Gastrointestinal Diseases Proceedings. Get inside your patients

Transcription

1 Gastrointestinal Diseases 2011 Proceedings Get inside your patients

2 Commitment to Veterinarians Pfizer Animal Health: Committed to Veterinarians and the World Pfizer Animal Health has reaffirmed its steadfast support for the veterinary profession. Through the Commitment to Veterinarians platform, Pfizer has pledged to comprehensively address the significant short- and long-term unmet needs facing practicing veterinarians and students in the United States. Pfizer Animal Health Commitment to Veterinarians focuses on three key areas for veterinarian support: Training and continuing education Research and development Investing in the future of the profession. For student support, Pfizer has launched a veterinary scholarship, administered by the AVMF. This program will provide in excess of $3 million U.S. dollars in its first three years, to veterinary medicine students across U.S. and Caribbean colleges of veterinary medicine. The goal of the scholarships is to increase diversity, promote leadership and contributions to the profession among students in all tracks. Pfizer has also launched www. VetStudentConnect.com, a new portal for students to apply for Pfizer scholarships and to learn about other assistance programs. In addition to the lack of diversity and decreasing numbers of mixed-practice and rural veterinarians, the veterinary profession is facing significant financial challenges. More veterinarians than ever face debt loads that may stay with them for a lifetime. The American Veterinary Medical Association recently estimated that the average veterinary student debt upon graduation totals $120,000. The dollars being allocated to important research programs that address animal disease are also dwindling. In efforts to ameliorate all of these problems, Pfizer Animal Health: Contributed more than $15 million last year alone to universities and allied organizations toward scholarships and fellowship opportunities. Leads the industry in science-based training and continuing education, providing more than 1,700 hours a years in diverse CE opportunities that focus on disease-state information. Invests $300 million annually in research and development more than any other animal health company which has led to new therapies that address unmet medical needs. Pfizer Inc. applies science and our global resources to improve health and well-being at every stage of life. We strive to set the standard for quality, safety, and value in the discovery, development, and manufacturing of medicines for people and animals. Our diversified global health care portfolio includes human and animal biologic and small molecule medicines and vaccines, as well as nutritional products and many of the world s best-known consumer products. Every day, Pfizer colleagues work across developed and emerging markets to advance wellness, prevention, treatments, and cures that challenge the most feared diseases of our time. Consistent with our responsibility as the world s leading biopharmaceutical company, Pfizer also collaborates with health care providers, governments, and local communities to support and expand access to reliable, affordable, health care around the world. For more than 150 years, Pfizer has worked to make a difference. To learn more about our commitment to animal health, please visit Symposium Proceedings Gastrointestinal Diseases Previous Next Contents

3 2011 Proceedings Gastrointestinal Diseases Contents Author Biographies 2 Tricks and Hints to Better Interpretation of 4 Gastrointestinal Imaging Dr. David S. Biller Managing Vomiting in Chronically Ill Dogs and Cats 20 Dr. Todd R. Tams Liver Disease: The 5 Most Common Conditions 34 You Will Encounter Dr. David C. Twedt Acute Canine Pancreatitis: The Clinical Challenges 49 of This Elusive Disease Dr. Nolie Parnell The opinions expressed in the articles in this publication are those of the authors and do not necessarily reflect the official label recommendations and points of view of the company or companies that manufacture and/or market any of the pharmaceutical agents referred to. Proceedings of a Symposium Held at the 2011 North American Veterinary Conference and the 2011 Western Veterinary Conference Published by The Gloyd Group, Inc., Wilmington, Delaware 2011 The Gloyd Group, Inc. All rights reserved. Printed in the United States. Previous Next Contents 1

4 About the Authors Dr. David S. Biller DVM, Diplomate, ACVR Manhattan, Kansas Dr. Biller received his DVM degree in 1980 from Auburn University. After a 1-year internship at New Haven Hospital for Veterinary Medicine in New Haven, Connecticut, and a 3-year medical staff position at South Shore Veterinary Associates in South Weymouth, Massachusetts, he completed a residency in radiology in the Department of Veterinary Clinical Sciences at The Ohio State University. He subsequently joined the faculty at the University of Wisconsin Madison, where his primary responsibilities were clinical teaching and research. He returned to Ohio State in 1991 as a radiologist. Dr Biller is presently Professor of Veterinary Medicine in the Department of Clinical Sciences and Head of Radiology at the College of Veterinary Medicine, Kansas State University. Dr Biller s major clinical interest is diagnostic ultrasonography of small and large animals. His major research interests are the use of diagnostic ultrasonography in diagnosis and evaluation of spontaneous animal diseases and the study of polycystic kidney disease in cats. Dr. Todd R. Tams DVM, Diplomate, ACVIM VCA Antech Los Angeles, California Dr. Tams is Chief Medical Officer for Veterinary Centers of America (VCA) and heads its Medical Advisory Board. He is also the firm s ambassador to US veterinary colleges and travels worldwide to educate veterinarians about internal medicine. He received his DVM degree from The Ohio State University in 1977, after which he worked 1 year at a mixed practice in Vermont. He then completed a 1-year internship at the West Los Angeles Animal Hospital, followed by a residency in internal medicine at Colorado State University. He was a staff internist at the Angell Memorial Animal Hospital in Boston and achieved board certification in internal medicine in Dr. Tams returned to Los Angeles in 1984 and, in addition to his position with VCA, he is a staff internist at the VCA West Los Angeles Animal Hospital. He was named a Distinguished Alumnus of The Ohio State University College of Veterinary Medicine in Dr. Tams has published two textbooks and has presented numerous US and international seminars on his special interest area, gastroenterology Symposium Proceedings Gastrointestinal Diseases Previous Next Contents 2

5 About the Authors Dr. David C. Twedt DVM, Diplomate, ACVIM Colorado State University Fort Collins, Colorado Dr. Twedt is a Professor and Section Chief in the Department of Clinical Sciences at Colorado State University and is also director of the Veterinary Endoscopy Teaching Center. A graduate of Iowa State University, he entered an internship and medicine residency at The Animal Medical Center in New York City with an interest in gastroenterology. Dr. Twedt then joined the staff of the Animal Medical Center and was a research associate at the Liver Research Center of Albert Einstein Medical School. He is a Diplomate of the American College of Veterinary Internal Medicine, for which he has served as president and chairman of the board and as president of the Internal Medicine specialty. He has also served as president of the Comparative Gastroenterology Society. His publication and research interests include liver, gastrointestinal disease, and endoscopy. He has lectured nationally and internationally in these areas. Dr. Twedt has also been the recipient of several teaching awards and is co-editor of Current Veterinary Therapy XIV. Dr. Nollie Parnell DVM, Diplomate, ACVIM Purdue University West Lafayette, Indiana Dr. Parnell, a Diplomate of the American College of Veterinary Internal Medicine, is currently a clinical associate professor in small animal internal medicine at Purdue University. She has been a faculty member at Purdue since 1997, providing instruction both in the classroom and on the clinical floor. Dr. Parnell is a 1993 graduate of North Carolina State University College of Veterinary Medicine. She completed both her internship and residency in small animal internal medicine at The Animal Medical Center in New York City. She has an interest in gastroenterology, especially small intestinal tract diseases, and the pancreas. She also has a passion for nutrition and is currently working toward board certification in the American College of Veterinary Nutrition. Previous Next Contents 3

6 Overview Tricks and Hints to Better Interpretation of Gastrointestinal Imaging Dr. David S. Biller DVM, Diplomate, ACVR Imaging of the gastrointestinal tract is indicated in cases of foreign body ingestion, vomiting, regurgitation, abdominal pain, abdominal distention, weight loss, anorexia, and abnormal findings on abdominal palpation. Imaging plays an important role in the diagnosis of these diseases as well as the decisions about appropriate treatment. There are several imaging modalities used in the evaluation of the gastrointestinal tract, including survey radiographs, contrast procedures such as pneumogastrograms, upper gastrointestinal studies, and ultrasonography. Each has its advantages and disadvantages, which will be discussed. The role of imaging in diagnosis and choice of therapies in hepatic and pancreatic disease, as well as the different imaging modalities for these organs, will also be discussed. The appearance of different diseases will be discussed and demonstrated with clinical examples. Foci A right lateral recumbent radiograph is recommended in determining gastric dilatation from gastric dilatation with volvulus (GDV), as gas should fill the pylorus in cases of GDV. Organomegaly, whether normal or abnormal, displaces the small intestine, the direction of which helps to determine differentials for the mass effect causing the displacement. Contrast radiography is often necessary to identify high small intestinal obstructions in the vomiting patient, as these patients tend not to have radiographic evidence of duodenal obstruction even though an obstruction is present. Inflammatory disease of the small intestine tend to increase the rate of intestinal motility (i.e., reducing transit time) and may, with chronicity and severity, cause irregularity of the mucosal surface and/or decrease the width of the bowel lumen. Animals should be fasted before gastrointestinal ultrasonography to decrease gas and ingesta present in the stomach, and a complete examination of the entire abdomen should be done to ensure that concurrent disease is not missed. When taking two survey views (lateral and ventrodorsal) of the abdomen, the author prefers the right lateral as the spleen is better visualized and there is better separation of the kidneys. Patient preparation for successful abdominal radiographs includes 12 hours of fasting if possible, an empty urinary bladder, and a hair-coat free of debris. Radiographic evaluation of changes associated with hepatomegaly mayinclude gross increase in size of hepatic shadow, rounding of the caudal hepatic borders, caudal displacement of the stomach, and dorsal elevation or left-sided displacement of the pylorus Symposium Proceedings Gastrointestinal Diseases Previous Next Contents 4

7 The pancreas is not normally seen on radiographs and changes that occur with pancreatic disease are likely to be related to ventral displacement of the duodenum; lateral displacement of the descending duodenum (right) and pylorus (left); displacement of the transverse and ascending colon; fluid or gas distention of the stomach, duodenum, and colon or loss of abdominal detail. Imaging of the gastrointestinal (GI) tract is indicated in cases of foreign body ingestion, vomiting, regurgitation, abdominal pain, abdominal distention, weight loss, anorexia, and abnormal abdominal palpation. Stomach Normal Radiographic Anatomy Radiographic anatomy of the stomach is variable and dependent upon species, breed, conformation, degree of gastric distention, volume and type of gastric contents, and position of the patient during the exposure. The stomach is usually within the rib cage. On the lateral radiograph, the vertical axis of the stomach should be approximately parallel to the 10th or 11th intercostal space. In deep-chested dogs, the gastric axis may be perpendicular to the spine. On the ventrodorsal radiograph in dogs, the cardia, fundus, and body are located to the left of midline. The pyloric portions are to the right of midline. The pylorus is on midline in cats, and the stomach is a J shape. Rugal folds are not well-visualized on survey radiographs. If there is negative (gas) or positive (iohexol or barium) contrast, rugal folds may be seen. The size and number of rugal folds vary depending on the degree of gastric distention, therefore assessment is very subjective. Positional Radiography Standard survey abdominal radiographs include a ventrodorsal and either a left or right lateral recumbent view. Which lateral radiograph is obtained is often based on personal preference. There are differences in the appearance of various organs, such as the kidneys, spleen, and GI tract, between the right and left lateral recumbent radiograph. This varied appearance is particularly noticeable in the GI tract, which is dependent on gas to provide contrast for visualization of the mucosal surface. Fluid and gastric contents are extremely mobile and tend to move to the dependent portion of the stomach during postural changes. Gas will rise to the nondependent portion of the stomach. For example, in right lateral recumbency gas accumulates in the fundus, and in left lateral recumbency redistribution to the pyloric region occurs. Gas in the GI tract serves as a negative contrast media. Specifically, the change in the animal s position for the opposite lateral abdominal radiographs allows for redistribution of gas already present in the stomach and small and large intestines. A fluid-filled pylorus can be misdiagnosed as a cranial abdominal mass when the right lateral recumbent radiograph is taken. When the left lateral abdominal radiograph is obtained, the pylorus will be filled with gas. The position of gas in the stomach changes in the following manner. If the animal is in left lateral recumbency, gas will be present in the pylorus if the stomach is in its normal location. Conversely, if the animal is in right lateral recumbency, gas will be present in the fundus. It is important to realize that the amount of gas affects which portions of the stomach will contain gas. In a severely gas-distended stomach, gas may be in all portions of the stomach on both lateral abdominal radiographs. The location Previous Next Contents 5

8 of the pylorus can still be determined in this situation. The right lateral recumbent radiograph is recommended in determining gastric dilatation from gastric dilatation with volvulus. In animals in the ventrodorsal position, gas is present in the body of the stomach; those in the dorsoventral position have gas in the fundus and pylorus Even in cases in which ileus is detected, it is often helpful to gain additional information to help with surgical planning and prognosis. Pneumogastrogram Indications for use of contrast media in evaluation of the stomach include: Suspicion of luminal or mural gastric masses Radiolucent gastric foreign bodies Hematemesis Recurrent or nonresponsive vomiting Gastric localization, identification, size, shape, and margination Motility evaluation. Preparation of the patient includes survey radiographs, which should always precede contrast studies. Contrast procedures should always be individualized. Negative contrast agent is room air. Other equipment includes a mouth gag and an orogastric tube. Technique includes administering approximately 6 to 12 ml/kg of gas via a gastric tube. Radiographs are routinely taken in right lateral and ventrodorsal positions, but for complete and accurate evaluation of the stomach dorsoventral and left lateral films may be taken. Abnormal Appearance of the Stomach Foreign Bodies Radiopaque foreign bodies of the stomach are usually easily identified. Radiolucent foreign bodies can be visible due to contrast of air that surrounds the foreign bodies. Cloth or porous foreign bodies frequently retain barium after the stomach is emptied (post gastrogram or upper GI series). Less permeable foreign bodies appear as filling defects in the barium-filled stomach. Gastric Dilatation Volvulus Gastric dilatation is defined as a moderately to severely distended stomach, filled primarily with gas, gas and fluid, fluid, or ingesta. Most important, the enlarged stomach retains its normal position. Gastric volvulus is differentiated from gastric dilatation by displacement (abnormal position) of the stomach due to rotation. The stomach may be distended (these animals may present in acute crisis, tympanic, and retching). The location of the pylorus and duodenum dorsocranial and near or to the left midline is the most common appearance of this malposition. With a low-volume positive-contrast gastrogram and a left lateral film, the pylorus may be demonstrated. A standard right lateral radiograph (view of choice) should fill the pylorus with gas in an animal with gastric dilatation volvulus. Other radiographic changes include compartmentalization (radiographic recognition of soft tissue bands that project into or across the gas-filled lumen of the rotated stomach). These soft tissue bands result from folding of the stomach in on itself as the folded wall projects into the lumen and is outlined by gas in the lumen. Splenomegaly and variations in the location of the body of the spleen due to torsion may occur. The gastric wall may be thin. Gas may be seen in the gastric wall or liver (portal vessels) due to wall necrosis. Reduced size of the caudal vena cava and cardiac silhouette (due to reduction in preload) esophageal dilatation (megaesophagus), and reflux paralytic ileus of the small intestine (which may also 2011 Symposium Proceedings Gastrointestinal Diseases Previous Next Contents 6

9 be due to pain) may be present. Tumors Most tumors originate from the lesser curvature but may occur in any location in the stomach. A filling defect may be present in the gastric lumen and may be polypoid, pedunculated, or sessile. Ulceration of gastric tumors is common. Radiographically, tumors may appear as a thickened or irregular gastric wall especially when contrasted with gas or barium. The stomach may be indistensable due to this thickening with a fixed or rigid appearance in sequential films. If the mass lesion is in the outflow region (pylorus), the stomach may appear severely distended with fluid, fluid and gas, or empty post vomiting. Emptying Delay in gastric emptying may be secondary to a mechanical or functional problem. Pyloric obstructions may result from hypertrophic changes, foreign bodies, and neoplasia. A primary ruleout for what radiographically appears as a moderately distended stomach and suspicion of pyloric obstruction is motility or functional problems due to the effects of such drugs as atropine, antispasmodics, or certain tranquilizers. With outflow obstruction, gastric emptying time may be delayed to 3 or as long as 6 hours. With contrast media, the pyloric canal may appear narrowed. Contrast media may be seen extending through this concentrically narrowed and elongated pylorus and identified as a beak (birds beak) or string sign. The pyloric tit is the peristaltic pouch, or outpouching of the pyloric antrum along the lesser curvature as a peristaltic wave pushes contrast media against the outflow obstruction. Small Intestine Normal Radiographic Anatomy The small intestine should be evaluated for margination (serosal surface definition). The margin should be smooth. It is normally visible due to the presence of fat in the serosa except if the animal is young (< 6 months) or emaciated or if abdominal fluid or cellular infiltrates are present. The normal diameter of the small intestine in dogs is < 2 to 3 rib widths or less than the dorsoventral dimension of the second lumbar vertebral body. The normal diameter in cats is up to 12 mm. The small bowel should be evenly distributed throughout the abdomen, occupying space not taken up by other organs. As organomegaly occurs, regardless of whether it is normal (distended stomach or urinary bladder) or abnormal (e.g., mesenteric lymphadenopathy, pancreatic enlargement, splenic mass) the intestine will be displaced. The direction of displacement helps to determine the differentials for the mass effect causing the displacement. In obese cats, intestines are commonly localized in the ventral abdomen to the right of midline. The small bowel should have a smooth, continuous, curved appearance. It is often necessary to have contrast studies (upper GI series) to identify normal or abnormal shape or diameter of small bowel. The radiopacity of the bowel loop is dependent upon whether it is empty, fluid-filled, gas-filled, or filled with fluid and gas combined. Fluid-filled or empty loops of bowel appear as white rope-like structures. Gas-filled loops appear as black, thin-walled tubes. A small amount of gas above fluid looks like a narrow radiolucent band with an apparent thickening of the bowel wall. A larger volume of gas reflects wall thickness more accurately and therefore bowel wall thickness should never be evaluated on survey films but only with use of contrast media (whether negative or positive). Evaluation of the Upper Gastrointestinal Contrast Series Size of lumen Contour of mucosal surface Previous Next Contents 7

