Ovine Clinical Hypocalcaemia (so-called “Lambing Sickness” in Ewes)

 Phil Rogers MRCVS, Grange Research Centre, Dunsany, Co. Meath

A seminar for Teagasc Sheep Advisers, Teagasc Office Athenry, Feb 22nd, 2003

 

SUMMARY

 

Hypocalcaemia means subnormal Ca in blood. The most common clinical manifestations of severe hypocalcaemia are "Lambing Sickness", a misnomer for clinical hypocalcaemia in ewes: it is RARE at lambing, and it has a very WIDE "onset time-window". Onset may be from 8 weeks before to 6 weeks after partus, but most frequently 2-4 weeks prepartum.

 

Clinical hypocalcaemia usually occurs in pregnant or recently-lambed ewes, but can arise in non-pregnant ewes, and in lambs & wethers under adverse conditions of diet: sudden changes of feed to grazing on lush green oats, barley or wheat; heavy cereal intakes; housing in dark pens (Vit D deficiency); feeding excess of beet pulp may induce secondary hypocalcaemia.

 

An energy deficit (which can also trigger ketosis, especially in ewes carrying multiple lambs), low Ca intake (3.5g/ewe/d) & excessive P in concentrates (6.9g/kg DM) can trigger hypocalcaemia.

 

Excess Ca throughout pregnancy may trigger hypocalcaemia in late pregnancy,

 

Excess Mg supplements in late pregnancy & stress before lambing are predisposing factors.

 

Scan ewes early in pregnancy; identify those with twins & triplets; ewes carrying 2 or 3 lambs need more nutrients (especially energy & protein) than those carrying singles.

 

Avoid having ewes overfat in the last 6 weeks of prepartum.

 

Avoid stress, where possible, especially: sudden changes of feed, sudden introduction of concentrates, sudden food scarcity.

 

Ensure good management after introduction of concentrates to minimise problems due to unequal feed intake.

 

Hypocalcaemia means subnormal calcium (Ca) in blood. It often exists without clinical signs (non-clinical form). The most common clinical manifestations of severe hypocalcaemia in ewes and cows are “Lambing Sickness” in ewes and “Milk Fever” in cows.

 

On February 17 2004, a search of the Commonwealth Agricultural Bureau abstracts database (CABI) for the terms: "(OVINE OR EWE OR EWES OR SHEEP).TI. & (HYPOCALCAEMIA OR HYPOCALCEMIA OR LAMBING- SICKNESS OR LAMBING ADJ SICKNESS).TI." found disappointingly few (circa 30) abstracts on the problem. This is in marked contrast to the high number of abstracts on bovine hypocalcaemia & milk fever.

 

The paucity of scientific literature on ovine hypocalcaemia reflects the low priority given to nutritional research in ewes, as compared with cows. It also means that Teagasc must rely for national advice on methods of control on wobbly foreign data plus uncontrolled field observations under Irish conditions by David Poole & his team in the Field Investigations Dept of An Foras Taluntais.

 

KEY BULLET POINTS

 

Lambing Sickness in ewes

Milk Fever in cows

This is a misnomer for clinical hypocalcaemia in ewes:

  • it is RARE at lambing,
  • and it has a very WIDE "onset time-window".

This is a misnomer for clinical hypocalcaemia in cows:

  • there is no fever,
  • and it usually has a precise “onset time window”.

Onset may be from 8 weeks before to 6 weeks after partus, but most frequently 2-4 weeks prepartum (Mosdol & Waage, 1981).

 

About 80% of cases occur in the last 6 weeks prepartum; worse in overfat ewes.

Onset usually is at partus +/- 1 day.

 

 

 

About 95% of cases occur then; worse in overfat cows.

AVOID routine high magnesium (Mg) supplementation of ewes (>2g Mg/ewe/d) in late pregnancy (prelambing).

 

 

High Mg supplements in late pregnancy reduce gastrointestinal Mg absorption and exaggerate hypocalcaemia.

Routine supplementation with 0.0g Ca + 15g Mg (30g Calmag)/d to COWS in the last 4-6 weeks prepartum helps to maintain maximal bone Ca-turnover.

 

This is an important part of milk fever prevention, because it ensures that the fall in blood Ca on the day of calving is not as severe as it would be without the Mg supplement.

 

CLINICAL HYPOCALCAEMIA IN EWES

Between-farm prevalence of hypocalcaemia 2-6 weeks before lambing ranged from 1 to >10%  after the drought broke in 1983 in Victoria. During the outbreaks herbage had low contents of Ca & DM. Predisposing factors could have been Ca deficiency (inadequate supplementation with limestone) during the drought & the stress of routine crutching before lambing (Larsen et al., 1986).

 

There are TWO forms of clinical hypocalcaemia in ewes:

  • (a) hypocalcaemic paresis, the most common form;
  • (b) hypocalcaemic tetany, a hyperaesthetic form (rare in ewes but not uncommon in bitches, cows and mares);

BACKGROUND & PREDISPOSING FACTORS

  • Clinical hypocalcaemia usually occurs in pregnant or recently-lambed ewes, but can arise in non-pregnant ewes, and in lambs & wethers under adverse conditions of diet:
    • sudden changes of feed to grazing on lush green oats, barley or wheat;
    • heavy cereal intakes;
    • housing in dark pens (Vit D deficiency);
    • feeding excess of beet pulp may induce secondary hypocalcaemia.

 

 

  • Fat ewes are especially susceptible.

 

  • Increased feed intake, especially by older ewes, may lead to acidosis, followed by inappetence & hypocalcaemia. Good management after introduction of supplementary rations is necessary to minimise problems due to unequal feed intake (Pickard et al., 1988).

 

  • An energy deficit (which can also trigger ketosis, especially in ewes carrying multiple lambs), low Ca intake (3.5g/ewe/d) & excessive P in concentrates (6.9g/kg DM) can trigger hypocalcaemia (Sweeney & Cuddeford, 1987). Gross dietary Ca deficiency predisposes to ewe hypocalcaemia.

 

  • Massive intakes of oral Ca in early pregnancy did not raise the risk of hypocalcaemic paresis (Luthman, 1977), but excess Ca throughout pregnancy may trigger hypocalcaemia in late pregnancy (Jonson et al., 1973).

