Acute Hypercalcemia Research Articles

Effect of acute hypercalcemia on human esophageal motility

In order to evaluate the effect of acute moderate hypercalcemia on both smooth and skeletal muscle function of the human esophagus, 12 subjects were given intravenous calcium chloride in normal saline. Serum calcium increased from a basal value of 9.6 ±0.1 mg per dl (mean ± 1 sem) to 11.4 ± 0.2 mg per dl at 90 min after initiation of calcium infusion (P < 0.01). Both amplitude and Dp/Dt of esophageal contractions decreased significantly in the skeletal muscle segment; however, amplitude and Dp/Dt increased significantly in the smooth muscle segment. Lower esophageal sphincter pressure remained unchanged. Duration of contractions and peristaltic wave speed were unaltered. Possible explanations for the divergent effect of hypercalcemia on the two types of esophageal muscle are discussed.

A reevaluation of the cause of acute hypercalcemia following intravenous administration of lead acetate.

The effect of intravenous (i.v.) injection of lead acetate (15 or 30 mg/kg) was studied in young adult male rats. The reaction of lead with rat plasma to produce colloidal material containing both calcium and phosphate was demonstrated both in vitro and in vivo. This material could be centrifuged down at 25,000 ×g from plasma aliquots to which lead had been added or from plasma samples obtained as early as 5 min after i.v. lead injection. The hypercalcemia and hyperphosphatemia reached their peak rapidly after lead injection, and even at the higher dose level these lasted less than 6 h.45Ca and32P were injected at times varying from 1 to 8 days prior to lead administration. Plasma radioactivity levels rose with their stable counterparts without affecting plasma nuclide specific activity. Lead uptake on bone surfaces could be detected within 5 min of injection, and continued to accumulate for at least 6 h. It is concluded that although lead attaches to bone surfaces, the hypercalcemia and hyperphosphatemia are caused by the direct interaction of lead with calcium and phosphate in solution in plasma. The formation of the colloidal material lowers ionic calcium and phosphate. In vivo, calcium and phosphate are immediately withdrawn from extravascular sources returning plasma concentrations to their initial value. The source of at least the calcium is believed to be bone. The attachment of lead to bone surfaces does not in itself release significant amounts of calcium and phosphate into blood.

DIURNAL VARIATIONS IN THE INFLUENCE OF THE ULTIMOBRANCHIAL GLANDS ON CALCIUM HOMEOSTASIS IN THE FROG (RANA PIPIENS)

The effect of the light-darkness cycle on the efficiency of the ultimobranchial and parathyroid glands in altering duodenal calcium transport and plasma and urinary concentrations of calcium was examined in the adult male frog (Rana pipiens). Frogs were unfed, but were allowed access to 0.05 M-CaCl2 in the surrounding medium after ultimobranchialectomy or parathyroidectomy. Calcium transport, as assayed by the everted gut-sac technique, was increased in ultimobranchialectomized frogs at sunrise, concomitant with acute hypercalcaemia and hypercalciuria. An opposite but chronic response was observed in parathyroidectomized frogs with intact ultimobranchial glands. The maximum response observed at sunrise occurred when the concentration of calcium in the plasma of control frogs was decreasing; the minimum response, which occurred 6 h after sunrise, was coincident with a diurnal peak in the concentration of calcium. Vitamin D3 (500 microgram/frog) enhanced calcium transport in ultimobranchialectomized frogs, which resulted in chronic hypercalcaemia and hypercalciuria. The results suggest that diurnal variations in the plasma concentration of calcium do not initiate ultimobranchial activity, but are a response to endocrine control synchronized with the transition from darkness to light.

Salmon Calcitonin in the Acute Treatment of Moderate and Severe Hyperealcemia in Man

The effect of i.v. infusions with salmon calcitonin was evaluated in the treatment of acute hypercalcemia in 12 patients. Clinical improvement and a less critical level of serum calcium were achieved within 24 hours for eight of the patients, for another two after treatment for 48 hours. In malignant conditions (six patients) calcitonin was less effective, which could be evaluated within 24 hours. In addition to rehydration, the rapid onset of action and the lack of side-effects make calcitonin a drug of first choice in the treatment of acute hypercalcemia.

