2016 SPRING: Feline Housesoiling | Canine Insulinoma | Is It Lymphoma? | Chocolate Toxicity | Local Analgesia | GI Ulcers in Fido | Continuing Education
Thinking Inside the Box: A Refresher on Feline Housesoiling
Beth L. Strickler, MS, DVM, DACVB
“Doc, Fluffy urinated yesterday on my finest Persian rug!” or “Doc, Mittens urinated right on my husband’s pillow!” Does this sound familiar? Do you struggle with helping clients whose cats are urinating outside the box? Feline housesoiling is one of the most common behavioral complaints presented to the primary care clinician. It is estimated that approximately 10% of all households with one or more cats have at least one cat with elimination problems. In a recent survey conducted by the author, 37% of cat owners visiting veterinary clinics for yearly wellness visits reported that their cat eliminated inappropriately, and only half of those owners had discussed the problem with their veterinarian. Cats should be screened at every wellness visit for elimination issues in the home as this may place the cat at risk for relinquishment or euthanasia.
The initial approach to a complaint of housesoiling is to obtain a full database – both medical and behavioral. If a screening urinalysis is normal, the minimum medical database for a housesoiling cat consists of a full physical exam (including examining the genitalia for structural abnormalities and checking the anal sacs), complete blood cell count, chemistry profile, thyroid test, urinalysis by cystocentesis with culture and sensitivity, and fecal examination. Radiographs, ultrasonography and cystography may also be necessary.
Once the medical contributions have been eliminated or identified, a behavioral history should be evaluated. The more information that is obtained during behavioral history gathering, the more likely the clinician is to sort out causes of housesoiling and establish an effective treatment plan. It is best if a clinician obtains a behavioral history using a standard behavior questionnaire so that contributing details are not overlooked.
Diagnosis of the motivation for the inappropriate elimination starts with identifying whether the cat is marking or inappropriately toileting. Marking (i.e., spraying) behavior occurs when the cat is standing and moving its back feet with the tail quivering while depositing a small amount of urine. The urine is deposited onto a vertical location, several inches off the ground. Most commonly the area where the urine is located has some social significance, such as doors, windows or new objects.
Cats usually continue to use the litter box for both urination and defecation. Male, female, intact and neutered animals may engage in this behavior (10% of reports are neutered males and 5% are spayed females). Urinalyses are typically normal in spraying cats.
When a cat is “toileting” (i.e. inappropriately urinating), urine is typically deposited on a horizontal surface. Normal to large volumes of urine are deposited, and the cat often reduces its use of the litter box. Urine may be found in a variety of areas such as the edges of rooms, rugs, beds, bathtubs or just outside the litter box. A cat who is depositing feces in appropriate locations may also be motivated by toileting issues. Feces may also be used for marking if it is placed in socially significant locations, but this is less common.
Surgical neutering as a treatment for marking behaviors may be 90% effective in intact males (regardless of age) and 95% effective in intact females. Beyond surgical intervention, it is important to identify and control the eliciting stimulus. Marking is a normal feline behavior. It serves a communicative function and may be associated with competition, conflict or territorial issues. Pheromones may be used to change the marking behavior from spraying to bunting (reports of success are up to 95% improvement, and some improve in 7-14 days). Psychotropic drugs can be useful if there is an anxiety component when used in conjunction with behavioral therapy. Fluoxetine, a selective serotonin reuptake inhibitor (SSRI), has been shown to be greater than 90% effective in reducing feline marking behaviors. Other SSRIs or tri-cyclic antidepressants (TCAs) may also be beneficial.
Although clinicians often find inappropriate elimination secondary to toileting issues as one of the more challenging behavioral problems, it can be rewarding when the puzzle is solved. The treatment protocol for cats with this behavioral disorder is dependent on the identified cause and consists of environmental and behavioral modification. Possible behavioral causes may include: litter box cleanliness, litter aversion, litter box aversion, location aversion, location preference, learned aversions, substrate preferences, social influences, environmental stressors, cognitive dysfunction and other miscellaneous causes. Referral to a veterinary behaviorist is often beneficial for these patients as the process of identifying causes and developing a treatment plan can be time-consuming and challenging.
