Metabolic Diseases

CHAPTER

14

Metabolic Diseases Simon F. Peek and Thomas J. Divers

The common metabolic problems of early lactation, milk fever and ketosis, are really management diseases. At the herd level, disease does or does not occur as a function of how cows are fed and handled during the late dry period and during transition to the nutrientdense rations needed to support high milk production in early lactation. Because infectious diseases are more effectively controlled by sound immunization, the economic importance of these common metabolic disorders and their prevention by sound nutritional and herd management has assumed ever greater relevance on the modern dairy. Feeding management includes sources, storage, preparation, ration formulation, delivery, and access. Good feeding management must be coupled with providing an environment as comfortable as possible to facilitate maximal feed consumption. In investigating herd problems of excessive metabolic diseases, all these factors must be considered. Individual cows may be predisposed to metabolic problems as a result of improper body conditioning, concurrent illness, genetics, and any other events that may decrease dry matter intake. In addition to calcium, the other macrominerals of relevance in dairy cattle are potassium, magnesium, and phosphorous, and although disorders involving these elements are of far lesser importance than hypocalcemia, they will also be considered within this chapter.

KETOSIS: CAUSES, CLASSIFICATION, AND PATHOPHYSIOLOGY Ketosis occurs when cows are in negative energy balance. This most commonly happens in the last 2 weeks of pregnancy or in early lactation. In the last weeks of gestation hormonal factors and decreased rumen capacity may cause a decrease in nutrient intake and/or an increase in lipolysis. At parturition the major demand is that of milk production such that negative energy balance continues. Although the volume of milk production and lactose formation is the predominant demand for energy, there is also a secondary (or possibly primary in some cows) lipid demand for milk fat synthesis. It appears obvious to us that our ability to feed cows in 590

the 2 weeks before freshening to 4 weeks after calving has not kept up with our advancements in genetics for milk production. There are many categories of ketosis in cattle but most involve a similar pathophysiology of lipolysis, excessive release of nonesterified free fatty acids (NEFAs), inadequate hepatic metabolism of increased amounts of NEFAs (incomplete oxidation results in production of ketone bodies), increased fatty acid storage as triacylglycerols in the liver (kidney and muscle to a lesser extent), and, in some cows, decreased hepatic secretion of very low-density lipids (VLDLs). Certain cows with primary ketosis may be genetically predisposed to hepatic lipidosis because of their inability to properly remove triglycerides from the liver. Pregnancy toxemia is mostly related to an inability to meet energy requirements for fetal development. It is equally common in heifers as multiparous cows and may be predisposed to by twin fetuses. Transient secondary ketosis can be defined as a transient increase in plasma beta-hydroxybutyrate (BHB) caused by a decline in feed intake directly related to another disorder (e.g., left displacement of the abomasum [LDA]). Subclinical ketosis refers to “clinically normal” cows in the first weeks of lactation that have BHB values greater than 1400 ␮mol/L or 14.4 mg/dl. Clinical effects can be seen as excessive weight loss, decreased appetite and production, and diminished reproductive performance. Subclinical ketosis may be present in 30% to 50% of early lactation cows in some herds. Primary clinical ketosis will refer to ketosis in early lactation cows (usually between 1 and 3 weeks in milk, and most commonly in cows in their second to fourth lactation) that are seemingly well fed, in proper body condition before calving, and have no other medical illness. These cows often have BHB levels greater than 3000 ␮mol/L or 26 mg/dl. Fat cow/fatty liver syndrome refers to the overly conditioned cow that becomes ill just before or at parturition and suffers from marked anorexia, relapsing milk fever, retained placenta, myopathy, and sepsis. Hepatic lipidosis may take at least three forms: (1) clinically silent in subclinical ketosis, (2) chronic fat mobilization following early-onset periparturient ketosis

Chapter 14 • Metabolic Diseases with an individual susceptibility as a result of either genetics and/or periparturient overconditioning, and (3) periparturient ketosis in the obese cow with massive lipid accumulation in the liver within the first days of lactation.

Clinical Signs and Diagnosis of Ketosis Primary or spontaneous ketosis is most common in the first month of lactation, with the majority of cases occurring between 2 and 4 weeks of lactation. Cows with either ketosis early (first week) in lactation or cows with persistent ketosis beyond 4 weeks of lactation are most likely to have more marked hepatic lipidosis. Cows with primary ketosis have reduced feed intake of total mixed rations (TMRs) and may prefer forages over concentrates if ingredient fed. Temperature, pulse, and respiration are normal or occasionally subnormal. The rumen in TMR-fed cows will be reduced in volume, have a lower contraction frequency, and also typically have a small fiber mat. In ingredient-fed cows, the rumen may be normal in size but with a large, doughy fiber mat. It is common to hear the heartbeat while listening to the rumen of affected cows. Ketones may be detected in the breath, urine, or milk. Some sensitive individuals can easily recognize this odor. A urine test for acetoacetate is widely available and is the most sensitive test, although specificity is not as high as with milk ketone tests. A color change to purple indicates the presence of acetoacetate (Figure 14-1). The rate and intensity of change are indicative of acetoacetate concentration, but the urine acetoacetate test may be affected by the hydration status of the cow and the concentration of the urine. Many cows with primary ketosis give a strong purple color on the urine test, although the urine of individuals with hepatic lipidosis may only cause a lighter purple coloration. The manure is drier in consistency than herdmates

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at the same stage of lactation. Affected cows appear dull with a dry hair coat and piloerection. Neurological signs such as persistent licking at herself or objects, aggressive behavior, and unusual head carriage may be seen with nervous ketosis. The pathogenesis of nervous ketosis is unknown. Inability to rise or ataxia resulting from weakness may be seen in some cows with primary ketosis, and these signs are directly related to hypoglycemia. Metabolic acidosis may occur in some cows and, although unpredictable, can be severe (bicarbonate of as low as 12 mEq/L) in a few cows. Cows with secondary ketosis have clinical signs related to the primary disease (most often displaced abomasum). Except for metritis, ketosis is rare in cows with systemic disorders such as peritonitis, septic mastitis, and salmonellosis. The urine ketostrips will often be a light purple color with secondary ketosis but may be dark purple if the cow is dehydrated and the urine concentrated. Therapy should correct the primary problem, and the ketosis should then resolve. If the ketosis persists, primary ketosis may be present. A proportion of cows with abomasal displacements will have primary ketosis, which is not surprising because there is a proven association between the two disorders. If BHB is measured and gives a concentration of greater than 1400 ␮mol/L, this may indicate primary ketosis. Cows with persistent ketosis for 1 to 7 weeks usually have hepatic lipidosis. Ultrasound examination or biopsy of the liver (Figure 14-2) can be used to confirm hepatic lipidosis, but this is seldom required because the diagnosis is easy but treatment more difficult. Cows with chronic ketosis/fat mobilization and hepatic lipidosis lose considerable amounts of weight, have a poor appetite, but continue to produce moderate amounts of milk considering their poor feed intake (Figure 14-3).

Figure 14-2 Figure 14-1 Urine ketostrip with urine-positive reaction to acetoacetate from a cow with primary ketosis.

Drawing depicting site and method of liver biopsy in a cow. Neither liver biopsy nor ultrasound is required for diagnosis of hepatic lipidosis in most cows. The diagnosis is based mostly on history, clinical examination, and laboratory findings.

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Figure 14-3

Figure 14-4

A 4-year-old Holstein cow with chronic ketosis, chronic fat mobilization, weight loss, and hepatic lipidosis. The cow recovered after 3 weeks of medical treatments.

Severe hepatic lipidosis observed at necropsy. The liver was from a recently fresh and obese cow.

