Continuing education and training: an answer to a long-term care dilemma?
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Biomedical subjects
Publications and source records attributed to R R Robinson.
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The effects of bovine parathyroid hormone (PTH) on phosphate transport were examined in proximal convoluted tubules, proximal straight tubules, and cortical collecting ducts isolated from the rabbit kidney. The lumen-to-bath flux of phosphate (JlbPO4) and the bath-to-lumen flux (JblPO4) were measured simultaneously with [33P]phosphate and [32P]phosphate. In the proximal convoluted segments perfused with an ultrafiltrate of normal serum, PTH reduced the fluid absorption rate from 1.21 +/- 0.10 to 0.60 nl/mm-min but did not affect JlbPO4, which averaged 5.45 +/- 0.97 pmol/mm-min, or JblPO4, which was 0.50 +/- 0.08 pmol/mm-min. During perfusion with low bicarbonate-high chloride fluids at pH 7.4, the PTH-induced changes in fluid absorption were eliminated but no change occurred in phosphate transport. On the other hand in proximal straight segments JlbP04 was lower at 2.64 +/- 0.41 pmol/mm-min and was directly inhibited by PTH to 1.90 +/- 0.34 pmol/mm-min (P less than 0.001). Net phosphate transport was not observed in cortical collecting ducts in the presence or absence of PTH. These data suggest that phosphate absorption in the proximal tubule involves more than one transport system, that the effects of PTH on fluid absorption are not interdependent with the effects on phosphate transport, and that the proximal straight tubule appears to be an important site of PTH-sensitive phosphate transport.
Standard clearance studies were performed in mechanically ventilated intact and acutely thyroparathyroidectomized (TPTX) rats to document and characterize the effect of hypercapnia (HC) on urinary phosphorus excretion (U(P)V). HC as compared to normocapnia (NC) was associated with an increase in U(P)V in intact (62.5 vs. 7.93 mug/min) and TPTX (30.5 vs. 0.59 mug/min) rats, an increase in filtered load of phosphorus in intact (218 vs. 191 mug/min) and TPTX (243 vs. 146 mug/min) rats, an increase in blood bicarbonate concentration in intact (27.8 vs. 26.0 meq/liter) and TPTX (24.5 vs. 22.3 meq/liter) animals, and a decrease in blood pH in intact (7.15 vs. 7.42) and TPTX (7.07 vs. 7.39) rats. Additional TPTX rats with NC and HC were studied during phosphorus infusion at a comparable filtered load of phosphorus (NC = 307 mug/min and HC = 328 mug/min). U(P)V was 18.5 mug/min in NC and 85.2 mug/min in HC animals. Intact NC animals infused with NaHCO(3) achieved a blood bicarbonate of 45.9 meq/liter compared to 26.0 meq/liter in intact NC NaCl-infused rats. U(P)V was 10.0 mug/min in the NaHCO(3) and 7.93 mug/min in NaCl-infused animals. In intact HC animals infused with NaHCO(3), blood pH was 7.36 compared to 7.42 in NC intact NaCl-infused animals. U(P)V was 83.2 mug/min in the HC bicarbonate-infused and 7.93 mug/min in the NC NaCl-infused rats. These experiments demonstrate that elevated blood carbon dioxide tension per se increases U(P)V. Increases in filtered load of phosphorus and blood bicarbonate which are associated with HC contribute to the phosphaturia as does parathyroid hormone. The phosphaturia is not dependent upon reduction of extracellular pH.
Two major categories of membranoproliferative glomerulonephritis (MPGN) designated type 1 and 2 MPGN are currently recognized, largely on the basis of characteristic morphologic and immunofluorescence features. In contrast to experience reported from outside the United States, type 2 MPGN has been observed rather infrequently in this country. In a retrospective clinicopathologic study, 24 kidney specimens obtained from 10 children and young adults including seven females and three males (mean age: 13 years) with type 2 MPGN were identified using light, immunofluorescence, and electron microscopy. The histopathologic findings were related to the clinical course of each patient. When initially seen all patients had hematuria and proteinuria, three were nephrotic, and five were mildly hypertensive. A single patient was mildly azotemic. Eight patients had experienced an upper respiratory ifnection preceding their illness, although only one patient had evidence of a streptococcal pharyngitis. During a period of follow-up averaging 10 years, eight patients were nephrotic at some time during their illness and seven were persistently so. Hypertension was a major problem in eight patients and renal function declined markedly within a year of its onset in five. Persistence of the nephrotic syndrome from early onset of the disease, especially when associated with hypertension, was an additional sign of poor prognosis. Four patients developed chronic renal failure and three received one or more renal allografts. Histologic evidence of recurrent disease was found in allografts from the three patients as early as 7 months after transplantation in the absence of clinical features indicative of recurrent glomerulonephritis. It is concluded that type 2 MPGN is a chronic progressive renal disease of unknown etiology and pathogenesis which chiefly afflicts children and young adults. Hypertension and the early and persistent presence of the nephrotic syndrome suggest a poor prognosis. The disease appears to be largely unresponsive to conventional forms of therapy. The disease recurs with great frequency in allografts, often in the absence of clinical evidence of recurrent glomerulonephritis.
