Clinical and pathological studies in cattle with hepatic disease.

In cattle with hepatic lipidosis, hepatic abscessation, leptospirosis, biliary calculi or fasciolosis, the progression of the disease was studied by serial measurements of serum total bile acid concentrations, plasma glutamate dehydrogenase, gamma-glutamyltransferase, 5'-nucleotidase and leucine aminopeptidase activities Terminalia avicennioides and by liver biopsy. Regardless of the cause of the hepatic disease, weight loss, anorexia, dullness and depression were consistent features. Signs of hepatic encephalopathy, such as blindness, head pressing, excitability, ataxia and weakness were less common and, together with pyrexia and jaundice, were grave prognostic signs. Plasma ammonia concentrations were significantly elevated compared to clinically normal cattle, but such changes were not always accompanied by a decline in plasma urea concentrations. In normal, healthy cattle, the plasma ammonia:urea concentration ratio is 9:1 and the plasma ammonia:glucose concentration is 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, carried a guarded prognosis. The study suggested that other factors, such as hypokalaemia, alkalosis, short-chain volatile fatty acids, and false and true neuro-transmitters, may be important in the pathogenesis of hepatic coma in cattle.

Tracheolaryngostomy as a treatment for laryngeal obstruction in cattle.

Inspiratory dyspnoea may be the result of chronic laryngeal obstruction or, rarely, because of tracheal collapse. Chronic laryngeal obstruction, as a result of necrobacillosis or infectious bovine rhinotracheitis, responds poorly to medical treatment. A tracheolaryngostomy technique under general anaesthesia is described with closure of the laryngotomy incision. Animals were selected for surgery following radiography and endoscopy. With a permanent cranial tracheostomy incision, calves could be managed easily by the farmer as a tracheotomy tube was found to be unnecessary 1 week after surgery once the postoperative swelling had subsided. The technique had a high success rate at 6 months follow-up. In animals with severe bronchopneumonia without laryngeal abscesses at endoscopy, tracheotomy and medical therapy with antibiotics and steroids may be successful. Chronic laryngeal obstruction is more common in double-muscled calves because of the anatomy of the upper airways, increasing laryngeal resistance to airflow.

Maternal undernutrition during late pregnancy in sheep. Its relationship to maternal condition, gestation length, hepatic physiology and glucose metabolism.

There is a paucity of information on the metabolic effects of undernutrition of the ewe carrying multiple fetuses in late pregnancy. In the present study the effects of induction of ketosis from 132 d gestation in ewes carrying twin fetuses were compared with a control group. The ewes were well fed up to 132 d. Ketotic ewes showed a loss of condition score from 3.7 (SE 0.11) at 130 d gestation to 3.0 (SE 0.15) 10 d later after clinical recovery, compared with control twin-pregnant ewes (P < 0.01). The weight loss during the same time period was from 70.6 (SE 2.7) kg at 130 d to 64.2 (SE 2.7) kg at 140.d gestation. As expected, both groups lost weight and condition score in the first 28 d of lactation. Induction of ketosis caused a significant shortening of the gestation period to 142.8 (SE 0.7) d compared with 150 (SE 0.4) d in normal twin-pregnant ewes (P < 0.001). Ewes with induced ketosis recovered clinically and showed a normal feed intake by 3.4 (SE 0.07) d; three required treatment. Induction of ketosis resulted in reduction of hepatic uptake of bromosulphthalein (P < 0.01) and its biliary excretion (P < 0.05), metabolic clearance rate (P < 0.001), fractional clearance (P < 0.001) and 15 and 30 min retention compared with control twin-pregnant ewes. Most values had returned to normal by the first week of lactation. It is thought that in human pregnancy similar changes in bromosulphthalein clearance may be related to reduced binding sites for bromosulphthalein in the liver caused by increased circulating oestrogens. Induction of ketosis resulted in a significant hypoglycaemic (P < 0.01), ketotic (P < 0.001) state compared with well-fed twin-pregnant ewes. These changes could be correlated with the severity of the clinical signs, together with a significant rise in plasma urea (P < 0.001) and NH3 (P < 0.05) concentrations. Again, the return of most of these values to normal by the first week of lactation lends support to the reversibility of hepatic lesions caused by fatty infiltration of the liver. The severity of this condition in naturally occurring cases suggests that factors other than undernutrition may be contributory, such as the general body condition of the ewe and glucose metabolism by the liver, including the conversion of propionate to glucose.