Affected cows may appear weak, which could be caused by hypoglycemia, muscle weakness from fatty accumulation in muscle, and/or hypokalemia. Some cows may die, be sold, or have complications caused by frequent treatment (e.g., phlebitis from glucose administration, oral trauma from forced feeding). Serum concentrations of hepatic-derived enzymes (aspartate aminotransferase [AST], gamma glutamyl transferase [GGT], and sorbitol dehydrogenase [SDH]) are often elevated, and serum cholesterol is frequently low in cows with hepatic lipidosis. However, these values are not consistently abnormal. Serum cholesterol generally returns toward normal value as the cow begins to eat better. Cows that are overconditioned before parturition and have periparturient ketosis (although a urine ketone test may be only weakly positive) rapidly develop hepatic lipidosis and have life-threatening illness (Figure 14-4). These cows have recurrent hypocalcemia and recumbency and, because of their heavy weight, often develop fatal myopathy (Figure 14-5). Most of these obese/ periparturient ketosis/hepatic lipidosis cows have retained placenta and may die of septic metritis even without a fetid smelling discharge (Figure 14-6). Their predisposition to sepsis with mild to moderate metritis may be caused by excessive fat deposition in the liver and diminished hepatic macrophage (Kupffer cells) function. Affected cows may also develop septic mastitis with repeated episodes of recumbency. Cows in late pregnancy may become ketotic. This usually occurs with multiple fetuses and is triggered by some other illness or external event that restricts access to feed. Early signs are identical to lactational ketosis. Without prompt treatment, the signs progress to extreme constipation followed by recumbency, renal failure, and death. Cows do not become blind as do sheep with pregnancy toxemia.

Figure 14-5 A large, overconditioned cow with ketosis and recurrent milk fever that resulted in a severe myopathy. The cow survived but required considerable therapy including flotation.

Treatment Treatment for ketosis is aimed at restoring energy metabolism to normal for milk production. The three most commonly used treatments are 500 ml of 50% dextrose given intravenously (IV) once or twice, glucocorticoid administration (e.g., 10 to 20 mg of dexamethasone once), and 300 ml of propylene glycol orally once or twice a day for 5 days. These treatments may be combined to suit the needs of the case and the abilities of the herdsman. The propylene glycol should be given as a drench and not mixed in the feed. Full recovery requires the return to normal feed intake, and supportive therapy may need to be continued for several days to allow time for the cow to maintain normoglycemia. Offering a choice of feedstuffs (i.e., brewer’s yeast) may

Chapter 14 • Metabolic Diseases

Figure 14-6 An overconditioned, fresh cow with ketosis that died of septic metritis. There was no obvious smell from the rear of the cow, and the metritis did not appear to be severe enough to make most cows systemically ill. The severe hepatic lipidosis most likely predisposed the cow to the fatal toxemia from a relatively moderate metritis.

help in restoring the cow’s appetite. Cows with nervous ketosis can be treated with chloral hydrate (40 g orally daily), which serves as both a sedative and as a substrate for glucogenic-producing bacteria. Cows with ketosis of pregnancy require more rapid intervention to prevent irreversible hepatic lipidosis and multiorgan failure. Induction of parturition or surgical delivery of the calves may be required. Intensive support of the cow with dextrose and force feeding is necessary. If therapy is discontinued in the first few days after parturition, these cows often have serious, sometimes fatal, relapses of ketosis within 48 hours. Cows with ketosis and hepatic lipidosis or “fatty liver disease” are challenging cases to treat. Cows with chronic fat mobilization and ketosis/hepatic lipidosis are often the “best cow in the herd” and produce a high milk volume. These cows do not get better overnight with any treatment and in fact may have already been treated with the above listed traditional therapy for ketosis for 1 to 3 weeks before veterinary attention is sought. Treatment should include continual 5% glucose administration in balanced electrolyte solutions with 40 mEq of KCl added per liter of fluid. Insulin (200 IU of zinc protamine, which can be purchased from compounding pharmacies) should be given subcutaneously (SQ) every 24 to 36 hours if a continuous glucose infusion is used. Insulin will promote glucose uptake in peripheral sites, which should inhibit lipolysis. Interestingly the mammary gland and brain of the dairy cow do not require insulin for glucose uptake. Another method of increasing insulin concentration is to give 250-ml boluses of glucose IV twice daily. An attempt should be made to prevent persistent hyperglycemia because this will cause

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excessive fluid loss in the urine and the hyperglycemia/ hyperinsulinemia may predispose to abomasal displacements. Niacin (12 g orally daily) will also inhibit lipolysis and is frequently administered daily to cows with chronic ketosis. Multi-B vitamins are commonly administered (slowly IV) on a daily basis. The most important treatment of cows with chronic fat mobilization and hepatic lipidosis is twice-daily forced feeding. Alfalfa meal, 4 oz of KCl, and rumen transfaunation from a healthy donor cow is our traditional gruel. If these treatments do not appear to be effective after 3 to 5 days, then it may be necessary to reduce the cows’ milk production by milking for 1 minute twice daily until the negative energy balance cycle is broken. Cows should test negative on the California mastitis test to qualify for the controlled milking. Usually the limited milking is required for 4 to 7 days before the ketosis is permanently resolved. We have performed this on many cows with chronic fat mobilization, and it, along with previously mentioned treatments, has been successful in all but one case. Additionally, owners have reported the milk production for the remainder of the lactation was very good. Although cows with chronic fat mobilization have delayed time of estrus and their production is diminished during the first 6 weeks of lactation, their prognosis for complete recovery is excellent. Time to recovery is variable, but most cows are well by 6 to 8 weeks into lactation. The most frequent complication associated with treatment of these cows is thrombophlebitis caused by multiple IV administrations of dextrose. Treatment of periparturient overweight cows with ketosis and hepatic lipidosis is intensive. Affected cows are administered IV fluids to combat hypotension and lactic acidosis. Glucose and calcium are often added to the fluids, although baseline blood glucose levels may be high in some of the cows. The cows should be force fed as described above and have only limited milk removed (if there is mastitis in a quarter, it should be stripped and intramammary antibiotics administered). Insulin therapy can be used as described previously for cows with chronic fat mobilization. Reduced neutrophil and hepatic macrophage function in these cows may allow septic conditions such as even mild metritis or mastitis to overwhelm the patient. Fresh feed, clean water, and salt should be available, and the cow should be housed in either a large well-bedded box stall with excellent footing or in a grass paddock. Along with sepsis, musculoskeletal injury is the most common reason for euthanasia of overweight cows with periparturient hepatic lipidosis. Every effort should be made to maintain calcium levels within normal limits by either slow continuous infusion or SQ administration; ideally ionized calcium should be closely monitored and the cow housed in an area that will provide the best comfort for standing up and lying down. If there has been any difficulty in rising, the cow should be administered flunixin

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meglumine (500 mg once or even twice daily if needed). The knees should be wrapped with soft cotton bandages to provide protection to the carpus area, which is often the first anatomical site to be adversely affected in cows that have difficulty rising. Although lipotropic medications such as choline and methionine are used by some clinicians for cattle with hepatic lipidosis, their value in the treatment probably is not significant. If lipotropic medications are used, rumen-protected choline is preferred. Electrolyte imbalances also should be addressed should laboratory facilities exist that allows easy assessment of these values.