Treatment may involve improving the cleanliness of the box, the size of the box, the location of the box, the type of litter, the depth of the litter, etc. What is most important is to determine what this individual cat prefers. If there are complicating factors secondary to anxiety, medications may be used in conjunction with behavior modification for toileting issues. Prognosis for toileting issues in many cases depends not on duration or cause but on an owner’s ability and willingness to manipulate the environment.
Dr. Beth Strickler can be reached for further questions and consults at 615.333.1212.
What is it?
Canine insulinoma is a tumor that arises from pancreatic beta cells which secrete insulin. These tumors most commonly occur in middle-aged to older medium to large breed dogs. Identified high risk breeds include German shepherd dogs, Labrador retrievers, golden retrievers, German pointers, Irish setters and boxers. Males and females are equally represented.
What are the signs?
Because neoplastic pancreatic beta cells fail to stop secreting insulin at low blood glucose levels, patients experience signs of hypoglycemia such as weakness, ataxia, disorientation and/or seizure activity. Catecholamine release stimulated by low blood glucose levels may also cause shaking, muscle tremors and anxiety. Clinical signs can go on for a few days to several weeks, are intermittent and are commonly exacerbated by fasting, exercise or excitement.
How is the diagnosis made?
The hallmark of insulinoma is a low blood glucose concentration (<60mg/dL) paired with a normal or elevated insulin level. Abdominal imaging is used to verify the presence of a pancreatic nodule and assess for any metastatic disease to the regional lymph nodes or liver or other visceral organs. It is important to note however that abdominal ultrasound will fail to identify a pancreatic nodule in ~50% of patients; therefore, a negative scan does not rule-out this disease. CT scan is a more sensitive technique for identification of primary pancreatic nodules, but the number of false positive metastatic lesions is high.
How is it treated?
Aggressive treatment of canine insulinoma consists of an exploratory laparotomy to remove the pancreatic nodule(s) and any metastatic lesions regardless of whether disease could be identified on imaging. Blood glucose levels should be stabilized prior to surgery (usually with a dextrose CRI) and monitored peri-operatively. The majority of canine insulinomas are visible or palpable at the time of surgery.
Medical management can be used in conjunction with surgery or when surgery is not possible or declined. Common medical strategies used to control hypoglycemia include dietary modification, prednisone therapy and diazoxide therapy. Diets high in fat, protein and complex carbohydrates should be fed in small, frequent meals and simple sugars avoided. Prednisone causes insulin antagonism while diazoxide suppresses insulin release from pancreatic beta cells. Octreotide, a somatostatin analogue, has also been utilized; however, given its significant cost, it is not commonly used in veterinary medicine. Streptozocin is a chemotherapy drug that has shown benefit in a subset of insulinoma patients; however, its use in dogs is limited by its nephrotoxicity. Recently, the tyrosine kinase inhibitor toceranib (Palladia®) has demonstrated activity in refractory insulinoma dogs offering another avenue of therapy.
Patients that undergo surgery have longer median survival times than patients treated with medical management alone. The median survival time of patients undergoing partial pancreatectomy and prednisone therapy in a recent study was 1316 days versus 196 days for patients treated with medical therapy alone.
Canine insulinoma can be a very rewarding disease to treat, and our oncologists can help determine the appropriate course of action for individual patients.
Is it Lymphoma?
We have all had patients in whom we suspect lymphoma based on our clinical assessment, only to have the cytology or biopsy results come back inconclusive or suggesting inflammation. This may be the result of poor sampling on our part, the presence of concurrent lymph node abnormalities such as inflammation or necrosis, or even a reflection of early emerging disease. What now? We could start corticosteroids, but if the patient actually has lymphoma, we might be doing more harm than good. Studies and clinical experience have suggested that treatment of lymphoma with corticosteroids alone will induce changes in the lymphoma cells making them less responsive to other chemotherapeutic agents when the final diagnosis of lymphoma becomes apparent. This leads to a shorter response to treatment for these patients and worse prognosis.
So what other options do we have when cytology or biopsy samples are inconclusive?
