Alternative pathways for training the general internist and the medical subspecialist.

Considerable attention is being directed from within the discipline of internal medicine to a perceived need for changes in the curriculum for postgraduate training of the internist. Much of this attention has been focused on the training required to properly prepare the general internist for the evolving system of health care. A proposal is presented to change the pattern of training of both the general internist and the medical subspecialist. After 2 years of core training, the general internist would enter 2 additional years of training that would include new material and additional experience in areas such as ambulatory and continuity care. After the core experience, the subspecialist would begin training in the subspecialty. The general internist would be certified as such, and the subspecialist would be certified only in the subspecialty. The proposal is based on the assumptions that 1) more general physicians are needed to meet the nation's health care needs; 2) more time will be required to properly train the general internist; 3) all of the additional and expanded training experiences for the generalist are not essential for training the subspecialist; and 4) the generalists of the future will not come from the ranks of subspecialists. The training needs of the general internist and the subspecialist should be viewed as separate, and curriculum changes should be considered without the restrictions of current patterns of training.

Volume reabsorption by the loop of Henle: a micropuncture study.

The observed extension of glomerulo-tubular beyond the proximal tube is thought to be due either to flow dependent reabsorption by non-accessible proximal segments and pars recta, or to osmotic volume flow out of the descending limb of the loop of Henle.

A study in vivo of peritubular oncotic pressure and proximal tubular reabsorption in the rat.

1. Peritubular capillary microperfusion was used to examine the effects of protein-free and hyperoncotic homologous plasma on fluid reabsorption by proximal convoluted tubules in the hydropenic rat. 3H-labelled p-aminohippurate was added to perfusates for the purpose of estimating the extent to which tubules under study were bathed by the perfusates. [14C]Mannitol was added to perfusates in order to detect contamination of collected tubular fluid by perfusates. 2. Hydrostatic pressures were monitored in the peritubular microvasculature and adjacent proximal tubules during perfusion. Evidence for secretion of p-aminohippurate from perfusate into tubules under study was determined by collecting tubular fluid from both early and late puncture site. Fractional and absolute reabsorption were not affected by either the protein-free or the hyperoncotic plasma. 3. When acetazolamide was added to the perfusate both fractional and absolute reabsorptive rates decreased by an average of 36%, indicating that the techniques were capable of detecting a decrease in proximal tubular reabsorption. 4. It is concluded that under the conditions of this study changes in peritubular capillary protein concentrations have no detectable effect on the rate of proximal convoluted tubule fluid reabsorption.

The relationship between sodium excretion and renin secretion by the perfused kidney.

The effect of altered tubular sodium reabsorption on renin secretion (RSR) was examined under conditions in which other factors influencing renin release could be controlled or excluded. To do this, isolated canine kidneys were perfused at constant pressure with blood circulating from donor animals. Volume expansion or hemorrhage of the donor dogs produced large changes in the animal's blood pressure, renal function, sodium excretion (UNaV), and RSR, but were without effect on renal hemodynamics, UNaV, or RSR in the perfused kidney. Hemodilution without volume expansion, resulted in hypotension, decreased UNaV and increased RSR in the donor dogs, and increased UNaV and suppressed RSR in the perfused kidney. These effects of hemodilution in the perfused kidney were partially reversed when plasma protein concentration was restored to control levels with hyperoncotic albumin, and, overall, there was a significant inverse relationship between electrolyte excretion and RSR. These results provide new evidence for the hypothesis that the rate at which sodium is delivered to the macula densa is an important determinant of the rate of renin secretion.

Parasympathetic pathways, renin secretion and vasopressin release.

1. The interrelationship between parasympathetic neural tone, renin secretion and vasopressin release was examined by observing the effect of bilateral cervical vagotomy on renin secretion in intact and acutely hypophysectomized dogs undergoing a water diuresis. 2. In intact dogs bilateral cervical vagotomy decreased the mean renin secretion from 1245 to 682 units/min (P less than 0.01) as urinary osmolality increased from 95 to 414 mosmol/kg (P less than 0.001). In contrast, in acutely hypophysectomized dogs cervical vagotomy failed to alter renin secretion significantly (834 to 893 units/min) and urinary osmolality was also unchanged (78 to 71 mosmol/kg). 3. The results suggest that a diminution in vagal tone may significantly alter renin secretion by stimulating vasopressin release. Exogenous vasopressin was associated with changes in urinary osmolality and renin secretion which were qualitatively similar to those seen after servical vagotomy. 4. We suggest that there is a neurohumoral reflex mechanism by which a fall in parasympathetic tone increases the release of vasopressin, which, in turn, suppresses renin secretion. The results are also compatible with the hypothesis that vasopressin inhibits renin release by a direct effect on the juxtaglomerular cells.

Effect of intraluminal flow on proximal tubular reabsorption.