10 Character of intraluminal shadow Thickness of bowel wall Flexibility and motility of bowel wall Position of small intestine Continuity of opaque column Transit time. Transit times associated with barium in dogs demonstrate that barium should enter the duodenum in 13 to 20 minutes, reach the jejunum in 30 minutes, be within the jejunum and ileum in 60 minutes, and reach the ileal colic junction in 90 to 120 minutes. Barium should clear the upper GI tract and be within the ilium and colon in 3 to 5 hours. The transit time of barium in cats varies greatly. It is usually from the stomach through to the ileum in about 60 minutes, although it can take as long as 4 hours. Organic iodides have a range of transit times through the small bowel of approximately 15 to 90 minutes. Most of the time, the organic iodide is in the ileum and colon within 60 minutes. The appearance of the small bowel mucosa or wall is best evaluated by using positive-contrast media. The mucosa should appear as a smooth, even surface or as a finely fimbriated edge. This fimbriation is due to barium dissection of groups of aggregated villi. In healthy young dogs, the mesenteric border of the duodenum has numerous or single, usually square or conically shaped depressions in the bowel overlying lymphoid follicles. These are pseudoulcers and are considered normal. They are not seen in cats. In healthy cats, distinct bead-like segments with contrast seen in the duodenum may be apparent. This string-of-pearls appearance is due to normally strong circular muscle contractions. The duodenum or jejunum of healthy cats may also demonstrate a linear filling defect during an upper GI. This pseudostring sign is due to an indentation or mucosal fold into the lumen acting as a linear lucency surrounded by barium. It is usually seen in only poorly distended intestinal segments. Abnormal Appearance on Survey Radiographs Patients with recent and extensive vomiting tend not to have radiographic evidence of duodenal obstruction, even though it may be present. Contrast radiography is often necessary to identify high small intestinal obstructions in the vomiting patient. Ileus is defined as an obstructive condition of the intestine. There are two types of ileus: mechanical and functional. Mechanical ileus is also referred to as dynamic or obstructive ileus. It is usually simple and nonstrangulating. The radiographic signs may be influenced by the degree, location, and duration of obstruction. Dilatation of small intestine secondary to mechanical obstruction results from swallowed air and saliva and accumulation of mucosal secretion into the digestive tract. Functional ileus, also referred to as paralytic or adynamic ileus, can be localized or generalized and may be a sequelae to mechanical ileus. The stages of development of functional ileus include muscle fatigue allowing stretching of the intestine, muscle ischemia secondary to stretching, and muscle necrosis. There are numerous causes of functional ileus. Extrinsic causes tend to be more generalized and include spinal cord injury, reflex to pain, peritoneal trauma or irritation, or vascular compromise. Intrinsic causes tend to be regional and are numerous, including edema, amyloidosis, acute inflammation, and enteritis just to name a few. Radiographic Signs of Mechanical Ileus Excessive gas and fluid accumulation in bowel loops 2011 Symposium Proceedings Gastrointestinal Diseases Previous Next Contents 8

11 Hairpin curves to the folded bowel loops Stacking or layering to loops of bowel Squaring off of distended loops of bowel Degree of dilatation increases as obstruction is more aboral Nonuniform dilatation of small intestine Abnormal Appearance on Contrast Radiographs Intraluminal disorders usually appear as radiolucent areas surrounded by positive-contrast media. They often delay intestinal transit time and cause ileus proximal to their location. These disorders should be evaluated with an upper GI series (positive-contrast media/barium). The following questions should be answered while evaluating this upper GI series: whether the lesion projects into the lumen, causing a narrowing or constriction; whether the lesion projects away from the lumen, causing an enlargement of the diameter of the lumen as a result of a defect in the bowel wall; and is there thickening and rigidity of the bowel wall, irregularity at the serosal or mucosal surfaces, or a combination of these changes. Radiographically, intramural disorders of the bowel may appear as a pedunculated, broad-base, smooth or irregular surface, and may expand the width of the bowel (benign tend to be smooth where as malignant tend to be irregular). The causes of intramural lesions include neoplasia, granuloma, abscess, scar, and hematoma. Inflammatory diseases of the small intestine (enteritis) tend to increase the rate of intestinal motility (reduced transit time). Chronic and/or severe lesions may cause irregularity of the mucosal surface. Chronic lesions may also reduce the width of the bowel lumen. Enteritis of sufficient severity and chronicity can alter or erode the mucosa. Ultrasonography of the Healthy Gastrointestinal Tract Initially, ultrasonography was considered to be a poor choice for evaluation of the GI tract because of the ultrasonographic barrier caused by luminal gas. Over the past 10 years, however, it has been applied successfully to diagnosis of several GI disorders, including gastric and intestinal foreign bodies, intussusception, uremic gastropathy, chronic pyloric hypertrophic gastropathy, enteric duplication, and GI neoplasia. Ultrasonography has proven useful not only in the diagnosis of morphologic GI disease but also in the evaluation of GI function. Maximizing resolution by using a high-frequency transducer is critical in the examination of the GI tract. Fasting the animal before ultrasonography also improves the results of the examination. Normal Ultrasonographic Appearance of the Stomach The animal should be fasted before ultrasonography if possible to decrease the amount of gas and ingesta in the stomach. A high-frequency transducer is important ( MHz) to maximize resolution. As with all ultrasound studies, the entire abdomen should be examined completely to ensure that concurrent disease is not missed. For example, GI disease is often associated with mesenteric lymphadenopathy or secondary to pancreatic disease. Complete ultrasonographic examination of the stomach includes evaluating wall thickness and layering, evaluating luminal contents, and quantifying peristaltic function. (Normal wall thicknesses of several abdominal structures are listed in Table 1.) The stomach should be scanned in both the longitudinal and transverse planes. As with radiographs, the appearance varies depending on the degree of distention and luminal contents. When the stomach is empty, it looks like a flower, especially in cats. In healthy dogs, the gastric wall is 3- to 6-mm thick when the stomach is moderately distended and may be slightly thicker when it is not distended. These thickness measurements of the stomach are taken between Previous Next Contents 9

12 rugal folds. Gastric rugae can be recognized in the fundus and body of the stomach, and their thickness depends on the degree of gastric distention. Ultrasonography allows for differentiation of the stomach layers, which alternate in echogenicity. Under optimal conditions, five separate layers can be identified: luminal mucosal interface (hyperechoic), mucosa (hypoechoic), submucosa (hyperechoic), muscularis (hypoechoic), and subserosa serosa (hyperechoic). The submucosa and subserosa serosa are hyperechoic because of the presence of relatively more fibrous connective tissue. The mean number of peristaltic contractions in the stomach is four to five per minute. The ultrasonographic appearance of the GI lumen depends on its contents. In a collapsed state, bowel lumen appears as a hyperechoic core ( mucosal stripe ) surrounded by a hypoechoic halo of bowel wall. This hyperechoic core represents mucus and small air bubbles trapped at the mucosal luminal interface. When fluid is present in the bowel lumen, an anechoic area is present between the walls of the bowel, which appears tubular in long-axis views and circular in short-axis views. Gas in the GI lumen causes a highly echogenic interface with reverberation artifact. The presence of fluid in the bowel lumen improves the sonographer s ability to evaluate the mucosal and submucosal layers of the GI tract, whereas the presence of luminal gas hinders it. As with the stomach, the layers of the intestine alternate in echogenicity. Under optimal conditions, five separate layers can be identified: the luminal mucosal interface (hyperechoic), mucosa (hypoechoic), submucosa (hyperechoic), muscularis (hypoechoic), and subserosa serosa (hyperechoic). Real-time ultrasonography to evaluate enteric motility should be included in the examination. The mean number of peristaltic contractions in the intestine is four to five per minute. Contractions are not seen in the colon. Ultrasonography of the Abnormal Gastrointestinal Tract Neoplasia The most common ultrasonographic features of GI neoplasia are thickening of the stomach or bowel wall, loss of the normal layered appearance, and alterations in the contour of the mucosal and/or serosal surfaces. Changes associated with GI neoplasia are most often focal but can also be diffuse, especially in the case of GI lymphoma in dogs. Wall thickening is usually asymmetric but can be symmetric. Loss of the normal layered appearance of the GI wall reflects infiltration of neoplastic and inflammatory cells, necrosis, edema, and hemorrhage. In some cases, examination of the wall layers provides information about the severity and depth of neoplastic involvement. Gastric leiomyomas can be incidental findings during routine abdominal ultrasonography and are usually identified as fairly small, round masses protruding into the gastric lumen in the area of the cardia. In many animals, gastric leiomyomas are not associated with clinical signs. Gastric adenocarcinoma and lymphoma in dogs typically cause severe thickening and irregularity of the gastric wall. The thickened areas are usually hypoechoic; normal layers are not apparent. Ultrasonographically (on transverse section), alimentary lymphoma in cats appears as a thick hypoechoic ring surrounding the hyperechoic mucosal surface. Ulceration Gastric ulcer disease can be a primary disorder (e.g., associated with nonsteroidal anti-inflammatory drug administration) or sequelae of other diseases e.g. liver disease or neoplastic or inflammatory diseases of the stomach). Ultrasonographically, gastric ulcers appear as hyperechoic linear foci in the 2011 Symposium Proceedings Gastrointestinal Diseases Previous Next Contents 10

13 gastric wall. These foci represent small gas bubbles trapped at the luminal surface of the ulcer crater. Occasionally, a focal loss of gastric mucosa and submucosa may be apparent ultrasonographically. The inflammation and edema associated with ulceration may cause a loss of the layered appearance of the deeper portions of the gastric wall. Unfortunately, ultrasonography seems to be insensitive for identifying gastric ulceration, especially when it is superficial. Uremic Gastropathy The ultrasonographic appearance of uremic gastropathy has been described with severe uremia resulting from end-stage renal disease. Ultrasonographic characteristics included gastric wall thickening and an echogenic line in the superficial gastric mucosa, representing gastric mucosal mineralization. The normal layered appearance of the gastric wall can be lost or preserved, reflecting variation in the depth of gastric wall inflammation, edema, and necrosis. Chronic Hypertrophic Pyloric Gastropathy Ultrasonographic findings characteristic of chronic hypertrophic pyloric gastropathy (CHPG) include gastric distention and thickening of the pyloric wall. Examination of the pylorus in a transverse plane shows an evenly thick hypoechoic ring (representing the muscularis) surrounding the pyloric lumen. Ultrasonographically, the thickness of the pyloric wall in animals with CHPG can exceed 9 mm and the thickness of the muscular layer can exceed 4 mm. Gastrointestinal Foreign Bodies Ultrasonography has been useful to identify several types of gastric and intestinal foreign bodies. The sonographic appearance of foreign material in the GI tract depends on its physical properties and the degree to which it attenuates sound. Objects that transmit sound are more accurately represented by their ultrasonographic image than are those that attenuate sound. All but the near margin of strongly attenuating objects are obscured by the acoustic shadow that they produce. Although this shadow prevents full visualization of the object, its presence can be an indicator that foreign material is present. Objects that attenuate sound produce a highly echogenic linear interface at their near surface, followed by an acoustic shadow that may have either a clean or dirty appearance. The shape of the echogenic line (i.e., curved, irregular, linear) may help to identify the type of foreign body present. It is important to distinguish the ultrasonographic pattern produced by strongly attenuating foreign objects from that of luminal gas, which can create a similar image. When a gastric foreign body is suspected but cannot be identified, administration of water via an orogastric tube may aid in visualization. The presence of a foreign body can also be suggested by ultrasonographic abnormalities of the surrounding GI structures. The identification of bowel distention with fluid or gas may signify obstruction and should prompt a careful search for foreign material that may be causing the obstruction. Linear foreign objects are often associated with bowel wall thickening and plication, which can be identified on ultrasonographic examination. Intussusception Ultrasonography has aided in the diagnosis of intestinal intussusception. In addition, we have observed cecal inversion in a dog and ileocolic intussusception in a cat, both of which were apparent ultrasonographically. The sonographic appearance of intussusception in a transverse plane has been described as a "target lesion" or as the "multiple concentric ring sign," reflecting the concentric layers of bowel wall in the intussuscepted segment. On longitudinal scan, intussusception has the appearance of a thickened segment of bowel with an excessive number of layers that alternate in echogenicity. It should be noted that other GI disorders can also cause "target" or "bull's eye" type lesions. Therefore, Previous Next Contents 11

14 when intussusception is suspected on a transverse image, the lesion must also be examined in a longitudinal plane. Ileus Both mechanical and paralytic ileus have been described as ultrasonographic findings. Mechanical ileus occurs proximal to an area of obstruction; paralytic ileus can be generalized (e.g., viral enteritis, hypokalemia) or focal (e.g., duodenitis secondary to pancreatitis). When ileus is present, the bowel appears dilated and fluid-filled and GI motility is decreased or absent. Inflammatory Disease With inflammatory bowel disease, the stomach and intestine may be normal on ultrasonography. Changes, especially with chronic disease, have been reported as focal to diffuse thickening, altered echogenicity, poor intestinal wall layer definition, and mild enlargement of adjacent lymph nodes. The most common finding with inflammation is extensive and symmetrical wall thickening with the layering retained. In comparison, neoplasia is more often localized, with greater thickness of the wall and loss of the normal layering. These categories can overlap, and therefore cytology or histopathology is required for definitive diagnosis. Acute enteritis or inflammatory bowel disease may demonstrate corrugation of the intestine on ultrasound examination. Liver Radiology Liver position, size, shape, margination, and opacity can be evaluated on standard abdominal radiographs. The liver is located predominantly in the intrathoracic portion of the abdominal cavity, with the cranial border outlined by the diaphragm lung interface. The caudal border is the stomach, cranial duodenal flexure, and the right kidney. The normal gallbladder is not visualized as a separate structure from the liver. Most alterations in liver position are accompanied or caused by changes in the diaphragm. Radiographic evaluation of changes in liver size is somewhat subjective and insensitive to subtle change. Radiographic changes associated with generalized hepatomegaly include gross increase in size of the hepatic shadow, rounding of the caudal hepatic borders, caudal displacement of the stomach and dorsal elevation or left-sided displacement of the pylorus. Pediatric patients normally have a proportionally larger liver than adults. Pseudohepatomegaly may occur with overexpansion of the thorax caused by pleural effusion, pulmonary masses, or air trapping, as with allergic bronchitis in cats causing caudal displacement of the diaphragm and subsequent caudal displacement of the liver. Poor visualization of the stomach may make interpretation of the size of the liver difficult. Gastric overdistention may mask liver volume and make it look small. Introduction of contrast media (positive or negative) into the stomach can facilitate evaluation of its axis and therefore better help determine hepatic size. Focal hepatic enlargement is a more difficult radiographic diagnosis and is based on a bulge or alteration in the hepatic contour or localized displacement of the structures adjacent to the liver. Causes of focal liver enlargement include cysts, granulomas, abscesses, neoplasia, regenerative nodules, and hematomas. Focal liver disease is best evaluated with ultrasonography. The radiographic changes associated with a small liver include reduced distance between the diaphragm and the stomach, cranial displacement of the pylorus, and a gastric axis that is vertical or angled cranially (i.e., the axis is dorsocaudal to ventrocranial) instead of parallel to the tenth intercostal space. Misinterpretation of a normal liver as small may occur in deep-chested breeds (not necessarily large or giant) in which the liver is more vertical. In very obese cats, the liver may be elevated above a large 2011 Symposium Proceedings Gastrointestinal Diseases Previous Next Contents 12

15 amount of falciform fat and may appear falsely small. Be sure to compare the fluid/soft tissue opacity of the liver with the fat opacity of the falciform. The liver is normally a homogenous soft tissue radiopacity. Increases in liver radiopacity are secondary to mineralizations in the biliary system or hepatic parenchyma. Decreases in radiopacity occur with accumulation of gas in the portal vessels, bile ducts, gallbladder, or hepatic parenchyma. Normal Ultrasonographic Appearance Ultrasonography often provides information about the liver that cannot be obtained from routine abdominal radiographs. Results of hepatic ultrasonography are rarely specific. Parameters of the liver that should be assessed include size, contour, echogenicity, beam penetration, vascularity, and ancillary abnormalities. Although ultrasonography has proven useful in evaluating a variety of liver disorders in dogs and cats, few hepatic lesions have a specific sonographic feature. An ultrasonographically normal hepatic appearance does not necessarily rule out liver disease, especially mild, diffuse disease with few stromal or parenchymal changes. Biopsy or fine-needle aspiration is indicated if clinical signs or laboratory findings suggest liver disease. A healthy liver is bounded cranially by a curvilinear echogenicity that represents the diaphragm lung interface and caudally by the stomach, spleen, and right kidney. Echogenicity of the liver is relatively homogeneous. It is less than that of the spleen and falciform fat, and slightly greater than or equal to that of the renal cortex (which is usually compared at the junction of the right kidney and the caudate lobe of the liver in the renal fossa). A healthy liver has smooth, sharp borders. The Biliary System The biliary system includes the gallbladder, cystic duct, intrahepatic and extrahepatic bile ducts, and the common bile duct. The gallbladder is an anechoic, round to pear-shaped structure that is found ventral and to the right of midline. The wall of the gallbladder is not normally seen ultrasonographically. The cystic duct is seen as a continuation of the neck of the gallbladder; it becomes the common bile duct at its junction with the extrahepatic bile ducts. The common bile duct continues its course through the pancreas and enters the duodenum at the major papilla. With the exception of the cystic and common bile ducts, biliary ducts are not visualized ultrasonographically in healthy dogs or cats. Moreover, it is difficult to determine where the cystic duct ends and the common bile duct begins. The normal diameter of the common bile duct in dogs is 3 mm or less, and 4 mm or less is normal in cats. The Vascular System Vascular structures in the liver appear as branching anechoic tubular or rounded structures. In the healthy liver, these represent hepatic and portal veins. The major portal vein (extrahepatic) is ventral to the caudal vena cava in the porta hepatis region. Intrahepatic portal veins are larger near the porta hepatis, whereas hepatic veins are larger near the caudal vena cava. The walls of the portal veins appear echogenic because of surrounding fat and fibrous tissue. Small portal veins and their surrounding fat produce many small parallel echoes that are normally visible throughout the hepatic parenchyma. Hepatic veins generally do not have an echogenic wall. However, major hepatic veins occasionally have some increased peripheral echogenicity at the point where they enter the caudal vena cava, but it is never as prominent as that of the wall of a similarly sized portal vein. Hepatic arteries are not normally visualized ultrasonographically. The caudal vena cava is ventral and to the right of the aorta and dorsal and to the left of the portal vein. These three vessels can be easily visualized through the right caudal intercostal spaces. The caudal vena cava can often be followed cranially through the liver to the diaphragm. Previous Next Contents 13

