**2. Nutrition-related metabolic disorders, their etiology and consequences**

The most important metabolic diseases in dairy cows, ewes and goats can be discussed as energy and/or fiber related, lipid related or vitamin and mineral related disorders. However, they are not easily categorized according to their cause, thus the pathogenesis and hallmarks of each disease should be considered for their categorization. Energy related disorders (related to energy density of the diet or feed intake) include fatty liver and ketosis, rumen acidosis, laminitis, displaced abomasums and milk fat depression. As energy density and fiber content of the diets are often inversely related, most of these diseases can be considered as fiber related too. Fatty liver and ketosis also can be categorized as lipid related disorders due to changes in lipid metabolism in affected animals (Grummer, 1993). The most important mineral/vitamin related disorders are hypocalcaemia, hypomagnesaemia, udder edema, retained placenta and metritis. Not all of them are ultimately caused by mineral composition of the diet, but may be prevented by manipulation of minerals or vitamins in the diet. Broken homeostatic mechanisms often become major etiological factors in the

© 2012 Crnkic and Hodzic, licensee InTech. This is an open access chapter distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. © 2012 Crnkic and Hodzic, licensee InTech. This is a paper distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

development of metabolic disease, and consequences varies from reduced production and impaired reproductive performances to increased risk to develop other diseases.

## **2.1. Fatty liver**

Fatty liver (hepatic lipidosis, fat cow syndrome) is a metabolic disorder characterized by a high content of lipids and triglycerides in the liver (Ingvartsen, 2006). The disease occurs in periparturient period, primarily in the first 4 weeks after calving (Grummer, 1993), and as a secondary disease of other production diseases that depress appetite or increase body fat mobilization. The clinical symptoms comprise depression, lack of appetite and weight loss, and the cows are weak and apathetic (Radostits et al., 2000). Most cows suffer from nonspecific clinical signs including reduced rumen motility and decreased milk yield. However, this disease occurs especially in its subclinical form and can be a problem for up to 50% of cows in early lactation (Ingvartsen, 2006).

Risk factors for fatty liver in dairy cows may be nutritional, managerial, and genetic. Prepartum risk factors include obesity, severe feed restriction, feeding excess energy, and long calving interval. Postpartum risk factors are different diseases and infection, fasting and feed restriction, as well as ketogenic diets and sudden feed changes (Bobe et al., 2004). Among the highest risk factors of fatty liver is a high rate of mobilization of body lipids around calving in overconditioned cows which have been overfed in late lactation and the dry period and had low feed intake around calving (Ingvartsen, 2006). Increased prepartum body weight gain or body condition increase liver fat content and indicate increased risk of fatty liver and related disorders. Therefore, the primary nutritional risk factor for fatty liver is obesity. In obese cows, lipolysis of adipose tissue is increased more during peripartal period than in cows with normal body condition. Obese cows have a greater decrease in feed intake around calving and, therefore, have a more severe negative energy balance (Bobe et al., 2004). During the negative energy balance body fat is mobilized into the bloodstream in the form of non-esterified fatty acids (NEFA). NEFA are taken by the liver in proportion to their supply, but the liver does not have capacity sufficient to oxidize and use all amount of NEFA for energy. Therefore, cows are predisposed to accumulate NEFA as triglycerides within the liver when large amounts of NEFA are released from adipose tissue (Overton & Waldron, 2004). Rate of triglyceride synthesis is proportional to plasma NEFA concentration, thus fatty liver is likely to develop when plasma NEFA are elevated (Grummer, 1993).

Severe negative energy balance caused by low feed intake around calving leads to increase in body fat mobilization and plasma NEFA concentration. Thus, the severity of fatty liver may be reduced if drop in feed intake before calving is prevented (Bertics et al., 1992).

Diets deficient in cobalt (Co) have been shown to cause fatty liver in sheep. It has been termed as ovine white liver disease. Hepatic lipidosis in goats due to feeding low levels of Co in their diet has also been reported (Johnson et al., 2004).

Fatty liver is associated with decreased health status and reproductive performance. In severe cases, milk production and feed intake are also decreased (Bobe et al., 2004). Although fatty liver is often a reversible condition, it predisposes cows to reduced liver function and to a number of other production diseases (Ingvartsen, 2006). The incidence of fatty liver is strongly associated with the incidence of especially ketosis and displaced abomasum because these disorders are related to severe negative energy balance too (Bobe et al., 2004). Inhibition of gluconeogenesis may also occur when triglycerides accumulate in liver (Overton & Waldron, 2004) and additionally increase the risk for ketosis. Different aspects of the immune response are also suppressed in cows with fatty liver (Bobe et al., 2004; Overton & Waldron, 2004) and those animals are more prone to infectious diseases. However, the exact costs of fatty liver are difficult to estimate because condition can be diagnosed only by liver biopsy (Bobe et al., 2004).

## **2.2. Ketosis**

30 Milk Production – An Up-to-Date Overview of Animal Nutrition, Management and Health

**2.1. Fatty liver** 

(Grummer, 1993).

cows in early lactation (Ingvartsen, 2006).

impaired reproductive performances to increased risk to develop other diseases.

development of metabolic disease, and consequences varies from reduced production and

Fatty liver (hepatic lipidosis, fat cow syndrome) is a metabolic disorder characterized by a high content of lipids and triglycerides in the liver (Ingvartsen, 2006). The disease occurs in periparturient period, primarily in the first 4 weeks after calving (Grummer, 1993), and as a secondary disease of other production diseases that depress appetite or increase body fat mobilization. The clinical symptoms comprise depression, lack of appetite and weight loss, and the cows are weak and apathetic (Radostits et al., 2000). Most cows suffer from nonspecific clinical signs including reduced rumen motility and decreased milk yield. However, this disease occurs especially in its subclinical form and can be a problem for up to 50% of

Risk factors for fatty liver in dairy cows may be nutritional, managerial, and genetic. Prepartum risk factors include obesity, severe feed restriction, feeding excess energy, and long calving interval. Postpartum risk factors are different diseases and infection, fasting and feed restriction, as well as ketogenic diets and sudden feed changes (Bobe et al., 2004). Among the highest risk factors of fatty liver is a high rate of mobilization of body lipids around calving in overconditioned cows which have been overfed in late lactation and the dry period and had low feed intake around calving (Ingvartsen, 2006). Increased prepartum body weight gain or body condition increase liver fat content and indicate increased risk of fatty liver and related disorders. Therefore, the primary nutritional risk factor for fatty liver is obesity. In obese cows, lipolysis of adipose tissue is increased more during peripartal period than in cows with normal body condition. Obese cows have a greater decrease in feed intake around calving and, therefore, have a more severe negative energy balance (Bobe et al., 2004). During the negative energy balance body fat is mobilized into the bloodstream in the form of non-esterified fatty acids (NEFA). NEFA are taken by the liver in proportion to their supply, but the liver does not have capacity sufficient to oxidize and use all amount of NEFA for energy. Therefore, cows are predisposed to accumulate NEFA as triglycerides within the liver when large amounts of NEFA are released from adipose tissue (Overton & Waldron, 2004). Rate of triglyceride synthesis is proportional to plasma NEFA concentration, thus fatty liver is likely to develop when plasma NEFA are elevated

Severe negative energy balance caused by low feed intake around calving leads to increase in body fat mobilization and plasma NEFA concentration. Thus, the severity of fatty liver may be reduced if drop in feed intake before calving is prevented (Bertics et al., 1992).

