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in the Dog and Cat BVM&S, PhD, MRCVS, DipACVIM, DipECVIM Cornell University, Ithaca NY, USA From a clinical perspective pancreatitis can be broadly categorized as acute, recurrent acute or chronic. It can be further classified according to its effect on the patient as mild or severe, non-fatal or fatal, and also by the presence of sequela such as abscess formation. Histologically, acute pancreatitis is characterized by findings that range from pancreatic edema to necrosis, variable infiltrates of mononuclear and polymorphonuclear cells, and local changes such as peri-pancreatic fat necrosis and thrombosis. Acute pancreatitis may resolve or persist and can be complicated by secondary infection and pseudocyst or abscess formation. While it is tempting to equate mild acute pancreatitis with pancreatic edema, and severe or fatal pancreatitis with pancreatic necrosis, this relationship has not been critically examined in patients with naturally occurring pancreatitis, as the pancreas is rarely visualized or biopsied in patients with mild, self-limiting pancreatitis. Chronic pancreatitis is characterized by fibrosis and low grade mononuclear inflammation and may be a sequela of recurrent acute pancreatitis or a subclinical disease process that may present as diabetes mellitus or exocrine pancreatic insufficiency (EPI). Etiology and Pathogenenesis The etiology and pathogenesis of spontaneous pancreatitis is poorly understood. The major factors which have been implicated (by association) as causes of acute pancreatitis in the dog and cat and the experimental evidence to support their involvement are summarized in Table 1. Table 1. Factors associated with the development of acute pancreatitis in dogs and cats.
Acute pancreatitis has only recently been considered a significant disease entity in cats. It is the authors impression that pancreatitis in cats seems to be more chronically active and severe in cats, than in the majority of dogs. While, pancreatitis in cats has been diagnosed as the sole or predominant disease entity in cats at necropsy, it has also been variably associated with diseases in other organs. e.g. the liver (cholestasis, cholangiohepatits, hydropic change, severe lipidosis), the kidney (mild to severe nephritis), the endocrine pancreas (diabetes mellitus), the lungs (pulmonary thrombosis) and the intestine (inflammation, ulceration). Effusions have also been noted in the pleural and peritoneal cavity. Whether these non-pancreatic abnormalities arise as a consequence of pancreatitis, or are associated with disease processes that cause pancreatitis, or are unrelated to pancreatitis is unclear at this time. Irrespective of the initiating cause pancreatitis is generally believed to occur when digestive enzymes are activated prematurely within the pancreas. Experimental pancreatic hyperstimulation with cholecystokinin (CCK: or its analogue cerulein), dietary supplementation with ethionine, and obstruction of the pancreatic duct lead to the formation of large intracellular vacuoles in acinar cells. Vacuole formation is thought to be a consequence of the uncoupling of exocytosis of zymogens and abnormal intracellular trafficking of digestive and lysosomal enzymes. These subcellular alterations are considered to precipitate the intracellular activation of digestive enzymes. Edematous pancreatitis induced by CCK hyperstimulation in dogs is characterized by a rapid, but self-limiting, burst of trypsinogen activation. It is of note that pancreatic necrosis in humans is associated with persistent trypsinogen activation, so it may be the ability of the pancreas to limit trypsinogen activation which stops edematous pancreatitis from progressing to necrotizing pancreatitis. Pancreatic hyperstimulation may also be of direct relevance to naturally occurring pancreatitis in dogs and cats. CCK is normally released by cells in the duodenum in response to intraluminal fat and amino acids and coordinates and stimulates pancreatic secretion and gallbladder contraction during digestion. It is possible that high fat diets exert their effects via the excessive release of cholecystokinin and that hypercalcaemia, organophosphates and high levels of circulating glucocorticoids also facilitate or cause pancreatic hyperstimulation; however, this is not proven. Often pancreatic inflammation is a self-limiting process, but in some animals reduced pancreatic blood flow and leukocyte and platelet migration into the inflamed pancreas may cause progression to pancreatic necrosis. Secondary infection may arise by bacterial translocation from the intestine. Release of active pancreatic enzymes and inflammatory mediators from the inflamed pancreas, such as Tumor Necrosis Factor-a (TNF-a), interleukin-1 (IL-1) and phospholipid platelet activating factor (PAF), amplifies the severity of pancreatic inflammation, and adversely affects the function of many organs (systemic inflammatory response), and cause derangement in fluid, electrolyte and acid-base balance. It is the development of multisystemic abnormalities that separates mild from severe, potentially fatal pancreatitis. Further study of the cellular mechanisms governing enzyme secretion and activation, leukocyte and platelet recruitment to the pancreas, bacterial translocation and the development of the systemic inflammatory response in pancreatitis will hopefully provide information which will be useful in treating acute pancreatitis in the patient population in the future. Diagnosis There is currently no single specific test for pancreatitis in dogs and cats and diagnosis is based on a combination of compatible clinical, clinicopathological and imaging findings. Surgical biopsy may be required to confirm a diagnosis, and to distinguish inflammation from neoplasia. Clinical findings Signalment and History
Dogs:
Cats: Physical Examination Physical findings in dogs with acute pancreatitis are highly variable and range from depression, to mild dehydration with signs of abdominal pain, to acute abdominal crisis with shock (tachycardia, prolonged capillary refill time, tacky mucous membranes, hypothermia), petechiation, icterus and ascites. An abdominal mass is palpated in some dogs. In cats dehydration and hypothermia have been most commonly observed. Icterus may also be present. Abdominal pain is infrequently elicited. The presence of a palpable cranial abdominal mass or abdominal pain has been reported in a quarter to a third of cats in some clinical series and cats with experimental and trauma - induced pancreatitis. Diagnostic approach and differential diagnosis
Dogs: Where abdominal pain is the major finding localizing abnormalities such as abdominal distension are rapidly pursued with radiography, ultrasonography and paracentesis while providing supportive treatment on the basis of physical findings and a minimum data base and awaiting the results of hematology, serum chemistry profile and urinalysis. Abdominal pain can arise from any intra-abdominal structure. Musculoskeletal disorders such as discospondylitis and prolapsed discs can be hard to distinguish from abdominal causes of pain. It is of note that diarrhea, which was bloody in some cases, was a more frequent sign than vomiting in dogs with experimental acute pancreatitis. Acute pancreatitis and its complications (infection, pseudocyst or abscess formation) should also be considered in the differential diagnosis of icterus and pyrexia. Some dogs with pancreatitis exhibit few localizing clinical signs. Diagnosis in these animals requires a high index of suspicion and use of versatile diagnostic tests such as ultrasonography.
Cats: Where vomiting is present it is approached by pursuing localizing findings such as abdominal pain or masses and by ruling out infectious, parasitic, metabolic and gastrointestinal causes. Hyperthyroidism should be ruled out in older cats by determination of serum total T4 concentration. Elevated hepatic enzymes, hyperbilirubinemia, hyperglycemia, and glucosuria are frequently encountered in cats with acute pancreatitis so pancreatitis should be strongly considered in these cats. The diagnostic approach to feline icterus is to first rule out pre-hepatic causes, and then to pursue hepatic or post-hepatic causes. The association of acute pancreatitis and hepatic lipidosis of increased mortality, cholangiohepatitis and inflammatory bowel disease has been shown in some studies. A high index of suspicion should be adopted for pancreatitis in cats with hepatic, biliary or intestinal disease. Cats with a confirmed diagnosis of hepatic lipidosis who have a peritoneal effusion should also be strongly suspected of having pancreatitis. Pancreatitis may be the cause of diabetes mellitus in some cats, but the true association between these diseases is unclear. One study suggests that cats with pancreatitis and diabetes mellitus are very sensitive to insulin. Transient euglycemia and reduced insulin requirements after removal of a pancreatic abscess suggest that pancreatic inflammation or infection can exacerbate diabetes mellitus in cats. Transient diabetes mellitus has also been reported in a cat that was suspected of having pancreatitis. Where a high index of suspicion for pancreatitis is present ultrasonography and enzymology (assay of feline TLI; beware in cats with IBD -see below) should initially be employed to help to detect pancreatitic inflammation. Pancreatic biopsy is required to achieve a definitive diagnosis. Clinicopathological findings Hematology:
Dogs:
Cats: Serum biochemistry :
Dogs:
Cats: Urinalysis: Enables azotemia to be characterized as renal or pre-renal. Transient proteinuria occurs in some dogs with acute pancreatitis, possibly as a consequence of pancreatic enzyme-mediated glomerular damage. The absence of white cell casts or bacteria helps to rule out pyelonephritis as a cause of abdominal pain. The presence of glucose or ketonuria should prompt consideration of diabetes mellitus. Pancreas specific enzymes: Classically, elevations in serum amylase and lipase activity have been used as indicators of pancreatic inflammation in dogs. However these tests are not very accurate because dogs with non-pancreatic disorders may have elevated enzyme activities. This may occur because both amylase and lipase are normally present in other organs and their serum activities may increase with non-pancreatic disorders including intestinal obstruction (amylase), corticosteroid administration (lipase) and renal disease (both enzymes). Dogs with confirmed pancreatitis may also have normal amylase and lipase activity. For example, in two recent case series of dogs with histologically confirmed pancreatitis, lipase was normal in 28 and 61% of dogs, and amylase was normal in 31 and 47% of dogs. This may be due to exhaustion of enzymes, thrombosis of pancreatic vessels, the presence of inhibitors, alterations in activity and perhaps increased clearance. In cats it seems fair to state that amylase and lipase are of no utility for diagnosing pancreatitis. These limitations have stimulated the development of assays for enzymes considered pancreatic in origin. Trypsin-like immunoreactivity (TLI) is one candidate. This species specific immunoassay measures circulating trypsinogen in healthy individuals and trypsinogen and trypsin in those with pancreatitis. In dogs circulating TLI is abolished by pancreatectomy, and extremely low concentrations occur in exocrine pancreatic insufficiency (EPI). Experimental and clinical studies have documented high concentrations of TLI in dogs with acute pancreatitis. TLI is therefore considered a useful indicator of pancreatic mass and potentially inflammation. Non-pancreatic diseases such as renal disease and possibly corticosteroids may increase circulating TLI. It is important to note that the utility of TLI for the diagnosis spontaneous pancreatitis in dogs has not been thoroughly evaluated, and the author has observed normal and subnormal concentrations in dogs with pancreatitis. A TLI test has also been developed for cats. Cats with exocrine pancreatic insufficiency and some cats with spontaneous pancreatitis have abnormal concentrations of TLI. Increased application of this test indicates that high TLI concentrations may occur in the face of normal pancreatic histology in cats