AUTOREGULATION

It is extremely important for the kidneys to keep the GFR at a level appropriate for the body because, as we have emphasized, the excretion of salt and water is strongly influenced by the GFR. We have also emphasized that the GFR is strongly influenced by renal arterial pressure. A rise in blood pressure causes an increased excretion of salt and water, a process called pressure natriuresis, whereas a fall in blood pressure diminishes excretion. These changes in excretion are mediated partly via changes in GFR. The effect is so strong that urinary excretion would tend to vary widely with the ordinary daily excursions of arterial pressure. Also, vascular pressure in the thin-walled glomerular capillaries is higher than in capillaries elsewhere in the body and hypertensive damage ensues if this pressure is too high.
Therefore, both to protect the glomerular capillaries from hypertensive damage and to preserve a healthy GFR, changes in GFR and RBF are severely blunted by mechanisms that we collectively call autoregulation. Consider first a situation in which mean arterial pressure rises 20%. Such a modest rise occurs many times throughout the day in association with changes in excitement level and activity. Pretend, for the moment, that all renal vascular resistances remain constant. By the basic flow equation (Q = ΔP/R), RBF would rise 20% also (actually slightly more if pressure in the renal vein is unaffected). What would this do to GFR? It would rise much more than 20%, in fact almost 50%. This is because net filtration pressure would rise almost 50%. In effect, fractional changes in upstream pressure (in the renal artery) are magnified in terms of net filtration pressure. Why is this? At the beginning of the glomerulus, capillary hydrostatic pressure is about 60 mm Hg and the pressures opposing filtration sum to 36 mm Hg, yielding a net filtration pressure of about 24 mm Hg. With an increase in arterial pressure to 120 mm Hg, capillary pressure would rise to about 71 m Hg, but there would be no increase in the pressures that oppose filtration–plasma oncotic pressure and Bowman’s capsule pressure. Therefore, net filtration pressure would rise to 71 – 36 = 35 mm Hg (an increase of almost 50%). The higher net filtration pressure would cause a parallel increase in GFR. (In turn, this would raise plasma oncotic pressure at the distal end of the glomerulus, tending to reduce filtration somewhat, but the total effect is still a major rise in GFR.) This emphasizes the crucial role of glomerular capillary pressure in glomerular filtration.
Now, what actually happens in the face of changes in mean arterial pressure? As is the case in many organs, blood flow does not change in proportion to changes in arterial pressure. The changes are blunted. A rise in driving pressure is counteracted by a rise in vascular resistance that almost offsets the rise in pressure. The word “almost” is crucial here. Higher driving pressures do indeed lead to higher flow but not proportionally. Within the range of mean arterial pressures commonly found in the human body4), RBF varies only modestly when mean arterial pressure changes. This is partly a result of a direct reaction of the vascular smooth muscle to stretch or relaxation—or the myogenic response—and partly the result of intrarenal signals that we describe shortly. The myogenic response is very fastacting and protects the glomeruli from short-term fluctuations in blood pressure. In addition to keeping changes in RBF fairly small, autoregulatory processes also keep changes in GFR fairly small. Again, GFR does rise with an increase in arterial pressure, just not substantially.

Autoregulation of renal blood flow (RBF). A similar pattern holds for glomerular filtration rate.

How do the intrarenal processes work? Much is by way of a process with the clumsy name of tubuloglomerular feedback. Tubuloglomerular feedback is feedback from the tubules back to the glomerulus (ie, an influence of events in the tubules that is exerted on events in the glomeruli). But for now the essence of tubuloglomerular feedback can be summarized as follows: As the filtration rate in an individual nephron increases or decreases, the amount of sodium that escapes reabsorption in the proximal tubule and the loop of Henle also increases or decreases. More sodium filtered means more sodium remaining in the lumen of the nephron and more sodium flowing from the thick ascending limb into the distal tubule. Recall that at the division between these nephron segments lies the macula densa, a special group of cells in the nephron wall where the nephron passes between the afferent and efferent arterioles. The macula densa cells sense the amount of sodium and chloride in the lumen. They act, in part, as salt detectors. One result of changing levels of luminal sodium chloride is to increase or decrease the secretion of transmitter agents into the interstitial space that affect the filtration in the nearby glomerulus. High levels of sodium flowing past the macula densa cause a decrease in filtration rate; low levels of sodium flowing past allow a higher filtration rate. It is as though each nephron adjusts its filtration so that the right amount of sodium remains in the lumen to flow past the macula densa. How can it adjust its filtration? The transmitter agents released by the salt-sensing macula densa cells produce vasoconstriction of the afferent arteriole, thereby reducing hydrostatic pressure in the glomerular capillaries. These same agents also produce contraction of glomerular mesangial cells, thereby reducing the effective filtration coefficient. Both processes reduce the single-nephron filtration rate and keep it at a level appropriate for the rest of the nephron.
In conclusion, we emphasize that autoregulation blunts or lowers the RBF and GFR responses to changes in arterial pressure but does not totally prevent those changes.