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Geriatric Medicine Johnny D. Hoskins, DVM, PhD, Diplomat ACVIM (Internal Medicine) Louisiana Geriatric Medicine: Liver and Pancreas Normal function of the liver does not appear to change significantly as a result of age. Despite this, older dogs are at greater risk for development of liver disease. The diagnosis of liver disease is initiated by the veterinarian's suspicion that liver disease might be present, followed by the case history and physical examination. The initial work-up for the older dog with suspected liver disease should begin with a complete blood cell count (CBC), serum chemistry profile, and urinalysis. This may be followed by liver function test, radiographic and/or ultrasonographic imaging studies, hepatic fine-needle aspiration, and, ultimately, liver biopsy. Chronic Inflammatory Hepatopathies. Infections, drugs, or copper accumulation can cause chronic hepatitis, or it can occur as an idiopathic process, possibly immune mediated. The pathologic process involved in chronic hepatitis often begins with necrosis, followed by infiltration of the liver with lymphocytes, plasma cells, or macrophages, which may lead to hepatic fibrosis and cirrhosis. Viral, such as infectious canine hepatitis and canine acidophil hepatitis, and bacterial, such as canine leptospirosis, infection can cause both acute and chronic hepatitis. Although these diseases tend to cause hepatic necrosis in their early stages, they may result in the same type of chronic injury seen with other chronic hepatopathies. Almost any drug has the capacity to produce an idiosyncratic reaction in any given individual; some drugs are more likely to be associated with chronic hepatic inflammation in dogs, especially older animals. Administration of primidone, phenobarbital, clomipramine, oxibendazole-diethylcarbamazine, or nonsteroidal antiinflammatory drugs (NSAIDs) has been associated with periportal hepatitis and hepatic vacuolar change. A familial predisposition to develop chronic hepatitis has been suggested in certain dog breeds. Breeds at increased risk for chronic hepatitis include the Airedale terrier, Boxer, Bulldog, Bedlington terrier, West Highland white terrier, Collie, Dachshund, Dalmatian, Doberman pinscher, American and English cocker spaniel, Skye terrier, Labrador retriever, standard poodle, German shepherd, golden retriever, keeshond, Kerry blue terrier, Norwich terrier, Old English sheepdog, Pekingese, Samoyed, and schnauzer. Abnormal hepatic retention of dietary copper and copper hepatopathy occurs in Bedlington terrier dogs. An autosomal recessive mode of inheritance is involved; only individuals homozygous for the recessive gene develop the excess copper accumulation in hepatic lysosomes. Diagnosis of copper associated hepatopathy in Bedlington terrier dogs can be made by examination of hepatic tissue for excessive copper storage or by performing genetic tests on DNA samples collected from suspected dogs. The frequency of the recessive gene in Bedlington terrier dogs is estimated to be as high as 50% in the United States, with a similar frequency in England. This means that more than 25% of in Bedlington terrier dogs are "affected," and another 50% are "carriers." The DNA samples can be collected using a soft cheek brush that is provided by a commercial genetic laboratory (VetGen, 3728 Plaza Drive, Suite 1, Ann Arbor, Michigan, 48108, Phone: (734) 669-8440, Toll Free: (800) 4-VETGEN, Fax: (734) 669-8441 or see their web site: www.vetgen.com). By gently brushing the inside of the dog's cheek, cells containing DNA are removed. The collected DNA samples then are analyzed to determine the genetic status of the suspect dog. Useful for dogs of any age, the DNA sample collection and analysis activities can be completed before puppies are purchased at 6 to 10 weeks. The results of the DNA testing also may be formally registered with the Orthopedic Foundation for Animals. For further information about the Orthopedic Foundation for Animal's Registry for Copper Toxicosis in Bedlington Terriers, contact: Orthopedic Foundation for Animals, 2300 East Nifong Boulevard, Columbia, MO 65201-3856, or telephone (573) 442-0418. Primary hepatobiliary disease associated with an increased accumulation of hepatic copper, albeit smaller amounts of tissue copper than in Bedlington terriers, has been described in Doberman pinscher, Skye terrier, West Highland white terrier, and American and English cocker spaniel dogs. The chronic hepatitis associated with an increased liver copper content in Doberman pinscher dogs occurs primarily in middle aged female dogs. A familial copper associated liver disease occurs in West Highland white terrier dogs. Liver disease has also been observed with unexpected frequency in American and English cocker spaniel dogs. The liver disease appears to be progressive, and dogs dying of hepatic cirrhosis have had hepatic copper concentrations three to five times normal. Primary copper hepatopathy as the inciting cause of liver disease should be considered in those breeds known to have an increased incidence of copper retention. The diagnosis is confirmed by liver biopsy, revealing copper-containing granules in excess of what might be considered normal for the degree of cholestasis and fibrosis seen. Dogs with chronic hepatitis of any cause usually have a slowly progressive onset of disease and are characterized by depression, weight loss, anorexia, and polyuria/polydipsia. Laboratory evaluation of dogs with chronic hepatitis can vary depending on the stage of disease. Initially, affected dogs will have marked increases in serum ALT and AST activities, with little evidence of cholestasis or liver dysfunction. As the disease progresses, cholestasis develops, with increases in serum ALP activity and total bilirubin concentration. Liver function progressively decreases, first seen in serum bile acid concentrations and later obvious in serum albumin, urea nitrogen, glucose, and coagulation factor concentrations. Abdominal radiographs are unremarkable except when a small liver or ascites accompanies advanced stages of the liver disease. Ultrasonography of the liver may be normal in the early stages of chronic hepatitis, or nonspecific changes in echogenicity may be detected. Potential ultrasonographic findings with hepatic cirrhosis include small liver, irregular liver lobe margins, focal lesions representing regenerative nodules, increased parenchymal echogenicity associated with fibrous tissue, and ascites. Splenomegaly may also be detected. Dogs with vacuolar hepatopathy of adrenal gland disease typically have a slowly progressive onset of disease and are associated with mild to mark elevation in ALP values. To completely rule out typical hyperadrenocorticism in this case would require doing low-dose dexamethasone suppression test. If the results of low-dose dexamethasone suppression test are normal, then evaluation of the sex hormones (estradiol, progesterone, testosterone) before and after ACTH stimulation are needed to help further define why the serum ALP value is high. The hormone assays are done at the University of Tennessee Endocrine Laboratory. Clinical management of atypical hyperadrenocorticism in dogs is open to question. There are no preferred medications know to correct this medical problem. Therapy for copper associated hepatopathy includes reduction in dietary copper and chelation therapy. Currently drugs used for copper chelation are penicillamine and trientine dihydrochloride. Penicillamine is effective at reducing hepatic copper concentrations, although the rate of hepatic "decoppering" is slow. Trientine is as effective as penicillamine at reducing hepatic copper concentrations and is currently being used when penicillamine-associated vomiting occurs. It is likely that Bedlington terriers, West Highland white terriers, and possibly Doberman pinschers