Small Mammal Clinical Pathology: Advanced

Karen L. Rosenthal, DVM, MS, Diplomate ABVP-Avian
Director, Special Species Medicine
Clinical Studies-Philadelphia
University of Pennsylvania
School of Veterinary Medicine
Philadelphia, PA, 19104

The WBC count in ferrets ranges from 2500 to 8,000 x 10³/mm³ cells. Typically, it is neutrophilic with lymphocyte counts usually below 50%. Both absolute and relative increases in the lymphocyte count might indicate the presence of lymphosarcoma. Severe, acute infections can elicit a left shift. The normal RBC count and hematocrit can be higher than what is expected in other mammals. In ferrets, isoflurane anesthesia can cause percentage reductions in indices of the erythron. Forty-five minutes after anesthesia the values return to normal ranges. Care should be exercised when subjecting anemic, geriatric, or debilitated ferrets to isoflurane-induced anesthesia.

Biochemistry values in ferrets are much like what is found in other mammals with few exceptions. Kidney function tests are more difficult to interpret than they are in the dog or cat. Blood urea nitrogen concentrations range as high as 30-35 mg/dl in normal ferrets. Creatinine is difficult to interpret in ferrets. Normally, it is below 0.5 mg/dl, frequently even at 0.1 mg/dl. Elevations in ferret creatinine concentration with acute renal disease are subtle or even non-existent. It appears that when ferret creatinine concentration is elevated, renal disease is severe and long standing. Elevations in phosphorus are commonly observed with chronic renal disease. This can be used to determine if chronic renal disease is present when the creatinine concentration is equivocal. Pancreatic beta cell tumors are common in older ferrets and, as such, accurate measurement of the blood glucose concentration is essential. Measurement of the liver enzymes appears similar to that of dog and cats. Alanine aminotransferase (ALT), serum alkaline phosphatase, and total bilirubin concentrations will increase with liver disease and/or liver function derangements. Alanine aminotransferase is found in cytoplasm and mitochondria. In ferrets, ALT is most concentrated in the liver.

Insulinoma is a very common disease of older ferrets. This disease is characterized by hypoglycemia due to a presumed increased production of insulin. The CBC is usually normal in these ferrets. The universal finding is a low blood glucose (below 65-70 mg/dl). Other causes of hypoglycemia such as septicemia and liver disease should be ruled out by history, signs, and diagnostic testing. If the blood glucose measurement is between 65 and 80 mg/dl and the diagnosis of an insulinoma appears equivocal, then perform a fasting blood glucose and insulin concentration. Fast the ferret for 2 - 4 hours and then perform venipuncture. If the blood glucose is lower than 80 mg/dl, then the diagnosis is made. An insulin concentration can be taken at this time and the results correlated with the blood glucose concentration. It appears that the insulin concentration is not always elevated in ferrets with insulinoma. It is not known why this occurs. Likely, insulin is produced episodically and when it is assayed, the concentration may be normal at that time. There are no other clinical pathology results needed to diagnose this disease. Definitive diagnosis is made on histopathology of diseased pancreas.

Adrenal gland disease is another common problem in ferrets. Clinical signs are usually used to diagnose this disease. Typical adrenal gland tests will not aid in the diagnosis of the disease. The CBC and biochemistry panel will usually show no abnormalities attributable to this disease. The urinalysis is usually normal. The typical assays used to diagnose adrenal gland disease in dogs are also normal. The best clinical pathology test for adrenal gland disease in ferrets is the adrenal gland androgen profile. It measures four hormones and at least one of which is elevated in almost all cases of adrenal gland disease in ferrets. These four hormones are estrodial, androstenedione, 17-OH-progesterone, and DHEAS. The cortisol:creatinine ratio is not specific for adrenal gland disease and may not be useful to diagnose this disease. Histopathology is definitive method of diagnosis. There are two conditions related to adrenal gland disease in ferrets that will cause changes, some dramatic, in the clinical pathology. Rarely, male ferrets with adrenal gland disease develop prostatic disease. The prostate may become infected and the urinalysis may show excessive mucus, crystals, bacteria, and red and white blood cells. An inflammatory leukogram is common and band cells may even be seen. In very rare cases, adrenal gland disease can cause a suppression of the bone marrow leading to a non-regenerative anemia. If this continues, both a thrombocytopenia and a leukopenia will be observed.

Recently, a new gastrointestinal disease has been seen in ferrets termed, "green diarrhea disease" or epizootic catarrhal enteritis (ECE). This disease appears to be highly infective, spreads rapidly amongst a group of ferrets, and is carried by fomites. Older ferrets (over a year of age) appear to develop a more severe form of this disease as younger ferrets may show no clinical signs of disease. A coronavirus has been postulated as the etiology of this disease. Hematology may reveal a slightly elevated WBC. In prolonged cases, a monocytosis can be observed. Biochemistry results may be abnormal depending on severity of disease. The more severe the disease, the more deranged the biochemistry results are. In severe forms of this disease, the ALT is greatly elevated. Values above 1000 U/l are not uncommon. As the disease progresses, the SAP may also be elevated. SAP has been shown to go as high into the 200 U/l range.

