Review/Oorsig Volume 22, Issue 03 - Page 22

Oorsig/Review P T H r ec ept or : pH 7.45 P T H r ec ept or : pH 7.35 PTH RECEPTOR RECEPTOR M g ++ M g ++ BONE OR KIDNEY CELL SURFACE ADENYL CYCLASE COMPLEX BONE OR KIDNEY CELL SURFACE ADENYL CYCLASE COMPLEX CYCLIC AMP CYCLIC AMP Diagrammes illustrating the effects of pH and Magnesium on the PTH receptor (Adapted from Goff J P 2008 The monitoring, prevention, and treatment of milk fever and subclinical hypocalcemia in dairy cows The Veterinary Journal 176:50-57) High levels of dietary Calcium in the period preceding calving leads to the release of calcitonin, inhibiting the number and activity of osteoclasts in bone. When Ca++ levels suddenly drop at the beginning of lactation, PTH is secreted in response to this, but there seems to be a refractory period of 48-72 hours during which adequate osteoclastic activity does not take place despite adequate PTH levels, due to the earlier calcitonin supression. This is exactly the time when most cows develop milk fever. Apart from this, it is now known that a metabolic alkalosis causes a change in the morphology of PTH receptors in bone and kidney cells, leading to secreted PTH to be ineffective when its effect is desirable. Diets that cause a metabolic acidosis (low blood pH) on the other hand activate PTH receptors making osteoclastic activity much more effective after PTH stimulation. For this reason anionic salts are added to dry cow rations to induce a mild metabolic acidosis, in order to prime PTH receptors leading to a much smoother change-over from an anabolic to a catabolic Calcium state. Magnesium is an important co-factor in the production, secretion and action of PTH and Vitamin D3, and a deficiency of dietary Magnesium may also predispose cows to milk fever. Magnesium acts on the production and secretion of PTH, but the main effect of Magnesium on Calcium metabolism is a binding site on the adenyl cyclase complex attached to the PTH receptor, which is responsible for cyclic AMP (second messanger) release into the cell. With inadequate Magnesium this binding site is not saturated, and PTH can not function optimally even at a low pH. 22 Predisposing factors of milk fever • • • Metabolic alkalosis When the pH of the intracellular fluid compartment is high (relative metabolic alkalosis), bone and perhaps also renal tissue are refractory to the effects of PTH. Likewise the stimulatory effects of PTH are enhanced during metabolic acidosis. Diets high in strong cations during the transitional phase, especially Na and K, tend to induce a metabolic alkalosis and milk fever will follow. Diets high in strong anions, primarily chloride (Cl) and sulphur (S) will induce a relative metabolic acidosis and will prevent milk fever. Other factors that will tend to cause a metabolic alkalosis in the peri-partum period is the secretion of colostrum that is relatively acidic, the presence of rumen hypomotility and where a high protein diet is fed (rumen alkalosis). Rumen alkalosis Will retard Ca absorption as Ca salts become more insoluble and are trapped in the rumen. Rumen intestinal stasis and reduced food intake Even brief periods of poor appetite or ruminal stasis may trigger hypocalcaemia as continuous function of the alimentary tract is vital to maintain the flow of nutrients for lactation. Dairy cows, being bred for milk production, continue to lactate even though this means that they deplete their bodies of