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Biomedical subjects

M G Cogan

Publications and source records attributed to M G Cogan.

At least 73 records · Page 4Linked to original sources
PubMed1982

Evidence for coupled sodium/hydrogen exchange in the rat superficial proximal convoluted tubule.

Recent in vitro studies from the rat and rabbit have suggested a tightly coupled sodium/hydrogen ion exchanger on the luminal membrane of proximal tubules. The steep sodium gradient from the lumen to cell supplies indirect energy for hydrogen ions to be pumped from the cell to the lumen. However, a proton translocating pump has been demonstrated in other epithelia, which is independent of sodium transport and directly driven by ATP. To examine the role that sodium might play in the process of acidification, rat proximal convoluted tubules and their surrounding peritubular capillaries were perfused in vivo with artificial ultrafiltrate-like perfusion solutions. Total CO2 absorption was measured by microcalorimetry during alterations in sodium transport by replacement of the sodium with an impermeant cation, choline, or by inhibition of the (Na+ + K+)-ATPase by removing potassium from both perfusion solutions. Under control conditions the absolute rate of total CO2 absorption was 140 pmol/mm X min. In the choline substitution and potassium removal experiments, absolute total CO2 absorption fell to 23 and 28 pmol/mm X min, respectively. The data suggest that: 1) in the rat superficial proximal convoluted tubule approximately 80% of the bicarbonate absorption is tightly coupled to sodium transport; 2) this process is driven indirectly by the (Na+ + K+)-ATPase system; and 3) the residual 20% of acidification appears to be mediated by another mechanism or may be a consequence of technical limitations.

Absorption↗
PubMed1982

Disorders of proximal nephron function.

The proximal nephron is responsible for reabsorbing 80 to 99 percent of several filtered solutes, including amino acids, glucose and bicarbonate. Separate, high-affinity sodium co-transport mechanisms are used. Increasing luminal concentration of each of these solutes stimulates its active transcellular reabsorption until there is saturation. Slightly less than half of the filtered chloride is reabsorbed, partly by passive mechanisms that are linked to the reabsorption of organic solutes and bicarbonate, as well as by less well defined independent cellular and/or paracellular mechanisms that appear to be sensitive to transepithelial osmotic pressure gradients. Proximal tubule reabsorption is isosmotic and isonatric, and about 50 to 60 percent of the filtered sodium and water in reabsorbed. Disorders or proximal nephron function include conditions in which luminal, cellular and/or peritubular factors affecting reabsorption are altered. Clinical disorders caused by modification of the luminal reabsorptive determinants include conditions in which tubular flow rate is increased or luminal composition is altered, as when non-reabsorbable solutes (mannitol) are filtered or when reabsorbable solutes (glucose) are filtered in concentrations exceeding their tubular transport capacity. Other disorders occur due to loss of affinity or capacity of the cellular active transport systems for specific solutes, such as amino acids (renal aminoacidurias), glucose (renal glycosurias) and bicarbonate (proximal renal tubular acidosis), or for all solutes (Fanconi syndrome). Finally, disorders due to changes in the peritubular factors affecting reabsorption include states of altered peritubular Starling forces or pH, which modify sodium chloride or sodium bicarbonate reabsorption, respectively.

Absorption↗
PubMed1982

Determinants of proximal bicarbonate, chloride, and water reabsorption during carbonic anhydrase inhibition.

To examine the magnitude and load dependency of proximal reabsorption during carbonic anhydrase inhibition with acetazolamide, Munich-Wistar rats were studied in hydropenia and following an increase in single nephron glomerular filtration rate (SNGFR) by either plasma or colloid-free Ringer expansion. During acetazolamide administration, when plasma loading increased SNGFR 50% compared with hydropenia, total CO2, chloride, and water proximal reabsorption rose proportionally, so that fractional proximal reabsorption rates remained constant (0.20-0.27). When SNGFR was comparably increased with Ringer expansion, total CO2, chloride, and water reabsorption were decreased relative to their respective rates during plasma expansion and, in fact, were not changed compared with hydropenic values. At all flow rates during carbonic anhydrase inhibition, end-proximal total CO2 and chloride concentrations were only slightly higher than in the glomerular ultrafiltrate, so that reabsorption was isohydric. In further studies, proximal reabsorption remained isohydric when the glomerular ultrafiltrate bicarbonate concentration was reduced in metabolic acidosis. In conclusion, absolute proximal reabsorption of bicarbonate, chloride, and water during carbonic anhydrase inhibition 1) proceeds isohydrically, with minimal anion concentration gradients generated, over a wide range of filtered loads, and 2) can be flow dependent (with plasma loading) as well as modulated by peritubular protein concentration, even though passive chloride transport is minimized.

Absorption↗
PubMed1982

Proximal reabsorption during metabolic acidosis in the rat.

