02/09/2023
FATTY LIVER DISEASE IN CATTLE
Fatty Liver Disease In Cattle
Fatty liver disease is a disorder of highly productive dairy cows resulting from an excessive negative energy balance at the onset of lactation. Mobilization of large amounts of body fat reserves in response to insufficient dietary energy supply results in a transfer of fatty acids to the liver. Excessive amounts are deposited in the hepatocyte as trigylcerides and can result in disturbed liver function and liver cell injury. The condition is associated with pronounced ketosis, feed intake depression, and decreased productivity; severe cases lead to liver failure and a fatal outcome. Diagnosis can be made directly by determining the liver fat content but is most commonly done indirectly by assessing severity and duration of negative energy balance. Treatment is similar to the treatment of ketosis, with supportive care.
INTRODUCTION:
Fatty liver disease is a consequence of negative energy balance at the onset of lactation in dairy cows. Liver lipid accumulation occurs when body fat stores are mobilized and release nonesterified long chain fatty acids (NEFAs) into blood, which to a considerable part reach the liver. If the amount of NEFAs reaching the liver exceeds the liver's capacity to process these, NEFAs are re-esterified and deposited inside the hepatocyte as triacylglycerol (TAG), a process termed liver lipid accumulation. A mild increase in liver TAG content is to be considered normal in high-yielding dairy cows, but larger amounts of TAG deposited inside the hepatocyte may disturb liver function and further exacerbate the negative energy balance.
Fatty liver disease is one of the important metabolic diseases of postparturient dairy cows. Although often considered a postpartum disorder, it usually develops before and during parturition. Periparturient depression of feed intake, and endocrine changes associated with parturition and lactogenesis contribute to development of fatty liver. Cows that are overconditioned at calving are at highest risk. Fatty liver can develop whenever there is a decrease in feed intake and may occur secondary to the onset of another disorder. Fatty liver at calving is commonly associated with ketosis.
ETIOLOGY:
Mobilization of body fat reserves that is triggered by hormonal cues in states of negative energy balance results in the release of NEFAs from adipose tissue. The liver retains ~15%–20% of the NEFAs circulating in blood and thus accumulates increased amounts during periods when blood NEFA concentrations are increased. The most pronounced increase occurs at calving, when plasma NEFA concentrations can exceed 1,000 mcM/L.
NEFAs taken up by the liver can either be oxidized or esterified. The primary esterification product is TAG, which can either be exported as part of a very low density lipoprotein (VLDL) or be stored in liver cells. In ruminants, export occurs at a very slow rate relative to many other species because of impaired VLDL synthesis. Therefore, under conditions of increased hepatic NEFA uptake and esterification, triglycerides accumulate. Oxidation of NEFAs leads either to the production of ATP in the tricarboxylic acid cycle or to the formation of ketones through peroxisomal or beta-oxidation. Ketone formation is favored when blood glucose concentrations are low. Conditions that lead to low blood glucose and insulin concentrations also contribute to fatty liver, because insulin suppresses fat mobilization from adipose tissue.
The greatest increase in liver TAG typically occurs in the first weeks of lactation. The extent of negative energy balance around calving or during disease in combination with the available amount of body fat determine the degree of TAG accumulation in the liver. Excessive TAG accumulation in liver cells results in disturbed liver function and cell damage.
Increases of the liver TAG content from < 10 g/kg liver wet weight in late gestation to 20–30 g/kg over the first 4 weeks of lactation are common in highly productive dairy cows and are not associated with clinical disease. Clinical signs related to fatty liver disease tend to become apparent with liver TAG contents of 150 g/kg liver wet weight and above. Although lipid accumulation in the liver is a reversible process, the slow rate of TAG export as lipoprotein causes the disorder to persist for an extended period. Depletion of the liver lipid content usually begins when the cow reaches positive energy balance and may take several weeks to fully subside.
CLINICAL FINDINGS:
The clinical presentation of fatty liver disease can vary from mild ketosis to liver coma, with fatal outcome depending on the severity of liver TAG accumulation. Mild clinical signs become apparent with liver TAG contents in the range of 100 g/kg liver wet weight, whereas liver coma is observed with values approaching or exceeding 300 g/kg.
