TALK+(not+finished)


 * Intro **
 * Calcium is an essential element involved in many physiological processes. These include neuromuscular function (muscle contraction; nerve signalling), blood clotting and hormonal secretion. It is also vital to the integrity of bone and teeth.
 * 99% of the calcium in the body of a cow is stored in the organic mineral matrix of the skeleton, which acts as a reserve of calcium ions in exchange with the lesser calcium pools: extracellular fluid and soft tissues
 * Dairy cows have been heavily selected for the ability to produce high milk yields. This requires them to ingest, store and utilise large quantities of calcium for much of the year, placing a very high importance on the ability of their homeostatic mechanisms to operate efficiently and keep the calcium balance.
 * The 'transition period' is the time at which a pregnant cow simultaneously endures parturition and the start of lactation meaning that the demand for energy and calcium very suddenly increases, all of which places a great strain on energy supply and calcium homeostasis.
 * Some cows fail to maintain calcium homeostasis, and a smaller percentage develop the metabolic disease milk fever, also called periparturient paresis, where calcium levels in circulation decline to such a point that homeostatic mechanisms may not be able to restore balance. It is an important condition as it affects productivity and longevity of cows and the profitability of dairy operations.


 * Calcium homeostasis **
 * Animals can only obtain calcium from dietary sources, and when levels in the diet are adequate cows absorb it via active transport across the brush border epithelial cells of the lumen in the small intestine. When dietary sources are abundant, calcium can be absorbed by the cow through the rumen and via passive diffusion between the epithelial cells of the small intestine.
 * Calcium is lost through urine and faeces, as well as to the foetus and milk production in pregnant or lactating animals.




 * Homeostatic control of calcium metabolism means intracellular and extracellular calcium (particularly plasma) concentrations are maintained within a narrow range. This is regulated mainly by intestinal absorption, renal reabsorption and bone turnover, where ionised calcium is exchanged between bone and the non-bone calcium pools.
 * The coordination of these mechanisms is achieved most significantly by interaction of calcitonin, parathyroid hormone, the active metabolite of vitamin D known as 1,25-dihydroxyvitamin D [1,25-(OH)₂D] or calcitriol, by levels of calcium itself and by all corresponding receptors.
 * When a decline in plasma calcium levels (a deviation from the setpoint) is detected, the parathyroid glands are stimulated to increase secretion of parathyroid hormone, causing the kidneys to increase tubular calcium reabsorption from the glomerular filtrate. The parathyroid hormone also triggers production of the renal enzyme 1α-hydroxylase by the kidney, resulting in conversion of circulating vitamin D to 1,25-dihydroxyvitamin D.
 * This active form of vitamin D is the most significant stimulator of calcium absorption from the intestine. This is achieved through increased formation of the calcium binding protein in the intestinal epithelial cells.
 * If the demand for calcium remains high, such as in lactating cows, and plasma calcium concentration is not restored and maintained by these mechanisms, circulating parathyroid hormone levels remain elevated. In coordination with active vitamin D, bone calcium resorption is stimulated. For short term needs, calcium salts are removed from bone in a process known as osteocytic osteolysis. In cases of prolonged demand for calcium by the body, osteoclastic bone resorption occurs, involving resorption of the bone matrix.
 * <span style="background-color: transparent; color: #000000; font-family: serif; font-size: 13px; text-decoration: none; vertical-align: baseline;">Once plasma calcium levels are restored to the setpoint, these mechanisms cease as the negative feedback loop decreases secretion of parathyroid hormone.
 * <span style="background-color: transparent; color: #000000; font-family: serif; font-size: 13px; text-decoration: none; vertical-align: baseline;">If plasma calcium levels increase beyond the setpoint, a reverse of these processes occur, stimulated by the hormone calcitonin, secreted by the thyroid.
 * <span style="background-color: transparent; color: #000000; font-family: serif; font-size: 13px; text-decoration: none; vertical-align: baseline;">Homeostatic control means plasma calcium in a healthy adult cow is ideally maintained between 8.5 and 10 mg/dL.



