Interpreting the serum chemistry profile in ferrets (Proceedings)

While the ferret is not considered to be a particularly exotic pet and in general its clinical medicine is very similar to feline clinical medicine, the interpretation of the ferret chemistry profile deserves special attention as there can be several pitfalls if ferret profiles are interpreted by comparing with cat or dog normal values. This lecture and handout will focus on some of the most important clinical pathology parameters and their interpretation.

As in other species, an exact diagnosis of a clinical problem should never be based on blood work alone, but should include an evaluation of other diagnostic tools such as biopsies. One abnormal parameter is rarely pathognomic for a problem, and often 2 or 3 clinical pathology parameters need to be assessed in order to better locate the potential origin of the clinical problem, especially if it is sub-clinical. If several different parameters are significantly altered a preliminary diagnosis can be with a high degree of certainty and then pursued with further diagnostics. Further diagnostics approaches, e.g. biopsies, should be recommended.

The recommended reading for a detailed discussion on GI and liver diseases of ferrets is the AFA proceeding 2006 (Burgess M. 2006).

Parameters to evaluate different organ function:

Pancreas

• Glucose:

     o Normal values 90-200 mg/dl

     o An extremely important parameter, as insulinoma is the most common form of cancer affecting the ferret in the USA.

          • Extremly common in ferrets older then 4 years and the blood glucose should be checked at least once a year.

     o Care has to be taken when using a human glucosometer as these devices will artificially read out lower values then the true value, usually 15-20 mg/dl lower).

          • In addition the (in)accuracy of these units is around 20 mg/dl.

     o The fasting glucose (4-6 hr fast) should be between 90-120 mg/dl.

     o If animal has been fasting for longer periods of time, the glucose will be low and is not considered diagnostic for insulinoma.

     o If the animal was eating with the last 4 hours and the glucose is below 90 mg/dl (< 60 mg/dl on the human glucometer) this is diagnostic for insulinoma.

     o Blood glucose alone is diagnostic for insulinoma, no other parameters need to be taken into consideration.

     o Repeated levels above 350 mg/dl might indicate diabetes mellitus. Which is rare in my experience.

          • It can also develop after a partial pancreactomy was performed.

Liver

• ALT (Alanine Aminotransferase):

     o Liver specific in ferrets (not in rabbits!) is released when liver cells are damaged. Activity in liver is 3-10 higher than in other tissues (in ferret).

     o Normal value 80-290 IU/L

     o High normal value than in other species

     o Steriods can increase ALT very fast.

     o Hepatic lipidosis, lymphocytic hepatitis, other forms of hepatitis often produce:

          • up to 800 mg/dl

          • with Alk. Phos. up to 100 mg/dl

          • Increase in AST as well

               • Same occurs in gastritis

     o Careful when diagnosing primary liver disease on blood work alone.

          • Check for increased billirubin, low total protein and icterus

          • Suggest biopsy in order to characterize liver lesion.

               • Lymphocytic hepatitis

               • Suppurative hepatitis

               • Vacuolar hepathopathy

               • Hepatic lipidosis

               • Cirrhosis

               • Hepatic neoplasia

               • Billiary cystadenoma

• GGT:

     o The biliary system is the primary source of plasma GGT. In addition to biliary GGT, significant levels of renal epithelial GGT can be found in the urine.

     o Normal around 5 IU/L

     o Over 10 IU/L high index of suspicion for liver problems.

          • Need to differentiate nature of elevation

          • Recommend abdominal ultrasound +/- US guided biopsy of liver to rule out primary liver pathology

          • Liver involvement is sometimes secondary to ascending inflammation from gut.

               • Suggest exploratory with multiple biopsies (GI tract, liver, lymphnode)

Kidney

• BUN:

     o Blood urea nitrogen (BUN) measures the amount of urea nitrogen, a waste product of protein metabolism, in the blood.

     o Normal range 10-40 mg/dl

     o I consider BUN a relatively insensitive test for evaluating renal disease in ferrets due to:

          o Pre renal factors influencing the BUN in ferrets include

               • High protein diet

               • Tendency to develop gastric ulcers very fast

          o Post renal elevations include

               • Urinary tract problems such as

                    • Urinary obstructions.

