Renal physiologists are studying how hydration status affects the mechanisms of urine concentration and dilution in humans. To do this, they developed a technique in experimental animals that permits sampling of tubular fluid in different parts of the nephron. A tubular fluid sample with an osmolarity of 110 mOsm/L is obtained from a healthy animal after 12 hours of water deprivation. Assuming the physiology of this animal mirrors human physiology, which of the following sites along the nephron was most likely sampled?
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Water deprivation results in antidiuretic hormone (ADH) release from the posterior pituitary gland. This hormone stimulates V2 receptors on principal cells in the renal collecting ducts, causing translocation of aquaporin 2 channels into the apical cell membrane. Aquaporin 2 is a water channel that spans the luminal membrane, enhancing the water permeability of the principal cells. In the presence of high ADH, the tubular fluid osmolarity follows this pattern:
In the proximal tubule, water is reabsorbed along with electrolytes. The tubular fluid in this segment remains isotonic with plasma (300 mOsm/L) whether the final urine is concentrated or diluted (Choice A).
In the descending limb of the loop of Henle, free water is drawn out of the tubules into the renal interstitium and the tubular fluid becomes hypertonic (> 300 mOsm/L, typically reaching 1200 mOsm/L when ADH levels are high) (Choice B).
The thick and thin ascending limbs of the loop of Henle are the primary region of urine dilution. These regions are impermeable to water; electrolytes such as NaCl are passively reabsorbed in the thin ascending limb (Choice C) and actively reabsorbed in the thick ascending limb. The tubular fluid becomes increasing hypotonic (< 300 mOsm/L) within this region.
The distal convoluted tubule is relatively impermeable to water, so the tubular fluid remains hypotonic. Reabsorption of solutes continues to occur; thus, fluid in the distal tubules is the most dilute (lowest osmolarity, approaching 100 mOsm/L).
In the presence of ADH, the collecting duct is highly permeable to water. Water leaves the tubular fluid driven by the high osmolarity of the medullary interstitium, and hypertonic urine is formed (up to 1200 mOsm/L). The collecting duct system is the primary region of urine concentration through the mechanism of ADH-mediated water absorption.
(Choice E) In contrast, when ADH levels are low, the collecting duct remains impermeable to water. Thus, tubular fluid in this segment can become as hypotonic as 50 mOsm/L while solutes continue to be removed. However, in this case ADH levels are high, so the distal convoluted tubule will be the region of lowest osmolality.
Educational objective:
Dehydration stimulates ADH secretion. ADH acts on the collecting ducts, increasing their permeability to water. Thus, in the presence of ADH, the collecting ducts contain the most concentrated fluid in the nephron, while the distal convoluted tubule contains the most dilute fluid.