will benefit from copper chelation or oral zinc therapy as part of their therapeutic plan. Other therapies that can be considered in dogs with chronic hepatitis include corticosteroids and antifibrotic drugs. Corticosteroids have immunosuppressive, antiinflammatory, and antifibrotic effects. Other antifibrotic agents such as colchicine can be used to prevent or treat hepatic fibrosis and cirrhosis. Free radicals may contribute to oxidative hepatocellular injury if not counteracted by cytoprotective mechanisms. Antioxidants, such as S-adenosylmethionine and vitamin E, are important in scavenging free radicals and preventing oxidative injury. Ursodeoxycholic acid is believed to be beneficial by expanding the bile acid pool and displacing potentially hepatotoxic hydrophilic bile acids that may accumulate in cholestasis. It also stimulates bile flow, stabilizes hepatocyte membranes, and has cytoprotective and immunomodulatory effects on the liver. Chronic hepatopathies frequently cause alterations in plasma proteins (hypoalbuminemia) and vascular hydrostatic pressures, resulting in ascites or edema. Chronic hepatopathies increase resistance to blood flow in the liver (portal hypertension), which can lead to acquired portosystemic shunts, increased lymph formation, increased plasma volume, and ascites/edema. Liver-induced ascites can be diagnosed by physical examination and laboratory evaluation of peritoneal fluid, blood, and urine. Ascitic fluid of liver disease is usually a transudate or modified transudate, which is further substantiated by the presence of hypoalbuminemia. Peripheral edema may occur in end-stage liver disease. Similar mechanisms that trigger ascites may cause peripheral edema (i.e., distal legs, ventral abdomen and thorax, ventral neck region). To reestablish the osmotic gradient in ascitic animals with hypoalbuminemia administer intravenous colloids such as hetastarch or dextrans at 10-20 ml/kg given over 1-2 hours and repeated as needed after a several infusions. Diuretics and a low sodium diet are used in the management of ascites/edema. Spironolactone is used to reduce ascites/edema without causing hypokalemia. If these measures are ineffective, furosemide may be substituted, although serum electrolyte concentrations should be frequently evaluated. Hepatic Fibrosis and Cirrhosis. The liver can respond to severe damage and necrosis by regeneration, mineralization, or fibrosis, depending on the severity of the challenge and the degree of damage to the supporting connective tissue structure. Loss of hepatocytes and connective tissue integrity caused by any disease can lead to hepatic fibrosis; thus, identification of hepatic fibrosis is not specific for any particular liver disease. When hepatic fibrosis is severe and leads to formation of small or large regenerative nodules limited by fibrous tissue, the term cirrhosis is used. Hepatic cirrhosis is considered an end stage liver disease. Because hepatic cirrhosis is advanced, most affected dogs will have significant clinical and laboratory evidence of hepatic dysfunction. As cirrhosis progresses, portal hypertension develops, and many dogs with hepatic cirrhosis have ascites and acquired portosystemic shunts. Most chronic hepatopathies will progress slowly, and fibrosis occurs in concert with the progression of necrosis and inflammation. Radiographic evaluation may reveal a small liver, and ultrasonography shows an increase in hepatic echogenicity and possibly the presence of acquired portosystemic shunts. Liver biopsy is required for definitive diagnosis of hepatic fibrosis and cirrhosis. Treatment for hepatic fibrosis is aimed at treating the underlying disease process and managing the complications of liver disease. Inhibition of collagen formation and lysis of excess hepatic fibrous tissue would be an additional goal of therapy for hepatic cirrhosis. When used for treatment of hepatic fibrosis in affected dogs, colchicine has produced improvement in clinical signs for several months. Corticosteroids and azathioprine have antifibrotic properties. Other drugs for the treatment of hepatic fibrosis include penicillamine, which inhibits collagen polymerization secondary to its copper chelating effects, and oral zinc, which decreases intestinal copper absorption and also has antifibrotic and hepatoprotective properties. Chronic Infiltrative Hepatopathies. Alterations in hepatic structure and function may occur when hepatocytes are infiltrated with lipid, glycogen, amyloid, or other substances. Although hepatic lipidosis is a common histopathologic finding in dogs with diabetes mellitus, it seldom becomes a clinical problem associated with liver dysfunction. Exogenous glucocorticoids and naturally occurring hyperadrenocorticism often lead to steroid hepatopathy in older dogs. Impairment of liver function can occur with severe steroid hepatopathy, but most dogs do not develop signs referable to hepatic dysfunction. Laboratory evaluation of dogs with steroid hepatopathy will usually reveal a marked increase in serum ALP and GGT activity, occasionally up to a 60 fold increase over normal values. Values for hepatocellular enzyme activities (ALT and AST) will usually be increased, but not to the magnitude of serum ALP and GGT. Serum total bilirubin concentrations are usually normal, which supports the idea that serum ALP activity increase is secondary to steroid induction, and not from cholestasis. If liver function tests are performed, there may be mild increases in fasting and postprandial serum bile acid concentration. Liver biopsy is seldom performed, but expected changes of increased hepatic vacuolization are seen on histopathologic evaluation. Hepatobiliary Neoplasia. Neoplasias involving the liver are primary hepatic tumors, metastatic carcinomas and sarcomas, and hemolymphatic tumors. In dogs, metastatic neoplasia is most common and can originate from the pancreas, spleen, mammary glands, adrenal glands, bones, lungs, thyroid glands, and gastrointestinal tract. Primary hepatic tumors may be epithelial or mesodermal origin and either benign or malignant. Benign tumors of the hepatocytes are called hepatocellular adenoma or hepatoma, and its malignant counterpart is called a hepatocellular carcinoma. Hepatocellular carcinoma is the most common primary hepatic tumor in dogs. The cause of these spontaneous primary hepatic tumors in dogs is not known. Primary hepatic tumors are most common in dogs that are 10 years of age or older. Dogs with hepatic tumors usually show vague, nonspecific signs of hepatic dysfunction that often do not appear until the more advance stages of hepatic disease. The most consistent signs are anorexia, lethargy, weight loss, polydipsia, polyuria, vomiting, and abdominal distention. Other less frequent findings include icterus, diarrhea, and excessive bleeding. Signs of central nervous dysfunction such as depression, dementia, or seizures can be attributed to hepatoencephalopathy, hypoglycemia, or central nervous system metastasis. On physical examination, a cranial abdominal mass or marked hepatomegaly is commonly detected in dogs with primary hepatic tumors. Ascites or hemoperitoneum may contribute to abdominal distention. Tumor rupture and hemorrhage are most likely with hepatocellular adenoma, hepatocellular carcinoma, and hepatic hemangiosarcoma. Generally, laboratory evaluation will usually show mild to moderate increases in liver enzyme activities, with some dogs displaying abnormal liver function based on serum bile acid concentrations. Hypoglycemia occurs in some dogs with hepatocellular carcinoma and other hepatic neoplasms. Abdominal radiographic findings include symmetric or asymmetric hepatomegaly or ascites. A right cranial abdominal mass causing caudal and left gastric displacement most often occurs. Thoracic radiographs should be obtained to determine pulmonary metastasis. Potential ultrasonographic findings