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
What tissues/cells are most affected by cobalamin deficiency?
Tissues/cells with a high turnover rate (enterocytes, blood cells)
What other condition can lead to an increase in serum MMA?
Renal insufficiency (cleared by the kidneys)
What percent of dogs with chronic enteropathy have a normal serum cobalamin with an elevated MMA (reflecting intracellular cobalamin deficiency)?
12%
What percent of dogs with chronic enteropathy have a low normal serum cobalamin with an elevated MMA (reflecting intracellular cobalamin deficiency)?
22%
Hypercobalaminemia can occur in cats with what diseases?
Hepatic disease, neoplasia
What abnormalities on a CBC are associated with cobalamin deficiency?
Non-regenerative anemia with megaloblastosis, neutropenia, and hypersegmented neutrophils
What are the clinical signs of congenital cobalamin deficiency?
Intermittent diarrhea, inappetence, low BCS, hyperammonemia, hypoglycemia, ketoacidosis, intermittent impaired swallowing, bradyarrhythmia
What mutations are responsible for congenital cobalamin deficiency? What breed is affected?
- Mutations in amnionless (AMN): Australian Shepherd, Giant Schnauzer
- Mutations in cubilin (CUBN): Border Collie (less severe), Beagle (more severe), Komondor
What percent of dogs with EPI have cobalamin deficiency?
82% (severe in 36% = <100 ng/L)
60% of all EPI cases are in what dog breed?
German Shepherd
Why do dogs/cats with EPI develop hypocobalaminemia?
Likely due to IF deficiency. Decrease release of cobalamin from haptocorrin has also been proposed, but supplementation with pancreatic enzymes does not improve serum cobalamin levels. Require parenteral cobalamin supplementation
Why does cobalamin deficiency occur in dogs with chronic enteropathy?
- Chronic mucosal disease in the ileum may lead to reduced epithelial expression or function of cubam (not proven)
- Secondary dysbiosis
What percent of dogs with chronic enteropathy are cobalamin deficient?
19-38%
How can hypocobalaminemia contribute to GI disease?
Cobalamin deficiency can lead to mucosal inflammatory infiltration and villous atrophy
What bacteria can bind to and utilize cobalamin-IF complexes?
Bacteroides (other bacteria can only use free cobalamin)
In cats with gastrointestinal disease treated with weekly injections of cobalamin for 6 weeks, what happened to their serum cobalamin at week 6, then 4 weeks and 10 weeks after discontinuation of treatment?
At week 6, cobalamin had significantly increased (from 111 to 2,330) and serum/urine MMA had decreased (372 to 1.6) but remained elevated. Over time, values became abnormal again. Clinical disease also worsened
In a colony of apparently healthy cats, serum cobalamin was inversely correlated with what parameter?
Age (over 7 years = lower cobalamin, but still well within reference - 540)
When administering parenteral hydroxocobalamin to juvenile beagles with congenital cobalamin malabsorption, what frequency of injection was required?
Monthly or every other month were both adequate (urine MMA remained low, no clinical signs)
What percent of cats with GI signs and hypocobalaminemia have a normal ultrasound?
1/3
In juvenile Beagles with congenital cobalamin malabsorption, what form of supplementation was as effective as parenteral?
Daily 1mg cyanocobalamin (maintained low serum/urine MMA, no clinical signs) - only 3 dogs though
Serum cobalamin concentration is stable for how many days in the refrigerator? How does light and room temperature affect the sample
5 days
Exposure to light and room temperature mildly decreased cobalamin (0.14% per hour)
Hydroxycobalamin (given IM) was as effective as cyanocobalamin when given how frequently to cats with GI disease?
Every 2 weeks
Is oral cobalamin supplementation efficacious in dogs and cats with chronic GI disease?