with inflammatory bowel disease or lymphoma. The reason for this is unclear. Non-pancreatic diseases such as renal disease and possibly corticosteroids may also increase circulating TLI in cats. At the present time it seems fair to conclude that the TLI assay is highly accurate for differentiating EPI from small intestinal disease. It appears less accurate in detecting pancreatitis. This is not surprising as pancreatitis is a very dynamic disease, which may influence the synthesis, secretion, elimination and activity of circulating marker enzymes such as TLI. The tissue specificity of TLI makes it an attractive alternative to amylase and lipase in dogs, and it is presently the only useful indicator in the cat. Radiography: Radiographic findings in cats and dogs with acute pancreatitis may include loss of serosal detail, increased opacity in the right cranial quadrant of the abdomen, displacement of the duodenum ventrally and/or to the right, dilated hypomotile duodenum and caudal displacement of the transverse large intestine. Punctate calcification is occasionally identified in dogs with long-standing pancreatitis; it indicates saponification of mesenteric fat around the pancreas. Although radiographic signs often are absent, and are non-specific, radiography remains a useful diagnostic method for pancreatitis largely because it may enable detection of other abnormalities that can cause similar signs (eg. gastric foreign body or intestinal obstruction). Radiography is a logical first choice imaging modality for animals with gastrointestinal signs. Negative or equivocal radiographic findings may be followed up with ultrasonography or an upper gastrointestinal contrast study. Thoracic radiographs may enable the detection of pleural fluid, edema or pnemonia which has been associated with pancreatitis in dogs and cats. Ultrasonography: The use of ultrasound for detecting pancreatic lesions is perhaps one of the most significant advances in the diagnosis of acute pancreatitis in dogs and cats. Ultrasonographic findings include enlarged, hypoechoic pancreas, cavitary lesions such as abscess or pseudocyst, dilated pancreatic duct, swollen hypomotile duodenum, biliary dilatation and peritoneal fluid. A recent study of dogs with fatal acute pancreatitis indicated that ultrasound supported a diagnosis of pancreatitis in 23/34 dogs. Findings in cats are also encouraging, but emphasize that a normal ultrasound does not rule out pancreatitis. The clinician should also be careful to consider differential diagnoses other than pancreatitis e.g. pancreatic neoplasia, pancreatic edema (associated with hypoproteinemia or portal hypertension) and enlarged peri-pancreatic structures, which can have an identical ultrasonographic appearance to pancreatitis. Fine needle aspirates of cavitary lesions may be useful to distinguish abscess from pseudocyst. Abdominal paracentesis: Examination of peritoneal fluid may aid the detection of various causes of acute abdominal signs such as pancreatitis, gastrointestinal perforation or ruptured bile duct. The accumulation of fluid in the abdomen or the pleural cavity has been variably encountered in cats with acute pancreatitis. Effusion in the abdomen or chest was present in 17/40 cats in one study, in the abdomen of 5/5 cats with hepatic lipidosis and pancreatitis, and the abdomen of 2/8 cats another. Prognostic indicators: Stratifying the severity of pancreatitis is useful when deciding how aggressive to be with medical and nutritional support, and in offering a prognosis. Severe pancreatitis requires aggressive support and carries a guarded prognosis, whereas mild pancreatitis often responds to short term symptomatic therapy and has agood prognosis. Clinical and clinicopathological criteria can be used to predict the severity of acute pancreatitis. The presence of shock or abnormalities such as oliguria, azotaemia, icterus, markedly elevated transaminases, hypocalcaemia, hypoglycaemia, hypoproteinaemia, acidosis, leukocytosis, falling haematocrit, thrombocytopaenia and DIC should be considered likely indicators of severe pancreatitis in the dog and cat. The measurement of components of the systemic inflammatory response such as TNF-?, and C-reactive protein, and IL-6 may also yield information about the severity of pancreatitis in dogs and cats, and in the future might lead to the administration of specific antagonists of this response. Indicators which are potentially useful in the diagnosis and prognosis of pancreatitis include assay of trypsinogen activation peptide (TAP), trypsin complexed with inhibitors and phospholipase A2. Trypsinogen activation peptide has been shown to accurately predict severity in humans with pancreatitis. This peptide is released when trypsinogen, a pancreas-specific enzyme, is converted to its active form and rapidly accumulates in the urine and plasma of dogs and cats with experimental acute pancreatitis. Phospholipase A2 is elevated in dogs with severe pancreatitis. Further validation of these markers is required before clinical application. Morphologic assesment of severity is accomplished in humans by use of contrast enhanced computed tomography (CE-CT). Where lack of pancreatic perfusion is encountered i.e. necrosis, fine needle aspiration is used to distinguish infected from sterile necrosis. Substantially reduced mortality has been achieved by the detection and surgical treatment of people with infected necrosis. The lack of availability of CT has restricted veterinary application to date, but the relative accessibility of the canine and feline pancreas to ultrasound guided needle aspiration holds the potential of the adoption of a similar approach. Treatment: Medical treatment is based on maintaining or restoring adequate tissue perfusion, limiting bacterial translocation and inhibiting inflammatory mediators and pancreatic enzymes; surgical treatment consists principally of restoring biliary outflow, removing infected necrotic pancreatic tissue, or coping with sequela such as pseudocysts. No studies have critically evaluated treatment modalities in dogs or cats with naturally occurring pancreatitis. Initial management: The initial medical management of dogs and cats with acute pancreatitis is invariably initiated before a diagnosis is confirmed and is based on the presenting clinical findings and the results of an initial database. Where dehydration or hypovolemia are encountered these are supported with intravenous fluid therapy. Lactated Ringers solution or 0.9% NaCl are common first choices. Potassium and glucose should be supplemented where necessary. The type of fluid should be tailored on the basis of electrolyte and pH measurements to restore normal electrolytes and acid-base balance. For example, dogs with a history of vomiting who are mildly dehydrated are usually given crystalloids such as lactated Ringer's solution at a rate that will provide maintenance and replace both deficits and ongoing losses over a 24h period. Dogs with signs of shock require more aggressive support. The volume deficit can be replaced with crystalloids at an initial rate of of 60-90ml/kg/h, then tailored to maintain tissue perfusion and hydration. Plasma (20ml/kg i.v.) or colloids (eg. degraded gelatine; Haemaccel®, Hoechst Animal Health, Milton Keynes at 10-20ml/kg/day i.v.). may be indicated in the presence of hypoproteinemia or shock. Colloids such as dextran 70 and hetastarch may also have antithrombotic effects that help maintain the microcirculation. Insulin therapy is initiated in diabetic patients. Stress hyperglycemia has to be diffrentiated from diabetes mellitus in cats. Where vomiting is a problem, oral intake is restricted, and antiemetics (metoclopramide or chlorpromazine), and antacids (e.g. famotidine) are prescribed when vomiting is persistent or severe. Prophylactic broad-spectrum antibiotics (e.g. amoxicillin ± enrofloxacin depending on severity) may be warranted in patients with shock, fever, diabetes mellitus or evidence of breakdowm of the GI barrier. Analgesia is an important aspect of caring for animals with pancreatitis. It can be provided using injectable opioids such as buprenorphine (0.005-0.01mg/kg SC q6-12hrs) or oxymorphone (0.05-0.1mg/kg cats, 0.1-0.2mg/kg dogs IM, SC Q 1-3hrs). It may be necessary to administer low dose sedation with acepromazine (0.01mg/kg IM) to patients who become dysphoric after opioids. It should be borne in mind that buprenorphine is a partial agonist and may antagonise the administarion of more potent analgesics in animals with sever pain. A transdermal fentanyl patch (Duragesic, Janssen) applied to a clipped clean area of skin is a good way of providing a longer duration of analgesia in dogs (10-20kg, 50µg/hr patch q 72hrs) and cats (25µg/hr patch q118hrs). Adequate fentanyl levels are not attained for between 6-48 hrs after application, so another analgesic should be administered in the short term. The author is wary of using non-steroidal analgesics in patients with acute pancreatitis due to concerns for GI ulceration, renal failure and potentially hepatotoxicity. Specific therapy: Once a diagnosis of pancreatitis is confirmed potentially more specific therapy can be employed. The majority of dogs with acute pancreatitis respond to fluid therapy and nothing by mouth for 48h. Hence, specific therapy is usually reserved for dogs that do not respond to fluid therapy or those with signs of multiorgan system involvement or DIC. Pancreatitis in cats seems to be more chronically active and severe than in dogs, thus cats with a confirmed diagnosis of pancreatitis generally need more support than the majority of dogs. The specific treatment of pancreatitis has evolved along two lines: 1. Stopping further pancreatitis from occurring. 2. Limiting the local and systemic consequences of pancreatitis. Therapies aimed at inhibiting pancreatic secretion (e.g. glucagon, somatostatin) or the intracellular activation of proteases (e.g. gabexate mesilate) which have been of benefit in ameliorating the severity of experimental pancreatitis have shown little benefit in the treatment of patients with spontaneous pancreatitis. This lack of success is probably related to the timing of therapy in relation to the development of pancreatitis; experimental therapy is usually initiated before or shortly after the induction of pancreatitis whereas most patients are not presented until 24-48hrs after the onset of pancreatitis. Support for this hypothesis is provided by the efficacy of somatostatin and gabexate mesilate in reducing pancreatitis in people undergoing elective procedures such as endoscopic retrograde cholecystopancreatography that are associated with pancreatitis. The lack of success with inhibiting the progression of spontaneous pancreatitis has led to increased emphasis on damage limitation; ameliorating the effects of inflammatory mediators or pancreatic enzymes on the patient and maintaining pancreatic perfusion. Coagulation abnormalities should be pursued and treatment with parenteral vitamin K can be assessed. Where a coagulopathy e.g. DIC, or hypoproteinemia are present, or the patient with pancreatitis is deteriorating, fresh frozen plasma (10-20ml/kg) may be beneficial in alleviating the coagulopathy, hypoproteinemia and restoring a more normal protease-antiprotease balanvce. The administration of heparin (75-150IU/kg TID) may be potentially useful in ameliorating DIC, promoting adequate microcirculation in the pancreas and clearing lipemic serum. In experimental pancreatitis isovolemic rehydration with dextran has also been shown to promote pancreatic microcirculation in dogs. A dopamine infusion had a protective effect when admisintered to cats within 12hrs of induction of experimental pancreatitis. Therapy to abrogate the systemic inflammatory response with antagonists of PAF (e.g lexipafant), IL-1 and TNF-? holds promise for the future. Oral pancreatic enzyme extracts have been reported to reduce pain in humans with chronic pancreatitis, though this is controversial. They are less likely to be effective in dogs as they do not appear to have a protease mediated negative feedback system. Dietary management: Precise recommendations of the dietary management of acute pancreatitis are hampered by the absence of controlled studies of the dietary management of acute pancreatitis.
