Bartter Syndrome and NKCC2

Because of the technical details in this article such as nephron and ascending limb, I recommend that the reader first learns the basic anatomy of kidney through other resources, including this one from National Kidney and Urologic Diseases Information Clearinghouse (NKUDIC). Here is a good picture of the movements of ions and other substances throughout the nephron that can help in following this article.

Basics of Bartter Syndrome

The main issue in Bartter Syndrome involves the sodium transfer in the thick ascending limb of the nephron. In Bartter Syndrome, the thick ascending limb loses the ability to effectively reabsorbs the sodium in the urine and this loss of sodium in the urine induces hypovolemia, or low blood volume. To compensate for hypovolemia, the body then urges for the stimulation of secretion of renin (enzyme) and aldosterone (hormone), which then increases the reabsorption of sodium and releases potassium ions. The overall result is that there is hypokalemia (low concentration of potassium ions) and alkalosis (reduced level of acidity of blood).¹

According to WebMD, patients with Bartter Syndrome usually have a normal blood pressure, which is surprising given the increased level of activation of renin and aldosterone.² In addition, the thick ascending limb is responsible for about 23% of the body's total reabsorption for NaCl, so the defect in this region is a pretty significant event.³

Investigating Bartter Syndrome in More Depth

This disorder's causes can be traced to the mutation in any of the four key proteins, which are Na-K-2Cl cotransporters (NKCC2), the ROMK K⁺ channel, the ClC-Kb Cl^- channel, or barttin.¹ For the purpose of this article, I will focus solely on NKCC2. First of all, in terms of its name, it is called Na-K-2Cl cotransporter because its job is to regulate the uptakes of Na-K-Cl, the three ions that all play very critical role in the body. It was determined in previous studies that there are six distinct forms of NKCC2.³

The mutations in NKCC2 are correlated to Bartter Syndrome Type I, which can take place in utero, or in the stage of fetus or embryo. Because Bartter Syndrome as a whole is autosomal recessive, there are unfortunately not that much data available. If you are interested in more genetic diseases in kidney though, here is one book that mentions Bartter Syndrome and several others that you may be interested.

Learning Why Genetic Mutations Matter to Physiology

For the remaining portion of this article, I want to ask this question to you, "How did we go from kidney to an obscure acronym for a protein?" The answer to this is that physiological changes that we observe are more or less the reflection of the changes in the gene. As discussed in this Berkeley website, a single germ line mutation can cause 1) no change to the phenotype, 2) minor change in the phenotype, or 3) major change in the phenotype.⁴ Reasons for these different levels are complicated but in essence, they are based on the type of mutations. Hence, this is how we had to reverse our investigation from nephron all the way to a protein.

The ways we behave in society are influenced by our genetics to a certain degree, and of course, the societal changes that we experience through our lives.

Works Cited

¹ Kim Barrett, et al., Ganong's Review of Medical Physiology, 23^rd ed. (New York: McGraw-Hill Company, 2010) 654.

² WebMD, "Bartter's Syndrome," http://www.webmd.com/ovarian-cancer/bartters-syndrome, last updated Feb. 21, 2010, accessed Jan. 31, 2011.

³ Patrick G.J.F. Starremans, Ferry F.J. Kersten, Nine V.A.M. Knoers, Lambertus P.W.J. van den Heuvel, and René J.M. Bindels. 2003 June 1. "Mutations in the Human Na-K-2Cl Cotransporter (NKCC2) Identified in Bartter Syndrome Type I Consistently Results in Nonfunctional Transporters." J. Am. Soc. Nephrol. 14: 1419-1426. This article is available for free on http://jasn.asnjournals.org/content/14/6/1419.full

⁴ University of California Museum of Paleontology, "The effects of mutation," http://evolution.berkeley.edu/evolibrary/article/0_0_0/mutations_05, accessed Jan. 31, 2011.