The mechanism by which proximal volume reabsorption is reduced during hyperchloremic metabolic acidosis was studied using free-flow micropuncture techniques in Munich-Wistar rats. Compared with control hydropenic conditions, absolute rates of proximal total CO2 and water reabsorption rates during NH4Cl-induced metabolic acidosis were diminished: from 557 +/- 35 to 204 +/- 19 pmol/min and from 13.0 +/- 1.0 to 9.7 +/- 0.6 nl/min, respectively. Inhibition of proximal volume reabsorption during metabolic acidosis was not attributable to alterations in the reabsorptive Starling forces, since peritubular capillary oncotic and hydraulic pressures were normal, or to acidemia itself, since acute respiratory acidosis was not found to decrease reabsorption. When partial repair of the acidosis was achieved by NaHCO3 infusion, absolute reabsorption of both total CO2 (390 +/- 48 pmol/min) and water (12.2 +/- 1.1 nl/min) significantly increased despite modest extracellular volume expansion. NaCl infusion in acidotic animals had no restorative effect on volume reabsorption. Mean values for single nephron glomerular filtration rate were similar under all conditions. Absolute chloride reabsorption tended to correlate better with absolute bicarbonate reabsorption and, hence, with the magnitude of the chloride concentration gradient developed than with the filtered chloride load. In conclusion, absolute proximal volume reabsorption during metabolic acidosis and its partial repair correlated with the absolute magnitude of bicarbonate filtered and reabsorbed. It is proposed that proximal volume reabsorption may be regulated, at least in part, by the anion composition of the glomerular ultrafiltrate.

Absorption↗
PubMed1982

Effect of luminal bicarbonate concentration on proximal acidification in the rat.

The effect of luminal bicarbonate concentration on proximal tubular acidification was studied. Rat proximal convoluted tubules were perfused in vivo with solutions of varying bicarbonate concentration, and bicarbonate absorption was measured using microcalorimetry. Bicarbonate absorption was found to increase linearly with mean luminal bicarbonate concentrations up to 45 mM, but above this level it showed evidence of partial saturation. Bicarbonate permeability was measured and found to be 2.6 +/- 0.3 x 10(-7) cm2/s. Using this permeability, net bicarbonate absorption could be divided into two parallel components, both sensitive to luminal bicarbonate concentration: 1) proton secretion and 2) a passive bicarbonate leak. Proton secretion, when examined as a function of luminal bicarbonate concentration, exhibited saturation kinetics with an apparent Km of 16 mM and a Vmax of 200 pmol . mm-1 . min-1.

Animals↗
PubMed1981

Influence of peritubular protein on solute absorption in the rabbit proximal tubule. A specific effect on NaCl transport.

The effect of removal of peritubular protein on the reabsorption of various solutes and water was examined in isolated rabbit proximal convoluted tubules (PCT) perfused in vitro. In 22 PCT perfused with ultrafiltrate (UF) and bathed in serum, volume absorption (Jv) was 1.44 nl/mm per min and potential difference (PD) was -3.6 mV. When these same PCT were bathed in a protein-free UF, Jv was reduced 38% without a change in PD. Simultaneous measurements of total CO2 net flux (JTCO2) and glucose efflux (JG) showed that less than 2% of the decrease in JV could be accounted for by a reduction in JTCO2 and JG, suggesting that removal of peritubular protein inhibited sodium chloride transport (JNaCl). Therefore, in eight additional PCT, JNaCl was measured, in addition to PD, Jv, JG, and JTCO2. In these PCT, the decrease in total solute transport induced by removal of bath protein was 201.7 +/- 37.5 posmol/mm per min. JG decreased slightly (9.1 +/- 3.9 posmol/mm per min); NaHCO3 transport did not change (9.2 +/- 6.6 posmol/mm per min); but JNaCl decreased markedly (160.6 +/- 35.7 posmol/mm per min). 80% of the decrease in Jv could be accounted for by a decrease in JNaCl. In 13 additional PCT perfused with simple NaCl solutions, a comparable decrease in Jv and JNaCl was observed when peritubular protein was removed without an increase in TCO2 backleak. In summary, removal of peritubular protein reduced Jv and JNacl, but did not significantly alter PD, JG, JTCO2, or TCO2 backleak. The failure to inhibit JG and JTCO2, known sodium-coupled transport processes, indicates that protein removal does not primarily affect the Na-K ATPase pump system. Furthermore, since PD and TCO2 backleak were not influenced, it is unlikely that protein removal increased the permeability of the paracellular pathway. We conclude that protein removal specifically inhibits active transcellular or passive paracellular NaCl transport.

Animals↗
PubMed1981

Prevention of prednisone-induced negative nitrogen balance. Effect of dietary modification on urea generation rate in patients on hemodialysis receiving high-dose glucocorticoids.