Ketosis as a Herd Problem Ketosis can be considered a herd problem when more than an acceptable incidence occurs in the cows at greatest risk—that is, cows less than 6 weeks into lactation. The average incidence in early postpartum cows in a New York study of 35 herds was 15%. Most herd owners would agree that 20% of fresh cows with ketosis represent a herd problem. Dr. Gary Oetzel and colleagues at the University of Wisconsin use an alarm level of 10% for clinical ketosis in well-managed dairies. The underlying circumstances leading to herd level problems with ketosis are not fully understood in all situations, but some specific examples of predisposing causes are known. Ketosis and hepatic lipidosis are closely interrelated. Probably all cows with clinical ketosis have greater than physiological accumulation of lipid in hepatocytes. Some are more severely affected than others. Feeding strategies to prevent ketosis really are no more than generally recommended practices of nutrition and feed bunk management. In many herds with a high incidence of ketosis, the problems originate with nutritional mistakes during the dry period and especially in the “close up” cows, 1 to 2 weeks before calving. Normal cows undergo a shift in their energy metabolism and its regulation as parturition approaches. There is a decrease in lipogenesis and esterification and a simultaneous increase in hormone-sensitive lipase activity. The process is initiated by prolactin and precedes the onset of lactation. Insulin secretion declines in preparation for lactation. The mammary gland of the dairy cow does not require insulin for glucose uptake, and low insulin would result in greater amounts of glucose being used by the udder for milk/lactose production and less being used via peripheral sites. There is an increase in NEFAs. The normal cow in energy equilibrium will reesterify the serum NEFAs in the liver and resecrete them as VLDLs. When energy deficits occur and NEFAs are produced in excess of liver capacity for esterification, they are oxidized to ketone bodies. This pattern of regulation of energy metabolism may persist until about 8 weeks into lactation, when lipid synthesis is again promoted. The system is also sensi-

tive to “stress,” which through sympathomimetic pathways may lead to excessive lipid mobilization and hepatic fat accumulation. The dry matter intake (DMI) of a cow frequently declines by up to 20% in late gestation to the day before calving. This decline (often from 15 kg/day DMI to 12 kg/day or less for the adult Holstein) in intake is accompanied by an increasing rate of lipid mobilization from body fat stores. The serum concentration of NEFAs correspondingly increases. NEFA levels in cows destined to develop pathologic hepatic lipidosis, when measured in the prepartum period, are above those of normal cows at their peak in early lactation. When NEFAs are measured within 7 days of calving, they can be useful in predicting the incidence of ketosis and, to some extent, displaced abomasum and retained placenta. Ideally NEFA values would remain 0.5 mmol/L or less during this period. The week before calving is the proper time to be measuring NEFAs because their measurement in random cows can be used to determine whether energy balance in the late dry period may be responsible for a high incidence of ketosis in a herd. BHB should be used postcalving to determine level of ketosis, including subclinical, in a herd. Values greater than 1400 mmol/L suggest ketosis, and many of these cows, if monitored and traced back, were only ingesting 12 kg or less DMI the week before calving and had elevated NEFAs. Milk component testing has also been used to monitor energy consumption in lactating cows. A milk fat/milk protein ratio more than 1.5 is considered a risk factor for ketosis. This could imply the importance of the demand for NEFAs for milk fat production. Attempts to decrease milk fat production in early lactation could have beneficial effects in preventing ketosis as long as milk production were not further increased. Because all cows undergo physiological accumulation of lipid in the liver during the periparturient period, conditions that lead to excessive lipid mobilization are most likely to result in severe hepatic lipidosis and ketosis. Obesity or other diseases that restrict feed intake are both potential causes. Conversely, the force feeding via rumen fistula of the difference between intake at 3 weeks prepartum and voluntary intake until calving reduced the increase in liver triglyceride accumulation from 23% to 16%. Most data suggest that an attempt should be made to gradually increase nonfiber carbohydrates (NFCs) in the last 2 weeks of gestation in an attempt to increase dry matter intake and maintain a positive energy balance in the cow. An additional benefit is an increase in plasma insulin, which inhibits lipolysis. This increase in NFC (to between 34% and 36%) should be a gradual increase such that the cow will be continually increasing caloric intake into the first few days of lactation. Further restriction of intake in the late dry period when a decline normally occurs can be a herd problem. A separate feeding group has been recommended for the

Chapter 14 • Metabolic Diseases springing cows with a diet formulated to greater nutrient density than for early dry cows. Mismanagement of this group has occurred, leading to outbreaks of postpartum ketosis. Dr. Guard describes a herd with a ketosis problem that offered its close up cows an appropriate ration. There were 3 in of bunk space for 15 to 25 cows. The area in front of the bunk was a deep mudhole. In addition, there was an electric fence surrounding the bunk and strung across the top to prevent cows from stepping into the feed. Creating a new 20-m feed bunk away from mud and electricity appeared to solve the ketosis problem. Although unlikely under modern management practices, Dr. Guard also describes simple starvation resulting in death from hepatic failure of about half of the periparturient cows during a 4-week period in a 300-cow herd. The manager was so concerned about fat dry cows that intake was limited to 5 kg of poor quality grass hay. The dying cows were thin with body condition scores of 2 to 2.5, but had severe hepatic lipidosis. The late dry period is not a time to try to get cows to lose weight! Cows that lose condition during the dry period have higher rates of not only ketosis but also of abomasal displacements, milk fever, and metritis. Ketosis and hepatic lipidosis have been produced experimentally in lactating cows by restricting intake to 80% of recommended nutrients and infusing butanediol, a precursor of BHB. In this model, hepatic lipidosis preceded clinical ketosis. This is not surprising because fatty infiltration of the liver impairs gluconeogenic capacity of rumen-derived propionate and amino acids, which are the two major substrates (55% and 25%, respectively) for hepatic gluconeogenesis. Clinical signs were not apparent in the experimental cows until hypoglycemia developed. Long dry periods per se appear to put cows at increased risk for clinical ketosis whether obesity develops or not. Many individual cows with severe ketosis that may be refractory to routine treatments have been discovered to have preceding dry periods of 3 or more months. I have particularly noticed this to be common in cows used for embryo transfer. The pathophysiology of this phenomenon has not been described, but many practitioners have made the same observation. Body condition scores greater than 4.0 are known to increase the incidence of ketosis (see Appendix 1). Undersupply of protein during the dry period and, in particular during the last 3 weeks before calving, has been shown experimentally to predispose cows to ketosis. The treatment group in this study was supplemented with animal source protein to increase the bypass fraction and total crude protein intake. General discussion of this work with nutritionists has suggested that simply increasing the crude protein in the diet of close up dry cows probably has the same benefit as using the more expensive animal source ingredients. If diets higher in NFC are fed to the close up cows this would provide the

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opportunity to increase microbial protein yield. The minimum requirement for metabolizable protein for close up cows and heifers is 900 g/day. For lactation, this increases to at least 1100 g/day. Lysine and methionine should be adequate and balanced in the diet. Excess dietary protein in any form, but particularly nonprotein nitrogen or readily soluble protein, may lead to herd problems with ketosis. Several outbreaks of ketosis affecting animals in many stages of lactation have occurred following the on-farm experimental addition of urea to the diet. Urea has been added for reasons varying from incomplete digestion of the corn grain in corn silage to just trying something because cows were not milking as expected. In all known cases of urea feeding ketosis outbreaks, recovery was spontaneous when the urea was removed from the diet. Dr. Guard worked with a 200-cow herd that developed about a 50% prevalence of ketosis during grazing of alfalfa pastures. Corrective action included confining the cows to the barn 12 hours/day, during which corn silage was offered with 120 ml of propylene glycol added per cow. Niacin supplementation has undergone experimental evaluation as a possible means of ketosis prevention and has become popular in the management of individually valuable, overconditioned embryo transfer donor cows that have experienced protracted dry periods. In one study niacin was supplemented at 6 g/day to cows beginning 2 weeks prepartum and continued at 12 g/day postpartum for 12 weeks. Cows receiving extra niacin had higher blood glucose and lower blood BHB than controls. In a second experiment evaluating dose response, niacin was fed at 0, 3, 6, or 12 g/day for 10 weeks postpartum. There was no observable effect of feeding at the 3-g level. Cows receiving 6 or 12 g/day had slightly higher milk production and blood glucose than those receiving 0 or 3 g/day. Despite these observations, the feeding of niacin to prevent ketosis has not been widely used. Cost and the inconvenience of providing a feed ingredient only to early lactation cows have both contributed to the lack of adoption. The most effective periparturient use of niacin may be in herds with a high incidence of ketosis (clinical or subclinical) or in overconditioned periparturient cows. The use of ionophores in close up and lactating cow diets now provides a strong management tool for the prevention of ketosis. The action of these antibiotics is to reduce acetate production and enhance propionate production by rumen bacteria. Because propionate is converted to glucose by the liver, an increase in its supply would diminish the likelihood of hypoglycemia and excessive lipid mobilization from fat stores. Administration of monensin by rumen-controlled release during the periparturient period decreased the incidence of ketosis by 50% and decreased both BHB and NEFA concentrations during this period. Intraruminal controlled release capsules are more effective than when the monensin is added to the

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feed. In situations where monensin is fed within a ration if dry matter intake decreases, the concentration of monensin may be too low to have the needed effect on the rumen microorganisms. No discussion on prevention of ketosis would be complete without considering cow comfort. Adequate space for both feeding and some exercise is critically important for the periparturient cow. Additionally, proper space and environment for resting are critical if cows are expected to ruminate properly. During hot weather, misting and fans should be used to improve cow comfort and feed intake. Frequent pen moves during the late dry period should also be avoided because this has a negative impact on dry matter intake because cows repeatedly establish and reestablish their social hierarchy and familiarity with new surroundings.