Diets deficient in cobalt (Co) have been shown to cause fatty liver in sheep. It has been termed as ovine white liver disease. Hepatic lipidosis in goats due to feeding low levels of

Fatty liver is associated with decreased health status and reproductive performance. In severe cases, milk production and feed intake are also decreased (Bobe et al., 2004).

Co in their diet has also been reported (Johnson et al., 2004).

Ketosis (acetonemia) is a metabolic disorder characterized by elevated concentrations of the ketone bodies (acetoacetate, beta-hydroxybutyrate and acetone), and a low to normal concentration of glucose in the blood. This disorder occurs both subclinically and clinically. Prevalence of subclinical ketosis is the highest in the first 2 weeks of lactation ranging from 8,9% to 34% in various studies (Ingvartsen, 2006; Rushen et al., 2008). Blood glucose in clinically affected cows fall below the level required to support nerve and brain function and cows often exhibit signs of central nervous system dysfunction. Ketotic cows also suffer inappetence which further exacerbates the negative energy balance. Milk production falls seriously which helps the cow to cope with the negative energy balance (Goff, 2006a).

Four main types of ketosis are: primary ketosis, secondary ketosis, butyric acid ketosis and underfeeding ketosis (Ingvartsen, 2006). Classical or primary ketosis (also called spontaneous or production ketosis) generally occurs in cows during the first 2 to 4 weeks of lactation (Goff, 2006a). It develops when the glucose demand exceeds the gluconeogenesis capacity of the liver resulting in increased ketogenesis, and thus in high concentrations of ketone bodies in blood, milk, and urine. The disorder is mainly seen in obese cows. Secondary ketosis results from another disease that depresses feed intake and increases body fat mobilization (Ingvartsen, 2006).

Butyric acid ketosis is caused by large amounts of butyrate in the feed and probably by related depressed feed intake. Silage with high butyrate concentrations results in an increased concentration of beta-hydroxybutyrate in the blood, and such silage is consumed in lower amount then normal one. Underfeeding ketosis occurs especially in cows that are fed insufficiently. Underfed animals are deficient in glucogenic precursors and this condition then leads to increased ketogenesis (Ingvartsen, 2006).

Another form of ketosis often seen in US dairies usually occurs in cows less than 10 days in lactation. It can often be difficult to treat as is generally accompanied by some degree of fatty liver (ketosis/fatty liver complex). Ketosis, like fatty liver, also occurs during periods of elevated plasma NEFA. Clinical symptoms are similar to classical ketosis, but ketotic state was actually preceded by an increase in fat accumulation in the liver (Goff, 2006a).

Major factors directly or indirectly increasing the risk of fatty liver and ketosis are: overconditioning at calving, excessive mobilization of body fat, low nutrient intake, some nutrient or diet specific factors and management and environmental stress (Ingvartsen, 2006). Ketosis is a metabolic condition that occurs primarily when a cow is in negative energy balance immediately after calving. To support the energy demands, the body mobilizes fat reserves. Excessive release of NEFA from fat depots may overwhelm the capacity of the liver to use the fatty acids as a fuel. They are instead converted to ketone bodies (Rushen et al., 2008). Feed intake is naturally depressed by about 20% around the time of calving. Simultaneous with the feed intake depression, plasma NEFA and liver triglyceride concentrations exhibited their greatest increase (Goff, 2006a). All factors exacerbating negative energy balance and depression of feed intake around calving increase the risk of ketosis, especially in overconditioned cows.

Negative energy balance, high blood levels of NEFA or beta-hydroxybutirate and ketosis reduce the response capacity of white blood cells so that invading bacteria can out compete the immune system of the cow (Zadoks, 2006). Hypoglycemia alone is not likely to exacerbate periparturient immunosuppression, but hyperketonemia appears to have multiple negative effects on immune functions (Overton & Waldron, 2004). Impaired immune functions around calving make cow more prone to infectious diseases. Cows that have suffered ketosis have a higher risk of ketosis in the following lactation (Ingvartsen, 2006). Affected animals produce 0,7-3,3 kg/day less milk in the rest of lactation (Fourichon et al., 1999) or about 200 kg annually (Guard, 1996). In addition, prolonged and pronounced negative energy balance in early lactation adversely affects reproductive performance of cows and increases the risk of other metabolic diseases (Rushen et al., 2008).

Ewes experience ketosis typically during the last month of pregnancy and is known as pregnancy toxemia (Schlumbohm & Harmeyer, 2003). Ovine pregnancy toxemia (twin lamb disease, pregnancy disease) occurs primarily in ewes carrying more than one fetus (Andrews et al., 1996; Schlumbohm & Harmeyer, 2003). It is usually seen when the plane of nutrition has been static or falling over the last month of gestation when the requirements of the ewe are increasing to allow the growth of the fetuses (Andrews et al., 1996). In goats, two clinical form of ketosis have been described: pregnancy toxemia during the last month of pregnancy and primary ketosis during the first month of lactation (Stelletta et al., 2008).

Limitation of the availability of glucose has been found to be a crucial factor for the development of pregnancy toxemia. Hyperketonemia lowered plasma glucose concentration and depressed endogenous glucose production in sheep by approximately 30%, and this facilitates the onset of pregnancy toxemia (Schlumbohm & Harmeyer, 2003).

Mortality is high if pregnancy toxemia is not treated, with only about 20% of affected ewes recovering without treatment. Encephalopathy can results from depressed glucose metabolism in the brain (Andrews et al., 1996).

#### **2.3. Rumen acidosis**

Ruminal acidosis is a nutritional disorder of ruminants generally resulting from ingestion of large amounts of feeds rich in readily fermentable carbohydrates, particularly when animals have not been gradually acclimated to those feeds (Bramley et al., 2008). The disorder usually occurs in high-producing dairy cows. Subacute or subclinical ruminal acidosis (SARA) is considered to be one of the major threats to the welfare of lactating dairy cows and may affect up to 20% of cattle in early to mid lactation (Rushen et al., 2008). Subclinical rumen acidosis is defined as a condition where rumen fluid pH is below 6,0 while acute rumen acidosis is when rumen pH is below 5,5 associated with rumen motility that is weak or ceased (Ingvartsen, 2006).

