GI Flashcards
Infectious disease associations with feline caudal stomatitis?
FeLV, FIV, calici, herpes, Pasteurella.
Not bartonella
What subset of cats responds poorly to full mouth extraction for stomatitis?
Calicivirus/prev medical management
Alternative management for caudal stomatitis?
Feline interferon gamma - can use if refractory after. full mouth extraction
Also ciclosporin; > 300 trough
What nerves are required for swallowing?
Vagal, facial, glossopharyngeal, trigeminal, hypoglossal
Cricopharyngeal dyssynchrony versus achalasia?
First functional - pharyngeal muscles too weak to propel bolus, second structural - bar
DON’T do surgery in former
How do you experimentally reproduce cricopharyngeal achalasia?
Vagal nerve pharyngeal branch transsection
Effect of oesophagitis on LES?
Eosphageal hypo motility/LES weakness, impair cholinergic pathways
What is Barret’s oesosphagus?
Replacement of normal squamous epithelium of distal oesophagus with metaplastic columnar epithelium
What contrast agent should be used if oesophageal perforation is suspected?
Iodinated - not barium
Most sensitive way to diagnose oesophagitis?
Scope - erythema, increased vascularity, oedema, mucosal striations with submucosal vascularity distal third
Increased granularity
Severe - exudative pseudomembrane and ulcer
NB squamocolumnar junction normal
What drugs prevent GERD during GA?
Nothing consistently
Sucralfate use in oesophagitis?
Physical barrier, promote ulcer healing.
Stim PGE2 and epidermal growth factor.
Negative ions bind positive disrupted tissue.
BUT only adheres in acid environment and oesophagus is mostly alkaline?
Outcome balloon versus bougienage oesophageal stricture?
No diff. Bougienage more force can be applied.
Factors causing gastric ulcer?
Acid, bile, decreased mucosal perfusion, decreased bicarbonate in protective mucous layer
Parietal cell acid secretion?
H+ K+ ATPase pump - not all active at the same time
Stim gastrin, acetylcholine, histamine (endocrine, neurocrine, paracrine)
Why is ranitidine pro kinetic?
Inhibits acetylcholinesterase activity
Renal failure and H2 blockers?
Renal excreted, drop dose or frequency
Why is omeprazole coated?
Unstable in acid environment of stomach
When should omeprazole be administered?
One hour before a meal to ensure onset coincides with max proton pump activity - only binds to active pumps
What pH to achieve haemostasis in GI bleeding?
Greater than 6 - omeprazole CRI
Omeprazole metabolism?
Cp450
Misoprostal mechanism of action?
PGE1, cytoprotective, increased bicarb/mucous secretion, increase turnover and blood supply of gastric mucosal cells.
Inhibits parietal cell proton pump activity.
Benefit of misoprostal?
Only prevention of NSAID ulceration
Sucralfate and renal failure?
Aluminium tox - impaired excretion.
Sucrose sulfate and aluminium salt.
Aluminium antacid?
Neutral salt formation, neutralise H+ to water, decrease pepsin activity, bind bile acids, stim PGE2
Neoplasia and Helicobacter?
Lymphoma and heilmannii in cats
Why are Tritrichomonas susceptible to 5-nitroimidazoles?
Use anaerobic metabolic pathways, reduce the drugs to cytotoxic nitro anions which disrupt protozoal DNA.
Ronidazole - only needs once daily dosing. NB ronidazole resistance
SE of ronidazole?
Dose and duration dependent neurotoxicity - NB narrow safety margin,
Most sensitive dx. for T. foetus?
Colon saline flush PCR, more sens if has diarrhoea
Asymptomatic T. foetus - yes or no?
Yes. Also 88 % spontaneous resolution of signs but not infection within 2y
Signs can also relapse
Which Giardia species and assemblage affects humans, dogs and cats?
Duodenalis.
A - from humans dogs and cats
B - most common humans, also dog
C and D - most dogs (species specific)
F - cat
A and B occ infect dogs and cats, unknown whether common transmission occurs
Drugs to treat Giardia?
Fenbendazole, pyrantel/praziquantel, metronidazole
What to use if Giardia + spore forming rod?
