GI Diet test samples

Gastrointestinal Disease:

How can Laboratory Tests Help?

A recent “Organ of the Month” outlined how histopathology can be used in the work-up of patients with gastrointestinal (GI) disease. In this companion piece we will review the clinical signs of GI disease, and highlight the value of laboratory tests.

Clinical Signs

Vomiting and diarrhoea are the most familiar signs of GI disease, but don’t forget to also
consider:

  • Is it really vomiting? Could it be regurgitation?
    • The key difference is that vomiting involves abdominal effort, but regurgitation is more passive, with minimal abdominal effort.
    • The diagnostic approach to regurgitation is very different to the approach to vomiting.
  •  Is the problem acute or chronic?
    • Acute GI disease is common in small animals, particularly dogs. Acute vomiting warrants imaging to rule out a GI obstruction; acute diarrhoea can often be managed with supportive care or non-specific therapy, with no further testing required.
    • Recurrent acute episodes of vomiting and/or diarrhoea, even if responsive to supportive care, suggest an underlying cause; further investigation is recommended.
  • Is the diarrhoea small bowel or large bowel in origin? Or are there signs of both?
    • Table 1 below summarises the key signs of small vs large bowel diarrhoea.
    •  Not every patient with have all the typical signs, and patients with GI disease can also show a mixed pattern (features of both small and large bowel disease).
    • Distinguishing small vs large bowel diarrhoea can help narrow down the differential diagnoses.

TABLE 1: Small vs Large Bowel Diarrhoea

  • Is appetite normal, increased, or decreased? Is there weight loss?
    • Not all patient with GI disease have vomiting and/or diarrhoea; changes in appetite and/or changes in weight can be the only signs of GI disease.
    • Weight loss despite a normal or increased appetite can be a sign of GI disease, particularly in cats, but also in dogs. If metabolic causes of polyphagia and weight loss (e.g. diabetes mellitus, hyperthyroidism) have been ruled out, think GI disease, even if vomiting and diarrhoea are absent.
  • Diet, lifestyle, environment, and preventive care?
    • Is the patient vaccinated and regularly dewormed
    • Are other animals in the household affected?
    • Was a new pet introduced recently?

Laboratory Tests

  • Panels, profiles, and screens are particularly useful in patient with GI disease for 2 main reasons:
    • They can tell us the consequences of the GI disease (e.g. low protein with a protein-losing enteropathy).
    • They can help us rule out extra-GI causes of GI signs (e.g. azotaemia as a cause of vomiting and hyporexia).
  • It is less common for haematology and biochemistry to pinpoint an exact cause of
    primary GI disease, but the results can help guide further work-up.
  • Analytes of particular interest include:
  • Red blood cell parameters
    • Microcytic, hypochromic anaemia (low MCV and low MCHC) can indicate iron deficiency or anaemia of chronic disease. Assessment of reticulocyte haemoglobin concentration can sometimes be helpful. Iron deficiency can result from chronic low-grade GI blood loss, which might not always be associated with grossly apparent melaena.
  • White blood cell parameters
    • Eosinophilia can be a marker for parasites, hypoadrenocorticism in dogs (see box below), or hyperthyroidism in cats.
  • Serum albumin and globulin
    • Protein-losing enteropathy (PLE) is a syndrome of excessive protein loss across the GI mucosa. It is not a specific disease, but can result from severe small intestinal
      disease, including inflammatory bowel disease, lymphoma, or lymphangiectasia.
    • Panhypoproteinaemia is the “classic” finding in PLE, with both albumin and globulin below the reference interval.
    • Hypoalbuminaemia alone is not uncommon with PLE, particularly if the underlying
      disease process is inflammatory, causing a relative increase in globulins (so the two disease processes “cancel out”).
    • There is no readily available test to directly prove that low albumin is due to GI loss. Therefore, other causes have to be ruled out:
    • Protein-losing nephropathy (ruled out with urinalysis and urine protein:creatinine ratio).
    • Decreased liver function (ruled out with dynamic bile acids testing).
    • Chronic inflammation or third spacing (should be apparent from the rest of the clinical data).
  • Calcium
    • Total calcium is expected to be low when albumin is low (because approximately 40% of calcium is bound to albumin) but ionised calcium can also be decreased
      with severe PLE (probably related in part to decreased vitamin D), therefore measurement of ionised calcium is recommended if calcium is low.
    • Ionised calcium measurement requires careful sample handling; please consult the laboratory before performing this test.
  • Electrolytes
    • Changes in potassium, sodium, or chloride can often be the result of GI disease.
    • Hypokalaemia can result from increased GI losses (e.g. through vomiting or diarrhoea), often compounded by decreased intake.
    • Hyponatraemia can be the result of GI fluid losses, leading to hypovolaemia.
    • Hypochloraemia can result from vomiting of gastric contents or decreased
      gastric emptying.
  • Liver enzymes
    • Liver enzyme activities can be increased secondary to primary GI disease. This is because all the blood from the GI tract reaches the liver through the portal system, thus exposing the hepatocytes to inflammatory mediators, toxins, or pathogens from the GI tract.
    • Liver enzyme activities can be increased secondary to primary GI disease. This is because all the blood from the GI tract reaches the liver through the portal system, thus exposing the hepatocytes to inflammatory mediators, toxins, or pathogens from the GI tract.
  • Cholesterol
    • Cholesterol can be low with PLE, due to loss from the lacteals.
    • Other causes of low cholesterol include decreased liver function and hypoadrenocorticism (see box).
    • Cholesterol can be low with PLE, due to loss from the lacteals.
    • Other causes of low cholesterol include decreased liver function and hypoadrenocorticism (see box).
  • Total T4
    • Total T4 is frequently included in laboratory screens of older dogs and cats.
    • Hyperthyroidism often causes GI signs (vomiting, diarrhoea, weight loss) in cats.
    • T4 should always be measured in cats with GI signs if > 8 years old.
    • Hypothyroidism is over-diagnosed in dogs and T4 measurement (in conjunction with TSH, at a minimum) is only recommended if typical signs are present.
    • The main GI sign of hypothyroidism in dogs is constipation. Vomiting, diarrhoea, and weight loss are not expected.
    • Faecal tests are beyond the scope of this article, but the following are often indicated
  • Parasitology
    • Flotation for worm eggs and coccidia.
    • Antigen tests (e.g. parvovirus, Giardia, Cryptosporidium).
    • PCR (e.g. for Tritrichomonas in cats).
  • Faecal culture
    • The value of these can be controversial as healthy dogs and cats can harbour organisms such as Campylobacter.
    • Salmonella and Campylobacter are particular concerns in patients that are raw-fed. Both of these are also zoonoses.
  • Specific Tests for Diet trials
    • While not a laboratory test, a diet trial is an essential step in the approach to chronic GI disease in dogs and cats. A diet trial for GI disease requires a careful history and the strict feeding of a novel antigen diet (or often a hydrolysed diet), with no other protein sources, for approximately 3-6 weeks. If the patient responds, ideally antigens should be reintroduced, one at a time, as a challenge.
    • Blood tests that detect IgE to specific food allergens are not useful for the diagnosis of food allergy (causing either skin disease or GI disease) and are not recommended for this
      purpose.GI Disease
  • GI “Function” Tests
    • Measurement of cobalamin (vitamin B12), folate, and trypsin-like immunoreactivity (TLI) are valuable in the work-up of GI disease.
    • TLI should always be assessed in conjunction with B12, because exocrine pancreatic insufficiency (EPI) is an important cause of low B12.
    • Cobalamin supplementation can be of clinical benefit when B12 is subnormal, or at the low end of the reference interval.
    • Non-haemolysed serum sample after a 12 hour fast is required for these tests.
    • See table 2 below for further information.

