SUMMARY
Milk fever is a commonly recognized metabolic disorder that occurs at or near calving, particularly in “high milk producing cows”. This review is aims to describe the pathophysiology and associated risk factors of milk fever in dairy cows. A significant number of mature dairy cows experience some degree of hypocalcemia during the first days post-calving due to the high volume of milk production and subsequent demand for calcium during this time. The occurrence of the disease is influenced by breed, body condition score, parity, and diet. When plasma calcium levels drop, parathyroid hormone and calcitriol rise in response. However, it takes time for these hormones to fully take effect. Parathyroid hormone also prompts the kidneys to produce 1, 25-dihydroxyvitamin D, which helps maintain calcium balance in the body. Metabolic alkalosis reduces the cow’s reaction to parathyroid hormone and makes dairy cows more prone to experiencing milk fever and subclinical hypocalcemia. Since calcium is required for nerve and muscle function, affected animals will begin to experience muscle weakness. As the condition progresses, the cow will become too weak to stand and ultimately become comatose over a matter of hours. Parturient paresis is a significant production disease in Ethiopia that should be taken into account. A combination of history, clinical examination, and laboratory testing are used to diagnose milk fever. If treated promptly and effectively, cows with milk fever can have a positive outcome when given an intravenous administration of calcium borogluconate. Any precautionary measure should be focused on preventing a drastic decrease in blood calcium levels during parturition.
Keywords: Calcium borogluconate; Dairy cow; Hypocalcemia; Milk fever; Parity
1. INTRODUCTION
Mammalian metabolism undergoes significant changes during the periparturient phase. At the start of lactation, the need for nutrients to produce milk increases, which also puts a significant strain on the animal’s metabolism. This burden is beyond the animal’s ability to adapt, leading to the development of various metabolic diseases (Paudyal et al., 2018). Milk fever is a commonly known metabolic disorder that takes place during or around the time of calving, especially in high milk yielding cows. This metabolic disorder is defined by a fast decrease in blood calcium (Tadesse and Belete, 2015). Calcium ions have a significant impact on various essential biological functions in the body, including muscle contraction, blood clotting, and the release of hormones. Additionally, they serve as structural components of the skeleton (Vig and Kinet, 2009).
Milk fever is a particular concern for cows that have recently given birth, as the rapid need for calcium during milk production puts a strain on the cow’s ability to maintain calcium balance in its body. In order to maintain a balance of calcium levels after calving, at the start of lactation, the cow will increase the reabsorption of calcium in the kidneys, increase its absorption in the intestine, and take calcium from its bones. During the initial month of lactation, it is anticipated that the cow will experience a decrease of 9-13% in her bone calcium levels in attempt to restore calcium balance in her body (Goff, 2008). The mechanisms that regulate normal blood calcium levels usually work well, but these homeostatic mechanisms fail and result in low levels of calcium in the blood. (Murray et al., 2008).
Therefore, the main objectives of this review are:
Several factors can contribute to the occurrence of milk fever in dairy cows, such as breed, age, milk production, lactation number, and diet (Mclaren et al., 2006). Hypocalcemia can be categorized as either clinical or subclinical depending on whether or not an animal displays detectable clinical sign. Both of them have additional impacts on the health of cows due to the onset of parturition and low levels of calcium, which result in a weakened immune system by inhibiting calcium signals in immune cells. As a result of having a weakened immune system, there is a greater likelihood of developing mastitis and metritis, and it also has a detrimental impact on reproductive abilities (Kimura et al., 2006).
Hypocalcemia causes a decline in muscle function, leading to reduced motility in the rumen and gastrointestinal tract. This, in turn, decreases the amount of feed intake, increasing the likelihood of various health issues such as displaced abomasum, ketosis, and fatty liver. Additionally, it also decreases milk production. (Mulligan et al., 2006)
Even though intravenous infusion of calcium salt solutions effectively treats the majority of clinical cases of hypocalcemia, cows that undergo this treatment subsequently have a higher vulnerability to other metabolic and infectious diseases (Quiroz-Rocha et al., 2009). In many countries, preventing parturient hypocalcemia is treated as a matter of great importance. It has been suggested that a particular control plan is applicable when the occurrence of milk fever exceeds 10% in cows with a high risk factor (Amaral-Phillips, 2017). Milk fever is also one of the major considerable production diseases in Ethiopia (Akalu, 2017).
