GI: Large intestine and ulcers Flashcards
How is water absorbed in the large intestine?
Passive osmosis following active absorption of sodium, primarily in the proximal colon
Absorption of sodium from the large intestine is mediated by what two hormones? What is the mechanism?
Aldosterone and glucocorticoids - stimulate the activity of the Na+/K+ ATPase pump
How is potassium absorbed in the large intestine?
K+/H+ exchanger
How is chloride absorbed in the large intestine?
Either by passive diffusion along the electrochemical gradient following sodium absorption or by a chloride/bicarbonate exchanger
What is the mechanism of action of sulfasalazine?
Pro-drug of 5-amino salicylic acid, which is an NSAID. The pro-drug is broken apart by bacteria in the colon, and the 5-ASA acts to directly inhibit prostaglandin and leukotriene synthesis in the colonic mucosa
What is a side effect of sulfasalazine?
KCS
What is the characteristic histopathologic finding with granulomatous colitis?
Macrophages full of Periodic-Acid-Schiff positive staining material underlying an ulcerated colonic mucosa
Where do adherent and invasive E coli replicate in granulomatous colitis?
Within the phagolysosomes of macrophages - leading to granulomatous lesions
How does enterotoxigenic E coli (ETEC) lead to small intestinal diarrhea?
Produces heat labile and heat stable toxins that stimulate excessive secretions by the small intestine
How do enteropathic E coli (EPEC) lead to diarrhea?
Cause attaching and effacing damage to intestinal epithelial microvilli through intimin expression. Most common in kittens and puppies
How do enterohemorrhagic E coli (EHEC) cause diarrhea?
Non-invasive, but produce Shiga-like toxins that kill colonocytes by inhibition of protein synthesis - leads to edema, submucosal hemorrhage and hemorrhagic diarrhea
What is Alabama rot?
Disease in Greyhounds that leads to ulcerative skin lesions and AKI. Some association with being fed raw meat, and enterohemorrhagic E coli has been implicated
Where is Prototheca acquired?
Animal waste and sewage contaminated food, soil, or water. Impaired host cellular immunity likely plays a role in infection/dissemination
Name 3 clinical signs of Protothecosis?
Chronic, intermittent bloody diarrhea, uveitis, neurologic signs
How is disseminated Prototheca treated?
Amphotericin B and itraconazole
Where is Histoplasma capsulatum acquired?
Warm, moist, nitrogen rich soil contaminated by bat or bird droppings. Mainly along the Ohio, Missouri, and Mississippi rivers
Describe the pathogenesis of Histoplasmosis
Spores are inhaled, then disseminated by macrophages to the GI tract and other organs. Alternatively, spores may be eaten and directly infect the GI tract. Leads to granulomatous inflammation
Name 3 clinical signs of Tritrichomonas foetus infection in cats
Chronic colitis with waxing and waning large bowel diarrhea, mucus/hematochezia, FOUL smell, anal irritation, fecal incontinence
What form does Tritrichomonas exist in?
Trophozoite form
What is the typical signalment of cats with Tritrichomonas?
Young (<1 yr), pedigree cats in crowded catteries, rehoming centers, or multi-cat households. BUT can remain latent and recrudesce in older, stressed cats
What is the best sample to test for Tritrichomonas?
High colonic washings that are centrifuged and allowed to settle - examine the sediment. Diarrhea samples NOT collected from litter also ok (litter can interfere with PCR)
What diagnostic tests can be used to identify Tritrichomonas?
- Identification of motile organisms on a direct wet mount - characteristic forward, jerky motion with an undulating membrane and 3 anterior flagella (sensitivity only 14%)
- Culture system: Feline In Pouch TF (must grow for 12 days)
- PCR
What is the treatment for Tritrichomonas? What are the side effects
Ronidazole - can cause neurologic signs that resolve with discontinuation of therapy
Describe the life cycle of Heterobilharzia americana.
Reservoir host - raccoons
Intermediate host - snails
Cercariae from the snail penetrate the dog’s skin and migrate through the lungs and the liver. Matures in the liver and lays eggs in the terminal mesenteric venules. Ova migrate through the bowel wall by releasing proteolytic enzymes => severe granulomatous inflammation
What are clinical signs and clinicopathologic changes seen with Heterobilharzia?
- Vomiting, large intestinal diarrhea, hematochezia
- Hypoalbuminemia, hyperglobulinemia, ELE, hypercalcemia from granulomatous disease
How is Heterobilharzia treated?
Fenbendazole with praziquantel
Where do the larvae of Trichuris live? What type of inflammation do they cause?
- Prefer the cecum and proximal colon
- Anterior portion burrows into the colonic wall, causing granulomatous inflammation. Can also cause cecal inversion
What biochemical abnormalities can be seen with Trichuris infection?
