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While an animal with only conjugated bilirubinaemia would most likely have post-hepatic jaundice (due to biliary tract or pancreatic disease most commonly), the majority of animals with hepatic or post-hepatic jaundice will have both unconjugated and conjugated bilirubinaemia. Guilford WG. Idiopathic inflammatory bowel diseases. 11. A loss of greater than 70% of liver function is required before hypoalbuminaemia occurs. 9 Three major isoenzymes contribute to total serum ALP: bone, liver, and corticosteroid isoenzymes.1,3,8, Bone ALP accounts for about one-third of the total serum ALP and is elevated with conditions associated with increased osteoblastic activity such as bone growth, osteomyelitis, osteosarcoma, and secondary renal hyperparathyroidism.3, Liver ALP is a membrane-bound enzyme present on biliary epithelial cells and hepatocytes. Alanine aminotransferase (ALT, formerly SGPT). Thyroid function and serum hepatic enzyme activity in dogs after phenobarbital administration. Chronically ill dogs may produce the G-ALP isozymes secondary to stress-induced glucocorticoid release. } Liver Enzyme Interpretation and Liver Function Tests | Today's Finally, drugs can induce excess hepatobiliary enzyme production in the absence of liver damage (see boxed text titled "Drugs that affect liver enzyme interpretation"). $resultElement.html("No File Found"); message = "You're already subscribed. Causes of elevated levels of bilirubin in dogs may vary. Clinicopathologic features of dogs with hepatic microvascular dysplasia with and without portosystemic shunts: 42 cases (1991-1996). 21 Causes of Elevated GGT + Proven Ways to Reduce It Medically reviewed by Puya Yazdi, MD | Written by Joe Cohen, BS | Last updated: May 29, 2023 Tests for gamma-glutamyl transferase (GGT) are important in the diagnosis of liver/biliary tract disease and useful in identifying alcohol abuse. . Distinct serum ALP isozymes can be extracted from some of these tissues in each species; eg, bone (B-ALP), liver (L-ALP), and glucocorticoid-induced (G-ALP) isoenzymes in canine serum. 6. Liver enzyme activities should be reevaluated two weeks after discontinuation of the suspected hepatotoxic agent. However, a normal total serum bile acid concentration does not rule out liver disease. High levels indicate stress, , pancreatitis or can be due to certain medications. Hepatomegaly is typically associated with any vacuolar hepatopathy (e.g. However, in dogs, a dosage of 200 mg/kg may be life-threatening, with susceptibility heightened by antecedent exposure to phenobarbital. Thereafter, values may plateau or continue to increase as high as 100-fold. Differences reflect physiologic adaptations during the transition from fetal and neonatal life stages, colostrum ingestion, maturation of metabolic pathways, growth effects, differences in volume of distribution and body composition, and nutritional intake. A complete minimum database, including a complete blood count and urinalysis, is required to rule out an underlying extrahepatic disease. 3rd ed. The histologic features include mild to moderate mononuclear periportal inflammatory infiltrates, lipidosis, and focal hepatocellular necrosis.17 These changes are likely secondary to inappropriate gastrointestinal absorption of toxic bacterial products such as endotoxin. Production And Regulation The liver is all about production, including: Production of bile, which aids the digestion of fats. In general, serum levels are not regarded as significant unless they are two to three times above normal. How I Approach a Dog with Increased Serum ALT - WSAVA 2019 Congress - VIN A full assessment of liver enzyme aberration considers: 1) the predominant pattern of enzyme change (hepatocellular leakage enzymes vs cholestatic enzymes), 2) the magnitude of increase of enzyme activity above the normal reference range (mild is < 3 times the upper reference range, moderate is 3-9 times, marked is >10 times), 3) the rate of cha. if (data.msg && data.msg.indexOf("already subscribed") >= 0) { jQuery.ajax({ In: Grant Guilford W, Center SA, Strombeck DR, et al, eds. Comazzi S, Pieralisi C, Bertazzolo W. Haematological and biochemical abnormalities in canine blood: frequency and associations in 1022 samples. Further diagnostic testing is also indicated if the patient in question is not of a breed predisposed to a hepatopathy, has no history of drug exposure, and has any of the following: An elevation of greater than three times the upper reference range limit in more than one enzyme activity A progressive increase in enzyme activities A single enzyme activity elevation and an increased bilirubin or