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Biomedical subjects

F S Wright

Publications and source records attributed to F S Wright.

At least 73 records · Page 4Linked to original sources

Epilepsy evoked by eating: the role of peripheral input.

A 13-year-old boy with documented epilepsy evoked by eating, a rare form of reflex epilepsy, experienced only partial control with anticonvulsant medication. Repetitive peripheral sensory input was necessary to evoke seizures in this patient. The seizures remitted completely after he lost several fingers in an accident. Decreased sensory input presumably altered the seizure threshold so that the seizures were eliminated.

Amputation, Traumatic↗

Studies of the sensing mechanism in the tubuloglomerular feedback pathway.

Two aspects of the single nephron feedback response previously observed by us have been reexamined. The first, the effect of modifying the composition of fluid used to perfuse the loop of Henle of a single nephron, was studied in rats by comparing flow-induced changes in stop-flow pressure (PSF) with three different perfusion solutions: artificial tubule fluid (ATF); 0.3 M mannitol (M); and mannitol plus 25 to 30 mM sodium chloride (M + E). The second, triggering of the feedback response by injection of ionic current into the distal tubule, was studied in similarly prepared rats by monitoring PSF while passing current. Increasing the rate of loop of Henle perfusion with either ATF or M + E resulted in similar decreases in PSF. In contrast, with M, changes in PSF were usually transient and if persistent were smaller than the changes observed with the other two solutions. When loops of Henle were perfused with ATF at a constant rate, injection of current into the early distal tubule making the lumen more negative resulted in decreases in PSF. Currents of opposite polarity caused no change in PSF if loop flow rate was low; these currents increased PSF if the loop flow rates had previously been high. Current-induced feedback responses were obtained with micropipette electrodes filled with either potassium chloride or lithium acetate. Addition of 10(-4) M furosemide blocked the current-induced feedback responses.

Animals↗

Feedback-mediated reduction of glomerular filtration rate during infusion of hypertonic saline.

An acute rise in plasma sodium concentration from 146 +/- 2.6 to 155 +/- 1.7 was produced in rats by the intraarterial infusion of 0.6 M sodium chloride (0.25 ml/min for 4 min followed by 0.25 ml/hr). A parallel fall in whole kidney GFR (from 0.45 +/- 0.02 to 0.36 +/- 0.04 ml/min per 100 g of body wt) and SNGFR measured in the distal tubule (31.4 +/- 3.01 to 27.9 +/- 2.40 nl/min) was observed. In contrast, proximally measured SNGFR (with feedback interrupted) rose from 32.7 +/- 2.73 to 37.1 +/- 2.84 nl/min. The loop of Henle flow, determined from distal SNGFR and (TF/P) inulin in late proximal fluid collected without interrupting tubular flow, rose from 13.7 +/- 1.50 to 17.0 +/- 1.42 nl/min as a consequence of a fall in proximal reabsorptive rate from 15.8 +/- 1.87 to 11.0 +/- 1.37 nl/min. Intraarterial infusion of hypertonic sodium bicarbonate resulted in comparable increases in plasma sodium concentration and inhibition of proximal reabsorption but did not produce a fall in filtration rate. We conclude (1) acute infusion of hypertonic sodium chloride results in an inhibition of proximal reabsorption and therefore in an increased rate of loop of Henle flow, (2) this increase in flow causes a fall in GFR through the tubuloglomerular feedback mechanism, and (3) acute infusion of hypertonic sodium bicarbonate does not result in a feedback-mediated fall in GFR, presumably because increased delivery of bicarbonate-rich fluid does not activate the feedback mechanism.

Animals↗

Potassium transport by successive segments of the mammalian nephron.

Potassium excreted by the kidney is derived largely from potassium secretion by the distal tubule and collecting duct. It is this secreted fraction that responds to systemic changes and is mainly responsible for regulation of potassium balance. A smaller fraction of the excreted quantity comes from potassium that is filtered and escapes reabsorption. Variations in the rate of reabsorption may alter potassium secretion under some circumstances. In the proximal tubule, reabsorption of potassium appears to involve interaction with a membrane mechanism. The contribution of descending limb potassium secretion to final potassium secretion is a present uncertain because of the inaccessibility of inner cortical distal tubules and collecting ducts in intact animals. Changes in plasma K, plasma aldosterone, and plasma acidity all appear to affect distal potassium secretion by influencing the uptake of potassium from blood to cell and thus raising the intracellular potassium. Changes in extracellular fluid volume, which increase urine flow and sodium excretion, appear to increase distal potassium secretion as a consequence of increases in the flow rate of luminal fluid. Flow-dependent changes in luminal potassium concentration may be involved but they do not appear to act by simply increasing the passive electrochemical driving force (assessed across the entire epithelium). Our understanding of the cellular mechanisms controlling renal potassium secretion is becoming clearer as it becomes possible to identify and to separate for a study a potentially confusing array of interacting variables.

