Veterinary Medicine

Portosystemic Shunts

1. What is a portosystemic shunt?

A portosystemic shunt is an abnormal vessel that connects the portal vein to a systemic vein. The most common locations for portosystemic shunts are a patent ductus venosus or a connection between the portal vein and caudal vena cava or azygous vein. Single extraheptic shunts are most common in small-breed dogs and cats, whereas single intrahepatic shunts are most common in large-breed dogs.

2. What is the difference between congenital and acquired portosystemic shunts?

Most acquired shunts are multiple and extrahepatic. Acquired shunts develop because of sustained portal hypertension from chronic liver disease and cirrhosis. Congenital portosystemic shunts are usually single and may be intra- or extrahepatic. The most common intrahepatic portosystemic shunt is a patent ductus venosus.

3. Are certain breeds associated with portosystemic shunts?

Congenital portosystemic shunts may occur in any breed of dog but are common in miniature schnauzers, miniature poodles, Yorkshire terriers, dachshunds, Doberman pinschers, golden retrievers, Labrador retrievers, and Irish setters. There are affected lines in miniature schnauzers, Irish wolfhounds, Old English sheepdogs, and Cairn terriers. Mixed breed cats are more commonly affected than purebred cats, but Himalayans and Persians seem to overrepresented as purebreds. Acquired portosystemic shunts are secondary to chronic hepatic disease and so may occur in any breed.

4. Where are most portosystemic shunts located?

Single extrahepatic shunts most commonly connect the portal vein (or the left gastric or splenic vein) with the caudal vena cava cranial to the phrenicoabdominal vein. Single intrahepatic shunts can be a communication of the portal vein to the caudal vena cava which is a failure of the ductus venosus to close. Shunts in the right medial or lateral liver lobes occur with an unknown pathogenesis.

5. Why do patients with portosystemic shunts have decreased liver function?

Portal venous blood is important because it brings hepatotropic growth factors and insulin to the liver. If insulin bypasses the liver in a shunt, significant quantities are utilized by other organs and the liver receives less benefit. Portal venous blood flow is important for normal liver development as well as glycogen storage, hypertrophy, hyperplasia, and regeneration. Congenital portosystemic shunts are often associated with hepatic atrophy, hypoplasia, and dysfunction.

6. What are the most common clinical signs of portosystemic shunts?

Failure to thrive and failure to gain weight are appropriately common. Most clinical signs are referable to hepatic encephalopathy, which is defined as clinical signs of neurologic dysfunction secondary to hepatic disease. Signs include ataxia, stupor, lethargy, unusual behavior, disorientation, blindness, and seizures. Some animals display anorexia, vomiting, and diarrhea. Polyuria and polydipsia may be present. Some animals have ammonium biurate urolithiasis, which may result in pollakiuria, hematuria, stranguria, or obstruction. Increased production of saliva (ptyalism) and abdominal distention due to ascites occur in some animals. Ptyalism is more common in cats.

7. What causes hepatic encephalopathy associated with portosystemic shunts?

Products of bacterial metabolism in the intestine, such as ammonia, short-chain fatty acids (SCFAs), mercaptans, gamma-aminobutyric acid (GABA), and endogenous benzodiazepines have been suggested as mediators of hepatic encephalopathy. In addition, the ratio of aromatic amino acids to branched-chain amino acids is often increased in patients with portosystemic shunts. The aromatic amino acids may act as false neurotransmitters. Phenylalanine and tyrosine may act as weak neurotransmitters in the presynaptic neurons of the CNS. Tryptophan causes increased production of serotonin, which is a potent inhibitory neurotransmitter. The GABA receptor has binding sites for barbiturates, benzodiazepines, and substances with similar chemical structure to benzodiazepines. These agents may be responsible for depression of the CNS in hepatic encephalopathy.

8. What factors may precipitate an hepatic encephalopathy crisis?

A protein rich meal, gastrointestinal bleeding associated with parastites, ulcers or drug therapy; administration of methionine- containing urinary acidifiers; or lipotropic agents may precipitate a crisis. Blood transfusions with stored blood may also contribute to a crisis as the ammonia levels can be high in the stored blood.

9. How is hepatic encephalopathy treated?

The animal should be evaluated for hypoglycemia immediately and treated appropriately if it is present. Appropriate fluid therapy based on acid-base and electrolyte status (see chapter 81) should be initiated to correct abnormalities. LRS should be avoided. Hypoglycemia, alkalosis, hypokalemia, and gastrointestinal bleeding should be identified and corrected. Ammonia concentration and production should be decreased by administering lactulose and neomycin (10-20 mg/kg orally every 6 hr) if a swallow response is present. Oral metronidazole may be used at a dose of 10 mg/kg every 8 hr in place of neomycin. If the animal is comatose, 20-30 ml/kg of lactulose diluted 1:2 with water or a 1:10 dilution of povidone-iodine solution may be given as an enema. Seizures may be treated initially with elimination of ammonia by enemas as listed above. Oral loading doses of potassium bromide may be useful. If seizures cannot be controlled, IV propofol as a constant rate infusion may be necessary, but respiratory support may be needed. Some animals with hepatic encephalopathy have difficulty in metabolizing benzodiazepines such as diazepam, which should be avoided. If these drugs do not control seizures, intravenous phenobarbital may be titrated slowly to effect. Patients often have decreased clearance of barbiturates.

10. What routine blood work and urinalysis abnormalities suggest portosystemic shunts?

Microcytosis is a consistent abnormality of complete blood cell count in animals with portosystemic shunts. Some animals manifest acid-base, electrolyte, and glucose disturbances (hypoglycemia). Because of vomiting and dehydration, prerenal azotemia may be present. There is no consistent finding with regard to alanine aminotransferase (ALT), aspartate aminotransferase (AST), and serum alkaline phosphatase (ALP); activities of these enzymes may be elevated, decreased, or normal in patients with portosystemic shunts. Hypoalbuminemia is common, as are coagulopathies. Some animals have isothenuric urine due to medullary wash-out; ammonium biurate crystals may be identified on microscopic examination of urine sediment.

11. What are the best ways to diagnose a portosystemic shunt?

Elevated serum pre- and postprandial bile acids in a young animal with signs of hepatic encephalopathy and stunted growth are consistent with but not diagnostic for portosystemic shunts. A nuclear medicine scan using transcolonic sodium pertechnetate Tc99m demonstrates radioactivity in the heart before the liver in an animal with portosystemic shunt. Nuclear medicine is rapid, noninvasive, and safe to the animal. The disadvantages are that the animal is radioactive for 24 hours, studies can be performed only by specially trained personnel, exact location of the shunt cannot be determined, and cases of hepatic microvascular dysplasia, which have shunting within the liver (as in Cairn terriers), may give false-negative results. When nuclear medicine facilities are unavailable, positive contrast portography may demonstrate the anomalous vessel. Portography, however, is technically demanding and invasive. Furthermore, a second surgical procedure is required to repair the shunt because of an otherwise dangerously long period of anesthesia. The major advantage of positive contrast portography is that it definitively locates the shunt.

12. What is the best way to manage a patient with portosystemic shunt?

Although medical management may be beneficial, surgical ligation of the shunt is optimal. In one study, animals that receive total ligation, even if it had to be done in two or more surgeries, showed more clinical improvement than patients with incomplete shunt ligation. In general, cats do not do as well with medical therapy.

13. Describe the preoperative management of a patient with portosystemic shunt.

In animals displaying hepatic encephalopathy, it is important to correct acid-base and electrolyte disturbances before surgery. Measures to control hepatic encephalopathy also should be performed before surgery, including a low protein diet, oral lactulose, and neomycin or metronidazole. A moderately protein-restricted diet with the bulk of calories coming from carbohydrates and fat is optimal. Vegetable and dairy proteins are better tolerated than meat and egg proteins. With each patient, the protein level should be increased to the maximum tolerated. Psyllium at 1-3 teaspoons per day has been advocated to help tolerance of proteins. Some have recommended supplementation with vitamins A, B, C, E, and K. Medical stabilization for 1-2 weeks before surgery is recommended for all patients with portosystemic shunts. A preoperative coagulation screen should be performed, and crossmatched fresh whole blood should be available. Fresh frozen plasma transfusions may be necessary for hypoalbuminemic patients. Most surgeons administer a broad-spectrum antibiotic (e.g., first-generation cephalosporin) intravenously before and during surgery.

14. What considerations must be given to drug therapy and anesthetic use in patients with portosystemic shunts?

Because liver function decreases in patients with portosystemic shunts, drugs that are potentially hepatotoxic should be avoided. In addition, hepatic clearance of drugs and anesthetic agents may be delayed.

15. What parameters should be monitored postoperatively in patients with portosystemic shunts?

After surgery, many patients with portosystemic shunts are hypoglycemic, hypothermic, and hypoalbuminemic. A postoperative database should include body weight, temperature, packed cell volume, total solids, and glucose. Additional useful information is provided by electrolytes and albumin. Maintaining hydration status and perfusion with a balanced electrolyte solution is important. Mucous membrane color, capillary refill time, pulse rate and quality, and temperature should be assessed, and the patient should be monitored for seizures. In addition, serial measurement of abdominal circumference is helpful because a number of patients develop portal hypertension and ascites postoperatively.

16. What are common postsurgical complications?

Sepsis, seizures, and portal hypertension are the most critical complications that may develop postoperatively, although pancreatitis and intussusceptions have been reported. Gastrointestinal hemorrhage also may result, which can precipitate a hepatic encephalopathy crisis. Animals with seizures should be treated with appropriate measures to normalize acid-base and electrolyte balance. Sepsis should be treated aggressively.

17. What are common signs of postoperative portal hypertension?

Portal hypertension most commonly results in abdominal distention secondary to ascites. In some cases, portal hypertension is subclinical and ascites resolves in several days. Some patients develop abdominal distention, pain, and hypovolemia; others have abdominal distention with severe pain, hypovolemia, cardiovascular collapse, hemorrhagic diarrhea, and septic or endotoxic shock.

18. How should postoperative portal hypertension be treated?

If the animal develops abdominal distention with no clinical signs of pain or discomfort, continued medical therapy is indicated. Most animals with pain and abdominal distention stabilize with colloid fluid therapy. Patients with severe pain, abdominal distention, bloody diarrhea, and cardiovascular shock should be treated for shock with fluids, stabilized as much as possible, and taken for exploratory surgery to remove the ligature or thrombus that has probably developed in a partially attenuated portosystemic shunt.

19. Why may a patient with portosystemic shunt become septic postoperatively?

A patient with portosystemic shunt may develop septic peritonitis postoperatively because of bacteremia in the portal vein. The monocyte-phagocyte system in the liver may not be fully functional. Sepsis may develop as a result of inadequate filtering of portal blood by the liver before the blood reaches the systemic circulation.

20. What is hepatic microvascular dysplasia?

Hepatic microvascular dysplasia is a congenital disorder with histologic vascular abnormalities that resemble those seen in portosystemic shunts.

21. Are there breed predispositions for hepatic microvascular dysplasia?

Cairn and Yorkshire terriers are most commonly affected with hepatic microvascular dysplasia. However, many other breeds, including dachshund, poodle, Shih Tzu, Lhasa Apso, cocker spaniel, and West Highland White terrier may be affected.