decreased albumin concentration. Any elevation in liver enzyme activity in dogs of breeds predisposed to a hepatopathy or associated with portosystemic vascular anomalies requires further diagnostic evaluation. It is not necessary to do the test if the patient is jaundiced and not anaemic, nor if liver enzyme changes permit an unequivocal diagnosis of liver disease to be made. Pancreatitis Pancreatitis causes increased levels of Gamma glutamyltransferase (GGT) in the liver. Gallbladder mucoceles, choleliths, and intrahepatic or extrahepatic bile duct dilatation can be identified ultrasonographically. jQuery("#mc-embedded-subscribe-form").submit(function(e){e.preventDefault();submitSubscribeForm(jQuery("#mc-embedded-subscribe-form"), jQuery("mce-success-response")); However, they have a lower specificity (a measure of a test's ability to exclude individuals without hepatobiliary disease), so some animals without liver disease will have elevations (false positive results). The half-life of the ALT enzyme is short. Signalment may be helpful since several breed-associated hepatopathies that are inflammatory, fibrotic, or both exist (Bedlington terriers, cocker spaniels, dalmatians, Doberman pinschers, Labrador retrievers, Skye terriers, West Highland white terriers) and portosystemic vascular anomalies have strong breed associations.10,11. Ultrasonographic assessment may help determine the method of liver biopsy; needle biopsies are ill advised in animals with microhepatica, ascites, or difficult-to-sample focal liver lesions. Sequential morphologic and clinicopathologic alterations in dogs with experimentally induced glucocorticoid hepatopathy. Testing for Liver Disease | VCA Animal Hospital | VCA Animal Hospitals A similar trend is evident in some dogs. Some affected dogs show clinical signs of illness, while others are asymptomatic. However, serum GGT and ALP activities decrease after liver injury at a similar rate in dogs, suggesting that they have a similar half-life. data: $form.serialize(), A declining ALT also may represent a paucity of viable hepatocytes in end-stage chronic hepatitis or severe acute liver disease. It also takes up toxic substances and converts them into harmless substances or makes sure they are released from the body. Gamma Glutamyl Transferase in domestic animals - PubMed The ALT activity persists for weeks until necrosis resolves. Post-hepatic obstruction of the biliary tract almost invariably causes secondary hepatocellular damage and hence both ALT and ALP will be elevated. 17. Philadelphia, Pa: WB Saunders Co, 1996;458-462. Gamma-glutamyl transferase (GGT) is a membrane-bound glycoprotein that plays a critical role in cellular detoxification (involved with glutathione availability), conferring resistance against a number of toxins and drugs. It is not as sensitive in dogs as ALP but does have higher specificity. Just click. Unfortunately, indiscriminate leakage limits their diagnostic utility. When severe, VH has a cholestatic effect that seemingly causes canalicular compression. The diagnosis was made on abdominal ultrasonographic examination, which revealed immobile, echogenic bile with a striated or stellate pattern within the lumen of the gallbladder (Figure 1).21 Cholecystectomy is recommended in these cases to prevent sequelae including cholecystitis, extrahepatic bile duct obstruction, and gallbladder rupture.21. Because AST is located within the mitochondria and free within the cytosol of hepatocytes, AST in fold increases greater than those of ALT may reflect mitochrondrial injury. Table 2: Drugs Associated with Acute Liver Disease in Dogs. GGT is an enzyme found throughout the body, but it is mostly found in the liver. Similar degrees of elevation may be seen with GGT activity, and in 50% to 80% of dogs a mild increase in ALT activity is noted.15 Other clinicopathologic changes that might provide clues to the presence of hyperadrenocorticism are mild polycythemia, a stress leukogram, mild thrombocytosis, hypercholesterolemia, hypertriglyceridemia, and isosthenuria.15. Bunch SE. 20. Serum activities of ALP, AST, CK, and LDH in neonates usually increase greatly during the first 24 hr of life. This toxin is highly dose dependent in dogs and cats. Occasionally, bile acids can be normal in patients with hepatic disease. However, the half-life of the intestinal, renal and placental isoenzymes are so short (two to six minutes) that serum elevations of ALP would rarely occur from these organs. Although increased AST activity in the absence of abnormal ALT activity implicates an extrahepatic enzyme source (notably in muscle injury), there are clinical exceptions that may relate to severity and zonal location of hepatic damage. 