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v
vi CONTRIBUTORS
To my mother, Peg,
who made our house a home.
xi
xii PREFACE
thread of being excellent teachers. I have the greatest respect for their contributions to our profession.
I also acknowledge the excellent assistance of the staff at Elsevier, and in particular my editors, Raymond
Kersey, Denise LeMelledo, and Mary Turner, for their encouragement, advice, and professionalism.
1
GASTROINTESTINAL
SYMPTOMS
Todd R.Tams
1
2 CHAPTER 1 GASTROINTESTINAL SYMPTOMS
failure, feline heartworm disease, hypoadrenocor- in other chapters throughout the text. Vomiting
ticism), the need for careful initial screening and diarrhea, the clinical signs that occur most
becomes even more important. It is essential that commonly with GI disease, are given the most
the patient’s history be well understood so that emphasis in this chapter.
diagnostic evaluation addresses the problem as
directly as possible.
This chapter provides an overview of the diag-
nostic approach to GI disorders based on the pre- BOX 1-1 Symptoms of
senting signs and symptoms. Emphasis is placed Gastrointestinal Disease
on the meaning of various historical and physical
Salivation Change in appetite
examination findings. Once an accurate review of
Halitosis Anorexia
the history has been established, a concise list of Regurgitation Polyphagia
most likely differential diagnoses can be estab- Dysphagia Pica
lished. A list of clinical signs that are associated Nausea Coprophagy
with digestive system problems appears in Box 1-1. Vomiting Borborygmus
Definitions of symptoms of GI disorders are listed Hematemesis Flatus
in Table 1-1. Symptoms discussed in this chap- Diarrhea Weight loss
ter include dysphagia; regurgitation; vomiting; Melena Polyuria/polydypsia (PU/PD)
grass ingestion/coprophagy/pica; diarrhea; borbo- Hematochezia Anemia
rygmus and flatulence; bloating, fullness, and Dyschezia Shock
Tenesmus Abdominal pain
abdominal discomfort; fecal incontinence; and
Constipation Abnormal mentation
constipation. Additional symptoms are discussed
with an insidious onset of clinical signs are more Sedation or general anesthesia is often required
likely to be afflicted with neoplasia (e.g., glossal for thorough examination of the oral cavity, pharynx,
neoplasia, pharyngeal tumors such as squamous and larynx. The dental arcade, tongue (including
cell carcinoma, fibrosarcoma, melanoma, tonsillar frenulum area), palate, tonsils, and tonsillar crypts
carcinoma, retropharyngeal mass causing compres- should be carefully evaluated for the presence of
sion).Weight loss and reluctance to eat are gener- inflammation, mass, or foreign body. Biopsies of
ally present in chronic cases. Presence of systemic masses should be deep to determine diagnosis and
signs, such as weakness that worsens with exercise, prognosis accurately. A superficial biopsy may fail
with or without cough and dyspnea, suggests to harvest neoplastic cells from a cancerous mass
myasthenia gravis. Signs of myasthenia gravis may because the changes at the surface may be limited to
be limited to pharyngeal dysfunction. Weakness inflammation and necrosis. Electrocautery can be
may also be caused by polymyositis or central used to control postbiopsy hemorrhage. It is impor-
nervous system disease. Dysphagia occurring in tant to evaluate the nasopharynx (for significant
conjunction with dementia suggests cerebral inflammation, foreign body, mass) and the proximal
disease as the underlying problem. Rabies vaccina- esophagus as well. On occasion I have found for-
tion history and potential for exposure (environ- eign bodies such as long blades of grass, peanut
ment) must always be determined early in the shells, or small needles lodged in the nasopharynx
evaluation of any patient with dysphagia. and not extending caudal to the free border of the
Thorough physical examination will successfully soft palate (i.e., not readily visible on initial oral
identify the cause of dysphagia in some cases. examination). Use of a flexible endoscope that is small
Physical signs may also alert the clinician to the enough to allow retroflexion over the soft palate greatly
presence of any significant complications (e.g., facilitates examination of the nasopharynx (Figure 1-1).
pneumonia) and help determine specific tests that Survey pharyngeal radiographs may be indi-
should be done to establish a definitive diagnosis. cated as part of the preliminary work-up if history
Physical examination should include a thorough or physical examination suggests that a mass, foreign
evaluation of the head (temporal muscle atrophy, body, or injury (e.g., hyoid bone fracture) may be
pain associated with muscles of mastication, ocular present. Contrast radiographic studies with
areas for inflammation or proptosis of one of the fluoroscopy while observing swallowing of both
eyes to suggest retrobulbar mass or cellulitis), oral liquids and food are required for differentiation of
cavity, external pharyngeal and cervical soft tissue pharyngeal and cricopharyngeal dysphagia.
areas for any mass effect, lymphadenopathy, or drain-
ing tract; recognition of any pain related to opening
of the mouth (e.g., masticatory muscle myositis,
retrobulbar inflammation, temporomandibular joint
disease); and a neurologic examination. Specific
neurologic tests include evaluation of cranial nerves
IX (glossopharyngeal) and X (vagus) by checking
the swallow and gag reflexes, respectively, evaluation
of cranial nerve XII (hypoglossal) via observation
and palpation of the tongue, and evaluation of gait
and strength. Focal lesions of the medulla oblongata
and diffuse neuromuscular disease may cause ataxia,
conscious proprioception deficits, and limb weak-
ness. Patients that exhibit any evidence of systemic
signs (e.g., weakness, polyuria/polydypsia [PU/PD],
muscle pain) in conjunction with dysphagia should
initially be evaluated by complete blood count
(CBC) (infection, inflammation, anemia of chronic
FIGURE 1-1 Lateral skull radiograph of a dog,
disease), biochemical profile (including creatine demonstrating correct placement of a flexible
phosphokinase [CPK] for polymyositis), and urinal- endoscope for posterior rhinoscopy. Examination of the
ysis. For example, a biochemical profile and urinaly- nasopharynx and choanae is facilitated by the use of a
sis may confirm that lingual ulceration or necrosis is scope with a tip deflection capability of 180 degrees or
due to uremia. more.
CHAPTER 1 GASTROINTESTINAL SYMPTOMS 5
An acetylcholine receptor antibody titer tents into the esophagus without associated eruc-
test (see Chapter 4) should be run if there is any tation or vomiting. This process may or may not
possibility of myasthenia gravis (signs of focal produce symptoms. The term expectoration
myasthenia gravis may be limited to pharyn- refers to expulsion of material from the respiratory
geal dysfunction and regurgitation). A Tensilon tract, an event that is usually associated with
(edrophonium chloride) test could also be coughing. Box 1-3 provides a differential list for
done, but the clinician should observe carefully for the problem of regurgitation.
and be prepared to treat cholinergic overstimula- Regurgitation is usually a clinical sign of an
tion if it occurs. If central nervous system disease is esophageal disorder. In most cases it results from
suspected, testing may include cerebrospinal abnormal esophageal peristalsis or esophageal
fluid analysis, nuclear scintigraphy, and/or obstruction. The most common cause of regurgi-
computed axial tomography or magnetic tation seen in clinical practice is megaesophagus.
resonance imaging (MRI). Megaesophagus refers to a specific syndrome
characterized by a dilated, hypoperistalic esopha-
gus. By definition and for use in this text, megae-
REGURGITATION sophagus is differentiated from other causes of
Regurgitation refers to a passive, retrograde esophageal dilation (e.g., esophageal foreign body,
movement of ingested material to a level proximal vascular ring anomaly, neoplasia) that may or may
to the upper esophageal sphincter. Usually this not be characterized by abnormal peristalsis.
occurs before ingested material reaches the stom- Megaesophagus is discussed in detail in Chapter 4.
ach. Regurgitation is not associated with the same Many patients with disorders causing regurgita-
spectrum of premonitory signs that often precede tion have owners who incorrectly but understand-
vomiting and retching. Although regurgitation ably interpret the problem as vomiting. Regardless
may occur during or shortly after eating, it is of the owner’s terminology, the clinician must carefully
essential that the clinician recognize that regurgi- differentiate the clinical signs of regurgitation and vomit-
tation may not occur until at least several hours ing. Characteristics of regurgitation and vomiting
after eating in some patients, especially those with are summarized in Table 1-2. Too often, dogs with
megaesophagus. Regurgitation is a clinical sign of megaesophagus are incorrectly diagnosed and
many disorders and should not be considered a treated for chronic vomiting because the clini-
primary disease. Regurgitation is a problem that cian failed to thoroughly review the history.
occurs uncommonly in cats. Significant complica- Regurgitation involves passive ejection of material
tions of regurgitation include aspiration pneumo- that usually includes undigested food that is often
nia and chronic wasting disease. The term reflux in tubular shape and devoid of bile. If there is no
refers to movement of gastric or duodenal con- food in the esophagus, regurgitated material may
From Tams TR:Vomiting, regurgitation, and dysphagia. In Ettinger SJ, ed: Textbook of veterinary internal medicine, ed 4, vol 1,
Philadelphia, 1995,WB Saunders.
6 CHAPTER 1 GASTROINTESTINAL SYMPTOMS
From Burrows CF: Vomiting and regurgitation in the dog: a clinical perspective. In Viewpoints in veterinary medicine, ed 2,
Lehigh Valley, Pa, 1993, Alpo Pet Foods.
consist entirely of thick white foam. The fre- signs, such as weakness (e.g., myasthenia gravis,
quency of regurgitation can vary dramatically, hypoadrenocorticism, polymyositis) or vomiting
from as few as 1 to 2 episodes per week in some (e.g., hypoadrenocorticism, toxin ingestion such as
patients with megaesophagus to as often as 10 to lead); and whether there are any signs of complica-
15 times per day. tions from regurgitation (e.g., coughing or dysp-
Vomiting involves active expulsion of food nea, suggesting that an aspiration event with
and/or fluid.Vomiting is accompanied by retching subsequent development of pneumonia has
and active abdominal contractions. Frequently occurred). Because the patient’s history is the
signs of nausea (salivation, restlessness, increased major factor in determining the extent of the
swallowing motions) occur prior to retching. diagnostic work-up, it should be thoroughly inves-
Occurrence of any of these associated signs should tigated. The importance of careful consideration of the
be discussed with the owner as the history is history is highlighted by the fact that some causes of
reviewed.Vomited material may include bile, and regurgitation, including certain disorders that result in
food may be present in various states of digestion. megaesophagus, are reversible if recognized and treated
Vomiting may occur seconds to minutes to many appropriately early enough in their course. Missed diag-
hours after eating. With regard to incidence, nosis may result in significant worsening of the patient’s
patients with vomiting disorders far outnumber long-term prognosis.
those with disorders associated with regurgitation.
It is important to note that some patients with a
history more suggestive of regurgitation may actu- Signalment
ally be vomiting. If it is unclear based on the his- The signalment, particularly age and breed, pro-
tory or clinical impression whether or not the vides important diagnostic clues. If regurgitation
patient is actually regurgitating rather than vomit- begins at the time of weaning onto solid food, a
ing, a survey thoracic radiograph should be made vascular ring anomaly (e.g., persistent right aortic
at the outset to look for evidence of esophageal arch) or congenital megaesophagus should be sus-
dilation. A barium swallow may be necessary to pected. Regurgitation is persistent, and affected
rule out esophageal dilation. patients are often malnourished and weak. Dog
In evaluation of a patient with regurgitation, breeds most commonly affected with vascular ring
important historical factors to be considered by anomalies include the German shepherd, Irish set-
the clinician include signalment; nature of onset of ter, English bulldog, and Boston terrier. Vascular
clinical signs (i.e., acute and persistent versus inter- ring anomalies are extremely uncommon in cats.
mittent [recent or chronic]); environment (e.g., Idiopathic megaesophagus is the most common
likelihood of foreign body or toxin ingestion); cause of regurgitation in dogs, including puppies.
pertinent history (e.g., recent anesthetic event sug- Idiopathic megaesophagus is now recognized
gesting possible development of a reflux-related somewhat more frequently in adults than in young
esophageal stricture); presence of any systemic patients. Idiopathic megaesophagus is known to be
CHAPTER 1 GASTROINTESTINAL SYMPTOMS 7
hereditary in wirehaired fox terriers and miniature addition, strictures occasionally develop in cats
schnauzers. A breed predisposition for idiopathic within 1 to 2 weeks after significant difficulty is
megaesophagus exists for the German shepherd, experienced in vomiting a large hairball and in
Great Dane, Irish setter, and golden retriever. dogs or cats as a sequela to frequent vomiting. An
Although idiopathic megaesophagus can occur at esophageal stricture may also develop as a sequela
any age, a later age of onset (8 to 12 years) seems to to caustic acid or alkali ingestion, foreign body
predominate. A recent study has shown that dogs trauma, lodgment of tablet or capsule medication
with acquired megaesophagus and focal myasthenia in the esophagus (e.g., doxycycline tablets in cats),
gravis have a bimodal age of onset of clinical signs, and thermal burns. Whereas esophageal strictures
with a younger group of dogs showing clinical may develop at any age, a majority of foreign body
signs at 2 to 4 years of age and an older group at obstruction cases occur in patients 2 to 3 years of
9 to 13 years of age. Although megaesophagus age or younger. Patients with strictures generally
related to focal myasthenia gravis has been reported demonstrate signs such as vomiting, dysphagia, per-
in a number of breeds, it may be more common in sistent gulping, and salivation before the onset of
golden retrievers and German shepherds. regurgitation. Because many esophageal foreign
Megaesophagus may rarely occur secondary to bodies are radiodense, the screening procedure that
hypoadrenocorticism. Retrospective studies have is most likely to readily differentiate acute regurgi-
shown that hypoadrenocorticism is more common tation caused by a foreign body from that of an
in young to middle-age female dogs (with a esophageal stricture is a survey thoracic radiograph.
majority younger than 7 years of age at the time of Contrast studies and/or esophagoscopy may be
diagnosis). Dogs with megaesophagus and hypo- required to confirm the diagnosis in some cases.
adrenocorticism often present with vomiting and Most disorders other than vascular ring anomaly,
diarrhea, as well as regurgitation. congenital megaesophagus, esophageal foreign body
obstruction, and esophageal stricture cause a grad-
ual onset of clinical signs. The clinician should
Nature of Clinical Signs inquire about details that might suggest a systemic
Regurgitation that begins acutely at a time other disorder. Although idiopathic megaesophagus is the
than weaning is most often due to an esophageal most common cause of regurgitation, every effort is
foreign body. Most esophageal foreign bodies still made to identify a potentially treatable cause.
that cause nearly complete or complete obstruc- Inquiries should be made about potential exposure
tion are bones (e.g., steak, chicken, pork chop). to toxins such as lead or thallium or exposure to
If the esophageal lumen is only partially ob- carrion that could cause botulism. Any clinical signs
structed, regurgitation may occur only after such as weakness, collapse, vomiting, and diarrhea
ingestion of solids. Although an acute onset of should be discussed, looking for evidence to sup-
regurgitation may also occur as a developing port a likely diagnosis of such disorders as myasthe-
esophageal stricture results in significant narrow- nia gravis, hypoadrenocorticism, polymyositis, or
ing of the esophageal lumen, generally there is a systemic lupus erythematosus.
more gradual onset over a period of 2 to 3 days,
with regurgitation of solids then becoming more
persistent. Physical Examination
If regurgitation begins acutely, the owner should Physical examination findings may vary consider-
be questioned carefully about the possibility of for- ably. If dysphagia, as well as regurgitation, is
eign body ingestion. Frequently owners will relate present, the same steps in physical examination
that a bone was purposely fed or that they observed previously outlined for evaluation of dyspha-
their pet on a foray into the garbage or saw evi- gia should be followed (oral examination, exter-
dence after the fact that the garbage had been nal palpation). Excessive salivation may suggest
invaded. If the patient has been free outdoors, there odynophagia associated with an esophageal foreign
may be no known history of foreign body inges- body or esophagitis. Many megaesophagus patients
tion. are thin and in poor condition. A Heimlich type
Because a majority of esophageal strictures of maneuver on the thorax or anterior abdomen
develop within 1 to 3 weeks of a general anesthetic may produce an externally visible bulge on the left
event, the history should be reviewed carefully side of the neck resulting from a gas-filled flaccid
regarding any recent anesthetic procedures. In cervical esophagus. Occlusion of the nostrils with
8 CHAPTER 1 GASTROINTESTINAL SYMPTOMS
compression of the thorax may also allow visuali- matosus (antinuclear antibody), and myasthenia
zation of a dilated cervical esophagus. Gurgling gravis (acetylcholine receptor antibody titer,
sounds and halitosis might result from fermenta- Tensilon test) are done if the history, physical
tion of food in a hypomotile esophagus. Thoracic examination, or baseline tests indicate that these
auscultation may reveal pulmonary crackles sec- primary disorders may exist. It is recommended
ondary to aspiration pneumonia. Fever, mucopu- that the acetylcholine receptor antibody titer test
rulent nasal discharge, coughing, and dyspnea also be run in any patient with acquired megaesopha-
suggest the presence of pneumonia. gus because many with focal myasthenia gravis do
Patients with intraluminal esophageal strictures not show classic signs associated with generalized
are often normal on physical examination. Other myasthenia gravis (weakness, collapse). Serum
examination findings, such as weakness and/or lead levels are indicated if lead toxicity is consid-
decreased palpebral reflex (myasthenia gravis), weak- ered a possibility.
ness and bradycardia (hypoadrenocorticism), muscle Endoscopic examination of the esophagus
pain (polymyositis), and signs that may include joint (esophagoscopy) is a valuable diagnostic and thera-
pain and shifting limb lameness (systemic lupus ery- peutic tool. Endoscopy is most effective in diagnosis
thematosus), erosive glossitis, and others, often occur of disorders that affect the mucosa (esophagitis, mass
with systemic disorders. Cats that regurgitate sec- lesions, strictures), for retrieval of foreign bodies, in
ondary to an anterior mediastinal mass often have a management of esophageal strictures with guided
noncompressible anterior chest cavity. Physical find- bougienage or balloon dilation, and as an adjunctive
ings in cats with Key-Gaskell syndrome, a neuro- step in diagnosis of hiatal hernia. Hiatal hernia is best
logic disorder characterized in part by regurgitation diagnosed using a combination of contrast radiogra-
due to megaesophagus, include persistent pupillary phy (with fluoroscopy if available) and endoscopy
dilation, decreased nasal and lacrimal secretions, (looking for anatomic and secondary inflammatory
bradycardia, and constipation. changes [esophagitis]). In most patients with mega-
esophagus, endoscopic examination is not necessary
for diagnosis and is rarely of benefit in determining a
Diagnostic Studies cause. Esophageal motility disorders in which clear
Survey radiography of the esophagus is the first radiographic evidence of marked esophageal dila-
and most important step in the diagnosis of a tion is lacking are best recognized by esophageal
regurgitation disorder. Radiographs are evaluated fluoroscopy and manometry studies. If this
for evidence of esophageal dilation, presence of a equipment is not available, esophagoscopy may be
foreign body, or thoracic mass. If survey radio- beneficial; in some cases pooling of fluid or mild
graphs fail to provide a definitive diagnosis, a esophageal dilation can be identified.
barium esophagram should be performed to
evaluate the cervical and thoracic esophagus.
Barium paste offers the best mucosal coating and
VOMITING
should be used to evaluate suspected mucosal or Most small animal practitioners agree that vomit-
mass lesions. Esophageal dilation is best detected ing is one of the most common reasons that dogs
with liquid barium suspension. Liquid barium and cats are presented for diagnosis and treatment.
mixed with food is best for evaluating disorders of Vomiting refers to a forceful ejection of gastric and
motility and examining for esophageal stricture often proximal small intestinal contents through
(strictures often allow fluid but not food to pass). the mouth. The vomiting act involves three stages:
Although young patients with congenital nausea, retching, and vomiting. It is emphasized
megaesophagus are not usually evaluated with that vomiting is simply a clinical sign of any of a
detailed diagnostic tests, patients with acquired number of disorders that can involve any organ
megaesophagus should be evaluated as thoroughly system in the body. Vomiting does not constitute
as possible. Baseline tests should include a CBC, a diagnosis in itself.
biochemical profile, serum thyroid hormone
analysis, urinalysis, and fecal examination for
Spirocerca lupi ova (in endemic areas). Specific tests Clinical Features
to evaluate for systemic disorders such as hypo- Because a wide variety of disorders and stimuli can
adrenocorticism (adrenocorticotropic hormone cause vomiting (Box 1-4), it may present the clini-
[ACTH] stimulation), systemic lupus erythe- cian with a major diagnostic challenge. Although
CHAPTER 1 GASTROINTESTINAL SYMPTOMS 9
Modified from Tams TR:Vomiting, regurgitation, and dysphagia. In Ettinger SJ, ed: Textbook of veterinary internal medicine, ed 4,
vol 1, Philadelphia, 1995,WB Saunders.
10 CHAPTER 1 GASTROINTESTINAL SYMPTOMS
vomiting does not always signify the presence of a ● Duration of signs and systems review
serious disorder, it may be the first indication of ● Content of the vomitus
intestinal obstruction, renal failure, pancreatitis, ● Time relation to eating
parvovirus enteritis, addisonian crisis, drug toxic- ● Nature (e.g., type, frequency) of vomiting
ity, neoplasia, and others. A complete historical ● Dietary and environmental history
review with emphasis on all body systems is essen-
tial for determining a realistic and effective initial The line of questioning should begin with
work-up plan and treatment protocol. All too determining if the vomiting is an acute problem
often, early concentration on only the GI tract or is chronic (longer than 2 weeks in duration)
leads to a misdiagnosis and inappropriate treat- and whether there has been any blood in the
ment for the cause of the vomiting. vomitus. The signalment, immediate signs, past
As previously discussed, it is essential that the pertinent history, and beneficial or deleterious
clinician make a clear differentiation between effects of any drugs that may have been adminis-
regurgitation and vomiting at the outset. If there is tered (either for the immediate symptoms or as
uncertainty about whether or not regurgitation is treatment for another disorder) should be
occurring after the history is reviewed, survey tho- reviewed. In particular it should be determined
racic radiographs should be made to evaluate for whether any nonsteroidal antiinflammatory
possible esophageal dilation. Contrast studies may drugs (e.g., aspirin, carprofen, etodolac, flunixin
occasionally be necessary to identify the presence meglumine [Banamine], phenylbutazone, ibupro-
of esophageal dilation. fen [Motrin, Nuprin], piroxicam [Feldene]) have
Consideration of the following historical fea- been used. Gastric and intestinal erosions and
tures is often useful in assessing and diagnosing potentially serious ulceration may develop in con-
disorders that cause vomiting (Box 1-5): junction with their use. Nephrotoxicity may also
signs such as PU/PD, coughing and sneezing, hours after eating, and occasionally projectile
dysuria, or dyschezia should also be addressed. vomiting occurs.
This routine systematic approach will help to Significant information can often be obtained
alleviate diagnostic “tunnel vision” on the part of from a complete description of the color and con-
the clinician. For example, a history of PU/PD sistency of the vomitus, especially when interpre-
and acute vomiting in an older intact female dog tation is made in conjunction with a review of
immediately suggests the possibility of pyometra clinical signs. As previously discussed, if food is
(also rule out primary renal disease), and the present, the degree of digestion and time since the
presence of dyschezia in conjunction with vom- most recent meal should be determined. Presence
iting may be consistent with vomiting secondary of bile in the vomitus is not unusual because vom-
to colitis (approximately 30% to 35% of dogs iting begins with jejunal retroperistalsis and intes-
with colitis also have vomiting, which may occur tinal contents are swept into the stomach before
before or in conjunction with the onset of large the actual act of vomiting. Bile may appear as a
bowel signs). yellow or green coloration. Bile is often present
A description of the vomiting episodes, includ- when vomiting is due to inflammatory bowel dis-
ing any association with eating or drinking, yields ease, idiopathic or secondary gastric hypomotility
important information in some cases. Normally all (bile alone or bile with food), intestinal foreign
food should be evacuated from the stomach by 7 bodies, and pancreatitis. Chronic intermittent bil-
to 10 hours after ingestion. The presence of food ious vomiting in small breeds of dogs, especially
and its state of digestion will depend on dietary when it occurs mostly in the early morning hours,
composition (with high-fat diets the stomach is most suggestive of reflux gastritis. The presence
empties more slowly), gastric secretions and motil- of bile helps to rule out a complete pyloric
ity, presence of any gastric outflow obstruction, obstruction.
and time elapsed since ingestion. Vomiting shortly Expulsion of large amounts of predominantly
after eating most commonly suggests dietary indis- greenish-colored fluid from a patient with acute
cretion or food intolerance, overeating, stress or vomiting is most consistent with a proximal to
excitement, gastritis, or a hiatal disorder. Vomiting mid small bowel obstruction. Lethargy, dehydra-
of undigested or partially digested food more than tion, and abdominal pain are generally present in
7 to 10 hours after eating is an important clinical affected patients. In general, the more proximal a bowel
sign that usually indicates a gastric motility dis- obstruction is located, the more fulminant the clinical
order or gastric outflow obstruction. Dogs with signs will be. Small amounts of blood may be pres-
hypomotility may vomit undigested food several ent in any case of gastric or duodenal mucosal
hours to 10 to 18 hours or more after eating and compromise with erosions or ulceration (e.g.,
often exhibit a cyclic pattern of clinical signs. This hypovolemia with resultant loss of integrity of the
disorder has been recognized much more fre- gastric mucosal barrier, drug-induced damage,
quently in recent years. Misconceptions com- acute or chronic gastritis or inflammatory bowel
monly lead to misdiagnosis and mismanagement disease, gastric or duodenal ulceration, or neopla-
of affected patients. It is often incorrectly assumed sia). Hematemesis may also be caused by a coagu-
that gastric retention means gastric outflow lopathy or ingestion of blood from another site
obstruction, and unnecessary surgery such as (e.g., mouth, nasal sinuses, lungs). Large clots of
pyloromyotomy may be performed. It is now well blood or “coffee grounds” (blood altered by and
recognized that pyloromyotomy procedures are not mixed with gastric juice) usually indicate a more
commonly indicated in dogs or cats with chronic significant degree of erosions or ulceration. Fresh
vomiting. blood is usually altered in the stomach to the dark
Causes of gastric outflow obstruction include brown or black color known as “coffee grounds”
foreign bodies, antral and/or pyloric mucosal in a matter of minutes. Presence of bright-red
hypertrophy, gastric and duodenal ulcers, antral blood in the vomitus thus indicates very recent or
or pyloric neoplasia or polyps, and external active hemorrhage.
compression on the antrum and pylorus (e.g., Clinicians should be aware that not all patients
abscess, mass). Foreign bodies are identified with gastric ulcers have hematemesis or even
much more commonly than the other disorders vomit. This fact highlights the importance of
listed in Box 1-4. All are characterized by vomit- obtaining a thorough history to determine if any
ing, which may occur shortly or a number of “ulcerogenic factors” could be present. Recent
CHAPTER 1 GASTROINTESTINAL SYMPTOMS 13
onset of hematemesis in a patient with chronic salivation (nausea), may occur as well. When pre-
vomiting is often a sign that a potentially serious sented with this pattern of clinical signs in patients
and worsening disorder is present. Such conditions in which metabolic disorders, GI parasitism, and
as neoplasia with ulceration, uremic gastritis, or adverse food reactions have been ruled out, the
chronic severe gastritis with erosive changes should clinician should strongly consider chronic gastritis,
be considered, and diagnostic evaluation to deter- inflammatory bowel disease, irritable bowel syn-
mine the cause should be expedited. Potential drome, and gastric motility disorders as leading
causes of hematemesis are listed in Box 1-6. differential diagnoses. A detailed work-up, includ-
A fecal odor suggests intestinal obstruction, ing gastric and intestinal biopsies, is often required
peritonitis with ileus, ischemic injury to the intes- for definitive diagnosis in these cases. It is impor-
tine, or stasis with bacterial overgrowth. Pro- tant to note that chronic intermittent vomiting is a
jectile vomiting is an imprecise term that is used common clinical sign of inflammatory bowel disease
to describe forceful ejection of vomitus from the in both dogs and cats. Diarrhea may or may not be
mouth, which is expelled a considerable distance. a concurrent problem in patients with inflamma-
Its occurrence suggests a significant degree of gas- tory bowel disease. Vomiting from systemic or
tric or proximal small bowel obstruction (foreign metabolic causes may be an acute or chronic sign,
body, large antral or pyloric polyps, neoplasia, and generally there is no direct correlation with
pyloric hypertrophy). In my experience this clini- eating and no predictable vomitus content.
cal sign occurs infrequently. The concomitant presence of diarrhea with
Chronic intermittent vomiting is a com- vomiting often provides important diagnostic clues.
mon presenting complaint in veterinary medicine. Vomiting preceding diarrhea suggests toxic inges-
Often there is no specific time relation to eating, tion, a progressively severe disease of the small
the content of the vomitus varies, and the occur- intestine such as viral enteritis (e.g., due to par-
rence of vomiting may be very cyclic in nature. vovirus or rotavirus), pancreatitis, or acute colitis.
Depending on the disorder, other signs, such as Also, infections with parasites, including Giardia and
diarrhea, lethargy, inappetence, weight loss, and roundworms, can cause vomiting that precedes the
From Willard M: Clinical manifestations of gastrointestinal disorders. In Nelson RW, Couto CG, eds: Essentials of small animal
internal medicine, St. Louis, 1992, Mosby–Year Book.
14 CHAPTER 1 GASTROINTESTINAL SYMPTOMS
Physical Examination
It is important to stress the enormous significance
of a complete history and physical examination in
evaluation of a vomiting patient. An all too fre-
FIGURE 1-2 Typical appearance of a puppy quite
quent error in clinical practice is to make a diag-
ill from parvovirus enteritis. This puppy was depressed,
nosis based on an incomplete history and cursory reluctant to move, and nauseated. Watery diarrhea
examination. This may lead to use of unnecessary was present in the cage.
diagnostic tests and inappropriate treatment.
Essential early diagnosis of a serious disorder may ends subsequently advancing along the intestinal
be missed. A systematic approach can be both lumen as a result of progressive peristalsis.
thorough and time efficient. Areas to receive Intestinal plication with potential for perforation
emphasis in a vomiting patient are listed here. results. It is extremely important that an oral examina-
The first step in physical examination is to tion with careful evaluation of the frenulum area be done
assess the patient’s overall attitude, posture, and in all vomiting cats. In some cases, mild tranquiliza-
energy level (i.e., active versus lethargic). This will tion (e.g., ketamine 5 to 8 mg intravenously) is
often assist the clinician in determining to some required so that a definitive examination can be
degree the seriousness of the patient’s condition done (Figure 1-3). Dogs occasionally have similar
and its degree of discomfort, if any exists. Observe foreign body positioning, so a careful oral exami-
the patient! Will any pain relief or antiemetic med- nation is important in this species as well. The cer-
ication to control nausea be needed? It is often vical soft tissues of vomiting cats should be
very reassuring to the owner when the clinician palpated for an enlarged thyroid nodule or nodules
begins the examination by showing interest in (hyperthyroidism commonly causes vomiting).
how the patient has been acting and feeling. Hyperthyroidism should be considered in any cat
Patients that are experiencing a significant degree 5 years of age and older. Cardiac auscultation may
of nausea often have a forlorn expression, swallow reveal rate and rhythm abnormalities that can
frequently, and salivate (Figure 1-2). Patients with
intestinal foreign body obstruction, pancreatitis,
gastric neoplasia, and other serious conditions are BOX 1-7 Causes of Salivation
often quite subdued at the time of presentation.
These types of observations can often be made as Nausea
Stomatitis (including chronic feline gingivitis/
the history is being discussed and recorded.
stomatitis/pharyngitis)
Careful observation should be continued through-
Direct oral stimulation (e.g., ingestion of caustic
out any subsequent period of hospitalization. materials, foreign body, electric cord injury, oral
The mucous membranes are evaluated for neoplasia)
evidence of blood loss, dehydration, sepsis, shock, Chemical poisoning (organophosphates, carbamates,
and jaundice. Salivation suggests the presence of metaldehyde)
nausea (common causes of salivation are listed in Esophagitis
Box 1-7). An oral examination may reveal a part Esophageal foreign body
of an oral or pharyngeal foreign body that may Portosystemic shunt (especially in cats)
extend to the stomach or intestine. The best Medications (especially in cats; e.g., trimethoprim/
example of this is a linear foreign body in a cat in sulfadiazine)
Rabies
which a portion of the foreign material loops
Conditioned reflex (Pavlovian response)
around the tongue at the frenulum, with the free
CHAPTER 1 GASTROINTESTINAL SYMPTOMS 15
Modified from Burrows CF: Vomiting and regurgitation in the dog: a clinical perspective. In Viewpoints in veterinary medicine,
ed 2, Lehigh Valley, Pa, 1993,Alpo Pet Foods.
PCV, Packed cell volume; Hb, hemoglobin; RBC, red blood cell count; WBC, white blood cell count; Na, sodium;
Cl, chloride; K, potassium; CO2, carbon dioxide; BUN, blood urea nitrogen; ALT, alanine aminotransferase; ALP, alkaline
phosphatase; Ca, calcium; TLI, trypsin-like immunoreactivity; PLI, canine pancreatic lipase immunoreactivity; T4, thyroxine;
BIPS, barium-impregnated polyethylene spheres.
CHAPTER 1 GASTROINTESTINAL SYMPTOMS 17
A B
FIGURE 1-5 A, Lateral abdominal radiograph from a 10-year-old feline immunodeficiency virus (FIV)–positive
cat with intestinal lymphoma. The cat had a gradually decreasing appetite, recent onset of intermittent vomiting,
and occasional episodes of nonproductive retching.Abdominal palpation revealed a doughy mass in the region of the
stomach. This radiograph shows that the stomach is distended and has a soft tissue/fluid opacity. The small intestine
and colon are normal. B, Air gastrogram (40 ml of air was injected through a small feeding tube into the stomach
while the cat was lightly tranquilized). A large mass density within the lumen of the stomach is consistent with a
gastric trichobezoar. This simple procedure allowed rapid confirmation that a foreign body was present in the
stomach. C, Trichobezoar that was surgically removed from the cat. The trichobezoar was 9 cm in length, and its
configuration was similar to the inside of the stomach.
cases in which a barium series is done until most laria are usually negative.Antigen tests are also fre-
of the barium has left the stomach because a large quently negative. Thoracic radiographs may
barium pool often obscures foreign objects. provide important clues in a cat with heartworm
Barium swallow with fluoroscopy is often disease. Suggestive findings include right ventricu-
necessary for diagnosis of hiatal hernia disorders lar enlargement, pulmonary lobar artery enlarge-
and gastroesophageal reflux disease. Endoscopy is ment, and pulmonary parenchymal disease. The
also useful for identifying these disorders. caudal lobar arteries usually show the earliest ra-
Serum bile acids assay is used to assess for diographic changes, with the left and the right
significant hepatic disease, including portosystemic being equally affected. These changes are best rec-
shunts and chronic severe liver disease, when the ognized on the ventrodorsal or dorsoventral views.
liver enzymes are normal or only mildly elevated. Some cats also have hyperglobulinemia. The pres-
Because vomiting is a frequent presenting sign in ence of both peripheral eosinophilia and basophilia
cats with heartworm disease, a feline heartworm is also suggestive of heartworm disease in cats.
antibody test should be done to investigate this Thyroid testing should also be done on vom-
possibility. In endemic areas testing cats for heart- iting cats 5 years of age and older to evaluate for
worm disease should be considered part of the hyperthyroidism. It is important to remember that
minimum database. Because most cats with heart- cats with hyperthyroidism may have thyroid hor-
worm disease are amicrofilaremic, tests for microfi- mone levels that fluctuate into the normal range
CHAPTER 1 GASTROINTESTINAL SYMPTOMS 19
Timing of Work-up
The frequency and duration of vomiting can vary
from weeks to years. In animals with chronic,
slowly progressive disorders, vomiting may be only
a sporadic event with or without occasional peri-
ods of increased frequency or severity possibly
associated with flare-ups of the disease process.
Clinicians often ask when a patient with a disorder char-
acterized by intermittent vomiting should undergo a
detailed diagnostic work-up. Indeed, it is not unusual
for some cats, several of my own included, to
vomit once or twice every 1 to 2 weeks or so for
FIGURE 1-7 Multiple Physaloptera nematodes (arrows) many months or years without any apparent unto-
lying on the gastric mucosa in a dog. These nematodes
ward effect. A variety of factors are usually
may cause the chronic vomiting and histologic lesions
of lymphocytic-plasmacytic gastritis. (From Jergens AE, involved in the decision-making process regarding
Moore FM: Endoscopic biopsy specimen collection when diagnostic evaluation should be undertaken.
and histopathologic considerations. In Tams TR, ed: The foremost factors include development of any
Small animal endoscopy, ed 2, St. Louis, 1999, Mosby.) concurrent worrisome signs, such as inappetence,
weight loss, signs of abdominal discomfort such
as cramping, presence of leukocytosis and/or
have eluded diagnosis up to this point can be read- hypoproteinemia, any signs of hyperthyroidism in
ily made on direct visualization of these areas. cats to suggest advancing inflammatory bowel dis-
Examination or biopsy may also reveal typhlitis. ease, and, very importantly, the degree of the
Ultrasonography can be useful in the diag- owner’s concern and level of interest in finding
nostic work-up of a number of disorders that can answers regarding his or her pet’s problem.
cause vomiting (see Chapter 2). Among the prob- In general, I recommend that a work-up be
lems that may be detected with ultrasonography started if the frequency of vomiting or degree of
are certain disorders of the liver (e.g., inflamma- any signs associated with the vomiting (e.g.,
tory diseases, abscessation, cirrhosis, neoplasia, vas- lethargy, discomfort, inappetence) begins to
cular problems) and gallbladder and bile ducts increase. Always keep in mind that as disease
(cholecystitis, choleliths, bile duct obstruction), GI processes worsen they are frequently more difficult
foreign bodies, intestinal and gastric wall thicken- to bring under control. With the availability of
ing, intestinal masses, intussusception, kidney dis- endoscopy and our ability to utilize it for exami-
orders, pancreatitis, and others. Needle aspirations nation and biopsy of the stomach and small intes-
and/or biopsies can be done at many sites under tine, in a significantly noninvasive manner when
ultrasound guidance. compared with surgery, it is definitely reasonable
Abdominal exploratory is indicated for a to recommend its use even in patients with mild
variety of problems, including foreign body clinical signs. A countless number of my patients
removal, intussusception, gastric mucosal hyper- from over the years come to mind during this dis-
trophy syndromes, procurement of biopsy samples, cussion, but two in particular should help make a
and resection of neoplasia. If the diagnosis is lasting point here. Both demonstrated only mild
unclear on examination, gastric and small intes- clinical signs, which included intermittent vomit-
tinal (two to three samples total) biopsies must be ing and mild occasional lethargy. Each, however, had
performed. In a majority of dogs and cats with a serious life-threatening problem that was fortu-
gastritis and inflammatory bowel disease, no gross nately diagnosed early enough for the patient to
abnormalities are detected at exploratory. Samples undergo meaningful treatment. A brief account of
should also be obtained from liver and any their histories follows.
