Inflammation is often characterized by infiltration of lymphocytes and plasma cells in many feline conditions: “inflammatory bowel diseases,” pancreatitis, cholangiohepatitis, “triaditis,” and stomatitis. Inflammation of any of these tissues may also be suppurative in nature or even granulomatous, but lymphocytic/plasmacytic (l/p) infiltrates are most common. This implies the presence of antigenic stimulation chronically and has implications in the therapeutic approach to any of these conditions.
Acute pancreatitis tends to be more severe and may be necrotizing, hemorrhagic with resultant complications and high mortality. Chronic (or acute on chronic) cases are much more common and need long-term therapeutic intervention for control.
More than 90% of the cases of feline pancreatitis are idiopathic.
Anything causing ischemia to the organ.
There is no evidence for glucocorticoids causing acute pancreatitis in dogs and even less in cats!
There is no evidence that fat in diets induces feline pancreatitis.
Pancreatitis should be included in a diagnostic rule-out list whenever there is a history of lethargy, anorexia, dehydration, hypothermia, vomiting (in only 35% in one paper), abdominal pain, abdominal mass effect, dsypnea, diarrhea, and ataxia. Concurrent problems may include hepatic lipidosis, cholangitis/cholangiohepatitis, idiopathic inflammatory bowel disease, enteritis, diabetes mellitus, and vitamin K1 responsive coagulopathy. As such, the clinical findings on examination may be vague. Pancreatitis is on my list of differentials for EVERY cat who is lethargic, “not himself,” inappetant and dehydrated, whether vomiting or not.
Statistically, 38% of cats diagnosed with hepatic lipidosis had concurrent acute pancreatitis and these patients were more likely to be cachectic and have coagulation abnormalities. This is very important, as these lipidotic cats have a worse prognosis.
Ultrasound is the most sensitive, commonly available, non-invasive evaluative tool that we have at this time.
The lack of hyperlipasemia cannot be depended on to rule-out pancreatitis.
TLI has been less sensitive and specific than hoped as a diagnostic tool.
Surgical biopsy is required to make the histopathological diagnosis.
Gently isolate the pancreas from the surrounding viscera and pack it off with a few gauze swabs prior to selecting either a gross lesion or routine selection of both poles for biopsy using fine iris scissors. Submit a small piece in a culture medium as well as formalin preserved samples, in case the lesion is reported as suppurative. You can gently lavage the pancreas with a small amount of an isotonic solution catching the liquid in the swabs.
Fluid therapy and pain relief are the cornerstones in supportive care.
Concurrent problems (such as lipidosis or enteritis) need to be addressed.
Feed; do not fast, unless the cat is vomiting.
Even with the vomiting cat, designing a nutritionally supportive protocol is of great importance due to this species’ predisposition for developing lipidosis. Thus, I fast cats for no longer than 48 hours utilizing anti-emetics as necessary. In these few intractably vomiting cats, total parenteral nutrition or jejunostomy tube feeding may be advisable for 7–10 days. Dr. Sharon Center has reported placing a weighted j-tube through a conventionally placed g-tube for jejunal feeding. It has been suggested that bland, low fat, high carbohydrate diets are most suitable however, I am not aware of any research done to support this recommendation. Cats, being obligate carnivores, don’t normally utilize carbohydrates well. In addition, as there is no evidence that dietary fat is implicated in the etiology of feline pancreatitis, nor any to support restriction in therapy, dietary recommendations cannot be made with certainty. I have had good success with feeding novel protein or enteric type diets to cats with pancreatitis.
Trickle feeding: For cats who are requiring nutritional support, but who are vomiting, it is useful to know about “trickle feeding.” This is a spin-off of the technique of parenteral/IV feeding that has been adapted to enteral (i.e., GI) feeding. If a cat with an esophageal or gastrostomy tube vomits whenever the volume fed is more than a ridiculously small amount (e.g., such that you would need to dedicate one staff person to administering that volume every 20 minutes around the clock), then “trickle feeding” is your answer. Rather than bolus the food in numerous, spaced feedings throughout the day, calculate out the kcals (and volume) that need to be fed, fill an empty IV bag with Clinicare or another liquid diet, attach it to an IV line, and run the line as a drip throughout the day attached to the feeding tube. It is best to have it regulated by a fluid pump. Use a fresh bag and new solution every 12–24 hours to prevent bacterial or yeast growth. If you are using a human diet, nutritional adjustments need to be made. Gastric emptying is not significantly affected either by the presence of a g-tube or the route of administration of food into the stomach.
