Dealing with Diarrhea in Dogs & Cats

What to Do About “The Trots” Dealing with Diarrhea In Dogs & Cats Wendy Blount, DVM • Contents of the gut are actually outside the body • This illustrates the importance to the integrity of the mucosal GI barrier, which must be selectively permeable • GALT (gut associated lymphoid tissue) monitors what and what does not enter into the body Gut Tissue Layers

1. Mucosa 2. Submucosa/Lamina Propria 3. Muscularis – Longitudinal smooth muscle – Submucosal nerve plexus – Circular smooth muscle – Myenteric nerve plexus – Longitudinal smooth muscle 4. Serosa - connects to mesentery, everywhere but esophagus and rectum Gut Tissue Layers

Memory Aid: “The Sun is Bright • Submucosa is white • Serosa is white • S#!t is white  And it’s Dark at Midnight.” • Mucosa is black • Muscularis is black DDx Diarrhea

• Extra-intestinal causes (13%) – Everything that causes vomiting – Exocrine pancreatic insufficiency • Intra-intestinal causes (87%) – 52% are food responsive – 12% IBD – 9% antibiotic responsive diarrhea – 3% prednisone responsive but no inflammation on histopath – 12% GI parasites

(Volkmann et al, 2012) Acute vs. Chronic Diarrhea

• Most cases of acute diarrhea respond to empirical therapy • HGE is a particular clinical picture that responds well if treated early • We will spend most of the hour talking about chronic diarrhea Diagnostics for Diarrhea

1. Empirical Treatment 2. MDB – CBC, panel, electrolytes – Urinalysis – Fecal flotation and direct smear (repeated) – Heartworm test for dogs, FeLV/FIV for cats – T4 and free T4 for cats (55% v, 30% d) 3. Abdominal x-rays and ultrasound, GI Lab tests 4. Endoscopy (always do GI panel first) 5. Diagnostic surgery – multiple organ biopsies Abdominal Radiographs and US

• Abdominal Radiographs lymphoma – obstruction (foreign body, intusussception) – ileus – Mass • Abdominal ultrasound - above plus – Increased intestinal thickness for IBD/lymphoma – Obliteration of the layers of the gut for neoplasia and normalphycomycosis Inflammatory bowel disease Abdominal Radiographs and US

• Abdominal Radiographs – obstruction (foreign body, intusussception) – ileus – Mass • Abdominal ultrasound - above plus – Increased intestinal thickness for IBD/lymphoma – Obliteration of the layers of the gut for neoplasia and phycomycosis – Muscularis:mucosa > 1:1 suggests lymphoma – Enlarged LN • >5mm abnormal – LSA or IBD • >3 cm probably neoplasia Abdominal Radiographs and US

• Abdominal Radiographs – obstruction (foreign body, intusussception) – ileus – Mass • Abdominal ultrasound - above plus – Increased intestinal thickness for IBD/lymphoma – Obliteration of the layers of the gut for neoplasia and phycomycosis – Muscularis:mucosa > 1:1 suggests lymphoma enlarged – EnlargedMesenteric LN lymph nodes • >5mm abnormal – LSA or IBD • >3 cm probably neoplasia MDB and GI Panel

• More often normal with LI except Boxer Colitis • Low albumin - SI disease + Boxer Colitis • Low albumin and globulin - GI bleeding – Especially if BUN increased, creat/phos normal, PCV low • Low B12 (TAMU GI Lab Form) – Distal small intestinal disease – EPI – Dysbiosis in upper small intestine in dogs • High B12 - not clinically significant MDB and GI Panel

• Low Folate - proximal intestinal disease • High folate - proximal intestinal dysbiosis • Low TLI indicates EPI – Dogs <2.5 mcg/L – definitely EPI – Dogs 2.5 – 3.5 mcg/L – borderline EPI – Dogs 3.5 – 5.7 mcg/L – subclinical EPI • Repeat in 30 days with strict fasting – Cats < 8 mcg/L – EPI – Cats 8-12 mcg/L – borderline EPI • Repeat in 30 days with strict fasting MDB and GI Panel

• High TLI >50 mcg/L in dogs & >100 mcg in cats – acute pancreatitis (30-40%) – short lived – malnutrition – Minimal elevation in renal disease • High PLI Canines – 200-400 mcg/L – borderline • Recheck 2-3 weeks – >400 mcg/L - pancreatitis MDB and GI Panel

• High PLI Felines – 3.6-5.3 mcg/L – borderline • Recheck 2-3 weeks – >5.4 mcg/L – likely pancreatitis • False positives for diabetes, IBD, hepatitis • Margie Scherck says this test is useless in cats • Dr. Suchodolski et al probably don’t agree • I have found it clinically useful for monitoring chronic recurring pancreatitis and adjusting therapy Small Intestinal Diarrhea Large Intestinal Diarrhea Large volume stool Small volume stool Digested blood - melenaPresence of Fresh blood? blood – hematochezia Fecal score 6-8 (watery) Fecal score 4-5 (soft) Mucus not often present Mucus on stool is common Maybe normal frequency Usually increased frequency Urgency, Dyschezia/Tenesmus Urgency, Dyschezia/Tenesmus possible common Can be flatulent Can be flatulent Steatorrhea if EPI No steatorrhea Weight loss common with Weight loss is rare except Boxer chronicity colitis, histoplasmosis, neoplasia Glutamine is preferred Fermentable fiber is a good enterocyte nutrient source of preferred enterocyte nutrient butyrate Low residue diet preferred High fiber diet preferred Small Intestinal Diarrhea Large Intestinal Diarrhea Large volume stool Small volume stool Digested blood - melena Fresh blood – hematochezia