include focal, multifocal, or diffuse changes in hepatic echotexture. Primary or secondary hepatic neoplasia and nodular hyperplasia often appear as focal or multifocal hypoechoic or mixed echogenic lesions. The diagnosis of primary or metastatic hepatic tumors cannot be made on the basis of ultrasonographic findings alone. Definitive diagnosis of hepatic neoplasia requires liver biopsy and histopathologic examination. The procedure of choice for a single large hepatic mass is laparotomy, because the excision of the mass can be performed concurrently. Ultrasound-guided biopsy is useful for diagnosing focal or diffuse involvement, but the small size of the biopsy sample can make the differentiation of nodular dysplasia versus primary hepatic tumor difficult. A surgical wedge biopsy is often necessary. Surgical removal of the affected liver lobe is the treatment of choice for primary hepatic tumors such as hepatocellular adenoma or carcinoma that involves a single lobe. Removal of a single mass lesion of hepatocellular carcinoma will typically provide one year of quality of life after surgery. Therefore, early detection before metastasis to other liver lobes provides the best chance for surgical control. A complete evaluation of the abdominal cavity for the evidence of metastasis should be performed and biopsy specimen of hepatic lymph nodes should always be obtained. When all liver lobes are affected, the prognosis is poor. Chemotherapy is not currently an effective treatment for control of hepatocellular carcinoma. Necrolytic Migratory Erythema. Necrolytic migratory erythema (diabetic dermatopathy, hepatocutaneous syndrome, superficial necrolytic dermatitis, metabolic necrolytic dermatopathy or metabolic epidermal necrosis) has been seen in dogs with diabetes mellitus, and glucagon secreting tumors of the pancreas but is most often associated with hepatic disease (hepatopathy of unknown origin, hepatopathy secondary to ingestion of mycotoxins, hepatopathy secondary to phenobarbital/phenytoin administration and hepatopathy possibly associated with primidone or phenobarbital administration). Older dogs are most likely to be affected with an average age of 10 years. Either sex may be affected, but an almost 2:1 male to female ratio is reported. Necrolytic migratory erythema is an ulcerative dermatosis, displaying, erythema, crusts and alopecia. It occurs most frequently periorally, periocularly, on the legs, feet and external genitalia and often in the groin region. The foot pads are usually hyperkeratotic and may be fissured and ulcerated. Lesions may follow a waxing and waning course. The lesions may be mildly pruritic or painful. These lesions are commonly complicated by secondary infections with bacteria and yeast. Cutaneous signs may precede evidence of internal disease by weeks or months. The disease should be suspected on the basis of the history and physical examination. The typical history would include a middle aged or older dog with a progressive crusting dermatitis affecting the face, distal extremities and external genitalia. Examination of skin biopsies of lesions on affected dogs reveals a unique combination of diffuse parakeratotic hyperkeratosis, epidermal necrosis, marked superficial epidermal edema, irregular epidermal hyperplasia and mild superficial perivascular dermatitis. The epidermal edema is both intercellular and intracellular edema and is localized to the upper half of the epidermis. Severe edema may result in intraepidermal clefts and vesicles. In dogs with hepatic disease associated with necrolytic migratory erythema, a unique "honeycomb" pattern is found on ultrasonographic evaluation of the liver. This pattern consists of variable sized hypoechoic regions surrounded by highly echogenic borders. These hypoechoic regions correspond to regenerative nodules bounded by severely vacuolated hepatocytes, numerous bile ductules and a network of reticulin and fine collagen fibers representing remnants of collapsed hepatic lobules. Clinicopathologic abnormalities vary, depending on the specific inciting organ system and the progression of the disease. Complete blood count abnormalities include anemia, neutrophilic leukocytosis and toxic neutrophilic changes. Serum biochemical abnormalities may include increased liver enzymes, total bilirubin, and bile acids. Hypoalbuminemia is a common finding and many dogs develop hyperglycemia as the diseases progresses. Glucagon concentrations are increased in some cases. In dogs with liver disease, severe, profound hypoaminoacidemia is often seen. Treatment is aimed at correcting the underlying metabolic disease. If the dog is diabetic, insulin therapy is indicated. In most cases however, regulation is difficult. Surgical excision of a glucagon-secreting tumor of the pancreatic alpha cells may be possible. Unfortunately, most cases are associated with irreversible chronic liver disease and hepatic cirrhosis, making treatment largely unrewarding. Therapy for dogs with severe hypoaminoacidemia (commonly seen with dogs with hepatic diseases) is nutritional support to include intravenous amino acid supplementation. The diet should consist of a good quality protein diet. Fatty acid, zinc and niacin supplementations have been utilized with some success. IV amino acid supplementation regimens vary from 250-500 ml IV of an 8-10% amino acid supplement given daily until dermatologic signs improve, to these doses given weekly for an extended period of time. IV amino acid supplements are re-administered in many patients when dermatologic signs return. Antibiotics and/or antifungal agents should be used to treat secondary skin infections. Hydrotherapy and shampoo therapy can help remove crusts and lessen the pruritus and pain that may be present. Glucocorticoid therapy has been associated with improvement in cutaneous signs, but should be used with caution as it may worsen the underlying metabolic disease. Gall Bladder Disease. Gall bladder disease is common in older dogs and cats. Not all cases with mucoceles require surgical removal of the gall bladder. Surgical removal of the gall bladder is done in those cases with repeated GI signs, increased serum liver enzymes, and cranial abdominal pain. The serum liver enzymes will usually not return to normal values once the gall bladder is removed. Finding choleliths is not a common reason for gall bladder removal. Drugs used in the management of chronic liver disease in older dogs
Holistic Medicine for Liver, Pancreas, Adrenal Diseases Standard Process canine adrenal support Liver Happy (Chinese Herb) Standard Process A-F Betafood Choline Standard Process Pancreatrophin Small Animal antioxidants Standard Process pituitrophin Ophiopogon powder (Chinese Herb) Palatech Geriatric Medicine: Urinary System Canine Diabetes Insipidus
In older dogs and cats with CRF, laboratory evaluation typically shows increased blood urea nitrogen and serum creatinine, hyperphosphatemia, metabolic acidosis, and nonregenerative anemia. The urine specific gravity is usually in the isosthenuric range (1.007 to 1.015). Some cats with CRF can have a urine specific gravity greater than 1.025. Other abnormalities may include hypokalemia, hypercholesterolemia, hypercalcemia or hypocalcemia, hyperamylasemia, and proteinuria. Survey abdominal radiography most often reveals reduced renal size with irregular renal contours, renal mineralization, and possible evidence of skeletal osteopenia. Renal ultrasonography may reveal increased cortical echogenicity, renal mineralization, renoliths, and reduced renal size. In addition to CRF and its vague history and physical findings, older dogs and cats should be thoroughly evaluated for the presence of co-existing diseases. Other diseases to consider include diabetes mellitus, hepatic disease, hyperadrenocorticism, cardiac disease, inflammatory bowel disease, chronic pancreatitis, and neoplastic disease. Hyperthyroidism should always be considered in cats older than 7 years. Classification of kidney disease