 

  • Temporary inhibition of bone resorption may induce hypocalcaemia (Luthman, 1977).

 

 

  • Normal concentration of Mg in ewe rations (5g/kg) does not predispose sheep to hypocalcaemia (Pickard et al., 1988). However, high dietary Mg levels can trigger an outbreak, especially when Ca intakes are low; high Mg can reduce the availability of dietary Ca (Tindall, 1986).

 

 

TREATMENT

Note that many late-pregnant ewes present with a COMBINATION of ketosis & hypocalcaemia, & that these disorders are very difficult to differentiate on clinical grounds, EVEN if one does ketone tests on urine (Bickhardt et al., 1998).

 

The practical implications of this are that downer ewes, or ewes with either paretic or tetanic signs in late pregnancy, usually receive “shotgun” treatment for BOTH ketosis & hypocalcaemia. Treatment of clinical hypocalcaemia in ewes may consist of

  • + s/c injection of Vit D analogue (cholecalciferol), + Vit E (alpha-tocopherol), + Na selenite + oral Na propionate (Bickhardt et al., 1998).

 

  • Add 15g DICAL/ewe/d (22% Ca, 18% P) to the supplement for TREATED ewes (Tindall, 1986).

 

  • If hypomagnesaemia is present also [very rare in the literature], also inject Mg sulphate s/c and feed or dose TREATED ewes with 3-5g Mg (6-10g Calmag)/ewe/d for a week or so. This may be useful to prevent RELAPSE in ewes ALREADY TREATED for hypocalcaemia. However, simultaneous hypomagnesaemia is uncommon in hypocalcaemic ewes. Therefore, Mg injection (and the subsequent oral Calmag) actually may add relatively little to the clinical outcome in ewes with normal blood Mg levels.

 

  • Even for ewes at grass AFTER lambing, a supplement of 5g Mg (10g Calmag)/ewe/d is adequate to PREVENT GRASS TETANY in most flocks. One might increase the Mg supplement to 7-14g Mg (0.5-1.0oz Calmag) under conditions of very high risk of tetany. Note, however, that, adjusting for a 10-fold difference in liveweight between cows & ewes, a dose of 7g Mg/ewe/d is very high relative to the effective tetany-prevention dose in cows (30-40g Mg/cow/d).

 

PREVENTION

There are very few definitive papers on control of ovine hypocalcaemia. The most recent refers to a novel idea – Calcigard (Wilson, 2001; Wilson et al., 2003), a patented product based on Soya Oil. The product successfully prevented experimental fasting-induced hypocalcaemia in ewes. Unfortunately, it has little if any practical application in preventing Lambing Sickness. This is because Calcigard was developed for use in COWS, in which the “time window” for hypocalcaemia is very narrow (partus +/- 1 day). The idea is to feed the oil to cows for 3 weeks prepartum to boost Ca absorption capacity by complexing dietary Ca, thereby reducing the bio-availability of Ca from pasture & stimulating the homeostatic mechanisms by so doing.

 

  • Scan ewes early in pregnancy; identify those with twins & triplets; ewes carrying 2 or 3 lambs need more nutrients (especially energy & protein) than those carrying singles.

 

  • Segregate ewes carrying singles v multiple lambs & feed accordingly.
    • Minimise unequal feed intake; this causes problems.
    • Avoid having ewes overfat in the last 6 weeks of prepartum.
    • Avoid underfeeding, even short-term underfeeding.

 

  • Avoid excessive Ca intakes in pregnancy; this exaggerates the risk of hypocalcaemia in ewes as well as in cows (Jonson et al., 1973). However, also avoid excessively low Ca intake, and excessively high P intake. High P reduces Ca absorption, and vice-versa.

 

  • Avoid high Mg supplements in pregnancy: Excessive oral Mg reduces Ca absorption. I do NOT recommend 0.5-1.0oz (14-28g) of Calmag/ewe/d prelambing. That amount provides 7-14g Mg/ewe/d; it is grossly excessive.

 

  • If farmers want to feed Mg routinely, keep it down to 1-2g Mg/ewe/d until lambing.

  • Avoid stress, where possible, especially:
    • sudden changes of feed, especially sudden introduction of concentrates.
    • sudden food shortage, even short-term; fasting or seriously reduced feed intakes can precipitate clinical hypocalcaemia within 2-3 days.
    • cold-stress; housing in harsh weather may help but hypocalcaemia can arise in housed sheep also (Tindall, 1986).
    • rough handling for crutching, etc.
    • any handling that causes fear or fright.

 

  • Consider acidification of the diet (Grant et al., 1992), but there are no other data on that method in the past 12 years.

 

REFERENCES

Barzanji-A-A-H, Daniel-R-C-W. | 1987 | Effect of hypocalcaemia on blood flow distribution in sheep. | Research in Veterinary Science; vol 42; no 1; pp 92-95; ISSN: 0034-5288; 9 ref. | Dep Vet Med, Univ, Brisbane , Queensland , Australia . | Cardiac output, the proportion of blood passing through arteriovenous shunts & blood flow distribution to various organs were measured & compared in 5 normocalcaemic & 5 hypocalcaemic sheep using radioactive microspheres. Hypocalcaemia was induced by infusing Na EDTA solution intravenously for 2h. There was evidence that microspheres were leached from liver, muscle, adrenal & thyroid tissues during the induction of hypocalcaemia. Hypocalcaemia reduced blood flow rates by more than 58% in all tissues examined except kidney (48%), heart (53%), lung (10%) & bladder (47%) & reduced cardiac output from 3.70+/-0.19 litres/min to 2.39+/-0.14 litres/min. Approximately 2.2% of cardiac output passed through arteriovenous shunts. This % was unaffected by hypocalcaemia. 

Bickhardt-K, Henze-P, Ganter-M. | 1998 | Clinical findings & differential diagnosis of ketosis & hypocalcaemia in sheep. | Deutsche Tierarztliche Wochenschrift; vol 105; no 11; pp 413-419; ISSN: 0341-6593; 25 ref. | Tierarztliche Hochschule, D-30173 Hannover , Germany . | 454 sheep with metabolic disorders were examined during a 20-year period (1978-1998), including 214 ewes with ketosis (pregnancy toxaemia), 195 ewes with hypocalcaemia, & 40 ewes with both disorders. There was little difference between the 3 groups in clinical findings, neither could they be distinguished by the occurrence of acetonuria. A universal treatment, regardless of the underlying condition, consisted of oral administration of Na propionate, Ca lactate & K chloride, commencing with s/c injection of Ca borogluconate, cholecalciferol, alpha-tocopherol & selenium. Prevention by appropriate feeding is discussed. 