If the cytology or biopsy results are inconclusive despite the suspicion for lymphoma, then the pathologist may suggest you perform additional testing. PARR, or PCR for antigen receptor rearrangement, flow cytometry and immunohistochemistry/immunocytochemistry are additional tests that might be useful for both supporting the presence of lymphoma as well as determining the lineage of lymphoma. These are mechanisms of evaluating the specific cell subtypes within a sample.
How does PARR work?
PARR can be useful for differentiating neoplastic lymphocytes from normal lymphocytes whether they are retrieved from pleural effusion, a mass effect, organ or an enlarged lymph node. Cancer cells are clones of a single cell. PCR amplification of the cellular DNA (responsible for encoding for the antigen receptors on the cell surface) within the lymphocytes is performed to determine if the DNA is derived from a single clone (same gene length and sequence) or is derived from multiple cell lines (variable and multiple gene lengths and sequences typical of normal immune responses). PARR testing can be performed on both cytology and biopsy samples. The beauty of PARR is that it can be tested on already stained cytology slides without the need to resample the area in question.
Varying with the lab, PARR is reported to have a sensitivity of up to 80% in dogs, i.e. 80% of dogs with lymphoma will be correctly identified. PARR is less useful in cats where it is reported to have a sensitivity of only 65%. PARR is reported to have a specificity in both dogs and cats of approximate 94%, i.e. 6% of pets without lymphoma will be falsely positive. Ehrilichia is one disease process known to cause a false positive, so ruling out tick diseases is recommended. Much like any testing, the results of the PARR test should be used in conjunction with your other test results when formulating a final diagnosis.
What is flow cytometry?
Studies indicate that lymphoma cells, due to their clonal expansion, typically demonstrate identical antigen receptors. By comparison, normal lymphocytes demonstrate a huge variety of antigen receptors. To perform flow cytometry, live cells are needed for testing. Lymph node aspirates, organ aspirates or blood can be submitted. To ensure the cells are viable when they reach the lab, aspirates are injected into a vial of sterile saline with a small quantity of the patient’s serum added to give the cells needed glucose and proteins for transport. Fluorescent-labeled antibodies which bind to proteins present on the cell surface of the lymphocytes are then added to the fluid. The labeled lymphocytes are run through the laser light of a flow cytometer producing a ‘scattergram’ which is used to determine whether the cells are homogeneous (typical of lymphoma) or heterogeneous. Because B- and T-cell type lymphomas express different surface antigens, the test is also useful for differentiating B- and T-cell types of lymphoma, as well as identifying other rare subtypes of lymphomas. Likewise, flow cytometry can differentiate leukemias from lymphomas and differentiate acute myelogenous leukemia subtypes. Since flow cytometry is an interpretive test, sensitivity and specificity are not available for this test.
How about immunochemistry?
Immunocytochemistry and immunohistochemistry utilize special stains applied to cytology and histopathology samples to identify cell markers that are typical for various types of cancers. The testing is useful for differentiating B- and T-cell lymphomas, mast cell tumors, melanomas, carcinomas and sarcomas. These are typically used on samples that are poorly differentiated or anaplastic, as a means of trying to identify the tumor type. Further studies may find immunohistochemistry, as well as flow cytometry, useful for identifying the presence of specific proteins or other cell markers which may be associated with multidrug resistance, rate of cell division or other factors useful for predicting prognosis or the best treatment protocol.
As our technology changes, we are better able to diagnose lymphoma and other cancers early in the course of the disease. Rather than adopting a wait-and-see approach, pursuing additional diagnostics may provide useful information with the potential to change the outlook for our patients’ prognosis and care.
Chocolate toxicity is one of the most commonly encountered poisonings in dogs. Chocolate is readily available, particularly during the holidays, and dogs (much like people) tend to find it irresistible.
Gastrointestinal, cardiac and neurological symptoms predominate. Mild symptoms include vomiting, restlessness, hyperactivity and polyuria. Moderate symptoms include tachycardia, arrhythmias, weakness, ataxia, diarrhea and muscle tremors. With severe intoxications, seizures and coma are possible. Hyperthermia, hypertension and hypokalemia can also develop. Pancreatitis is a possible sequela due to the high fat content in chocolate. The highest concentration of theobromine is found in cocoa, dark chocolate and baking chocolate, and the lowest in white and milk chocolates. As little as ¼ cups of semi-sweet chocolate chips is toxic to a 10 kg dog.
