Hepatobiliary and Pancreatic Diseases (PDF)

Hepatobilliary and pancreatic diseases Prof Kamalan Jeevaratnam DAHP, DVM, MMedSc (Mal); PhD (Cambridge), FRCVS (UK) School of Veterinary Medicine Facul...

Hepatobilliary and pancreatic diseases Prof Kamalan Jeevaratnam DAHP, DVM, MMedSc (Mal); PhD (Cambridge), FRCVS (UK) School of Veterinary Medicine Faculty of Health and Medical Sciences University of Surrey [email protected] Friday, 11 October 2024 1  Lecture outcomes Describe the pathophysiological process involved with the clinical presentation seen in hepatobilliary and pancreatic diseases. Determine the appropriate history and clinical examination necessary for diagnostic work-up of hepatobilliary and pancreatic diseases. Understand the different diagnostic modalities available for the investigation of hepatobilliary and pancreatic diseases. Describe principles of treatment and prognosis for hepatobilliary and pancreatic diseases. Friday, 11 October 2024 2  Clinical signs and presentation Non specific – typically GI related signs but can also involve neurological and haemopoietic abnormalities. Vomiting and/or diarrhoea (pasty faeces – discolouration) Loss of appetite Polyuria/polydipsia Weight loss – chronic typically Distended abdomen (ventral oedema) Painful abdomen Lethargy Abnormal behaviour Photosensitization – horses Colicy – horses Friday, 11 October 2024 3  History and physical examination Signalment Species and breed variability Age – vary depending on condition History Time of onset, duration, previous dietary history, recent change in behaviour, use of pesticides, exposure to other environmental sources, preventive healthcare history Physical examination General examination – emphasis on mucous membranes and abdominal area Distended painful abdomen, palpable liver in smaller animals, lymph node enlargement in infection, bruising (clotting deficiency), yellowish discoloration, anaemia, pyrexia, Friday, 11 October 2024 4  Liver function test Many liver test not specific to liver – elevations could be primary or secondary Interpretation must consider – history, clinical findings, medications. Aspects to consider – type, severity, duration and species. Functional role of liver means that there is no one single test to make a definitive diagnosis for liver disease. Most routine biochemical profile will provide indication of liver function Bilirubin Albumin Glucose Blood Urea Nitrogen Cholesterol Ammonia Routinely studied liver enzymes: Alanine aminotransferase (ALT) Aspartate aminotransferase (AST) Alkaline phosphatase (ALP) Gamma-glutamyltransferase (GGT) Sorbitol dehydrogenase (SDH)?? Bile acid stimulation test Clotting factors Friday, 11 October 2024 5  Liver enzymes in brief ALT AST ALP GGT Leakage enzyme – Leakage enzyme – Biliary disease or drug Biliary disease or drug hepatocellular injury, hepatocellular injury induction induction, primary hepatic necrosis Lesser in amount compared Enzymes in tissue that line neoplasia, advanced Hepatocyte cytoplasm rich in to ALT the biliary tract necroinflammatopry disease ALT – damage to hepatocyte Extrahepatic injury - Skeletal Present in a few tissues – Increased related to causes leakage muscle also has AST – so if bone and liver isoenzyme impaired bile flow Typically associated with inflamed AST can rise. (if AST diagnostically important No isoenzyme so bone chronic hepatitis > ALT – likely muscle in Bone source is from disorders does not alter GGT ALT elevations in young dog origin). Validate further with osteoblastic activity – young In small animal not hugely associated with portal creatinine kinase (CK). animals or osteosarcoma advantageous over ALP – vascular abnormalities Compare values with ALT to Increased also due to especially in dogs Elevations 2X normal or get a biochemical picture – glucocorticoid GGT can be elevated with persistent require further serial biochemical picture High ALP without glucocorticoid – but this is investigation! useful hyperbilirubineamia – drug not seen in cats Plasma half life is approx 2.5 Plasma half life is approx 1 or adrenal function GGT in large animal – bile days day Plasma half life is approx 70 duct or liver disease. hours (dogs) and 