Rumen acidosis classically occurs when an animal consumes the excess of grain (Stone, 2004). Fermentation of the high grain diet reduces rumen pH which can cause undesirable changes in microbial populations within the rumen (Goff, 2006a). Rumen pH is lowered due to large quantities of volatile fatty acids and lactic acid produced during grain fermentation (Bramley et al., 2008). Lactic acid production is not the hallmark of rumen acidosis in dairy cows, as observed in beef feedlot cattle. Instead, it is the total organic acid load induced by the high grain diet combined with the inability of the cow to buffer the acids with salivary secretions (Goff, 2006a; Stone, 2004). However, lactate accumulation may occur in cows after calving if the shift in fermentable carbohydrates between the diets fed before and after calving is too dramatic (Stone, 2004).

Low rumen pH can cause rumenitis, metabolic acidosis, lameness, hepatic abscesses formation, pneumonia, and even death (Bramley et al., 2008). Reduced ruminal efficiency, liver and lung abscesses, and laminitis all can be related to SARA (Stone, 2004).

## **2.4. Laminitis**

32 Milk Production – An Up-to-Date Overview of Animal Nutrition, Management and Health

the risk of ketosis, especially in overconditioned cows.

Major factors directly or indirectly increasing the risk of fatty liver and ketosis are: overconditioning at calving, excessive mobilization of body fat, low nutrient intake, some nutrient or diet specific factors and management and environmental stress (Ingvartsen, 2006). Ketosis is a metabolic condition that occurs primarily when a cow is in negative energy balance immediately after calving. To support the energy demands, the body mobilizes fat reserves. Excessive release of NEFA from fat depots may overwhelm the capacity of the liver to use the fatty acids as a fuel. They are instead converted to ketone bodies (Rushen et al., 2008). Feed intake is naturally depressed by about 20% around the time of calving. Simultaneous with the feed intake depression, plasma NEFA and liver triglyceride concentrations exhibited their greatest increase (Goff, 2006a). All factors exacerbating negative energy balance and depression of feed intake around calving increase

Negative energy balance, high blood levels of NEFA or beta-hydroxybutirate and ketosis reduce the response capacity of white blood cells so that invading bacteria can out compete the immune system of the cow (Zadoks, 2006). Hypoglycemia alone is not likely to exacerbate periparturient immunosuppression, but hyperketonemia appears to have multiple negative effects on immune functions (Overton & Waldron, 2004). Impaired immune functions around calving make cow more prone to infectious diseases. Cows that have suffered ketosis have a higher risk of ketosis in the following lactation (Ingvartsen, 2006). Affected animals produce 0,7-3,3 kg/day less milk in the rest of lactation (Fourichon et al., 1999) or about 200 kg annually (Guard, 1996). In addition, prolonged and pronounced negative energy balance in early lactation adversely affects reproductive performance of

Ewes experience ketosis typically during the last month of pregnancy and is known as pregnancy toxemia (Schlumbohm & Harmeyer, 2003). Ovine pregnancy toxemia (twin lamb disease, pregnancy disease) occurs primarily in ewes carrying more than one fetus (Andrews et al., 1996; Schlumbohm & Harmeyer, 2003). It is usually seen when the plane of nutrition has been static or falling over the last month of gestation when the requirements of the ewe are increasing to allow the growth of the fetuses (Andrews et al., 1996). In goats, two clinical form of ketosis have been described: pregnancy toxemia during the last month of pregnancy and primary ketosis during the first month of lactation (Stelletta et al., 2008). Limitation of the availability of glucose has been found to be a crucial factor for the development of pregnancy toxemia. Hyperketonemia lowered plasma glucose concentration and depressed endogenous glucose production in sheep by approximately 30%, and this

Mortality is high if pregnancy toxemia is not treated, with only about 20% of affected ewes recovering without treatment. Encephalopathy can results from depressed glucose

Ruminal acidosis is a nutritional disorder of ruminants generally resulting from ingestion of large amounts of feeds rich in readily fermentable carbohydrates, particularly when animals

cows and increases the risk of other metabolic diseases (Rushen et al., 2008).

facilitates the onset of pregnancy toxemia (Schlumbohm & Harmeyer, 2003).

metabolism in the brain (Andrews et al., 1996).

**2.3. Rumen acidosis** 

Laminitis and laminitis-related hoof problems (sole ulcer, white line abscess, solar hemorrhage, etc.) are one of the leading causes of lameness in cows. Laminitis has been associated with nutrition, and specifically with ruminal acidosis either in its acute or subacute form. Exact relationship between laminitis and SARA is not known. One of the theories states that damage of the ruminal epithelium induced by acidosis allows absorption of histamine and endotoxins into the blood. These and possibly other compounds affect circulation within the hoof and cause inflammation leading to the condition known as laminitis (Stone, 2004). Cows fed the higher level of crude protein may have increased incidence and duration of lameness. It is considered that products of degradation of protein excess in the rumen may be the causative agents for lameness.

It is widely accepted that nutrition helps maintain claw health through the production of good quality horn (Baird & Muelling, 2009). For example, heifers fed on hay before calving might have better foot health than those fed silage, even if both groups are being fed the same diets postpartum. Forage type and level of moisture in the diet could influence lameness and this effect is exerted even before first calving (Logue & Offer, 2001).

It has also been shown that nutritional supplements such as biotin and zinc (Zn) can help reduce lameness through improving claw horn quality (Baird & Muelling, 2009; Goff, 2006a). Biotin is essential for two major metabolic pathways in keratinisation, keratin protein synthesis and lipogenesis. Other vitamins also may play important roles in

maintaining claw integrity, including vitamin A and vitamin E. Zinc, as a component of many enzyme systems, has a role in major functions during keratinisation including the formation of structural proteins (Baird & Muelling, 2009). This element improves claw integrity by speeding wound healing and epithelial tissue repair. Other trace minerals that impact claw condition include iodine (I), selenium (Se), copper (Cu), manganese (Mn) and Co. Calcium and phosphorus (P) are also needed for normal claw growth and integrity.

Laminitis reduces profitability of the dairy herd. It is estimated that 15% of cows culled for slaughter are culled due to laminitis. In clinically lame cows, milk yield was reduced from 4 months before and for the 5 months after treatment. The total mean estimated reduction in milk yield per lactation was approximately 360 kg (Green et al., 2002).

## **2.5. Displaced abomasum**

Displaced abomasum is a multifactorial disease where the abomasum is dilated as a result of gas accumulation and dislocated to the left (left-displaced abomasum) or to the right (rightdisplaced abomasum) in the stomach in relation to the normal placing (Ingvartsen, 2006). The passage of feed to the intestines is partly or totally blocked. Approximately 80-90% of the incidences are left-displaced abomasums. The disease is most frequent in high producing cows in early lactation and 80–90% of the cases are seen in the first 4 weeks postpartum (Shaver, 1997). It occurs in approximately 3,5% of dairy cows each year (Goff, 2006a).

Nutrition has been implicated as a major risk factor in the etiology of displaced abomasums, but the precise cause is still unclear. Low feed intake and increased negative energy balance prepartum have been found to increase the risk of displaced abomasums in cows (Goff, 2006a; Ingvartsen, 2006). Cows fed high concentrate diets in early lactation or diets with inadequate particle size are also at increased risk of displaced abomasums (Goff, 2006a). Sudden changes in the diet and rapid increase in concentrate allowance in early lactation are also the risk factors. Some feeds increase the risk of the disease compared to others. Thus, a higher risk of displaced abomasum has been found for cows fed silage compared to those fed hay, probably because silage is often finely chopped. Risk can be almost eliminated if cow eats a kilogram of straw daily (Ingvartsen, 2006).

