Hypocalcaemia while sporadic, occasionally causes major losses especially in pregnant and lactating ewes. It was estimated for example that between 100,000 and 300,000 pregnant ewes die from hypocalcaemia each year in Victoria (Caple et al 1988). Some of the conditions under which sheep become hypocalcaemic seem straightforward. For example, weaned lambs and ewes on a calcium deficient diet develop weak bones and are unable to maintain adequate blood calcium levels. However, under a range of circumstances sheep with adequate skeletal reserves of calcium develop clinical hypocalcaemia. Even sheep on adequate dietary intakes of calcium and skeletal reserves can nonetheless develop hypocalcaemia. This paper briefly reviews calcium metabolism in sheep and the syndromes associated with hypocalcaemia before discussing some of conundrums (at least in the mind of this author) regarding hypocalcaemia in sheep.
Experimental studies indicate that calcium requirements increase steadily after about day 65 in the pregnant ewe. Most of this initial requirement is met by bone resorption and reaches a peak in late gestation through to early lactation. While calcium absorbed from the intestine increases steadily during pregnancy it was not until early lactation (about day 25) that most of the calcium leaving the body pool is supplied by enhanced intestinal absorption. In late pregnancy and in lactation the amount of calcium available to the body pool is limited by the capacity of the intestine to absorb calcium rather than the amount of calcium in the diet. Maternal calcium balance remains negative until about day 40 of lactation when four times as much calcium is absorbed from the intestine and three times as much resorbed from bone than at conception. Ewes lose about 20% of their skeletal calcium during pregnancy and lactation but replace most of this one month after the end of lactation (Braithwaite et al (1969, 1970), depending on calcium intake during pregnancy and lactation (Caple et al 1988).
Parathyroid hormone (PTH) and vitamin D3 metabolites especially 1, 25 dihydroxycholecalciferol (activated in the kidney from dietary and solar derived precursors) are both necessary for the active resorption of calcium from bones, the active absorption of calcium from the alimentary tract and for renal tubular resorption. These homeostatic mechanisms function most efficiently in a state of mild metabolic acidosis, with adequate vitamin D, dietary energy, protein, fibre and phosphorus levels, optimal magnesium levels and low dietary calcium intakes. They are inhibited by the converse and by epinephrine, norepinephrine and corticosteroids (Shils 1980, Lucas et al 1982). Older ewes have lower rates of calcium accretion into bones (Caple et all 1988) and a reduced population of intestinal vitamin D mediated receptors (Underwood and Suttle 1999) than younger ewes, which presumably helps explain their increased susceptibility to hypocalcaemia.
Sheep veterinarians encounter several clinical syndromes associated with hypocalcaemia. However, these syndromes are not mutually exclusive. For example, hypocalcaemia induced by inanition is exacerbated in chronically calcium deficient sheep (and perversely in sheep fed calcium rich diets).
1. Hypocalcaemia due to dietary calcium deficiency
In southern Australia, calcium deficiency (sometimes but not always associated with hypocalcaemia) is most commonly encountered in sheep on grain rations without calcium supplementation (Franklin et al 1948, Peet et al 1984, Peet et al 1985, Watt 2006). Cereal and some other grains are both calcium deficient and rich in phosphorus. Maize contains about 0.2 g calcium per kg, wheat 0.6, and barley and oats 0.9g/kg compared to a recommended dietary calcium intake of about 3g/kg DM (Underwood and Suttle, 1999).
2. Hypocalcaemia induced by short term feed deprivation (and other stressors including transport).
Franklin (1948) noted, 'a sudden check in the food supply of ewes, especially if they are in lamb, is almost invariably associated with a sharp decrease in serum calcium.' Sheep of any description can become hypocalcaemic if they are held off feed for a day or more and especially subjected to concurrent handling, transport or otherwise stressful procedures (Blumer et al 1939, Simmons 1975, Larsen et al 1986, West 1990). Late pregnant ewes with an escalating demand for calcium for foetal bone development are particularly susceptible (Sansom 1982).
3. Hypocalcaemia in pregnant and lactating ewes due to an inability to meet calcium requirements.
In south eastern Australia, outbreaks of spontaneous clinical hypocalcaemia have occurred in ewes on lush feed after a drought, in ewes and lambs in short grass based improved pastures (Larsen et al 1986, Caple et al 1988) and on grazing cereals and in ewes drought fed on grain (despite adequate calcium supplementation) (Watt 2006). Post drought hypocalcaemia may be exacerbated when ewes are unable to replenish skeletal reserves during the drought. In the cases reported by Larsen (1986), some affected ewes also suffered osteodystrophy suggesting that they did not adequately replenish skeletal reserves.