CHAPTER 1 GASTROINTESTINAL SYMPTOMS 21
In early 1988 I examined a 10-year-old were run. Radiography was bypassed in favor of
neutered male domestic short hair (DSH) cat with endoscopy (greater sensitivity and likelihood of
a history of intermittent vomiting of 7 weeks’ definitive diagnosis). Endoscopy revealed a large
duration. There was a gradual increase in fre- mass in the fundus of the stomach, which was
quency over the last 2 weeks, no weight loss, and a found to be lymphoma (Figure 1-8). Intestinal
normal appetite. Although the owner did not have biopsy specimens revealed moderate lymphocytic-
a great deal of money to spend, he expressed con- plasmacytic enteritis. After 5 months of che-
cern about his cat’s well-being and requested that motherapy (no surgery was done), the mass was
we try to find out what was wrong while keeping no longer detectable at endoscopy (Figure 1-9).
his cost-containment concerns in mind. The cat After 1 year of chemotherapy there was no histo-
weighed 12 lb, and physical examination was unre- logic evidence of lymphoma and chemotherapy
markable other than signs of vague anterior was discontinued. Subsequent yearly endoscopic
abdominal discomfort. A CBC, biochemical pro- examination and biopsy of the stomach and
file, serum T4, feline leukemia virus (FeLV), feline duodenum revealed no evidence of recurrence of
immunodeficiency virus (FIV) test, and a urinalysis the lymphoma. Interestingly, the cat still had a
A B
FIGURE 1-8 A, Close-up endoscopic view of a large mass in the gastric fundus of a 10-year-old cat with a
7-week history of intermittent vomiting. B, Biopsy forceps are advanced into the mass under endoscopic guidance.
The histologic diagnosis was lymphoma. (From Tams TR: Gastroscopy. In Tams TR, ed: Small animal endoscopy, ed 2,
St. Louis, 1999, Mosby.)
A B
FIGURE 1-9 Five-month follow-up endoscopic examination of the cat described in Figure 1-8. Treatment
involved chemotherapy (prednisone, cyclophosphamide, vincristine) alone. No surgery was done. A, Forward view
of proximal stomach at mild distention. The mass is no longer visible, and the rugal folds are smooth. B, Same site as
A with moderate distention. The mucosa at the original site of the mass appears whiter than the surrounding
mucosa. (From Tams TR: Gastroscopy. In Tams TR, ed: Small animal endoscopy, ed 2, St. Louis, 1999, Mosby.)
22 CHAPTER 1 GASTROINTESTINAL SYMPTOMS
moderate degree of inflammatory bowel disease, the pylorus (Figure 1-10). The pyloric canal was
and antiinflammatory therapy (prednisone) was occluded an estimated 300 degrees. The remain-
maintained. If the dose was decreased too much, der of the stomach and duodenum were grossly
vomiting began to recur. The cat lived to the age and histologically normal. Histologic examination
of 17 years, 7 years beyond the diagnosis of gastric of the mass revealed it to be an adenocarcinoma.
lymphoma. The distal antrum, pylorus, and proximal duode-
In 1992 I evaluated a 9-year-old neutered male num were resected, and the dog recovered
Bouvier with a history of intermittent vomiting of uneventfully. This patient experienced an excellent
5 months’ duration (only one to two episodes per quality of life. Upper GI endoscopy was performed
week and with no worrisome associated signs). at 6-month intervals to examine the stomach and
The owners became concerned because they felt proximal small intestine, and there were no gross or
the dog was sleeping a little more than normal, and histologic abnormalities detected (Figure 1-11).
they requested that their regular veterinarian There was also an exploratory laparotomy done at
begin investigating the problem. A CBC, bio- one point for removal of a cloth linear foreign
chemical profile, serum T4, urinalysis, fecal exami- body. This allowed a thorough examination of the
nation for parasites, and survey radiographs of the abdominal cavity, and there was no evidence of
thorax and abdomen were unremarkable. The dog recurrence of neoplasia. The dog lived 30 months
was then referred for endoscopy, which revealed a beyond the diagnosis of gastric neoplasia, and there
large proliferative mass involving the entire pyloric was never any recurrence of adenocarcinoma in
canal and the proximal duodenum just aboral to the stomach region. Unfortunately, euthanasia was
A B
C D
FIGURE 1-10 Endoscopic views of the stomach and proximal duodenum of a 9-year-old male Bouvier with a
history of intermittent vomiting of 5 months’ duration. A, The antral walls are normal.A proliferative mass is
visualized in the pyloric orifice. B, Close-up view of the pyloric mass. The mass is occluding a majority of the
pyloric orifice. The remaining orifice space is visualized at the six o’clock position. C, Pyloric canal near the
pyloroduodenal junction. The mass extended into the proximal duodenum. The histologic diagnosis was
adenocarcinoma. D, The major duodenal papilla is visualized in the upper center in the field of view.
CHAPTER 1 GASTROINTESTINAL SYMPTOMS 23
GRASS INGESTION/
COPROPHAGY/PICA
It is not uncommon for dogs and cats to ingest
grass and for dogs to demonstrate a tendency
toward coprophagy or pica. Occasionally, certain
FIGURE 1-11 Six-month follow-up endoscopic view cats may excessively lick materials such as soil, lit-
from the dog described in Figure 1-10. The ter, wool, and other items. Although the tendency
anastomosis site between the proximal gastric antrum to do this may be related to a group of syndromes
and the duodenum is in the field of view (note ridged termed ingestive behavior problems, these condi-
area extending from five o’clock to twelve o’clock
tions may also occur as a result of some type of
position). There was no gross or histologic evidence of
digestive system disorder. Questions are frequently
tumor recurrence.
asked about the significance of these activities,
especially grass ingestion and coprophagy. A brief
performed at 30 months because of prostatic ade- discussion of each problem follows.
nocarcinoma.
These two case histories clearly demonstrate
the value of timely diagnosis of potentially life- Grass Ingestion
threatening problems. Frequently dogs and cats Many dogs and some cats enjoy eating grass for no
with intermittent vomiting have much more proven reason and with no apparent untoward
minor problems; however, it is difficult to antici- effects. For some it may represent a normal physi-
pate which are the patients that will have the more ologic event. Perhaps these animals simply enjoy
severe problems. One of the clinician’s most “grazing,” or they may be seeking a source of
important roles is to advise and educate owners in roughage to supply minerals or fiber. If grass inges-
a responsible manner. Shouldn’t we as clinicians at tion is not associated with any immediate symp-
the very least make owners aware of the diagnostic toms of a GI disturbance, such as nausea, bloating,
capabilities that we have at our disposal today? or vomiting, its significance is probably minor and
There is no question that a majority of our canine there is no need for concern on the part of the
and feline patients with GI symptoms have treat- owner. Cats that do not get vegetable matter in
able disorders. The important point is that we diagnose their diets may have a tendency to eat parts of
the chronic and potentially serious disorders early enough house plants. This problem can often be success-
to make a difference. fully eliminated by providing a small flower pot
with grass for the cat to eat. For cats that develop
an undesirable habit of eating certain house plants,
Summary measures such as removal of the plant or aversion
The cause of chronic vomiting can be determined taste-smell conditioning with pepper sauce or
in most dogs and cats, and early diagnosis is facili- vinegar often work. Plant ingestion may cause
tated when a systematic diagnostic approach is fol- vomiting from irritant or toxic effects, and it
lowed. In my experience, once adverse food should certainly be discouraged if these symptoms
reactions, GI parasites, drug reactions, and meta- develop.
bolic causes have been ruled out, the most common I commonly encounter canine patients that are
causes of chronic vomiting encountered in prac- reported to ingest grass only at times when they
tice are inflammatory disorders (gastritis, inflam- seem to be experiencing some type of distress
matory bowel disease), gastric hypomotility, related to the digestive system. The most common
obstructive disorders (foreign bodies, hypertrophy of these is nausea, exhibited by such signs as lick-
syndromes), and neoplasia. The most clinically ing of the lips, exaggerated swallowing motions,
useful (i.e., high yield of important information salivation, and often disinterest in eating food.
24 CHAPTER 1 GASTROINTESTINAL SYMPTOMS
behavior. The idea of coprophagy is revolting to feces during confinement situations (e.g., cage
most humans, and there is potential for its occur- confinement in a kennel). Coprophagy may then
rence to seriously alter an owner’s attitude toward become a habit. Dogs with exocrine pancreatic
his or her dog. Most will try any suggestions insufficiency (EPI) may become coprophagic,
offered by their veterinarian, trainer, or any other probably secondary to polyphagia and as a conse-
opinionated person. Some owners, however, come quence of specific nutritional deficiencies. In fact,
to accept their dog’s habit. Many dogs also display a any disorder that causes polyphagia can also
great preference for ingesting cat feces. Potential potentially cause coprophagy. In addition to
causes of coprophagy are listed in Box 1-8. malassimilation disorders, other problems that have
Many theories, none scientifically accepted, been reported to be associated with coprophagy
about why coprophagy occurs in dogs have been include hyperadrenocorticism, intestinal para-
proposed by veterinarians and laypeople. It is sitism, and hyperthyroidism; glucocorticoid ther-
adaptive behavior during the first 3 weeks of nurs- apy also appears to be associated with coprophagy.
ing for the mother to keep the nest free of urine A few significant deleterious consequences are
and feces. It is possible that, for some dogs, con- usually associated with coprophagy. The severe
suming the feces of the young may predispose halitosis that results is particularly offensive to
them to coprophagy in nonmaternal situations. It most owners. Depending on the timing of their
is also possible that the habit of coprophagy may activity, dogs may find themselves relegated to
be an example of neonety, that is, the retention of areas where they are unable to gain access to the
juvenile behavior in the adult dog. owner. The potential for acquiring parasitic infec-
Common reasons for coprophagy probably tions from ingesting stools always exists. Bacterial
include boredom, lack of attention from an owner, and viral infections can also be transmitted in this
unresolved conflictual situations in the environ- way. Occasionally dogs with access to horse
ment, insufficient exercise, consumption of nutri- manure are presented in acute distress that results
tionally incomplete rations, poor hygiene in the from partial or complete intestinal obstruction.
environment, and digestive system disorders that Surgery is sometimes necessary to relieve these
result in malabsorption or maldigestion. Bored or impactions.
fastidious dogs might first begin ingesting their The diagnostic evaluation for the problem of
coprophagy starts with obtaining a thorough his-
tory. A differential diagnosis should be made
regarding the likelihood of the presence of a sig-
BOX 1-8 Possible Causes of
nificant medical problem versus environmental
Coprophagy problems or primary behavior tendencies. The
BEHAVIORAL quality of the diet should be assessed. If a poor
Learned habits from puppyhood quality diet is being fed, it may simply be enough
Carryover of maternal behavior to nonmaternal to change to a higher quality ration, preferably one
situations with a high digestibility ratio. Dogs that are fed
only one meal per day may have a lesser tendency
ENVIRONMENTAL/BEHAVIORAL toward coprophagy if food is provided two to
Poor sanitation three times a day.
Unresolved conflictual situations
Questioning regarding the environment
Boredom (lack of sufficient exercise and interaction
with humans and other animals)
includes information about hygiene practices, level
Confinement in close quarters (e.g., boarding of daily exercise that patient gets, amount of inter-
[kennel] situations) action with humans or other animals, and whether
there are any known stresses or conflicts that the
MEDICAL DISORDERS patient undergoes in its environment. Delayed
Parasitism cleanup and disposal of stools can contribute to
Nutritional deficiency the initiation and maintenance of a habit of
Exocrine pancreatic insufficiency coprophagy. Efforts must be made by the owner to
Intestinal malabsorption remove stools from the environment as quickly as
Hyperadrenocorticism possible. Boredom can be a contributing factor to
Hyperthyroidism
coprophagy. Dogs that spend much of their time
Any cause of polyphagia
alone all day, especially outdoors, may eventually
26 CHAPTER 1 GASTROINTESTINAL SYMPTOMS
concerns and other issues surrounding the applica- Decisions frequently revolve around such ques-
tion of this procedure need to be taken into con- tions as, What are the most meaningful initial
sideration. For some this form of treatment may be clinical tests? When and for how long should
unacceptable. The reader should consult the refer- empirical treatment be tried? What are the most
ences at the end of the chapter for an overview of appropriate medications to use for empirical
using this kind of treatment to solve behavioral treatment trials? When should a detailed diagnos-
problems. tic work-up, which often includes GI function
testing and intestinal biopsies, be recommended?
This section and the chapters on small intestinal
Pica (Chapters 6 and 7) and large intestinal (Chapter
Pica is defined as a craving for and ingestion of 8) disorders describe an organized approach to
unnatural articles of food. Dogs may eat dirt the problem of diarrhea that is applicable to any
(geophagy), cloth, carpet, rocks, sticks, cat litter, or practice setting.
other materials or may show a distinct interest in Diarrhea is defined simply as passage of feces
licking carpet or concrete. Cats may eat soil, grass, that contain an excess amount of water. This
or even cat litter. Anemic cats sometimes lick soil, results in an abnormal increase in stool liquidity
litter, walls, or rusty objects. Wool sucking is an and weight. In some patients there may simply
abnormal behavior disorder known to occur in be an increase in frequency of defecation.
Siamese, part-Siamese, and Burmese cats. Cats Diarrhea has also been described in broad, sim-
with this tendency may actually destroy woolen ple terms as “the too rapid evacuation of too
articles by sucking or chewing on them. loose stools.” Definitions notwithstanding, how-
Nutritional deficiencies should be corrected if ever, it is most important that the clinician care-
they exist. The diagnostic approach is similar fully determine exactly what the owner means
to that followed for coprophagy. Dietary and when the term diarrhea is used. The owner’s
environmental factors should be investigated. interpretation is often not as encompassing as
Occasionally, geophagic animals are found to be the clinician’s. To some people diarrhea indicates
iron deficient. Dogs that lick or chew on foreign only profuse, watery stools. In fact, any variance
objects may have acute or chronic vomiting that from what is considered normal for a patient in
may be related to the presence of a gastric or intes- terms of frequency and consistency should be
tinal foreign body. I have seen dogs with large considered potentially abnormal and worthy of
clumps of carpet fibers that probably took weeks discussion.
to months to build up before endoscopic retrieval Although a variety of symptoms can be caused
or gastrotomy became necessary to remove the by intestinal disorders, diarrhea is the hallmark sign
material. of intestinal dysfunction. It can result from pri-
Most of the time, animals with pica have a mary intestinal disease (e.g., parasitism, various
behavioral tendency rather than a true medical inflammatory disorders, infectious problems, neo-
disorder. Treatment usually involves preventing plasia), disorders of the liver or pancreas that affect
access, if at all possible, to favored objects or limit- normal intestinal digestive and absorptive pro-
ing access to one to two items. Taste aversion cesses, and a number of other factors or conditions
methods can also be tried. Thyroid hormone sup- that adversely affect intestinal function in some
plementation works well in some wool-sucking way (e.g., dietary indiscretion, adverse food reac-
cats. tions, drugs [e.g., antibiotics, cardiac glycosides],
systemic disorders including renal failure, hypoad-
renocorticism).
DIARRHEA Diarrhea is often classified according to loca-
In addition to vomiting, diarrhea is one of the tion (small or large intestinal in origin), mecha-
most common presenting complaints that veteri- nism(s) of diarrhea (osmotic—decreased solute
narians deal with on a daily basis. Surveys have absorption, secretory—hypersecretion of ions,
confirmed that a majority of practicing veteri- exudative—increased permeability, and abnor-
narians rank definitive diagnosis and manage- mal motility), and etiology. Most small animals
ment of chronic intermittent and chronic with diarrhea can be successfully treated.
persistent diarrhea as one of the most challenging Clinicians are cautioned, however, that patients
and frustrating aspects of their medical practices. with diarrhea that do not respond satisfactorily to
28 CHAPTER 1 GASTROINTESTINAL SYMPTOMS
routine care within a reasonable period of time, as fresh blood, straining, and any change in fre-
determined by the patient’s overall condition, quency of defecation are discussed. A rough esti-
frequency of clinical signs (increasing?), and pres- mate of fecal water content is made (e.g., Are the
ence of any significant laboratory abnormalities, stools profuse and watery in nature? Generally
should be thoroughly investigated to determine soft formed?). Small bowel diarrhea is character-
the cause of the problem before it becomes signif- ized by passage of increased volumes of fecal
icantly chronic and potentially nonresponsive to material.
any treatment that is administered. Intestinal biopsy The vaccination history, dietary history, and
is often required for diagnosis in patients with chronic, environmental history (potential for dietary
poorly responsive diarrhea. indiscretion, exposure to any infectious or para-
sitic agents) are always discussed, and valuable
diagnostic clues are often elucidated, especially in
Historical Findings—Overview patients with acute diarrhea. Any recent history
It is clear that a great number of problems can of drug administration should also be reviewed,
cause diarrhea. The clinician is faced with the because some pharmaceuticals could be impli-
tasks of formulating a well-directed diagnostic cated as causative agents (more so in patients with
plan from a variety of available clinical tests and acute diarrhea). Sometimes the patient’s lifestyle
accurately selecting an effective therapeutic regi- plays an important role in the development of
men from a wide array of diets and pharmaceuti- diarrhea. For example, working dogs such as
cals. This all too often has to be accomplished sled or police dogs may experience diarrheal
with cost-containment factors foremost in the episodes during stressful times. Sled dogs some-
owner’s mind.As a result it is extremely important times exhibit explosive diarrhea, with or without
that a thorough history be obtained so that a lim- blood, at the start of or during a race. In police
ited list of most likely diagnostic possibilities can dogs (frequently German shepherds), diarrhea,
be accurately determined. This is best done by which may be consistent with either small or
asking a broad-based series of questions in an large bowel type of signs, and other GI symptoms
orderly manner. Box 1-10 provides a list of ques- can be related to intense work situations. Home
tions to ask when interrogating an owner whose environment and a patient’s individual personal-
pet has diarrhea. ity type (e.g., excitable, aggressive) may play a
The first step involves establishing the dura- role in causing diarrhea in dogs with irritable
tion of clinical signs as clearly as possible. It is bowel syndrome.
important to ascertain how frequently a patient’s The initial phase of the interview is completed
stools are actually observed. Patients that live with an assessment of the patient’s overall condi-
primarily outdoors or that are only casually tion, with emphasis on attitude (alert/respon-
watched when they are outside may have been sive/active versus variable degrees of lethargy) and
experiencing abnormal defecations longer or whether there has been any weight loss. The cli-
more persistently than the owner may actually nician has now had an opportunity to gain per-
realize. Emphasis is also placed on a review of the spective regarding how the case should be
clinical course (e.g., acute and short duration, approached diagnostically and therapeutically
acute onset and then persistent for several weeks and, very importantly, whether or not there
or more, intermittent initially but now more should be some sense of urgency in expediting
persistent, chronic [more than 1 month] and the initial plan (e.g., parvoviral enteritis, intussus-
unrelenting). ception, symptoms including abdominal pain,
Next, a clear description of the nature and chronic wasting disease associated with a severe
character of the stool is obtained. This will help protein-losing enteropathy condition). More
differentiate small bowel from large bowel disor- detailed information regarding the meaning of
ders (Table 1-4). Tests and treatment often vary historical findings is provided in the following
for small and large intestinal disorders, making discussion.
this initial characterization very important.
Because large bowel type of problems occur so
commonly, I often begin by asking questions rel- Stool Characteristics
ative to this area of the GI tract. Specifically, the Table 1-4 outlines historical and gross fecal char-
presence or absence of mucus (Figure 1-13), acteristics useful in differentiation of small and
CHAPTER 1 GASTROINTESTINAL SYMPTOMS 29
large bowel disorders.When asking owners ques- what mucus in fecal material may look like.
tions about stool characteristics, it is often neces- Indeed, sometimes mucus is difficult to identify,
sary for clinicians to describe what they mean in especially in liquid stools in which there is thor-
simple terms. For example, owners sometimes mis- ough admixture of mucus with water or when
interpret questions about presence of mucus in loose stool is mixed in with cat litter.
the stool. If there is uncertainty, it is useful for the Occasionally patients with frequent urgency to
clinician to use such descriptive terms as “clear defecate will expel only clear mucus. This might
gel,” “appearance of a clear coating around the be described by the owner as a “thick, ropy, clear
stool,” or even “appearance of ‘gloppiness’ to the liquid.” I have on occasion observed owners
stool.” Owners who initially denied presence of entering the examination room with a thick
mucus may change their answer to a more accu- strand of clear mucus on their arm, having been
rate one once they have a better understanding of deposited there by their cat or small dog as they
30 CHAPTER 1 GASTROINTESTINAL SYMPTOMS
DEFECATION
Frequency Usually increased to 2-4 times a day but Almost always increased. May be as
may remain normal in some patients frequent as 3-10 times per day (average
3-5). The combination of increased
frequency of defecation and passage of
decreased amounts of stool strongly
suggests large intestinal involvement.
Dyschezia Absent Frequent in dogs, less common in cats
Tenesmus Absent Frequent in dogs, less common in cats
Urgency May be present in cases of acute severe Frequent. Common reason for owner
enteritis, with rapid transit of large being awakened during the night to
volumes of fluid through the allow a dog outdoors to defecate. Often
gastrointestinal tract causes restless or anxious behavior in
well-trained house dogs as they await an
opportunity to get outdoors.
ASSOCIATED SIGNS
Weight loss Usually occurs as disease becomes Unusual. May occur in conjunction with
more chronic. Occurs with both severe colitis, diffuse neoplasia, or
malabsorptive and maldigestive histoplasmosis. If both small and large
disease processes. bowel signs are present, any weight loss
that has occurred is more likely due to
the small intestinal disease component
Vomiting Common in patients with inflammatory May occur in 30%-35% of patients with
bowel disorders and acute infectious acute colitis. Sometimes occurs before
disorders onset of abnormal stools.
Appetite Usually normal or decreased. May be Usually remains normal. May be decreased
cyclic, often decreasing in if disease is severe (neoplasia,
conjunction with flare-ups of histoplasmosis).
symptoms. May be ravenous in some
CHAPTER 1 GASTROINTESTINAL SYMPTOMS 31
gastroscopy and colonoscopy have normal findings resolution of signs can be expected. Significant
on stomach biopsy. In fact, in some of these weight loss and/or inappetence occur in associa-
patients, vomiting actually precedes the onset of tion with primary large bowel disorders only when
diarrhea by several hours to 1 to 2 days.Vomiting they are severe (e.g., severe colitis, including histio-
and inappetence often precede the onset of diar- cytic ulcerative colitis of boxer dogs, diffuse neo-
rhea in dogs with parvovirus enteritis. These facts plasia, or histoplasmosis).
highlight the importance of looking for physical
evidence of intestinal disorders in patients pre-
sented for acute vomiting. This is accomplished Physical Examination
through a physical examination, which must Physical examination of patients with diarrhea is
include a rectal examination to evaluate for similar to the thorough evaluation that is done on
increased mucosal sensitivity (suggestive of procti- vomiting patients (see earlier discussion). Along
tis/colitis) and stool characteristics. Dogs with with the history, physical findings help direct the
severe enteritis that have not yet passed any stool clinician regarding what specific tests, if any, should
may release a large amount of watery, bloody diar- be done and how quickly work-up should be expe-
rhea as soon as a rectal examination is performed. dited. Particular attention is paid to the patient’s
The presence of weight loss and inappetence in attitude, hydration, and posture. Depression and
conjunction with chronic diarrhea suggests a sig- dehydration occurring in conjunction with acute
nificant small intestinal disorder (e.g., inflammatory diarrhea suggest an infectious or toxicity-related
bowel disease, lymphangiectasia, histoplasmosis, cause. Careful evaluation for any signs of sepsis
neoplasia), and their presence should hasten the (fever or hypothermia, tachycardia, tachypnea, and
clinician’s efforts toward making a definitive diag- signs of shock, which may include changes in
nosis. The combination of chronic diarrhea, mucous membrane color to brick red or, alterna-
weight loss, and increased appetite in cats suggests tively, pale, cool extremities and injected mem-
hyperthyroidism, inflammatory bowel disease, EPI, branes) is conducted initially and at any indication
(rare in cats), and occasionally lymphosarcoma that a patient’s condition may be destabilizing again.
(some cats with GI lymphoma actually have an Abnormal posture (e.g., arched back) may indicate
increased rather than decreased appetite). This abdominal pain that can be associated with acute or
combination of signs in dogs is most consis- chronic disorders. The neck should be carefully
tent with EPI. Characteristics of diarrhea in palpated in cats with diarrhea for evidence of an
patients with EPI include voluminous “cowpile”- enlarged thyroid nodule (indicating hyperthy-
consistency stools that are often rancid in nature. roidism). Body weight and overall physical stature
Coprophagy is an ancillary sign that frequently should be noted. The act of defecation, especially if
occurs in dogs with EPI. Weight loss and inappe- there is a history of dyschezia or tenesmus, should
tence rarely occur in dogs and cats with intestinal be observed by the clinician whenever possible.
disorders limited to the large bowel. Careful abdominal palpation is done to exam-
Young to middle-age dogs that have chronic ine for thickened bowel (inflammatory or neoplas-
unrelenting diarrhea with minimal to no weight tic infiltration), intussusception, presence of a mass
loss and a consistently normal appetite most often that could be causing partial intestinal obstruction
have a more significant problem in the large intes- with resultant diarrhea, and lymphadenopathy
tine than in the small bowel. I have found that the (benign or neoplastic). Hepatomegaly suggests the
large bowel signs in these patients are often mild to possibility of hepatic disease in a causative role, and
subtle (e.g., mild dyschezia with transient flare-ups, patients with acute or chronic severe small bowel
soft stools that only occasionally contain blood, diarrhea may have markedly increased fluid in the
intermittent passage of mucus). The prevailing sign small bowel. Sensitivity localized to the caudal
is that the stools are never consistently normal. If dorsal abdomen can often be detected in patients
small bowel disease is present as well it is generally with colitis. This area is often not palpated care-
mild, so inappetence and weight loss would not be fully enough by veterinary clinicians.
expected. The most common combination of A rectal examination is always done in dogs to
findings is mild to moderate colitis, mild inflamma- examine for increased mucosal sensitivity, presence
tory bowel disease of the small intestine, and intes- of narrowing (e.g., infiltrative disease, stricture),
tinal bacterial overgrowth. Each of these problems foreign body, or mass effect, and to obtain a fresh
needs to be treated appropriately before adequate stool sample for gross examination. The finger
CHAPTER 1 GASTROINTESTINAL SYMPTOMS 35
should be rotated 360 degrees in the rectal canal so Giardia cysts. Examination of duodenal lavage
that as much mucosal contact as possible is made. fluid, obtained via endoscopy or at laparotomy, for
Rectal polyps, which are often soft, can easily be trophozoites may also be done but is impractical as
missed on cursory examination. The perineal area an early diagnostic test. A fecal enzyme-linked
is also examined for evidence of perianal fistulas, immunosorbent assay (ELISA) for Giardia-
perineal hernia, and anal gland disease, all of which specific antigen has also become available (Figure
can cause symptoms of large bowel disease. 1-18). This is a sensitive test and can be easily per-
formed in-house or at commercial laboratories.
My preference when examining for parasites in
Diagnostic Plan patients with acute diarrhea is to run both a zinc
Specific diagnostic studies performed in patients sulfate assay and a test for Giardia antigen. This
with diarrhea are generally determined by the fol- gives me a high level of confidence in my efforts
lowing considerations: (1) duration (acute versus to more accurately determine whether or not
chronic [2 to 3 weeks or more]); (2) presence of intestinal parasites are present. Empirical treatment
associated clinical signs such as inappetence, for parasites using such drugs as fenbendazole
weight loss, frequent vomiting, severe bloody diar- (Panacur) or febantel (contained in Drontal Plus,
rhea, listless behavior (expedite diagnostic efforts if Bayer, along with pyrantel pamoate and prazi-
any of these signs are present); (3) environmental quantel) for whipworms and giardiasis may also
history; (4) signalment; (5) localization of the diar- suggest a diagnosis if their use is successful in
rhea to either small or large bowel or both; (6) fre- resolving the diarrhea.
quency of diarrhea (intermittent versus chronic Although diet-induced enteropathies are com-
and persistent); and (7) physical examination find- mon, they are sometimes difficult to diagnose
ings. This will help the clinician determine definitively. Acute diarrhea may result from
whether a conservative step-by-step approach is overeating, a sudden change in diet (especially to a
feasible (e.g., diagnostic dietary trials, empirical canned meat-based food), ingestion of spoiled
treatment for parasites if screening fecal examina- food, food intolerance, or food sensitivity. The
tions are negative for parasites, treatment for mild diagnosis is most likely to be made based on his-
acute colitis) or a more aggressive diagnostic effort tory, ruling out other causes, and response to
is indicated. When evaluating patients with treatment. Strict dietary trials with hypoaller-
chronic diarrhea, the list of diagnostic tests need genic diets are indicated more for patients with
not be extensive, just well directed (Figure 1-17). more chronic signs (e.g., 2 weeks or longer in
duration). Dietary therapy for patients with acute
diarrhea includes dietary restriction for 24 to 48
Acute Diarrhea hours (to place the intestinal tract in a state of phys-
Diet-induced problems, viral infections, and parasites are iologic rest) followed by gradual reintroduction of
the major causes of acute diarrhea in dogs and cats. food using a bland, readily digestible but low-fat
Because intestinal parasites may be a factor in any diet (e.g., chicken and rice or boiled hamburger
diarrheic state, fecal examinations (direct and and rice in a 1:4 ratio, or a commercial diet of sim-
flotation) should be routinely done in all patients. ilar formulation) provided in small, frequently fed
Multiple examinations may be required to identify amounts for several days. Finally, either the regular
Giardia and Trichuris infections. Examination of diet is resumed or a change is made to a new main-
fresh saline smears may identify ova, larvae, or tenance diet if the previous food is considered
motile protozoan parasites. High magnification unsatisfactory or is thought to have played a
with moderate light intensity should be used. causative role in development of the diarrhea.
Adding a drop of iodine may enhance the visibility Patients with such signs as depression, dehydra-
of Giardia trophozoites and will stop any motion tion, and fever in conjunction with acute diarrhea,
of the organism. Unfortunately, saline smears are with or without blood, should be evaluated for
not very reliable for diagnosis of Giardia infections systemic abnormalities. The minimum database
(only 40% of dogs infected with Giardia were always includes a CBC, looking for leukocytosis
diagnosed in one study when saline smears were or leukopenia, presence or absence of left shift, and
done using fresh stool on 3 separate days). The supportive evidence for dehydration (elevated
most accurate practical test for Giardia is zinc sul- packed cell volume [PCV] and total solids). A
fate centrifugal flotation for identification of blood smear can be evaluated quickly and easily
HISTORY
PHYSICAL EXAMINATION
Partial or no response
FIGURE 1-17 Sequential diagnosis of chronic small bowel diarrhea in dogs and cats. ZnSO4, Zinc sulfate; CBC,
complete blood count; UA, urinalysis; ELISA, enzyme-linked immunosorbent assay; T4, thyroxine; FeLV, feline
leukemia virus; FIV, feline immunodeficiency virus; TLI, trypsin-like immunoreactivity.
CHAPTER 1 GASTROINTESTINAL SYMPTOMS 37
Microscopy positive/Giardia (GSA 65) positive Microscopy negative/Giardia (GSA 65) positive
FIGURE 1-18 This schematic illustrates how the Giardia antigen test works (ProspecT Giardia Rapid Assay,
Remel). On the left side there is a depiction of an intestine that contains Giardia trophozoites, Giardia cysts (the oval
objects), and Giardia antigen (the small triangles). All three are being passed in the stool, and a direct saline smear for
trophozoites, a zinc sulfate test for Giardia cysts, and a Giardia antigen test could all be positive. The right schematic
shows a patient that has Giardia trophozoites in the intestine, but there are no trophozoites or cysts being passed in
the feces. The only test that will be positive in this situation is an antigen test. Humans and animals that are infected
with Giardia can shed cysts intermittently. Therefore, if an antigen test is not done, the diagnosis will be missed if
there are no cysts present in the stool sample. I prefer to run this test in addition to running a zinc sulfate test to
help make an accurate diagnosis for Giardia. This test can also be used after a course of treatment to check to see if a
Giardia infection has been successfully eradicated (the test is run 14 days after the conclusion of therapy).
for an estimated white blood cell count. In patients Fecal shedding of viral particles often decreases
with hemorrhagic gastroenteritis, there may be a rapidly, however, so a negative result does not rule
dramatic increase in PCV to levels as high as 70% out infection. Fecal cultures to examine for
to 75%. This degree of increase in PCV contrasts Salmonella spp., Campylobacter jejuni,Yersinia entero-
with that in parvovirus infection and is the key to colitica, and Shigella are indicated in some situations
diagnosis of hemorrhagic gastroenteritis. If CBC (e.g., kennel outbreaks, patients recently obtained
results will not be readily available, a blood smear from pet stores or shelters, households where more
should be examined for estimation of the white than one animal has diarrhea). It is extremely
blood cell count. Serial blood counts may be important that proper technique be used when
necessary because leukocytosis or leukopenia may obtaining feces for stool culture (see Chapter 6).
be transient. A CBC may also suggest a possible
diagnosis of hypoadrenocorticism (lymphocytosis,
eosinophilia, mild anemia). Electrolytes (includ- Chronic Diarrhea
ing sodium and potassium), serial blood glucose Diarrhea that has not responded to conventional
assessments for evidence of sepsis, and urinalysis therapy within 2 or 3 weeks can be considered
both for baseline evaluation of renal function and chronic. It is then appropriate to recommend that
for serial urine specific gravity levels as an aid in the problem be more thoroughly evaluated by
monitoring hydration in patients with normal using specific diagnostic tests. Considerable
renal function should also be run. expense may be involved in some cases, so it is
Hemagglutination, hemagglutination inhibi- always best to start by reviewing the history once
tion, or ELISA tests are used to test for fecal again (including differentiation between small and
shedding of viral antigen. In-office ELISA tests large intestinal involvement or determining that
have proven useful in detecting fecal shedding of both areas are likely involved) to be as accurate as
parvovirus in acute cases and are probably more possible in selecting tests that are likely to provide
sensitive and specific than is hemagglutination. useful information. Suggested diagnostic strategies
38 CHAPTER 1 GASTROINTESTINAL SYMPTOMS
for small intestinal and large intestinal diarrhea are current degree of seriousness of the condition and
presented separately here. An algorithm for thus aids in the decision regarding whether a
sequential diagnosis of chronic small bowel diar- detailed work-up, including intestinal biopsies,
rhea is presented in Figure 1-17. should be expedited versus the feasibility of pursu-
ing conservative therapeutic trials first (e.g., time-
Small Intestinal Diarrhea consuming strict dietary trials). In general, dogs
Chronic small intestinal diarrhea can be broadly with GI signs and a total protein of less than 5.5
categorized into three groups: maldigestive dis- g/dl should undergo intestinal biopsy. Dogs with
ease, malabsorptive disease, and functional mild hypoproteinemia (5.5 to 5.9 g/dl) should be
disorders. A majority of canine and feline patients watched carefully. Cats develop hypoproteinemia
with chronic small intestinal diarrhea seen in clini- much less commonly than dogs. Hypoproteinemia
cal practice have malabsorptive type of problems. usually indicates a significant degree of disease in
There are many causes of intestinal malabsorption. cats, and intestinal biopsies should definitely be
Maldigestive disease is principally caused by EPI. done if the intestine is considered to be the likely
Maldigestive Disease source of the problem.
