Tubuloglomerular feedback

In the physiology of the kidney, tubuloglomerular feedback (TGF) is a feedback system inside the kidneys. Within each nephron, information from the renal tubules (a downstream area of the tubular fluid) is signaled to the glomerulus (an upstream area). Tubuloglomerular feedback is one of several mechanisms the kidney uses to regulate glomerular filtration rate (GFR). It involves the concept of purinergic signaling, in which an increased distal tubular sodium chloride concentration causes a basolateral release of adenosine from the macula densa cells. This initiates a cascade of events that ultimately brings GFR to an appropriate level.Body water: Intracellular fluid/Cytosol In the physiology of the kidney, tubuloglomerular feedback (TGF) is a feedback system inside the kidneys. Within each nephron, information from the renal tubules (a downstream area of the tubular fluid) is signaled to the glomerulus (an upstream area). Tubuloglomerular feedback is one of several mechanisms the kidney uses to regulate glomerular filtration rate (GFR). It involves the concept of purinergic signaling, in which an increased distal tubular sodium chloride concentration causes a basolateral release of adenosine from the macula densa cells. This initiates a cascade of events that ultimately brings GFR to an appropriate level. The kidney maintains the electrolyte concentrations, osmolality, and acid-base balance of blood plasma within the narrow limits that are compatible with effective cellular function; and the kidney participates in blood pressure regulation and in the maintenance of steady whole-organism water volume Fluid flow through the nephron must be kept within a narrow range for normal renal function in order to not compromise the ability of the nephron to maintain salt and water balance. Tubuloglomerular feedback (TGF) regulates tubular flow by detecting and correcting changes in GFR. Active transepithelial transport is used by the thick ascending limb (TAL) cells to pump NaCl to the surrounding interstitium from luminal fluid. The Tubular fluid is diluted because the cell's walls are water-impermeable and do not lose water as NaCl is actively reabsorbed. Thus, the TAL is an important segment of the TGF system, and its transport properties allow it to act as a key operator of the TGF system. A reduction of GFR occurs as a result of TGF when NaCl concentration at the sensor site is increased within the physiological range of approximately 10 to 60 mM. The TGF mechanism is a negative feedback loop in which the chloride ion concentration is sensed downstream in the nephron by the macula densa (MD), cells in the tubular wall near the end of TAL and the glomerulus. The muscle tension in the afferent arteriole is modified based on the difference between the sensed concentration and a target concentration. Vasodilation of the afferent arteriole, which results in increased glomerular filtration pressure and tubular fluid flow, occurs when MD cells detect a chloride concentration that is below a target value. A higher fluid flow rate in the TAL allows less time for dilution of the tubular fluid so that MD chloride concentration increases. Glomerular flow is decreased if the chloride concentration is above the target value. Constricting the smooth muscle cells in the afferent arteriole, results in a reduced concentration of chloride at the MD. TGF can stabilizes the fluid and solute delivery into the distal portion of the loop of Henle and maintain the rate of filtration near its ideal value using these mechanisms. The macula densa is a collection of densely packed epithelial cells at the junction of the thick ascending limb (TAL) and distal convoluted tubule (DCT). As the TAL ascends through the renal cortex, it encounters its own glomerulus, bringing the macula densa to rest at the angle between the afferent and efferent arterioles. The macula densa's position enables it to rapidly alter afferent arteriolar resistance in response to changes in the flow rate through the distal nephron. The macula densa uses the composition of the tubular fluid as an indicator of GFR. A large sodium chloride concentration is indicative of an elevated GFR, while low sodium chloride concentration indicates a depressed GFR. Sodium chloride is sensed by the macula densa mainly by an apical Na-K-2Cl cotransporter (NKCC2). The relationship between the TGF and NKCC2 can be seen through the administration of loop diuretics like furosemide. Furosemide blocks NaCl reabsorption mediated by the NKCC2 at the macula densa, which leads to increased renin release. Excluding loop diuretic use, the usual situation that causes a reduction in reabsorption of NaCl via the NKCC2 at the macula densa is a low tubular lumen concentration of NaCl. Reduced NaCl uptake via the NKCC2 at the macula densa leads to increased renin release, which leads to restoration of plasma volume, and to dilation of the afferent arterioles, which leads to increased renal plasma flow and increased GFR. The macula densa's detection of elevated sodium chloride concentration in the tubular lumen, which leads to a decrease in GFR, is based on the concept of purinergic signaling.