- To review the general aspects of milk fever in dairy cows.
- To highlight the pathophysiology and associated risk factors of milk fever in dairy cows.
- To point out status of disease in Ethiopia.
2. LITERATURE REVIEW
2.1. Etiology
Initiation of lactation in dairy cows presents difficulties in maintaining the balance of calcium levels in their bodies. This is because the demand for colostrum and milk increases during the period around parturition, while DMI temporarily decreases. Consequently, there is a temporary decrease in calcium levels in the body, known as hypocalcemia (Reinhardt et al., 2011). Milk fever occurs when there is a significant lack of metabolizable calcium in the bloodstream. The level of calcium in the colostrum is around twice as high as the calcium concentration in the milk produced later in lactation (Tsioulpas et al., 2007). When a cow generates 10 liters of colostrum during one milking session, it also experiences a calcium loss of approximately 23 grams (Kamiya et al., 2010).
Calcium is eliminated from the cow through various processes such as fecal elimination, filtration in the kidneys, and transport to the fetus through the placenta, deposition in bones, and secretion in the mammary gland. When around half of the calcium in the blood is depleted, there is a high risk of milk fever happening (DeGaris and Lean, 2008). Hypocalcemia happens when a dairy animal is unable to maintain the balance of calcium in its body due to a sudden and significant release of calcium. The crucial factor in the development of milk fever is the delay in the functioning of calcium homeostatic mechanisms (Oetzel, 2011).
Generally, there are three main factors that can impact calcium balance within the body. The first cause is when there is a significant amount of calcium lost in the colostrums, which surpasses the ability of the intestines and bones to absorb and replenish it. The second reason is a decrease in the ability to absorb calcium from the intestine at parturition, while the last reason is a lack of ability to release calcium from storage in the bones, possibly due to not enough functioning parathyroid gland activity during dry period (Mulligan et al., 2006). The inadequate functioning of the parathyroid gland causes a lack of the parathyroid hormone (PTH) (Radostits et al., 2007).
2.2. Epidemiology and Risk Factors of Milk Fever
With the continuing intensification and commercialization of livestock production systems, the economic implications of animal diseases are becoming increasingly important at both farm and national levels. On average, 5-10% of dairy cows experience clinical milk fever, and studies suggest that in some herds, this percentage can be as high as 34% (DeGaris and Lean, 2008). According to Kimura et al. (2006), the majority of cows in their second or subsequent lactation experience a temporary decrease in calcium levels after giving birth. Different herds have different levels of milk fever, which suggests that the way they are managed can influence the incidence of milk fever (McLaren et al., 2006).
2.2.1. Breed Roche and Berry (2006) reported that 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 and a higher content of calcium in the colostrum. Moreover, Jerseys have approximately 15% fewer receptors in their intestines compared to Holsteins. Reducing the number of receptors would lead to a decrease in the ability of the target tissue to respond to and be sensitive to 1, 25-(OH)2 D3. As a result, there would be a decrease in the resorption of calcium from bones and the absorption of calcium in the intestine (Lean et al., 2006; Lisegang et al., 2008).
Table 1: Incidence of milk fever according to breed of cow
| Breed of cow | Total number of Parturitions | Number of milk fever cases | Incidence of milk fever(%) |
|---|---|---|---|
| Jersey | 406 | 60 | 14.78 |
| Holstein | 872 | 42 | 4.82 |
| Overall | 1278 | 102 | 102 |
Source: Roche and Berry, 2006
2.2.2. Parity Parity is often considered as one of the main factors influencing susceptibility to milk fever (Lisegang et al., 2008). The occurrence of subclinical hypocalcemia tends to increase with increasing parity, impacting about 25% of young cows and nearly 50% of older cows with two or more parity. There is a belief that heifers, in particular, are less prone to a certain condition because they have a higher level of bone depletion/repletion activity. They are also more capable of extracting calcium from their calcium reserves in comparison to cows that have given later parity cows. Moreover, later parity cows produce more colostrum and milk making the demand for calcium greater (Reinhardt et al., 2011).