Treatment of hypercalcaemic syndrome in tumour patients, especially with mithramycin

In 36 patients with neoplastic diseases 72 episodes of hypercalcaemia with serum-calcium levels greater than or equal to 2.75 mmol/l were treated (19 breast carcinoma; 9 bronchial or lung carcinoma; 5 multiple myeloma; 1 each jejunal carcinoid, malignant lymphoma, phaeochromocytoma). Cardinal symptoms were mental, neuromuscular and renal during the hypercalcaemic episodes. Mithramycin is preferred to other methods (infusion of sodium chloride and frusemide, prednisone, sodium-potassium-phosphate infusion) of treating acute or subacute hypercalcaemia. Mithramycin in a single injection of 20-25 microgram/kg body-weight intravenously is usually sufficient to counteract a hypercalcaemic phase for at least 7-10 days, often much longer. There was a highly significant fall in serum-calcium levels from two days onwards after mithramycin injection. Toxic side-effects were minimal and restricted to transitory increase in transaminase levels, initially 5-6 times normal with a maximum on the third day and normalisation on the fifth day after mithramycin administration.

Serum gastrin response to acute and chronic hypercalcaemia in man: studies on the value of calcium stimulated serum gastrin levels in the diagnosis of Zollinger‐Ellison syndrome

In this study the effect of calcium infusion over 3 h without gastric aspiration on serum gastrin was determined in fifteen normal subjects, ten patients with duodenal ulcer, nine with stomal ulcer, five with total gastrectomy, six with achlorhydria and sixteen with proved or presumed Zollinger-Ellison (ZE) syndrome. Serum gastrin only rose significantly in the patients with ZE-syndrome or achlorhydria. An increase of above or below 50% of basal value seems to be a valuable criterion by which to differentiate between patients with and without ZE-syndrome. Serum gastrin levels in forty-four patients with chronic hypercalcaemia (72+/-24 pg/ml, mean+/-SD) were not significantly different from the levels in 100 normal subjects (66+/-18 pg/ml; P greater than 0.10). However, in one patient with ZE-syndrome and in two patients with achlorhydria serum gastrin values were markedly higher during chronic hypercalcaemia than during normocalcaemia. It is concluded that acute or chronic hypercalcaemia without gastric aspiration does not lead to hypergastrinaemia in the absence of ZE-syndrome or achlorhydria.

Renal hemodynamic and autoregulatory responses to acute hypercalcemia.

Renal hemodynamic and autoregulatory responses to acute hypercalcemia.

The influence of acute hypercalcemia on the level of plasma growth hormone during oral glucose tolerance test.

The influence of acute hypercalcemia on the level of plasma growth hormone during oral glucose tolerance test.

Effects of hypercalcemia on water and sodium excretion by the isolated dog kidney.

The effects of acute hypercalcemia on hemodynamics and on water and sodium excretion were studied on the blood-perfused isolated dog kidney. This model advantageously eliminates various factors which modify medullary osmolality and intrarenal hemodynamics, as well as collecting duct permeability. Calcium ion directly inhibits sodium reabsorption in the proximal tubule and in the ascending limb of Henle's loop, leading to increased sodium excretion rate and to decreased free water generation. The vasoconstrictive action of calcium, leading to decreased glomerular filtration rate, may mitigate the strong natriuretic effect of this ion.

