Interpretation of Laboratory Parameter Changes in Patients With GI Disorders
Faculty of Veterinary Medicine, Clinic of Small Animal Medicine, Centre for Clinical Veterinary Medicine, LMU Munich, Munich, Germany
In patients with gastrointestinal symptoms (GIS), the following laboratory parameters should be determined in order to rule out extraintestinal causes of disease:
- Blood urea nitrogen (BUN), creatinine and urine specific gravity to rule out renal failure
- Serum bile acids or ammonia to rule out portosystemic shunting and liver dysfunction
- Serum basal cortisol concentration to rule out hypoadrenocorticism
- (Not always elevated in mild/chronic forms)
A recently performed study showed that 6/151 dogs (4%) presented for chronic GIS were diagnosed with hypoadrenocorticism (HA). Hyperkalemia/hyponatremia were not observed in those dogs, and HA could not be separated from other disorders causing chronic GIS based on any information from the history or based on laboratory parameters. Therefore, it has been suggested that basal serum cortisol levels should be measured as a screening test for hypoadrenocorticism in every dog with chronic GIS, followed by an adrenocorticotropic hormone (ACTH) stimulation test in cases with a basal serum cortisol concentration <2 µg/dl.
Packed cell volume (PCV) determination can provide important information about the hydration status of a patient and is easy to perform. In some dogs with acute onset of gastrointestinal signs, the degree of dehydration might be underestimated by relying only on clinical parameters. Specifically, in dogs with blood in feces, PCV helps to distinguish between GI bleeding (PCV is decreased or low normal in a dehydrated patient) and hemorrhagic enteritis. In dogs with acute hemorrhagic diarrhea syndrome, PCV is often significantly increased, and in some patients PCV is within the reference interval. In this patient group, a decreased PCV would be an unusual finding. Additional parameters, which might be seen in association with GI bleeding, include melena, regenerative microcytic anemia (iron deficiency), thrombocytosis, disproportionally elevated BUN compared to creatinine, low total protein/albumin. To detect the presence of small amounts of blood in the feces, a guaiac fecal occult blood test (hemoccult test) can be performed. Since this test can show false positive results due to different dietary components (e.g., red meat, vegetables, vitamin C in fruits), a specific feeding regime should be initiated 3 days before testing (e.g., rice and cottage cheese for dogs, Hills k/d chicken for cats).
Neutrophils are frequently elevated due to stress response in patients with GIS. However, if neutrophils are significantly elevated (>25 x 109/l), or if a significant left shift is present (band neutrophils >1.5 x 109/l) in a GI patient, an inflammatory response is likely. In this case, clinician should check for a possible bacterial infection as well as for translocated bacteria (blood culture, or culture of aspirated material from enlarged abdominal lymph nodes should be performed). Significant neutrophilia and a left shift is usually an indication for antibiotic treatment after obtaining samples for culture. Antibiotics are also indicated in GI patients with GIS and significant neutropenia. Patients with the combination of neutropenia and destroyed intestinal mucosal barrier, typically seen in dogs with parvovirosis, are especially prone to sepsis. In general, patients with combination of increased intestinal permeability (e.g., hemorrhagic diarrhea, protein losing enteropathy) and reduced immune competence (e.g., neutropenia, immunosuppressive treatment, liver dysfunction, portosystemic shunting) have an increased risk for systemic bacterial infection.
Laboratory tools to assess the intestinal function and/or the severity of intestinal disease include: albumin, cobalamin (vit B12), folate (vit B9), C-reactive protein (CRP) concentrations, and canine pancreatic lipase immunoreactivity (cPLI). Low album in concentration due to intestinal loss always reflects a severe form of gastrointestinal disease, termed protein losing enteropathy. In rare cases, hypoadrenocorticism can mimic a primary intestinal disease causing protein loss into the gastrointestinal tract. After ruling out hypoadrenocorticism, parasites and focal intestinal disorders, intestinal biopsies are usually indicated for diagnosis. In general, patients with significant gastrointestinal protein loss have a guarded prognosis.
Similar to albumin, cobalamin concentration is also a prognostic factor. Cobalamin concentration should be determined in every case of suspected GI or pancreatic disorder. Since cobalamin is absorbed in the ileum, hypocobalaminemia in a patient with intestinal disease can help locate the location from which biopsy samples should be taken. It is important to know that patients with intestinal disorders can develop hypocobalaminemia due to insufficient absorption, and that hypocobalaminemia on the other hand can cause intestinal mucosal changes leading to diarrhea. Specifically, young dogs with failure to thrive and/or with chronic diarrhea should be tested for hypocobalaminemia, which can be due to a genetic defect of the cobalamin receptor in the ileum (Imerslund-Gräsbeck syndrome). In all cases with low cobalamin concentrations, treatment is indicated either as weekly cobalamin injection or as daily oral cobalamin supplementation.
Folate is absorbed in the proximal small intestine. Folate malabsorption can be present in patients with significant intestinal disease. Similar to cobalamin, folate can help define the location where biopsy samples should be taken. In contrast to cobalamin, it is not clear if folate supplementation is necessary and beneficial for GI patients.
C-reactive protein (CRP) is an acute phase protein whose elevated concentration generally reflects an inflammatory disease. CRP can be increased in dogs with chronic inflammatory intestinal disorders and might help in monitoring the response to treatment.
It has been reported that an elevated cPLI is associated with a worse outcome in dogs with inflammatory bowel disease and therefore might help the clinician to assess the prognosis of the disease. The exact cause of the cPLI elevation in dogs with IBD is currently unknown, but may be suggestive of IBD-associated pancreatitis.
In summary, laboratory evaluation is always indicated in patients with chronic GIS and in certain patients with acute clinical signs in order to rule out extraintestinal causes of disease, detect complication factors, assess the severity of the disease and provide prognosis for the patient. In all cases with chronic diarrhea, it is recommended to measure hematological parameters, serum biochemical parameters with electrolyte concentrations, serum basal cortisol, bile acid, cobalamin and folate concentrations, and trypsin-like immunoreactivity (TLI). Canine PLI might be helpful to assess the prognosis and CRP to monitor treatment success. Specific gastrointestinal permeability testing and determination of serum or fecal concentration of specific inflammatory markers such as calprotectin and S100A12 are currently not routinely used in veterinary medicine, since their clinical usefulness is not clearly defined.