Metronidazole as has activity cf C perfringens
Albendazole problem?
Bone marrow suppression
Febantel and pyrantel for Giardia?
Synergistic
Probiotics help with giardia?
Not in dogs
Hygiene?
Bath dog on last day of treatment
Problem with Giardia antigen?
Don’t know how long it persists.
2-5% false positive
Most sensitive faecal float Giardia?
Centrifugal floatation, three in 5 days
Parvo environmental resistance?
Resistant because non-enveloped
What parvovirus causes disease in cats?
CPV 2b
When does parvovirus infect rapidly dividing cells?
5 - 7 d
WBC picture in Parvo?
Neutro-lymphopenia but can get lymphocytosis even when neutrophil count still decreased.
Viral stim lymph and neuts consumed in intestine
What does Parvo ELISA detect?
Viral antigen.
False neg - decreased shedding in later stage or dilution (CPV2c?)
False pos - vaccine up to 5d later
PCR diff from vax - quant, higher virus load?
Antiemetic in parvo?
Maropitant more weight gain cf ondansetron
Feline interferon in parvo?
Decreased mortality and clin signs in dogs
Toll like receptors in IBD?
TLR 4 and 5 polymorphisms in GSD
TLR 5 other breeds
mRNA - upreg TLR 2, 4, 9 - TLR 2 corr with dz severity
Mucosal immune cell changes IBD?
Increased Th1 cytokines in cats IBD
Dogs - CD11c pos dendritic cells DECREASED (?exaggerrated inflamm?)
pANCA?
Perinuclear antineutrophilic cytoplasmic antibodies
Poor sens good spec dog IBD
How many dogs relapse after diet trial?
8 % - so few actually food intolerant
How many CE dogs failed food and AB respond to steroid?
30 %
Ileum bx?
Often required to find feline lymphoma or lymphangiectasia
Types of hiatal hernia?
I - sliding, oesophagus and stomach
II - paraoesophagheal, stomach alone
III - widened hiatus, oesophagus cardia and fundus
IV - liver stomach SI
Causes of hiatal hernia?
Congenital in brachys esp Frenchie
Acquired any increase abdo pressure or negative thoracic pressure
How to dx hiatal hernia on oesophagoscopy?
J manoeuvre - separation between diaphragmatic impression and squamocolumnar junction <2cm
What breed gets gastrooesophageal intussusception?
GSD
Bacterial content of GI tract?
Increases from distal SI - 60 % faecal mass = bacteria
What is a microbiome?
Collective genome of GI microbes
What is the function of the gut bacteria?
Metabolism - ferment non-digestible material eg produce SCFAs for colonocyte energy. SCFAs antiinflamm (induce Treg)
Vitamin synthesis (A K B12 biotin folate)
Deconjugate bile acids (primary to secondary)
Epithelial protection - compete with pathogens and excrete antimicrobial substances, increase barrier integrity
Deconjugated bile acids in the GI tract?
Decrease inflammation, inhibit C difficile spore germination, increase GLP 1
What happens in dysbiosis?
Decreased diversity, less bacteroides, more clostridia
What happens to the microbiome in chronic enteropathy?
Lowest diversity, change doesn’t improve with therapy, more proteobacteria inc e coli, less bacteroides/fusobacteria, if transfer microbiome to healthy animal increase IBD susc
Association of dysbiosis and clinical signs in GI dz?
No, but does corr with histopath severity
Effects of prebiotic?
Nondigestible CHO eg fructooligosaccharide - produce SCFA to increase Treg and decrease colonic pH
Some evidence that improves dysbiosis/faecal score in dogs and cats
Probiotic IBD?
VSL 3 increase Foxp3 in IBD dog mucosa
Others imp dysbiosis, faecal scores, D+ incidence , clin signs FRE
What is a synbiotic?
Combo of pre and probiotic
Faecal microbiota transplant?
One case report eosinophilic IBD, 8 dogs with refractory C perfringens
Large study of parvo puppies - - faster resolution
Antibiotics and microbiome?
Tylosin decreases diversity and increases primary bile acids
Metro decreases diversity and decreases secondary bile acids
Probiotics can ameliorate GI signs from AB admin
GI defence mechanisms?
