GI Ettinger Flashcards
Which cell in the stomach makes intrinsic factor?
Parietal cells
What are the 3 major components of acid secretion?
Histamine, Gastrin, ACh
Which hormone is responsible for decreasing gastrin, histamine, and acid secretion when stomach pH
Somatostatin
What are the components of the gastric mucosal barrier?
§ Tightly opposed epithelial cells § Bicarbonate rich mucous § Abundant mucosal blood supply § Prostaglandins (PGE2) are important in modulating · Blood flow · Bicarbonate secretion · Epithelial cell renewal
What factors slow emptying of stomach?
Carbs, AA, fats
Release of CCK in response to FA and AA
What are the 3 major digestive enzymes in the stomach?
Pepsin (releases as pepsinogen in response to ACh and histamine) Gastric lipase (in response to pentagastrin, histamine, PGE2, and secretin, active in SI) Intrinsic factor (dogs)
Which breeds get hypertrophic gastropathy?
Basenji, small breed dogs (shih Tzu)
Which breed gets atophic gastritis?
Lundehund
What can stoamtocytosis tell you on a CBC?
Stomatocytosis has been described in Drentse Patrijshond dogs with familial stomatocytosis-hypertrophic gastritis
What are causes of metabolic alkalosis?
· Metabolic alkalosis
o Associated with pyloric/duodenal outflow obstruction
o Associated with parvo and pancreatitis
o Gastrinomas
§ Also associated with aciduria
§ hypoCl/K due to gastric acid hypersecretion
Conservation of volume at expense of pH (renal reabsorb HCO3 and exchange Na for H+ = promotes acidic urine (paradoxical aciduria)
What breed when given IV secretin will have a high gastrin level w/o a gastrinoma?
Basenjis (with enteropathies)
What gastric tumors are found in these locations? Pyloric antrum, cardia, diffuse
§ Pyloric antrum · Adenocarcinoma (lesser curvature also) § Cardia · Leiomyoma § Diffuse · LSA
What is the most common site of an adenomatous polyp?
Pyloric antrum
Which breeds are predisposed to PLE?
SCWT, Yorkie, Basenji, Lundehund, Shar-Pei
What AA def can results in high ammonia in cats?
Arginine def
Which coag factor is NOT made by the liver?
Factor VIII
What defines DIC?
Prolonged PT/PTT Decreases fibrinogen thrombocytopenia increased FDPs (all of which can be seen with liver dz too)
What is the most toxic bile acid?
Lithocholic acid
How can diuretics exacerbate HE?
Alkalosis and HypoK!!!
What tropic factors are important for hepatic growth?
Insulin and Glucagon (from portal blood)
What is the toxin in cycad?
Cycasin (converted to MAM (methylazoxymethanol) by GI microbes) and unnamed neuro toxin
What is the MOA of cycad toxin?
Cycasin: MAM results in GI, hepatotoxin, neurotoxin
MAM alkylates DNA/RNA
What are the target organs of cycad toxin?
Cycasin: LIVER, GI, Neuro
What is the clinical presentation of cycad toxin?
Cycasin: within 24 hrs (GI signs and neuro signs)
What are the main clin path signs of cycad toxin?
50-60% increased transaminases
30-50% increased bili
50% increased PT/PTT
30% decreased platelets
What are the histopath features of cycad toxin?
Cycasin: MIXED
Acute: Centrilobular necrosis and neutrophilic inflammation
Chronic: LP inflammation, fibrosis, biliary hyperplasia
What is the definitive test for cycad toxin?
None, hx of eating plant = Look for plant in vomit
What antidotes are recommended for cycad toxin?
Charcoal! Shown to be protective!!!!
What is the prognosis for cycad toxin?
Cycasin: Guarded - 30-50% mortality
What are the known prognostic indicators for cycad toxin?
Higher ALT, T bili, lower albumin (at presentation), prolonged coag = NONSURVIVORS
Early charcoal admin was PROTECTIVE!!
What is the toxin in amanita?