HYPOCALCEMIA Pathophysiology The normal blood calcium concentration in adult cows is between 8.5 and 10 mg/dl, which translates into a total plasma pool of only about 3 g in a 600-kg individual. It is evident that to meet the calcium needs of colostrum production, fetal maturation, and incipient lactation at the end of gestation (collectively these requirements may reach 30 g/day), adult cows will need to mobilize substantial amounts of calcium from bone and increase the efficiency of gastrointestinal tract absorption. Intestinal absorption of calcium is heavily dependent on the production of 1,25-dihydroxyvitamin D3 by the kidney in response to parathormone (PTH) secretion. The third component of calcium homeostasis, namely, enhanced renal absorption of calcium, is quantitatively very small in terms of its contribution to increased calcium availability in the transitioning adult cow. Regulation of calcium homeostasis within plasma levels that maintain critical muscular, nervous, and other cellular functions is achieved through the action of PTH. The normal physiologic response to decreasing calcium levels is to produce PTH, which acts to increase osteoclastic bone resorption (direct PTH effect), increase intestinal absorption (via 1,25-dihydroxyvitamin D3), and enhance renal tubular resorption of calcium. PTH secretion is exquisitely sensitive to small decreases in plasma calcium, but the response can be blunted by hypomagnesemia, partly explaining the well-documented link between clinical hypomagnesemic tetany and hypocalcemia, even in nonlactating cattle. There are several other important factors that interfere with PTH activity at a tissue level that can serve to blunt the individual’s ability to respond efficiently to the increased demands of lactation, despite appropriate PTH secretion. Perhaps the most important factor, and one that has been the subject of a great deal of interest and research in recent years, is the role that acid-base status plays. Metabolic alkalosis predis-

poses to both milk fever and subclinical hypocalcemia principally because it interferes with skeletal calcium resorption and intestinal absorption by conformationally altering the PTH-receptor interaction at the tissue level. By altering this interaction, downstream signaling events that should result in increased plasma calcium do not occur despite PTH secretion. The first observations that dietary acidification could reduce the incidence of hypocalcemia by Ender and Dishington in 1971, and the subsequent exploitation of this paradigm by many researchers such as Oetzel and Goff, have led to the widespread practice of anionic salt supplementation to the diets of dry cows as a means by which milk fever and subclinical hypocalcemia rates can be reduced because of relative acidification of cattle in late gestation. It is worth noting that strong univalent cations, such as potassium and sodium, probably influence the development of milk fever via their alkalinizing effects and subsequent diminished tissue responsiveness to PTH, far more than does calcium in the diet during the late dry and early lactational period. Low calcium diets can theoretically be fed as a means of reducing milk fever incidence because prolonged exposure to high PTH levels can overcome the negative effects of alkalinization on tissue responsiveness; however, these prolonged and low calcium diets are impractical to formulate and deliver. A more detailed discussion on cation-anion diets and the manipulation of pH in the transition cow can be found in a later section in this chapter. There are other factors that contribute to the development of hypocalcemia in dairy cattle, specifically age, breed, and endocrinologic factors such estrogen levels. With increasing age there is a reduced pool of calcium available for absorption from bone as a result of diminishing numbers of bone cells, and this is a reason why heifers, in whom osteoblastic activity is high, do not suffer from clinical milk fever. A further age-related change is the reduction in PTH receptors in peripheral tissues of older cattle. It has long been observed by practitioners that the incidence of milk fever is higher in Jersey cattle than in Holsteins, and although the absolute explanation for this is uncertain, two factors that likely contribute to this breed predilection are the higher calcium concentration in colostrum and milk from Jerseys and the lower number of intestinal receptors for 1,25-dihydroxyvitamin D3 within the breed compared with Holsteins. Although estrogens increase predictably in the last few days of gestation and this hormone has a negative effect on calcium mobilization from bone, it does not appear to be a significant contributor to the incidence of milk fever nor the severity of hypocalcemia.

Clinical Signs Parturient hypocalcemia or milk fever may occur from about 24 hours before to 72 hours after parturition. The initial signs are restlessness, excitability, and anorexia.

Chapter 14 • Metabolic Diseases Many cows at this stage will protrude their tongue when stimulated around the head. This activity otherwise only occurs in cows as a displacement activity when they would rather kill you or run away but cannot. The ability to regulate core temperature is gradually lost. Therefore rectal temperature will be either high or low depending on ambient temperature. Cutaneous circulation is depressed, leading to cool extremities when the ambient temperature is less than 68.0° F/20.0° C. Rumen contractions will progress from weak to absent. Skeletal muscle weakness develops over several hours. Cows may stagger or fall but more commonly are found down and unable to rise. Heart rate increases during the development of hypocalcemia, yet cardiac output decreases as a result of reduced venous return and weaker cardiac muscle. Bloat occurs because of failure to eructate. Death may occur within 12 hours of the onset of signs caused by suffocation secondary to bloat or cardiovascular collapse. Historically texts have divided hypocalcemia into three stages, with stage 1 characterized by the cow still being able to stand, stage 2 by recumbency, and stage 3 by coma and unresponsiveness.

Treatment Parenteral administration of calcium borogluconate has been the most common treatment of hypocalcemia for many years worldwide. Concentrations of calcium, calcium salt formulations, and other elemental and carbohydrate components within the infusion solution vary widely according to personal preference and the perceived needs of the cow. There is no doubt that treatment with calcium borogluconate solutions IV or SQ leads to rapid recovery of skeletal muscle tone and smooth muscle function in the gastrointestinal tract. Cows often will eructate, defecate, or urinate during the IV administration of calcium, and many truly uncomplicated cases of stage 2 hypocalcemia are capable of standing before or shortly after the infusion is finished. Individuals with stage 3 hypocalcemia may take longer to generate the ability to stand unassisted but are still frequently able to stand within minutes of receiving IV calcium. Cattle that are recumbent on slippery surfaces such as concrete free stall alleys should be moved or slid to good footing. This procedure may help prevent exertional myopathy and other musculoskeletal injuries that are common to hypocalcemic cows that struggle to rise on slippery surfaces. Serum calcium concentration is normally between 8.5 and 10 mg/dl. The degree of hypocalcemia that develops at parturition is not perfectly correlated with the clinical signs. At a level of 7 mg/dl, most cows will be able to stand but have moderate bloat and anorexia. At a level of 5 mg/dl, most cows will be down. At levels less than 4 mg/dl, most cows will be comatose. A standard 500-ml bottle of 23% calcium borogluconate contains 10 g of calcium. A mature Holstein in good condition weighing