5. Your diagnostic test findings may point to three extrahepatic causes-hyperadrenocorticism, hypothyroidism, and gastrointestinal disorders. With the exclusion of these underlying disorders, cats with HL usually have a higher fold increase in ALP relative to GGT; this has important diagnostic utility in discerning the underlying cause of HL. Enzymes must be present in a high enough concentration for some spillover into the circulation to occur. Am Coll Vet Intern Med 2005. Causes of Bloat (GDV) in Dogs | Preventive Vet contentType: "application/json; charset=utf-8", Several drugs have been associated with hepatotoxicity in dogs (Table 2).12 If a potentially hepatotoxic drug or supplement is being administered, discontinue it; if abrupt cessation is not possible, taper the drug and add another drug of a different class. Understanding Blood Work: The Biochemical Profile for Dogs - PetPlace Valentine BA, Blue JT, Shelley SM, et al. Cholecystocentesis can also be performed to obtain bile for culture in cases in which subclinical infection is suspected. AST is found in muscle cells as well as liver cells, so an elevation in AST without a similar elevation in ALT may indicate muscle damage rather than liver damage . Necroinflammatory disorders involving biliary structures, the portal triad, or pancreas are often associated with a greater fold increase in GGT than in ALP. Recognizing whether enzyme abnormalities are persistent or cyclic helps categorize likely causes. Imaging studies help detect primary underlying disorders that have secondarily influenced the liver, causing increased enzyme activity. Pharmacokinetics of liver transaminases in healthy dogs: potential clinical relevance for assessment of liver damage (abst), in Proceedings. Elevated triglyceride and/or cholesterol levels can have genetic causes. In asymptomatic patients, a systematic approach is required to obtain a definitive diagnosis. Diagnosing Liver Disease in Dogs: What do the Tests Really Mean Administration of dexamethasone (3 mg/kg/day) or prednisone (4.4 mg/kg/day, IM) may increase GGT activity within 1 wk to 4- to 7-fold above normal and up to 10-fold within 2 wk. Aspartate aminotransferase (AST) AST is an enzyme found mostly in the heart and liver and to a lesser extent in skeletal muscle. In the case of focal or diffuse neoplasia, a fine-needle aspiration biopsy may yield diagnostic samples. The second determinant is the serum enzyme's half-life. Less dramatic increases are found in cases of hepatic necrosis, hepatitis, and nodular hyperplasia. Therefore, mild bilirubinuria (up to 2+) can occur in normal dog urine of greater than 1.025 specific gravity. It is also present in the pancreas, kidney tubules, and epithelial cells of mammary tissue. Additional clinicopathologic changes that might be seen with inflammatory bowel disease include a peripheral eosinophilia and mild hypoalbuminemia, hypoglobulinemia, and hypocholesterolemia.17 With chronic pancreatitis, hyperlipidemia, hypertriglyceridemia, or mild hyperglycemia may be noted.16 Further work-up should include an abdominal ultrasonographic examination followed by endoscopy with intestinal biopsy or evaluation of serum canine pancreatic lipase immunoreactivity in suspected cases of inflammatory bowel disease and pancreatitis, respectively. All rights reserved. A full assessment of liver enzyme aberration considers: 1) the predominant pattern of enzyme change (hepatocellular leakage enzymes vs cholestatic enzymes), 2) the magnitude of increase of enzyme activity above the normal reference range (mild is < 3 times the upper reference range, moderate is 39 times, marked is >10 times), 3) the rate of change (increase or resolution) with sequential sampling, and 4) the nature of the course of change (fluctuation vs progressive increase or decrement). What Causes Elevated Liver Levels in Dogs? - Vetinfo.com Such tests include hepatic function tests (measuring serum bilirubin, blood ammonia, and total serum bile acid concentrations), hepatobiliary histologic examination, or interpreting hepatobiliary enzyme activities in concert. While elevated liver enzymes can be indicators of health complications outside of the liver, we will stick to the complications that directly impact the liver. In other cases, such as with a diffuse vacuolar hepatopathy, inflammatory disease, or neoplasia, a diagnostic sample can likely be obtained by performing a Tru-Cut biopsy. Production of blood proteins, clotting factors and substances important to the making of red blood cells. However, although the liver is the largest solid organ in the body, its plain film evaluation is unreliable. Examples of classic