Permeability of the blood-brain barrier to calcium in adrenal insufficiency

Experiments purporting to prove a marked breakdown of the blood-cerebrospinal fluid barrier to calcium ions in the absence of glucocorticoids have been reported in the literature4, 5. The phenomenon, if confirmed, would be of considerable fundamental and applied significance. It would imply that this usually tight barrier was dependent on endocrine activity. Further, it would suggest a mechanism for the known action of glucocorticoids in reducing cerebral oedema. We have studied the permeability of both the blood-brain and blood-cerebrospinal fluid barriers to calcium with the view of confirming this observation. In the rat, both at normal and elevated plasma calcium levels, we have been unable to find evidence in support of this finding. Similarly, in the lightly anaesthetised adrenalectomised rabbit, no increase in cerebrospinal fluid calcium was seen during acute hypercalcaemia. Male CSE-Wistar rats weighing approximately 350 g were adrenalectomised by the lumbar approach under ether anaesthesia. The animals were allowed to recover and were maintained on small animal diet with 0.9 ~o saline as drinking water ad libitum for a minimum of 8 days before infusions were carried out. In the rat maintained on saline, the cardiovascular system has returned to normal 8 days after adrenalectomy 6. Solutions were infused into the femoral vein of rats anaesthetised with intraperitoneal Nembutal (6 mg/100 g body weight; 4.5 mg/100 g in adrenalectomised animals). Intact controls and adrenalectomised animals were perfused in parallel. Infusion schedules were devised to maintain constant blood levels of either calcium-45 or of raised total calcium. Blood levels were monitored by sampling from the cannulated femoral artery on the same side. The effectiveness of the adrenalectomy was confirmed by corticosterone analysis on the last sample of blood taken from the surgically stressed animal. Corticosterone was estimated fluorimetrically by a modification of the Zenker-Bernstein method s. For studies at normal plasma levels, 45Ca as a calculated amount of radioisotope in a total calcium concentration of 5 mg/100 ml was infused with a Har-

Furosemide, mithramycin, and salmon calcitonin in hypercalcemia.

Twenty-nine patients with acute hypercalcemia secondary to carcinoma, myeloma and parathyroid adenoma have been treated with large doses of furosemide, mithramycin, or salmon calcitonin perfusion. With furosemide administration the treatment was successful in 6 of 10 patients. Furosemide was injected intravenously at the rate of 125 mg every 3 hours. With mithramycin perfusion only 2 of 8 patients have a return of the serum calcium levels to normal. With salmon thyrocalcitonin 3 of 10 patients obtained a good result. It can be interesting to suggest the association of furosemide and salmon calcitonin infusion to treat hypercalcemia of myeloma.

Hypercalcemic and Hypocalcemic Crises

THE crisis of acute hypercalcemia constitutes one of the more common endocrine emergencies. Within the past few years, new therapeutic modalities have become available for the medical management of this entity. We review these modalities and suggest a regimen for the rational treatment of the hypercalcemic patient. In addition, a system of medical management will be presented for the treatment of the patient with acute hypocalcemia. Hypercalcemic Crisis Diagnosis.— Acute hypercalcemia can have a variety of manifestations. 1 Common symptoms include nausea and vomiting (with subsequent dehydration), anorexia, constipation, and polyuria. Severe abdominal pain is common and frequently is related to an associated peptic ulcer or pancreatitis. Other symptoms include weakness ranging from mild fatigue to neuromuscular paralysis, fever, and coma. Objective signs include ectopic calcification, such as band keratopathy, nephrocalcinosis, arterial calcification, and skin calcification. A decreased Q-T interval is seen on the electrocardiogram. The most common causes of

Unresponsiveness of exocrine rat pancreas to calcemic challenges (hypercalcemia, EDTA hypocalcemia or calcitonin administration) which influence stomach function.

In the rat, stimulated exocrine pancreatic secretion is not influenced by acute hypercalcemia, EDTA hypocalcemia or calcitonin administration. This unresponsiveness is in contrast to the reaction of the rat stomach to calcemic challenges.

Pathogenic role of cyclic AMP in the impairment of urinary concentrating ability in acute hypercalcemia.

A possible association between the impairment of urinary concentrating ability and an impairment of the vasopressin-dependent cyclic AMP system in hypercalcemia was investigated in rat kidneys both in vivo and in vitro. The increases of urinary osmolality and negative free water clearance and the increase of urinary cyclic AMP excretion by vasopressin injection were significantly less in the hypercalcemic rats than in the control rats. The increase of cyclic AMP concentration by vasopressin in renal medullary tissue was significantly less in the slices obtained from the hypercalcem'c rats than in those obtained from the control rats. The activation of adenylate cyclase by vasopressin was significantly less in the group with an increased concentration of calcium in media than the control group, but phosphodiesterase activity was not affected by calcium concentration in the media. These data suggest that the impaired urinary concentrating ability in hypercalcemic kidneys is due at least in part to the direct inhibitory effect of calcium on the vasopressin-dependent cyclic AMP system at the level of adenylate cyclase in renal medulla.