22. What are the clinical signs of hepatic microvascular dysplasia?

Clinical signs are not consistently seen, but in severe cases they are quite similar to those seen with portosystemic shunts. Hyperammonemia and ammonium biurate cystalluria rarely develop. A dog may have hepatic microvascular dysplasia with elevated bile acids but be sick for another cause.

23. When should hepatic microvascular dysplasia be considered as a differential diagnosis?

Hepatic microvascular dysplasia should be considered in a patient with clinical signs consistent with a portosystemic shunt, increased bile acid concentration, and consistent liver biopsy results. Scintigraphy is consistently normal.

24. What is the treatment for hepatic microvascular dysplasia?

Treatment should not be done if the patient is subclinical. If signs of hepatic encephalopathy are present, treatment is indicated as for patients with portosystemic shunts. It is unknown at this time whether subclinical patients will develop signs of disease.


Perineal Hernia

Perineal hernias have been clinically recognized in the dog for more than 100 years and are most common in older, intact male dogs. They are rarely seen in cats or female dogs. Four types of perineal hernias have been described, but the most common type is the caudoventral perineal hernia, which occurs between the levator ani, external anal sphincter, and internal obturator muscles. Sciatic hernias occur between the sacrotuberous ligament and the coccygeus muscle, dorsal hernias occur between the levator ani and coccygeus muscles, and ventral hernias occur between the levator ani and ischiourethralis or ischiocavernosus muscles. Most perineal hernias are unilateral, although bilateral herniation can occur, with the right side being predisposed. Herniation may involve only rectal tissues, but eventually prolapse of pelvic organs, such as the urinary bladder, prostate, or other abdominal tissues (e. g., fat, intestine), into the weakened area can occur. In dogs, neurogenic atrophy of the levator ani muscles, gender-based variations in pelvic muscle anatomy, and gonadal hormonal influence are all thought to be factors in the development of perineal hernias. The degree of stretching and deviation of the rectal wall and the presence or absence of abdominal organs in the hernia are all factors that determine clinical signs.

History and Physical Examination

In more than 90% of affected dogs, perineal swelling and tenesmus are the most common clinical signs; however, constipation, dyschezia, and hematochezia are also reported. Dysuria and stranguria accompany the signs of rectoanal disease if the bladder is retroflexed and trapped in the ischiorectal fossa. With longstanding bladder entrapment, azotemia and signs of renal failure (e. g., anorexia, vomiting) also occur. Less commonly, persistent dribbling of urine or other signs of urinary incontinence may be present instead of signs of urinary obstruction. In cats with perineal herniation, concurrent severe obstipation or megacolon is the most common predisposing factor. The physical examination often reveals a visible perineal swelling or a reducible perineal swelling. External palpation of a defect in the musculature just lateral to the external anal sphincter is often sufficient for confirmation of the hernia. However, in some pets the hernia is palpated rectally only as a defect in the pelvic diaphragm. A digital examination can also be performed to detect any other rectal wall abnormalities (e. g., deviation, sacculation, or diverticulum). In general, the combination of historical and physical examination findings is sufficient to confirm the diagnosis of perineal hernia. Further evaluation, either with ultrasonography or contrast studies, may be necessary to determine the extent of hernia contents (e. g., the presence of intestine, bladder, or prostate) prior to repair. The major differential diagnoses are rectal diverticulum, neoplasia, prostatic or paraprostatic cyst, and seroma / hematoma.


The pathogenesis of perineal hernias is not completely understood. Because most patients are older male dogs, gonadal hormonal influences have been strongly suggested. The evidence supporting this idea derives from the fact that castrated dogs are rarely affected with perineal hernia; however, no difference in the levels of testosterone and estrogen 17-beta have been found between normal dogs and dogs with perineal hernia. Some have suggested that, rather than hormone concentrations, the number or affinity of hormone receptors may be the important factor in the development of perianal muscle weakness. Another potential factor is that in male dogs, the levator ani muscles are weaker and thinner and have a weaker attachment to the external anal sphincter. The fact that brachycephalic breeds (e. g., Boston terrier, boxer, Welsh corgi, and Pekinese) appear to be predisposed to the development of perineal hernias suggests that an anatomic or breed-specific defect is important. Evidence against a strictly hormonal cause tor hernia development is the fact that in cats, the benefits of castration have not been demonstrated, a finding illustrated by a retrospective study in which 19 of 20 cats with perineal hernias had been either castrated or spayed.

Aside from anatomic and hormonal theories, another factor considered important in disease development is damage to the pudendal nerve or to the first, second, or third sacral nerves, which results in neurogenic atrophy of the levator ani muscles. However, it is not known whether damage precedes development or occurs as a result of the hernia.

In addition to primary predisposing factors, perineal hernias in dogs may occur secondary to persistent tenesmus and constipation, which results in muscular weakness in the pelvic floor or may occur as a result of severe prostatic disease or paraprostatic cysts. In cats, perineal hernias most commonly occur secondary to constipation resulting from megacolon. Other factors associated with perineal hernias in cats are perianal masses, chronic fibrosing colitis, and previous perineal urethrostomy.


Definitive surgical repair (perineal hemiorrhaphy) is the treatment of choice in most instances. The primary aim of the surgical repair is to replace muscular support of the pelvic diaphragm. Preoperative preparations may include preanes-thetic blood work, electrocardiography, abdominal ultrasound, and chest radiographs if indicated to rule out complicating factors for anesthesia or secondary causes of hernia formation. Stool softeners (e. g., lactulose) and a highly digestible diet (i. e., to reduce fecal volume) should be initiated several days before surgery. If the bladder is retroflexed and trapped within the hernia, catheterization should be attempted immediately. If this is unsuccessful, the bladder should be emptied by cystocentesis; then, with the bladder decompressed, the hernia is reduced and the bladder is pushed back into the abdominal cavity if possible.

Regardless of whether the bladder is properly repositioned, a transurethral Foley urinary catheter should be placed and a closed collection system should be attached until surgery can be performed. Urine cultures should be obtained and appropriate antibiotics administered for all animals with perineal hernia involving bladder entrapment. Preoperative antibiotics (e. g., cefoxitin used as a single agent) are recommended for protection against contamination by enteric coliforms.

Several techniques for perineal hernia repair have been reported, including standard hemiorrhaphy, transposition of the superficial gluteal muscle, an internal obturator transposition technique, a combination of the gluteal and obturator muscle transpositions, and a special technique in which small intestinal submucosa is used to repair the defect. The reader is referred to a surgical text for a detailed description of the specific surgical techniques used in hemiorrhaphy. Traditional hernia repair involves closure of the triangular area formed by the external anal sphincter, levator ani, coccygeus, and obturator muscles. However, with this method of repair, the rate of hernia recurrence is high (10% to 45%), and postoperative complications are common.

The current standard for repair is the obturator transposition technique because of its much lower rate of recurrence and lower complication rate. The use of porcine small intestinal submucosa as a biomaterial for perineal hemiorrhaphy is relatively new and has shown promise both as a primary means of repair and as an augmentation technique when the internal obturator muscle is weak or when a salvage procedure is required. Other surgical procedures that may be required in the repair of this disorder include repair of diverticuli or rectal deviations, removal of prostatic cysts and, in cats with megacolon, a subtotal colectomy. Castration is recommended hut is not an essential aspect of treatment, especially if the length of the procedure increases the risk for an older dog.

After surgery, a highly digestible (low residue) diet and stool softeners should be provided indefinitely to prevent straining and recurrence. Local perineal swelling is common and resolves with application of hot compresses. In dogs for which surgical repair is not possible, the treatment approach is to reduce fecal volume, impaction, and straining by feeding a low-residue diet and administering stool softeners, laxatives (e. g., lactulose), and enemas as needed. In most cases, dietary and conservative management of hernias is not rewarding in the long term.


In general, the prognosis for long-term repair of perineal hernias is guarded. The rates of recurrence are related to the type of surgical repair done and the skill of the surgeon. Most surgeons agree that the obturator transposition technique, combined with one of the other approaches, is the best surgical option currendy available. However, the more severe the preoperative clinical signs, the longer the signs have been present, and the existence of bilateral involvement all increase the likelihood of a higher recurrence rate, regardless of the technique used. Other postoperative complications include infection, seroma or hematoma formation, fecal incontinence, rectal prolapse (especially if a bilateral repair is required), sciatic nerve paralysis or sciatic pain, and urinary complications, including incontinence or obstruction (caused by sutures in or scarring of the urethra).


Rectal or Anal Stricture

Rectal or anal strictures cause narrowing of the lumen due to scar tissue that forms as a result of rectal inflammation, rectal trauma (from injury or surgery), or proliferative neoplastic disease in the rectum. The clinical picture (e. g., constipation, dyschezia, and, ultimately, vomiting or anorexia) is indistinguishable from that presented by extraluminal narrowing of the colon due to neoplasia, prostatic disease, or pelvic fracture.

History and Physical Examination

The typical history is an older dog that has chronic constipation or progressively more difficulty defecating. Affected dogs have persistent tenesmus, prolonged posturing to defecate, and frequent attempts to defecate, with on. y a narrow ribbon of feces or no feces produced. If concurrent colorectal inflammatory or neoplastic disease is present, hematochezia, mucoid feces, or diarrhea may be observed. As the duration and severity of the obstruction worsen, other systemic signs may be observed (e. g., lethargy, anorexia, vomiting, weight loss). Several conditions can predispose dogs to the development of a rectal stricture, including recent rectal or anal surgery, chronic rectal or anal inflammation, rectal neoplasia, and ingestion of foreign material that causes rectal trauma as it is passed.

Digital rectal examination is sufficient to identify a narrow and often very tight rectal or anal opening. Benign strictures are firm, thick, annular fibrotic bands that must be differentiated from neoplastic strictures, which tend to be asymmetric, masslike formations. However, annular rectal adenocarcinoma cannot be distinguished from a benign fibrotic stricture by palpation alone. The only other physical abnormality found in dogs with rectal stricture is an enlarged colon with hard or impacted feces.


In most dogs, the history and physical examination are sufficient to identify a stricture. The key aspect of diagnosis is determining whether the stricture is malignant or benign. Radiographs and ultrasound scans of the abdomen and pelvis are important, because they rule out other causes of constipation / obstipation, such as pelvic fractures, prostatomegaly, and abdominal masses that affect the colon or sublumbar lym-phadenopathy. Contrast radiography is not usually necessary to make a diagnosis of stricture, but it may be helpful for determining the extent of the stricture if the opening is too narrow for physical analysis. Rectal probe ultrasonography can be used to determine the extent of rectal involvement or to detect other lesions. Ultimately, however, biopsy is necessary to determine whether the lesion is benign or malignant. Biopsy of tissue can be obtained through rigid proctoscopy, flexible endoscopy, or direct visualization by prolapse of the affected rectal tissues. A major limitation on the use of either a rigid or a flexible scope to obtain biopsy specimens is that passage of the scope and distention of the rectum (for visualization) often is impossible. In such cases, direct prolapse or surgical biopsies must be obtained.


