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| Year : 1981 | Volume
: 27
| Issue : 2 | Page : 90-8 |
Serum calcium and gastric acid-pepsin secretion.
Pimparkar BD, Gandhi UM, Bodas PV
How to cite this article:
Pimparkar B D, Gandhi U M, Bodas P V. Serum calcium and gastric acid-pepsin secretion. J Postgrad Med 1981;27:90 |
A possible relation between serum calcium and gastric secretion was suggested nearly 50 years ago in experiments in innervated (Pavlov) gastric pouches. Since then several others have studied the problem from time to time. However, there are scarce reports of correlation between serum calcium and human gastric acid-pepsin output. Hence, it was decided to study serum calcium levels in normal control and duodenal ulcer subjects and to correlate them with pentagastrin stimulated gastric acid-pepsin secretion.
Ninety five radiologically proved duodenal ulcer and eighteen normal control subjects, (all males), were studied. The normal controls were included in the study only if they fulfilled the following criteria: a negative clinical evaluation, normal upper gastrointestinal X-rays, negative stool for any parasitic infestation, negative history of diarrhoea, normal hemoglobin and normal serum protein levels.
Each subject, besides good clinical evaluation, had routine laboratory investigations such as hemogram, stool, urine and X-ray chest. The clinical symptomatology was recorded on a special proforma. Serum calcium was estimated by the method of Clark and Collip,[12] serum phosphorus by the method of Fiske and Subbarao,[23] serum alkaline phosphatase by the method of King and Armstrong,[34] serum total proteins and albumin by the method of Reinhold.[48]
Gastric acid-pepsin output was measured both at basal state and after stimulation with pentagastrin, using a dose of 6 ug/kg which has been shown in our previous studies to be the optimum dose.[45] The technique of pentagastrin test has also been discribed previonsly,[42],[43],[44] and was the same as used by Makhlouf et al.[35], [36] Acid was estimated titrimetrically using phenolphthalein as an indicator for total acid while pepsin was estimated by the method of Anson and Mirsky,[2] as modified by Hunt.[30] The effect of pentagastrin on serum calcium, phosphorus, alkaline phosphatase and blood sugar was studied simultaneously during these tests and is published separately.[46]
For the sake of brevity only total acid values are shown. Post-stimulatory one hourly secretion of acid and pepsin were designated as maximal acid and pepsin output, (MAO and MPO). Peak acid output, (PAO), and peak pepsin output, (PPO), were also calculated. The values for all are expressed as mean ± S.E. and further analysed statistically using correlation coefficient, `r'.
[Table 1] shows the mean + S.E. values for age, weight, hemoglobin, total serum proteins, serum albumin, serum calcium, phosphorus and alkaline phosphatase. It also shows similar, (Mean ± S.E.), values for basal, maximal, and peak acid-pepsin outputs, in both normal control and duodenal ulcer subjects. The mean + S.E. values for age, weight, total serum proteins, serum albumin, serum calcium, phosphorus and alkaline phosphatase did not show any significant difference between the two groups. As expected, basal, maximal and peak acid-pepsin outputs were significantly higher in duodenal ulcers than those in normal control subjects, `p' being significant. [Table 2] shows the correlation coefficients, `r', between basal, peak and maximal acid outputs and various other factors. There was no correlation between the basal, peak and maximally stimulated acid outputs and hemoglobin, total serum proteins, serum albumin, serum calcium, and alkaline phosphatase in both normal control and duodenal ulcer subjects.
[Table 3] shows the correlation coefficient (`r') between the basal, peak and maximal pepsin secretion and various other factors. Again, there was no correlation between the basal, peak and maximally stimulated pepsin and hemoglobin, serum total proteins, serum albumin, serum calcium, and alkaline phosphatase in both the groups. As reported previously,[43],[44],[45] there was a highly significant correlation between BAO and BPO and MAO and MPO in both the groups suggesting that whenever acid output was high or low, the pepsin output was also similarly high or low, respectively in both the groups.