Phosphorus limits pasture production on most farms in south-eastern Australia. This results in low clover content of pastures, low winter and spring pasture production, inadequate carry-over feed in summer and lack of dry residues in the pasture in autumn. The requirement to supplement ewes with grain, usually wheat, in drought periods is also increased. All of these result in poor body condition of ewes, poor milk production, poor growth of lambs, osteoporosis in lambs and ewe replacements with inadequate bone reserves. In addition, breeding ewes may be unable to replace their bone calcium reserves lost during pregnancy and lactation when grazing pasture from soils with a low Olsen P content. These ewes when exposed during late-gestation to inclement weather, changes in diet, exercise associated with driving during mustering, prolonged transport, and stress associated with management procedures such as shearing and crutching may become susceptible to hypocalcaemia. They may not be able to mobilise Ca from bone reserves fast enough to prevent clinical hypocalcaemia. This may be especially so when ewes are either fed a diet with a high dietary fixed cation-anion balance or starved. Both these result in an increase in base excess that may further reduce the ability of ewes to mobilise Ca from bone (Caple pers comm., Grant 1998).
4. Osteoporosis with associated hypocalcaemia in young sheep
Osteoporosis (with or without hypocalcaemia) is occasionally seen in young sheep from 10 weeks to 15 months of age. Caple et al (1988) considered that the condition was usually due to a low milk supply from the ewe, but a combination of malnutrition, calcium deficiency, copper deficiency, vitamin D deficiency and gastrointestinal parasitism could be involved. Hypocalcaemia with associated bone disorders is routinely diagnosed in young sheep (and at least hypocalcaemia in ewes) on grazing cereals.
5. Induced hypocalcaemia.
A range of plant species including soursob (Oxalis pes-caprae), fat hen (Chernopodium album), pigweed (Portulaca oleracea) soft roly-poly (Salsola kali) and Setaria, Cenchrus and Panicum spp grasses accumulate oxalates (McBarron 1976, Seawright 1982). Oxalates can bind calcium, producing hypocalcaemia and death. Young sheep and pregnant and lactating ewes are most susceptible. The rumen can adapt to oxalates over 3-4 days so hungry, naive stock are most at risk (Bourke, 2005). Excess magnesium (Kemp 1985) and vitamin D deficiency (Caple et al 1988, Goff 2004) can also induce hypocalcaemia.
6. Other syndromes in which hypocalcaemia may occur
As feed deprivation produces hypocalcaemia in sheep, any disease that causes anorexia could precipitate some degree of hypocalcaemia. Mild hypocalcaemia is seen secondary to pregnancy toxaemia and has been reported secondary to acidosis (Pickard, Field and Kenworthy, 1988) and hypomagnesaemia (L'Estrange and Axford 1964, Herd 1965, Schuster et al, 1969).
Sub-clinical hypocalcaemia has been proffered as a major limitation to sheep productivity by reducing digestive efficiency and uterine function (Ginter, 2005). Hypocalcaemia (and even sub-clinical hypocalcaemia) does suppress rumen and abomasal motility (Huber et al 1981, Daniel 1983) and depress appetite and therefore performance in young sheep (Field 1975, Underwood and Suttle 1999). However, this author is not aware of evidence to show a productivity benefit to supplementing subclinical ewes with calcium.
Hypocalcaemia has occasionally been implicated in uterine inertia and uterine and vaginal prolapse (Nodsol and Waage 1981, Plant 1990). This author has not seen this association in practice.
Sykes (2007) commented that hypocalcaemia (in sheep) is almost always the result from failure of the endocrine mechanism to promote influx of Ca from bone and the alimentary tract rather than from inadequate dietary Ca. Within the Australian context, this is not always the case. Many grains including cereals are known to be calcium deficient. Both young and adult sheep develop skeletal defects and become hypocalcaemic following long-term grain feeding without calcium supplementation (Franklin et al 1948).
However, in most other instances an inability to meet calcium demands is a key feature of hypocalcaemia in sheep in southern Australia. The challenge is to determine how best to manage this inability.
In some instances, the feeding of additional calcium (sometimes in combination with sodium chloride and magnesium oxide) provides additional dietary calcium sufficient to overcome inadequate calcium absorption and mobilisation. As Braithwaite (1978) noted, calcium absorption involves two processes, 'a non-saturable diffusional one, related to intestinal Ca concentration, and a saturable active one, independent of concentration but related to body needs.' Therefore feeding additional calcium in the face of an inability to meet calcium demand should increase calcium absorption simply by increasing the intestinal calcium concentration. In the experience of this author and many others, supplemental calcium is effective in preventing the hypocalcaemia and bone problems that can occur in sheep grazing cereals.