Hyperkalemia and hyponatremia (pseudo-Addison’s)
Large intestinal adenocarcinoma most commonly develops in what location? What breeds are over-represented?
- Distal colon and rectum
- Westies, GSD, Collies
Where are leiomyosarcomas most commonly found?
Cecum
In cats, what is the most common large intestinal tumor and where is it located? What breed is predisposed?
- Adenocarcimona (46%, lymphoma only 41%) - distal colon and ileocolic junction.
- Siamese
Do canine or feline colonic tumors have a higher rate of local metastasis?
Feline - 60%
What is the MST of dogs with colorectal adenocarcimona?
1.6 months without surgery, 7 months longer with surgical excision
What breed is over-represented for adenomatous colo-rectal polyps?
Miniature dachshund
What is pseudopolyposis?
Multiple nodules are found throughout the colon - not true polyps as the lack a stalk, but are benign. Treated with glucocorticoids
What are the clinical signs of colonic vascular ectasia (angiodysplasia)?
Marked hematochezia, occasionally requiring transfusions. Areas of coalescing, tortuous mucosal blood vessels on endoscopy.
What is the treatment of colonic vascular ectasia (angiodysplasia)?
Surgical resection of the affected region recommended. Argon laser ablation and electrocautery can be tried. Estrogens and progesterone used commonly, octreotide may be helpful
Megacolon develops through 2 mechanisms. Name them and discuss causes
- Hypertrophic megacolon: develops as a consequence of obstruction (malunion of pelvic fractures, tumors, foreign bodies) - may be reversible with early intervention or may lead to dilated megacolon
- Dilated megacolon: develops due to electrolyte abnormalities, neuromuscular disorders, or idiopathic. Irreversible
Name 3 metabolic causes of constipation
Dehydration, hypokalemia, hypercalcemia, hypothyroidism
What are emollient laxatives?
- Anionic detergents that increase the miscibility of water and lipid in the digest - impairs water absorption
- Ex. Docusate (DSS)
What are hyperosmotic laxatives?
Poorly absorbed polysaccharides (lactulose), magnesium salts (citrate, hydroxide, sulfate), hypertonic sodium phosphate or PEGs. Osmotically draw water into the colon. Fermentation of lactulose also results in organic acids that stimulate colonic fluid secretion and propulsive motility
Why are enemas containing sodium phosphate contraindicated in cats and small dogs?
Cause fatal hypernatremia, hyperphosphatemia, and hypocalcemia
What nerve provides sympathetic stimulation to the descending colon and rectum? What does sympathetic stimulation do?
- Hypogastric nerves - originating from L1-4 or L5
- Sympathetic stimulation decreases motility and tightens the internal anal sphincter
What nerve provides parasympathetic stimulation to the descending colon/rectum? What does parasympathetic stimulation do?
- Pelvic nerve - originating from the sacrum
- Parasympathetic stimulation increases colonic and rectal motility
What nerve provides somatic innervation to the striated muscle of the external anal sphincter, thus providing voluntary control of contraction?
Pudendal nerve - originating from the sacral spinal cord
What is the gastrocolic reflex?
Intake of food induces propagating pressure waves, which move food into the rectum
What is the recto-sphincteric inhibition reflex?
Increased intrarectal pressure leads to reflexive relaxation of the internal anal sphincter
In patients with sphincter incontinence (no conscious recognition of feces passage), neurologic disease in what location should be suspected?
Sacrococcygeal disease
Perineal hernias most commonly occur in what signalment of dog? What are the presenting complaints?
- Middle age to older, intact male dogs
- Chronic tenesmus, constipation, and perineal swelling. Can have paradoxical diarrhea caused by fluid and mucus bypassing a retained fecal mass
What are the most common causes of rectal prolapse?
Severe, persistent straining from colitis or parasites. Other urogenital or large intestinal disease can cause it due to straining
What causes perianal fistulas?
Suspected to be a immune mediated mechanism in genetically susceptible dogs, leading to ulceration and fistulous tracts in the perineal area
80% of perineal fistula cases are in what breed?
German Shepherd
What percent of dogs with perineal fistulas have concurrent colitis?
50%
What does histopathology of a perineal fistula reveal?
Dense sheets of plasma cells and perivascular lymphoid nodules, increased expression of Th1 cytokines
Upregulation of what may contribute to the ulcerative nature of perineal fistulas?
MMPs - MMP 9 and 13
What diagnostic can be used to identify a colonic torsion in dogs?
Pneumocolon
In cats undergoing a subtotal colectomy for idiopathic megacolon, what was the major perioperative complication rate? What complications occurred?
