ABSTRACT
Ketosis is associated with both negative energy balance and hypoglycemia. In dairy cows, ketosis occurs in the first 3-8 wk of lactation. At this stage of lactation, the cow is in negative energy balance, insulin concentration is decreased, glucagon concentration is increased, hormonesensitive lipase activity is increased, and there is increased mobilization of NEFA. At the same time, the cow may be hypoglycemic due to an insufficient rate of gluconeogenesis relative to the amount of glucose needed by the mammary gland for the synthesis of lactose and the glycerol portion of milk fat as well as the glucose needs of other body tissues. Ketosis also occurs in cows less than 10 days in lactation. A predisposing factor for periparturient ketosis is low dry matter intake at calving.[3] In ewes and does, the condition is most commonly associated with the last month of gestation in females carrying twins. Intake declines and the rate of gluconeogenesis is not adequate to meet the demands of fetal tissues as well as glucose needs of other body tissues.[4] Cows with clinical ketosis will decrease feed intake and milk production, but they may
CytokineEggs
spontaneously recover from the disease. In ewes and does, the condition is often fatal. They may recover if birth occurs or if lambs or kids are removed by cesarean section.[1]
The presence of ketone bodies in urine or milk are signs of ketosis. Diagnosis is difficult prior to observation of clinical signs. Serum concentrations of BHB from 1.2 to 1.4 mM may indicate subclinical ketosis.[5] Serum BHB of 1.4 mM in the first week of lactation was associated with decreased milk production and increased risk of clinical ketosis.[6] Milk is more convenient to sample and test for ketone bodies. Validation of rapid and inexpensive methods to screen large numbers of cows for acetone or BHB can be used to evaluate a herd for subclinical ketosis or to evaluate feed management.[7] Treatments include intravenous administration of glucose, feeding glucose precursors such as propylene glycol, administration of glucocorticoid hormones, and the use of methanogenic inhibitors. Propylene glycol, which is not fermented and is converted to pyruvate after absorption, may be administered as a drench or included in the grain mix. Administration of glucocorticoid hormones, such as dexamethasone, will promote increased gluconeogenesis from amino acids. Methanogenic inhibitors, such as chloral hydrate, can also be used to increase propionate production in the rumen and, consequently, increase gluconeogenic precursors.[1,5] Monensin, an ionophore, changes ruminal metabolism and can be delivered in the feed or with a controlled release capsule. A meta-analysis of its impact on health showed that administration of monensin decreased the risk of ketosis.[8]
Fatty Liver in Ruminants
The fat content of liver is normally less than 5% of the wet weight. Fatty liver is the condition arising from the pro-
gressive infiltration of fat into the liver lobule. Fat content in the liver may increase to 30% of wet weight. Fatty liver is often associated with conditions of undernutrition such as ketosis due to the central role of the liver in the metabolism of fat (Fig. 1). During undernutrition, increased release of NEFA from adipose tissue results in increased uptake of NEFA by the liver. In the liver, NEFA can enter the mitochondria for conversion to acetyl CoA and either formation of ketone bodies or complete oxidation. The NEFA that do not enter the mitochondria can be esterified to form phospholipids, cholesterol esters, and TAGs. With adequate glucose availability, CPTI activity is decreased and NEFA are esterified, forming TAG.[2] These esterified compounds must be combined with apoproteins and incorporated into VLDLs for export from the liver. Hepatic apoB-100 concentration, a component of VLDL, is decreased in cows with ketosis and fatty liver.[9]
In dairy cows, fatty liver is present in early lactation in conjunction with hypoglycemia and negative energy balance. However, evaluation of liver biopsies from cows around calving showed that liver triglyceride content peaked around calving. By day 1 postpartum, approximately half of the cows had more than 15% liver triglyceride. The association of fatty liver with ketosis may be due to impaired gluconeogenic capacity in the liver in conjunction with fatty infiltration.[10] In fatty liver, TAG synthesis in the liver increases, and transport of fat in lipoprotein out of the liver decreases. In general, the ability of ruminants to secrete VLDL is lower than that of other species. Decreased secretion may be due to inadequate synthesis of the protein portion of the lipoprotein.