Clinical and pathological studies in horses with hepatic disease.

In horses with hepatic necrosis, lipidosis, neoplasia and cirrhosis, progression of the disease was studied by serial measurements of total serum bile acid concentrations and of plasma glutamate dehydrogenase (GD) and gamma glutamyl transferase (gamma GT) and by liver biopsy. Plasma ammonia concentrations were significantly elevated compared to clinically normal horses, but such changes were not always accompanied by a decline in plasma urea concentration. A fall in plasma glucose concentration carried a guarded prognosis. These were all invaluable aids in early diagnosis and throughout the disease course. The study suggests that other factors, such as hypokalaemia, alkalosis, short chain volatile fatty acids, false and true neurotransmitters, may be important in the pathogenesis of hepatic coma in the horse.

Comparison of bromosulphthalein and indocyanine green clearance in sheep.

The kinetics of indocyanine green removal from the blood after a single intravenous injection were measured in sheep and compared with those of a single dose of bromosulphthalein given to the same animals 48 hours later. A single dose of 1.5 mg kg-1 of indocyanine green (ICG) was cleared in a double exponential manner. The hepatic uptake of ICG was not significantly different from that of bromosulphthalein (BSP) but its rate of excretion in bile was significantly lower (P < 0.05) and its rate of plasma reflux significantly higher (P < 0.05). The plasma distribution volumes of the two compounds were similar but the mean (SD) plasma clearance of ICG (435 [228.6] ml min-1) was significantly lower than that of BSP (626 [291.9] ml min-1) (P < 0.05). The retention of ICG 30 minutes after the injection was significantly higher than that of BSP (P < 0.01).

Evaluation of total serum bile acid concentrations for the diagnosis of hepatobiliary disease in cattle.

Serum bile acid concentrations were measured in 41 clinically healthy cattle of different breeds. There was no diurnal variation in values and age and sex had no effect. There was no significant difference between serum and plasma bile acid concentrations in clinically healthy cattle. Serum bile acids were stable on storage at -20 degrees C. The total serum bile acid concentrations, together with other tests of hepatic disease, were evaluated in cattle with various types of hepatobiliary disease (hepatic lipidosis, hepatic abscessation, leptospirosis, biliary calculi, fascioliasis), respiratory, cardiovascular and infectious diseases, and in various other conditions not affecting the liver. Total serum bile acids were the most specific and sensitive indicators of a wide variety of hepatic diseases and were significantly correlated with the degree of clinical illness.

Effect on liver function of acetonaemia and the fat cow syndrome in cattle.

The effect of fatty infiltration on liver function was studied in 29 dairy cows aged 6 +/- 0.4 (SEM) years with primary acetonaemia, secondary acetonaemia or the fat cow syndrome. The average interval from calving at diagnosis was 16.4 +/- 2.0 days and the animals had been anorexic for a mean of 5.6 +/- 0.8 days. Fatty infiltration of the liver occurred well before calving and was associated with severe clinical illness and intercurrent infections. The percentage of fatty infiltration in the liver (mean 53.1 +/- 2.8 per cent) was significantly correlated with both the degree of clinical illness (P less than 0.001) and the period of anorexia (P less than 0.05). Alterations in uptake, conjugation and excretion at the hepatocyte level were determined by measuring bromsulphthalein clearance, and plasma total bilirubin and total bile acid concentrations. Values for all three were positively correlated with the extent of fatty infiltration. Plasma albumin, urea and glucose concentrations were reliable indicators of the liver's synthetic function and together with plasma aspartate aminotransferase, iditol and glutamate dehydrogenase were correlated with the degree of hepatic lipidosis.

The clearance of bromosulphthalein from plasma as a measure of the changes in hepatic function during pregnancy and lactation in ewes.

Single intravenous injections of bromosulphthalein (BSP) were given to sheep and the change in plasma BSP concentration with time was analysed by computer to obtain the proportionality transfer constants 'a', 'h' and 'b' and plasma volume. The BSP half-time, fractional clearance and retention values were also calculated. Alterations in BSP clearance were compared with changes in bilirubin and liver specific enzyme activities in ewes in late pregnancy and early lactation. The measurement of BSP clearance, particularly the proportionality transfer constants, yielded more information about the alterations in hepatocellular function during pregnancy and lactation than the changes in clinical chemistry. It is suggested that these alterations in liver function are physiological rather than pathological at these times.