16 Abnormal Ultrasonographic Appearance Diffuse Disease Diffuse hepatic diseases, which cause less distortion of normal hepatic architectural landmarks, are more difficult to detect ultrasonographically than are focal processes. Many diffuse hepatic diseases do not cause ultrasonographically detectable changes until they reach an advanced stage. Therefore, a normal ultrasound examination does not preclude the presence of disease. Diffuse liver disease can appear as overall increased, decreased, or mixed echogenicity. Hyperechogenicity of the liver is indicated by the following ultrasonographic findings: 1) greater echogenicity of the liver than the renal cortex, spleen, and/or falciform fat; 2) increased attenuation of sound by the liver, resulting in poor visualization of its deep portion; and 3) poor visualization of intrahepatic portal vein borders. Liver size is an important consideration when evaluating hyperechoic diseases. Rounding of the caudal ventral liver margin indicates an enlarged liver. Differential diagnoses in patients with normal to enlarged, diffusely hyperechoic livers include fatty infiltration, steroid hepatopathy, lymphosarcoma, diabetes mellitus, and toxic hepatopathies. Increased attenuation appears to be the earliest appreciable acoustic change with steroid hepatopathy. When steroid hepatopathy is suggested by increased hepatic echogenicity, careful evaluation of the adrenal glands should be included in the ultrasound examination. When compared with the adjacent falciform ligament, severe hepatic fatty infiltration in cats appears hyperechoic and has increased sound attenuation, resulting in a decreased ability to see structures. In one study, hyperechogenicity of the liver when compared with falciform fat was shown to be the best ultrasonographic criteria for diagnosis of hepatic lipidosis with 91% sensitivity, 100% specificity, and 100% positive predictive value. When hepatic lipidosis is suspected in cats, the pancreas is always evaluated because of the high incidence (5 of 13 cats in one report) of concurrent acute pancreatitis. Acute pancreatitis with hepatic lipidosis has a poorer prognosis than does hepatic lipidosis alone, and patient management requires considerably different medical and nutritional therapies. Hyperechoic diffuse liver disease accompanied by a small liver with irregular margins indicates cirrhosis or end-stage liver disease. Cirrhosis may appear heterogeneous with increased echogenicity ventrally and may be associated with decreased blood velocity and flow in the portal vein (as evaluated by Doppler ultrasonography). Ancillary changes that may occur with cirrhosis include portal and splenic vein dilatation (secondary to portal hypertension) and ascites. Decreased echogenicity is characterized by a liver that is less echogenic than the adjacent renal cortex. Portal vein walls will be accentuated in hypoechoic liver disease (starry-sky appearance). Causes of hypoechoic diffuse liver disease include suppurative hepatitis, lymphosarcoma, leukemia, chronic passive hepatic congestion (look for dilated hepatic veins), and histoplasmosis. Suppurative hepatitis often causes a marked decrease in hepatic echogenicity but is not usually associated with any other sonographic abnormalities. Chronic hepatic congestion results in hepatomegaly, enlargement of the hepatic veins and caudal vena cava, and decreased hepatic echogenicity. Lymphosarcoma may appear as focal, multifocal, or diffuse disease. Ultrasonography has been shown to be an insensitive means of detecting hepatic lymphosarcoma. Liver lobe torsion and strangulation due to a diaphragmatic hernia may appear hypoechoic because of congestion. Focal Disease The number, size, echogenicity, delineation, and shape of the lesions are important considerations when describing focal liver disease. Focal liver disease is easier to recognize than diffuse liver disease because abnormal foci are surrounded by normal parenchyma. Several focal diseases have been recognized in small animal patients, including cysts, hematomas, abscesses, granulomas, hyperplastic nodules, primary and metastatic neoplasms, infarcts, and calcification Symposium Proceedings Gastrointestinal Diseases Previous Next Contents 14

17 Hepatic cysts may be present in the liver as single or multiple lesions. Ultrasonographically, cysts are round, smooth, anechoic structures that demonstrate through transmission. They may be septated or may contain internal echoes. Hepatic cysts are generally not associated with clinical signs unless they are so large or numerous that they cause discomfort. Hematomas usually demonstrate increased echogenicity initially and decreased to mixed echogenicity as they mature. Large, mature hematomas may be well demarcated and may exhibit mineralization. Hepatic abscesses have a variable ultrasonographic appearance, ranging from anechoic to hyperechoic. The internal echogenicity of an abscess depends on its cellularity and whether it contains microbubbles. Through transmission may be evident if the cellularity of the abscess is low. Gas in a hepatic lesion, identified as a highly echogenic interface with reverberation at the nondependent margin, is suggestive of abscess formation. Granulomas also vary in appearance, depending on their cellular composition and duration. Hyperplastic hepatic nodules are benign lesions comprising variable amounts of hepatocytes, lipid, blood-filled sinusoids, and areas of atrophic or necrotic parenchyma. Ultrasonographically, hyperplastic hepatic nodules appear as hypoechoic to hyperechoic nodules of varying sizes and are indistinguishable from primary or metastatic hepatic neoplasia. Hyperplastic nodules may cause the liver margin to become irregular or bumpy, and very large nodules may have a mass-like appearance. The size and number of lesions associated with primary hepatic neoplasia varies. It may appear as diffuse widespread inhomogeneity with areas of mixed echogenicity or as focal or multifocal lesions of variable echogenicity. The mixed echogenic pattern associated with neoplastic lesions is most likely related to regions of hemorrhage and/or necrosis in and around the area of neoplasia. The lesions of metastatic hepatic neoplasia are generally multiple and spherical. The three most common ultrasonographic patterns are 1) focal hypoechoic areas, 2) target lesions (echogenic center surrounded by a hypoechoic rim), and 3) diffuse inhomogeneity, resulting in a "mottled" appearance. Hepatic ultrasonographic changes have been characterized for hepatocutaneous syndrome (canine superficial necrolytic dermatitis); the pattern looks like a honeycomb or Swiss cheese. The liver appears to contain variably sized ( cm) hypoechoic areas surrounded by echogenic borders. On histopathologic examination, the hypoechoic areas are hyperplastic nodules surrounded by areas of collapsed hepatic parenchyma (hyperechoic border). Cystic liver masses, or hepatobiliary cystadenomas, have been reported in cats. They are usually benign. They have thin, smooth cyst capsules and most often appear anechoic. They tend to demonstrate through transmission. Abscesses, hematomas, and other types of cysts (parasitic and neoplastic) should be considered as differential diagnoses in patients with cystic liver masses. Hepatic calcification can be due to granulomatous disease, hematomas, neoplasia, or parasitic cysts. Since hematomas, abscesses, primary and secondary neoplasms, and nodular hyperplasia are ultrasonographically similar, tissue core biopsy or fine-needle aspiration is necessary for a definitive diagnosis. Vascular Disease Hepatic vascular disease includes disorders of the hepatic veins (e.g., chronic passive congestion), arteriovenous fistulas, and disorders of the portal veins (e.g., portosystemic shunt). The caudal vena cava and hepatic veins may be enlarged secondary to right heart failure (e.g., pericardial effusion, heartworm disease) or posthepatic obstruction of the caudal vena cava. Enlargement of the portal vein due to portal hypertension may be present in animals with cirrhosis. Hepatic arteriovenous malformations or Previous Next Contents 15

18 fistulas appear ultrasonographically as tortuous round or tubular anechoic structures in the hepatic parenchyma. Ultrasonographic findings associated with portosystemic shunts include a small liver, a decrease in the number and size of intrahepatic branches of the portal and hepatic veins, and the presence of anastomosis between the portal vein and the systemic circulation. A transverse scan from the right intercostal space is the most useful imaging technique for identification of portocaval shunts. They are best visualized by examining the caudal vena cava and portal vein at the porta hepatis and in the area just caudal to this region. Intrahepatic shunts are seen as an anastomosis between the portal vein and caudal vena cava in the hepatic parenchyma. Extrahepatic shunts are visualized as abnormal vessels anastomosing with the caudal vena cava just caudal to the liver. In our experience, other ultrasonographic findings that may be associated with portal systemic shunts include enlargement of the caudal vena cava, splenomegaly secondary to portal hypertension, evidence of portal hypertension and hepatofugal portal blood flow on Doppler ultrasonography, and accumulation of tortuous vessels in the splenic or renal hilus or near the colon (multiple acquired portosystemic shunts). Biliary Disease There was no significant difference in the prevalence of gallbladder sludge among healthy dogs (53%), dogs with hepatobiliary disease (62%), or dogs with other diseases (48%). In dogs with hepatobiliary disease or other diseases, the mean age of those with sludge was higher than that of those without sludge (P < 0.05). The results of this study indicate that gallbladder sludge in dogs is not necessarily associated with hepatobiliary disease and should be considered an incidental finding (1). Although biliary diseases are uncommon in small animals, they comprise a group of disorders for which ultrasonography is an important diagnostic tool for example, cholecystitis, cholelithiasis, and obstructive biliary disease. The most common ultrasonographic abnormality associated with cholecystitis is thickening of the gallbladder wall. The appearance of the wall may be even-layered (onion skin) or uneven-layered. The onion skin appearance can also result from abdominal effusion of any cause. When effusion is present, the acoustic interface between the fluid and the gallbladder makes the wall ultrasonographically apparent. Cholelithiasis typically does not cause clinical signs. Choleliths are highly echogenic structures that demonstrate posterior shadowing. The size and depth of the stone, its mineral content, and the transducer frequency determine the amount of shadowing that is produced. Echogenic bile and stones that contain no minerals (cholesterol stones) do not produce shadows. Normally, choleliths fall to the dependent portion of the gallbladder when the position of the animal is changed. Ultrasonography is the diagnostic imaging method of choice for evaluation of biliary obstruction. The following observations have been made after experimentally induced obstruction of the common bile duct in dogs: The earliest indication of obstruction is distention of the gallbladder and cystic duct, with loss of the normal tapering of the neck of the gallbladder (24 h postligation). Dilatation of the common bile duct occurs before the observation of icterus. Dilatation of bile ducts begins distally and progresses proximally. The gallbladder reaches maximum size 48 hours postligation. Dilatation of the intrahepatic bile ducts is detected ultrasonographically 5 to 7 days postligation Symposium Proceedings Gastrointestinal Diseases Previous Next Contents 16

19 Enlargement of the extrahepatic bile ducts and gallbladder has been found to persist despite reestablishment of normal bile flow after obstruction. The common bile duct can be distinguished from the portal vein based on its more ventral location and because acoustic enhancement occurs deep to biliary structures. In addition, the common bile duct becomes tortuous with chronic obstruction. Severe obstructive biliary disease often causes the appearance of multiple cystic structures near the hepatic hilus as the sound beam cuts through the very tortuous common bile duct several times. Ultrasonographic detection of biliary duct dilatation alone may not be a reliable indicator of biliary obstruction; therefore, evaluation of gallbladder dynamics is needed for a full evaluation of biliary function and patency. Gallbladder mucocele is an abnormal accumulation of mucus with distention of the gallbladder. Ultrasonographically, these gallbladders are subjectively distended and have an immobile stellate or finely striated bile pattern. Pericholecystic hyperechoic fat or fluid suggestive of gallbladder rupture. Cystic or common bile ducts may be distended. Gallbladders have a variable wall thickness. Pancreas Radiology The pancreas is shaped like a boomerang. There are three parts: the right lobe, which lies adjacent to the descending duodenum; the body, which lies at the junction between the pylorus and duodenum; and the left lobe, which lies adjacent to the greater curvature of the stomach. The pancreas is not normally seen. With a diseased pancreas, the duodenum may be displaced ventrally. On the ventrodorsal view, there is usually lateral (right) displacement of the descending duodenum and the pylorus is displaced to the left (widening of the duodenal pyloric angle). The transverse colon as well as ascending colon may be displaced centrally and caudally. Fluid and gas distention of the stomach, duodenum and colon may be present. Localized loss of abdominal detail (ground-glass appearance) may occur with inflammation of the pancreas. The most common change radiographically on survey films is actually no change at all. Changes that may occur and be visualized relative to pancreatic disease and an upper GI series include fixed position and shape to the duodenum; widened proximal duodenal flexure (the angle between the pylorus and duodenum); and thickening and rigidity of the duodenum, pylorus, and greater curvature of the stomach. Gastric outflow obstruction and duodenal distention (ileus) may also be visualized. Ultrasonography Ultrasonography is the imaging method of choice for evaluation of the pancreas in small animals. It can provide information about the size, shape, and contour of the pancreas and may suggest the presence of inflammation, abscess formation, or neoplasia. Ideally, patients should be fasted before abdominal ultrasonography to minimize interference from GI gas. There are several limitations to pancreatic ultrasonography: The normal pancreas is not always seen as a discrete structure; thus, it is actually the pancreatic area, and not the organ itself, that must be examined. Ultrasonography lacks specificity. For the most part, ultrasonographic findings do not allow differentiation between inflammatory and neoplastic processes. Previous Next Contents 17

20 The proximity of the pancreas to gas in the stomach, colon, and duodenum may prevent complete and accurate evaluation of the pancreatic region. Despite these disadvantages, ultrasonography can provide valuable diagnostic information in most animals with inflammatory or neoplastic diseases of the pancreas if it is done properly and with patience. The healthy pancreas is difficult to image as a distinct organ. Therefore, familiarity with the anatomy of adjacent structures is crucial to successful evaluation of the pancreatic area. The left lobe of the pancreas is dorsocaudal to the stomach and dorsocranial to the transverse colon. Its distal aspect can be visualized cranial to the left kidney and medial to the spleen. The pancreatic body lies caudal to the pylorus. It is ventral to the portal vein and the caudate process of the liver and craniomedial to the right kidney. The right lobe of the pancreas is found dorsomedial to the descending duodenum, ventral to the right kidney, and ventrolateral to the portal vein. Both the cranial and caudal pancreaticoduodenal veins are located in the parenchyma of the right lobe and run parallel to the descending duodenum. Normally, pancreatic parenchyma has a homogeneous echotexture. The pancreaticoduodenal vein may be apparent in the right lobe. The left lobe of the healthy pancreas occasionally is seen in the triangular region defined by the spleen, stomach, and left kidney. Gas in the adjacent stomach and transverse colon makes imaging of all but the most distal portion of the left lobe difficult. Pancreatitis Ultrasonography has proven to be a reliable tool for identifying changes associated with pancreatic inflammation and is currently considered the imaging method of choice for evaluating pancreatitis and pancreatic neoplasia. Ultrasonography provides several distinct advantages in the diagnostic evaluation of pancreatitis: It can identify abnormalities in animals with pancreatitis. In many cases, it also provides information about the severity of inflammation. It is noninvasive and can be repeated frequently, providing a means of following disease progression and/or resolution. It allows evaluation of peripancreatic structures, such as the biliary system, duodenum, and stomach, which are often secondarily involved in acute pancreatitis. It is an important tool for identifying complications of pancreatitis, such as biliary obstruction, abscess formation, and pseudocyst formation. The ultrasonographic findings that characterize pancreatitis represent changes in either the pancreas itself or in peripancreatic structures. The most common ultrasonographic abnormality noted in animals with pancreatitis is a hypoechoic mass dorsomedial to the descending duodenum and caudal to the stomach. This mass represents the inflamed pancreas, and although its overall echogenicity is usually decreased, it may sometimes appear inhomogeneous. The peripancreatic mesentery and associated fat are often hyperechoic but may have variable echogenicity. The edges of the pancreas are distinct if the inflammation is mild but become poorly defined when severe pancreatitis is present, probably as a result of the edema, necrosis, and hemorrhage that accompany severe pancreatic inflammation. The overall pancreatic image tends to become better defined with more distinct edges as inflammation subsides. Improved resolution of the pancreatic margins may be partially related to saponification of surrounding fat. The ultrasonographic 2011 Symposium Proceedings Gastrointestinal Diseases Previous Next Contents 18

21 changes associated with chronic pancreatitis are often less severe than those associated with acute pancreatitis, although it is difficult to differentiate one condition from another based on ultrasonography alone. Changes in peripancreatic structures also contribute to the ultrasonographic diagnosis of pancreatitis. Free peritoneal fluid secondary to focal peritonitis may be apparent in the pancreatic region. The descending duodenum typically becomes dilated and fluid-filled, with thickened walls and no apparent peristalsis. With severe duodenitis, the duodenal wall may have a corrugated appearance. Potential complications of pancreatitis include pseudocyst or phlegmon formation, abscess formation, and biliary obstruction. Pancreatic phlegmons are edematous masses of indurated pancreas and adjacent tissue with varying degrees of necrosis that develop within several days of the onset of acute pancreatitis. They may resolve spontaneously or may cause persistent fever and abdominal pain. Pancreatic abscesses result from secondary infection of necrotic pancreatic tissue or of a phlegmon. Ultrasonographically, pancreatic phlegmons and abscesses appear as pancreatic masses of mixed echogenicity and variable size. Gas in a pancreatic mass, identified as an echogenic interface with reverberation, suggests abscess formation. Pancreatic pseudocysts appear ultrasonographically as primarily anechoic masses but they may contain some internal echoes. They cause mild acoustic enhancement of distal structures. Unfortunately, ultrasonography cannot usually differentiate between pancreatic phlegmons, abscesses, or pseudocysts. Extrahepatic biliary obstruction is another complication of acute pancreatitis that may necessitate surgery. Neoplasia Ultrasonographic identification of pancreatic neoplasia is difficult. Exocrine pancreatic neoplasia resembles pancreatitis ultrasonographically, making their differentiation difficult. In most cases, diagnosis of exocrine pancreatic neoplasia is based on histopathology following surgical biopsy or necropsy in an animal in which signs of pancreatitis were unresponsive to medical therapy. Insulinomas, which are clinically important causes of hypoglycemia in dogs and ferrets, may be detected ultrasonographically, although the frequency with which they are visualized is limited because of their small size. They appear as well-defined hypoechoic nodules that are spherical or lobulated. The liver and regional lymph nodes should be examined ultrasonographically for any animal in which pancreatic neoplasia is suspected. Reference Brömel C, Barthez PY, Léveillé R, Scrivani PV. Prevalence of gallbladder sludge in dogs as assessed by ultrasonography. Vet Radiol Ultrasound. 1998;39: Table 1. Normal Wall Thickness* / Biller: Gastrointestinal Imaging Area Dogs, mm Cats, mm Stomach mm Duodenum Jejunum Ileum Colon * Larger dogs have thicker walls. Previous Next Contents 19