Gastric acid denatures protein, enzymes and bacteria cause proteolysis, AB peptides (defensins), peristalsis
Microvillus membrane, tight junctions, unstirred water layer
Immune system - gut associated lymphoid tissue
Where are microfold cells found and what do they do?
Peyer’s patch, present luminal antigen to DCs and macros
What MHC interacts with which T cell?
I - CD8
II - CD4
How do APCs stim CD4 lymphocytes?
IL1 - they stim CD8 cytotoxic with IL2
Why is IgA not broken down in GI tract?
Secretory IgA - gets secretory component from pIgR on enterocyte as passes through
NB dimeric with joining J chain
What lymphocytes live in the upper villus lamina propria in dogs and cats?
Dog - alpha beta TCR CD4
Cat - CD8 > CD4
Mostly v differentiated due to antigenic stim
What other inflammatory cells normally live in LP?
Eosinophil (esp crypts) and small number neutrophils, mast cells
What are the inductor and effector tissues of the GI tract?
Inductor - peyers patch
Effector - lamina propria
Where do dendritic cells live in GI?
PP and LP, follicular ones store antigen for B cell stim
Live below enterocyte layer in villus lamina propria, sample luminal antigen - generate immune response or tolerance
Primary product of plasma cells in GIT?
IgA, mostly pericryptal LP
What cells express TLRs GIT?
Macros/APCs/enterocytes
When do enterocytes use MHCII?
Dogs - antigen presentation in healthy
Cats - only in inflammation
Innate lymphoid cells?
1 - NK - IFNgamma
2 - IL 5/13
3 - IL17/22
Intraepithelial lymphocytes?
Evolutionarily older gamma delta chain TCR
T helper cell cytokines?
Th1 - IL2 IFNgamma - intracellular pathogens/neoplasia. cellular immunity. activate CD8 and macro
Th2 - IL 4 - 6, 13 - Ig class switching and B cell differentiation to plasma cells
Th17 - IL 17, inflammatory
Th3 - TGFbeta - oral tolerance effectors
Treg - IL10, oral tolerance - NB CD 25 CD 4+ Foxp3+
How does lymphoid homing work in GALT?
Alpha 4/beta 7 on lymphocyte and mucosal addressin cell adhesion molecule 1 (MAdCAM1) on endothelial cell, chemokine/receptors
Lipopolysaccharide recognised by?
TLR 4 and NOD2
Nucleotide binding oligomerisation domain
Flagellin recognised by?
TLR 5
Lipopeptides recognised by?
TLR 2
Where do TLR and NOD live?
TLR membrane, NOD intracellular
Parasite/virus/bacteria/commensal TLR response pathway?
Parasite - IL4, STAT 6, Th2, eosinophil basophil mast cell
Virus - IFN, STAT 4, Th1, IFNgamma, macrophage
Pathogen bacteria - NFKB - ubiquitation - IL1beta, IL6, IL8, Th17 - expansion - IL17
Commensal - no ubiquitation, IL12/27, Treg and Th3 - IL10 and TGF beta
TLR dog IBD?
2 4 9
5 GSD
Inhibitor of gastric acid secretion?
D cells - somatostatin - stim by low pH and vagus
Somatostatin inh histamine from ECL cell
PGE2 also inh acid
Where do proton pumps live?
In the cytoplasm when not activated
Transporters on parietal cells?
H+K+ATPase, Cl bicarb, Cl-K+
NET: H+ and Cl- to lumen, bicarb and Na to blood basolateral
What effect does COX1 inh have on GI mucosa?
Decreased PGE2 - decreased bicarb mucous vascular activity, increased neutrophil activation and free radical production
What topical effects do NSAIDs have on GIT?
Mitochondrial injury of mucosa
Corticosteroid effects on GIT?
Decreased mucosal cell growth, decreased mucus, decreased prostaglandin, increased acidity
Features of NSAID induced ulcer?
No marked mucosal thickening/irregular edges (cf tumour) - find in antrum/near duodenal papilla
Antiulcer goal?
pH > 3 > 75 % of the time
What happens when you give H2 blocker and omeprazole concurrently?
Decrease omeprazole action (pumps not activated)
Should PPIs be used in IMT?