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700 kg will have about 210 L of extracellular fluid. If her calcium level is 5 mg/dl, her calcium deficit is 10.5 g. Thus one standard bottle of calcium will increase serum calcium to 10 mg/dl. Most practitioners will give all or part of a second bottle of calcium, perhaps giving it SQ, to provide extra calcium for anticipated ongoing losses. The heart rate normally decreases to some degree during infusion of IV calcium solutions to hypocalcemic cows. A sudden increase in heart rate or arrhythmia that develops during infusion may require slowing or stopping the infusion. Calcium solutions to be administered IV should be warmed to body temperature before administration. SQ treatment alone is inadequate for down cows because of the slow rate of absorption with impaired circulation. Oral gels and liquids have become increasingly available and utilized by producers for treatment and/or prevention of hypocalcemia. Among the simple calcium salts, only calcium chloride has proven to be adequately bioavailable for therapy of clinical milk fever. Liquid forms of calcium chloride, when given as a drench to down cows, tend to be highly caustic and have caused aspiration pneumonia and death. The use of oral calcium supplements requires functional swallowing reflexes to prevent these caustic materials from entering the trachea such that the severity of hypocalcemia and muscle weakness should be assessed in an individual before their use. Increasingly, calcium propionate has been incorporated into drench mixtures given to early lactation cows that are off feed. A total of 1.5 lb of calcium propionate administered orally provides approximately 140 g of calcium, whereas 1 lb provides approximately 90 g of calcium and calcium propionate has the advantage of also providing an energy source (propionate) and not being caustic. Evidence-based research suggests that the relapse rates and clinical response of true milk fever cases to oral calcium administration compare favorably with those seen with conventional IV therapy. However, personal clinician and farm experience often dictates that IV calcium administration is elected for the treatment of recumbent milk fever cases, but on many dairies, calcium administration to anorectic cows that may only be mildly hypocalcemic has moved completely to the oral route. In the majority of uncomplicated cases of milk fever, a single treatment is all that is required. Should relapse occur, consideration should be given to supplementing magnesium in addition to calcium. A convenient method for supplementing magnesium for an individual is to use magnesium hydroxide rumen laxative boluses or magnesium oxide for a few days after parturition. Excessive use may cause systemic alkalosis and decrease ionized calcium. Practitioners vary in their advice of complete milkout of mature cows at risk of milk fever. Partial milk removal may lessen the development of hypocalcemia. However, cows not fully milked out may leak milk and be predisposed to environmental mastitis.

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Part II • Diseases of Body Systems

MILK FEVER AS A HERD PROBLEM The 1996 and 2002 National Animal Health Monitoring System surveys document that the incidence of milk fever in dairy cows in the United States was 5.9% and 5.2%, respectively, for the 12-month periods preceding publication. When the incidence of milk fever exceeds 20% in mature cows, most veterinarians would agree that this is excessive and represents a herd problem. On wellmanaged dairies, the incidence of milk fever should not exceed 8% in mature cows, and I use this cutoff point as a herd alarm level at the University of Wisconsin. With the changing distribution of ages within modern dairying, such that the proportion of first-calf heifers is much higher on many dairies than was once customary, the relative parity distribution on a farm needs to be carefully considered when judging whether there is a problem with milk fever incidence on any given dairy. The most common age distribution of clinical cases of milk fever is twice the rate in third and greater lactations compared with second calvings and none in first calvings. The occurrence of milk fever is dependent on the nutritional management of cows during the dry period and, in particular, during the last 3 weeks before calving. If practitioners wish to investigate parturient hypocalcemia as a subclinical entity, I suggest sampling cattle of all ages about 12 to 24 hours after calving and using a cutoff of 30% as an alarm level for parturient hypocalcemia using adult cow reference values from the laboratory in question. Historically, maintaining calcium intake at less than 60 g/day and keeping the dietary calcium/phosphorus ratio at around 1.5:1 was thought to be adequate for prevention of milk fever, but we now know that simplistic approach to be flawed. The 2001 National Research Council (NRC) publication on nutrient requirements states that a 680-kg mature body weight dry cow at 270 days of gestation should receive 21.5 g of absorbable calcium (because absorption coefficients for most calcium-containing feed components are between 70% and 90%, the total calcium amount in the diet on an absolute weight basis is higher than the absorbable value given here), 20 g of phosphorus, 15 g of magnesium, and 52 g of potassium per day (these NRC guidelines are for a standard diet without anionic salt supplementation). These translate into concentrations of 0.45% Ca, 0.23% P, 0.12% Mg, and 0.52% K, respectively. Many diets formulated for dry cows with conventional forages and grains will exceed all minimum requirements except for magnesium. More recent experiences have illustrated that prevention of milk fever by following traditional nutritional guidelines is sometimes impossible to achieve because of high calcium forages and high cationic (particularly potassium containing), and therefore alkalinizing, transition diets. The maintenance of the late gestation dry cow in a state of mild metabolic acidosis by manipulation

of the inorganic cation-anion difference has empirically solved some herd problems with excessive cases of milk fever. This can best be achieved by feeding HCl containing SoyChlor (West Central, Ralston, IA) to the close up dry cows. The amount of the product fed (usually 2 to 3 lbs/cow/day) and its effectiveness can be easily monitored by checking urine pH. After 5 days of feeding this high-chloride supplement, the urine pH should be between 6.0 and 7.0 and it should be maintained at this level until parturition. Other nutritional advisors have approached herd problems by concentrating on the potassium/magnesium ratio in the dry cow diet to achieve similar results. The two common problems in formulating dry cow diets to achieve a low incidence of milk fever are the farm-specific necessity to feed legume forages, which are relatively high in calcium, and the increasingly higher concentrations of potassium in forages grown on soils either fertilized with potash or those with heavy applications of manure. The latter has become more significant as liquid manure systems have become the norm. Liquid manure storage and handling is considered environmentally sound because it prevents many soluble nutrients from escaping into surface water around the barnyard and is preferred as convenient and economical on large dairies. However, as dairies have expanded and become the sole business of many farmers, the animal units per crop acre have increased with subsequently more manure to dispose of per acre. This manure in liquid form provides more soluble nutrients for plant uptake and recycling to the cows. Oetzel reviewed the literature on diet and milk fever and found that the incidence was very low at daily calcium intakes of less than 50 g, increased with calcium intake up to about 120 g/day, and then declined at higher calcium intakes. This paradoxical relationship with calcium intake helped refute some of the earlier thinking about calciumintake restriction being of primary importance. In evaluating these experimental diets, the cation minus anion difference was calculated. Measured cations included sodium and potassium (calcium and magnesium); anions included chloride, sulfate, and phosphate. The incidence of milk fever increased as the sum of cations minus anions increased. The equation most predictive for the incidence of milk fever was (Na ⫹ K) ⫺ (Cl ⫹ S) expressed as milliequivalent per kilogram dry matter. Typical dry cow diets are ⫹100 to ⫹250. Further experiments to test this hypothesis of strong ion balance on calcium mobilization and activity have shown that, when the difference is manipulated around parturition, serum calcium homeostasis is altered. When cations minus anions was negative (around ⫺100) in prepartum diets, serum calcium was increased after calving relative to controls. Salts used to manipulate the diet of dry cows to achieve greater anionic content include ammonium chloride, ammonium sulfate, calcium sulfate (gypsum), and