Vitamin-D-resistant idiopathic hypoparathyroidism. Acute hypercalcemia during acute renal failure

Vitamin-D-resistant idiopathic hypoparathyroidism. Acute hypercalcemia during acute renal failure

Acute pancreatitis secondary to iatrogenic hypercalcemia: implications of hyperalimentation.

An unusual case of acute pancreatitis and hypercalcemia in a patient receiving hyperalimentation is presented along with discussion of the relationship of pancreatitis, hypercalcemia and hyperparathyroidism, and the treatment of hypercalcemic crisis. This is believed to be the first report of pancreatitis secondary to acute hypercalcemia produced by chronic calcium intake as part of the hyperalimentation infusion.

Hyposthenuria in hypercalcemia. A possible role of intrarenal blood-flow (IRBF) redistribution.

The intrarenal blood flow (IRBF) distribution has been studied in dogs during acute and chronic calcium intoxication, using clearance technique,85Kr disappearance curves, autoradiograms, and silicone rubber injections. The purpose of this study was to determine whether a modification of the IRBF could be responsible for the decrease of the cortico-medullary osmotic gradient and the hyposthenuria generally observed in these conditions. Acute hypercalcemia was produced in 12 dogs by infusing a solution of CaCl2 into the left renal artery. 20 min after starting infusion (PCa in renal vein = 7.34 mEq/l), the urinary osmolarity and the TcH2O were slightly decreased on the experimental side (P<0.05). C.PAH was also depressed (P<0.005), while E.PAH remained constant. The85Kr curves and the autoradiograms reflected a redistribution of IRBF toward the deeper region of the kidney. In 10 dogs chronically intoxicated with vitamin D, (PCa=6.68 mEq/l) the U.osm and TcH2O were markedly depressed (P<0.001). Renal tissue analysis showed a significant fall of the cortico-medullary osmotic gradient of Na. In parallel, a decrease in C.PAH was observed.85Kr curves demonstrated a significant redistribution of IRBF with a decrease of the percent of initial radioactivity in the cortex. Autoradiograms and silicone rubber vascular casts also demonstrated a vasodilatation of the vasa recta of the medulla. These data therefore support the conclusion that a redistribution of IRBF contributes to the hyposthenuria observed during hypercalcemia.

Urinary excretion of free cortisol in hypercalcaemia.

ABSTRACT Human and animal studies have uniformly demonstrated increased hypothalamic-pituitary-adrenocortical (HPA) activity during acute hypercalcaemia. The HPA-activity during chronic hypercalcaemia was investigated by means of free urinary cortisol excretion. No difference in HPA activity could be demonstrated between a hyperparathyroid hypercalcaemic and a normocalcaemic group of patients. Based on these results it is suggested that during chronic hypercalcaemia, the HPA feed back mechanism overcomes the influence of hypercalcaemia on the HPA-axis.

Experimental hypercalcaemia and whole blood clotting.

Experimental hypercalcaemia was induced in rats by (1) transplantation of the solid Walker 256 tumour, and (2) intraperitoneal injections of calcium gluconate. Whole blood clotting was studied by means of thromboelastography and whole blood clotting times in polystyrene and glass test tubes. At serum calcium levels between 10.3 and 11.5 m-equiv/l a slight delay in clot formation was found which was reversible by the addition of EDTA to whole blood. Acute, calcium-gluconate-induced hypercalcaemia, however, leads to a significant shortening of the clotting time in the polystyrene tube and to a lesser degree in the glass tube. Maximal factor XII activation in vitro with ellagic acid levels the difference of clotting times again. From these experiments it is concluded that acute hypercalcaemia induces a hypercoagulable state, possibly by partial contact activation, and thus may favour thrombus formation in vivo.

Enkele Endocrinologische Afwijkingen Van Het Calcium En Fosfor Metabolisme

SummaryAfter a short evaluation of various methods for the investigation of the calcium and phosphate metabolism follows a review of the related endocrinologic pathology : deviations in the production of calcitonin and the different forms of hyperparathyroidism. Finally the treatment of acute hypercalcemia is discussed.