Mechanism of toxicity
Theobromine and caffeine belong to the methylated xanthine alkaloid family (methylxanthines), and they are the primary toxic principles in chocolate. Excessive ingestion of chocolate-containing products results in stimulation of the central nervous system, heart and skeletal muscle and causes smooth muscle relaxation. Methylxanthines inhibit the breakdown of cyclic AMP and antagonize adenosine receptors, resulting in alterations to neurotransmitter and hormone-mediated actions. The consequences include excessive stimulation of the cerebral cortex and myocardium (theobromine), and medulla, respiratory center and skeletal muscles (caffeine). These toxins also cause diuresis and increase the release of catecholamines, particularly norepinephrine. The half-life of elimination of theobromine (at 17.5 hours) is long in the dog, so symptoms can be prolonged.
Theobromine and caffeine content in chocolate products (mg/oz)
Note: 1 oz = 28.4 grams
|Cocoa bean mulch||56-900||unknown|
|Mild signs (vomiting, hyperactivity)||20 mg/kg theobromine|
|Cardio-toxicity||40 mg/kg theobromine|
|Seizures||60 mg/kg theobromine|
|LD50 theobromine||250-500 mg/kg (dogs); 200 mg/kg (cats) theobromine|
|LD50 caffeine||140-150 mg/kg (dogs), 100-150 mg/kg (cats) theobromine|
- Induce vomiting, if vomiting has not yet occurred, with apomorphine 0.04 mg/kg IV/IM/subconjunctival (or 3% hydrogen peroxide, 1 tsp/10 lbs not to exceed 15 mls if apomorphine is not available).
- Give activated charcoal (1-3 g/kg), repeated every 4-6 hours for a total of 2-3 doses due to enterohepatic recirculation. The first dose can contain sorbitol.
- Severe tachycardia can be treated with propranolol at 0.02-0.06 mg/kg IV slowly. (Address anxiety and dehydration/hypovolemia as causes of tachycardia before starting propranolol.)
- Hospitalize for monitoring, IV fluids, encourage frequent urination.
Note: Inducing emesis and oral administration of activated charcoal is contraindicated if the patient is mentally dull, unconscious, or having seizures, due to the risk of aspiration. Gastric lavage is recommended in these patients.
At BluePearl Veterinary Partners, our critical care service can provide emergency and around-the-clock intensive care of pets with chocolate toxicity. Therapy and monitoring can include gastrointestinal decontamination, gastric lavage, IV fluid therapy, continuous ECG monitoring, treatment of severe tachyarrhythmias, and seizure management. As methylxanthines can be reabsorbed across the bladder wall, for severe intoxications, urinary catheter placement can also be performed.
For support of the pet with chocolate toxicity or other poisonings, please contact our critical care service.
Indications for Local Analgesia
Local analgesia is an underused technique that can greatly enhance the overall analgesia in a patient; lead to use of less systemic drugs; and may be used in situations in which sedation, heavy systemic analgesia or anesthesia is contraindicated. Many animals that present to emergency are in shock, and those that are not in decompensated shock may be in compensated shock. Those in compensated shock are able to compensate because their sympathetic nervous system is maintaining their blood pressure and helping to maintain their oxygen delivery. In the intensive care unit, critically ill animals are dynamic with potentially minute-to-minute changes in cardiac output, blood pressure and oxygen delivery.
Almost all sedatives, analgesics and anesthetics blunt the sympathetic nervous system to some extent. This effect puts animals in the emergency department and critical care unit at risk for decompensation when receiving systemic drugs for analgesia, sedation or anesthesia. Local analgesic techniques may aid in decreasing systemic drug requirements in these patients.