Chapter 14 • Metabolic Diseases magnesium sulfate (Epsom salts). These salts are relatively expensive and unpalatable. Their successful use requires that they be fed in a blended diet such as a total mixed ration. Current costs for such diets are U.S. $0.30 to 0.40 per cow per day. Typically they are included in the diet of close up cows due to calve within 3 weeks. In herds without separate feeding facilities for this group, they may be fed throughout the dry period. Anionic salt feeding is discontinued at calving with the effect on serum calcium concentration persisting for a few days. There is a delayed rebound hypocalcemia following the discontinuation of anionic salt feeding. In most circumstances, this rebound occurs several days after calving when the dry matter intake of the cow is adequate to provide the calcium necessary to support the current milk production, and no clinical effects are seen. These salts have been mostly replaced by the feeding of SoyChlor (see the previous discussion on this product). Some herds have had disappointing to disastrous results with the now nearly outdated anionic salt supplementation. When such disasters occur, there are some commonplace explanations to consider. First, there is the possibility that supplementation has negatively affected palatability to the point where dry matter intakes have decreased significantly. Unfortunately it is not uncommon for overzealous anionic salt supplementation to be instituted in the face of a milk fever outbreak, with the undesirable effect that feed intake decreases dramatically and the metabolic problems on the dairy become confounded by negative energy balance peripartum and clinical ketosis. In addition, there is concurrence that anionic salt supplementation necessitates an increase in the amount of calcium in the diet of close up cows. For example, NRC guidelines specify that under conditions of anionic salt supplementation, the amount of absorbable calcium in the diet should be increased to at least 95 g/day (0.98%). Calcium intakes of up to 150 g/day or higher may be necessary in some cases of anionic salt supplementation to prevent milk fever. Occasionally high chloride content forages will overacidify the diet of transition cows and cause ruminal acidosis. Because the degree of dietary acidification will be ultimately related to urinary pH, measurement and monitoring of the latter are attractive tools for herd monitoring. Therefore the urine pH of dry cows has been suggested as a parameter to monitor or judge the effectiveness of any anionic salt program. Cows on unsupplemented diets typically have urine pH of 8 to 8.5. The pH may be as low as 5.5 with excessively heavy anionic salt or HCl acid supplementation. There are studies that suggest that dietary cation-anion difference (DCAD) and milk fever prevention is best served by a target urinary pH of between 6.0 and 7.0, although further research on this is warranted. Occasionally practitioners will encounter high urinary pH values (7.0 or higher) in a herd that is supposedly feeding anionic salts. In many

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instances, this situation will relate to high potassium content forages, and the solution will be either higher anionic salt supplementation or less high DCAD forages being fed. The role of high potassium intake (greater than 150 g/day) during the dry period has been linked to a high incidence of milk fever regardless of dietary calcium level. It is common to find no supplemental magnesium when investigating such herds. The interaction of potassium, magnesium, and calcium is not fully understood and may be separate from the strong ion effect discussed earlier. Potassium is the major cation in forages and cereal grains. The concentration of potassium in the rumen dictates the transruminal electrical potential. As the amount of ingested potassium increases, ruminal fluid potassium concentration also increases. This reciprocally decreases rumen sodium concentration. The observed transruminal electrical potential increases from about 5 to 60 mV as sodium is isotonically replaced by potassium. The primary site of magnesium absorption in ruminants is across the rumen epithelium via passive carrier-mediated transport. The rate of absorption is inversely related to the transmural potential. The presence of sodium in rumen fluid is not observed to be important to magnesium absorption because replacement of sodium with lithium has no effect on magnesium uptake. Thus high potassium intake also directly leads to decreased bioavailability of magnesium. Supplementing the diet of the dry cow with magnesium in the form of magnesium oxide to provide 1 g of magnesium for every 4 g of potassium up to a maximum of 65 g of magnesium per day has been successful in managing many herd milk fever problems. Alternatively, magnesium sulfate could be fed to address both the K/Mg ratio and the dietary cation-anion difference. Magnesium oxide and magnesium sulfate are relatively unpalatable and must be mixed with other feeds or salt to achieve the desired intake. Long-term success in feeding cows to minimize the incidence of milk fever and related magnesium deficiencies will be aided by better understanding of the potassium uptake by forage species. Most grasses and alfalfa respond with greater yields when soil potassium is plentiful. Manure storage systems to control environmental degradation return more potassium to the soil. As purchased grains and concentrates are brought to the farm, there is a net accumulation of potassium. As we inadvertently feed more and more potassium to our dry cows, the occurrence of fresh cow problems may be increasing. Anionic salt feeding should be viewed as a temporary solution to a milk fever problem. Other options in devising diets with a healthy balance of minerals are being developed. Land intentionally underfertilized with potash and not manured may be set aside for production of dry cow forages. Some dairy managers are purchasing feed from farms with historically low potassium supplementation and no manuring.

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HYPOPHOSPHATEMIA The clinical relevance of hypophosphatemia in high producing dairy cattle has long been a matter of conjecture and debate among practitioners and academics. Undoubtedly many veterinarians include phosphorus supplementation in either oral or IV form in their therapy of repeat milk fevers and persistently recumbent cattle, but convincing scientific evidence for hypophosphatemia as a contributor or absolute cause of recumbency is lacking. The normal reference range for plasma phosphorus is 5.6 to 6.5 mg/dl, and it is common for anorectic cattle to demonstrate blood levels below this reference range. Measurement of phosphorous levels in blood taken from the jugular vein routinely underestimates phosphorus obtained from the coccygeal vein by up to 0.8 mg/dl (Oetzel, Madison, WI, 2006, personal communication). Mild hypophosphatemia (between 2 and 4 mg/dl) is not associated with discernible clinical signs in the absence of other significant macroelement or electrolyte disturbances. Cattle with severe hypophosphatemia (plasma phosphorus ⬍1 mg/dl) may be recumbent, but the absolute relevance of their hypophosphatemia is clouded by the fact that such individuals are usually hypocalcemic, hypoglycemic, and hypomagnesemic. It should always be remembered that most cows with milk fever will also be hypophosphatemic (cows with plasma calcium ⬍5 mg/dl will typically have phosphorus values of ⬍2 mg/dl) and that IV treatment with calcium alone will be followed by normalization of blood phosphorus within a few hours.

Treatment Increasingly oral phosphorus supplementation has become an integral part of oral drenching solutions administered to nonrecumbent, but anorectic dairy cattle. The biologically active form of phosphorus is in the form of inorganic phosphate, and any attempts to therapeutically address real or perceived hypophosphatemia should reflect this. Sodium monophosphate is the preferred form of phosphorus supplementation either for oral or IV use. Sterile Fleet solutions are a good source of phosphorus and can be given subcutaneously or intravenously when diluted. Calcium or magnesium phosphate should not be given IV for fear of precipitation. Oral phosphorous supplementation can be given in the form of 200 to 250 g of sodium monophosphate (providing approximately 50 g of phosphate), usually combined with other drench components such as calcium, energy sources, and magnesium.

HYPOMAGNESEMIA Hypomagnesemia in dairy cattle very rarely assumes the severe clinical presentation with which veterinarians who work with pastured, spring-calving beef herds will be all too familiar. Normal plasma magnesium concentration

is in the range of 1.8 to 2.3 mg/dl, but it should be remembered that measured blood values are a poor indicator of whole body magnesium status for this predominantly intracellular cation. Initial muscle fasciculations, followed by hyperexcitability will be seen in cattle whose magnesium values decrease rapidly to 1.0 mg/dl or less, and untreated this will progress to convulsions, tetany, and death as levels decrease still lower. Unfortunately blood levels, particularly in advanced cases in which convulsions and tetany have led to significant muscle damage and subsequent leakage of magnesium out of cells, are an unreliable means of definitive diagnosis. Ocular fluids, urine and cerebrospinal fluid will more reliably determine the antemortem magnesium status of an animal found moribund, or if sampled within 12 hours of death. Magnesium absorption is reduced when the concentration of ammonia or ammonium is high in rumen fluid. The combined effect of a low magnesium and high nitrogen content in rapidly growing grass causes clinical signs of hypocalcemia and hypomagnesemia. The mechanism of high ammonia concentration leading to inhibition of magnesium absorption is not known. Dry cow diets based on ammoniated corn silage or the use of urea as the primary protein supplement may inadvertently lead to secondary magnesium deficiency. The clinical signs of affected cows are similar to milk fever rather than the classic grass tetany of hypomagnesemia. On rare occasions downer cows in early lactation may result if excess nonprotein nitrogen or soluble protein is fed without adequate magnesium supplementation. It is much more common to encounter milder hypomagnesemia (plasma levels of 1.3 to 1.8 mg/dl) in anorectic dairy cattle in early lactation, and such mild hypomagnesemia is frequently accompanied by mild hypophosphatemia and mild hypocalcemia. Severely hypomagnesemic cattle are also typically mildly to moderately hypocalcemic. The clinical relevance of low grade hypomagnesemia in lactating dairy cattle is hard to characterize; however, chronic, low magnesium levels are thought to limit productivity and predispose to hypocalcemia. Sampling of individual, anorectic cows for a herd issue with hypomagnesemia is of dubious value, but the demonstration of plasma magnesium levels of less than 2.0 mg/dl in the majority of cows sampled within 12 to 24 hours of freshening on a farm should be taken as a problem with magnesium availability or absorption in the transition diet. Similar testing can be performed on groups of cows in early lactation. Because dietary magnesium absorbed in excess of requirements for maintenance and lactation is excreted in urine, a useful measure of herd magnesium status is to evaluate urinary magnesiumcreatinine ratios for about 10 cows per group. This ratio corrects for the degree of water conservation by the kidney and better reflects magnesium status than does magnesium concentration alone. Guidelines for target values of this ratio have not been developed by North American laboratories as they have been in New Zealand.