Displaced abomasum develops if three major conditions are met. The first one is reduced contractility and atony of abomasum which is gas-dilated. The next condition is that the mesentery shall stretch for the abomasum to be able to dislocate, and a third condition is the space in the abdominal cavity (Ingvartsen, 2006). The conditions leading to atony and reduced motility are still unclear, but hypocalcaemia around calving is a possible factor. Reduction in blood Ca concentration around calving results in a reduction of abomasal contractility, which can lead to its atony and dilatation (Shaver, 1997). Hypocalcemic cows after calving have 3,4 to 4,8 times increased risk of development of abomasal displacement (Massey et al., 1993).

Volatile fatty acids (VFA) in the abomasum also have been reported to reduce abomasal motility. Effects of VFA on motility may be exacerbated by low ruminal absorption of VFA during the transition period (Shaver, 1997). Hypocalcaemia also may play a role in this process. Due to reduced feed consumption, slow contractions and inadequate filling of the rumen which therefore does not reach the ventral abdominal wall, empty space appears for movement of abomasum. Then usually more fatty acids escape absorption in the rumen and reach the abomasum. Those VFA, along with hypocalcaemia and accumulated gases, contribute to reducing abomasum contractility and development of atony (Goff & Horst, 1997c). Thus, inadequate feed consumption and insufficient rumen fill with reduced motility and strength of abomasal contractions together contribute to the onset of this disorder (Goff & Horst, 1997c).

Low intake of concentrates during the prepartum period also may increase the risk of left displaced abomasum because absorptive capacity of the ruminal papillae is not increased sufficiently and microbial population of the rumen is not adapted prior to intake of high energy postpartum diets (Shaver, 1997). Too rapid increase of concentrates after calving may reduce roughage intake and potentially increase the risk of displaced abomasum (Ingvartsen, 2006). Uncomplicated ketosis, fatty liver, retained placenta, and metritis are also risk factors for left displaced abomasums (Bobe et al., 2004; Shaver, 1997).

Treatment of displaced abomasum often requires surgical treatment, and deaths are not uncommon so that potential losses due to disease are very high. In addition, cows that recover from abomasal displacement produce about 350 kg less milk during the next month (Shaver, 1997) or 0,8-2,5 kg/day in the rest of lactation (Fourichon et al., 1999). According to Guard (1996) the average losses amounted to about 380 kg of milk annually.

## **2.6. Milk fat depression**

34 Milk Production – An Up-to-Date Overview of Animal Nutrition, Management and Health

milk yield per lactation was approximately 360 kg (Green et al., 2002).

1997). It occurs in approximately 3,5% of dairy cows each year (Goff, 2006a).

cow eats a kilogram of straw daily (Ingvartsen, 2006).

**2.5. Displaced abomasum** 

(Massey et al., 1993).

maintaining claw integrity, including vitamin A and vitamin E. Zinc, as a component of many enzyme systems, has a role in major functions during keratinisation including the formation of structural proteins (Baird & Muelling, 2009). This element improves claw integrity by speeding wound healing and epithelial tissue repair. Other trace minerals that impact claw condition include iodine (I), selenium (Se), copper (Cu), manganese (Mn) and Co. Calcium and phosphorus (P) are also needed for normal claw growth and integrity.

Laminitis reduces profitability of the dairy herd. It is estimated that 15% of cows culled for slaughter are culled due to laminitis. In clinically lame cows, milk yield was reduced from 4 months before and for the 5 months after treatment. The total mean estimated reduction in

Displaced abomasum is a multifactorial disease where the abomasum is dilated as a result of gas accumulation and dislocated to the left (left-displaced abomasum) or to the right (rightdisplaced abomasum) in the stomach in relation to the normal placing (Ingvartsen, 2006). The passage of feed to the intestines is partly or totally blocked. Approximately 80-90% of the incidences are left-displaced abomasums. The disease is most frequent in high producing cows in early lactation and 80–90% of the cases are seen in the first 4 weeks postpartum (Shaver,

Nutrition has been implicated as a major risk factor in the etiology of displaced abomasums, but the precise cause is still unclear. Low feed intake and increased negative energy balance prepartum have been found to increase the risk of displaced abomasums in cows (Goff, 2006a; Ingvartsen, 2006). Cows fed high concentrate diets in early lactation or diets with inadequate particle size are also at increased risk of displaced abomasums (Goff, 2006a). Sudden changes in the diet and rapid increase in concentrate allowance in early lactation are also the risk factors. Some feeds increase the risk of the disease compared to others. Thus, a higher risk of displaced abomasum has been found for cows fed silage compared to those fed hay, probably because silage is often finely chopped. Risk can be almost eliminated if

Displaced abomasum develops if three major conditions are met. The first one is reduced contractility and atony of abomasum which is gas-dilated. The next condition is that the mesentery shall stretch for the abomasum to be able to dislocate, and a third condition is the space in the abdominal cavity (Ingvartsen, 2006). The conditions leading to atony and reduced motility are still unclear, but hypocalcaemia around calving is a possible factor. Reduction in blood Ca concentration around calving results in a reduction of abomasal contractility, which can lead to its atony and dilatation (Shaver, 1997). Hypocalcemic cows after calving have 3,4 to 4,8 times increased risk of development of abomasal displacement

Volatile fatty acids (VFA) in the abomasum also have been reported to reduce abomasal motility. Effects of VFA on motility may be exacerbated by low ruminal absorption of VFA Nutrition influences both the quantity and composition of milk fat. In modern dairy production cows are fed diets with high level of concentrates to maximize milk production but such diets often causes drop in milk fat. Condition is known as milk fat depression (MFD) or low-fat milk syndrome. Although milk volume and yield of other milk constituents may not be affected or may be even increased, depression of fat in milk can be a serious economic problem for dairy producers. This syndrome is not a disease, but rather metabolic consequence of attempts to reach the higher milk production in animals.

Milk fat depression refers to a marked reduction in milk fat yield with no change in milk yield or yield of other milk components (Harvatine et al., 2009). It represents a level of milk fat production below the genetic potential of the cow, usually as below 3,2% fat in milk for Holstein, or below 4,2% fat in the milk for a Jersey herd. When problem with MFD exists, the ratio of milk fat/milk protein will be less than 1,0 for Holstein herds. In severe cases the ratio will be less than 0,8. Milk fat yield can be reduced up to 50% and the effect is specific for milk fat (Bauman et al., 2008). The problem has been observed in many feeding situations and dietary conditions, including high level of concentrates and low level of dietary fiber, and diets supplemented with unsaturated oils. The fat content of milk can also be affected by the physical characteristics of the roughage, including grinding and pelleting (Perfield & Bauman, 2005). In diet-induced MFD, the yield of all individual fatty acids is reduced, but the decline is greatest for short- and medium-chain fatty acids that are synthesized *de novo* in mammary gland (Bauman et al., 2008).