Cabello-G, Wrutniak-C. | 1989 | Effects of transient, corrected ovine maternal hypocalcaemia on neonatal endocrine & metabolic function. | Research in Veterinary Science; vol 47; no 1; pp 54-59; ISSN: 0034-5288; 28 ref. | Unite Differentiation Cellulaire Croissance, INRA-ENSA, 9 place Viala, 34060 Montpellier , France . | The newborn changes in plasma levels of thyroid stimulating hormone, iodothyronines, cortisol, insulin, glucose, urea & representative parameters of lipid metabolism, were monitored in 8 control lambs & 10 lambs born from hypocalcaemic mothers. 8h after lambing, plasma total lipid, free fatty acids, cholesterol & phospholipid levels were higher in animals from hypocalcaemic mothers than in control lambs. Moreover, these lambs were clearly hyperthyroid during, at least, the first 48h of life. In lambs born from hypocalcaemic mothers, plasma insulin levels were depressed, despite normal glucose concentrations. Plasma cortisol levels were higher than in control lambs, suggesting an endocrine response to a prolonged stress. All these results showed that hypocalcaemic & related metabolic events occurring near the term of pregnancy in ewes could induce newborn hyperthyroidism, hypoinsulinaemia & metabolic alterations in their offspring. 

Cockcroft-P-D, Whiteley-P. | 1999 | Hypocalcaemia in 23 ataxic/recumbent ewes: clinical signs & likelihood ratios. | Veterinary Record; vol 144; no 19; pp 529-532; ISSN: 0042-4900; 5 ref. | Department of Clinical Veterinary Medicine, Madingley Road , Cambridge CB3 0ES , UK . | 23/2000 ewes in a UK flock were identified as having acute onset ataxia and/or having become recumbent in late pregnancy & early lactation. The presence or absence of 15 clinical signs were recorded. 13 of the ewes (57%) were hypocalcaemic & 10 (43%) were normocalcaemic. In the hypocalcaemic group, loss of anal reflex, constipation, tachycardia, hyposensitivity, ruminal stasis, ruminal tympany, salivation & tachypnoea were recorded in 50% or more of the cases. In the normocalcaemic group, tachycardia, tachypnoea & ataxia were recorded in 50% or more of the cases. Constipation, ruminal stasis, salivation & hyposensitivity had likelihood ratios of 3 & above for being associated with hypocalcaemia. Ruminal stasis & hyposensitivity had the likelihood ratios of 0.10 & 0.11 respectively for not being associated with hypocalcaemia.

Daniels-R-C-W. | 1979 | (I) Changes in bromosulphalein fractional clearance & plasma volume in induced hypocalcaemia in cows. (II The effect of reducing plasma Ca levels on some plasma enzyme levels in cows & sheep. | British Veterinary Journal; vol 135; no 1; pp 25-39; ISSN: 0007-1935; 23 ref. | Dep Vet Med, Univ , St Lucia , Queensland 4067, Australia . | Induction of hypocalcaemia to a mean plasma Ca level of 0.82+/-0.60 mmol/l (mean+/-SEM) in 5 cows did not change BSP fractional clearance rates significantly, but reduced plasma volumes by approximately 24%. This reduction did not appear to be due to the effects of recumbency resulting from the hypocalcaemia. Elevations of plasma AAT, CPK & LDH occurred in cows in which hypocalcaemia was induced by the infusion of 4.7% Na2EDTA. Levels of alpha HBDH during the same period did not differ significantly from those obtained during a control infusion of 0.9% saline in the same cows over a similar period, suggesting that the rise in LDH levels was due to isoenzymes other than LDH-1 & LDH-2. The rises in AAT, CPK & LDH were due to release from skeletal muscle tissue & the effects of recumbency may have contributed. In 6 wethers increase of plasma CPK activity, which was not due to the effects of recumbency, occurred in hypocalcaemia induced by the infusion of 4.7% Na2EDTA solution. 

Daniels-R-C-W, Moodie-E-W. | 1979 | Induced hypocalcaemia in cows & sheep. 1. Changes in plasma inorganic P levels. | British Veterinary Journal; vol 135; no 5; pp 440-451; ISSN: 0007-1935; 22 ref. | Dep Veterinary Medicine, Univ Queensland , Brisbane , Australia . | There were 8 cows aged 4 years or over, not lactating, either not pregnant or pregnant for less than 3 months. Hypocalcaemia was induced in each cow until the recumbent comatose stage by infusion of 4.7% Na ethylenediamine tetraacetate (Na2EDTA). The cows were allowed to recover spontaneously except that 2 had to be treated to prevent death. The 7 controls got saline infusion. A 2nd group of 6 cows had hypoglycaemia induced to a stage just preceding recumbency then each was treated with Ca borogluconate intravenously. The 3rd group of 8 cows were cast & restrained in sternal recumbency for 3 h; the 3 controls remained standing. 6 sheep 15-30 months old had hypoglycaemia induced but were supported to prevent recumbency. They were allowed to recover spontaneously; 6 controls got saline. Blood was collected before infusion & 1, 2, 3, 4, 5, 6, 10 & 22h after it began from cows of the 1st group & the sheep, & at 30-min intervals from cows of the 2nd group with another sample taken within 5 min of the infusion of Ca borogluconate. Plasma Ca & inorganic P were estimated in blood taken initially & 2, 3 & 4h after start of infusion of Na2EDTA. Regression coefficient of plasma inorganic P concentration on plasma Ca concentration calculated from pooled results for the 8 cows during induction of hypocalcaemia was 0.400 (p <0.01) with correlation coefficient 0.843. For the total period of induction & spontaneous recovery in the 6 cows of the 1st group there was a similar relation & a regression coefficient of 0.448. Results for the 2nd group of 6 cows supported that relation but the more frequent sampling showed that regressions differed significantly between cows. There was no significant difference in response of inorganic P between treated sheep & controls although changes in inorganic P tended to follow those of Ca in the treated sheep & there were significant differences between individual regression coefficients. Inorganic P had a significant mean increase of 0.46 mmol/litre for 6 cows immediately after treatment with Ca borogluconate. Forced recumbency of cows resulted in a significant fall, p <0.001, in inorganic P. Possible reasons for the changes in inorganic P are discussed. 