necrotizing hepatotoxins are carbon tetrachloride, acetaminophen, and nitrosamine. Hi! ALP activity in dogs has the lowest specificity of routinely used liver enzymes as a result of its complexity associated with induction of different isozymes. Vet Clin North Am Small Anim Pract 1993;23:659-670. ALP is slightly more sensitive than GGT for detection of cholestatic disease in dogs. Liver ALP can also be induced by corticosteroid or phenobarbital administration.3,5,7,9, Corticosteroid ALP isoenzyme is produced in the liver and is located on the hepatocyte plasma membranes lining the bile canaliculi and sinusoids.3 Corticosteroid ALP has a similar half-life to liver ALP. Am J Vet Res 1981;42:1310-1318. In cases of nodular hyperplasia, homogenous hypoechoic masses or mixed hypoechoic to hyperechoic lesions may be noted but cannot be differentiated from primary or secondary neoplasia.13 Ultrasonography can also reveal changes in liver echogenicity; unfortunately, no change is classic for a specific disease. There are several reasons for this discordance. If a shunt cannot be confirmed but is still suspected, scintigraphy (colorectal or transplenic) can be considered. All rights reserved. Cholestasis results in increased synthesis and regurgitation of the enzyme from the biliary system into the serum. Vet Clin North Am Small Anim Pract 1985;15:243-256. We made an updated version of this article in 2018. J Small Anim Pract 2004;45:343-349. Dogs treated with phenytoin or primidone develop only a modest increase in serum GGT activity (up to 2- to 3-fold), unless they develop anticonvulsant hepatotoxicosis that is often associated with marked enzyme activity. We do not control or have responsibility for the content of any third-party site. Diagnostic comparison of needle and wedge biopsy specimens of the liver in dogs and cats. When levels are increased in the blood, it means that the enzymes have leaked out of the liver cells due to cell damage. var product_id = jQuery('.free_recipe_btn').data('product-id'); 3. 8 No definitive studies determining the half-life of GGT have been performed in cats or dogs. Liver Disease in Dogs: Symptoms and Causes - WebMD Consider testing for hypothyroidism (free T4 concentration, thyroid-stimulating hormone test) in dogs that are of breeds prone to this condition and that exhibit concurrent weight gain, decreased exercise tolerance, or skin and coat changes. This results in the loss of appetite, abdominal pain, fever, profuse vomiting, and lethargy in affected dogs. function submitSubscribeForm($form, $resultElement) { In patients with portosystemic shunts, twofold to threefold increases in serum ALP, ALT, and AST activities have been recorded while patients with microvascular dysplasia may have normal to mild increases in these enzyme activities.20 Microcytic red blood cells are commonly noted in cases of portosystemic shunts but are not seen in cases of microvascular dysplasia. Hepatic lipidosis, glucocorticoid hepatopathy, vacuolar hepatopathy, storage disorders, amyloidosis, and iron toxicity. A gamma-glutamyl transferase (GGT) test measures the amount of GGT in the blood. Any liver injury causes a peak increase in ALT level in dogs. Serum globulins. Like ALP, GGT lacks specificity in differentiating between parenchymal hepatic disease and obstructive biliary disease. Substantial increases in ALP with moderate increases in ALT will occur in most dogs with hyperadrenocorticism. Glucocorticoids and other enzyme inducers in dogs do not clinically influence serum GGT in cats. End-stage fibrosis of many inflammatory hepatic diseases. In patients with nodular hyperplasia, other serum liver enzymes activities (transaminases) may be elevated, but hepatic function test results are usually normal. Vascular liver diseases. Asymptomatic dogs with increases in serum hepatobiliary enzyme activities may have either extrahepatic disease or primary hepatobiliary disease (Table 1). Elevated liver enzymes in senior dogs- what does it really mean? Acute, severe, diffuse necrosis is associated with either no change or only mild increases (1- to 3-fold normal) in GGT activity that resolve in ~10 days. The increased ALP seemingly reflects canalicular dysfunction or compression. The largest increases in ALT develop with hepatocellular necrosis and inflammation. Bone remodeling secondary to neoplasia may not substantially affect serum ALP activity or may cause only a trivial increase (2- to 3-fold) in dogs. 2. 4. Center SA. Philadelphia, Pa: WB Saunders Co, 1996;782-788. Mathews KG, Bunch SK. Gamma glutamyl transpeptidase (GGT). 10. 