It is generally accepted that induction of MFD requires both an altered rumen environment and the presence of unsaturated fat in the rumen which biohydrogenation pathways are altered (Perfield & Bauman, 2005). Changes in ruminal microbial processes are an essential component for the development of MFD and are often associated with a decrease in rumen pH and a shift in the acetate/propionate ratio.

Historically, there have been several theories proposed to explain the basis for diet-induced MFD. The biohydrogenation theory was proposed by Bauman & Griinari (2001) focusing on the latest research in MFD problem. The authors sugested that "under certain dietary conditions the pathways of rumen biohydrogenation are altered to produce unique fatty acid intermediates which are potent inhibitors of milk fat synthesis". The theory was born after identification of *trans*-10,*cis*-12 conjugated linoleic acid (CLA) as a highly potent inhibitor of milk fat synthesis (Bauman & Griinari, 2001). This isomer is a rumen precursor of t*rans*-10 18:1 in biohydrogenation pathway that may arise under certain dietary conditions, including high concentrate/low fiber diets. The biohydrogenation of linoleic acid in rumen involves the formation of *trans*-11 18:1 and *cis*-9,*trans*-11 CLA as the main intermediates. However, under certain dietary situations the other pathways of biohydrogenation can happen and some of the intermediates produced during the process may be potent inhibitors of milk fat synthesis (Bauman & Griinari, 2001). The most extensively studied is *trans*-10,*cis*-12 CLA. Minimal quantities of this isomer markedly inhibited milk fat synthesis and a curvilinear reduction in milk fat yield occurred with increasing *trans*-10,*cis*-12 CLA in the rumen content (Baumgard et al., 2001).

Isomer *trans*-10,*cis*-12 CLA alone does not completely explain the extent of the decrease in milk fat. Additional biohydrogenation intermediates produced in the rumen probably inhibit milk fat synthesis and two of them (*trans*-9,*cis*-11 and *cis*-10,*trans*-12 CLA) have already been identified (Bauman et al., 2008).

Consequences of MFD are almost exclusively related to losses in yield of milk fat and lower price of milk. As problem is normally reversible, health consequences are usually not a matter of concern. However, MFD inducing diet is usually risky for rumen homeostasis due to high level of carbohydrates and low level of effective fiber which may reduce ruminal pH and cause acidosis (Bergen, 2009). If acidosis is not compensated and drop in ruminal pH is not prevented, the condition may become an important animal health issue.

## **2.7. Parturient hypocalcaemia**

The lack of Ca in the diet does not lead to any changes in health or production for a long time because it is compensated by mobilization of Ca reserves in the skeleton. The change of Ca content in the blood may not occur until the cows show symptoms of osteoporosis and bone fractures. A unique example, however, is an acute hypocalcaemia in dairy cows that occurs in the periparturient period as a result of sudden loss of great amounts of Ca in colostrum along with temporary dysfunction of the mechanisms of Ca mobilization from bones. From a relative inactivity in the dry period, these mechanisms often fail to achieve full activity quickly enough to maintain normocalcaemia around calving (Horst et al., 1994). More pronounced hypocalcaemia causes progressive neuromuscular dysfunction which is manifested as a specific clinical syndrome known as paresis puerperalis (milk fever, parturient paresis, calving paralysis). More often, however, and in a larger number of cows, hypocalcaemia exists in a subclinical form with very few or no symptoms (subclinical hypocalcaemia).

36 Milk Production – An Up-to-Date Overview of Animal Nutrition, Management and Health

synthesized *de novo* in mammary gland (Bauman et al., 2008).

pH and a shift in the acetate/propionate ratio.

already been identified (Bauman et al., 2008).

**2.7. Parturient hypocalcaemia** 

reduced, but the decline is greatest for short- and medium-chain fatty acids that are

It is generally accepted that induction of MFD requires both an altered rumen environment and the presence of unsaturated fat in the rumen which biohydrogenation pathways are altered (Perfield & Bauman, 2005). Changes in ruminal microbial processes are an essential component for the development of MFD and are often associated with a decrease in rumen

Historically, there have been several theories proposed to explain the basis for diet-induced MFD. The biohydrogenation theory was proposed by Bauman & Griinari (2001) focusing on the latest research in MFD problem. The authors sugested that "under certain dietary conditions the pathways of rumen biohydrogenation are altered to produce unique fatty acid intermediates which are potent inhibitors of milk fat synthesis". The theory was born after identification of *trans*-10,*cis*-12 conjugated linoleic acid (CLA) as a highly potent inhibitor of milk fat synthesis (Bauman & Griinari, 2001). This isomer is a rumen precursor of t*rans*-10 18:1 in biohydrogenation pathway that may arise under certain dietary conditions, including high concentrate/low fiber diets. The biohydrogenation of linoleic acid in rumen involves the formation of *trans*-11 18:1 and *cis*-9,*trans*-11 CLA as the main intermediates. However, under certain dietary situations the other pathways of biohydrogenation can happen and some of the intermediates produced during the process may be potent inhibitors of milk fat synthesis (Bauman & Griinari, 2001). The most extensively studied is *trans*-10,*cis*-12 CLA. Minimal quantities of this isomer markedly inhibited milk fat synthesis and a curvilinear reduction in milk fat yield occurred with

increasing *trans*-10,*cis*-12 CLA in the rumen content (Baumgard et al., 2001).

not prevented, the condition may become an important animal health issue.

Isomer *trans*-10,*cis*-12 CLA alone does not completely explain the extent of the decrease in milk fat. Additional biohydrogenation intermediates produced in the rumen probably inhibit milk fat synthesis and two of them (*trans*-9,*cis*-11 and *cis*-10,*trans*-12 CLA) have

Consequences of MFD are almost exclusively related to losses in yield of milk fat and lower price of milk. As problem is normally reversible, health consequences are usually not a matter of concern. However, MFD inducing diet is usually risky for rumen homeostasis due to high level of carbohydrates and low level of effective fiber which may reduce ruminal pH and cause acidosis (Bergen, 2009). If acidosis is not compensated and drop in ruminal pH is

The lack of Ca in the diet does not lead to any changes in health or production for a long time because it is compensated by mobilization of Ca reserves in the skeleton. The change of Ca content in the blood may not occur until the cows show symptoms of osteoporosis and bone fractures. A unique example, however, is an acute hypocalcaemia in dairy cows that occurs in the periparturient period as a result of sudden loss of great amounts of Ca in Hypocalcaemia was defined as the content of total Ca in blood below 2 mmol/L with or without clinical signs of paresis (Oetzel et al., 1988; Radostits et al., 2000), which is roughly equivalent to 1 mmol/L of ionized Ca (Massey et al., 1993; Oetzel, 1996).

