The macula densaRegulation of GFR
You might want to read the nephron overview and glomerular filtration entries.



The macula densa

As the distal proximal tubule rises from the renal medulla, it makes close contact with the glomerulus. The cells on the side of the tubule facing the glomerulus have a distinct appearance and constitute the macular densa (Figure 1). These cells sense the NaCl content of the tubule and make changes to GFR appropriately.

macula densa

Figure 1: The macula densa is a region of specialised cells lining the distal convoluted tubule. It monitors tubular NaCl concentrations and adjusts glomerular filtration accordingly. It is ideally situated close to the afferent arteriole which governs glomerular filtration and the granular cells which surround the afferent arteriole and secrete renin when appropriately stimulated.

A high concentration of NaCl in distal tubular fluid usually results from an excessive glomerular filtration rate (GFR), such that there is not time for the NaCl to be reabsorbed in the renal tubules. Under these circumstances, macula densa cells release adenosine, which constricts the nearby afferent arteriole, reducing glomerular perfusion and hence GFR.

On the other hand, low tubular NaCl usually results from excessive reabsorption because GFR is low. When this occurs, the macular densa cells release prostaglandin E2 (PGE2), which triggers release of renin from the granular cells (AKA juxtaglomerular cells) surrounding the afferent arteriole as it enters the glomerulus. Renin release activates the renin-angiotensin system increasing blood pressure and consequently renal perfusion.

Another way to think about GFR and NaCl reabsorption is to picture the renal tubule as a long conveyor belt shifting NaCl through the nephron. Pumps and transporters try to reabsorb sodium (like workers removing items from a conveyor belt in a factory) as it moves along. When the conveyor belt is moving slowly (low GFR) it is easy to grab every bit of NaCl off the conveyor belt before it reaches the end (the macula densa). However, if the conveyor belt is moving too quickly (high GFR), some of the NaCl is left on the belt at the end. By speeding up or slowing down the conveyor belt (GFR) you control the amount of NaCl on it at the end.


NaCl and GFR adjustments

The exact molecular details of exactly how changes in NaCl lead to adenosine or PGE2 release are still incompletely understood and the subject of ongoing research. Accumulation of Na+ in macular densa cells leads to release of adenosine (or ATP, which subsequently breaks down to adenosine), due to cell swelling as water follows excess Na+ into cells (Figure 2). The exact mechanism linking cellular swelling to adenosine/ATP release is not certain at present. Just how reduced intracellular NaCl is detected by macula densa cells and leads to PGE2 production is not well defined at present. One view holds that it is intracellular Cl- that is the trigger. PGE2 is known to be produced by cyclooxygenase-2, but just how the activity of this enzyme is regulated by Cl- (or Na+) isn't clear.

macula densa renin

Figure 2: Figure 2: NaCl sensing and responses by macular densa cells. Under normal circumstances, Na+ is pumped into macula densa cells from the tubular lumen by the Na+/K+/Cl- cotransporter, and out of the basal surface of the cells via the Na+/K+ ATPase pump. When tubular Na+ is high, Na+ enters the cells at a rate which saturates the Na+/K+ ATPase pump, so that Na+ accumulates within the cells. This causes cell swelling and adenosine (or ATP which subsequently breaks down to adenosine) is released, constricting the nearby afferent artery, reducing GFR. By contrast, when tubular NaCl is low, the intracellular concentration if NaCl is reduced in macula densa cells PGE2 is released, causing renin release from granular cell, increasing blood pressure (and hence, GFR) via the renin-angiotensin system.



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