The question remains however, why should sheep suffer from hypocalcaemia on grazing cereals? After all, at least in the 14 analyses collated Dove (2007) these forages contain adequate calcium. He considered that the daily requirement of calcium was 0.15 to 0.26% of DM. Underwood and Suttle (1999) considered that 'it would be surprising if performance suffered on any diet providing an average of 3 g Ca per kg DM (0.3% of DM) throughout the year.' Cereals from oats to winter wheat and triticale all had calcium levels from 0.28 to 0.58 % DM. Three of the fourteen samples were however magnesium deficient (two wheat samples and one triticale sample) and nine were deficient in sodium.
Hypocalcaemia has also been reported as a common problem in pregnant and lactating ewes grazing improved pastures in southern Australia particularly on lush pastures subsequent to a drought (Blumer et al 1939, Larsen et al 1986, Grant et al 1988). Larsen et al (1986) noted that pasture calcium levels were significantly lower in the winter of 1983 (post drought) than in the winter of 1976. All post-drought pasture levels were above 0.43% DM. Grant et al (1988) observed hypocalcaemia when pastures levels ranged from 0.38% DM in April, to 0.51% in October. While these levels should be adequate, sheep consuming half the maximum dry matter intake especially on pastures of lower than usual calcium levels would be unable to meet dietary calcium demands (Larsen 1987).
A common observation was that clinical hypocalcaemia was exacerbated by or triggered by activities that interrupted grazing (Blumer et al 1939, Larsen et al 1986, Grant et al 1988). This indicates that ewes in a marginal calcium balance were unable to respond to a cessation of dietary calcium by homeostatic means.
Several suggestions have been made as to why hypocalcaemia occurs in the face of apparently adequate dietary calcium. The first is that some pastures have an unfavourable dietary cation anion balance (DCAB). Another is that excess levels of vitamin A inhibit the function of vitamin D in promoting calcium absorption from the alimentary tract. It has also been suggested that as grazing cereals are often high in phosphorus, leading to a nutritional secondary hyperparathyroidism. Finally, calcium may be absorbed less efficiently from high moisture content pastures than dry feed.
Diets in which the 'strong' anion fraction is absorbed more rapidly than the cation fraction induce a metabolic acidosis with slightly reduced blood pH, markedly reduced urine pH and improved calcium absorption (Parkinson et al 2007). As improved pastures have a DCAB of from 20 to + 100mEq/100 g, they have potential to induce metabolic alkalosis and therefore inhibit calcium absorption. Grant et al (1988) were initially unable to explain the low availability of calcium in winter and spring pastures in southern Australia. They subsequently concluded (Grant et al 1992) that DCAB might predispose (pregnant) ewes to hypocalcaemia. Experimentally they lowered blood and urine pH and raised blood calcium levels by feeding rations supplemented with ammonium chloride to produce a fixed anion excess compared to a control ration (sodium chloride) and a ration with a fixed cation excess (sodium chloride and sodium bicarbonate).
Sykes (2007) observed that high DCAB values are often measured in spring pastures in New Zealand without the expected levels of hypocalcaemia. He considered that many other factors might be involved and that a simpler and cheaper approach is to avoid parturition in areas in which heavy K fertiliser has been used. High dietary potassium substantially reduces magnesium absorption. Magnesium in turn has a role in calcium metabolism. The activity of both parathyroid hormone (PTH) and 1, 25 dihydroxycholecalciferol are magnesium dependent (Sykes 2007). However, Sykes added that the response of skeletal calcium resorption to magnesium levels is curvilinear and decreases by 50% at both high and low dietary magnesium levels.
Nutritional secondary hyperparathyroidism is a metabolic disorder of horses, dogs and cats in which a diet containing exceeds phosphorus, insufficient calcium or both leads to excessive bone resorption. (Johnson and Watson 2005). However, there is no evidence that nutritional secondary hyperparathyroidism or vitamin A antagonism of vitamin D occurs in ruminants (I Caple pers comm., J Glastonbury pers. comm.). Larsen (1987) cited the ARC (1980) to conclude that sheep (unlike non-ruminants), can tolerate large variations in Ca: P ratios and that pasture P levels are unlikely to influence calcium absorption or excretion in ewes. Glastonbury added, 'the histology of the physes from so called "rickets" lambs do have some features of hyperparathyroidism but I have not seen hyperplastic parathyroids in lambs.'
Calcium may also be absorbed less efficiently from lush pastures (Caple et al 1988).This may in part due to decreased salivation, leading to increased plasma bicarbonates, which can also turn off the osteoclasts (Caple pers comm.).