The incidence of duodenal ulcer in hyperparathyroidism is high.[1] [9] [20] [28] [32] [41] [49] [50] [53] [59] The frequent coincidence of parathyroid adenomas in the Zollinger Eilison Syndrome,[7] [18] [19] [20] [29] [39] [54] [57] [60] [61] [62] [63] and in the multiple endocrine adenoma-peptic ulcer syndrome,[4], [33] suggested a possible interrelation of serum calcium values and gastric secretion that may be of clinical importance. Further clinical interest arises from the treatment of peptic ulcer by means of frequently administered calcium salts which may occasionally result in hypercalcemia and milk-alkali syndrome [38].[59] Studies in vitro have demonstrated that there is a narrow critical range of calcium concentration required for secretory activity in isolated sheets of frog gastric mucosa.[25], [31] Achlorhydria has been reported in hypocalcemic subjects[3], [15] Donegan and Spiro[15] reported the absence of free gastric acid in basal secretion in a hypoparathyroid patient with serum calcium levels below 7.0 mg %. Further, they were able to restrore free gastric acid by infusion of calcium in their hypoparathyroid patient. The critical level of plasma calcium at which gastric acid secretion was restored was about 7.0 to 7.5 mg%. Infusion of calcium has been reported to increase acid-pepsin output in normal controls and in patients with duodenal ulcer, hyperparathyroidism, Zollinger-Ellison syndrome and familial multiple endocrine tumor peptic ulcer sydrome.[5],[6],[7],[13],[40],[47],[52],[54],[58] Whereas most studies in man show that parenteral calcium leads to an increase in gastric secretion, parenteral calcium has been found to inhibit gastric secretion in animals.[22] [24] [47] [58] This may be due either to species variation or due to variation in method.[52] The effects of acute and chronic hypercalcemia may differ since, Smallwood,[52] in infusion experiments, clearly showed that the secretory changes did not parallel the serum calcium levels. The increased gastric secretion is not directly related to the actual calcium levels but rather to the sharp rise in serum calcium following an acute calcium load. The rise in gastric secretion of acid-pepsin after calcium infusion is discernible in one hour, reaches a peak in 3 to 4 hours and is more than 2 to 4 times greater than basal acid-pepsin output and about 30% greater than the peak acid output after histalog or histamine stimulation.[13], [40], [52]
Several mechanisms for the action of calcium are suggested. Calcium may have a direct effect on the parietal cell, since it is blocked by simultaneous magnesium infusion.[6],[21] There is evidence to suggest that calcium may facilitate release of acetylcholine at the neuromuscular end plate[14], [56] in preganglionic parasympathetic fibres;[27] and in postganglionic parasympathetic fibres.[57] Further, in the case of motor end plate, the apparent facilitation of acetyl choline release is blocked by magnesium,[21] by anticholinergics or by ganglion blocking agents[6], [47], [56] suggesting vagal synergism. Calcium has been reported to cause the release or elaboration of gastrin.[47], [54] Trudeau and McGuigan,[54] demonstrated excellent correlation between the plasma calcium and serum gastrin levels and marked increase in serum gastrin concentration by calcium infusion but not by infusion of parathormone in a patient with Zollinger-Ellison syndrome. Similar results were reported in normal control and duodenal ulcer patients by Reeder et a1[47] who also showed that the injection of atropine consistently diminished the calcium induced gastric acid secretion but did not decrease the elevated levels of serum gastrin. Wilson et a1[60] reported hypercalcemia and hypergastrinemia in 20 patients with hyperparathyroidism, (HPT). Removal of hyperfunctioning parathyroid glands resulted, in parathormone and calcium concentrations returning to normal but the fasting gastrin, integrated gastrin response to a meal, and stimulated acid output were not significantly changed indicating that an elevated parathormone or calcium concentration is not the cause of hypergastrinemia in HPT but rather these two endocrine disturbances may coexist. Basso and Passaro[7] found that the acid response to calcium in the Zollinger-Ellison syndrome was prompt, large and sustained while it was gradual in onset and less in amount in duodenal ulcer patients indicating that calcium stimulates the release of gastrin from non-beta cells and that it potentiates the response of gastrin. However, this potentiation is controversial since Christiansen and Handel[11] could not confirm these findings. Similar results of no potentiation after calcium and histamine stimulation were obtained by Dalal et al.[13] Thus, vagal synergism with the increased levels of gastrin is required for the stimulation of acid secretion by calcium.
The mean values for serum calcium and phosporus in this group of 95 subjects with duodenal ulcer were within normal limits. This finding indicates that hyperparathyroidism is not a common cause of ulcer, at least in Bombay from where these patients came.
Although majority of ulcer subjects secreted significantly increased amounts of acid and pepsin as compared to those in normal controls [Table 1], this increased secretion was not due to increased serum calcium levels as these were not significantly different from those in normal controls. Hypersecretion in ulcer subjects is thought to be due to either increased parietal cell mass[10], [37] or due to vagotonia;[16], [17], [51] it also could be due to hypergastrinemia. It was not possible for us to estimate serum gastrin when we undertook these studies. Just as Christiansen and Handelll and Dalal et al[13] found no potentiation by calcium of pentagastrin or histamine stimulated secretion, we have reported no potentation of calcium by pentagestrin.[46] Thus, our results indicate that hyperparathyroidism and hypercalcemia are not a common cause of hypersecretion in the usual duodenal ulcer subjects.
This project was supported by a Research Grant from the Indian Council of Medical Research. The authors are grateful to Dr. J. S. Mishra, the Superintendent, and the Medical Director, Medical Research Center of the Bombay Hospital Trust for giving all the facilities to carry out the Research. Thanks are also due to Mrs. K. D. Lotlikar for statistical analysis.
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