Seldin and Giebischs The Kidney: Physiology and Pathophysiology

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Gentry learned about the idiosyncrasies of satellite-based Internet service in Uganda when he joined the Yale-Makerere collaboration, a partnership that includes the School of Medicine, Makerere University and Mulago Hospital in Kampala. Since Yale attendings and residents have traveled to Kampala for rotations at Mulago Hospital, and Ugandan residents are now coming to Yale for clinical training.

While visiting Mulago Hospital in the spring of , Gentry streamlined Internet use for physicians by setting up a home page that links directly to such often-used functions as e-mail and online journals. Meanwhile a Yale resident compiled CDs that allow Ugandan colleagues to bypass the Internet—the disks contain copyright-free information on diseases such as HIV, tuberculosis and malaria. Gentry next began building up the library for the Department of Medicine at Mulago Hospital, where the medical textbooks were 20 years old.

Gentry collected 50 essential texts that were hand-delivered to Kampala. Up-to-date books are a godsend, said Ugandan resident Fred Okuku, M. Gentry said the Makerere collaboration has been a natural extension of his work on Cedar Street. He contends that emphasis on one developmental line at the expense of the other, however, can lead to a variety of mental disorders.

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In analyzing these influences, Barber cites direct-to-consumer advertising; the promise of the quick fix; and the blurring of the distinction between mental illness—for which medication might be appropriate—and everyday emotional problems. Barber then offers therapeutic alternatives to prescription antidepressants. Long Professor of Cellular and Molecular Physiology and professor of medicine nephrology Academic Press This edition has more than 40 new chapters and 1, illustrations, providing comprehensive coverage of renal physiology and pathophysiology.

The topics move from the molecular biology of the kidney and its cell physiology to clinical issues surrounding renal function and dysfunction.

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These studies were made possible by the technical skill and imagination of Giebisch, Malnic, and Klose, and by the development by this group of a refined microflame photometer that allowed for very accurate measurements of sodium and potassium in nanoliter samples of tubular fluid. Furthermore, they provided the first insight into the cellular mechanisms of potassium transport by the distal tubule.

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Although the first paper was published in , our basic understanding of renal potassium transport that was derived from this series of papers is as true today as it was 45 years ago 2 , 9 , These classic papers also provided additional, novel insights into potassium transport by the distal tubule. First, they characterized the effects on distal potassium transport of a variety of metabolic conditions e. As noted above, these elegant studies revealed that in essentially all conditions the proximal tubule and loop of Henle reabsorbed a constant fraction of the potassium filtered by the glomeruli, that potassium transport by the distal tubule depends on the metabolic state, and that potassium is reabsorbed by downstream nephron segments, later shown to be the medullary collecting duct.

These results were in general agreement with clearance and stop-flow studies performed by Berliner and colleagues 1 , 2 and Mudge and colleagues reviewed in Refs. Using microelectrodes to measure the electrical potential difference across the distal tubule, combined with measurements of potassium concentrations in tubular fluid and plasma, Giebisch and colleagues demonstrated that potassium is secreted down its electrochemical gradient, and thus, its secretion is passive and linked indirectly to the rate of sodium reabsorption, which is about 10 times the rate of potassium secretion They also proved in these manuscripts that the rate of sodium reabsorption was not limiting for potassium secretion, a common notion at the time, and that potassium secretion did not depend on the rate of sodium reabsorption per se, but on the electrical potential difference PD across the distal tubule, which is determined in part by sodium reabsorption.

Thus they showed that when sodium reabsorption is stimulated the increase in the PD enhanced the electrochemical driving force and stimulated potassium secretion. By contrast, inhibition of sodium reabsorption by amiloride reduces the PD and thereby decreases potassium secretion. These observations were seminal, because it was thought at the time that potassium secretion was coupled to sodium reabsorption by a 1: These papers also set the stage for a subsequent, more refined series of studies over the next several decades, which revealed that potassium secretion is a two-step process: Moreover, in their study on potassium adaptation they clearly demonstrated that although potassium and hydrogen ion excretion are inversely related, the majority of potassium secretion is not tightly coupled with hydrogen in the distal tubule, a contradiction of the dogma at the time.

Finally, based on the observation that there was less potassium in the urine than at the end of the distal tubule, Giebisch and colleagues proposed that potassium was reabsorbed downstream of the distal tubule, most likely by the collecting duct 4 — 8 , In conclusion, these six studies published by Giebisch and colleagues 4 — 8 , 12 in the American Journal of Physiology led to a paradigm shift in the field by unequivocally demonstrating that the distal tubule plays a major role in determining the amount of potassium excreted in the urine, and by elucidating the basic mechanism of potassium secretion by the distal tubule as well as its regulation by a variety of metabolic factors and drugs.

Each paper is a classic. Giebisch for helpful discussions, for providing key references, and for his mentorship and friendship. Paul Muller 11 , who had built a similar device to measure the concentrations of sodium and potassium in single Ranvier nodes. Similar devices would be developed in other laboratories, with the assistance of Dr.

Giebisch, enabling micropuncture to become commonplace in many laboratories throughout the world. National Center for Biotechnology Information , U. Am J Physiol Renal Physiol. Published online Nov Author information Copyright and License information Disclaimer.