Fecal score 6-8 (watery)Both – raspberry Fecal jam score stools 4-5 (soft) Mucus not often present Mucus on stool is common Maybe normal frequencyFecal Score? Usually increased frequency Urgency, Dyschezia/Tenesmus Urgency, Dyschezia/Tenesmus possible common Can be flatulent Can be flatulent Steatorrhea if EPI No steatorrhea Weight loss common with Weight loss is rare except Boxer chronicity colitis, histoplasmosis, neoplasia Glutamine is preferred Fermentable fiber is a good enterocyte nutrient source of preferred enterocyte nutrient butyrate Low residue diet preferred High fiber diet preferred Small Intestinal Diarrhea Large Intestinal Diarrhea Large volume stool Small volume stool Digested blood - melena Fresh blood – hematochezia Fecal score 6-8 (watery) Fecal score 4-5 (soft) Mucus not often presentPresence of Mucus Mucus? on stool is common Maybe normal frequency Usually increased frequency Urgency, Dyschezia/Tenesmus Urgency, Dyschezia/Tenesmus possible common Can be flatulent Can be flatulent Steatorrhea if EPI No steatorrhea Weight loss common with Weight loss is rare except Boxer chronicity colitis, histoplasmosis, neoplasia Glutamine is preferred Fermentable fiber is a good enterocyte nutrient source of preferred enterocyte nutrient butyrate Low residue diet preferred High fiber diet preferred Small Intestinal Diarrhea Large Intestinal Diarrhea Large volume stool Small volume stool Digested blood - melena Fresh blood – hematochezia Fecal score 6-8 (watery) Fecal score 4-5 (soft) Mucus not often present Mucus on stool is common Maybe normal frequencyFrequency of Usuallydefecation? increased frequency Urgency, Dyschezia/Tenesmus Urgency, Dyschezia/Tenesmus possible common Can be flatulent Can be flatulent Steatorrhea if EPI No steatorrhea Weight loss common with Weight loss is rare except Boxer chronicity colitis, histoplasmosis, neoplasia Glutamine is preferred Fermentable fiber is a good enterocyte nutrient source of preferred enterocyte nutrient butyrate Low residue diet preferred High fiber diet preferred Small Intestinal Diarrhea Large Intestinal Diarrhea Large volume stool Small volume stool Digested blood - melena Fresh blood – hematochezia Fecal score 6-8 (watery) Fecal score 4-5 (soft) Mucus not often present Mucus on stool is common Maybe normal frequency Usually increased frequency Urgency, Dyschezia/TenesmusUrgency to defecateUrgency, and straining? Dyschezia/Tenesmus possible common Can be flatulent Can be flatulent Steatorrhea if EPI No steatorrhea Weight loss common with Weight loss is rare except Boxer chronicity colitis, histoplasmosis, neoplasia Glutamine is preferred Fermentable fiber is a good enterocyte nutrient source of preferred enterocyte nutrient butyrate Low residue diet preferred High fiber diet preferred Small Intestinal Diarrhea Large Intestinal Diarrhea Large volume stool Small volume stool Digested blood - melena Fresh blood – hematochezia Fecal score 6-8 (watery) Fecal score 4-5 (soft) Mucus not often present Mucus on stool is common Maybe normal frequency Usually increased frequency Urgency, Dyschezia/Tenesmus Urgency, Dyschezia/Tenesmus possible common Can be flatulent Can be flatulent Flatulence? Steatorrhea if EPI No steatorrhea Weight loss common with Weight loss is rare except Boxer chronicity colitis, histoplasmosis, neoplasia Glutamine is preferred Fermentable fiber is a good enterocyte nutrient source of preferred enterocyte nutrient butyrate Low residue diet preferred High fiber diet preferred Small Intestinal Diarrhea Large Intestinal Diarrhea Large volume stool Small volume stool Digested blood - melena Fresh blood – hematochezia Fecal score 6-8 (watery) Fecal score 4-5 (soft) Mucus not often present Mucus on stool is common Maybe normal frequency Usually increased frequency Urgency, Dyschezia/Tenesmus Urgency, Dyschezia/Tenesmus possible common Can be flatulent Can be flatulent Steatorrhea if EPIFatty stools? No steatorrhea Weight loss common with Weight loss is rare except Boxer chronicity colitis, histoplasmosis, neoplasia Glutamine is preferred Fermentable fiber is a good enterocyte nutrient source of preferred enterocyte nutrient butyrate Low residue diet preferred High fiber diet preferred Small Intestinal Diarrhea Large Intestinal Diarrhea Large volume stool Small volume stool Digested blood - melena Fresh blood – hematochezia Fecal score 6-8 (watery) Fecal score 4-5 (soft) Mucus not often present Mucus on stool is common Maybe normal frequency Usually increased frequency Urgency, Dyschezia/Tenesmus Urgency, Dyschezia/Tenesmus possible common Can be flatulent Can be flatulent Steatorrhea if EPI No steatorrhea Weight loss common with WeightWeight loss? loss is rare except Boxer chronicity colitis, histoplasmosis, neoplasia Glutamine is preferred Fermentable fiber is a good enterocyte nutrient source of preferred enterocyte nutrient butyrate Low residue diet preferred High fiber diet preferred Small Intestinal Diarrhea Large Intestinal Diarrhea Large volume stool Small volume stool Digested blood - melena Fresh blood – hematochezia Fecal score 6-8 (watery) Fecal score 4-5 (soft) Mucus not often present Mucus on stool is common Maybe normal frequency Usually increased frequency Urgency, Dyschezia/Tenesmus Urgency, Dyschezia/Tenesmus possible common Can be flatulent Can be flatulent Steatorrhea if EPI No steatorrhea Weight loss common with Weight loss is rare except Boxer chronicity colitis, histoplasmosis, neoplasia Glutamine is preferred PreferredFermentable Diet? fiber is a good enterocyte nutrient source of preferred enterocyte nutrient butyrate Low residue diet preferred High fiber diet preferred Small Intestinal Diarrhea Large Intestinal Diarrhea Large volume stool Small volume stool Digested blood - melena Fresh blood – hematochezia Fecal score 6-8 (watery) Fecal score 4-5 (soft) Mucus not often present Mucus on stool is common Maybe normal frequency Usually increased frequency Urgency, Dyschezia/Tenesmus Urgency, Dyschezia/Tenesmus possible common Can be flatulent Can be flatulent Steatorrhea if EPI No steatorrhea Weight loss common with Weight loss is rare except Boxer chronicity colitis, histoplasmosis, neoplasia Glutamine is preferred Fermentable fiber is a good enterocyte nutrient source of preferred enterocyte nutrient butyrate Low residue diet preferred High fiber diet preferred Empirical Therapy for Diarrhea

