydrostatic and oncotic peritubular capillary pressures. Owing to highly selective protein ultrafiltration, glomerular capillary oncotic pressure rises and subsequently transfers the augmented pressure to the peritubular capillaries. Several hormones, such as atrial natriuretic peptide, modulate proximal tubule reabsorption.
The thick ascending limb is impermeable to water while active transport occurs by a Na:K:2Cl cotransport mechanism, inhibited by furosemide (frusemide). Approximately 25 per cent of the filtered sodium and chloride and 15 per cent of the filtered water entering the loop are ultimately reabsorbed. Consequent to greater solute than water reabsorption, a hypotonic tubule fluid and hypertonic medullary interstitium are generated. The distal convoluted tubule, interposed between the loop of Henle and the collecting tubules, is virtually impermeable to water and reabsorbs roughly 10 per cent of the filtered sodium load. This reabsorption is load dependent and is inhibited by thiazide, amiloride, and spironolactone. The cortical and medullary collecting ducts constitute the final segments of the nephron, where water permeablility is negligible in the absence of ADH which enhances water reabsorption. Aldosterone augments sodium reabsorption and potassium/hydrogen secretion via stimulation of Na+,K+-ATPase pumps. The final urine volume and osmolality are precisely tuned in the collecting tubules. The kidney can produce minimum and maximum urinary concentrations of 50 mosmol/l and 1200 mosmol/l respectively. Since daily waste product excretion (e.g. urea) adds up to about 600 mosmol, minimum obligatory urine volume amounts to 500 ml/day (600 mosmol/1200 mosmol/l).
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