22 Overview Managing Vomiting in Chronically Ill Dogs and Cats Todd R. Tams, DVM, Diplomate, ACVIM Acute and chronic vomiting are among the most common reasons that dogs and cats are presented for evaluation. Remember: Vomiting is a clinical sign of many disorders that can involve any organ system in the body. There are myriad causes of vomiting. As a result, clinicians must identify and differentiate basic problems that resolve quickly with minimal diagnostics and basic supportive care (with or without short-term pharmacologic therapy) from disorders that necessitate detailed diagnostic evaluation over a period of time and that may require multiple therapeutic maneuvers. Foci Vomiting is a clinical sign of many disorders that can involve any organ system in the body. From the outset, differentiating between regurgitation passive, retrograde movement of ingested material, usually before it has reached the stomach and vomiting is crucial. A complete history and thorough physical examination are essential, and clinicians are reminded not to overlook rectal examination and fecal testing for parasites in vomiting dogs. It is important to determine a possible link to any drugs that may have been administered, including nonsteroidal anti-inflammatory drugs (NSAIDs) or those that may be implicated in acute pancreatitis, including azathioprine, thiazide diuretics, furosemide, sulfonamides, tetracycline, L-asparaginase, and others. Vomiting can be considered chronic when it has occurred for more than 5 to 7 days and does not respond to initial symptomatic therapy. In the author s experience, once adverse food reactions, GI parasites, drug reactions, and metabolic causes are ruled out, the most common causes of chronic vomiting are inflammatory disorders, gastric hypomotility (underdiagnosed), obstructive disorders, and neoplasia. The most effective antiemetics are those that act at both the vomiting center and the chemoreceptor trigger zone. Maropitant is the only antiemetic developed for use in animals and is indicated for treatment of acute vomiting. Other effective antiemetics, developed for use in humans, include ondansetron, dolasetron, and chlorpromazine. Metoclopramide is less effective as a prokinetic drug than cisapride; many animals with gastric hypomotility respond well to metoclopramide but some have a suboptimum response Symposium Proceedings Gastrointestinal Diseases Previous Next Contents 20

23 In dogs with inflammatory bowel disease, it is important to note that any concurrent disease, including parasitism, bacterial overgrowth, and GI hypomotility, must be diagnosed and managed concurrently for best overall patient response. Vomiting refers to a forceful ejection of gastric and occasionally proximal small intestinal contents through the mouth. Vomiting involves three stages: nausea, retching, and vomiting. Serious consequences of vomiting include volume and electrolyte depletion, acid base imbalance, and aspiration pneumonia. It is essential that the clinician clearly differentiate between regurgitation and vomiting at the outset. Regurgitation is defined as passive, retrograde movement of ingested material, usually before it has reached the stomach. Regurgitation is a sign of an esophageal disorder. Failure to recognize the difference between regurgitation and vomiting often leads to misdiagnosis. Regurgitation may occur immediately after uptake of food or fluids or may be delayed for several hours or more. There are myriad causes of vomiting, ranging from more basic problems, such as eating too rapidly; ingestion of garbage, toxins, or foreign bodies; parasites; and adverse food reactions, to more complex causes, such as infectious disorders (e.g., leptospirosis), infiltrative inflammatory or neoplastic GI disease, or renal failure (Table 1). The cause of vomiting should be determined whenever possible to enable specific therapy. A suggested systematic diagnostic approach is outlined in Table 2. A complete history and thorough physical examination are essential. Clinicians are reminded not to overlook the importance of rectal examination and fecal testing for parasites in vomiting dogs. Common disorders, such as GI parasites, should never be overlooked as a cause of vomiting. Missing an early diagnosis of GI parasites (e.g., Giardia) due to failure to test appropriately can lead to a more prolonged clinical course and unnecessary added problems for the patient and expense for the client. The line of questioning should begin with determining whether the vomiting is acute or chronic (i.e., longer than 5 7 days in duration) and whether the vomitus contains blood. Signalment, immediate signs, pertinent history, and beneficial or deleterious effects of any drugs that may have been administered (either for the immediate symptoms or as treatment for another disorder) should be reviewed, particularly whether any NSAIDs have been used. Acute pancreatitis may also be a component of a drug reaction; agents that have been implicated include azathioprine, thiazide diuretics, furosemide, sulfonamides, tetracycline, L-asparaginase, and others. Consideration of the following historical features is useful in assessment and diagnosis: 1. Duration of signs: Chronic vomiting is characterized as occurring for more than 5 to 7 days or that which has failed to respond to initial symptomatic therapy and requires further investigation 2. Signalment: For example, always consider a foreign body in a Labrador Retriever with vomiting, consider pyometra in an intact female dog, and pertinent history 3. Dietary and environmental factors: Need specific dietary information, and always consider the environment (e.g., potential access to toxins, exposure to infectious diseases including parvovirus, leptospirosis) 4. Systems review: History of, for example, polyuria/polydipsia (PU/PD), coughing and sneezing, dysuria or dyschezia 5. Time relation to eating: Vomiting of undigested or partially digested food more than 8 to 10 hours after eating often indicates a gastric motility disorder (more common) or gastric outlet obstruction (less common); dogs with the gastric parasite Physaloptera often vomit very shortly after eating 6. Content of the vomitus: Food, clear fluid, bile, blood, material with fecal odor 7. Type and frequency of vomiting: Projectile? Chronic intermittent? Cyclic? Morning vomiting only? Previous Next Contents 21

24 In my experience, once adverse food reactions, GI parasites, drug reactions, and metabolic causes have been ruled out, the most common causes of chronic vomiting encountered in practice are inflammatory disorders (gastritis, inflammatory bowel disease [IBD]), gastric hypomotility (underdiagnosed in clinical practice), obstructive disorders (foreign bodies), and neoplasia. The most clinically useful (i.e., high yield of important information while being cost-effective) diagnostic procedures include hemogram and complete biochemical profile evaluation, urinalysis, fecal examination, survey abdominal radiography, thyroid and heartworm testing in cats, pancreatic lipase immunoreactivity screening for pancreatitis if the history suggests this disorder, ultrasonography, and endoscopy. Therapeutic Overview Initial nonspecific management of acute vomiting includes NPO (in minor cases a 6- to 12-hour period may be all that is required), fluid support, and antiemetics. Adverse food reactions and dietary sensitivity are diagnosed via dietary trials, and therapy involves elimination of offending ingredients. Often, a duration of 3 to 4 weeks, or even less in some cases, is sufficient to assess whether a specific diet will be effective in managing gastrointestinal disorders, whereas patients with primarily dermatologic manifestations of a food sensitivity disorder may require dietary trials that are 6 to 12 weeks in duration. For an erosive or ulcerative injury, elimination of predisposing causes is essential, and symptomatic therapy to enhance mucosal defenses is administered. GI hypomotility is managed with diet and prokinetic drugs. Inflammatory diseases are managed with immunosuppressive medications either alone or in combination, parasites are managed with anthelmintics, foreign bodies are removed either via endoscopy or surgery, diseased gallbladders are resected, gastric hypertrophy syndromes are managed surgically, and neoplasia is managed with surgery and/or chemotherapy. It is important to note that cats with GI lymphoma often respond well to chemotherapy, especially those with chronic lowgrade lymphocytic lymphoma. The earlier a diagnosis is established, the better. As there are many causes of vomiting, there are also many ways to treat it. A detailed discussion of all therapeutic agents and foods that might be used in managing vomiting is beyond the scope of this discussion. Here we will focus specifically on primary antiemetic therapy, prokinetic therapy, and management of IBD. Antiemetic Drugs The most effective antiemetics are those that act at both the vomiting center and the chemoreceptor trigger zone (CTZ). Vomiting is a protective reflex, and when it occurs only occasionally treatment is not generally required. However, patients that continue to vomit should be given antiemetics to help reduce fluid loss, pain, and discomfort. The most effective antiemetic drugs include maropitant, ondansetron, dolasetron, chlorpromazine, and metoclopramide. Metoclopramide is reasonably effective as a central antiemetic drug in dogs but not very effective for cats. Maropitant is now a commonly used antiemetic drug in both dogs and cats. Maropitant Most drugs used to control vomiting in animals have been developed for use in humans. There has been a need for a broad-spectrum antiemetic drug for use in animals that is effective in a variety of situations, has a rapid onset of action, is safe and affordable, and is available in both injectable and oral preparations. Maropitant citrate is a newer broad-spectrum antiemetic drug that is indicated for treatment of acute vomiting. Although currently labeled for use in dogs, this drug has been used in safe and effective management of many cats. Maropitant is a neurokinin-receptor antagonist that blocks the pharmacologic action of the neuropeptide substance P in the central nervous system. Substance P is found in significant concentrations in the nuclei comprising the emetic center and is considered a key 2011 Symposium Proceedings Gastrointestinal Diseases Previous Next Contents 22

25 neurotransmitter involved in emesis. By inhibiting the binding of substance P within the emetic center, maropitant provides broad-spectrum effectiveness against both neural and humoral causes of vomiting. Clinical trials and clinical experience, since August 2007 when the drug was released for use in the United States, have shown maropitant to be very effective for controlling a variety of causes of acute vomiting. It is administered as a once-daily injection (1 mg/kg SC, IM, or slowly IV for dogs, mg/ kg for cats), which is a significant advantage over many other antiemetic drugs. It also has a rapid onset of action. Maropitant is available in tablet form for outpatients, which makes it a very attractive choice for use in small animal practice. It is the drug of choice for prevention of motion sickness in dogs and cats. Some clinicians have experience using maropitant orally on a long-term basis for management of animals with vomiting and inappetence associated with chronic renal disease (usually in conjunction with an H 2 -receptor antagonist e.g., famotidine). Ondansetron and Dolasetron Ondansetron is a potent antiemetic drug that has proven to be very effective in both humans and animals for control of severe vomiting. Ondansetron acts as a selective antagonist of serotonin S3 receptors, a principal mediator of the emetic reflex. S3 receptors are found primarily in the CTZ, on vagal nerve terminals, and in the gut in enteric neurons. In my experience, ondansetron yields very good results in controlling or at least significantly decreasing the frequency of vomiting in dogs and cats with frequent or severe vomiting, including dogs with severe parvovirus enteritis, pancreatitis patients, and cats with hepatic lipidosis. Maropitant is extremely effective as well, however, and it is now used much more frequently in dogs than ondansetron. The recommended dose of ondansetron is 0.1 to 0.15 mg/kg IV given as a slow push every 8 to 12 hours (based on patient response). Dolasetron is also a 5-HT3-receptor antagonist antiemetic drug, with action similar to ondansetron. It is a less expensive alternative to ondansetron and only needs to be administered once daily, which is a significant advantage. Indications are for control of frequent vomiting that is poorly responsive to lessexpensive front-line antiemetic drugs. The dose is 0.5 to 0.6 mg/kg IV once daily. Dolasetron is generally well tolerated in animals. It is used frequently in cats as a front-line drug for acute vomiting, especially in hospitalized patients. Chlorpromazine Chlorpromazine is a phenothiazine drug that is still a very good first choice for pharmacologic control of vomiting in most cases. Phenothiazine antiemetics (chlorpromazine, prochlorperazine) have a broadspectrum effect and are effective in controlling vomiting due to a variety of causes. Chlorpromazine acts on the emetic center, the CTZ, and the peripheral receptors. The recommended dose is 0.2 to 0.5 mg/ kg SC or IM, SID to TID as needed to control vomiting. At this dose, there is a minimal sedative effect. Any sedation resulting from use of chlorpromazine, unless pronounced, is not considered a deleterious side effect in fact, it is often considered a beneficial effect by decreasing the discomfort and distress that can be associated with nausea. A potential side effect of phenothiazine drugs is hypotension, which can result from an alpha-adrenergic blocking action, causing arteriolar vasodilation. This is of minimal concern in well-hydrated patients, and in dehydrated patients it is readily controlled with IV fluid support. For patients with vomiting due to renal or liver disease that are already depressed, the dosage of chlorpromazine is often reduced to 0.2 to 0.3 mg/kg SID to BID. This lower dose is often effective for controlling vomiting and is not likely to cause significantly more sedation. Previous Next Contents 23

26 Reflux Esophagitis: Don t Overlook It Significant reflux esophagitis probably occurs in animals with persistent vomiting much more commonly than we recognize. Dogs with parvovirus enteritis that are debilitated and recumbent are especially at risk. Patients with pancreatitis, linear intestinal foreign body, and any other cause of frequent vomiting are equally at risk. Vomited fluid that is retained in the esophagus is not cleared adequately in weak and recumbent animals. As a result, the esophageal mucosa is bathed with gastric acid and activated enzymes that cause mucosal injury. Because significant discomfort can result from esophagitis, timely recognition and treatment are important. Treatment of esophagitis in animals with persistent vomiting includes use of an injectable histamine H 2 -receptor antagonist (e.g., famotidine) and a cytoprotective drug in suspension form (sucralfate). Metoclopramide is also beneficial because of its prokinetic (gastric-emptying) effect and because it increases lower esophageal sphincter tone. H 2 -receptor antagonists are used to decrease gastric acid production, thereby decreasing acid volume available for reflux. H 2 -blockers also reduce the volume of gastric fluid produced. I most often use famotidine at a dose of 0.5 mg/kg IV every 12 hours if I am concerned that esophagitis is present. Management of Gastric Hypomotility Gastric motility disorders are being recognized with increasing frequency in veterinary medicine but are still often overlooked. Gastric stasis, characterized by abdominal discomfort, periodic bloating, borborygmus, nausea, and vomiting, may be associated with a number of clinical states that include inflammatory disorders (e.g., chronic gastritis, IBD), gastric ulcers, gastroesophageal reflux, infiltrative lesions (e.g., neoplasia), and chronic gastric dilatation. Metabolic disturbances that may cause gastric stasis include hypokalemia, hypercalcemia, acidosis, anemia, and hepatic encephalopathy. Shortterm continued vomiting that is observed in some cases after apparent recovery from viral enteritis may be due to abnormal gastric motility. Transient (3 14 days) gastric hypomotility may also occur after gastric or abdominal surgery. Motility disorders with no organic cause may be best classified as idiopathic. For any of these disorders, the primary cause should be treated, and prokinetic therapy (e.g., metoclopramide, cisapride) may be a valuable short-term adjunct to therapy in these cases, along with feeding low-fat foods in divided amounts. In dogs with idiopathic gastric hypomotility, long-term therapy may be required (months to years, possibly lifelong). If long-term therapy is required, the lowest dosage frequency that controls clinical signs is given. Initially, prokinetic drugs, such as metoclopramide or cisapride, are administered three times a day and then if vomiting is well controlled the dosage frequency is decreased to twice daily after a month or two, and then to once a day if possible. Some dogs require two to three doses per day for an indefinite period, one dose per day is sufficient in some patients, and in others therapy may be discontinued altogether. Prokinetic therapy has also been useful in treating dogs that have chronic vomiting characterized by episodes occurring routinely in the early morning that contain bilious fluid. In this situation, the medication is generally administered once daily at bedtime. Dietary Therapy Some dogs with milder forms of functional gastric motility disorders respond to dietary changes alone. Maneuvers may include feeding canned rather than dry food, feeding smaller meals rather than one to two larger meals per day, and switching to a low-fat diet. Because fats and proteins delay gastric emptying, switching to a low-fat and higher-carbohydrate diet may be beneficial. If dietary therapy alone is ineffective, prokinetic therapy should be instituted Symposium Proceedings Gastrointestinal Diseases Previous Next Contents 24

27 Promotility Therapy Several clinical applications for use of prokinetic therapy in dogs and cats with chronic vomiting have been identified. These include gastric motility disorders and gastroesophageal reflux disease, as well as primary or adjunctive therapy for antral and pyloric mucosal hypertrophy and as treatment for nausea and vomiting caused by various other disorders. Metoclopramide In general, patients weighing less than 4.5 kg receive 2.5 mg per dose PO, those weighing 5 to 18 kg receive 5 mg per dose PO, and those weighing more than 18 kg receive 10 mg per dose PO. Metoclopramide is given 30 to 45 minutes before meals and again at bedtime. Animals that require medication on a long-term basis may need only 1 to 2 doses daily. Metoclopramide is less effective as a prokinetic drug than cisapride (see later discussion). While many animals with gastric hypomotility respond well to metoclopramide, some have a suboptimum response. If a patient with a suspected gastric hypomotility disorder has an inadequate response to metoclopramide, cisapride should be tried next. Some adverse effects may occur with metoclopramide. These effects are uncommon in animals, and somewhat more common in humans. Motor restlessness and hyperactivity may occur. The reaction can range from mild to quite dramatic. Alternatively, drowsiness and depression occasionally occur. Side effects are infrequent in cats but clients have reported disorientation, frenzied behavior, and hiding tendencies associated with the medication. Hospitalized animals may chew excessively at catheter sites or be aggressive toward hospital staff. Sometimes these effects are subtle, and house staff needs to be observant. The side effects are reversible by administering diphenhydramine 2.2 mg/kg IV or discontinuing metoclopramide, but they generally do not subside when lower doses of the drug are given. Unless side effects are infrequent, metoclopramide should be discontinued if adverse reactions are seen. Cisapride does not cause these adverse reactions. Metoclopramide crosses the blood brain barrier cisapride does not. In general, metoclopramide should not be given to epileptic patients. Other contraindications include evidence of significant mechanical obstruction, simultaneous use of anticholinergic agents (antagonism of metoclopramide s effects), and pheochromocytoma. Cisapride Cisapride is a potent GI prokinetic drug. It is no longer on the market for use in humans because of an association with fatal arrhythmias. However, there are no reports of similar complications in dogs and cats, and cisapride continues to be readily available to veterinarians through compounding pharmacies. Cisapride has broader promotility effects than metoclopramide (e.g., demonstrated efficacy in management of colonic inertia is excellent). It is unique among prokinetic agents in that it does not have antidopaminergic properties. Whereas metoclopramide antagonizes the inhibitory effects of dopamine and can cross the blood brain barrier, cisapride has no effect on the central nervous system. Cisapride is a benzamide derivative that promotes GI motility by increasing the physiologic release of acetylcholine from postganglionic nerve endings of the myenteric plexus, leading to improved motor activity of the esophagus, stomach, small bowel, and large bowel. In contrast to metoclopramide, which has a central effect at the CTZ in addition to its peripheral effects, cisapride has no known direct antiemetic properties. Previous Next Contents 25