Micropuncture techniques in the rat were used to reinvestigate the possibility that intraluminal flow rate per se may influence net volume reabsorption by the proximal tubule. An experimental design was devised which lowered intraluminal flow without affecting filtration rate of the nephron under study or without directly affecting other renal hemodynamics. In 11 rats flow of tubular fluid between early and late proximal tubular sites was reduced by partially collecting tubular fluid at the early puncture site. In 42 nephrons the rate of flow of tubular fluid was reduced an average of 45% without changing nephron filtration rate and there was an associated reduction in reabsorption between the two sites which averaged 29%. This indicated 63% balance between delivery of tubular fluid and the rate of reabsorption between two sites along proximal tubules. The results of these studies indicate that a reduction in delivery of normal filtrate along the proximal tubule is associated with a concordant reduction in the absolute rate of reabsorption. Since this relationship occurred in the absence of changes in renal hemodynamics or even a change in filtration rate of the nephron under study it is concluded that changes in intraluminal load per se play an important role in the phenomenon of glomerulotubular balance.

An effect of extrarenal beta adrenergic stimulation on the release of renin.

The present study was undertaken to examine whether the beta adrenergic agonist, isoproterenol, increases plasma renin activity (PRA) by activation of intrarenal or extrarenal pathways. The effects of intravenous (i.v.) and renal arterial infusion of isoproterenol on PRA and renin secretion rate (RSR) were compared in anesthetized dogs. In 12 studies in 9 dogs i.v. infusion of isoproterenol (0.009-0.018 mug/kg per min) was associated with an increase in PRA from 14.7 to 35.7 ng/ml per 3 hr (P < 0.001). PRA decreased to 19.4 ng/ml per 3 hr (P < 0.001) after cessation of the infusion. In innervated kidneys RSR increased from 1640 to 5062 U/min (P < 0.02) and decreased to 2132 U/min after cessation of the infusion (P < 0.05). In denervated kidneys the control RSR was significantly lower (455 U/min) but still increased during i.v. infusion of isoproterenol to 2762 U/min (P < 0.001) and decreased to 935 U/min (P < 0.001) after the infusion was stopped. These changes in PRA and RSR were associated with an increase in cardiac output averaging 49% and a large decrease in total peripheral resistance. These effects of i.v. isoproterenol to increase RSR were not mediated by changes in renal perfusion pressure since this was held constant by adjusting a suprarenal aortic clamp. In addition, there were no changes in glomerular filtration rate, renal plasma flow, or electrolyte excretion in either denervated or innervated kidneys during i.v. infusion of isoproterenol, and the concentration of potassium in plasma was unchanged. Prior hypophysectomy abolished the antidiuretic effect of i.v. isoproterenol but did not prevent the effect on RSR. In contrast, renal arterial infusion of isoproterenol at the same dose had no apparent effect on PRA and RSR in seven studies in five dogs and also did not produce changes in cardiac output, peripheral resistance or renal hemodynamics. These results do not provide evidence for a role of intrarenal beta adrenergic receptors in the control of renin release and indicate that the effect of beta adrenergic stimulation with isoproterenol to increase the release of renin is mediated by an extrarenal mechanism. Since the effect of i.v. isoproterenol occurred in the absence of changes in plasma potassium concentration, renal perfusion pressure, glomerular filtration rate, renal plasma flow, and electrolyte excretion and was not abolished by renal denervation, the possibility must be considered that the effect on renin secretion is mediated by circulatory factors. The changes in systemic hemodynamics which occurred with i.v. but not renal arterial infusion of isoproterenol may be involved in the initiation of such a pathway.

The mechanism of decreased intestinal sodium and water absorption after acute volume expansion in the rat.

Studies were performed in rat small intestine in vivo to determine the effect of saline infusion on intestinal transport of Na(+) and H(2)O. Saline infusion decreased net Na(+) flux (J(n) (Na)) from 12.7 +/-0.8 to 6.4 +/-1.5 muEq/hr per cm in the jejunum when the intestinal perfusate contained both Na(+) and glucose. A similar fall in J(n) (Na) occurred in ileum. When mannitol was substituted for glucose in the perfusate, control absorption decreased 29% in jejunum and 18% in ileum, but saline infusion still caused a decrease in J(n) (Na) quantitatively similar to that seen when glucose was present. When choline was substituted for Na(+) in the perfusate, there was net movement of Na(+) from blood to lumen during control and this net secretion was increased further after saline infusion. These observations suggest that saline infusion has a similar effect to decrease intestinal J(n) (Na) under three widely different conditions of basal sodium transport. Permeability of intestinal mucosa to inulin was very low under basal conditions but increased fivefold after saline infusion, and the unidirectional flux of Na(+) from blood to lumen doubled. This increase in unidirectional flux of Na(+) was greater than the observed decrease in J(n) (Na).Thus, saline infusion decreased net absorption of Na(+) and H(2)O from small intestine through mechanisms which did not appear to be dependent upon the rate of Na(+) flux from lumen to blood, and in association with an increased flux of inulin and Na(+) into the intestinal lumen. The data suggest that the effect of saline infusion to decrease net absorption from the intestine could be due either to an increase in passive permeability of the epithelium which could disrupt solute gradients within the membrane or to an increase in flow of solution into the intestinal lumen.