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NEPHROTIC SYNDROME AND DERMATITIS HERPETIFORMIS
1139 NEPHROTIC SYNDROME AND DERMATITIS HERPETIFORMIS
SIR,-Dr Davies and Dr Davies (Oct. 27, p. 911) report the presence of nephrotic syndrome in two patients with dermatitis herpetiformis (DH). They point out the relation between DH (and cceliac disease) and HLA-DRw3, which is also associated with idiopathic membranous nephropathy, and suggest that evidence of nephritis be sought in patients with gluten-sensitive disease. We recently reported the case of a young woman with immune-complex glomerulonephritis and coeliac disease in whom antibodies to wheat proteins were found in serum.’ Withdrawal of gluten from the diet resulted in the disappearance of immune complexes from serum and resolution of both renal and intestinal disease. Dietary antigens may be tant but unrecognised cause of immune-complex
imporglomeru-
an
lonephritis. Department of Immunological Medicine, Hammersmith Hospital,
R. F. DYCK
London W12
tC02, and pK’, calculated. We consider it desirable that plasma water and sodium level are also calculated to ensure accuracy in pKBcalculation (see below). In the 1920s the pK’, of saline bicarbonate was shown".12 to increase with reduction in ionic strength. If plasma behaves similarly, alteration in pK’, is to be expected when hypernatracmia or dilution hyponatrxmia develop. Recently we investigated the effect on pK’ of varying plasmasodium (Na+) level. Fresh plasma was diluted with deionised water to lower the Na+-Ievel to 40 mmol/1. Dry NaCI was added to 5 ml volumes to give Na+-levels of 70, 100, 140, 180, and 220 mmo]A. Samples were equilibrated in a tonometer (I.L. 237) at 37°C with 5% CO2, 12% O2, and 83% N2 for 30 min; and measurements made of pH and PC02 (at 37°C) (Corning 175 pH/blood gas system) in quintuplicate, of CO2 content (Corning 965 tC02 analyser) of Na+ and K+ (flame photometry) in duplicate; and of plasma water (temperature compensated refractometer). Plasma from six healthy people was treated thus, and pK’, values were calculated by substitution into the Henderson-Hasselbalch equation (after rearrangement). For these calculations, the solubility factors was corrected for the measured molal concentration of Na+ in plasma water and fractional plasma water content." Calculated values for pK’, were corrected to pH 7-4, using the relationship between pK’, and pH reported by Ripens et al.’a
ACTUAL OR STANDARD BICARBONATE?
SIR,-Dr Howorth (Oct. 20, p. 849) pointed out that "actual plasma bicarbonate" is calculated, not measured, from measured values of pH and PC02, by substitution in the Henderson-Hasselbalch equation: pH=pK’1+log sPC02). The calculations subsume values for pK’l and s, usually 6.1, and 0-031 mmol/1 plasma/mm Hg, respectively but neither pK’l nors are true constants, and several investigators have reported abnormal values for pK’l in acutely ill patients.2-4 They determined pKBby substituting measured values for pH, PC02, and tC02 in a rearranged HendersonHasselbalch equation, making the approximation: [HC03]p
([HC03]/
tCOcsPC02. Others have found no, or only a few, abnormal values for pK’1’5-8 and Howorth suggests that there is no reason to anticipate alteration in usual values for pK’l in acutely ill patients; and he inclines to the view that apparently abnormal values arise from methods giving wider scatter in pK’l when measurements are done on whole blood that has not been tonometered9 and/or from variation in tC02 caused by continuing metabolism in blood cells during the interval between pH and PCOz measurements, and measurement of tC02." That is, he considers abnormal pK’, values to reflect only imprecision or error in p’, determination. We, on the other hand, believe that the considerable frequency of hyponatraemia or hypernatraemia in the acutely ill affords good reason to anticipate genuine change in pK’ 1; and we advise that where appraisal of acid-base balance is sought in such patients measurements be made of pH, PC02, and 1. Katz A,
Dyck RF, Bear RA. Celiac disease associated glomerulonephritis. Clin Nephrol 1979; 11:39-44.
with
immune
complex
2. Trenchard D, Noble MIM, Guz A. Serum carbonic acid pK’1 abnormalities in patients with acid base disturbances. Clin Sci 1967; 32: 189-200. 3. Natelson S, Nobel D. Effect of the variation of pK’1 of the Henderson-Hasselbach equation on values obtained for total CO2 calculated from PCO2 and pH values. Clin Chem 1977; 23: 767-69; Clin Chem 1978; 24: 1082-83. 4. Hyde TA. Actual or standard bicarbonate. Lancet 1979; ii: 796. 5. De Raedt H, Vandenberg E, van de Woesture KP. Direct and indirect determination of partial pressure of CO2 in the arterial blood of patients with respiratory insufficiency. Clin Sci 1968; 35: 347-52. 6. Sinclair MJ, Hart RA, Pope HM, Campbell ESM. The use of the HendersonHasselbalch equation in routine medical practice. Clin Chim Acta 1968; 19: 63-9. 7. Austin WH, Ferrante V, Anderson C. Evaluation of whole blood pK’1 in the acutely ill patient. J lab Clin Med 1968;72:129-35. 8. Austin WH. Further comments on the variation of pK’1: computation of (HCO3-) independent of pK’1 and solubility coefficient. Clin Chim 1978; 24: 1081-82. 9. Austin WH, CO2 solubility, pK’1 and related factors in acid-base balance. In: Durst RA, ed. Blood pH, gases and electrolytes: NBS Spec Publ 450. National Bureau of Standards, Washington, D.C., 1977: 143-51. 10. Rispens P. Is pK’1 really constant? In: Maas, AHJ ed. Blood pH and gases. Utrecht: University Press, 1979: 50-55.