Yes
Dogs: improved cobalamin from 223 to 1017 when given daily in a retrospective (JAVMA 2016)
Cats: improved cobalamin from 128 to 2701 when given 0.25mg daily (JFMS 2016)
What is one of the most common causes of spontaneous intestinal perforation in cats?
Lymphoma
What is the MST for dogs with primary intestinal lymphoma?
62 days , even with CHOP
What cell type is predominately found in canine primary intestinal lymphoma or small cell intestinal lymphoma?
T cell
In dogs with low grade (small cell) GI lymphoma, how is it treated and what is the MST?
424 days, 70% responded to prednisone and chlorambucil
In the 2020 JVIM study evaluating intestinal endoscopic biopsies from cats, what was the agreement between upper and lower SI samples? How often was LSA diagnosed in lower intestinal samples?
Moderate agreement (kappa = 0.7)
Only 2.3% diagnosed from lower intestinal samples
In the 2020 JVIM study evaluating intestinal endoscopic biopsies from cats, what percent of samples were re-classified as LSA after integrating IHC and clonality testing?
67% of the IBD/possible LSA cases were re-classified as definitely LSA. No LSA case was reclassified as IBD
What IHC stain is used to identify T cells? B cells?
T cells: CD3
B cells: CD20, CD79a, or PAX-5
What is the sensitivity and specificity for PARR in the diagnosis of feline small cell GI lymphoma?
Sensitivity 86%, specificity 33% :( always combine with IHC
In addition to IHC and PARR, what diagnostic could be considered for differentiating feline IBD from SCL?
Histology guided mass spectrometry: sensitivity 87%, specificity 91%, accuracy 89%
On TEG, what changes are noted in dogs with chronic enteropathy compared to healthy controls?
Higher MA (hypercoagulable) longer clot lysis times (hypofibrinolysis). MA correlated with serum albumin, vitamin D, and plasma antithrombin levels
What is Wells-like syndrome?
Acute onset eosinophilic cellulitis - deeply erythematous macules, papules, and plaques (worse over the inguinal/abdominal region) with acute onset vomiting and hematochezia
Wells-like syndrome (acute onset erythroderma) is associated with what conditions in dogs?
IBD, pancreatitis, adverse food reaction, drug reactions
What is the prognosis with Wells-like syndrome (acute onset erythroderma)?
Good - GI signs resolved with 5 days, skin lesions within 20 days after diagnosis
What serum amino acids are significantly lower in dogs with IBD compared to controls?
Methionine, proline, serine, tryptophan
Which serum amino acid was negatively correlated to CCECAI scores?
Serine (r = -0.67 though, so only moderate correlation) - could be a new biomarker?
When comparing ultrasound to full thickness biopsy in cats with GI disease, what is the positive predictive and negative predictive values?
PPV is high (82% to 91%), NPV is low (27-40%). It was higher for mucosal lesions than submucosal or muscularis lesions. Therefore, most cats with mucosal ultrasonographic lesions will have mucosal histologic lesions
What causes functional iron deficiency?
Systemic inflammation (increased cytokine production) leading to increased hepcidin production and the cellular internalization of ferroportin
What is ferroportin and how does internalization of this structure lead to iron deficiency?
Iron export protein located on the basolateral membrane of GI cells. Internalization results in defective iron absorption. Reticuloendothelial cell iron store are increased, but cannot be exported into the blood => relative iron deficiency
What percent of cats with IBD had functional iron deficiency?
35%
In cats with chronic GI disease, total iron binding capacity was lower in cats with what other biochemical change?
Increased MMA
What percent of cats with GI signs and thickening of the SI on ultrasound had IBD or SCL?
96%
What are the most common signs of mirtazepine toxicity?
Vocalization (56%), agitation (31%), vomiting (26%), ataxia (16%), restlessness (14%), tremors (14%), hyper salivation (13%). Onset in 15 mins to 3 hours, recovered by 12-48 hours
What bacterium were present in greater numbers in the adherent mucus of cats with small cell LSA compared to IBD?