28 Cisapride increases lower esophageal pressure and lower esophageal peristalsis better than placebo and/or metoclopramide. It significantly accelerates gastric. Small intestinal and colonic motor activity are also significantly enhanced. The most relevant uses of cisapride in animal patients include treatment of gastroparesis, especially in patients that experience significant side effects from metoclopramide (e.g., hyperactivity and other dystonic reactions), or in cases that have not responded adequately to other drugs, including metoclopramide, idiopathic constipation, gastroesophageal reflux disease (if H 2 -receptor antagonists or proton pump inhibitors and dietary management alone are not effective), and postoperative ileus. Cisapride is extremely well-tolerated in animals. I have used cisapride in dogs and cats that have had neurologic side effects from metoclopramide. I have observed no adverse reactions to cisapride in any of these patients, including those that experienced very bizarre behavioral changes in response to metoclopramide. The suggested dose of cisapride is 0.1 to 0.5 mg/kg PO, SID to TID depending on the clinical situation. The dose can be gradually increased if necessary, especially for cases in which long-term therapy is needed (e.g., chronic gastric hypomotility). As is recommended for metoclopramide, cisapride should be administered no closer than 30 minutes before feeding. Management of Inflammatory Bowel Disease in Dogs IBD is a common cause of vomiting in dogs. It is important that the clinician formulate a treatment protocol based on a correlation of clinical course, laboratory and gross findings, and histologic findings rather than relying on histologic changes alone. Therapeutic intervention may include dietary therapy alone on a trial basis, or dietary therapy combined with pharmacotherapy using either single-agent or combination-drug therapy. Drugs used in management of canine IBD may include corticosteroids (prednisone, dexamethasone, budesonide), metronidazole, azathioprine, and cyclosporine. Ancillary therapy can include other agents in selected cases, including probiotics; cobalamin; and various alternative therapies, such as acupuncture. It is emphasized that any concurrent disease, including parasitism (e.g., Giardia and Cryptosporidium), bacterial overgrowth, and GI hypomotility, must be diagnosed and managed concurrently for best overall patient response. Corticosteroids Corticosteroids are the initial treatment of choice for lymphocytic plasmacytic and eosinophilic enteritis in most cases. Mild to moderate cases (as determined by clinical signs, normal protein levels, and degree of inflammatory cell infiltrate on biopsy) often respond to prednisone at a dose of 0.5 to 1.5 mg/kg divided twice daily for 2 to 4 weeks followed by a gradual decrease in 50% increments at 2-week intervals. Alternate-day or every-third-day treatment can often be reached by 2 to 3 months. Treatment can often be discontinued altogether by 3 to 6 months, and dietary therapy is continued long-term. Moderate to severe cases and any case in which total protein is less than 5.5 g/dl should be treated more aggressively using an initial prednisone dose of 2.2 mg/kg per day for 2 to 4 weeks before an attempt is made to decrease the dose. Use of combination drug therapy (prednisone and metronidazole) in these cases at the outset is recommended to expedite control of clinical signs and to prevent disease progression. Budesonide If tolerance to prednisone is poor, the next best option is to try budesonide, metronidazole, or cyclosporine. Budesonide is one of a group of novel locally acting corticosteroids. Budesonide 2011 Symposium Proceedings Gastrointestinal Diseases Previous Next Contents 26

29 undergoes high first-pass metabolism in the liver, and 90% is converted into metabolites with low corticosteroid activity. It has minimal systemic availability. In general, budesonide is administered to small dogs as a 1-mg dose once per day. It has been used at higher doses of 2 to 3 mg per day for larger dogs. Large dogs receive 3 mg once daily initially, and the dose is later tapered to alternate-day administration for longer-term use. The daily dose should not exceed 3 mg. Potential adverse effects include PU/PD when budesonide is used at the high end of the dose range, and GI ulceration. Metronidazole Metronidazole has both antibacterial and antiinflammatory effects. This drug is administered at 10 to 20 mg/kg two times daily. A major advantage of using combination therapy is that the corticosteroid dose can usually be decreased from the high initial dose in a timely manner, thus decreasing the likelihood of significant corticosteroid-related side effects. Also, I have successfully used metronidazole alone for long-term management of dogs with mild to moderate lymphocytic plasmacytic enteritis that were intolerant to corticosteroids. Azathioprine In cases of protein-losing enteropathy (PLE), dogs with marked hypoproteinemia (total protein < 4.5 g/dl) caused by lymphocytic plasmacytic enteritis often respond well to an aggressive therapeutic course (prednisone, metronidazole, and azathioprine combined). Azathioprine is started early in PLE with IBD. The canine dose is 2 to 2.5 mg/kg once daily. If azathioprine is used at the outset, the prednisone dose is decreased by 50% from 2.2 mg/kg per day after 3 to 4 weeks or based on clinical improvement. Azathioprine is generally used for 3 to 9 months in dogs. Once adequate control is achieved, the daily dose is decreased by 50%, and subsequently alternate-day therapy is used. Side effects are uncommon in dogs but may include anorexia, jaundice (hepatic damage), poor hair growth, and bone marrow suppression. In addition, azathioprine may induce pancreatitis. A CBC should be run to monitor for evidence of anemia or leukopenia at 3-week intervals for the first 2 months and then once every several months. Cyclosporine A Cyclosporine A has been shown to be effective in steroid-resistant IBD in humans as well as in perianal fistula management in both humans and dogs. Allenspach and colleagues evaluated the pharmacokinetics and clinical efficacy of oral cyclosporine A treatment in 14 dogs with steroidrefractory IBD. Improvement was noted in 12 of 14 dogs. T-cell lysis is a possible mechanism of action. The antiinflammatory effect of cyclosporine A in human IBD is believed to be due to suppression of activated T cells infiltrating the mucosa, thereby decreasing the amount of proinflammatory cytokines and ultimately the clinical signs of disease. The drug was given at a dose 5 mg/kg SID as solo therapy. Previous therapy had included immunosuppressive doses of steroids in all dogs and metronidazole in some. Dietary Therapy Dietary therapy involves feeding either a limited ingredient/novel protein source diet or a hydrolyzed protein diet. In most cases, diets that are highly digestible and have low residue work best for small intestinal disease. If a decision is made to initially manage an animal with dietary therapy alone, the dietary trial should be done for at least 3 to 4 weeks. If biopsies reveal moderate to severe IBD and/ or if any degree of patient compromise is present, pharmacotherapy should be included along with the dietary management. In my experience, animals with this degree of disease rarely respond to dietary manipulation alone. Studies are under way to further evaluate the effect of dietary therapy on IBD management. Previous Next Contents 27

30 Management of Inflammatory Bowel Disease in Cats Management of IBD in cats is similar to that of dogs the few exceptions are mostly related to dosage. Corticosteroids are the cornerstone of treatment for idiopathic IBD in cats. Mild to moderate cases often respond to prednisone or prednisolone at a starting dose of 1 to 2.2 mg/kg divided twice daily for 2 to 4 weeks followed by a gradual decline in 50% increments at 2-week intervals. Cats with inflammatory changes graded as mild usually respond quite well to the lower dose. and alternate-day or every-third-day treatment can often be achieved by 2 to 3 months. Treatment can occasionally be discontinued altogether by 3 to 6 months. If biopsies reveal moderate to severe disease, prednisolone given at 2.2 to 4.4 mg/kg divided twice daily is used for the first 2 to 8 weeks or until clinical signs resolve. I prefer prednisolone over prednisone in cats with moderate to severe inflammatory disorders because it may have improved bioavailability in some cats. This dose of corticosteroid is usually well tolerated. In these cases, a dose of 1 to 2.2 mg/ kg per day may be necessary in the long term (months to years) to maintain clinical remission. Use of combination drug therapy may also be required at the outset to control clinical signs and prevent progression of the disease. Cats with hypoproteinemia and histologic changes graded as severe often respond quite well to an aggressive therapeutic course. Budesonide Budesonide, a glucocorticoid, represents a new alternative for management of IBD in cats, especially in severe cases that have proven to be refractory to prednisolone, metronidazole, azathioprine, and dietary management. In general, budesonide is administered to cats at 1 mg once per day. Budesonide can be used in combination with other drugs. Since cats tolerate corticosteroids very well, there is little indication to use budesonide as initial therapy for IBD. However, it may be an attractive option for use in diabetic cats that also have IBD, or for patients in which conventional therapies have not been sufficiently effective. Metronidazole When combination therapy is indicated, metronidazole is usually the first choice to be used in conjunction with prednisolone. A dose of 10 to 20 mg/kg two times daily is used for IBD. Ideally, at least several months of metronidazole therapy is given once it is started. In some cats with severe disease, long-term consecutive use or 1- to 2-month cycles of treatment may be required. Side effects at this low dose are uncommon, but nausea or vomiting may occasionally be seen. Methylprednisolone Acetate Methylprednisolone acetate can be used as the sole treatment for cats with mild to moderate IBD; it can also be used as adjunctive therapy when oral prednisone and/or metronidazole are used as the primary treatment and flare-ups of clinical signs occur. However, consistent control of clinical signs in cats with moderate to severe IBD is more difficult when methylprednisolone acetate is used alone sole use of this drug should be reserved for situations in which the owner is unable to consistently administer tablet or liquid prednisolone preparations. Initially 20 mg is given SC or IM and is repeated at 2-week intervals for two to three doses. Injections are then given every 2 to 4 weeks or as needed for control. Azathioprine If remission is not maintained with corticosteroids and metronidazole, then azathioprine should be used. The most important side effect of this drug in cats is bone marrow suppression. I use a maximum starting dose in cats of 0.3 mg/kg once every other day. At this low dose, side effects are rare. Alternatively, if clinical signs do not resolve on the initial azathioprine dose, it can be increased slightly if there is no evidence of bone marrow suppression. Because of a lag effect, therapeutic results often are not apparent until 2 to 3 weeks after treatment is started. Azathioprine is generally used for 3 to 9 months; however, most cats with IBD do not require azathioprine treatment Symposium Proceedings Gastrointestinal Diseases Previous Next Contents 28

31 A CBC should be run to monitor for anemia and leukopenia at 3- to 4-week intervals for the first 2 months and then once monthly. Significant side effects are most often identified during the first 3 to 6 weeks of treatment. There is usually no physical evidence of early azathioprine toxicity in cats. Mild leukopenia (e.g., cells/mm) is usually the first abnormality that is identified. This drug is best compounded to a suspension form for most accurate dosing. Chlorambucil Another immunosuppressive drug that is used in some cats with severe IBD is chlorambucil. Some clinicians use this drug as an alternative to azathioprine (they are not used in conjunction). Chlorambucil is an alkylating agent such agents alter DNA synthesis and inhibit rapidly proliferating cells. Chlorambucil is administered initially at 0.1 to 0.2 mg/kg per day in conjunction with prednisolone at 2.2 mg/kg/day. The small pill size (2 mg) allows for easy dosing. Most cats receive one-half tablet (1 mg) per day. Various dosage schedules for cats have been published. An alternate schedule is 0.15 to 0.3 mg/kg every 72 hours. Toxicities are uncommon but may include anorexia, vomiting, and diarrhea, but these problems generally resolve rapidly when chlorambucil is reduced from daily to every-other-day administration. Bone marrow suppression is possible but uncommon, and when it does occur it is mild and rapidly reversible. Once the desired clinical response is achieved, chlorambucil is gradually tapered over several months while prednisolone is continued as the primary maintenance drug. Cobalamin Significant tissue-level cobalamin deficiency is present in some animals with GI disease and is usually secondary to reduced cobalamin absorptive capacity. Therapy involves administering injectable cobalamin at the following schedule: 250 mcg subcutaneously once a week for 6 weeks, then every 2 weeks for the next 6 doses, then once monthly. Most generic cobalamin preparations contain 1 mg/ ml (1000 mcg/ml). It is important to note that multivitamin and B-complex injectable formulations contain significantly lower concentrations of cobalamin and cause pain on injection. Therefore, it is recommended that these preparations not be used for cobalamin supplementation. Unless the intestinal disease resolves completely, long-term and perhaps lifelong supplementation with cobalamin may be necessary. The frequency of injections on a long-term basis is determined by regular measurement of serum cobalamin concentration. Because food allergens may play a role in the cause of IBD, specific dietary therapy may be beneficial. Often, moderate to severe IBD is either temporarily responsive or only minimally responsive to even careful dietary manipulations. However, long-term control with a drug administration schedule involving the lowest possible dose may be aided by specific dietary management. This should be started as soon as a diagnosis is made and continued as drug therapy is decreased later. Chicken-, duck-, lamb-, or venison-based diets are often tried initially. A gradual change to commercial diets that are low in additives and formulated with chicken or lamb as their primary ingredient is then attempted. Suggested Reading Allenspach K, Rufenacht S, Sauter S, Grone A. Pharmacokinetics and clinical efficacy of cyclosporine treatment of dogs with steroid-refractory inflammatory bowel disease. J Vet Intern Med. 2006;20: DeNovo RC. Diseases of the stomach. In: Tams TR, ed: Handbook of Small Animal Gastroenterology. 2nd ed. Philadelphia: WB Saunders; German AJ. Inflammatory bowel disease. In: Bonagura JD, Twedt DC, eds. Current Veterinary Therapy XIV. St. Louis: Elsevier; Tams TR. Gastrointestinal symptoms. In: Tams TR, ed: Handbook of Small Animal Gastroenterology. 2nd ed. Philadelphia: WB Saunders; Tams TR. Chronic diseases of the small intestine. In: Tams TR, ed: Handbook of Small Animal Gastroenterology. 2nd ed. Philadelphia: WB Saunders; Previous Next Contents 29

32 Willard MD, Carsten EW. Esophagitis. In: Bonagura JD, Twedt DC, eds. Current Veterinary Therapy XIV. St. Louis: Elsevier; 2009.Table 2. Diagnosis of Vomiting Table 1. Causes of Vomiting / Tams: Managing Vomiting Dietary Problems Sudden diet change Ingestion of foreign material (e.g., garbage, grass, plant leaves) Eating too rapidly Intolerance to specific foods Food allergy Drugs Intolerance (e.g., antineoplastic drugs, cardiac glycosides, such antimicrobial drugs as erythromycin or tetracycline, arsenical compounds) Blockage of prostaglandin biosynthesis (NSAIDs) Injudicious use of anticholinergics Accidental overdose Toxins Lead Ethylene glycol Zinc Xylitol Others Metabolic Disorders Diabetes mellitus Hypoadrenocorticism Renal disease Hepatic disease Sepsis Acidosis Hyperkalemia Hypokalemia Hypercalcemia Hypomagnesemia Heatstroke Disorders of the Stomach Obstruction (e.g., foreign body, pyloric mucosal hypertrophy, external compression) Chronic gastritis (superficial, atrophic, hypertrophic) Parasites (Physaloptera spp [dogs and cats], Ollulanus tricuspis [cats]) Gastric hypomotility Bilious vomiting syndrome Gastric ulcers Gastric polyps Gastric neoplasia Gastric dilatation Gastric dilatation volvulus 2011 Symposium Proceedings Gastrointestinal Diseases Previous Next Contents 30

33 Table 1 (Continued). Disorders of the Gastroesophageal Junction Hiatal hernia (axial, paraesophageal, or diaphragmatic herniation; gastroesophageal intussusception) Disorders of the Small Intestine Parasitism Enteritis Intraluminal obstruction (foreign body, intussusception, neoplasia) Inflammatory bowel disease (idiopathic) Diffuse intramural neoplasia (lymphosarcoma) Fungal disease Intestinal volvulus Paralytic ileus Disorders of the Large Intestine Colitis Obstipation Irritable bowel syndrome Abdominal Disorders Pancreatitis Zollinger Ellison syndrome (gastrinoma of pancreas) Peritonitis (any cause, including feline infectious peritonitis) Inflammatory liver disease Bile duct obstruction Gallbladder disease Steatitis Prostatitis Pyelonephritis Pyometra Urinary obstruction Diaphragmatic hernia Neoplasia Neurologic Disorders Psychogenic (pain, fear, excitement) Motion sickness (rotation or unequal input from the labyrinths) Inflammatory lesions (e.g., vestibular) Edema (head trauma) Autonomic or visceral epilepsy Previous Next Contents 31

34 Table 2. Diagnosis of Vomiting / Tams: Managing Vomiting Stage 1: Baseline Assessment History and physical examination Conservative vs. more aggressive diagnostic plan based on patient s condition and clinician s concern Conservative Approach Fecal examination* Selected diagnostics Specific/symptomatic therapy Fecal examination* Parvovirus test if indicated Survey radiographs Appropriate specific/supportive therapy serious or Systemic Clinical Signs Complete blood count Complete biochemical profile Urinalysis T 4 (cats) Heartworm antibody test (cats) Stage 2: Further Assessment (if vomiting persists or initial tests indicate that further investigation should be performed promptly) Special blood tests Corticotropin stimulation Canine PLI or feline PLI (pancreatitis) Leptospirosis serology Bile acids assay (to assess liver function) Coagulation tests (consider in patients with hematemesis/melena) Contrast radiography Barium contrast Air contrast gastrogram (to further assess for gastric foreign body) BIPS (barium-impregnated polyethylene spheres; with food to assess GI motility) Ultrasonography Evidence of GI or non-gi disease Aspirates or biopsy Abdominocentesis Nuclear Scintigraphy Transcolonic portal angiography for detection of portosystemic anomaly GI motility study 2011 Symposium Proceedings Gastrointestinal Diseases Previous Next Contents 32