No evidence for effect on survival
How might omeprazole and clopidogrel interact?
In theory decrease metabolism to active clopidogrel metabolite, but in vitro no evidence the anti-platelet effect is impacted
How might omeprazole and mycophenolate interact?
If increase pH, no change to mycophenolic acid which is absorbed - could decrease efficacy?
Also may impact azole and iron absorption
Why are H2 blockers ineffective?
Tachyphylaxis - ECL cells start making more histamine
Absorption of what medications are impacted by sucralfate?
Ciprofloxacin, theophylline, doxycycline, digoxin
NOT enroflox
Where does the gas come from in GDV?
Aerophagia or carbon dioxide and H2 from bacterial fermentation
Risk factors for GDV?
Great Dane, once daily feeding, fast eating, relative with GDV, older
What would you see on a GDV X-ray?
Pylorus moves dorsal and left, right lat rad popeye
Prognostic indicators for GDV?
Lactate > 6-9, no decrease in lactate, increase delta lactate
How often would you encounter histopathological gastritis in healthy and symptomatic dogs?
Around the same, 1/3rd
Pathophys of gastritis?
Decreased anti inflamm TGFbeta IL10
Increased inflamm IL 8 AND IL1beta
Altered barrier function
Cytokine correlation with lymphoplasmacytic gastritis in dogs?
Corr IL10 w/ IFNalpha/IL1beta/IL8
Breed assoc gastritis?
Basenji - hypertrophy fundic mucosa
Drentse Patrijshond - fundic mucosal hypertrophy, stomatitis, icterus, haemolysis, anaemia and polyneuropathy
Brachy - pyloric mucosal hypertrophy
Gastric lymphofollicular hyperplasia?
Young/brachycephalic
Features of Helicobacter?
Gram neg, microaeerophilic, motile, spiral, flagellated
Produce urease
Helicobacter species in animals?
Large unlike small pylori in humans.
Heilmannii, felis, bizzozeronii, salomonosis
Dogs type 2 & 4 heilmannii (humans 1) but dog ownership is assoc with helicobacter…
Prevalence of Helicobacter?
Approaching 100 % in some dogs and cats whether vomiting or not
Effect of Helicobacter infection?
Might be commensal, with loss tolerance.
Higher gastritis scores in helicobacter dogs in some studies.
Severe polymorphonuclear/mononuclear inflammation seen in humans not seen in dogs
Helicobacter diagnosis?
Brush cytology most sensitive
Can get false pos with urease test (other bacteria) or false neg if patchy or pH altering drugs
Histopath - mod Steiner’s silver stain
Histopath changes with Helicobacter?
In mucous, might be intracellular, mild/mod mononuclear inflamm, lymphoid hyperplasia.
Gastric gland and parietal cell degeneration/necrosis
Pylori most severe
Evidence to treat Helicobacter?
Various protocols (ABs/bismuth/omeprazole) improve frequency of vomiting, and many cases neg with histopath improvement.
BUT infection recurs with no recurrence of the clinical signs, many dogs need other therapies.
Clarithromycin does intracellular.
Risk factor for Helicobacter recurrence?
Housing with other animals
What parasites do you find in the stomach mostly?
Ollulanus tricuspid (cat) - very small, nodular gastritis, cause lymphocytic inflamm and lymph follicular hyperplasia - respond fenbendazole
Physaloptera (dog and cat) - large, eggs transparent - give pyrantel (2 doses cat) - insect intermediate/hedgehog paratenic
What cytokines correlate with gastric atrophy?
IL 10 and IL1beta
What is mason’s trichrome for?
Fibrosis histopath
What dogs get atrophic gastritis?
Lundehunds - poss predisposed to gastric carcinoma
Lack of parietal cells, neuroendocrine cell hyperplasia
What does hospitalisation do to gastric emptying time?
Increases it
Most accurate way to assess gastric emptying?
Radioscintigraphy
AUS valid alternative in cats
Ondansetron mechanism of action?
5HT3 antagonists central and peripheral
Metoclopramide mechanism of action?
Dopamine antagonist (only relevant dog as cats no dopamine on CRTZ which is why apomorphine doesn’t work). 5HT3 antagonist.