Milk fever (MF) is non-febrile disease of adult dairy cows accompanied by general weakness, circulatory collapse and depression of sensation (Oetzel, 1988). It is one of the most common metabolic disorders in intensive dairy production (Horst, 1986) and a typical nutritional disorder (Ender et al., 1971). The disease attacks 5-10% of adult dairy cows in the U.S. and Europe annually, primarily those with high productivity. The classic syndrome of MF occurs immediately before or after parturition with about 87% of cases in the first 48 hours after calving and only about 9% cases before or during the parturition (Oetzel, 1988). The disease is characterized by pronounced hypocalcaemia which is accompanied by hypophosphataemia in most cases, and by more or less serious hypermagnesaemia (Phillippo et al., 1994).

Phenomena like paresis may rarely occur in beef cows, ewes (before or after lambing) and more frequently in dairy goats (Oetzel, 1988). In mares, the disease can occur several weeks after birth and is known as milk tetany or eclampsia (Radostits et al., 2000).

Milk fever has been recognized as a nutritional disorder with various endocrine abnormalities which occur more or less as a secondary phenomenon (Ender et al., 1971). The characteristic of the disease is an acute inability to mobilize Ca from bone (Horst, 1986) despite apparently normal endocrine dynamics in most affected cows (Radostits et al., 2000). The problem seems to lie in the reduced sensitivity of target tissues (bone, kidneys and intestines) on calcitropic hormones due to reduced number of receptors or because of their dysfunction (Horst et al., 1994).

Widely accepted theory for a long time was that MF was caused by a high content of Ca in the diet consumed before calving, as well as by unfavorable ratio of Ca/P. However, further studies emphasized importance of the high content of monovalent cations in the diet, mainly potassium (Block, 1984; Ender et al., 1971; Goff & Horst, 1997b; Horst & Goff, 1997). As a relative excess of cations in the diet affects blood acid-base balance toward alkalosis, the disruption of integrity of tissue receptors is related to metabolic alkalosis that normally exists in cows at the time of calving (Goff, 2000). Thus, the primary cause of MF is considered to be the temporary inability of cow tissues to adequately respond to stimuli generated by calcitropic hormones, mainly parathyroid hormone (PTH) (Goff et al., 1991; Goff, 2000).

In addition to monovalent ions, risk factors also include dietary magnesium (Sansom et al., 1983), dietary P (Curtis et al., 1984), and possibly vitamin D (Goff, 2000; Horst, 1986). Animal factors as the risks for hypocalcaemia include age (Curtis et al., 1984; Dishington, 1974) and breed (Goff, 2000; Oetzel, 1988). Adult cows are at increased risk for the disease. Occurrences are more frequent from the third lactation onwards, reaching the plateau of 12- 15% in cows 6-10 years of age (Curtis et al., 1984; Dishington, 1974). The most predisposed breeds for milk fever are Jersey and Guernsey, followed by Holstein and Brown Swiss. In the case of Jerseys possible reasons are considered to be the higher milk production per unit of body weight (Oetzel, 1988) and a higher content of Ca in the colostrum (Goff, 2000). In addition, the number of receptors in the intestine is about 15% lower in Jerseys than in Holsteins (Goff, 2000; Horst et al., 1997).

Depending on the age, breed, feeding regimen and housing conditions, as many as 50-80% of cows can suffer MF annually in some herds (Oetzel, 1988). Concerning that well-timed treatment of MF easily solves the problem and is relatively inexpensive, the disease was not considered as a factor of economic importance in dairy production for a long time (Radostits et al., 2000). However, later findings confirmed its close relationship with other health disorders in the puerperium (Curtis et al., 1985; Massey et al., 1993). Many of these disorders are now considered as complications of hypocalcaemia. They generally occur as a complex, rarely as isolated diseases (Curtis et al., 1985) and include most of metabolic and reproductive disorders in periparturient period: dystocia, retained placenta, metritis, uterine prolapse, ketosis, mastitis and displaced abomasum (Horst et al., 1997). Risk of occurrence of each of them is much higher in hypocalcemic cows (Curtis et al., 1985). A well known physiological effect of hypocalcaemia is atony of smooth and skeletal muscles because their contractility is a function of Ca concentration in extracellular fluid (Ramberg et al., 1984). Most of the possible complications are related specifically to reduced contractility and to atony of smooth muscles of digestive and reproductive tract (Beede, 1995).

Spontaneous recovery of MF is usually not possible and approximately 75% of affected cows die if treatment fails (Oetzel, 1988). Even under normal conditions about 8% of treated cows still die due to various complications, 12% of them are culled (Guard, 1996) and about 25% require another treatment. Due to increased susceptibility to other health disorders and possible complications, the production life of cows that experienced MF was reduced by an average of 3-4 years (Horst et al., 1997).

Subclinical hypocalcaemia influences in the same manner as the clinic one, but to a lesser extent. As is more common in the herd, adverse effects of subclinical hypocalcaemia on herd economy can be equal or even greater than the effects of MF due to its broader influence on feed intake, secondary disease conditions, and milk production during early lactation (Horst et al., 1994).

#### **2.8. Hypomagnesaemia**

Magnesium is an essential mineral with many functions in the body but its homeostasis is not hormonally regulated. The concentration of Mg in the blood is dependent exclusively on its absorption from the diet. If Mg secretion in milk and its endogenous losses exceeds absorption from the forestomachs hypomagnesaemia occurs because of the lack of hormonal control. Hypomagnesaemia is common problem in ruminants and may be one of the major health problems of cattle, sheep and goats in large scale production systems especially in temperate climates (Mayland, 1988; Stelletta et al., 2008).

38 Milk Production – An Up-to-Date Overview of Animal Nutrition, Management and Health

Holsteins (Goff, 2000; Horst et al., 1997).

average of 3-4 years (Horst et al., 1997).

et al., 1994).

**2.8. Hypomagnesaemia** 

In addition to monovalent ions, risk factors also include dietary magnesium (Sansom et al., 1983), dietary P (Curtis et al., 1984), and possibly vitamin D (Goff, 2000; Horst, 1986). Animal factors as the risks for hypocalcaemia include age (Curtis et al., 1984; Dishington, 1974) and breed (Goff, 2000; Oetzel, 1988). Adult cows are at increased risk for the disease. Occurrences are more frequent from the third lactation onwards, reaching the plateau of 12- 15% in cows 6-10 years of age (Curtis et al., 1984; Dishington, 1974). The most predisposed breeds for milk fever are Jersey and Guernsey, followed by Holstein and Brown Swiss. In the case of Jerseys possible reasons are considered to be the higher milk production per unit of body weight (Oetzel, 1988) and a higher content of Ca in the colostrum (Goff, 2000). In addition, the number of receptors in the intestine is about 15% lower in Jerseys than in