35 Table 2 (Continued). Stage 3: Invasive Procedures Flexible GI endoscopy (minimally invasive): Examination, biopsy, foreign body retrieval Laparoscopy Biopsies (e.g., liver, pancreas) Aspirates (e.g., gallbladder, lymph nodes, mass lesion) Intestinal biopsy Surgical intervention: Therapeutic or exploratory with multiple biopsies GI = gastrointestinal; PLI = pancreatic lipase immunoreactivity; T 4 = thyroxine. *GI parasites, including Giardia, should always be considered in dogs with acute or intermittent vomiting. Best baseline testing on a single fecal sample include centrifugal flotation and Giardia antigen test. Endoscopy is a diagnostic or therapeutic tool that can be used in any of the three stages, depending on the clinical situation. Previous Next Contents 33

36 Overview Liver Disease: The 5 Most Common Conditions You Will Encounter David C. Twedt, DVM, Diplomate, ACVIM Throughout much of recorded history, there was a belief that the liver was the center of life. As we learn more of the complexity of this organ and all its metabolic functions, we come to realize that there is a lot of truth in those early thoughts. Liver disease can result from many different insults, metabolic derangements, and genetic abnormalities, and liver damage can also occur in many ways. To this end, for clinicians to understand liver disease they must simply understand all of medicine. Detection of liver disease requires an accurate history, physical examination, and biochemical testing. Identification of abnormal liver enzyme levels usually indicates liver damage but rarely provides a diagnosis or reveals a cause. This article will cover what I consider to be the 5 most common clinical liver conditions the veterinarian will encounter. Those conditions include normal dogs with abnormal liver enzymes, sick dogs with abnormal liver enzymes, and icteric dogs. The first section will provide a brief review of liver enzymes and liver function tests. Foci Identification of abnormal liver enzymes usually indicates liver damage but rarely provides a diagnosis or reveals a cause; definitive diagnosis requires the inclusion of other clinical findings. Elevated liver biochemical enzymes and abnormal liver function tests can be indicative of specific areas of disease: Elevated alanine and aspartate aminotransferase levels may indicate hepatocellular damage, elevated alkaline phosphatase and gamma-glutamyl transferase may indicate cholestasis or drug-induction, while hypoalbuminemia or prolonged clotting times may indicate hepatic dysfunction, and increased total serum bile acid concentration may indicate decreased efficiency or integrity of the enterohepatic circulation. An asymptomatic patient with elevated liver enzymes should have the values confirmed on subsequent laboratory evaluations to avoid unnecessary and costly testing; if subsequent results are still elevated the tests can be repeated in 4 to 6 weeks, or a more complete diagnostic evaluation can be initiated. It is important to exclude nonhepatic disease or pharmaceuticals that could secondarily affect the liver ( reactive hepatopathies ), causing secondary hepatopathy; a review of liver biopsies revealed this to be the most common (25%) cause of abnormal hepatic enzymes. In the author s opinion, early identification of chronic hepatitis and appropriate therapy result in prolonged survival and a favorable prognosis Symposium Proceedings Gastrointestinal Diseases Previous Next Contents 34

37 Laboratory Tests Abnormal liver enzymes are common. A study of 1022 blood samples taken from both healthy and sick dogs and cats in one diagnostic laboratory found that 39% had alkaline phosphatase (ALP) increases and 17% had alanine aminotransferase (ALT) increases (1). The identification of liver biochemical abnormalities in conjunction with clinical findings suggests certain diagnostic possibilities and indicates the need for further investigation. Liver biochemical enzymes can be insensitive or nonspecific for primary liver disease, and some of the enzymes can also have isoenzymes from other tissue not associated with the liver. An understanding of liver biochemical tests is essential when evaluating the patient in question. Abnormalities on liver biochemical tests are categorized into groups that reflect 1) hepatocellular injury, 2) cholestasis, or 3) impaired metabolic function or synthetic capacity. Hepatocellular Injury Increases in either ALT or aspartate aminotransferase (AST) activity indicate hepatocellular membrane damage and enzyme leakage. Canine and feline hepatocyte cytoplasm is rich in ALT and contains lesser amounts of AST. Altered permeability of the hepatocellular membrane caused by injury or metabolic disturbance results in a release of this soluble enzyme. Conceptually, ALT and AST should be considered hepatocellular leakage enzymes. Subsequent to an acute, diffuse injury the magnitude of increase crudely reflects the number of affected hepatocytes. It is, however, neither specific for the cause of liver disease nor predictive of the outcome. The plasma half-life of ALT activity in dogs is 60 hours; however, ALT concentrations may take days to weeks to decrease following an acute insult. Persistent increases of ALT are characteristic of chronic hepatitis in the dog. I believe that ALT increases should be investigated when they are more than two times the normal values or are persistently abnormal. A variety of tissues, notably skeletal muscle and liver, contain high levels of AST. Hepatic AST is located predominately in hepatocyte mitochondria (80%) but is also soluble in the cytoplasm. Skeletal muscle inflammation invariably increases serum AST levels (and ALT to a much lesser extent) that exceed serum ALT activity and can be further determined to originate in muscle by measuring the serum creatine kinase activity, a specific muscle enzyme. Clinical experience in veterinary medicine indicates that there is value in interpreting serum activities of ALT and AST for liver disease. Following an acute injury resulting in a moderate to marked increase in ALT and AST concentrations, serum AST will return to normal more rapidly (hours to days) than serum ALT (days), due to the difference in plasma half-life and cellular location (2). By determining these values every few days following an acute insult, a sequential biochemical picture indicative of resolution or persistent pathology is obtained. Cholestasis and Drug-Induction ALP and gamma-glutamyltransferase (GGT) show minimal activity in normal hepatic tissue but can increase in the serum subsequent to increased enzyme production stimulated by either impaired bile flow or drug-induction. These enzymes have a membrane-bound location at the canalicular surface ALP is associated more with the canalicular membrane and GGT is associated more with the epithelial cells that make up the bile ductular system (3). With cholestasis, surface tension in the canaliculi and bile ductules increases, and these surface enzymes are then up-regulated into production. ALP is also present in a number of tissues, but the only two that are diagnostically important are the bone and liver. The plasma half-life for hepatic ALP in dogs is 66 hours in contrast to 6 hours for cats, and the magnitude of enzyme increase (presumably a reflection of the synthetic capacity) is greater for dogs than for cats. Bone as a source of ALP results from osteoblastic activity, and levels are elevated in young, growing dogs before closure of the epiphysial plates or in some bone tumors or lytic lesions. In the adult without bone disease, increased serum ALP activity is usually of hepatobiliary origin. A study identified some dogs with osteogenic bone tumors to have increased ALP concentrations (4) increased Previous Next Contents 35

38 ALP tended to indicate a poorer prognosis, probably from diffuse bone metastasis. Osteomyelitis and secondary renal hyperparathyroidism is a minor source of ALP from bone. An increase in serum ALP and GGT activity can be induced by glucocorticoids (endogenous, topical, or systemic), anticonvulsant medications, and possibly other drugs or herbs. There is remarkable individual variation in the magnitude of these increases, and there is no concomitant hyperbilirubinemia. A moderate to marked increase in serum ALP activity without concurrent hyperbilirubinemia is most compatible with drug-induction and warrants a review of the patient s history (topical or systemic glucocorticoids) or evaluation of adrenal function. Increased ALP has long been attributed to a glucocorticoid-stimulated production of a novel ALP isoenzyme in dogs that can be distinguished from the cholestasis-induced hepatic ALP isoenzyme by several procedures. It was initially thought that the glucocorticoid-associated isoenzyme could be used as a marker of exogenously administered corticosteroids or increased production of endogenous glucocorticoids. Unfortunately, the glucocorticoid-associated isoenzyme is also associated with hepatobiliary disease, and differentiating steroid-induced ALP from liver ALP is rarely helpful. Hepatic GGT is located predominately on the hepatocyte and bile ductular canalicular membrane. In dogs, increased levels of GGT have lower sensitivity (50%) but higher specificity (87%) for hepatobiliary disease than total ALP (5). If both ALP and GGT are elevated, specificity for liver disease increases to 94% (5). In dogs, the most marked elevations in GGT result from diseases of the biliary epithelium, such as bile duct obstruction, cholangiohepatitis, cholecystitis, and glucocorticoid administration (3). Bone does not contain GGT, and administration of anticonvulsant medications to dogs does not increase GGT activity in serum. Colostrum and milk have high GGT activity, and nursing animals have increased serum GGT activity. Liver Function On a routine biochemical profile, it is important to note the liver function tests, including measurement of bilirubin, albumin, glucose, BUN, and cholesterol. Albumin is produced only in the liver and if not excreted from the body (GI or renal), sequestered, or diluted, a low concentration suggests significant hepatic dysfunction. It may take greater than 60% dysfunction for albumin concentrations to decline, and 75% or greater dysfunction for glucose to drop. Major clotting factors are also made in the liver (except factor 8); therefore, prolonged clotting times suggest hepatic dysfunction. Liver disease and abnormal results on function tests suggest hepatic failure and a guarded prognosis. The most sensitive function test that is readily available in small animals is serum bile acids. The fasting total serum bile acid (FSBA) concentration is a reflection of the efficiency and integrity of the enterohepatic circulation (6). Pathology of the hepatobiliary system or the portal circulation results in increased FSBA levels before the development of hyperbilirubinemia, negating its usefulness in icteric patients. An increase is not specific for a particular type of pathologic process but is associated with a variety of hepatic insults and abnormalities of the portal circulation. The current suggestion with regard to FSBA levels is to use them to differentiate between congenital portal vascular anomalies and liver insufficiency before development of jaundice. Increased FSBA levels can contribute to the decision to obtain histologic support for the diagnosis of this last group of hepatic diseases. When the fasting value is greater than 25 µmol/l in dogs and cats, histologic findings are very likely to indicate a lesion. When FSBA concentrations are normal or in the gray zone, they should be followed by a 2-hour postprandial measurement of serum total bile acids (PPSBA), looking for an increase greater than 25 µmol/l (7). The diagnostic value of determining PPSBA concentration is increased sensitivity for the detection of hepatic disease and congenital portal vascular anomalies. In 2011 Symposium Proceedings Gastrointestinal Diseases Previous Next Contents 36

39 dogs, the specificity of fasting and postprandial bile acids for hepatobiliary disease is 95% and 100% when cutoff values greater than 15 µmol/l and 25 µmol/l, respectively, are used. However, it is prudent to recognize that a small number of healthy dogs have been reported with PPSBA values above 25 µmol/l. The FSBA value occasionally exceeds that of the PPSBA; the reason is unclear but probably multifactorial. It has been shown that 1) the peak PPSBA concentration for individual dogs varies, 2) fasted dogs store about 40% of the newly produced bile in the gallbladder, and 3) a meal stimulates release of only between 5% to 65% gallbladder bile. These physiologic variables, in addition to physiologic variation in intestinal transit time and concurrent underlying intestinal disease, undoubtedly contribute to the dichotomy. Recently, urinary bile acids have become available as a diagnostic tool. Identifying increases in these acids provides information similar to what is obtained from serum bile acids and neither test appears to be better than the other. Urinary bile acid measurement is useful for screening litters of young puppies for suspected inherited vascular anomalies because urine collection is simpler than paired serum samples. In summary, there are a variety of markers with variable sensitivity and specificity that reflect hepatic tissue and portal vasculature pathophysiology. We support the conclusion of another study that found that the optimal test combination is the serum ALT activity and bile acid concentrations. This pairing provided the best sensitivity and specificity for liver disease in dogs. Clinical experience indicates that elevated serum AST concentration along with elevated ALT helps to support a diagnosis of hepatocellular disease, and PPSBA concentration enhances the evaluation of hepatic function, with chronic hepatitis being a likely possibility. Normal Dog, Abnormal ALT and ALP An asymptomatic patient with increased levels of liver enzymes on biochemical testing should have the value confirmed at least once to exclude a spurious result from laboratory error and to avoid unnecessary and costly additional testing. A careful history is essential to exclude drug-associated enzyme elevations. The signalment of the patient may also provide an insight to the possible cause of the enzyme increase. For example, old dogs frequently have benign nodular hyperplasia, neoplasia, or systemic disease, whereas younger to middle-aged dogs commonly have chronic hepatitis. Certain breeds are also predisposed to chronic hepatitis. A careful physical examination may also provide clues to the diagnosis. The most common cause of abnormal liver enzymes is not primary liver disease but rather reactive hepatic changes occurring secondary to a primary nonhepatic disease. This would include such conditions as intra-abdominal disorders (inflammatory bowel disease, nutritional abnormalities), cardiovascular disease, or metabolic derangements, just to name a few. Generally these secondary changes in the liver are reversible once the primary disease is treated. Successful resolution of the nonhepatic disease and continued abnormal liver enzymes would then be an indication for further investigation. If no likely explanation for the laboratory abnormalities can be found, the clinician has two options: Begin a diagnostic evaluation of the patient starting with bile acid determinations, or reevaluate the patient s liver enzymes at a later date. A rational waiting period for reevaluation in my opinion is 4 to 6 weeks, given what is known about the half-life of liver enzymes and the time needed for liver recovery from an acute occult injury. It is best not to delay retesting beyond 6 weeks in the event that an active disease process is present. During the waiting period, one may consider trial therapy using antibiotics or liver support therapy. Liver support therapy would include antioxidants, such as S- adenosylmethionine Previous Next Contents 37

40 or milk thistle (silibin) therapy. Identification of persistent abnormal liver enzymes or abnormal liver enzymes and abnormal bile acid concentrations should dictate further investigation. Generally, the next evaluation involves imaging using radiographs or preferably ultrasonography. During ultrasonography, I routinely perform fine-needle aspiration and cytology. However, it is important to note that hepatic cytology does not always correlate with histopathologic interpretation (8). In most instances, imaging and biochemical testing and liver cytology cannot replace liver biopsy. Biopsy is required for a definitive determination of the nature and extent of hepatic damage and to appropriately direct the course of treatment. The method for liver biopsy procurement may be surgery, laparoscopy, or needle biopsy. Each has certain advantages and disadvantages, and the decision of which procedure to use should be made in light of all the other diagnostic information, always considering what is in the best interest of the patient and client. Normal Dog, Abnormal ALP The identification of an older asymptomatic dog with significant elevations in only ALP is quite common, and determining the underlying cause can often be frustrating. Causes for ALP increases include bone (osteoblastic activity), hepatic cholestasis, and steroids (9). Bone as the source of elevated ALP is usually easy to rule out, but differentiating cholestasis from steroid-induced elevation is a little more difficult. A study evaluating cases of histologic evidence of steroid hepatopathy found that patients had steroid-induced elevation, Cushing s disease, or some other (usually serious) illness. The authors concluded that chronic stress from disease could result in vacuolar hepatopathy (10). Initial evaluation of these patients should proceed as previously described by ruling out exposure to drugs or supplements and assessing for the possibility of nonhepatic disease, including endocrine, gastrointestinal, and neoplastic disorders. History and physical examination should be repeated to ensure that clinical abnormalities are truly absent. Options for further evaluation include monitoring ALP over time or pursuing additional diagnostics. For most cases, ALP should be monitored over 4 to 6 weeks. If progressive or persistent increases occur, further workup is indicated as previously described. Abdominal ultrasonography should be done and bile acids measured to rule out obvious structural and functional abnormalities of the liver and biliary system. I have observed on ultrasonography evidence of primary hepatic neoplasia in asymptomatic patients having elevated ALP levels as the only clinical abnormality. The decision for additional monitoring or immediate evaluation may also be based somewhat on the degree of ALP elevation. Moderate-to-severe increases are more often associated with hepatobiliary disease or exposure to glucocorticoids and are unlikely to resolve over time. Common hepatic causes of ALP elevation in asymptomatic patients include neoplasia, benign nodular hyperplasia, idiopathic vacuolar hepatopathy, and breed-related conditions. Idiopathic vacuolar hepatopathy is associated with vacuolated hepatocytes containing glycogen. The histologic diagnosis of vacuolar hepatopathy is quite common, and a study evaluating cases having this diagnosis found that most patients had had steroid administration, Cushing s disease, or some other serious nonhepatic illness. The authors concluded that chronic stress from disease could result in vacuolar hepatopathy (10). In a small percentage of cases of vacuolar hepatopathy, steroids and stress could not be implicated. We now believe that most cases of steroid liver are the result of abnormal production of adrenal hormones, most commonly progesterone or 17-hydroxyprogesterone. An adrenal steroid panel should be obtained in conjunction with adrenocorticotropic hormone stimulation. Some also refer to this condition as atypical Cushing s disease because liver biopsy changes are identical to those of typical steroid hepatopathy. The disease often does not progress, and therapy is controversial; however, some 2011 Symposium Proceedings Gastrointestinal Diseases Previous Next Contents 38

41 report that melatonin or traditional hyperadrenocorticism therapy resolves both hepatic changes and the elevations in corticosteroid-induced ALP. We have also observed that some of these dogs have hypertension and proteinuria and occasionally develop a biliary mucocele. A common finding in Scottish Terriers is ALP elevation, often without concurrent laboratory abnormalities (11). In one study, Scottish Terriers were shown to have a high incidence of increased levels ALP (12). An additional report describes seven Scottish Terriers being evaluated for increased ALP with no identifiable cause after thorough imaging, adrenocortical testing, or liver biopsy, suggesting that a benign familial hyperphosphatasemia may be present (13). A study that we performed in Scottish Terriers with abnormal ALP levels were found to have elevated endogenous steroid hormone precursors (i.e., 17-hydroxyprogesterone). However, similar abnormalities in 17-hydroxyprogesterone and progesterone were present in Scottish Terriers with normal ALP. Currently, the underlying cause for elevated ALP levels in Scottish Terriers is unknown; however, the condition appears to be benign, although I have found a number of patients with vacuolar hepatopathies to have concurrent proteinuria and hypertension that should be addressed. Hepatic nodular hyperplasia is a common intrahepatic event included in this section because, although it is a relatively benign process, it causes increased levels of hepatic enzymes and histologic changes that include macroscopic or microscopic hepatic nodules containing vacuolated hepatocytes (14). On gross evaluation, the nodules may suggest chronic hepatitis or neoplasia. The cause is unknown but in dogs seems to be a change associated with aging most affected animals are older than 10 years of age. Laboratory findings include increased ALP levels, but mild increases in ALT and AST concentrations may also occur. Liver function remains unchanged, although the incidence of nodules may progress with age. Ultrasonography may be normal (because many changes are microscopic and thus not observable on ultrasonography) or may show single or multiple hyper- or hypoechoic nodules. Biopsy confirms the diagnosis; however, wedge section is preferred, as needle biopsy may not demonstrate the nodules. There is no specific therapy. Young Dog Pre-Spay, Abnormal ALT Increased ALT levels in healthy dogs younger than 1 year of age is common in my experience; however, the cause is often undetermined. As discussed in this paper, it is important to exclude all types of nonhepatic disease that may secondarily cause reactive hepatopathy. This is uncommon in young dogs as they are usually very healthy, and I have also noted that primary liver disease is uncommon in dogs younger than 1 year of age. Chronic hepatitis or copper-associated hepatitis usually does not result in laboratory changes until dogs are several years of age or older. We have observed some young dogs having ALT increases that return to the normal range at maturity. The explanation for this phenomenon is unknown, but it may be that hepatic visceral larval migrans causes ALT leakage or that the increase occurs during normal hepatic growth in developing dogs. Another probable cause of ALT elevations in young dogs would be hepatic vascular anomalies. Bile acids (measurement of fasting bile acid and postprandial bile acids) are very sensitive tests for hepatic vascular anomalies and young dogs with unexplained elevations in ALT concentrations should have bile acids determined screening for hepatic vascular anomalies. If the levels are normal, I generally do no further workup and just recheck the ALT when the dog is 1 year of age or older. However, if they are abnormal I recommend investigation for a vascular anomaly. Two major types of these anomalies have been recognized: microscopic portal vein hyperplasia (PVH) or macroscopic portosystemic shunt (PSS). Dogs with macroscopic PSS often have clinical signs of the disease, bile acid concentrations are usually >100 µmol/l, and the anomaly can be documented using various types of imaging studies. Diagnosing microscopic hepatic vascular anomalies in dogs is more problematic. It is thought that microscopic PSS Previous Next Contents 39