EPI is uncommon in dogs and cats. In the past EPI Baseline tests, including CBC to identify
was greatly overdiagnosed and many patients were leukocytosis (which suggests inflammatory dis-
needlessly and ineffectually placed on pancreatic ease), eosinophilia (eosinophilic enteritis, chronic
enzyme replacement therapy. Much of the confu- previously undiagnosed endoparasitism), absolute
sion was caused by the lack of a reliable and defin- lymphopenia (often observed in lymphangiecta-
itive test for EPI. Tests commonly used in the past, sia), and anemia (blood loss, anemia of chronic
including the x-ray film digestion test for fecal disease, nutrient malabsorption); biochemical
trypsin activity and the fat (lipomul) absorption profile (e.g., hypoalbuminemia, hypoproteinemia,
test, proved to be insensitive and extremely unreli- abnormal liver enzymes, exclusion of metabolic
able. Tests for steatorrhea (staining feces for fat disorders); and urinalysis to evaluate renal func-
with Sudan stain), amylorrhea (staining for starch tion and check for proteinuria, should be run in all
with Lugol’s solution), and creatorrhea (staining patients with chronic diarrhea. Even if a CBC and
for protein with standard stains) are reasonable and biochemical profile were run previously, during
inexpensive in-house screening tests that can be the early days of onset of the diarrhea, it is often
run, but a significant drawback is that there can be useful to repeat these tests at a later time because
false-negative and false-positive results. The ben- tests that were previously normal may then be
tiromide (BT-PABA) test is sensitive and reli- found to be abnormal (see example in Table 1-5).
able but cumbersome to perform. Hypoproteinemia most often results from disor-
Without question the most sensitive and spe- ders of the small intestine (protein loss involves
cific test for EPI is the serum trypsin-like albumin or both albumin and globulin), liver (pri-
immunoreactivity (TLI) assay. This test simply marily hypoalbuminemia due to decreased produc-
involves obtaining a serum sample after fasting the tion), and protein-losing glomerulonephropathy
patient for 12 to 18 hours (see Chapter 10). Serum (primarily hypoalbuminemia). Although the com-
TLI has been validated for use in both dogs and bination of chronic diarrhea and hypoproteinemia
cats. Previously the fecal proteolytic activity (FPA) is usually consistent with small intestinal disease,
assay was the test of choice in cats. Although EPI there may still be concurrent disease in the liver or
is an uncommon disease, it is recommended that a kidneys. It may therefore be necessary in some
TLI test be run in patients with chronic diarrhea cases to evaluate these organs thoroughly (e.g., bile
so that EPI can be definitively ruled out early in acids assay for liver function, urine protein:
the course of diagnostic evaluation. Failure to run creatinine ratio to more accurately identify
this simple and inexpensive test may result in degree of proteinuria).
needless intestinal biopsies for diagnosis of a sus- Fecal cytology may be useful in evaluating
pected malabsorption disorder. patients with chronic diarrhea. A thin smear of
Malabsorptive Disease stool is stained (e.g., with new methylene blue,
Malabsorptive intestinal disease can be divided Diff-Quik, Wright’s) and examined under high
into protein-losing and non–protein-losing power or oil immersion for the presence of
enteropathies. Use of this classification scheme inflammatory cells. Increased numbers of neu-
helps the clinician determine to some extent the trophils appear with inflammatory small or large
CHAPTER 1 GASTROINTESTINAL SYMPTOMS 39
intestinal disease or secondary to invasive bacterial The next step in diagnosis of suspected malab-
enteritis. sorptive disease, after baseline evaluation has been
The clinician or owner may reasonably elect completed, is to look for evidence of intestinal
to try therapeutic trials as the next step in bacterial overgrowth. The most accurate means of
noncompromised normoproteinemic patients. diagnosis is to obtain samples of duodenal fluid for
Therapeutic trials could include treating for both qualitative and quantitative analysis. This
adverse food reactions (dietary intolerance, food must be done using meticulous sterile technique
sensitivity); occult parasitic infections (especially either at laparotomy or with endoscopic instru-
giardiasis and whipworm infestation) if this has mentation. Quantitative duodenal culture is
not already been done (also, successful treatment expensive and cumbersome and is generally avail-
of giardiasis may require longer than one course of able only in academic institutions. The most prac-
treatment); small intestinal bacterial overgrowth; tical method of testing for intestinal bacterial
and Clostridium perfringens enterotoxicosis (usually overgrowth is by measuring serum concentrations
causes large bowel diarrhea). Dietary trials using of vitamin B12 (cobalamin) and folate (see
hypoallergenic diets or high-quality commercial Chapter 7). These assays can be done in both dogs
foods with a novel protein source are the pri- and cats. Because bacterial overgrowth is not
mary diagnostic tool for identifying adverse food uncommon in patients with pancreatic insuffi-
reactions. Radioallergosorbent tests, which ciency, the cobalamin and folate assays should be
determine serum levels of antigen-specific run if this disorder is suspected. In fact, I generally
immunoglobulin E, have shown poor correlation submit enough serum to run all three special assays
with oral challenge, skin, and intragastric tests for (TLI, cobalamin, and folate) rather than running
food allergy. A response to treatment for any of the just one or two of the tests. If intestinal bacterial
conditions listed above supports a diagnosis and overgrowth is diagnosed, it may be the primary
precludes further work-up. Dietary trials are gen- problem or it may be present secondary to some
erally prescribed for 3 to 4 weeks in patients with other abnormality that has allowed it to persist.
GI disorders. Some patients will respond favorably Treatment for bacterial overgrowth involves
within 3 to 14 days. antibiotics, which may have to be administered for
40 CHAPTER 1 GASTROINTESTINAL SYMPTOMS
as little time as 1 to 2 weeks or as long as many lesions that may not be reached with endoscopic
weeks to months. If a decision is made to treat for instrumentation, a mass is present, or there is
bacterial overgrowth rather than do further tests, 2 lymphadenopathy or an intussusception).
to 3 weeks is an adequate trial period. If the prob- The definitive diagnostic step in many patients
lem is not resolved at this point, it is generally best with chronic, nonresponsive diarrhea is to perform
to move ahead and look for other concurrent intestinal biopsies either via endoscopy or sur-
problems. gery. In a majority of cats and dogs with chronic diarrhea
In addition to intestinal bacterial overgrowth that exists with or without associated clinical signs (e.g.,
and EPI, low serum cobalamin concentrations vomiting, appetite change, weight loss), a definitive diag-
have been observed in dogs and cats with severe nosis can be established based on endoscopic examination
intestinal disease, in giant schnauzers with inappe- and biopsies. The advantages and limitations of
tence and failure to thrive and the laboratory endoscopy are discussed in detail in Chapter 3. In
findings of anemia, leukopenia, and methyl- most patients with chronic diarrhea, it is preferred
malonyl aciduria, and in many shar-peis with that both upper and lower endoscopy be done so
intestinal disease. It is important to evaluate serum that sections from both the small and the large
cobalamin levels in cats with chronic GI disorders intestine can be evaluated histologically to deter-
because supplemention with cobalamin by injec- mine the extent of a disease process as accurately
tion can be quite beneficial therapeutically (see as possible. In addition, in a majority of dogs
Chapter 7). weighing more than 8 to 10 lb, a pediatric endo-
At this stage the next best step is usually to scope can be advanced into the ileum via the
perform intestinal biopsies. Other procedures that colon by an experienced operator. Thus, complete
might be indicated in some patients include con- colonoscopy followed by ileoscopy allows for
trast radiography and abdominal ultra- more detailed evaluation of the small intestine
sonography. Contrast studies of the small (i.e., both upper and lower small intestine are
intestine may help identify segmental lesions, examined and sampled for biopsy). This is espe-
tumors, or foreign bodies. Accurate interpretation cially important in cases in which a disease process
of mucosal lesions on contrast studies is very diffi- may not yet diffusely involve the small intestine
cult. The decision regarding whether or not a (e.g., occasionally, benign inflammatory disease or
contrast study is done is usually based on physical lymphoma will be found in the ileum but not in
examination findings (suggestion of a mass or the duodenum). Ileum biopsy samples can often
well-localized pain) and survey radiographs. be obtained from cats by advancing the biopsy for-
Ultrasonography is frequently recommended over ceps through the ileocolic junction area with the
contrast radiography in patients with suspected endoscope tip situated in the ascending colon.
intestinal disease because intestinal wall thickness Multiple forceps biopsy samples (6 to 10) are
can be much more accurately assessed and lesions obtained from each area of intestine examined.
such as masses and enlarged lymph nodes can be If an exploratory laparotomy is done to obtain
readily detected and also aspirated under ultra- intestinal biopsies, the entire bowel should be
sonographic guidance. carefully evaluated. Biopsies of focally abnormal
Ultrasound scanning of the intestinal tract pro- areas should be performed (full-thickness samples)
vides an evaluation of peristalsis, wall thickness and along with one to two normal areas. Many patients
diameter, lesion location, and appearance of lumi- with chronic small bowel diarrhea have grossly normal
nal contents. Ultrasound is particularly useful in intestine as observed at surgery. Biopsy samples must still
identification of obstruction and its various causes be procured! Two or three full-thickness samples are
(e.g., masses, foreign objects, inflammatory disease, obtained (duodenum and ileum, or duodenum,
intussusception). Thickening of the bowel wall can jejunum, and ileum). A biopsy of any other tissue
occur in either inflammatory or neoplastic disease that appears abnormal (e.g., liver, pancreas, stom-
processes. Probably the greatest value in perform- ach, lymph nodes) should also be performed dur-
ing contrast radiography and/or abdominal ultra- ing exploratory laparotomy.
sonography in a patient with chronic diarrhea lies Biopsies are not often performed as early as they
in helping make a decision on whether endoscopy should be in patients with chronic GI disorders.
will be adequate for obtaining diagnostic intes- Although the availability of endoscopy and its
tinal biopsy samples or whether exploratory sur- minimal risk in obtaining tissue samples is well
gery is indicated (e.g., if there are focal intestinal recognized, some clinicians still wait too long to
CHAPTER 1 GASTROINTESTINAL SYMPTOMS 41
advise owners that a biopsy procedure is definitely example, hypoproteinemia should be thoroughly
needed. Progressive symptoms such as persistent or investigated whether or not a patient is demon-
worsening diarrhea, weight loss, and decrease in strating significant symptoms. If screening tests
appetite, as well as abnormal laboratory parameters indicate that the intestinal tract is most likely
such as hypoproteinemia, are reliable indicators involved, a strong effort should be made to obtain
that biopsies should be performed. It is important biopsy samples. A representative case example is
to remember, however, that some chronic intes- illustrated in Table 1-6. This patient should have
tinal disorders may manifest with only mild symp- undergone a small intestinal biopsy procedure
toms until the disease becomes serious. The much closer to the time the total protein and
patient’s condition may then rapidly decline. albumin levels were determined to be 4.1 g/dl and
Routine tests such as a hemogram and bio- 1.6 g/dl, respectively, rather than 10 weeks later,
chemical profile are generally very useful in when the protein level dropped to 2.8 g/dl and
screening for significant intestinal problems. For the patient was in a somewhat more compromised
condition. Screening tests for liver and kidney dis- colon may be missed unless a complete examina-
ease done during the initial screening period were tion of the colon is done with a flexible endo-
normal. scope. Another advantage of using a flexible
Treatment is then based on a review of the lab- endoscope is that ileoscopy may be accom-
oratory tests and biopsy results. It is emphasized plished in many dogs after complete colonoscopy.
that some patients with chronic diarrhea may have Biopsy samples should always be obtained during
several disorders at the same time (e.g., inflamma- colonoscopy, regardless of gross appearance.
tory small bowel disease, intestinal bacterial over- Indeed, it is not uncommon for patients with
growth, colitis). A thorough work-up will lead to histologic evidence of colitis to have grossly nor-
diagnosis of each disorder, with subsequent devel- mal colonic mucosa. If biopsy samples are not
opment of a comprehensive treatment plan. The obtained, the diagnosis may well be missed.
likelihood of more rapid resolution of symptoms is Although it is a sound idea to evaluate patients
much greater when each existing problem is with chronic large bowel diarrhea thoroughly by
properly treated. including a CBC, biochemical profile, urinalysis,
and survey abdominal radiographs in the work-up,
Large Intestinal Diarrhea it is not always financially feasible for the owner to
As previously stated, large bowel disorders are com- approve this detailed approach. If cost containment
mon in dogs and cats. In mild cases, a diagnosis is is essential, emphasis should be placed on a thor-
often established based on fecal parasite exami- ough history, physical examination with careful
nation (e.g., hookworms, whipworms, coccidia, abdominal palpation and rectal examination,
and Giardia); positive response to empirical serial fecal examinations for parasites (preferably
treatment for difficult-to-diagnose parasite using zinc sulfate concentration with centrifuga-
problems (Giardia and whipworms); response to tion because this test is more reliable for detecting
dietary trials (high-fiber diet, elimination diets); Giardia), fecal or rectal scrape cytology, and
or response to empirical treatment for acute colonoscopy with biopsy. A great majority of
colitis. patients with disease localized to the large intestine
Diagnostic tests for chronic large bowel diar- will be diagnosed correctly if this approach is fol-
rhea principally involve the following: lowed. However, if there is any evidence of sys-
temic signs, such as PU/PD, inappetence, weight
1. Fecal cytology to look for increased numbers
loss, or vomiting, in addition to large bowel diar-
of C. perfringens spores and inflammatory cells
rhea, baseline data, including CBC, biochemical
(specifically neutrophils), which suggest bacter-
profile, urinalysis, and survey abdominal radio-
ial or primary inflammatory disease. Fecal or
graphs, should be obtained. The scope of any fur-
rectal scrape cytology is also useful in identify-
ther work-up is then expanded based on these
ing Histoplasma organisms.
results (e.g., panhypoproteinemia suggests that a
2. Fecal culture if history or fecal cytology sug-
small intestinal disorder is concurrently present,
gests the possibility that bacterial infectious dis-
azotemia and low urine specific gravity indicate
ease exists (Campylobacter, Salmonella).
renal disease). It is once again emphasized that if
3. Enterotoxin assay on stool to evaluate for C.
there is any possibility that both small and large
perfringens enterotoxicosis.
intestinal disease are present, biopsies of both
4. Colon biopsy via colonoscopy (preferred
regions should be performed. All too often,
technique) or surgery.
incomplete diagnosis and only partially effective
Complete colonoscopy with examination of treatment regimens are established if a less than
the rectum, descending, transverse, and ascend- thorough approach is made once the step of intes-
ing colon, cecum, and ileocolic orifice area is pre- tinal biopsies is reached.
ferred. Although examination and biopsy of the
descending colon with a rigid colonoscope is BORBORYGMUS AND
commonly diagnostic in patients with large bowel
diarrhea, such problems as occult trichuriasis, in
FLATULENCE
which whipworms may be grossly evident in the Borborygmus is a term used to describe a rumbling
cecum but not in the descending colon, ileocolic type of gut sound. Borborygmi are due to a moving
or cecocolic intussusception, typhlitis, or neoplasia gas-fluid interface in the gut. These sounds usually
that is localized in the transverse or ascending originate in the stomach. Borborygmi most com-
CHAPTER 1 GASTROINTESTINAL SYMPTOMS 43
monly affect the dog. They are rarely heard emanat- dency to bloat, with or without belching, (2)
ing from cats. Borborygmus and flatulence com- assumption of an arched back stance, which might
monly result from dietary indiscretion; however, indicate cramping, and (3) excessive expulsion of
these signs may be exaggerated in malassimilation or flatus. Generally these symptoms occur only indi-
in any condition that promotes bacterial fermenta- vidually in a patient. It is rare for any single patient
tion of malabsorbed carbohydrates and proteins. to exhibit all three of these main symptoms.
They may also occur as a matter of course in some These symptoms should not be treated cava-
normal patients or in association with functional lierly or be dismissed too rapidly as insignificant by
bowel disorders (e.g., irritable bowel syndrome). the clinician. Although in some patients the prob-
Owners of patients that display these symptoms, lem may simply be related to aerophagia, as may
especially flatulence, invariably highlight informa- be caused by excitement, eating too rapidly, or eat-
tion about their occurrence as they discuss their pet’s ing foods that are high “gas producers,” in other
history. Indeed, sometimes offensive flatulence is the patients a more serious disorder may be present.
primary reason for seeking veterinary consultation. For example, some dogs with gastric hypomotility
Gas is normally present in the GI tract. The two disease or gastric outflow obstruction tend to
most common sources of intestinal gas in humans experience bloating or a feeling of abdominal dis-
and animals are swallowed air and bacterial fermen- tention. Many of these dogs exhibit intermittent
tation. In adult humans the volume of intraluminal to frequent signs of nausea, and vomiting fre-
intestinal gas present at any one time varies from 140 quently occurs. Pronounced borborygmi may be
to 260 ml. No such figures are available for animals. present. There may be intermittent inappetence as
Most (99%) of the gas present in the GI tract is com- well. Early in the course of the disorder there may
posed of five gases: nitrogen, oxygen, carbon dioxide, be minimal symptoms, but as the disorder pro-
hydrogen, and methane. All of these gases are odor- gresses, there may be significant patient dis-
less. The unpleasant odor that may be detected in comfort. This is also true of the patient with
flatus is probably imparted by other gases that are inflammatory bowel disease or irritable bowel syn-
present in trace amounts and by hydrogen sulfide drome that tends to stand at times with an arched
and mercaptans metabolized from sulfur-containing back because of abdominal discomfort related to
substances present in certain foods. gas pain. Diagnostic efforts should be undertaken
The upper GI tract contains oxygen, nitrogen, to determine the cause of the symptoms in these
and carbon dioxide, whereas the colon contains patients. Treatment often provides significant
hydrogen, methane, and carbon dioxide. The relief. Although patients with excessive flatus do
source of oxygen and nitrogen is inspired air. not often exhibit signs of discomfort, they may be
Carbon dioxide is produced by the interaction of affected by a malassimilation disorder that warrants
acid and alkaline substances in the stomach. Much diagnostic efforts.
of the carbon dioxide generated is absorbed
through the bloodstream. Gas generated in the
lower intestinal tract is the result of bacterial fer- Diagnosis
mentation. Fermentation by the colon flora results Diagnosis involves a review of historical factors,
in the production of variable amounts of hydrogen, physical examination, and selected tests based on
methane, carbon dioxide, and oxygen. the primary symptoms and the degree of signif-
The GI transit time for gas is considerably icance that the clinician affords them. The eval-
shorter than for liquids or solids. Gas introduced to uation of a patient with flatulence includes
the stomach of humans can be passed in as little determination of the daily diet and whether
time as 15 minutes. Overdistention of the GI tract there exist opportunities for dietary indiscretion.
with gas can potentially lead to significant dis- Legumes, such as soybean meal, and vegetables
comfort. Patients will frequently continue to shift such as beans, cabbage, lentils, and brussel sprouts
positions or assume an arched stance when experi- are known as “gas producers.” Legumes contain
encing gas-related discomfort. large quantities of oligosaccharides that are
indigestible because the normal gut lacks the
enzymes necessary to metabolize them. Ten per-
Historical Features cent to 20% of ingested carbohydrates may be
The complaints described by owners of dogs with malabsorbed, and protein substrates, when fer-
“gaseousness” problems include the pet’s (1) ten- mented, may contribute to gaseous constituents.
44 CHAPTER 1 GASTROINTESTINAL SYMPTOMS
Spoiled foods are likely to yield increased quanti- cant reduction in the percentage of highly odorif-
ties of odiferous gases. Milk products may cause erous episodes. In vivo hydrogen sulfide levels
gaseousness in patients with lactase deficiency. were significantly reduced. Treatment for exces-
The owner should also be questioned about the sive flatus is discussed in more detail in Chapter 7.
patient’s eating habits. Excessive aerophagia may
occur when liquid or solid food is bolted or eaten
rapidly. For some patients this may simply be habit, BLOATING, FULLNESS,
whereas in others it may result from a sense of AND ABDOMINAL
competition with other animals in the immediate
vicinity for rights to the food. Patients that are
DISCOMFORT
quite active (e.g., working dogs) may have a Bloating, fullness, and abdominal discomfort are
tendency to be aerophagic and produce excessive nonspecific symptoms that may be encountered
flatus as a result. in both organic and “functional” (e.g., irritable
When the flatulence is fairly recent in occur- bowel syndrome, disorders characterized by
rence and is accompanied by other signs, such as deranged motility) digestive tract disorders. These
inappetence, weight loss, evidence of abdominal syndromes do not seem to occur as commonly in
discomfort, and diarrhea, a detailed work-up is in animals as they do in humans. Although in human
order. Depending on the patient’s environment medicine they have been presumed over the years to
and the dominant symptoms, this may include be associated with a central problem of increased
fecal analysis for evidence of Giardi (both zinc gaseousness, it is now known that most of these
sulfate centrifugal flotation and a Giardia antigen patients’ symptoms do not originate in excessive
test), TLI assay to investigate for EPI, cobalamin intestinal gas. Rather, the responsible mechanisms
and folate assays for intestinal bacterial over- appear to involve disordered intestinal motility and a
growth, survey and possibly contrast radio- heightened pain response to intestinal distention. It
graphs of the GI tract (with particular attention is now thought that gas, even in small volumes, may
paid to transit time, as well as to any morphologic trigger symptoms even though the total quantity of
abnormalities), and endoscopy to obtain gastric gas in the intestinal tract is not greater than in
and intestinal biopsy samples (rule out infiltrative asymptomatic subjects. Patients with these problems
disorders). may be symptomatic more often if they tend to be
Treatment often involves dietary manipulation aerophagic as well.
(with change to foods that are highly digestible The symptom complex of bloating, fullness, and
and low in fiber, with a moderate protein content abdominal discomfort certainly is recognized to
and a novel protein source), feeding smaller meals occur in dogs but can be difficult to detect unless
more frequently if too rapid ingestion of food is the owner is an astute observer. Clinicians are cau-
considered a problem, and treatment of any pri- tioned to not overlook the possibility that patients
mary disorder that might be identified by the tests with these vague symptoms have a significant dis-
listed above. Occasionally, gas-reducing drugs are order, not in terms of being life-threatening,
used. Pharmacologic management attempts may because this is rarely the case, but rather in terms of
include adsorbents, antifoaming agents, or various causing significant discomfort.
enzyme preparations. Response to these products Disorders that tend to cause these symptoms in
is often variable. Charcoal is an absorbent that has dogs include gastric and/or intestinal motility
been commonly used in humans. Simethicone is derangement and inflammatory bowel disease.
an antifoaming agent that reduces surface tension Diagnostic tests that should be considered
and promotes coalescence of bubbles so that they include survey abdominal radiographs to
can be more easily passed. Simethicone is not examine for presence of excessive bowel gas (rarely
absorbed from the GI tract and can be used safely positive), radiographic studies to evaluate intes-
in dogs and cats, although its effectiveness is tinal motility (e.g., BIPS, nuclear scintigraphy), and
unknown. both upper and lower GI endoscopy to obtain
An antiflatulence treat preparation was studied small and large bowel biopsy samples. Normal
and shown to be beneficial for reduction of the intestinal biopsy results support a diagnosis of dys-
offensive odor of flatulence in dogs. The treats motility (irritable bowel syndrome), whereas
included activated charcoal, Yucca schidigera, and abnormal biopsy results are generally consistent
zinc acetate. Treated dogs experienced a signifi- with some degree of inflammatory bowel disease.
CHAPTER 1 GASTROINTESTINAL SYMPTOMS 45
Treatment is often based on biopsy results and logic problems. Neurologic problems may include
clinical interpretation of the symptom complex peripheral neuropathies, cauda equina syndrome,
exhibited by the patient. Dietary manipulation, and congenital defects of the caudal vertebral col-
including use of high-fiber diets for irritable bowel umn and spinal cord (e.g., sacrocaudal agenesis
syndrome, and various types of pharmacologic of Manx cats). Incontinence may be related to
management are usually employed. Inflammatory aging in some patients. Also, any disease that
bowel disease is discussed in Chapter 7. Irritable causes rapid transit of large volumes of diarrhea
bowel syndrome is discussed in Chapter 8. (e.g., severe enteritis) may produce transient fecal
incontinence in patients with healthy continence
mechanisms.
FECAL INCONTINENCE The mechanisms of anal continence are com-
Fecal incontinence denotes uncontrolled release of plex, and a detailed description is beyond the
rectal contents. Although it is not a common dis- scope of this discussion. In the dog and cat the
order in dogs and only rarely occurs in cats, the internal and external anal sphincter muscles and
ramifications of this problem for a household pet the puborectalis muscle (the caudal portion of the
and its owner are highly significant. Pets with a levator ani muscle) play major roles in maintaining
fecal incontinence problem that cannot be reason- continence. The most important muscle in main-
ably controlled are often euthanized because of the taining the sphincter component of the conti-
impracticality of maintaining the animal on a nence mechanism may be the puborectalis muscle.
long-term basis in terms of the problems associ- The external anal sphincter is innervated by the
ated with fecal soiling. caudal rectal branch of the pudendal nerve, origi-
There are many potential causes of fecal incon- nating from the sacral spinal cord segments (S1 to
tinence (Box 1-12). Most incontinence disorders S3). Bilateral transection of the pudendal nerve or
can be classified as neurogenic or nonneurogenic. sacral cord lesions will result in fecal incontinence.
Causes include anatomic disruption of the anal However, unilateral transection usually does not
sphincters or pudendal nerve trauma resulting lead to major dysfunction because the remainder
from surgery (e.g., perineal hernia repair, perianal of the innervated external anal sphincter muscle
fistula repair, anal sac removal, tumor removal), can compensate for the denervation. Surgical pro-
obstetric trauma or other injuries (e.g., lacerations, cedures involving full-thickness circumferential
bite wound trauma with subsequent ascending resection at the anorectal area always carry the risk
bacterial neuritis as may occur from a cat fight of ensuing fecal incontinence. The internal anal
injury), and various non–surgery-related neuro- sphincter is innervated by branches of the pelvic
nerve (afferent and efferent) and pudendal and include both urinary and fecal soiling and irrita-
hypogastric nerves (efferent). tion around the perineal and abdominal skin.
The colon also plays an important role in help- Occasionally there is complete paralysis of the
ing to maintain fecal continence through its pelvic limbs as well. Aging patients with gradual
reservoir function. Reflex activity in the colon onset of incontinence are most likely to have some
appears to allow the external anal sphincter to type of neurologic problem.
retain fecal material while the internal anal Once the existence of incontinence has been
sphincter relaxes, thereby allowing the colon to established, the clinical evaluation begins with an
dilate and accommodate increases in fecal mass. assessment of the frequency, severity, and circum-
Simultaneously there is a brief (several minutes) stances surrounding the incontinent episodes.
decrease in propulsive contractions in the colon, How acute are the symptoms? Are the episodes
which also helps facilitate the accommodation associated with urgency, or is there no prior warn-
process. The colon continues to readapt with sub- ing? The owner should be asked whether or not
sequent peristaltic delivery of fecal material until a the dog still assumes an appropriate posture for
time when defecation is appropriate. If the colon is defecation, and, if so, does this take place at an
presented with large volumes of watery fecal appropriate time and place? Some dogs with mild
material in a short period of time, as may occur in incontinence still do this on a fairly routine basis
patients with severe viral or bacterial enteritis, this but on occasion will inappropriately release stool
reservoir function can become overwhelmed and when asleep, during periods of relaxation, or while
transient incontinence (urge incontinence) may on a walk. These episodes may occur in response
result. Urge incontinence can also be associated to increased rectal pressure related to the presence
with moderate to severe proctitis or colitis, in of stool that overrides a now compromised conti-
which the patient experiences significant discom- nence mechanism.
fort (perhaps a “burning” sensation) with a result- Excitement may also cause spontaneous evacua-
ant sense of urgency to defecate and overriding of tion of stool. In some patients incontinence
the continence mechanism. episodes become much more frequent (i.e., major
The internal and external anal sphincter mus- incontinence versus partial), and this suggests a
cles and the puborectalis muscle are primarily severe anorectal sensory disorder. Unconscious anal
responsible for maintaining a high-pressure zone dribbling of small amounts of fluid and residue may
in the terminal rectum that maintains continence become common, especially during periods of
at rest. Studies have shown that the internal anal increased abdominal or rectal pressure (e.g., associ-
sphincter contributes 50% to 80% of the resting ated with coughing, excitement, or exercise).
tone in the high-pressure zone. The primary The owner should also be asked if the patient
function of the external anal sphincter is to can urinate normally. Because micturition relies
actively contract over short periods of time to on nerve pathways similar to those involved in
resist the action of peristaltic waves. fecal continence, abnormalities involving both
functions suggest that the fecal incontinence is of
neurologic origin.
Diagnosis If the fecal incontinence has been a very recent
Important factors in diagnosis include obtaining a development, questions regarding trauma are
detailed history so that any potential causative fac- asked. Lumbosacral and sacrocaudal fracture, sub-
tors (e.g., trauma, difficult whelping, history of sig- luxation, and luxation can cause fecal inconti-
nificant constipation problems) can be elucidated, nence (distended bladder and atonic tail often
physical examination (including neurologic assess- result as well). In cats these injuries are commonly
ment), and completion of any indicated diagnostic associated with getting their tails caught by some-
tests. thing. Cats with bite wounds around the tailhead
The signalment is very important in evaluating may develop abscessation and ascending bacterial
a patient with fecal incontinence. Manx and other neuritis and meningomyelitis of the caudal spinal
tailless cats and Old English sheepdogs, bulldogs, cord. Any history of anorectal surgery is reviewed.
and Boston terriers may be affected with an agen- Generally symptoms develop and are reported
esis of the sacrocaudal vertebrae and spinal cord. shortly after any surgery in which nerve damage
The neurologic deficit is present from birth but occurs. Any incidence of significant straining
is often first noted at weaning. Clinical signs episodes should also be discussed. Severe proctitis,
CHAPTER 1 GASTROINTESTINAL SYMPTOMS 47
strain to defecate, it is important that owners with constipation. The primary indication would
become familiar with their pet’s normal defecation be to evaluate an intraluminal mass or stricture
patterns (frequency, amount, time of day). This is site. Ultrasonography may be useful for localiz-
especially important regarding cats with mega- ing a site of obstruction.
colon. It is useful to teach owners of cats with a
history of a constipation problem how to palpate
the colon so that they can recognize a state of con- Treatment
stipation early enough to seek treatment, well The treatment of constipation and obstipation is
before development of obstipation. reviewed in detail in Chapter 8. Treatment often
Diagnostic testing during the initial detailed involves dietary manipulation (high-fiber diets)
assessment of the patient should include a CBC, used alone or in combination with stool softeners.
biochemical profile, urinalysis, and thyroid The promotility drug cisapride, used in conjunc-
studies. These tests are done to investigate tion with a stool softener such as lactulose, is often
for systemic problems that can cause colonic iner- effective in managing colonic inertia problems.
tia (peripheral neuropathies, hypercalcemia, Manual deobstipation under general anesthesia is
hypokalemia, hypothyroidism). Survey radio- generally required in dogs and cats with severe
graphs of the abdomen, lumbosacral spine, and constipation or obstipation. Balloon catheters for
pelvis are made to confirm the presence and assess dilation of colonic strictures are available and are
the degree of constipation and to look for evi- used under endoscopic guidance. Surgery is
dence of such causes as prostatomegaly, enlarged required for removal of masses, severe benign stric-
sublumbar lymph node, presence of a mass, nar- tures and any malignant stricture, and some for-
rowed pelvic canal, and stricture (Figure 1-20). eign body impaction cases. Colectomy may be
Colonoscopy is not commonly required in patients indicated for the occasional cat with megacolon
that does not respond to combination therapy
using cisapride, stool softeners, and dietary man-
agement.
REFERENCES
Beaver BV: Feline ingestive behavior. In Beaver BV, ed:
Feline behavior: a guide for veterinarians, Philadelphia,
1992,WB Saunders.
Berk JE: Gaseousness. In Berk JE, Haubrich WS, eds:
Gastrointestinal symptoms, Philadelphia, 1991, BC Decker.
Burbridge HM, Guilford WG: Barium-impregnated
polyethylene spheres (BIPS): clinical observations, Vet
Radiol Ultrasound 37:79, 1996.
Burrows CF: Diarrhea in the dog: a clinical perspective.
FIGURE 1-20 Severe obstipation in a 13-year-old In Viewpoints in veterinary medicine, ed 2, Lehigh Valley,
spayed female DSH cat. Note that the fecal column Pa, 1993, Alpo Petfoods.
ends abruptly ventral to L6. There are small Burrows CF: Vomiting and regurgitation in the dog: a
radiopaque densities posterior to the fecal column that clinical perspective. In: Viewpoints in veterinary medicine,
are presumably in the colon. Enemas and ed 2, Lehigh Valley, Pa, 1993,Alpo Petfoods.
transabdominal manual manipulation performed under Dean PW, Bojrab MJ: Defecation and fecal continence.
sedation failed to move the fecal mass any closer to the In Bojrab MJ, ed: Disease mechanisms in small animal sur-
anus. Exploratory laparotomy revealed an annular gery, Philadelphia, 1993, Lea & Febiger.
constricting lesion in the colon approximately 4 cm Friedman G: Diet and irritable bowel syndrome. In
proximal to the rectum. The histologic diagnosis was Friedman G, ed: The irritable bowel syndrome: realities
adenocarcinoma. Mesenteric lymphadenopathy and and trends, Gastroenterol Clin North Am 20:313, 1991.
extensive nodular involvement in the mesentery were Giffard CJ et al.: Administration of charcoal, Yucca schidi-
also found. The annular adenocarcinoma in the colon gera, and zinc acetate to reduce malodorous flatulence
caused nearly complete obstruction of the descending in dogs, J Am Vet Med Assoc 218(6):892, 2001.
colon. In cats with idiopathic constipation and Guilford WG:Approach to clinical problems in gastroen-
obstipation, the fecal mass generally extends into the terology. In Guilford et al., eds: Strombeck’s small animal
rectum (see Figure 1-19). gastroenterology, ed 3, Philadelphia, 1996,WB Saunders.
50 CHAPTER 1 GASTROINTESTINAL SYMPTOMS
Giulford WG, Lawoko C: Validation of radiopaque Polsky R: Electric shock collars: are they worth the
markers for assessment of gastric emptying rates of risks? J Am Anim Hosp Assoc 30:463, 1994.
food in dogs, J Vet Intern Med 10:170, 1996. Richter KP: Diseases of the rectum and anus. In Kirk
Hedlund CS: Surgery of the perineum, rectum, and RW, Bonagura JB, eds: Current veterinary therapy XI,
anus. In Fossum TW, ed: Small animal surgery, St. Louis, Philadelphia, 1992,WB Saunders.
1997, Mosby. Tams TR: Endoscopic examination of the small intes-
Lorenz MD: Coprophagy and pica. In Lorenz MD, tine. In Tams TR, ed: Small animal endoscopy, ed 2, St.
Cornelius LM, eds: Small animal medical diagnosis. Louis, 1999, Mosby.
Philadelphia, 1987, JB Lippincott. Tams TR: Gastroscopy. In Tams TR, ed: Small animal
Luescher UA, McKeown DB, Halip J: Stereotypic or endoscopy, ed 2, St. Louis, 1999, Mosby.
obsessive-compulsive disorders in dogs and cats. In Voith Tams TR: Vomiting, regurgitation, and dysphagia. In
V, Marder A, eds:Advances in companion animal behav- Ettinger SJ, ed: Textbook of veterinary internal medicine, ed
ior, Vet Clin North Am Small Anim Pract 21:401, 1991. 4, Philadelphia, 1995,WB Saunders.
Niebauer GW: Rectoanal disease. In Bojrab MJ, ed: Willard M: Clinical manifestations of gastrointestinal
Disease mechanisms in small animal surgery, Philadelphia, disorders. In Nelson RW, Couto CG, eds: Small animal
1993, Lea & Febiger. internal medicine, ed 2, St. Louis, 1998, Mosby.
C H A P T E R
2
RADIOLOGY AND
ULTRASONOGRAPHY
OF THE DIGESTIVE
SYSTEM
Linda J. Konde
Pamela A. Green
Charles R. Pugh
51
52 CHAPTER 2 RADIOLOGY AND ULTRASONOGRAPHY OF THE DIGESTIVE SYSTEM
from the base of the tongue caudally. Aspiration vena cava. On the VD view the esophagus is to the
pneumonia is rare in oral dysphagia. left of the trachea, approximately on midline.
Pharyngeal dysphagia results in decreased pha- Esophagram
ryngeal peristalsis. Weakened contractility impairs Indications include regurgitation of undigested
movement of a bolus through the pharynx. On the food, persistent vomiting or gagging, suspected
survey film the pharynx may appear distended foreign object or mass, and assessment of position
with gas. Contrast medium is retained in the or compression of the esophagus.
oropharynx, pharyngeal isthmus, laryngopharynx, The following materials are needed for an
and piriform recesses. Contrast medium can be esophagram:
seen in the trachea. Aspiration pneumonia is
1. A dose syringe.
often seen in pharyngeal dysphagia.
2. Barium paste, micropulverized barium suspen-
Cricopharyngeal dysphagia is due to insufficient
sion, or a food-barium mixture. Barium paste
relaxation of the cricopharyngeal sphincter. This
offers the best mucosal coating and should be
is the most common form of oropharyngeal dys-
used to evaluate suspected mucosal or mass
phagia (Figure 2-3). On the survey film, gas may
lesions. Liquid barium suspension is used to
be seen in the cervical esophagus. There is con-
evaluate an enlarged esophagus because a large
trast reflux into the nasopharynx and trachea, and
volume may be required to fill the esophagus.
there is contrast retention in all other pharyngeal
A food-barium mixture is used to evaluate
regions. Aspiration pneumonia may be seen in
motility because peristalsis may be adequate for
cricopharyngeal dysphagia.
liquids and insufficient for solid food. Some
strictures may allow fluid to pass normally but
Esophagus will restrict passage of solid food.
3. Aqueous organic iodide (used if perforation is
Radiographic Anatomy
suspected).
Because the esophagus has the same opacity as that
of surrounding soft tissue structures in the neck Administer the contrast medium orally in the
and mediastinum, it is not usually seen on survey buccal pouch.The dose is approximately 10 to 20
radiographs. However, normal transient dilation of ml, to be administered before each exposure.
an air-filled esophagus may be visualized. Com- Obtain lateral and VD oblique views (esophagus
mon nonpathologic causes of air in the esophagus and spine are superimposed on the straight VD
include aerophagia, anxiety, dyspnea, and anesthe- view).
sia. In the dog a normal esophagram shows barium
On the lateral view the cranial thoracic esoph- outlining longitudinal, parallel folds and a small
agus is dorsal to the trachea, and caudally it is diverticulum at the thoracic inlet (Figure 2-4); the
located about halfway between the aorta and the diverticulum is more pronounced in brachy-
cephalic breeds.
In the cat a normal esophagram shows a cranial
esophageal mucosal pattern that is similar to that
of the dog; caudally the mucosa has transverse
mucosal folds, referred to as a herringbone pattern
(Figure 2-5). Esophageal distention by a bolus of
contrast medium in transit may be seen in all
patients.
Radiographic Signs of Esophageal Disease
Megaesophagus (Figure 2-6). Megaesophagus
appears as an enlarged esophagus containing fluid,
ingesta, or air. There is ventral deviation of the tra-
chea. A “tracheoesophageal stripe”—a thickened
FIGURE 2-3 A dog with cricopharyngeal achalasia. soft tissue opacity composed of dorsal tracheal wall
There is accumulation of contrast medium in the and ventral esophageal wall—is more often seen
pharyngeal isthmus (I ). Some contrast medium is on the left lateral view. The “stripe” is visible
present in the esophagus, but there is considerable when there is air in the esophagus, as well as in the
accumulation in the trachea. trachea. On the VD view the terminal esophagus
54 CHAPTER 2 RADIOLOGY AND ULTRASONOGRAPHY OF THE DIGESTIVE SYSTEM
A B
FIGURE 2-4 A, Lateral view of a normal canine esophagram. Note the normal longitudinal folds outlined by
contrast medium. B, Ventrodorsal oblique view of a normal canine esophagram. The patient is at an oblique angle
to avoid summation of the spine and esophagus.