Previously, rectal strictures were managed by surgical techniques, such as rectal pull-through or rectal myotomy procedures. More recently, bougienage and balloon dilatation techniques have gained favor, because when performed properly, they are often successful in dilating the stricture site without incurring the severe complications that frequently accompany surgical correction (e. g., fecal incontinence, infection, dehiscence, or restricture). To facilitate appropriate visualization and comfort for these procedures, the dog or cat should be anesthetized, and if possible the procedure should be done with endoscopic or fluoroscopic assistance.

For bougienage of rectal strictures, a metal bougie of increasing size (over several separate but successive procedures) is passed into the stricture site and advanced slowly, stretching the fibrous tissue without causing significant tearing, which tends to increase inflammation and the likelihood of restricture.

Like esophageal strictures, rectal strictures also can be successfully dilated using balloon dilatation techniques, and this approach is frequently preferred over bougienage. The diameter of the balloon and the number of dilatations required to achieve a sustained opening in the rectal lumen are quite variable, but chronic strictures in larger animals may require several procedures to achieve functional success. In general, for small dogs (less than 7 kg) and cats, balloons with a diameter of 10 to 15 mm are used; for medium-sized dogs, the balloon diameter is 20 to 30 mm; and for large dogs (greater than 16 kg), it is 30 to 40 mm. These numbers are guidelines, because animals with severe rectal strictures may require much smaller balloons for the initial procedure to prevent excessive tissue tearing. In dogs with recent strictures or those without excessive fibrosis, one or two dilatation procedures 4 to 5 days apart may be all that is required to dilate the affected tissue successfully. However, when rectal wall thickening is present or the reduction in the lumen is greater than 75%, four to six dilatation procedures may be required to achieve functional success. The purpose of performing multiple procedures several days apart (but no more than 7 days) is to increase the diameter of the stricture waist gradually, without excessive tearing or inflammation; this gradual approach reduces the likelihood of restricture (which tends to occur in 7 to 10 days). Careful visualization of the procedure ensures that tearing and hemorrhage are kept to a minimum and reduces the risk of deep tears or significant hemorrhage, which increase the likelihood of restricture or rectal perforation. Adjunct therapy should include administration of broad-spectrum antibiotics, a highly digestible (low-residue) diet, and use of lactulose or stool softeners to maintain a soft fecal consistency. The use of corticosteroids to reduce the occurrence of restricture has not been studied, and such therapy should be undertaken cautiously if rectal tears or bacterial contamination is suspected.


For most benign rectal strictures, the prognosis is guarded to fair, because balloon procedures may allow return to near normal functionality; however, unless the predisposing cause of the stricture is corrected, it is likely to recur. The risk of severe complications after balloon procedures is lower than for surgical repair techniques, primarily because the risk of inducing fecal incontinence is greatly diminished. The prognosis for all neoplastic strictures is poor, owing both to the difficulty in managing the primary problem and to the poor response to balloon or other management techniques.



Constipation; Cause

The etiopathogenesis of idiopathic megacolon is still incompletely understood. Several reviews have emphasized the importance of considering an extensive list of differential diagnoses (e. g., neuromuscular, mechanical, inflammatory, metabolic and endocrine, pharmacologic, environmental, and behavioral causes) for the obstipated cat (Box Differential Diagnosis of Constipation in the Cat). A review of published cases suggests that 96% of cases of obstipation are accounted for by idiopathic megacolon (62%), pelvic canal stenosis (23%), nerve injury (6%), or Manx sacral spinal cord deformity (5%). A smaller number of cases are accounted for by complications of colopexy (1%) and colonic neoplasia (1%); colonic hypo- or aganglionosis was suspected, but not proved, in another 2% of cases. Inflammatory, pharmacologic, and environmental and behavioral causes were not cited as predisposing factors in any of the original case reports. Endocrine factors (e. g., obesity, hypothyroidism) were cited in several cases, but were not necessarily impugned as part of the pathogenesis of megacolon. It is important to consider an extensive list of differential diagnoses in an individual animal, but it should be kept in mind that most cases are idiopathic, orthopedic, or neurologic in origin. Behavioral (e. g., stress) or environmental (e. g., competition for the litter box) factors, or both, may play an important role in the development of this lesion, but they have not been very well characterized in retrospective or prospective studies.

Differential Diagnosis of Constipation in the Cat

Neuromuscular Dysfunction

Colonic smooth muscle: idiopathic megacolon, aging

Spinal cord disease: lumbosacral disease, cauda equine syndrome, sacral spinal cord deformities (Manx cat)

Hypogastric or pelvic nerve disorders: traumatic injury, malignancy, dysautonomia

Submucosal or myenteric plexus neuropathy: dysautonomia, aging

Mechanical Obstruction

Intraluminal: foreign material (bones, plant material, hair), neoplasia, rectal diverticula, perineal hernia, anorectal strictures

Intramural: neoplasia

Extraluminal: pelvic fractures, neoplasia


Perianal fistula, proctitis, anal sac abscess, anorectal foreign bodies, perianal bite wounds

Metabolic and Endocrine

Metabolic: dehydration, hypokalemia, hypercalcemia Endocrine: hypothyroidism, obesity, nutritional secondary hyperparathyroidism


Opioid agonists, cholinergic antagonists, diuretics, barium sulfate, phenothiazines

Environmental and Behavioral

Soiled litter box, inactivity, hospitalization, change in environment

Constipation: PaThophysiology

Megacolon develops through two pathologic mechanisms: (1) dilation and (2) hypertrophy. Dilated megacolon is the end stage of colonic dysfunction in idiopathic cases. Cats affected with idiopathic dilated megacolon have permanent loss of colonic structure and function. Medical therapy may be attempted in such cases, but most affected cats eventually require colectomy. Hypertrophic megacolon, on the other hand, develops as a consequence of obstructive lesions (e. g., malunion of pelvic fractures, tumors, foreign bodies).

Hypertrophic megacolon may be reversible with early pelvic osteotomy, or it may progress to irreversible dilated megacolon if appropriate therapy is not instituted.

Constipation and obstipation are earlier manifestations of the same problem. Constipation is defined as infrequent or difficult evacuation of feces but does not necessarily imply a permanent loss of function. Many cats suffer from one or two episodes of constipation without further progression. Intractible constipation that has become refractory to cure or control is referred to as obstipation. The term obstipation implies a permanent loss of function. A cat is assumed to be obstipated only after several consecutive treatment failures. Recurring episodes of constipation or obstipation may culminate in the syndrome of megacolon.

The pathogenesis of idiopathic dilated megacolon appears to involve functional disturbances in colonic smooth muscle. In vitro isometric stress measurements have been performed on colonic smooth muscle obtained from cats suffering from idiopathic dilated megacolon. Megacolonic smooth muscle develops less isometric stress in response to neurotransmitter (acetylcholine, substance P, cholecystokinin), membrane depolarization (potassium chloride), or electrical field stimulation, when compared with healthy controls. Differences have been observed in longitudinal and circular smooth muscle from the descending and ascending colon. No significant abnormalities of smooth muscle cells or of myenteric neurons were observed on histologic evaluation. These studies initially suggested that the disorder of feline idiopathic megacolon is a generalized dysfunction of colonic smooth muscle and that treatments aimed at stimulating colonic smooth muscle contraction might improve colonic motility. More recent studies suggest that the lesion may begin in the descending colon and progress to involve the ascending colon over time.

Clinical Examination

History Constipation, obstipation, and megacolon mav in observed in cats ol any age, sex, or breed; however, most cases are observed in middle-aged (mean: 5.8 vears) male cats (70% male, 30% female) of domestic shorthair (DSH) (46%), domestic longhair (15%), or Siamese (12%) breeding. Affected cats are usually presented for reduced, absent, or painful defecation for a period of time ranging from days to weeks or months. Some cats are observed making multiple, unproductive attempts to defecate in the litter box, whereas other cats may sit in the litter box for prolonged periods of time without assuming a defecation posture. Dry, hardened feces are observed inside and outside of the litter box. Occasionally, chronically constipated cats have intermittent episodes of hematochezia or diarrhea due to the mucosal irritant effect of fecal concretions. This may give the pet owner the erroneous impression that diarrhea is the primary problem. Prolonged inability to defecate may result in other systemic signs, including anorexia, lethargy, weight loss, and vomiting.

Physical examination

Colonic impaction is a consistent physical examination finding in affected cats. Other findings will depend upon the severity and pathogenesis of constipation. Dehydration, weight loss, debilitation, abdominal pain, and mild to moderate mesenteric lymphadenopathy may be observed in cats with severe idiopathic megacolon. Colonic impaction may be so severe in such cases as to render it difficult to differentiate impaction from colonic, mesenteric, or other abdominal neoplasia. Cats with constipation due to dysautonomia may have other signs of autonomic nervous system failure, such as urinary and fecal incontinence, regurgitation due to megaesophagus, mydriasis, decreased lacrimation, prolapse of the nictitating membrane, and bradycardia. Digital rectal examination should be carefully performed with sedation or anesthesia in all cats. Pelvic fracture malunion may be detected on rectal examination in cats with pelvic trauma. Rectal examination might also identify other unusual causes of constipation, such as foreign bodies, rectal diverticula, stricture, inflammation, or neoplasia. Chronic tenesmus may be associated with perineal herniation in some cases. A complete neurologic examination, with special emphasis on caudal spinal cord function, should be performed to identify neurologic causes of constipation (e. g., spinal cord injury, pelvic nerve trauma, Manx sacral spinal cord deformity).

Diagnosis of Constipation

Although most cases of obstipation and megacolon are unlikely to have significant changes in laboratory data (e. g., complete blood count, serum chemistry, urinalysis), these tests should nonetheless be performed in all cats presented for constipation. Metabolic causes of constipation, such as dehydration, hypokalemia, and hypercalcemia may be detected in some cases. Basal serum T4 concentration and other thyroid function tests should also be considered in cats with recurrent constipation and other signs consistent with hypothyroidism. Although hypothyroidism was documented in only one case of obstipation and megacolon, obstipation is a frequent clinical sign in kittens affected with congenital or juvenile-onset hypothyroidism. Constipation could also theoretically develop after successful treatment of feline hyperthyroidism.

Abdominal radiography should be performed in all constipated cats to characterize the severity of colonic impaction and to identify predisposing factors such as intraluminal radioopaque foreign material (e. g., bone chips), intraluminal or extraluminal mass lesions, pelvic fractures, and spinal cord abnormalities. The radiographic findings of colonic impaction cannot be used to distinguish between constipation, obstipation, and megacolon in idiopathic cases. First or second episodes of constipation in some cats may be severe and generalized but may still resolve with appropriate treatment.

Ancillary studies may be indicated in some cases. Extraluminal mass lesions may be further evaluated by abdominal uhrasonography and guided biopsy, whereas intraluminal mass lesions are best evaluated by endoscopy. Colonoscopy mav also be used to evaluate the colon and anorecuim for suspected inflammatory lesions, strictures, sacculations, and diverticula. Barium enema contrast radiography may be used if colonoscopy is not possible. Both colonoscopy and barium enema contrast radiography will require general anesthesia and evacuation of impacted feces. Cerebrospinal fluid analysis, CT or MRI, and electrophysiologic studies should be considered in animals with evidence of neurologic impairment. Finally, colonic biopsy or anorectal manometry will be necessary to diagnose suspected cases of aganglionic megacolon.