• Everything we talked about for vomiting • Deworm fenbendazole - 50 mg/kg x 3-10 days • Rules out Giardia and whipworms • Antibiotics x 7-14 days – Metronidazole as for vomiting • 250 mg – ¼ tab per 10 lbs PO BID • 500 mg – ¼ tab per 20 lbs PO BID – Amoxicillin 10mg/lb PO BID – Tylan powder 1/8 tsp (325 mg) per 35-65 pounds • 5-20 mg/kg BID • Probiotics – Culturelle®, ProViable®, Fortiflora® Empirical Therapy for Diarrhea

• Highly digestible diet for chronic small bowel diarrhea – Purina EN, EN Natural, EN low fat – Hill’s i/d, i/d low fat, i/d stews – Royal Canin Gl Puppy, Gl Moderate Calorie, GI Low Fat, GI High Energy – Homemade diets – Feeding Guide 1. Boiled chicken and white rice (50:50) 2. Boiled hamburger and white rice (50:50) 3. Farina recipe Empirical Therapy for Diarrhea

• Hill’s Microbiome for acute diarrhea • High fiber diet large bowel diarrhea – Purina OM, DCO – Hill’s w/d, r/d, Microbiome – Royal Canin Weight Control, GI Fiber Response Benji Boy

• 3 year old neutered male papillon • Hx – never been sick before, except got stepped on by a cow 6 weeks ago, and he hasn’t been right since • Wheezes in the lungs • Trauma to the right inguinal area • Healed with time • CC – anorexia and lethargy, vomits 1-2x a week • Exam – NSAF Benji Boy

• CBC – WBC 22,450/ul • Neutrophil 16,390/ul • Monocytes 2,360/ul • Basophils 140/ul • Electrolytes – normal • Panel – SAP 262 U/L • Fecal flotation – negative • Abdominal x-rays & US – NSAF • Tx • Denosyl 90 mg PO SID • Clavamox 62.5 mg PO BID x 7d Benji Boy

• 5 days later – not eating or drinking, still does not feel good, in pain • Exam – mild to moderate discomfort on abdominal palpation, grunts • Temp 104.7oF • cPL - >400 • Abdominal US Benji Boy

• 5 days later – not eating or drinking, still does not feel good, in pain • Exam – mild to moderate discomfort on abdominal palpation, grunts • Temp 104.7oF • cPL - >400 • Abdominal US • Pancreas enlarged and mottled in echotexture, ascites in the cranial abdomen 2-3mm lines, Corrugation of the duodenum Benji Boy

• Dx - Pancreatitis • Hospitalized to treat for pancreatitis • IV fluids • Continue Denosyl • Cerenia® • Buprenex for pain • Ampicillin and enrofloxacin • Eating in a few days, fever down, sent home on antibiotics, Cerenia, and Denosyl® Benji Boy

• 2 weeks later • CC - Did well for awhile, now there is straining to defecate and fresh blood and mucus on the stool, eating well. • Wt - 6 months ago 14 pounds, 1 month ago 12 pounds, now 11.5 pounds • Exam – no pain on abdominal palpation, rectal exam and rest NSAF • Fecal – negative • Rx – metronidazole 62.5 mg PO BID x 7 days • Fenbendazole 2.5cc PO SID x 3 days Benji Boy

• 3 weeks later • CC – got better for awhile, but now worse - anorexia, vomiting, diarrhea • Wt – 9 lbs • Exam – NSAF • Fecal – negative • rectal scraping – no fungal organisms seen • Tx – Cerenia and Tylan while awaiting GI lab results Benji Boy

• 5 days later – appetite better • GI panel – B12, PLI, TLI normal • Folate low • Proximal small intestinal disease • Recommend intestinal biopsies • Declines referral for flexible endoscope • Diagnostic surgery for multiple biopsies • liver, stomach, duodenum, jejunum, ileum • Rigid scope colon biopsies Benji Boy • Histopath • Moderate suppurative hepatitis • Inflammatory bowel disease (EP inflammation in the duodenum and jejunum, villous blunting, crypt lesions) • Tx – prednisone 5 mg PO BID x 2 weeks, then 5 mg PO SID • 3 weeks later – Benji doing great • 10.2 lbs • Owner - “Dr. Blount is the smartest vet in the universe” Benji Boy • 1 week after that (8 weeks after 1st visit) • CC - not feeling well • GI signs have stopped, but Benji cries out when you pick him up • Owner – “Dr. Blount, are you sure you know what you are doing?” Benji Boy • Exam • Wt 11.5 lbs (way up) • Mucopurulent discharge from the eyes • Cranial drawer sign both stifles • Pain on palpation of the muscles and long bones • T – 104.7oF