Animals↗

Characteristics of feedback control of glomerular filtration rate.

Increases in the flow rate of fluid through the loop of Henle are associated with decreases in the rate at which fluid is filtered by the glomerulus in the same nephron. The anatomical basis for this negative feedback phenomenon is very likely the close relationship between the macula densa segment of the distal tubule and the vascular components of the juxtaglomerular apparatus. Convincing evidence indicating the existence of a feedback control mechanism has come largely from micropunture experiments in which flow through single Henle loops is controlled while either filtration rate by, or capillary pressure in, the glomerulus of the same nephron is measured. Aspects of the negative feedback response that have been characterized quantitatively include the magnitude of the changes in glomerular function, the rates of tubule fluid flow that elicit the changes, and the sensitivity of the response in different physiological circumstances. Some information about the sensing step in the feedback pathway in rats has come from microperfusion experiments employing changes in the composition of fluids used to perfuse the loop of Henle or changes in the electrical driving forces across the wall of the distal tubule. Taken together, results of experiments using these different approaches indicate that changes in loop of Henle flow rate may be sensed by a process that requires transport of some constituent of distal tubule fluid, possibly the chloride ion, from the distal tubule lumen into some compartment within the juxtaglomerular apparatus.

Animals↗

Luminal influences on potassium secretion: transepithelial voltage.

In vivo microperfusion techniques were used to evaluate whether changes in luminal fluid flow rate affect late distal tubule transepithelial voltage (VTE) and to determine whether flow-dependent changes in K secretion by the renal distal tubule of the rat that we observed previously could be attributed to changes in electrical driving forces. Results showed that increasing the perfusion rate from 6 to 26 nl/min of solutions containing either 94, 46, or 15 mM sodium and 2 mM potassium caused VTE to become 10-12 mV less lumen negative. Since increasing perfusion rate decreases VTE, a flow-dependent voltage change is not responsible for the effect of increasing luminal flow rate to increase distal K secretion. To evaluate the possible contribution of changes in luminal Na and K concentrations to the flow-dependent changes in VTE, the effects of changing either Na or K concentration at constant flow rate were examined. These studies showed that 1) changes in luminal Na concentration within the physiological range (44-94 mM) have no detectable effect on VTE; 2) increases in luminal K concentration within the physiological range (5-16 mM) significantly increase VTE; and 3) the flow-dependent depolarization of VTE is primarily caused by flow-dependent changes in luminal K concentration.

Animals↗

Failure of tubule fluid osmolarity to affect feedback regulation of glomerular filtration.

Experiments were performed in Sprague-Dawley rats in order to distinguish between sodium chloride and total solute concentration as possible luminal signals capable of eliciting tubuloglomerular feedback responses. Early proximal flow rate (VEP), an index of nephron filtration rate, was measured without perfusion of the loop of Henle and during retrograde perfusion with solutions containing 20, 35, 60 to 100 mM NaCl and varying amounts of either urea or mannitol to achieve total solute concentrations of 130, 280, or 400 mosM. Perfusion flow rate was kept constant at 20 nl/min. Perfusion with a solution containing 20 mM NaCl and made hypo-, iso-, or hypertonic with urea or mannitol caused little or no change in VEP. Perfusion with a 35 mM NaCl solution made hypo-, iso-, or hypertonic with mannitol resulted in a fall of VEP of 6-7 nl/min. When NaCl concentration was 60 mM, VEP fell by 10-14 nl/min with solutions made hypo-, iso-, or hypertonic with urea or mannitol. With 100 mM NaCl solutions made hypo-, iso-, or hypertonic with mannitol, VEP fell approximately 12 nl/min. These results indicate that feedback responses are determined by the NaCl concentration of the perfusate and that this NaCl dependency is not modified by varying perfusate osmolarity between 130 and 400 mosM with urea or mannitol as osmotic agents.

Animals↗

Luminal influences on potassium secretion: sodium concentration and fluid flow rate.

Two methods of in vivo continuous microperfusion were used to evaluate separately luminal sodium concentration and fluid flow rate as factors regulating potassium secretion by the renal distal tubule of the rat. Emphasis was placed on evaluating changes in sodium concentration (43-97 mM) and flow rate (4-27 nl/min) within the physiological range. Absolute rates of Na, K, Cl, and H2O transport were measured. Results showed that increasing early distal flow rate without increasing early distal Na concentration significantly increased the absolute rate of potassium secretion by the distal tubule. In contrast, increasing early distal Na concentration, distal Na delivery, and distal Na absorption did not affect potassium secretion if flow rate was not changed. Further studies showed that reducing early distal Na concentration below the physiological range (to 15 mM) caused the direction of net sodium transport to be reversed but did not significantly reduce potassium secretion. Increasing early distal K concentration (to 34 mM) caused the direction of net potassium transport to be reversed. The rate of potassium secretion appears to depend in part on the luminal potassium concentration. Increases in luminal flow rate may increase the rate of potassium secretion by lowering the luminal K concentration.

