Microperfusion of Isolated Tubules

Abstract

“The responsibility for maintaining the composition of the blood in respect to other constituents devolves largely upon the kidneys. It is no exaggeration to say that the composition of the blood is determined not by what the mouth ingests but by what the kidneys keep; they are the master chemists of our internal environment, which, so to speak, they synthesize in reverse. … Bones can break, muscles can atrophy, glands can loaf, even the brain can go to sleep, without immediately endangering our survival, but when the kidneys fail to manufacture the proper kind of blood, neither bone, muscle, gland nor brain can carry on. Recognizing that we have the kind of blood that we have because we have the kind of kidney that we have, we must acknowledge that our kidneys constitute the major foundation of our physiological freedom. Superficially, it might be said that the function of the kidneys is to make urine; but in a more considered view one could say the kidneys make the stuff of philosophy itself” (Smith, 1939). It has been almost four decades since Homer W. Smith expressed that opinion during the course of the Ninth Porter Lecture which he delivered at the University of Kansas. In the 38 years that have passed since his lectureship, significant advances have been made in our knowledge of the mechanisms of solute and water transport by which the kidney regulates our internal milieu. Smith and his colleagues developed in great measure the facts and theory underlying much of modern renal physiology through the use of clearance methods for reliably evaluating glomerular filtration rate, renal blood flow, and net tubular reabsorptive and secretory transport. With the renaissance of micropuncture that occurred in the 1950s, further characterization of the functional capacities of the individual segments of the mammalian nephron was undertaken. This process continues to the present day. However, clearance techniques cannot precisely localize function to specific nephron segments, cannot always clearly separate reabsorption or secretion of substances that undergo both processes, cannot accurately distinguish variation among nephrons, and cannot incisively define transport mechanisms. Although in situ micropuncture techniques can accomplish many of these goals, only those segments of the nephron that lie along either the cortical or papillary surfaces of the kidney are accessible to direct micropuncture (Figure 1).