What’s the catch? Benji Boy • CBC – WBC 52K – segs, monos • Panel – SAP 1132 U/L • Lytes - normal • Radiographs • Pelvis • Front limbs • Rear limbs Benji Boy Benji Boy Benji Boy DDx Periosteal proliferation • Pulmonary hypertrophic osteopathy • Hepatozoon spp. Thoracic radiographs – normal Abdominal ultrasound – normal MiraVista Histoplasma Ag – negative (tests) Hepatozoon americanum – positive (order kit) • Clindamycin 25 mg/kg PO BID x 2 weeks • Albon 25 mg/kg PO BID x 2 weeks • Pyrimethamine 1.25 mg once daily x 2 wks • Then decoquinate 50 mg/kg once daily Benji Boy Benji did well as long as he took decoquinate He needed an occasional round of Albon, clindamycin, pyrimethamine – 2-3x a year Did well for several years, until he had a severe episode Referred to TAMU for re-evaluation, and they made no new diagnosis Benji was euthanized at 8 years of age Lessons from Benji Boy • IBD is not a disease, it is a lesion description • IBD can be secondary, even when evidence of chronicity is on histopath • IBD almost never causes fever or high WBC • Pancreatitis is often not primary • Immunosuppressive therapy for one disease can unmask infectious disease that is present • Pay attention to symptoms unexplained by Dx • Recent history is not always related to current CC • Just because someone says you are the smartest vet in the universe, doesn’t mean you are DDx Eosinophilic IBD

• Food allergy • Parasitic infection • Mast Cell Tumor • Fungal infection • Idiopathic IBD • Feline Hypereosinophilic Syndrome • Protozoal disease • Basophils on Benji’s first CBC were a clue Inflammatory Bowel Disease

• Inflammatory reaction to food and/or bacteria • Uncommon in dogs <1 yr old • Food intolerance more common in young dogs, or parasites • Symptoms – Weight loss – Vomiting and/or diarrhea – Appetite decreased to increased, pica Inflammatory Bowel Disease

• CIBDAI – Canine IBD Activity Index – Total Score from 0-18 – Six things rated from 0-3: 1. Activity level 2. Appetite 3. Weight loss 4. Vomiting 5. Stool Consistency 6. Stool frequency Inflammatory Bowel Disease Inflammatory Bowel Disease

8 watery and clear Inflammatory Bowel Disease

• Clues on the lab work: – Mild increase in liver enzymes (leaky gut) – Low albumin is a negative prognostic indicator – Low albumin *and* low globulin *without* anemia and *with* chronic diarrhea suggests PLE – Low albumin *and* low globulin *with* anemia suggests GI blood loss • Regardless of presence of melena, hematochezia or diarrhea Inflammatory Bowel Disease