Chapter 14 • Metabolic Diseases There, average values for a group of cows of less than 1.0 suggest that the cows are magnesium deficient (or would respond with less disease or more milk if magnesium were supplemented). Hypermagnesemia is rarely encountered, but when it is it usually suggests either compromised renal function or is an iatrogenic phenomenon resulting from the zealous administration of oral magnesium salts to off-feed cattle or both.

Treatment Treatment of cattle with hypomagnesemic grass tetany represents an emergency to save the animal’s life. Maniacal or convulsing cattle will occasionally first need to be sedated before parenteral administration of magnesium. Xylazine or barbiturates, depending on the severity of neurologic signs, can be used. IV magnesium administration is appropriate in such cases, but caution needs to be taken with regard to the speed of infusion because of its potential cardiotoxicity. Elevating serum magnesium from less than 1.0 mg/dl to within the normal reference range in a severely hypomagnesemic grass staggers case will require approximately 2 to 3 g of magnesium. If commercial solutions containing multiple macroelements such as calcium and phosphorus are used, the magnesium content of these should be checked before infusion to verify that there is adequate magnesium present. The infusion should be performed over at least 5 to 10 minutes. To prevent relapses over the next 12 to 24 hours, a further 250 ml of 20% magnesium sulfate solution can be administered SQ over at least four sites. It is appropriate to select infusion solutions that also contain calcium because many individuals will be concurrently hypocalcemic, and the relapse rate appears to be lower and the initial response rate greater in cattle that receive parenteral calcium also. Many practitioners will administer oral magnesium salts as further insurance against recurrence, but this requires that the animal has regained good protective upper airway reflexes and also runs the risk of overstimulation and a return to tetany if used prematurely in severe cases. Undoubtedly, however, oral magnesium supplementation is a safe and effective way to address less severe hypomagnesemia in cattle. Many drenches, commercial or home made, that are used as nonspecific supportive enteral fluid therapy in lactating cows now contain 200 to 250 g of magnesium sulfate. Repeated use of magnesium salts will result in catharsis and elevation of serum magnesium above the normal reference range; however, only IV magnesium administration represents a potentially acute cardiotoxic risk.

HYPOKALEMIA Potassium homeostasis is a complicated issue in the periparturient cow and one that is impacted by numerous factors including dry matter intake, concurrent metabolic

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disease, drug treatments, acid-base balance, and inability to accurately measure the intracellular K concentration, which is 98% of the total body potassium. Moderate, clinically occult hypokalemia is an anticipated electrolyte disturbance in cattle that are off-feed for any reason. Normal plasma potassium is between 3.8 and 5.6 mEq/L, and many cattle with common postparturient diseases such as metritis, LDA, or ketosis will have measured potassium values slightly below this range. Severely hypokalemic cows in which the plasma potassium has decreased to less than 2.5 mEq/L may demonstrate progressive weakness and become recumbent. Recumbency may be anticipated when the potassium level decreases to less than 2.0 mEq/ L. Typical premonitory signs of obvious muscle fasciculations and increased time lying down will have been noticed by the astute producer, but the progression to being recumbent and unable to stand can be measured in just a few hours. It should be emphasized, however, that severe hypokalemia is a rare cause of recumbency in dairy cattle compared with hypocalcemia or musculoskeletal and dystocia-related trauma. Previously there has been an observed link between the repeated use of the mixed glucocorticoid/mineralocorticoid isoflupredone acetate and the occurrence of the severe hypokalemia syndrome. Retrospective clinical observations have been validated by experimental reproduction of severe hypokalemia and weakness following multiple administrations of the drug. However, it has become evident in recent years that the condition can be seen in the absence of isoflupredone acetate administration. Consistent management and nutritional or other factors in herds experiencing this problem are uncertain; however, many affected cattle have a history of chronic refractory ketosis, or at least repeated treatments for presumed ketosis with a variety of agents that may induce hyperglycemia. Theoretically the repeated administration of hyperglycemia-inducing agents, such as 50% dextrose, propylene glycol, and glucocorticoids, will act to increase urinary loss and drive potassium intracellularly. This intracellular shifting may be exacerbated by the inevitable metabolic alkalosis that accompanies prolonged inappetence in cattle. Cattle with prolonged anorexia may also have whole body potassium depletion caused by inadequate intake in feed, coupled with continued obligate losses in urine and feces. Administration of any drugs with mineralocorticoid action will further exacerbate urinary losses. The clinical manifestation of severe hypokalemia is a flaccid paralysis (Figure 14-7, A and B) that resembles the profound weakness and flaccidity seen with botulism. Many affected animals are unable to even support the weight of their heads and hence are mistaken for more conventional milk fever cases, but fail to respond to usual calcium treatments and become downers. Aggressive oral treatment with potassium chloride appears to be as, if not more, effective than high volume potassiumsupplemented IV fluid administration in correcting the severe hypokalemia. Recommendations include oral administration of up to 0.5 lb of potassium chloride orally

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Part II • Diseases of Body Systems Because of the observed risk of worsening hypokalemia in cattle repeatedly treated for ketosis, it is prudent to consider lower level potassium supplementation to such individuals. Indeed, the inevitably of mild hypokalemia in association with anorexia in the postpartum cow has led to the inclusion of potassium supplementation by many practitioners to cows that receive oral fluids for whatever reason. Low level supplementation in the order of 60 to 125 g is well tolerated and safe when large volume orogastric fluids are administered.

A

SUGGESTED READINGS

B

Figure 14-7 A and B, Cow with severe hypokalemia and recumbency. The cow exhibited flaccid paralysis manifested as an inability to support the weight of the head or maintain herself in sternal recumbency.

twice daily to cattle with confirmed severe hypokalemia (⬍2.5 mEq/L) and weakness. Administration of such large amounts of potassium to cattle is inappropriate in all but the most severe hypokalemic states and will inevitably lead to catharsis in the following days. However, clinical experience suggests that recumbent individuals with severe hypokalemia do very poorly unless they regain the ability to stand within 24 to 48 hours of the onset of treatment. The use of devices such as slings, hip lifters, and flotation tanks should be considered, but severely hypokalemic cattle are potentially difficult to manage in flotation tanks as a result of their marked flaccidity.