Fusobacterium and Bacteroides
For every 1 unit increase in serum haptoglobin, the odds of what disease in cats increased by 1.4%?
IBD or small cell lymphoma - haptoglobin increased in both, but cannot differentiate the two
90% of conjugated bile acids are resorbed in the ileum through what transporter, which was decreased in dogs with chronic enteropathy?
Apical sodium-dependent bile acid transporter
What two general inflammatory markers were higher in dogs with chronic enteropathy than healthy dogs? Which one correlated with histopath scores?
CRP and high-mobility group box 1 (HMGB1). HMGB1 correlated with histopathology
Dogs with IBD had decreased percentages of what lymphocytes in circulation?
TCRgamma-delta T cells, CD21+ B cells
What is alpha1-proteinase inhibitor?
Produced by the liver, protects agains the effects of trypsin, chymotrypsin, and neutrophil proteases by inhibiting them
Why is alpha1-proteinase inhibitor useful in the diagnosis of GI disease?
Similar molecular weight as albumin and will be lost through the GI tract at the same rate. But unlike albumin, it is not degraded by proteolysis in the intestines, so it can be quantified in feces. Marker of PLE and often increases before hypoalbuminemia (early detection)
How many samples are needed for alpha1-proteinase inhibitor measurement?
Due to day to day variation, 3 fecal samples should be collected on 3 consecutive days
In one study, a CRP >9 distinguished what two groups of dogs with chronic enteropathies?
Dogs requiring anti-inflammatory or immunosuppressive treatment from dogs responding to an elimination diet or antibiotic trial (sensitivity 72%, specificity 100%)
Seropositivity for perinuclear anti-neutrophilic cytoplasmic antibodies (pANCA) was higher in what dogs with chronic enteropathies?
Higher in food response enteropathy (61% of dogs) than in steroid responsive (0-37%). Also higher in Soft Coated Wheatens with PLE or PLN (can be detected 2 years before hypoalbuminemia)
What is calprotectin?
Belongs to a family of damage-associated molecular patterns, expressed and released by activated macrophages and neutrophils. Ligand for TLR4
Fecal calprotectin is a surrogate marker of what?
Disease severity in canine chronic enteropathy. Values >15 also distinguish partial or non-responders from dogs that achieve complete remission (sensitivity 80%, specificity 75%)
Serum calprotectin can be increased with what drug?
Corticosteroids
What is calgranulin C and what is it used for?
Also a DAMP. Fecal concentrations correlate with clinical signs and endoscopic, but not histopath, lesions.
German Shepherd with chronic enteropathy had lower mRNA expression of what cytokines compared with non-GSDs with chronic enteropathy?
IL-13 and IL-33
What receptor do parvovirus and feline panleukopenia virus use to enter cells?
Transferrin receptor
What type of cell do parvovirus and panleukopenia virus require to replicate? What tissues does it infect?
A mitotically active cell - invades more rapidly dividing cells such as the GI tract, thymus, LNs, and bone marrow
How are parvovirus and panleukopenia virus transmitted?
Fecal oral. Fomites are important - can persist for over a year in the environment
How do parvovirus and panleukopenia virus result in neutropenia?
Infection of the bone marrow as well as sequestration of neutrophils in the damaged GI tract
Where in the GI tract do parvovirus and panleukopenia virus replicate? What are the clinical consequences?
Epithelial crypt cells - destroys the stem cells, leading to villus atrophy, malabsorption, increased intestinal permeability and secondary bacterial translocation (sepsis)
Puppies that are in utero or up to 2 weeks of age develop what when infected with parvovirus?
Myocarditis leading to sudden death or CHF - can be delayed up to 2 months after infection
Leukopenia develops in what percent of dogs with parvovirus?
1/3
What is the sensitivity and specificity of in house ELISA assays for parvovirus?
Sensitivity: 77-80%
Specificity: 92-98%
(False negatives common)
How is canine distemper virus spread?