Alpha-amanitin (1 cap can kill!)
What is the MOA of amanita?
Alpha-amanitin: Inhibits RNA polymerase II (no transcription or protein synthesis)
Apoptosis of hepatocytes
Insulin Release
What are the target tissues of amanita?
LIVER
Intestines (crypts)
Kidneys (prox tubules)
What is the onset of CS with amanita?
GI phase: 6-12 hrs - Severe gastroenteritis
Recovery: 12-24 hrs
HEPATIC FAILURE: 36-48 hrs
Fulminate liver and kidney failure
What are the clin path changes with amanita?
Hypoglycemia (releases insulin)
Coagulopathy
Azotemia
Increased AST, ALT, ALP, bili
What are the histopath findings with amanita?
Pan-lobular hepatocellular necrosis
Acute tubular necrosis
How do you make a definitive diagnosis of amanita?
LC/MS or ELISA for alpha-amanitin (toxin)
Early in urine or in vomit (also see mushrooms)
Later kidney or liver
What is the antidote for amanita?
Silibinin has helped!!!
Charcoal (if early)
What is the prognosis for amanita in dogs?
Poor
50% mortality in dogs
What is the toxin in cyanobacteria?
Microcysts aeruginosa (blue green algae) = Microcystins
What is the MOA in cyanobacteria toxin?
Microcystins: Inhibit serine-threonine phosphatases = Build up of phosphorylated proteins = Necrosis = Apoptosis = Massive HEMORRHAGE
What are the target organs of cyanobacteria?
Microcystins: Liver, Kidney (prox tub) and Neuro (anabaena)
What is the presentations of cyanobacteria?
Microcystins: ACUTE (hours) - GI, respiratory, liver, tremors, seizures, comas
What are the clin path findings with cyanobacteria?
Increased ALP, GGT, bili
Marked increased in ALT (can be less if microcystoin inhibits tansminase synthesis??)
What is the histopath finding for cyanobacteria?
Hepatic necrosis - MASSIVE hemorrhage
Acute renal tubular necrosis
How is a definitive diagnosis of cyanobacteria made?
ELISA (confirmed with LC/MS) or MMPB method to detect all forms of toxin)
Best in vomit!!!, can check water source too
Liver (toxin level)
What is the antidote for cyanobacteria?
NONE
Rifampin in mice/rats can inhibit uptake
What is the prognosis for cyanobacteria?
GRAVE
What is the toxin with aflatoxin?
Aspergillus = Aflatoxin B1 converted to AFB1 8,9 epoxide
esp dogs and poultry
What is the MOA of aflatoxin?
P450 converts to AFB1 8,9 epoxide
Inhibits RNA polymerase
Bind to mitochondrial DNA
Depletes GSH
What are the target tissues of aflatoxin?
Liver
Kidney (prox tubules) - CASTS before azotemia
What is the CS onset of aflatoxin?
Highly variable, most are chronic (>1 month of eating food)
What are the clin path findings with aflatoxin?
Increased LEs, icterus, low cholesterol, decreased AT and protein C
What are the histopath findings with aflatoxin?
Acute: Centrilobular necrosis Diffuse hepatocyte lipid vacuolization
Chronic: MIXED
How do you make a definitive diagnosis of aflatoxin?
ELISA, HPLC, LC/MS for toxin AFB1 in food source (>60 ppb)
Serum, liver, urine = Alfatoxin M1
What is the antidote for aflatoxin?
Replenish GSH (N-acetylcysteine or SAMe) Sulfhydryl groups may bind AFB1 8,9 epoxide too
What is the prognosis for aflatoxin?
Guarded, 60% mortality
What are the prognostic indicators for aflatoxin?
100% predictive of death = CASTS
Longer PT/PTT, decreased AT, decreased protein C, increased bili, decreased albumin and cholesterol = Risk factors for mortality
What is the MOA of xylitol?
Rapid, severe increased in insulin from Beta cells (6X more than glucose)!!
Hepatic depletion of ALP (from metabolism via pentose phosphate pathway)
What are the target organs of xylitol?
