Term
| What are the three recognized causes of EPI in dogs and cats (EPI is not recognized in cattle and horses)? |
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Definition
Pancreatic acinar atrophy in dogs- hereditary immune mediated in german shepherds and rough coated collies
Chronic pancreatitis in dogs and cats- may or may not have concurrent diabetes mellitus if there is destruction of islet cells
Pancreatic duct obstruction in dogs and cats- impaired secretion of pancreatic enzymes leads to maldigestion but since this obstruction would also probably cause acute pancreatitis the patient might more likely present with acute illness and not develop a maldigestive state associated with chronic diarrhea and weight loss |
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Term
| What secondary intestinal abnormalities are associated with exocrine pancreatic insufficiency in dogs and cats? |
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Definition
increased mucosal maltase and sucrase activity, increased microvillar membrane proteins, bacterial overgrowth
**these changes can also lead to malabsorption |
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Term
| What substances are measured by TLI? |
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Definition
| Mostly trypsinogen, but also small amount of trypsin and trypsin bound to anti-proteases (alpha1-antitrypsin) |
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Term
| While TLI is highly specific to the pancreas, TLI was still measurable in animals post pancreatectomy. What other tissue sources of TLI exist? |
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Definition
| Human small intestine (paneth cells), biliary epithelium, ovarian and hepatobiliary neoplasms |
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Term
| Why can't we measure serum trypsin activity to assess exocrine pancreatic function? |
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Definition
| There are many trypsin inhibitors in serum |
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Term
| In what species are there validated TLI assays? |
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Definition
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Term
| What is the most common cause of increased [TLI] in dogs and cats? |
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Definition
Pancreatic acinar cell damage cause by pancreatitis- trypsinogen or trypsin enters blood via lymph and peritoneal fluid
**while this is specific (90%) to severe pancreatitis in dogs its not sensitive (many dogs with pancreatitis will not have elevated TLI) and in a small study of cats there may or may not be clinically relevant increases in [TLI] with pancreatitis and the problem of many false negatives remains |
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Term
| What condition is associated with increased TLI in horses? |
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Definition
strangulating intestinal obstruction and endotoxic shock
** hypothesized that trypsin is released from pancreatic acinar cells as a result of poor perfusion of splanchnic tissues but another possibility could be increased protein binding (e.g. to APPS) of TLI molecules |
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Term
| Other than pancreatic acinar cell damage/injury, what conditions can be associated with increased [TLI] |
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Definition
decreased GFR
stimulation by food intake or cholecystokinin and secretin administration |
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Term
| What vitamin deficiency has been associated with increased [TLI] in cats? |
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Definition
cobalamin deficiency in cats with GI disease
**cause was not determined but TLI decreased in 50% of cats that were given parental cobalamin therapy |
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Term
| T/F decreased [TLI] in clinically healthy dogs (predisposed breeds) identify subclinical immune mediated lymphocytic pancreatitis (aka pancreatic acinar cell atrophy) |
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Definition
True-
decreased [TLI] was observed in clinically healthy german shepherds and rough coated collies, and ~45% of them went on to develop clinical EPI within 6-46 months of the initial abnormal [TLI] |
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Term
| What conditions are associated with decreased PLI? |
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Definition
decreased pancreatic acinar tissue as a result of :
Chronic pancreatitis in dogs and cats
Pancreatic acinar atrophy (german shepherds and rough coated collies)**
**although PLI is consistently decreased in dogs with EPI, TLI is preffered for the diagnosis because it more clearly differentiates affected dogs from healthy, and may have greater diagnostic sensitivity compared with PLI |
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Term
| Why is the serum immunoassay to detect [TAP] only capable of detecting increased [TAP]? |
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Definition
| The analytical detection limit is near the lower plasma concentrations found in healthy dogs |
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Term
| How would you interpret increased plasma [TAP] (trypsinogen activation peptide) AND increased urinary TAP:Cr? |
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Definition
Pancreatic acinar cell damage**
**in cats serum [TAP] and urinary TAP:Cr appear to be increased in cases of spontaneous or induced pancreatitis, however TAP:Cr were not significantly increased compared to healthy cats |
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Term
| How would you interpret increased plasma [TAP] but normal or decreased urine TAP:Cr? |
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Definition
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Term
| What are two potential outcomes of cobalamin deficiency? |
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Definition
impaired folate metabolism and DNA synthesis
*cobalamin is a cofactor necessary for conversion of N5-methyltetrahydrofolate to tetrahydrofolate (aka folate; used for DNA synthesis
defective formation of neuronal lipids
*cobalamin is a cofactor for the enzyme that converts methylmalonyl COA --> succinyl COA, without it methylmalonic acid accumulates |
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Term
| What type of assay is most commonly used to measure [cobalamin] aka cyanocobalamin (B12)? |
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Definition
| Competitive protein binding assays |
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Term
| What are some sample considerations when measuring cobalamin? |
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Definition
| serum is sample of choice, heparinize or hemolytzed plasma should be avoided, light can degrade cobalamin |
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Term
| Although increased cobalamin is an uncommon finding, what two considerations should still be kept in mind when interpreting cobalamin that is WRI or decreased? |
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Definition
cobalamin supplementation (oral or parentral)
hepatocellular damage- hepatocytes are the primary storage site for cobalamin so hepatic necrosis could increase serum [cobalamin] however the magnitude and duration is unknown |
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Term
| What is the most common cause of decreased [cobalamin]? |
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Definition
| decreased absorption (ileum) |
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Term
| What pre-absorptive conditions can be associated with decreased [cobalamin]? |
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Definition
Exocrine pancreatic insufficiency: failure to secrete bicarbonate rich fluid into intestine results in a persistence of R protein-cobalamin complexes. Lack of intrinsic factor (esp. in cats, because they lack gastric intrinsic factor) may also impair intestinal absorption of cobalamin
Intestinal bacterial overgrowth, bacteria bind to and utilize cobalamin reducing the amount available for absorption in the ileum |
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Term
| What dog breeds have an inherited deficiency in the cobalamin/intrinsic factor receptor (cubulin, amnionless, megalin) |
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Definition
| Giant schnauzers border collies, australian shepherds, beagles, komondors |
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Term
| How can there be a functional folate deficiency despite normal [folate]? |
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Definition
Tetrahydrofolate is the functional form of folate used for DNA synthesis, however, the folate assay measures predominantly N5-methyltetrahydrofolate (modified from ingested folate by intestinal brush boarder).
