Chemistry basics

Results of chemistry tests provide information on the function of various body systems and yield clues or even diagnosis as to the presence of underlying disease. Chemistry tests should always be interpreted with respect to what is known about the patient (signalment, history, clinical signs, results of other diagnostic testing) and should not be interpreted in isolation. It helps to interpret chemistry tests by thinking of mechanisms responsible for the changes and by grouping results together.

Variables affecting results

Many factors other than disease influence the results of chemistry tests. These factors may be preanalytical, analytical and post-analytical. For more information, see test basics section of this site.

• Preanalytical: These are variables associated with the patient, sample collection and sample handling. These generally affect the composition of the body fluid before analysis and can have a major impact on result interpretation. Some of these patient- or sample-related variables, such as hemolysis, icterus and lipemia can be semi-quantified (mild, moderate, marked) by visually assessing the sample or quantified with automated analyzers. The analyzer used at Cornell University provides a quantitative measurement of these variables and we provide guidelines as to how these common interferences may affect our provided results (for more information on these interferences, see related links).
• Analytical: These are factors which influence the analytical procedure, such as precision and accuracy.
• Post-analytical variables: This involves the different ways data from the laboratory is presented, stored and transferred to the clinician.

Whenever possible, these variables should be controlled in order to minimize their effect on test outcome (for more information on these variables, see related links).

Mechanisms for change

Throughout this site and particularly in the chemistry section, we have organized result interpretation based on mechanisms. These mechanisms are organized as follows:

• Artifact: This includes common interferences, such as lipemia, hemolysis and icterus, which cause false increases in test results due to interference with methods.
• Physiologic: Changes expected due to signalment (species, breed, age, sex).
• Iatrogenic: These are changes that we induce through drug administration. Some could be an artifact (interfere with test measurement, e.g. ) whereas other can cause real changes in the animal, e.g. phenobarbital treatment for seizures in dogs increases hepatocellular leakage enzymes (such as ALT), reflecting liver injury. In contrast, bromide treatment for seizures in dogs falsely increases chloride results when measured by ion-selective electrodes. The latter would be placed under artifacts.
• Pathophysiologic: Depending on the test, this is generally separated into the following:
  • Input: Dietary intake, absorption in the gastrointestinal tract, or production in the body. This can be affected by hormones.
  • Movement between cells, tissues or compartments: Constituents can move in and out of cells or between intravascular and extravascular compartments (including the gastrointestinal tract or body cavities).
  • Output: This can occur through multiple routes, including the urinary system, gastrointestinal system, respiratory system, and skin. he most common sources of loss are the gastrointestinal and urinary tracts, followed by the skin.

Result interpretation

Results for chemistry tests are generally interpreted in two ways:

• On an individual basis: Results for individual chemistry tests are generally interpreted with respect to reference intervals. Reference intervals should be established for each analyzer, since they will vary between laboratories (based on the animal population and number of animals used to determine the intervals, analyzer and method used to measure the analyte). The degree of change above or below the upper or lower reference limit that is actionable (of diagnostic relevance) differs between analytes and is highly subjective (and a matter of opinion). Mild changes in one analyte (e.g. ALT) are less clinically relevant than others (e.g. potassium). For some test results, a consensus statement has been provided to aid with interpretation (e.g. urinary protein to creatinine ratios). Although we are clued into look at those “H” and “L” flags, sometimes normal results may actually be abnormal. For example, dehydration may increase electrolyte concentrations to within the reference interval in an animal that has electrolyte depletion. It cannot be over-emphasized that all laboratory data should be interpreted with respect to the patient (clinical signs, results of diagnostic imaging or other testing, suspected or known diagnoses). If the laboratory results do not fit with the patient, repeat testing (on a fresh sample) may be warranted.
• Grouping results (pattern recognition): There is a wealth of information provided on chemistry profiles, which can be overwhelming. To facilitate interpretation, chemistry tests can be grouped together on the basis of body system or physiologic process. Grouping tests into common systems is the best way to interpret chemistry data as it enables pattern recognition. Patterns of change within and among these groups can provide useful diagnostic information about disease involvement of various organ systems. Grouping tests together can also help you select additional tests to identify disease processes in certain body systems. Test selection is important if cost is a factor in laboratory testing. The following is one way of grouping chemistry tests (most, but not all of which, are on routine chemistry panels and is the way most of this section is organized):
  • Electrolytes: Sodium, potassium and chloride
  • Acid-base: Bicarbonate, anion gap.
    Note: Acid base status is dependent on electrolytes, so these should be interpreted together.
  • Minerals: Calcium, phosphate and magnesium.
    Note: All the above are strongly influenced by kidney function, so results of renal testing (urea nitrogen, creatinine, urinalysis) should be evaluated concurrently. Also, many bovine practitioners order mineral and electrolyte panels.
  • Protein metabolism: Total protein, albumin, globulin, A/G ratio.
  • Kidney function: Urea nitrogen, creatinine.
    Note: Urine should be assessed along with biochemical indicators of renal function, including urine concentrating ability (urine specific gravity) and chemical constituents of urine (proteinuria, glucosuria). In addition, kidney function affects proteins, minerals, electrolytes and acid-base balance, as well as hematopoiesis (site of erythropoietin production).
  • Liver:
    • Injury (hepatocellular leakage enzymes): Alanine aminotransferase (ALT), aspartate aminotransferase (AST), sorbitol dehydrogenase (SDH), glutamate dehydrogenase (GLDH), lactate dehydrogenase (LDH).
  • Cholestasis:
    • Cholestastic enzymes: Alkaline phosphatase (ALP), gamma glutamyl transferase (GGT).
    • Bilirubin: Total and direct bilirubin
  • Function: Total bilirubin, indirect bilirubin, bile acids, ammonia.
    Note: The liver is responsible for production of most proteins in the body (with the exception of immunoglobulins which are produced by B lymphocytes), including coagulation factors, albumin, acute phase proteins, cholesterol, transferrin, and urea.
  • Blood flow (shunting): Bile acids, ammonia.
  • Pancreatic function: Amylase, lipase (including pancreatic lipase), trypsin-like immunoreactivity (TLI)
  • Energy metabolism
  • Carbohydrates: Glucose, fructosamine.
  • Lipids: Cholesterol, triglycerides, non-esterified fatty acids (NEFA), β-hydroxybutyrate (BHB), transition dairy cow energy metabolite assessment.
  • Muscle injury: Creatine kinase (CK), AST, ALT, LDH.
  • Iron metabolism: Iron, total iron binding capacity (TIBC), percentage saturation of transferrin.

Related links

• Variables affecting results: This section provides more detail on non-disease variables (pre-analytical, analytical, and post-analytical) that affect test results, including lipemia, icterus, hemolysis, and drugs.
• Interference indexes: This section provides information on the index values for lipemia (turbidity), hemolysis and icterus provided on clinical chemistry test results from Cornell University.