                    • Infections (prostatitis, etc)

                         › Often due to adrenal disease!!

          o Might go up to 200-300 mg/dl with normal or mildly elevated creat.

     o Drug interaction:

               • drugs such as steroids or NSAIDS may cause GI ulcers, therefore increasing the BUN value

               • Levels have been shown to decrease with the administration of diuretics, aminoglycosides, amphotericin B and chloramphenicol (not a ferret specific fact)

• Creatinine:

     o Creatinine is a nitrogenous waste product produced by the breakdown of creatine, which is an important part of muscle. A serum creatinine test measures the amount of creatinine in the blood and is an indirect indicator of renal glomerular filtration rate and can estimate renal function.

     o It has been demonstrated that creatinine is an insensitive indicator of renal failure in ferrets perhaps related to their capacity for extrarenal elimination of creatinine. Ferrets also have a considerably lower and narrower range of creatinine in the blood than other mammals.

     o Narrow range at normal 0.2 – 0.6 mg/dl

     o Is considered relatively insensitive as an indicator of renal failure.

     o The normal creatinine level averages approximately half the level of the dog and cat.

     o If > than 0.8 mg/gl than renal suspect

          • Elevations of BUN up to 300 mg/dl have been seen with a mild increase of creat. to 2-3 mg/dl

          • Three-fourths of renal function must be lost before abnormalities in creatinine concentration are seen

          • In contrast to BUN, Creatinine is not influenced by diet or GI ulcers

     o Lab artifacts:

          • Elevated levels: False-high serum test values can result when using Jaffe's reaction, a chromogen color reaction when the sample contains non-creatinine chromagens, such as ketones, glucose, fructose, ascorbic acid, protein, urea, and ascorbic acid

          • Decreased levels: Creatinine deteriorates in plasma samples older than 24 hours leading to unreliable results. Bilirubin can also cause sampling errors.

• Phos., Calcium, Potassium

     o These three parameters can be used to assess renal function

          • In conjunction with BUN and Creat.

     o Suspect true renal failure if:

          • Phos > 10 mEq/L AND

          • Cal < 8 mg/dl AND

          • Potas > 6 mEq/L

GI tract

• Lipase:

     o Enzyme that breaks down triglycerides into monoglycerides and free fatty acids.

     o Normal values 0-200 U/L

     o While in other species, lipase is primarily produced in the pancreas, with a small amount being produced by the gastric mucosa, it appears that the ferret produces more lipase in the stomach than in the pancreas1.

          • Therefore elevations of lipase appear more diagnostic for GI problems than for pancreatic problems.

     o Elevated if > 500 IU/L from commercial labs. or > 1000 IU/L from the IDEXX Vet-test)

     o Significant elevation most commonly seen cases of mild to severe GI disease like IBD and/or Eosinophilic Granulomatous Disease

          • Check Globulin for evaluation as well.

          • Run CBC to check for peripheral eosinophilia

     o In my opinion, lipase is one of the most commonly underused clin. path parameter to date.

     o Steriods will increase lipase levels in other species (dogs, etc)

          • Most likely in ferrets as well.

• Globulin:

     o Globulins are proteins that are mostly involved the immune defense system. Any protein that is not albumin is classified as a globulin

     o Normal values 2-2.9 mg/dl

     o Often elevated with chronic inflammatory conditions such as IBD

          • Check Lipase for elevation in cases of IBD

          • Most confirmed cases of IBD have high levels (> 3-5 mg/dl)

          • Consider Aleutian disease if elevation goes beyond 6 mg/dl

          • Increases in dehydration

     o Decreased globulins are generally the result of decreased production (i.e. liver failure) or increased loss.

     o Lipase and Globulin should always be interpreted with eachother to check for signs of IBD

     o I usually recommend GI biopsies to diagnose IBD in these cases.

     o It has been speculated that chronic unmanaged cases of IBD might develop into GI lymphoma.

     o Lab error:

          • Globulin levels are often calculated by subtracting albumin from the total protein. Any error in the measurements of albumin or total protein will give you erroneous globulin levels.

References

Burgess, M. (2006) Gastrointestinal and hepatic diseases in A comprehensive Veterinary Symposium, Advanced Course. Management of the Ferret. AFA meeting Pittisburgh, Pennsylvania. Oct 6-7 2006 pp. 79-97 (order online at www.ferret.org)

Hamosh, M., T.R. Henderson, and P. Hamosh, Gastric lipase and pepsin activities in the developing ferret: nonparallel development of the two gastric digestive enzymes. J Pediatr Gastroenterol Nutr, 1998. 26(2): p. 162-6