GI: Small Intestine Flashcards
What is Imerslund-Grasbeck syndrome? What breeds has it been identified in?
Selective cobalamin malabsorption, likely due to a mutation in the cubilin receptor. Aussies, Beagles, Collies, and Giant Schnauzers
Name 4 clinical signs of Imerslund-Grasbeck syndrome
Inappetence, diarrhea, failure to thrive, liver degeneration and hepatoencephalopathy, neutropenia, anemia, and proteinuria
What is found in the urine of dogs with Imerslund-Grasbeck syndrome?
Methylmalonic aciduria
Why does large bowel diarrhea often accompany small bowel diarrhea, even if only the small intestine is diseased?
Malabsorption results in small bowel, osmotic diarrhea. However, bacterial fermentation of the unabsorbed solutes creates products (hydroxylated fatty acids, unconjugated bile acids) that cause colonic secretion as well
What does permeability diarrhea result from?
Inflammation or neoplastic infiltrates causing exudation
Name 5 causes of secretory diarrhea
Bacterial endotoxins (C. perfringens, E. coli, etc), hydroxylated fatty acids or unconjugated bile acids from bacterial fermentation, Giardia, stimulant laxatives (castor oil), inflammation
What test can be used to diagnose PLE if hypoalbuminemia is absent?
Fecal alpha-1 protease inhibitor
What breed develops both PLE and PLN?
Soft Coated Wheaten terriers
What is fecal calprotectin and what does it correlate to?
Molecule released with neutrophil elastase activity. Correlates with histologic inflammation in canine IBD, but not necessarily with clinical signs
Campylobacter species have been isolated from what percent of healthy dogs?
100% - likely a commensal. May cause disease in immunocompromised patients or with co-infections
When Campylobacter causes disease, describe its pathogenicity
Invades intestinal epithelial cells, resulting in ulcerative enterocolitis
What do Campylobacter species look like on a fecal smear? How do you definitively diagnose them?
Slender, seagull shaped bacteria
PCR
When should Campylobacter infections be treated?
If the owner is immunocompromised (low zoonotic risk) or with severe clinical signs
How is Campylobacter treated?
Erythromycin, tylosin, or clindamycin
Name 4 outcomes after infection with Salmonella
- Transient subclinical infection
- Acute gastroenteritis
- Bacteremia and endotoxemia
- Carrier state
What is the receptor for Salmonella invasion, leading to GI translocation?
Cystic fibrosis transmembrane conductance regulator (CFTR) protein
A seasonal, acute, febrile illness and diarrhea in cats, known as “songbird fever” is caused by what organism?
Salmonella typhimurium - carried by migrating songbirds in the Mediterranean
Why is antibiotic treatment not recommended in asymptomatic animals or patients with mild diarrhea caused by Salmonella?
Antibiotics can induce a carrier state
If needed, what antibiotic should be used to treat Salmonella?
Fluoroquinolones for at least 10 days - less likely to cause a carrier state
A granulomatous enterocolitis with mesenteric lymphadenopathy in 5 Bassett Hounds was associated with what pathogen?
Mycobacterium avium
What fluke carries Neorickettsia organisms?
Nanophyetus salmonicola
What clinical signs are caused by Neorickettsia and when do they occur?
One week after ingesting salmon and the fluke - high fever, hemorrhagic gastroenteritis, vomiting, oculonasal discharge, peripheral lymphadenopathy
How is Neorickettsia diagnosed?
Operculated fluke eggs in the feces are suggestive. Intracytoplasmic inclusion bodies in macrophages from LN aspirates
How is Neorickettsia treated? How is the fluke treated
Oxytetracycline for at least 5 days
Fluke: praziquantal
How does blue green algae cause death?
Synthesize an anti cholinesterase that leads to vomiting, diarrhea, ataxia, and rapid death
What are the routes of infection for roundworms (Toxocara spp)?
Primarily transplacental (T canis) and transmammary (T canis and felis). Can be fecal oral too
Migrating juvenile Toxocara canis can cause damage to what organs?
Hepatic, pulmonary, and ocular damage
Describe symptoms of roundworm infection
Most common in puppies, kittens. Diarrhea, weight loss, failure to thrive, rough haircoat, potbellied appearance
In humans, Toxocara can cause what disease?
Visceral, ocular, and neural larval migrans
What are the primary routes of infection for hookworms (Ancylostoma spp)?
Transplacental, transmammary (not in cats), ingesting larvae in feces, migration through the skin
Describe the clinical findings with hookworm infections?
Can cause severe anemia, diarrhea, vomiting, dehydration, poor growth
How is hookworm treated?
Pyrantel
What is the most common tapeworm in the US? What is the intermediate host?
Dipylidium caninum
Fleas
What are the most common coccidial parasites of dogs and cats?
Isospora species
What are the clinical signs of Isospora infection?
Usually aclinical. Can cause mucoid, occasionally bloody diarrhea in puppies/kittens or immunosuppressed animals with heavy infections
If using a zinc sulfate fecal float to identify Giardia, how many samples need to be run?
3 within 5 days (95% sensitivity) - due to intermittent shedding
Other than a fecal float, how can Giardia be detected? What is the sensitivity and specificity?
Giardia fecal ELISA - 95% specific, 90% sensitive
How is Giardia treated?
- Metronidazole 25mg/kg PO q12 x 5 days eliminated 2/3 of cases
- Fenbendazole 50mg/kg PO q12 x 3-5 days usually effective
What are potential mechanisms that lead to a breakdown of oral tolerance, leading to food allergies?
