Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2015 Apr 2;372(14):1349-58.
doi: 10.1056/NEJMra1404726.

Molecular physiology of water balance

Mark A Knepper, Tae-Hwan Kwon, Soren Nielsen
Review

Molecular physiology of water balance

Mark A Knepper et al. N Engl J Med. .
No abstract available

PubMed Disclaimer

Figures

Figure 1.
Figure 1.. Feedback Loop Governing Regulation of PlasmaOsmolality through Control of Arginine VasopressinSecretion and Thirst.
An increase in plasma osmolality activates hypothalamicosmoreceptors to stimulate vasopressin secretionby the posterior pituitary gland. The resulting increasein the level of plasma vasopressin leads to anincrease in renal water reabsorption and a decrease inwater excretion. Increased water reabsorption reducesplasma osmolality. Osmosensing in the hypothalamusalso stimulates thirst and drinking to help restore plasmaosmolality. AVP denotes arginine vasopressin, PVNparaventricular nucleus, and SON supraoptic nucleus.
Figure 2.
Figure 2.. Relationships among Plasma Vasopressin Concentration, Rate of Water Excretion, and Solute Excretion (Osmolar Clearance).
Water excretion decreases with increased levels of plasma vasopressin, whereas solute excretion remains relatively constant. This results in concentrated urine at a high vasopressin concentration and dilute urine at a low vasopressin concentration.
Figure 3.
Figure 3.. Renal Tubule.
The segments shown in orange are targets for vasopressin regulation through the V2 receptor. Loop of Henle segments generate a corticomedullary osmolality gradient through the process of countercurrent multiplication. Connecting-tubule and collecting-duct segments are those that manifest regulated osmotic water transport through the action of vasopressin to regulate the water channel aquaporin-2. The macula densa is the point along the nephron where contact is made with the glomerulus of the same nephron. It provides a feedback signal (luminal sodium chloride concentration) that regulates the glomerular filtration rate to stabilize the sodium chloride concentration in the luminal fluid delivered to the distal convoluted tubule.
Figure 4.
Figure 4.. Collecting-Duct Principal Cell.
In the presence of vasopressin, water enters the principal cell from the lumen through aquaporin-2 (right) and exitsto the interstitium through aquaporin-3 and aquaporin-4. Regulation of aquaporin-2 by vasopressin is a result ofcyclic AMP (cAMP)–dependent activation of a protein kinase network that causes increased transcription of AQP2and redistribution of aquaporin-2 to the luminal membrane. The redistribution results from inhibition of aquaporin-2 endocytosis and stimulation of aquaporin-2 exocytosis. Intercalated cells mediate acid–base transport andare thought to be water-impermeable. Gαs denotes heterotrimeric G-protein alpha subunit.
See this image and copyright information in PMC

Comment in

  • Molecular Physiology of Water Balance.
    Knepper MA, Kwon TH, Nielsen S. Knepper MA, et al. N Engl J Med. 2015 Jul 9;373(2):196. doi: 10.1056/NEJMc1505505. N Engl J Med. 2015. PMID: 26154805 No abstract available.
  • Molecular Physiology of Water Balance.
    Morelle J, Goffin E, Devuyst O. Morelle J, et al. N Engl J Med. 2015 Jul 9;373(2):196. doi: 10.1056/NEJMc1505505. N Engl J Med. 2015. PMID: 26154806 No abstract available.

References

    1. Verney EB. The antidiuretic hormone and the factors which determine its release. Proc R Soc Lond B Biol Sci 1947; 135:25–106. - PubMed
    1. Danziger J, Zeidel ML. Osmotic homeostasis. Clin J Am Soc Nephrol 2014. July 30 (Epub ahead of print). - PMC - PubMed
    1. Fenton RA, Knepper MA. Mouse models and the urinary concentrating mechanism in the new millennium. Physiol Rev 2007;87:1083–112. - PubMed
    1. Fenske WK, Christ-Crain M, Horning A, et al. A copeptin-based classification of the osmoregulatory defects in the syndrome of inappropriate antidiuresis. J Am Soc Nephrol 2014;25:2376–83. - PMC - PubMed
    1. Windle RJ, Forsling ML, Smith CP, Balment RJ. Patterns of neurohypophysial hormone release during dehydration in the rat. J Endocrinol 1993;137:311–9. - PubMed

MeSH terms