Clinical Pathology for Exotic Small Mammals

Introduction

Small mammals, such as rabbits (Oryctolagus cuniculus) and rodents, are stoic by nature and have evolved to mask their illness to avoid predation. This behavior can create a false sense of security in owners and a clinical challenge for veterinarians. In some cases, an animal that appears clinically normal may in fact have a terminal illness. Use hematology and biochemistry analysis to characterize the true physiological status of these species and aid in disease diagnosis.

Blood samples

The blood volume of a mammal is approximately 10% of the animal’s body weight. In general, 1% of total blood volume can be safely collected for sample processing or approximately 1.0 ml per 100 grams of body weight. Consider the animal’s history and physical examination findings when determining the volume of blood that can be safely collected. If an animal is debilitated, geriatric, or has experienced acute blood loss, collect a reduced volume of blood such as 0.5 ml per 100 grams. Laboratories or analyzers that can handle microtainer samples can typically perform a complete blood count (CBC) and plasma chemistry analysis on 0.6 to 1.0 ml of blood. There are some newer pieces of equipment, such as Abaxis VetScan™ (Union City, CA), that can perform chemistry analysis on 100 µl (0.1 ml) of whole blood.

Place blood samples into appropriate collection tubes immediately after collection. Ethylenediaminetetraacetic acid (EDTA) is generally preferred for hematological samples, but lithium heparin may also be used. Place blood for biochemistry analysis into a lithium heparin or no-additive vial. Centrifuge plasma samples in heparin vials immediately to separate cells from plasma, and centrifuge serum samples in red top tubes as soon as blood clots. If blood cells are not separated from serum or plasma, then glucose levels may be lower than normal, and phosphorus and potassium levels higher than normal. See Venipuncture in Small Mammals for advice on blood sample collection techniques.

Hematology

Unlike the lower vertebrates, birds, reptiles, amphibians, and fish, the CBC in exotic small mammals can be determined using an automated cell counter. The CBC routinely includes a packed cell volume, total white blood cell count, and a differential.

Red blood cells

Use packed cell volume or hematocrit to assess a patient’s general health and hydration status. Most small mammal hematocrits range from 30-55%, however ferrets (Mustela putorious furo) generally have packed cell volumes that exceed 40-45%. Evaluate erythron morphology in an anemic animal to estimate prognosis. Most laboratories include information on differences in erythrocyte cytoplasmic color, such as polychromasia, or cell size, such as anisocytosis.

Non-regenerative anemia may occur with chronic infection, renal disease, malnutrition, or neoplasia. The average red blood life span is 57 days in the rabbit, compared to 100-120 days in the dog or 70-78 days in the cat. This relatively short erythrocyte lifespan is associated with increased polychromasia to replace aging red blood cells in rabbits. Regenerative anemia is an uncommon finding in most small mammals, however causes may include heavy fleabite infestation, trauma, intestinal hemorrhage, and intravascular hemolysis caused by lead toxicity. Rabbits with uterine adenocarcinoma may exhibit vaginal bleeding leading to mixed regenerative and non-regenerative anemia.

White blood cells

White blood cell counts for most mammals fall between 5,000 to 15,000 cells/µl. White cell counts for rabbits and geriatric ferrets are generally lower, however, measuring 4,000 to 10,000  cells/µl and 3,000 to 6,000 cells/µl respectively. In most small mammals, stressors, such as transport, handling, or chronic disease produce mild to moderate leukocytosis, neutrophilia, and lymphopenia.

Small mammals have the same white blood cells seen in domestic mammals: neutrophils, lymphocytes, monocytes, eosinophils, and basophils. One exception is the rabbit, which has heterophils instead of neutrophils. Heterophils are polymorphonuclear white blood cells that possess a large number of small pink granules and a lesser number of large, red granules within the cytoplasm. As a general rule, the function of white cells in small mammals is similar to that described for other mammals. Monocytes are a common finding with chronic inflammation. Both neutrophils and heterophils play a role in the acute inflammatory response, however neutrophils create purulent discharge or pus while heterophils create cheesy or caseous debris as seen in birds and reptiles. A pus-filled abscess may be lanced and drained, while caseous inflammation requires surgical debridement.

Blood smears

Prior to making differential blood smears, I prefer to mix 1 drop of 22% bovine albumin (Gamma Biologicals, Inc, Houston, TX) to 5 drops of whole blood to stabilize cell membranes and improve cell visualization. When interpreting the blood cell differential, first determine the primary leukocyte for that species. The lymphocyte is the most common leukocyte in mice (Mus musculus), rats (Rattus norvegicus), gerbils (Meriones unguiculatus), guinea pigs (Cavia porcellus), as well as rabbits less than 12 months of age. Neutrophils tend to predominate in prairie dogs (Cynomys spp.). Neutrophils/heterophils and lymphocytes may be present in approximately equal numbers in chinchillas (Chinchilla lanigera) and rabbits greater than 13 months.

