Diet-induced pseudohypoparathyroidism: A hypocalcemia and milk fever risk factor.

Subclinical hypocalcemia may affect half of all multiparous cows, and clinical hypocalcemia or milk fever affects approximately 5% of dairy cows each year. This disorder of calcium homeostasis can be induced by several dietary factors. Recent studies implicate high dietary potassium and high dietary cation-anion difference (DCAD) with increased risk of milk fever. The hypothesis tested in this study was that high-DCAD diets fed to prepartum cows reduce tissue sensitivity to parathyroid hormone (PTH), inducing a pseudohypoparathyroid state that diminishes calcium homeostatic responses. Multiparous Jersey cows were fed low- or high-DCAD diets in late gestation, creating a compensated metabolic alkalosis in the high-DCAD cows and a compensated metabolic acidosis in the low-DCAD cows. They then received synthetic PTH injections at 3-h intervals for 48 h. Parathyroid hormone is expected to cause an increase in plasma calcium by increasing renal production of 1,25-dihydroxyvitamin D and increasing bone calcium resorption. Plasma calcium concentration increased at a significantly lower rate in cows fed the high-DCAD diet. Cows fed the high-DCAD diet also produced significantly less 1,25-dihydroxyvitamin D in response to the PTH injections than cows fed the low-DCAD diet. Serum concentrations of the bone resorption marker carboxyterminal telopeptide of type I collagen were numerically lower in cows fed the high-DCAD diet but this difference was not statistically significant. These data provide direct evidence that high-DCAD diets reduce tissue sensitivity to PTH. The metabolic alkalosis associated with high-DCAD diets likely induces a state of pseudohypoparathyroidism in some dairy cows at the onset of lactation, resulting in hypocalcemia and milk fever.

Peripartal alterations of calcitonin gene-related peptide and minerals in dairy cows affected by milk fever.

BACKGROUND: Milk fever, a metabolic disease of dairy cattle, is associated with perturbations of calcium homeostasis, the pathogenesis of which is not yet completely understood. OBJECTIVE: The aim of this study was to investigate plasma concentrations of calcitonin gene-related peptide and selected minerals and metabolites in periparturient cows with and without milk fever. METHODS: Plasma concentrations of calcitonin gene-related peptide, as well as calcium, phosphate, magnesium, iron, glucose, lactate, and cortisol, were determined in multiple plasma samples from Jersey cows with and without spontaneous milk fever. RESULTS: Cows affected by milk fever (n = 5) had lower concentrations of calcitonin gene-related peptide (P = .038) and inorganic phosphate (P < .001) in plasma than did the controls (n = 5). Also, these cows tended to have lower calcium concentrations (P = .071). Magnesium, iron, lactate, glucose, and cortisol concentrations were comparable between both groups of cows (P > .10). Around the day of calving, plasma concentrations of lactate, glucose, and cortisol increased and the concentration of iron decreased in all cows (P ≤ .01). CONCLUSIONS: Despite the limited number of cows evaluated, this report is the first to indicate lowered concentrations of calcitonin gene-related peptide as part of the metabolic changes during milk fever in cows. Further work with a larger cohort of animals is warranted to understand the precise role of calcitonin gene-related peptide and the potential associations with disturbances in plasma minerals typically observed during milk fever.

Historical and current perspectives on the treatment, control and pathogenesis of milk fever in dairy cattle.

Milk fever has been recognised in cattle for about 215 years and its clinical signs have not changed since they were described by Victorian veterinary surgeons in the mid-nineteenth century. It was only 80 years ago that abnormal parathyroid gland function was associated with the pathogenesis of the hypocalcaemia characteristic of the disease, and the current basis for its treatment with intravenous calcium salts was established. Although this treatment is effective, most recent research has focused on preventing the disease through an understanding of the endocrine control of extracellular calcium homeostasis. In the 1970s the synthetic vitamin D analogue 1alpha-hydroxycholecalciferol was developed for intramuscular injection before a cow calved, but variable results encouraged other preventive strategies to be considered, including restricting the dietary intake of calcium, and manipulating the dietary cation-anion balance of cows before they calved. Currently, the role of extracellular calcium receptors in the parathyroid gland is under investigation as a preliminary step to devising more effective treatments and/or preventive methods for milk fever.