Specific therapy for CRF consists of treatment developed to slow the progression of renal lesions by influencing the disease responsible for the renal lesions. Examples would include the administration of antimicrobial agents for bacterial pyelonephritis, correction of hypercalcemia causing hypercalcemic nephropathy, removal of tumors or uroliths responsible for obstructive uropathy, administering antifungal drugs for fungal infections, and the correction of abnormal renal perfusion that has caused ischemic renal lesions. General guidelines of the medical management of older dogs and cats diagnosed with CRF are presented in Tables 1 and 2. The medical management is intended to maximize residual renal function, slow the progression of renal failure, and alleviate the signs of uremia; these effects are achieved by correcting fluid, electrolyte, acid-base, endocrine and nutritional status. Those animals that have uncompensated CRF and are unable to eat or accept oral medications because of severe uremia will require intensive fluid therapy before attempting any conservative therapy (Table 3). These animals usually require initial treatment with intravenous fluids for at least 24 to 72 hours. In addition, symptomatic treatment of gastrointestinal signs (nausea, anorexia, vomiting, hematemesis, diarrhea, and oral ulcerations) is with a H2 receptor blocker (cimetidine, ranitidine, or famotidine) to reduce gastric hydrochloric acid production. Sucralfate may be administered as a gastrointestinal protectant. Vomiting may be treated with antiemetics such as metoclopramide. Renal function is evaluated subsequently after correction of prerenal azotemia. The ultimate disposition and long-term management of the animal is then outlined for the animal owner. Dietary therapy remains the cornerstone of long-term management of the animal with compensated CRF. The goals of nutritional therapy are (1) to reduce or ameliorate the clinical signs of uremia by reducing the production of proteinaceous waste products; (2) to minimize the electrolyte, vitamin, and mineral disturbances associated with excessive consumption of protein and certain minerals; (3) to provide daily protein, calorie, and mineral requirements; and (4) to slow the progression of the CRF. It is currently recommended that dogs with mild to moderate CRF be fed a diet that contains at least 13% gross energy as protein. It is also recommended that euhydrated dogs with serum creatinine concentration less than 4.5 mg/dl be maintained on 2.0 to 2.2 gm/kg per day of high biologic quality dietary protein. Euhydrated dogs with serum creatinine concentrations greater than 4.5 mg/dl should be fed approximately 1.3 gm/kg per day of protein. Cats have a dietary protein requirement that is substantially higher than in dogs. Cats with CRF should be fed a diet that provides at least 21% of gross energy as protein. There are a number of commercially prepared dietary products available for feeding dogs and cats with varying degrees of CRF that achieve the above requirements when fed in quantities sufficient to maintain caloric requirements. Reducing phosphorus retention and hyperphosphatemia is a major medical goal in animals with CRF; it may reduce renal secondary hyperparathyroidism, renal osteodystrophy, soft tissue calcification and progression of renal failure. Dietary therapy should first be attempted to normalize serum phosphorus concentration. As CRF progresses, dietary phosphorus restriction alone will fail to prevent hyperphosphatemia. Intestinal phosphate-binding agents can then be administered if hyperphosphatemia occurs despite dietary phosphorus restriction. Intestinal phosphate-binding agents that are aluminum-based (aluminum carbonate, aluminum hydroxide, and aluminum oxide) or calcium-based (calcium acetate, calcium citrate, and calcium carbonate) compounds are available over-the-counter from most pharmacies in liquid, tablet, and capsule form. Sucralfate, a complex polyaluminum hydroxide salt of sulfate, may also be effective as an intestinal phosphate binder. The calcium-based products do pose a potential risk of causing hypercalcemia; calcium acetate is the most effective calcium-based phosphorus-binding agent and has the lowest risk of causing hypercalcemia. Phosphorus-binding agents should be given with each meal to enhance the effectiveness of phosphorus binding activity. They may be mixed with the food or given 15 to 30 minutes before each meal. These agents must be given with a phosphorus-restricted diet and capsules or tablets are preferable. The dosage of phosphate-binding agents should be adjusted according to the serum phosphorus concentration. Serial monitoring of serum calcium and phosphorus concentrations at 14-day intervals should assess if adequate therapy is being done. Oral alkalinization therapy is recommended when the serum bicarbonate decreases to or below 17 mEq/L. Sodium bicarbonate and potassium citrate (most useful in cats) are the most commonly used alkalinizing agents for treatment of metabolic acidosis. Tablets may be crushed and given with food or administered as a solution. The alkalinizing agent should be administered in small divided doses throughout the day to minimize fluctuations in blood pH and to normalize serum bicarbonate concentration within the expected normal reference range. The serum bicarbonate should be assessed 14 days after initiating therapy. Oral potassium replacement therapy is always indicated for cats with CRF, even in the absence of clinical signs of hypokalemia. Potassium gluconate is the preferred form and may be administered orally in a powder form, tablets, gel, or elixir. Oral potassium is usually given at a dose of 2 to 6 mEq/cat per day, depending on the size of the cat and severity of hypokalemia. The dosage should then be adjusted based on clinical response. Long-term potassium supplementation at a dosage of 2 to 3 mEq/day is recommended for all cats with CRF, irrespective of the measured serum potassium concentration. Arterial hypertension should be confirmed by recording increased arterial blood pressures measured during three separate determinations by indirect Doppler ultrasonography or oscillometry. Hypertension exists when systolic blood pressures exceed 184 mm Hg in dogs and 165 mm Hg in cats; diastolic blood pressures exceed 130 mm Hg in dogs and 124 mm Hg in cats; and the mean arterial pressure exceeds 152 mm Hg in dogs and 139 mm Hg in cats. Immediate medical therapy should be initiated in those animals with obvious signs associated with hypertensive disease (ocular hemorrhage, hypertensive retinopathy, and retinal detachment) and coexistent elevations in measured arterial pressures. Dietary sodium and protein restriction are the basis of nonpharmacologic control of hypertension. Sodium intake should be reduced slowly over a period of 1 to 2 weeks to allow the animal to adapt to sodium restriction. Canine and feline diets formulated for CRF are both sodium and protein restricted. Dietary therapy alone is rarely effective in controlling hypertension. This then necessitates the administration of antihypertensive drugs, such as angiotensin-converting enzyme (ACE) inhibitors, calcium-channel blockers, adrenergic receptor antagonists, arteriolar vasodilators, and diuretics. Angiotensin-converting enzyme inhibitors are the preferred therapy for systemic hypertension for dogs; enalapril, benazepril, or lisinopril are the initial ACE inhibitor of choice. Amlodipine, a calcium-channel blocker, is the current drug of choice for hypertension in cats. Blood pressures often decrease within 12 to 48 hours of administration of these drugs. Serial measurements of blood pressure and frequent monitoring of serum concentrations of creatinine, blood urea nitrogen, and electrolytes are important when using these drugs. The administration of low doses of vitamin D (calcitriol or 1,25 dihydroxyvitamin D) in combination with effective control of serum phosphorus concentrations reduces the degree of secondary renal hyperparathyroidism and its associated skeletal abnormalities in dogs with CRF. Calcitriol is the most active form of vitamin D and is formed in the kidney by 1?