Daniels-R-C-W. | 1980 | Induced hypocalcaemia in cows & sheep. 2. Changes in plasma K levels. 3. Changes in plasma Mg levels. | British Veterinary Journal; vol 136; no 1; pp 45-56; ISSN: 0007-1935; 22 ref. | Dep Vet Med, Univ, Brisbane , Queensland , Australia . | Mean plasma K levels were significantly lowered by 0.39 mmol/1 & 0.48 mmol/1, respectively, for a decrease of 1 mmol/1 in EDTA titratable plasma Ca level in 2 groups of cows in which hypocalcaemia was induced to the 'recumbent comatose' stage by the infusion of Na2EDTA over approximately 3h. In these cows plasma K levels did not return to normal in parallel with plasma Ca & did not start to rise until at least 2h after the nadir of hypocalcaemia. Plasma K levels remained relatively constant in a control experiment in which saline infusions over a similar period of time were carried out in the larger group of cows. Analysis of variance of the results in this group of cows showed a significant cow x infusion interaction. No difference in response of plasma K levels was observed in 2 groups of 6 wethers, one of which was infused with 0.9% saline & acted as a control group while the other was infused with Na2EDTA & hypocalcaemia induced. The possible roles of parathormone & stress in producing the observed changes in plasma K levels are discussed. (Observations on changes in plasma Mg concentration in cows in which hypocalcaemia (plasma Ca down to 1.10 mmol/1) was induced by the infusion of Na2EDTA failed to show any significant mean differences in response when compared with changes in levels in the same cows infused over a similar period of time with 0.9% saline. A significant cow x infusion interaction suggested between-cow variation in differences in response of plasma Mg to the 2 infusions. Regression coefficients of plasma Mg on plasma Ca differed significantly between cows during the induction of hypocalcaemia. In a group of 6 merino wethers, a significant mean fall in plasma Mg occurred in association with induced hypocalcaemia when compared with a control group infused with saline. The regression coefficients of plasma Mg on plasma Ca concentrations from the pooled results were 0.072+/-0.024 (+/-Sb) & 0.054+/-0.021 mmol/1 (+/-Sb) for the induction phase & induction-plus-recovery phases of hypocalcaemia, respectively. 

Elias-E, Shainkin-Kestenbaum-R. | 1990 | Hypocalcaemia & serum levels of inorganic P, Mg, parathyroid & calcitonin hormones in the last month of pregnancy in Awassi fat-tail ewes. | Reproduction, Nutrition, Development; vol 30; no 6; pp 693-699; ISSN: 0926-5287; 29 ref. | Ben Gurion University of the Negev , PO Box 653 , Beersheva 84105 , Israel . | Serum levels of Ca, inorganic P, Mg , parathyroid (PTH) & calcitonin (CT) hormones of fat-tail Awassi ewes were determined during the last month of pregnancy. The incidence of hypocalcaemia (HCE) was 13.4% of the obstetrical cases examined. 26 (81.3%) of 32 ewes with HCE were >/= 4 yr of age or older. Significant decreases in serum Ca levels (normal values or controls; 10.04+/-0.22% (w/w)) to pathological values (4.30+/-0.35% (w/w)) caused severe clinical manifestations in 75% of affected ewes. This HCE was accompanied by a significant increase in the PTH level (142.6+/-9.1 pmol/litre in comparison to 99.7+/-9.3 pmol/litre) in controls, & significant decrease in serum CT level (98.2+/-7.6 pg/ml in comparison to 144.6+/-25.7 pg/ml in controls). Ca borogluconate i/v yielded normal Ca values which were accompanied by a decrease in serum PTH & an increase in CT to normal values. 

Elias-E. | 1991 | Hypocalcaemia & oestradiol-17 beta levels in Awassi fat-tail ewes with uterine prolapse. | Israel Journal of Veterinary Medicine; vol 46; no 4; pp 134-137; ISSN: 0334-9152; 18 ref. | Isan Center for Comparative Medicine, Ben Gurion University of the Negev, PO Box 653, Beer Sheva 84105, Israel. | Blood samples were taken from 34 Awassi ewes in Bedouin flocks, presenting uterine prolapse. Serum levels of Ca, inorganic P, Mg & oestradiol-17 beta (E2) were measured in these ewes & in 6 control ewes after normal lambing. Serum Ca concentration was significantly reduced with no accompanying changes in P or Mg levels, in ewes presenting uterine prolapse 13h or more after lambing. Levels of oestradiol-17 beta displayed a normal pattern of decrease after lambing without correlation to serum Ca levels. Parturient hypocalcaemia may play a major role in the aetiology of uterine prolapse. 

Fenwick-D-C, Daniel-R-C-W. | 1992 | Investigation of some pathophysiological effects of prolonged hypocalcaemia in sheep induced by infusing Na3EDTA solution for 4h daily on 3 consecutive days. | British Veterinary Journal; vol 148; no 4; pp 301-313; ISSN: 0007-1935; 29 ref. | Department of Physiology & Pharmacology, University of Queensland , St Lucia 4072, Australia . | Hypocalcaemia was induced in a group of 5 aged Merino ewes (with low erythrocyte K status) by the i.v. infusion of 4.7% Na2EDTA solution for 4 h/d on 3 consecutive days. A similar control group was infused with 5.0% dextrose solution (10 ml/h) for the same period. Blood samples were taken immediately before infusion each day, hourly for 7 h, then at 8:00 each morning for a further 5 d. Studies were made on the changes in plasma (P) Ca, PNa, PK, PMg, PProtein (PProt), inorganic P (PiP), erythrocyte (E) Na, EK, EMg, PCVs, & mean corpuscular cell volumes (MCV). Significant decreases occurred in PiP concentrations but these were only temporary, suggesting that PiP is unlikely to be involved in the complications of prolonged hypocalcaemia. Significant prolonged decreases in PNa, PK & EK & significant prolonged decreases in PNa, PK & EK & significant prolonged increases in PCVs suggested that fluid replacement therapy supplemented with Na & K may be worthy of further study in the treatment of ruminants affected by apparent biochemical or physiological complications to prolonged hypocalcaemia. 

