Tubuloglomerular feedback 5436642 217170772 2008-06-04T22:21:02Z Diberri 35331 that's redundant, isn't it? if I'm wrong, please explain In the [[renal physiology|physiology of the kidney]], '''tubuloglomerular feedback''' ('''TGF''') is one of several mechanisms the kidney uses to regulate [[glomerular filtration rate]] (GFR). Changes in GFR are detected by the [[renal tubule]], which sends [[feedback]] signals to the [[glomerulus]], initiating a cascade of events that ultimately brings GFR to an appropriate level. ==Background== Normal renal function requires that the flow through the [[nephron]] is kept within a narrow range. When tubular flow (that is, GFR) lies outside this range, the ability of the nephron to maintain solute and water balance is compromised. Additionally, changes in GFR may result from changes in [[renal blood flow]] (RBF), which itself must be maintained within narrow limits. Elevated RBF may damage the [[glomerulus]], while diminished RBF may deprive the kidney of oxygen. Tubuloglomerular feedback provides a mechanism by which changes in GFR can be detected and rapidly corrected for on a minute-to-minute basis as well as over sustained periods. Regulation of GFR requires both a mechanism of detecting an inappropriate GFR as well as an effector mechanism that corrects it. The [[macula densa]] serves as the detector, while the [[glomerulus]] acts as the effector. When the macula densa detects an elevated GFR, it releases several molecules that cause the glomerulus to rapidly decrease its filtration rate. (Technically, the macula densa detects a SNGFR, single nephron GFR, but ''GFR'' is used here for simplicity.) ==Mechanism== The [[macula densa]] is a collection of densely packed epithelial cells in the [[distal convoluted tubule]]. As the [[loop of Henle]] ascends through the renal cortex, it encounters its own [[glomerulus]], bringing the macula densa to rest at the angle between the [[afferent arteriole|afferent]] and [[efferent arteriole]]s. This places the macula densa in a unique position to rapidly alter glomerular resistance in response to changes in the flow rate through the distal nephron. The [[distal renal tubule]] uses the composition of the tubular fluid as an indicator of GFR. A large amount of sodium chloride is indicative of an elevated GFR, while low sodium chloride indicates a depressed GFR. Sodium chloride is sensed by the macula densa by an apical [[Na-K-2Cl cotransporter]] (NKCC2). Detection of elevated sodium chloride levels triggers the release of signaling molecules from the macula densa, causing a drop in GFR. This drop is thought to be mediated largely by [[vasoconstriction|constriction]] of the [[afferent arteriole]]. Precisely how the macula densa's detection of elevated sodium chloride leads to a decrease in GFR remains unknown. One proposed mechanism is that delivery of sodium chloride to the macula densa enhances the conversion of [[adenosine triphosphate|ATP]] to [[adenosine]]. Adenosine may then bind to [[adenosine receptor|adenosine A<sub>1</sub> receptors]] on [[extraglomerular mesangial cell]]s, triggering a rise in intracellular [[calcium]] levels. This calcium signal may be propagated via [[gap junction]]s to adjacent cells, including granular cells of the [[juxtaglomerular apparatus]] and [[vascular smooth muscle]] cells of the afferent arteriole, resulting in afferent arteriole vasoconstriction and a decrease in [[renin]] release.<ref>{{cite journal |author=Vallon V |title=Tubuloglomerular feedback and the control of glomerular filtration rate |journal=News Physiol. Sci. |volume=18 |issue= |pages=169–74 |year=2003 |pmid=12869618 |doi= |url=http://physiologyonline.physiology.org/cgi/content/full/18/4/169}}</ref> ==Modulation== There are several factors that may modulate the sensitivity of tubuloglomerular feedback. A decreased sensitivity results in that a higher tubular perfusion is allowed, while, in contrast, an increased sensitivity results in a lower tubular perfusion. Factors that ''decrease'' TGF sensitivity include:<ref name="boron">{{cite book |author=Walter F., PhD. Boron |title=Medical Physiology: A Cellular And Molecular Approaoch |publisher=Elsevier/Saunders |location= |year= |pages= |isbn=1-4160-2328-3 |oclc= |doi=}}</ref> *[[atrial natriuretic peptide]] *[[nitric oxide]] *[[cAMP]] *[[prostacyclin|PGI<sub>2</sub>]] *[[high protein diet]] *[[adenosine]] Factors that ''increase'' TGF sensitivity include:<ref name="boron"/> *[[adenosine]] *[[prostaglandin E2]] *[[thromboxane]] *[[5-hydroxyeicosatetraenoic acid|HETE]] *[[angiotensin II]] ===High protein diet=== The increased load on the kidney of [[high protein diet]] is a result of an increase in [[renal reabsorption|reabsorption]] of [[sodium chloride|NaCl]]. This causes a decrease the sensitivity of tubuloglomerular feedback, which, in turn, results in an increased [[glomerular filtration rate]]. This increases pressure in [[glomerular]] capillaries.<ref name="boron"/> When added to any additional renal disease, this may cause permanent glomerular damage. ==References== * {{cite book | title = Brenner & Rector's The Kidney | edition = 7th ed. | publisher = Saunders, An Imprint of Elsevier | year = 2004}} * {{cite book | author=Eaton, Douglas C., Pooler, John P. | year=2004 | title=Vander's Renal Physiology | edition=8th edition | publisher=Lange Medical Books/McGraw-Hill | id=ISBN 0-07-135728-9}} <references /> [[Category:Kidney]] [[Category:Physiology]] [[Category:Reflexes]]