Aerosolization of oronasal droplets. Enveloped virus, does not survive more than 1 hour in the environment
What cell type does distemper initially infect?
Monocytes in the lymphoid tissue of the upper respiratory tract and tonsils, then spreads throughout the reticuloendothelial system
Distemper virus binds to what molecule on the surface of host cells? What cells is this molecule expressed on?
The distemper hemagglutinin binds to SLAM on the host cells - lymphocytes, macrophages, DCs
What causes in the initial lymphopenia and fever after distemper infection?
Massive virus-mediated destruction of CD4+ T cells
In the second stage of distemper viremia, what cells are infected? When does this occur?
8-9 days post-infection: infects respiratory, GI, CNS, urinary tract, skin, and more lymphocytes
What does distemper virus form inside host cells?
Both intracytoplasmic and intranuclear inclusions
What are the initial symptoms of distemper?
Fever, bilateral serous oculonasal discharge, conjunctivitis, nonproductive cough, vomiting, diarrhea
Dogs that mount a delayed or intermediate immune response may recover from the acute infection but not fully clear the distemper virus. This leads to what chronic signs?
CNS signs, uveitis, KCS, chorioretinitis, optic neuritis, enamel hypoplasia, nasal and footpad hyperkeratosis
What percent of dogs with distemper develop CNS signs and when do they occur?
30% of dogs
1-6 weeks after infection
What is “old dog encephalitis”?
Delayed, progressive immune-mediated demyelinating leukoencephalomyelitis that occurs weeks to years after recover from the acute phase of distemper infection (not necessarily old dogs haha)
What are the most common secondary infections that occur with distemper?
Respiratory bacterial infections, leading to bronchopneumonia (Bordetella, etc)
What are some of the common neurologic signs with distemper?
Myoclonus, chewing gum seizures, blindness (many others can occur)
What feline virus is also in the Parvoviridae family, and like parvovirus, infects rapidly dividing cells and persists in the environment?
Feline panleukopenia virus
Kittens infected with panleukopenia virus late in gestation or within the first week of life develop cerebellar hypoplasia. What causes this?
Viral destruction of Purkinje cells and granule precursor cells within the cerebellar external granule layer
What percent of cats with feline panleukopenia virus are leukopenic?
65%
What is the mortality rate for feline panleukopenia virus?
50%
Name 3 functions of the lymphatic system
Extracellular fluid homeostasis, fat absorption/transport, immune system function
Name the 4 divisions of the lymphatic system
Lymphatic capillaries, pre-nodal vessels, post-nodal vessels, collecting vessels
Within capillaries, lymphatic endothelial cells do not have support (mural) cells. How do they attach to the surrounding extracellular matrix?
Via fine collagen filaments
Describe the junctions between lymphatic endothelial cells in the lymphatic capillaries
Only the cell edges overlap, forming “flap like” valves that operate like swinging doors, receiving interstitial fluid in a 1 way system
In the intestines, the lymphatic system is described in 3 layers. Name them
Central villus lymphatics (lacteals) which connect to submucosal lymphatics, smooth muscle lymphatics (separate)
What factors have been shown to increase the risk of death in dogs with PLE?
CCEAI score (for each unit increase, hazard of death increased by 22.9%, <8 did better), blood urea <7 mmol/L
Detection of hyperechoic mucosal striations on ultrasound were associated with clinical PLE in what percent of dog? With histologic confirmation of lacteal dilation in what percent of dogs?
Clinical PLE in 78%
Histologic confirmation in 95%
A protein that causes loosening of the intraepithelial cell junctions and therefore leakage of fluid into the intestinal lumen has been found to have increased expression in dogs with PLE. What is the protein?
Zonulin-1
What percent of dogs with PLE have secondary lymphangiectasia resulting from LP enteritis?
68%
What breed of dog is predisposed to crypt lesions (dilated, cystic crypts packed with sloughed epithelial cells, mucus, leukocytes, debris)?