To assess whether increasing dietary protein and calorie intake can ameliorate the negative nitrogen balance induced by 70 to 120 mg/d prednisone, we studied nitrogen intake and net urea generation rate in patients undergoing hemodialysis for 10 to 14 days after renal transplantation. Seven patients receiving prednisone with moderately restricted protein (0.73 +/- 0.03 g/kg of body weight per day) and calorie (20 +/- 4 kcal/kg of body weight per day) intake had high urea nitrogen generation rates (199 +/- 18 mg/kg.d) and protein catabolic rates (1.45 +/- 0.12 g/kg.d) and were in marked negative protein balance (-0.72 +/- 0.12 g/kg.d). An increase in protein (1.30 +/- 0.06 g/kg.d) and calorie (33 +/- 3 kcal/kg.d) consumption in another eight prednisone-treated patients resulted in protein balance (-0.02 +/- 0.12 g/kg.d) without further increasing urea generation (174 +/- 9 mg/kg.d). Six control patients undergoing hemodialysis after surgery who were not receiving prednisone had lower urea generation rates (109 +/- 15 mg/kg.d) and were in nitrogen balance. Nitrogen wasting is therefore not an inevitable consequence of high-dose glucocorticoid therapy and can be effectively prevented by simple nutritional modification without increasing hemodialytic requirements.

Adult↗
PubMed1980

The renal acidoses.

In metabolic acidosis of renal origin, the defect may involve bicarbonate reclamation by the proximal tubule, acid excretion by the distal tubule, or both. Mechanisms, diagnosis, complications, and management are described for both the proximal and the distal renal tubular acidoses. Specific attention is also devoted to the several syndromes of generalized distal nephron dysfunction and to uremic acidosis.

Acidosis, Renal Tubular↗
PubMed1979

Control of proximal bicarbonate reabsorption in normal and acidotic rats.

This free-flow micropuncture study examined the dependence of bicarbonate reabsorption in the rat superficial proximal convoluted tubule to changes in filtered bicarbonate load, and thereby the contribution of the proximal tubule to the whole kidney's response to such changes. The independent effects of extracellular fluid (ECF) volume expansion and of acidosis on proximal bicarbonate reabsorption were also examined. When the plasma volume contraction incurred by the micropuncture preparatory surgery was corrected by isoncotic plasma infusion ( congruent with1.3% body wt), single nephron glomerular filtration rate (SNGFR), and the filtered total CO(2) load increased by 50%. Absolute proximal reabsorption of total CO(2) (measured by microcalorimetry) increased by 30%, from 808+/-47 during volume contraction to 1,081+/-57 pmol/min.g kidney wt after plasma repletion, as fractional total CO(2) reabsorption decreased from 0.90 to 0.77. Aortic constriction in these plasma-repleted rats returned the filtered load and reabsorption of total CO(2) to the previous volume contracted levels. In other animals isohydric ECF expansion with plasma (5% body wt) or Ringer's solution (10% body wt), or both, produced no further diminution in fractional proximal total CO(2) reabsorption (0.76-0.81). Metabolic acidosis was associated with very high fractional proximal total CO(2) reabsorptive rates of 0.82 to 0.91 over a wide range of SNGFR and ECF volumes. At a single level of SNGFR, end-proximal total CO(2) concentration progressively decreased from 5.6+/-0.5 to 1.6 +/-0.2 mM as arterial pH fell from 7.4 to 7.1. Expansion of ECF volume in the acidotic rats did not inhibit the ability of the proximal tubule to lower end-proximal total CO(2) concentrations to minimal levels. In conclusion, bicarbonate reabsorption in the superficial proximal convoluted tubule is highly load-dependent (75-90%) in normal and acidotic rats. No inhibitory effect of ECF volume per se on proximal bicarbonate reabsorption, independent of altering the filtered bicarbonate load, could be discerned. Acidosis enabled the end-proximal luminal bicarbonate concentration to fall below normal values and reduced distal bicarbonate delivery.

Absorption↗
PubMed1978

Radiation nephritis and intravascular coagulation.

A 23 year old male with embryonal cell carcinoma of the testicle was treated with radiation, receiving 2250 Rads to his abdomen twice, only once with kidney shielding. He developed acute renal failure approximately eleven months later. Associated with the renal failure were hemolytic anemia, thrombocytopenia, hypofibrinogenemia, and other evidence for intravascular coagulation. The kidney biopsy showed fibrinoid necrosis of arteries and arterioles. By electron microscopy, there was extensive endothelial cell damage and subendothelial electron lucent material compatible with radiation nephritis. The renal pathologic abnormalities suggest that the local renal vascular injury induced by radiation could have been responsible for intravascular coagulation in the kidneys and the systemic hematologic abnormalities. Prednisone appeared to accelerate the renal and hematologic dysfunction and heparin is proposed as a more promising therapy.

Adult↗
PubMed1977

Chronic active hepatitis and membraneous glomerulonephritis.

A 26-year old man with documented HBs antigenemia of five years' duration developed the nephrotic syndrome. Histologic patterns of chronic active hepatitis and membraneous glomerulonephritis were found. The glomeruli stained positively for Ig-G, complement and HBs Ag. The relationship of HBs Ag-positive chronic active hepatitis and membraneous glomerulonephritis is discussed.

Adult↗