Treatment of Constipation

The specific therapeutic plan will depend upon the severity of constipation and the underlying cause (Table Drug Index — Constipation). Medical therapy may not be necessary with first episodes of constipation. First episodes are often transient and resolve without therapy. Mild to moderate or recurrent episodes of constipation, on the other hand, usually require some medical intervention. These cases may be managed, often on an outpatient basis, with dietary modification, water enemas, oral or suppository laxatives, colonic prokinetic agents, or a combination of these therapies. Severe cases of constipation usually require brief periods of hospitalization to correct metabolic abnormalities and to evacuate impacted feces using water enemas, manual extraction of retained feces, or both. Follow-up therapy in such cases is directed at correcting predisposing factors and preventing recurrence. Subtotal colectomy will become necessary in cats suffering from obstipation or idiopathic dilated megacolon. These cats, by definition, are unresponsive to medical therapy. Although pelvic osteotomy is described for cats with pelvic canal stenosis, subtotal colectomy is an effective treatment and is considered the standard of surgical care.

Drug Index — Constipation

Drug Classification And Example Dose
Rectal Suppositories
Dioctyl sodium sulfosuccinate (Colace, Mead Johnson) 1-2 pediatric suppositories
Glycerin 1-2 pediatric suppositories
Bisacodyl (Dulcolox; Boehringer Ingelheim) 1-2 pediatric suppositories
Warm tap water 5-10 mL / kg
Warm isotonic saline 5-10 mL / kg
Dioctyl sodium sulfosuccinate (Colace, Mead Johnson) 5-10 mL / cat
Dioctyl sodium sulfosuccinate (Disposaject, PittmanMoore) 250 mg (12 ml) given pre rectum
Mineral oil 5-10 mL / cat
Lactulose (Cephulac. Merrell Dow; Duphalac, Reid Rowell) 5-10 mL / cat
Oral Laxatives
Bulk laxatives
Psyllium (Metamucil, Searle) 1-4 tsp mixed with food, every 24 or 12 hours
Canned pumpkin 1-4 tsp mixed with food, every 24 hours
Coarse wheat bran 1-4 tblsp mixed with food, every 24 hours
Emollient laxatives
Dioctyl sodium sulfosuccinate (Colace, Mead Johnson) 50 mg orally, every 24 hours
Dioctyl calcium sulfosuccinate (Surfax, Hoechst) 50 mg orally, every 24 or 12 hours as needed
Lubricant laxatives
Mineral oil 10-25 ml orally, every 24 hours
Petrolatum (Laxatone, Evsco) 1-5 ml orally, every 24 hours
Hyperosmotic laxatives
Lactulose (Cephulac, Merrell Dow, Duphalac, Reid Rowell) 0.5 ml / kg orally, every 12 to 8 hours as needed
Stimulant laxatives
Bisacodyl (Dulcolax, Boehringer Ingelheim) 5 mg orally, every 24 hours
Prokinetic Agents
Cisapride (compounding pharmacies) 0.1-1.0 mg / kg orally every 12 to 8 hours
Tegaserod (Zelnorm, Novartis) – dogs 0.05-0.10 mg / kg orally, twice a day
Ranitidine (Zantac, Claxo SmithKline) 1.0-2.0 mg / kg orally, every 12 to 8 hours
Nizatidine (Axid, Eli Lilly) 2.5-5.0 mg / kg orally, every 24 hours


Removal of Impacted Feces

Removal of impacted feces may be accomplished through the use of rectal suppositories, enemas, or manual extraction.

Rectal suppositories

A number of pediatric rectal suppositories are available for the management of mild constipation. These include dioctyl sodium sulfosuccinate (emollient laxative), glycerin (lubricant laxative), and bisacodyl (stimulant laxative). The use of rectal suppositories requires a compliant pet and pet owner. Suppositories can be used alone or in conjunction with oral laxative therapy.


Mild to moderate or recurrent episodes of constipation may require administration of enemas, manual extraction of impacted feces, or both. Several types of enema solutions may be administered, such as warm tap water (5 to 10 mL / kg), warm isotonic saline (5 to 10 mL / kg), dioctyl sodium sulfosuccinate (5 to 10 mL / cat), mineral oil (5 to 10 mL / cat), or lactulose (5 to 10 mL / cat). Enema solutions should be administered slowly with a well-lubricated 10 to 12F rubber catheter or feeding tube. Enemas containing sodium phosphate are contraindicated in cats because of their propensity for inducing severe hypernatremia, hyperphos-phatemia, and hypocalcemia in this species.

Manual extraction

Cases unresponsive to enemas may require manual extraction of impacted feces. Cats should be adequately rchydrated and then anesthetized with an endotracheal tube in place to prevent aspiration should colonic manipulation induce vomiting. Water or saline is infused into the colon while the fecal mass is manually reduced by abdominal palpation. Sponge forceps may also be introduced rectally (with caution) to break down the fecal mass. It may be advisable to evacuate the fecal mass over a period of several days to reduce the risks of prolonged anesthesia and perforation of a devitalized colon. If this approach fails, colotomy may be necessary to remove the fecal mass. Laxative or prokinetic therapy (or both) may then be instituted once the fecal mass has been removed.

Laxative Therapy

Laxatives promote evacuation of the bowel through stimulation of fluid and electrolyte transport or increases in propulsive motility. They are classified as bulk-forming, emollient, lubricant, hyperosmotic, or stimulant laxatives according to their mechanism of action. Hundreds of products are available for the treatment of constipation. Table Drug IndexConstipation summarizes those products that have been used with some success in cats.

Bulk-forming laxatives

Most of the available bulk-forming laxatives are dietary fiber supplements of poorly digestible polysaccharides and celluloses derived principally from cereal grains, wheat bran, and psyllium. Some constipated cats will respond to supplementation of the diet with one of these products, but many require adjunctive therapy (e. g., other types of laxatives or colonic prokinetic agents). Dietary fiber is preferable because it is well tolerated, more effective, and more physiologic than other laxatives. Fiber is classified as a bulk-forming laxative, although it has many other properties. The beneficial effects of fiber in constipation include increased fecal water content, decreaseo intestinal transit time, and increased frequency of defecation. Fiber supplemented diets are available commercially, or the pet owner may wish to add psyllium (1 to 4 teaspoon per meal), wheat bran (1 to 2 tablespoon per meal), or pumpkin (1 to 4 tablespoon per meal) to canned cat food. Cats should be well hydrated before commencing fiber supplementation to maximize the therapeutic effect. Fiber supplementation is most beneficial in mildly constipated cats, prior to the development of obstipation and megacolon. In obstipated and megacolon cats, fiber may in fact be detrimental. Low-residue diets may be more beneficial in obstipated and megacolonic cats.

Emollient laxatives

Emollient laxatives are anionic detergents that increase the miscibility of water and lipid in digesta, thereby enhancing lipid absorption and impairing water absorption. Dioctyl sodium sulfosuccinate and dioctyl calcium sulfosuccinate are examples of emollient laxatives available in oral and enema form. Anecdotal experience suggests that dioctyl sodium sulfosuccinate therapy may be most useful in animals with acute but not chronic constipation. As with bulk-forming laxatives, animals should be well hydrated before emollient laxatives are administered. It should be noted that clincial efficacy has not been definitively established for the emollient laxatives. Dioctyl sodium sulfosuccinate, for example, inhibits water absorption in isolated colonic segments in vitro, but it may be impossible to achieve tissue concentrations great enough to inhibit colonic water absorption in vivo. Dioctyl sodium sulfosuccinate at a dose of 30 mg / kg / day had no effect on fecal consistency in beagle dogs. Further studies are required to determine the clinical efficacy and therapeutic role of dioctyl sodium sulfosuccinate in the management of the constipated cat.

Lubricant laxatives

Mineral oil and white petrolatum are the two major lubricant laxatives available for the treatment of constipation. The lubricating properties of these agents impede colonic water absorption and permit greater ease of fecal passage. These effects are usually moderate, however, and, in general, lubricants are beneficial only in mild cases of constipation. Mineral oil use should probably be limited to rectal administration because of the risk of aspiration pneumonia with oral administration, especially in depressed or debilitated cats.

Hyperosmotic laxatives

This group of laxatives consists of the poorly absorbed polysaccharides (e. g., lactose, lactulose), the magnesium salts (e. g., magnesium citrate, magnesium hydroxide, magnesium sulfate), and the polyethylene glycols. Lactose is not effective as a laxative agent in all cats. Lactulose is the most effective agent in this group. The organic acids produced from lactulose fermentation stimulate colonic fluid secretion and propulsive motility. Lactulose administered at a dose of 0.5 mL / kg body weight every 8 to 12 hours fairly consistently produces soft feces in the cat. Many cats with recurrent or chronic constipation have been well managed with this regimen of lactulose. The dose may have to be tapered in individual cases if flatulence and diarrhea become excessive. Magnesium salts are not currently recommended in the treatment of feline constipation and idiopathic megacolon. Some veterinarians have reported anecdotal successes with the polyethylene glycols.

Stimulant laxatives

The stimulant laxatives (bisacodyl, phenolphthalein, castor oil, cascara, senna) are a diverse group of agents that have been classified according to their ability to stimulate propulsive motility. Bisacodyl, for example, stimulates NO-mediated epithelial cell secretion and myenteric neuronal depolarization. Diarrhea results from the combined effect of increased mucosal secretion and colonic propulsion. Bisacodyl (at a dose of 5 mg orally, every 24 hours) is the most effective stimulant laxative in the cat. It may be given individually or in combination with fiber supplementation for long-term management of constipation. Daily administration of bisacodyl should probably be avoided, however, because of injury to myenteric neurons with chronic use.

Colonic Prokinetic Agents

Previous studies of feline colonic smooth muscle function have suggested that stimulation of colonic smooth muscle contraction might improve colonic motility in cats affected with idiopathic dilated megacolon. Unfortunately, many of the currently available gastrointestinal prokinetic agents have not proved useful in the therapy of feline constipation, either because of significant side effects (e. g., bethanechol) or because the prokinetic effect is limited to the proximal gastrointestinal tract (e. g., metoclopramide, domperidone, erythromycin). The 5-HT4 serotonergic agonists (e. g., cisapride, prucalopride, tegaserod, mosapride) appear to have the advantage of stimulating motility from the gastroesophageal sphincter to the descending colon with relatively few side effects. Cisapride, for example, increases gastroesophageal sphincter pressure, promotes gastric emptying, and enhances small intestinal and colonic propulsive motility. Cisapride enhances colonic propulsive motility through activation of colonic neuronal or smooth muscle 5-HT receptors in a number of animal species. In vitro studies have shown that cisapride stimulates feline colonic smooth muscle contraction, although it has not yet been conclusively shown that cisapride stimulates feline colonic propulsive motility in vivo. A large body of anecdotal experience suggests that cisapride is effective in stimulating colonic propulsive motility in cats affected with mild to moderate idiopathic constipation; cats with long-standing obstipation and megacolon are not likely to show much improvement with cisapride therapy. Cisapride was widely used in the management of canine and feline gastric emptying, intestinal transit, and colonic motility disorders throughout most of the 1990s. Cisapride was withdrawn from the American, Canadian, and certain Western European countries in July 2000 after reports of untoward cardiac side effects in human patients. Cisapride causes QT interval prolongation and slowing of cardiac repolarization via blockade of the rapid component of the delayed rectifier potassium channel (IKr). This effect may result in a fatal ventricular arrhythmia referred to as torsades de pointes. Similar effects have been characterized in canine cardiac Purkinje fibers, but in vivo effects have not yet been reported in dogs or cats. The withdrawal of cisapride has created a clear need for new gastrointestinal prokinetic agents, although cisapride continues to be available from compounding pharmacies throughout the United States. Two new prokinetic agents, tegaserod and prucalopride, are in differing stages of drug development and may prove useful in the therapy of gastrointestinal motility disorders of several animal species.

