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