A B
C D
FIGURE 2-6 A, Lateral view of a dog with megaesophagus. The trachea is ventrally depressed by an enlarged, air-
filled esophagus. Note the “tracheoesophageal stripe” (open arrows), which is seen when air is in the esophagus as
well as in the trachea. Dorsal and ventral esophageal walls are seen caudally (arrowheads). B, Ventrodorsal view of the
dog in A. This view is centered on the caudal esophagus. The air-filled esophagus appears as two linear opacities on
either side of midline that taper into the diaphragm (arrowheads). C, Lateral view of a dog with mild
megaesophagus. No abnormalities are seen with barium liquid. D, Same dog as in C. When food-barium mixture is
used, esophageal dilation is seen, suggesting abnormal esophageal motility. Use of food mixed with barium should
be considered when evaluating esophageal swallowing dysfunction.
liver is small or has herniated through the appear uniform and parallel in a distended stom-
diaphragm into the thorax. ach and undulant and tortuous in a nondistended
On the VD view the stomach position in the stomach. The rugal pattern is negligible in the
dog is slightly different from that in the cat: In the body and pyloric areas of a normal stomach.
dog the fundus is cranial-left, the body is midline, Gastrogram
and the pylorus is cranial-right. In the cat the fun- Indications include chronic vomiting, hemateme-
dus and body are cranial-left and the pylorus is sis, suspected foreign object or mass, pyloric dis-
midline or slightly to the right of the spine. ease, and identification of stomach position.
Stomach location varies with stomach disten- The following materials are needed for a gas-
tion, but the stomach is usually between the tenth trogram: micropulverized barium suspension
and thirteenth ribs. Competent assessment of liver diluted to 50% with warm water; gas source (room
size and diagnosis of liver masses depend on air, carbonated beverage, gas-producing tablets or
knowledge of normal stomach position. granules); water-soluble iodinated contrast medi-
The variably sized stomach may contain non- um (used only if a gastric perforation or rupture is
persistent air, fluid, or mineral opacities. The wall suspected); and a stomach tube, mouth gag, and
of the fundus has pronounced rugal folds that large-dose syringe.
56 CHAPTER 2 RADIOLOGY AND ULTRASONOGRAPHY OF THE DIGESTIVE SYSTEM
A B
FIGURE 2-7 A, Ventrodorsal view of a cat with persistent right aortic arch. Note the abrupt change in diameter
of the esophagus at the heart base. The right aortic arch compresses the esophagus, causing deviation of contrast
medium to the left (arrow). B, Lateral view of a dog with persistent right aortic arch. Contrast medium outlines
the dilated cranial thoracic esophagus. There is a change in esophageal diameter at the heart base. The esophagus is
partially dilated caudal to the vascular ring anomaly.
A B
FIGURE 2-8 Survey ventrodorsal (A) and lateral (B) views of a dog with an esophageal foreign object. An opacity
is located in the area of the caudal esophagus on both views (arrows). Two views are necessary to determine the
exact location of soft tissue opacity.
In a positive or negative gastrogram the following iodinated contrast mixed with 0.7 ml warm
technique is best used to identify stomach position water per lb.
or gastric foreign objects: 3. Administer the contrast medium via a stomach
tube rather than orally to achieve maximum
1. The stomach should be empty. stomach distention. Make sure that the tube is not
2. Use the following doses: for barium, 1.5 to 2 in the trachea (by palpation or radiograph).
ml of previously diluted (50%) micropulverized 4. Obtain right and left lateral views, VD and
barium per lb; for room air, 1.5 to 2 ml of air dorsoventral views, and additional oblique
per lb; for oral iodinated contrast, 0.7 ml of views as needed.
CHAPTER 2 RADIOLOGY AND ULTRASONOGRAPHY OF THE DIGESTIVE SYSTEM 57
A B
FIGURE 2-9 A, Lateral view of a dog with megaesophagus. The trachea is ventrally depressed by an air-filled
esophagus. A “tracheoesophageal stripe” is seen (closed arrowheads), and the caudal esophagus is dilated (open arrows).
No obvious cause for the dilated esophagus is seen. B, Lateral esophagram of dog in A. A smooth, curvilinear filling
defect is in the caudal esophagus, which is caused by an intramural esophageal mass located proximal to the
gastroesophageal junction. Contrast studies should be performed to determine the cause of megaesophagus.
Diagnosis was leiomyosarcoma.
C D
FIGURE 2-11 Lateral (A) and ventrodorsal (B) views of normal canine double-contrast gastrogram. Contrast
medium is pooling in the fundus. Note the smooth mucosal surface and peristalsis in the body of the stomach. Filling
defects seen in the wall of the fundus on the ventrodorsal view are normal rugal folds. Lateral (C) and ventrodorsal
(D) views of normal feline double-contrast gastrogram. Rugal pattern, seen as lucent linear filling defects, is normally
more evident in the fundus. Note that the cardiac area is slightly irregular.This is a normal finding in cats.
1. Thickened, irregular, or indistinct rugal folds opacities that accentuate rugal folds on survey
2. Prominent rugal folds in the pylorus and body radiographs
3. Rigid stomach wall that is nondistensible, is
Gastric Dilatation-Volvulus (Figures 2-16 and
often thickened, and lacks peristalsis
2-17). The following radiographic signs indicate
4. Hyperperistalsis or hypoperistalsis
gastric dilatation-volvulus:
5. Barium precipitation caused by abnormal
stomach contents, such as blood, excess mucus, 1. Gastric dilatation.
or incorrect pH 2. Compartmentalization of the stomach (double
6. Stomach emptying that is delayed or more bubble sign) due to the stomach’s folding on
rapid than normal itself.
7. Calcification of gastric mucosa, secondary to 3. Pylorus located dorsally and to the left of mid-
chronic renal disease, appearing as faint linear line, and fundus located ventrally and to the
CHAPTER 2 RADIOLOGY AND ULTRASONOGRAPHY OF THE DIGESTIVE SYSTEM 59
FIGURE 2-12 A dog with pyloric hypertrophy. A FIGURE 2-13 Gastrogram of a dog with a gastric
small, annular filling defect (arrows) extends into the foreign object (ball). The ball appeared as a soft tissue
pyloric antrum just proximal to the pylorus. A small opacity on survey radiographs. When surrounded by
amount of barium extends into the pyloric canal. barium, the ball appears radiolucent. The lucent filling
defect is completely surrounded by barium, suggesting
an intraluminal foreign object.
A B
FIGURE 2-14 A and B, Ventrodorsal views of a cat that swallowed a toy fish. Note the normal irregular cardia.
The toy fish is clearly seen as a lucent filling defect in the stomach. Between the two views the position of the toy
has changed. This mobility indicates that the object is intraluminal.
Small Intestine
Radiographic Anatomy
The duodenum is located about halfway between
the spine and the ventral body wall on the lateral
view. It descends along the right body wall and
ascends in the midabdomen on the VD view.
Jejunum is evenly distributed throughout the
FIGURE 2-15 Lateral view of a dog with severe abdomen. The ileum is that portion of the distal
ulcerative gastritis. The mucosal margin is irregular, small intestine that joins with the colon and is
with spicules of barium extending into small ulcers in located in the right midabdomen.
the stomach wall. This is primarily seen in the body Intestinal shape is uniform and tubular with tran-
and pyloric antrum. Barium appears smudged, sient narrowings due to peristalsis. Intestinal contents
suggesting poor mixing of contrast medium. This is
include nonpersistent air, fluid, or mineral opacity.
probably due to abnormal stomach contents.
A general guideline used to evaluate intestinal
size is that the diameter should be no larger than
one to two rib widths or no larger than the height
of a lumbar vertebral body (not the vertebral arch
or dorsal spine, just the body).
A B
FIGURE 2-16 Lateral (A) and ventrodorsal (B) views of a dog with gastric dilatation-volvulus. There is
compartmentalization of the stomach. The fundus (F) is the largest compartment. The pylorus (P) is displaced
dorsally and to the left.
CHAPTER 2 RADIOLOGY AND ULTRASONOGRAPHY OF THE DIGESTIVE SYSTEM 61
A B
FIGURE 2-17 Lateral survey (A) and contrast study (B) of a dog with gastric dilatation-volvulus. Rugal folds are
identified in the ventrally displaced fundus (F). Pattern of rugal folds is helpful in identifying fundus of stomach.
A B
FIGURE 2-19 A, Ventrodorsal view of a dog with an intramural gastric mass. There is an abrupt change in
diameter of stomach lumen (open arrow). This is referred to as a “shelf sign.” Stomach wall is markedly thickened
(closed arrowheads). B, An intramural mass is seen on the lesser curvature of the stomach body (arrows). Barium is
adherent to an irregular mucosal surface.
Radiographic Signs of Small Intestinal Disease Foreign Objects. Radiopaque foreign objects are
Excess Gas. Causes of excess gas in the small visible on survey radiographs (Figure 2-24).
intestine without dilation include aerophagia, Radiolucent foreign objects may be seen on sur-
enteritis, anorexia, recent enema, and incomplete vey radiographs. On a contrast study, foreign
or high obstruction where vomition relieves objects cause a lucent intraluminal filling defect in
gas/fluid distention; and, with dilation, paralytic the contrast medium (Figure 2-25).
ileus, obstructive ileus due to foreign objects, neo- Bowel proximal to the foreign object may be
plasia, abscess, and granuloma. dilated with fluid or gas. If bowel has been perfo-
rated, there may be free abdominal gas, loss of
abdominal visceral detail, and fluid opacity in the
abdomen.
Linear Foreign Objects. Survey radiographs may
show numerous end-on loops of small intestine.
This is not a definitive sign because hyperperistal-
sis may give this appearance.
A contrast study reveals plication or gathering
of small intestinal loops (Figure 2-26). Do not
confuse plication with the normal “string of
beads” sign in cats. The “string of beads” appears
as a symmetric widening and narrowing of the
intestinal lumen. Plicated intestine has a serpen-
tine appearance.
Perforation may occur, causing free gas and/or
peritonitis.
Enteritis—Nonulcerative. Radiographic signs of
nonulcerative enteritis include rapid intestinal
transit time; severe accentuation of the fimbriated
villous pattern; persistent narrowing or “stringing”
of small intestinal lumen diameter, not to be con-
fused with normal peristalsis; hypercontractility or
hyperperistalsis; and precipitation of barium due
FIGURE 2-24 There is a smooth soft tissue opacity to abnormal luminal contents, such as blood,
(foreign object) in the descending duodenum (arrows). excess mucus, or abnormal pH.
This opacity is visible because it is surrounded by air. Enteritis—Ulcerative (Figure 2-27). Radio-
The duodenum proximal to the foreign object is dilated. graphic signs of ulcerative enteritis include severe
Large Intestine
FIGURE 2-28 Ventrodorsal view of a dog that had Radiographic Anatomy
surgery 3 days previously to correct an intussusception.
The cecum and ascending colon are located in the
Free air (A) is seen in the abdomen, presumably caused
by the surgery.A second barium study was performed right midabdomen. The transverse colon parallels
because of suspected recurrence of intussusception. the caudal border of the greater curvature of the
Arrows indicate lumen of intussuscipiens; arrowheads stomach. The descending colon is in the left
show lumen of intussusceptum. Free barium seen in abdomen, and the rectum descends into the pelvic
the abdomen (B) indicates intestinal rupture. canal. The large intestine assumes the shape of a
question mark (?) on the VD view. On the lateral
view the regions of large intestine are usually
superimposed in the midabdomen.
A B
FIGURE 2-31 A, A large amount of free abdominal gas is present (arrowheads). Gas outlines serosa of stomach,
abdominal surface of diaphragm, and dorsal caudal abdomen. There is loss of abdominal visceral detail. B, Small
amounts of free abdominal gas are more difficult to discern. Several small gas accumulations are seen superimposed
over the bladder (arrowheads). These gas opacities are not associated with bowel. There is loss of abdominal detail
due to peritonitis and free abdominal fluid.
FIGURE 2-32 Positional studies are of value in determining the presence of small amounts of free abdominal gas.
The patient is placed in left lateral recumbency, and an exposure is made using a horizontal beam. Free abdominal
gas accumulates against the abdominal wall (arrowheads).
68 CHAPTER 2 RADIOLOGY AND ULTRASONOGRAPHY OF THE DIGESTIVE SYSTEM
inflammatory large bowel disease. Do not perform the lesion, place a purse-string suture around
a barium enema within 2 hours of enema (spasms the anus, and tighten the suture after position-
induced), 6 to 12 hours after colonoscopy ing the tip of an additional catheter just inside
(spasms induced), or within 3 to 4 days after colon the anus. A small amount of contrast medium
biopsy (may rupture colon). given through the second catheter will outline
The following materials are needed for a bar- the extent of a rectal lesion.
ium enema:
A normal-appearing barium enema study
1. Pediatric or adult-sized balloon catheters.* (Figure 2-33) shows uniform distention of the
2. Gravity-flow enema bag with tubing† or dose colon and cecum and a smooth mucosal surface.
syringe with adapter and three-way valve. A redundant or long convoluted colon is a nor-
3. Micropulverized barium diluted to 50% with mal variant, and a spasm at the catheter tip is
warm tap water. common.
4. Aqueous organic iodides diluted to 50% with Radiographic Signs of Large Intestinal Disease
tap water, used only if perforation is suspected. Megacolon or Dilation of Large Intestine. This dis-
Barium is the contrast medium of choice to ease has numerous causes: neurologic disease such
achieve satisfactory mucosal definition. as trauma to the spine, spinal neoplasia, or congen-
5. Room air. ital spinal abnormalities; mechanical obstruction
such as neoplasia, foreign objects, extrinsic masses
The following technique is employed for a bar-
compressing or infiltrating the colon wall, or
ium enema:
narrowed pelvic canal from malunion of pelvic
1. A 24-hour fast is desirable, and multiple high- fractures; abnormal diet; and psychogenic factors.
volume, warm-water enemas are essential to There are no published guidelines for determining
clean out the large intestine. Feces in the colon megacolon, so diagnosis of abnormal colonic dila-
can obscure small lesions and mimic mass lesions. tion is subjective.
2. General anesthesia is desirable to eliminate Colitis and Typhlitis (Figure 2-34). Radio-
colonic spasms, facilitate manipulation and graphic signs of these diseases include mucosal
positioning, and alleviate patient anxiety and irregularity (“cobblestone” appearance); increased
discomfort. wall thickness; spasticity and shortening of colon
3. Avoid using narcotics that induce severe colonic and/or cecum; and mucosal ulceration.
spasms. Emphysematous Colitis. Survey radiographs
4. Use 2.3 ml/lb of diluted (50%) barium liquid show gas in the bowel wall. Extensive amounts of
as a general guideline because the dose is gas in the wall parallel luminal gas, in a linear fash-
extremely variable. Infuse contrast medium ion, distinctly showing mucosal surfaces.
slowly through an inflated balloon catheter. On a barium study contrast covers the mucosal
5. Obtain a VD film after 2.3 ml/lb is adminis- surface and gas in the colon wall is still visible.
tered or if there is resistance to flow. Administer Ileocolic Intussusception. On survey films a tubu-
more contrast medium as required. lar soft tissue mass outlined by colonic gas may be
6. Obtain lateral,VD, and two oblique views. seen. The leading edge of the intussusceptum has
7. Perform a double-contrast study, best for evalu- an oval or rounded shape (Figure 2-35).
ating mucosal detail, by removing most of the On a contrast study barium surrounds the
positive contrast medium and slowly infusing intussusceptum, which appears as an intraluminal
room air into the colon. Repeat exposures in radiolucent filling defect. Barium may define
lateral,VD, and oblique positions. linear bands, sometimes referred to as a “coil
8. If a rectal lesion is suspected, the balloon spring” appearance, in the wall of the intussus-
catheter may obscure the lesion. A method to cipiens, as it contracts on the intussusceptum
outline rectal lesions, if endoscopy is not avail- (Figure 2-36).
able, is to inflate the balloon catheter cranial to Colonic or Cecal Intramural Masses. These vary
widely in appearance (Figure 2-37). On survey
*
Picker Enema Tubes. Picker International, Denver, CO films fecal impaction may occur proximal to the
80239. mass.A solid soft tissue mass may be seen; the mass
†
Rapidfil Enema System. Picker International, Denver, may be focal or diffuse.There is annular constric-
CO 80239. tion or eccentric invasion of the colon by a mass.
CHAPTER 2 RADIOLOGY AND ULTRASONOGRAPHY OF THE DIGESTIVE SYSTEM 69
A B
FIGURE 2-33 Normal dog (A) and cat (B) barium enema. There is smooth mucosal coating by contrast medium
and even distention of the large intestine. Note the question mark configuration of the canine and feline colon. A,
Ascending colon; C, cecum; D, descending colon; T, transverse colon.
A B
FIGURE 2-36 A and B, Two examples of ileocolic intussusception identified on a barium enema. The
intussusceptum (I ) appears as lucent filling defect within the colon. Abnormal rounded leading edge is visible (curved
arrow). Faint linear bands in the intussuscipiens are outlined by barium (arrowheads).
A B
FIGURE 2-37 A, Survey radiograph of a dog with an intramural colonic mass. Gas is seen in the colon distal to
the mass (M), and feces can be seen proximal to the mass. B, Same dog as in A. Barium enema shows an annular
colonic mass. Note the abrupt change in colonic diameter caused by the nondistensible intramural mass.
On a barium study an irregular or smooth well visualized on the lateral view, with sharply
mucosal surface is seen. Ulceration may be diffuse defined edges and a triangular shape that projects
and spiculated or large and cavitated. Polypoid just beyond the ribs. In the cat the ventrocaudal
masses cause luminal lucent filling defects on bar- liver border is often displaced dorsally by falci-
ium study. form fat and may be located in the cranial midab-
domen.
Normal liver size is best defined by the location
Liver of the stomach. On the lateral view the stomach axis
Normal Anatomy from the fundus to the body should be parallel to
The liver has a soft tissue opacity; therefore inter- the ribs, although this varies somewhat with breed,
nal structures are not defined. Much of the liver is body conformation, and stomach distention. On the
silhouetted by the diaphragm, stomach, and right VD view an empty stomach is usually located
kidney, making it difficult to evaluate the liver between the tenth and thirteenth ribs. The pylorus
borders. The ventrocaudal liver border is usually and body are located more on midline in the cat.
CHAPTER 2 RADIOLOGY AND ULTRASONOGRAPHY OF THE DIGESTIVE SYSTEM 71
A B
FIGURE 2-39 A, Lateral radiograph of a cat with an enlarged liver. On the survey film there is increased soft
tissue opacity in the cranial abdomen. Liver cannot be delineated. B, Same cat as in A. Contrast medium in the
stomach shows caudodorsal gastric displacement by an enlarged liver.
the right side, there is often axial displacement most likely associated with emphysematous chole-
of the stomach on the VD view. cystitis.
3. Asymmetric liver enlargement is usually due to
liver masses. Concurrent displacement of the
Pancreas
stomach, kidneys, spleen, and colon is directly
influenced by the location of the mass. The Normal Anatomy
liver borders are often spherical or nodular. The normal pancreas is not visible radiographi-
cally. The pancreas is located medial to the
Positive or negative contrast in the stomach can descending duodenum and caudal to the pylorus
aid in evaluating liver size (Figure 2-39).
Small Liver. This is commonly due to chronic
liver disease and cirrhosis, portal vein anomalies, or
physical displacement of the liver into the chest
(diaphragmatic hernia). On the radiographic study,
the stomach axis becomes more vertical or may be
directed cranially, liver borders may be sharply
defined or nodular, and free abdominal fluid often
occurs secondary to chronic cirrhosis. With
diaphragmatic hernia, soft tissue opacity is present
in the thorax and the diaphragmatic outline is not
well defined.
Portal Vein Anomalies—Angiography. On angiog-
raphy a patent ductus venosus or other portosys-
temic shunt may be identified (Figures 2-40 and
2-41). Portal circulation in portocaval or portosys-
temic shunts is decreased or absent.
Gallbladder Diseases. These are difficult to diag-
nose on a survey radiograph. Changes in size and
shape are not usually perceived. Only changes in
opacity can be consistently detected radiographi-
cally. FIGURE 2-40 Venous phase of a cranial mesenteric
Mineral opacity in the area of the gallbladder or arterial injection of contrast medium. The portal vein
biliary system is usually due to calculus formation, (PV ) bypasses the liver through a patent ductus venosus
which is a rare occurrence in the dog and cat. Gas (PDV ) to empty into the caudal vena cava (CVC ).
in the area of the gallbladder also is rare and is Normal portal circulation through the liver is not seen.
CHAPTER 2 RADIOLOGY AND ULTRASONOGRAPHY OF THE DIGESTIVE SYSTEM 73
and greater curvature of the stomach. The trans- Radiographic Diagnosis of Pancreatic
verse colon lies caudal to the area of the pancreas. Disease
Any significant pancreatic enlargement may be Unfortunately, more than 50% of dogs with
appreciated in these areas. pancreatic disease have no detectable radio-
graphic abnormalities. Any radiographic changes
seen in pancreatic disease are nonspecific, with
similar changes detected in acute or chronic
pancreatitis and pancreatic neoplasia. The ill-
defined increased opacity in the pancreatic
region can be related to edema, necrosis, fibrosis,
abscessation, or tumor spread. Changes include
the following:
1. Loss of detail and increased soft tissue opacity
in the area of the pancreas. This loss of detail
may be subtle, and diagnosis relies heavily on
judgment and experience in evaluating
radiographs. Close comparison of other areas
of the abdomen, such as the spleen and fundic
border of the stomach, with the pancreatic
area may facilitate the diagnosis (Figure 2-
42).
2. On the VD view the pylorus may be displaced
toward midline and the duodenum displaced to
the right abdominal wall. This causes an
increase in the size or width of the cranial duo-
denal flexure. A barium study may be necessary
FIGURE 2-41 Percutaneous splenic portography to confirm this finding.
shows numerous tortuous splenic veins draining into 3. The transverse colon may be displaced cau-
both the portal vein ( pv) and the caudal vena cava (vc). dally away from the greater curvature of the
There is some portal blood flow through the liver stomach on both the lateral and the VD
(arrow). S, Spleen. views.
A B
FIGURE 2-42 A, Lateral radiograph of a dog with clinical signs of pancreatitis. There is loss of abdominal visceral
detail in the cranial ventral abdomen. A hazy, streaky fluid opacity is apparent in this region. C, Transverse colon.
B, Ventrodorsal radiograph of a dog with clinical signs of pancreatitis. There is an increased soft tissue opacity in
the area of the pancreas (arrowheads).
74 CHAPTER 2 RADIOLOGY AND ULTRASONOGRAPHY OF THE DIGESTIVE SYSTEM
4. The duodenum may be displaced dorsally or surrounding tissue, resulting in echoes that are
ventrally on the lateral view. very bright or white
5. The duodenum may have persistent gas dila- 2. Hypoechoic—a tissue that produces low-
tion or may appear “fixed” in position on serial intensity echoes, when compared with those of
radiographic studies. surrounding tissue, resulting in echoes that are
6. A barium study may show the duodenum to dark gray
have a thickened wall, corrugation or spasm, 3. Anechoic—an area in which there is no echo
stricture formation, ulceration, and/or atonic- formation, resulting in a black image
ity (Figure 2-43). These changes are nonspe- 4. Isoechoic—a tissue that produces echoes that
cific and cannot be considered as definitive are the same as those of surrounding tissues
evidence of pancreatic disease. 5. Complex or heterogeneous echogenicity—a
mixture of any of the above echo patterns
or image in lateral recumbency with the top Real-time scanning of the GI tract allows eval-
hindleg pulled away from the body. Breed con- uation of individual wall layers, peristalsis, wall
formation and GI gas affect transducer and thickness and diameter, lesion location, and
patient positioning. Transducer and patient appearance of luminal contents. The presence of
positioning vary, depending on the structure or intraluminal bowel gas does not preclude evalua-
disease processes imaged. For example, patent tion of the bowel wall located between the lumen
ductus venosus, small liver, pancreas, and gall- gas and the transducer.
bladder diseases are often best imaged from the Normal gastric wall thickness is 3 to 5 mm in
right lateral abdomen. dogs (Figure 2-44) and 1.1 to 3.6 mm in cats; small
7. To avoid the problem of gastric or intestinal gas intestinal wall thickness in dogs is 3 to 4.5 mm
shadowing, perform imaging early in the morn- (Figure 2-45) and 1.6 to 2.6 mm in cats; and colon
ing (before feeding or significant aerophagia), fill wall thickness is 2.5 to 3 mm in dogs and 1.3 to
the stomach with water, or perform positional 2.5 mm in cats.
studies to circumvent the gas interference prob- The proximal duodenum can usually be identi-
lem. Images are difficult to obtain and interpret fied by its continuity with the pylorus. The colon
if contrast medium is in the stomach or GI tract. and cecum may be identified by relative location,
size, and shape; these often contain considerable
gas and/or feces.
Normal Sonographic Anatomy The jejunum is randomly arranged. Therefore
of the Gastrointestinal Tract it is best to perform a survey scan of the jejunum
The GI tract is composed of four major histologic and then isolate and trace individual loops.
layers. Each layer is sonographically displayed as
alternating hyperechoic and hypoechoic bands. Sonographic Diagnosis of
Five distinct layers may be seen with high- Gastrointestinal Disease
frequency transducers: Thickening of the gastric or bowel wall is the
most common abnormality detected.This change
1. Lumen and mucosal surface—hyperechoic
is considered a nonspecific finding because it can
2. Mucosa—hypoechoic
occur in inflammatory and neoplastic bowel wall
3. Submucosa—hyperechoic
disease. Bowel wall thickening may be diffuse or
4. Muscularis—hypoechoic
focal, and focal thickening may be eccentric or
5. Serosa—hyperechoic
concentric. As a rule the layered appearance of
Often, only three layers are distinguished when bowel wall tends to be conserved in inflammatory
the transducer frequency is 5.0 MHz or less: disease and disrupted by neoplasia. Asymmetric,
mucosal surface, muscular layer, and serosa. focal change is common with neoplasia. Diffuse,
symmetric thickening is typical of inflammatory inflammatory disease. Masses with a mixed echo
bowel disease (Figure 2-46) but can be seen with pattern are more commonly associated with neo-
diffuse neoplasia, such as lymphosarcoma (Figure plasia, hematoma, abscess, and granuloma.
2-47). Inflammatory bowel disease (IBD) in cats Motility is usually decreased or absent through
can appear as normal wall thickness or can show the affected area. A biopsy is needed for definitive
mild to moderate wall thickening, primarily diagnosis because benign and malignant lesions
involving the muscle layer. Enlarged mesenteric can appear similar on ultrasound. Some examples
lymph nodes have been associated with IBD, so of GI tract neoplasia are seen in Figures 2-48,
biopsy is very important to differentiate IBD 2-49, 2-50, and 2-51.
from neoplasia. Cats with IBD may have concur- Adynamic (nonobstructive, paralytic) ileus is
rent cholangiohepatitis and pancreatitis. Dis- indicated by distended loops of small intestine and
ruptive, asymmetric changes can occur with variable peristalsis. Dynamic (obstructive) ileus is
hematoma or abscessation. Carcinomas are usu- indicated by distended loops of small intestine larger
ally disruptive and concentric. Mucosal irregular- than in adynamic ileus (Figure 2-52), minimal
ity may be present in either neoplastic or deformity from adjacent structures, and variable
CHAPTER 2 RADIOLOGY AND ULTRASONOGRAPHY OF THE DIGESTIVE SYSTEM 77
FIGURE 2-50 Transverse scan of the stomach (arrows) FIGURE 2-51 Transverse scan of the cardia region of
in a 9-year-old shih tzu with anorexia, intermittent the stomach (large arrows) in a 16-year-old Lhasa apso
vomiting, and weight loss. The stomach wall is with hematuria and vomiting once with possible blood
markedly thickened and diffusely hypoechoic with loss in the vomitus. A circumscribed, oval, hypoechoic mass
of wall layers. Diagnosis was adenocarcinoma. (small arrows) with a hyperechoic margin is seen at the
L, Lumen. cardia of the stomach. The mucosa appears intact over
the mass. Diagnosis was leiomyoma.
78 CHAPTER 2 RADIOLOGY AND ULTRASONOGRAPHY OF THE DIGESTIVE SYSTEM
A B
FIGURE 2-56 A, Transverse scan of small intestine (large arrows) in a 5-year-old Labrador retriever with
nonspecific signs of abdominal pain and anorexia. One loop of small intestine (arrowheads) is surrounded by another
loop (arrows), consistent with intussusception. B, Same dog as in A. Foreign material (FB), seen within the
intussusceptum (arrowheads), surrounded by the intusscipiens (arrows), shows as a slightly irregular hyperechoic linear
echogenicity with intense acoustic shadowing deep to the foreign material. Surgery confirmed the intussusception
and the presence of cloth in the affected small bowel, which may have caused the intussusception.
A B
FIGURE 2-59 Sagittal (A) and transverse (B) scans of a normal canine liver. D, Diaphragm; gb, gallbladder.
FIGURE 2-63 Liver scan of an Irish wolfhound presented for depression and icterus with elevated bilirubin and
alkaline phosphatase. There is a very thick hyperechoic gallbladder wall. The gallbladder (gb) is not distended. The
entire liver is hypoechoic. Multiple anechoic tubular structures with defined hyperechoic walls are seen throughout
the liver (arrowheads). These most likely represent portal veins that are better visualized owing to surrounding
hypoechoic liver. Sonographic changes suggest cholecystitis and cholangiohepatitis. Surgery showed a diffusely
enlarged liver filled with dark, inspissated bile. Diagnosis was cholangiohepatitis with severe canalicular bile stasis,
consistent with a toxic insult. D, Diaphragm.
liver in dogs. Vessel walls appear more echogenic Inflammation or infection of other organs, such as
and more numerous, and gallbladder wall may be pancreatitis, prostatitis, or gastroenteritis, may also
more prominent or thickened. Hypoechoic livers cause the liver to appear diffusely hypoechoic, pos-
have been associated with diseases that accumulate sibly secondary to septicemia.
fluid in hepatocytes, such as acute hepatitis, Hyperechogenicity of the liver is subjectively
cholangiohepatitis (Figure 2-63), hepatic venous determined by comparison with known surround-
congestion (will also see dilated hepatic veins and ing normal tissues and decreased visualization of
caudal vena cava), and hepatic necrosis. Lym- hepatic vasculature. Some infiltrative processes, par-
phosarcoma may also appear diffusely hypoechoic. ticularly feline lipidosis, will cause attenuation of
These disorders are the more common causes for the sound beam in the deeper parts of the liver
hypoechoic livers, but other processes are possible. (Figure 2-64). Disease processes that are associated
84 CHAPTER 2 RADIOLOGY AND ULTRASONOGRAPHY OF THE DIGESTIVE SYSTEM
with hyperechoic liver include lipidosis, steroid hypoechoic, hyperechoic, anechoic, or isoechoic
hepatopathy (due to increased glycogen storage), or have a combination of any of these echogenici-
cholangiohepatitis, chronic hepatitis, cirrhosis, dia- ties. Ultrasound can help determine the number
betes mellitus, and lymphosarcoma. This list is not and location of lesions and association with struc-
all-inclusive, and other processes are possible. tures such as the portal vein, caudal vena cava, and
Patchy liver echo patterns with mixed hypo- gallbladder, which may affect the decision on
echoic, hyperechoic, and isoechoic regions are a whether to attempt surgical excision.
nonspecific change that suggests a diffuse disorder. Anechoic focal lesions can be caused by true
Some of the areas may show or mimic nodularity. cysts, biliary pseudocysts, parasitic cysts, enlarged
The changes may reflect a mixture of normal liver, end-on bile ducts, abscesses, and arteriovenous fis-
inflammation, fatty infiltration, hepatopathy, hepatic tulas (Figure 2-67). Hyperechoic, hypoechoic, and
necrosis, hyperplasia, neoplasia, and other disease mixed echoic masses can be caused by metastatic
processes (Figure 2-65). Histologic diagnosis is nec- or primary neoplasia, lymphosarcoma, abscesses,
essary for definitive diagnosis. Hepatocutaneous granulomas, nodular hyperplasia, biliary cystade-
syndrome has a fairly characteristic diffuse echopat- nomas, and hematomas (Figures 2-68 to 2-75).
tern of hyperechoic, “lacey” strands that surround Correlating history and clinical findings is helpful
ovoid to spherical hypoechoic zones (Figure 2-66). in forming a differential diagnosis, but biopsy is
Focal Liver Disease needed for definitive diagnosis.
Ultrasound is useful to describe the appearance of Gallbladder Disease
focal lesions in the liver. The size, shape, number, 1. Extrahepatic biliary obstruction (experi-
margin definition, and echogenicity are easily mental) results in the following:
characterized, except for very small masses, such as a. Rapid gallbladder distention
seen with carcinomatosis, which may not be b. Bile duct enlargement by 48 hours
detected. Focal lesions in the liver can appear c. Extrahepatic duct dilation by 3 days
FIGURE 2-65 Sagittal scan of the liver in an 8-year- FIGURE 2-66 Sagittal scan of the liver in an 11-year-
old German shepherd–mix that was on long-term old Skye terrier with a 3- to 4-week history of severely
phenobarbital for seizures. Liver enzyme levels were inflamed, thickened, painful footpads on all four feet.
elevated. Ultrasound shows a nonhomogeneous liver Liver enzyme levels were elevated. The liver is diffusely
echogenicity with patchy hyperechoic zones nonhomogeneous with numerous hypoechoic nodules
throughout the liver. Diagnosis was moderate hepatitis intermixed with hyperechoic strands. Overall liver
with nodular hyperplasia and vacuolar hepatopathy, texture appears coarse and has been described as a
possibly secondary to chronic phenobarbital “Swiss cheese–like” or “honeycomb” appearance.
administration. Diagnosis was hepatocutaneous syndrome.
CHAPTER 2 RADIOLOGY AND ULTRASONOGRAPHY OF THE DIGESTIVE SYSTEM 85
FIGURE 2-67 Transverse scan of the liver in a 10-year-old domestic short hair cat presented for routine
vaccinations. A mass was palpated in the cranial abdomen. Ultrasound shows a large, thin-walled, anechoic structure
(C ) with a small connecting anechoic structure (C ). A small portion of liver (L) is seen. Diagnosis was probable
congenital hepatic cyst.
d. Intrahepatic duct dilation by 7 days each other. One channel is a portal vessel, and
(Figure 2-76). the other is a bile duct. The duct may have a
Pathologic biliary obstruction is usually tortuous appearance. Large intrahepatic duct
mechanical secondary to liver, biliary, pancre- dilations can be tubular or may look cystic, due
atic, or duodenal inflammatory or neoplastic to cross-sectioning of the duct.
disease. These diseases can be sonographically 2. Thickened gallbladder wall
visualized. Obstruction from biliary calculi is a. Diffusely hyperechoic wall, with or without
rare but is easily imaged. Mild intrahepatic duct shadowing, is often seen with cholecystitis,
dilation is seen on an ultrasound image as two calcification or fibrosis, acute hepatitis, and
parallel, anechoic channels in close proximity to cholangiohepatitis.
86 CHAPTER 2 RADIOLOGY AND ULTRASONOGRAPHY OF THE DIGESTIVE SYSTEM
A B
FIGURE 2-69 A, Transverse scan of the liver (arrows) in a 13-year-old springer spaniel with a history of weight loss
and anorexia for 2 days. Focal, hypoechoic masses are seen within the liver. A large, mixed echoic mass was seen on
another scan of a different area of liver. Diagnosis was metastatic hepatocellular carcinoma. B, Sagittal scan of the
liver in an 11-year-old domestic short hair cat. A circumscribed, hypoechoic mass (arrows) is apparent. Diagnosis was
metastasis from a cecal adenocarcinoma.
FIGURE 2-70 Transverse scan of the liver (L) in a 13-year-old golden retriever with vague signs of lethargy and
anorexia. A mixed hypoechoic and patchy anechoic mass (arrows) is seen in the midliver and left liver. Margins on
the mass are not sharply defined. Diagnosis was hepatocellular carcinoma.
b. Focal hyperechoic areas, with or without fluid. Abdominal imaging should help dif-
shadowing, are commonly associated with ferentiate wall edema from abdominal fluid
mineralization, fibrosis, or calculi. (Figure 2-77).
c. “Halo” or double rim around gallbladder d. Generalized wall thickening, with or with-
wall usually indicates wall edema or inflam- out irregular mucosa, is consistent with
mation but can be seen with free abdominal inflammation (Figure 2-78). Nondistended
CHAPTER 2 RADIOLOGY AND ULTRASONOGRAPHY OF THE DIGESTIVE SYSTEM 87
gallbladder walls may appear slightly thick- c. Polypoid, echoic masses in gallbladder may
ened in normal patients. be due to glandular cystic hypertrophy.
3. Gallbladder and bile duct masses d. Biliary sludge may mimic mass lesions. If
a. Calculi/concretions are hyperechoic and necessary, positional (gravitational) sono-
usually show shadowing deep to the calculus graphic studies should be performed to fur-
(Figure 2-79). ther characterize gallbladder echoes.
b. Neoplasia is variable with circumscribed or
ill-defined echogenicity in area of gallblad-
der or bile duct, with or without biliary Normal Sonographic Anatomy
obstruction (Figure 2-80). of the Pancreas
The pancreas can be imaged in normal dogs, cats,
and most ferrets.
The right limb of the pancreas is found dorso-
medial to the descending duodenum. The pres-
ence of the pancreaticoduodenal vein within the
pancreas facilitates pancreatic identification (Figure
2-81). The left limb is more difficult to image in
the dog because of its close relationship with the
stomach and transverse colon and overlying gas;
however, with perseverance it can often be located.