Fenwick-D-C, Daniel-R-C-W. | 1992 | Blood pathophysiological changes in sheep following a prolonged (18-hour) period of hypocalcaemia induced by Na2EDTA solution. | British Veterinary Journal; vol 148; no 5; pp 425-434; ISSN: 0007-1935; 19 ref. | Department of Physiology & Pharmacology, University of Queensland , Qld 4072, Australia . | 6 aged Merino ewes were used in an experiment in which 5 were infused with 4.7% Na2EDTA solution i.v. for 18h at a rate designed to produce hypocalcaemia & maintain recumbency, & 5 with 0.9% Na chloride solution at the same rate for the same period (4 were infused at different times with both solutions). Blood samples were collected every 3h & analysed for plasma Ca, Na, K, Mg, & inorganic P (PiP), erythrocyte Na, K & Mg, & PCV. 3 of the hypocalcaemic sheep took 36-64h to regain their feet. Plasma Ca & K, & erythrocyte Na showed significant decreases in the group infused with Na2EDTA compared with the group infused with saline while PCVs were significantly greater in the former group. The sheep model used could be suitable for the study of the effects of prolonged hypocalcaemia & recumbency in cows.

Grant-I-M, Bingham-A-M, Caple-I-W. | 1992 | Acid-base balance & susceptibility of ewes to hypocalcaemia. | Proceedings of the Australian Society of Animal Production; vol 19; pp 412-415; 11 ref. | University of Melbourne , Department of Veterinary Science, Werribee, 3030, Australia . | The effect of acid-base balance on the susceptibility of ewes to hypocalcaemia was studied in groups of ewes fed on diets in which the fixed cation-anion balance (Na + K - Cl) was -4.1, 29.1 & 82.3 mequiv/100g DM, respectively. Ewes fed on the diet with a fixed cation excess (82.3 mequiv/100g DM) had higher urine pH & lower urine Ca concentration. They also had lower blood ionized Ca concentration after an overnight fast, & tended to develop hypocalcaemia more rapidly during EDTA infusion than ewes fed on a diet with a fixed anion excess (-4.1 mequiv/100g DM). Dietary fixed cation-anion balance may be a factor which predisposes pregnant ewes to hypocalcaemia. 

Jones-B, Luthman-J. | 1978 | Feeding-induced hypocalcaemia. Studies on the uptake of 47Ca from the GIT of sheep. | Acta Veterinaria Scandinavica; vol 19; no 2; pp 204-214; ISSN: 0044-605X; 9 ref. | Dep Medicine II, Swedish Univ Agricultural Sciences, S-750 07 Uppsala , Sweden . | Ewes 2-6 years old in 4 groups of 8 were taken from pasture & fed only on hay for 1 month. Then concentrate was added to the ration of 3 groups at 0.2, 0.4 or 0.6 kg/d. The pelleted concentrate was oats & barley each 41% soya bean oilmeal 8%, rapeseed oilmeal 3.6% & cottonseed oilmeal 6.4%. Blood was sample at regular intervals. The hay had Ca 4.9, P 1.3 & Mg 1.3g/kg & the concentrates had 1.5, 4.0 & 1.6g/kg. Values for metabolizable energy & digestible protein were calculated. 6 rams about 7 months old, 26-32kg LW, were used to study the gastrointestinal absorption of 47Ca given into the rumen. They were fed only on hay for 1 month then got 100 mu Ci 47Ca. 10d later concentrate up to 0.6 kg/d was given. 5d later a 2nd injection of 47Ca was given. Twelve yearling heifers were used to study the effect of concentrate on blood Ca. 6 animals were controls given hay to appetite, & the others got hay to appetite & 3kg concentrate a day. Serum Ca, inorganic P, Mg & alkaline phosphatase were estimated. Concentrate 0.4 kg/d was required to induce a profound drop in serum Ca. The same changes occurred in heifers at 3 kg/d. The isotope studies showed that the fall in serum Ca was probably not caused by a reduced gastrointestinal uptake of Ca. 

Jonson-G, Luthman-J, Mollerberg-L, Persson-J. | 1973 | (Feeding of minerals to flocks of sheep affected with hypocalcaemia). | Nordisk Veterinaermedicin; vol 25; no 2; pp 97-103. | Veterinarhogskolan, Stockholm , Sweden . | Serum values of Ca, P, Mg & alkaline phosphatase were measured in samples from 14 ewes which required treatment for hypocalcaemic paresis, & the mean values of the same parameters were determined for 3 flocks in which cases of hypocalcaemia had occurred. The results are tabulated. Serum Ca values were very low in the paretic ewes, a mean of 3.4+/-1.3mg/100 ml. Some ewes showed pronounced hypophosphataemia. One of the affected flocks showed a low mean serum Ca value, 8.2+/-1.3mg/100 ml. Records & analysis of the feed of the 3 flocks showed that all had been fed an excess of Ca during the whole of pregnancy, & it is suggested that this may have contributed to the development of hypocalcaemia towards the end of pregnancy. 

Jonsson-N-N, Daniel-R-C-W. | 1997 | Effects of hypocalcaemia on blood flow to the ovaries of the sheep. | Journal of Veterinary Medicine. Series A; vol 44; no 5; pp 281-287; ISSN: 0931-184X; 24 ref. | Queensland Department of Primary Industries, Mutdapilly Research Station, MS 825 Peak Crossing 4306, Queensland , Australia . | The effect of hypocalcaemia on blood flow to the ovaries was studied in 6 Merino cross sheep 12-18 months old, non-pregnant, in Queensland , Australia . Different levels of hypocalcaemia were induced in 5 sheep by i.v. infusion of 4.7% Na2-EDTA at a rate of 60-90 ml /h. The control sheep was infused with 60 ml of 0.9% NaCl. Blood flow to the ovaries was measured before & after the induction of hypocalcaemia using 113Sn & 46Sc radiolabelled microspheres. The plasma Ca++ decreased from 1.07-1.35 mmol/litre before infusion to 0.39-1.17 mmol/litre after infusion & ovarian blood flow decreased from 39.9-177 ml 100 g-1 min-1 to 39.6-152 ml 100 g-1 min-1. The following model was developed: ovarian blood flow (% of resting)=0.54 Ca++ (% of resting)+58.4. According to this model, a reduction in plasma ionized Ca of 50% would reduce ovarian blood flow by 16%. 