Animals↗

Effects of potassium depletion on renal tubular chloride transport in the rat.

Potassium depletion (KD) causes renal chloride-wasting. To investigate the effects of KD on renal tubular reabsorption of chloride, balance, clearance, micropuncture, and microinjection studies were performed on potassium-depleted rats. KD was produced by omitting potassium from the diet and by administration of DOCA on days 2 and 3; rats were studied on days 9 to 12. Diets were chloride-free in both control and KD groups. In the KD group, balance experiments confirmed greater chloride depletion and continued chloride-wasting, and clearance studies showed an increased FECl. Muscle potassium was reduced by 27% as compared to control. Whole kidney and single nephron GFR were reduced in KD rats to 72 and 74% of control. Fractional (6 +/- 6% vs. 22 +/- 4%, P less than 0.05) and absolute chloride reabsorption in the proximal tubule was not different. Fractional reabsorption of delivered chloride was reduced in the loop of Henle (92 +/- 0.8% in KD vs. 95 +/- 0.7% in control, P less than 0.02). Transtubular chloride ratio (0.28 +/- 0.02 vs. 0.21 +/- 0.02, P less than 0.02) was increased at the early distal tubule. Fractional delivery of chloride (8 +/- 0.9 vs. 5 +/- 0.5%, P less than 0.02), and fluid (26 +/- 1 vs. 22 +/- 1%, P less than 0.05) were also increased in KD at the early distal tubule. Recovery of chloride 36 injected into late distal tubules was 88 +/- 1% on a normal chloride intake, 62 +/- 2% in chloride depletion, and 88 +/- 2% in potassium and chloride depletion. Thus, KD depresses chloride reabsorption in the proximal tubule and in the loop of Henle, and it decreases chloride 36 efflux from the collecting duct.

Animals↗

Renal potassium transport: contributions of individual nephron segments and populations.

General features of the processes that contribute to renal potassium excretion are understood from clearance, stop-flow, micropuncture, and in vitro microperfusion experiments. However, the complex architecture of the kidney has made it difficult to examine individual nephron segments in all parts of the kidney. Accordingly, the extent to which distinguishable nephron populations, such as superficial and deep, may differ in their contributions to overall potassium excretion are not known. Also, the nature of transport processes across the successive segments of the nephrons (including not only the underlying cellular mechanisms, but even the direction of transport) is not known for all segments in any one nephron population. Excreted potassium is derived both from filtered potassium that escapes reabsorption and from secreted potassium. The filtered portion is large in amphibians and may be larger than generally recognized in mammals. The remainder is secreted primarily by distal nephron segments (distal tubule and cortical collecting duct). Potassium is also secreted into descending limbs of Henle loops; apparently this fraction is recycled from collecting ducts, and so does not represent an additional quantity of potassium transferred from blood to tubule fluid. Systemic factors that affect potassium excretion (potassium intake, sodium chloride intake, mineralocorticoid hormone levels, acid-base balance, and diuretic treatments) do so by modifying the net uptake of potassium from blood to cell and by altering the rate of fluid flow through the distal nephron. Under most circumstances, the distal nephron in the cortex appears to secrete potassium and the medullary collecting duct reabsorbs potassium. Although it is clear that successive nephron segments transport potassium in different ways, evidence to date does not indicate that potassium is handled differently by superficial nephrons compared to nephrons whose glomeruli lie in the deeper levels of the cortex.

Acid-Base Equilibrium↗

Evaluation of research needs in nephrology in urology. Obstructive and neuromuscular disorders affecting the urinary system.

Obstructive and neuromuscular disorders are common problems of the urinary tract. They cause considerable morbidity and some mortality. In all problem areas research efforts have been and continue to be limited. The principal reason for the lack of research efforts in these areas is the lack of trained established investigators interested in the problems of the urinary tract. Unfortunately, most basic scientists with the research and investigative background to solve many of these problems see them as mundane and not worthy of investigation. In addition, these same basic scientists are out of touch with clinical urologic diseases and probably do not appreciate the magnitude of the problems. In our opinion the solution is 2-fold: to train qualified investigators in urology and nephrology, and to interest, educate and collaborate with the basic scientists about these clinical problems of the urinary tract.

Action Potentials↗