Clinico-pathological findings in peripartum dairy cows fed anion salts lowering the dietary cation-anion difference: involvement of serum inorganic phosphorus, chloride and plasma estrogen concentrations in milk fever.

In our previous study, it was demonstrated that the administration of anion salts, which slightly lower the dietary cation-anion difference (DCAD), in the prepartum period is safe and effective for preventing milk fever in multiparous cows. In the present study, several clinico-pathological constituents in serum and urine, which might be related to milk fever, were analyzed using stored samples from the previous study to identify clinico-pathological parameters for easily evaluating the efficacy of lowering DCAD and to further investigate the mechanism by which lowering DCAD prevents milk fever. Among the parameters analyzed in the present study, inorganic phosphorus (iP) was involved in milk fever because the serum concentration and urinary excretion of iP were significantly higher in the group of primiparous cows (heifer group), which did not develop hypocalcemia, than those in other groups of multiparous cows. Serum chloride concentrations in the heifer group and the group of multiparous cows fed anion salts (anion group) tended to remain higher than those in other control groups of multiparous cows suggesting that serum chloride concentration may be utilized for evaluating the status of metabolic acidosis and the efficacy of lowerng DCAD in dairy cows fed anion salts. In addition, plasma estradiol-17beta concentration in the heifer group tended to be lower at parturition compared with that in other multiparous groups suggesting that estrogen known as a potent inhibitor of bone resorption may be involved in developing milk fever.

Pathological changes in the myocardium of hypocalcaemic parturient cows.

Three parturient cows in lateral recumbency which were moaning and had tachycardia, arrhythmia and dyspnoea were thoroughly examined. They were hypocalcaemic (0.70-1.27 mmol/litre) and were euthanized within four days, because they failed to respond to calcium treatment. By light microscopy the most characteristic pathological changes in the heart were necrotic changes scattered throughout the myocardium. Electron microscopy revealed abnormalities in the myocytes which were characterised by focal myofibrillar lysis, irregular splitting, streaming and spreading of the Z band and myofibrillar disarray.

Calcium metabolism in hypocalcemic cows with myocardial lesion.

This paper deals with blood levels of calcium (Ca), inorganic phosphorus, parathyroid hormone and 1,25-dihydroxyvitamin D in 6 cows treated for milk fever. Four of the cows stood within 1 day after Ca therapy, whereas 2 other cases showed an unsatisfactory response to Ca therapy and did not rise. The necropsy revealed microscopic necrotic myocardial lesions scattered in the heart of these 2 unrecovered cows. The degree of hypocalcemia and hypophosphatemia were similar in the 6 cows. However, the recovery from hypophosphatemia was markedly delayed in the cows will an unsatisfactory response.

Parturient paresis and hypocalcemia in ruminant livestock.

Parturient paresis (hypocalcemia) is most likely to affect dairy cattle around the time of parturition. It causes progressive neuromuscular dysfunction and flaccid paralysis. Older dairy cows, cows with a history of parturient paresis during a previous lactation, high-producing cows, and cows from the Jersey and Guernsey breeds are at highest risk for developing parturient paresis. Nonparturient hypocalcemia may also occur and is related to events other than parturition, such as severe stress, that temporarily overwhelm the mechanisms of calcium homeostasis. Beef cattle, sheep, and goats are affected less frequently by hypocalcemia than are dairy cows. Because these species are not as stressed for milk production as dairy cattle, nonparturient hypocalcemia makes up a higher proportion of cases in nondairy ruminants. Clinical signs of hypocalcemia in beef cattle, sheep, and goats tend toward hyperesthesia and tetany rather than the classic flaccid paralysis that occurs in dairy cattle with parturient hypocalcemia. Prompt and effective treatment of hypocalcemia helps to reduce the incidence of secondary complications, such as muscle damage or mastitis. The standard treatment regimen of 500 ml of 23 per cent calcium gluconate, administered intravenously, will elicit a favorable response in approximately 75 per cent of recumbent cows within 2 hours of treatment. Relapses following successful initial therapy are common and may be prevented in part by supplementation of intravenous treatment with an additional 500 ml of 23 per cent calcium gluconate administered subcutaneously. Proper nursing care following treatment speeds recovery and reduces the incidence of secondary complications owing to hypocalcemia.