A similar relationship with parity was noted with clinical milk fever affecting less than 1% of heifers, but surpassing 6% for cows of third and greater parity. The increased risk and occurrence of milk fever is partially caused by a cow’s number of parity and its previous history of milk fever. The past occurrences of milk fever play a significant role in determining whether or not a cow will experience low calcium levels and milk fever during subsequent births. This is likely because these specific cows have a reduced ability to promptly react to biological signals and increase the number of vitamin D receptors (VDR) in a timely manner (Krehbiel, 2014).
Parity is often considered as one of the main factors influencing susceptibility to milk fever (Lisegang et al., 2008). The occurrence of subclinical hypocalcemia tends to increase with increasing parity, impacting about 25% of young cows and nearly 50% of older cows with two or more parity. There is a belief that heifers, in particular, are less prone to a certain condition because they have a higher level of bone depletion/repletion activity. They are also more capable of extracting calcium from their calcium reserves in comparison to cows that have given later parity cows. Moreover, later parity cows produce more colostrum and milk making the demand for calcium greater (Reinhardt et al., 2011).
Table 2: Percentage of milk fever in cows with different parity in Gondar town.
| Parity | No. of cows | No. of positive cows | Percentage of milk fever |
|---|---|---|---|
| < 3 | 147 | 25 | 17.0 |
| 3-4 | 147 | 25 | 17.0 |
| > 4 | 90 | 66 | 73.3 |
| Total | 384 | 116 | 30.2 |
2.2.3. Body condition score Cows that have a high body condition score (BCS) before calving are more prone to metabolic disorders. There is a strong correlation between milk fever and body condition score (BCS), where having a higher BCS raises the likelihood of experiencing milk fever (DeGaris and Lean, 2008). This is because dairy cows that have a higher body condition score (BCS) at calving tend to produce milk with more calcium, which makes them more susceptible to milk fever. On the other hand, cows that are over conditioned tend to consume less calcium due to a reduced appetite during the critical period around calving. This increases their chances of developing hypocalcemia (Roche and Berry, 2006).
2.2.4. Dietary factors Diets that include a high daily intake of calcium for dry cows are linked to a higher occurrence of parturient paresis. At this stage, passive absorption becomes the primary way to meet the body’s calcium maintenance needs as active absorption of calcium from food and the breakdown of bone tissue are lowered. Cows in such a state cannot rapidly replenish calcium levels lost in milk, leading to a severe deficiency in calcium (Bhanugopan and Lievaart, 2014). Consuming too much phosphorus in the diet towards the end of pregnancy can cause milk fever and make hypocalcemia worse. This occurs because high phosphorus levels in the blood directly interfere with the kidneys’ production of 1, 25-(OH)2 D3, which in turn reduces the body’s ability to absorb calcium from the intestines (Oetzel, 2011).
2.3. Pathophysiology
Mineral nutrition is critical for the effectiveness of lactation in dairy cattle (Ericksona and Kalscheur, 2020). Out of all the minerals present in an animal’s body, calcium is the most abundant, with the majority (99%) being found in the bones. It plays a crucial role in the skeletal system of vertebrates and is vital for muscle movement and proper functioning of the nervous system. The intracellular calcium portion has a function in transmitting signals within cells, whereas the calcium found in the bones is always being swapped with fluids outside of the cells. A certain amount of ionized calcium is necessary in the blood of an animal in order to sustain regular bodily functions (Cecilia, 2011).
