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How I approach... The Dog with Altered Hepatic Enzymes
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Elevated liver enzymes on routine biochemistry screens are a daily occurrence in small animal practice; Jordi Puig discusses how he decides if such findings are significant or not.
Jordi Puig
DVM, Dipl. ACVIM (SAIM), Dipl. ECVIM-CA (Internal Medicine), Ars Veterinary Hospital, Barcelona, Spain.
Dr. Puig graduated from the Autonomous University of Barcelona in 2008 and after a short period in general practice undertook an internship and then a residency at the Animal Health Trust in the United Kingdom. He gained his Diploma from the American College of Veterinary Internal Medicine (Small Animal Internal Medicine) in 2014 and the European College of Veterinary Internal Medicine – Companion Animals (Internal Medicine) in 2017. He joined Ars Veterinary Hospital in 2015, where he is currently head of the Small Animal Internal Medicine Department. He is interested in all aspects of internal medicine, with a research focus on gastroenterology and endocrinology.
Key Points
- Liver enzyme levels do not indicate hepatic functionality; this requires evaluating parameters which reflect the liver’s capacity for synthesis and/or excretion of compounds, such as bile acids.
- A single measurement does not provide enough information in most cases, and serial monitoring is much more helpful.
- The biochemical changes found in patients with a secondary hepatopathy are usually caused by a non-specific reactive hepatitis.
- Where there is advanced liver disease, such as cirrhosis, any increase in hepatic enzymes may be slight.
Introduction
The correct diagnosis of a hepatobiliary disease can be a difficult task. An increase in liver enzymes is a common finding in all veterinary practices, and we must comprehend its meaning in order to establish a suitable diagnosis and treatment. Understanding the advantages and disadvantages of diagnostic laboratory testing is essential in order to avoid incorrect interpretation of results.
Basic principles of liver enzymology
Most methods used to measure enzyme levels are based on the calculation of their activity. The enzyme unit (U) is the amount of an enzyme that catalyzes the conversion of one μmol of substrate per minute ( 1 ). Ranges vary between laboratories and methodologies, and when comparing results it must always be in relation to the magnitude of the increase and not simply with absolute numbers. Additionally, remember that hemolysis, jaundice, or lipemia can alter the sample results, depending on the analytical method used.
The magnitude of the increase in enzyme activity tends to be in proportion to the severity of liver damage; however such tests do not predict liver function, the cause of the problem, or the prognosis. For example, where there is advanced illness such as cirrhosis, the increase in liver enzymes may be slight. Likewise, the duration of any increase depends mainly on the average half-life of the enzyme, the cause of the damage, and the severity of the process. Because of this, a single measurement rarely provides enough information for the clinician, and serial monitoring is much more revealing. Any increase in liver enzymes can be graded into 3 stages ( 2 ):
- Mild: < 5 times the upper limit of the reference range
- Moderate: 5-10 times the upper limit of the reference range
- Severe: > 10 times the upper limit of the reference range
The main mechanisms that cause increased serum liver enzymes are cell damage and the induction of enzyme synthesis. The enzymes are mainly found in the hepatocyte mitochondria, cytoplasm, or cell membrane. Where enzymes are elevated due to cell damage, the leaking of enzymes depends on their concentration and location within the cell. For example, an increase in enzymes located in the mitochondria suggests greater damage than an increase in enzymes located only in the cytoplasm. Liver enzymes are generally classified into two groups, those that indicate cell damage (alanine aminotransferase and aspartate aminotransferase) and those that indicate enzyme synthesis (alkaline phosphatase and gamma-glutamyl transferase) ( 3 ).
Finally, the measurement of liver enzymes is not proof of functionality. The assessment of liver function is based on evaluating parameters which reflect its capacity for synthesis and/or excretion, such as bilirubin, glucose, cholesterol, urea, albumin, or the bile acid stimulation test (Table 1). [...]
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