Tegaserod is a potent partial nonbenzamide agonist at 5-HT4 receptors and a weak agonist at 5-HT1D receptors. Tegaserod has definite prokinetic effects in the canine colon, but it has not yet been studied in the feline colon. Intravenous doses of tegaserod (0.03 to 0.3 mg / kg) accelerate colonic transit in dogs during the first hour after intravenous administration. Tegaserod at doses of 3 to 6 mg / kg orally has also been shown to normalize intestinal transit in opioid-induced bowel dysfunction in dogs, and it may prove useful in other disorders of intestinal ileus or pseudo-obstruction. Gastric effects of tegaserod have not been reported in the dog, so this drug may not prove as useful as cisapride in the treatment of delayed gastric emptying disorders. In vitro studies suggest that tegaserod does not prolong the QT interval or delay cardiac repolarization as has been occasionally reported with cisapride. Tegaserod was marketed under the trade name of Zelnorm in the United States in September 2002 for the treatment of constipation-predominant IBS in women. As with many other drugs in companion animal medicine, tegaserod has not been licensed for the treatment of canine or feline gastrointestinal motility disorders.

Prucalopride is a potent 5-HT4 receptor agonist that stimulates giant migrating contractions and defecation in the dog and cat. Prucalopride also appears to stimulate gastric emptying in the dog. In lidamidine-induced delayed gastric emptying in dogs, prucalopride (0.01 to 0.16 mg / kg) dose-dependendy accelerates gastric emptying of dextrose solutions. Prucalopride has not yet been marketed in the United States or elsewhere.

Misoprostol is a prostaglandin E, analogue that reduces the incidence of nonsteroidal anti-inflammatory drug (NSAID)-induced gastric injury. The main side effects of misoprostol therapy are abdominal discomfort, cramping, and diarrhea. Studies in dogs suggest that prostaglandins may initiate a giant migrating complex pattern and increase colonic propulsive activity. In vitro studies of misoprostol show that it stimulates feline and canine colonic smooth muscle contraction. Given its limited toxicity, misoprostol may be useful in cats (and dogs) with severe refractory constipation.

Ranitidine and nizatidine, classic histamine H2 receptor antagonists, may also stimulate canine and feline colonic motility. These drugs stimulate contraction apparently through inhibition of tissue acetylcholinesterase and accumulation of acetylcholine at the motor endplate. It is not yet clear how effective these drugs are in vivo, although both drugs stimulate feline colonic smooth muscle contraction in vitro. Cimetidine and famotidine, members of the same classification of drug, are without this effect.

Constipation; Surgery

Colectomy should be considered in cats that are refractory to medical therapy. Cats have a generally favorable prognosis for recovery after colectomy, although mild to moderate diarrhea may persist for weeks to months postoperatively in some cases. Although pathologic hypertrophy may be reversible with early pelvic osteotomy in some cases, subtotal colectomy is an effective treatment for this condition regardless of duration, and pelvic osteotomy is not required.

Prognosis of Constipation

Many cats have one or two episodes of constipation without further recurrence, although others may progress to complete colonic failure. Cats with mild to moderate constipation generally respond to conservative medical management (e. g., dietary modification, emollient or hyperosmotic laxatives, colonic prokinetic agents). Early use of colonic prokinetic agents (in addition to one or more laxative agents) is likely to prevent the progression of constipation to obstipation and dilated megacolon in these cats. Some cats may become refractory to these therapies, however, as they progress through moderate or recurrent constipation to obstipation and dilated megacolon. These cats eventually require colectomy. Cats have a generally favorable prognosis for recovery after colectomy, although mild to moderate diarrhea may persist for 4 to 6 weeks postoperatively in some cases.


Small Intestine: Special Tests

In cases of malabsorption, intestinal biopsy is usually necessary to obtain a definitive diagnosis. However, exocrine pancreatic insufficiency should be ruled out before biopsy, because signs of malabsorption are nonspecific. It is also well recognized that biopsies from up to 50% of patients are considered normal by light microscopy. Therefore, usually before biopsy, a number of indirect tests are performed to assess for intestinal damage, altered permeability, and dysfunction.

Diagnosis of Exocrine Pancreatic Insufficiency

Because the signs of exocrine pancreatic insufficiency cannot be distinguished from primary causes of small intestine, serum trypsin-like immunoreactivity (TLI) measurement must be performed in all cases.

Serum Folate and Cobalamin Concentrations

The assay of serum folate and cobalamin concentrations can be performed on the same serum sample taken for the trypsin-like immunoreactivity test. This assay has limited value in the diagnosis of small intestine diseases, but subnormal folate and cobalamin concentrations secondary to gastrointestinal disease may be detected. Cobalamin deficiency is more common, and the response to treatment of the underlying gastrointestinal disease may be suboptimal if this vitamin deficiency is not corrected. In dogs, the severe cobalamin deficiency recognized in several breeds has been linked to an IF-cobalamin receptor deficiency. Cobalamin deficiency is a common sequel to small intestinal disease in cats, and systemic metabolic consequences have been recognized. Determination of the serum folate and cobalamin concentrations is not recommended for the diagnosis of canine SIBO.

Indirect Assessment of Intestinal Absorption

Attempts to assess intestinal function by measuring the mediated absorption of numerous substrates (e. g., lactose, glucose, vitamin A, D-xylose, triglyceride, and starch tolerance tests) are no longer performed because of a similar lack of sensitivity and specificity.

Xylose/3-O-methyl-D-glucose test The differential absorption of these two sugars eliminates the nonmucosal effects that blight the xylose test, and initial results suggest that the test may be of value in dogs and cats.

Intestinal Permeability

Intestinal permeability is an index of mucosal integrity and is assessed by measuring unmediated uptake of nondigestible probe markers. Tests use a nonmetabolizable probe marker that is excreted in the urine. The permeability probe chromium-51-labeled ethylenediamine tetraacetic acid (51Cr-EDTA) was used in original studies, but the need for a gamma-emitter limited its safe use.

Errors related to nonmucosal factors (including the gastric emptying rate, intestinal transit time, and completeness of urine collection) can be eliminated by concurrently measuring the absorption of two probes with different pathways of absorption. Calculation of their excretion ratio eliminates errors from extramucosal factors because both probes should be affected equally. The ratio, which is altered by villus atrophy or epithelial damage or both, offers a simple, sensitive diagnostic test.

A 5-hour urine collection is performed after oral administration of two sugars. A number of candidates can be used for the probe molecules, and a mixture of one large simple sugar (e. g., lactulose, cellobiose, raffinose) and one small one (e. g., rhamnose, arabinose, mannitol) can be chosen. The cellobiose / mannitol excretion ratio and lactulose / mannitol ratio have been used in companion animals, but with advances in the high-performance liquid chromatography (HPLC) assay of these sugars, the Iactulose / rhamnose test has become the standard test of small intestine permeability.

Tests for Protein-Losing Enteropathy

Historically, intestinal protein loss has been detected by measuring the fecal loss of 51Cr-labeled albumin. The test is unpleasant to perform and potentially hazardous and has largely been discarded, although it remains the standard by which other tests, such as the assay of fecal alpha1-PI, are judged.

Breath Tests

Breath tests are used to assess bacterial metabolism in the gastrointestinal tract. Bacteria synthesize a gas, which is absorbed and excreted in breath. Breath hydrogen tests have been used most extensively because mammalian cells cannot produce hydrogen, and therefore any that is measured must be bacterial in origin. Such tests can assess carbohydrate malabsorption, bacterial colonization of the small intestine, and oro-cecal transit time.

A variety of protocols has been used, including xylose to assess malabsorption, lactulose to assess orocecal transit, and a test meal to assess small intestine bacterial fermentation. Also, a number of recent studies have attempted to standardize the techniques for companion animals. However, these techniques are not widely used even in referral centers.

Unconjugated Bile Salts

The principle of the serum conjugated bile acids test is that conjugated bile salts secreted into the intestine in bile are deconjugated by certain bacterial species and absorbed by the small intestine. Therefore, in theory, increases in small intestine bacterial numbers might result in an increase in serum unconjugated bile acids (SUBA). Preliminary work suggested that the test was sensitive and specific for canine SIBO, although a recent study has questioned its utility.

Miscellaneous Tests

A number of tests for intestinal bacterial metabolites have been devised to detect SIBO. These include the nitrosonaphthol test, urinary indican excretion, bacterial release of sulfapyridine from sulfasalazine, and bacterial release of p-amino benzoic acid (PABA) from a bile salt conjugate (PABA-UDCA). However, none of these tests are widely used in companion animals.


Inflammatory Bowel Disease

Inflammatory bowel disease is a collective term that describes a group of disorders characterized by persistent or recurrent gastrointestinal signs and histologic evidence of intestinal inflammation on biopsy material. The disease bears little resemblance to inflammatory bowel disease (Crohn’s disease and ulcerative colitis) of humans, and indiscriminate use of the term “IBD” is no more useful than a dermatologist making a diagnosis of “chronic dermatitis. Although a number of recognized diseases are associated with chronic intestinal inflammation (Box Causes of Chronic Small Bowel Inflammation), the cause of idiopathic inflammatory bowel disease is, by definition, unknown. Variations in the histologic appearance of the inflammation suggest that idiopathic inflammatory bowel disease is not a single disease entity, and the nomenclature reflects the predominant cell type present. Lymphocytic-plasmacytic enteritis (lymphocytic-plasmacytic enteritis) is the most common form reported; eosinophilic (gastro-) enteritis (EGE) is less common; and granulomatous enteritis is rare. Neutrophilic infiltration is a feature of human inflammatory bowel disease but is infrequent in idiopathic inflammatory bowel disease of dogs and cats.

Causes of Chronic Small Bowel Inflammation

Chronic infection

  • Giardia sp.
  • Histoplasma sp.
  • Toxoplasma sp.
  • Mycobacteria sp.
  • Protothecosis
  • Pythiosis
  • Pathogenic bacteria (Campylobacter, Salmonella spp., pathogenic Escherichia coli)

Food allergy

Small bowel inflammation associated with other primary gastrointestinal diseases

  • Lymphoma
  • Lymphangiectasia

Idiopathic causes

  • Lymphocytic-plasmacytic enteritis (lymphocytic-plasmacytic enteritis)
  • Eosinophilic gastroenterocolitis (EGE)
  • Granulomatous enteritis (same as regional enteritis?)