-hydroxylation of 25-hydroxycholecalciferol. Renal 1?-hydroxylase activity and formation of calcitriol are stimulated by parathormone. Calcitriol normally regulates parathormone synthesis by feedback inhibition. Calcitriol deficiency develops early in the course of CRF due to the inhibitory effects of phosphate retention on 1?-hydroxylase activities in renal tubular cells. This is temporarily restored at the expense of a persistent increase in parathormone concentration. With progression of CRF, loss of viable renal tubular cells limits calcitriol synthetic capacity and calcitriol concentrations remain low. Calcitriol deficiency causes skeletal resistance to parathormone action and raises the set point for calcium-induced suppression of parathormone release. These activities limit the skeletal release of calcium and allows hyperparathyroidism to persist regardless of whether serum ionized calcium concentrations are normal or increased. Calcitriol supplementation at oral dose of 2.5 to 3.5 ng/kg daily is initiated early in CRF (serum creatinine greater than 2 mg/dl; 170 µmol/L). At this stage of CRF, hyperparathyroidism is not established and low doses of calcitriol will prevent its development. It is suggested that a baseline serum parathormone concentration be determined before initiating calcitriol therapy to document the magnitude of hyperparathyroidism, and serial measurements of serum parathormone concentration are done to document the effectiveness of the combination of phosphorus restriction and the calcitriol treatment. Serum parathormone concentration should be measured 8 weeks after initiating calcitriol therapy to determine if a dosage increase is needed. The short half-life (4 to 6 hours) and short duration of action (4 days) allows adjustment in dosage to alleviate hypercalcemia, if present. Serum phosphorus concentrations should be decreased, if necessary, to 6 mg/dl (1.9 mmol/L) prior to initiating calcitriol therapy. Phosphorus restriction and normalization of serum concentration of phosphorus is important to allow calcitriol therapy to effectively lower serum parathormone concentration. Animals with advanced hyperparathyroidism and serum parathormone concentrations in excess of ten times normal may require twice-weekly pulse dosing of calcitriol (dosed at 20 ng/kg orally twice a week). This allows the administration of higher doses and serum concentrations of calcitriol without causing hypercalcemia that would occur with daily dosing of calcitriol. Serum calcium concentration is measured 1 and 2 days after the third dose of calcitriol to monitor for hypercalcemia and the calcitriol dose is adjusted downward if hypercalcemia is detected. Serum parathormone concentration is measured at 1 month after initiation of pulse therapy, and if not significantly suppressed, calcitriol dosage is adjusted upwards by 5 ng/kg. Serum calcium concentration is again measured 1 and 2 days after the third dose of calcitriol to monitor for hypercalcemia. Pulse dosing can then be replaced by daily dosing (2.5 to 3.5 ng/kg daily) once the serum concentration of parathormone is normalized and maintained for 2 to 3 months. A progressive, nonregenerative anemia is a characteristic finding in older dogs and cats with moderate to advanced CRF. The magnitude and the progression of the anemia correlate with the degree of CRF and worsen as renal function declines further. Erythropoietin deficiency has been identified as the primary cause of the nonregenerative anemia in animals with CRF. Several strategies for the management of the nonregenerative anemia should be considered. Prevent unnecessary blood loss by considering the quantity of blood collected from animals with a small body size (cats and small dogs) for diagnostic tests and monitoring purposes. Chronic low-grade gastrointestinal blood loss may contribute to the severe anemia in CRF animals. Therapeutic trials with H2-receptor antagonists may be necessary to reduce chronic gastrointestinal blood loss. Indicators of a positive response to H2-receptor antagonist administration include improvements in hematocrit and/or appetite. A transfusion of whole blood or packed red cells may be necessary for the severely anemic CRF animal that needs rapid correction of their anemia. Compatible blood products, as determined by cross matching and/or blood typing procedures should be used, even for the first transfusion. Repeated transfusions may be needed for long-term maintenance of the animal's hematocrit. A post-transfusion target hematocrit should be in the low end of the normal reference range to minimize the complications of an abrupt increase in blood volume and viscosity, such as circulatory overload, hypertension, and seizures. Recombinant human erythropoietin produces a rapid and effective erythroid response in dogs and cats with naturally occurring CRF. Significant increases in red blood cell count, hematocrit, and hemoglobin concentration can be found within the first month of initiating recombinant human erythropoietin therapy, which may be sustained indefinitely. In addition to the positive effects on hematopoiesis for dogs and cats in CRF, there are positive effects such as improved energy, increased appetite and alertness, and weight gain noted in most treated animals. Hypokalemia frequently observed in uremic cats resolves with recombinant human erythropoietin administration and is probably due to increased dietary intake of potassium. The most common problem associated with recombinant human erythropoietin administration in dogs and cats is the development of recombinant human erythropoietin antibodies, as indicated by the progressive decline in hematocrit, red blood cell count, and hemoglobin concentration. It is estimated that about 25% of treated animals develop anti-recombinant human erythropoietin antibodies. These antibody titers will decline after recombinant human erythropoietin therapy is stopped and pretreatment levels of erythropoietin will be attained, reversing the suppressed erythropoiesis. Other side effects of recombinant human erythropoietin therapy include seizures, systemic hypertension, and iron depletion. Allergic reactions, including mucocutaneous or cutaneous drug reactions, fever, and arthralgia, have also been observed in dogs and cats early in the course of recombinant human erythropoietin therapy. Most adverse reactions resolve within a few days and some adverse reactions have not returned when recombinant human erythropoietin therapy was reinitiated. Erythropoietin-replacement is indicated for dogs and cats symptomatic for the nonregenerative anemia of CRF. Erythropoietin-replacement is usually beneficial in animals with moderate to severe anemia (hematocrit < 21% in dogs and hematocrit < 19% in cats). The recommended initial dose of recombinant human erythropoietin is 50 to 100 U/kg of body weight subcutaneously three times a week (like on a Monday, Wednesday, Friday basis) until the ideal target hematocrit of 37% to 45% for dogs and 30% to 40% for cats is attained. As the ideal target hematocrit range is approached, the recombinant human erythropoietin administration interval is decreased to twice a week. A lower initial dose (50 U/kg three times a week) is prescribed if a slower erythropoietic response is desired. If the ideal target hematocrit range is not attained within 8 to 12 weeks, then the initial amount of recombinant human erythropoietin administered per time may be increased by 25 U/kg in a stepwise manner. The amount of recombinant human erythropoietin administered to maintain the