** Failure of homeostasis and development of hypocalcaemia **
 * <span style="background-color: transparent; color: #000000; font-family: serif; font-size: 13px; text-decoration: none; vertical-align: baseline;">Dairy cows generally lactate 10 months out of the year, are pregnant from around 3 months into each lactation (3 months after last calving), and as such the ‘dry period’, or cessation of lactation, actually occurs when they are pregnant. They give birth once a year, around 8 weeks after the start of the dry period.
 * <span style="background-color: transparent; color: #000000; font-family: serif; font-size: 13px; text-decoration: none; vertical-align: baseline;">The calcium demand for foetal growth is much less than that required for lactation, so during this time of the dry period, typically while pregnant, calcium homeostasis operates successfully in healthy cows. It also means that physiological mechanisms behind bone resorption of calcium and intestinal absorption of calcium are at their least active for the year.
 * <span style="background-color: transparent; color: #000000; font-family: serif; font-size: 13px; text-decoration: none; vertical-align: baseline;">The onset of lactation generates a sudden, very high demand on calcium homeostasis. There is often an imbalance between the high calcium output in the large quantities of colostrum produced and the influx of calcium to maintain the extracellular pool (plasma) from bone, kidney and intestine. Most animals are able to adapt through these homeostatic mechanisms.
 * <span style="background-color: transparent; color: #000000; font-family: serif; font-size: 13px; text-decoration: none; vertical-align: baseline;">An initial period of subclinical hypocalcaemia is fairly common, at the onset of lactation, just before or after parturition. Up to 50% of adult cows develop subclinical hypocalcaemia within the first few weeks of lactation. This simply means that there is a decline in calcium ion concentration in tissue fluids, because of the demand by the mammary gland, that is not restored in a normal timeframe by increased release of parathyroid hormone.
 * <span style="background-color: transparent; color: #000000; font-family: serif; font-size: 13px; text-decoration: none; vertical-align: baseline;">Prolonged release of parathyroid hormone increases intestinal absorption, renal reabsorption and bone resorption of calcium, and in most cases the hypocalcaemia remains subclinical during this ‘transient period’ until calcium balance can be restored by these homeostatic mechanisms.
 * <span style="background-color: transparent; color: #000000; font-family: serif; font-size: 13px; text-decoration: none; vertical-align: baseline;">However, sometimes a cow will not adapt and recover calcium balance. Anywhere between 5 and 20% of cows will develop milk fever, a severe metabolic disease, each year. It normally occurs within 12 to 24 hours of parturition, but can occur several weeks before or after, as well as unfortunate occurrences of relapse weeks after the start of lactation.
 * <span style="background-color: transparent; color: #000000; font-family: serif; font-size: 13px; text-decoration: none; vertical-align: baseline;">Also known as parturient or periparturient paresis, milk fever is hypocalcaemia serious enough to present clinical signs, or usually when plasma calcium levels are between 8 mg/dL and 6 mg/dL. In the most severe cases where clinical signs last several hours or more, plasma calcium concentrations are less than 5.5mg/dL. The animals that develop milk fever are unable to adapt to the increased demand for calcium, meaning that there is a serious failure of homeostasis. If allowed to proceed, the course of the disorder is swift and in several increasingly worse stages. Many will die if left untreated.

<span style="font-family: 'Times New Roman',Times,serif;">**<span style="background-color: transparent; color: #000000; font-size: 16px; text-decoration: none; vertical-align: baseline;">Clinical signs and pathology of disease **
 * <span style="background-color: transparent; color: #000000; font-family: serif; font-size: 13px; text-decoration: none; vertical-align: baseline;">Initially there are signs of anorexia, listlessness and muscle weakness leading to an awkward gait when walking. Body temperature usually declines as condition worsens, revealing the deceptive nature of the term milk fever, as fever is not a clinical symptom.
 * <span style="background-color: transparent; color: #000000; font-family: serif; font-size: 13px; text-decoration: none; vertical-align: baseline;">Soon the cow is likely to lie in sternal recumbency with its head pulled around to face its side, as muscles weaken further due to the lack of calcium required for muscle contraction. Calcium must be present for calcium channels to operate and for troponin-C molecules to form in muscle tissue, allowing muscle contraction. This also commonly results in ruminal atony and constipation due to a loss of smooth muscle contractile function. Bloat therefore is a related symptom.
 * <span style="font-family: 'Times New Roman',Times,serif; font-size: 10pt; line-height: 115%;">When the cow is no longer able to stand, the condition is known as ‘downer cow’.
 * <span style="font-family: 'Times New Roman',Times,serif; font-size: 10pt; line-height: 115%;">If the cow is parturient it can be a great threat to the calf as stasis of the muscles means that the birthing process is essentially suspended.
 * <span style="font-family: 'Times New Roman',Times,serif; font-size: 10pt; line-height: 115%;">A weak pulse can be detected at this stage of the decline, along with weak heart sounds and tachycardia. Heart muscle contractile function is compromised
 * <span style="font-family: 'Times New Roman',Times,serif; font-size: 10pt; line-height: 115%;">By the time the cow is almost losing consciousness, it is laterally recumbent with a temperature as low as 32°C (normal temp 38-38.5°C); it can appear dead at this latest stage of milk fever.
 * <span style="font-family: 'Times New Roman',Times,serif; font-size: 10pt; line-height: 115%;">Death can occur in a few to several hours, and is likely at a rate of 60-70% without treatment.
 * <span style="font-family: 'Times New Roman',Times,serif; font-size: 10pt; line-height: 115%;">Related conditions that affect cows that are suffering or have suffered milk fever are numerous and varied in cause. Complications are common.