9.9% - dehiscence, death, renal failure, necrosis
In cats undergoing a subtotal colectomy for idiopathic megacolon, what was the MST? What was associated with shorter survival?
- MST not reached, did very well
- Shorter survival associated with BCS <4, preexisting heart disease, major preoperative complications, long term postoperative liquid feces
In cats undergoing a subtotal colectomy for idiopathic megacolon, what percent had recurrence of constipation and when did it occur?
32% at a median of 344 days
In cats undergoing a subtotal colectomy for idiopathic megacolon, removal of the ICJ was associated with what?
Long term liquid feces, poor owner perceived outcome
What is the most common cause of chronic diarrhea in dogs?
IBD (71%) - 66% of those cases were diet responsive
In dogs with acute diarrhea (<3) did treatment with Clavamox improve clinical recovery?
No - all dogs recovered within a median of 2 days
In dogs with acute diarrhea (<3) did treatment with Clavamox alter dysbiosis or induce resistance in E coli?
- No difference in dysbiosis index (-2.6 in the antibiotic group vs -0.8 in placebo)
- Proportion of resistant E coli increased during treatment and for 3 weeks after (100% in antibiotic vs 0.2% placebo)
In dogs with acute diarrhea, how did treatment with a probiotic paste (Enterococcus faecium) affect outcomes?
- Shorter duration of diarrhea (32 hours vs 47 hours), rate of resolution 1.6x faster
- Fewer dogs required additional medical intervention (3.5% vs 14.8% of dogs)
In dogs with acute diarrhea treated with metronidazole, how did metronidazole treatment affect outcomes?
- Shorter time to resolution of diarrhea (2.1 days vs 3.6 days)
- Decreased culture of C. perfringens (23% vs 78% of dogs)
What organism was found in more cats with neutrophilic IBD vs cats with LP IBD?
Campylobacter coli
What parasite was found in high concentrations in shelter dogs compared to pet dogs in the Phoenix area?
Giardia (40% vs 10% in pet dogs)
In a study of 237 dogs with AHDS, what percent recovered with symptomatic care only (no antimicrobials)? What percent survived to discharge?
- 62% recovered with no antimicrobials
- 96% survival to discharge
- Dogs with SIRS signs were more likely to receive antimicrobials, less likely to survive (77% survival)
How did the microbiota of dogs with AHDS differ from healthy controls?
Reduced diversity - decreased Firmicutes, increased Proteobacteria, increased C. perfringens and Providencia
What percent of dogs with AHDS are positive for C. perfringens toxins netE and netF by PCR compared to healthy dogs?
48% of dogs with AHDS compared to 12% of healthy controls
In dogs with granulomatous colitis, what percent display E coli resistance to fluoroquinolones?
63% in one study - treated with meropenam or doxycycline
What percent of dogs with granulomatous colitis responded to antibiotics in the 2020 JVIM study?
- Positive long term outcome in 80% of cases
- 8/9 dogs susceptible to fluoroquinolones had a complete response
- 9/13 dogs had a complete or partial response to meropenam or doxycycline
Fluoroquinolone resistance was associated with gene mutations in dogs with granulomatous colitis?
gryA and parC
When testing for Giardia, differences in commercial in-clinic immunoassay sensitivities can be mitigated when what test is performed concurrently?
Zinc sulfate fecal floatation
What is the probability of a positive T. foetus test on fecal samples collected via fecal loop vs samples collected by colonic flush?
Fecal loop has increased probability - OR 2.04
What percent of cats treated with ronidazole have a second positive test result for T. foetus?
21%
What dosing frequency of omeprazole was required for the resolution of duodenal peptic ulcers in a dog? What was the target pH?
- Twice daily (q12)
- pH >3 for at least 75% of the day
Fecal occult blood testing was able to identify what volume of blood in the feces?
15mg/kg hemoglobin detected in all cats (1.5mL blood); however, in one cat, testing detected 1.5mg/kg hemoglobin
What is the most common complication with video capsule endoscopy and what factors increase this risk?
Incomplete studies in 25% of dogs with GI disease - oral administration of the capsule (vs endoscopic), administration of opioids or simethicone, chronic enteropathy, and gastric transit time > 6 hours
What is the sensitivity of ultrasound and CT for detecting non-perforated gastric or intestinal ulcers?
65 and 67%, respectively
In meloxicam induced ulceration, what serum biochemical parameter increased as ulceration occurred and correlated with gastroscopic scoring of the lesion?
Serum gastrin
Hospitalization may result in what change to motility?
Prolonged gastric emptying time
In a double blinded study in which dogs were given clopidogrel, prednisone, or both for 28 days, which groups had higher numbers of gastric erosive lesions?