42 results from primary PVH of the portal vein branches within the liver. The condition was initially referred to as hepatic microvascular dysplasia; however, hepatic portal vein hypoplasia has now been suggested to be more accurate by the WSAVA Liver Standardization Group because it may better reflect the cause of this condition (15). It is believed that the primary defect in affected dogs is the result of hypoplastic, small intrahepatic portal veins. The condition is thought to be a defect in embryologic development of the portal triad (artery, vein, and bile ducts). With reduced size or number of small portal veins, there is a resultant increase in arterial blood flow in an attempt to maintain hepatic sinusoidal perfusion. The hepatic arteries then become torturous and abundant in the triad (portal arterialization). Sinusoidal hypertension occurs under this high-pressure arterial system. Lymphatic and venous dilatation results with opening up of embryologic sinusoidal vessels; as a result, acquired microscopic shunts develop to transport some of this blood to the central vein, thus by-passing the sinusoidal hepatocytes. Portal shunting of blood increases iron uptake, resulting in hepatic iron granuloma formation. Ascites or portal hypertension does not generally occur. Because similar histologic changes occur in dogs having congenital macroscopic PSS, the diagnosis can be confusing. If macroscopic intrahepatic or extrahepatic PSS is not observed through imaging studies, then PVH becomes the probable diagnosis. Angiography or portal scintigraphy are normal with PVH. A needle biopsy is not always sufficient to provide enough portal areas for diagnosis, and consequently a larger wedge or laparoscopic biopsy is preferred. Also, because of the patchy nature of the hepatic lesions multiple biopsies from different lobes should be obtained. PVH was first described in Cairn Terriers and now is believed to occur in many other small-breed dogs. Yorkshire Terriers and Maltese may be overrepresented (16). Dogs with PVH have abnormal serum bile acid concentrations (usually moderate elevations <100 µmol/l) and variable liver enzymes (most often ALT). Most have no clinical signs and require no specific therapy. We suspect that, because of histological changes observed in some PVH cases and elevations in ALT, there may be some degree of oxidative damage occurring and antioxidant supplementation might be considered. The long-term prognosis is considered good for most dogs, but because the disease is relatively new and long-term follow-up is lacking, we await further data with regard to the long-term prognosis. There is an uncommon fibrosis variant of PVH that is associated with portal arterialization, portal bile duct proliferation, significant hepatic fibrosis, portal hypertension, and secondary acquired PSS (17). This condition has also been referred to as idiopathic noncirrhotic portal hypertension or congenital hepatic fibrosis because of the significant fibrosis in the portal areas and development of portal hypertension and ascites (18). Dogs with congenital portosystemic vascular anomalies from a single intra- or extrahepatic shunting vessel usually have signs associated with hepatic encephalopathy but do not have portal hypertension or develop ascites. However, this subgroup of dogs with PVH and fibrosis develop ascites, portal hypertension, and secondary PSS. The hepatic histology demonstrates portal tracts associated with multiple arterioles, small or absent portal veins with variable portal fibrosis, lymphatic distention, and variable bile duct proliferation. The pathology is void of inflammatory infiltrates. There are also increased amounts of iron in the liver. The fibrosis and bile duct replication may be a nonspecific reaction from increased growth factors that promote arterial proliferation. The PVH with fibrosis is observed in dogs that are generally younger than 3 years of age, and there is no breed prevalence. However, large breeds, such as Golden Retrievers, Doberman Pinschers, Cocker Spaniels, and Rottweilers, may be overrepresented. The clinical presentation is similar to dogs with congenital intra- or extrahepatic shunts, except most dogs with fibrosis and portal hypertension have ascites. The liver enzymes are generally increased, with hypoalbuminemia and very high bile acid concentrations. Workup of these patients fails to identify a single shunting vessel, but marked portal 2011 Symposium Proceedings Gastrointestinal Diseases Previous Next Contents 40

43 hypertension associated with multiple acquired PSSs is often found. Ultrasonography is often helpful, showing microhepatia, hepatofugal portal blood flow, and multiple abnormal extrahepatic collateral shunts. Portal contrast studies demonstrate acquired portal shunts, and pressure measurements document portal hypertension. The prognosis for this condition is generally guarded, but some dogs are reported to have prolonged survival through use of antifibrotic agents and hepatic encephalopathy therapy. Sick Dog, Abnormal ALT and ALP Reactive Hepatopathy When presented with a sick dog and abnormal liver enzymes, it is important in the initial workup to consider drugs as well as primary nonhepatic disorders that could secondarily affect the liver and cause abnormal liver enzymes. Liver changes occurring secondary to a primary nonhepatic disorder are referred to as reactive hepatopathies. Most reactive hepatopathies cause increases in laboratory tests that evaluate hepatocellular integrity (ALT, AST) and tests of hepatic cholestasis (ALP, GGT). In most cases, there are few if any abnormalities in tests that evaluate hepatic function (bilirubin, albumin, glucose, and BUN) and most animals with secondary liver disease also retain normal serum bile acid concentrations, which again supports the concept that hepatocellular dysfunction in most of these disease conditions is generally minimal. This group is characterized by nonspecific hepatocellular degeneration or necrotic changes without evidence of significant, chronic, progressive inflammation. The reason the liver often undergoes these changes is because it is involved in many metabolic and detoxification functions. Endogenous toxins, anoxia, metabolic changes, nutritional changes, and endogenous stress-related glucocorticoid release are examples of conditions responsible for most of these changes. Histologic findings associated with secondary reactive changes include descriptors, such as vacuolar degeneration, hydropic degeneration, swollen hepatocytes, lipidosis, intracellular or intrahepatic cholestasis, mild multifocal hepatitis, and periportal or variable hepatic necrosis. These changes are devoid of the typical progressive chronic inflammatory cell infiltrates characteristic of chronic hepatitis that is discussed below. An example to explain the concept of a secondary reactive hepatopathy is inflammatory bowel disease. Animals having a secondary reactive hepatopathy it is not unusual to observe mild inflammatory changes around portal triads presumed to be the result of abnormal portal uptake of gastrointestinal toxins. Throughout the liver and closely associated with portal areas are Kupffer cells (fixed macrophages) that function to filter the blood of injurious toxins, inflammatory mediators, and bacteria. When this macrophage system is abnormally insulted, the Kupffer cells release their own inflammatory mediators that in turn insult the hepatocytes. Another example would be the septic dog in which reactive changes could be due to endogenous cortisol release from stress and secondary to endotoxin or cytokine alteration. In a review of consecutive liver biopsies at Colorado State University, histologic findings grouped as nonspecific reactive changes made up the largest category of abnormalities (approximately 25%). In this group, we were able to identify an associated disease in many cases that could explain the likely cause for the hepatic enzyme increases and histologic changes. Concurrent diseases identified in these patients included neoplasia and gastrointestinal, renal, autoimmune, dermatologic, dental, infectious, and cardiac disease, as a few examples. In some cases, an underlying disease may not be identified. The ALT values on average are one to two times normal and ALP values one to three times normal. It is interesting to note that when I reviewed 32 dogs having reactive hepatopathies, serum bile acids were measured in 8 cases and the results in all 8 cases were within the normal reference range, again suggesting that hepatic function remains intact. Previous Next Contents 41

44 This category appears to represent the most common histologic changes in dogs and is by far the most common cause of elevated liver enzymes. Based on this fact, dogs presented with elevations in ALT and ALP should always have primary nonhepatic disease ruled out first. These changes are usually very reversible, and no specific hepatic therapy is required short of treating the primary disease. The liver changes resolve once the primary cause is successfully treated, and additional therapy providing good liver support, such as antioxidants, may be warranted. When an underlying disease is not detected and liver enzymes remain abnormal, further investigation is indicated. Bile acids may help direct the urgency of investigation, as abnormal bile acid concentrations indicate decreased hepatic function, cholestasis, or PSS. Chronic Hepatitis In my review of 150 consecutive liver biopsies, the next most common condition identified was chronic hepatitis (23%), followed by hepatic neoplasia and vacuolar hepatopathy and acute hepatitis. These disorders generally require liver biopsy for a definitive diagnosis and to plan a course of therapy. Of these categories, the most important one to diagnose is chronic hepatitis. With early identification of chronic hepatitis and appropriate therapy, I believe many cases can have prolonged survival and a favorable prognosis. Chronic hepatitis is characterized by hepatocellular death from apoptosis or necrosis, a variable mononuclear or mixed inflammatory infiltrate, regeneration, and fibrosis. The proportion and distribution of these components vary widely. Fibrosis on liver biopsy indicates to me chronic disease and often more serious consequences. Cirrhosis, a sequel of some chronic hepatitis cases, is often associated with portal hypertension, ascites, and multiple portosystemic collateral shunting. Some may have manifestations of liver failure (e.g., hyperbilirubinemia, coagulopathies, edema due to hypoalbuminemia, ascites, and hepatic encephalopathy). The cause of chronic hepatitis is generally never determined (19). Copper-associated chronic hepatitis has been documented in a number of breeds as an inherited cause. Copper accumulation in the liver increases to a level that becomes toxic to the hepatocyte, causing cellular death. Infectious causes of chronic hepatitis have been associated with leptospirosis and experimental infectious canine hepatitis virus. Chronic liver injury has also been reported in dogs with aflatoxicosis and hepatitis induced by various drugs. Some dogs treated with the anticonvulsant drugs primidone, phenytoin, and phenobarbital can develop chronic hepatitis. I have also observed hepatitis in dogs given long-term NSAIDs, and there could be a casual relationship in some cases, because we know that NSAIDs can cause acute liver damage as an idiosyncratic reaction. Finally, immune-associated hepatitis may occur in dogs. Circulating autoantibodies are important diagnostic markers used to identify autoimmune liver disease in humans. Canine autoantibodies (antinuclear antibody, antimitochondrial antibodies, smooth muscle antibodies, and liver membrane autoantibodies) are often present in dogs having chronic hepatitis, but their importance in classifying chronic hepatitis in dogs is unknown and may be secondary to liver damage (20). Nonetheless, immune-mediated mechanisms are believed to be associated with certain cases of chronic hepatitis, and this is supported by the fact that some dogs respond favorably to immunosuppressive therapy. Lastly, there is a lobular dissecting hepatitis characterized by rapid, diffuse inflammation throughout the liver lobule. This condition is observed in younger dogs (often Standard Poodles) and is associated with rapid development of hepatic encephalopathy and ascites. Several breeds have an increased incidence and suspected genetic basis of hepatitis. Some of these breeds have copper-associated chronic hepatitis. Other breeds in which hepatitis has not been associated with copper include Standard Poodles, Cocker Spaniels, Springer Spaniels, and Scottish Terriers (21) Symposium Proceedings Gastrointestinal Diseases Previous Next Contents 42

45 Diagnosis of abnormal copper accumulation requires liver biopsy. The measurement of serum copper or serum ceruloplasmin levels are not helpful as values are normal. Excess copper in the liver can be demonstrated using rhodanine stain or rubeanic acid stain. Definitive determination of excess hepatic copper requires quantitative analysis of tissue copper measured on the biopsy sample (22). Normal concentrations of copper in the canine liver are less than 400 mcg/g (ppm) dry weight. Liver concentrations in dogs with secondary copper accumulation are usually less than 1000 mcg/g dry weight, whereas breed-associated hepatotoxicities generally have higher concentrations (>750 mcg/g). The location of copper secondary to hepatic cholestasis is generally in zone 1 (periportal). Liver disease with concurrent copper accumulation is reported in Bedlington Terriers, Doberman Pinschers, West Highland White Terriers, Skye Terriers, Dalmatians, and most recently Labrador Retrievers. We occasionally see other purebred dogs as well as mixed-breed dogs with high copper concentrations and suspect that some may have primary copper retention. The average age at presentation generally ranges from 4 to 10 years. It is interesting to note that in both our series and in studies by others, it is uncommon to observe chronic hepatitis/cirrhosis in dogs older than 10 years of age. I believe that old dogs (> 11 years of age) generally do not present with chronic hepatitis/cirrhosis, or if they do they are at or near end-stage disease. The clinical signs parallel the extent of hepatic damage. Early in the disease, there are few if any clinical signs. Only after the disease progresses do the clinical signs specific for liver disease become evident. Frequent early signs are gastrointestinal, including vomiting, diarrhea, and poor appetite or anorexia. Ascites, jaundice, and hepatic encephalopathy may then occur as the disease progresses. With development of these late signs, the long-term prognosis is generally poor. The laboratory findings include consistently elevated ALT and ALP; however, the magnitude of increase is not necessarily marked. One report found that 75% of cases at diagnosis had abnormal bilirubin elevation (mean elevation of 2.6 mg/dl) (23). Serum proteins are variable. As the lesions become more severe, albumin levels decline. Serum bile acids are abnormal in most cases of significant chronic hepatitis, and measurement of bile acids seems to be a good screening test for patients with unexplained elevations in ALT and ALP. In our study, all dogs diagnosed with chronic hepatitis had abnormal bile acid concentrations and increases in both ALT and AST. The combination of increased ALT, AST, and bile acids seems to provide the most definitive evidence of chronic hepatitis. There is little information on the prognosis of chronic hepatitis with and without therapy. The prognosis in dogs with advanced chronic hepatitis and cirrhosis is guarded. Strombeck and Gribble found mean survival times ranging from 6 to 16 months with therapy (24). This study also identified that dogs with hypoalbuminemia, hypoglycemia, and coagulopathies have a very guarded prognosis, and many died within 1 week of diagnosis. A second study of 79 dogs found that survival time in those with cirrhosis was less than 1 month, and mean survival in dogs with chronic hepatitis ranged from about 20 to 30 months (25). Most of these dogs did not have advanced disease and had concurrent corticosteroid treatment. Low albumin levels, ascites, and hepatic encephalopathy are all poor prognostic indicators. Therapy for chronic hepatitis has four general goals: 1) remove the cause, 2) provide an adequate diet, 3) provide specific therapy, and 4) provide general liver support. The therapy for chronic hepatitis involves removing the primary cause if it can be identified this is the only proven management technique in chronic hepatitis in dogs. Much of the therapy is directed at providing adequate liver support. This often involves the use of multiple therapies. Dietary therapy should be considered in all cases; however, only general guidelines can be given. Palatability is important to ensure that adequate energy requirements are met. Next, there is a Previous Next Contents 43

46 misconception about diet and liver disease that liver patients should be placed on a protein-restricted diet. Protein restriction should only be instituted in patients that have clinical evidence of protein intolerance (i.e., hepatic encephalopathy). The goal of dietary therapy is to adjust the quantities and types of nutrients to provide adequate nutrition but avoid the production of excess nitrogen by-products associated with liver disease. As a general recommendation, one should feed a highly digestible diet contributing 15% to 20% of protein on a dry-matter basis (26). High carbohydrate and moderate fat content is important to supply caloric needs. Mineral supplementation containing high concentrations of both copper and iron should be avoided and involves feeding the lowest amount of copper available (ideally < 5 mg/kg [ppm] on a dry-matter basis). The benefit of decreasing inflammation in dogs with chronic hepatitis is unproven, although the author s clinical impression suggests that antiinflammatory therapy is beneficial in some cases. The treatment of chronic hepatitis is quite controversial, and no good controlled studies in animals support corticosteroid use in every case. Strombeck and Gribble found that corticosteroid treatment in some dogs with chronic hepatitis prolonged survival (24). They studied a wide variety of diseases and concurrent therapies, but it nonetheless appears that corticosteroids offer benefit in at least some cases (possibly around 25%). A suggested dose of 1 to 2 mg/kg/day of either prednisone or prednisolone should be instituted. When clinical improvement is suspected or after several weeks of administration, the dose is tapered to 0.5 mg/kg/day or every other day. The only accurate way to evaluate a response to any therapy is to take another biopsy in 6 months to 1 year. This is because the patient will develop a concurrent steroid hepatopathy with increased liver enzymes, making laboratory determination of any improvement impossible. Because of steroid hepatopathy in addition to the other negative side effects of steroids, I now tend to use alternate immunosuppressive therapy. Azathioprine is an effective immunosuppressant drug that has been shown to increase survival in humans when treated for chronic hepatitis in conjunction with corticosteroids. There are no studies in dogs with chronic hepatitis using azathioprine, but we have recently also observed azathioprine-induced secondary hepatopathies. Consequently, I now tend to use cyclosporine in cases of chronic hepatitis because of its excellent immune suppression and a generic form is available and less expensive. I have observed resolution in a number of dogs treated with cyclosporine alone at a dose of 5 mg/kg BID. I advise monitoring cyclosporine blood levels and adjusting the dose appropriately. When liver enzymes decline, I reduce the dose to daily administration. The advantage of this therapy, although expensive, is the lack steroid side effects, secondary steroid hepatopathy, ability to monitor progress through liver enzymes, and the excellent clinical response we have observed in many cases. Chronic hepatitis associated with copper accumulation requires copper chelator or zinc therapy. Hepatic copper levels greater than 1000 mcg/g dry-weight liver should have chelator therapy for some period of time. Chelators bind with copper either in the blood or the tissues and then promote copper removal through the kidneys. Penicillamine (Cuprimine; 250 mg capsules) is the most common copper chelator therapy recommended for use in dogs. The dose is 15 mg/kg BID given on an empty stomach. A second copper chelator is trientine (Syprine) that is manufactured for use in patients intolerant to penicillamine. Zinc therapy can be used once the liver is decoppered with chelators. Oral zinc therapy works by causing an induction of the intestinal copper-binding protein metallothionein. Dietary copper binds to the metallothionein with a high affinity that prevents transfer from the intestine into the blood. When the intestinal cells die and are sloughed, metallothionein-bound copper becomes excreted through the stool. An initial induction dose of 15 mg/kg body weight (or mg BID) of elemental zinc is suggested (27). Following 1 to 3 months of induction the dose can be reduced in approximately half. The goal is for serum zinc concentrations to be greater than 200 mcg/dl but less than 500 mcg/dl. Zinc must be administered on an empty stomach and often induces vomiting Symposium Proceedings Gastrointestinal Diseases Previous Next Contents 44