Also cholinergic (increase myenteric plexus acetylcholine) and 5HT4 agonist
Cisapride mechanism of action?
Cholinergic 5HT4
Erythromycin mechanism?
Motilin agonist MMC III (large)
Maropitant?
NK1 antagonist central and peripheral
Phenothiazine mechanism?
Alpha 2 antagonist - central
Intestinal pseudoinstruction?
Leiomyositis
Opioid GI effects?
Increase antral contractions/intestinal tone but decrease propulsion. increase anal sphincter and ileocecal junction tone.
Mechanisms of diarrhoea?
Luminal disturbance Brush border membrane disease Microvillar membrane damage Enterocyte dysfunction Epithelial barrier dysfunction Disordered motility Mucosal inflammation Hypersensitivity Nutrient delivery failure Congenital abnormalities
Where are bile salts absorbed?
Ileum
What does Ecadherin do?
Maintains tight junctions between enterocytes
IBD decreases Ecadherin and alpha catenin
What is the difference between vincristine and parvo crypt lesions?
Arrest/destruction, respectively
What causes intestinal hyper motility?
SI ischaemia, enterotooxigenic bacteria, osmotic fluid retention
Decreased - undigested food in SI decreases gastric emptying
What causes secretory diarrhoea?
Bacterial toxins, bacterial fermentation products, Giardia, laxatives, inflammation
What might cause malabsorption?
Luminal factors - increased motility, defective substrate hydrolysis
Transport eg lymphatic problem or vascular compromise
Mucosal dysfunction
How should you measure alpha1protease inhibitor and what does it mean?
Three fresh faecal samples, no rectal collection. Sensitive for PLE. Not degraded in intestine.
D xylose test?
Marker of substrate absorption, insensitive in dog and indiscriminately in cats
Unconjugated bile acids?
Increased if bacterial activity increases - can’t differentiate from normal postprandial increase in BAs
What factors do pathologists assess on GI bx?
Villus stunting, epithelial injury, crypt distension, lacteal dilation, mucosal fibrosis, cellularity. Grade mild mod severe
What bacteria has been associated with acute haemorrhage diarrhoea syndrome?
C perfringens (with enterotoxin)
Predisposed breed for AHDS?
Mini schnauz
ABs in AHDS?
Amoxiclav didn’t improve outcome but caused amox resistant E coli
Metro decreased time to resolution and decreased C perfringens persistence
No effect of adding metro two amox
Probiotic in AHDS?
E faecium shorten duration with less requirement for AB rescue
Why might food hypersensitivity occur?
Barrier function altered, unusual antigen presentation, loss of tolerance, upreg immune, microbiome abnormal
Most common antigens for food hypersensitivity?
Dog - beef dairy chicken wheat
Cat - beef chicken fish
Pathophys food hypersensitivity?
Either type I with IgE or delayed (dendritic cell Th1 response) - IV
What type of GI inflammation might be more likely to be food responsive?
Eosinophilic
Size of antigens?
7 - 10 kD too small for IgE cross linking, < 1. ultra hydrolysed too small for presentation
Hydrolysed better than novel protein
Pseudo allergic food response?
Histamine from mast cells - strawberry/shellfish, mackerel has histamine
Pathophys gluten sensitive enteropathy?
Irish setter, may become asymptomatic.
Autosomal recessive.
Direct intestinal mucosal tox, no T cell/Ig response, but might be immune med (increase CD4/decrease CD8)
Secretory IgA deficiency?
Might be assoc GSD ARD (serum IgA irrelevant).
Decreased intestinal IgA despite increased mucosal IgA plasma cells.
Problem - when mutations in heavy chain found was all GSD not just ARD
Immune dysfunction in ARD?
Increased LP CD4 cells and cytokines
Decreased TLR5 in GSD, TLR 2 and NOD2 others
ABs decrease cytokines not bacterial numbers
Brush border enzymes ARD?
Reversible changes found - damage due to luminal bacteria?
Histopath in ARD?
No change/mild changes
Evidence for antibiotic trials?
Decrease D+ with tylosin, relapse when stop, rescue with tylosin
What kind of antibiotic is tylosin?