Prednisone and pred/clopidogrel combo groups both had erosions (not worse between the groups). Clopidogrel alone did not cause erosions
In a double blinded study in which dogs were given aspirin prednisone, or both for 28 days, which groups had higher numbers of gastric erosive lesions?
Everyone except placebo.
- Aspirin did induce punctate erosions and hemorrhages on day 14 but not day 28
- Pred caused hemorrhages, punctate and invasive erosions at day 14 and 28 (11 times higher odds than placebo)
- Pred and aspirin caused SO MANY erosions and some ulcers (31 times higher odds than placebo)
In both clinical trials investigating prednisone combined with aspirin or clopidogrel, what clinical signs were seen in dogs with erosions/ulcers?
None
What factors were associated with gastroduodenal ulceration or erosion in a study of 168 dogs on necropsy?
NSAID administration (OR 6.3), glucocorticoid administration (OR 3), gastrointestinal neoplasia (OR 13.5), and gastrointestinal mechanical disease, such as foreign body, GDV (OR 4.8). Also working dog breeds (OR 2.8)
In a study of dogs receiving NSAIDS for a median of 6 months, what percent of dogs had GI erosions?
83% compared to 27% of control dogs with GI disease
What is the optimum pH and time at that pH for the treatment of GI ulcers in people? For clot stabilization?
Ulcers: pH >3 for 75% of the day and >4 for 67% of the day
Clot stabilization: pH >6
What drugs achieve the goals for treatment of gastoduodenal ulceration in dogs?
Esomeprazole IV, famotidine CRI
Pantoprazole IV did not reach the goals, but did increase pH
In an ex vivo model of gastric mucosal injury, application of sucralfate induced what changes?
Improved gastric barrier function at the time of injury and at recovery
Which of the following drugs achieved the goals defined to treatment of duodenal ulceration in cats: oral esomeprazole, lansoprazole, or dexlansoprazole?
Esomeprazole only: 54% MPT above pH 3, but only 4% MPT above pH 4. Others were worse
In cats treated with omeprazole for 60 days, what changes were noted on blood work or imaging?
- Higher serum gastrin
- No change in calcium, magnesium, cobalamin
- No change in bone mineral density
In cats treated with omeprazole for 60 days, what happened to gastric acidity after abrupt withdrawal of omeprazole?
Rebound hyperacidity
Is 0.5mg/kg or 1mg/kg esomeprazole IV q12 more effective?
Not significantly different, can use either
What is esomeprazole?
The S only isomer of omeprazole (which is a racemic mixture)
When carprofen is administered to healthy dogs, adding omeprazole does what to the fecal microbiome?
Increases the dysbiosis index and increases fecal calprotectin (inflammation marker)
Administering famotidine for 14 days does what to gastric pH?
pH initially increased in days 1/2. However, pH decreases (by 1.63) by day 12/13 along with MPT >3 (by 33%) and MPT >4 (by 45%). Gastrin increases over time as well. Diminishing acid suppression over time
What is the main mechanism of action of sucralfate?
In the presence of gastric acid, sucralfate breaks into sucrose sulfate and aluminum salts. The negatively charged sulfate groups bind electrostatic ally to positive charged proteins in ulcerated areas - 5x greater affinity for ulcerated areas than normal mucosa
What are two secondary mechanisms of action for sucralfate?
Decreases pepsin activity
Stimulates release of protective prostaglandins, leading to increased mucosal blood flow, mucus production
What drugs does sucralfate interfere with?
- Drugs that are dependent on acidic gastric pH (ex PPIs, Azole class anti-fungals, mycophenolate)
- Drugs that are affected by the aluminum component of sucralfate (tetracyclines, ciprofloxacin)
Which histamine receptor 2 antagonist inhibits cytochrome P450, which can lead to drug interactions?
Cimetidine
Which histamine receptor 2 antagonist was not more effective than placebo at increasing gastric pH in dogs and cats (IV or oral)?
Ranitidine
What are clinical situations where famotidine may be useful?
Immediate relief of symptoms on an as needed basis (bilious vomiting) or short term (prevention of reflux under anesthesia). Due to the decreased effect after 2-3 days of use, long term acid suppression is not an appropriate use
What is the mechanism of action of proton pump inhibitors?
From disulfide bonds with the active proton-pumping H+/K+ ATPase enzymes
In a healthy dog, the intragastric pH is less than ____ 85% of the time
<2
What is the proposed mechanism of action for why H2RAs become ineffective with daily use?
May result in gastrin-induced up regulation of enterochromaffin-like cell synthesis of histamine = more histamine to compete with H2RAs at the parietal cell receptors
How does gastric acid promote iron absorption?
Reduces the ferric acid form of iron to the more soluble ferrous form