Larsen-J-W-A, Constable-P-D, Napthine-D-V. | 1986 | Hypocalcaemia in ewes after a drought. | Australian Veterinary Journal; vol 63; no 1; pp 25-26; ISSN: 0005-0423; 8 ref. | Dep Agric, Vet Field Serv, State Government Office, Ballarat, Vic 3350, Australia . | The prevalence of hypocalcaemia ranged from 1% to over 10% 2-6 weeks before lambing in flocks in western Victoria after the drought broke in 1983. Serum Ca values were 1-1.2 mM, & the response to Ca borogluconate was rapid. The dominant pasture species were Trifolium subterraneum (usually rich in Ca & Arctotheca calendula). Samples of herbage collected during the outbreaks had low contents of Ca, Mg, K & DM. Predisposing factors could have been inadequate supplementation with limestone during the drought & the stress of routine crutching before lambing. 

Luthman-J. | 1977 | Hypocalcaemia in ewes in late pregnancy: a cultural disorder? | Svensk Veterinartidning; vol 29; no 6; pp 217-221; ISSN: 0346-2250; 12 ref. | Inst Medicin II, Klinikcentrum, Veterinarhogskolan, 750 07 Uppsala 7, Sweden . | Several trials & studies on ewes are reported. In late pregnancy normal ewes had Ca 9.67, P 4.79 & Mg 2.64mg/100 ml serum & alkaline phosphatase 35 mU/ml & ewes with paresis had 3.63, 4.04 & 2.64 mg & 18 mU. Sometimes in flocks with cases of paresis all sheep had low blood Ca, but without clinical sign, & slight stress might induce paresis. Serum P was generally high in flocks with hypocalcaemia. Massive overdoses of Ca in early pregnancy did not increase the risk of hypocalcaemic paresis. Abrupt introduction of concentrate of any type reduced serum Ca, in one test after 3-10d. As hypocalcaemia developed, hydroxyproline decreased in blood. It was thought that hypocalcaemia might be induced by temporary inhibition of bone resorption; that was supported by testing the reaction to protamine by vein. 

Luthman-J, Persson-J. | 1977 | Feeding-induced hypocalcaemia. Preliminary studies in sheep. | Nordisk Veterinaermedicin; vol 29; no 2; pp 90-95. | Dep Medicine II, Veterinary College , S-750 07 Uppsala , Sweden . | 30 ewes aged 4-8 years were accustomed to being fed 1.5kg hay/d & got a supplement of pelleted concentrate at 0.5kg/d at the time of mating. After about 3 months of pregnancy, controls continued on hay alone & others got also 0.5kg crushed oats or pelleted concentrate for 30d. Hay had Ca 6.2 & P 1.8g/kg, crushed oats had 0.9 & 3.6g/kg & concentrate had 7.4 & 5.6g /kg. In another experiment 6 nonpregnant ewes 1-2 years old got 1.5kg hay/d for 3 weeks then 0.5kg concentrate was added. Serum Ca, P, hydroxyproline, total protein, urea N & alkaline phosphatase were estimated at intervals & results are presented graphically. There was hypocalcaemia about 2 weeks after the addition of oats or pelleted concentrate to diets of pregnant or nonpregnant ewes although concentrate increased the intake of Ca/d by about 40%.

Matthews-M, Editor: Budge-G. | 1999 | Hypocalcaemia in ewes post drought in Hawkes Bay . | 29th Seminar of the Society of Sheep & Beef Cattle Veterinarians NZVA, Hastings, New Zealand, 1-3 March 1999; Publication - Veterinary Continuing Education, Massey University; no 189; pp 131-133; ISSN: 0112-9643; 1 ref. | Veterinary Services (HB) Ltd, Hastings , New Zealand . |  

Mosdol-G, Waage-S. | 1981 | Hypocalcaemia in the ewe. | Nordisk Veterinaermedicin; vol 33; no 6/8; pp 310-326; 59 ref. | Dep Obstetrics, Veterinary College of Norway , PB 8146 Dep, Oslo 1, Norway . | Hypocalcaemia was defined as a disorder in which the plasma Ca was less than 2 mM. Of 78 female sheep with clinical signs of hypocalcaemia 74.4% had hypocalcaemia judged by their plasma Ca; of 99 with an uncertain clinical diagnosis of hypocalcaemia, 21.2% had it, judged by their plasma Ca. The disorder occurred from about 2 months before to 1.5 months after parturition, but most frequently 2-4 weeks before parturition. Tendency to hypocalcaemia increased with age & parity. Plasma Ca was highest in affected sheep that remained standing & lowest in those with tetany. ASAT (asparaginic acid aminotransferase), ALAT (alanine aminotransferase), bilirubin, Hb & packed cell volume (PVC) were significantly higher in sheep with hypocalcaemia than in normal controls. With hypocalcaemia, plasma Ca was related negatively to PCV & positively to plasma P concentration. About 20% of affected sheep died; those had higher mean plasma Ca & lower Mg at 1st treatment than those that recovered. Mortality rate was greater in sheep treated after than in those treated before parturition. Of those that recovered, 25% required more than 1 treatment. Among sheep that developed hypocalcaemia while pregnant 22% of their young died; the main reason was probably premature birth. The differential diagnosis of hypocalcaemia is discussed in the light of clinical & biochemical findings in sheep with normal serum Ca, in which hypocalcaemia had been diagnosed clinically, with or without certainty of the diagnosis. 