displays the geometric mean of regression lines y on on y (y=corrected pK’l; x=mmol Na+/kg plasma water). Each point is the mean of five estimates ofpKB+l1 SE;
x
Fig.
1
and
x
and the mean of two estimates of Na+; residual variance=l - 35 x 10-5, n-2=4. Plasma from a further six healthy people was similarly diluted and analysed. Dry NaHC03 was added to diluted plasmas to return the bicarbonate level to that present in undiluted plasmas. Variable amounts of dry NaCI were then added as in the previous experiments; and measurements made as before. Fig. 2 displays the geometric means of the regression lines calculated: line 1, using pooled data from all six plasmas where NaHC03 was not added (36 paired values, each pK’ the mean of five measurements on samples from one person); line 2, using pooled data from the other six plasmas with NaHC03 added. Each point is the grand mean of pK’, (±ISE) and the grand mean of Na. Residual variances are 1-08 x 10-5, and 0-88 x 10-5, respectively (n-2=34 in both cases). Clearly plasma does behave like a dilute saline-bicarbonate, and pK’, is likely to change in very ill patients in whom plasma Na levels are likely to rise or fall. 11.
Warburg EJ.
Studies
on
carbonic acid
compounds
and
hydrogen
ion activi-
in blood and salt solutions. Biochem J 1922; 16: 311-49. 12. Hastings AB, Sendroy J. The effect of variation in ionic strength ties
on the apparent first and second dissociation constants of carbonic acid. J Biol Chem 1925; 65:445-55. 13. Tibi L, Bhattacharya SS, Flear CTG. Plasma sodium concentrations and
pK’1. Clin Sci 1979; 57: 20-21 P. 14.
Rispens, P, Dellebarre CW, Eleveld D, Helder W, Zylstra WG. The apparent first dissociation constant of carbonic acid in plasma between 16 and 42.5° Clin Chim Acta 1968; 22: 627-37.
SIR,-Dr Davies and Dr Davies (Oct. 27, p. 911) report the presence of nephrotic syndrome in two patients with dermatitis herpetiformis (DH). They point out the relation between DH (and cceliac disease) and HLA-DRw3, which is also associated with idiopathic membranous nephropathy, and suggest that evidence of nephritis be sought in patients with gluten-sensitive disease. We recently reported the case of a young woman with immune-complex glomerulonephritis and coeliac disease in whom antibodies to wheat proteins were found in serum.’ Withdrawal of gluten from the diet resulted in the disappearance of immune complexes from serum and resolution of both renal and intestinal disease. Dietary antigens may be tant but unrecognised cause of immune-complex
imporglomeru-
an
lonephritis. Department of Immunological Medicine, Hammersmith Hospital,
R. F. DYCK
London W12
tC02, and pK’, calculated. We consider it desirable that plasma water and sodium level are also calculated to ensure accuracy in pKBcalculation (see below). In the 1920s the pK’, of saline bicarbonate was shown".12 to increase with reduction in ionic strength. If plasma behaves similarly, alteration in pK’, is to be expected when hypernatracmia or dilution hyponatrxmia develop. Recently we investigated the effect on pK’ of varying plasmasodium (Na+) level. Fresh plasma was diluted with deionised water to lower the Na+-Ievel to 40 mmol/1. Dry NaCI was added to 5 ml volumes to give Na+-levels of 70, 100, 140, 180, and 220 mmo]A. Samples were equilibrated in a tonometer (I.L. 237) at 37°C with 5% CO2, 12% O2, and 83% N2 for 30 min; and measurements made of pH and PC02 (at 37°C) (Corning 175 pH/blood gas system) in quintuplicate, of CO2 content (Corning 965 tC02 analyser) of Na+ and K+ (flame photometry) in duplicate; and of plasma water (temperature compensated refractometer). Plasma from six healthy people was treated thus, and pK’, values were calculated by substitution into the Henderson-Hasselbalch equation (after rearrangement). For these calculations, the solubility factors was corrected for the measured molal concentration of Na+ in plasma water and fractional plasma water content." Calculated values for pK’, were corrected to pH 7-4, using the relationship between pK’, and pH reported by Ripens et al.’a
ACTUAL OR STANDARD BICARBONATE?