Neutrophil:lymphocyte ratio

The proportion of the dominant white blood cell to the secondary cell or the neutrophil/heterophil: lymphocyte (H:L ratio) should range from 1:1 to 3:1. In both rabbits and ferrets, inflammatory responses are not necessarily characterized by elevated white cell counts, but instead alterations in the differential such as an inverse H:L ratio with heterophilia and lymphopenia. Sepsis may be associated with a profound heterophilia exceeding 90% and a reduction in the platelet count. The presence of band heterophils in peripheral blood smears is rare with inflammation or infection in the rabbit.

Biochemistry

Biochemistry profiles for exotic small mammals generally include glucose, aspartate aminotransferase (AST), alkaline phosphatase (ALP), alanine transaminase (ALT), creatine phosphokinase (CPK), total protein, albumin, globulin, calcium, phosphorus, potassium, sodium, chloride, blood urea nitrogen (BUN), and creatinine.

• Blood glucose levels can be influenced by intrinsic and extrinsic factors. Hypoglycemia is common in animals offered inappropriate or inadequate diets. The most common cause of hypoglycemia in ferrets is insulinoma. Normal fasting blood glucose levels in ferrets are typically about 90 mg/dL; post-prandial blood glucose levels are approximately 120 mg/dL. Hyperglycemia is rare in exotic small mammals, although this finding may be associated with stress, neoplasia, hepatic lipidosis, diabetes mellitus, and pancreatitis.
• There is a link between hepatic cell death and ALT activity; therefore this enzyme may be used as an initial screening parameter for the condition of the liver.
• AST is generally found in muscle and liver. Restraint may be associated with spikes in AST.
• CPK is consistently found in skeletal, smooth, and cardiac muscle. Elevations in CPK can occur in any disease process associated with muscle wasting or destruction.
• ALP is a non-specific enzyme found in a variety of tissues. Elevations of ALP are common in young, growing animals or animals with bony lesions.
• Total protein values consist of two components: albumin and globulin. Hypoproteinemia is often reported in cases of malnutrition. Elevation in albumin (hyperalbuminemia) is common in dehydrated animals. Hyperglobulinemia may indicate inflammation or infection. Perform serum electrophoresis to determine the globulin fraction responsible for the elevated plasma protein.
• Rabbits are unique among mammals, in that the amount of calcium absorbed by the intestines is directly proportional to the amount of dietary calcium irrespective of the individual’s metabolic needs. Therefore calcium levels may also be elevated up to 15 mg/dL in rabbits fed diets high in calcium (i.e. alfalfa-based). Hypocalcemia is rare, however lactation tetany can occur in nursing rabbits or guinea pigs during late gestation or early lactation.
• The calcium to phosphorous ratio should range from 1.5:1 to 2.5:1. Renal disease may be associated with hypocalcemia or hypercalcemia. Although the most common cause of hyperphosphatemia is decreased renal excretion due to renal insufficiency, dietary changes such as excessive mineral or vitamin D supplementation, intestinal disorders (particularly ischemic bowel), or hemolysis can also produce hyperphosphatemia.
• Fluctuations in electrolytes can occur with dietary imbalances, diarrhea, vomiting, and inappropriate laboratory technique.  Hypernatremia and hyperchloremia are common sequelae to dehydration and dietary over-supplementation, while hyponatremia and hypochloremia may occur in cases of malnutrition. Hyperkalemia is common in renal disease, and hypokalemia may occur in cases of re-feeding syndrome.
• Urea is the primary catabolic end product of nitrogen in mammals. Elevations in BUN can occur with dehydration, renal disease, or blockage of urine outflow. Creatinine is also used to assess renal function in mammals. Normal creatinine levels in the ferret tend to be lower (0.1-0.5 mg/dL) when compared to the cat or dog, so slight elevations in a ferret can be indicative of disease.
• Obese rabbits or guinea pigs deposit large amounts of fat in the liver. Anorexia, caused by any condition such as gastrointestinal stasis or dental disease, may lead to hepatic lipidosis, a potential critical care emergency associated with elevations in triglycerides and cholesterol.

Conclusion

Use hematology and biochemistry analysis to characterize the true physiological status of small mammals and to aid in disease diagnosis. Obtain a blood sample that ranges from 0.5 to 1.0 ml per 100 g body weight. Most hematological and biochemistry parameters may be assessed just as one would in small animal medicine. Exceptions include the rabbit heterophil, interpretation of the H:L ratio, and a few biochemistry parameters such as blood glucose in ferrets and calcium in rabbits.

References