The left limb is usually visualized in the cat
between the transverse colon and the stomach
(Figure 2-82).
Gross adjacent anatomic landmarks are
described as follows: The right lobe is found
dorsal or dorsomedial to the duodenum, cra-
nioventral to the right kidney, ventrolateral to
the portal vein, and between the ninth and tenth
FIGURE 2-71 Scan of a large liver mass in a 12-year- intercostal spaces to the level of the fourth lum-
old German Shepherd–mix with normal liver enzyme bar vertebra. The left lobe is found dorsocaudal
levels. The mass constitutes most of this image, with no to the stomach, dorsocranial to the transverse
normal liver parenchyma visible. It has a mixed colon, ventrolateral to the portal vein, ventral to
hyperechoic and hypoechoic echo pattern and poorly the aorta and caudal vena cava, and dorsomedial
defined margins. Diagnosis was hepatocellular carcinoma. to the spleen.
B
CHAPTER 2 RADIOLOGY AND ULTRASONOGRAPHY OF THE DIGESTIVE SYSTEM 91
FIGURE 2-80 Oblique scan of the gallbladder (GB) and common bile duct (large arrows) in the cat seen in Figure
2-76. The bile duct is markedly dilated and is obstructed by an echogenic mass (small arrows) that appears to be
intraluminal. The mass was determined to be benign fibroplasia of unknown cause.
A B
FIGURE 2-81 Sagittal scan of a normal dog pancreas showing the dorsal relationship to the duodenum (A) and
the anechoic pancreaticoduodenal vein present within the pancreas (B).
FIGURE 2-83 Sagittal scan of the pancreas (arrows) in an 8-year-old tortiseshell cat with a history of anorexia and
hiding. The pancreas is mildly enlarged and nonhomogeneous with patchy hypoechoic zones and has slightly
irregular margins. Sonographic diagnosis was pancreatic inflammation. The cat’s signs resolved with medical therapy.
FIGURE 2-84 Oblique scan through the area of the pancreas in a 9-year-old poodle-mix with vomiting, diarrhea,
shaking, anorexia, and fever. The WBC was 20,700, and the alkaline phosphatase level was mildly elevated. The
pancreas is markedly enlarged, hypoechoic to anechoic, irregular in shape, and surrounded by hyperechoic tissue.
Sonographic diagnosis was acute pancreatitis with localized peripancreatic inflammation. The dog recovered
following 1 week of medical therapy.
and nonhomogeneous (Figure 2-83). The pan- (Figures 2-84 and 2-85). Peripancreatic hyper-
creas usually enlarges and is hypoechoic in moder- echoic mesentery and/or anechoic fluid may be vis-
ate to severe pancreatitis. Anechoic cavitations may ible. Decreased motility or thickening of proximal
occur owing to necrosis, abscess, or hemorrhage duodenum may be apparent. Intrahepatic and extra-
CHAPTER 2 RADIOLOGY AND ULTRASONOGRAPHY OF THE DIGESTIVE SYSTEM 93
FIGURE 2-85 Oblique scan of the pancreas (arrows) in an 8-year-old Irish setter with shaking, groaning, and
abdominal pain. Ingestion of garbage had occurred 2 days previously. There was mild elevation of alkaline
phosphatase level. The pancreas appears markedly enlarged with mixed hypoechoic and anechoic zones surrounded
by echogenic tissue. The anechoic regions were thought to be either hemorrhage and/or necrosis. Sonographic
diagnosis was acute pancreatitis. Medical therapy was instituted, and a recheck ultrasound 1 week later showed
approximately 50% decrease in size with persistent nonhomogeneous echo pattern. The dog continued to improve
with resolution of signs 2 weeks later.
FIGURE 2-86 Sagittal liver scan of a mixed-breed dog presented with icterus and neurologic abnormalities.
Gallbladder (GB) is distended. An anechoic cystic structure (C) is seen caudal to the gallbladder and liver. A
pancreatic cyst was suspected. Laparotomy located a cystic bile-filled mass between the left and the right pancreatic
limbs attached to omentum and an atrophic left pancreas. Diagnosis was a cystic structure with residual pancreatic
tissue in the fibrous wall.
hepatic biliary duct obstruction may be observed. or multiple, may occur (Figures 2-86 and 2-87).
In the healing stage there may be homogeneous or Nodular hyperplasia may develop in the pancreas
irregular increased echogenicity, presumably due to (Figure 2-88), as well as diffuse pancreatic hyper-
fibrosis and/or calcification. Calcification may or plasia, which appears as a normal echogenicity but
may not show shadowing, depending on its thick- very enlarged with smooth borders, based on one
ness. Anechoic pseudocyst formation, either single case that was histologically confirmed.
94 CHAPTER 2 RADIOLOGY AND ULTRASONOGRAPHY OF THE DIGESTIVE SYSTEM
B
CHAPTER 2 RADIOLOGY AND ULTRASONOGRAPHY OF THE DIGESTIVE SYSTEM 95
Rivers BJ et al.: Canine gastric neoplasia: utility of ultra- tory bowel disease, pancreatitis, and nephritis in cats,
sonography in diagnosis, J Am Anim Hosp Assoc 33:144, J Am Vet Med Assoc 209:1114, 1996.
1997. Whiteley MB et al.: Ultrasonographic appearance of
Schwarz LA, Penninck DG, Leveille-Webster C: Hepatic primary and metastatic canine hepatic tumors: a
abscesses in 13 dogs: a review of the ultrasonographic review of 48 cases, J Ultrasound Med 8:621, 1989.
findings, clinical data and therapeutic options, Vet Yeager AE, Mohammed H: Accuracy of ultrasonogra-
Radiol Ultrasound 39:357, 1998. phy in the detection of severe hepatic lipidosis in cats,
Weiss DJ, Gagne JM, Armstrong PJ: Relationship Am J Vet Res 53:597, 1992.
between inflammatory hepatic disease and inflamma-
C H A P T E R
3
ENDOSCOPY AND
LAPAROSCOPY IN
VETERINARY
GASTROENTEROLOGY
Todd R.Tams
Biopsies of digestive system organs are commonly ization that are required for postoperative recov-
indicated in the practice of small animal medicine. ery; and an unwillingness on the part of many
Before the advent of endoscopy, laparoscopy, and owners to subject their pets to any type of major
ultrasonography in veterinary medicine, the rou- procedure unless “it is really necessary.”
tine method of obtaining tissue samples was by Exploratory laparotomy has and always will be
laparotomy. Liver samples were routinely obtained an excellent diagnostic procedure. The use of
using either blind percutaneous or keyhole biopsy isoflurane anesthesia combined with our ever-
techniques, or wedge or needle samples were pro- increasing ability to provide better preoperative,
cured surgically. intraoperative, and postoperative support for our
The primary advantage of a surgical approach animal patients, which includes more routine use
to organ biopsy is that, depending on the size of of effective analgesic agents, has helped make
the incision, a large area of the digestive organs can exploratory laparotomy a safer procedure. However,
be examined and palpated in conjunction with the trend in human medicine over the last 20 years
evaluation of other structures (e.g., lymph nodes, has moved strongly toward using the least invasive
kidneys, ureters, prostate). Disadvantages of lapa- methods possible to examine and, when indicated,
rotomy include the invasive nature of the proce- obtain biopsy samples from abdominal tissues.
dure when compared with endoscopy, laparoscopy, There has been a similar but more recent trend in
or ultrasonography; the longer periods of hospital- veterinary medicine, beginning first in university
97
98 CHAPTER 3 ENDOSCOPY AND LAPAROSCOPY IN VETERINARY GASTROENTEROLOGY
and specialty practices and now encompassing ians practicing in affluent areas can justify purchas-
many smaller practices. It is quite clear that, in situ- ing. An endoscope is one of the most versatile and
ations in which it has been determined that biopsies diagnostically valuable pieces of equipment that a
are necessary, owners prefer and are more likely to veterinary practice can have in its armamentar-
allow procedures that are considered less invasive ium. The selection of equipment to be used for
and as causing less overall discomfort to their pet. performing endoscopy often depends on its versa-
Indeed, most owners are aware of the tremendous tility of application, durability, and expense. Many
advances in diagnostic technology in the human practices have been able to financially justify the
medical field, and they are often anxious to have purchase of high-quality endoscopic equipment.
these methods utilized in the diagnosis of their pet’s When consideration is given to the purchase of an
disorder. endoscope, the most important factors to be
Endoscopy, laparoscopy, and ultrasonography reviewed should be the probable frequency of
have many applications in veterinary medicine. usage and versatility of the instrument rather than
As awareness of the tremendous diagnostic potential the purchase price.
of these procedures has increased among veterinari- Other important considerations are the quality
ans, many clinicians are beginning to purchase of the optical system and ease of operating the
equipment and learn these new techniques or are endoscope. Significant differences exist, so equip-
more readily making this technology available to ment purchases should be made carefully! Too fre-
their clients on a referral basis. Applications for use quently veterinarians rank a lower purchase price
of ultrasonography for diagnosis of disorders of as one of the most important factors. This can be a
the digestive system, as well as many case examples, significant mistake because even the most skilled
are presented in Chapter 2. Endoscopy and endoscopist may find performing a complete
laparoscopy are discussed in this chapter, with examination and making the correct diagnosis dif-
emphasis on the clinical utility of these techniques. ficult while using an endoscope of poor quality.
My recommendation to veterinarians inter-
ested in purchasing their first endoscope is to buy
ENDOSCOPY a single high-quality endoscope that may be used
Endoscopy is one of the best and yet most funda- for a variety of procedures (e.g., esophagogastro-
mental methods of examining the gastrointestinal duodenoscopy, colonoscopy, bronchoscopy, and
(GI) tract. It is now a well-established procedure in nasopharyngoscopy in dogs) in cats and small
veterinary medicine. The opportunity to directly dogs, as well as in large dogs. A pediatric endo-
examine and obtain tissue samples from the esoph- scope with four-way tip deflection capability
agus, stomach, and intestinal tract in a minimally meets these criteria well (Figure 3-1). Endoscopes
invasive way has greatly altered the clinical
approach to diagnosis and has made significantly
more accurate the treatment of disorders of the
digestive system. Despite the tremendous diagnos-
tic advantages that endoscopy offers, it is still best
used by the clinician as an adjunctive procedure in
the evaluation of GI disease.A thorough review of
the history, complete physical examination, and
selected laboratory and radiographic examinations
as appropriate for each individual case are still
important for thorough patient evaluation. When
used judiciously, endoscopy offers a valuable alter-
native to exploratory surgery for direct examina-
tion of tissues, procurement of biopsy samples, and
retrieval of foreign bodies.
FIGURE 3-1 Storz pediatric veterinary endoscope.
Specifications include 8.5mm–diameter insertion tube,
Selection of an Endoscope 100-degrees forward-viewing field of view, 150-cm
Endoscopic equipment is no longer considered a working length, 2.5mm–diameter accessory channel,
luxury that only large referral centers or veterinar- and four-way tip deflection.
CHAPTER 3 ENDOSCOPY AND LAPAROSCOPY IN VETERINARY GASTROENTEROLOGY 99
Modified from Tams TR: Endoscopy. In Kirk RW, Bonagura JD, eds: Current veterinary therapy X. Philadelphia, 1989,WB
Saunders.
likelihood of reflux esophagitis (e.g., distal esopha- In most patients with megaesophagus, endo-
geal erythema, gastroesophageal sphincter dilation, scopic examination is not necessary for diagnosis
pooling of fluid in the distal esophagus). Monitor- and is rarely of benefit in determining a cause of
ing distal esophageal pH with a probe and perform- the disorder. Megaesophagus is a specific syn-
ing a suction biopsy of the distal esophageal mucosa drome characterized by generalized esophageal
provide a more sensitive means of diagnosis of dilation and hypoperistalsis, and it is differentiated
reflux esophagitis than visualization alone. from other causes of esophageal dilation such as
Esophageal motility disorders in which there is esophageal foreign body, vascular ring anomaly or
not easily detected radiographic evidence of other stricture disorders, and neoplasia. If pneu-
marked esophageal dilation are best recognized by monia is ruled out in a megaesophagus patient that
esophageal fluoroscopy and manometry studies. is anorexic, esophagoscopy may be indicated to
Endoscopic examination of the esophagus reveals examine for esophagitis.
certain appearances, however, that may suggest the
possibility of a motor abnormality, and, in hospitals
where fluoroscopy equipment is not available, Diagnosis of Gastric
esophagoscopy can still be useful as a diagnostic Abnormalities
aid. Often a diagnosis of clinically significant Indications for gastroscopy include signs referable
decreased lower esophageal sphincter pressure can to gastric diseases, including nausea, salivation,
be inferred from the presence of grossly evident vomiting, hematemesis, melena, and anorexia.
esophagitis lesions and variable degrees of dilation Gastroscopy mainly defines abnormalities of the
of the gastroesophageal junction. gastric mucosa, but it may also reveal distortion of
102 CHAPTER 3 ENDOSCOPY AND LAPAROSCOPY IN VETERINARY GASTROENTEROLOGY
the stomach’s normal anatomic relationships by removal and endoscopy-guided percutaneous gas-
displacement or extrinsic compression as a result trostomy tube placement. Gastrostomy tube place-
of a mass or enlargement of an adjacent organ ment is a quick and simple procedure (see Chapter
structure. With proper technique the entire 12) and provides an excellent means of temporar-
mucosal surface of the stomach and the antral- ily feeding an anorectic or debilitated patient.
pyloric canal can be examined. The most com- In patients with chronic upper GI disorders,
mon disorders diagnosed include chronic gastritis, gastroscopy should be performed in conjunction
gastric foreign bodies, and gastric motility disor- with esophagoscopy and duodenoscopy. Important
ders (Figure 3-3). Ulcers, neoplasia, and hyper- diagnostic clues may be evident in any or all of
trophic gastropathy can be readily diagnosed but these areas during the course of an examination.
are less commonly found (Figure 3-4). Special Follow-up gastroscopy is a valuable aid in moni-
therapeutic considerations include foreign body toring response to therapy in chronic gastritis and
ulcer patients. Follow-up biopsies are especially
important in patients with chronic severe histio-
cytic and granulomatous gastritis, chronic fibros-
ing gastritis, and gastric lymphoma. Important
information that is useful in determining treat-
ment protocol adjustments can often be obtained.
In evaluating a patient with signs suggestive of a
gastric disorder, gastric mucosal biopsy samples
should be obtained even if gross lesions are not
present. It is common for a patient with chronic
A gastritis to have lesions identifiable only on micro-
scopic examination. Different classifications of gas-
tritis (e.g., lymphocytic-plasmacytic, eosinophilic,
histiocytic) and degrees of involvement (e.g., mild,
moderate, severe) can be determined from mucosal
biopsy samples; these findings are extremely
important in determining specific therapeutic reg-
imens. If gross lesions are identified (e.g., localized
hyperemic changes, nodules, or masses), forceps
biopsies should be obtained from these areas, as
well as from several normal areas. Six to eight bi-
opsy samples are obtained from different areas of the
gastric body and fundus if the stomach is grossly
normal. Biopsy samples are best obtained from the
B surface of a gastric fold. The size of the tissue sam-
ples obtained may be inadequate if the stomach is
too distended with air because the folds become
too flattened. When the endoscope is first ad-
vanced to the stomach during the course of an
examination, air is insufflated to distend the gastric
walls so that thorough mucosal evaluation is
enhanced. Suctioning some of the air out just
FIGURE 3-3 Endoscopic photos from feline stomach. before taking biopsy samples greatly increases the
A, Normal stomach of a cat, showing the midgastric gastric fold surface area from which samples can be
and distal gastric body. Rugal folds are clearly in view,
obtained. It is more difficult to obtain a tissue sam-
and the mucosa is smooth. B, Chronic gastritis in a cat.
This is a retroversion view of the proximal stomach,
ple of adequate size from the gastric antrum than it
with the endoscope in a curved position looking back is from other parts of the body unless there is hyper-
on itself.The gastric mucosa is irregular throughout, trophy or discrete raised or cratered lesions.
and there are erosive changes on the rugal fold in the Clues that a gastric motility disorder may be
right field of view. Biopsies confirmed a diagnosis of present include pooling of bile or gastric fluid or
chronic moderate lymphocytic-plasmacytic gastritis. finding undigested food in the stomach of a patient
CHAPTER 3 ENDOSCOPY AND LAPAROSCOPY IN VETERINARY GASTROENTEROLOGY 103
A B
FIGURE 3-4 Gastric ulcers. A, Two peripyloric ulcers in a 14-year-old dog that was receiving nonsteroidal
antiinflammatory drug (NSAID) therapy for severe osteoarthritis. The pyloric orifice (center) is open, and ulcers are
seen to the left and above the pylorus. The dog had intermittent vomiting and inappetence. B, Large perforated
gastric ulcer in an 8-year-old chow that had received naproxen (an NSAID) once daily for 7 days. On the sixth day
vomiting and inappetence were first noted by the owner. Naproxen was discontinued on the seventh day, but the
clinical signs persisted. Nine days after naproxen was discontinued, the dog was presented for endoscopy. The dog
was bright and alert. The complete blood count (CBC) and biochemical profile were normal (packed cell volume
[PCV] = 48%). On advancement into the gastric antrum the endoscope revealed a very deep ulcer with a thick rim
(entire upper left quadrant). The pyloric orifice is at the lower left (7 o’clock position). The meshlike tissue seen through
the ulcer crater is omentum (there was a complete omental seal). The ulcer area was subsequently resected
surgically. (From Tams TR: Gastroscopy. In Tams TR, ed: Small animal endoscopy, St. Louis, 1999, Mosby.)
that has been fasted 8 to 10 hours or more. The encountered, however. If endoscopic findings do
stomach normally empties within 7 to 10 hours not correlate with clinical signs, or if there is a poor
after a meal. There is often mucosal hyperemia response to therapy, exploratory surgery should be
caused by superficial irritation from bile, but, recommended.
despite this gross abnormality, gastric biopsies in
idiopathic gastric motility disorders are usually nor-
mal. Diagnosis of Duodenal
Because biopsy samples obtained from some Abnormalities
masses with standard biopsy forceps are relatively With a flexible pediatric endoscope (9-mm diame-
small, sufficient tissue for definitive diagnosis is ter or less), the duodenum can be directly examined
sometimes not obtained. Several biopsy samples in most cats and dogs.An endoscope with a diame-
from the same site of a mass should be taken, each ter of 8.5 to 9 mm can consistently be advanced to
time extending the biopsy forceps more deeply the duodenum in cats and dogs weighing as little as
into the tissue (Figure 3-5). If tissue from only the 3 to 4 lb by an experienced endoscopist. The distal
surface of a neoplastic mass is obtained, a mistaken duodenum or proximal jejunum can often be
diagnosis of granulomatous or fibrous disease may reached in cats and small dogs (Figure 3-6). Certain
be made. Samples from ulcerative lesions are best portions of the duodenum, including the area
taken by grasping the wall or the junction of the immediately beyond the pylorus and the medial
wall and the gastric mucosa. Gastric polyps are wall of the descending segment, are sometimes dif-
reliably diagnosed on endoscopic biopsy in dogs ficult to view other than tangentially, especially as
and cats. the endoscope is initially advanced through this
A major shortcoming of gastroscopy is that area. In small patients (especially cats) care must be
neoplastic diseases involving only the serosa or taken not to be too forceful in advancing the endo-
deep layers of the gastric wall cannot be identified scope through areas where there is increased resis-
or definitively diagnosed on mucosal biopsy. This tance. It is possible to perforate the duodenum if too
pattern of tissue involvement is not commonly much force is applied in tight areas.
104 CHAPTER 3 ENDOSCOPY AND LAPAROSCOPY IN VETERINARY GASTROENTEROLOGY
A B
FIGURE 3-5 Gastric adenocarcinoma in a dog with chronic vomiting, weight loss, and recent anorexia. A, Marked
proliferative changes in the lower gastric body, with complete loss of the normal rugal architecture. B, Close-up
view of a mass in the midgastric body. The mass was rigid and had a very dense wall (suggestive of neoplasia).
Masses such as this one should be biopsied as deeply as possible. If only superficial tissue is obtained, the endoscopist
may fail to retrieve neoplastic cells. The first four attempts to biopsy the mass yielded only very small tissue samples,
but on the fifth attempt the biopsy instrument advanced inside the mass.A number of large tissue samples were then
obtained. (From Tams TR: Gastroscopy. In Tams TR, ed: Small animal endoscopy, St. Louis, 1999, Mosby.)
A B
FIGURE 3-6 A, Grossly normal duodenum in a dog. B, Small intestine biopsy technique. Endoscopic forceps have
been advanced into the duodenal mucosa.
Clinical signs of small intestinal disease include evaluated more thoroughly with endoscopic
vomiting, diarrhea, melena, change in appetite, examination and biopsy. Frequently the only
and weight loss. By far the greatest value of duo- major sign in patients with inflammatory bowel
denoscopy is its capability of definitively diagnos- disease is vomiting. If only gastric biopsies are per-
ing inflammatory small bowel disorders via formed in these patients, the diagnosis may be
biopsy. In fact, recognition that inflammatory missed. In inflammatory disease the small bowel
bowel disease commonly occurs in dogs and cats mucosa may appear normal or it may have varying
became increasingly apparent as patients with var- degrees of irregularity, fissures, or follicular-like
ious patterns of GI symptomatology began to be changes.
CHAPTER 3 ENDOSCOPY AND LAPAROSCOPY IN VETERINARY GASTROENTEROLOGY 105
Endoscopy offers an alternative approach to parasites are observed because the parasites could
obtaining small bowel biopsy samples in cases of either represent an additional and unrelated prob-
protein-losing enteropathy when there is concern lem regarding the primary disorder or might be a
that full-thickness surgical biopsy sites may heal primary causative factor of the clinical signs.
slowly. This is an especially important considera- During duodenoscopy, saline lavage can be per-
tion in patients with a total protein level less than formed through polyethylene tubing advanced
3.5 g/dl. Multiple biopsy samples can be safely through the accessory channel of the endoscope in
obtained using endoscopic biopsy forceps. In addi- an effort to retrieve Giardia trophozoites. Direct
tion, the hospital stay is significantly shortened smears of the aspirates should be examined within
when endoscopy rather than surgery is performed, 20 minutes of collection with light microscopy at
making this procedure more cost effective. The ×100 and ×400.Although endoscopy-guided duo-
most common causes of protein-losing enteropa- denal lavage has been considered a very good test
thy in dogs are inflammatory bowel disease (by far for diagnosing occult giardiasis, the availability of
the most common), lymphoma, and lymphangiec- the fecal enzyme-linked immunosorbent assay
tasia. Lymphangiectasia, a disorder of the intestinal (ELISA) for detecting Giardia-specific antigen, a
lymphatics that results in malabsorption, has a very sensitive and practical test, now precludes the
characteristic histologic appearance, and in some need for duodenal lavage in most diagnostically
cases pronounced gross changes can be seen at elusive cases of giardiasis.
endoscopic examination. Often there is a charac- Neoplasms that involve the small bowel mucosa
teristic patchy milky white appearance of the can be reliably diagnosed on biopsy if a large
mucosa. In some patients, however, gross changes enough sample of representative tissue is obtained.
may be noted only at exploratory laparotomy. Any masses that are found should be sampled as
Occasionally the diagnosis will be missed if only deeply as possible. Lymphoma is the most com-
the descending duodenum is examined and sam- mon type of intestinal neoplasia in dogs and cats.
pled. I have found this to be more of a problem in GI lymphomas are believed to be less common in
rottweilers than in other breeds. dogs than in cats. The diffuse type of lymphoma is
Frequently biopsies reveal only mild the most amenable to diagnosis by endoscopy.
lymphocytic-plasmacytic enteritis. In dogs that are Focal areas of lymphoma in the jejunum or proxi-
markedly hypoproteinemic, as is often the case in mal ileum may be missed because of insufficient
those with lymphangiectasia, this degree of histo- endoscope length (most cases of GI lymphoma in
logic change is not significant enough to substan- dogs and cats involve diffuse rather than focal neo-
tiate a diagnosis of inflammatory bowel disease as plastic infiltrates). Also, if lymphoma involvement
the primary cause of the hypoproteinemia. Also, is primarily in deeper muscle layers of the intes-
lymphangiectasia is often associated with mild tinal wall, mucosal biopsy samples as obtained with
lymphocytic-plasmacytic infiltrates in addition to endoscopy forceps may not be deep enough to
its characteristic lesion of dilated lacteals. Therefore procure representative tissue. However, this prob-
the clinician needs to be aware that enteroscopy lem is minimized by using proper instrumentation
limited to the upper small bowel may not establish and technique and by routinely obtaining multiple
the definitive diagnosis in some patients with lym- samples (8 to 12) from the duodenum and, when-
phangiectasia. It is strongly recommended that both ever possible, the ileum.
duodenoscopy and ileoscopy be performed in When lymphoma is present but not definitively
patients with chronic small bowel diarrhea, espe- diagnosed on the tissue submitted for examina-
cially when hypoproteinemia is present. This tion, the mucosal tissue that is obtained is rarely
approach provides the greatest opportunity for mak- normal. Usually moderate to severe lymphocytic-
ing the correct diagnosis when endoscopy rather plasmacytic inflammatory infiltrates are present
than surgery is done to obtain biopsy samples. over or adjacent to neoplastic foci. A positive
Intestinal parasites (generally ascarids) are occa- biopsy finding such as this may give the clinician
sionally encountered on direct examination of the false assurance that a definitive diagnosis has been
upper small intestine. These parasites can easily be reached. Poor or an only temporarily positive
snared with biopsy forceps or foreign body response to treatment that is initiated on the basis
graspers and pulled up through the accessory of biopsy results may then be an indication that
channel. As is always done during endoscopy pro- some other, more significant disorder is present.
cedures, biopsy samples are still obtained even if Further biopsy samples should then be obtained,
106 CHAPTER 3 ENDOSCOPY AND LAPAROSCOPY IN VETERINARY GASTROENTEROLOGY
via either endoscopy or surgery. Surgery is gener- My experience to date has shown that in a
ally the recommended procedure at this point majority of patients with inflammatory bowel dis-
because a much more extensive evaluation of the ease, intestinal involvement is diffuse. Duodenal
GI tract can be accomplished. It should be empha- and jejunal changes are often similar in type
sized that with proper instrumentation and technique, in and degree to those in the ileum. Sometimes a dif-
conjunction with tissue examination by a pathologist ferent cell type predominates in the ileum as
experienced in evaluating the typically small tissue sam- compared with the duodenum, but usually no
ples procured using endoscopic instrumentation, the cor- alteration in the treatment protocol is neces-
rect diagnosis will be made in a great majority of animals sary. Occasionally, however, there are significant
that undergo endoscopy. changes in the ileum when duodenal samples from
the same patient are either normal or only mildly
abnormal. I have examined several dogs with
Diagnosis of Abnormalities chronic diarrhea in which lymphoma was diag-
of the Ileum nosed on biopsies of the ileum, whereas duodenal
As previously stated, examination and biopsy of samples revealed presence of only mildly abnormal
the ileum are important in patients with chronic inflammatory infiltrates. If ileoscopy had not been
diarrhea or weight loss that is clinically consistent done in these patients, the diagnosis would have
with a small intestinal disorder. Although it is not been missed! Also, the degree of inflammatory
always possible to enter the ileum in dogs and is infiltrates is occasionally significantly more intense
rarely accomplished in cats because of the narrow in the ileum than in the colon. Table 3-3 lists
diameter of the ileocolic orifice, the ileocolic valve hematologic and histopathologic findings from a
can be readily identified during complete colonos- dog in which this was the case. I have also
copy as long as the ascending colon and ileoceco- observed a patient with panhypoproteinemia that
colic junction area are relatively clean (Figure had mild lymphocytic-plasmacytic duodenitis.
3-7). Biopsy samples can be blindly obtained from This degree of inflammatory disease is rarely sig-
the ileum if the endoscope tip can be aligned with nificant enough to cause a protein-losing enter-
the ileocolic orifice so that the biopsy forceps can opathy. The patient did not respond to conventional
be passed through it and into the ileum. In dogs therapy for inflammatory bowel disease. Sub-
weighing more than 8 to 10 lb, I strongly prefer to sequently, exploratory surgery identified adeno-
obtain biopsy samples with the endoscope posi- carcinoma in the terminal ileum, at a site where
tioned in the ileum, whenever possible, so that any the diagnosis might have been made earlier if
grossly abnormal areas can be pinpointed with the ileoscopy had been done.
biopsy forceps. These examples highlight the need to consider
The only disadvantage of ileoscopy compared doing ileoscopy in patients with GI disorders char-
with duodenoscopy is that the patient must be pre- acterized mostly by chronic diarrhea and weight
pared for complete colonoscopy with a combina- loss. It is my impression that it is more important
tion of fasting and colonic lavage. Ileoscopy done to recommend ileoscopy in dogs than in cats.
in conjunction with duodenoscopy also requires Finally, if only colonoscopy is being done on a
more anesthesia time and is therefore more expen- patient, using a flexible endoscope, it is wise to
sive than if only one or the other is done. However, obtain ileum biopsy samples during the course of
the great advantage of examining both the upper the procedure if access to the ileum can be gained.
and the lower small bowel in patients with signs of In this way, at least some information about the
chronic small intestinal disease is that a number small intestine can be obtained. In my experience,
of tissue samples can be obtained from a greater most but not all patients with signs limited to large
area of the intestinal tract. Histologic characteristics bowel diarrhea have normal ileum biopsies. If the
of the small intestine can then be more thoroughly ileum is abnormal, the treatment protocol might
evaluated. The large intestine is also routinely have to be altered.
examined, and samples from it are obtained at the
same time, even if there are no symptoms of
colonic disease, because it has to be traversed to Diagnosis of Large Intestinal
reach the ileum anyway. The thorough nature of Disorders
this approach usually provides representative tissue Flexible colonoscopy provides a means of thor-
for making an accurate diagnosis. oughly examining the entire colon to the level
CHAPTER 3 ENDOSCOPY AND LAPAROSCOPY IN VETERINARY GASTROENTEROLOGY 107
C D
FIGURE 3-7 A, Radiograph showing the position of a flexible endoscope with the tip located close to the
ileocecocolic area of a dog. With a flexible endoscope complete colonoscopy can be done, and in most dogs over 8
to 10 lb (and even in some smaller dogs when a pediatric endoscope is used) the endoscope can be passed into the
ileum. B, Endoscopic view of the ileocolic orifice area in a dog. The ileocolic orifice in dogs usually appears as a
broad, slightly raised papillary form. The cecal orifice is immediately below and is usually open. A biopsy forceps
instrument has been advanced through the ileocolic orifice. C and D, Normal ileocolic orifice area of a cat. C, The
ileocolic orifice appears as a very small opening (see D), and the cecum in the cat is simply a small blind pouch.
D, An endoscopic biopsy instrument has been advanced through the ileocolic orifice. Since it is not usually possible
to pass an endoscope into the ileum of most domestic cats, ileum biopsies are frequently obtained by passing a
biopsy forceps into the ileum under endoscopic guidance.
108 CHAPTER 3 ENDOSCOPY AND LAPAROSCOPY IN VETERINARY GASTROENTEROLOGY
BIOPSY RESULTS
Stomach: mild lymphocytic-plasmacytic gastritis
Duodenum: mild lymphocytic-plasmacytic duodenitis
Ileum: moderately severe atrophic lymphocytic-plasmacytic ileitis
Colon: moderate lymphocytic-plasmacytic-eosinophilic colitis
PCV, Packed cell volume; WBC, white blood cell count; ALT, alanine aminotransferase; SAP, serum alkaline phosphatase; TLI,
trypsin-like immunoreactivity.
*Clinical signs were most consistent with a small bowel disorder. The dog had lost 18 lb in the last 3 months. Note the marked
degree of panhypoproteinemia. The cobalamin level was quite low, whereas the folate level was normal. The subnormal
cobalamin level was considered to be most consistent with intestinal bacterial overgrowth, which is common in shar-peis. It
could also indicate significant disease in the ileum, although many dogs with ileal disease have a normal cobalamin level.
Biopsies identified the most significant degree of disease to be in the ileum and colon. If only duodenal small bowel biopsies
had been done, the true degree of small intestinal disease would have been misinterpreted, and treatment, especially drug doses
prescribed, would most likely not have been aggressive enough. Also note the degree of histologic abnormality in the large
intestine. This case example highlights the importance of doing ileoscopy and colonoscopy, as well as duodenoscopy, in dogs
with chronic diarrhea.
of the ileocolic junction. The cecum in dogs can are the two most common causes of this problem
also be entered and examined. Indications for in cats.
colonoscopy include signs of inflammatory dis- The most commonly diagnosed disorders
ease (e.g., hematochezia, tenesmus, increased include a variety of mucosal inflammatory dis-
frequency of defecation), chronic diarrhea, orders (lymphocytic-plasmacytic colitis is the most
constipation, fecal incontinence, and evaluation common) and rectal polyps. Colonic strictures,
of a rectal or colonic mass. A second colonos- histoplasmosis, parasitic typhlitis, inverted cecum,
copy with follow-up biopsy is also useful as a ileocolic intussusception, and neoplasia are seen
means of monitoring response to therapy and in less commonly but can be reliably diagnosed by
making decisions regarding treatment protocol colonoscopy. Colonoscopy is much more accurate
adjustments in patients with inflammatory and than contrast radiography in obtaining a definitive
neoplastic disorders. Colonoscopy is generally diagnosis of large intestinal disorders.
done only after dietary trials, therapeutic A majority of patients with idiopathic colitis
deworming either to treat known parasitism or have grossly normal mucosa. Confirmation of the
to rule out the possibility of occult parasitism diagnosis requires that the colon be properly pre-
(especially whipworms), and empirical treatment pared so that high-quality biopsy samples can be
for colitis have been tried and have proven inef- obtained from various levels of the colon. If the
fective in resolving symptoms. Colonoscopy ileocolic area can be reached, an attempt should be
should be done early in the course of symptoms made to obtain biopsy samples from the ileum as
that include hematochezia occurring with well. In patients with chronic diarrhea that is not
formed stools. The most common cause of this clearly limited to large bowel signs, it is best to
problem in dogs is rectal polyps. Abrasive mate- obtain biopsy samples from both the small and the
rial passing through the colon and chronic colitis large intestine.
CHAPTER 3 ENDOSCOPY AND LAPAROSCOPY IN VETERINARY GASTROENTEROLOGY 109
LAPAROSCOPIC INSTRUMENTATION
Veress needle
Laparoscope (telescope)
Fiberoptic light cable
Gas insufflation tubing
Laparoscope cannula (sleeve) with trocar
Second puncture cannula with trocar
Tactile (palpating-measuring) probe
Set of assorted rubber sealing caps
FIGURE 3-16 Gas insufflation unit for laparoscopy.
Tru-Cut biopsy needle
Gauges that measure gas supply, intra-abdominal
Biopsy forceps
pressure, gas flow rate, and amount of gas insufflated are
Modified from Magne ML,Tams TR: Laparoscopy: located on the front of the unit. A Veress needle is
instrumentation and technique. In Tams TR, ed: Small shown connected to the gas insufflation tubing by a
animal endoscopy, St. Louis, 1999, Mosby. Luer-Lok attachment.