Clinical Presentation

Idiopathic inflammatory bowel disease is a common cause of chronic vomiting and diarrhea in dogs and cats, but its true incidence is unknown. In reality it is often overdiagnosed because of difficulties in interpretation of histopathologic specimens and failure to eliminate adequately other causes of mucosal inflammation. No apparent gender predisposition occurs in dogs and cats, but in both species inflammatory bowel disease is most common in middle-aged animals. gastrointestinal signs, which may have been variably controlled by dietary manipulation, are sometimes seen from an earlier age. Although inflammatory bowel disease can potentially occur in any dog or cat breed, certain predispositions are recognized, such as lymphocytic-plasmacytic enteritis in German shepherds and Siamese cats, lymphoproliferative enteropathy in basenjis, and protein-losing enteropathy / protein-losing nephropathy (protein-losing enteropathy / PLN) in soft-coated wheaten terriers. Shar Peis often have a severe lymphocytic-plasmacytic enteritis with hypoproteinemia and extremely low serum cobalamin concentrations. In cats an association, called triaditis, has been reported for inflammatory bowel disease, lymphocytic cholangitis, and chronic pancreatitis.

Clinical Signs Associated with Inflammatory Bowel Disease

Vomiting of bile with or without hair in cats and grass in dogs


Small intestinal — type diarrhea

  • Large volume
  • Watery
  • Melena

Thickened bowel loops

Large intestinal — type diarrhea

  • Hematochezia
  • Mucoid stool
  • Frequency and tenesmus

Abdominal discomfort / pain

Excessive borborygmi and flatus

Weight loss

Altered appetite

  • Polyphagia
  • Decreased appetite / anorexia
  • Eating grass

Hypoproteinemia / ascites

Vomiting and diarrhea are the most common clinical signs, but an individual case may show some or all of the signs in Box Clinical Signs Associated with Inflammatory Bowel Disease.Sometimes an obvious precipitating event (e. g., stress, dietary change) is present in the history, but clinical signs may wax and wane. The nature of signs crudely correlates with the region of the gastrointestinal tract affected: gastric signs are more common if gastric or upper small intestine inflammation is present; in cats, vomiting is often the predominant sign of small intestinal IBD; and Li-type diarrhea may be the result of colonic inflammation or may result from prolonged small intestine diarrhea. The presence of blood in the vomit or diarrhea is associated with more severe disease, especially eosinophilic inflammatory infiltrates. Severe disease is associated with weight loss and protein-losing enteropathy, with consequent hypoproteinemia and ascites. Appetite is variable; polyphagia may be present in the face of significant weight loss, whereas anorexia occurs with severe inflammation. Milder inflammation may not affect appetite, although postprandial pain can be significant even without other signs. Systemic consequences of inflammatory bowel disease can occur, although reports are sparse.

Etiology and Pathogenesis

The underlying etiology of small animal inflammatory bowel disease is unknown, and comparisons have been made with similar human conditions. In this regard, the breakdown of immunologic tolerance to luminal antigens (bacteria and dietary components) is thought to be critical, perhaps resulting from disruption of the mucosal barrier, dysregulation of the immune system, or disturbances in the intestinal microflora. Therefore antigens derived from the endogenous microflora are likely to be important in disease pathogenesis, and a potential role for diet-related factors is suggested by the clinical benefit of dietary therapy in some cases of canine inflammatory bowel disease.

Genetic factors are likely to contribute to the pathogenesis of inflammatory bowel disease, and in humans the strongest associations are with genes of the human MHC (human leukocyte antigen [HLA]). Furthermore, some human patients with Crohn’s disease have a mutation in the NOD2 gene on chromosome 16. This gene’s product detects bacterial lipopolysac-charide and can activate the proinflammatory transcription factor NF-kB. Such a link may explain the development of aberrant immune responses to bacteria in certain individuals. Genetic factors are also likely in dogs, given the recognized breed predispositions, although studies are lacking


Intestinal biopsy is necessary for a definitive diagnosis of inflammatory bowel disease, although the clinical signs and physical findings may be suggestive (see Box Clinical Signs Associated with Inflammatory Bowel Disease). The term idiopathic inflammatory bowel disease is limited to cases in which histologic evidence of inflammation is found without an obvious underlying cause. All other etiologies, including infectious, diet-responsive, and antibacterial-responsive conditions, should be excluded. Therefore before intestinal biopsy is undertaken, laboratory evaluation and diagnostic imaging are performed. Such tests cannot provide a definitive diagnosis of inflammatory bowel disease, but they can help eliminate the possibility of anatomic intestinal disease (e. g., tumor, intussusception), extraintestinal disease (e. g., pancreatitis), and known causes of intestinal inflammation. Furthermore, by determining whether focal or diffuse intestinal disease is present, the clinician can choose the most appropriate method of intestinal biopsy.

Hematology Occasionally neutrophilia, with or without a left shift, is noted. Eosinophilia may suggest EGE, but it is neither pathognomonic nor invariably present. Anemia may reflect chronic inflammation or chronic blood loss.

Serum biochemistry No pathognomonic changes are seen in 1BD, but diseases of other organ systems should be recognized and excluded. Hypoalbuminemia and hypoglobulinemia” are characteristic of protein-losing enteropathy, whereas hypocholesterolemia may suggest malabsorption. Intestinal inflammation in dogs may cause a “reactive hepatopathy, ” with mild elevations in liver enzymes (alanine aminotransferase (ALT] and alkaline phosphatase [ALP]). In contrast, because of the shorter half-lives of liver enzymes in cats, increases are more likely to be the result of hepatocellular or cholestatic disease.

Fecal examination Fecal examination is most important for eliminating other causes of mucosal inflammation, such as nematodes (e. g., Trichuris, Uncinaria, Ancylostoma, and Strongyloides spp.), Giardia infection, and bacterial infection (e. g., Salmonella or Campylobacter spp. or clostridia). Given that fecal parasitology may not always detect Giardia organisms, empirical treatment with fenbendazole is recommended in all cases.

Increased fecal alphap1-PI concentrations would be expected in dogs with inflammatory bowel disease, as well as significant intestinal protein loss even before hypoproteinemia develops (see above).

Folate and cobalamin Serum concentrations of both these vitamins are affected by intestinal absorption, therefore proximal, distal, or diffuse inflammation can result in subnormal folate concentrations (proximal inflammation) or cobalamin concentrations (distal inflammation) or both (diffuse inflammation). Although such alterations are not pathognomonic for inflammatory bowel disease, deficiencies may require therapeutic correction. Measurement of serum folate and cobalamin is now commercially available for cats, and cobalamin deficiency associated with inflammatory bowel disease has been documented. Cobalamin deficiency has systemic metabolic consequences, and anecdotal evidence suggests that deficient cats with inflammatory bowel disease require parenteral supplementation to respond optimally to immunosuppression.

Diagnostic imaging Imaging studies document whether focal or diffuse disease is present and whether other abdominal organs are affected. Such information, in conjunction with specific clinical signs, allows the clinician to choose the most appropriate method of biopsy. Plain radiographs may be useful for detecting anatomic intestinal disease; contrast studies rarely add further information. Ultrasonographic examination is superior to radiography for documenting focal anatomic intestinal disease and is particularly useful in cats with inflammatory bowel disease. Ultrasonography permits evaluation of intestinal wall thickness and can document mesenteric lymphadenopathy. Ultrasound-guided fine needle aspiration (FNA) can provide samples for cytologic analysis, which may aid in diagnosis.

Intestinal biopsy Intestinal biopsy is necessary to document intestinal inflammation. Endoscopy is the easiest method of biopsy, but it has limitations, because samples are superficial and in m6st cases can be collected only from the proximal small intestine. In some cases exploratory laparotomy and full-thickness biopsy are necessary, although the procedures are more invasive and can be problematic if severe hypoproteinemia is present. These techniques may be more suitable for cats, given the tendency in this species for multiorgan involvement.

Histopathologic assessment of biopsy material remains the gold standard for inflammatory bowel disease diagnosis, and the pattern of histopathologic change depends on the type of inflammatory bowel disease present. However, the limitations of histopathologic interpretation of intestinal biopsies are recognized. The quality of specimens can vary, agreement between pathologists is poor, and differentiation between normal specimens and those showing inflammatory bowel disease and even lymphoma can be difficult. Grading schemes for the histopathologic diagnosis of inflammatory bowel disease have been suggested, but these have not yet been widely adopted.

IBD activity index In humans, activity indices are used to quantify the severity of inflammatory bowel disease; this helps practitioners to assess the response to treatment and to make a prognosis by allowing comparisons between published studies in the literature. Recently an activity index was suggested for canine inflammatory bowel disease, and this may aid disease classification in the future.

Other diagnostic investigations Given the limitations of histopathology, other modalities are required. One approach would be the use of immunohistochemistry or flow cytometry to analyze immune cell subsets. However, such techniques are labor intensive and poorly standardized and are unlikely to be generally available in the foreseeable future.


Whatever the type of inflammatory bowel disease, treatment usually involves a combination of dietary modification and antibacterial and immunosuppressive therapy. Unfortunately, objective information on efficacy is lacking, and most recommendations are based on individual experience. The authors usually recommend a staged approach to therapy whenever possible; initial treatment involves antiparasiticides to eliminate the possibility of occult endoparasite infestation. Thereafter, sequential treatment trials with an exclusion diet and anlibacterials are pursued; immunosuppressive medication is used only as a last resort. However, in some cases, clinical signs or mucosal inflammation is so severe that early intervention with immunosuppressive medication is essential. If clinical signs are intermittent, the owners should keep a diary to provide objective information as to whether treatments produce genuine improvement.

Dietary modification The diets recommended for patients with inflammatory bowel disease are antigen limited, based on a highly digestible, single-source protein preparation. An exclusion diet trial should be undertaken to eliminate the possibility of an adverse food reaction, and most clients are happy to try this, given concerns over the side effects of immunosuppressive drugs. An easily digestible diet decreases the intestinal antigenic load and thus reduces mucosal inflammation. Such diets may also help resolve any secondary sensitivities to dietary components that may have arisen from disruption of the mucosal barrier. After the inflammation has resolved, the usual diet often can be reintroduced without fear of an acquired sensitivity.

Well-cooked rice is the preferred carbohydrate source because of its high digestibility, but potato, corn starch, and tapioca are also gluten free. Fat restriction reduces clinical signs associated with fat malabsorption. Modification of the n3 to n6 fatty acid ratio may also modulate the inflammatory response and may have some benefit both in treatment and in maintenance of remission, as in human inflammatory bowel disease. However, no direct studies have been done to prove a benefit in canine inflammatory bowel disease. Supplementation with oral folate and parenteral cobal-amin is indicated if serum concentrations are subnormal.