Papasteriadis-A. | 1973 | Hypocalcaemia in sheep in Greek conditions. | Epistemonike Epeteris Kteniatrikes Sholes, Aristoteleion Panepistemion Thessalonikes; vol 14; pp 1-32. |   | Of all sheep brought to the medical clinics of the Veterinary College of Thessaloniki for examination, 20% had metabolic disorders & 42.8% of those, 8.4% of the total, had hypocalcaemia. Hyperphosphataemia was constantly associated with the condition. Nutritional factors & dark pens were incriminated. Parenteral administration of vit. D gave beneficial results. The principal causes in adult sheep were: heavy cereal intakes resulting in primary hypocalcaemia & hyperphosphataemia; excess of beet pulp inducing secondary hypocalcaemia; sudden changes of feed to grazing on lush green oats, barley or wheat. In addition, lambs were kept in dark pens leading to vitamin D deficiency. Values for serum minerals are tabulated. Preventive management is discussed. 

Persson-J, Luthman-J. | 1975 | Further studies on theophylline-induced hypocalcaemia in sheep. | Acta Veterinaria Scandinavica; vol 16; no Fasc.1; pp 39-50; ISSN: 0044-605X. | Dep Med II, Royal Vet Coll, S-104 05 Stockholm 50, Sweden . | The effects of various doses of theophylline on the plasma levels of Ca, inorganic P & Mg were studied in sheep. The dose of 0.25mg/kg /min during 40 min produced a hypocalcaemia, which was abolished by thyroidectomy. At a higher dose (1mg/kg/min) thyroidectomy reduced, but did not block the hypocalcaemic effect of theophylline. Young sheep showed a greater Ca response than adult ewes. The decrease in plasma Ca was in no case accompanied by hypophosphataemia. Plasma Mg decreased in all groups after 1mg/kg/min, & was not influenced by thyroidectomy. Theophylline increased the urinary excretion of Ca & Mg. It is concluded that theophylline-induced hypocalcaemia in sheep is in part a result of increased calcitonin secretion but that also other mechanisms must be involved, e.g. a direct effect of theophylline on bone. 

Pickard-D-W, Field-B-G, Kenworthy-E-B. | 1988 | Effect of Mg content of the diet on the susceptibility of ewes to hypocalcaemia in pregnancy. | Veterinary Record; vol 123; no 16; pp 422; ISSN: 0042-4900; 1 ref. | Dep Anim Physiology, Univ, Leeds , LS2 9JT , UK . | In a flock of 120 ewes, 4 weeks before the expected lambing date, rations containing 2g Mg & 5g Ca/kg (Group 1), 2 mg Mg & 15g Ca/kg (Group 2), 5g Mg & 15g Ca/kg (Group 3) or 10 mg Mg & 15g Ca/kg (Group 4) were introduced in 2 feeds/d at a rate of 400g/ewe/d, increasing to 500g/d after 3d. All rations contained 7g P/kg. 7 ewes (4 in Group 4, 2 in Group 2 & one in Group 1) showed clinical hypocalcaemia after 4d. However, when 6 of these ewes were transferred to individual pens & fed the same rations at up to 900g/d, no further incidents of hypocalcaemia were seen. In another flock of 96 ewes, fed the same rations as above with supervised feeding, only one case of hypocalcaemia occurred in a ewe fed 10 mg Mg & 15g Ca/kg. The normal concentration of Mg in ewe rations (5g/kg) does not predispose sheep to hypocalcaemia. The authors suggest that increased feed intake, especially by older ewes, may lead to acidosis, followed by inappetence & then hypocalcaemia, & that good management after supplementary rations have been introduced is necessary to minimise problems due to unequal feed intake. 

Popof-M. | 1979 | Uses of biochemical tests on urine & blood in diseases of sheep. II. Analytical study in ketosis, hypocalcaemia, enterotoxaemia & urolithiasis. | Point Veterinaire; vol 9; no 43; pp 65-70; ISSN: 0335-4997. | 44, Rue de Cronstadt, 750015 Paris , France . | Symptoms in 59 ewes with ketosis ranged from slight locomotor disorder & withdrawal from the flock, through posterior paresis to coma. Frank ketonuria with acid pH was pathognomonic. All 15 ewes with acute hypocalcaemia were extremely depressed. Most showed very alkaline urine & glycosuria. Blood Ca was as low as 48mg/litre (100mg/litre is normal). Enterotoxaemia was observed in 46 adult sheep & 77 lambs. Symptoms ranged from sudden tympanites, through opisthotonos with pedalling movements, to coma. The urine in this condition showed acid pH & the presence of glucose, but ketones were usually absent. Hyperglycaemia was common. Urolithiasis was observed in 4 rams, 5 ram lambs & 2 ewe lambs. Urinary pH was neutral or alkaline. 

Saba-N, Cunningham-N-F. | 1971 | Plasma corticosteroid levels in ovine pregnancy toxaemia & hypocalcaemia. | Research in Veterinary Science; vol 12; no 5; pp 483-485; ISSN: 0034-5288. | Central Vet Lab, Weybridge, Surrey . | Both pregnancy toxaemia & clinical hypocalcaemia can cause sufficient stress in ewes to raise plasma adrenal steroid levels. 

Smith-F-G-Jr, Alexander-D-P, Buckle-R-M, Britton-H-G, Nixon-D-A. | 1972 | Parathyroid hormone in foetal & adult sheep: the effect of hypocalcaemia. | Journal of Endocrinology; vol 53; no 3; pp 339-348; ISSN: 0022-0795. | Dept Physiol, St Mary's Hospital Med Sch, London , W2. | Radioimmunoassay revealed parathyroid hormone (PTH) in the plasma of 2/5 foetuses, 3/5 ewes & all 3 non-pregnant adults. Induction of hypocalcaemia by EDTA infusion increased PTH concentration & urinary phosphate excretion in all 5 foetuses & non-pregnant adults. During induction of hypocalcaemia plasma Ca was inversely related to PTH, except in ewes. The parathyroid glands appear to be active from an early stage in foetal life & they responded to changes in serum Ca.