Endoscopic vs. Full thickness biopsies – Need 10-12 mucosal biopsies to get information as accurate as one full thickness biopsy – It’s not uncommon for lymphoma to be present only in the muscularis – may need full thickness – Endoscopic biopsies can be helpful to diagnose IBD and lymphangiectasia, but may or may not diagnose lymphoma if present Inflammatory Bowel Disease Interpreting Histopathology 1. inflammatory cells in the lamina propria • Lymphocytes, plasma cells, eosinophils • **This alone does not make IBD** 2. Blunting, atrophy and fusion of the villi 3. Crypt lesions (edema, distortion, abscessation) 4. LP fibrosis – Idiopathic IBD will look just like reaction to parasites, protozoa or food – Chronicity must be established to diagnose IBD – IBD does not invade the muscularis as lymphoma does 5. IBD lesions most often found in duodenum > jejunum > ileum > colon > stomach Inflammatory Bowel Disease Treatment 1. Empirical treatment has already failed 2. Dietary Trial, with more antibiotics • Hypoallergenic or hydrolyzed diet (NOT i/d or EN) • Can see response as early as 2 weeks 3. Immunosuppressives • Prednisone – 75-80% respond – 1 mg/kg PO BID x 3 weeks, then 0.5 mg/kg PO BID x 3 weeks, then wean to lowest effective dose over months • Others if pred is not effective or not tolerated • azathioprine, cyclosporine, budesonide, chlorambucil • Norsworthy uses a CCNU protocol for cats • May not be needed long term if there is response to diet 4. B12 and folate as indicated by GI panel Inflammatory Bowel Disease Treatment – Simpson et al, 2012 – LP enteritis Dogs with normal albumin are likely to respond to diet, and likely do not need corticosteroids Dogs with low albumin and B12 are not likely to respond to diet alone, likely need corticosteroids, and may have a poor prognosis Inflammatory Bowel Disease Treatment – Norsworthy IBD Protocol for cats that are difficult to medicate PO • CBC to ensure neutrophils > 1,500/ul • Lomustine 9 mg PO for cats 7-10 lbs • DepoMedrol 20-40mg SC/IM • If response is good, repeat in 4-6 weeks • If response is good, repeat in 6 weeks • Then every 8 weeks, as long as response is good and there is no liver toxicity • Check liver panel before 3rd treatment and before every treatment thereafter (ALT, albumin) Inflammatory Bowel Disease Treatment – Mandigers et al, 2010 • Compared results for hydrolyzed diet and intestinal diet such as EN or I/D for chronic diarrhea • Initial response the same – 88% • After 3 years – 13/14 on hydrolyzed diet were still in remission – 1/6 on intestinal diet still in remission – 2/3 in both groups relapsed when fed the original diet Hydrolyzed diet is superior to intestinal diet for empirical treatment of dogs with chronic diarrhea Inflammatory Bowel Disease Monitoring – CIBDAI – 75% reduction is ideal – Histopath can be used to monitor – improves with successful treatment – Repeating histopath can also reveal other underlying causes, when therapy is not going well – Prednisone, other immunosuppressants and other antibiotics can be weaned down to the lowest effective dose Inflammatory Bowel Disease Azathioprine – Start at 2 mg/kg PO SID x 1-2 weeks, then 1 mg/kg PO SID x 2-4 weeks, then QOD • Lower for very large dogs – Can take weeks to take effect – No studies to show efficacy, even though many internist like to use it • If steroids not effective, or to spare side effects – Side effects (though generally well tolerated): • Pancreatitis • Bone marrow suppression • hepatotoxicity Inflammatory Bowel Disease Azathioprine • Monitoring – CBC in 3-4 weeks • Then every 2 months x 3 • Then every 6 months – Panel in 3-4 weeks • Then every 6 months • Difficult to monitor for liver side effects if cholangiohepatitis already exists Inflammatory Bowel Disease Chlorambucil – Recent study shows it may be more effective when added to pred than azathioprine (Dandrieus et al, 2013) – Median survival much longer – Dose - 6-8 mg/m2 PO QOD Inflammatory Bowel Disease Budesonide – Theoretically more locally acting, less systemically absorbed than prednisone – Similar response to therapy as prednisone – Systemic side effects may happen, but also may be less likely – May be preferred for diabetics – 1-5 mg PO SID – 3 mg/m2 PO SID – More expensive than prednisone Inflammatory Bowel Disease Cyclosporine – 5 mg/kg PO SID – Use therapeutic drug monitoring to adjust dose – Can be used alone for steroid refractory IBD – Produced a 50% reduction in CIBDAI in these refractory patients Inflammatory Bowel Disease B12 and Folate – Intrinsic factor binds to B12 to prevent its digestion • Intrinsic factor made by the pancreas in the cat and the stomach/pancreas in the dog – B12 complex is absorbed in the ileum, folate in proximal SI – About one third of dogs with chronic diarrhea will have low B12 – B12 deficiency is more common in cats with chronic GI disease – B12 <200 carries worse prognosis – Dose: 250-1500ug SC once weekly for 4-6 weeks, then once monthly, and monitor to adjust dose Lissette 9 yr SF greyhound CC: weight loss, lethargy, diarrhea X 6-8 weeks (small bowel type) Hx: multiple fecal flotations and direct smears negative • Unresponsive to treatment with metronidazole, ProPectalin, fenbendazole, Albon Exam: QAR, seems thick through the middle Lissette CBC: PCV 37%, lymphocytes 500/ul Serology: • Albumin 1.7 g/dl, globulin 2.0 g/dl • Cholesterol 56 g/dl Abdominocentesis: water like fluid • Pure transudate TAMU GI Lab: • TLI – mildly decreased, PLI normal • B12 – 254 (low normal), folate 3.5 (n. 8-24) Lissette Fecal cytology: no pathogens seen Abdominal US: Lissette Fecal cytology: no pathogens seen Abdominal US: Lissette Fecal cytology: no pathogens seen Abdominal US: Mucosal stripes • small bowel (mucosa) thick by 1-2 mm • Mucosa:muscularis 5:1 MiraVista Histoplasma AG: • Neg Dx PLE: DDx • IBD • Lymphangiectasia • Lymphoma • Severe intestinal dysbiosis Lissette Endoscopy: declined for now Tx: B12 1000 mcg weekly • Prednisone 0.5 mg/lb/day x 2 weeks, then begin reducing to lowest effective dose • Hill’s low fat i/d • ProViable® Probiotics x 30 days • ProViable Forte® x 1 week Response: diarrhea much improved, but worsening of ascites until uncomfortable (3 wks) Lissette Endoscopy: accepted Preparation: • Therapeutic Abdominocentesis – 3.5L • Hetastarch 10 ml/lb given over 20 minutes, 2 days prior to scope • Repeat 3 views thoracic rads + abd US • Bile acids to rule out liver failure • Urine P:C ratio to rule out PLN • Furosemide 1 mg/lb PO BID Lissette Endoscopy: Lissette Endoscopy: Lissette Endoscopy: Lissette Endoscopy: lymphangiectasia Tx: • Continue prednisone, B12, probiotics at lowest effective doses, added folate • Ultra low fat diet – home made diet • Hetastarch