Bacteriostatic macrolide, works on G pos and neg cocci
E coli and Salmonella resistant
Oxytet in ARD?
Rapid development plasmid mediated resistance but still works
No change bacterial number - select for less harmful?
Causes of secondary SIBO?
Anatomic, achlorhydria, EPI, motility, mucosal disease, obstruction
Excess lumen substrate, decreased bacterial clearance, morphologic or functional mucosal derangement
IBD genetic/immune system changes?
GSD - polymorphism TLR 4,5 and NOD 2
Other dogs - polymorphism TLR 5 and also decreased
Boxers with granulomatous colitis - NCF2
Cats - increased MHC II and Th1 cytokines
Dog - decreased CD11c pos dendritic cells, increase TLR 2/4/9. Decreased Treg
Dog - circulating TCR gamma delta increase, CD21+ increase
Amino acid changes IBD?
Dog - decreased methionine, proline, tryptophan
Serine neg corr with clin dz index
Features of lymphocytic plasmacytic enteritis?
Increased CD4+ cells in lamina propria, increased IgG pos plasma cells, matrix metalloproteinase expression changes
Bile acid changes IBD?
Faecal primary increase, secondary decrease, improve with tx
Sodium dependent bile transporter also decreased in CE and negatively correlated with histopath
Bactericidal permeability increasing protein expression?
Differentiates IBD from lymphoma (BPI increase IBD vs lymphoma)
What happens to taurine in cats with IBD?
Decreases but remains in RI
Vitamin D and IBD?
Decreases as clin score increases. No binding protein difference.
Also assoc vitE/chol/alb/CRP/histopath
Age and type of inflammation in IBD?
Eosinophilic younger, LPC older (NB siamese)
FSEF - ragdoll
GSD overrep all
Frequency of hypocobalaminaemia/decreased folate?
50 % 14 % respectively.
How often do you find intralesional bacteria in FSEF?
50 %
Ideal IBD diet?
Gluten free, highly digestible hydrolysed protein, increased omega 3, low fat, mixed fibre
What might predict cyclosporin/steroid resistance?
P-glycoprotein efflux pump activity in lymphocytes
Evidence for dietary tx in CE?
Dogs - hydrolysed/novel protein no diff, hydrolysed/easily digestible no diff but prolonged response with hydrolysed
Cats - hydrolysed better than intestinal diet, no diff with fat content
Evidence AB tx in CE?
Rifamixin and metronidazole decrease CRP imp clin signs
Tylosin responsive D+
HUC dogs enro
No diff add metro to pred
Tylosin > oxytet
Immunosupp and CE?
Pred remission 60 - 100 % cats and dogs
Cyclosporin improve many steroid refractory dogs in one study (not another). Response short lived.
Pred/budesonide equal effect
Probiotic and CE?
VSL3. increase tight junction - same outcome pred/metro when combined with elimination in one study
Other studies no difference
Difference between CIBDAI and CCECAI? FCEAI?
CCECAI has alb, ascites and pruritiis
FCEAI has liver enzymes, proteins, phosphate and endoscopy
IBD px?
FRE younger with more large bowel signs, lower CCECAI scores and normal albumin - better outcome
Negative outcomes - severe disease, decreased cobalamin (regardless of supplementation), pancreatic dz and hypoalbuminaemia
Cat respond better overall
Eosinophilic guarded px?
IGF1 decreases with successful tx
What impact does cobalamin have on mucosa?
Decrease corr with mucosal inflamm, villous atrophy, intra-ep lymphocytes in the ileum and albumin
Use of alpha1proteinase inhibitor in GI diagnostics?
Decrease in serum or increase in faeces with protein loss.
Cautious interp <1 or steroids.
More specific than sensitive, but more sensitive than decreased albumin
Increased more if crypt abscesses/lacteal dilation
Use of faecal dysbiosis index in GI diagnostics?
Very specific for IRE dogs vs healthy
Bacterial diversity worse in CE, FRE too - maybe improve after tx but not normal
CRP in GI diagnostics?
> 9.1 dist FRE and ARD from IRE - very specific fairly sens. 100 % PPV to dist from NRE.