LIVER (>0.5 g/kg) Beta cells (>0.1 g/kg)
What are the clinical presentation with xylitol?
30 min-1 hrs - Hypoglycemia
9-72 hrs = Acute hepatic failure
What are the clin path findings with xylitol?
Marked increased ALT, bili
Hypoglycemia
Coagulopathy
HypoK, HypoPhos
What is the histopath findings with xylitol?
Periacinar-mid zonal necrosis
What is the definitive diagnosis of xylitol?
HX, no tests for it
What is the antidote for xylitol?
Early emesis, SAMe, dextrose
Charcoal DOES NOT bind it
What is the prognosis for xylitol?
Good if early, guarded if prolonged hypoglycemia and LEs increased
What is a prognostic indicator for xylitol?
Hyperphosphatemia - Poor prognosis
What is the MOA of carprofen?
Idiosyncratic cytotoxic hepatocellular reaction (maybe IM) - Labs?
What are the target organs for carprofen?
LIVER, kidney, GIT
What breed is susceptible to carprofen tox?
Labs
What is the onset of carprofen tox?
VARIABLE - 5-30 days (longer onset in labs)
What are the clin findings in carprofen tox?
Increased ALT and bili
2/3 = Proteinuria, glucouria, and granular casts!!!
What is the histopath of carprofen tox?
MIXED (necrosis and inflammation)
What is the antidote for carprofen tox?
STOP carprofen!!
What is the prognosis for carprofen tox?
Good, 100% labs recover
Only 50% in other breeds
Does the dose and duration of carprofen predict the prognosis?
NO!!
What is the toxin in diazepam?
Oral dosing in cats - converted to “reactive metabolite” of unknown structure = Idiosyncratic
What is the target tissue for oral diazepam in cats?
LIVER
What is the onset of CS in diazepam liver failure in cats?
Within first 7 days after oral dosing
What are the clin path findings with diazepam in cats?
Relative decrease in glucose, marked increase ALT»»»ALP, prolonged PT/PTT
Increased CK
What is the histopath with oral diazepam in cats?
Centrilobular necrosis (MASSIVE!)
What is the antidote for oral diazepam in cats?
STOP diazepam
Silymarin within 24 hrs, SAMe and N-Acetylcystein worked in one cat
What is the prognosis for oral diazepam liver failure in cats?
GRAVE - MOST died within 1-5 days of onset of CS!!!!
What are two complications of gastrinomas?
Acid hypersecretion = GI bleeding
Gastric mucosal hyperplasia - Outflow obstructions
What are the stimulation test for gastrinomas?
Secretin stimulation and Ca stimulation to increased gastrin
What are the tx for gastrinomas?
- Sx
- Octerotide
- Antacids
What are risk factors for pancreatitis?
- Dietary indiscretion (high fat)
- Hyperlipidemia (Min Schnauzer)
- Hereditary (SPINK1 Mini Schnauzer)
- Drugs (azathioprine, KBR, vincristine)
- HyperCa
- Endocrine dz (HypoT4, HAC, DM - weak associations)
- Sx manipulation and trauma
- Infections (B. canis rossi)
- Autoimmune
- Neoplasia
Can steroids result in pancreatitis?
NO! Can increased lipase (some dogs) w/o pncreatitis
What are the 4 safegaurds within pancreas?
- Zymogens (inactive)
- Zymogens granules are separate from lysosomes (physically)
- Pancreatic Secretory Trypsin Inhibitor (PSTI) - immediate inhibition of trypsin
- Larger antiproteases in circulation (alpha 2 macroglobulin)
What is the process of acute pancreatitis?
- Apical Block: Zymogens are not secreted
- Colocalization of zymogens and proteases (overwhelm pancreatitic secretory trypsin inhibitor = Phospholipase A2, elastase, chymotryspin, lipase)
- Recruitment of neutrophils and ROS production
- Change in pancreatic circulation = vasconstriction
- Activation of complement and change in permeability
- Cytokine Storm!!!