and abdominocentesis PRN • Furosemide 1 mg/lb PO BID • When prednisone stopped working, tried azathioprine • Therapies stopped working 1 year later, and Lissette was humanely euthanized • MCTs can worsen diarrhea, and dogs hate them Chase 1 yr M wire haired JRT - UTD CC: he stretches after he eats Hx: started at 6 months, and getting worse • No vomiting or diarrhea • Unresponsive to treatment with metronidazole, famotidine, metoclopramide, cisapride, omeprazole, fenbendazole, hydrolyzed diet, Hill’s i/d, Purina EN, Tylan, Probiotics, Pancreatic Enzymes Exam: BAR, well hydrated, in perfect body condition Chase Multiple fecal floats, directs, Cytologies: no parasites seen CBC, panel, lytes, UA: NSAF Abdominal rads, US: NSAF TAMU GI Panel, Bile Acids, ACTH stim: NSAF Barium Series: NSAF, transit times normal Endoscopy: Lymphangiectasia Prognosis: Chase will likely not live past middle age Chase Tx: very low fat diet • Better, but still stretching on w/d • Did very well on Royal Canin GI low fat • Switched to Natura Ultra Low Fat Follow Up: • Chase has abdominal pain and will not eat when he has a dietary indiscretion • sometimes has bloody colitis stools when he is stressed • Responds very well to metronidazole, famotidine and time Chase Monitoring: • CBC, UA, GI panel, bile acids, Fecal, HW test yearly • TAMU GI panel and serum chemistries every 6 months • Has had several abdominal ultrasounds during episodes of abdominal pain (1-2 per year) • Never any significant abnormalities on any of these tests • He had his 15th birthday last month  Trip Similar presentation to Lissette Diagnosis - Lymphangiectasia Had a better response to same therapy Ascites resolved, came off diuretics Albumin improved from 0.9 to 2.2 Doing well 4 years later on alternating days prednisone and azathioprine, B12 and folate supplementation, probiotics and ultra low fat diet Lessons from Lissette, Chase & Trip • Early scoping for chronic GI problems can allow early intervention • Proper diet can prevent development of pathology associated with lymphangiectasia • Once lacteal dilation, PLE and destructive inflammatory changes take place, more medications are needed and prognosis can become irreversibly poor • Some dogs with lymphangiectasia can do well long term if very low fat diet and necessary meds are started early in the process Lymphangiectasia – Dilated & Obstructed lymphatics – cannot absorb fats well – Chyle is retained in the dilated lacteals and lymphatics is the gut wall and mesentery – Lymphatics rupture and release chyle into the intestinal lumen, which are lost • Albumin and other proteins (PLE) – globulins, clotting factors, AT3 • Fats • lymphocytes Lymphangiectasia – Loss of oncotic pressure • Peripheral edema • Ascites, pleural effusion (transudate, modified transudate) – Fat malabsorption and weight loss – Fat soluble vitamin depletion • A, D, E & K – Thromboembolic disease from loss of AT3 – Once lipogranulomas form, they are inflamed, painful and difficult to reverse Lymphangiectasia Primary Lymphangiectasia – idiopathic – Congenital malformation of lymphatics Secondary Lymphangiectasia – Chronic inflammatory intestinal disease – Fibrosing disease – Neoplasia – Lymphatic obstruction – thoracic duct obstruction, portal hypertension, pericardial disease, right heart failure Lymphangiectasia Diagnosis – Endoscopy can be diagnostic – Disease can be segmental, and limited to the muscularis, so you can miss it on endoscopy – Sometimes full thickness biopsies are needed, but they are risky in dogs with PLE and low serum proteins – Lipogranulomas can sometimes be seen on ultrasound Lymphangiectasia Diagnosis – Endoscopy can be diagnostic – Disease can be segmental, and limited to the muscularis, so you can miss it on endoscopy – Sometimes full thickness biopsies are needed, but they are risky in dogs with PLE and low serum proteins – Lipogranulomas can sometimes be seen on ultrasound Lymphangiectasia Treatment – Low fat diet is the most important treatment • long-chain triglycerides stimulate lymph flow • low fat diet can help decrease lymph flow, lymphatic distension, and the rate of enteric protein loss • <20% fat calories and high quality (BV) protein – Some patients may require vitamins A, D, E, K – Anti-inflammatory prednisone when disease becomes advanced – Can try other immunosuppressives when severe – Some patients may need to take Plavix® Boxer Colitis – Aka Histiocytic Ulcerative Colitis – Aka Granulomatous Colitis – Similar to Crohn’s Disease in people Signalment: – Young dogs less than 4 years of age – Boxers, French Bulldogs, English Bulldogs – Less often mastiffs, malamutes, Dobermans – Genetic defect in ability to clear intracellular bacteria Boxer Colitis Symptoms: – Large bowel diarrhea – Marked cachexia, unlike other causes of colitis – Hypoalbuminemia, unlike other causes of colitis – Mild anemia Colonoscopy – Erythemic, ulcerated mucosa, cobblestoned – Histopathology • Inflammatory – macrophages, lymphocytes, neutrophils • PAS positive organisms in macrophages – E coli • Goblet cells disappear, beneficial bacteria need mucus Boxer Colitis FISH Analysis – Fluorescent In Situ Hybridization $125 for first section, and $50 for each additional – Fluorescent probes attach to bacterial ribosomal DNA – Can find bacteria even with lots of inflammation – On fixed histopath samples – False negatives if on antibiotics – Intramucosal E coli in boxer colitis – FISH negative after treatment – There are increased mucosal bacteria seen on FISH analysis in cats with IBD Boxer Colitis Historically Unsuccessful Treatments: – Dietary therapy – Metronidazole – Sulfasalazine – Tylan – Prednisone – azathioprine Boxer Colitis Treatment: – Enrofloxacin 10 mg/kg/day – If resistant to enrofloxacin, consider chloramphenicol or TMPS – Boxer Colitis Panel can guide therapy in resistant cases (Dr. Kenny Simpson at Cornell) – payment form • Culture and sensitivity of colonic mucosa with special broth media • FISH Analysis • histopath Monitoring – Clinical and histologic improvement Waddles Sig: 3 year old male poodle CC: vomits once a week, otherwise seems to feel fine Exam: BCS 3.5/9, heart and lung sounds are muffled on the right side, cryptorchid MDB: CBC, panel, lytes, UA, HW Test, fecal NSAF Waddles Thoracic Radiographs: Waddles Thoracic Radiographs: Waddles Barium Study Waddles Thoracic Ultrasound Waddles Dx – diaphragmatic hernia with one lobe of the liver & gallbladder herniated into the thorax Tx - Owners chose not to repair surgically, due to financial limitations Waddles lived a long and productive life as a cryptorchid breeding animal Antibiotic Responsive Diarrhea – Formerly known as SIBO (Small Intestinal Bacterial Overgrowth)