Antibacterial therapy Treatment with antimicrobials can be justified in inflammatory bowel disease, partly to treat secondary small intestinal bacterial overgrowth and partly because of the importance of bacterial antigens in the pathogenesis of inflammatory bowel disease. Ciprofloxacin and metronidazole are often used in human inflammatory bowel disease, and metronidazole is the preferred drug for small animals. The efficacy of metronidazole may not be related just to its antibacterial activity, because it may exert immunomodulatory effects on cell-mediated » immunity. Furthermore, other antibacterials (e. g., tylosin) may also have immunomodulatory effects and have efficacy in canine inflammatory bowel disease.

Immunosuppressive drugs The most important treatment modality in idiopathic inflammatory bowel disease is immunosuppression, although this should be used only as a last resort. In human inflammatory bowel disease, glucocorticoids and thiopurines (e. g., azathioprine, 6-mercaptopurine) are used most widely. In dogs, glucocorticoids are used most frequendy, and prednisone and prednisolone are the drugs of choice. Dexamethasone should be avoided, because it may have deleterious effects on enterocytes. In severe inflammatory bowel disease, prednisolone can be administered parenterally, because oral absorption may be poor. The initial dosage of 1 to 2 mg / kg given orally every 12 hours is given for 2 to 4 weeks and then tapered slowly over the subsequent weeks to months. In some cases therapy can be either completely withdrawn or at least reduced to a low maintenance dose given every 48 hours.

Signs of iatrogenic hyperadrenocorticism are common when the highest glucocorticoid dose is administered. However, signs are transient and resolve as the dosage is reduced. If clinical signs of inflammatory bowel disease consistently recur when the dosage is reduced, other drugs can be added to provide a steroid-sparing effect. Budesonide, an enteric-coated, locally active steroid that is destroyed 90% first-pass through the liver, has been successful in maintaining remission in human inflammatory bowel disease with minimal hypothalamic-pituitary-adrenal suppression. A preliminary study showed apparent efficacy in dogs and cats, but limited information is available on the use of this drug.

In dogs, azathioprine (2 mg / kg given orally every 24 hours) is commonly used in combination with prednisone / prednisolone when the initial response to therapy is poor or when glucocorticoid side effects are marked. However, azathioprine may have a delayed onset of activity (up to 3 weeks) and, given its myelosuppressive potential, regular monitoring of the hemogram is necessary. Azathioprine is not recommended for cats; chlorambucil (2 to 6 rag / m given orally every 24 hours until remission, followed by drug tapering) is a suitable alternative. Other immunosuppressive drugs are methotrexate, cyclophosphamide, and cyclosporine. Methotrexate is effective in the treatment of human Crohn’s disease, but it is not widely used in companion animals; it often causes diarrhea in dogs. Cyclophosphamide has few advantages over azathioprine and is rarely used. However, cyclosporine may show promise for the future, given its T lymphocyte-specific effects and efficacy in canine anal furunculosis. Unfortunately, it is expensive, and studies in human inflammatory bowel disease have shown variable efficacy and toxicity.

Novel therapies for inflammatory bowel disease Novel therapies are increasingly used for human inflammatory bowel disease in an attempt to target more accurately the underlying pathogenetic mechanisms. These therapies include new immunosuppressive drugs, monoclonal antibody therapy, cytokines and transcription factors, and dietary manipulation (Table Novel Therapies for Human Inflammatory Bowel Disease). In the future, such therapies may be adopted for small animal inflammatory bowel disease.

Novel Therapies for Human Inflammatory Bowel Disease

Therapy Mechanism Of Action
Drug Therapy
Tacrolimus Immunosuppressant macrolide
Mycophenolate Inhibits lymphocyte proliferation; reduces IFN-gamma production
Leukotriene antagonists (zileuton, verapamil) Inhibit arachidonic acid cascade
Prostaglandin (PG) targeting agents Mucosal protection from PC analogs; anti-inflammatory effects from PC antagonists
Thromboxane synthesis inhibitors Anti-inflammatory effects
Oxpentifylline Inhibits TNF-αlpha expression
Thalidomide Inhibits TNF-αlpha and IL-12 expression; reduces leukocyte migration; impairs angiogenesis
Bone Marrow and Stem Cell Transplantation
Bone marrow grafts Unknown; immunomodulation (?)
Dietary Manipulation
Protein hydrolysate diets “Hypoallergenic”
Fish oil therapy Diverts eicosanoid metabolism to LTB5 and PGE3
Short chain fatty acid therapy
Butyrate Provides nutrition for enterocytes
Probiotics and prebiotics Antagonize pathogenic bacteria; immunomodulatory effects
Cytokine Manipulation
Systemic IL-10 Down-modulatory cytokine
Anti-IL-2 monoclonal antibody (MAb) Counteracts proinflammatory effects
Anti-IL-2R (CD25) MAb Inhibits IL-2 effects
Anti-IL-12 MAb Counteracts proinflammatory effects
Anti-IL-11 MAb Downregulates TNF-alpha and IL-1beta
Recombinant IFN-alpha Anti-inflammatory; antiviral (?)
Anti-IFN-gamma MAb Immunomodulatory effect on Th 1 cells
Anti-TNF-αlpha MAb Counteracts proinflammatory effects; induces inflammatory cell apoptosis
Endothelial Cell Adhesion Molecules and Their Manipulation
ICAM-1 (antisense oligonucleotide) Reduces immune cell trafficking
Anti-alpha4 / beta7 MAb Reduces immune cell trafficking
Other Immune System Modulations
Intravenous immunoglobulin Saturates Fc receptors; other (?)
T-cell apheresis Immunomodulation
Anti-CD4 antibodies Immunomodulation
Transcription Factors
NF-kB antisense oligonucleotide Inhibits proinflammatory cytokine expression
ICAM-1 antisense oligonucleotide Reduces immune cell trafficking

IFN, interferon; IL, interleukin; ICAM, intercellular adhesion molecule; LTB, leukotriene B; MAb, monoclonal antibody; PG, prostaglandin; PGE, prostaglandin E; Th 1, T helper 1; TNF, tumor necrosis factor

Mycophenolate mofetil recently has been used to treat human inflammatory bowel disease, although its efficacy is variable. Drugs that target TNF-α (e. g., thalidomide and oxpentifylline) may be suitable for the treatment of canine inflammatory bowel disease because of the importance of this cytokine in disease pathogenesis. Human open-label trials have demonstrated a beneficial effect for thalidomide in refractory Crohn’s disease. Oxpentifylline has shown efficacy in studies in vitro, but clinical results have been less rewarding. Anti-TNF-alpha monoclonal antibody therapy, which has also undergone trials in human inflammatory bowel disease, has the additional beneficial effect of inducing apoptosis in inflammatory cells. Species-specific monoclonal antibodies will be needed for canine and feline inflammatory bowel disease.

Finally, modulation of the enteric flora with probiotics or prebiotics may have benefits in targeting the pathogenesis of inflammatory bowel disease. A probiotic is an orally administered living organism that exerts health benefits beyond those of basic nutrition. In addition to having direct antagonistic properties against pathogenic bacteria, they modulate mucosal immune responses by stimulating either innate (e. g., phagocytic activity) or specific ( e. g., secretory IgA) immune responses. However, care should be taken to select the most appropriate organisms, which are likely to vary between host species.

Prebiotics are selective substrates used by a limited number of “beneficial” species, which therefore cause alterations in the luminal microflora. The most frequently used prebiotics are nondigestible carbohydrates, such as lactulose, inulin, and FOS. Both probiotics and prebiotics can reduce intestinal inflammation in mouse models of inflammatory bowel disease. Preliminary placebo-controlled trials with probiotics and prebiotics in human inflammatory bowel disease patients have shown promising results, although similar trials in canine and feline inflammatory bowel disease are still awaited.

Lymphocytic-Plasmacytic Enteritis

Basenji Enteropathy

A severe, hereditary form of lymphocytic-plasmacytic enteritis has been well characterized in basenjis, although the mode of inheritance is unclear. It has been likened to immunoproliferative small intestinal disease (IPSID) in humans, because both conditions involve intense intestinal inflammation. However, IPSID is characterized by an associated gammopathy (alpha heavy chain disease) and a predisposition to lymphoma. Affected basenjis often have hyper-globulinemia but not alpha heavy chain disease and may be predisposed to lymphoma. The intestinal lesions in basenjis are characterized by increases in CD4+ and CD8+T cells.

Clinical Signs

Signs of chronic intractable diarrhea and emaciation are most rommon Lymphocytic-plasmacytic paslritis, with hypergasirmemia and mucosal hyperplasia, may be seen in addition to the enteropathy. Protein-losing enteropathy often occurs, with consequent hypoalbuminemia, although edema and ascites are not common. Clinical signs are usually progressive, and spontaneous intestinal perforation may occur.


The approach to diagnosis is the same as before, and ultimately depends on histopathological examination of biopsy specimens.


Treatment generally is unsuccessful, with dogs dying within months of diagnosis. However, early, aggressive combination treatment with prednisolone, antibiotics, and dietary modification may achieve remission in some cases.

Familial Protein-Losing Enteropathy and Protein-Losing Nephropathy in Soft-Coated Wheaten Terriers

Recendy a clinical syndrome unique to soft-coated wheaten terriers was characterized. Affected dogs present with signs of protein-losing enteropathy or PLN or both. A genetic basis is likely, and although the mode of inheritance is not yet clear, pedigree analysis of 188 dogs has demonstrated a common male ancestor. The disease is probably immune mediated, given the presence of inflammatory cell infiltration. A potential role for food hypersensitivity has been suggested, because affected dogs have demonstrated adverse reactions during provocative food trials and alterations in antigen-specific fecal IgE concentrations.

Clinical Signs

Signs of protein-losing enteropathy tend to develop at a younger age than PLN. Clinical signs of the protein-losing enteropathy include vomiting, diarrhea, weight loss, and pleural and peritoneal effusions. Occasionally, thromboembolic disease may occur.


Preliminary laboratory investigations, as in most dogs with protein-losing enteropathy, demonstrate panhypoproteinemia and hypocholesterolemia. In contrast, hypoalbuminemia, hypercholesterolemia, proteinuria, and ultimately azotemia are seen with PLN, Histopathologic examination of intestinal biopsy material reveals evidence of intestinal inflammation, villus blunting, and epithelial erosions, as well as dilated lymphatics and lipogranulomatous lymphangitis.

Treatment and Prognosis

The treatment for protein-losing enteropathy is similar to that described for general inflammatory bowel disease, but the prognosis is usually poor.

Eosinophilic Enteritis

Other Forms of Inflammatory Bowel Disease

Granulomatous Enteritis

Granulomatous enteritis is a rare form of inflammatory bowel disease characterized by mucosai infiltration with macrophages, resulting in the formation of granulomas. The distribution of inflammation can be patchy. This condition is probably the same as “regional enteritis,” in which ileal granulomas have been reported. Granulomatous enteritis has some histologic features in common with human Crohn’s disease, but obstruction, abscessation, and fistula formation are not noted. Conventional therapy is not usually effective, and the prognosis is guarded, although a combination of surgical resection and anti-inflammatory treatment was reported to be successful in one case. In cats, a pyogranulomatous transmurai inflammation has been associated with FIPV infection.