Several options have been suggested to improve the calcium nutrition of pregnant and lactating ewes. These options aim to increase calcium intake or to stimulate homeostatic mechanisms prior to increased demands of pregnancy and lactation.
The manipulation of the dietary cation-anion balance (DCAB) is a popular method of managing hypocalcaemia in North American dairy cows and has become more widely adopted in Australasian dairy herds (Parkinson et al 2007). However, as Parkinson et al point out, at the high range 'it is highly unlikely that enough anionic salts can be safely incorporated into the diet to reduce the DCAB to the required level without significantly reducing dry matter intake at the same time.' Because hypocalcaemia is sporadic and some anionic salts are unpalatable, the routine incorporation is anionic salts to ewes is rarely practiced.
Pre-lambing ewes especially on pastures with reduced calcium content (due to either inadequate legume or inadequate availability and especially if older (with diminished vitamin D receptors) and multiparous (with consequent increased calcium demand) struggle with calcium homeostasis and are borderline hypocalcaemic. These ewes, if subjected to food deprivation are highly susceptible to clinical hypocalcaemia when mustered for procedures such as shearing or crutching. They normally respond to calcium borogluconate although Larsen (2007) also recommends drenching either the affected ewes or the entire susceptible mob with a proprietary mix of dicalcium phosphate, calcium carbonate and magnesium oxide (Unimix R) to provide longer duration calcium supplementation (Grant 1998).
In dairy cattle, it has been long established that a low calcium ration prior to calving activates the homeostatic mechanisms that increase gut calcium absorption (and perhaps the mobilisation of calcium from bone reserves) (Boda and Cole 1956, Parkinson 2007). It has also been established that ewes fed a low calcium ration during pregnancy absorbed calcium more efficiently (29.2%) than control ewes that absorbed calcium at 16.6% efficiency (Braithwaite 1978) and both ewes and cows fed high calcium rations. In wethers it has been shown that this increased absorption efficiency takes several weeks to develop (Braithwaite 1974). An alternative to feeding a ration low in calcium is to feed an additive that binds calcium, therefore reducing its availability. Mature twin bearing ewes fed a vegetable oil supplement for three weeks had higher blood calcium levels after fasting than control ewes (Wilson (2001).
Sykes (2007) commented that supplying high levels of dietary calcium 'in anticipation of later increased demand' is counter-productive. However Sansom et al (1982) warned that recommendations appropriate for dairy cattle might not suit sheep producers. They commented that sheep do not suffer 'milk fever' at parturition, as cattle do, but can become clinically hypocalcaemic at any time within 4-6 weeks before lambing. They therefore suggested that an appropriate recommendation might be to avoid 'diets rich in calcium' during the first two-thirds of pregnancy and Ca supplementation fed only during the last six weeks.
However, this author saw cases of hypocalcaemia in drought fed ewes, on rations adequate for calcium, in mid-lactation (Watt 2006). This may be a sporadic and unusual occurrence. If the onset of hypocalcaemia risk can be predicted it seems appropriate to delay the commencement of calcium supplementation to closely precede the risk period. In the case of ewes fed grain in a drought, it may therefore be appropriate to not to supplement calcium prior to lambing (assuming bone calcium reserves were replenished) but to commence post lambing. This is consistent with the advice offered by Buckley and Bourke (1983). However, if the problem is one of hypocalcaemia in the pregnant ewe, failure to supplement calcium may exacerbate the problem. Equally, failure to supplement ewes that have been unable to replenish bone calcium levels (post drought for example) could exacerbate hypocalcaemia.
While hypocalcaemia is a sporadic condition that in some instances occurs inexplicably, recommendations can be made to prevent it. Firstly, older pregnant (and especially twin bearing) ewes are most susceptible. Avoid any practices that cause temporary feed deprivation. If this is unavoidable, have injectible calcium and perhaps an oral calcium supplement (such as Unimix R) on hand. The feeding of a calcium supplements prior to anticipate increased calcium demand is contraindicated but calcium supplementation immediately preceding an anticipated increased calcium demand or in the face of an outbreak of hypocalcaemia is warranted. The feeding of calcium supplements (and also magnesium and sodium) is usually warranted when sheep are grazed on cereals.
While the opinions expressed on the conundrums of hypocalcaemia are mine, I have benefitted from discussion with Ivan Caple, John Glastonbury, John Larsen and Ian Lugton. Paragraph 3 under the section 3. Hypocalcaemia in pregnant and lactating ewes and young sheep due to an inability to meet calcium requirements, was largely written by Ivan Caple.