114 CHAPTER 3 ENDOSCOPY AND LAPAROSCOPY IN VETERINARY GASTROENTEROLOGY
Various ancillary instruments are available for problems that necessitate examination and biopsy
use during laparoscopy (Figure 3-17). The most of the liver and/or pancreas.
commonly used biopsy instrument is a double- Laparoscopy provides a superb view of the liver
spoon forceps (Figures 3-18 and 3-19). Although (Figure 3-20). Color, consistency, and contour of
operating laparoscopes with a channel for inser- the liver are rapidly documented. A probe can be
tion of accessory instruments are available, most inserted through the second puncture cannula for
veterinary laparoscopists prefer to use a double- the purpose of palpating the surfaces of the liver to
puncture technique for biopsy. An accessory can- evaluate for friability or excessive rigidity, to lift
nula is inserted to the abdomen through a second and separate the liver lobes in view so that the
small incision. This technique allows greater undersides can be examined, to palpate the gall-
mobility of accessory instruments (palpation bladder, and to displace omentum from a surface
probes, biopsy instruments). Alternatively, a biopsy that must be examined (Figure 3-21). The liver is
needle can be inserted directly through the generally evaluated through a right lateral midab-
abdominal wall and then directed to the biopsy dominal approach. A significantly greater area of
site under laparoscopic guidance. liver can be visualized from the right side com-
pared with a ventral or left approach. The right
lateral, right medial, and caudate lobes of the liver
Indications and the gallbladder and extrahepatic biliary tract
The primary indications for laparoscopy in evalua- can be thoroughly examined from the right side.
tion of diseases of the digestive system involve A left approach is generally made only if disease
second puncture cannula, this can be done quickly from liver disease. It is not uncommon for cats
and safely. One of the most significant advantages with chronic cholangitis or cholangiohepatitis to
of laparoscopy-guided biopsy as compared with have concurrent chronic fibrosing pancreatitis.
ultrasound-guided or blind percutaneous biopsy Simultaneous biopsy of liver and pancreatic tissue
techniques is the direct visualization of the biopsy during laparoscopy aids in establishing extent of
procedure itself. Once experience is gained, even involvement in this syndrome.
biopsies of small livers can be rapidly performed The pancreas can usually be visualized through
(Figure 3-23). In cases in which extra tissue sam- a right abdominal approach. It may be necessary to
ples are needed for culture and/or quantitative displace omentum from the pancreas in order to
copper analysis, the procedure can still be quickly visualize it clearly. The right wing of the pancreas
completed.An additional advantage to direct visu- is found adjacent to the duodenum. Usually only a
alization is that a gross description of the liver can small portion of the left pancreatic lobe can be
be communicated to the pathologist. Finally, with seen. In some obese patients it is difficult to find
use of spoon biopsy forceps sample size is some- the pancreas. Biopsy samples of the pancreas are
what larger than what is obtained with needle generally obtained only if the organ is grossly
biopsy instruments, meaning that there is a greater abnormal. The safest technique is to use grasping
certainty that representative liver tissue is being forceps to procure a small piece of the right pan-
obtained for microscopic examination. creatic wing. The central duct area must be
Indications for biopsy of the pancreas include avoided. Parapancreatic fat nodules that represent
ruling in or out acute pancreatitis when other tests either calcification, fibrosis, or necrotic tissue may
have failed to establish clearly a diagnosis (i.e., be found. Great care in trocar placement must be
obvious pancreatitis is not an indication for lapa- exercised when performing laparoscopy in any
roscopy), identification of chronic recurring pan- patient that is likely to have acute pancreatitis.
creatitis, and differentiation of pancreatic disease
Contraindications
Because laparoscopic procedures are generally
short in duration (10 to 30 minutes when done by
an experienced operator) and not considered sig-
nificantly invasive, the risks are not as great as those
that can be associated with exploratory lapa-
rotomy. By the time a decision to recommend
laparoscopy is made, there has been ample opportu-
nity for the clinician to evaluate the patient thor-
oughly through history, serial physical examinations,
selected laboratory tests, and radiography. There
are several absolute contraindications for perform-
ing laparoscopy. These include acute or unstable
cardiopulmonary conditions, presence of an uncor-
rectable or severe coagulopathy, cases in which
extensive intraabdominal adhesions could have
FIGURE 3-23 Microhepatia and cirrhosis in a 3-year- developed, bowel obstruction, abdominal herniation
old cocker spaniel with a 3-week history of (diaphragmatic or inguinal), and septic peritonitis.
intermittent vomiting and anorexia. Liver enzyme A relative contraindication must be balanced
levels were only mildly elevated, but both resting and against the need for diagnosis and risks of alterna-
postprandial bile acid values were markedly increased. tive methods of diagnosis. The latter options usu-
Several small lobes of liver can be seen to the left of the
ally include either ultrasound-guided biopsy
gallbladder. The caudal vena cava is seen between two
of the lobes (8 o’clock position). The oval window of the
(sedation is still required) or general anesthesia and
diaphragm is in the background (light area at the top of laparotomy. With administration of proper patient
the field). The dog lived 15 months after the diagnosis support and use of the safest possible sedation and
of severe liver disease was made. NOTE: Laparoscopy anesthetic protocols (e.g., ketamine and diazepam
is an ideal method for safely and quickly obtaining liver or propofol and the general anesthetic agent isoflu-
biopsies in patients with a small liver. rane or sevoflurane), many elderly or compromised
CHAPTER 3 ENDOSCOPY AND LAPAROSCOPY IN VETERINARY GASTROENTEROLOGY 117
patients can tolerate laparoscopy with minimal or even minor procedures. Owners should be warned
no problems. Ascites can complicate laparoscopy. that this possibility exists before any type of proce-
The main problem involves clouding of the field of dure in a patient with severe liver disease. Minor
view. When ascites is present, it is usually best to complications include subcutaneous emphysema
remove as much of the fluid as possible before the and subcutaneous leakage of ascites fluid around the
procedure. This is best accomplished using either puncture site. These are usually transient problems.
diuretics, if the ascites is mild and the procedure is
not scheduled to be done for several days to a
week, or centesis, on the day before or the day of REFERENCES
the procedure if the ascites is moderate to severe.
Brady PG: Endoscopic removal of foreign bodies. In
Silvis SE, ed: Therapeutic gastrointestinal endoscopy, New
Complications York, 1985, Igaku-Shoin.
Freeman LJ, Kolata RJ,Trostle S: Minimally invasive sur-
The complication rate associated with laparoscopy gery of the gastrointestinal system. In Freeman LJ, ed:
depends on operator experience, accurate patient Veterinary endosurgery. St. Louis, 1999, Mosby.
assessment and recognition by the clinician of Lightdale CJ: Indications, contraindications, and compli-
appropriate indications and any possible contraindi- cations of laparoscopy. In Sivak MV, ed: Gastroentero-
cations, and quality of the laparoscopic equipment logic endoscopy. Philadelphia, 1987,WB Saunders.
used. As an invasive procedure, laparoscopy is Magne ML,Tams TR: Laparoscopy: instrumentation and
remarkably safe. Most surveys in human and veteri- technique. In Tams TR, ed: Small animal endoscopy. St.
nary medicine indicate that, as is the case with most Louis, 1999, Mosby, pp 397-408.
procedures, errors and complications of laparoscopy Morgenstern L: A new era of keyhole surgery,
Gastrointest Endosc Clin North Am 3:183, 1993.
are more common when the technique is still being
Nord HJ: Technique of laparoscopy. In Sivak MV, ed:
learned. Complications during laparoscopy can be Gastroenterologic endoscopy, Philadelphia, 1987, WB
avoided with a high degree of success when the Saunders.
operator uses a systematic approach and careful Quilici PJ: Laparoscopic cholecystectomy, Gastrointest
attention to detail. Potential major complications Endosc Clin North Am 3:221, 1993.
that can occur include air embolism (related to Tams TR: Endoscopic examination of the small intes-
abdominal insufflation), cardiopulmonary arrest, tine. In Tams TR, ed: Small animal endoscopy, St. Louis,
pneumothorax (from diaphragmatic puncture by a 1999, Mosby.
misguided instrument), damage to internal organs, Tams TR: Endoscopic removal of gastrointestinal for-
bleeding, and infection. Because laceration of a eign bodies. In Tams TR, ed: Small animal endoscopy, St.
major vessel can occur when attempting to obtain Louis, 1999, Mosby.
Tams TR: Endoscopy, In Kirk RW, Bonagura JD, eds:
biopsy samples from a small liver with a needle
Current veterinary therapy X. Philadelphia, 1989, WB
instrument, it is recommended that grasping forceps Saunders.
be used instead in this situation (see Figure 3-19). In Twedt DC: Laparoscopy of the liver and pancreas. In
fact, this is the instrument that I routinely use to Tams TR, ed: Small animal endoscopy. St. Louis, 1999,
obtain liver samples in almost all liver biopsy cases. Mosby.
Patients with end-stage liver disease are at risk of Willard MD: Colonoscopy. In Tams TR, ed: Small animal
decompensating at any time and in association with endoscopy. St. Louis, 1999, Mosby, pp 217-245.
C H A P T E R
4
DISEASES OF THE
ESOPHAGUS
Todd R.Tams
The esophagus is a muscular tube that transports functions as a physiologic sphincter. It acts as a
ingested material from the pharynx to the stom- zone of high resting pressure that promotes unidi-
ach. In the resting state the esophagus is collapsed; rectional flow from the esophagus to the stomach
however, it is capable of distending to accommo- and helps prevent reflux of gastric contents into
date passage of both fluid and solid materials. It is the esophagus. In dogs the LES consists of an outer
divided into three sections—the cervical, the tho- layer of striated muscle and an inner layer of
racic, and the short abdominal portions—and it is smooth muscle, whereas in cats the LES is com-
bounded at each end by sphincters. The upper posed entirely of smooth muscle. Mechanisms for
esophageal sphincter (UES) separates the cervical prevention of gastroesophageal reflux include a
esophagus from the oropharynx. It is composed of variety of anatomic factors in addition to the LES
fibers from the paired cricopharyngeal muscles itself. The entire abdominal segment of the esoph-
and a portion of the thyropharyngeus muscle. agus, as well as the surrounding structures, plays a
Innervation of the muscles of the UES is involun- role. Gastric rugal folds, the diaphragmatic crus,
tary and arises through the glossopharyngeal nerve the oblique angle of the distal esophagus as it
and the pharyngeal branches of the vagus nerve. enters the stomach, and compression of the
The UES remains closed at all times, opening intraabdominal esophagus by the fundus when the
only to allow passage of a bolus. It closes promptly stomach is distended all contribute to LES
after the bolus is passed. The duration of opening integrity and help prevent gastric reflux.
of the UES is determined by a central neural The LES opens and closes in response to neural
mechanism that senses the volume of the bolus activity (vagal tone) associated with the swallowing
that is being propelled aborally by the pharynx. mechanism. Its function can also be influenced,
The state of consistent closure of the UES main- however, by hormones, by drugs (e.g., acepro-
tains a high-pressure zone that serves as an impor- mazine, atropine, diazepam, propofol, xylazine,
tant defense mechanism, helping protect against halothane, and isoflurane decrease LES pressure,
esophagopharyngeal reflux and aspiration of whereas metoclopramide, cisapride, bethanechol,
ingesta. erythromycin, and domperidone increase LES pres-
The lower esophageal sphincter (LES) or gas- sure), and by local events such as inflammation. In
troesophageal junction (GEJ) comprises the junc- response to esophageal peristaltic contractions, the
tion between the esophagus and stomach. The LES LES undergoes a phase of initial relaxation that is
118
CHAPTER 4 DISEASES OF THE ESOPHAGUS 119
followed by postdeglutition contraction. Initial muscularis mucosa. The muscularis mucosa has
relaxation begins when an esophageal peristaltic minimal contribution to peristaltic activity. The
contraction occurs in the proximal esophagus. esophagus receives its innervation from the sym-
Postdeglutition contractions prevent reflux of a pathetic and the vagus nerves, including the recur-
food bolus following its passage into the stomach. rent laryngeal branches. The vagal supply is the
Boluses are moved through the esophagus by a more important of the two. Branches of the thy-
series of strong, well-coordinated contractions, roid arteries supply blood to the cervical esopha-
which are produced by intense muscular activity. gus; the bronchoesophageal arteries supply the
The esophagus of the dog is relatively longer than cranial portions of the thoracic esophagus, and the
that of humans. Animals rely much more on branches of the aorta, the intercostals, and the gas-
propulsive esophageal activity than do humans, in tric arteries supply the remaining portion of the
whom gravity also plays a significant role in move- esophagus.
ment of material through the esophagus. In fact, it The most common esophageal disorders that
has been shown that the canine esophagus is able are seen in clinical practice are megaesophagus,
to develop 10 times the pressure that develops in esophagitis, esophageal strictures, and esophageal
the human esophagus. foreign bodies. These problems are discussed in
The swallowing process has been divided into detail in this chapter. Less common problems that
three major phases: oropharyngeal, esophageal, and are discussed include vascular ring anomalies,
gastroesophageal. Primary esophageal contractions hiatal disorders, and esophageal neoplasia. A list of
are triggered by the oropharyngeal phase of swal- esophageal diseases based on signalment appears in
lowing. Secondary peristaltic waves occur in Table 4-1.
response to the effects of esophageal luminal dis-
tention and tactile stimuli. These waves begin
proximal to the bolus. Progression of primary and
MEGAESOPHAGUS
secondary peristaltic waves depends on the size Megaesophagus is a syndrome characterized by
and the location of boluses present in the esopha- generalized esophageal dilation and hypoperistalsis,
gus. Solids initiate stronger primary peristaltic which is often severe. It is differentiated from local-
contractions than do liquids. Secondary peristaltic ized cases of esophageal dilation most of which are
contractions are more frequently required to clear caused by mechanical problems with esophageal
liquids than to clear solids from the esophagus. dilation occurring proximal to the site of obstruc-
The speed of esophageal peristalsis is much faster tion (e.g., vascular ring anomalies, strictures, for-
in dogs (75 to 100 cm/sec) than in cats (1 to 2 eign bodies, neoplasia). There may or may not be
cm/sec). This is because striated muscles contract abnormal peristalsis associated with these disor-
faster than smooth muscles. Among the most ders. Clinicians should be aware that not all
common clinical disorders of the esophagus patients with esophageal motility disorders have
observed in dogs are problems related to esopha- megaesophagus. Some patients have various
geal motility (e.g., variable degrees of esophageal degrees of esophageal hypomotility (e.g., slow
hypomotility, megaesophagus). The primary symp- stimulation of secondary waves of esophageal con-
tom of these disorders is regurgitation, which traction, or “sluggish motility”) that may be seg-
results from an inability of the esophagus to trans- mental or diffuse. Survey thoracic radiographs are
port ingested material to the stomach in a timely often normal in these patients. Mild to moderate
manner. esophageal hypomotility is best evaluated with flu-
The esophagus has four distinct layers: the oroscopic studies in which both liquid contrast
adventitia, the muscularis, the submucosa (which alone and liquid with food are used to study the
contains glands, nerves, and blood vessels), and the strength and coordination of esophageal peristalsis.
mucosa.With no serosal layer present, the submu- Megaesophagus may be congenital or acquired
cosal layer of the esophagus is considered to have (adult onset). In most clinical practices, adult-onset idio-
the greatest holding strength when sutured. In pathic megaesophagus is seen somewhat more commonly
dogs, the muscle layer of the esophagus is com- than congenital megaesophagus. A familial predisposi-
posed entirely of striated muscle. In cats, the cra- tion for congenital megaesophagus has been iden-
nial two thirds of the esophagus is striated muscle, tified for many breeds of dogs (Great Dane,
and the distal one third is smooth muscle. The only German shepherd, Irish setter, golden retriever,
smooth muscle in the esophagus of a dog is the Labrador retriever, greyhound, Newfoundland,
120 CHAPTER 4 DISEASES OF THE ESOPHAGUS
shar-pei), as well as for Siamese cats (although many pure-breed dogs. Breeding of affected ani-
megaesophagus rarely occurs in cats). Congenital mals is not recommended.
megaesophagus is known to be inherited in wire-
haired fox terriers and miniature schnauzers. It is
transmitted in wirehaired fox terriers as a simple Etiology
autosomal-recessive trait, whereas in miniature The pathogenesis of megaesophagus is poorly
schnauzers it is transmitted as a simple autosomal- understood. Physiologic studies in dogs with megae-
dominant or a 60% penetrance autosomal-recessive sophagus suggest that a defect exists in the afferent
trait. The acquired form has been reported in neural pathway. Efferent neuromuscular pathways
CHAPTER 4 DISEASES OF THE ESOPHAGUS 121
appear to be intact. It has been shown that dogs with ommended that patients with acquired megaesophagus be
idiopathic megaesophagus do have cyclical migrat- evaluated for the presence of a primary disorder. It is
ing motor complex activity and that the upper and emphasized, however, that the majority of patients with
lower esophageal sphincter responses to swallowing megaesophagus have idiopathic disease, and treatment
are intact and normal. Mechanisms may be similar centers on general management principles. Selected pri-
for both congenital and acquired idiopathic mega- mary disorders are discussed in more detail later in
esophagus. Diminished motor responses of the upper this chapter.
and lower esophageal sphincters to intraluminal
stimuli have been identified.
Megaesophagus in dogs was previously incor- Congenital Idiopathic
rectly compared with a human esophageal disor- Megaesophagus
der called achalasia, which is characterized by Congenital idiopathic megaesophagus involves
failure of the lower esophageal sphincter to relax generalized esophageal dilation of unknown cause,
properly and ineffective peristalsis of the with signs of regurgitation usually beginning at or
esophageal body. Treatment of this human disor- shortly after weaning. Occasionally, regurgitation
der involves cardiomyotomy. Achalasia has never does not begin until 2 to 6 months after weaning.
been proven to occur in animals. Esophageal Congenital disease should be considered in any
sphincter tone is normal, not increased, in dogs young patient with megaesophagus. The inci-
with megaesophagus. Cardiomyotomy is therefore dence is highest in Great Danes, German shep-
clearly not indicated in dogs with megaesophagus. herds, golden retrievers, Shar-peis, Irish setters,
Acquired megaesophagus occasionally occurs wirehaired fox terriers, and miniature schnauzers,
secondary to other disorders, especially diseases although many other breeds can be affected by the
that can cause diffuse neuromuscular dysfunction disease.A hereditary mechanism has also been sus-
(e.g., focal or generalized myasthenia gravis, pected in young cats, especially Siamese cats.
hypoadrenocorticism, and dysautonomia in cats). Multiple animals in a litter can be affected.
Causes of megaesophagus are listed in Box 4-1. The most important differential diagnosis in
Because appropriate management of some of these disor- young dogs and cats with regurgitation that
ders may lead to resolution of megaesophagus, it is rec- occurs around the time of weaning is vascular
ring anomaly. Vascular ring anomalies occur
quite uncommonly. Differentiation can often be
BOX 4-1 Causes of Megaesophagus made on survey thoracic radiographs (general-
Idiopathic ized dilation of the entire esophageal body is usu-
Congenital ally readily identified with megaesophagus)
Acquired (adult onset) (Figure 4-1). Contrast studies are done on
Neuromuscular patients with suspected vascular ring anomaly to
Myasthenia gravis (focal or generalized) highlight both the presence of an obstruction
Polymyositis and polymyopathy just cranial to the heart and the severity of dila-
Systemic lupus erythematosus tion proximal to the obstruction. Other impor-
Dysautonomia (cats) tant differential diagnoses in young patients with
Giant cell axonal neuropathy regurgitation include esophageal stricture and
Polyradiculoneuritis
foreign body.
Dermatomyositis
Botulism
Treatment for congenital megaesophagus pri-
Brainstem trauma or neoplasia marily involves elevated feedings (45 to 90 degrees
Toxic of upper body elevation). The consistency of the
Lead food that is fed depends entirely on what type is
Thallium associated with the least postprandial regurgita-
Organophosphates tion. Promotility therapy (cisapride) may also be
Endocrine attempted, although this drug is not expected to
Hypoadrenocorticism be useful in dogs because it is a smooth muscle
Hypothyroidism prokinetic agent and the canine esophagus con-
Miscellaneous sists entirely of skeletal muscle. Treatment details
Pyloric stenosis (cats)
for megaesophagus are discussed later in this
Congenital lower esophageal stricture
chapter.
122 CHAPTER 4 DISEASES OF THE ESOPHAGUS
be performed, with emphasis on cranial nerves IX myasthenia gravis is described in more detail later
(glossopharyngeal) and X (vagus). in this chapter.
Other tests that the clinician should consider in
Diagnosis the evaluation of patients with megaesophagus,
Acquired megaesophagus is most commonly diag- depending on clinical course and physical find-
nosed by the presence of generalized esophageal ings, include the following:
dilation on survey thoracic radiographs, without Adrenocorticotropic Hormone Stimula-
evidence of obstruction. If cervical radiographs are tion Test for Hypoadrenocorticism. Hypo-
obtained, dilation of the cervical esophagus will adrenocorticism is an uncommon cause of
usually be noted as well. Contrast studies (liquid megaesophagus. Proposed causes of esophageal
barium) are occasionally necessary to confirm the dilation include the effects of abnormal sodium
presence of a dilated, hypoperistaltic esophagus. In and potassium concentrations on membrane
many patients with obvious megaesophagus, it is potential and neuromuscular function, as well as a
unnecessary to perform contrast studies. The risk physiologic deficiency of cortisol, which may
of aspiration of contrast material must always be cause muscle weakness.
considered. I most commonly perform a contrast Hypoadrenocorticism has a predilection for
study when I suspect an esophageal motility disor- young to middle-aged females. The most com-
der and when the thoracic esophagus is not readily mon clinical signs include anorexia, vomiting,
recognized on survey films. The technique for lethargy, and weakness. Diarrhea also may occur.
contrast radiography of the esophagus is discussed Most dogs that have megaesophagus associated
in Chapter 2. with hypoadrenocorticism demonstrate one or all
Occasionally dogs with megaesophagus are first pre- of these signs in addition to regurgitation.
sented because of symptoms related to aspiration pneu- However, occasionally there may be only regurgi-
monia. Therefore when evaluating thoracic radiographs tation. In addition, some of these dogs have atypi-
from dogs with pneumonia, one must always look closely cal hypoadrenocorticism, in which sodium and
for any evidence of esophageal dilation. potassium levels are normal. This complicates the
Once the presence of megaesophagus is con- diagnosis, so the clinician must maintain a high
firmed, appropriate ancillary tests should be per- index of suspicion. An adrenocorticotropic hor-
formed. A complete blood count, a complete mone (ACTH) stimulation test is required for
biochemical profile (including creatine kinase diagnosis. ACTH stimulation should also be per-
[CK]), and total serum thyroxine levels should be formed to confirm the diagnosis in patients with
evaluated in all cases (TT4). Leukocytosis (neu- characteristic hyponatremia and hyperkalemia.
trophilia) with or without a left shift is consistent With proper treatment the megaesophagus will
with aspiration pneumonia. Biochemical tests of most likely resolve.
particular interest include evaluations of sodium Tests for Hypothyroidism: f T4ED and
and potassium (hyponatremia and hyperkalemia cTSH Assay. It has been proposed that mega-
are present in approximately 90% of dogs with esophagus may be associated with hypothyroidism.
hypoadrenocorticism); CK and aspartate transami- Very few dogs with hypothyroidism appear to
nase (AST) (which may be elevated in patients develop megaesophagus. Tests including an f T4ED
with polymyositis); and cholesterol (hypercholes- and cTSH assay are warranted if baseline thyroid
terolemia may suggest the possibility of hypothy- tests are subnormal. However, it is considered to
roidism). In addition to baseline serum thyroxine be a rare occurrence for megaesophagus to resolve
level evaluation, free T4 by equilibrium dialysis in response to treatment for hypothyroidism.
(f T4ED) and a canine thyroid-stimulating hor- Occasionally, a patient may have both hypothy-
mone (cTSH) assay can also be done to more roidism and focal myasthenia gravis. It is possible
thoroughly examine for hypothyroidism. An that the focal myasthenia gravis could resolve
acetylcholine receptor antibody titer should either spontaneously or as a result of treatment for
also be obtained in all adult dogs with megaesoph- hypothyroidism, with megaesophagus resolving as
agus to test for focal myasthenia gravis. Focal myas- well.
thenia gravis occurs in the absence of muscle weakness. Blood Lead Level for Lead Poisoning.
This is probably the second most common cause of Sources of lead include old paints, toys, lubricants,
acquired megaesophagus (a greater number of cases are hobby materials, automotive materials, plaster
idiopathic). Megaesophagus secondary to acquired board, roofing materials, fishing sinkers, and
CHAPTER 4 DISEASES OF THE ESOPHAGUS 125
improperly glazed dishes. Young (less than 1 to 2 clinical signs of generalized myasthenia gravis are
years), inquisitive patients are most commonly episodic weakness and decreased exercise toler-
affected. Clinical signs of lead toxicity often ance. Difficulty with barking and with swallowing
include both gastrointestinal (GI) and neurologic and prehending food also may be present. Mild
abnormalities. Anorexia, vomiting, diarrhea, cases may be difficult to differentiate from
and/or abdominal pain are often demonstrated. polymyositis, in which decreased exercise toler-
Regurgitation occurs in patients that develop ance, dysphagia, and regurgitation associated with
esophageal hypomotility and dilation secondary to megaesophagus also may occur. Edrophonium
lead toxicosis (a careful review of the history is chloride, a short-acting anticholinesterase drug,
necessary to determine that both regurgitation given at a dose of 0.05 to 0.1 mg/lb intravenously
and vomiting, rather than vomiting alone, are usually produces dramatic improvement in patients
occurring). Megaesophagus is not common in with myasthenia gravis that have collapsed or that
patients with lead toxicity. Neurologic abnormali- are exercise intolerant. The response occurs within
ties may range from sudden epileptic seizures to a 1 to 2 minutes but lasts only for several minutes.
variety of behavioral changes, including excitabil- All dogs with myasthenia gravis should be
ity, hysteria, continued barking or whining, dull- tested for hypothyroidism, since it is estimated that
ness, and apparent blindness. A blood lead level of 20% of dogs with myasthenia gravis will concur-
greater than 40 µg/dl is suggestive of lead poison- rently have hypothyroidism.
ing, and a level of greater than 60 µg/dl is diagnos- Electromyography. This study may be useful
tic. Abdominal radiographs may reveal radiopaque in the diagnosis and the differentiation of polymy-
material in the GI tract, and there may be nucle- opathy, polymyositis, myasthenia gravis, and
ated red blood cells and basophilic stippling on polyneuropathy. For example, in myasthenia gravis,
stained blood smears. In most cases administration electromyography (EMG) and nerve conduction
of the antidote of choice (calcium ethylenedi- velocity studies are usually normal. On repetitive
aminetetraacetic acid) is sufficient to correct the nerve stimulation, a decremental response is seen
clinical manifestations of lead toxicity. If treated that is most characteristic of myasthenia gravis.
early enough, megaesophagus will resolve. The decremental response disappears when edro-
Antinuclear Antibody and Lupus Ery- phonium chloride is given. EMG in patients with
thematosus Tests for Systemic Lupus polymyositis may demonstrate positive sharp
Erythematosus. In my experience, systemic waves, fibrillation potentials, and bizarre high-
lupus erythematosus (SLE) is an uncommon cause frequency discharges. There is no decremental
of megaesophagus in patients. Antinuclear anti- response to repetitive nerve stimulation, which
body (ANA) tests performed on patients with differentiates polymyositis from myasthenia gravis.
megaesophagus are rarely positive. Physical find- In most patients with megaesophagus, endo-
ings that should prompt the clinician to test for scopic examination is not necessary for diagnosis
SLE as a cause of megaesophagus include gait and is rarely beneficial in determining a cause for
abnormalities (e.g., stilted gait, shifting limb lame- the disorder. Patients with mild esophageal motility
ness), joint swelling or pain (polyarthritis), muscle disorders may have a completely normal endo-
pain (polymyositis), concurrent evidence of scopic examination; alternatively, there may be
immune-mediated hemolytic anemia or immune- various degrees of fluid pooling. In contrast,
mediated thrombocytopenia, and skin lesions, patients with megaesophagus almost always demon-
which may include ulceration, erythema, crusting, strate fluid retention and often small to moderate
and alopecia. Nonspecific signs of SLE may amounts of food residue. Many patients with
include weakness, lethargy, and anorexia. megaesophagus have grossly normal esophageal
Edrophonium Chloride (Tensilon) Chal- mucosa. However, in some patients there may be
lenge Test for Myasthenia Gravis. This test evidence of esophagitis (e.g., mucosal erosions,
is used to detect generalized myasthenia gravis or, patchy erythema, or focal hemorrhage occurring
if a decreased or absent palpebral reflex is found secondary to mucosal contact with the endoscope
on physical examination, focal myasthenia gravis. tip), which is most likely related to putrefaction of
Most patients with generalized myasthenia gravis retained contents or reflux of gastric acid and
are thought to have at least some degree of activated enzymes. The two primary rule-outs for
esophageal dysfunction, ranging from mild hypo- patients with megaesophagus that become inappetent are
motility to megaesophagus. The most common pneumonia and esophagitis.
126 CHAPTER 4 DISEASES OF THE ESOPHAGUS
FIGURE 4-5 A, Specialized feeding chairs for dogs with megaesophagus. These chairs were designed by Donna
Imhoff, a veterinary technician who has substantial experience in managing dogs with megaesophagus, and her
husband. The chair provides full upright support for dogs to facilitate both feeding and holding them comfortably
upright for the desired amount of time after they have eaten. The chair can be adjusted to accommodate patients of
various sizes. Use of these chairs has the additional advantage of freeing the pet’s owner from having to physically
hold the patient in an upright position, and thus it is also more likely that the patient will be kept upright for the
full recommended period of time. B, A tilt feature can be added to the highchairs to make it easier for the patient
to reach the food bowl. (Courtesy Donna Imhoff, North Shore Animal League, Port Washington, NY.)
128 CHAPTER 4 DISEASES OF THE ESOPHAGUS
food. I recommend trying gruels only if the semi- evidence that they are of any value in the treat-
moist consistency is not well tolerated. Some dogs ment of megaesophagus. Their use is therefore not
do not do well at all on liquid gruel diets, and this recommended.
food consistency may be more easily aspirated. The GI prokinetic drug cisapride is a benza-
Some dogs do best when fed a series of “meatballs” mide derivative that promotes GI motility, increases
fashioned from canned food. Others can tolerate antroduodenal coordination, and enhances LES
dry food fairly well, either with or without water tone. It has broader promotility effects than meto-
added to the food. The important point is that clopramide does. Cisapride has promotility effects
each patient can respond to various food consisten- in the esophagus of cats (distal esophagus where
cies in different ways. Owners should be instructed there is smooth muscle), the stomach, the small
to conduct food trials in order to determine the intestine, and the large intestine. It increases LES
best regimen for their own pet. pressure, the amplitude of contractions in the distal
Specific pharmacologic agents have been used esophagus, and the rate of gastric emptying.
in efforts to improve esophageal emptying. The Cisapride, in theory, is likely to be of little benefit
promotility drug metoclopramide has been inef- in dogs with megaesophagus because it stimulates
fective in my experience. Metoclopramide can smooth muscle motility and the canine esophagus
increase lower esophageal contractions slightly in is almost exclusively striated muscle. However, cis-
normal patients but does not improve con- apride has been found to be helpful in decreasing
tractile activity in patients with megaesophagus. significantly the frequency of regurgitation in sev-
Nifedipine is a calcium channel antagonist that eral dogs with megaesophagus in our hospital
promotes relaxation of the LES. It was tried with series. These were cases that were being managed
the thought that decreasing LES tone might make very diligently by their owners with elevated feed-
it easier for the esophagus to pass food into the ing programs but with poor responses (i.e., there was
stomach. Calcium channel antagonists, however, an ongoing high frequency of regurgitation).
can cause serious side effects, and there is no Concurrent with the institution of cisapride
CHAPTER 4 DISEASES OF THE ESOPHAGUS 129
ever having a gastrostomy tube placed. In sum- Oral administration of antibiotics is contraindi-
mary, the two main indications for use of a gastros- cated in seriously ill patients because of their low
tomy tube are (1) significant weight loss with and erratic serum levels. There are also problems
ongoing regurgitation despite elevated feedings in ensuring that the medication is transported in a
and (2) aspiration pneumonia, in which it is best to timely manner to the stomach in a patient with
avoid using the esophagus until the pneumonia is megaesophagus.
resolved and it is demonstrated that persistent As previously mentioned, patients with mega-
regurgitation will not be a problem. esophagus occasionally develop esophagitis. The
Treatment for aspiration pneumonia includes primary signs of esophagitis are decreased appetite
aggressive fluid therapy, antibiotics, coupage, nebu- and lethargy. Salivation also may be evident.
lization, and nutritional support. Ideally, a tracheal Esophagitis should be suspected once pneumonia
wash should be done in patients with moderate to is ruled out. Treatment may include administration
severe pneumonia as soon as the diagnosis is made. of a sucralfate (Carafate) suspension or H2-receptor
The initial choice of one or more antibiotics antagonist therapy to lower gastric acid levels or
depends on cytologic studies and Gram stain both. A proton pump inhibitor (e.g., omeprazole,
results. The use of bactericidal antibiotics with lansoprazole, esomeprazole) is used to completely
a good gram-negative spectrum is recom- block acid release in patients with moderate to
mended pending culture and sensitivity results. severe esophagitis, instead of an H2-receptor antag-
Trimethoprim-sulfonamide (Tribrissen) and onist. There is often rapid improvement once spe-
enrofloxacin (Baytril) are good initial choices for cific treatment is instituted. Duration of therapy
mild pneumonia. Patients with mild pneumonia depends on patient response. Management of
can often be treated with oral antibiotics on an esophagitis is discussed in more detail later in this
outpatient basis. chapter.
If moderate to severe bacterial pneumonia is Dogs that seem to experience frequent bouts of
present and there is marked respiratory insuffi- mild pneumonia sometimes do best when main-
ciency, aggressive antimicrobial therapy should be tained on long-term antibiotic therapy. In these
instituted immediately. This usually involves com- cases, the antibiotics used are often rotated every 6
bination therapy using cephalosporins (e.g., ce- to 8 weeks. Likewise, an H2-receptor antagonist or
fazolin [Kefzol], 10 to 15 mg/lb every 8 hours proton pump inhibitor is sometimes used on a
intravenously or intramuscularly, or cefoxitin long-term basis in dogs with chronic esophagitis.
[Mefoxin], 10 to 15 mg/lb every 6 to 8 hours Too often patients with megaesophagus are
intravenously) and aminoglycosides (gentamicin quickly assigned a poor prognosis. Granted, some
[Gentocin], 1 to 2 mg/lb intravenously or subcu- patients do poorly on any form of therapy and
taneously every 6 to 8 hours or 2.7 to 4.5 mg/lb euthanasia may unfortunately be inevitable.
intravenously or subcutaneously once every 24 However, many patients with megaesophagus can
hours, or amikacin [Amiglyde-V] 3 mg/lb every 8 be successfully managed for months to years.
hours or 9 mg/lb once every 24 hours intra- Owners who are willing to invest time and effort
venously, intramuscularly, or subcutaneously). in the care of their pet with megaesophagus
Alternatively, imipenem (Primaxin) provides are often rewarded. To highlight this point,
excellent four-quadrant coverage. Imipenem is three cases of note are presented in Figures 4-9
administered as sole antimicrobial therapy at 2.5 to and 4-10.
5 mg/lb intravenously every 8 hours. Imipenem is
a beta-lactam antibiotic. Beta-lactam agents have
little if any dose-dependent toxicity. Imipenem has Megaesophagus Secondary to
the same toxicity potential as that of other pen- Acquired Myasthenia Gravis
cillins (e.g., ampicillin). The best use of this drug is Clinical Signs
in patients with renal compromise that cannot be Myasthenia gravis occurs both as an acquired
given aminoglycosides safely. If the creatinine level autoimmune disorder and as a congenital, famil-
is greater than 4 mg/dl, imipenem is adminis- ial one. Acquired myasthenia gravis is an autoim-
tered at 12-hour, rather than 8-hour, intervals. mune disorder of neuromuscular transmission
Imipenem should be delivered over 30 minutes in resulting from the actions of autoantibodies against
the intravenous line. nicotinic acetylcholine receptors at neuromuscular
junctions. Conjointly there is complement medi-
CHAPTER 4 DISEASES OF THE ESOPHAGUS 131
FIGURE 4-9 A, Contrast radiograph of an 8-year-old Irish wolfhound with adult-onset idiopathic megaesophagus.
Note that there was aspiration of a small amount of barium into the airways. The dog was presented because of
regurgitation. There was an excellent response to elevated feedings (the owner used a ladder and helped support the
dog from the side). The diet consisted of kibble soaked in water. B, Photograph of the dog taken 5 months after the
diagnosis was made. The dog regurgitated on average only two times per week.
ated destruction of the junction folds, altering the Clinical signs include premature fatigue during
neuromuscular junction formation, or it may exercise (manifested by a spastic pelvic limb gait
accelerate the internalization and the degradation followed by tetraparesis and then collapse), tachyp-
of the acetylcholine receptor. Myasthenia gravis nea and dyspnea, and sialosis. More recently, a focal
manifests itself in several clinical forms: form of myasthenia gravis, in which megaesophagus
occurs in the absence of detectable generalized weak-
● Generalized myasthenia gravis: Manifests pre-
ness, has been recognized. The primary clinical sign
dominantly as tetraparesis, but there may be
is regurgitation. Other clinical signs that may occa-
primarily pelvic limb paresis.
sionally be observed in focal myasthenia gravis
● Focal myasthenia gravis: Affects the cranial
include pharyngeal and laryngeal muscle weakness
nerves mainly around the larynx and pharyn-
(dysphagia and dyspnea), weakness of the facial mus-
geal region.
cles, and a decreased palpebral reflex. In some dogs
● Acute fulminant myasthenia gravis: Flaccid
there is a change in the quality of the bark or an
tetraparesis, acute respiratory distress.
inability to bark. A myopathy or a neuropathy
Megaesophagus associated with generalized should always be considered as a differential diagno-
myasthenia gravis has been well documented. sis in laryngeal or pharyngeal problems.
132 CHAPTER 4 DISEASES OF THE ESOPHAGUS
FIGURE 4-10 Two young German shepherd dogs with esophageal motility disorders. The dog on the left had
congenital megaesophagus (also shown in Figure 4-1). Persistent right aortic arch was diagnosed in the dog on the
right at 4 months of age. Surgery was successful in relieving the esophageal obstruction, but esophageal dilation
persisted. The dogs are not related. Each of these dogs was adopted and cared for by a veterinarian on our staff.
Note their excellent body condition. Long-term treatment for megaesophagus included twice daily elevated
feedings. The diet consisted of a mixture of kibble, canned food, and water blenderized to an oatmeal consistency.
Regurgitation rarely occurred, and both dogs remained highly energetic.
ized myasthenia gravis, but if this is going to hap- the time of weaning, the diagnosis will almost
pen it generally occurs within the first few weeks always be made by 6 months of age. Rarely, signif-
after onset of clinical signs. Radiographs are also icant clinical signs may not be apparent until later
obtained periodically to monitor esophageal size. in life. As the proximal esophagus becomes more
Esophageal function may return to normal, but dilated, food may be retained for longer periods
remission may require days to months. Owners before regurgitation occurs. Affected patients
should also be warned that the disease may recur. become malnourished and weak and are smaller
Several clinicians have reported seeing an occa- than their littermates. Coughing with respiratory
sional dog with both hypothyroidism (confirmed distress is common and indicates a secondary aspi-
by a TSH response test) and focal myasthenia ration pneumonia.
gravis. In some cases the myasthenic condition
resolved after treatment for hypothyroidism was Diagnosis
instituted. The primary differential diagnosis for vascular ring
anomaly is congenital megaesophagus. Foreign
VASCULAR RING body obstruction also should be considered.
Diagnosis is based on survey and contrast radiog-
ANOMALIES raphy of the thorax. Survey radiographs of vascular
Vascular ring anomalies are congenital malforma- ring anomaly show esophageal dilation with food
tions of the great vessels and their branches that and air. The dilation tapers to normal at the base
entrap the intrathoracic esophagus and cause of the heart. With PRAA the normal opacity
obstruction. Although a number of different con- caused by the bulge of the aortic arch is absent.
genital vascular ring anomalies can occur in dogs Contrast studies of vascular ring anomaly reveal a
and cats, persistent right aortic arch (PRAA) is by characteristic constricted appearance over the base
far the most common (95%). Other anomalies that of the heart, with variable degrees of esophageal
have been reported include persistent right ductus dilation proximal to the site of obstruction.
arteriosus, aberrant left or right subclavian arteries, Fluoroscopy demonstrates a loss of motility of the
double aortic arch, and esophageal compression by proximal esophagus. Esophageal motility distal to
the left subclavian and brachiocephalic arteries the stricture is usually normal. In the rare instance
(found in English bulldogs). Vascular rings are that the diagnosis cannot be confirmed by radiog-
quite uncommon in cats. raphy, esophagoscopy can provide useful infor-
In PRAA the right rather than the left fourth mation in differentiating a mural lesion from
aortic arch forms the functional adult aorta. The extraluminal compression. With extraluminal
esophagus becomes entrapped by the aorta on the compression of the esophagus, a full circumference
right, by the pulmonary trunk on the left, by indentation may be seen from the lumen side.
the ligamentum arteriosum dorsolaterally on the Endoscopy is also useful for ruling out esophageal
left, and by the base of the heart ventrally (Figure foreign body and in removal if one is found.