6 hours Continued increase in GGT (cat) for horses with acute liver disease Young foals – No elevation in GGT from suckling Friday, 11 October 2024 6  Bile acid stimulation test Starve Sample Feed Wait for Sample 12 hours blood animal 2 hours blood Bile acid concentrations will be increased under the following situations: Hepatocellular dysfunction: Inability of the hepatocyte to produce or extract bile acids from the portal circulation. Abnormal portal blood flow: Portosystemic shunts or microvascular dysplasia will cause portal blood to “bypass” the liver, not allowing hepatocytes to efficiently extract the bile acids that would be normally presented to them. Cholestasis: Any interference with the transporters that deliver bile from the hepatocyte to the biliary canalicular system will result in an increase in bile acid concentrations. Thus, there is no point in measuring bile acids in animals that are known to be cholestastic (increased direct bilirubin etc), because the cholestasis will mask our ability to detect hepatic dysfunction or abnormal blood flow. Horses: Horses lack gall bladders and only random bile acid concentrations are measured in these species. Slightly increased concentration (up to approximately 20 μmol/L) can result from decreased feed intake for a period of several days or longer. In one study, higher bile acid concentrations were associated with decreased survival and inflammatory or portal fibrotic pathologic lesions in the liver. Note that young foals under 2 weeks of age can have higher bile acid concentrations than adults. Bile acid concentrations approximate adults by about 6 weeks of age in foals. Ruminants: Ruminants have extremely variable serum bile acids concentration in health, http://www.eclinpath.com/chemistry/liver/liver- rendering the test insensitive for the detection of liver dysfunction (shunts are very rare in ruminants). function-tests/bile-acids/bile-acid-circulation/ Friday, 11 October 2024 7  Other relevant biomarkers Trypsin like immunoreactivity Exocrine pancreatic insufficiency (EPI) occurs as a consequence of insufficient synthesis and secretion of digestive enzymes by the pancreatic acinar tissue. The functional reserve of the pancreas is considerable, Canine 5.7 - 45.2 µg/L however, and EPI only develops when the exocrine secretory capacity is reduced to less than 10 - 15% of Feline 12.0 - 82.0 µg/L normal. At this point residual pancreatic function together with extra-pancreatic mechanisms of digestion cannot support adequate nutrient digestion and so weight loss, diarrhea, and other clinical signs ensues. Pancreatic lipase immunoreactivity During pancreatitis, pancreatic lipase is released into the bloodstream and can be used as a diagnostic Feline (Spec fPL ) 0 - 3.5 µg/L marker for the disease.Beyond the pancreas, lipases Canine (Spec cPL ) 0 - 200 µg/L are released from various other organs, adding to the total serum lipase activity. Cobalamin Absorbed in the distal small intestine (specifically in the ileum). Values below the control range are often seen in patients with EPI, bacterial overgrowth in the upper small intestine, or disease affecting the distal small intestine. There is no known significance of values exceeding the control range. Cobalamin Folate Folate Canine 251 - 908 ng/L 7.7 - 24.4 µg/L Absorbed in the proximal small intestine only. Values Feline 290 - 1,500 ng/L 9.7 - 21.6 µg/L above the control range are consistent with bacterial overgrowth in the upper small intestine. Values below the control range are consistent with disease affecting the proximal small intestine. Friday, 11 October 2024 8  Imaging Radiology Ultrasonography # Assess size and opacity of liver # Differentiate between diffuse and focal # Hepatomegaly – caudal displacement of hepatic disease stomach; extension of hepatic shadow beyond # Hyperechoic – fibrosis, lipidosis, steroid costal arch hepathopathy, neoplasia # Microhepatica – reduced hepatic shadow, # Hypoechoic – suppurative disease, passive cranial displacement of stomach congestion, lymphoma Referral: contrast studies, CT/MRI Friday, 11 October 2024 9  http://www.lbah.com/word/liver-disease-summary-page/ Friday, 11 October 2024 10  