Calcium metabolism during calving is one of the most critical animal health parameters that affect production, reproduction and feed conversion efficiency (McClearn et al., 2020). During the process of parturition in dairy cows, there is a sudden rise in the amount of calcium being stored for the production of milk. The amount of calcium needed increases to 2-5 times more than what is required during the dry period. This shows that the amount of calcium lost through milk on a daily basis will not be balanced with the amount of calcium that cows can absorb from their gut based on their individual requirements (Taylor et al., 2008). Due to the inability to absorb enough calcium through diet, cows that produce colostrum and milk experience a sudden increase in demand for calcium. As a result, dairy cows often develop milk fever to varying during the early postpartum. This is because they have to mobilize calcium from their bones and reabsorb it in their kidneys (Penner et al., 2008).
The absorption of calcium in the intestines and the breakdown of calcium in the bones are regulated by parathyroid hormone, which is released by the parathyroid glands. Additionally, the production of 1, 25-dihydroxyvitamin D in the kidney also plays a role in this process (Goff, 2008). Decrease in the level of calcium in the blood raises the concentration of parathyroid hormone. If the calcium level in the blood is normal, the secretion of parathyroid hormone is reduced. Parathyroid hormone prompts the kidneys to produce 1, 25-dihydroxyvitamin D, which helps maintain calcium balance in the body. Furthermore, the parathyroid hormone increases the renal absorption of calcium (Taylor et al., 2008).
Due to the stimulation of 1, 25-(OH)2 D3 and PTH secretion, there is an increase in the resorption of calcium from bones and the absorption of calcium from the intestines. Milk fever is caused by a disruption in the balance of calcium in the body, which is influenced by various nutritional factors (Oetzel and Miller, 2012). Metabolic alkalosis further reduces the cow’s reaction to parathyroid hormone and makes dairy cows more prone to experiencing milk fever and subclinical hypocalcemia. It primarily happens when cow consume diets that contain high levels of cations, particularly sodium and potassium, while lacking sufficient amounts of anions, particularly chlorine and sulfur. During metabolic alkalosis, the structure of the PTH receptor changes, leading to reduced sensitivity of the tissues to PTH. Thus, maintaining the proper interaction between PTH and its receptor is crucial for maintaining calcium balance in the body (DeGaris and Lean, 2008).
When plasma calcium levels drop, parathyroid hormone (Parathormone) and calcitriol rise in response. However, it takes time for these hormones to fully take effect; so that, parathormone takes at least a week to mobilize calcium from bone, while calcitriol takes a day or two to improve calcium absorption efficiency. Therefore, almost all animals experience hypocalcemia after parturition, although high yielders typically experience milk fever. Additionally, older cows with slower bone metabolism and less effective gastrointestinal absorption are more susceptible to the condition (Bezerra et al., 2014).
Figure 1: The homeostatic response of a cow to low blood calcium concentration
The homeostatic response of a cow to low blood calcium concentration
2.4. Clinical sign
Many cases of milk fever do not display noticeable symptoms in animals. Hypocalcemia can be categorized as either clinical or subclinical depending on whether or not an animal displays detectable clinical sign. Clinical milk fever is the most extreme condition of low calcium levels in a cow, causing an inability to stand up. This form of hypocalcemia is easily identifiable and is characterized by blood calcium levels lower than 5 mg/dL. Subclinical hypocalcemia leads to milder imbalances in calcium levels in the blood and does not manifest any visible symptoms. In the condition known as subclinical hypocalcemia, the concentration of calcium in the blood falls within the range of 5.5 to 8.0 mg/dL (Wubishet et al., 2016). Based on the degree of hypocalcemia and time of occurrence the clinical sign of milk fever are grouped in to three stages (Oetzel, 2011).
Stage I: At this stage, animals are able to move around but show signs of hypersensitivity, excitability and may be mildly ataxic. This phenomenon is often overlooked because it only lasts for a short period, which is less than one hour and is only visible when animals are standing. The smooth muscles become paralyzed, which causes an inability to swallow, resulting in loss of appetite and a halt in the movement of food in the rumen. Only small amounts of dry feces are passed and urination is suspended. If calcium treatment is not initiated, cows are likely to advance to the second more critical phase (Fikadu et al., 2016).
