Review Question - QID 216319

The collecting duct of the medulla would be expected to have the highest osmolality in this patient who is treated with a vasopressin analog because urine can be concentrated up to 1200 mOsm in this segment of the nephron. This segment of the nephron is labeled "E" in Figure A.

Arginine vasopressin (AVP), also known as antidiuretic hormone (ADH), is a peptide secreted by the posterior pituitary gland that regulates water excretion in the kidney through the V2 receptors. AVP functions by selectively increasing water permeability in the collecting tubules and ducts via aquaporin 2 (AQP2), increasing NaCl reabsorption in the thick ascending limb (TAL) of the loop of Henle, and increasing urea reabsorption by the inner medullary collecting duct (IMCD). Increased NaCl reabsorption in the TAL and urea reabsorption in the IMCD increases urinary concentrating ability via a countercurrent exchange multiplier. Aquaporins avidly transport water across cell membranes; thus, increasing AQP2 in the luminal side of cells in the collecting ducts in conjunction with the countercurrent exchange multiplier increases urine osmolality. The net effect of AVP thus leads to tubular fluid in the inner medullary collecting duct (IMCD) being concentrated up to 1200 mOsm, the highest osmolality in the nephron.

Bankir et al. review the role of vasopressin (AVP) in nephron physiology. In particular, the authors discuss the role of AVP acting on the vasopressin 2 (V2) receptor in modulating water and solute flow in the cortical and medullary collecting ducts. The authors recommend further study of copeptin, a fragment of the pre-provasopressin molecular that is both easier to measure and a good surrogate marker of AVP.

Figure/Illustration A shows a labeled diagram of a juxtamedullary nephron, which have their glomeruli near the corticomedullary border (the black line between the tan cortex and the brown medulla). A refers to the proximal convoluted tubule, B refers to the descending limb of the Loop of Henle, C refers to the outer medullary collecting duct, D refers to the distal convoluted tubule, and E refers to the IMCD. An unlabeled superficial cortical nephron is also seen on the right.

Incorrect Answers:
Answer 1: A shows the proximal convoluted tubule (PCT). The PCT reabsorbs filtered fluid isosmotically regardless of the final osmolality of the urine. Therefore, filtrate in this region of the nephron would be expected to have osmolality around 300 mOsm, which is less than that of the IMCD (1,200 mOsm) in the setting of antidiuresis with AVP.

Answer 2: B shows the descending limb of the loop of Henle. Although the osmolality of fluid in this segment is expected to rise, the arrow shown is not as deep in the medulla as the arrow in the collecting duct, making the IMCD a better choice.

Answer 3: C refers to the outer medullary collecting duct. The collecting duct is classically divided into four portions in order of increasing depth: initial collecting duct, cortical collecting duct, outer medullary collecting duct, and IMCD. AVP acts on all of these portions, leading to increasing osmolality with greater depth in the setting of antidiuresis. Thus, the IMCD would be expected to have greater osmolality than the outer medullary collecting duct in this patient taking AVP.

Answer 4: D refers to the distal convoluted tubule (DCT). The DCT is a highly permeable segment of the nephron. Therefore, even in the setting of antidiuresis, the DCT is unable to concentrate beyond plasma osmolality. This segment is expected to be around 120 mOsm, compared to up to 1200 mOsm in the IMCD.

Bullet Summary:
Vasopressin is a small peptide that promotes antidiuresis by increasing water reabsorption in the collecting duct, leading to increasing tubule fluid hyperosmolality along the collecting duct.