Diyala University Stage : 4th Stage Faculty of Veterinary Medicine Subject: Internal Medicine By: Dr. TAREQ RIFAAHT MINNAT (No.6) Special examination of the liver When disease of the liver is suspected after a general clinical examination, special techniques of palpation, biopsy and biochemical tests of function can be used to determine further the status of the liver. Palpation and percussion The liver lies beneath the costal arch and cannot normally be palpated. If it is grossly enlarged or displaced posteriorly it may be palpated by pushing the fingers behind the right costal arch. The liver may be enlarged in chronic liver fluke infestation and congestive heart failure. The exact location of the liver can be confirmed by percussion. BIOPSY Biopsy of the liver has been used extensively as a diagnostic procedure in infectious equine anemia, and other species of plants, and experimental work on copper and vitamin A deficiency. The technique requires some skill and anatomical knowledge. The most satisfactory instrument is along, small-caliber trocar and cannula to which is screwed a syringe capable of producing good negative pressure. The sharp point of the instrument is introduced in an intercostal space on the righthand side (the number depending on the species) and advanced across the pleural cavity so that it will reach the diaphragm and diaphragmatic surface of the liver at an approximately vertical position. The point of insertion is made high up in the intercostal space so that the liver is punctured at the thickest part of its edge. For example, in cattle the biopsy is made in the 11th intercostal space at a point on an imaginary line between the right elbow and tuber coxa. The instrument is rotated until the edge of the cannula approximates the liver capsule; the trocar is then withdrawn, the syringe is attached and strong suction is applied; the cannula is twisted vigorously and advanced until it reaches the visceral surface of the liver. If its edge is sufficiently sharp the cannula will now contain a core of liver parenchyma and if the instrument is withdrawn with the suction still applied a sample sufficient for histological examination and microassay of vitamin A, glycogen or other nutrient is obtained. 1 Diyala University Stage : 4th Stage Faculty of Veterinary Medicine Subject: Internal Medicine By: Dr. TAREQ RIFAAHT MINNAT (No.6) Medical Image of The Liver Ultrasonography: Ultrasonography of the liver is used as an aid to diagnosis of diseases of the liver of large animals. A complete ultrasonographic assessment of the liver can provide detailed information about the size, position and parenchymal pattern of the liver. In cattle, the liver, caudal vena cava, portal vein and gallbladder can be visualized. Ultrasonography is the only practical method for the diagnosis of thrombosis of the caudal vena cava. Ultrasonographic technique Examination of the liver of cattle is done with a 3.5 MHz linear transducer on the right side of the abdomen while the cows are standing. The hair is clipped and the skin shaved between the sixth intercostal space and a hand's breadth behind the last rib. After application of transmission gel to the transducer the cows are examined, beginning caudal to the last rib and ending at the sixth intercostal space. Each intercostal space is examined dorsally to ventrally, with the transducer held parallel to the ribs. The texture and the visceral and diaphragmatic surface of the liver are scanned, and the hepatic and portal veins, caudal vena cava and biliary system are examined. Breed and age of cow does not influence the ultrasonographic appearance of the liver, particularly position, size, and vasculature of the liver and gallbladder. During pregnancy, the diameter of the caudal vena cava increases slightly and that of the portal vein decreases. Ultrasonography has been used to detect thrombosis of the caudal vena cava in a cow with ascites and cholelithiasis in horses. Percutaneous ultrasound-guided cholecystocentesis in cows is an excellent method of obtaining samples of bile for demonstration of Fasciola hepatica and Dicrocoelium dendriticum eggs and fordetermination of bile acids. The procedure is done on the right side in the ninth, 10th or 11th intercostal space. 