Bertics SJ, Grummer RR, Cadorniga-Valino C, et al: Effect of prepartum dry matter intake on liver triglyceride concentration and early lactation, J Dairy Sci 75:1914-1922, 1992. Bobe G, Young JW, Beitz DC: Invited review: pathology, etiology, prevention, and treatment of fatty liver in dairy cows, J Dairy Sci 87:3105-3124, 2004. Carrier J, Stewart S, Godden S, et al: Evaluation and use of three cowside tests for detection of subclinical ketosis in early postpartum cows, J Dairy Sci 87:3725-3735, 2004. Coffer NJ, Frank N, Elliott SB, et al: Effects of dexamethasone and isoflupredone acetate on plasma potassium concentrations and other biochemical measurements in dairy cows in early lactation, Am J Vet Res 67:1244-1251, 2006. Curtis CR, Erb HN, Sniffen CJ, et al: Path analysis of dry period nutrition, postpartum metabolic and reproductive disorders, and mastitis in Holstein cows, J Dairy Sci 68:2347-2360, 1985. Dann HM, Morin DE, Bollero GA, et al: Prepartum intake, postpartum induction of ketosis, and periparturient disorders affect the metabolic status of dairy cows, J Dairy Sci 88:3249-3264, 2005. Drackley JK, Veenhuizen JJ, Richard MJ, et al: Metabolic changes in blood and liver of dairy cows during either feed restriction or administration of 1,3-butanediol, J Dairy Sci 74:4254-4264, 1991. Duffield TF: Monitoring strategies for metabolic disease in transition dairy cows. In Proceedings, World Buiatrics Congress, Quebec, Canada, pp. 34-35, 2004. Duffield TF, LeBlanc S, Bagg R, et al: Effect of a monensin controlled release capsule on metabolic parameters in transition dairy cows, J Dairy Sci 86:1171-1176, 2003. Dufva GS, Bartley EE, Dayton AD, et al: Effect of niacin supplementation on milk production and ketosis of dairy cattle, J Dairy Sci 66:2329-2336, 1983. Elcher R: Evaluation of the metabolic and nutritional situation in dairy herds: diagnostic use of milk components. In Proceedings, World Buiatrics Congress, Quebec, Canada, pp. 36-38, 2004. Ender F, Dishington IW, Helgebostad A: Calcium balance studies in dairy cows under experimental induction and prevention of hypocalcemic paresis puerperalis, Z Tierphysiol Tierernahr Futtermittelkd 28:233-256, 1971. Geishauser T, Leslie K, Kelton D, et al: Monitoring for subclinical ketosis in dairy herds, Comp Cont Educ 23:S65-S71, 2001. Gerloff BJ: Feeding the dry cow to avoid metabolic disease, Vet Clin North Am (Food Anim Pract) 4:379-390, 1988. Goff JP: Macromineral disorders of the transition cow, Vet Clin North Am Food Anim Pract 20:471-495, 2004. Goff JP: Major advances in our understanding of nutritional influences on bovine health, J Dairy Sci 89:1292-1301, 2006. Goff JP: Treatment of calcium, phosphorous and magnesium balance disorders, Vet Clin North Am Food Anim Pract 15:619-640, 1999. Hayirli A: The role of exogenous insulin in the complex of hepatic lipidosis and ketosis associated with resistance phenomenon in postpartum dairy cattle, Vet Res Commun 30:479-774, 2006. Head MJ, Rook JAF: Some effects of spring grass on rumen digestion and metabolism of the dairy cow, Proc Nutr Sec (Lond) 16:25-34, 1957.

Chapter 14 • Metabolic Diseases Holtenius P, Hjort P: Studies on the pathogenesis of fatty liver in cows, Bov Pract 25:91-94, 1990. Jenkins TC, Palmquist DL: Effects of fatty acids or calcium soaps on rumen and total nutrient digestibility of dairy rations (Holstein cows), J Dairy Sci 67:978-986, 1984. Kim IH, Suh GH: Effect of the amount of body conditions loss from the dry to near calving periods on the subsequent body condition change, occurrence of postpartum diseases, metabolic parameters and reproductive performance in Holstein dairy cows, Theriogenology 60:1445-1446, 2003. LeBlanc SJ, Lissemore KD, Kelton DF, et al: Major advances in disease prevention in dairy cattle, J Dairy Sci 89:1267-1279, 2006. Martens H, Blume I: Effect of intraruminal sodium and potassium concentrations and of the transmural potential difference on magnesium absorption from the temporarily isolated rumen of sheep, Q J Exp Physiol 71:409-415, 1986. Melendez P, Goff JP, Risco CA, et al: Incidence of subclinical ketosis in cows supplemented with a monensin controlled-release capsule in Holstein cattle, Florida, USA, Prev Vet Med 73:33-43, 2006. Moore SJ, VandeHaar MJ, Sharma BK, et al: Effects of altering dietary cation-anion difference on calcium and energy metabolism in peripartum cows, J Dairy Sci 83:2095-2104, 2000. Morrow DA, Hillman D, Dade AW, et al: Clinical investigation of a dairy herd with the fat cow syndrome, J Am Vet Med Assoc 174:161167, 1979. Oetzel GR: Meta-analysis of nutritional risk factors for milk fever in dairy cattle, J Dairy Sci 74:3900-3912, 1991. Oetzel GR: Monitoring and testing dairy herds for metabolic disease, Vet Clin North Am Food Anim Pract 20:651-674, 2004.

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Oetzel GR, Fetmian MJ, Hamar DW, et al: Screening of anionic salts for palatability, effects on acid-base status, and urinary calcium excretion in dairy cows, J Dairy Sci 74:965-971, 1991. Overton TR, Waldron MR, Smith KL: Transition cow management systems in the context of varied dry period length, Cornell Dairy Nutrition Conference, 2005. Peek SF, Divers TJ, Guard C, et al: Hypokalemia, muscle weakness and recumbency in dairy cattle, Vet Ther Res Appl Vet Med 1:235-244, 2000. Pinotti L, Baldi A, Politis I, et al: Rumen-protected choline administration to transition cows: effects on milk production and vitamin E status, J Vet Med A Physiol Pathol Clin Med 50:18-21, 2003. Pravettoni D, Doll K, Hummel M, et al: Insulin resistance and abomasal motility disorders in cows detected by use of abomasoduodenal electromyography after surgical correction of left displaced abomasum, Am J Vet Res 65:1319-1324, 2004. Rukkwamsuk T, Kruip TA, Wensing T: Relationship between overfeeding and overconditioning in the dry period and the problems of high producing dairy cows during the postparturient period, Vet Q 21:71-77, 1999. Sutherland RJ, Bell KC, McSporran KD, et al: A comparative study of diagnostic tests for the assessment of herd magnesium status in cattle, N Z Vet J 34:133-135, 1986. Vernon RG: Lipid metabolism during lactation: a review of adipose tissue-liver interactions and the development of fatty liver, J Dairy Res 72:460-469, 2005. West HJ: Liver function of dairy cows in late pregnancy and early lactation, Res Vet Sci 46:231-237, 1989.

APPENDIX

Body Condition Scoring*

BCS=1

BCS=2

BCS=4

BCS=3

BCS=5

*Courtesy of Elanco Products Company, A Division of Eli Lilly and Company, Lilly Corporate Center, Indianapolis, Indiana 46285, U.S.A.

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APPENDIX • Body Condition Scoring

605

BCS=1

BCS=2

BCS=3

Deep cavity around tailhead. Bones of pelvis and short ribs sharp and easily felt. No fatty tissue in pelvic or loin area. Deep depression in loin.

Shallow cavity around tailhead with some fatty tissue lining it and covering pin bones. Pelvis easily felt. Ends of short ribs feel rounded and upper surfaces can be felt with slight pressure. Depression visible in loin area.

No cavity around tailhead and fatty tissue easily felt over whole area. Pelvis can be felt with slight pressure. Thick layer of tissue covering top of short ribs, which can still be felt with pressure. Slight depression in loin area.

BCS=4

BCS=5

Folds of fatty tissue are seen around tailhead with patches of fat covering pin bones. Pelvis can be felt with firm pressure. Short ribs can no longer be felt. No depression in loin area.

Tailhead is buried in thick layer of fatty tissue. Pelvic bones cannot be felt even with firm pressure. Short ribs covered with thick layer of fatty tissue.