Stage II (Sternal recumbency): The clinical signs of stage II milk fever typically last for the duration of 1 to 12 hours. The cow that is affected turns its head towards its flank, or if its head is stretched out, a curved shape resembling the letter S appears in its neck. The tetany of the limb present in first stage is not present but the cow is unable to stand and the eyes are usually dry and staring. It exhibits incoordination when walking and its temperature is subnormal, her muzzle dry, coldness of skin and extremities. The heart rate will be rapid exceeding 100 beats per minute, gastrointestinal atony predisposes to constipation and mild bloating (Tadesse and Belete, 2015).
Figure 2: Cow in sternal recumbency.
Source: Kimura et al., 2006
Stage III (Lateral recumbency or Downer cow): This condition is characterized by inability to stand and a progressive loss of consciousness leading to coma. The cow was lying on her side, with her legs stretched out. Bloating often occurs when a cow is in a sideways position. The temperature drops significantly and the sound of the heart becomes almost inaudible, while the heart rate rises to 120 beats per minute or higher (Radostits et al., 2007). According to Murray et al. (2008), if not treated, cows in this stage will not live for more than a couple of hours.
Figure 3: Cow in sternal recumbency.
Source: Kimura et al., 2006
2.5. Diagnosis and Treatment
2.5.1. Diagnosis A combination of information gathering, clinical examination and laboratory testing is used to diagnose milk fever. Cow’s age, breed, lactation stage, milk yield, calving day and response to intravenous calcium borogluconate solution were obtained during history tracing (Wubishet et al., 2016). The confirmation of the diagnosis is done through a laboratory analysis of the blood and the fast and distinctive reaction to treatment using calcium borogluconate. The blood experiences significant changes including a reduction in levels of calcium and phosphorus (Radostits et al., 2007). Animals exhibiting a serum calcium level ranging from 5.5 to 7.5 mg/dl demonstrate symptoms indicating stage I hypocalcemia. Stage II hypocalcemia is observed when the calcium levels range from 3.5 to 6.5 mg/dl, while stage III occurs when the concentration of calcium drops to as low as 2 mg/dl. Extended time spent lying down leads to tissue death in the muscles due to lack of blood flow. This causes an elevation in the levels of CPK and AST, which are enzymes found in the bloodstream that indicate muscle damage (Fikadu et al., 2016).
2.5.2. Treatment The aim of treating milk fever is to increase the calcium levels in the bloodstream to a point where it can effectively support cellular functioning. Early treatment of milk fever is necessary, particularly if the cow is lying down, as this can lead to serious damage to the musculoskeletal system (Oetzel, 2011). The most efficient method of returning plasma calcium levels to normal is to administer an intravenous injection of calcium salts. Cows in stage II and III of milk fever should receive immediate treatment by slowly administering 500 ml of 23% calcium borogluconate intravenously. Taking an excessive amount of calcium can potentially lead to severe heart complications that may result in death (Doze et al., 2008).
The aim of treating milk fever is to increase the calcium levels in the bloodstream to a point where it can effectively support cellular functioning. Early treatment of milk fever is necessary, particularly if the cow is lying down, as this can lead to serious damage to the musculoskeletal system (Oetzel, 2011). The most efficient method of returning plasma calcium levels to normal is to administer an intravenous injection of calcium salts. Cows in stage II and III of milk fever should receive immediate treatment by slowly administering 500 ml of 23% calcium borogluconate intravenously. Taking an excessive amount of calcium can potentially lead to severe heart complications that may result in death (Doze et al., 2008).
2.6. Prevention and Controlt
The management of milk fever is crucial as it is a fundamental disease that significantly affects the productivity and reproductive capabilities of dairy cows (Kimura et al., 2006). The main aspect of preventing milk fever is effectively managing a pregnant cow in the later stage of pregnancy. This involves controlling the amount of calcium the cow consumes during the dry period, allowing it to adjust to a lack of calcium and be able to meet the calcium demands when it begins producing milk after calving (Sharma, 2015).