Dogs: Alternative strategies of minimizing pancreatic stimulation include total parenteral nutrition and feeding distal to the CCK releasing part of the intestine via a jejunostomy tube but these options are usually reserved for dogs with persistent vomiting or severe pancreatitis. Recent studies in people indicate that acute pancreatitis may be exacerbated by the early admisnistration of TPN (before 5 days), and that enteral nutrition, administered via a naso-jejunostomy tube, can attenutae the systemic inflammatory response and may decrease complications.
Cats: As discussed above the endoscopic or surgical placement of a jejunostomy tube and feeding a liquid diet distal to the duodenum, and TPN are other solutions to providing balanced nutrition and minimizing pancreatic secretion that may prove useful in refractory cases. Patient Monitoring: Patients with suspected or confirmed pancreatitis should be carefully monitored to enable early detection of shock or other systemic abnormalities. Minimal monitoring for stable patients includes regular assessment of vital signs and fluid and electrolyte balance. In those with systemic abnormalities, monitoring should be more aggressive and may include vital signs, weight, haematocrit, total protein, fluid intake and output, blood pressure (central venous and arterial), electrolytes and glucose, acid-base status, platelets and coagulation status. Monitoring amylase, lipase or TLI on a sequential basis may also help to support resolution or progression of pancreatic inflammation. Ultrasound-guided fine needle aspiration of the pancreas may enable infected pancreatic necrosis to be detected. Ultrasonography may also enable detection of delayed consequences of acute pancreatitis such as pancreatic abscessation, pseudocyst formation and biliary obstruction. Surgical intervention: Surgery is potentially indicated to remove devititalized tissue in patients with infected pancreatic necrosis and to investigate and relieve persistent biliary obstruction. The removal or drainage of abscesses is another indication for surgery. Resection or surgical drainage of pancreatic pseudocysts is not always necessary as these can resolve spontaneously or following percutaneous drainage. Pancreatitis that is recurrent or is unresponsive to treatment may also require surgery to confirm a diagnosis and to exclude pancreatic cancer. Surgery has often been necessary to confirm an antemortem diagnosis of acute pancreatitis in cats. The increased application of ultrasonography and measurement of TLI has led to a reduced dependency on surgery in cats with high TLI and sonographic abnormalities. However it should be stressed that cats with pancreatitis often have concomitant abnormalities in other organ systems e.g. liver and gut, and biopsy of these organs and the pancreas may be indicated to optimize diagnosis and treatment. Transient euglycemia and reduced insulin requirements were noted after the removal of a pancreatic abscess in one cat suggest that surgical intervention may be beneficial in these cases. Prognosis:
Dogs:
Cats: Suggested further reading:
Akol, KG., Wasahbau, RJ., Saunders, HM, Hendrick MJ (1993). Acute pancreatitis in cats with hepatic lipidosis. Journal of Veterinary Internal Medicine 7, 205-209.
MANAGEMENT OF PERSISTENT VOMITING The clinical importance of vomiting stems from its association with a large, and varied group of diseases, and the potentially life threatening consequences of vomiting per se, such as aspiration pneumonia, fluid and electrolyte depletion, acid-base derangement and oesophagitis. Patient management should always be aimed at determining the medical significance of vomiting and detecting and treating the cause of vomiting. Where the cause is undetermined it is necessary to adopt a rational approach to controlling emesis. Initiation of vomiting: Vomiting is a reflex act which is initiated by stimulating the vomiting center in the medulla. The vomiting center can be stimulated directly, or indirectly via the chemoreceptor trigger zone (CRTZ) which is situated in the area postrema. The blood brain barrier may be limited at this point enabling blood borne substances such as toxins or drugs to stimulate the CRTZ. Neurological input from the vestibular nucleus can also stimulate the CRTZ (dog) or the vomiting center. Disease or irritation of the gastrointestinal tract, abdominal organs or peritoneum and cerebral diseases can directly stimulate the vomiting center via visceral receptors and vagal afferents. Once the vomiting center is adequately stimulated a set of visceral events is initiated - these include the sequential inhibition of proximal gastrointestinal motility, a retrograde power contraction in the small intestine and antral relaxation which enables transfer of intestinal contents to the stomach. These events are followed by moderate amplitude contractions in antrum and intestine, shortening of the intra abdominal esophagus. Dilatation of the cardia and lower esophageal sphincter enables transfer of gastric contents to the esophagus during retching and vomiting. Retching often precedes vomiting and is characterized by rhythmic inspiratory movements against a closed glottis. Negative intrathoracic pressure during retching prevents expulsion of esophageal contents. During vomiting the abdominal muscles contract and the intrathoracic and intrabdominal pressures are positive which results in the forceful expulsion of gastric contents from the mouth.
 Causes of Vomiting: There are so many potential causes of vomiting that it is often easiest to think in broad terms initially i.e. gastric, intestinal, intra-abdominal non-GIT, metabolic-endocrine, drugs, toxins, dietary, neurologic, infectious diseases and consider more specific causes when vomiting is localized to one of these groups (Table 1). Patient evaluation and diagnostic approach: The initial plan for vomiting animals is to separate those whose problems are acute and self-limiting from those who require more thorough investigation and treatment. If vomiting is acute and the animal is systemically well, the packed cell volume and total protein can be measured to evaluate hydration status and a faecal examination performed to detect endoparasites. In these patients further diagnostic testing is usually not warranted as vomiting often resolves on its own or after short term symptomatic therapy. If the animal is systemically unwell, has been vomiting for more than a week, or has vomiting associated with hematemesis, bloody diarrhea or abdominal pain a more aggressive work-up is necessary to define the nature of the problem. Most non-gastrointestinal causes of vomiting, and gastrointestinal causes such as a foreign body or intussusception, are usually detected, or ruled out, by taking a detailed history, performing a thorough physical examination, routine laboratory tests (CBC, profile, UA, Faecal and amylase/lipase/TLI- T4, FelV, FIV, ACTH stim. where indicated) and abdominal radiographs. Abdominal ultrasound is useful for detecting pancreatic lesions and confirming GI thickening and sampling masses and parenchymal abnormalities. If these tests are negative or show abnormalities compatible with primary gastric or intestinal disease, endoscopic examination of the stomach and upper duodenum or contrast radiography are the principal diagnostic options. Endoscopy enables detailed examination and sampling of the gastric and duodenal mucosa with minimal patient discomfort and is generally accepted as the best method of evaluating mucosal abnormalities. Radiographic contrast studies (± fluoroscopy) are a good way of examining functional (emptying) disorders of the stomach and the anatomy and patency of the intestinal tract distal to the duodenum. Some patients require both endoscopy and radiography to adequately evaluate their disorder. Table 1. Causes of vomiting
Therapy for vomiting: Patient management should be aimed at detecting, and treating the cause and consequences of vomiting. Parenteral fluid therapy (usually IV) should be tailored to correct dehydration and electrolyte and acid base abnormalities. Dietary alterations in patients with persistent vomiting are NPO for 24-48hrs where vomiting is acute and severe followed by a gradual transition to a bland diet when vomiting decreases. Patients with chronic intermittent vomiting may benefit form a diet which is high in carbohydrate, restricted in fat and moderate in protein as this facilitates gastric emptying and digestion. Limited antigen diets can be employed in patients with chronic intermittent vomiting which is thought to be due to food intolerance. Gastric protectants (e.g. sucralfate) can be used to bind toxins and protect the GI mucosa where vomiting is associated with gastritis or gastric ulceration. Inhibitors of gastric acid secretion (usually H2 antagonists) are used to limit gastric erosion/ulceration in vomiting patients with gastritis / ulceration and those considered at risk of developing GI ulceration (e.g. shock) or esophagitis. Inhibition of gastric acid may also limit the hypochlolraemia and alkalosis which is associated with gastric outflow obstruction. Mucosal cytoprotection with PGE analogs may be beneficial where persistent vomiting is associated with NSAID administration. Antiemetics are indicated in patients with vomiting which is compromising hydration status, affecting electrolyte and acid base balance, and those at high risk for oesophagitis or aspiration pneumonia, and those which are is distressed by repeated vomiting. Surgery is indicated to remove large foreign bodies, treat some causes of pyloric outflow obstruction and to obtain full thickness GI biopsies.
 Pharmacological control of vomiting: The pharmacological control of vomiting involves antagonising the central and peripheral receptors which cause emesis and stimulating receptors which promote ordered gastrointestinal motility. The receptor subtypes involved in vomiting and examples of drugs which are commonly employed in the management of vomiting are summarised below. Drugs which act at these receptors may limit or effect emesis. Some drugs have more than one mechanism of action e.g. Phenothiazines (e.g.chlorpromazine) are antagonists of a1 and a2 adrenergic, H1- and H2-histaminergic and d2-dopaminergic receptors ; Metoclopramide antagonizes D2-dopaminergic and 5HT3-serotonergic receptors and has cholinergic effects on smooth muscle. Antiemetics are contraindicated in patients with gastrointestinal infection or toxicity where they may limit expulsion of the infectious or toxic agent. The side effects of some drugs may also limit their application : phenothiazines may cause hypotension and sedation and decrease the seizure threshold in animals with epilepsy. Non selective cholinergic receptor antagonists (other than the non-available M1 specific antagonist- pirenzipine) e.g. atropine, scopolamine, aminopentamide, isoprpopamide, may cause ileus, delayed gastric emptying and dry mouth. Prokinetic agents e.g. metoclopramide, cisapride, erythromycin are contraindicated where there is a suspicion of intestinal obstruction. Certain antiemetics are not recommended / require caution / are ineffective when used in the cat e.g. ondansetron, metoclopramide, scopolamine, erythromycin, pirenzipine It should be noted that all of the antiemetics except yohimbine are not approved for use in the dog or cat.