Depending on the age, breed, feeding regimen and housing conditions, as many as 50-80% of cows can suffer MF annually in some herds (Oetzel, 1988). Concerning that well-timed treatment of MF easily solves the problem and is relatively inexpensive, the disease was not considered as a factor of economic importance in dairy production for a long time (Radostits et al., 2000). However, later findings confirmed its close relationship with other health disorders in the puerperium (Curtis et al., 1985; Massey et al., 1993). Many of these disorders are now considered as complications of hypocalcaemia. They generally occur as a complex, rarely as isolated diseases (Curtis et al., 1985) and include most of metabolic and reproductive disorders in periparturient period: dystocia, retained placenta, metritis, uterine prolapse, ketosis, mastitis and displaced abomasum (Horst et al., 1997). Risk of occurrence of each of them is much higher in hypocalcemic cows (Curtis et al., 1985). A well known physiological effect of hypocalcaemia is atony of smooth and skeletal muscles because their contractility is a function of Ca concentration in extracellular fluid (Ramberg et al., 1984). Most of the possible complications are related specifically to reduced contractility and to

Spontaneous recovery of MF is usually not possible and approximately 75% of affected cows die if treatment fails (Oetzel, 1988). Even under normal conditions about 8% of treated cows still die due to various complications, 12% of them are culled (Guard, 1996) and about 25% require another treatment. Due to increased susceptibility to other health disorders and possible complications, the production life of cows that experienced MF was reduced by an

Subclinical hypocalcaemia influences in the same manner as the clinic one, but to a lesser extent. As is more common in the herd, adverse effects of subclinical hypocalcaemia on herd economy can be equal or even greater than the effects of MF due to its broader influence on feed intake, secondary disease conditions, and milk production during early lactation (Horst

Magnesium is an essential mineral with many functions in the body but its homeostasis is not hormonally regulated. The concentration of Mg in the blood is dependent exclusively on

atony of smooth muscles of digestive and reproductive tract (Beede, 1995).

Clinical hypomagnesaemia is also called hypomagnesemic tetany, grass tetany, spring tetany, or lactational tetany. Clinical signs usually occur when the animal is both hypomagnesaemic and hypocalcaemic (Robinson et al., 1989). In its subclinical form, however, hypomagnesaemia may be risk factor for other diseases. Around calving it may be the important risk factor for MF (Sansom et al., 1983; Schonewille et al., 2008).

Hypomagnesaemia may develop due to Mg deficiency in the diet or due to its low utilization in the gut. It may also occur because of a need for increased amounts of Mg during parturition and early lactation (Mayland, 1988). Clinical hypomagnesaemia in cows with plasma Mg concentrations bellow 0,4 mmol/L is manifested as grass tetany (Schonewille et al., 2008). Grass tetany has been investigated extensively, but its complex etiology is not well understood. Large number of factors influences the development of the disease (Robinson et al., 1989). It appears within 2-4 weeks after cattle or sheep have been turned out to rapidly growing pasture. Ewes with twins are more susceptible to grass tetany than are ewes with single lamb (Mayland, 1988). Specifically, older lactating animals consuming lush, intensively fertilized, cool-season grasses during the early spring are the most frequently affected (Robinson et al., 1989). Older animals also have reduced ability to mobilize body reserves of Mg. Lower average environmental temperatures (<14°C) facilitate the onset of the disorder (Mayland, 1988). However, periods of rapid plant growth during any season, resulting in forage of low Mg and high moisture, high nitrogen (N) and K, present dietary conditions that increase the potential for the development of tetany (Robinson et al., 1989). Grass tetany also may develop if animals graze forage that is high in digestible protein, but low in digestible energy (Mayland, 1988).

Grass tetany generally occurs when the dietary intake of total Mg is not particularly low, but factors which increase the animal's requirement for Mg or reduce the availability of dietary Mg are present (Mayland, 1988). The Mg concentrations in forage and subsequently in the blood of cattle are influenced strongly by high amounts of fertilizer K and, to some extent, fertilizer N. Absorption of Mg by plants is reduced by high levels of K in the soil (Mayland, 1988; Robinson et al., 1989). Mg absorption by ruminants is also reduced by a high intake of K (Schonewille et al., 2008), and by high content of Ca and P in the diet (Sansom et al., 1983). High concentrations of N in the forage may additionally decrease the availability of Mg (Mayland, 1988).

Absorption of Mg is dependent on the concentration of Mg in the rumen fluid and the functionality of the Mg active transport process across the rumen wall. The active transport mechanism is critical for the animal when dietary Mg concentration is less than 0,25%. Several factors, such as dietary K, can inhibit Mg absorption by this pathway. At high concentration of Mg in the rumen it will be absorbed by passive transport, and this mechanism is not affected by high K but only by the solubility of Mg in the rumen fluid. This mechanism requires dietary Mg to be not less than 0,35% (Goff, 2006b).

Mg deficiency results in reduced appetite which decreases total nutrient intake (Robinson et al., 1989), thus chronic hypomagnesaemia results in reduced feed intake and milk production. It may progress quickly into acute hypomagnesaemia which terminates in convulsions, coma and death. One-third of animals with clinical symptoms die (Mayland, 1988). Even mild form of hypomagnesaemia (Mg <0,85 mmol/L) significantly reduces the mobilization of Ca from the skeleton around calving (Goff, 2000; Sansom et al., 1983). That is why hypomagnesaemia may be a risk factor for parturient hypocalcaemia and milk fever. According to Sansom et al. (1983) possible reasons for inhibition of Ca mobilization are considered to be:


### **2.9. Udder edema**

Udder edema occurs sporadically in cows and heifers near parturition, peaking in severity during the immediate prepartum period. Unless complicated, recovery of edema is spontaneous within a few days after calving. However, if edema is sufficiently severe it can interfere with suckling by the calf, milking, and may cause other complications including udder inflammation. Edema is caused by excessive accumulation of fluid underneath the skin and at least some mammary edema is associated with pregnancy and parturition, especially in primigravid heifers (Malven et al., 1983).

Investigations of the causes of udder edema and the development of strategies to reduce its prevalence have progressed in very limited degree during last several decades (Goff, 2006a). Some authors (Schmidt & Schultz, 1959) proposed that severity of udder edema is based on an inherent physiological phenomenon, because a cow may tends to have the same amount of edema each year regardless of the feeding. Feeding program had little if any effect on udder edema (Randalu et al., 1974). "Steaming up" method of feeding dry pregnant cows and high level of concentrates in their diet was initially blamed for high incidences of udder edema. However, investigation found that the amount of edema at calving was not related to grain feeding during the dry period or after calving (Schmidt & Schultz, 1959). Edema also is not correlated with the body condition of the cows (Schmidt & Schultz, 1959). However, addition of Na or K to the diet before calving can increase the incidence and severity of udder edema in dairy cows and first calf heifers (Nestor et al., 1988). In practical terms, high level of NaCl in the feed during the dry period may be one of the major factors in the development of udder edema around calving. Conflicting results from some earlier studies on effect of grain on udder edema could be explained with salt content of the diets. However, KCl as a replacement for NaCl results in edema of about the same severity (Randalu et al., 1974).

Cows with severe edema that requires veterinary treatment are more likely to have additional health problems. Authors found higher culling rates for cows with more severe edema. Thus, there would be a substantial economic benefit to minimizing edema in dairy herds (Dentine & McDaniel, 1984).