Decreases with treatment
perinuclear Anti Neutrophilic Cytoplasmic ABs in GI diagnostics?
ABs against neutrophil granule components.
Predict PLE/PLN in SCWT > 2 y before albumin decreases
Increased in FRE versus NRE/IRE
Not sens but specific
3-bromotyrosine in GI diagnostics?
Eosinophil peroxidase metabolite, measure in serum
Increased in IRE > FRE and in FRE > healthy
Not associated with eosinophilia or CIBDAI
N-methylhistamine in GI diagnostics?
Marker mast cell activation. Serum and faeces.
Faecal increased in Norwegian lundehund and SCWT with CE.
Urine increased other dogs with CE,
Corr with histopath but not mast cell numbers.
Calprotectin in GI diagnostics?
S100A8/A9. Neutrophil elastase. Faeces.
Is a TLR 4 ligand, released as DAMP. Affected by steroids and serum is non specific.
Decreased in serum and increased in faeces of CE. Can differentiate responders from partial/non-responders. Increased in SRE versus ARD/FRE.
Corr with calgranulin, CIBDAI and clinical disease. NO! CORR CRP.
Decreases with tx. Faecal best.
Calgranulin C in GI diagnostics?
S100A12. Pattern recognition receptor RAGE (receptor advanced glycation end products) = target.
NOT affected by steroids.
Corr with clinical and histopath, increased in IRE/NRE versus FRE/ARDand NRE from partial/full. Measure in faeces. Increases.
SRAGE in GI diagnostics?
Abrogates RAGE signalling.
Decreased in CE, no corr with anything but weakly with duodenal lesions but does increase with remission.
Basenji enteropathy?
Increased globulin decreased albumin lymphoplasmacytic gastroenteritis mucosal hyperplasia increased CD 4 and 8 lymphs increased gastrin.
Hereditary. Px poor but remission reported.
Familial PLE/PLN SCWT?
NPH51/KIRREL2 gene mutation, common male ancestor.
PLE before PLN.
pANCA post.
Villus blunting inflamm ep erosions might be food hypersensitivity.
Poor. px cf IBD.
Lundehund PLE?
Lymphangitis. chronic gastritis gastric carcinoma. Atrophic gastritis.
severe lymphatic vessel changed lymphogranulomas around lymphatic vessels.
Breeds predisposed to PLE?
SCWT rottie Yorkie maltese lundehund sharpei
Prevalence of hypocobalaminaemia in PLE?
Up to 75 %, assoc with alpha 1 proteinase inhibitor in serum in yorkies
Histopath differences PLE versus CE?
Villous stunting, crypt distension, lacteal distension, intraepithelial lymphocytes, LP neuts
See crypt abscesses more.
Low albumin correlated with increased villous/proprial mucosal lacteal width in the ileum.
Lymphatic endothelial cell IHC might help to identify proprial mucosal lymphangiectasia.
What vitamin deficiencies might you encounter in PLE?
Fat soluble - A D E K
NB Mg Ca
How often would endoscopic bx identify lymphangiectasia?
Transmucosal in 3/4 so around this much - better sens if bx ileum.
Colloid will decrease oedema and increase the biopsy size.
Prediction of therapy response in PLE?
Many respond to low fat diet. Lower CCECAI versus those that needed steroids or didn’t respond. Better survival if FRE.
Negative px - CCEAI, decreased urea, decreased vitD, hypocobal, inc CRP, calprotectin and calgranulin, clonality,
Secondary immunosuppressive drugs in PLE?
Chlorambucil superior to azathioprine.
70 % response cyclosporin in one study.
Intestinal pseudoobstruction in cats?
Lymphoma/smooth muscle alpha actin deficiency
Risk factors for intussusception?
Ileocolic most common.
Congenital hT4, parvo, AKI, lepto, neoplasia, intestinal motility increase
How much SI removal is tolerated?
85 % - after this get short bowel syndrome.
Adaptive hyperplasia might compensate.
If take IC valve get SIBO
Altered cytokines in colitis?
Mostly Th1, IFN gamma, IL2, IL12, TNF alpha
Increased CD3 pos T lymphs, IgA, IgG plasma cells
Mechanism of sulfasalazine?