Strategies for managing persistent vomiting
 Osmotic diarrhea is considered to arise as a consequence of water retention by unabsorbed substances in the intestinal lumen e.g. secondary to maldigestion or malabsorption. Secretory diarrhea is caused by hypersecretion of fluids and electrolytes by the villus crypts e.g. in response to stimulation by E.Coli, or hydroxylated fatty acids. Permeability diarrhea is characterised by increased leakiness of the intestine due to decreased mucosal integrity or increased intestinal hydrostatic pressure e.g. mucosal inflammation or infiltration may decrease mucosal integrity, whereas lymphatic obstruction or portal hypertension increase hydrostatic pressure. Motility disorders are poorly characterised, but diarrhea is more often a result of decreased segmental motility, rather than hypermotility. Most intestinal disease in dogs and cats involves several patho-mechanisms so attempts to categorise animals presented for the investigation of diarrhea using these criteria are usually redundant.e.g. the accumulation of inflammatory cells within the intestine in response to antigenic challenge and other less well defined stimuli, can exert its effects both directly and indirectly by the production of inflammatory mediators such as prostaglandins and leukotrienes. The net result is abnormal mucosal absorption, secretion, permeability and intestinal motility. General approach The initial plan for animals with diarrhea is to separate those whose problems are acute and self-limiting from those who require more thorough investigation and treatment. Acute diarrhea Patients with acute diarrhea who are bright and alert and are not dehydrated may require no further work-up as signs often resolve on their own or after short term symptomatic therapy. Patients with acute diarrhea who are dull or depressed, febrile, dehydrated, tachycardic or bradycardic or have abdominal discomfort, melaena, haematochezia or frequent vomiting with no specific indication of primary intestinal disease require a work-up to define the nature of the problem Where obvious physical abnormalities such as intestinal masses, thickening or plication, localise the problem to the small intestine the work-up is aimed at determining and treating the cause of the problem using diagnostic imaging, non-invasive biopsy and surgery. Chronic diarrhea Diarrhea which has lasted for 3 or more weeks is considered chronic. The approach to patients with chronic diarrhea is based on the origin of diarrhea - large bowel or small bowel, and the presence of other specific or localising clinical findings. Differentiation is important as the diagnostic and therapeutic approaches to small and large bowel diarrhea are different. Differentiation is made on the basis of information furnished by the owner in response to questions about faecal characteristics, volume and frequency and related signs such as vomiting, weight loss, tenesmus and dyschezia. The diagnostic approach to patients with chronic diarrhea who are unstable or have localising findings e.g.abnormalities on abdominal palpation, is centered around defining and supporting systemic abnormalities and determining the cause with diagnostic imaging and surgery. The approach to patients with chronic diarrhoea who are stable, and have no specific localising clinical findings is targeted on the basis of location - large or small bowel diarrhoea. Chronic diarrhea Small bowel diarrhea is a consequence of diseases which affect the small intestine or related structures such as the exocrine pancreas. Causes of Chronic Small Bowel Diarrhea
Large bowel diarrhea is usually caused by colonic dysfunction. Refer to Large bowel diarrhea notes for DDX, approach, investigations and treatment of disease of the large bowel Patient evaluation and diagnostic approach Signalment Identify the age and breed of the patient - infectious and parasitic diseases are common in young animals, whereas neoplasia and metabolic disorders are more common in middle aged to older animals. Certain conditions are more common in certain breeds e.g. protein losing enteropathies in the Lundehund and Soft Coated Wheaten Terrier. History - Presenting complaint/s e.g. diarrhoea, vomiting, weight loss - Duration of complaints - when was the patient last normal? - Character of the presenting complaint/s - nature of the diarhhoea or vomitus e.g. amount, colour, contents, blood, tenesmus - onset, frequency, severity and progression of signs - weight loss or change in appetite - Diet - type and amount, any changes? - Access to foreign bodies or toxins - Vaccination status - Husbandry - indoor or outdoor, supervised?, kennelled?, other pets - Past medical history including treatment and response. - Systems review Appetite, defaecation (formed/diarrhoea), vomiting or regurgitation, water intake and urination, coughing or sneezing, oculonasal discharges, exercise tolerance, changes in muscle mass or weight, changes in haircoat, changes in behaviour, sexual activity Characterise diarrhea as small or large bowel
Small or Large Bowel Diarrhea?
Small bowel diarrhoea is also more commonly associated with failure to thrive, changes in appetite, borborygmi, flatus, abdominal discomfort, ascites and oedema than large bowel diarrhoea. Physical examination Particular attention should be paid to hydration status and examination and palpation of as much of the gastrointestinal tract and abdomen as possible.The thyroid gland should be palpated in cats >6yo. A thorough rectal examination should be performed in all dogs with clinical signs of intestinal disease to examine stool consitency, detect occult melaena and determine the presence of non-gastrointestinal causes of tenesmus such as perineal hernia or prostatomegaly. Interpretation of clinical signs and physical abnormalities Clinical signs Diarrhea accompanied by weight loss suggests malabsorption of nutrients is severe or chronic. Weight loss or failure to thrive without diarrhoea can be caused by small intestinal disease. Vomiting is a common consequence of inflammation or obstruction of the intestine. Abdominal discomfort is often noted in animals with inflammatory, obstructive and erosive disorders of the small intestine. Fresh or digested blood (hematochezia or melena) in feces can occur in inflammatory and erosive or ulcerative small intestinal diseases. A combination of vomiting, diarrhea, abdominal pain and haematochezia is common in patients with infectious enteritis. Excessive borborygmi are suggestive of malabsorption or maldigestion of nutrients. Coprophagia and pica may be observed in chronic intestinal disorders and exocrine pancreatic insufficiency. Polyphagia is common in dogs with exocrine pancreatic insufficiency and cats with hyperthyroidism. Anorexia or inappettance often accompany inflammatory, obstructive or neoplastic disorders. Ptyalism is common in cats with orally anchored linear foreign bodies and portosystemic vascular anomalies. Interpretation of physical findings in animals with signs of gastrointestinal disease
Investigation of chronic small bowel diarrhea Initial investigations consist of fecal analysis, CBC, profile, urinalysis, serology and hormone analysis where indicated. Choices of other diagnostic tests such as radiography, ultrasound, endoscopy, intestinal biopsy and tests of pancreatic and intestinal function are made on the basis of clinical and clinicopathological findings. The approach to patients with chronic small bowel diarrhea who are stable, have no specific localising clinical findings and are negative for faecal parasites is usually to:
In patients with chronic vomiting, abdominal discomfort, dullness or marked clinicopathological abnormalities the differential diagnosis of these other problems is considered and the diagnostic emphasis is often on abdominal radiographs or ultrasound to define the relationship of these problems to the intestines. Where melaena is present metabolic status should be evaluated to detect diseases associated with GI ulceration (renal disease, hepatic disease, hypoadrenocorticism). Causes of melena Ingestion of blood oral, nasal, pharyngeal, pulmonary bleeding Gastrointestinal erosion/ulceration
Coagulopathies thrombocytopaenia, factor deficiencies, D.I.C. The complete blood count should detect anemia, microcytosis or thrombocytopenia. A reticulocyte count and tests of haemostasis may be required to determine the cause of the anemia and melena. Radiographs, ultrasound, endoscopy or intestinal biopsy are employed to localise the site and cause of gastrointestinal bleeding.  Laboratory evaluation of chronic small bowel diarrhoea Faecal analysis Giardia (trophozoites, cysts), Coccidia, other endoparasites. Faecal analysis for Clostridial endospores (> 5 spores/HPF) and enterotoxins may be helpful in confirming the presence of Clostridial an their toxins. Faecal culture for Salmonella in animals with bloody stools, or fever, or chronic undefined diarrhoeaFaecal culture cannot be used to diagnose small intestinal bacterial overgrowth. Undigested or unabsorbed fat and starch are detected in faeces using Sudan stain or Lugol's iodine respectively. These tests are useful for determining if maldigestion or malabsorption is occurring but are not reliable for differentiating their cause. Quantitative analysis of faecal fat on 72 hour faecal collections is cumbersome and restricted to research centres. The analysis of faeces for blood can be useful for determining the cause of anaemia where obvious blood or melaena are absent. Faecal blood can be detected using appropriate detection system. These tests are usually very sensitive and the patient must be on a meat free diet for 72hrs prior to interpretation. Drugs such as cimetidine may cause false positive test results. Tests to detect faecal proteolytic activity in dogs with chronic small bowel diarrhoea have been superseded by the assay of Trypsin-Like Immunoreactivity (TLI). Determination of faecal proteolytic activity using radial diffusion is useful in distinguishing exocrine pancreatic insufficiency in cats with small bowel diarrhoea, though fTLI has now been established. An assay to detect alpha-1 antitrypsin in faeces is under development for quantitating intestinal protein loss. Hematology Anemia - Microcytosis (MCV < 63fl), decreased red cell haemoglobin and thrombocytosis are common in dogs with iron deficiency secondary to GI blood loss from intestinal parasites or tumours (Ddx portosystemic vascular anomalies or fibrosing liver disease in young dogs with signs of gastrointestinal disease). Macrocytosis (MCV> 53fl) may be observed in cats with hyperthyroidism and FeLV. Eosinophilia may be suggestive of intestinal parasitism, mast cell tumours, hypoadrenocoticism, eosinophillic enteritis or hypereosinophilic syndrome. Neutrophilia ± a left shift may be encountered in inflammatory or infectious conditions. Lymphopaenia is commonly associated with stress, protein losing enteropathies and immunodeficiency. Serum Biochemistry Detect non-intestinal diseases which cause gastrointestinal signs i.e. kidney disease, renal disease, hypoadrenocorticism. Metabolic consequences of diarrhoea ± vomiting e.g. hypokalemia, hyponatremia. Hyperkalaemia combined with hyponatremia suggests that an ACTH stimulation test should be performed to detect hypoadrenocorticism or pseudo-hypoadrenocorticism associated with Salmonella / whip worms / GI ulderation. Mild to moderate increases in liver enzymes such as ALT (up to 500 IU/l) are common in cats with hyperthyroidism and cats and dogs with intestinal disease. Hypocholesterolaemia is often observed in dogs with protein losing enteropathy, EPI and other chronic enteropathies. Plasma bile acids and ammonia are useful for detecting liver dysfunction or shunting in dogs with GI signs. Hypoglycaemia in dogs or cats with signs of gastrointestinal disease should arouse the suspicion of sepsis, liver disease, hypoadrenocorticism or pancreatic tumour. Hypoalbuminemia + hypoglobulinemia R/0 protein losing enteropathies Hypoalbuminemia with normal or increased globulin concentration has to be distinguished from protein losing nephropathies and liver disease. Chronic diarrhea associated with hypoalbuminaemia usually requires intestinal biopsy to define the cause of protein losing enteropathy. Non-intestinal causes of protein losing enteropathy such as congestive heart disease, caval obstruction or portal hypertension should also be considered. When globulin concentratiouns are normal or elevated renal and hepatic causes should also be pursued. Protein losing enteropathies
