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Glomerular Filtration and Clearance  Indicators present in the plasma are used to
                                       measure GFR. They must have the following
       The glomerular filtration rate (GFR) is the total  properties:
       volume of fluid filtered by the glomeruli per  — They must be freely filterable
       unit time. It is normally about 120 mL/min per  — Their filtered amount must not change due
           2
       1.73 m of body surface area, equivalent to  to resorption or secretion in the tubule
       around 180 L/day. Accordingly, the volume of  — They must not be metabolized in the kidney
       exchangeable extracellular fluid of the whole  — They must not alter renal function
       body (ca. 17 L) enters the renal tubules about  Inulin, which must be infused intravenously,
    Kidneys, Salt, and Water Balance  lute H 2O excretion (= urine output/time = V U) is  (! A) is calculated as the plasma concentra-
       10 times a day. About 99% of the GFR returns to
                                       fulfills these requirements. Endogenous crea-
       the extracellular compartment by tubular re-
                                       tinine (normally present in blood) can also be
                                       used with certain limitations.
       absorption. The mean fractional excretion of
                                        The amount of indicator filtered over time
       H 2O is therefore about 1% of the GFR, and abso-
                                 .
                                       tion of the indicator (P In, in g/L or mol/L) times
       about 1 to 2 L per day. (The filtration of dis-
                                       the GFR in L/min. The same amount of indica-
       solved substances is described on p. 154).
                                       tor/time appears in the urine (conditions 2 and
         The GFR makes up about 20% of renal
                                                            .
                                       3; see above) and is calculated as V U (in L/min),
       plasma flow, RPF (! p. 150). The filtration frac-
       tion (FF) is defined as the ratio of GFR/RPF. The
                                       times the indicator conc. in urine (U In, in g/L or
                                                        .
                                             .
       peptide hormone that increases efferent arte-
                                             VU ! U In
                                                  [L/min] (! A).
                                        GFR !
       riolar resistance (R e) while lowering afferent
                                              P In
    7  filtration fraction is increased by atriopeptin, a  mol/L, resp.), i.e. P In ! GFR = V U ! U In, or:  [7.8]
                                       The expression on the right of Eq. 7.8 repre-
       arteriolar resistance (R a). This raises the effec-
       tive filtration pressure in the glomerular capil-  sents clearance, regardless of which substance
       laries without significantly changing the over-  is being investigated. Therefore, the inulin or
       all resistance in the renal circulation.  creatinine clearance represents the GFR. (Al-
         The effective filtration pressure (P eff) is the  though the plasma concentration of creat-
       driving “force” for filtration. P eff is the glomer-  inine, P cr, rises as the GFR falls, P cr alone is a
       ular  capillary  pressure  (P cap ! 48 mmHg)  quite unreliable measure of GFR.)
       minus the pressure in Bowman’s capsule (P Bow  Clearance can also be regarded as the
       ! 13 mmHg) and the oncotic pressure in  completely indicator-free (or cleared) plasma
       plasma (π cap = 25 to 35 mmHg):  volume flowing through the kidney per unit
         P eff ! P cap –P Bow –π cap  [7.6]  time. Fractional excretion (FE) is the ratio of
       P eff at the arterial end of the capillaries equals  clearance of a given substance X to inulin
       48–13–25 = 10 mmHg. Because of the high fil-  clearance (C X/C In) and defines which fraction
       tration fraction, the plasma protein concentra-  of the filtered quantity of X was excreted (cf.
       tion and, therefore, π cap values along the glo-  p. 154). FE " 1 if the substance is removed from
                                                            +
                                                               –
       merular capillaries increase (! p. 378) and P eff  the tubule by reabsorption (e.g. Na , Cl , amino
       decreases. (The mean effective filtration pres-  acids, glucose, etc.; ! B1), and FE # 1 if the
       sure, P eff, is therefore used in Eq. 7.7.) Thus, fil-  substance is subject to filtration plus tubular
       tration ceases (near distal end of capillary)  secretion (! B2). For PAH (! p. 150), tubular
       when π cap rises to about 35 mmHg, decreasing  secretion is so effective that FE PAH ! 5 (500%).
       P eff to zero (filtration equilibrium).  The absolute rate of reabsorption or secre-
         GFR is the product of P eff (mean for all glo-  tion of a freely filterable substance X (mol/
       meruli), the glomerular filtration area A (de-  min) is calculated as the difference between
       pendent on the number of intact glomeruli),  the filtered amount/time (GFR · P X) and the ex-
                                                    .
       and the water permeability k of the glomerular  creted amount/time (V U · U X), where a positive
       filter. The ultrafiltration coefficient K f is used to  result means net reabsorption and a negative
       represent A · k. This yields    net secretion. (For inulin, the result would be
         GFR ! P eff ! K f.      [7.7]  zero.)
  152
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