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Hyperuricemia was induced in rats ingesting a diet supplemented with 2 1/2+ uric acid and 5% oxonic acid (an inhibitor of hepatic uricase activity). After seven days, inulin clearance (CIn) and superficial nephron glomerular filtration rate (SNFR) were significantly lower than values recorded in healthy rats (CIn:0.94 +/- 0.10 vs. 3.61 +/- 0.13 ml/min/kg of body wt; SNFR: 54.9 +/- 3.2 vs. 129.7 +/- 6.7 nl/min/kg of body wt). Filtration rate reduction was accompanied by an increased concentration of urate in renal tissue. Gross examination of the kidney revealed the presence of whitish streaks containing negatively birefringent crystals throughout the medulla and papilla. Histological examination revealed dilatation of the collecting ducts with flattening of the epithelium and intraluminal crystalline deposits. Intraluminal hydrostatic pressure was markedly higher than that observed in healthy rats in both proximal (21.5 +/- 1.7 vs. 11.4 +/- 0.3 mm Hg) and distal convoluted tubules (20.3 +/- 2.0 vs. 7.6 +/- 0.5 mm Hg). In another group of rats ingesting a similar diet, CIn was reduced to 1.49 +/- 0.20 ml/min/kg of body wt. Partial or complete restoration of CIn toward normal was effected within seven additional days by the oral ingestion of a large volume of an alkali solution (CIn:2.63 +/- 0.44 ml/min/kg of body wt) or by the cessation of treatment with oxonic-uric acid (CIn: 4.70 +/- 0.28 ml/min/kg of body wt). These results demonstrate that oxonic/uric acid-induced hyperuricemia is accompanied by severe filtration rate reduction, and they suggest strongly that intraluminal obstruction, via the deposition of uric acid, plays an important role in its pathogenesis.
In a retrospective clinicopathological study, 48 kidney biopsy specimens from 16 children (mean age, 7 years) and 17 adults (mean age, 33 years) with histological evidence of focal glomerular sclerosis (FGS) were examined using light, immunofluorescence and electron microscopy. The histopathological findings were related to the clinical course of each patient. At the clinical onset of the disease, the nephrotic syndrome was seen more commonly in children (12/16) than adults (7/17), while the incidence of both hypertension (children 1/16 versus adults, 9/17) and renal insufficiency (children, 0/16 versus adults, 7/17) was greater in adults. Despite a shorter average follow-up, (adults 3 10/12 years versus children, 7 years), the incidence of hypertension (adults, 13/17 versus children, 7/16) and renal functional impairment (adults, 13/17 versus children, 3/16) remained greater in the adult patients. One child and three adults died in renal failure while two adults underwent transplantation and on requires regular dialysis therapy. Nine of 15 pediatric patients treated with corticosteroids experienced partial or complete remission in either their nephrotic syndrome or level of urine protein excretion, while just 3 of 6 adult patients treated with corticosteroids experienced a partial remission, but never became protein-free. There was an excellent correlation in all patients between the degree of functional renal impairment and the extent of glomerular and nonglomerular histopathological damage in the kidney. It is concluded that in the adults, FGS represents a more severe and progressive disease process and is less responsive to therapy.
The characteristics of inorganic phosphate transport in isolated perfused proximal tubules of the rabbit were examined using radioisotopic techniques. When tubules were perfused with an ultrafiltrate of rabbit serum, the mean lumen-to-bath flux of phosphate in the convoluted segment was 6.60 +/- 1.41 (SE) pmol/mm-min with a simultaneous back-to-lumen flux of 0.45 +/- 0.08. In the straight portion of the proximal tubule, the lumen-to-bath flux was significantly lower (P less than 0.01) at 2.22 +/- 0.48 pmol/min-min with a bath-to-lumen flux of 0.31 +/- 0.05. The lumen-to-bath flux was not affected by increases in the intraluminal phosphate concentration from 2.00 +/- 0.19 to 3.12 +/- 0.34 mM or by the isohydric replacement of bicarbonate in the ambient fluids with chloride. However, phosphate absorption was completely inhibited by ouabain 10(-5) M in the bath. These data indicate that phosphate absorption in these segments occurs by a mechanism other than independent diffusion and is saturated at phosphate concentrations characteristic of normal glomerular filtrate. There is no evidence for significant phosphate transport from bath to lumen.