End result = Massive inflammation
What % of dogs with pancreatitis have amylase and lipase within RR?
About 50%
Can be increased in 50% dogs that do NOT have pancreatitis too
What is the most sensitive and specific test for pancreatitis?
cPLI
Spec cPL
SNAP cPL (good to exclude pancreatitis, so if normal NOT pancreatitis; abnormal SNAP may not be pancreatisi check Spec cPL)
What are potential complications with pancreatitis?
Pancreatitic cytokines = Systemic effects
- AKI
- DIC
- Cardiac arrhythmias
- ALI (neutrophilic inflammation)
- EPI
- Pseudocytes
- Pancreatitic encephalopathy (dog)
- MODS
- SIRS
- Chronic relapsing pancreatitis
What is the principle behind use of plasma in pancreatitis cases?
More alpha 2 macrolobulin (protease) BUT there is no proof in vet med that it is of benefit
What protease inhibitor has shown some benefit in pancreatitis?
Aprotinin
Which anti-emetic may be benefit in pancreatitis since inflammed pancreas can secrete substance P?
Maropitant
Is there a benefit of ABX with pancreatitis?
None seen with cochrane review
What are tx for chronic pancreatitis?
Seen in Mini Schanzuers Spec cPL >400 + waxing adn waning CS (every few days) Ultra low fat diet (RC GI low fat) Hypoallergenic diet Prednisone (14 days with taper) Cyclosporine
Why should you not used TLI to dx pancreasitis?
Lacks sens for pancreatitis
Can increased with renal failure!
What are not useful tests to dx pancreatitis?
Amylase/Lipase Trypsinogen Activation Peptide (TAP) Trypsin alpha1 proteinase inhibitor Alpha 2 macroglobulin CRP
How long can the PLI remain elevated after pancreatitis?
10-12 days
Can PLI predict severity on histopath of pancreatitis?
NO!
What are the ranges of PLI for pancreatitis?
DOGS >400
CATS >5.4
Is the PLI affected by renal failure?
NO!
But TLI is affected by renal failure
What are the two main forms of EPI?
Acinar atropy (GSD, collies) - Endocrine functional Chronic pancreatits = Atrophy and fibrosis (all parts of endocrine lacking too)
Which single pancreatic enzyme def has been reported in dogs?
Lack of pancreatic lipase (will have normal TLI, but CS of EPI)
Are there markers of progression in EPI?
NO! Can be subclinical for years
Early immunosuppression is NOT recommended
What is the diagnostics of choice for EPI?
TLI Low
Can fecal pancreatitic elastase be used to dx EPI?
Yes, but need to verify with cTLI
Since false + 23% (low elastase and normal cTLI)
What % EPI dogs have Vit B 12 def?
About 82%
What is a potential complication of EPI?
Mesentric torsion!
What is associated with a shorter survival in EPI dogs?
Concurrent Vit B12 defs (need to check B12 in every patient with EPI)
What % EPI dogs have poor response?
About 20%
What are potential reasons for treatment failure in EPI dogs?
- IBD, DM, SIBO - Need to tx
2. Need PPI - To prevent pancreatic enzymes from being destroyed
What is a complication with pancreatitic extract in EPI dogs?
Oral bleeding (need to reduce dose and wet it)
Why can GI disease result in high false + fecal pancreatitic elastase-1?
Due to high neutrophil elastase
What are 3 reasons to have a normal TLI with EPI?
- Pancreatic duct obstruction
- Congenital def intestinal enteropeptidase
- Selective pancreatic enzyme def (NOT trypsin)
Is EPI inherited in GSD?
Based on test mating - NO!
What are 6 options for pancreatic dz in cats?
- Acute necrotizing panceratitis
- Acute suupurative panc (Neutrophils = Younger cats)
- Chronic panc (lymphocytic inflammation and fibrosis)
- Panc Neoplasia (adenocarc - ductal)
- Pancreatic Nodular Hyperplasia (unknown significance)
- EPI?? (mainly from chronic panc, can occur with flukes too - Eurytrema procyonis)
What are risk factors for panc in cats?
