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Splay (physiology)

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In physiology, splay is the difference between urine threshold (the amount of a substance required in the kidneys before it appears in the urine) and saturation, or TM, where saturation is the exhausted supply of renal reabsorption carriers.[1][2][3][4][5] In simpler terms, splay is the concentration difference between a substance's maximum renal reabsorption vs. appearance in the urine.[6] Splay is usually used in reference to glucose;[1] other substances, such as phosphate, have virtually no splay at all.

The splay in the glucose titration curve is likely a result of both anatomical and kinetic difference 

among nephrons.[7] A particular nephron's filtered load of glucose may be mismatched to its capacity to reabsorb glucose. For example, a nephron with a larger glomerulus has a larger load of glucose to reabsorb.[7] Also, different nephrons may have different distributions and densities of SGLT2 and SGLT1 along the proximal tubule and, thus, have different tubular maximum for glucose (TmG).[7] Therefore, some nephrons may excrete before others[8][9][10] and also because "the maximum reabsorption rate (or Tm) cannot be achieved until the amount/min of glucose being presented to the renal tubules is great enough to fully saturate the receptor sites".[11] John Field of the American Physiological Society said "Since the splay may occur when the residual nephrons are said to be free of anatomic abnormalities, the possibility exists that changes in the kinetics of glucose reabsorption may have been induced".[12]

One study found that glucose reabsorption exhibited low splay and another also found that the titration curves for glycine showed a large amount of splay whereas those for lysine showed none[13] and the kinetics of carrier-mediated glucose transport possibly explains the level of splay in renal titration curves. As splay can be clinically important, patients with proximal tubule disease, mainly caused by hereditary nature and often in children, have a lower threshold but a normal Tm. Therefore, splay is suggested, probably because "some individual cotransporters have a low glucose affinity but maximal transport rate (renal glycosuria).[14] Studies also show that if sulfate is reabsorbed by a Tm-limited process, it will have low splay and, in animals, the limits of citrate concentration normal in the body, citrate titration curves show a large amount of splay therefore a Tm for citrate reabsorption may actually happen. Also, tubular transport is Tm-limited and the reabsorption mechanism being saturated at a plasma concentration more than 20 times than usual shows a low level of splay.[13] Renal abnormalities of glucose excretion, causing glycosuria,[15] may happen as either a result of reduced Tm for glucose or because of an abnormally wide range of nephron heterogeneity so splay of the glucose excretion curve is increased.[16][17] Two causes are also listed for splay: "heteroginicity in glomerular size, proximal tubular length and number of carrier proteins for glucose reabsorption" and variability of TmG nephrons.[18] Splay also occurs between 180 and 350 mg/dL %.[18][19][20]

References

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  1. ^ a b Sembulingam, K.; Sembulingam, Prema (2012). Essentials of Medical Physiology. JP Medical Publishers. p. 323. ISBN 978-9350259368. Retrieved September 11, 2015.
  2. ^ Feher, Joseph (2012). Quantitative Human Physiology: An Introduction. Academic Press. p. 647. ISBN 978-0123821638. Retrieved September 11, 2015.
  3. ^ Rhoades, Rodney A.; Bell, David R. (2012). Medical Physiology: Principles for Clinical Medicine. Lippincott Williams & Wilkins. pp. 399–406. ISBN 978-1609134273. Retrieved September 11, 2015.
  4. ^ USMLE Step 1 Physiology Lecture Notes. Kaplan, Inc. 2015. p. 213. ISBN 978-1625236920. Retrieved September 11, 2015.
  5. ^ Costanzo, Linda S. (2013). Physiology. Elsevier. ISBN 978-1455728138. Retrieved September 11, 2015.
  6. ^ Costanzo, Linda S. (2001). Physiology Cases and Problems. Lippincott Williams & Wilkins. pp. 177–181. ISBN 0781724821. Retrieved September 11, 2015.
  7. ^ a b c Medical Physiology. Walter F. Boron, Emile L. Boulpaep (3rd ed.). Philadelphia, PA. 2017. p. 773. ISBN 978-1-4557-3328-6. OCLC 951680737.{{cite book}}: CS1 maint: location missing publisher (link) CS1 maint: others (link)
  8. ^ Joshi, Vijaya D.; Mendhuwar, Sadhana Joshi (2015). Physiology: Prep Manual for Undergraduates. Elsevier. pp. 174–175. ISBN 978-8131238042. Retrieved September 11, 2015.
  9. ^ Bullock, John; Boyle, Joseph; Wang, Michael B. (2001). Physiology, Volume 578. Lippincott Williams & Wilkins. pp. 348–349. ISBN 0683306030. Retrieved September 11, 2015.
  10. ^ Sanoop, K. S.; Mridul, G. S.; Nishanth, P. S. (2012). Physicon - The Reliable Icon In Physiology. JP Medical. pp. 125–359. ISBN 978-9350259009. Retrieved September 11, 2015.
  11. ^ Janssen, Herbert F. (1994). Bucket Diagrams: A Problem-solving Approach to Renal Physiology. Texas Tech University Press. p. 172. ISBN 0896723232. Retrieved September 11, 2015.
  12. ^ Field, John, Handbook of Physiology: Renal physiology, page 598, American Physiological Society
  13. ^ a b Koushanpour, Esmail; Kriz, Wilhelm (2013). Renal Physiology: Principles, Structure, and Function. Springer Publishing. pp. 218–234. ISBN 978-1475719123. Retrieved September 11, 2015.
  14. ^ Boron, Walter F.; Boulpaep, Emile L. (2012). Medical Physiology, 2e Updated Edition: with STUDENT CONSULT Online Access. Elsevier. ISBN 978-1455711819. Retrieved September 11, 2015.
  15. ^ Johnson, Leonard R. (2 October 2003). Essential Medical Physiology. Academic Press. pp. 385–387. ISBN 0123875846. Retrieved September 11, 2015.
  16. ^ Lote, Christopher (22 June 2012). Principles of Renal Physiology. Springer Publishers. pp. 57–58. ISBN 978-1461437857. Retrieved September 11, 2015.
  17. ^ Stave, Uwe (2013). Perinatal Physiology. Springer Publishers. p. 599. ISBN 978-1468423167. Retrieved September 11, 2015.
  18. ^ a b Kharana, Indu (2014). Textbook of Human Physiology for Dental Students. Elsevier. pp. 282–283. ISBN 978-8131238134. Retrieved September 11, 2015.
  19. ^ Premanik, Debasis; Premanik, Aparna (2006). Principles of Physiology. Academic Publishers India. pp. 271–272. ISBN 8189781340. Retrieved September 11, 2015.
  20. ^ Dudek, Ronald W. (2008). High-yield Physiology, Part 845, Volume 2008. Lippincott Williams & Wilkins. p. 83. ISBN 978-0781745871. Retrieved September 11, 2015.
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