Urinalysis A urinalysis is performed to aid in the interpretation of serum urea and creatinine and as part of a baseline evaluation to detect or rule out urogenital disorders in patients with signs of intestinal disease. Urate crystalluria may prompt the investigation of hepatic dysfunction as a cause of clinical signs. In the presence of an inactive urine sediment the urinary protein creatinine ratio is useful for determining if the kidney is involved in the development of hypoalbuminaemia in patients with intestinal signs. Serology and hormone assays T4should be measured in cats (>6yo) with chronic diarrhoea. FIV and FeLV status should be evaluated where the potential for infection with these agents exists. ACTH stimulation test is used to confirm hypoadrenocoticism or pseudohypoadrenocorticism where this is suspected from serum biochemistry. An ACTH stimulation test may also be used to screen for atypical hypoadrenocorticism (pituitary dependant) in patients with unexplained chronic diarrhea or eosinophilia. Serology for Histoplasma particularly in dogs from endemic areas with chronic diarrhea, PLE and weight loss - examine for GI thickening, chorioretinitis, lung changes, lymph node enlargement - GIT espy, hepatic involvement, bone marrow. Tests of pancreatic function Pancreatic function tests are most commonly employed in dogs with chronic diarrhea who are bright and alert with few signs other than chronic diarrhea, occasional vomiting, weight loss or polyphagia and normal to mildly abnormal clinicopathologic tyest results. Tets of faecal proteolytic activity and intestinal chymotrypsin activity (BT-PABA) have been largely superceded by the assay of trypsin-like immunoreactivity (see notes on exocrine pancreatic insufficiency) Trypsin-like immunoreactivity (TLI) is a sensitive and specific test for detecting exocrine pancreatic insufficiency (TLI <2.5µg/l) in the dog and is performed in dogs with chronic small bowel diarrhea. It may also be useful in detecting pancreatitis in dogs with abdominal pain. The TLI assay is species specific and a cat specific assay has recently been developed and is undergoing evaluation in cats. Exocrine pancreatic insufficiency is extremely rare in cats and is usually associated with chronic diarrhea and polyphagia, and can be detected by assaying faecal proteolytic activity or the newly developed fTLI test (TLI = 8µg/l). Diagnostic imaging Radiographs and ultrasound are low yield in many patients with chronic diarrhoea but are performed to screen for partial obstructions caused by intussusceptions, tumours or foreign bodies, to evaluate intestinal thickness and to detect mesenteric lymphadenopathy and concurrent abnormalities of the liver, kidney and spleen. Radiography Survey abdominal radiographs are often unhelpful in patients with chronic diarrhoea or abdominal effusions but provide a broad picture of the target area and are a prelude to ultrasonographic evaluation of specific areas. Contrast radiography is useful in evaluating disorders associated with delayed gastric emptying and detecting intestinal lesions between the upper duodenum and ileo-ceco-colic valve which are not accessible by endsocpy. The use of barium impregnated pellets may prove to be useful for the detection of partial small intestinal obstructions. Endoscopy has superseded contrast radiography for the investigation of mucosal lesions of the stomach, duodenum and large bowel. Ultrasonography Ultrasound is particularly useful for detecting intestinal lesions such as intussusceptions, masses and foreign bodies, and for assessing intestinal wall thickness. The results of radiography and ultrasound provide a rational basis for selecting endoscopic biopsy (±duodenal juice analysis) or a laparotomy. Normal or diffusely thickened intestines can initially be evaluated endoscopically while focal lesions usually require guided aspiration or laparotomy. Tests of intestinal function When a clinical problem cannot be adequately defined or localised to the small intestine a variety of tests can be used to assess small intestinal function. Intestinal function tests have the potential benefit of allowing an overall assessment of small intestinal function, rather than the small snapshot provided by a biopsy. Before undertaking these tests it should be stressed that most of them have not been adequately characterised or validated in dogs and cats and should be regarded as an adjunct to other diagnostic procedures. They should always be critically evaluated in the context of the whole patient. Cobalamin and folate The measurement of circulating concentrations of cobalamin and folate may give an indication of the site and cause of intestinal dysfunction in dogs. The use of cobalamin and folate concentrations as an indirect indicator of intestinal disease has not been reported in the cat, though cobalamin deficiency may occur in cats with exocrine pancreatic disease, and IBD / lymphoma (personal observation). Plasma concentrations of cobalamin and folate are labile and reflect the balance between dietary intake, bacterial utilisation and production, and intestinal absorption and body losses. Factors influencing serum concentrations of cobalamin and folate
Low serum cobalamin concentrations have been observed in dogs with EPI, severe intestinal disease and apparent idiopathic small intestinal bacterial overgrowth (SIBO) (please refer to the section on SIBO). Cobalamin deficiency has been recognised in Giant Schnauzers with inappettance and failure to thrive with laboratory findings of anaemia, leukopaenia and methyl-malonyl aciduria. These abnormalities appear to be a consequence of the defective synthesis of the ileal cobalamin-intrinsic factor receptor and are completely reversed by the parenteral administration of cobalamin. Some Sharpeis also appear to have a deficiency of cobalamin. The physiological significance of the low cobalamin concentrations detected in other gastrointestinal diseases has not been reported. Low serum folate concentrations have been observed in dogs with severe jejunal disease and some Irish Setters with a gluten-sensitive enteropathy. High folate concentrations have been reported in experimentally induced SIBO (blind loops), EPI, German Shepherds with apparent SIBO and some Irish setters with a gluten-responsive enteropathy. Plasma cobalamin and folate concentrations may also be affected by dietary content, supplementation and certain medications e.g. sulphasalazine. The interpretation of circulating cobalamin and folate concentrations with regard to small intestinal disease is only valid if exocrine pancreatic insufficiency, dietary supplementation, parenteral administration have been excluded and attention is paid to dietary vitamin content. In my experience the finding of a low folate or low cobalamin concentration is useful in supporting the presence of an intestinal problem. Where low cobalamin is detected and EPI, intestinal obstruction and presumed idiopathic SIBO have been excluded localisation of the problem to the ileum can be inferred. Cobalamin and folate are insensitive indicators of SIBO (see section on SIBO). The combination of low cobalamin and high folate is more suggestive of idiopathic SIBO than finding increased folate alone. Concomitant increases in folate and cobalamin are more consistent with high dietary intake or supplementation than SIBO. Finally, normal serum concentrations of cobalamin and folate neither exclude nor support a diagnosis of intestinal disease. Breath hydrogen The measurement of hydrogen in breath samples obtained from dogs and cats gives an indication of hydrogen production by intestinal bacteria. By sequentially determining hydrogen after a test meal information on the site and amount of bacterial hydrogen production within the intestine can be inferred. This technique has proved valuable in the investigation of intestinal transit time and dietary digestibility in dogs and cats ; significant hydrogen production in healthy animals occurs when the test meal is metabolised to hydrogen by colonic bacteria. This test may also be used to determine if small intestinal bacterial overgrowth (SIBO) is present ; the detection of a double peak of hydrogen is considered suggestive of SIBO. An early single peak, rather than a double peak, may be more consistent with rapid intestinal transit than SIBO. At this time it is prudent to regard breath hydrogen testing as experimental until test meals, collection procedures and data interpretation have been optimised and standardised for dogs and cats. Tests of intestinal absorption, permeability and protein loss The measurement of xylose in plasma or urine after an oral dose has been used to evaluate intestinal absorption in dogs and cats. This test was largely abandoned in dogs when the development of the TLI assay enabled accurate discrimination of exocrine pancreatic insufficiency and small intestinal disease. Xylose absorption in cats was never adopted due to the small amount absorbed in normal cats. The measurement of the urine concentrations of xylose and other sugars such as lactulose, rhamnose and 3-methyl glucose after an oral dose has been used to evaluate intestinal absorption and leakiness (permeability) in humans. These tests purport to give information on both the capacity and the route of sugar absorption (cellular or paracellular) by measurement of the total amount or proportion of sugars to each other in urine after an oral dose. Sugar permeability tests have been recently evaluated in dogs and cats with intestinal disease. These tests may be useful for characterising the nature of intestinal damage and assessing its recovery following treatment. They may be particularly applicable to the study of ill-defined conditions such as dietary enteropathies and inflammatory bowel disease. The analysis of sugars is by HPLC and is restricted to specialised laboratories. Clinical adoption of these techniques requires the establishment of appropriate control ranges and evaluation of permeability in a variety of intestinal and non-intestinal complaints. Thus permeability must at present be regarded as experimental rather than clinical. The excretion of 51Cr EDTA in urine has also been used to evaluate intestinal permeability (leakiness) in dogs. The faecal excretion of 51Cr EDTA albumin after intravenous administration has been used to evaluate protein loss in dogs. As this compound is radioactive clinical application has been limited. A non-radioactive indicator of intestinal protein loss would be useful for diagnosing and monitoring protein losing enteropathies. Preliminary investigations suggest that the measurement of faecal concentrations of alpha-1-protease inhibitor may be useful in this respect, but further results are required before clinical