Magnesium plays a very important role in Ca metabolism as it is a key intermediate in the resorption of calcium from bone by parathyroid hormone. In dairy cows achieving the correct BCS at calving and drying off is also critical for the prevention of milk fever (Roche et al., 2009). Another prevention strategy is reducing the number of absorbable dietary cations and/ or increasing the number of absorbable dietary anions. Vitamin D has significant role in prevention of milk fever in dairy cows by monitoring calcium homeostasis (Sakha et al., 2014)
3. MILK FEVER STATUS IN ETHIOPIA
In Ethiopia, dairy cattle are mainly fed on natural pasture (grazing and/or hay), crop residues and different agro-industrial and locally available by-products as supplementary feeds. Macro-minerals are very important nutrients in dairy rations and producers will continue to focus on optimizing production, health and efficiency of their dairy herds. Over feeding and under feeding of calcium, absence of mineral supplementation and improper supplementation was the major cause of the milk fever.
Parturient paresis is one of the major considerable production diseases in Ethiopia. While milk fever has been observed sporadically in dairy cows, there has been a noticeable rise in its occurrence in Gondar small holder dairy farms, particularly among highly productive cows with high milk yields. In general, the occurrence of milk fever in this town was 30.2%. Overall the prevalence of milk fever around this town was 30.2%. The occurrence of milk fever was significantly associate with milk yield, parity, and breed in which 55(50.92%), 66(73.3%) and 110(31.9%) milk yield, parity and breed of the cows respectively. The majority of cows suffering from milk fever (63.2%) experienced quick improvements after receiving a single bottle of 400ml, 1% calcium borogluconate. On the other hand, 36.8% of the cows experienced a relapse after the initial treatment and required additional doses for three consecutive days (Anteneh et al., 2012).
According to Akalu (2017) the prevalence rate of milk fever in Addis Ababa is 27 percent. From 430 H. Friesian cross breed examined cows, only 107 (24%) had parturient paresis and from 102 Jersey cross breed cows examined only 38 (37%) showed the disease and this Jersey cross breed cows are more susceptible to parturient paresis than H. Friesian cross breed. Similarly the time of occurrence showed depend on parturition because from a total of 145 cows affected with parturient paresis 103 (31%) occurred during calving.
Milk fever is the third prevalent (1.4%) postpartum problems in dairy cows around wolatia soddo. This problem could be associated with ration particularly minerals. It predisposes the cow to uterine infection and breed, age parity body condition and management are important risk factors for disease to occur. Local breeds are less susceptible to milk fever than cross or exotic breeds (Ayele et al., 2014). Milk fever and other metabolic disorders are still diseases that would threaten the growing of dairy industry. Milk fever is the third ranked disease of dairy cows in Mekelle with prevalence rate of 7.69% (Emuru et al., 2015).
4. CONCLUSION AND RECCOMENDATIONS
Milk fever is detrimental disorders that affect mineral element status, lactation and reproductive performance of too many dairy cows. This is a specific problem that occurs in cows immediately after calving, when there is a sudden demand for calcium at the onset of lactation. Factors such as milk yield, breed, parity and diet contribute to the occurrence of milk fever in dairy cows. If the cow’s body is not able to react promptly to this requirement, it experiences hypocalcemia. When plasma calcium levels drop, parathyroid hormone (Parathormone) and calcitriol rise in response cows experiencing hypocalcemia will display tremors and will no longer be able to stand. Early treatment with intravenous calcium supplementation is beneficial for the management of parturient paresis. It is also one of the primary production diseases of significant concern in Ethiopia. For this reason, there has been significant attention given to the nutrition and management of dairy cows during the transition period in order to prevent and control milk fever in dairy cows. Based on above conclusion the following recommendations are forwarded:
- There should be implementation of a well-monitored feeding strategy for dairy cattle, especially during the pre-partum period.
- Dairy farmers should be advised about predisposing factors of the disease.
- The owners of dairy farms and private owners should be aware of the disease and prepare themselves on how to manage peripartum intake of calcium.
- At calving, the cow should receive an oral dose of a calcium salt in a gel, as set out later, followed by a diet with high calcium content.
- Owners should avoid over-fattening of cows around calving by either reducing the energy concentration of the ration or restricting the intake.