<span style="font-family: 'Times New Roman',Times,serif;">**<span style="background-color: transparent; color: #000000; font-size: 16px; text-decoration: none; vertical-align: baseline;">Predisposing factors **
 * <span style="background-color: transparent; color: #000000; font-family: serif; font-size: 13px; text-decoration: none; vertical-align: baseline;">Age
 * <span style="background-color: transparent; color: #000000; font-family: serif; font-size: 13px; text-decoration: none; vertical-align: baseline;">Clinical hypocalcaemia is very rare in cows at first lactation, but the incidence increases considerably in cows in their third lactation and older. Studies have shown that younger animals have more efficient intestinal absorption mechanisms and can adapt more readily to low calcium diets by increasing this efficiency than older animals. This is likely explained by the studies showing that the intestinal receptors for 1,25-dihydroxyvitamin D decline in quantity with age. Older animals are also less able to mobilise calcium from bone, and have a greater milk production which has been shown to be positively correlated with risk of hypocalcaemia due to the greater demand for calcium.
 * <span style="background-color: transparent; color: #000000; font-family: serif; font-size: 13px; text-decoration: none; vertical-align: baseline;">Breed
 * <span style="background-color: transparent; color: #000000; font-family: serif; font-size: 13px; text-decoration: none; vertical-align: baseline;">Different studies have suggested that dairy cow breeds such as Channel Island, Swedish Red and White, and Jerseys are all more susceptible to milk fever than Holsteins in particular. One study showed that intestinal receptors for 1,25-dihydroxyvitamin D are around 15% less in Jerseys than Holsteins.
 * <span style="background-color: transparent; color: #000000; font-family: serif; font-size: 13px; text-decoration: none; vertical-align: baseline;">Metabolic alkalosis
 * <span style="background-color: transparent; color: #000000; font-family: serif; font-size: 13px; text-decoration: none; vertical-align: baseline;">This condition is mostly caused by a diet that supplies more cations (for example potassium K, sodium Na, calcium Ca and magnesium Mg) than anions (for example chloride Cl, sulphate SO₄ and phosphate PO₄), causing a difference in electrical charge in body fluids. Hydrogen ions, having a positive charge, must be lost to restore neutrality, leading to an increase in pH of the blood.
 * <span style="background-color: transparent; color: #000000; font-family: serif; font-size: 13px; text-decoration: none; vertical-align: baseline;">Metabolic alkalosis has been shown to blunt the homeostatic response of dairy cows to parathyroid hormone because it is believed that it causes a change in conformation of the parathyroid hormone receptor in all target tissues. This means bone calcium is not resorbed as efficiently and renal reabsorption of calcium is not as high. Active vitamin D formation by the kidneys is also inhibited so intestinal calcium absorption cannot be so effectively enhanced. Thus the cow cannot benefit from these homeostatic mechanisms and restore plasma calcium.
 * <span style="background-color: transparent; color: #000000; font-family: serif; font-size: 13px; text-decoration: none; vertical-align: baseline;">Hypomagnesaemia
 * <span style="background-color: transparent; color: #000000; font-family: serif; font-size: 13px; text-decoration: none; vertical-align: baseline;">This is attributed to development of hypocalcaemia as low levels of magnesium also interferes with the ability of parathyroid hormone to act on its target tissues, particularly in relation to magnesium’s action as a co-factor allowing parathyroid hormone to stimulate cyclic AMP production (necessary for operation of calcium channels).

<span style="font-family: 'Times New Roman',Times,serif;">**<span style="background-color: transparent; color: #000000; font-size: 16px; text-decoration: none; vertical-align: baseline;">Control (prevention) **


 * Prevention of hypocalcaemia, not just milk fever, should be a major goal of dairy farms.
 * To prevent hypocalcaemia it is necessary to reduce diet cations, in particular potassium and to increase diet anions, particularly chloride and sulfate.
 * This will induce a compensated metabolic acidosis in the cow restoring the ability of parathyroid hormone to regulate blood calcium levels.
 * In some cases diet potassium is so high and unavoidable that another tactic for prevention of hypocalcaemia may be considered.
 * If total absorbed diet calcium is substantially less than required by the cow it is possible to stimulate the secretion of parathyroid hormone before calving which can stimulate bone Ca resorption and intestinal Ca absorption mechanisms prior to calving to prevent milk fever.