application. Intestinal Biopsy Biopsy of the intestine is frequently required to achieve a diagnosis in patients with chronic diarrhea due to malabsorption. In diffuse intestinal diseases and in animals with hypoproteinaemia endoscopy provides a minimally invasive low risk way of obtaining a biopsy. Utility of Endoscopy for investigation of small intestinal abnormalities Helpful Inflammatory bowel disease Duodenal Ileocaecocolic disease Unhelpful Motility/functional disorders Jejunal lesions Proximal ileal lesions Duodenoscopy also enables duodenal juice to be collected for analysis. Sterile tubing can be passed down the biopsy channel and duodenal juice aspirated for microscopic evaluation and quantitative bacteriology. Quantitative bacterial culture is widely considered to be the best method of determining if intestinal bacterial overgrowth is a potential cause of signs of intestinal disease in dogs. Small intestinal bacterial overgrowth has not been identified in cats. The specialised sample handling requirements and culture techniques required for duodenal juice have restricted its use to a few referral centres. Duodenal aspirates can also be evaluated for the presence of parasites such as Giardia, though isolation rates are less consistent than 3 faecal flotations. Endoscopic biopsies are, however, restricted to the mucosa and are small, difficult to process and orientate, and can be obtained only from the proximal duodenum and occasionally the distal ileum. Thus surgical biopsies are necessary in patients with focal intestinal lesions and in those whom endoscopic biopsy has not yielded a result. Surgical biopsies should be taken from multiple sites along the small intestine even if the intestine looks grossly normal. A small dermatologic punch aids the surgeon in obtaining full thickness biopsies and biopsy sites are sutured in an appropriate fashion. Extreme care is required where the bowel looks grossly abnormal and in hypoproteinaemic patients to ensure leakage does not occur. Precautionary measures such as serosal patch or omental wraps are indicated Biopsies of mesenteric lymph nodes should also be obtained. Other abdominal organs such as the liver, and pancreas can be grossly examined and biopsies obtained if necessary. The information which can be obtained from intestinal biopsies depends on the expertise of the pathologist. Minimum evaluation should include routine microscopic examination of H&E stained sections. In surgical biopsies the pathologist should be able to give an indication of villus height, ratio of crypt to villus and the type and degree of cellular infiltrate and intraepithelial lymphocyte count. Staining for different lymphocyte sub-types, assessment of marker enzymes, electron-microscopy and mucosal enzymology are restricted to specialist centres, but may be useful in sub classifying intestinal disorders. CHRONIC DIARRHOEA DUE TO SMALL INTESTINAL DISEASE IDIOPATHIC INFLAMMATORY BOWEL DISEASE Idiopathic inflammatory bowel disease is the term used to describe a diverse group of intestinal disorders which are characterised by cellular infiltrates of the intestinal mucosa. Diagnosis is based on the description of histological findings in intestinal biopsies and the exclusion of known causes of intestinal inflammation e.g. endoparasites, dietary sensitivity. The most common inflammatory infiltrates are lymphocytes and plasma cells or eosinophils. Neutrophils or granulomatous inflammation are encountered less commonly. Lymphoplasmacytic enteritis Lymphoplasmacytic enteritis is the most common type of inflammatory bowel disease in dogs and cats. It is characterised by the accumulation of excessive numbers of lymphocytes and plasma cells in the lamina propria of the intestine. The degree of cellular accumulation is variable and is subjectively categorised as mild, moderate and severe. Moderate to severe lymphoplasmacytic enteritis is often associated with a protein losing enteropathy. A severe form of the condition has been reported in Basenjis. The extent of inflammation appears variable and ranges from the duodenum to the small and large bowel. Clinical findings Chronic small bowel diarrhea accompanied by weight loss or vomiting are the most frequent findings in dogs whereas vomiting is the most common clinical sign in cats. Vomitus often contains bile. Hairballs are frequent in cats. Other findings include changes in appetite, excessive borborygmi and abdominal discomfort. The severity of disease is variable, ranging from intermittent diarrhoea and vomiting in mild cases to intractable small bowel diarrhea, inappettance and weight loss in severe ones. The severity of the disease is thought to reflect the degree of cellular infiltrate. Physical findings range from normal to thickened intestines ± mesenteric lymphadenopathy, marked weight loss, and ascites or oedema in animals with severe protein losing enteropathy. Diagnosis A diagnosis of idiopathic lymphoplasmacytic enteritis is made by excluding systemic, parasitic, infectious, pancreatic and structural causes of chronic diarrhoea and demonstrating excessive numbers of lymphocytes and plasma cells in intestinalbiopsies. Where vomiting is the presenting complaint gastric disorders must also be excluded. There are no specific clinicopathological changes associated with lymphoplasmacytic enteritis. Hypoproteinaemia associated with low albumin and globulin may be apparent in dogs, but is rare in cats. Low albumin may be associated with normal to raised globulin, particularly in Basenjis. Leukocytosis may be present in some animals. Survey radiographs are normal but ultrasound may reveal diffuse thickening, mesenteric lymphadenopathy or small abdominal effusions in severe cases. Intestinal function tests are usually by-passed in patients with localising signs such as intestinal thickening or mesenteric lymphadenopathy and hypoproteinaemic patients in favour of endoscopic or surgical biopsy.The degree of lymphoplasmacytic infiltrate in intestinal biopsies is classified as mild moderate or severe. Villus atrophy is usually minimal. Severe villus atrophy and lymphoplasmacytic infiltrate is common with lymphosarcoma and has also been encountered in some dogs with an enteropathy that resembles chronic tropical sprue in man. Treatment Treatment is based on the degree of cellular infiltrate and associated clinical and clinicopathological findings. Mild to moderate intestinal inflammation may be associated with dietary sensitivity or intolerance, or potentially idiopathic small intestinal bacterial overgrowth. A therapeutic trial with a highly digestible diet which is restricted in fat, gluten-free and limited to a single protein source may be undertaken to determine if dietary sensitivity or intolerance are present. Up to six weeks may be required to see a response. Similarly a therapeutic trial (21days) with Tylosin (10mg/kg PO TID), metronidazole (15mg/kg PO BID) or oxytetracycline (10-20mg/kg PO TID) for small intestinal bacterial overgrowth may be warranted. Dietary modification is seldom effective in cats with LPE and idiopathic SIBO has not been recorded in cats. In patients who fail this trial and those with moderate to severe infiltrates, or hypoproteinaemia the administration of immunosuppressive agents is often required to achieve a response. Oral prednisolone (1-2mg/kg PO BID) is the initial drug of choice. It is usually administered at an immunosuppressive dose for 2-3 wks and then decreased by 50% every 2-3wks and then continued on an alternate day basis for 2-3 months. If clinical response is poor or the adverse effects of prednisolone predominate azathioprine can be added to the regimen. In dogs it is usually given every day (2mg/kg PO SID) for five days and then on alternate days to prednisolone. Cats are more sensitive to azathioprine and the dose is 0.3mg/kg PO SID. the white cell count should be monitored every 2-4wks when azathioprine is being given. Metronidazole (15mg/kg PO BID 10-14d then SID 10-14d) can also be used in conjunction with corticosteroids and has effects on bacteria and the immune system. Successful treatment is accompanied by a decrease in clinical signs and an increase in plasma proteins. Once an a patient has had 2-3 months remission from signs it may be possible to gradually withdraw immunosuppressive therapy. If signs recur daily medication is continued until signs resolve then gradually reduced. in patients who respond poorly to therapy or relapse after an initial response Lymphosarcoma should be ruled out. Prognosis The prognosis for lymphoplasmacytic enteritis is variable and depends on its severity. Many patients require prolonged treatment with glucocorticoids and diet. As no accurate criteria exist for predicting response it is wise to give a guarded prognosis. Eosinophilic enteritis Eosinophilic enteritis is characterised by the excessive accumulation of eosinophils in the lamina propria. It is speculated that it may result from an immunologic reaction to parasites or diet. the disease may also involve other areas of the gastrointestinal tract. Clinical findings Chronic small bowel diarrhoea accompanied by vomiting or weight loss are the principal clinical signs. Large bowel signs or vomiting predominate in some cases. Physical findings range from normal to focally or diffusely thickened intestines and marked weight loss. Diagnosis The diagnosis of eosinophillic enteritis is achieved by adopting a similar approach to that described for lymphoplasmacytic enteritis (see above). Clinicopathologic abnormalities may include peripheral eosinophilia. Mast cell neoplasms, hypoadrenocorticism and endoparasites can produce a similar spectrum of clinical signs and should be ruled out. The degree of eosinophilia can be extreme in cats and may be associated with eosinophillic infiltrates in the spleen, liver, lymph nodes and bone marrow. Intestinal protein loss is less common than lymphoplasmacytic enteritis. Treatment Some patients may respond to a strict exclusion diet, though prednisolone (2mg/kg PO SID) is usually required. In dogs signs usually resolve within a couple of weeks and prednisolone can be tapered. Feeding an easily digestible diet which is restricted to a single novel protein source may help to maintain clinical remission. Prophylactic administration of an anthelminthic such as fenbendazole (50mg/kg PO SID 3 days) is warranted to treat potential visceral larval migrans which has been associated with eosinophilic gastroenteritis. Cats with hypereosinophillic syndrome often respond very poorly to treatment with immunosuppressive agents, diet and anthelminthics. Prognosis The prognosis is guarded as relapse is common. The prognosis in cats with hypereosinophilic syndrome is poor. Other inflammatory enteropathies Other enteropathies which are characterised by neutrophilic or granulomatous inflammation have also been described infrequently small animals. Some of these may be associated with bacterial infections such as Streptococcus, Campylobacter, Yersinia and Mycobacteria and fungal infections such as Histoplasma. Special stains and culture of mucosal biopsies and intestinal lymph nodes and other abdominal organs should be undertaken in cases of granulomatous enteritis to detect infectious organisms. Serology,chest radiographs and bone marrow biopsies may help to diagnose systemic fungal disease.The prognosis for idiopathic granulomatous or neutrophilic enteropathies is guarded to poor. LYMPHANGIECTASIA
