General renal pathophysiology

General renal pathophysiology • 1. Relationship between plasma solute concentration and its excretion by kidneys • 2. Renal perfusion and filtration

2. Renal perfusion and filtration • Autoregulation of the kidneys • Autoregulation of perfusion of an organ means keeping its perfusion constant in spite of fluctuations of the systemic blood pressure • As with all organs, Ohm´s formula is valid also for a perfusion (renal blood flow) of the kidneys. Specifically: • P • RBF = -------, where P = Pa - Pe a R = Ra + Re • R • R must be variable, however, as both renal perfusion and GFR are constant in a broad range of systemic pressures (90-190 mm Hg mean arterial pressure or 11-25 kPa) (Fig. 17). Further term: renal plasma flow

The equation R = Ra + Re is approximately valid, as vasa afferentia and vasa efferentia represent the main points of vascular resistence in the kidneys (Fig. 18).

The upper formula could therefore be rewritten as • P P • RBF = ------------ = -------------, • R Ra + Re • which implies that RPF declines with either rise of Ra, Re or of both of them. • RBF is regulated in accord with a double, mutually conflicting aim: • in a sense of autoregulation when the decline of the systemic pressure is moderate • the kidneys are “cut off” when the decline of the systemic pressure is large  • prerenal azotemia, possibly with morphological consequences (acute tubular necrosis), Fig. 19 B, C.

Renal autoregulation of the kidney shoud not be confused – regarding their mechanisms - with theregulation of circulating volume, though RAS seems to play a role in both of them (not proven in case of autoregulation so far, however) The circulating volume is homeostased mainly by means of the endocrine RAS against disturbing factors such as loss or overplus of water, salt etc. (Fig.20)

The kidney autoregulation ensures homeostasis of kidney perfusion and GFR in spite of fluctuations of systemic pressure (e.g. when the position of the body in space is changed) and is conditioned by: • - sc. myogenic (Bayliss) reflex (passively • distracted vessels contract, incl. in vitro; a • result of Ca entry into the smooth muscle cells) • -tubuloglomerular feedback (TGF), which may • be represented by a local (paracrine) RAS • (Fig.21)

RENAL AUTOREGULATION RPF GFR EGM MD GC  RENIN Re Ra 21

JGA : RAS OR OTHER VASOACTI- VE SUBSTANCES MYOGENIC „REFLEX“ (BAYLISS) Ra . Re ? VTUB OSM Na+ Cl - Ca2+ . . . ? SYST.BP RBF  GFR KEPT KONSTANT PO2 IN KIDNEYS KEPT KONSTANT  DISTENTION REGULATION OF WATER AND SOLUTES 21

Renin is formed mainly in the juxtaglomerular apparatus, under the influence of • - the baroreceptors in afferent arterioles (they • react on a lowered perfusion pressure, see • Goldblatt´s clamp, renovascular hypertension) • - macula densa reacting on the electrolyte • composition in the distal tubulus • - vegetative nerves: sympaticus enhances, • parasympaticus loweres the production of • renin • The further role of RAS is both paracrine and endocrine, however

GFR • Factors determining GFR: • The pressures in the glomerular capillary behave differently compared to the systemic circulation. • It seems that the point of attaining equilibrium between hydrostatic and oncotic pressure components is situated within the capillary under the physiologic conditions; the point may move along the length of the capillary easily, however (Fig. 22)

Starling equation is commonly used for calculation of GFR, it has an array of weak points, however: - some of their factors are not mutually independent - it presupposes constant pressures along the capillary; futher, that we know the extent of filtration area etc. - it does not encompass the share of perfusion in GFR The hydrostatic pressure in the capillary is conditioned by a relatively complicated interplay of afferent and efferent pressures and resistence (Figs.23,24)

FACTORS DETERMINING GFR STARLING FORCES vGC GFR = F * Lp * PUF PUF = (PGC - PBS) - (GC - BS)  P  RePa + RaPe PGC = Ra + Re 23

On the other hand, it is evident that GFR is conditioned also by perfusion, though in a manner which is not exactly describable so far A linear relationship between GFR and RBF could be presupposed only under physiological conditions (the point of equilibrium is attained within the capillary) If the hydraulic conductivity declines in relation to the plasma flow velocity under pathological conditions, the point of equilibrium “escapes beyond the horizon” and GFR does not parallel the RPF. In a limit case, GFR ceases to be dependent on RPF at all (Fig.25)

RENAL PLASMA FLOW vGC GFR Lp SERIOUSLY PATHOL. . ? PATHOL. PHYSIOL. RPF 25

It is evident that a unified formal description of glomerular filtration is a distant goal so far. Elasticity of vessels, so far neglected, may be one of the causes. The interconnection between RPF and GFR could be symbolized as follows: Ohm´s law Ra + Re RPF PUF Lp F GFR

Typical pathophysiological changes of RPF • and GFR • Changes of RPF and GFR in particular pathophysiolo- • gical situations are describable only semiquantitatively • so far, as a result of difficulties mentioned (Fig.26)

F  GFR 26

Commentary to the Fig.26: 1: Normal situation, filtration equilibrium is attained at the border of 1st and 2nd third of the capillary length 2. Lowered hydraulic conductance (nephritic diseases), filtration equilibrium is not attained, GFR declines 3. Contraction of vas afferens (e.g., strenuous exercise)  RBF 4. Postglomerular resistence enhanced (Ra + R e) GFR 5. Plasma proteins  (multiple myeloma, amyloidosis, hemolysis) GFR 6. Glomerulonephritis: (Ra + R e) RPF. Decline of conductivity hampers attaining of filtration equilibrium GFR

General renal pathophysiology