2 Diyala University Stage : 4th Stage Faculty of Veterinary Medicine Subject: Internal Medicine By: Dr. TAREQ RIFAAHT MINNAT (No.6) Percutaneous ultrasound-guided portocentesis in cows is an excellent method for measuring the composition of hepatic portal blood and comparing it with peripheral blood. Ultrasonography and digital analysis can be used for the diagnosis of hydropic degeneration of the liver of cows instead of biochemical analysis.Diffuse hepato-cellular disease such as fatty liver in dairy cows can also be detected and evaluated. Ultrasonography has been used to evaluate the liver-kidney contrast in the diagnosis of fatty liver infiltration in dairy cattle. Radiography: Lateral abdominal radiography can be used to determine the size and location of the liver in foals. Fluoroscopy and contrast media injected into the mesenteric vein have been used to detect the presence of portosystemic shunts in foals and calves. Laboratory test for hepatic disease and function Hepatic disease is difficult to diagnose based on clinical findings alone and the use of laboratory tests is necessary. The results and interpretation of such tests, however, depend on the nature of the lesion, the duration and severity of the disease, and species variations. Specific tests that identify the exact nature of the lesion are not available, and a combination of tests is usually necessary to make a diagnosis. For example, it is suggested that testing for serum bile acids, arginase and gamma-glutamyl transferase (GGT) gives a sensitive indicator of cholestasis and/or hepatocellular necrosis, and a liver biopsy would form the minimum combination of tests for the diagnosis and prognosis of hepatic disease in the horse. Total serum bile acids, plasma glutamate dehydrogenase, GGT and liver biopsy are useful in the horse with liver disease. Based on experimentally induced liver disease in cattle, it is suggested that the serum activities of sorbitol dehydrogenase (SDH), GGT and aspartate aminotransferase (AST, formerly known as SGOT), and the BSP clearance' test, provide sensitive indicators of hepatocellular injury in cattle. All laboratory tests are aids to diagnosis and must be carefully interpreted in conjunction with clinical and other available data. This is particularly 3 Diyala University Stage : 4th Stage Faculty of Veterinary Medicine Subject: Internal Medicine By: Dr. TAREQ RIFAAHT MINNAT (No.6) important in the laboratory investigation of liver disease in the horse. No one test will provide sufficient information, and a combination of tests is necessary. Depending on the time of sampling in relation to the pathological processes developing and the presence of complicating or secondary pathology there may be elevations in alkaline phosphatase (ALP ) and GGT. A horse with chronic hepatic lesions may aleukocytosis and neutrophilia, hypoalbuminemia, hyperbetaglobulinemia, increased ALP and GGT and, depending on other factors, there may be increases in AST, SDH, total lactate dehydrogenase and others. The laboratory tests for the diagnosis of hepatic disease and to evaluate hepatic function in farm animals can be divided into those that measure: o Excretory rate of parenterally administered substances such as BSP o Ability of the liver to remove substances from the serum and detoxify them o Serum levels of liver enzymes that increase following hepatic injury Indirect assessment of hepatic function such as blood glucose, serum proteins, clotting factors and urinalysis. Hepatic function: The sulfobromophthalein sodium(BSP) clearance test has been used in cattle, sheep and horses, and although little information is available the test appears to have diagnostic value. This test uses an injected dye, BSP, for diagnosis of liver disease. After the injection, several blood samples are taken to determine the blood level of the dye. These levels will indicate the liver's ability to excrete the dye and thus the general functioning of the liver. This test is very diagnostic of inactive cirrhosis of the liver. The time required by the normal liver to reduce the plasma concentration of BSP to half the initial concentration is taken as the standard BSP half-life and in cattle is 2.5-5.5 minutes, in sheep 2.0 minutes and in normal horses about 2.0 minutes All horses with confirmed liver disease have a reduction in plasma BSP clearance against time.The results are modified by the ability of the liver to excrete BSP via the biliary system and to store it in hepatocytes. Factors other than liver disease that increase the half-life significantly are starvation in horses, competition with bilirubin for excretory capacity, and youth, foals 4 Diyala University Stage : 4th Stage Faculty of Veterinary Medicine Subject: Internal