PG synthetase inhibitor. Decreases prostacyclin /leukotriene.
Can’t use in cats, deficient glucuronyl transferase
How many colitis cats respond to pred?
80 %
What age of dogs are more likely to respond to an elimination diet for colitis?
Young
T/F: colitis as a separate entity without other GI disease is common
False - SI usually affected too
Suppurative inflammation in feline GI bx?
Campylobacter
Dietary management for colitis?
Best response hydrolysed, also adding psyllium to digestible diet
Usually respond in 2w
Benefits of fermentable fibre - holds water, SCFA for colonocytes
What organism is associated with histocytic ulcerative colitis?
E coli, attaching invading, in macrophages. PAS pos.
E coli replicates in phagolysosome.
Can affect ileum
Breeds HUC?
Boxer frenchie some others
Usually young
Histopath HUC?
CD3 pos, IgG PCs, increased MHC II
Lymphoplas, ulcerated, loss of goblet cells, loss of surface epithelium, mixed infiltrate in LP and submucosa as progresses.
May have histiocytes in LNs.
Management of HUC?
Up to 100 % respond with just enro, often 2w, sustained in most. Sometimes need long term enro (low number). E coli resistance assoc with clin relapse.
Alternative to enro - chloramphenicol/TMPS (intracell)
Percentage of enro resistant e coli HUC?
about 1/3, with resistance to other macro penetrating drugs too. Only sens amikacin.
Inc prevalence treated with enro, assoc with resistance and poor outcome.
Mechanism of action of lactulose?
Metabolised to lactic acid which is osmotic
What drugs could you use as colonic pro kinetics?
Cisapride, tegaserod (5HT4)
Pathophys of feline idiopathic megacolon?
Functional smooth muscle disturbance - decreased acetylcholine/substance P and CCK response
What cytokine changes are described in perianal fistula?
Increased Th1 cytokines - IL 1 beta, IL 6, TNFalpha,
Macrophage derived metalloproteinase enzymes s
Genetic changes in GSD with perianal fistula?
IgA def, MHCII, NOD 2 SNP, ADAMT (inverse with matrix metalloproteinase), CTNND2
Perianal fistula histopath?
Plasma cells and perivascular lymphoid nodules.
Best drug for perianal fistula?
Ciclosporin or tacrolimus, 90 % partial for both. May not get complete remission.
Recurrence 30 - 50 %.
Only consider surg if no response over 6w.
Sensitivity of cytology for septic abdo?
57 - 100 % depending on site of collection and prev AB
Cell count > 13000 perfect sens/spec dogs, less sens cats
What amino acid is decreased in PLE?
Tryptophan
Where does lipogranulomatous lymphangitis have a predilection for?
Ileum/ileocolic junction
Assoc of albumin/serum alpha 1 proteinase inhibitor with histopath?
Lower in those with crypt abscess/lacteal dilation - moderate sens/spec
T/F: citrulline is higher in CE?
False, no difference and not corr with anything else
What might IL1 beta do to intestinal barrier function?
Decrease - only demonstrated in colon with occludin
Does 250ug per week for 6w normalise cobalamin in all GI dz cats?
Cobalamin but not markers of cell def - approx half still increased serum MMA
What animals would have increased netE and netF?
In faeces of AHDS, C perfringens pore forming toxins
Colorectal polyp metalloproteinase?
MMP 2 and 9 increased miniature dachs eps in inflamed tissue samples
Gelatinase and serine protease
Mechanism of action of opiate antitussives?
Kappa or mu receptor agonism - can be antagonised with naloxone
Codeine features?
1/10 analgesia cf morphine but equal antitussive effect
Difference between hydrocodone and codeine?
Hydrochodone more potent.
sedation becomes limiting factor for dosing.
Why is the oral dose of butorphanol higher than IV?
High first pass metabolism
What impact might bronchodilators have on vasculature?
Interfere with ventilation perfusion matching
Mechanism of action of bronchodilators?
Beta 2 agonist - increase adenylate cyclase and therefore cAMP activity, relax bronchial smooth muscle.
Mast cells - stabilising effect
Increase mucociliary clearance?
Albuterol (salbutamol)/terbutaline
