from Leadership Medica n. 271/2009
An integrated physiologic model
The study of kidney physiology and cardiovascular system physiology has long unveiled several points of contact from which the existence of integrated mechanisms between the two systems has readily been inferred. In the past years a historical foundation was laid down by A.C. Guyton who wrote “a renal fraction does exist, i.e. the portion of the total cardiac output that enters the kidney, this fraction has been assessed to be around 21% of the total cardiac output since the total cardiac output of a resting healthy adult male is about 5,600 cc/m’ and the relevant blood supply to the two kidneys is about 200 cc/m’; this renal fraction may range from 12 % to 30% even in healthy subjects at rest” (1).
This basic notion has for many years suggested that the kidney “depurative” function, which takes place through a process of glomerular capillariy plasma filtration, correlated only with the blood flow rate of the same glomeruli as a function of the quantity of blood the heart was able to supply to peripheral circulation. This same notion was at the basis of the so-called “pre-renal renal failure” observed in clinical practice, i.e. a renal dysfunction resulting from heart and/or systemic conditions involving a decreased cardiac output. On these grounds the kidney was universally thought to be an hemodynamically passive organ whose functional efficiency only relied on the amount of blood received from the heart. Hence the kidney was considered as an organ whose main function seemed to be confined to either reducing or increasing the glomerular filtration rate in response (and in the same percentage) to heart output reduction or increase.
However, as early as 1984 Katoli reported that renal parenchymal afferent nerve fibers are able to send adenosine-mediated general nerve impulses to the diencephalon and that these impulses result in arterial hypertension with increased norepinephrine plasma levels (2).
In 1987 Katoli completed his studies reporting the occurrence of a “renal reflex”, between the renal tissue and the orthosympathetic autonomic nervous system (3).
More recently, Ciriello J. (4), Johns E.J. (5) and Phillips J.K (6) have reported that the renal afferent nerve fibers in question reach the different levels of the central nervous system thus interacting, with other impulses coming from other districts, in the genesis of the orthosympathetic descending efferent nerve fibers and participating in the regulation of systemic blood flow, vascular tone and arterial hypertension.
Against this background one first new notion has been added to modern renal physiology which maintains that the kidney is not a passive “observer” of the oscillations of the renal blood flow rate serving exclusively as a filter of the blood that is however supplied to it. Quite the contrary, the kidney is an organ equipped with chemoceptive and mechanoceptive sensors through which renal blood flow rate increases and decreases are perceived which trigger different amounts of diancephalon-targeted and proximal brainstem-targeted nerve impulses that are involved in the modulation of the orthosympathetic activity and result in cardiovascular effects meant to rectify the renal blood flow rate increases and decreases in question by inducing variations in both arterial pressure and heart rate.
This sequence of orthosympathetic efferent impulses from the diencephalon-proximal brainstem areas, which is “also” made of impulses whose generation is “directed” by the kidney itself, reaches the renal tissue by scattering impulses on bundles of nerve fibers that make their way into specific intrarenal areas (afferent arteriole, efferent arteriole, macula densa, distal tubule), gently stimulating the specific functions of these latter (7)(8)(9). These observations have led to the formulation of a second notion of renal physiology under which the kidney is able to modulate the orthosympathetic systemic function by self-regulating all of its individual functional units and not only parenchymal blood perfusion. Finally, the latest renal physiology (from 2005 to 2008) studies carried out by Xu J. and Li G. have highlighted the existence of a third hormone produced by the kidney (besides renin and erythropoietin). The production of this hormone, referred to as “renalase”, which is able to catabolize norepinephrine and the other catecholamines in the blood flow by means of a monoaminoxidase-like mechanism, is stimulated by the increase in the blood concentration of the same catecholamines (10)(11)(12). The kidney is therefore able to counter any orthosympathetic activity increases by providing a mechanism of protection against renal and systemic damage from arterial hypertension and heart failure. Hence it can be concluded that, thirty years after A.C. Guyton studies, modern renal physiology considers the kideney as a chemo/mechanoceptive “sensor” which senses systemic emodynamic oscillations playing a role in their neurovegetative regulation in order to fulfill four objectives: i) ensuring an optimal blood perfusion for glomerular filtration, ii) regulating and coordinating the activity of its various functional units (afferent arteriole, efferent arteriole, macula densa, distal tubule), iii) containing the onset of systemic arterial hypertension, and iv) playing a proactive cardioprotective role. In conclusion, the need is felt to conduct new studies to explore haw the physiologic response to neurovegetative stimuli correlates to the renal function level indicated by the glomerular filtration rate (GFR) in a view to demonstrating that a decreased GFR results in cardiovascular alterations whose size is directly proportional to the same GFR reduction.
Professor Maurizio Mingarelli
Specialista in Nefrologia
Docente a contratto in Fisiologia Umana - Dipartimento di Scienze Biomediche Facolta’ di Medicina Universita’ di Foggia
1. Guyton A.G. Trattato di Fisiologia Medica traduzione italiana IV’ edizione Piccin Editore : pag 405 (1977)
2. Katoli R.E. et coll. J.Hypertension 2(4):349-359 (1984)
3. Katoli R.E. et coll Clin. Exp.Hypertension A. 9 (1): 221-226 (1987)
4. Ciriello J. Curr. Hypertens.Rep. 4(apr):136-142 (2002)
5. Johns E.J. Experimental Physiology 90 (2) : 163-168 (2004)
6. Phillips J.K Clin. Exp. Pharmacol. Physiol. 32(5-6): 415-418 (2005)
7. DiBona G.F. Am.J.Physiol.Regul.Integr. Comp.Physiol.279: R1517-1524 (2000)
8. Denton M.K. Proceedings Australian Physiological Pharmacol-Society, 34: 85-91 (2004)
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10. Xu J. J.Clin.Inv. (115): 1275-1280 (2005)
11. Xu J. Curr. Opin. Nephrol. Hypertens. (16): 373-378 (2007)
12. Li G. Circulation 117(10) : 1277-1282 (2008)
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