A 34-year-old missionary in southern Asia is traveling to a remote village and becomes stranded when his bus breaks down. He has no access to water for 36 hours, during which his urine osmolality reaches 1100 mOsm/L. Urine concentration depends primarily on the serum level of vasopressin, which is regulated by the neurohypophysis in response to plasma osmolality and blood volume. Which of the following nephron segments responds to vasopressin by increasing absorption of a specific solute that is important for generating a high medullary concentration gradient?
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Vasopressin, or antidiuretic hormone (ADH), is the primary physiologic inhibitor of free water excretion. This hormone acts on 2 major receptors, V1 and V2. Stimulation of the V1 receptor causes vasoconstriction and increased prostaglandin release; stimulation of the V2 receptor results in an antidiuretic response. ADH is secreted in response to plasma hyperosmolality and, to a lesser extent, depletion of the effective circulating volume. Water deprivation initially increases plasma osmolality, resulting in increased ADH secretion. This causes the kidney to produce concentrated urine, which helps to counteract the rise in plasma osmolality by reducing urinary free water excretion.
The medullary portion of the collecting duct is of particular importance in the production of maximally concentrated urine as the medullary interstitium is the region of highest osmolarity in the kidney. In the setting of high serum ADH levels, a large osmotic gradient drives the absorption of free water into the hypertonic medullary interstitium. As water leaves the tubular fluid, urea concentration greatly increases. ADH also increases the number of passive urea transporters in the inner medullary collecting duct, allowing a substantial fraction of the highly concentrated urea to diffuse down its concentration gradient into the medullary interstitium. When ADH levels are high, this urea resorption contributes up to 50% of total osmolarity of the medulla, further increasing the water-absorbing capacity of the nephron.
(Choice A) ADH also increases water absorption in the cortical segment of the collecting duct, reducing the amount of free water delivered to the medullary collecting duct. This prevents excess water from being absorbed into the medullary interstitium, which would otherwise dilute the osmotic gradient and reduce the maximum achievable urine concentration.
(Choice B) The early distal tubule is impermeable to both water and urea.
(Choice D) The proximal tubule is permeable to urea and resorbs about half of the filtered load. However, it does not respond to ADH.
(Choice E) The thin ascending limb of the loop of Henle is permeable to urea, which passively diffuses down its concentration gradient into the tubular lumen. Secretion of urea into the thin part of the loop of Henle allows urea to recirculate and concentrate in the tubular system, further increasing its contribution to the medullary osmotic gradient.
Educational objective:
Antidiuretic hormone acts on the medullary segment of the collecting duct to increase urea and water reabsorption, allowing for the production of maximally concentrated urine.