Mammalian acidosis: The Kidney

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The mammalian cortical amassing duct (CCD) is a part of the kidney which sets the electrolyte and fluid stability by a secretion and reabsorption plan (Staruschenko, 2012). It consists of basic cells that are in between renal intercalated cells (ICs), water transport, Na and K. There are sorts of intercalated cells specifically α and β. The α is an acid-secreting mobileular that makes use of the basolateral AE1 exchanger to secrete quantities and reabsorbs bicarbonate whilst the β-ICs is based at the basolateral B1 and the apical pendrin exchanger to release bicarbonate (HCO3). The capabilities of the renal ICs are to spur secretion of H+ and HCO3 secretion and the reabsorption of the K+ and Cl.

There are two forms of intercalated cells namely α and β. The &alpha is an acid-secreting cell that uses the basolateral AE1 exchanger to secret portions and reabsorbs bicarbonate while the β-ICs relies on the basolateral B1 and the apical pendrin exchanger to secret bicarbonate (HCO3). The general functions of the renal ICs are to facilitate secretion of H+ and HCO3 secretion and the reabsorption of the K+ and Cl.

The α and β play a significant role in stabilizing the acidity of the kidney fluids. Studies have shown that at least these two types of ICs are present in rabbits, rats and mouse and an additional IC that is neither α nor β. The non α non β IC is also present in the connecting tubule (CNT and the CCD of rats and mouse and rabbits. It consists of the H+ -ATP base but lacks the AE1(Kim et. al, 1999). The ICs play a primary role in HCO3 secretion. They form between thirty and forty percent of the cells found in the outer medullary collecting duct (OMCD), the CNT and the CCD. Studies show that there are at least two ICs, commonly the α and β, in the CCD and CNT of rats, rabbits, and mouse. Significant studies have been conducted recently to understand the functions of the ICs as well as establish their relationships in various conditions.

One of the studies carried out is to determine if and the maternal acid-base affects the intercalated cell differentiation in the progeny. The kidneys respond to a low pH by increasing the amount of H+ secreted from the promixial and by increasing the simulation of NH3 synthesis consequently raising the capacity of net acid produced. The hypothesis that CCD respond to acidosis by changing the ICs was tested. The H+ secretion is simulated, and the HCO3 secretion inhibited whenever the CCD detects the increased acidity. In other instances, it changes the amount of α and β-ICs when it is chronic acidosis.

The objective of the study was to determine if maternal acidosis influences ICs progeny differentiation (Riley, 2015). The methodology involved modifying the pregnant rabbit’s diet. The regular alkaline ash diet was replaced with ammonium chloride which is acidic during the last two weeks of gestation. The litters’ kidneys were then harvested at one and there weeks (there and two kits respectively). Tissue was then extracted from each of the kidneys and sectioned into 4-6µm thick slides for testing. Immunofluorescence staining of the AE1, B1 and the pendrin was done to identify the different IC subtypes. The particular IC type’s number was determined through a cell count and compared to those of normal adult rabbits.

Results showed that maternal acidosis delayed β intercalated cells differentiation in the progeny. The CCD revealed that there were fewer β-ICs were seen in the 1-week old kits than to the normal adult rabbits. Similar differences were observed in the AE1/B1 staining. There were fewer ICs in the one-week-old kits as compared to those in the adult rabbits. The number of α-ICs was, however, comparable to those in adult rabbits. This, therefore, showed that the IC differentiation was incomplete and that the acidosis delayed the β-IC production.

References

Kim, J., Kim, Y., Cha ,J., Tisher, C.& Madsen, K. (1999). Intercalated cell subtypes in connecting tubule and cortical collecting duct of rat and mouse. J Am Soc Nephrol,10, 1–12.

Riley, A. (2015). Maternal acidosis down-regulates beta-intercalated cell differentiation in progeny. Unpublished Research Scholar Report. Strong Children’s Research Center.

Schwartz, J., Gao, X., Tsuruoka, S., Purkerson, J. M., Peng, H., D’Agati, V., … Al-Awqati, Q. (2015). SDF1 induction by acidosis from principal cells regulates intercalated cell subtype distribution. Journal of Clinical Investigation, 125(12), 4365-4374.

Schwartz J., Tsuruoka, S., Vijayakumar, S., Petrovic ,S., Mian, A., Al-Awqati, Q. (2002). Acid incubation reverses the polarity of intercalated cell transporters, an effect mediated. J Clin Invest,109,1, 89–99.

Staruschenko, A. (2012). Regulation of transport in the connecting tubule and cortical collecting duct. Compr Physiol,2,1541-1584.

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