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Applied Renal Physiology     31



                           C x ¼ GFR þ T x =P x                 As pressure increases, flow can remain constant only if
                                                                resistance increases proportionately. The site of this resis-
            Thus, the clearance of a substance experiencing net  tance change in the kidneys is the afferent arteriole.
            reabsorption is less than GFR (T x is negative), and the  Autoregulation is intrinsic to the kidneys and occurs in
            clearance of a substance experiencing net secretion is  the isolated, denervated kidney and in the adrenalecto-
            greater than GFR (T x is positive). The ratio of the clear-  mized animal. However, it is impaired by anesthesia in
            ance of a substance to inulin clearance gives an indication  proportion to the depth of anesthesia. The afferent
            of the net handling of that substance by the kidneys. If the  arterioles are maximally dilated at mean arterial pressures
            ratio is less than 1.0, the substance experiences net  of 70 to 80 mm Hg, and at lower pressures, GFR declines
            reabsorption; if it is greater than 1.0, it experiences net  linearly with RBF (i.e., autoregulation is lost). It is likely
            secretion.                                          that autoregulation of RBF is a consequence of the need
                                                                to regulate GFR closely and thus maintain tight control
            RENAL BLOOD FLOW AND                                over water and salt balance.Two physiologic mechanisms
            RENAL PLASMA FLOW                                   contribute to autoregulation. The myogenic mechanism
                                                                is based on the principle that smooth muscle tends to
            The kidneys receive 25% or more of cardiac output. The  contract when stretched and relax when shortened. As
            major sites of resistance within the kidneys are the afferent  the afferent arteriole is stretched by increased perfusion
            and efferent arterioles, with an approximately 80% to 90%  pressure, it constricts, thus limiting transmission of this
            decrease in perfusion pressure across this region of the  increased pressure to the glomerulus and minimizing
            renal vasculature (Fig. 2-6). Blood flow is not uniform  any change in glomerular capillary hydrostatic pressure
            throughout the kidneys. In dogs, more than 90% of   and SNGFR. The myogenic mechanism represents a
            RBF is normally directed to the renal cortex, less than  coarse control that operates with a delay of 1 to 2 seconds.
            10% to the outer medulla, and only 2% to 3% to the inner  Tubuloglomerular feedback represents a local
            medulla. 51  The actual rate of flow to the renal cortex is  intrarenal negative feedback mechanism for individual
            approximately 100 times that of resting muscle and is  nephrons. The morphologic basis for this physiologic
            required for glomerular filtration. Blood flow to the  mechanism is the JGA. Increased sodium chloride con-
            medulla is similar to that of resting muscle, and this  centration or transport in the distal tubule is sensed by
            reduced flow is necessary for normal function of the uri-  the extraglomerular mesangial cells of the JGA as they
            nary concentrating mechanism.                       monitor sodium chloride transport across the tubular
                                                                cells of the macula densa. Transport of NaCl by the tubu-
            AUTOREGULATION                                      lar cells of the macula densa requires functional NKCC2
                                                                                -
                                                                           þ
                                                                       þ
            Autoregulation refers to the intrinsic ability of an organ to  (the Na ,K , 2Cl cotransporter) and ROMK (a potas-
            maintain blood flow at a nearly constant rate despite  sium channel) in the luminal membranes and functional
                                                                        þ
                                                                   þ
            changes in arterial perfusion pressure. In the kidneys,  Na ,K -ATPase in the basolateral membranes. 46
            between perfusion pressures of 80 and 180 mm Hg,    Transcellular transport of NaCl causes generation of
            GFR and RBF vary less than 10% (Fig. 2-7). Flow (Q)  adenosine, which together with angiotensin II causes
            is equal to pressure (P) divided by resistance (R).  afferent arteriolar constriction in the parent glomerulus.
                                         Renal   Afferent      Efferent  Peritubular  Intrarenal  Renal
                                         artery  arteriole Glomerulus  arteriole  capillary  vein  vein


                                    100

                                     80
                                   Pressure (mm Hg)  60



                                     40


                                     20

                                     0
                        Figure 2-6 Pattern of hydrostatic pressure and vascular resistance in the renal circulation. (Drawing by
                        Tim Vojt.)
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