## **2.10. Retained placenta**

40 Milk Production – An Up-to-Date Overview of Animal Nutrition, Management and Health

possible reasons for inhibition of Ca mobilization are considered to be:

or completely interrupt secretion of PTH,

takes place in the presence of PTH.

especially in primigravid heifers (Malven et al., 1983).

disabled,

**2.9. Udder edema** 

This mechanism requires dietary Mg to be not less than 0,35% (Goff, 2006b).

mechanism is not affected by high K but only by the solubility of Mg in the rumen fluid.

Mg deficiency results in reduced appetite which decreases total nutrient intake (Robinson et al., 1989), thus chronic hypomagnesaemia results in reduced feed intake and milk production. It may progress quickly into acute hypomagnesaemia which terminates in convulsions, coma and death. One-third of animals with clinical symptoms die (Mayland, 1988). Even mild form of hypomagnesaemia (Mg <0,85 mmol/L) significantly reduces the mobilization of Ca from the skeleton around calving (Goff, 2000; Sansom et al., 1983). That is why hypomagnesaemia may be a risk factor for parturient hypocalcaemia and milk fever. According to Sansom et al. (1983)

a. influence on PTH secretion; there are indications that serious Mg deficiency may impair

b. interference with the action of PTH on target tissues; the integrity of interaction between PTH and its receptors is disrupted and activity of initiated enzymes is

c. interference with the metabolism of vitamin D; the first phase of vitamin D hydroxylation in the liver requires Mg2+ ions, while the second phase in the kidney

Udder edema occurs sporadically in cows and heifers near parturition, peaking in severity during the immediate prepartum period. Unless complicated, recovery of edema is spontaneous within a few days after calving. However, if edema is sufficiently severe it can interfere with suckling by the calf, milking, and may cause other complications including udder inflammation. Edema is caused by excessive accumulation of fluid underneath the skin and at least some mammary edema is associated with pregnancy and parturition,

Investigations of the causes of udder edema and the development of strategies to reduce its prevalence have progressed in very limited degree during last several decades (Goff, 2006a). Some authors (Schmidt & Schultz, 1959) proposed that severity of udder edema is based on an inherent physiological phenomenon, because a cow may tends to have the same amount of edema each year regardless of the feeding. Feeding program had little if any effect on udder edema (Randalu et al., 1974). "Steaming up" method of feeding dry pregnant cows and high level of concentrates in their diet was initially blamed for high incidences of udder edema. However, investigation found that the amount of edema at calving was not related to grain feeding during the dry period or after calving (Schmidt & Schultz, 1959). Edema also is not correlated with the body condition of the cows (Schmidt & Schultz, 1959). However, addition of Na or K to the diet before calving can increase the incidence and severity of udder edema in dairy cows and first calf heifers (Nestor et al., 1988). In practical terms, high level of NaCl in the feed during the dry period may be one of the major factors in the development of udder edema around calving. Conflicting results from some earlier studies on effect of grain on Inadequate antioxidant status or "oxidative stress" of the cow contributes to a poorly functioning immune system and increases the risk of mastitis as well as retained placenta (retained fetal membranes, placental retention). Fetal membranes are retained if not expulsed longer than 12 hours after parturition. Se and vitamin E are important dietary antioxidants and their low levels in the diet are associated with a high incidence of mastitis and retained fetal membranes (Goff, 2006a). Subsequently, addition of vitamin E or Se may improve antioxidant status and decrease the incidence of those diseases. The similar effects can be obtained by addition of beta-carotene in the diet. Blood lymphocyte proliferation was higher in cows supplemented with beta-carotene, and phagocytic activity of blood neutrophils was enhanced as well as intracellular killing by blood neutrophils. Therefore, dietary beta-carotene can elevate blood beta-carotene and enhance peripartum host defense mechanisms by enhancing lymphocyte and phagocyte function (Michal et al., 1994).

Hypocalcaemia, among others, may be an important risk factor in the development of retained placenta. Muscle weakening or absence of uterine contractions in hypocalcemic animals does not contribute to the expulsion of fetal membranes (Goff & Horst, 1997c; Oetzel, 1988). In cows with hypocalcaemia placental retention is 3,2 to 4 times more frequent than in normocalcemic cows (Curtis et al., 1985). Hypocalcaemia also delay the physiological involution of uterus and increases the incidence of metritis (Beede, 1995). Moreover, hypocalcaemia is considered as one of the main causes of uterine prolapse, also due to loss of uterine muscles tone.

Cows with retained placenta were 3 times more likely to develop mastitis than animals without retained placenta (Overton & Waldron, 2004). It has been reported that placental retention, metritis and mastitis predisposes dairy cows to foot problems. Moreover, uncomplicated ketosis, retained placenta, metritis, and hypocalcaemia at parturition are also risk factors for left displaced abomasums (Shaver, 1997). Cows with retained placenta or metritis produce 0,3-2,3 kg/day less milk during subsequent lactation (Fourichon et al., 1999). In the case of retention alone, Guard (1996) stated that losses are on average 350 kg of milk annually.

#### **2.11. Metritis**

Metritis and endometritis are inflammatory uterine diseases. They frequently occur soon after calving and may severely compromise reproductive performances. Metritis and

endometritis refer to the inflammation of the uterus and of its endometrial lining - both conditions are referred to subsequently as metritis (Urton et al., 2005). Younger cows were more likely to have dystocia or assisted deliveries, while older cows were most likely to have retained placenta and metritis (Lewis, 1997).

In some herds, up to 40% of the postpartum cows may be diagnosed with, and treated for uterine infections. However, the exact causes of uterine infections are unknown but are associated with several factors. Cows with dystocia, retained placenta, or stillbirths, and other metabolic disorders are more likely to develop metritis than healthy cows. Impaired immune functions before and after calving seem to predispose cows to severe uterine infections. It has been suggested that the function of neutrophils is impaired in cows that develop uterine infections. Thus, methods for regulating immune function in periparturient cows may have potential for preventing uterine infections. However, prevention of uterine infections is still difficult because the primary causes cannot be defined clearly (Lewis, 1997). Malnutrition influences the ability of the immune system to function, which affects the incidence of diseases such as mastitis and metritis (Goff, 2006a).

Cows suffering metritis exhibit reduced milk yield and reproductive performances (Urton et al., 2005). Few cows die from uterine infections, but affected animals are more likely to be culled for poor reproductive performances. The estimated cost to producers for each cow with metritis was 106 U.S. dollars (Lewis, 1997). Many of the financial costs of metritis are indirect, such as increased days open or predisposition to other diseases, and are thus difficult to measure. As mentioned previously, metritis is one of the diseases that predispose dairy cows to foot problems and left displaced abomasums (Shaver, 1997).

In contrast, the effects of metritis on milk production can be measured immediately, and losses during first four months after calving can be almost 270 kg. Also, besides reduced milk production in sick animals, some pharmaceuticals for treatment of uterine infections contaminate milk with residues, and the milk must be discarded. This is how uterine infections may have an indirect effect on milk production (Lewis, 1997).