hematocrit within the desired target reference range varies by individual animal and must be established empirically by monitoring the animal's response. In general, a dose of 50 to 100 U/kg once or twice a week is usually sufficient. Temporary cessation of recombinant human erythropoietin treatment may be required if the animal's hematocrit exceeds the desired target reference range. All animals receiving recombinant human erythropoietin therapy should be provided oral or parenteral iron supplementation to prevent iron depletion and facilitate the erythropoietic response. Oral supplementation with iron sulfate is preferred and its starting dose is 50 to 100 mg per day for cats and 100 to 300 mg per day for dogs. Some cats don't tolerate the oral iron supplementation, and then use iron dextran at 50 mg intramuscularly every 3 to 4 weeks. Because commercial diets formulated to contain reduced quantities of protein, phosphorus, sodium, and acid metabolites are the cornerstone of managing compensated CRF, anorexia may pose a major therapeutic challenge. Many animals with CRF, primarily older cats, refuse to eat some or all commercial diets offered to them. To avoid this food aversion, commercial diets formulated for long-term management of CRF should not be fed until the underlying causes of nausea, anorexia, and vomiting are resolved. Dietary changes should always be made gradually, over a period of 1 to 2 weeks. If possible, commercial diets should be chosen that resemble preferred diets with respect to texture and flavor. Foods may be warmed to enhance palatability. Dry foods may be moistened with water. Fresh and aromatic food is more likely to be desirable. Homemade or commercial diets may be modified with flavoring agents to provide favorable odors and enhance palatability. A flavoring agent, such as clam juice, bouillon, gravy, animal fat, butter, garlic, and dehydrated cottage cheese, may be used to enhance the palatability of the commercial diet. Cats that refuse protein-restricted diets should be allowed to eat as much protein as the uremia will allow. Some cats refuse protein-restricted diets entirely and eat only commercial cat food, chicken liver, chicken breast, all-meat baby food, fish, or shrimp. A general observation is that a cat or dog with CRF and uremia is more likely to die sooner eating nothing than when allowed to eat whatever it wants. Force-feeding, tube feeding, or placement of an esophagostomy tube or percutaneous gastrostomy tube may provide nutritional support in the hope that the animal will eventually begin eating voluntarily. Pharmacologic appetite stimulants are usually only marginally successful in animals with CRF. Benzodiazepines, such as oxazepam and diazepam, may be effective in the some animals. Diazepam may be given orally or intravenously but is most effective when given intravenously. In sick cat, the appetite-stimulating properties of benzodiazepines seem to wane in a few days and are generally unsatisfactory for long-term maintenance of the cat's appetite. Nausea, vomiting, and anorexia due to uremic gastropathy may be treated with H2-receptor antagonists such as cimetidine, ranitidine, or famotidine. Sucralfate may be used instead of an H2-receptor antagonist. Since sucralfate may interfere with the absorption of many other drugs, the other drugs should be given 30 minutes prior to the administration of sucralfate. Antiemetic drugs such as metoclopramide may also be used alternatively or as a supplement to H2-receptor antagonists and sucralfate. Other key factors should also be considered in the management of CRF. Avoiding high environmental temperature, change of residence, unnecessary travel, introduction of a new pet, and hospitalization should minimize stress in animals with CRF. The veterinarian should avoid prescribing any nephrotoxic drugs or drugs that require renal excretion in animals with CRF. Dosage regimens should be adjusted to compensate for decreased renal function if circumstances dictate that drugs that require renal excretion must be administered. Table 1. Guidelines for Long-Term Management of Older Dogs Diagnosed with Chronic Renal Failure Include: Dietary therapy
Dietary therapy
My standard treatment for the immune-mediated hemolytic anemia with thrombocytopenia is prednisone 4 mg/kg BID until the PCV/platelets rises and then 2 mg/kg BID until the PCV/platelets is stable for 1-2 months and then taper the prednisone over the next 2-3 months. At the same time, the dog is on azathiopurine at 2 mg/kg PO SID, every other day and is the last drug to be tapered. From here on, this dog should not be vaccinated or receive any penicillin, sulfa, or cephalosporin drugs. All of these dogs will relapse so extended initial drug therapy for the immune-mediated hemolytic anemia and not use certain drugs and not vaccinate are the ways to try to decrease the likelihood of a relapse. Has anyone any experience or opinion about using the leflunomide and cyclosporine concurrently, in addition to prednisone? IVIG, two previous RBC transfusions, and one week of prednisone and cyclosporine has not resulted in any improvements. Specialists are using leflunomide at 4 mg/kg daily initially, then decreasing to 2 mg/kg daily. The 4 mg/kg daily seems to cause some stomach upset though. Geriatric Medicine: Endocrine Problems
Spontaneous hyperadrenocorticism may have its origin in the pituitary gland or adrenal cortex. Pituitary-dependent causes (PDH) represent about 80% of the spontaneous causes in dogs. The remaining 10% to 20% of spontaneous cases are caused by unilateral or bilateral adrenocortical neoplasms.
Trilostane is an enzyme blocker which prevents the synthesis of cortisol. In contrast to o,p'-DDD, a cytotoxic drug, trilostane reportedly does not damage cells but is effective only until the drug is metabolized. In the United Kingdom, trilostane is officially registered for use in dogs under the trade name Vetoryl. The product for use in humans is listed as Modrenal. The current recommended initial dose is 30 mg once daily for dogs that weigh 3 to 10 kg; 60 mg once daily for dogs weighing 10 to 19 kg; 120 mg for dogs that weigh 20 to 40 kg, and 120 to 240 mg for dogs weighing more than 40 kg. Re-evaluations are suggested after 1, 3, 6, and 13 weeks, and then after 6 and 12 months. Each recheck should include a history, physical examination, and an ACTH stimulation test. The ACTH stimulation test should be completed 2 to 6 hours after administration of the trilostane. The target range for serum or plasma cortisol concentration should be between 1 and 2 mcg/dl. However, it is readily apparent that these dose recommendations result in tremendous dose disparity among dogs. A dog that weighs 3 kg, being given 30 mg once daily receives 10 mg/kg while a dog that weighs 20 kg receiving 120 mg would receive 6 mg/kg and one that weighs 40 kg could receive as little as 3 mg/kg. These doses disparities can result in severe negative side effects. Experience at UC-Davis differs quite a bit from that in the literature and the United Kingdom. It is not clear why the results have not been similar. It seems that the most common reason for choosing this drug over o,p'-DDD is safety. In other words, trilostane has been viewed as much safer and, perhaps, more effective in controlling clinical signs of pituitary-dependent hyperadrenocorticism. Some of the dogs we have treated have done remarkably well on a once daily protocol. However, a significant percentage of dogs we have treated with trilostane have become ill (including deaths), either from glucocorticoid deficiency or from glucocorticoid and mineralocorticoid deficiency (hypoadrenocorticism). Some of the iatrogenic hypoadrenocortic dogs appear to have this condition permanently. In addition, treated dogs that fail to exhibit resolution of polyuria despite having ACTH stimulation test results within the recommended range do occur. Therefore, trilostane