Yorkshire Terrier (90-100% of dogs)
In one study, dogs with food-responsive PLE could be differentiated from dogs that did not respond to diet based on what index?
CCECAI less than 8 were more likely to be food responsive
Administration of human serum albumin to dogs with PLE resulted in acute and delayed hypersensitivity reactions in what percent of dogs?
Acute: 9.5%, delayed 9.5%
One was fatal (PTE)
What amino acid is significantly decreased in dogs with PLE?
Tryptophan
What percent of dogs with chronic enteropathy (and not PLE) are hypercoagulable as measured by TEG?
44%
What hormone is increased in obese dogs? What hormone is higher in lean dogs?
Obese dogs - leptin
Lean dogs - adiponectin
How does the microbiome of obese dogs compare to lean dogs?
Obese dogs have less diversity and Proteobacteria predominate, compared to Firmicutes predominating in lean dogs
What is focal lipogranulomatous lymphangitis and where does it occur in dogs?
Transmural granulomatous inflammation, most common in the distal ileum and ileocolic junction
How is focal lipogranulomatous lymphangitis treated and what is the remission rate?
Surgical resection of the area followed by immunosuppressive prednisone. 80% achieved remission in one study of 10 dogs
What abnormalities on a blood smear should increase the clinical suspicion for lymphoma over IBD in dogs?
Anemia (53% lymphoma, 22% IBD), more than 3 RBC abnormalities, eccentrocytes
What is chronic intestinal pseudo-obstruction?
Impaired intestinal motility resulting in clinical signs of obstruction without evidence of mechanical occlusion of the lumen (most severe form of motility disorders)
How does leiomyositis result in ileus?
Infiltration of lymphocytes between functional myocytes prevents normal contractility
What is the median survival time of dogs with intestinal leiomyositis and pseudo-obstruction?
19 days
What form of vitamin D is obtained from animal sources? From plant sources?
Animal: cholecalciferol (D3) - more bioavailable, especially for cats
Plant: ergocalciferol (D2)
After absorption in the enterocytes, what does vitamin D bind to and how is it transported?
Binds to vitamin D binding protein (VDBP) and chylomicrons, transported through the lymphatics to the liver
In the liver, what enzyme converts D2 or D3 and what are they converted to?
25-hydroxylase converts to 25(OH)D also known as calcidiol
What happens to 25(OH)D in the body?
Binds to vitamin D binding protein in the liver, travels to the kidney
What enzyme converts 25(OH)D and what is it converted to?
1-alpha hydroxylase converts to 1,25(OH)2D also known as calcitriol in the renal tubules
What is the most active form of vitamin D?
Calcitriol, although other forms have some activity
What receptor/transcription factor mediates the genomic effects of vitamin D?
Retinoic acid receptor
What enzyme breaks down calcitriol and what is it broken down into in dogs?
- 24-hydroxylase breaks calcitriol down into 1-alpha,24,25(OH)3D
- Not identified in cats
Dogs with chronic enteropathy and low calcidiol concentrations that what other biochemical changes compared to dogs with chronic enteropathy and normal vitamin D?
Higher CCECAI scores, lower alpha-tocopherol, cholesterol, and albumin, higher CRP, worse histopath scores for inflammation
What is the best technique for handling gastric and duodenal biopsy samples?
Mounting on a moisturized synthetic foam sponge has less artifact than free floating in formalin, resulting in more confident diagnosis from pathologists
Reusable biopsy forceps provide equivalent biopsy quality to disposable forceps up to how many uses?
Up to 15 uses tested, still good
How many gastric or duodenal biopsies are required to diagnose villus atrophy, lymphangiectasia, or mild/moderate cellular infiltrates?
6-7 adequate or 10-15 marginal biopsies
How many gastric or duodenal biopsies are required to diagnose crypt lesions?
13 adequate or 28 marginal samples