Although chronic lithium therapy has been associated with a defect in the urinary concentrating mechanism, short-term renal effects of lithium have received little attention in the intact animal. Solute-free water reabsorption (T-cH2O) and free water clearance (CH2O) were measured in primates of the genus Galago under control conditions and while animals were receiving either 0.5 mmol/kg-h or 1.0 mmol/kg-h lithium chloride (135 mM) intravenously. CH2O was unchanged by lithium infusion (P greater than 0.10), whereas T-cH2O was significantly depressed at all levels of osmolal clearance (P smaller than 0.01). Spontaneous recovery of near-normal T-cH2O was documented in two animals within 1 wk following acute lithium infusion. In addition it was observed that lithium-induced depression of T-cH2O could be partially prevented by pretreatment with intravenous amiloride. These results suggest that alterations in the renal concentrating mechanism can occur rapidly following the onset of lithium administration. They also imply that impairment of the renal concentrating mechanism by lithium is due at least in part to antagonism of the action of vasopressin on the collecting duct.
A prospective study was undertaken to evaluate the relative contribution of changes in sympathetic nervous system activity, as reflected by changes in dopamine-beta-hydroxylase (DBH) activity, to the pathogenesis of oral contraceptive-induced hypertension. Precontraceptive and serial post contraceptive determinations of blood pressure, plasma renin activity (PRA), DBH activity, and changes in body weight were obtained in twelve control patients and forty-one oral contraceptive users. Forty-four percent of oral contraceptive users had increases in blood pressure but remained normotensive and 17% became frankly hypertensive. The precontraceptive and average post contraceptive levels of mean arterial pressure (MAP), PRA and DBH activity in each patient were compared using paired group analysis. Control patients (group I) exhibited no significant changes in these variables, while the patients with contraceptive-induced increases in MAP (groups III and IV) underwent significant, parallel increases in DBH activity. Finally, the linear regression of changes in MAP on the percent change in DBH activity was examined. The positive slopes in groups III and IV differed significantly from the negative slope of the controls (group I). The data have been interpreted to reflect an inappropriate oral contraceptive-induced stimulus to sympathetic nervous system activity, leading to increases in MAP in susceptible individuals.
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The activity of dopamine beta-hydroxylase (DBH) in plasma ranged from 2 to 100 units per liter of plasma in 82 apparently healthy subjects (ages 22 to 35 years). A nonnormal pattern of distribution was evident: 62 subjects had values below 35 units (18 +/- 1), while 13 of the remaining 20 subjects had values above 60 units (80 +/- 5). Those with low DBH activity had lower values for urinary catecholamine excretion (31 +/- 3 micrograms), with normal and stable blood pressure; those with high DBH activity had higher values for urinary catecholamine excretion (72 +/- 6 micrograms), with greater lability of arterial blood pressure. The DBH activity was significantly elevated in patients with labile (74 +/- 2 mm-Hg) or fixed (57 +/- 2 mm-Hg) essential hypertension. The results indicate that plasma DBH activity is low and that it falls within a narrow range in young adults with normal and stable blood pressure.
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Renal clearance and recollection micro-puncture experiments were conducted to evaluate the possible role of a distal tubular feedback mechanism in the phenomenon of renal autoregulation in dogs. Single nephron glomerular filtration rate (SNGFR) was measured from collection sites in both the proximal (proximal SNGFR) and distal tubules (distal SNGFR). Single nephron autoregulatory behavior was assessed by evaluating the response of SNGFR to a reduction in renal arterial pressure imposed by means of an aortic constrictor. Whole kidney function was evaluated by parallel measurements of renal blood flow and inulin clearance. Whole kidney autoregulation was observed when renal arterial pressure was decreased from 141 +/- 3 (SE) mm Hg to 101 +/- 2 mm Hg; renal blood flow and GFR were not significantly altered from control values of 3.76 +/- 0.2 ml/min.g and 0.69 +/- 0.04 ml/min.g kidney weight, respectively. In 11 autoregulating preparations, proximal transit time was likewise unchanged from the control value of 26 +/- 2 s, indirectly suggesting that the superficial nephrons also participated in the autoregulatory response. However, proximal SNGFR decreased significantly from 88 +/- 7 nl/min to 66 +/- 6 nl/min, a reduction which was proportional to the decrease in arterial pressure. In 14 dogs in which both proximal SNGFR and distal SNGFR were measured at control blood pressure (136 +/- 5 mm Hg), distal SNGFR was 47 +/- 4 nl/min, a value significantly lower than that for proximal SNGFR (79 +/- 6 nl/min). In contrast to the results based upon proximal collections, distal SNGFR was not significantly altered following aortic constriction (44 +/- 5 nl/min vs. 47 +/- 5 nl/min) therefore exhibiting autoregulation in association with that observed for the whole kidney. These experiments indicate that though superficial nephrons do possess autoregulatory capability, interruption of distal delivery due to complete collection from the proximal tubule interferes with that nephron's ability to manifest an autoregulatory response. They support the concept that a feedback mechanism, related to some function of distal delivery, is of significance in the intrinsic regulation of SNGFR. The data further suggest that quantitative estimates of SNGFR based on complete proximal collections may not be representative of those throughout the superficial cortex of the dog, at least in certain experimental circumstances.