4-11). This anatomic “ring” results in obstruction Foreign bodies can become lodged secondary to
and progressive dilation of the esophagus cranial to the PRAA.
the base of the heart.
Vascular ring anomalies are inherited. There is Treatment
a breed predilection for German shepherds and Definitive management of vascular ring anomaly is
Irish setters. There is also a higher than expected limited to surgical correction of the constricting
incidence among Boston terriers and English band forming the vascular ring. For PRAA this
bulldogs. There is no reported breed predilection involves ligation and transection of the ligamen-
for cats. Multiple puppies in a litter may be tum arteriosum.
affected. Breeding affected patients is not recom- It is best to stabilize and strengthen the patient
mended. as much as possible before subjecting it to a thora-
cotomy. Elevated feedings having a gruel consis-
Clinical Signs tency are given frequently and in small enough
The most common clinical sign in puppies and amounts to minimize regurgitation. A gastrostomy
kittens is an acute onset of regurgitation at or tube can be used if oral feeding is poorly tolerated.
shortly after the time of weaning to solid foods. In If pneumonia is present, it should be treated
patients that do not show significant signs around aggressively and resolved before surgery.
CHAPTER 4 DISEASES OF THE ESOPHAGUS 135
FIGURE 4-11 Persistent right aortic arch. A, Normal development of the aortic arch viewed from the patient’s left
side. Inset shows normal embryonic development of the great vessels from a dorsoventral view. B, When the
embryonic right fourth aortic arch becomes the adult aorta, esophageal constriction occurs. Inset shows dorsoventral
view of the vascular malformation. (From Birchard SJ, Sherding RG, eds: Manual of small animal practice, ed 2,
Philadelphia, 2000, WB Saunders.)
The prognosis for complete recovery after sur- Many patients significantly improve after surgery.
gery is guarded to poor. Regurgitation of some If esophageal disease persists, an elevated feeding
degree persists in most dogs that undergo surgical protocol should be followed. Surveillance for signs
correction. The esophageal dilation that exists of aspiration pneumonia is always maintained.
early in the course of the disease persists to some A retrospective study examined whether the
degree indefinitely in most patients. In addition, degree of esophageal dilation affects long-term
esophageal dilation caudal to the vascular ring site outcome. Ten dogs and four cats with PRAA
can occur, possibly due to neuromuscular disease. were studied through 6 months after surgery.
Recovery of normal esophageal function is more Of all the animals, 35.7% (mean age 2.5 months)
likely when surgery is performed at an early age. had a very good outcome, 42.9% (mean age 2.7
136 CHAPTER 4 DISEASES OF THE ESOPHAGUS
months) had a good outcome, and 21.4% (mean Inflammatory changes can range from mild
age 5.7 months, range 3 to 9 months) had a poor mucosal inflammation that may or may not be
outcome. A measurement scheme was devised. grossly evident, to moderate to severe ulceration
After barium contrast esophagography the maxi- and transmural involvement.Any disorder that causes
mum diameter of the esophageal dilation cranial acute or chronic frequent vomiting can potentially
to the heart base (Oe) was compared with the cause esophagitis. This especially includes causes of
height of the body of the 5th thoracic vertebra at severe vomiting, such as intestinal foreign bodies,
its narrowest point (T5). The degree of esophageal gastric foreign bodies, acute pancreatitis, parvoviral
dilation was classified as mild, moderate, and severe enteritis, and gastrinoma. Dogs with parvoviral
on the basis of the ratio Oe: T5. All measurements enteritis that are debilitated and recumbent are espe-
were made to the nearest millimeter. The ratio of cially at risk. Vomited fluid that is retained in the
Oe:T5 for normal dogs and cats, based on esophagus is not cleared adequately in weak and
esophageal contrast studies on 10 normal cats and recumbent patients. As a result the esophageal
25 normal dogs, was considered to be less than or mucosa is bathed with gastric acid and activated
equal to 1. Mild dilation was considered to be less enzymes that will cause mucosal injury.
than or equal to 2.5, moderate less than or equal to Other causes of esophagitis include esophageal
4, and severe greater than 4. foreign bodies (extent of injury depends on the
In this study a majority of the patients with a size, texture, and duration of lodgment) and chem-
mild or moderate degree of dilation had a good to ical and thermal injuries (e.g., ingestion of hot
very good outcome after surgery. Of three patients food). The latter two factors are uncommon causes
that had a poor outcome (two cats and one dog), of esophagitis. Chemical injury may result from
two had a severe degree of dilation (one cat and ingestion of toxic chemicals or from failure of the
one dog), and one had a moderate degree of dila- esophagus to transport capsule or tablet medication
tion. Although more animals must be evaluated completely to the stomach. It is not infrequent in
using this scheme, it appears that the degree of humans for medications taken without water to
preoperative esophageal dilation does affect the become lodged somewhere in the esophagus.
long-term outcome in patients with PRAA. When certain medications dissolve there, mucosal
irritation results. Medication associated esophagitis
from caustic compounds such as NSAIDs and
ESOPHAGITIS doxycycline have been associated with esophagitis
Inflammatory diseases of the esophagus occur or even stricture formation. Owing to anatomic
more commonly than they are recognized. The and physiologic differences between the canine
major causes of esophagitis are listed in Box 4-2. esophagus and the human esophagus (canine
esophageal muscle is entirely striated; the human
esophagus is mostly smooth muscle), this irritation
BOX 4-2 Causes of Esophagitis is somewhat less likely to be a problem in dogs than
in humans. However, it is likely to be more com-
Gastroesophageal reflux (physiologic) mon in cats than in dogs. There have been reports
Anesthesia-related reflux of severe esophagitis occurring in patients second-
Foreign body passage or impaction ary to injury from ingested capsule medication
Food retention as that which may occur with
(e.g., doxycycline, chloramphenicol). There is also
megaesophagus
Any cause of persistent, severe vomiting: e.g.,
potential for a stricture to develop secondary to
parvoviral enteritis, acute pancreatitis, renal fail- esophagitis. In fact, doxycycline-induced esophagi-
ure, gastrinoma (vomited gastric content is very tis with esophageal stricture formation has been
high in acid), gastric and intestinal foreign bodies reported in cats.
Caustic injury: e.g., toxic irritants, acids, alkalis,
capsule or tablet medications that lodge in the
esophagus Gastroesophageal Reflux
Infectious agents such as calicivirus, candida, Disease
phycomycosis in immunocompromised animals A study was reported recently on normal cats in
Thermal injury: e.g., rapid ingestion of which the passage of tablets and capsules when
heated food
given alone (dry swallow) and when followed
Radiation
by a water bolus (wet swallow) was evaluated.
CHAPTER 4 DISEASES OF THE ESOPHAGUS 137
This investigation was undertaken as a result of the inflammation may not be visible grossly. A
experience with cats developing esophagitis and variety of factors can contribute to its develop-
esophageal strictures subsequent to doxycycline ment in individual patients. It can be a particularly
tablet administration. Thirty healthy cats of vari- difficult diagnosis to make without special instru-
ous ages were used in this study. Each cat was mentation (e.g., pH probe monitoring, endoscopy)
given a 20-mg barium tablet and a 190-mg (size 4) because in many patients clinical signs are quite
capsule both as a dry and wet swallow. A wet swal- subtle. History and recognition of suggestive clini-
low consisted of immediately following adminis- cal signs constitute the basis for performing diag-
tration with 6.0 ml of water orally via syringe. nostic procedures or instituting empirical therapy.
Fluoroscopy was used to evaluate tablet or capsule Because significant discomfort can result from reflux
passage at 30, 60, 90, 120, 180, 240, and 300 sec- episodes, it is important that reflux esophagitis be diag-
onds following administration. Dry swallows and nosed and treated in a timely manner.
wet swallows were evaluated. Successful passage
was defined as complete passage into the stomach Gastroesophageal reflux disease
at a given time interval. in humans
The percentage of dry tablet swallows that suc- Gastroesophageal reflux disease (GERD) is among
cessfully passed into the stomach was 0.0% at 30 the most common GI disorders that affect people.
and 60 seconds, 6.7% at 90 seconds, 13.3% at 120 It is estimated that up to 50% of adults in the
seconds, 26.7% at 180 and 240 seconds, and 36.7% United States experience heartburn type of symp-
at 300 seconds. Wet tablet swallows successfully toms at least once a month. GERD is a very diffi-
passed 90.0% of the time at 30 seconds, 93.3% at cult diagnosis to establish in animals, largely
60 seconds, and 100.0% of the time thereafter. because our patients are not able to describe for us
The percentage of dry capsule swallows that suc- the fact that they are experiencing the symptoms
cessfully passed was 16.7% at each time interval. of this disorder and there are no hallmark signs,
Wet capsule swallows successfully passed 96.7% of and it can also be difficult to diagnose definitively
the time at 30 seconds and 100% of the time in humans.There is still no single test that can uni-
thereafter. For each time interval, wet swallows formly detect GERD. Of all the GI disorders that
achieved significantly greater percentage passage affect humans, the symptom pattern for GERD is
into the stomach when compared with dry swal- among the most specific of any GI disorder.
lows. However, there are now well-recognized supra-
The results of this study show that tablets or cap- esophageal and extraesophageal reflux symptoms
sules given as a dry swallow in cats have prolonged (e.g., laryngeal problems, cough) that will not be
retention in the esophagus. A water bolus following diagnosed with just a standard history. The tests
tablet or capsule administration results in signifi- used in human medicine to investigate for GERD
cantly faster passage through the water bolus for cats are endoscopy, looking for esophagitis or other
receiving oral tablets or capsules to prevent possible GERD complications, and 24-hour pH probe
medication associated esophagitis. It is therefore now recording. Barium swallow is also performed in
recommended that cats that receive oral tablet or capsule some cases, mostly to screen for other upper GI
medications without food be given approximately 6 ml of disorders. None of these tests is always diagnostic,
water immediately after the medication to promote rapid however (e.g., it is known that 30% to 70% of
clearing from the esophagus and transit to the stomach. It patients undergoing endoscopy for GERD symp-
is also probably a good idea to do the same in dogs when- toms may have a grossly normal examination), and
ever medications are not given in food. some gastroenterologists therefore use parallel tests
Gastroesophageal reflux is the most com- to determine the presence of GERD. More
mon cause of esophagitis in animals and humans. recently another diagnostic approach in humans
This disorder is discussed in detail in this section. that has received attention is a therapeutic trial of
The term reflux refers to movement of gastric or high dose proton pump inhibitor (PPI) therapy.
duodenal contents into the esophagus without The basis for this test centers on the ability of the
associated eructation or vomiting. As such this can high dose PPI therapy to completely inhibit gastric
be a “silent” disease. Reflux esophagitis is a disor- acid secretion. If symptoms do not resolve on high-
der in which esophageal inflammation of variable dose PPI therapy, they are not likely caused by
degree occurs as a result of mucosal contact with GERD. There are sensitivity and specificity issues
gastric or duodenal fluid or ingesta. In many cases with this test as well, however.
138 CHAPTER 4 DISEASES OF THE ESOPHAGUS
Veterinarians should recognize that GERD is ical attention for what they consider a minor, nor-
very common in people and that it likely occurs in mal physiologic event. The frequency in animals is
animals much more commonly than we are able to unknown, since signs of mild reflux are extremely
recognize. Therefore we should maintain a high difficult to detect.
index of suspicion for this disorder when pre- Manometric measurements of the LES have
sented with patients that may be exhibiting any of shown that a decrease in resting pressures is the
the potential signs of esophagitis. major factor in the pathogenesis of gastro-
esophageal reflux. Reflux occurs primarily by one
Pathophysiology of three different mechanisms: transient complete
Normal LES function is essential to the prevention relaxation of the LES, transient increase in intraab-
of gastroesophageal reflux and esophagitis. The dominal pressure, or spontaneous free reflux asso-
LES is located at the GEJ and is a zone of high ciated with a low resting pressure of the LES.
resting pressure that acts to prevent reflux of gas- Human studies have shown that in normal indi-
tric contents into the esophagus. In response to viduals, reflux episodes are almost always caused by
esophageal peristaltic contractions, the LES under- transient sphincter relaxation. The predominant
goes a phase of initial relaxation that is followed by reflux mechanism in reflux esophagitis patients
postdeglutition contraction. Initial relaxation varies, although transient LES relaxation seems to
begins when an esophageal peristaltic contraction be most common. This transient relaxation mech-
is in the proximal esophagus. Postdeglutition con- anism may explain why some reflux esophagitis
tractions prevent reflux of a food bolus following patients have resting LES pressure values that over-
its passage into the stomach. lap those of normal controls.
Reflux of small amounts of fluid is considered a Transient changes in intraabdominal pressure
normal physiologic phenomenon in both animals may intermittently overcome a hypotensive LES;
and humans. Functional defense mechanisms pre- however, complete sphincter relaxation alone does
vent esophageal mucosal damage when these not guarantee that significant reflux will occur.
minor reflux episodes occur. These defenses Factors that may influence reflux in this situation
include acid clearance by means of one or two include body position, intragastric volume, intra-
esophageal peristaltic sequences that empty all or gastric pressure, and relaxation of the diaphrag-
most of the acid from the esophagus, local mucosal matic hiatus. Significant reflux can occur in
protective factors, and neutralization of any post- animals that undergo general anesthesia, especially
peristaltic residual acid by bicarbonate-rich saliva. when there is ingesta or fluid retention in the
It has been shown in humans that some individu- stomach. Anesthetic agents promote relaxation of
als can experience significant reflux episodes with- the LES, and any procedure that involves position-
out developing demonstrable esophageal mucosal ing the patient with the rear quarters elevated
changes. Although clinical signs of reflux may be (e.g., tilting the surgery table so that the head and
experienced (heartburn, indigestion, dyspepsia), the upper body are below the lower body) can
significant sequelae such as esophagitis, esophageal promote gravitational flow of gastric contents to
stricture, and chest pain often never develop. the esophagus. Mild to severe esophagitis may
Although the relationships and factors respon- result, and in some cases esophageal stricture for-
sible for individual variations in response to reflux mation occurs. Clinical situations in which a
are unknown, a number of factors are probably reflux episode may be exacerbated must be recog-
involved in determining how significant a problem nized, and preventive measures must be taken to
reflux episodes will be in an individual. These decrease serious sequelae.
include volume and frequency of reflux, the dura-
tion of contact between the refluxate and the Mechanisms of Esophageal
esophageal mucosa, character of the refluxed Mucosal Damage
material, competency of esophageal clearing Although both acid and pepsin were implicated in
mechanisms, and gastric emptying patterns. It has the past as the major injurious agents in reflux dis-
been estimated that up to 7% of the general ease, it now appears that the importance of acid has
human population has symptoms of heartburn been overemphasized and that of pepsin minimized.
daily, and a much larger percentage experiences Animal studies have shown that pepsin, rather than
these symptoms monthly (approximately 50% as acid, is a major causative agent of erosive esophagitis
previously stated). Many humans never seek med- resulting from reflux of acid gastric contents.
CHAPTER 4 DISEASES OF THE ESOPHAGUS 139
Of the potentially injurious agents in acid gas- esophageal mucosa are the major factors determining the
tric contents (e.g., acid, bile salts, pepsin, and likelihood and severity of mucosal injury.
trypsin), pepsin produces a mucosal injury consis-
tent with both the macroscopic and the micro- Etiology
scopic appearance of reflux esophagitis in Pharmacologic agents that have been associated
symptomatic human patients. Hydrochloric acid with decreased LES pressure and reflux include
(HCl) at physiologic pH values does not appear to atropine and other anticholinergic drugs, mor-
break the esophageal squamous mucosal barrier to phine, meperidine, diazepam, and pentobarbital.
hydrogen ion back diffusion or to cause esophagi- Phenothiazine-derivative tranquilizers also can
tis. Pepsin, however, can cause mucosal permeabil- decrease LES pressure. Glycopyrrolate does not
ity changes, resulting in severe hydrogen ion back cause as significant an effect on the LES as atropine
diffusion. Rabbit esophageal perfusion studies have does. For this reason, some clinicians use glyco-
demonstrated that pepsin causes significantly more pyrrolate rather than atropine as their standard
esophageal injury than does bile, trypsin, or acid preanesthesia agent.
alone. In these studies the extent of injury Pregnancy in humans is associated with an
increased in a dose-dependent manner as pepsin increased frequency of heartburn, a sensation of
concentration was increased. Pepsin injury was chest pain that is due to esophageal pain from
characterized by mucosal erosion and ulceration mucosal contact with refluxate. This was origi-
with submucosal hemorrhage. Acid, bile, and nally thought to be due to reflux exacerbated by
trypsin damage was generally limited to submu- increased gastric pressure from an enlarging
cosal edema without mucosal disruption. uterus. However, it is now recognized that elevated
Excessive alkaline gastroesophageal reflux pro- progesterone levels decrease LES pressure, increas-
duces inflammatory changes comparable to those ing the likelihood of reflux. Reflux esophagitis in
seen with excessive acid gastroesophageal reflux. humans can also be predisposed by high-fat or
The alkaline nature of refluxed material alone does spicy foods, chocolate, alcohol, and nicotine.
not appear to produce mucosal damage. Rather, The most common causes of reflux esophagitis in dogs
with alkaline reflux the pancreatic enzyme trypsin and cats are general anesthesia and persistent vomiting
has been shown to be the factor that causes the due to any cause (e.g., pancreatitis, gastric or intestinal
most significant damage. Pepsin causes minimal foreign body, parvoviral enteritis). Hiatal hernia disor-
esophageal changes in the presence of an alkaline ders, neuromuscular disorders (e.g., myasthenia
environment. Trypsin is present in the gastric con- gravis) that interfere with function of the esopha-
tents of patients with decreased pyloric tone and gus and LES, delayed gastric emptying, and duo-
duodenogastric reflux. The pH of the refluxate denogastric reflux are also important, but less
appears to control which agent will be the most common, disorders that are associated with reflux
active in causing esophageal damage. Pepsin’s opti- esophagitis episodes.
mal pH range for proteolytic activity is 2 to 4.5, During anesthesia there is suppression of nor-
and it is the most injurious agent when the reflux- mal esophageal motility and decreased LES pres-
ate is acid. Trypsin’s optimal pH range for prote- sure. As a result, acid and other refluxed agents
olytic activity is 5 to 8. cannot be cleared as quickly as in an awake animal
The bile salt taurodeoxycholate has been found with normal esophageal defenses. Problems tend
to protect the esophageal mucosa from the injuri- to occur more commonly in patients that have
ous effects of acid and pepsin, but the effect of undergone prolonged surgical procedures; how-
trypsin in the alkaline medium has been potenti- ever, it has been shown that reflux can occur
ated. Bile salts decrease pepsin’s proteolytic activity, between 5 and 15 minutes after induction of anes-
and the protective bile salt effect is dose related. thesia. Therefore reflux should be considered a
The combination of bile, trypsin, and an alkaline possibility in any patient that undergoes anesthe-
refluxate could potentially cause the most severe sia. In a study involving 100 dogs, it was found that
degree of esophageal injury. Bile salts may play an the frequency of gastroesophageal reflux was 25%
important role in modulating the injurious effect with regard to the type of surgery, 48% of the cases
of acid and pepsin in certain clinical settings. The of reflux appeared during orthopedic surgery, 24%
concentration of injurious agents in the refluxed gastric during abdominal surgery, and 28% during other
fluid and the duration of their contact with the types of surgery (e.g., skin, eyes). Consideration
140 CHAPTER 4 DISEASES OF THE ESOPHAGUS
should be given to routinely treating these patients to empty before anesthetic induction, since the
for reflux esophagitis for several days during the combination of anesthesia and an incompletely
immediate postoperative period. It may also be evacuated stomach would increase the likelihood
beneficial to pretreat patients scheduled to of a reflux episode and subsequent development of
undergo a prolonged (greater than 1 to 2 hours) esophagitis.
surgical procedure with an H2-receptor antagonist Duodenogastric reflux may be damaging for
before induction of anesthesia (e.g., administer two reasons: It increases gastric volume available
injectable famotidine or ranitidine 1 to 2 hours for gastroesophageal reflux, and it adds bile and
prior). As the duration of anesthesia increases, the other potentially damaging duodenal fluid com-
risk of a significant reflux event also increases. ponents to the gastric contents. Patients that have a
Some clinicians have also instituted a post- chronic intermittent pattern of vomiting bile fluid
operative practice of lavaging the esophagus with may have duodenogastric reflux and should be
saline or warm water after long surgical proce- watched carefully for signs of esophagitis.
dures, so as to dilute and remove offending sub-
stances before significant mucosal damage can Diagnosis of Esophagitis
occur. This can be done either under endoscopic The clinical signs of esophagitis vary considerably,
guidance or simply by passing a tube blindly into depending on the degree of inflammation present.
the esophagus for lavage purposes, while the The clinician must maintain a high index of suspi-
patient is still intubated. Use of an endoscope cion because in many cases only subtle clinical
offers the advantage of lavage and suction under signs may be evident. With mild esophagitis there
direct visualization. In addition to the anesthetic may be increased swallowing motions, salivation,
agents used, tilting of the surgery table so that the and inappetence. In more severe cases there may
patient’s abdomen is elevated relative to the thorax be gulping, regurgitation, dysphagia due to pain,
and improper preparation (e.g., incompletely evac- total anorexia, and signs that suggest esophageal
uated stomach) also can play a major role in exac- pain, such as reluctance to move, standing with the
erbating reflux. Moderate to severe esophagitis can head extended, reluctance to lie down, and trem-
result in esophageal stricture formation (see later bling. Heartburn pain in humans can be quite
discussion). intense, and it is suspected that a similar situation
Most hiatal hernia patients have some degree of exists in animals. Esophageal hemorrhage may
reflux esophagitis. Decreased LES pressure leads to occur in severe cases.
esophageal reflux in most patients with sliding The immediate past medical history must be
hiatal hernias. Hiatal hernia patients are often pre- reviewed carefully because it may provide impor-
sented for evaluation because of clinical signs that tant clues regarding both diagnosis and etiology.
suggest a significant degree of esophagitis (e.g., Signs such as increased attempts at swallowing,
salivation, inappetence, decreased activity, regurgi- salivation, regurgitation, and inappetence that
tation). Treatment involves both management of occur within 1 to 4 days of an anesthetic proce-
esophagitis and medical management or surgical dure strongly suggest reflux esophagitis. Coughing
correction of the hiatal hernia. may indicate aspiration pneumonia. Patients with
Gastric emptying and gastric motility may be persistent vomiting should be observed carefully
reduced in some patients with gastroesophageal for signs of esophagitis. Severe esophagitis must be
reflux. Delayed emptying of liquids or solids identified and treated early, since one of the poten-
would be expected to increase esophageal reflux. tial sequelae is stricture formation.
However, only a fraction of human patients with Chronic reflux esophagitis occurs most com-
reflux esophagitis have delayed gastric emptying. monly in patients with hiatal hernia disorders.
Detailed studies have not been performed in ani- Clinical signs include hypersalivation, regurgita-
mals, but clinical signs and endoscopic evidence of tion, and vomiting, which often are noted shortly
esophagitis have not been commonly observed in after the patient eats. There also may be coughing,
animals with gastric motility disorders. Probably dyspnea, and exercise intolerance. Hiatal hernias
the most important clinical situation regarding are most commonly identified in immature patients.
animals with gastric motility disorders involves Physical examination is usually unremarkable,
general anesthesia. Every effort must be made to but there may be physical evidence of glossitis
ensure that there is sufficient time for the stomach or pharyngitis related to ingestion of a caustic
CHAPTER 4 DISEASES OF THE ESOPHAGUS 141
(0.25 to 0.5 mg/lb orally every 24 hours, or every Promotility drugs increase LES pressure, thereby
12 hours if there is severe esophagitis) is generally decreasing reflux, and stimulate more rapid gastric
used for 2 to 3 weeks in dogs and cats with acute emptying by increasing gastric contractions. They
reflux esophagitis. I prefer to use famotidine also enhance relaxation of the pylorus for more
because of its long dosage interval and the fact that effective aboral movement of gastric contents and
it is associated with fewer side effects. Another increase distal esophageal contractions. One prob-
H2-receptor antagonist that can be tried is nizati- lem with metoclopramide is that it may cause
dine (Axid).The dosage is 1.25 to 2.5 mg/lb orally bothersome side effects such as restlessness, hyper-
every 24 hours. Ranitidine and nizatidine also activity, and occasionally aggressive behavior. In
have a gastric prokinetic effect. Long-term ther- my experience, these side effects are not common
apy should be used in hiatal hernia patients with in dogs and cats, but owners should always be fore-
chronic reflux esophagitis if corrective surgery warned of the possibility that they may occur. If
either is not performed or is unsuccessful. side effects occur, they usually will be noted
PPIs are drugs that completely inhibit gastric within 1 hour of the first or second dose and sub-
acid secretion in response to all modes of stimula- side within 3 to 4 hours. Unfortunately, lowering
tion. PPIs include omeprazole (Prilosec), lansopra- the dose does not usually alleviate side effects. The
zole (Prevacid), esomeprazole (Nexium, the S dosage of metoclopramide is 0.1 to 0.2 mg/lb
optical isomer of omeprazole), pantoprazole (Pro- (maximum starting dose, 10 mg) two to three
tonix), and rabeprazole (Aciphex). Omeprazole is times daily 30 to 45 minutes before feeding and at
the PPI that has been used most frequently in ani- bedtime. Cimetidine or famotidine and metoclo-
mal patients. PPIs decrease acid secretion by pramide are often used concurrently. Occasionally,
inhibiting H+,K+ATPase (commonly called the the side effects of metoclopramide will be
proton pump), thereby blocking the final, com- increased when it is used with cimetidine.
mon step in the secretion of gastric acid. PPIs con- One significant advantage of cisapride is that,
trol both basal and meal-stimulated acid secretion. unlike metoclopramide, it is not associated with
Therefore the acid suppression achieved by a PPI any significant side effects in animals. I have used
is more complete and longer lasting than can be cisapride in many patients that have experienced
attained with an H2-receptor antagonist. neurologic side effects from metoclopramide. I
In humans, PPIs have now been shown to be have observed no adverse reactions to cisapride in
superior to H2-receptor antagonists in manage- any of these patients, even in those whose side
ment of erosive esophagitis. Concurrently it is effects from metoclopramide included very bizarre
now also recommended in veterinary medicine behavior changes. The suggested dosage of cis-
that animals with esophagitis are better managed apride is the same as that recommended for meto-
with a PPI than with an H2-receptor antagonist. clopramide (see previous paragraph).
Although PPIs are more expensive, they produce Early studies in humans showed promise for use
quicker relief from symptoms in humans and total of cisapride as primary therapy for reflux esophagi-
treatment time is also reduced in some patients. tis. However, more recent studies have been disap-
Results from human trials that investigated the use pointing. Cisapride provides symptomatic relief
of PPIs in gastroesophageal reflux disease patients in less than half of patients with results comparable
with nonerosive disease have demonstrated the to those achieved with standard doses of an H2-
superiority of PPI therapy over H2-receptor receptor antagonist. And cisapride used in combina-
antagonists. PPIs are now considered the most tion with an H2-receptor antagonist is less effective
effective first-line treatment for nonerosive reflux for symptomatic relief of esophagitis symptoms in
esophagitis. More rapid responses have also been humans than that achieved with a PPI. So cisapride
observed in animal patients treated with the PPI and metoclopramide can play an important adjunc-
omeprazole. Therefore if esophagitis is judged to tive role in management of reflux esophagitis, but
be greater than mild in degree, it is probably best prokinetic agents used alone are not likely to be
to choose a PPI over an H2-receptor antagonist as very successful. Effective acid control is essential.
the primary therapy for controlling acid release. One of the most important forms of reflux
The recommended dosage for omeprazole is 0.3 esophagitis therapy involves use of sucralfate
mg/lb once daily. (Carafate) to provide an esophageal mucosal cyto-
Prokinetic drug therapy with metoclopramide protective effect. Sucralfate is an aluminum salt
or cisapride provides several beneficial effects. that has been shown to bind selectively to areas of
CHAPTER 4 DISEASES OF THE ESOPHAGUS 143
injured GI tract mucosa and to form a local pro- ical situations that can potentiate development of
tective layer that binds pepsin and bile and pre- the disorder is very important. Early treatment
vents them from causing further mucosal damage. often minimizes mucosal injury and in severe cases
Sucralfate cytoprotection against pepsin- may help decrease the likelihood of stricture for-
induced esophageal lesions has been demonstrated mation. One of the clinical situations in which
using a liquid preparation in short-term experi- early recognition is most important involves
ments in rabbits. A study in cats demonstrated a patients that have undergone general anesthesia,
protective effect of liquid sucralfate against inter- especially, but not exclusively, for a prolonged sur-
mittent, repeated esophageal exposure to acid over gical procedure. Clinicians and nursing personnel
a period of days. Sucralfate acts not only by adher- should monitor for signs of esophageal reflux
ing to damaged mucosa but also by enhancing (e.g., salivation, pronounced gurgling, and regur-
normal mucosal defenses. Based on this informa- gitation of fluid from the mouth or nostrils).
tion, it is recommended that administration of Recommended early treatment measures include
sucralfate in a liquid form be considered for using low-grade suction attached to a feeding tube
patients with evidence of esophagitis. Its greatest that has been passed into the esophagus in an
value may be in treatment of acute reactions in the attempt to remove retained fluid before its con-
esophagus and in prevention of further damage. tents can cause mucosal injury. If there is concern
Sucralfate should also be considered for use as a that a significant amount of reflux has occurred, an
preventive medication in situations in which a sig- endotracheal tube can be used to lavage the
nificant reflux episode could potentially occur esophagus. Warm water is instilled as a diluting
(e.g., emergency surgery in a patient with an agent and then suctioned. Care must be taken to
incompletely evacuated stomach). The recom- ensure that the endotracheal tube is cuffed ade-
mended dosage is 1 g per 65 lb given orally every quately in order to prevent aspiration. The best
6 to 8 hours. For treatment of esophageal disor- method is to use an endoscope for direct visualiza-
ders, a suspension form of sucralfate should be tion, lavage, and suction, following a prolonged
used. Sucralfate is now commercially available in anesthetic event.Any retained fluid can be quickly
suspension form. Alternatively, sucralfate tablets suctioned through the endoscope. The endoscope
can be mixed into suspension. Sucralfate tablets should be used to examine the stomach as well.
readily dissolve in lukewarm water (10 to 15 ml). Any fluid that is present should be suctioned; oth-
Once the suspension is thoroughly mixed, it is erwise, it might be refluxed to the esophagus dur-
administered as a gavage. ing the recovery period. Sucralfate or sucralfate
A short course (several days to 2 weeks) of cor- and an H2-receptor antagonist are then adminis-
ticosteroid therapy (e.g., prednisone, 0.25 to 0.5 tered for 24 to 72 hours. This approach is very
mg/lb orally every 12 hours) may be indicated in effective in helping prevent significant postopera-
severe reflux esophagitis to minimize fibrosis and tive esophagitis and possibly later formation of
possible stricture formation. Corticosteroids are esophageal strictures. If signs of esophagitis
not indicated in mild cases of esophagitis. develop despite this therapy, a PPI such as omepra-
Patients with moderate to severe esophagitis zole should be used and H2-receptor antagonist
should be held nothing by mouth (NPO) for 24 to therapy is discontinued.
72 hours. When food is resumed, a high-protein, Clinicians are also cautioned to be more attentive
low-fat diet is indicated. High-protein diets to patients that might have esophagitis secondary to
enhance LES function, whereas high-fat diets frequent or severe vomiting (e.g., caused by GI foreign
interfere with LES function. Patients that have bodies, parvoviral enteritis, acute pancreatitis, or renal
been held NPO are generally started on a gruel- failure). Esophagitis can easily develop in these
consistency diet for the first several days. Owners situations, and it no doubt adds significantly to
of overweight patients that are prone to develop- the discomfort that the patient is already experi-
ing esophagitis (e.g., due to hiatal hernia) should encing. In these cases, both sucralfate and an
be encouraged to initiate weight reduction meas- H2-receptor antagonist are used to treat esophagi-
ures for their pet. tis. I use famotidine injectable at 0.25 mg/lb
Animals with evidence of reflux esophagitis following intravenously every 12 hours. An antiemetic
anesthesia should be treated early and aggressively, since drug such as chlorpromazine (Thorazine) is
there is potential for esophageal stricture formation. injected to help decrease the frequency of
Early recognition of esophagitis symptoms in clin- vomiting. Sucralfate is given orally, usually 30 to
144 CHAPTER 4 DISEASES OF THE ESOPHAGUS
60 minutes after antiemetic therapy has been Anesthesia-related reflux is the most common
administered. cause of esophageal stricture. Stricture formation
The duration of therapy in patients with reflux can occur after relatively short anesthetic proce-
esophagitis depends on the cause and degree of dures (e.g., for ovariohysterectomy), as well as after
inflammation. For moderate to severe esophagitis, long procedures. It appears that prolonged anes-
4 to 8 weeks of therapy or more may be required thesia, especially when followed by inability of a
to achieve full healing of the esophagus. For patient to resume sternal or upright posture, pro-
esophagitis related to frequent or severe vomiting motes gastroesophageal reflux that may persist
(e.g., parvoviral enteritis, pancreatitis, toxic enteri- even beyond the duration of the anesthesia, and
tis, linear foreign body), treatment is usually thereby initiating and perpetuating to some
administered for 5 to 7 days, and only longer if degree the transition from severe esophagitis to
clinical signs or endoscopic findings warrant. As stricture formation.
discussed later in this chapter, patients with a hiatal Clinical signs of dysphagia and regurgitation are
hernia may require long-term therapy using either usually evident by 5 to 14 days after the anesthetic
a PPI alone or a PPI with sucralfate. Patients episode. Occasionally, significant clinical signs are
should be monitored carefully for signs that can be not evident until 4 to 6 weeks later. Variable
associated with esophagitis, and use of endoscopy degrees of luminal narrowing can occur, and in
as both a diagnostic and a monitoring tool should some patients the lumen diameter at the stricture
be encouraged. site is extremely narrow (sometimes as small as 1 to
2 mm) (Figure 4-13). Stricture length also varies.
ESOPHAGEAL Occasionally, one or two additional strictures will
develop at other sites in the esophagus.
STRICTURES
Esophageal strictures occasionally occur in dogs Clinical Signs
and cats. Stricture usually occurs secondary to Clinical signs generally progress over 5 to 14 days
severe esophagitis that extends into deeper layers after their onset. The predominant sign is regurgi-
of the esophagus, inciting fibroblastic proliferation. tation of solid food. In some patients there ini-
Common causes of this degree of esophagitis in tially is vomiting during the recovery phase after
dogs and cats are reflux of gastric acid and an anesthetic event that is followed by occa-
enzymes during general anesthesia, persistent sional vomiting over the ensuing several days.
vomiting in patients that are also weak and recum- Regurgitation may then begin to occur. As a stric-
bent (e.g., patients with parvoviral enteritis, pan- ture worsens, only gruels can be successfully trans-
creatitis), medications that induce esophagitis ported to the stomach. In strictures associated with
when they become lodged in the esophagus (e.g., a very narrow luminal diameter (1 to 2 mm), only
that caused by NSAIDs in dogs, doxycyline tablets water is likely to be retained.Affected patients typ-
in cats), ingestion of strong acid or alkali, foreign ically remain active and alert and have excellent
body trauma, and thermal burns. Severe stricture body condition. Signs of pain or discomfort are
may also occur in cats that develop esophagitis uncommon. The appetite is usually ravenous.
after a large hairball has been vomited or has Weight loss may occur over time as a result of
become lodged in the esophagus. I have treated decreased caloric intake associated with regurgita-
cats that developed a severe esophageal stricture tion.
within 7 to 14 days after vomiting a hairball as
long as 12 to 15 cm. Presumably, the coarse texture Diagnosis
of the hair significantly irritates the esophageal Esophageal strictures occur more commonly than
mucosa as it sits in and subsequently is ejected many clinicians may recognize. A review of a
from the esophagus. Acid and enzymes that are patient’s recent medical history is the first step in
mixed in the hair material add to the damage. making an early diagnosis of esophageal stricture.
Figure 4-12 illustrates a case in which a large hair- Most patients with an esophageal stricture have
ball was lodged in the esophagus for approximately undergone general anesthesia within the previous 2
36 hours before it was removed. Severe esophagitis to 3 weeks. Most patients that begin regurgitating
resulted, and within 10 days there was a stricture, shortly after an anesthetic event have an esophageal
despite aggressive early medical management for stricture. A recent history of frequent severe vom-
esophagitis. iting in dogs or cats, onset of regurgitation associ-
CHAPTER 4 DISEASES OF THE ESOPHAGUS 145
A B
C D E
FIGURE 4-12 Esophageal foreign body in a cat with subsequent development of esophageal stricture. A, Note the
long area of increased opacity in the dorsocaudal thorax (later confirmed to be a hairball). The history included
salivation, increased respiratory rate, and anorexia. B, Esophagoscopy confirmed a diagnosis of esophageal foreign body
(hairball). The hairball was very tightly wedged in the esophagus. It could be neither pulled orad nor pushed back into
the stomach. A gastrotomy was done, and the hairball was pulled back to the stomach and removed. C, Immediate
postoperative esophagoscopy, showing erosive damage of the esophagus (twelve o’clock and five o’clock positions).