There are no pathognomonic clinical signs of fatty liver disease in cattle. The condition is often associated with feed intake depression, decreased milk production, and ketosis. Increased blood NEFA concentration has been associated with impaired immune function and a proinflammatory effect, presumably reflecting in increased incidence of clinical mastitis, metritis, and other periparturient infectious diseases. However, cause and effect has not been established. Metabolic consequences of TAG accumulation in the liver include reduced gluconeogenesis, ureagenesis, hormone clearance, and hormone responsiveness. Consequently, hypoglycemia, hyperammonemia, and altered endocrine profiles may accompany fatty liver.
Fatty liver is likely to develop concurrently with other diseases such as metritis, mastitis, abomasal displacement, or hypocalcemia, typically disorders that are seen at or shortly after calving. Field observations suggest that response to treatment of concurrent disorders is poor if cows have extensive TAG accumulation in the liver. Cows slow to increase in milk production and feed intake after calving are likely to have fatty liver. However, fatty liver is probably the result rather than the cause of poor feed intake.
Fatty liver is often associated with obese cows and is often seen in downer cows that have decreased feed intake over prolonged periods of time. Overconditioned cows exhibit more pronounced feed intake depression before and after calving than nonobese cows and, therefore, are susceptible to fatty liver. Although obesity predisposes to fatty liver disease, it is not restricted to obese cows. Similarly, obese cows do not necessarily have fatty liver. Other factors thought to potentially predispose to fatty liver disease are clinical and subclinical periparturient hypocalcemia that is associated with hampered insulin secretion, or lameness in dry cows that is associated with decreased standing and eating times in late gestation and early lactation.
PREVENTION AND TREATMENT:
Prevention of fatty liver disease must focus on optimizing cow animal well-being during the dry period. Crowding, sudden ration changes, limited feed bunk space, heat stress, and lameness all may contribute to the reduction of feed intake in the days and weeks before calving. Excessive body condition at the time of dry-off and factors negatively affecting feed intake in the last weeks of gestation are important risk factors.
The critical time for prevention of fatty liver is ~1 week before through 1 week after parturition, when cows are most susceptible. Cows that are candidates for preventive measures are those that are overconditioned or starting to go off feed. Propylene glycol, 300–600 mL/day, given as an oral drench during the final week prepartum, has effectively reduced plasma NEFAs and the severity of fatty liver at calving. Propylene glycol can be fed, but feeding may not be as effective if the full dose is not consumed in a short period of time. Glycerol (up to 1 kg/cow, once daily) has been suggested as a less expensive and more palatable alternative to propylene glycol.
Glucose or glucose precursors are effective for the control of ketosis and fatty liver disease because they trigger an insulin response. Insulin is antilipolytic, ie, it decreases lipid mobilization from adipose tissue. A single 100 IU IM dose of a 24-hour, slow-release insulin immediately after calving may be prophylactic.
Approaches to treat fatty liver disease are similar to those used to treat ketosis and depend on the severity of the clinical presentation. Mild cases are often treated with oral doses of propylene glycol (250–300 g/cow, twice a day), glycerol (up to 500 g/cow, twice a day) or sodium propionate (200 g/cow, twice a day). The objective with these treatments is to obtain peaks in blood glucose and thereby peaks in insulin secretion. More severe cases of ketosis and fatty liver disease may be treated with a single or repeated IV bolus administration of 500 mL of 50% dextrose solution and can be combined with the administration of propylene glycol (250 mL, PO, twice a day).
Use of glucocorticoids in cows with fatty liver is controversial because of their potential lipolytic effect. Recent literature suggests that short-term treatment with dexamethasone does not induce lipolysis in dairy cows. The gluconeogenic effect of glucocorticoids that is well documented in several monogastric species has thus far not been confirmed in cattle. In cattle, increased blood glucose concentrations after parenteral administration of glucocorticoids have primarily been attributed to an impaired glucose uptake by the mammary gland. In addition, glucocorticoids are thought to have a positive effect on feed intake.