Medicine By: Dr. TAREQ RIFAAHT MINNAT (No.6) less than 6 months of age having a Significantly slower clearance time. Precise timing of samples is needed because of the rapid excretion rate . In sheep, where severe hepatic dysfunction is accompanied by a steep rise in blood ammonia levels, and where this is reflected in the development of spongy degeneration in the brain, the level of glutamine in the cerebrospinal fluid is also elevated. Glutamine is a byproduct of the metabolism of ammonia in brain cells. Acute ammonia toxicity is manifested by tetany, ataxia and pulmonary edema, and affected animals are likely to die before the effects of subacute poisoning, hepatic encephalopathy, are seen. Icteric index Measurement of the icteric index of plasma, by comparing its color with a standard solution of potassium dichromate, cannot be considered to be a liver function test but it is used commonly as a measure of the degree of jaundice present. The color of normal plasma varies widely between species depending upon the concentration of carotene. Horse, and to a less extent cattle, plasma is quite deeply colored, but sheep plasma is normally very pale. The color index needs to be corrected for this factor before the icteric index is computed. Hyperbilirubinemia occurs in many diseases of cattle and in most cases is related to a failure of the liver to remove unconjugated bilirubin from the serum rather than to a failure of the liver to excrete conjugated bilirubin.The cause may be associated with anorexia, which resembles the hyperbilirubinemia associated with fasting in sick horses. Adult cattle with hepatic disease do not consistently have high serum bilirubin concentrations and visible jaundice does not occur frequently in cattle with hyperbilirubinemia. Total bilirubin concentrations in adult cattle should be 0.4 mg/dL but young healthy calves may have mean concentrations 0.57 mg/dL and even higher, up to 1.7 mg/dL. 5 Diyala University Stage : 4th Stage Faculty of Veterinary Medicine Subject: Internal Medicine By: Dr. TAREQ RIFAAHT MINNAT (No.6) Serum hepatic enzyme : The determination of serum levels of hepatic enzymes is used commonly for the detection and evaluation of hepatic disease. The interpretation of elevated values of enzymes in plasma is dependent not only on the tissue and site of origin but also on the half-time of clearance of the enzyme. Sorbitol dehydrogenase (also called L-iditol dehydrogenase (ID) is almost completely selective as an indicator of liver damage and is the preferred test for hepatic damage in sheep and cattle. Lactate dehydrogenase (LDH) is abundant in liver, kidney, muscle and myocardium . Aspartate aminotransferase or L-alanine aminotransferase (ALT, previously known as SGPT) are of some value as an indicator of liver damage because of their high content in liver but are generally considered to be too nonspecific to be of great diagnostic value. Arginase is a specific indicator of hepatic disease because it is not found in appreciable quantities in other organs. Arginase has a short blood half-life, which makes it useful for the diagnosis of acute hepatic disease but not for less severe forms. Gamma-glutamyl transferase is an enzyme widely distributed in a variety of equine tissues. Specific activity of GGT in the horse is highest in the kidney, pancreas and liver. Serum GGT activity is used as a diagnostic criterion for hepatobiliary diseases in cattle, sheep and horses. In the horse, increases in serum GGT may be associated with hepatocellular damage and liver necrosis in_a variety of natural and experimentally induced liver diseases. In foals during the first month of life values were 1.5-3 times higher than the upper physiological reference values for healthy adult horses. In neonatal foals, the serum ALP, GGT and SDH activities were increased during the first 2 weeks of life. Glutamate dehydrogenase (GD) occurs in high concentration in the serum of ruminants and horses with liver disease . Ornithine carbamoyl-transferase (OCT) levels are also elevated even in chronic diseases, but only when there is active liver necrosis and not when the lesions are healing . 