- Inadequate mucosal barrier
- Abnormal microbiome
- Abnormal presentation of dietary antigens to the immune system
- Immune system dysregulation
What types of hypersensitivity reactions may occur in food allergies?
Type 1 - IgE mediated
Type 3 - immune complex deposition
Type 4 - delayed hypersensitivity
To completely abolish ALL antigenicity, peptides need to be less than what size? What diet accomplishes this?
<1kD
Ultamino
The majority of hydrolyzed diets break peptides down into what size? How is this anti-allergenic?
7-10kD; small enough to avoid cross linking IgE molecules on mast cells (avoids type I hypersensitivity reactions), but could still theoretically induce type IV reactions
What breed displays inherited (autosomal recessive) gluten sensitive enteropathy?
Irish Setters
What are the clinical signs of gluten sensitive enteropathy in Irish Setters?
Poor weight gain and chronic, intermittent diarrhea after weaning
Idiopathic, antibiotic responsive diarrhea is most commonly recognized in what dog breed?
German Shepherds
What are the clinical signs of idiopathic antibiotic responsive diarrhea?
Chronic, intermittent diarrhea, weight loss or stunted growth, excessive gas production, usually polyphagia/pica. Worsens with steroids
Neutrophilic enteritis in cats has been associated with what bacteria?
Campylobacter coli
Describe the clinical signs of Basenji enteropathy
Chronic, intractable diarrhea and emaciation, spontaneous intestinal perforation can occur
What is the cause of Basenji enteropathy? What other clinical conditions can occur?
Severe, hereditary lymphoplasmacytic enteritis. Can also display hyperglobulinemia, hypergastrinemia, mucosal hyperplasia, and PLE
What is the treatment for Basenji enteropathy?
Early intervention with prednisone, antibiotics, and diet. But most die with months of diagnosis
What is the genetic basis for PLE/PLN in Soft Coated Wheaten Terriers?
Traces back to one male. Mutations in NPHS1 and KIRREL2 genes implicated. Likely immune mediated
Do Soft Coated Wheaten Terriers develop PLE or PLN first?
Usually PLE
Ultrasonographic loss of wall layering in the small intestine is highly predictive of what disease process?
Neoplasia - 50 fold increase in the likelihood of neoplasia if loss of wall layering is noted
What is the survival time of cats with small cell GI lymphoma treated with prednisolone and chlorambucil?
19-29 months
What is the survival time of cats with large cell GI lymphoma treated with multi agent chemo?
7-10 months
What cells do gastrointestinal stromal cell tumors (GIST) arise from?
Interstitial cells of Cajal
What is an important histologic marker of GISTs?
c-Kit
How do leiomyosarcomas induce hypoglycemia?
Production of insulin-like growth factor II-like peptides
What paraneoplastic syndromes can be seen with leiomyosarcomas?
Hypoglycemia, erythrocytosis, nephrogenic diabetes insipidus
What cat breed may be predisposed to intussusception?
Maine Coons
Cobalamin in ingested bound to dietary proteins. What occurs in the stomach?
Cobalamin is released from dietary proteins by pepsinogen and gastric acid. It then binds to haptocorrin (aka R protein aka transcobalamin I) to protect it from bacterial utilization
After binding to haptocorrin in the stomach, what happens to cobalamin in the duodenum?
Pancreatic proteases separate cobalamin from haptocorrin, and free cobalamin then binds to intrinsic factor (IF)
Where is intrinsic factor synthesized in the dog and cat?
Dog: primarily the exocrine pancreas, small amount in the stomach
Cat: only the exocrine pancreas
How is cobalamin absorbed in the ileum?
Cobalamin-IF complex binds to the cubam receptor in the brush border of the ileum and is absorbed by receptor-mediated endocytosis
The cubam receptor is comprised of two subunits. What are they?
Amnionless (AMN) and cubilin (CUBN)
What percent of cobalamin is absorbed by passive diffusion across the mucosal epithelium, rather than by the cubam receptor?
1%
What happens to cobalamin within the enterocyte?
Within the lysosome, cobalamin is separated from intrinsic factor and cubam. Cobalamin then binds to a transport protein, transcobalamin for transport in the blood
Which form of transcobalamin is available for uptake at target tissues?
Transcobalamin II
What is the function of cobalamin in cells?
Essential cofactor for the intracellular enzymes methionine synthase and methylmalonyl-CoA mutase
What is the function of methionine synthase?
Catalyzes the regeneration of methionine and tetrahydrofolate from homocysteine
Disorders associated with a deficiency in intracellular cobalamin can lead to a decrease in what other functional vitamin?
Functional folate (from decreased methionine synthase activity)
What is the function of methylmalonyl CoA mutase?
Catalyzes the reaction from methylmalonyl CoA to succinyl CoA, which is a key molecule in the TCA cycle
What two products accumulate with intracellular cobalamin deficiency?
Homocysteine and methylmalonyl CoA (MMA)
How can excess MMA lead to hyperammonemia?
MMA can inhibit the activity of an enzyme in the urea cycle, impairing the conversion of ammonia to carbamoyl phosphate
How is cobalamin excreted?
Undergoes biliary excretion and a large amount is conserved by enterohepatic recirculation. Some renal excretion but is reabsorbed in the tubules
What receptor in the renal tubule reabsorbs cobalamin?
Megalin
How is cobalamin routinely measured in the US and Europe?
Automated chemiluminescence assay
Is homocysteine or MMA more specific for intracellular cobalamin deficiency?
MMA - homocysteine can also increase with folate or B6 deficiency, renal insufficiency or hypothyroidism