- Concurrent biliary dz (cholangitis)
- Concurrent GI disease (IBD) - Direct communication from bile duct to pancreatic duct - Reflux
- Ischemia
- Infeciton (toxo, FHV-1, FIP, Eurytrema, Amphimerus, virulent calici)
- Pancreatic Obstructions (neoplasia, fluke, stone)
- Trauma (high rise)
- Organophosphates
- Lipodystrophy
- HyperCa (exp)
- Nutrition = UNDERWEIGHT cats
What is a common electrolyte abnormality in cats with AP?
HypoCa - 65% - Worse prognosis (more common than in dogs)
What are 4 complications of AP in cats?
- Chronic panc
- EPI
- Hepatic Lipidosis *even worse if together
- DM
Why are H2 and H1 blockers recommended in feline panc?
Histamine and bradykinin induced vascular permeability can be blocked to prevent hemorrhage and necrosis
Which test has been validated in cats for AP?
fPLI
What are pulmonary manifestations of GERD?
From chronic microaspiration events
- Aspiration pneumonia
- Chronic Bronchitis
- Interstitial Pulmonary Fibrosis
What is the tx for Spirocerca?
Doramectin
What are the 3 defensive lines to prevent epithelial damage?
- Mucus and Bicarbonate Barrier
- Epithelial cell mechanisms; barrier function of apical plasma membrane, intrinsic cell defenses
- Blood flow mediated removal of back diffused H and energy supply
If all FAIL = Epithelial Cell Injury!!
What are the effects of NSAIDs on mucosa?
- Direct effect (uncoupling mitochondria)
- COX 1 inhibition: Neutrophil activation and ROS
- COX 2 inhibition: Neutrophil activation and ROS; Also inhibits GF production and impairs repair
What is the stomach worm in cats?
Ollulanus tricuspids
Ingesting cat vomit
Tx: Fenbendazole
What is a stomach worm in dogs/cats? Where is it from?
Physalloptera; Ingestion of cockroach/beetle (IH) or lizards
Tx: Pyrantel
What is the recommend tx for Helicobacter?
Amoxicillin, Clarithromycin, and omeprazole for 3 weeks
What is the tx for Campylobacter?
Fluoroquinolones
Which hookworm can result in pedal pruritus in greyhounds?
Uncinaria stenocephala
What is a treatment for round worms?
Fenbendazole
What is a tx for hookworms?
Pyrantel
What is a tx for tapeworms?
Praziquantel and flea control
An increase in which TRL is seen with IBD?
TLR2
Also 4, 9
Does clinical improvement with IBD mean that there is histopath improvement?
NO!
What are the 5 steps of cobalamin absorption?
- Cobalamin released from food in stomach
- Binds to cobalamin binding protein (Haptocorrin - from salivary and gastric source)
- In duodenum: Haptocorrin degraded (by pancreatic proteases) and Cobalamin binds to intrinsic factor (pancreas and stomach in dog and ONLY pancreas in cats)
- Cobalamin-IF binds to receptors (cubilin) in microvillus
- Cobalamin transcytose portal blood bound to tanscobalamin 2 - mediated absoprtion by target cells
Can undergo enterohepatic recirculation with haptocorrin in bile
In which breed can you see Vit 12 def (cubilin defects)?
Border Collies
Giant Schnauzer
Beagles
Aust Shap
Name several compounds that are associated with hepatic encephalopathy?
Ammonia Tryptophan Glutamine Aromatic AA/Branch Chained AA SCFA GABA Endogenous benzodiazepines Bile Acids Phenol Flase neutrotransmitters
What are the proposed mechanisms of how ursodeoxycholic acid works?
- Replace more hydrophobic hepatotoxic bile acids in circulation
- Induced choleresis
- Stabilization of mitochondrial function (preventing apoptosis)
- Immunomodulation (increased glutathione, decreased Ig from B cells, activate GC receptors)
Which breed gets lobular dissecting hepatitis?
