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CHAPTER • 2



                               Applied Renal Physiology






                               Stephen P. DiBartola

                               “Superficially it might be said that the function of the kidneys is to make urine; but in a more considered view, one
                               can say that the kidneys make the stuff of philosophy itself.”
                                                                                                   Homer W. Smith




            Each day the glomeruli of the kidneys filter an enormous  any substance may be calculated, but the clearance of
            volume of plasma water, and the tubules must reabsorb  certain substances (e.g., inulin, p-aminohippuric acid
            most of this water along with vital solutes so that only a  [PAH], and creatinine) provides important information
            small volume of water and unneeded solutes are excreted  about renal function (see later discussion of measurement
            as urine. For example, a normal 10-kg dog may have a  of glomerular filtration rate and measurement of renal
            glomerular filtration rate (GFR) of 4 mL/min/kg. In  blood flow and renal plasma flow).
            the course of one day, this dog would filter 57.6 L of
            plasma water in its kidneys. If 60% of body weight is  GLOMERULAR FILTRATION
            water, this volume represents almost 10 times the dog’s
            total body water. The same dog may have a urine output
            of 33 mL/kg/day. Thus, more than 99% of plasma water  GLOMERULAR MORPHOLOGY
            filtered by the glomeruli is reabsorbed by the tubules. The  The glomerular capillary wall or filtration barrier consists
            proximal tubules and loops of Henle reabsorb approxi-  of three components: the capillary endothelium, base-
            mately 85% of the filtered water and solutes, whereas  ment membrane, and visceral epithelium (Fig. 2-2).
            the collecting ducts adjust the final composition of urine  The glomerulus is a unique vascular structure consisting
            to compensate for fluctuations in intake and prevent  of a capillary bed interposed between two arterioles: the
            changes in the volume and composition of body fluids.  afferent and efferent arterioles. The glomerular capillary
            The major functions of the various segments of the neph-  divides into several branches, each of which forms a lob-
            ron are depicted in Figure 2-1.                      ule of the glomerulus. The capillary endothelium of the
                                                                 glomerulus is fenestrated by openings 50 to 100 nm in
            CONCEPT OF RENAL                                     diameter. These openings exclude cells from the ultrafil-
            CLEARANCE                                            trate, but macromolecules are not restricted based on
                                                                 size. The luminal surface of the endothelium is covered
            An appreciation of the concept of clearance is crucial to  by negatively charged sialoglycoproteins that contribute
            understanding how renal function is evaluated clinically.  to the charge selectivity of the filtration barrier.
            The renal clearance of a substance is the volume of plasma  The glomerular basement membrane is composed of
            that contains the amount of the substance excreted in the  the lamina rara interna on the endothelial side, the central
            urine in 1 minute. It is the volume of plasma that must be  lamina densa, and the lamina rara externa on the epithelial
            filtered each minute to account for the amount of the  side. The lamina rara interna and lamina rara externa con-
            substance appearing in the urine each minute under   tain polar noncollagenous proteins that contribute to the
            steady-state conditions. If the concentration of the sub-  negative charge of the filtration barrier. The lamina densa
            stance in urine is U x and the urine flow rate is V, the  contains nonpolar collagenous proteins that contribute
            amount of the substance excreted in the urine per minute  primarily to the size selectivity of the filtration barrier.
            is U x V. If the concentration of the substance in plasma is  The filtration barrier is permeable to molecules with
            P x , the volume of plasma that contains the same quantity  effective molecular radii less than 2 nm and impermeable
            of that substance or the volume of plasma that must be fil-  to those with radii greater than 4 nm.
            tered per minute to account for that amount in the urine is  The visceral epithelial cells or podocytes constitute
            U x V/P x , the standard clearance formula. The clearance of  the outermost portion of the filtration barrier. They cover


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