is neither more effective nor safer than o,p'-DDD. Of greatest concern is that trilostane has been less predictable regarding under dose, overdose, resolution of signs, or need for dosing more often than once daily. UC-Davis current recommendation is to initiate trilostane therapy at 1 mg/kg once daily. That dose is continued for about one week until a veterinary recheck can be completed. Owners are instructed to collect a small urine sample from their dog before leaving home the morning of the scheduled recheck prior to trilostane administration. Trilostane should then be given and the dog should be seen by the veterinarian 2 to 3 hours later. The goal of therapy is an owner who is completely pleased with the response. As aids in achieving this goal, both urine and blood tests are indicated. The urine should be checked, at a minimum, for specific gravity, glucose, and urine cortisol-to-creatinine ratio (UCCR). An ACTH stimulation test should be started at the time that the dog is seen, again about 2 to 3 hours after trilostane administration. The UCCR result should be within the reference interval and the post-ACTH serum cortisol concentration should be between 1.5 and 5.5 mcg/dl. If the serum cortisol concentration is within that goal and the UCCR is abnormal, the medication should be given BID. If the serum cortisol concentration is too high, the trilostane dose should be increased and if the serum cortisol concentration is too low, the dose should be decreased. This approach should be utilized at each recheck until the dog is doing well. Hyperestrinism in Dogs Hyperestrinism in dogs may be a new and emerging disease entity. In sample submissions to the Clinical Endocrinology Service in 2005 at The University of Tennessee, 40% of adrenal panels had elevated estradiol levels present (>70 pg/ml). In hyperestrinism cases, estradiol is the estrogen that is increased, ACTH stimulation and LDDS tests are usually normal for cortisol, thyroid function is normal or controlled, liver problems are frequent, and typical (very elevated serum alkaline phosphatase, hepatomegaly, steroid hepatopathy, hyperechoic liver by ultrasound study), PU/PD is frequent, panting may be present, haircoat problems often are present, skin biopsy results suggest an endocrinopathy, there is no change in estradiol level in response to ACTH stimulation or LDDS tests as currently conducted, resistance to mitotane may occur, and increase often occurs in response to trilostane. Effective treatment options for hyperestrinism in dogs is limited at the present time, and drugs that could be expected to be efficacious (aromatase inhibitors) often are limiting due to cost. Melatonin and phytoestrogen treatment may be effective for some dogs. Mitotane will likely be effective if the source of estradiol is the adrenal tissues. Trilostane treatment frequently results in increased estradiol levels, and this may be a reason why less than effective treatment with the drug sometimes occurs. Geriatric Medicine: Endocrine Problems
Geriatric Medicine: Endocrine Problems Hyperthyroidism in cats is usually caused by a solitary adenoma or multinodular adenomatous hyperplasia. Thyroid carcinomas are uncommon, comprising 2% of all hyperthyroid cases.
Geriatric Medicine: Gastrointestinal Tract With the possible exception of some types of neoplasia, there are no specific age-related small intestinal diseases of older dogs or cats. Acute small intestinal diarrhea can also occur in older animals, such as bacterial enteritis (salmonellosis, campylobacteriosis, yersiniosis, enteropathogenic E. coli infection) protozoal enteritis (Giardia), enteritis caused by helminthes, or ingestion of garbage and/or intoxicants. Inflammatory Bowel Disease Inflammatory bowel disease broadly refers to a group of idiopathic gastrointestinal disorders characterized by the infiltration of the mucosa with varying numbers of inflammatory cells. Despite the high prevalence of ulcerative colitis and Crohn's disease in human medicine and inflammatory bowel disease in animals and a plethora of studies, no clear pathogenesis is known. Interactions between the mucosal immune system, host genetic susceptibility (e.g. basenji with lymphoplasmacytic enteritis or boxers with ulcerative colitis), and environmental factors are important. Inflammatory bowel disease is though to occur either due to an abnormal immune response (e.g. host hypersensitivity precipitated by increased intestinal permeability, defective suppressor function of gut-associated lymphoid tissue, and other yet to be defined primary immunological events) or due to an appropriate immune response to an enteric pathogen. Either way, cellular components (activated intestinal B and T lymphocytes) and molecular elements (cytokines, complement, eicosanoids) contribute to mucosal inflammation. Lymphocytic-plasmacytic enteritis (or enterocolitis) (LPE) is the most common form of inflammatory bowel disease in cats and dogs. Some breeds seem at increased risk for LPE such as German shepherd dogs, Chinese shar-pei, soft-coated Wheaten terrier, and possibly purebred cats. Basenjis and Lundehunds have an own particular form of severe immunoproliferative lymphocytic-plasmacytic enteritis. Eosinophilic enteritis, which is considerably less common than lymphocytic-plasmacytic enteritis (more frequent in dogs than in cats), might be a variant of inflammatory bowel disease or an allergic manifestation to dietary or parasitic antigens. A severe form is hypereosinophilic syndrome, which exists in cats and rarely in dogs. German shepherd dogs and Irish setters might be predisposed to eosinophilic inflammatory bowel disease. Several inflammatory bowel disease variants are occasionally diagnosed such as chronic histiocytic-ulcerative colitis, suppurative colitis or granulomatous enterocolitis (regional enteritis). History and Clinical Signs. Animals with inflammatory bowel disease normally present with chronic small, large, or mixed diarrhea (depending on location of inflammation), vomiting, anorexia, lethargy, and weight loss. The animal may be cachectic if mucosal damage is severe, and edema or ascites may be detected if the disease process is sufficiently advanced to cause protein-losing enteropathy. Thickened intestinal loops may occasionally be palpated. Diagnosis. Differential diagnoses of disorders resembling inflammatory bowel disease in older dogs and cats include intestinal neoplasia, lymphangiectasia, fungal infection, chronic parasitism (including giardiasis), feline infectious peritonitis, and feline hyperthyroidism. A definite diagnosis of inflammatory bowel disease can only be made on intestinal biopsies taken by endoscopy, laparoscopy, or laparotomy. Hematology might reveal thrombocytopenia in lymphocytic-plasmacytic enteritis and eosinophilia in eosinophilic enteritis (more common in cats than dogs). The serum chemistry profile may show pan-hypoproteinemia in animals with protein-losing enteropathy due to inflammatory bowel disease. Cats have not uncommonly liver involvement with inflammatory bowel disease and increased serum liver enzymes activities. Serum folate concentration may be increased, suggesting bacterial overgrowth or may be normal to decreased, suggesting severe proximal small intestinal disease. Serum cobalamin activity is either normal or decreased, suggesting distal small intestinal disease. Treatment Plan. Management of inflammatory bowel disease may include controlled diets, dietary fiber supplementation, and administration of antimicrobial, antiinflammatory, and immunosuppressive drugs. No large trials have been conducted and treatment remains largely empirical. Dietary Therapy: Because dietary antigens are thought to play an important role in the pathogenesis of inflammatory bowel disease, modification of the diet is normally done. These diets have as characteristic highly digestible protein and carbohydrate