Sweeney-H-J, Cuddeford-D. | 1987 | An outbreak of hypocalcaemia in ewes associated with dietary mismanagement. | Veterinary Record; vol 120; no 5; pp 114; ISSN: 0042-4900; 4 ref. | Royal (Dick) Sch Vet Studies, Easter Bush, Roslin, Midlothian , UK . | 43/350 purebred Llyn ewes became comatose & 5 died within 12h. The ewes were within 2 weeks of lambing & most carried twins. All but 2 of the remainder responded to injection of  Ca borogluconate (40 ml of 40% solution i/v plus 40 ml s/c). The diet consisted of swedes for 3h/d, hay & 0.3kg of a mixture of whole barley & fish-meal pellets. The supplement was inadequately mixed & had a mean Ca & P content of 4.8 & 6.9g/kg DM, respectively. Serum Ca ranged from 0.74-1.18 mmol/litre (normal 2.86-3.24), inorganic phosphate was correspondingly low, & Mg normal. An energy deficit was indicated by elevated 3-hydroxybutyrate (1.30-2.09 mmol/litre) representing a deficit of 3.5 MJ metabolisable energy/d. Ca intake/ewe was 3.5g/d whereas 10.1g/d is recommended for a 60kg ewe carrying twins. Also contributory to the condition was the variation in the Ca content of the concentrate. 

Tindall-J-R. | 1986 | Hypocalcaemia in housed ewes. | Veterinary Record; vol 118; no 18; pp 518-519; ISSN: 0042-4900. | Prospect House, Church Brow, Clitheroe, Lancs , UK . | Muscular incoordination with a high incidence of prolapse of the uterus & intestine occurred in 40/800 intensively fed, housed ewes in late pregnancy. 12 ewes died. Blood Ca was subnormal. When Dical was fed at 15g/ewe/d, the condition subsided, & blood Ca returned to normal. Analysis of the feed showed that Ca & P levels in the previous diet were adequate but Mg levels were high. It was concluded that the availability of dietary Ca was reduced by Mg.

Vihan-V-S, Rai-P. | 1985 | Studies on blood serum changes in experimental hypocalcaemia in sheep. | Indian Veterinary Journal; vol 62; no 7; pp 573-576; ISSN: 0019-6479; 11 ref. | Dep Med, CSA Univ Agric Technol, Mathura Campus, Uttar Pradesh , India . | Hypocalcaemia induced in sheep by intravenous jugular infusion of 5% Na EDTA was followed by a significant decrease in blood Ca from 12.3+/-0.47mg/100 ml to 3.5+/-0.29mg/100 ml in 2 h, significant decreases in inorganic P (from 6.1+/-0.35 to 2.1+/-0.06), total proteins (8.0+/-0.44 to 3.9+/-0.09g/100 ml) albumin (5.1+/-0.28 to 2.5+/-0.12) & globulin (2.9+/-0.1-1.4+/-0.1g/100 ml) & significant increase in serum aspartate aminotransferase (from 40.7+/-4.34 to 75.3+/-4.06 units/ml). Glucose & Mg concentrations were not affected. 

Wilson-G-F. | 2001 | Stimulation of Ca absorption & reduction in susceptibility to fasting-induced hypocalcaemia in pregnant ewes fed vegetable oil. | New Zealand Veterinary Journal; vol 49; no 3; pp 115-118; ISSN: 0048-0169; 14 ref. | Institute of Veterinary , Animal & Biomedical Sciences, Massey University , Palmerston North, New Zealand . | This study tested the hypothesis that susceptibility to fasting-induced hypocalcaemia could be reduced by prior stimulation of the ability of late-pregnant ewes to absorb Ca from the GIT (GIT) by feeding of vegetable oil supplement. The supplement was expected to decrease the availability of the Ca supplied from a pasture diet, & stimulate the animals' homeostatic system. Mature ewes pregnant with twins (n=28) & grazing at pasture, were randomly allocated to treated or control groups, 6 weeks prior to their expected date of parturition (d0). Treated ewes (n=14) were drenched with 25 ml soyabean oil twice/d for 3 weeks. Plasma Ca concentrations were determined on d0, 8 & immediately before & after a 20h fast that began on d21, which was intended to simulate the reduced feed intakes that occur on the day of parturition. An index of the ewes' ability to absorb Ca from the GIT was obtained using orally dosed Sr as a tracer & the extent of Ca mobilization from bone was assessed by measuring hydroxyproline concentrations in plasma before fasting on d21. Plasma Ca concentrations were significantly higher in treated than control ewes after fasting (P<0.001). The Ca absorption index was also higher in treated than control ewes at the end of the 3 week treatment period (P=0.014), but degree of bone mobilization assessed by concentration of hydroxyproline in plasma did not differ significantly between groups. Susceptibility of late-pregnant ewes to fasting-induced hypocalcaemia was reduced using a soyabean oil supplement. The inclusion of one or more dietary ingredients capable of binding or forming complexes specifically with Ca in the diet of late pregnant ruminants may provide a novel, practical method of reducing periparturient hypocalcaemia. 

Wilson-G-F, Editor: Enemark-J-M-D, Thilsing-T, Jorgensen-R-J. | 2003 | Development of a novel concept (Calcigard) for activation of Ca absorption capacity & prevention of milk fever. | Proceedings of the Abildgaard Symposium on hypocalcaemia, acidosis & Ca homeostasis, 16-17 August 2001, The Royal Veterinary & Agricultural University, Frederiksberg, Denmark; Acta Veterinaria Scandinavica, Supplementum; no supp. 97; pp 77-82; ISSN: 0065-1699; Publisher: The Danish Veterinary Association; Vanlose; Denmark; 16 ref. | Institute of Veterinary , Animal & Biomedical Sciences, Massey University , Palmerston North, New Zealand . | The background to the development of a novel concept for the prepartal activation of Ca absorption capacity as a means of preventing parturient hypocalcaemia & milk fever in grazing ruminants is described. It was hypothesised that this objective could be achieved by decreasing the bio-availability of Ca from pasture for a 3 week period. Soya bean oil was chosen as a supplement, from a number of potential binding agents, to form poorly digestible Ca soaps in the GIT. 28 mature twin-pregnant ewes in late pregnancy were used as assay animals to test the hypothesis, & they proved to be a sensitive experimental model for dairy cows. Following the treatment period, overnight starvation was used to challenge Ca homeostasis. Ca absorption capacity was assessed indirectly by measuring strontium concentrations in plasma following oral dosing with strontium chloride. Strong support for the hypothesis was obtained as the 14 Treated ewes were protected from severe fasting-induced hypocalcaemia (P=0.002), & this was associated with a greatly increased capacity of the ewes to absorb Ca. The feeding strategy developed in this experiment led to the production of a Calcigard concentrate supplement which was subsequently shown to protect cows from hypocalcaemia & milk fever, & stimulate production.