Intestinal lymphangiectasia is characterised by the abnormal distension of lymphatic vessels within the mucosa. Lymphangiectasia is a consequence of a localised or generalised lymphatic abnormality or increased portal pressure e.g. right sided heart failure, caval obstruction or hepatic disease. Lymphatic abnormalities are often associated with lipogranulomatous inflammation which is visible as small white granules on the intestinal mesentery. Tumour infiltration of lymphatics or lymph nodes can also cause lymphangiectasia. In some cases lymphangiography reveals a generalised lymphatic abnormality. Dilatation of lymphatics is associated with the exudation of protein rich lymph into the intestine and severe malabsorption of long chain fats. Yorkshire Terriers and Soft Coated Wheaten Terriers and the Lundehound seem to be over represented, suggesting a possible familial cause in some dogs. Clinical findings Intestinal lymphangiectasia is fairly common in dogs, but rare in cats. The clinical findings are essentially a consequence of the intestinal loss of protein and range from weight loss to chronic diarrhoea, ascites, oedema and chylothorax. Diagnosis A diagnosis of protein losing enteropathy is initially suspected on the basis of clinical findings associated with panhypoproteinaemia. Hypocholesterolaemia and lymphopaenia are common findings. in lymphangiectasia. Renal protein loss and decreased hepatic function should be excluded when diarrhoea is absent or only albumin is decreased. Survey abdominal radiographs are usually unhelpful. Chest radiographs enable the detection of pleural fluid. Ultrasonography may reveal diffuse intestinal thickening and enable aspiration of mesenteric lymph nodes if enlarged and collection of subclinical abdominal effusions for analysis. Diagnosis requires mucosal biopsy to differentiate lymphangiectasia form other protein losing enteropathies. Endoscopic biopsies are often adequate. Surgical biopsy should be undertaken carefully with appropriate precautionary measures for dehiscence. Treatment The cause of lymphangiectasia is usually not determined. Treatment is usually supportive and symptomatic. Dietary recommendations are the similar to those for other patients with small bowel diarrhoea, but fat restriction may have to be more severe. Medium chain triglyceride (MCT oil, coconut oil 0.5-2ml/kg body weight per day added to food) is usually added to the diet to provide an easily assimilable source of calories. Prednisolone is often necessary (1-2mg/kg PO BID) and may work by decreasing lipogranulomatous inflammation. Prednisolone is tapered to the lowest effective dose once remission is achieved. Adjunct therapy with metronidazole or tylosin can also be given. Prognosis The response to therapy is variable with some patients staying in remission for several years while others pursue a path towards fulminant hypoproteinaemia. The prognosis is always guarded. SMALL INTESTINAL BACTERIAL OVERGROWTH
Small Intestinal Bacterial Overgrowth Small intestinal bacterial overgrowth (SIBO) = an abnormal accumulation of bacteria in the small bowel. The intestinal flora of healthy dogs and cats Humans have total bacterial counts less than 5 (log10 cfu/ml or gram) small intestinal juice/tissue and anaerobic bacterial counts less than 4 5 (log10 cfu/ml or gram). Gram positive aerobic bacteria such as Streptococci and Staphylococci predominate; anaerobic bacteria such as Clostridia and Bactericides are extremely uncommon. Those findings in humans are not applicable to healthy dogs and cats. At least 24 papers have been published which describe the small intestinal bacterial flora of healthy dogs or cats. The majority of studies indicate that both the healthy dog and cat harbor a large number of diverse bacteria in the small intestine. The total bacterial counts in the proximal small intestine of healthy dogs ranges from 0-9.43 (log10 cfu/ml or gram) and anaerobes from 0 to 8.18 (log10 cfu/ml or gram). Similarly cats have total duodenal bacterial counts ranging from 2 to 8.3 (log10 cfu/ml or gram), and anaerobic bacteria from 2 to 8.05 (log10cfu/ml). Common aerobic bacterial species in dogs and cats include Streptococcus species, Staphylococcus spp, Bacillus spp, Escherichia coli, Corynebacterium spp, Enterobacter cloacea, Pseudomonas spp, and Pasturella multocida. Clostridium spp, Bifidobacterium spp, Eubacterium spp and Bacteroides spp are common anaerobes. Lactobacillus spp, are also common. Differences in environment, diet, age of the animals, breed, culture technique and country of origin may potentially account for the variation in the numbers and type of flora reported in healthy dogs and cats.
Small Intestinal Bacterial Overgrowth in humans The syndrome of SIBO in humans is characterized by a variety of clinical signs including steatorrhea, weight loss, anorexia, abdominal pain, vomiting, anemia, and malnutrition due to carbohydrate, fat, protein or vitamin malabsorption. It is also called the blind loop, stagnant loop or stasis syndrome due to the frequent association of anatomic abnormalities of the GI tract with overgrowth of indigenous microbes. The syndrome was first described in the 1890's when an association between intestinal strictures and anemia was described. Factors influencing the bacterial population of the small intestine Intestinal obstruction: foreign objects, strictures, tumors or intussusception, and surgical procedures can create an area of stasis or blind loop in the intestine which leads to the proliferation of enteric bacteria Disordered motility/ pseudoobstruction: Neurological diseases such as diabetic neuropathy, scleroderma or an abnormal interdigestive motility pattern can disrupt the normal peristaltic movements of the gut leading to bacterial colonization Decreased gastric acidity : is considered a major defense of small bowel colonization, and bacterial overgrowth can occur secondary to gastric achlorhydria from gastritis, surgical procedures or drugs such as H2-receptor antagonists. However It is noteworthy that selective vagotomy in dogs decreases gastric acid secretion, but does not cause intestinal bacterial proliferation. This observation suggests that the cause of bacterial proliferation in dogs with gastric resection may be procedure, rather than acid related. Increased substrate availability: intestinal mucosal diseases, which cause malabsorption or maldigestion, would be expected to cause an increase in substrate availability Exocrine pancreatic insufficiency: The pancreas is also considered influential in limiting intestinal bacteria due to it's effects on substrate availability and the bacteriostatic/cidal peptides normally present in pancreatic secretions. Removal of the ileocecocolic region: Experimental studies in dogs have shown higher numbers of small intestinal bacteria and steatorrhea in animals when the ileocecal valve is surgically removed Idiopathic SIBO : While SIBO is most often secondary, it has been suggested that primary or idiopathic SIBO occur in people and dogs. However, more recent studies in people have revealed that neuromuscular or vascular disorders causing motility dysfunction may underlie some of these idiopathic cases. SIBO in dogs and cats The syndrome of small intestinal bacterial overgrowth has been used to describe patients with signs such as diarrhea and weight loss that are associated with a gastrointestinal abnormality which is considered to cause small intestinal bacterial proliferation. It has also been applied to patients with similar clinical signs without an obvious cause for bacterial proliferation that respond to antibiotics. The literature on the normal flora of dogs and cats indicates that SIBO can be defined as: bacterial counts > 9.43 (log10 cfu/ml or gram) in dogs, > 8.3 (log10 cfu/ml or gram) in cats OR anaerobic bacterial counts > 8.18 (log10cfu/ml or gram) in dogs, > 8.05 (log10 cfu/ml or gram) in cats. Interestingly a disease, which fulfills those criteria, has yet to be described in the dog and cat. Diseases other than SIBO which may improve with antibiotic therapy
Reports of secondary SIBO in dogs and cats The initial descriptions of SIBO in dogs describe a clinical syndrome characterized by chronic diarrhea or steatorrhea, similar to humans with SIBO, in dogs with experimental blind loops, truncal vagotomy, gastric achlorhydria and congenital intestinal anomalies. A report of suspected SIBO caused by gastric achlorhydria was published in 1981. The dog was an adult Basenji presented with a history of garbage ingestion followed by weight loss and diarrhea. It was hypoalbuminemic, anemic and had a fasting gastric pH of 7. This dog was considered to have SIBO secondary to achlorhydria induced by gastritis- but SIBO or achlorhydria was never adequately confirmed. Interestingly this patient is very similar to Basenji dogs with immunoproliferative small intestinal disease in which clinical signs resolve when they are treated with antibiotics. It is suspected that clinical signs in affected Basenjis are related to a loss of tolerance to a normal bacterial flora rather than bacterial overgrowth per se (Lothrop CD personal communication). None of these early investigators established a control range for the intestinal flora of healthy dogs and most relied on values derived in humans (total bacteria >5 (log10 cfu/ml)/ml). Small intestinal bacterial overgrowth was subsequently diagnosed in dogs with exocrine pancreatic insufficiency (EPI). SIBO was based on a cut-off value >5 (log10 cfu/ml). The bacterial flora of dogs with EPI created by pancreatic duct ligation increases after the induction of EPI but returns towards baseline after supplementation with pancreatic enzymes. These observations suggest that increases in bacterial numbers in EPI are a consequence of increased substrate availability secondary to EPI. It is interesting to note, that the bacterial counts in this paper did not exceed 6.4(log10cfu/ml) and antimicrobials were not needed to control clinical signs. Most dogs with naturally acquired EPI respond to treatment with enzyme supplementation and do not require antibiotics. However, some dogs need, and respond to, antibiotic therapy. In those dogs the balance between damage and repair is altered by EPI- Increased degradation of microvillar enzymes by the increased (relatively) bacterial flora vs. decreased degradation by pancreatic enzymes in the face of decreased synthesis of microvillar enzymes. Does idiopathic SIBO occur in dogs and cats? In 1983 Batt et al. described small intestinal bacterial overgrowth in German Shepherd dogs which had no obvious underlying cause of SIBO. This study compared bacterial counts from German Shepherd dogs with diarrhea, with those obtained in six healthy dogs. Those investigators proposed that SIBO was present based on the presence of >5 (log10 cfu/ml) of bacteria in dogs with diarrhea. Unfortunately the intestinal fluid aspirated from the dogs was variably diluted or frozen before culture. The abnormal clinical signs and the associated intestinal mucosal changes in affected dogs were responsive to antibiotic therapy, suggesting that the bacterial flora was an important cause of the diarrhea. However, whether the clinical signs were caused by excessive numbers of bacteria or an enteropathy which renders the intestine more susceptible to damage by a normal flora, is unresolved. Subsequent investigators have used the cut-off value described by Batt et al., despite clear evidence indicating higher bacterial numbers in healthy dogs and cats. Further confusion over the reality of idiopathic SIBO in dogs was caused by a report which described a group of healthy GSD with duodenal bacterial counts >5 (log10 cfu/ml) as having SIBO. The authors explicitly stated that 'All dogs appeared clinically normal" and '...one would not expect that these dogs had alimentary tract disease by observing or working with them.' The lack of clinical signs in these dogs is in stark contrast to the syndrome of SIBO in humans, experimental animals, and the GSD originally described by Batt et al. that was characterized by diarrhea, weight loss and altered concentrations of cobalamin and folate. The authors refuted the suggestion that they had cultured intestinal fluid from healthy dogs. More recently in a study of 107 dogs, 52 were diagnosed as having idiopathic SIBO (intestinal bacteria greater than >5 (log10 cfu/ml)) and no identifiable underlying cause. Such a high prevalence of idiopathic SIBO serves to further question the validity of the 5 (log10 cfu/ml) cut-off vale for the diagnosis of SIBO. To resolve this confusion:
Indirect tests to diagnose SIBO: The high numbers of bacteria in the small intestine of dogs and cats will affect the interpretation of indirect tests such as Breath hydrogen, Serum deconjugated bile acids, Serum cobalamin and folate concentrations and Intestinal permeability. This is not surprising when one considers the inherent differences between germ free animals and those with a normal flora. It should be anticipated that many normal dogs and cats would have test results resembling those of humans with SIBO. Extrapolation from human reference ranges, based on a normal flora < 5 (log 10 cfu/ml) is inappropriate. It is critical that indirect tests are initially evaluated in substantial numbers of healthy patients and cut-off values for each test, and reference ranges for bacterial numbers for the sample collection and culture technique employed, are established. Treatment Treatment of suspected SIBO is directed at correcting underlying anatomic or structural abnormalities, treating EPI, and controlling the abnormal flora with antibiotics. Suitable antibiotics include oxytetracycline (20mg/kg TID PO), tylosin (10mg/kg TID PO), or metronidazole (15 mg/kg BID PO). In dogs with idiopathic SIBO/ intolerance antibiotic therapy is usually given for 28 days. Dietary modification also appears to be important and anecdotal evidence supports the use of highly digestible, low fat diets. Prognosis Many animals with undefined antibiotic responsive enteropathies relapse when antibiotics are stopped and require further courses, or long term maintenance therapy Prognosis for secondary SIBO depends on the underlying disease. CHRONIC ENTEROPATHIES RELATED TO DIET
Abnormal responses of the intestine to food are generally categorised as sensitivities (which are immune mediated) or intolerance's (which have a pharmacological or toxic basis). Dietary sensitivity or intolerance can cause acute or chronic gastrointestinal signs (please refer to diarrhoea caused by diet, drugs and toxins). Dietary sensitivity is probably much less common than dietary intolerance but it is often difficult or impossible to determine whether an adverse reaction to diet is a sensitivity or an intolerance. For example Gluten sensitive enteropathy in Irish Setters may be a consequence of an immunological or a toxic response to gluten, or both. Dietary intolerance or sensitivity also seems to play a role in idiopathic inflammatory bowel disease. Clinical findings Chronic diarrhoea, weight loss or failure to thrive, or vomiting are often present in patients with chronic reactions to food. Borborygmi, flatus or abdominal discomfort may also be noticed. The history may incriminate the diet e.g. out of date, poor quality or signs may be associated with certain foodstuffs. Animals with chronic dietary sensitivity/intolerance are stable and usually have no physical abnormalities apart from weight loss. Diagnosis The diagnostic work-up should rule out infectious, metabolic parasitic, pancreatic and structural causes of diarrhoea. Routine haematology and biochemistry are usually normal, though eosinophilia may be detected. Radiography or ultrasound are within normal limits. Major differential diagnosis at this point are inflammatory bowel disease and idiopathic small intestinal bacterial overgrowth. Tests of small intestinal function or a therapeutic trial with diet or antibiotics may be employed to determine if a dietary or bacterial problem is present (see below). Irish setters with gluten sensitive enteropathy are reported to have increased intestinal permeability and a low or high folate. Tests for circulating antibodies to food proteins and intradermal skin testing are rarely of any use in achieving a diagnosis of dietary sensitivity. Endoscopic monitoring of intragastric challenge with a variety of antigens is a potentially useful way of screening different dietary antigens but has not been sufficiently validated for clinical application. Alternatively the clinician can by-pass function tests or treatment trials and proceed with endoscopic biopsy to assess the morphologic appearance of the intestine and culture duodenal juice if facilities are available. Biopsy is indicated if therapeutic trials fail. Dietary intolerance/sensitivity may be associated with mild to moderate cellular infiltrates (increased intraepithelial lymphocytes) and villus atrophy. Demonstration of the resolution of intestinal abnormalities in response to the elimination of a dietary component and re-appearance of abnormalities on challenge are required to confirm a diagnosis of dietary sensitivity/intolerance. Treatment This is most often attempted by feeding an easily digestible gluten free diet which is restricted to a novel protein source where possible (see Treatment of diarrhoea). It may be necessary to feed the diet for up to six weeks before a response is observed. Where idiopathic SIBO cannot be excluded i.e. no bacteriology results are available and mucosal abnormalities are mild, a treatment trial with antibiotics may be undertaken (see small intestinal bacterial overgrowth) before a prolonged dietary trial. Where SIBO has been ruled out and response to diet is poor a course of prednisolone (0.5-2mg/kg PO SID for 2-3wks then taper) may augment dietary therapy. When a restricted diet induces remission additional dietary components can be slowly added to the diet to enable selection of diets which will be tolerated. Prognosis The prognosis is good if offending foodstuffs can be eliminated. INTESTINAL NEOPLASIA
Lymphosarcoma and adenocarcinoma are the most common intestinal tumours in dogs and cats. Leiomyoma, fibrosarcoma are less common while mast cell and plasma cell tumours are rare. Lymphosarcoma can infiltrate the bowel diffusely whereas other tumours are more discrete. Clinical signs usually include weight loss and anorexia. Diarrhoea, melaena, vomiting, abdominal discomfort, abdominal effusion and anaemia may also occur. Intussusception and intestinal perforation may occur as a consequence of intestinal tumours. Intestinal lymphosarcoma Lymphosarcoma (LSA) is characterised by the mucosal and sub-mucosal infiltration of neoplastic lymphocytes which cause malabsorption. Focal forms of lymphosarcoma may cause obstruction. The tumour is thought to be related to feline leukaemia virus in cats (though they are usually FeLV negative) and is of unknown aetiology in dogs. In some animals lymphoplasmacytic enteritis may progress to LSA. Clinical findings Weight loss, chronic small bowel diarrhoea and progressive inappettance are common features of intestinal LSA. Vomiting may also be noted. Physical examination may reveal diffusely thickened or nodular intestines ± mesenteric lymphadenopathy. Hepatosplenomegaly and generalised lymphadenopathy are less frequently detected. Signs of hypoproteinaemia may be evident. Diagnosis Middle aged or older dogs and cats are most commonly affected. Routine biochemistry often reveals a protein losing enteropathy in dogs with LSA. Anaemia which is either normocytic normochromic non-regenerative or microcytic and hypochromic, and neutrophilia may also be present. Ultrasound is useful for evaluating intestinal thickness and detecting mesenteric lymphadenopathy. Diagnosis can be made by demonstrating neoplastic lymphocytes in aspirates or biopsies from enlarged intestinal or peripheral lymph nodes, but is more often made by intestinal biopsy. Endoscopic biopsies may miss the lesion or show lymphoplasmacytic enteritis.Serum concentrations of cobalamin are often very low in cats with GI lymphoma, serum folate concentrations may also be reduced. Treatment and prognosis Dogs respond poorly to therapy. Cats with lymphocytic lymphoma may show a dramatic and lasting response (av. 17-20 mo.) to treatment with chlorambucil (15mg/m2 PO per day for 4 days, every three 3wks) and prednisone (10mg PO /cat/day). Supplemental cobalamin (1ml SC q 2-3wks) and folate / B complex vitamins should also be given. Lymphoblastic lymphoma is much less responsive. Intestinal adenocarcinoma Intestinal adenocarcinoma is common in middle aged to older dogs and cats. They occur most frequently in the jejunum and ileum in cats and the duodenum in dogs. Siamese cats seem to be over-represented. Clinical findings Adenocarcinomas are focally infiltrative and clinical signs tend to be those of partial obstruction. Palpation may reveal focal thickening of the intestine. Ulceration is frequent and melaena and pallor may be apparent. Diagnosis Anaemia may be normocytic normochromic or hypochromic and microcytic suggesting iron deficiency. Occasionally the anaemia is Coombs positive. Radiography or ultrasound help to reveal non-palpable masses. Diagnosis is made by percutaneous aspiration or surgical biopsy. Treatment Surgical resection is the treatment of choice. Prognosis Prognosis is poor to grave. Remissions of up to 2 years have been reported but is usually around 6 months. Chemotherapy has not been demonstrated to be effective Other neoplasms Leiomyomas, fibrosarcomas and mast cell tumours tend to be focally invasive and clinical signs, diagnosis and treatment are similar to intestinal adenocarcinoma. Diagnosis is based on histologic confirmation of the tumour type. Adenomatous polyps affecting the small intestine have been reported in middle aged cats. Clinical signs were vomiting, haematemesis or diarrhoea. Anaemia was severe and life threatening in some cases. Upper GI endoscopy or contrast radiography are most useful in detecting these lesions which are usually located in the proximal duodenum. Surgery is the treatment of choice and can be curative. SHORT BOWEL SYNDROME
Short bowel syndrome is the name given to the syndrome which results when large amounts (>2/3rds) of the small intestine are absent because of resection or rarely a congenital anomaly. Too little of the intestine remains to allow adequate absorption of nutrients and electrolytes and diarrhoea results. the syndrome may be transient after intestinal reaction because of the ability of the intestine to undergo adaptive hyperplasia. Clinical findings Small bowel diarrhoea and weight loss are the main clinical signs Diagnosis is usually based on the history of intestinal resection and associated signs. Where a congenital lesion is suspected he diagnosis is made after ruling out other causes of diarrhoea and demonstrating an abnormality with contrast radiography. Treatment Dietary therapy for chronic diarrhoea and vitamin supplementation are basic requirements. Antimicrobial agents may be necessary if the ileocaecocolic valve has been resected and intestinal bacterial overgrowth is suspected. If a response to diet and antibiotics antisecretory agents (loperamide, diphenoxylate) or antacids (cimetidine 5-10mg/kg PO TID) may be required. In cases where diarrhoea and weight loss are unresponsive parenteral nutrition may be required. Prognosis The prognosis depends on the amount of intestine left and response to therapy. Some animals un |