Observations on gamma-glutamyl transferase, 5'-nucleotidase and leucine aminopeptidase activities in the plasma of the horse.

In 18 horses there was no effect of age or sex on plasma activities of gamma-glutamyl transferase (gamma-GT), 5'-nucleotidase (5'-NT) and leucine aminopeptidase (LAP). All the enzymes were equally stable after storage for one month at -20 degrees C and there was no significant difference between their activities in serum and plasma in clinically normal horses. The pattern of release of gamma-GT, 5'-NT and LAP into plasma was studied in 114 horses which had a variety of orthopaedic, gastrointestinal, cardiovascular and hepatic (necrosis, lipidosis, neoplasia and cirrhosis) conditions. A definitive diagnosis of hepatic disease was established by histological examination of the liver. gamma-GT and 5'-NT were leaked into plasma in hepatic disease and gamma-GT was the more sensitive indicator of liver damage. There was some evidence that gamma-GT and 5'-NT plasma activities may increase in hepatic necrosis as well as in biliary obstruction. LAP was insensitive and not hepatic specific in the horse.

Evaluation of total plasma bile acid concentrations for the diagnosis of hepatobiliary disease in horses.

Plasma bile acid concentrations were measured in normal horses. There was no diurnal variation in values, and age and sex had no effect. There was no significant difference between serum and plasma bile acid concentrations in clinically normal horses. Plasma bile acids were stable on storage for one month at -20 degrees C. The total plasma bile acid concentrations together with total and direct bilirubin concentrations and plasma activities of aspartate aminotransferase, glutamate and iditol dehydrogenase were evaluated in horses with various types of hepatobiliary disease (hepatic necrosis, lipidosis, neoplasia and cirrhosis), gastrointestinal disease, cardiovascular, orthopaedic and various other conditions not affecting the liver. Total plasma bile acids together with plasma glutamate and iditol dehydrogenase activities were the best indicators of liver disease. Total plasma bile acid concentrations were the most sensitive indicator of a wide variety of hepatic diseases but alone were unhelpful in differential diagnosis and were of more value when combined with the other tests of hepatic disease.

Liver function of dairy cows in late pregnancy and early lactation.

The possibility that alterations in liver function may occur during late pregnancy as well as after calving has been investigated in healthy dairy cows and the results compared with those from non-pregnant non-lactating cows. There were significant alterations in plasma total bilirubin, glucose, total ketone body and urea concentrations, in bromsulphthalein clearance and in plasma aspartate aminotransferase and creatine kinase activities in periparturient cows compared with non-pregnant non-lactating cows. Of these, only the alterations in glucose, ketone bodies and urea concentrations and bromsulphthalein half-time and retention were markedly different before calving. The degree of fatty infiltration of the liver was significant two weeks before as well as two weeks after calving which differed from previous reports. It seems likely that the changes in the liver in dairy cows are functional and reversible and related to the metabolic demands of late pregnancy and early lactation. The results suggest that such changes in the liver occur well before calving.

Clearance of bromosulphthalein by the liver of sheep.

The application of a serial sampling technique for assessing bromosulphthalein (BSP) clearance by the liver of sheep is described. After a single intravenous injection BSP was almost completely cleared by the liver into the bile. Clearance by the liver was in two phases which allowed the calculation of the proportionality transfer constants a (from plasma to liver), h (from liver to bile) and b (from liver back to plasma). The ratio of a:h was approximately 4:1 in sheep. The proportionality transfer constants had the advantage over fractional clearance and retention tests of relating the test more precisely to the condition of the liver at the cellular level. The single injection method was simple, non-invasive and repeatable and suitable for conscious animals.

Clearance of bromosulphthalein from plasma as a measure of hepatic function in normal horses and in horses with liver disease.

Single intravenous injections of bromosulphthalein (BSP) were given to horses and the change in plasma concentration of BSP with time was analysed by computer to obtain the proportionality transfer constants 'a', 'h' and 'b'. No age, weight or sex differences in BSP clearance were found in normal horses. The technique was non-invasive, repeatable and suitable for conscious animals. The measurement of the transfer constants 'a', 'h' and 'b', helped to provide an accurate guide to diagnosis and prognosis of liver disease.