Anti-emetics: When the use of anti-emetics is being considered, bear in mind that, as the liver metabolizes these agents, their clearance rates may be decreased. Doses should be reduced accordingly.
|0.5 mg/kg q8h IM
|0.1 mg/kg q6h IM
|2.0–4.0 mg/kg q8h PO, 2.0 mg/kg q8h IM
|8.0 mg/kg q8h PO
|0.5–0.8 mg/kg q12h IM, SQ
|1–2 mg/kg constant rate infusion IV over 24 hours
|0.1–0.15 mg/kg slow push IV q6–12 hours prn
|0.6 mg/kg IV q24h
Analgesia is of critical importance in the comfort of the patient, but also in the progression of the disease/inflammation through the negative physiological effects of pain. PAIN CAUSES DISEASE AND PREVENTS HEALING. Even if obvious abdominal pain isn’t present, I recommend a test dose of 0.1–0.2 mg/kg oxymorphone IV to see if the patient improves over the approximately four hour effective period. If that is the case, then constant rate infusion of a narcotic may be considered or a transdermal fentanyl patch (Duragesic™) for continuous relief. Torbugesic™ is not as effective for visceral pain as the opiod agonists are.
Corticosteroids are indicated if a l/p form is reported or in an acute shock presentation. Other anti-inflammatories are not currently recommended; nor have any benefits been seen with the use of antacids, anticholinergics, GI hormones (somtostatin, glucagon), or calcitonin. Dopamine has been useful in acute experimental feline pancreatitis. Metronidazazole may be useful for both its immunomodulatory and antimicrobial effects.
Antibiotics are only indicated if the diagnosis of a suppurative pancreatitis has been made. In this case, antimicrobial selection is best made with the knowledge of a sensitivity spectrum. Note that a suppurative pattern may be seen on histology in a sterile pancreatitis caused by enzyme damage. Complications of ACUTE pancreatitis that may arise include DIC, thromboembolism, cardiac arrhythmia, sepsis, acute tubular necrosis, pulmonary edema, and pleural effusion. It has been suggested that a low dose of dopamine (5 mcg/kg/min) diminishes the severity of the disease. To prevent bacterial translocation, cover these patients with broad-spectrum antibiotics.
Prognosis depends on the type of pancreatitis as well as the degree of duration and severity. Many cats have chronic, low-grade smoldering pancreatitis and with accurate diagnosis and appropriate therapy, can live long lives.
Inflammatory Bowel Disease may cause vomiting, diarrhea, both or neither in cats. Symptoms seen depend on the degree of inflammation and impairment of absorption as well as the location (where and how much) of the inflammatory lesions. Gastric inflammatory changes and those in the upper small intestines will be likely to cause vomiting. Colitis in the cat may also cause vomiting! Occasionally cats will be asymptomatic other than weight loss. Palpably thickened intestinal loops may be present and enlargement of the mesenteric lymph node may be noted. Mild dehydration may be evident.
Folate and cobalamin. Cats, unlike dogs, do not appear to develop small intestinal bacterial overgrowth (SIBO), rather, the normal cat has a much higher population of GI flora than does that of dogs. Thus, subnormal folate levels are not indicative of SIBO in cats; however, folate deficiency may occur with severe, chronic malabsorptive proximal small intestinal disease. In addition, 50% of cats with exocrine pancreatic insufficiency (EPI) have subnormal folate levels. Cobalamin deficiency is most likely the result of malabsorption secondary to EPI in cats. Some cats with chronic intestinal disease (e.g., triaditis or "IBD" may be deficient in either of these vitamins and may benefit by supplementation if their assays verify subnormal levels. The GI lab at Texas A&M University runs a feline folate and cobalamin panel. Supplementation for subnormal levels: folate is given orally (0.5–1.0 mg q24h X one month); cobalamin must be given parenterally (125–250 mcg/week SC or IM once a week X 4–6 weeks).