47 Other therapy for chronic hepatitis includes ursodeoxycholic acid (ursodiol [Actigall]. This drug is a synthetic hydrophilic bile acid that essentially changes the bile acid pool from more toxic to less toxic. Ursodeoxycholic acid has been shown to increase bile acid dependent flow and to reduce hepatocellular inflammatory changes, fibrosis, and possibly some immunomodulating effects (28). The hepatoprotective characteristics make one believe that ursodeoxycholic acts as an antioxidant. The dose for ursodeoxycholic acid is 15 mg/kg daily. Antioxidants can also be given to provide liver support promoting optimal hepatic function. Vitamin E, d-alpha tocopherol is a membrane-bound antioxidant. S-adenosyl-methionine (SAMe) [Denosyl] is a precursor of the antioxidant glutathione in the hepatocyte. Milk thistle has been used for centuries as a natural remedy for liver disease. Silymarin is the active extract and consists of bioflavonoligans that have been reported to work as antioxidants, scavenging free radicals and inhibiting lipid peroxidation. Marin (Nutramax Labs) contains silibin-phosphatidylcholine complex, and it is the phosphatidylcholine that increases intestinal absorption. The Icteric Dog Clinical icterus is usually identified in dogs when serum bilirubin concentrations approach 2.5 mg/ dl or higher. Icterus can be divided into prehepatic causes, hepatic causes, and posthepatic causes (5). CBC, biochemical profile, and urinalysis will help classify the icterus. Prehepatic icterus is caused by hemolytic disease associated with a decreasing hematocrit and regenerative anemia. Because the liver has such a reserve capacity to handle unconjugated bilirubin, hematocrit must fall significantly (usually into the teens) before icterus is evident. Hepatic and posthepatic icterus are a little more difficult to differentiate. Posthepatic icterus is generally associated with marked increases in ALP and GGT with variable increases in ALT, and AST concentrations. Abdominal ultrasonography generally helps support either hepatic or posthepatic disorders, such as bile duct obstructions, gallbladder mucocele, cholecystitis, cholelithiasis, and pancreatitis. It is also difficult to differentiate pancreatic from biliary tract disease because the clinical and laboratory findings are frequently similar. With acute pancreatitis the liver can be involved in two ways. First, release of inflammatory cytokines from the necrotic pancreas directly insults hepatocytes; second, extensive pancreatic inflammation may extend to and impinge on the common bile duct resulting in a mechanical extrahepatic obstruction. In some cases, acute hepatic inflammation or cholestatic disease mimic the changes seen in pancreatitis. The clinician must consequently use all information available, including the biochemistry results and imaging information to make a diagnosis. The Spec cpl test is the best laboratory test for the diagnosis of pancreatitis in dogs or cats. Amylase and lipase are of little value in diagnosing pancreatitis in dogs. Routine abdominal radiographs are useful in detecting effusions, changes in organ size, and masses. Ultrasonography provides the best imaging technique for detecting parenchymal changes, contour irregularities, cystic changes, or mass involvement. The pancreas can be seen in nearly all cases; however, pancreatitis can be missed in up to one third of the cases. Ultrasonography is very helpful in detecting biliary tract changes. Cholelithiasis can be observed with ultrasonography but not usually with radiography because canine choleliths are generally radiolucent. Dilatation of the intrahepatic bile duct is also suggestive of biliary obstructive disease. Mucocele To date, over 130 cases of gallbladder mucocele have been documented in the literature. A gallbladder mucocele is an enlarged gallbladder with immobile stellate or finely striated patterns of mucoid material in the lumen detected with ultrasonography (29). The changes often result in biliary obstruction or gallbladder perforation and peritonitis. Smaller breeds and older dogs are overrepresented. Shetland Sheepdogs and Cocker Spaniels are most commonly affected (30). Most dogs are presented for nonspecific clinical signs, such as vomiting, anorexia, and lethargy. Abdominal pain, icterus, and hyperthermia are common findings on physical examination. Most have serum elevations of total bilirubin, ALP, and GGT levels and variable ALT, although some dogs are Previous Next Contents 45

48 asymptomatic and a mucocele is diagnosed incidentally on abdominal ultrasonography. Shetland Sheepdogs tend to have hyperlipidemia and recently shown to have a genetic defect in the MDR 3 hepatobiliary transporter gene that is involved in phosphocholine transport from the liver to the bile (31). It is believed that the lack of phosphocholine entering the bile may predispose to mucocele formation. Risk factors identified for mucocele formation include endocrine disease (hypothyroidism, Cushing s disease), idiopathic vacuolar hepatopathy (progesterones), and high-fat diets. Gallbladder mucoceles appear ultrasonographically as an immobile accumulation of anechoic-tohypoechoic material characterized by stellate or finely striated bile patterns (wagon-wheel or kiwi-fruit appearance). This should be differentiated from biliary sludge by the absence of gravity-dependent bile movement; the mucocele is nonmovable. Gallbladder wall thickness and appearance are variable and nonspecific. The cystic, hepatic, or common bile duct may be normal in size or dilated, suggesting biliary obstruction. In one series, loss of gallbladder wall integrity and gallbladder rupture was present in 50% of the dogs and positive aerobic bacterial culture was obtained from bile in most of these dogs (31). Gallbladder wall discontinuity on ultrasonography indicated rupture, whereas neither of the bile patterns predicted the likelihood of gallbladder rupture. Cholecystectomy is the treatment for mucoceles. There are reports of resolution of mucoceles using ursodeoxycholic acid (ursodiol), but surgery remains the preferred therapy (32). Ursodeoxycholic acid is thought to upregulate the MDR 3 gene that may be the cause of mucocele production in some dogs. Mucosal hyperplasia is present in all gallbladders examined histologically but infection is not always present, suggesting biliary stasis and mucosal hyperplasia as the primary factors involved in mucocele formation. Based on information to date, the recommended course of action for a gallbladder with immobile ultrasonographic stellate or finely striated bile with clinical or biochemical signs of hepatobiliary disease is cholecystectomy. A mucocele is reported to be the most common cause of a gallbladder perforation. Following cholecystectomy and the postoperative recovery period, the prognosis is excellent, especially when the liver enzymes are normal. The mortality rate is about 20%, and liver disease with elevated liver enzymes persists in some cases. Cholecystitis/Cholelithiasis Bacterial cholangitis and cholecystitis is occasionally found in dogs but is quite common in cats. These animals often present with acute signs and laboratory findings of cholestatic liver disease. Fever, leukocytosis, and icterus are common. Biliary tract perforation results in bile peritonitis. Ultrasonography is a sensitive and specific indicator of extrahepatic biliary tract disease. A thickened gallbladder and duct wall is common with cholecystitis. In suspected cases with a potential bacterial component, it is reasonable to perform ultrasound-directed or laparoscopy-assisted gallbladder aspiration. Gas within the lumen or wall is occasionally observed as emphysematous cholecystitis. This disorder is usually secondary to a combination of gallbladder wall ischemia and proliferation of gas-forming bacteria, such as Escherichia coli or Clostridium perfringens, and has been reported as a complication of diabetes mellitus. The most common isolates in bacterial cholecystitis are E coli, followed by Enterococcus, Enterobacter, Klebsiella, Streptococcus, Pseudomonas, Bacteroides, and Clostridium species. Treatment involves 3 to 4 weeks of appropriate antibiotic therapy based on culture. With suspicion or evidence of gallbladder perforation, cholecystectomy is indicated. Cholelithiasis and choledocholithiasis account for less than 1% of patients with liver disease. Cholesterol gallstones are common in humans but very rare in dogs and cats. Most often, canine and feline choleliths are bilirubin pigment gallstones with variable amounts of calcium salts. I believe most develop secondary to a biliary infection resulting in deconjugation of soluble bilirubin with precipitation of bile being the nidus of stone formation. Miniature Schnauzers and Toy Poodles are reported to have a higher 2011 Symposium Proceedings Gastrointestinal Diseases Previous Next Contents 46

49 incidence of cholelithiasis. Choleliths are usually clinically silent; however, clinical signs are usually related to cholecystitis and include vomiting, anorexia, icterus, fever, and abdominal pain. Some dogs with vague abdominal pain have choleliths. In some cases, bile duct obstruction or biliary tract rupture and peritonitis may occur. In clinical cases, surgical removal is indicated and appropriate antibiotic therapy initiated. References 1. Comazzi S, Pieralisi P, Bertazzolo W. Haematological and biochemical abnormalities in canine blood: frequency and associations in 1022 samples. J Small Anim Pract. 2004;45: Brovida C, Rothuizen J. Liver and pancreatic diseases. In: Ettinger SJ, Feldman EC, eds. Textbook of Veterinary Internal Medicine: Diseases of the Dog and Cat. St. Louis, MO: Elsevier Saunders; 2010: Center SA, Slater MR, Manwarren T, et al. Diagnostic efficacy of serum alkaline phosphatase and gammaglutamyltransferase in dogs with histologically confirmed hepatobiliary disease: 270 cases ( ). J Am Vet Med Assoc. 1992;201: Bunch S. In: Nelson RW, et al, eds. Small Animal Internal Medicine. St. Louis: Mosby; Webster CRL, Cooper JC. Diagnostic approach to hepatobiliary disease. In: Bonagura JB, Twedt DC, eds. Kirk s Current Veterinary Therapy XIV. St Louis, MO: Saunders Elsevier; 2008: Anwer MS, Meyer DJ. Bile acids in the diagnosis, pathology, and therapy of hepatobiliary diseases. Vet Clin North Am Small Anim Pract. 1995;25: Center SA, Baldwin BH, Erb HN, et al. Bile acid concentrations in the diagnosis of hepatobiliary disease in the dog. J Am Vet Med Assoc. 1985;187: Simpson JW, Else RW. Diagnostic value of tissue biopsy in gastrointestinal and liver disease. Vet Rec. 1987;120: Twedt DC, Gary AT. Evaluation of elevation of serum alkaline phosphatase in the dog. In: Bonagura JB, Twedt DC, eds. Kirk s Current Veterinary Therapy XIV. St Louis, MO: Saunders Elsevier; 2008: Sepesy LM, Center SA, Randolph JF, Warner KL, Erb HN. Vacuolar hepatopathy in dogs: 336 cases ( ). J Am Vet Med Assoc. 2006;229: Zimmerman KL, Panciera DL, Panciera RJ, et.al. Hyperphosphatasemia and concurrent adrenal gland dysfunction in apparently healthy Scottish Terriers. J Am Vet Med Assoc. 2010;237: Nestor DD, Holan KM, Johnson CA, Schall W, Kaneene JB. Serum alkaline phosphatase activity in Scottish terriers versus dogs of other breeds, J Am Vet Med Assoc. 2006;228: Gallagher AE Panciera DL, Panciera RJ. Hyperphosphatasemia in Scottish terriers: 7 cases. J Vet Intern Med. 2006;20: Prause LC, Twedt DC. Hepatic nodular hyperplasia. In: Bonagura JD, ed. Kirk s Current Veterinary Therapy XII. Philadelphia: WB Saunders;2000: Cullen JM, van den Ingh TS, Bunch SE, et al. Morphological classification of circulatory disorders of the canine and feline liver. In: Rothuizen J, et al, eds. WSAVA Standards for Clinical and Histological Diagnosis of Canine and Feline Liver Diseases. Edinburgh: Saunders/Elsevier; 2006: Christiansen JS, Hottinger HA, Allen L, et.al. Hepatic microvascular dysplasia in dogs: a retrospective study of 24 cases. J Am Anim Hosp Assoc. 2000;36: Van den Ingh TS, Rothuizen J, Meyer HP. Portal hypertension associated with primary hypoplasia of the hepatic portal vein in dogs. Vet Rec. 1995;137: Bunch SE, Johnson SE, Cullen JM. Idiopathic noncirrhotic portal hypertension in dogs: 33 cases ( ). J Am Vet Med Assoc. 2001;218: Watson PJ. Chronic hepatitis in dogs: a review of current understanding of the aetiology, progression, and treatment. Vet J. 2004;167: Weiss DJ, Armstrong PJ, Mruthyunjaya A. Anti-liver membrane protein antibodies in dogs with chronic hepatitis. J Vet Intern Med : Andersson M, Sevelius E. Breed, sex and age distribution in dogs with chronic liver disease: a demographic study. J Small Anim Pract. 1991;32:115. Previous Next Contents 47

50 22. Rolfe DS, Twedt DC. Copper-associated hepatopathies in dogs. Vet Clin North Am Small Anim Pract. 1995;25: Webster CRL. History, clinical signs, and physical findings in hepatobiliary disease. In: Ettinger SJ, Feldman EC, eds. Textbook of Veterinary Internal Medicine: Diseases of the Dog and Cat. St. Louis, MO: Elsevier Saunders;2005; Strombeck DR, Gribble D. Chronic active hepatitis in the dog. J Am Vet Med Assoc. 1978;173: Sevelius E. Diagnosis and prognosis of chronic hepatitis and cirrhosis in dogs. J Small Anim Pract. 1995; 36: Bauer JE. Hepatic disease, nutritional therapy, and the metabolic environment. J Am Vet Med Assoc. 1996;209: Brewer GJ, Dick RD, Schall W, et.al. Use of zinc acetate to treat copper toxicosis in dogs. J Am Vet Med Assoc. 1992;201: Leveille-Webster CR. Ursodeoxycholic acid therapy. In: Bonagura JD, ed. Kirk s Current Veterinary Therapy XIII. Philadelphia: WB Saunders; 2000: Crews LJ, Feeney DA, CR, et al. Clinical, ultrasonographic, and laboratory findings associated with gallbladder disease and rupture in dogs: 45 cases ( ). J Am Vet Med Assoc. 2009;234: Aguirre AL, Center SA, Randolph JF, et al. Gallbladder disease in Shetland Sheepdogs: 38 cases ( ). J Am Vet Med Assoc. 2007;231: Besso JG, Wrigley RH, Gliatto JM, et al. Ultrasonographic appearance and clinical findings in 14 dogs with gallbladder mucocele. Vet Radiol Ultrasound. 2000;41: Walter R, Dunn ME, d Anjou M, et al. Nonsurgical resolution of gallbladder mucocele in two dogs. J Am Vet Med Assoc. 2008; 232: Symposium Proceedings Gastrointestinal Diseases Previous Next Contents 48

51 Acute Canine Pancreatitis: The Clinical Challenges of This Elusive Disease Dr. Nolie Parnell, DVM, Diplomate, ACVIM Overview Acute pancreatitis is inflammation of the pancreas that leads to autodigestion of the parenchyma as well as a systemic inflammatory response. Studies published have reported pancreatic changes ranging from 1.7% to 30% at necropsy (1, 2). Not all dogs in these studies had clinical signs suggestive of pancreatitis. Whether that demonstrates that the lesions found are not clinically significant or that pancreatitis is underdiagnosed in dogs is unclear. Despite this difficulty in interpretation, pancreatitis remains an important differential diagnosis for acute vomiting and abdominal pain in dogs. Foci Published studies have reported that pancreatic changes found at necropsy range from 1.7% to 30%; however, not all dogs in these studies had clinical signs suggestive of pancreatitis. Possible causes of pancreatitis include dietary indiscretion and eating table scraps, hypertriglyceridemia, and such drugs as sulfonamides, furosemide, and potassium bromide, but not corticosteroids. Mild pancreatitis is differentiated from severe pancreatitis by lack of such complications as pancreatic necrosis, pancreatic pseudocyst, pancreatic abscess, organ failure, hypotension, biliary obstruction, and metabolic derangements of hyperglycemia and hypocalcemia. Measurement of serum amylase and lipase levels is neither sensitive nor specific for the diagnosis of pancreatitis. Abdominal ultrasonography has greatly improved the veterinarian s ability to definitely diagnose pancreatitis and should be used in conjunction with other findings to confirm the diagnosis. The four goals of medical treatment of pancreatitis are to restore the integrity of circulatory system (correct dehydration), reduce the volume of pancreatic secretions, provide relief from pain, and limit or manage complications. Unlike human patients, infectious complications from pancreatitis are considered uncommon in dogs; therefore, antibiotics seem unlikely to have any beneficial effects. Dogs with severe acute pancreatitis, or dogs with mild acute pancreatitis in which food is unsuccessfully reintroduced within 72 hours, should have an assisted feeding method initiated. Clinical Presentation Although the precise cause of pancreatitis is often unknown, several causes and risk factors have been identified. Dog breeds, such as Miniature Schnauzers, Shetland Sheepdogs, and Yorkshire Terriers, have been reported as overrepresented (3). A recent study showed that dietary indiscretion and eating table scraps was associated with an increased risk for pancreatitis (4). Hypertriglyceridemia is considered a risk factor for pancreatitis in Miniature Schnauzers (5). Drugs, such as sulfonamides, furosemide, and Previous Next Contents 49