Wheat pasture poisoning. II. Tissue composition of cattle grazing cereal forages and related to tetany.

Thirty-two aged Hereford and Angus cows (avg 10.2 yr old) grazed mixed cereal (wheat and rye) pastures from December 6, 1979 to April 23, 1980 (138 d). On d 104 (March 19), five cows developed tetany. On the day of tetany, the mean plasma Ca of the cows with tetany was 4.1 mg/dl. Cows with tetany had plasma Mg concentrations of 1.7 mg/dl on the day of tetany, but 15 d before tetany and 6 d post-tetany, levels were lower (1.2 mg/dl). Cows with tetany had large increases in plasma parathyroid hormone (PHT) as well as vitamin 1, 25 dihydroxy D3 [1,25(OH)2D], plasma glucose, lactic acid and beta-hydroxybutyric acid. Plasma K of these cows followed a similar trend as plant K, except it was not as pronounced. Plasma inorganic P of these same cows was exceedingly low, less than 3 mg/dl several times, although the forage P did not indicate a P deficiency. Levels of plasma hydroxyproline in these cows indicated that bone resorption may have been low during most of the grazing season, even though levels of plasma hydroxyproline were initially high and high subsequent to tetany. High levels of plasma glucose and lactic acid were associated with the time of tetany. Apparently, cows developed inappetence around the time of tetany, as suggested by the high levels of plasma beta-hydroxybutyric acid. Cows with wheat pasture poisoning appeared to respond to the severe hypocalcemia with large increases in plasma 1,25(OH)2D. Plasma 1,25(OH)2D changes were similar to plasma hydroxyproline changes (and possible bone resorption rates) and seemed inversely proportional to plasma Ca and directly proportional to plasma PTH concentrations. Generally, cerebrospinal fluid (CSF) composition was not affected as much as plasma composition, except for the low levels of CSF Ca. These data indicate that a metabolic deficiency of Ca (hypocalcemia) was the cause of tetany.

Model for parathyroid hormone secretion and metabolism in calves.

A model for parathyroid gland response to differing calcium and magnesium concentrations is proposed based on direct determinations of parathyroid hormone (PTH) secretion rate. A proportional control seems adequate for physiological variations of calcium and magnesium levels. At extreme hypocalcemia, nonlinearities are observed: a model involving the depletion of a storage compartment is proposed, the size of which is calculated. PTH distribution was studied in another group of animals; sampling was made from the saphenous artery and the thoracic duct. Concentrations of plasma and lymph-intact PTH and carboxy-terminal fragments were determined by means of two different radioimmunoassays. The analysis of the results leads to the formulation of a five-compartment model, which shows that the metabolism of intact PTH is only partly due to the formation of carboxy-terminal fragments, most being directly secreted or catabolized. Linking these models for secretion and distribution of PTH, simulation studies were undertaken and compared with published data. This model is then discussed in comparison with previous work concerning other polypeptide hormones.

Parathyroid gland response to epinephrine: a rate-sensitivity mechanism.

A model for parathyroid gland response to an epinephrine infusion is proposed. It is based on direct measurements of the parathyroid hormone (PTH) secretion rate as measured directly after cannulation of the venous drainage of single superior parathyroid glands of calves. When epinephrine was infused into a jugular vein, a large increase of PTH secretion rate was observed at the beginning of the infusion. The PTH secretion rate thereafter fell, but it was still significantly above the control rate. At the end of the epinephrine infusion a sharp decrease was observed when the infusion was terminated. These observations are consistent with a rate-sensitive control mechanism. Calculation of the parameters yielded a model, which was then linked with a kinetic model for PTH distribution. Simulation studies were undertaken to predict plasma PTH concentration in response to an epinephrine infusion. Good agreement was found between predicted results and previously published work. The role of this rate-sensitive mechanism in the parathyroid gland is discussed.

Comparison of the effects of calcium and magnesium on parathyroid hormone secretion rate in calves.

Parathyroid hormone (PTH) secretion rate was measured in seven calves by using a technique which involved RIA of parathyroid venous blood collected during timed intervals and measured volumetrically. Infusion of solutions of NA2EDTA and MgCl2 into the jugular vein was used to alter plasma calcium and magnesium concentrations. In four calves, elevation of plasma magnesium concentration rapidly decreased the PTH secretion rate that had been stimulated by induced hypocalcemia. In three calves, equimolar and opposite changes in plasma calcium and magnesium concentrations were induced by simultaneous infusions of Na2EDTA and MgCl2. Despite the equimolar increase in plasma magnesium concentration, PTH secretion was increased in response to the decline in plasma calcium concentration. In three experiments, the concentration of each cation was kept constant during periods in which the concentration of the other cation was varied. The effect of variations in plasma magnesium concentration on PTH secretion rate was approximately 1/3-1/2 as great as that observed with changes in plasma calcium concentration. These observations indicate that the effect of magnesium on PTH secretion rate is similar to that of calcium, but not equipotent.

Sigmoidal relationship between parathyroid hormone secretion rate and plasma calcium concentration in calves.

Parathyroid hormone (PTH) secretion rate was measured in 16 anesthetized calves by using a technique involving radioimmunoassay of parathyroid venous blood which was collected during timed intervals and measured volumetrically. The calves ranged in age from 2-14 weeks. Plasma calcium concentration was altered by infusion of solutions of CaCl2 or disodium ethylenediamine tetracetate (Na2 EDTA) into the jugular vein. When plasma calcium concentrations exceeded 10.5 mg/100 ml, a basal, non-suppressible secretion rate of 0.3 ng/kg/min was maintained despite the induction of hypercalcemia. Slight changes in secretion rate were observed in response to changes of plasma calcium in the range between 9 and 10.5 mg/100 ml. Below 9 mg/100 ml, a small decrease in plasma calcium concentration evoked a pronounced increase in secretion rate. A maximal secretion rate of about 5.5 ng/kg/min was attained at a plasma calcium concentration of approximately 7.5 mg/100 ml and it was not increased by more severe hypocalcemia. These observations confirm the sigmoidal relationship between PTH secretion rate and plasma calcium concentration which was previously suggested by measurement of PTH concentration in peripheral plasma of hypocalcemic, parturient cows.