Analyte Selection
What are we looking for? Analyte Selection
Specific analytes determined for any herd metabolic profile will be dependent upon the metabolic profile sampling strategy described previously. The original CMP test measured 13 different analytes that included packed cell volume, hemoglobin, glucose, blood urea nitrogen (BUN), total protein, albumin, calcium (Ca), inorganic phosphorus (Pi), magnesium (Mg), potassium (K), sodium (Na), copper (Cu), and iron (Fe). The following is a brief overview of possible analytes that could be measured in serum or plasma at most veterinary diagnostic laboratories and their ability to provide either diagnostic or disease risk information.
Energy Balance
Energy balance is by and far one of the most critical nutritional factors impacting on animal health, lactation, and reproductive performance. Traditionally, we have monitored changes in energy balance via body weight and condition score changes over time. This procedure may not be a sensitive enough tool when dealing with the transition cow.
Nonesterified fatty acids (NEFA) have become the mainstay in determination of energy balance. Many research studies have shown good correlations between energy balance and serum NEFA concentrations. Concentration of NEFA directly reflects the amount of adipose (fat) tissue breakdown taking place. Excessively high NEFA concentrations due to negative energy balance either prepartum or early postpartum are predictive for increased risk of ketosis, left displaced abomasums, and most other periparturient diseases.
ß-hydroxybutyrate, one of the ketone bodies, is another parameter useful in assessing energy status. However, BHB can come from diestary sources (poorly fermented silage) and not reflect aberrant metabolism. Prior to calving, BHB concentrations are not predictive for disease risk but may be elevated if the animal is in negative energy balance or consuming ketogenic silage. Following calving, BHB concentrations are diagnostic for disease and predictive for periparturient disease problems.
Blood glucose concentration, as an independent test, is not a good indicator of energy status as a result of tight homeostatic control. However, glucose concentrations measured in conjunction with other tests may provide some further insight into underlying mechanisms of disease (Type I vs. Type II ketosis).
Protein Evaluation
At present there is no single metabolite that can be measured that directly reflects protein status. As a result, multiple parameters are needed to assess protein status including UN, creatinine, total protein, albumin and creatine kinase (Ck). Urea nitrogen concentrations are influenced by a wide variety of interrelated parameters including: dietary protein intake and rumen degradability, dietary amino acid composition, protein intake relative to requirement, liver and kidney function, muscle tissue breakdown, and dietary carbohydrate amount and rumen degradability. Creatinine is used to assess renal function and its impact on UN values. Creatin kinase is released from muscle when it is catabolized to supply needed amino acids or when injured.
Total protein and albumin reflect availability of amino acids and their concentration decline in the face of protein deficiency. However, this occures over a period of time. Albumin has a relatively short half-life and can reflect protein deficiency problems over a period of a month or two. Albumin was found to be associated with postpartum disease and can be used to predict disease risk in close-up and fresh periods. Other nutrients, namely iron and vitamin A, might also reflect protein status as both require a carrier protein synthesized in the liver. Lower concentrations of either nutrient may be observed when amino acid availability is limited, liver function is compromised, or both.
Liver Function
Liver function can be assessed through a variety of enzymes: gamma-glutamyltransferase (GGT), aspartate aminotransferase (AST), and sorbitol dehydrogenase (SDH) and total bilirubin concentrations in the blood. Unfortunately, an elevation in any of these parameters does not suggest anything more than some insult has occurred to the liver. Muscle catabolism or injury can result in elevated blood AST activities. Bilirubin values are most specific to bile flow problems that overt liver cell damage.
Since these parameters are not specific to liver function, other liver function indices have been advocated. A liver activity index parameter that accounts for changes in albumin, cholesterol and total bilirubin over the first 28 days follwing calving has been defined. Although a robust diagnostic tool, its use requires multiple samples from the same cow over a period of time. This would preclude its use within a typical metabolic profiling approach.
Calculating the NEFA to cholesterol ratio (molar bases) to assess the liver's ability to export incoming NEFA has been advocated. Calculated NEFA to cholesterol ratio was predictive for postpartum disease in the close-up dry and fresh cows.
Macromineral Evaluation
Macrominerals Ca, Pi, K, Mg, Na, chloride (Cl), and sulfer (S) are of extreme interest as to their status relative to their role in milk fever, alert downer cows, and weak cow syndrome. Unfortunately, most of these minerals are tightly regulated in the body through a variety of homeostatic processes. Blood concentrations of macrominerals are not reflective of dietary status when the homeostatic system is functioning property. Phosphorus, K, Mg, and S are macrominerals in which blood concentrations are somewhat sensitive to dietary intake. Electrolytes Na,Cl, and K are altered when renal or digestive function is compromised or in extreme dietary deficiency states.
Assessment of Ca concentrations around the time of calving is a useful indicator of how well the Ca regulatory system is working and potential for clinical or subclinical hypocalcemia problems. Despite concerns about homeostatic regulation, pre- and postpartum concentrations of Ca, Mg, Na, and K were found to be predictive of specific postpartum disease risk. Surprisingly, blood P concentrations were not found to be predictive of disease risk, but abnormal values still may provide some diagnostic significance.
Other Possible Analytes
Research into the role of inflammatory mediators as a contributing factor to periparturient disease pathogenesis has led to interest in measuring markers of an activated inflammatory response as part of metabolic profiling. Specific acute phase proteins ceruloplasmin and haptoglobin have been routinely determined by some investigators. Analytical tests for these acute phase proteins are not readily available outside of research laboratories at the current time. Other acute measures of inflammatory mediator activation (i.e., heat shock proteins) and oxidative stress markers may provide further insight, but are not currently available for use in metabolic profiling.