Signalment: – Young large breed dogs, especially GSD – Defect in mucosal barrier and low IgA levels – Causes dysbiosis – changes in bacterial flora Antibiotic Responsive Diarrhea Symptoms: – Small intestinal diarrhea – Most polyphagic, but can be anorexic – Response to antibiotics and relapse when therapy stopped – Histopath normal to boring, and occasionally with inflammatory cells that might be mistaken for IBD • Usually no signs of chronicity – Low B12, variable folate (SI diarrhea in general) Antibiotic Responsive Diarrhea Treatment: – Antibiotics for 4-6 weeks • Some resolve • Some need long term therapy – Tylosin 5-20 mg/kg PO BID (cut with cornstarch for small dogs – use tablespoons) • #3 capsule holds 130mg (65mg 1:1, 43mg 1:2, 32mg 1:3) • #1 capsule holds 240 mg (80mg 1:2) • #0 capsule holds 345mg (172mg 1:1) • #00 capsule holds 430mg (215mg 1:1, 107mg 1:3) – Metronidazole 10 mg/kg PO BID – Oxytetracycline 10-20 mg/kg PO TID Antibiotic Responsive Diarrhea Treatment: – Diet – low fat, highly digestible • Purina EN low fat • Hill’s i/d low fat • Royal Canin GI Low Fat • California Naturals ultra low fat – B12 + folate as indicated on GI panel – Probiotics, prebiotics Hemorrhagic Gastroenteritis – See Vomiting section – Clostridium perfringens found on 10/11 dogs with HGE, and 1/11 of control dogs – Manage acute episodes with IV fluid and beta lactam antibiotics – High soluble (fermentable) fiber diet often helps – Or highly digestive diet with probiotics/prebiotics – Hill’s Microbiome may be a great choice Probiotics – Used to be considered “alternative” medicine, now considered conventional standard of care – Compete with pathogens – Produce antimicrobials – Produce protective organic acids – Enhance IgA secretion Probiotics Which should you use? – Product should list organisms in the container – Refrigeration is not necessarily needed, if packaging is adequate – VSL3® is recommended by some GI gurus – Culturelle® is a favorite of Scott Weese – Fortiflora® and ProViable® are other “go to’s” – More organisms is not necessarily better – Prebiotics – fructo-oligosaccharides that nourish probiotic bacteria Not usually needed for acute diarrhea, though studies show diarrhea stops 1 day earlier Probiotics Improved Toll like receptor expression For antibiotic responsive diarrhea – No response to probiotics alone after relapse when antibiotics stopped For food responsive IBD – improvement in fecal score when treated with probiotics as well as diet For idiopathic IBD – Probiotics decreased CIBDAI and improved histopathology Fecal Transplantation For chronic diarrhea (Weese, 2013) C difficile in people 1. Screen donors for enteropathogens • Giardia, Salmonella, Campylobacter, Tritrichomonas, Clostridium, Cryptosporidium, etc. (TAMU GI Lab) 2. Collect fresh sample from donor 3. Prepare fecal suspension – mix with saline, blend and filter 4. Warm water enema for recipient 5. Give fecal suspension to recipient as a 45 minute retention enema 6. Both patients clinically normal for 3 months Feline Hairballs – No longer considered just a nuisance to prescribe a hairball remedy or diet for – May indicate underlying problems resulting in either increased hair intake or decreased motility • Overgrooming – Pruritus – Hair loss – behavior problem – endorphin release – Neuropathic or musculoskeletal pain – Abdominal pain (bladder, bowel) • Upper GI motility disorder Cats Are Carnivores – Cats have carnivore dentition & retractable claws for holding prey • Dogs grind their food, cats do not • Cats have no lateral-medial movement of the jaws • Cat teeth lack occlusal surfaces for grinding – the molars and premolars interdigitate and are fewer • Cats crack their kibble into smaller pieces and swallow it – Cats don’t digest starches & sugars well • Cats lack salivary amylase, so digestion begins in the feline stomach • Cats do not have tastebuds to taste sweet • Feline pancreatic amylase production is 5% of dogs Cats Are Carnivores – Cats need double the protein as dogs • 5g/kg protein daily to maintain nitrogen balance • The only reason ever to restrict protein in a cat is to prevent hepatic encephalopathy • Cats waste muscle when protein is restricted (low creatinine is a clue) • Cats do not down regulate proteinases well • Increased transaminases and deaminases that remove the amino groups from the amino acids, converting them to keto- acids to be used for energy or glucose production • Pyridoxine (vitamin B6) is a prosthetic group of all transaminases. Feline requirement for pyridoxine is about four times that of a dog. • Cats can not convert tryptophan to niacin (vitamin B1), as an dogs, so they require four times the niacin compared to dogs Cats Are Carnivores – Cats need more taurine and arginine than dogs • These AA are rich in animal products • Cats have decreased ability to produce arginine, and increased need for it • Taurine is an essential amino acid for cats, but not for dogs – Cats have a GI tract adapted to eating protein • GI tract length in cats is relatively shorter (4:1) than dogs (6:1), with respect to body length • short colon that limits their ability to digest and absorb starches and fiber by fermentation • Big cats express ingesta from entrails before eating them Cats Are Carnivores – Cats rely on gluconeogenesis (production of glucose from proteins) for energy, as opposed to producing glucose from soluble carbohydrates • Adult cats have very low glucokinase activity in the liver as compared to dogs • In dogs, maximum gluconeogenesis occurs long after a meal is absorbed, and in cats maximum gluconeogenesis occurs as soon as proteins begin absorption from the gut • Cats have an alternative gluconeogenic pathway that uses the non-essential amino acid Serine (found in large quantities in muscle, milk and egg) to produce glucose • The intestinal sugar transport system of the cat is not adaptable to varying dietary levels of carbs • Cats have low intestinal disaccharadiase levels (sucrase, maltase, isomaltase) Cats Are Carnivores – Cats have the ability to digest and utilize high levels of dietary fat (as is present in animal tissue) • Cats don’t get pancreatitis from high fat meals • Cats have a special need for arachadonic acid, since they can not make it from linoleic acid as can the dog • Animal fats are rich in arachadonic acids – Cats can not convert beta carotene and other carotenoids (in plants) to vitamin A as dogs can • Vitamin A occurs naturally only in animal tissue – Cats have more significant post-prandial hyperglycemia than dogs after eating high starch and high sugar diets. Cats Are Carnivores – Clearly, many cats seems to thrive on high carb diets, despite not being designed to eat them • Commercial dry cat foods are 25-35%+ carbs • Hundreds of low carb canned foods to choose from • Dry Foods <10% carbs: – Wellness CORE – Innova EVO – Nature’s Variety Raw Instinct, Others becoming available – Paleolithic diet is ideal for cats – “species appropriate nutrition” • 50% protein, 40% fat, <10% carbs Cats Are Carnivores Who Cares???? – Many feline medical conditions respond to species appropriate diet • Inflammatory bowel disease • Struvite uroliths • Diabetes mellitus, pancreatitis • Idiopathic hypercalcemia • Renal failure • Hepatic lipidosis • Obesity Feline Megacolon/Constipation – Constipation is often a sign of dehydration, not just poor colonic tone and contraction – Constipated cats often vomit, especially after defecating • Cats have colon receptors that communicate with the vomiting center via afferent nerves, unlike dogs • Cats with constipation are more likely to vomit than dogs – Colonocyte lifespan is 4-7 days, so recovery from colitis can be quick Feline Megacolon/Constipation – Treatment • REHYDRATE!!! • Dietary fiber - high soluble fiber for diarrhea, high insoluble fiber for constipation early on, then low residue diet as pathology continues to megacolon • Physical removal of hard feces – sedation/removal or even subtotal colectomy • Royal Canin Fiber Response – can prevent subtotal colectomy • Need huge amounts of canned pumpkin to get adequate fiber • Don’t add Miralax until the animal is rehydrated Subtotal Colectomy