Standard Poodles
Where is copper location in inherited copper storage dz?
Centrolobular
Where is copper located if you have secondary copper accumulation?
Periportal
What is the mutation seen in Bedlington terriers with copper hepatopathy?
COMMD1 or MURR1
What is the tx for copper hepatopathy?
Low copper diets
- Penicillamine (which increased metallothionein that binds copper) - Trientine is another option
- Zinc (increased metallothionein in enterocytes to prevent copper uptake, lost with enterocyte)
What is zone 3 necroinflammatory hepatitis?
Associated with IBD and see in Maltese
ASCITES!!! Portal Hypertension
Inflammation veno-occlusive dz (lymphs and eosins around hepatic v.)
What is noncirrhotic portal hypertension?
Portal v hypoplasia with portal hypertension
Seen in Dobies, Rotties, and Cockers
Have abdominal effusion with acquired shunts
What is portal v. hypoplasia?
MIcroscopic malformation in hepatic microvascular
Thought to nonprogressive
Can be asymptomatic
increased bile acids with normal Protein C, CBC, chem, AUS, scinitgraphy
Can be seen with macroscopic PSS too
Why do PSS get microcytosis?
iron transport defect
What % of shunty dogs can have normal bile acids?
21%
How can Protein C help with PSS vs Portal v hypoplasia?
Low with PSS
Normal (>70%) in MVD
Does hepatic bx allow for discrimination btwn PSS and protal v. hypoplasia?
NO!
How does portal hypertesion lead to ascites?
Progressive splanchnic dilation - Peripheral vasodilation
Compensatory hyperdynamic changes (increased CO), compensatory failure, increased circulating volume
RAAS activation and ADH release = Na and Water retenion = Ascites
What are precipitating factors of HE?
Increased production of ammonia in GIT (high protein meal, GI bleeding)
Increased systemic generation of ammonia (blood transfusion, poor quality protein)
Factors affecting uptake and metabolism of ammonia in CNS (metabolic alkalosis, hypoK, hypoglycemia, inflammation, infections, sedation/anesthesia)
What is a major complication of feline PSS correction?
75% neurologic complications = Central blindness
What is the lesion in neutrophilic cholangitis in cats? Signalment, tx
Neutrophils in bile ducts and epithelium
Acute and chronic forms - Ill cats
Associated with pancreatitis, IBD, triaditis
Tx: ABX
What is the lesion in lymphcytic cholangitis in cats?
Small lymphocytes in portal area, portal fibrosis, biliary duct proliferation
Not always ill but have jaundice, ASCITES, increased globulins
TX: Steroids
What is the cat live fluck?
Platynosum
Tx: Praziquantel
What is lymphocytic portal hepatitis?
Nonspecific thought to be an aging change
Older cats
What has been identified as a mutation in Shelties with GB mucoceles?
ABCB4 transport mutation (phospholipid transporter)
Dog with what disease are 29X more likely to develop a GB mucocele?
HAC
Does biliary rupture and bile peritonitis have prognostic factor?
NO!!
What is the progression with complete occlusion of the CBD?
24 hrs = GB distension
48-72 hrs = Extrahepatic bile duct distension
5-7 days = Intrahepatic ductal dilation
What is hepatic lipidosis?
Enhanced mobilization of peripheral fat to lover and impaired dissemination of lipid from hepatocytes = Severe hepatic dysfunction
Do all cats with HE have increased ammonia?
NO!! Ptyalism could be from HE
What was associated with worse survival in Hepatic lipidosis?
HypoK
Advanced age
Decreased PCV
What are the mainstays in Tx of hepatic lipidosis?
- Feeding!!! High quality protein!!!
- B vitamins (B1 and B12)
- Fat soluble vits (E and K1)
- Amino Acids = L-carnitine and taurine
- Antioxidants = SAME and ursodiol
- electrolytes: HypoK and HypoMg
Which breed gets idiosyncratic hepatotoxicty to sulfas?
Dobies!!