3rd ed. Pre-operative liver screen selection: a comparison for glutamic pyruvic transaminase and serum alkaline phosphatase. My dog has raised liver enzymes, what does that mean? What it doesn't tell us, is why. It takes several days for induction of membrane-associated enzyme to gear up and spill into the systemic circulation. 1. Abstract. Choleliths can be associated with cholecystitis and may indicate a subclinical hepatobiliary infection. Such dogs with glycogen-associated VH (lacking exogenous glucocorticoid exposure) may demonstrate normal dexamethasone suppression and adrenocorticotropic hormone (ACTH) response tests. Increases in hepatobiliary enzyme activities-alanine transaminase (ALT), aspartate transaminase (AST), gamma-glutamyltransferase (GGT), and alkaline phosphatase (ALP)-are commonly encountered on serum chemistry profiles in these animals. Increased serum AST activity, in the absence of increased ALT activity, indicates an extrahepatic source, most likely muscle injury.4 Marked elevations in AST activity are suggestive of irreversible hepatocyte injury with release of mitochondrial AST stores. Physical examination findings may include coat changes and hepatomegaly (due to hyperadrenocorticism), a stunted or pot-bellied appearance and poor body condition (due to a portosystemic vascular anomaly), mild abdominal discomfort (due to chronic pancreatitis), or thickened intestines (due to inflammatory bowel disease). If elevated ALP activity is noted with a concurrent increase in serum GGT activity, specificity for liver disease increases to 94%.8, Serum GGT activity is largely derived from the hepatobiliary system. What Does the Biochemical Profile Mean? 2023 MJH Life Sciences and dvm360 | Veterinary News, Veterinarian Insights, Medicine, Pet Care. Although glycogen-associated VH was initially characterized as a glucocorticoid-initiated lesion, it is now established that nearly 50% of dogs with glycogen-associated VH lack overt exposure to steroidogenic substances. Moderately increased bilirubin can occur in a variety of non-hepatic diseases as well as in conditions such as prolonged anorexia, catabolic states, and infection. The magnitude of serum ALT activity elevation is roughly proportional to the number of injured hepatocytes.3 Serum ALT activity may also increase because of induction of enzyme synthesis by corticosteroid use and, possibly to a lesser extent, by phenobarbital therapy.3,5 Serum ALT half-life is 2.5 days.6, Increases in serum ALT activity have the highest sensitivity (80% to 100%) for hepatic inflammation and necrosis, vacuolar hepatopathy, and primary neoplasia (hepatocellular carcinoma, cholangiocarcinoma) but have less sensitivity (50% to 60%) in cases of hepatic congestion, metastatic neoplasia, and portosystemic vascular anomalies.3, The highest tissue concentrations of AST are present in the liver, skeletal muscle, and cardiac muscle. Serum half-life is about 40-60 hours in the dogs: following an acute hepatic injury, ALT will increase within 12 hours and serum enzyme activity generally peaks at about 24-48 hours and then begins to decrease. Hepatic vascular diseases. The low serum GGT activity in dogs (0 to 10 IU/L) may be related to relatively less liver GGT than in some other domestic animals. Liver ALP half-life is 70 hours.3,8 The largest increases in liver ALP activities are associated with focal or diffuse cholestatic disorders and primary hepatic neoplasms (hepatocellular and bile duct carcinoma). Cholecystitis can be diagnosed based on . In young growing cats, increased B-ALP activity may simulate enzyme activity seen in hepatobiliary disease. Oops! Unable to subscribe. 8. Overview of Hepatic Disease in Large Animals By Jonathan H. Foreman , DVM, DACVIM, College of Veterinary Medicine, University of Illinois at Urbana-Champaign Last review/revision Aug 2014 | Modified Oct 2022 View the Pet Owner Version Clinical Findings: Diagnostic Testing: Treatment and Management: Hepatic disease is common in large animals. Serum bile acids are therefore useful but not infallible for differentiating elevated ALP values due to steroids (endogenous or exogenous) or hepatobiliary disease. Nonetheless, duration and magnitude of transaminase activities measured sequentially can predict disease activity and severity and roughly estimate the number of involved cells. gamma-Glutamyltransferase (GGT) activity in canine kidney, pancreas, and liver is similar to previously reported values for other species. 18. Investigating liver function with paired fasting and postprandial total serum bile acids (TSBAs) or urine bile acid/creatinine measurements (urine collected 48 hr after meal ingestion) may expedite a decision to pursue liver biopsy when clinical signs remain vague and enzymes are only mildly increased.