CHOLANGITIS/CHOLANGIOHEPATITIS COMPLEX (CCHC)
Inflammation of the biliary tree and/or liver parenchyma may be suppurative or non-suppurative. The non-suppurative form is more common and is often lymphocytic/plasmacytic in character. The clinical presentation includes a vague history of inappetance/anorexia OR polyphagia, lethargy, as well as possibly nausea, vomiting, diarrhea and weight loss. The signs may have a chronic intermittent occurrence. On physical examination, signs of dehydration, weight loss, muscle wasting, icterus, salivation, palpable liver margins, cranial abdominal tenderness or firmness may be present. Suppurative and non-suppurative CCHC cannot be differentiated based on history and physical examination alone; both forms may or may not present with an elevated temperature. Biopsy is required for differentiation. Wedge biopsy provides necessary architectural information that a Tru-cut or fine needle aspirate doesn’t.
Cats with CCHC often have hyperbilirubinemia and bilirubinuria, but these do not differentiate the conditions from other hepatic, pre-hepatic or post-hepatic causes of icterus. In patients with bilirubinuria, lack of urobilinogen should increase suspicion of extra-hepatic bile duct obstruction. Increases in activities of serum alkaline phosphatase (ALP), alanine transferase (ALT), and gamma glutamyl transferase (GGT) may be present to varying degrees but do not distinguish between suppurative and non-suppurative CCHC. Cats with hepatic lipidosis usually have markedly increased ALP activity compared to ALT activity and have normal GGT activity. In contrast, cats with CCHC usually have ALP and ALT increases of equal magnitude or the increase in ALT is greater than ALP; GGT activity is usually increased as well. Bilirubinuria is ALWAYS significant in the cat.
It is important to realize that some patients may have chronic CCHC resulting in decreased functional liver mass and therefore no increases in ALT, ALP, or bilirubin may occur. There may be variable changes in albumin, glucose, BUN, and cholesterol. If you believe that liver disease is possible, a liver function test is indicated. Use the combination of pre- and post-prandial serum bile acid measurement to assess liver function. With cirrhosis, penacillamine or methotrexate may be beneficial in reducing the progression of fibrosis.
Hepatic biopsy is preferred over FNA or Tru-cut biopsy. With FNA, not only are you restricted in what you harvest, but also the condition of that sample is mutilated by the aspiration action and slide preparation. Some types of cells do not exfoliate readily (mesenchymal neoplasias such as fibrosarcoma, for example); with FNA, you only get a cytological diagnosis of whatever cells are sampled easily and may not get a real picture of the underlying disease process. Additionally, orientation of the cellular reaction within tissue is critical in differentiating what role neutrophils or lymphocytes play. For example, peribiliary inflammation and periportal inflammation define different disease processes and may indicate different therapy and different prognosis.
Vitamin K1. Fifty percent of cats with HL have prolonged PIVKA (Proteins Induced in Vitamin K Absence or Antagonism) times or other prolonged coagulation tests and require vitamin K1 therapy. It takes cats < 7 days to become vitamin K deficient. Cats who have been on antibiotics may have fewer organisms in their bowels to make vitamin K. Vitamin K is absorbed in the proximal small bowel and recycled by the liver (via the vitamin K epoxidase cycle). Thus, in small bowel disease (such as IBD induced fat malabsorption), as well as in liver diseases (especially in hepatic lipidosis), low vitamin K levels may predispose to occult coagulopathies. Factors II, VII, IX and X, as well as protein C and protein S (antithrombotic proteins), are vitamin K dependent. If the patient is jaundiced or nauseous, then the vitamin K1 must be given SC rather than orally because intestinal absorption is poor (0.5–1.0 mg/kg q24h X 3–4 days or until coagulation normalizes). If too much vitamin K1 is given, an oxidative toxicity may develop and supplementation of vitamin E as an antioxidant may be required.