Although shock patients in general are at risk for systemic decompensation with systemic sedatives and anesthetics, there are specific conditions in which these drugs should be particularly avoided or delayed if at all possible. Specific examples include head trauma, pulmonary contusions, pneumothorax, myocardial contusions (and subsequent arrhythmias), diaphragmatic hernia, liver fractures, splenic fractures, urinary tract rupture, severe anemia/hypoproteinemia and neurologic abnormalities. Avoidance of anesthesia and sedation in these cases is beneficial for the reasons indicated:
- Arrythmias: can be worsened or induced
- Head trauma: can alter blood flow to the brain and worsen trauma/neurologic status
- Liver/spleen fractures: Can cause intraoperative hemorrhage and hypotension
- Lungs with pulmonary contusions: more prone to atelectasis and subsequent hypoxemia
- Pneumothorax: can be worsened with positive pressure ventilation
- Urinary tract injuries: can cause severe life-threatening electrolyte disturbances (especially hyperkalemia)
In addition, many anesthetic drugs are protein-bound and become more bioavailable in animals that are acidemic, a common consequence of shock and trauma. Avoidance of anesthesia until full assessment and proper resuscitation is attained is critical. However, sometimes sedation or anesthesia in these cases cannot be avoided. Use of local analgesic techniques in these life-threatening situations frequently decreases the need for systemic drug use and makes for a safer overall procedure.
Because local anesthetics directly block nerve impulses, they decrease pain in an alternative way compared with systemic analgesics. When used preemptively, this decreases the likelihood of wind-up of the pain pathways, ultimately helps prevent hyperalgesia, and aids in the multimodal approach to patient analgesia.
Drug selection is an important part of the local anesthetic protocol. Most local anesthetics function by blocking sodium channels in the nerve membrane. When sodium is blocked, the nerve cannot conduct an impulse, and therefore no sensation can be transmitted. Local anesthetics cause analgesia but can also cause complete loss of motor function depending on the properties of the drug, location and myelination of the nerve; or the dose and size of the nerve fibers. Generally, local anesthetics cause nerve blockade in a particular order by first numbing pain, then warmth, touch, deep pressure and finally motor function. However, large peripheral nerves are an exception to this and tend to have motor blockade before sensory blockade, as well as cause proximal extremity analgesia prior to distal extremity blockade. Local anesthetic drugs differ in their side effects, onset of action and duration of action. Consideration of these drug factors should influence drug selection. Additionally, repeated dosing or application may be needed or taken into consideration.
|Lidocaine||1-2 mg/kg||Short-acting analgesia for local infiltration, intrapleural and intraperitoneal blocks, and occasionally epidural use|
|Bupivicaine||1-2 mg/kg||Longer-acting analgesia for local infiltration, intrapleural, intraperitoneal and epidural use.|
|Dexmedetomidine||0.001-0.005 mg/kg||Epidural, intraarticular, or perineurally|
|Preservative-free morphine||0.1 mg/kg||Epidural|
We would like to thank our colleague from BluePearl in Utah, Vicki L. Campbell, DVM, DACVECC, DACVAA, for allowing us to use this article for Companion.
Gastrointestinal Ulcers in Fido?
Gastrointestinal (GI) ulcerations are inflammatory lesions that extend into the deeper layers of the gastrointestinal tract, going beyond the mucosa. GI ulceration is the result of factors that alter, damage or overwhelm the normal defense and normal repair mechanisms of the GI mucosal barrier. There is no predilection for a particular age group or breed, and signs can be extremely variable from patient to patient. Some patients may have no clinical signs, while others may be in immediate need of intensive support and hospitalization, including blood transfusions.
There are many potential causes of GI ulceration ranging from medication adverse effects to cancer. Some cases are clear-cut, such as a classic case of high-dose aspirin administration in a dog with arthritis. However, others require advanced diagnostics to pinpoint the cause.
Some of the more common causes of GI ulceration in our pets include:
- the ingestion of certain medication (nonsteroidal and steroidal anti-inflammatory drugs)
- metabolic disorders such as kidney failure, liver disease, gastrinoma and hypoadrenocorticism (Addison’s disease)
- stress, pain, and/or major medical illness/surgery
- dietary indiscretion or the ingestion of foreign objects
- pancreatitis (inflammation of the pancreas)
- microscopic disease of the GI tract including inflammatory bowel disease or certain types of cancer (lymphosarcoma)
- gastrointestinal tumors
- toxins such as lead or caustic substances
Symptoms – What to Watch For
There are a number of symptoms that patients with gastrointestinal ulceration may exhibit. The most common include any/all of the following:
- vomiting (with or without digested blood)
- abdominal pain
- pale gums
A presumptive diagnosis of GI ulceration can sometimes be made on the basis of history and clinical findings such as the previously mentioned aspirin administration or known foreign body ingestion. A full diagnostic work-up is recommend, regardless of the cause.