<span style="font-family: 'Times New Roman',Times,serif;">**<span style="background-color: transparent; color: #000000; font-size: 16px; text-decoration: none; vertical-align: baseline;">Treatment **
 * <span style="font-family: 'Times New Roman',Times,serif; font-size: 10pt;">Treatment of milk fever and hypocalcaemia should be done as early as possible, especially if recumbency is present.
 * <span style="font-family: 'Times New Roman',Times,serif; font-size: 10pt;">The pressure exerted by the weight of the cow can cause a ‘crush syndrome’ eﬀect in as little as 4 hours, causing ischemia of the muscles and nerves followed by necrosis of these tissues resulting in the downer cow syndrome.
 * <span style="font-family: 'Times New Roman',Times,serif; font-size: 10pt;">The fastest way to restore normal plasma Ca concentration is to administer an IV injection of Ca salts (commonly Ca borogluconate).
 * <span style="font-family: 'Times New Roman',Times,serif; font-size: 10pt;">The most eﬀective IV Ca dose is about 2 g Ca/100 kg BW.
 * <span style="font-family: 'Times New Roman',Times,serif; font-size: 10pt;">A good rule of thumb is to administer the Ca at a rate of 1 g/min.
 * <span style="font-family: 'Times New Roman',Times,serif; font-size: 10pt;">If administered too rapidly, fatal arrhythmia of the heart and cessation during systole can occur.
 * <span style="font-family: 'Times New Roman',Times,serif; font-size: 10pt;">Intravenous Ca treatments elevate blood Ca above normal for about 4 hours.
 * <span style="font-family: 'Times New Roman',Times,serif; font-size: 10pt;">Calcium salts can also be injected subcutaneously, but absorption is variable since blood ﬂow to the periphery is often compromised.
 * <span style="font-family: 'Times New Roman',Times,serif; font-size: 10pt;">The amount of Ca that can be injected into a single subcutaneous site should be limited to 1–1.5 gCa (50–75 mL of most commercial preparations).
 * <span style="font-family: 'Times New Roman',Times,serif; font-size: 10pt;">Ca preparations designed for intramuscular administration are also available (Ca levulinate or Ca lactate).
 * <span style="font-family: 'Times New Roman',Times,serif; font-size: 10pt;">Most of these preparations must be limited to 0.5–1.0 g Ca/injection site to avoid tissue necrosis.
 * <span style="font-family: 'Times New Roman',Times,serif; font-size: 10pt;">To get an eﬀective dose of Ca into the clinically hypocalcaemic animal might therefore require 6–10 injections into widely separated spots.
 * <span style="font-family: 'Times New Roman',Times,serif; font-size: 10pt;">This can greatly impact meat quality in the site of injection and have therefore fallen out of favour.
 * <span style="font-family: 'Times New Roman',Times,serif; font-size: 10pt;">Oral Ca treatments are not recommended as treatments for clinical milk fever cases, though they can be eﬀective aids in prevention of milk fever.

<span style="font-family: 'Times New Roman',Times,serif; font-size: 14px; line-height: 21px;">**CONCLUSION**

<span style="font-family: 'Times New Roman',Times,serif; font-size: 110%;">**REFERENCES**

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<span style="display: block; height: 1px; left: -10000px; overflow-x: hidden; overflow-y: hidden; position: absolute; text-indent: -18pt; top: 2180px; width: 1px;"> · When the cow is no longer able to stand, the condition is known as ‘downer cow’. <span style="display: block; height: 1px; left: -10000px; overflow-x: hidden; overflow-y: hidden; position: absolute; text-indent: -18pt; top: 2180px; width: 1px;"> · If the cow is parturient it can be a great threat to the calf as stasis of the muscles means that the birthing process is essentially suspended. <span style="display: block; height: 1px; left: -10000px; overflow-x: hidden; overflow-y: hidden; position: absolute; text-indent: -18pt; top: 2180px; width: 1px;"> · A weak pulse can be detected at this stage of the decline, along with weak heart sounds and tachycardia. Heart muscle contractile function is compromised. <span style="display: block; height: 1px; left: -10000px; overflow-x: hidden; overflow-y: hidden; position: absolute; text-indent: -18pt; top: 2180px; width: 1px;"> · By the time the cow is almost losing consciousness, it is laterally recumbent with a temperature as low as 32°C (normal temp 38-38.5°C); it can appear dead at this latest stage of milk fever. <span style="display: block; height: 1px; left: -10000px; overflow-x: hidden; overflow-y: hidden; position: absolute; text-indent: -18pt; top: 2180px; width: 1px;"> · Death can occur in a few to several hours, and is likely at a rate of 60-70% without treatment. <span style="display: block; height: 1px; left: -10000px; overflow-x: hidden; overflow-y: hidden; position: absolute; text-indent: -18pt; top: 2180px; width: 1px;"> · Related conditions that affect cows that are suffering or have suffered milk fever are numerous and varied in cause. Complications are common.