6 Diyala University Stage : 4th Stage Faculty of Veterinary Medicine Subject: Internal Medicine By: Dr. TAREQ RIFAAHT MINNAT (No.6) Alkaline phosphatase levels are used as a test of hepatic excretory function in the horse and are of value in that species but variations in normal cattle have such a wide range that results are difficult to interpret. Of the tests available for testing of biliary obstruction the serum ALP test is preferred. However, there is a similar response to damage in other tissues. Serum bile acids The concentration of total serum bile acids has been reported as a sensitive and specific indicator of hepatobiliary disease in humans and animals. Abnormalities of bile acid metabolism may be detectable in animals with liver disease that have little evidence of hepatic dysfunction as determined by other common liver function tests. Bile acids are the end-products of the metabolism of cholesterol by the liver. They are excreted in the bile and reabsorbed from the intestine either unchanged or after further transformation by bacterial action. In experimental chronic corper poisoning in sheep, the total bile acid concentration in the plasma is a more sensitive indicator of hepatic damage than the concentration of plasma bilirubin or the activity of transaminases. The rise in total serum bile acid concentration usually correlates well with the severity of liver disease. In cattle, there is extreme variability among all types and ages of animals and the variation is even greater in beef cattle than in dairy cattle.48Values for calves 6 weeks of age and for 6-month-old heifers are significantly lower than values for lactating dairy cows. Blood ammonia levels The microbial deamination of amino acids in the intestinal tract is the major source of ammonia which is absorbed by the intestine into portal venous blood and converted into urea by the liver. The concentration of blood ammonia can be an indication of functional hepatic mass. Generally, plasma ammonia concentration is a sensitive and specific indicator of hepatic disease in the horse, although it may fluctuate widely even on the same day and the concomitant low plasma urea concentration anticipated because of the liver's reduced synthetic ability is often not apparent. In cattle with hepatic disease, plasma ammonia levels are significantly elevated compared to normal animals but not always accompanied by a decline in plasma urea concentrations. In healthy 7 Diyala University Stage : 4th Stage Faculty of Veterinary Medicine Subject: Internal Medicine By: Dr. TAREQ RIFAAHT MINNAT (No.6) cattle, the plasma ammonia:urea concentration ratio is 9:1 and the plasma ammonia:glucose concentration 11:1. In hepatic disease, a plasma ammonia:glucose ratio 40:1 or plasma ammonia:urea ratio 30:1, particularly with a rising total ketone body concentration and a declining glucose concentration, represents a guarded prognosis. Principles of treatment in diseases of the liver In diffuse diseases of the liver No general treatment is satisfactory and the main aim should be to remove the source of the damaging agent. In acute hepatitis is to tide the animal over the danger period of acute hepatic insufficiency until the subsidence of the acute change and the normal regeneration of the liver restores its function. Death may occur during this stage because of hypoglycemia. Oral or intravenous injections of glucose to maintained the level of blood glucose. Intake an adequate of calcium salts should be insured by oral or parenteral administration. There is some doubt as to whether protein intake should be maintained at a high level, as incomplete metabolism of the protein may result in toxic effects, particularly in the kidney. Amino acid mixtures, especially those containing methionine, are used with apparently good results. The same general recommendations apply in prevention as in the treatment of acute diffuse liver disease. Diets high in carbohydrate, calcium and protein of high biological value and a number of specific substances are known to have a protective effect against hepatotoxic agents. In chronic, diffuse hepatic disease fibrous tissue replacement causes compression of the sinusoids and is irreversible except in the very early stages, Removal of fat from the liver by the administration of lipotrophic factors including choline and maintenance on a diet low in fat and protein may reduce the compressive effects of fibrous tissue contraction. 8 Diyala University Stage : 4th Stage Faculty of Veterinary Medicine Subject: Internal Medicine By: Dr. TAREQ RIFAAHT MINNAT (No.6) A high-protein diet at this stage causes stimulation of the metabolic activity of the liver and an increased deposit of fat, further retarding hepatic function. Local diseases of the liver require: surgical or medical treatment depending upon the cause, and specific treatments. 9