Unlike the dog, in the cat, the pancreatic duct enters the common bile duct before it opens into the duodenum. When there is disease (e.g., inflammation, infection, neoplasia, stasis) in the small bowel, it may ascend into the common bile duct and, from there, affect the pancreas and the rest of the biliary tree. Similarly, disease in the biliary tree or pancreas may affect the other two regions. When this occurs, it is termed “triaditis.” This complex is so common, that ultrasonographic evaluation of the abdomen is very helpful to try to determine which organs are involved.
Cholecystitis generally presents as a vague malaise with inappetance and dehydration, (pretty much like everything else in the cat). Vomiting may be present. While this too may involve a lymphocytic/plasmacytic inflammatory infiltrate of the gall bladder wall, it more often is suppurative. If surgical evaluation occurs, and the gall bladder looks inflamed or if it does not compress and empty normally, or if ultrasound is suggestive of cholecystitis, bile aspiration and culture (aerobic and anaerobic) should be performed.
EXTRA HEPATIC BILE DUCT OBSTRUCTION (EHBDO)
This is a cause for acute onset of vomiting and malaise in a patient. Plain radiographs may show a radiodense object in the region of the gall bladder; ultrasound confirms that the location is the bile duct, as well is able to detect inspisations that are not radiodense. A urinalysis will detect this problem early, as there will be the presence of bilirubin but a lack of urobilinogen in the sample. Blood work will show a marked increase in bilirubin and eventually cholestasis (increased SAP) and some hepatocellular injury (increased ALT). This constitutes an emergency and requires surgical correction.
GASTROINTESTINAL (GI) LYMPHOMA
Lymphoma is the most common form of GI neoplasia in cats. In the past, alimentary lymphoma has been given a poor/grave prognosis in most of the literature. In Keith Richter’s paper at ACVIM 2001, he reports distinguishing the lymphoCYTIC from the lymphoBLASTIC lymphomas in a group of 67 cats by taking extensive endoscopic biopsies. In this study, Dr. Richter found that with lymphoCYTIC lymphoma, 90% involved the small intestine and might have been missed with endoscopy. For lymphoBLASTIC lymphoma, approximately 50% of the cases involved small bowel only; the remainder involved stomach or stomach and small bowel. Histologically, 25% of the 67 cases had lymphoBLASTIC lymphoma, 75% had lymphoCYTIC.
LymphoCYTIC GI lymphoma is readily treated using prednisone and clorambucil at home! The median disease free interval was 20.5 months (range 5.8–49 months). Rescue was achieved with cyclophosphamide. Cats with lymphoBLASTIC lymphoma responded poorly to chemotherapy using either CVP (cyclophosphamide, vincristine, pred) or ACOPA (CVP + doxorubricin and L-asparaginase). Of interest also was his observation that cats with lymphoBLASTIC lymphoma were more likely to have recurrences of abdominal masses.
GI biopsies. Good quality biopsy samples are essential. Diagnostically, more is better. Endoscopy is a wonderful tool with certain advantages and disadvantages. The biggest problem with endoscopy is the limited areas one can visualize and the limitations of partial thickness biopsy. GI lymphoma may be “patchy,” may be limited to the serosal and muscularis layers of the bowel, can be missed, and the remaining tissue may have lymphocytic/plasmacytic infiltrates and be interpreted as IBD. In addition, it is important to recognize that severe IBD may progress to lymphoma. Thus, it is important to make a definitive diagnosis of IBD early on and suppress the inflammatory response.
Endoscopy. In a retrospective study comparing radiographic, ultrasonographic and endoscopic findings in cats with upper GI IBD, Dr. JL Baez (ACVIM 1999) found that the clinical signs and ultrasound findings correlated best with histologic grade of IBD and that ultrasound identified more abnormalities than upper GI endoscopy. Optimizing endoscope use: After examining the stomach and proximal duodenum, remove the endoscope and prepare for exploratory celiotomy (laparotomy). After a look around, when you are ready to biopsy the intestinal tract, make an incision in the proximal duodenum, insert the endoscope and slide the bowel up over the endoscope. This allows you to visualize the inside (mucosal surface) of the intestine and place stay sutures at spots that you think should be biopsied. Withdraw the scope and now you can take full thickness biopsies of those suspicious areas as well as areas that look abnormal from the serosal aspect of the bowel.
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