ileum

colon ileum

NO!! colon ileum Subtotal Colectomy

• Cut ileum at an angle to match opening with the colon of larger diameter • Avoid a blind pouch in the colon • Cut shorter at the antimesenteric side to avoid avascular necrosis • Take care to preserve blood supply to gut segments that you leave. – Ligate arcuate arteries first – Then resect poorly perfused tissue – Make sure not to twist the mesentery and occlude perfusion Subtotal Colectomy Feline GI Lymphoma • Small cell lymphoma, aka LGAL (Low Grade Alimentary Lymphoma) • Second hand smoke is a significant risk for all feline lymphoma • IBD a precursor to intestinal LSA • Full thickness biopsies often required for diagnosis • SI (jejunum, ileum) > colon > stomach • 80% small cell, 20% large cell • T cell more often than B cell • Mesenteric LN enlargement/cytology can not distinguish IBD from small cell LSA • Clinical signs the same for LSA and IBD, except progression and response to therapy Feline GI Lymphoma

• When do you run flow cytometry or PARR? – PARR = Lymphoma PCR • When not responding to therapy for either IBD or lymphoma and you want to confirm the diagnosis – Cats with lymphoma can have IBD pathology as well • PARR shows 35% false negatives • Flow cytometry – Homogenous cell size indicates lymphoma – Heterogenous cell size indicates IBD • CSU Submission Form – CSU Lymphoma Guide Feline GI Lymphoma

• Treatment – VCP – 73% remission, median survival 239 days – CHOP Wisconsin – 64-75% remission, median survival 563 days – Chlorambucil + prednisone – 76% remission, median survival 19 months • 100% response for rescue chemotherapy cyclophosphamide + pred Feline GI Lymphoma

• Prognosis – Small cell lymphoma does very well with treatment (median survival 2 years) – Large cell lymphoma poor prognosis – 85% of cats undergoing chemo have some sort of adverse reaction (dogs much lower) – 83% of owners of cats undergoing chemo say they would do it again APUDomas – APUD – Amine Precursor Update and Decarboxlylation • aka enterochromaffin or argentaffin cells • Make hormones – gastrin, cholecystokinin, secretin, glucagon, vasoactive intestinal peptide, somatostatin, motilin, insulin, etc. – APUDomas secrete one of these peptides – Insulinoma, gastrinoma, carcinoid (serotonin), multiple endocrine neoplasia (MEN) Summary • This PowerPoint – 1 slide/page, 6 slides/page • Laboratory Information • Auburn – Molecular Diagnostics – Submission Form • Auburn – Molecular Diagnostics – PCR Submission Kit • CSU – Immunopathology – Lymphoma Diagnostics Form • CSU – Immunopathology – Lymphoma Guide • Cornell – FISH – Submission Form • Cornell – Boxer Colitis Panel - Submission Form • Cornell – FISH – Credit card Payment Form • MiraVista – Fungal Antigen Form, Test Menu • TAMU GI Lab – GI Test Form, Shipping Information Summary Scientific Articles • ACVIM Consensus Statement – Enteropathogenic Bacteria in Pets • ACVIM Consensus Statement – Guidelines for Evaluation of GI Biopsies • Comparative Gastroenterology – ProViable® • Nutramax – ProViable® and Dysbiosis • Nutramax - Saccharomyces • Nutramax – Treatment of B12 Deficiency • Purina – Fortiflora® • D Williams – Skinny Old Cats Summary Vet Handouts • Honeckman - Canine IBD Activity Index (CIBDAI) • Norsworthy – Experiences with CCNU • Purina – Fecal Score Sheet • Purina – Large vs Small Bowel Diarrhea Summary Client Information Handouts • Antibiotic Responsive • Feline Hairballs Diarrhea • Feline Lymphoma • Boxer Colitis • Flatulence • Campylobacter • Giardia • Colitis • Giving Injections • Constipation & Megacolon • Home Made Diet Feeding • Coronavirus Guide • Diarrhea • Inflammatory Bowel Disease • Exocrine Pancreatic • Intestinal Parasites Insufficiency • Lymphangiectasia • Farina Diet • Protein Losing Enteropathy • Fecal Transplant Summary • Client Drug Handouts • Folate • Amoxicillin • Furosemide • Azathioprine • Hetastarch • Budesonide • Metronidazole • CCNU • Opiate antidiarrheals • • Chlorambucil Oxytetracycline • Praziquantel • Chloramphenicol • Prednisone • Clindamycin • Probiotics • Cyanocobalamin • Pyrantel • Cyclosporine • Pyrimethamine • Decoquinate • Sulfasalazine • Enrofloxacin • Trimethoprim sulfa • Fenbendazole • Tylosin Acknowledgements

• Adam Honeckman, DVM, ACVIM Casselberry, Florida

• Margie Scherck, DVM, ABVP Vancouver, British Columbia, Canada