Ultrasound Friday, 11 October 2024 11  Treatment General options Fluid therapy – replace fluid losses, flush toxins. Diet – small amounts and often, balance carbohydrate and good quality protein. Anti-inflammatory/steroids – reduce inflammation – contraindicated in some cases. Antibiotics – generally in infectious condition but in some cases may be given as a preventative. Supplement – a wide range available: Vitamin B, E, K, milk thistle, zinc Lactulose – reduce ammonia – helps bind them and excrete via feaces. Anti-emetics Anti-ulcers – help prevent erosion from circulating toxins s-adenosylmethionine (SAMe) Friday, 11 October 2024 12  Treatment options in small animal Friday, 11 October 2024 13  Dietary management Dietary management Friday, 11 October 2024 14  Hepatic lipidosis Feline hepatic lipidosis is a common form of hepatobiliary disease in domesticated cats. Typical clinical findings include anorexia, weight loss, muscle wasting, icterus, hepatomegaly, and increased serum liver enzyme activities. Although the cause of the disorder remains undetermined, its pathogenesis likely involves the unique pathways of protein and lipid metabolism in cats. Diagnosis is based on history, physical examination, clinical pathology, radiography, abdominal ultrasound, cytology of fine-needle liver aspirates, and liver biopsy. When hepatic lipidosis is suspected, a clinical investigation into predisposing conditions should be made. Friday, 11 October 2024 15  Exocrine pancreatic insufficiency Occurs when there is insufficient digestive enzymes – inadequate digestion. Signs develop gradually or rapidly depending on severity – typically visible symptoms occur when 85%-90% of pancreas have atrophied. Weight loss (normal appetite), small bowel diarrhoea, increased feacal volume, steatorrhoea, copraphagia, borborygmus, poor coat condition. Types - Pancreatic Acinar Atrophy; Chronic Pancreatitis; Congenital Hypoplasia; Neoplasia. Breed predisposition exist (GSD, rough coated collies, chow chow) but any breed can be affected. Dx: history, clinical signs, lab test, (imaging??). Tx: enzyme replacement, dietary modification, vitamin supplementation, antibiotic therapy, glucocorticoid therapy. Friday, 11 October 2024 16  Portosystemic shunt Common congenital anomaly of the hepatobiliary system in dogs. Vascular communication bypassing liver – single of multiple shunts. Signalment, history and clinical signs often are good indicators. Wide variety of clinical signs – hepatic encepholapthy common; failure to thrive Medical and surgical management vary depending on contraindications. Canine breed predisposition – pure breeds more than cross breeds – schnauzers, maltese, retrievers, Labradors, terriers Friday, 11 October 2024 17  Feline inflammatory liver disease Most common primary hepatic disorder of cats in the UK. Cholangitis vs cholagiohepatitis – WSAVA standardization – cholangitis since inflammatory disruption of hepatic parenchyma not consistent feature (if present is an extension of primary cholangitis). Classification – inflammatory cell type Neutrophilic cholangitis Lympohocyctic cholangitis Fluke associated cholangitis – UK prevalence low! Other diseases also have liver associated inflammatory disease but this is primary inflammatory disease. Friday, 11 October 2024 18 Friday, 11 October 2024 19  Pancreatitis Friday, 11 October 2024 20  Diagnostic algorithm for feline pancreatitis Friday, 11 October 2024 21  Triaditis syndrome Concurrent cholangitis, pancreatitis and inflammatory bowel disease Unique ductal anatomy in cats! – what is it? Diagnosis Conduct diagnostic testing in suspected cases – routine test If biopsy – multiple biopsy samples always essential – different regions Assess for cholangitis Assess for pancreatitis Assess for IBD Treatment Treat cholangitis Treat pancreatitis Treat IBD Enteral feeding should be considered in all cats Friday, 11 October 2024 22 Friday, 11 October 2024 23  References BSAVA Manual of canine and feline gastroenterology Clinical medicine of the dog and cat – 3rd edition – Schaer & Gaschen – CRC Press. 3rd edition – 5-minute Veterinary Consult InPractice – BMJ http://www.eclinpath.com/ Friday, 11 October 2024 24