VN March 2023

Vetnuus | Maart 2023 36 Biochemistry analysis by organ system Dr Coetzee de Beer The liver The detection of liver disease through biochemistry is complicated by the fact that there are no specific‘liver enzymes’that can be evaluated conclusively in each and every case. Liver disease can be broadly classified into three conditions: hepatocellular rupture; decreased hepatic function; and cholestasis. These conditions can occur either separately or concurrently. Hepatocellular rupture releases intracellular enzymes which then reach elevated levels in the blood. These so-called ‘leakage enzymes’ include: a. Aspartate Aminotransferase (AST). This cytosolic enzyme is found in many tissues in the body, but the highest concentrations are found in skeletal muscle and liver. Significant elevations usually represent either muscular or hepatocellular damage. AST therefore must be interpreted alongside Creatine Kinase ( CK – released from damaged muscle) to distinguish between the two. In general, an elevated AST with a normal CK indicates hepatocellular rupture. However, CK has a much shorter half-life than AST; a single-point muscle injury (eg an injection) 4-7 hours before sample collection could duplicate this biochemistry pattern. Although AST is considered to be the most useful liver enzyme, it cannot be considered in isolation as an indicator of liver disease. b. Glutamate Dehydrogenase (GLDH) , a mitochondrial enzyme, is the most specific enzyme for the detection of liver disease, but its sensitivity is low – because it is bound to mitochondria, extensive and severe liver damage is required before elevations are detectable. c. Lactate Dehydrogenase (LDH) is not specific to any tissue; its main advantage lies with a half-life shorter than CK – persistent elevations in the presence of normal CK is strongly suggestive of liver disease. d. Alanine Aminotransferase (ALT) and Alkaline Phosphatase (ALP) are not considered useful in detecting liver disease in birds. ALT in birds is very non-specific for the liver, and normal levels have been shown in cases with severe liver damage. ALP elevations are more commonly associated with bone disease in birds. Decreased liver function can occur with any number of liver diseases – not all of which involve hepatocellular rupture. Chronic cirrhosis, amyloidosis and hepatic lipidosis can all be having an adverse effect on liver function without causing any cellular damage. In these cases a “liver function test” is necessary to detect the problem. Bile acids serve this purpose well. Produced in the liver, they are excreted in bile into the small intestine where they act to emulsify fat. Most of the bile acids are then resorbed in the small intestine, enter the portal system and are taken up by the liver to be recycled. Elevated levels occur when there is impairment of the liver’s ability to remove bile acids from the portal circulation. A 2-4-fold increase in bile acids indicates a significant decrease in liver function. It needs to be noted though that a severely dysfunctional liver (eg end-stage cirrhosis) may not be able to produce normal levels of bile acids, leading to low to normal results. Total protein , especially albumin , may also be decreased with decreased liver function. Cholestasis occurs when the biliary system is partially or totally obstructed. This can be seen with biliary neoplasia, pancreatic disease, or diffuse swelling of the entire liver. Gamma Glutamyl Transferase (GGT) is an enzyme found in the cell membranes of the bile ducts. Elevations can be seen in cholestatic disease (eg bile duct carcinoma) but it is considered to be a relatively insensitive test for liver disease in psittacines. Bilirubin is not produced in birds – they utilize biliverdin instead. There are no commercial assays for biliverdin. The kidney The end product of protein metabolism in birds is uric acid . It is produced in the liver, enters the circulation, and is then secreted by renal tubules (>90%) or filtered in the glomerulus (< 10%). Significant loss of renal tubules will therefore see elevations of uric acid. Dehydration is less likely to cause hyperuricaemia because glomerular filtration is relatively unimportant. At first glance it would appear that uric acid offers a sensitive and specific test for renal disease. There are, however, several confounding factors. Firstly, species differences; carnivorous birds have higher normal uric acid levels than granivorous birds. Secondly, age; juvenile birds may have lower levels than adults. Thirdly, although significant elevations usually indicate renal disease, normal levels do not mean the kidneys are normal; mild increases could indicate early renal disease or dehydration (or both). There must be severe renal damage before uric acid levels begin to rise. Because of this relative insensitivity of uric acid in detecting renal disease, levels are best interpreted alongside a determination of the bird’s water intake and loss, and a physical examination. To distinguish renal disease from dehydration, the patient’s hematocrit, total protein and blood urea nitrogen (BUN) should be evaluated concurrently. Dehydration can lead to decreased glomerular filtration rates Technical I Article