SIR,-Dr Howorth (Oct. 20, p. 849) pointed out that "actual plasma bicarbonate" is calculated, not measured, from measured values of pH and PC02, by substitution in the Henderson-Hasselbalch equation: pH=pK’1+log sPC02). The calculations subsume values for pK’l and s, usually 6.1, and 0-031 mmol/1 plasma/mm Hg, respectively but neither pK’l nors are true constants, and several investigators have reported abnormal values for pK’l in acutely ill patients.2-4 They determined pKBby substituting measured values for pH, PC02, and tC02 in a rearranged HendersonHasselbalch equation, making the approximation: [HC03]p
([HC03]/
tCOcsPC02. Others have found no, or only a few, abnormal values for pK’1’5-8 and Howorth suggests that there is no reason to anticipate alteration in usual values for pK’l in acutely ill patients; and he inclines to the view that apparently abnormal values arise from methods giving wider scatter in pK’l when measurements are done on whole blood that has not been tonometered9 and/or from variation in tC02 caused by continuing metabolism in blood cells during the interval between pH and PCOz measurements, and measurement of tC02." That is, he considers abnormal pK’, values to reflect only imprecision or error in p’, determination. We, on the other hand, believe that the considerable frequency of hyponatraemia or hypernatraemia in the acutely ill affords good reason to anticipate genuine change in pK’ 1; and we advise that where appraisal of acid-base balance is sought in such patients measurements be made of pH, PC02, and 1. Katz A,
Dyck RF, Bear RA. Celiac disease associated glomerulonephritis. Clin Nephrol 1979; 11:39-44.
with
immune
complex
2. Trenchard D, Noble MIM, Guz A. Serum carbonic acid pK’1 abnormalities in patients with acid base disturbances. Clin Sci 1967; 32: 189-200. 3. Natelson S, Nobel D. Effect of the variation of pK’1 of the Henderson-Hasselbach equation on values obtained for total CO2 calculated from PCO2 and pH values. Clin Chem 1977; 23: 767-69; Clin Chem 1978; 24: 1082-83. 4. Hyde TA. Actual or standard bicarbonate. Lancet 1979; ii: 796. 5. De Raedt H, Vandenberg E, van de Woesture KP. Direct and indirect determination of partial pressure of CO2 in the arterial blood of patients with respiratory insufficiency. Clin Sci 1968; 35: 347-52. 6. Sinclair MJ, Hart RA, Pope HM, Campbell ESM. The use of the HendersonHasselbalch equation in routine medical practice. Clin Chim Acta 1968; 19: 63-9. 7. Austin WH, Ferrante V, Anderson C. Evaluation of whole blood pK’1 in the acutely ill patient. J lab Clin Med 1968;72:129-35. 8. Austin WH. Further comments on the variation of pK’1: computation of (HCO3-) independent of pK’1 and solubility coefficient. Clin Chim 1978; 24: 1081-82. 9. Austin WH, CO2 solubility, pK’1 and related factors in acid-base balance. In: Durst RA, ed. Blood pH, gases and electrolytes: NBS Spec Publ 450. National Bureau of Standards, Washington, D.C., 1977: 143-51. 10. Rispens P. Is pK’1 really constant? In: Maas, AHJ ed. Blood pH and gases. Utrecht: University Press, 1979: 50-55.
displays the geometric mean of regression lines y on on y (y=corrected pK’l; x=mmol Na+/kg plasma water). Each point is the mean of five estimates ofpKB+l1 SE;
x
Fig.
1
and
x
and the mean of two estimates of Na+; residual variance=l - 35 x 10-5, n-2=4. Plasma from a further six healthy people was similarly diluted and analysed. Dry NaHC03 was added to diluted plasmas to return the bicarbonate level to that present in undiluted plasmas. Variable amounts of dry NaCI were then added as in the previous experiments; and measurements made as before. Fig. 2 displays the geometric means of the regression lines calculated: line 1, using pooled data from all six plasmas where NaHC03 was not added (36 paired values, each pK’ the mean of five measurements on samples from one person); line 2, using pooled data from the other six plasmas with NaHC03 added. Each point is the grand mean of pK’, (±ISE) and the grand mean of Na. Residual variances are 1-08 x 10-5, and 0-88 x 10-5, respectively (n-2=34 in both cases). Clearly plasma does behave like a dilute saline-bicarbonate, and pK’, is likely to change in very ill patients in whom plasma Na levels are likely to rise or fall. 11.
Warburg EJ.
Studies
on
carbonic acid
compounds
and
hydrogen
ion activi-
in blood and salt solutions. Biochem J 1922; 16: 311-49. 12. Hastings AB, Sendroy J. The effect of variation in ionic strength ties
on the apparent first and second dissociation constants of carbonic acid. J Biol Chem 1925; 65:445-55. 13. Tibi L, Bhattacharya SS, Flear CTG. Plasma sodium concentrations and
pK’1. Clin Sci 1979; 57: 20-21 P. 14.
Rispens, P, Dellebarre CW, Eleveld D, Helder W, Zylstra WG. The apparent first dissociation constant of carbonic acid in plasma between 16 and 42.5° Clin Chim Acta 1968; 22: 627-37.