Proliferative Enteritis

Proliferative enteritis is characterized by segmental mucosal hypertrophy of the intestine. Although many species can be affected, the condition is most common in pigs. A similar but rare condition has been reported in dogs. There have been suggestions of an underlying infectious etiology, and Lawsonia intracellularis has been implicated, although this has not yet been proved. Other infectious agents with a proposed link are Campylobacter spp. and Chlamydia organisms

Veterinary Medicine


1. Define coma. How is it different from stupor or obtundation?

Coma is a disorder of consciousness defined by absence of awareness. The comatose animal appears asleep but is unable to respond to external stimuli or physiologic needs except by reflex activity. Stupor implies a state of depressed consciousness responsive to some stimuli, even though it may lapse back into unconsciousness when the stimulus is withdrawn. An animal is considered obtunded when it is not alert, when it is disinterested in its environment, or when it has a less than normal response to external stimuli.

2. What parts of the brain must be affected to produce coma?

Consciousness is maintained by sensory stimuli passing through the ascending reticular activating system (ARAS) from the rostral brainstem to the cerebral cortex. Decreased consciousness results from global lesions of both central hemispheres or a lesion affecting the ARAS.

3. How does coma change emergency management?

With any emergency, ensuring a patent airway, providing adequate ventilation, and restoring circulating blood volume are necessary to prevent irreversible organ damage. The danger with animals suffering coma from increased intracranial pressure is that any therapeutic maneuver or drugs that increase brain blood volume may lead to irreversible brainstem herniation. In administering fluids and analgesics and in handling such patients, care must be taken to prevent iatrogenic increases in intracranial pressure.

4. Describe the initial treatment of comatose patients.

1. Check for a patent airway and ensure that ventilation is adequate. The partial pressure of carbon dioxide in arterial blood (PaCO2) should be kept below 35 mmHg to reduce cerebral blood flow and minimize cerebral edema.

2. Ensure adequate perfusion and cardiovascular function. Fluid therapy should be individualized because supernormal blood volume and pressure contribute to increased intracranial pressure.

3. Elevate the head and avoid compressing the jugular veins with catheters, bandages, or positioning.

4. Maintain body temperature between 99°F and 102°F.

5. Control seizures with diazepam and, if necessary, phenobarbital.

6. Supply glucose as needed to maintain blood levels between 100 and 200 mg / dl.

7. Supplemental oxygen is important to ensure that the partial pressure of oxygen in arterial blood (PaO2) is above 60 mmHg. To avoid handling the animal’s head, an oxygen cage is preferable to face mask or nasal insufflation. Supplemental oxygen is not a substitute for ventilatory support and does not prevent hypercarbia. If the animal becomes hypercarbic, ventilatory support may be necessary to prevent increased intracranial pressure.

5. How does a history of trauma affect emergency management of coma?

Trauma causes structural damage to the brain through contusion, laceration, and hemorrhage. The presence of hemorrhage within the calvarium complicates therapy because aggressive fluid administration and oncotic agents such as mannitol may worsen intracranial hemorrhage. Patients with head trauma should be evaluated carefully for signs of focal neurologic deficits, which may indicate a space-occupying hemorrhage. The therapeutic goals in cases of head trauma include normalizing blood pressure by carefully titrating crystalloid fluid therapy; and maintaining tissue oxygenation through supplemental oxygen. Hyperventilation of head trauma patients is no longer recommended as the reduced blood flow may worsen ischemic injury.

6. When should mannitol be used in patients with increased intracranial pressure? What are the contraindications?

Mannitol, an osmotic diuretic, dehydrates tissues and is effective in reducing brain tissue volume. In the presence of diffuse cerebral edema, it is the most effective agent to decrease intracranial hypertension. Its effects depend on an intact blood-brain barrier. Mannitol may cause a dramatic elevation in intracranial pressure before it exerts its action and reduces tissue volume. Mannitol is contraindicated in patients with hypovolemic shock, active bleeding, or cardiovascular compromise. It may lead to volume overload and continued hemorrhage. If mannitol leaks into tissues, it may draw excessive fluids with it. This is a major concern with space-occupying intracranial hemorrhage. Mannitol may leak into the hematoma, bringing with it more fluid and further compressing the cerebrum.

7. What are the general pathophysiologic categories of coma?

• Bilateral, diffuse cerebral disease

• Compression of the rostral brainstem (midbrain, pons)

• Destructive lesions of the rostral brainstem

• Metabolic or toxic encephalopathies

8. Describe the diagnostic approach to comatose patients.

Potential brain disease first should be classified according to location of the lesion and clinical course over time. History, physical examination, and serial neurologic examinations are the most useful tools. The clinician should assume increased intracranial pressure (ICP) in any animal with altered consciousness. Care should be taken to avoid anything that would further increase intracranial pressure. Neurologic examination of the comatose patient should determine whether the lesion is focal, multifocal, or diffuse. The examination should be repeated frequently to determine whether the patient is improving, unchanged, or worsening. Primary central nervous system (CNS) disease causing coma and stupor should be considered when lateralizing signs or cranial nerve deficits are noted. Generalized disease of the cortex, cerebellum, or brainstem suggests a primary process outside the central nervous system. Diagnostic tests to look for evidence of toxic or metabolic disease or organ dysfunction help to differentiate primary CNS disease from other causes.

9. What initial laboratory evaluations should be performed in comatose patients?

Acute coma without a history of trauma suggests a toxic or metabolic disorder. Owners should be questioned about access to various drugs and poisons, including antidepressants, tranquilizers, alcohol, and ethylene glycol. Blood should be drawn immediately for serum chemistries, looking for evidence of organ dysfunction. Blood glucose can be tested easily on admission. Hypoglycemia may be treated quickly while its cause is investigated. A complete blood count may reveal signs of systemic infectious disease or thrombocytopenia. Urinalysis may reveal calcium oxalate crystals in cases of ethylene glycol intoxication, ammonium biurate crystals with hepatic insufficiency or casts and isosthenuria with acute renal failure. Activated clotting time (ACT) can be tested quickly to assess the intrinsic and common coagulation pathways; ACT is markedly prolonged in patients with acquired coagulopathies. Once the results of the screening tests have ruled out organ dysfunction and metabolic disease, cerebral spinal fluid analysis and either computed tomography or magnetic resonance imaging should be performed.

10. What are the major causes of coma?

Trauma Metabolic diseases
Intracranial mass lesions Diabetic mellitus
Abscess Hypoglycemia
Granuloma Hepatic encephalopathy
Neoplasia Myxedema coma
Uremic encephalopathy
Hemorrhage Drugs
Vascular disease Barbiturates
Coagulopathy Opiates
Hypertension Alcohol
Embolism Tranquilizers
Inflammatory diseases Bromides
Canine distemper Toxins
Granulomatous meningoencephalitis Ethylene glycol
Bacterial and fungal meningitis Lead
Protozoal infections Carbon monoxide

11. Describe changes in pupil size, position, and reaction to light that help to determine location and severity of disease.

Symmetric pupils with normal direct and consensual response to light require a functional ventrorostral brainstem, optic chiasm, optic nerves, and retinas. Increased intracranial pressure and hemiation of the cerebellum under the tentorium cerebelli stimulate the nuclei of the oculomotor (third cranial) nerve, causing brief miosis of both pupils. As the pressure increases and the nuclei are irreversibly damaged, the pupils become fixed and dilated.

Anisocoria suggests primary CNS disease. If the pupils are unequal at rest but both respond normally to light and darkness, a unilateral cerebrocortical lesion contralateral to the larger pupil is likely. If the dilated pupil does not respond to light or darkness, a unilateral oculomotor nerve III lesion is present.

Metabolic diseases may cause symmetric miosis, whereas increased sympathetic tone may cause symmetric mydriasis. However, both respond normally to light and darkness. Symmetric miosis with no response to light or darkness is seen with damage to the pons, iridospasm, or bilateral sympathetic denervation (Homer’s syndrome).

12. What abnormal breathing patterns may be seen in comatose patients?

Lesions of the medulla may damage the basic rhythmic control of inspiration and expiration. Functional transection of the brainstem cranial to the medulla allows ventilation to continue but in gasps rather than smooth inspiration and expiration. Damage to the midpons cranial to the apneustic area results in apneustic respiration, characterized by prolonged inspiration and short expiration. Cheyne-Stokes respiration is characterized by deep breathing followed by periods of apnea or shallow respirations and indicates that normal feedback mechanisms no longer function. With normal control of ventilation impaired, the deep breathing causes a drop in CO2 of arterial blood. This drop is detected by the respiratory center in the brainstem, and respiration is inhibited. Progressive deterioration or compression of the brainstem often causes a slowing of respirations associated with rapid progression toward death.

13. What is the oculovestibular reflex? How can it be used to assess comatose patients?

Infusion of cold water into an ear canal normally induces horizontal nystagmus with the fast phase opposite the direction of the infused ear. Infusion of warm water induces horizontal nystagmus with the fast phase toward the infused ear. This caloric test of the oculovestibular reflex requires integrity of the brainstem, medial longitudinal fasciculus, and cranial nerves III, IV, VI, and VIII.

14. What is hepatic encephalopathy?

Hepatic encephalopathy is a clinical syndrome characterized by abnormal mentation, altered consciousness, and impaired neurologic function in patients with advanced liver disease and severe portosystemic vascular shunts. Hepatic encephalopathy results when the liver fails to remove toxic products of gut metabolism from the portal blood. Ammonia, mercaptans, short-chain fatty acids, and gamma-aminobutyric acid (GABA) agonists have been implicated in the pathogenesis of hepatic encephalopathy.

15. How is hepatic encephalopathy diagnosed?

Hepatic encephalopathy is suspected in patients with bizarre behavior after eating or with altered mentation and elevated liver enzymes. With hepatocellular damage both alanine transferase (ALT) and aspartate transferase (AST) are elevated. With congenital portosystemic shunts or end-stage liver failure, ALT and AST may be normal. Chemical parameters that suggest poor liver function include low blood urea nitrogen, low blood glucose, low albumin, lower serum cholesterol, and elevated serum bilirubin. Fasting and postprandial serum bile acids are markedly abnormal. Blood ammonia levels may be normal or elevated. Nuclear scintigraphy may be used to quantitate blood flow around the liver with portosystemic shunts.

16. What treatments are available for patients with hepatic encephalopathy?

Withdrawal of dietary protein is necessary to prevent production of intestinal ammonia. A 10% povidone iodine enema solution rapidly suppresses colonic bacteria and impairs ammonia production. Lactulose (1-4-beta-galactosidofructose; Cephulac, Merrell-Dow) is hydrolyzed by intestinal bacteria to lactic, acetic, and formic acid. With the lower intestinal pH, ammonia (NH3) accepts an additional H+ proton to form the less diffusible ammonium ion (NH4), effectively trapping ammonium within the colon. Lactulose is an unabsorbed solute and also causes an osmotic diarrhea, decreasing intestinal transit time and absorption. Lactulose may be given orally but should be given rectally in patients with altered mentation. Patients with chronic intractable portosystemic encephalopathies may benefit from the benzodiazepine antagonist flumazenil.