Lymphosarcoma (LSA) is not an uncommon disease in pet ferrets. Signs of LSA in ferrets range from an incidental finding to acute dyspnea and death. The CBC in some cases of LSA will show evidence of disease. The relative and absolute lymphocyte count may be elevated. The important aspect is that the circulating lymphocytes show bizarre appearances, have mitotic figures, and are very young cells. The biochemistry panel is typically normal unless LSA has invaded an internal organ and resulted in dysfunction. Diagnosis of LSA in ferrets is usually dependent on histopathology. Cytology is performed on a biopsy of a lymph node or mass and examined. It is sometimes difficult even for the most experienced pathologist to discern lymph node hyperplasia from neoplasia.

In most areas of the United States, heartworm disease is a very unlikely threat to pet ferrets. Most pet ferrets are kept indoors and are not exposed to mosquitoes. Ferrets are not the primary host for these organisms. If heartworm disease is suspected in a ferret, there are a number of clinical pathology changes that should be expected. The biochemistry results are usually normal. The CBC is may show an elevation in the eosinophil cell count. There may be a normal total white blood cell count. Some people have made the observation that there is an increase in the excretion of bilirubin in the urine. There are a number of tests to determine the presence of heartworm in dogs and cats. The problem with any of these tests in ferrets is that none of them have been validated for use in ferrets. Also, an infected ferret typically has less than 4 adults in its heart and no circulating microfiliria. The heartworm antigen tests can be used on ferret samples but will likely be negative. Ferrets do not have enough of a worm burden for that test to be positive. The heartworm antibody test is not applicable in ferrets as it measures feline antibody. Clinical pathology is a poor way to determine if a ferret is infected with heartworms. At present, the best ante-mortem test appears to be cardiac ultrasound.

Rabbits normally have WBC that range from 4,000 to 9,500 x 10³/mm³. It is not unusual for up to 70% of the WBC's to be lymphocytes although typically there are equal numbers of lymphocytes and neutrophils. A number of studies have shown and clinical experience concurs that when rabbits have acute bacterial infections the total WBC count infrequently increases significantly but the differential count changes. A neutrophilia and lymphopenia are seen with acute bacterial infections. Also, nucleated RBC's are observed in the beginning stages of infection. Because bacterial infections in rabbits are a common occurrence, it is important to realize that an associated leukophilia is not always present. Band cells are also rarely seen even in acute, severe bacterial infections. The hematocrit in rabbits is much like that in dogs and cats.

Plasma biochemistry values in rabbits are much like what is found in other mammals. Renal disease will increase both BUN and Cr concentrations. In chronic renal disease, an increase in the phosphorus concentration can be observed. Interpreting high calcium concentrations can be difficult as clinically normal rabbits can have calcium concentrations as high as 16 mg/dl. Rabbits appear to be more efficient than other mammals in absorbing calcium from their gastrointestinal tract. It is important to realize that high serum calcium concentrations in rabbits are not always associated with disease and may be an indication that the diet is too high in calcium. Alanine aminotransferase concentration may not be as good an indicator of hepatocellular disease in rabbits as it is in other mammals. Alanine aminotransferase concentration is reduced in rabbits and there is less organ specificity. It appears that only after chronic and/or severe liver disease are there elevations in rabbit ALT activity. Rabbits produce little or no amylase resulting in very low serum amylase activities.

Two infections in rabbits that may or may not be endemic in the rabbit population are Pasteurella multocida and Encephiltozoon cunuculi infections. P. multocida is a severe bacterial infection in rabbits. In other animals, this organism can cause minor disease and is easily treated. It is thought to cause significant morbidity and mortality in pet rabbits. Many infectious disease conditions are attributed to P. multocida. It is really unknown if this bacteria is responsible for as much disease as it is blamed for. It can be difficult to diagnose definitively as bacterial cultures are not always performed in rabbits, cultures may show no growth, or the infection may be in a place inaccessible to culture. There are P. multocida antibody assays that can be performed on rabbit blood. These tests are probably not very useful in the pet rabbit. Even a rising titer (the best way to interpret antibody tests) does not prove that P. multocida is responsible for the signs of disease. Probably the best use of this test is as a herd health indicator when specific-pathogen-free rabbits are kept in a laboratory situation. In pet rabbits, it is difficult to justify using this test.

The same could be said of the E. cuniculi test. E. cuniculi is a protozoal parasite of rabbits. It is shed in the urine. It may or may not cause clinical disease in rabbits. Some have attributed neurologic disease to E. cuniculi. Others believe it is a cause of renal disease in rabbits. No definitive studies have been performed in pet rabbits to prove or disprove these theories. Since this is a protozoon, it is difficult to find this organism in the live rabbit. Even in post mortem examination, this protozoon is usually not found. An assay exists to measure the antibody titer to E. cuniculi. The significance of a positive or negative titer in a pet rabbit is unknown. Again, in a laboratory animal setting, rising titers might mean contamination has occurred. In pet rabbits, there may be little reason to perform this test as the results are difficult to interpret in terms of clinical significance.