Cobalamin is a required cofactor for the enzyme (methionine synthase) that catalzyes this reaction so cobalamin deficiency can result in functional folate deficiency despite normal [folate] |
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Term
| Describe the principle of competitive binding assays for measuring serum [folate] |
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Definition
beta-lactoglobulin (milk folate binder) binds primarily to N5-methyltetrahydrofolate.
**other assays involving denaturation of endogenous binding proteins (high temp or pH) and release of folate have also been used. There are immunometric assays as well. |
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Term
| T/F RBC have high concentrations of both cobalamin and folate, as such hemolysis can cause false elevations of both vitamins |
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Definition
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Term
| What conditions are associated with increased serum [folate] due to increased absorption of folate in the small intestine (proximal)? |
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Definition
Small intestinal bacterial overgrowth-
Bacteria produce folate. The overgrowth can be secondary to EPI or other causes (e.g. impaired gastric acid secretion, decreased peristalsis, defective mucus barrier or IgA immunodeficiency)
Low intestinal pH-
maximal folate absorption occurs in acidic environment. Decreased intestinal pH may be secondary to EPI (less bicarbonate secretion) or increased gastric acid secretion
High dietary intake-
At high intestinal concentrations folate can passively diffuse into enterocytes |
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Term
| What concurrent vitamin deficiency has been associated with increased [folate] in cats? |
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Definition
cobalamin deficiency
**cobalamin deficiency decreased folate utilization (impaired conversion of N5-methyltetrahydrofolate to tetrahydrofolate) |
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Term
| What are the two major cases of decreased [folate]? |
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Definition
proximal small intestinal disease with impaired absorption
dietary deficiency (hard to do with commercial diets, all cheese diet resulted in folate deficiency in a dogs) |
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Term
| What is alpha-1 protease inhibitor? |
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Definition
a protein that inhibits activity of proteases in feces.
**it is normally present in plasma, interstitial fluid and lymph, but oddly, not in the intestinal lumen (but how does it get into the poop?) |
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Term
| What is the assay for alpha1-protease inhibitor in feces? |
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Definition
ELISA, offered at Texas A&M GI lab
sample: send three voided fecal samples pooled |
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Term
| How should you interpret increased fecal [alpha1 protease inhibitor]? |
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Definition
protein losing enteropathy (inflammatory, infectious, neoplastic) **can be detected prior to hypoproteinemia
GI blood loss or blood contamination of the fecal sample during collection (e.g. don't manually collect the feces) |
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Term
| Describe the principle of xylose absorption tests |
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Definition
| xylose is a simple sugar that is not commonly ingested and is not normally present in liver or blood. It is passively absorbed in the small intestine and excreted in the urine (freely filtered, not absorbed or secreted). The peak blood [xylose] after oral administration reflects the amount of xylose absorbed in the intestine. Similarly the amount of xylose in the urine reflects the amount absorbed in the intestine. |
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Term
| What conditions are associated with flat xylose absorption curve (low [xylose])? |
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Definition
reduced absorption due to:
intestinal mucosal disease
incomplete delivery of xylose to SI (vomiting, delayed gastric
emptying)
rapid transit time (diarrhea)
Decreased GFR |
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Term
| What is the primary indication for doing a glucose absorption test in horses? What are expected results in normal horses? |
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Definition
Chronic weight loss
Normal horses should have serum [glucose] 85-100% (or approximately 2x) baseline [glucose] |
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Term
| What is the major indication for the lactose tolerance test? |
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Definition
Used primarily in foals to detect lactase deficiency, which is usually secondary to intestinal mucosal damage
*lactase is present in the small intestinal brush boarder of foals and young horses (<3yrs) |
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Term
| Describe the principle of the lactose tolerance test in horses |
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Definition
| lactose is administered orally, serial blood samples are collected and {glucose] determined, assuming normal glucose absorption and metabolism blood [glucose] should reflect the magnitude of lactase activity in intestine **peak [glucose] should be at least 35 mg/dL above baseline, or 150-250% above baseline |
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Term
| What infectious diseases in horses are associated with lactase deficiency? |
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Definition
viral enteritis (e.g. rotavirus)
clostridium difficile enterocolitis |
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Term
| what conditions other than lactase deficiency could result in abnormal oral lactose tolerance test (e.g. no increase in [glucose])? |
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Definition
glucose malabsorption due to small intestinal disease
excessive cellular utilization of absorbed glucose |
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Term
| In what context is urine [sucrose] elevated in horses? |
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Definition
| gastric ulcers, the magnitude of urine [sucrose] correlates to the severity of gastric ulceration |
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