Table 2: Cobalamin, Folate, and TLI Summarised

1The significance of a high B12 has not been proved in dogs or cats. Increased B12 has been associated with serious underlying disease in humans, but studies in dogs and cats to date have produced conflicting results, and rely on small data sets with significant sources of bias.

2If TLI is low, but not subnormal, trial enzyme therapy for EPI could be justified in some cases, as there might be a “grey zone” for these results. Please call the laboratory to discuss with one of our medicine consultants.

  • Faecal occult blood test
    • This test can be considered if GI blood loss is a concern, but sensitivity and specificity are low.
    • Specificity can be improved (false positives reduced) by feeding a home-cooked diet without red meat for 3 days prior to sample collection. Iron supplements and
      vitamin C should also be avoided.
      ▪ Sensitivity can be improved by sampling 2 separate portions of the faeces, from 3
      consecutive samples, and pooling for submission.
      ▪ Please call and speak to a medicine consultant at the laboratory for more details,
      if you are considering this test.

HYPOADRENOCORTICISM: THE GREAT IMITATOR

Hypoadrenocorticism should always be a consideration for a patient with GI signs. Loss of function of the adrenal cortex can result in hypocortisolaemia alone (sometimes called “atypical” hypoadrenocorticism) or loss of both cortisol and aldosterone (so-called “typical” hypoadrenocorticism or Addison’s disease).


Atypical hypoadrenocorticism is associated with normal electrolytes (eunatraemic, eukalaemic). Don’t let normal electrolytes prevent you from considering hypoadrenocorticism!


Hypoadrenocorticism (typical or atypical) can mimic GI disease with some or all of the following findings:

  • Vomiting, diarrhoea, hyporexia, weight loss
  • Hypoalbuminaemia
  • Hypocholesterolaemia
  • Mild increases in liver enzyme activities
  • Eosinophilia

The diagnosis should be confirmed with an ACTH stimulation test.
The diagnosis can be ruled out if basal cortisol is > 55 nmol/L.


(NB: basal cortisol can never confirm the diagnosis).

Useful References (all open-access)

Gold AJ, Langlois DK, Refsal KR. Evaluation of basal serum or plasma cortisol concentrations
for the diagnosis of hypoadrenocorticism in dogs. J Vet Intern Med. 2016;30(6):1798-1805. doi:10.1111/jvim.14589

Kather S, Grützner N, Kook PH, Dengler F, Heilmann RM. Review of cobalamin status and disorders of cobalamin metabolism in dogs. J Vet Intern Med. 2020;34(1):13-28. doi:10.1111/jvim.15638

Siani G, Mercaldo B, Alterisio MC, Di Loria A. Vitamin B12 in Cats: Nutrition, Metabolism, and
Disease. Animals (Basel). 2023;13(9):1474. Published 2023 Apr 26. doi:10.3390/ani13091474

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