source, relative hypoallergenicity and are gluten-free, low in lactose and fat, nutritionally balanced, and high palatability. Animals appear to benefit from being fed a diet containing a protein to which they have not been previously exposed (novel proteins such as venison, rabbit, lamb, whitefish, or turkey). Only recently a "sacrificial protein" has been advocated in inflammatory bowel disease. In this approach, a first novel protein is fed to animals in the early phase of therapy when the bowel is still markedly inflamed and the mucosal barrier porous. After 6 weeks or when the prednisone dose is decreased from immunosuppressive to antiinflammatory, the protein source is changed again at which time it is hoped that mucosal inflammation has been controlled. The second dietary protein is less likely to result in acquired food hypersensitivity. Recurrence of signs after challenge with known allergens such as soya, beef, or gluten is essential to document the specific dietary sensitivity. Altering the dietary ratio of omega-6 to omega-3 polyunsaturated fatty acids might alter the inflammatory response in the gut, but controlled studies in animals with inflammatory bowel disease are not yet available. Finally, increasing the fiber content of the diet might increase fecal consistency, bind potential colonic irritants, improve abnormal motility, and produce beneficial short-chain fatty acids. Wellness, Evo, Halo Spots Stew, and Nature's Variety Instinct are a few grain-free "natural"/premium type canned foods. A number of flavors of Fancy Feast canned also contain no grain or gluten. Fancy Feast it is a palatable food, and is my choice for cats that are "addicted" to dry food. There are several grain-free dry foods on the market (Innova Evo, Orajen, and Wellness Core). These foods are extremely calorie dense and will contribute to obesity quickly. They are also, like any dry food, too low in water content for my preferences for the feline species. Dr. Elizabeth Hodgkins book "YOUR CAT: Simple New Secrets to a Longer Stronger Life" has a very client friendly discussion of why canned food is better than dry, and a good appendix on how to read a pet food label. While it is controversial, first choice for many patients is actually a raw meat based diet, which is what I feed my own cats. Bravo, a company in Connecticut, tests every batch of their food for E. coli, Salmonella, and Listeria. This company make a very high quality product. Antimicrobial Therapy: On the premise that an abnormal bacterial flora or enteric pathogens may be a cause or complicating factor, the use antimicrobial therapy is reasonable. Oral oxytetracycline appears to be effective and has the advantage of being inexpensive. Other choices include metronidazole and tylosin. Some owners find that they can reduce the antimicrobial dose to once daily and still bring about a remission of signs. Experimentation with various antimicrobial agents and/or diet combination may work best in a particular animal. Immunosuppressants: The initial drugs for lymphocytic-plasmacytic enteritis and eosinophilic inflammatory bowel disease are prednisone or prednisolone at an initial dose of 1 to 2 mg/kg orally twice daily for 2 weeks and then tapered in 50% decrements every 2 weeks if signs improve. In mild to moderate cases alternate or every third day treatment can often be achieved in 3 to 4 months and potentially discontinued after 6 months for both cats and dogs. In severe cases the reduction should be much more gradual and a moderate dose (0.5 mg/kg daily) might be needed long term. Methylprednisolone acetate can be used in cats with mild to moderate inflammatory bowel disease as sole or adjunctive therapy. If remission cannot be maintained on corticosteroid use alone or in combination with metronidazole or if the side effects of corticosteroids are intolerable, then the concurrent use of azathioprine is indicated. While in dogs the dose is 2.0 to 2.5 mg/kg daily, azathioprine can also be used carefully in cats but in a markedly reduced dose of 0.3 mg/kg once every other day. The owner should be advised about the possible side effect of azathioprine-induced pancreatitis in dogs and to check the white blood cell count weekly (and stop the treatment if the white blood cell count falls below 4500 /µl). Chronic colitis is better treated with sulfasalazine, which consist of 5-aminosalicylic acid linked by azo-bond to sulfapyridine. It is delivered relatively intact to the colon where bacteria cleave the azo-bond. The 5-aminosalicylic acid moiety is poorly absorbed and has local antiinflammatory properties. On resolution of clinical signs, sulfasalazine can be gradually tapered by 25% at 2-week intervals and eventually discontinued while maintaining dietary management. The dose of sulfasalazine is much less in cats. Newer immunosuppressive drugs such as cyclosporin or 5-lipoxygenase inhibitors (Zileuton) or newer 5-aminosalicylic acid preparations (enteric coated mesalazine, olsalazine) might find some use in refractory cases of inflammatory bowel disease, but no information is available so far. Supplemental Therapy: If weight loss and mucosal disease is severe, it is probable that secondary vitamin deficiencies may be present. Parenteral injection of cobalamin (750 microgram/month) and oral folic acid administration (5 mg/day for 1 to 6 months) may be beneficial in dogs since deficiencies of these vitamins may be due to impaired mucosal uptake. Diarrhea in hypoproteinemic animals may be exacerbated by decreased plasma oncotic pressure (<4.0 g/dl). Plasma transfusion or human albumin or hetastarch infusion often bring about dramatic resolution of signs in conjunction with other aggressive therapy. Ascites if present should not be treated by paracentesis since it removes protein from the body and may exacerbate hypoproteinemia. Diuretic therapy using spironolactone is indicated if the ascites is sufficient to cause respiratory distress. Furosemide should only be used in emergency situations when rapid fluid loss is required. Small Intestinal Tumors Adenocarcinoma, lymphoma, and leiomyosarcoma are the most common malignant intestinal tumors of dogs while cats mostly have lymphomas. All tumors are more common in older animals, but there is no breed or sex predisposition. Lymphoma in cats sometimes results from lymphocytic-plasmacytic enteritis and afflicted cats are usually feline leukemia virus negative. Signs include vomiting, diarrhea, and weight loss and are related to malabsorption and protein-losing enteropathy secondary to infiltration of the intestinal wall. Abnormal bacterial flora is not uncommonly seen especially if the tumor causes partial intestinal obstruction. Survey abdominal and contrast radiographs are rarely helpful to diagnose intestinal tumors when abdominal mass(es) cannot be palpated. Abdominal ultrasound helps in localizing masses, shows irregular thickened mucosa with loss of the normal layers and may show a lymphadenopathy or local spread. Ultrasound-guided fine needle aspirates or even true-cut biopsies can sometimes be obtained from an intestinal mass. Endoscopy is only helpful when the tumor is located in the descending limb of the duodenum. Exploratory laparotomy and intestinal and mesenteric node biopsy are confirmatory. Solitary tumors should be surgically resected (even alimentary solitary lymphomas due to the risk of obstruction). Lymphomas will then be followed-up with standard chemotherapy protocols. The prognosis for alimentary lymphomas in dogs is guarded, while cats respond moderately well to a combination protocol including doxorubicin and l-asparaginase. Adenocarcinomas have a poor prognosis in both species unless diagnosed very early in which case resection of a localized lesion can produce marked clinical improvement. Leiomyomas and leiomyosarcomas are often slow-growing tumors with a good prognosis following complete surgical excision.   |