A complete blood cell count (CBC), biochemical profile and urinalysis should be performed in all cases. A CBC will evaluate for the presence of infections, inflammation and anemia, sometimes associated with gastrointestinal ulceration. A biochemical profile evaluates organ function, which is important to establish if there may be an underlying metabolic disorder.
Screening abdominal radiograph, although often within normal limits, may support the diagnosis of an ulcer secondary to a tumor or foreign body, although an ulcer cannot be seen. An abdominal ultrasound evaluates the abdominal organs and helps assess for the presence of tumors that may be associated with ulcers; however, ultrasound often will not identify the GI ulcer itself.
Gastrointestinal endoscopy is the gold standard in diagnosing GI issues. A contrast upper GI study with barium may identify ulcers. It is a safe test; however, is quite time consuming, and although helpful in some patients, results are not always conclusive. It may facilitate the removal of foreign bodies, evaluate for ulcers, and sample tissue for the presence of inflammation or cancer, which may cause the ulcer. It does require general anesthesia in our veterinary patients; however, it is a fairly quick and safe procedure.
Other tests may be recommended on a case-by-case basis. These may include a liver function test for certain liver disorders, an ACTH stimulation test to rule out hypoadrenocorticism (Addison’s disease), and/or a blood lead level if lead exposure is a possibility.
Management of gastrointestinal ulcers centers on treatment of the primary cause and blocking excessive stomach acid production. Rarely, in severe cases control of bleeding and blood transfusions may be indicated.
Drugs that decrease acid production by the stomach expedite the resolution of GI ulcers. Examples include Pepcid® (famotidine) and Prilosec® (omeprazole). In severe cases, Cytotec® (misoprostol), a synthetic prostaglandin, may also be used to protect the intestinal tract. Gastrointestinal protectants and adsorbents sooth and coat an irritated GI lining and help bind harmful agents. A commonly used medication is Carafate® (sucralfate). Anti-emetic drugs and/or antibiotics are considered to treat some patients on a case-by-case basis. Pain medication should be considered in pets with ulcer disease. Ulcers can cause intense abdominal discomfort, and affected patients may benefit greatly.
Endoscopy or surgery may be indicated to remove foreign objects or tumors causing ulcers, biopsy associated tissue with the ulcer, or remove an area of persistent hemorrhage (surgery). Fluid therapy may be necessary in some patients with severe GI ulceration to correct dehydration. Additionally, blood transfusions may be indicated in the severely anemic patients.
BluePearl is strongly committed to the veterinary community. One of the ways we demonstrate this commitment is through our continuing education program, which is subsidized in part by our Partners in Education.
All BluePearl CE lectures are free and open to all area veterinary professionals. Registration is required, please. Dinner will be provided at 6:30PM, and presentation will be at 7:00PM. To register, please email Nicole Young at firstname.lastname@example.org. For the most current information about BluePearl CE, please check our online calendar of events regularly.
|Apr 21||7PM||Doctor||Swallowing/Esophageal Motility Disorders
Marc Bercovitch, DVM, DACVIM
|BluePearl Franklin||2 hours|
|May 17||7PM||Tech||Radiographic Techniques for Veterinary Technicians
Amy Hall, LVMT
|BluePearl Franklin||1 hour|
|May 19||7PM||Doctor||Heat Stroke
Kristen Datte, DVM, DACVECC
|BluePearl Franklin||2 hours|
|Jun 16||7PM||Doctor||Mast Cell Tumors
Pamela Lucas, DVM, DACVIM-Oncology
|BluePearl Franklin||2 hours|
|Jul 21||7PM||Doctor||Coagulation Disorders in Small Animals
Andrea Monnig, DVM, DACVECC
|BluePearl Franklin||2 hours|