Sucralfate suspension, famotidine, metoclopramide, and corticosteroids were instituted for severe esophagitis. There was
concern that an esophageal stricture might develop. D, Appearance of the esophagus 4 days after surgery. The mucosa
was quite irregular and friable. There is evidence of esophageal narrowing and early stricture formation. E, Endoscopic
appearance of an esophageal stricture identified at 10 days. Balloon dilation procedures were initiated.
ated with administration of NSAIDs to dogs, doxy- advancing endoscopic biopsy forceps through the
cycline tablets to cats, or other medications, or stricture and then opening the cups once the
recent vomiting of a large hairball by a cat also instrument has been passed. As the biopsy instru-
should heighten suspicion of esophageal stricture. ment is then retracted, the open cups will stop at
A diagnosis is established either by endoscopy the distal border of the stricture. A determination
or by barium contrast radiography using a swallow of stricture length also can be made by insufflating
of barium and either static radiographs or fluo- air into the esophagus, using the endoscope, and
roscopy (Figure 4-14). In some cases barium liquid then making a lateral survey thoracic radiograph.
mixed with food is required to demonstrate an esophageal There is an increased opacity at the stricture site as
stricture, since liquid barium may pass easily through a compared with the surrounding air.
stricture without delineating its presence. Endoscopy Esophageal neoplasia occasionally causes intra-
allows evaluation of the appearance and pliability mural stricture formation, and there usually is an
of the esophageal wall and luminal diameter. The appearance of mucosal irregularity and intralumi-
endoscope is often too large to pass through the nal mass effect. However, rarely a malignant stric-
stricture area, so an assessment of stricture length ture will appear benign with no intraluminal mass
often is not possible from direct examination effect typical of neoplasia. If any uncertainty exists
alone. Stricture length can be assessed, however, by regarding the cause of a stricture (e.g., no recent
146 CHAPTER 4 DISEASES OF THE ESOPHAGUS
A B
FIGURE 4-13 Severe cranial thoracic esophageal stricture in an 11-month-old cat that had been anesthetized
14 days before. There was a 5-day history of regurgitation that progressively worsened, resulting in referral for
endoscopy. A, The extremely narrow esophageal lumen (approximately 1.5 mm) is visible just to the left of center.
Note the white fibrous connective tissue around the lumen. Because the stricture was too narrow to attempt
bougienage and balloon catheters had not yet been developed when this case was seen, stricture resection was
performed through a right thoracotomy. Resection of 1.5 cm of esophagus was performed. B, Endoscopic
examination 4 weeks after esophageal resection and anastomosis. Mild narrowing of the lumen remains, but the
endoscope was easily advanced. Note the suture tags and the esophageal lumen beyond the anastomosis site. The cat
was asymptomatic. (From Tams TR: Esophagoscopy. In Tams TR, ed: Small animal endoscopy, St. Louis, 1990,
Mosby–Year Book.)
history of anesthesia to suggest a reflux episode), The advantages of this technique over bougienage
biopsies should be done to differentiate a truly include decreased risk of esophageal perforation,
benign stricture from a malignant one. Brushings longer symptom-free periods between procedures,
for cytologic examination are useful for rapid and a smaller total number of procedures required
assessment while one waits for biopsy results. If the to resolve the problem.
lumen at the stricture site is extremely narrow, Bougienage
biopsy specimens should be taken before and after A wide variety of esophageal dilation devices
dilation. Also, a mass impinging on the outside of whose diameters increase in stepwise fashion are
the esophagus may compress the esophageal lumen available, including mercury-filled bougies and
enough to cause a stricture effect. In this situation Pilling bougies. Bougies have either rounded tips
the esophageal mucosa will appear normal. The or tapered ends with bases that are wider than the
endoscopist will note that the esophageal walls do tips. The narrow tip is advanced to the stricture
not readily distend in response to air insufflation. site under endoscopic guidance, and the wider
Additionally, it may not be possible to advance the area of the bougie dilates the stricture as the
endoscope through the narrowed area. bougie is advanced through it. Care must be exer-
cised to ensure that the bougie tip is directed into
Treatment the stricture opening and not too far lateral to it.
Treatment options for benign esophageal stricture There is risk of perforation if the latter occurs.
include surgical procedures such as resection and Other dilators that can be used in selected cases
anastomosis or patch grafting, bougienage, and include endotracheal tubes (for cervical esophageal
balloon catheter dilation. In humans laser therapy strictures in small patients) and the flexible endo-
and prosthesis has also been utilized. The success scope itself.
rate in animals treated with surgical procedures has The key to successful bougienage is to repeat
been reported as less than 50% and in those treated the procedure as often as necessary to maintain
with bougienage techniques as 50% to 75%. improved luminal diameter. In many patients two
Surgical resection may result in restricture at the to three bougienage procedures per week are nec-
site of the anastomosis. Balloon catheter dilation is essary during the first several weeks of treatment
much more successful than either surgery or bougienage. before the desired effect is reached. After a stric-
CHAPTER 4 DISEASES OF THE ESOPHAGUS 147
the balloon. Fluoroscopy is certainly not necessary Mild to moderate hemorrhage around the
to perform the procedure safely, however, and in stricture site is a normal postdilation finding. If
most cases it is not used. there is no hemorrhage, the stricture was not
Once positioned, the balloon is distended dilated to any significant degree. With a very
with water or dilute contrast medium, and the aggressive dilation, long and fairly deep longitudi-
luminal pressure is monitored with the pressure nal splits may occur in the esophageal wall. It is
gauge. This increased pressure is associated with generally best to act a little conservatively during
effacement of the waist, indicating dilation of the initial dilation procedures so as to minimize the
stricture (Figure 4-16). A dilation time of 2 to 4 likelihood of perforation that could result from
minutes at 40 to 45 psi seems to be adequate for using too large a balloon. Usually 2 to 3 progres-
stricture dilation in dogs and cats (initially a time sively larger balloons are used in sequence during
of 2 minutes is used so that initial response can each individual anesthesia. Because esophageal stric-
be determined). After dilation, the balloon is tures tend to close down again fairly quickly after being
deflated and the catheter removed. Immediate dilated, two to three individual dilation procedures are
postdilation endoscopy is recommended to ensure routinely scheduled during the first 7 days. Subsequent
resolution of the stricture. Dilation periods of 4 procedures are scheduled based on patient response dur-
minutes are usually used in cases in which frequent ing the first 1 to 2 weeks.
procedures have not yet successfully solved the Factors that help determine the number of bal-
problem. loon dilation procedures that will be necessary
B
CHAPTER 4 DISEASES OF THE ESOPHAGUS 149
include severity and length of the stricture, num- vomited a large hairball). Esophagoscopy is the
ber of strictures, and the ease of the initial stricture ideal procedure to monitor for progression or
dilation. In general, tight strictures and those that regression of esophagitis. Clinicians must recognize
were several millimeters long require more dila- that once severe esophagitis is present, a stricture can form
tions than those of moderate severity and shorter very rapidly.
length. Patients with multiple strictures tend to The prognosis for resolution of an esophageal
require more dilations than those with single stric- stricture disorder is excellent when balloon dila-
tures. tion is used. Sometimes mild permanent narrow-
A stricture that has been present for longer than ing remains at the stricture site, but this is usually
several months may become so fibrotic that it may clinically insignificant. Cats and small dogs can
not be possible to dilate the stricture with bal- manage well with an esophageal diameter of 1 cm
loons. Therefore, once the presence of a stricture or less if food consistency is limited to soft meals.
is confirmed, proper treatment should be insti- A diameter of 1 to 1.5 cm is necessary in medium
tuted.A case in which an attempt to dilate a cervi- to large dogs. Many patients are eventually able to
cal esophageal stricture was not made until eat foods of normal consistency.
9 months after it was diagnosed is illustrated in
Figure 4-17. Surgery was required to remove the
stricture.
HIATAL DISORDERS
After bougienage or balloon dilation is begun, The esophageal hiatus is the opening in the
intensive therapy for esophagitis is instituted. This diaphragm through which the esophagus passes
includes H2-receptor antagonist therapy, metoclo- from the thorax into the abdominal cavity.
pramide, sucralfate suspension, and prednisone Anatomic abnormalities of the hiatus may cause
(0.25 to 0.5 mg/lb/day). Food, usually chopped symptoms of esophageal disease. Hiatal lesions may
canned consistency, is usually resumed later on the allow hiatal hernia, paraesophageal hiatal hernia,
same day or on the following day. If there is severe gastroesophageal intussusception, or diaphragmatic
esophageal damage, it might be necessary to place hernia to occur. Hiatal hernias are protrusions of
a gastrostomy tube so that adequate nutritional the abdominal esophagus, GES, and sometimes a
support can be given. Most patients eat well very portion of the gastric fundus through the
soon after a dilation procedure, even if there is sig- esophageal hiatus into the caudal mediastinum
nificant esophageal mucosal tearing. cranial to the diaphragm. Hiatal hernias likely
Prednisone is used to decrease fibroblastic occur more commonly than they are recognized
activity. Whether or not it really helps to decrease in dogs and cats.
or prevent further stricture formation is contro- Congenital or acquired enlargement of the
versial. I have observed patients in which an esophageal hiatus or laxity of the surrounding
esophageal stricture developed despite aggressive phrenicoesophageal ligaments may predispose to
therapy (famotidine, sucralfate, metoclopramide, hiatal hernias. Most hernias are probably congeni-
and prednisone) for acute moderate to severe tal. Acquired hiatal hernias may occur secondary
esophagitis that was diagnosed early in its course to high positive intraabdominal pressure (e.g.,
via endoscopy. This therapeutic regimen is given blunt abdominal trauma, vomiting) or very nega-
both to treat the existing esophagitis and, it is tive intrathoracic pressure associated with chronic
hoped, to decrease the likelihood of stricture for- upper airway obstruction (e.g., laryngeal collapse).
mation. Unfortunately, this approach does not Hiatal hernias are seen more commonly in
always work. Some specialists have begun to take brachycephalic breeds such as English bulldogs and
the additional step of injecting intralesional triam- in shar-peis. Although most symptomatic animals
cinolone with a Wang needle, under endoscopic with congenital hiatal hernia demonstrate clinical
guidance, after dilating severe esophageal strictures signs by 1 year of age, significant signs may not
in an effort to further decrease fibroblastic activity. occur until later. Patients with acquired hernias
Endoscopy guided laser treatment used as an may develop signs at any age.
adjunct to ballooning is also being investigated.
It is emphasized that careful surveillance for Clinical Signs
development of a stricture is warranted in animals The most common clinical signs of hiatal hernia
that are most at risk (e.g., those with anesthesia- are regurgitation, dysphagia, hypersalivation, and
related esophagitis and those that have recently vomiting. Hematemesis may occasionally occur.
150 CHAPTER 4 DISEASES OF THE ESOPHAGUS
A B
C D
FIGURE 4-17 Chronic severe esophageal stricture that was not amenable to balloon dilation. A, A 6¹⁄₂-year-old
male Labrador retriever that underwent a gastrotomy at an emergency clinic 10 months earlier for suspected foreign
body removal. No foreign body was found. After the surgery there was intermittent vomiting. At 2 weeks the dog
began to regurgitate solid food, and at 4 weeks esophagoscopy revealed a stricture in the cervical esophagus. Balloon
dilation was recommended, but the dog’s owner chose conservative management, which consisted of feeding a gruel
diet. Nine months after the stricture was diagnosed, however, the owner decided to proceed with balloon dilation
because he could not maintain the dog’s weight. Weight loss totaled 33 lb since the initial diagnosis. B, Endoscopic
photograph of the proximal cervical esophagus. Note the fibrotic band in the near field. An esophageal stricture is
visible beyond the band. C, Close-up view of the stricture. There is a fibrotic ring around the stricture, and the
narrowed lumen curves on the far side of the stricture. A 7.9-mm endoscope could not be advanced into or
through the stricture. D, Under endoscopic guidance, a 15-mm balloon catheter was advanced through the stricture.
In this radiograph both the endoscope and the dilated balloon are visible. The stricture is delineated by the
narrowed waist in the balloon (just ventral to the proximal border of the fifth cervical vertebra). At 45 psi for 4
minutes the stricture did not dilate. E, The largest balloon available (20 mm dilated) was then used. At 45 psi for 9
minutes the stricture did not dilate because of severe fibrosis. The short stricture is clearly visible on this radiograph.
Surgery was later done to resect the stricture, and the dog recovered uneventfully. During the following year the
dog gained 33 lb. Histologic examination of the stricture revealed severe fibrosis. It is strongly recommended that
balloon dilation be done on esophageal strictures early in their course.
CHAPTER 4 DISEASES OF THE ESOPHAGUS 151
Small hiatal hernias may be asymptomatic. bulging into the lumen of the distal esophagus.
Symptoms may be evident only occasionally in A careful assessment of the esophageal mucosa, the
animals in which herniation occurs intermittently. GEJ, and the stomach is important in the determi-
In fact, the diagnosis is often difficult to prove in nation of the treatment plan. Finding reflux
patients because many cases probably involve only esophagitis helps raise suspicions of a hiatal disor-
sporadic movement. Most hiatal hernia cases are der. Endoscopic findings of cranial LES displace-
associated with some degree of reflux esophagitis. ment and a large esophageal hiatus, in conjunction
Malpositioning or a lack of support of the gastro- with appropriate clinical signs, is suggestive of a
esophageal sphincter reduces gastroesophageal sliding hiatal hernia. When the endoscope is
pressure and leads to gastroesophageal reflux. Most passed from the esophagus into the stomach, it
of the clinical signs are related to esophagitis and should be retroflexed, after the stomach is insuf-
altered esophageal motility. flated with air, to view the LES from the gastric
side. With gastric insufflation there may be cra-
Diagnosis nial displacement of the LES and cardiac region
Various types of hiatal disorders have been of the stomach through a weakened or enlarged
described. These are depicted in Figure 4-18. The esophageal hiatus.
most common type of hiatal hernia in dogs and cats
is a sliding hiatal hernia with cranial displacement of Treatment
the abdominal esophagus, gastroesophageal junc- Surgical correction is indicated in patients with a
tion, and a portion of the stomach through an symptomatic hiatal hernia. Fundoplication proce-
enlarged and lax hiatus. Paraesophageal hernias are dures have been described. Other techniques
uncommon. In this type of hernia the gastro- include diaphragmatic hiatal reduction and plica-
esophageal junction remains fixed in the intraab- tion, esophagopexy, and left-sided fundic gas-
dominal location and the gastric fundus protrudes tropexy. Medical management for esophagitis is
through a defect in the diaphragmatic hiatus parallel instituted as soon as the diagnosis is made. If sur-
to the esophagus. Gastroesophageal reflux disease is gery is not corrective, medication may have to be
less commonly associated with paraesophageal her- continued indefinitely in order to control symp-
nias because the LES remains functional and in a toms of reflux esophagitis. Medical management
normal intraabdominal position. (H2-receptor antagonist, prokinetic therapy, and a
Gastroesophageal intussusception is a rarely low-fat diet) without surgery is often useful in
encountered syndrome. Gastroesophageal intussus- patients with mild symptoms related to intermit-
ception results when the gastric cardia invaginates tent herniation.A PPI (e.g., omeprazole) is recom-
into the terminal esophagus. The gastroesophageal mended over an H2-receptor antagonist for
sphincter does not move cranial into the thorax as moderate to severe esophagitis (see section earlier
occurs with a hiatal hernia. Entrapment of the in this chapter on management of esophagitis).
stomach in the esophagus may result in acute
esophageal obstruction. ESOPHAGEAL
Survey thoracic radiography may confirm the
diagnosis in some cases. Findings include an
FOREIGN BODIES
increased opacity in the caudal dorsal mediastinum Dogs and cats occasionally experience lodgment
caused by presence of the stomach in the thoracic of a foreign body in the esophagus. Although this
cavity. Positive contrast esophagrams may reveal problem occurs most commonly in young dogs
displacement of a portion of the stomach into the and cats, older animals also may be affected.
thorax. Contrast radiography is used to determine Because of their more indiscriminate eating habits,
the location of the GEJ and to evaluate the dogs tend to experience foreign body problems
mucosal pattern of the lower esophagus. Compressing more commonly than cats do.
the abdomen during radiography in patients with a sus- Major factors in determining whether a for-
pected hernia may help force part of the stomach into the eign body will pass uneventfully or be retained
thorax and increase the likelihood of obtaining diagnostic are its size and its configuration (e.g., rough ver-
films. sus smooth edges, presence or absence of projec-
Occasionally the diagnosis is made at endoscopy. tions, and width). There are four areas of
Endoscopy may confirm gastroesophageal intus- physiologic narrowing in the esophagus: the
susception, in which gastric rugal folds are seen UES, the thoracic inlet, the heart base area, and
152 CHAPTER 4 DISEASES OF THE ESOPHAGUS
Phrenicoesophageal
ligaments
Gastroesophageal
junction
A
Diaphragm Diaphragm
Peritoneal
covering
Gastroesophageal Gastric
junction fundus
Cardia
Gastroesophageal
junction
B C
Diaphragm
Gastroesophageal
junction
Gastric
Gastric cardia
fundus
Gastroesophageal
D Phrenicoesophageal junction E
ligament
FIGURE 4-18 A, Diagram of a normal gastroesophageal junction. B-E, Diagrams of hiatal abnormalities: B, sliding or
axial hiatal hernia, C, paraesophageal or rolling hiatal hernia, D, combination of sliding and paraesophageal hernia, and,
E, gastroesophageal intussusception. (Hedlund CS: Surgery of the digestive system. In Fossum TW, ed: Small animal
surgery, ed 2, St. Louis, 2002, Mosby).
the distal esophagus just proximal to the GEJ. ence bones and fishhooks are the most common
Most foreign bodies become impacted in one of objects found in the esophagus. Needles are the
the latter three areas in dogs and cats.A variety of most common foreign bodies found in cats.
foreign bodies can be involved, but in my experi- Although there is potential for a sharp object to
CHAPTER 4 DISEASES OF THE ESOPHAGUS 153
perforate the aorta at the aortic arch or through esophageal perforation. Alternatively, esophagoscopy
the esophagus to cause a communication to the can be done to confirm or deny suspicions of an
chest cavity, this is an extremely rare occurrence. esophageal foreign body.
Failure of blunt objects to pass through the A complete blood count should be obtained if
esophagus spontaneously should raise suspicion the patient is febrile, has aspiration pneumonia, or
that there is an esophageal motility disorder or a demonstrates evidence of esophageal perforation.
pathologic area of narrowing, such as a benign or
malignant esophageal stricture. Treatment
Once a foreign body has been localized, a decision
Clinical signs must be made whether to observe for its passage
Clinical signs related to foreign body impaction in or to remove it endoscopically or surgically. Most
the esophagus are often acute and usually include esophageal foreign bodies are amenable to endo-
salivation, which may become bloody, and regur- scopic retrieval. As a rule, any foreign object retained
gitation. There also may be odynophagia, dyspha- in the esophagus should be removed as soon as possible
gia, forceful retching, lethargy or restlessness, and or, if this cannot be done, at least advanced to the stom-
anorexia. Occasionally, a foreign body remains ach. Although uncommon, the risk of esophageal
undetected in the esophagus for a number of days perforation always exists, especially when a sharp
to even weeks. Chronic signs usually include or pointed object is involved. Lodged esophageal
depression, anorexia, salivation, and regurgitation. foreign bodies can also cause significant pain. In
There also may be clinical evidence of an most cases an esophageal foreign body does
esophageal foreign body complication such as not have to be removed as a true “emergency”
esophageal perforation with resultant pleuritis, procedure. Exceptions include foreign body
mediastinitis, and pyothorax. Other potential impaction in the proximal esophagus that is caus-
sequelae include esophageal stricture, diverticula, ing respiratory distress because of tracheal com-
and severe esophagitis. pression and a wedged sharp object such as a bone
that is causing significant patient distress. This may
Diagnosis be evidenced by groaning, copious salivation, or
The diagnosis of a retained foreign body may be forceful gagging. If the situation does not require
readily apparent from the history. For example, an rapid intervention, the patient should be stabilized
owner may have observed the patient ingesting a as needed with intravenous fluids, antibiotics, and
bone found during a garbage foray, reported a pain relievers, and a thorough radiographic assess-
missing section of a toy, or found a fishing line ment should be completed. Ideally, endoscopy
attached to a hook dangling from the pet’s mouth. should be undertaken within 4 to 6 hours of
In other cases there is no specific relevant history, presentation. Endoscopy is indicated as the initial
and in yet others the owner may deny any possi- procedure of choice for all esophageal foreign
bility of foreign body ingestion. bodies. If endoscopic equipment is not available,
Survey radiographs of the cervical soft tissues the patient should be referred to an appropriate
and thorax should be the first studies performed facility.
because radiopaque objects can easily be localized If pleural effusion is detected on thoracic ra-
in most cases. Lateral films of the neck are particu- diographs, the chest should be tapped to obtain a
larly important in recognizing bone fragments sample for cytology, Gram stain, and culture and
impacted in the cervical esophagus. There may be sensitivity. Pyothorax is best managed with place-
evidence of an esophageal foreign body. Thoracic ment of a chest tube for drainage and lavage. Once
radiographs should be carefully evaluated for any the patient is stabilized, a thoracotomy is done as
evidence of esophageal perforation, including soon as possible either alone or in conjunction with
pneumomediastinum and pleural effusion. Also, endoscopy to remove the foreign body and to eval-
survey radiographs must be evaluated carefully for uate and repair the esophageal wall. In my experi-
evidence of additional foreign bodies that may be ence, it is rare for even bone foreign bodies that
less obvious than an easily recognized radiopaque have been lodged in the esophagus for several days
object. Contrast radiography is occasionally neces- to weeks to cause complete esophageal perforation.
sary to identify radiolucent objects. An iodinated Safe extraction of an esophageal foreign body
compound (e.g., Gastrografin) should be used requires an adequate preliminary evaluation and
instead of barium if there is a possibility of the selection of proper equipment, including
154 CHAPTER 4 DISEASES OF THE ESOPHAGUS
appropriate grasping forceps or snare. Although be advanced to the stomach and repositioned so
flexible endoscopes are used most commonly, rigid that the sharp end trails. This technique works
equipment is also excellent for esophageal foreign well when irregular pieces of material such as
body retrieval. A laryngoscope and curved grasp- plastic are involved. Alternatively, objects with
ing forceps should also be readily available in case sharp or irregular edges can be removed with the
their use becomes necessary. As with any type of aid of an overtube to prevent mucosal damage.
endoscopic procedure, the patient is maintained After the esophageal foreign body is removed, the
under general anesthesia in left lateral recumbency. entire esophagus should be inspected for damage,
The endotracheal tube is especially important in and the stomach also should be examined for the
preventing tracheal compression as a large foreign presence of any foreign material. There is usually
body is pulled retrograde through the esophagus some degree of mucosal laceration at the site of
and in preventing aspiration of any object that bone impaction in the esophagus. The extent of
might be inadvertently dropped in the pharynx damage should be carefully evaluated and appro-
during retrieval. The endoscope should be passed priate medication instituted after the procedure.
under direct visual guidance through the pharynx If the foreign body cannot be retrieved in a ret-
and the UES to avoid striking any foreign body rograde manner, an attempt should be made to
material that may be present in the proximal advance it to the stomach. Bones are usually rapidly
esophagus and that consequently has the potential decalcified by gastric juices, and the remaining frag-
for causing mucosal damage. The esophageal ments will pass through the intestinal tract without
mucosa should be carefully evaluated for any for- incident. If a bone is firmly wedged in the distal
eign body–related damage as the endoscope is esophagus at the time of presentation, it may be best
advanced. Air should be insufflated to distend the to direct all efforts to advancing it to the stomach
esophageal walls so that visualization is enhanced, rather than risking any problems by pulling it retro-
but the patient’s respiratory status must be moni- grade. Foreign bodies other than bones that are
tored while this is being done. Air may be forced advanced to the stomach are removed via gas-
around an impacted foreign body and into the trotomy. If the foreign body cannot be removed
stomach, which can lead to significant gastric dis- endoscopically and cannot be advanced into the
tention. The distention should be relieved as stomach, an esophagotomy should be done. With
quickly as possible. In most cases, this can be done availability of either rigid or flexible endoscopic
by periodically passing the endoscope around the equipment, this is rarely necessary.
foreign body and into the stomach so that the air The esophageal wall is invariably damaged by
can be suctioned. Air insufflation to a perforated esoph- impaction by a bone or another sharp object and
agus can result in acute respiratory signs and death. The subsequent retrieval efforts (Figure 4-19). Most
anesthetist is advised to monitor both respiratory character lacerations heal uneventfully, however, and when
and degree of gastric distention during the procedure. careful endoscopic techniques are used, surgical
Successful extraction of a foreign body intervention is rarely necessary. The mucosa
requires adequate visualization, a firm grasp of the should be carefully inspected once the bone is
object, and removal with minimal force to avoid removed. The degree of damage is usually directly
further damage. The tip of a flexible endoscope related to the length of time the foreign body was
should not be used as a “ramming rod” to dislodge lodged and can be worsened by retrieval efforts. If
or advance an object because such action could there is significant erosive damage, treatment for
cause significant damage to the endoscope. Once severe esophagitis should be administered as
freed, most objects can be pulled back to the tip described earlier in this chapter. Pain relief med-
of the endoscope, and the endoscope and foreign ication also should be given as needed. Effective
body can then be gently removed simultaneously. analgesia may include fentanyl CRI, morphine
Undue force should not be exerted. Gentle manipula- administered SQ or IM q6h, oxymorphone or
tion is the rule. If at all possible, pointed objects hydromorphone, or a fentanyl patch with an
such as bones and needles should be withdrawn injectable opioid administered in conjunction
with the pointed end trailing. If there is a sharp- until the patch has been in place long enough for
ended object (e.g., toothpick or needle) posi- effective blood levels of fentanyl to be reached.
tioned proximally, the grasping prongs can Water is generally offered 12 hours after bone
sometimes be used to cover it so that the removal, and soft food can be offered at 18 to 24
esophageal mucosa is protected, or the object can hours. If there is any concern about esophageal
CHAPTER 4 DISEASES OF THE ESOPHAGUS 155
B C
FIGURE 4-19 Esophageal foreign body (pork bone) in a 4-year-old 14-lb mixed-breed dog. The owner had given
the bone to the dog as a treat and observed frequent gagging episodes 1 hour later. Radiographs were not obtained
at the referring hospital until 3 days after bone ingestion. Clinical signs included intermittent gagging, salivation,
nausea, and regurgitation shortly after eating. A, Lateral thoracic radiograph showing a large irregular bone lodged
in the esophagus at the heart base. B, Endoscopic appearance of the bone. The bone had been lodged for 3 days
before examination. C, The bone was successfully retrieved. Severe esophageal trauma resulted from lodgment of
the bone and efforts to remove it. Postendoscopy treatment included sucralfate suspension, intravenous famotidine,
subcutaneous amoxicillin, butorphanol for pain, intravenous fluids, and NPO for 36 hours. Several follow-up
endoscopies were done over the following 2 weeks to examine for stricture formation. No stricture developed, and
the esophagus was grossly normal at 2 weeks. (From Tams TR: Endoscopic removal of gastrointestinal foreign
bodies. In Tams TR, ed: Small animal endoscopy, St. Louis, 1990, Mosby–Year Book.)
been reported include pulmonary alveolar car- Larval migration and worm nodules in the esopha-
cinoma, gastric carcinoma, thyroid carcinoma, gus can cause aortic aneurysms, spondylosis in adja-
mammary adenocarcinoma, and squamous cell cent vertebral bodies, esophageal granulomas, and
carcinoma. esophageal neoplasia. Fibrosarcoma and osteosar-
Esophageal neoplasia is discussed in detail in coma of the esophagus are often associated with
Chapter 11. Spirocerca lupi will be described in this S. lupi.An interesting feature of the spondylosis is that
section. Mass lesions arising from the periesophageal it forms immediately below vertebral bodies, with
tissues may cause esophageal obstruction by com- no bridging to another vertebral body until the dis-
pressing the walls of the esophagus. This type of ease is very advanced. Hypertrophic osteopathy has
obstruction is somewhat more common in cats been reported in cases of esophageal fibrosarcoma
than in dogs. Anterior mediastinal lymphoma is with and without pulmonary metastasis.
most common. Other causes include thymic Diagnosis of S. lupi esophageal granulomas may
masses, lymphadenopathy, and lung masses. I have be made by lesion appearance and location. Ova may
observed a cat with a periesophageal stricture and occasionally be identified in the feces. In one recent
pleural effusion that had an undifferentiated sar- report of seven cases, ova were found in the feces of
coma (based on cytologic analysis of the effusion). only two of the dogs. Six dogs had signs of
The endoscopic appearance associated with esophageal disease, and one dog did not. Four dogs
periesophageal compression includes normal had evidence on thoracic radiographs of a caudodor-
mucosa and collapsed walls. The characteristic sal mediastinal mass. Two of these dogs had spondyli-
sign is an inability to dilate the esophagus with air. tis of midthoracic vertebrae. Endoscopy identified a
It is often also difficult to advance the endoscope single esophageal nodule in five dogs, three nodules
through the narrowed esophageal lumen. in one dog, and six nodules in the other.
Disophenol had been the only anthelmintic
Clinical Signs proven effective against the adult stage of S. lupi. It
Esophageal tumors usually occur in older patients. is not effective against larval stages. Further, it is no
Many dogs and cats with primary esophageal tumors are longer available. Doramectin (Dectomax, Pfizer
asymptomatic until quite late in the course of the disease. Animal Health) has now been shown to be effec-
The diagnosis is often initially made as an inciden- tive in treatment of S. lupi. Treatment before
tal finding on survey thoracic radiographs that are doramectin became available was limited to surgi-
made for some other reason.When clinical signs do cal excision of the esophageal granulomas.
develop, they primarily include slowly progressive In the study cited here, doramectin was adminis-
regurgitation and inappetence. There also may be tered at a dosage of 90 µg/lb SQ every 2 weeks for
salivation, dysphagia, fetid breath, and weight loss. three treatments. Endoscopy was then performed at
Mediastinal lymphoma occurs most commonly 2, 4, and 6 weeks after treatment. Six weeks after
in young cats. Regurgitation occurs when the treatment, clinical signs had resolved in six dogs.
mass becomes large enough to compress the The esophageal lesions were completely resolved in
esophagus. Other potential signs include dyspnea four of the dogs and reduced in size in the other
from pleural effusion, a noncompressible cranial three dogs. Two dogs with incomplete resolution
thorax, and Horner’s syndrome. Diagnosis and were subsequently treated with doramectin admin-
treatment are discussed in Chapter 11. istered orally at 225 µg/lb daily for 6 weeks.
Spirocerca Lupi Esophageal nodules resolved in all dogs, as con-
S. lupi is a nematode parasite of dogs in the south- firmed by endoscopy, and there was no recurrence
ern United States. There is a developmental period at 3 years. No adverse clinical signs were noted.
of 6 months. The parasite lives in the wall of the
esophagus. The parasite lays eggs that pass into the
lumen of the esophagus and subsequently pass ESOPHAGEAL
through the GI tract and out of the body in the DISORDERS OF
feces. Coprophagic beetles ingest eggs, which then
hatch and encyst in the beetle. This stage is infec-
CHINESE SHAR-PEIS
tive for dogs. Birds and rodents may act as transport Shar-peis have a high incidence of disorders of the
hosts. Following ingestion, the encysted larvae are GI tract. These include abnormal esophageal
freed and migrate through the wall of the stomach motility, hiatal hernias, inflammatory bowel dis-
and the aorta to the esophagus, where they mature. ease, and small intestinal bacterial overgrowth.
CHAPTER 4 DISEASES OF THE ESOPHAGUS 157
Stickle R et al.: Radiographic evaluation of esophageal Vigneri S et al.:A comparison of five maintenance ther-
function in Chinese Shar Pei pups, J Am Vet Med Assoc apies for reflux esophagitis, N Engl J Med 333:1106,
201:81, 1992. 1995.
Tams TR: Endoscopic removal of gastrointestinal for- Willard MD: Disorders of the oral cavity, pharynx, and
eign bodies. In Tams TR, ed: Small animal endoscopy, ed esophagus. In Nelson RW, Couto CG, eds: Essentials of
2, St. Louis, 1999, Mosby. small animal internal medicine, ed 2, St. Louis, 1998,
Tams TR: Reflux esophagitis. In Kirk RW, ed: Current Mosby.
veterinary therapy X, Philadelphia, 1989,WB Saunders.
C H A P T E R
5
DISEASES OF THE
STOMACH
Robert C. DeNovo
FUNCTIONAL
pyloric sphincter, which connects to the duode-
ANATOMY num. The primary function of the antrum is to
The stomach is a pouch-shaped organ positioned grind food into smaller particles, whereas the
transversely between the lower esophageal sphinc- pylorus limits the size of food particles that pass
ter (LES) and the pylorus. The stomach has four into the duodenum and prevents reflux of duode-
functionally distinct anatomic and functional nal contents into the stomach.
regions (Figure 5-1). The cardia, fundus, and body The stomach wall has three layers: the mucosa,
are located to the left of midline, whereas the the muscularis, and the serosa. The mucosa con-
antrum lies mostly in a transverse position to the sists of the surface epithelium, the glandular lam-
right of midline. Convergence of muscles of ina propria, and the muscularis layer. Columnar
the esophagus and stomach forms the gastric inlet surface epithelial cells of the mucosa secrete copious
or cardia. The main function of the LES and car- amounts of mucus and bicarbonate that protect
dia is to allow entry of ingesta into the stomach the underlying tissue from the damaging effects of
while preventing reflux of gastric contents into the luminal acid and proteolytic pepsin. The lamina pro-
esophagus. The fundus is the dome-shaped por- pria contains glands composed of columnar epithe-
tion of the stomach located left and dorsal to the lial cells that are functionally different in each part of
cardia. The fundus dilates during gastric filling the stomach. Glands in the cardia secrete mucus
to accommodate a volume of ingesta without and pepsinogens, whereas glands in the fundus and
increasing intragastric pressure. The body is the body have parietal cells that secrete hydrochloric
large middle portion of the stomach extending acid and chief cells that secrete pepsinogens.
from the cardia and fundus to the antrum. The These chemicals hydrolyze dietary proteins and
body stores ingesta and secretes hydrochloric acid, inactivate ingested microbes. Glands in the antrum
pepsin, and lipase for the initial phase of digestion. also secrete pepsinogens and mucus and contain
The distal third of the stomach is the tubular- specialized G cells that secrete gastrin, which is a
shaped antrum, which extends from the incisura potent secretagogue for acid production. The
angularis of the lesser curvature to the pylorus. muscularis consists of an inner circular and an
The pylorus is the most distal and narrowly tubu- outer longitudinal layer of smooth muscle, with a
lar part of the stomach. The pylorus is composed thin oblique muscle layer in between. The thick-
of a thick muscular wall to form the small-lumen ness of the muscular coat increases distally through
159
160 CHAPTER 5 DISEASES OF THE STOMACH
A Duodenum
Body and gastroduodenal motility is coordinated by the
Inc
distention accompanied by unproductive retching, distention occur more gradually and include
particularly in larger-breed dogs, are cardinal signs ascites, peritonitis, organomegaly, tumor, Cushing’s
of gastric dilatation-volvulus (GDV). In this syndrome, and obesity.
instance distention is primarily caused by air in the
stomach. Delayed gastric emptying, caused either
by pyloric outflow obstruction or by abnormal Laboratory Evaluation
gastric motility, is often characterized by postpran- Laboratory tests help to distinguish primary GI
dial distention from retention of fluid and ingesta causes of vomiting from metabolic causes and to
in the stomach. Nongastric causes of abdominal assess patient status for complications. Complete
CHAPTER 5 DISEASES OF THE STOMACH 163
GASTRIC NEOPLASIA
blood counts (CBCs) are often normal in patients fuse or protracted vomiting can cause significant
with primary gastric disease; however, a CBC can abnormalities. These changes, however, do not reli-
provide clues to the cause of vomiting. Chronic ably indicate the cause of the problem. Dehydration
gastric bleeding can result in nonregenerative is the most common problem caused by vomiting.
anemia, often with characteristics of iron deficiency Hypokalemia frequently occurs as a result of loss of
(microcytosis, hypochromasia, thrombocytosis). potassium both in the vomitus and urine, coupled
Acute gastric hemorrhage can cause either a regen- with lack of dietary intake. Hypochloremia occurs
erative or nonregenerative anemia, depending on from loss of chloride-rich gastric secretions and
severity and duration of bleeding. Parvovirus usu- from reduction of chloride reabsorption in the dis-
ally causes profound neutropenia, whereas other tal nephron that occurs when the patient is
enteric viruses cause no characteristic changes in hypokalemic. The acid-base status of the vomiting
the CBC. Acute pancreatitis, bacterial enterocolitis, patient can be acidotic, alkalotic, or normal depend-
and inflammatory bowel disease (IBD) can cause a ing on the composition of the vomitus and the pres-
neutrophilic leukocytosis. Eosinophilia in the vom- ence of dehydration, lactic acidosis, or metabolic
iting patient can occur from parasitism, eosinophilic disease such as renal insufficiency. Many vomiting
gastroenteritis, and adrenocortical insufficiency. patients have normal acid-base status because of
Biochemical tests provide important diagnostic simultaneous loss of gastric hydrochloric acid and
and therapeutic information in the vomiting bicarbonate-rich duodenal juice. Others will have
patient. Normal biochemical test results eliminate metabolic acidosis caused by dehydration, prerenal
most metabolic causes of vomiting. One exception azotemia, and lactic acidosis from decreased tissue
is cortisol-dependent hypoadrenocorticism, in perfusion. Hypochloremic metabolic alkalosis indi-
which electrolyte concentrations are normal cates that loss of a substantial amount of gastric con-
despite the patient having clinical signs typical of tents has occurred and is most indicative of gastric
Addison’s disease. In this instance an adrenocorti- outflow obstruction. Duodenal or biliary obstruc-
cotropic hormone (ACTH) stimulation test is tion, acute pancreatitis, or renal failure can cause
needed to rule out hypoadrenocorticism as a cause similar imbalances from loss of large quantities of
of vomiting. Hypoproteinemia occurs infrequently gastric juice. If the vomiting patient is hyperkalemic,
as a result of chronic infiltrative or granulomatous hypoadrenocorticism and oliguric or anuric renal
disease such as gastric lymphoma, carcinoma, or failure are the most likely causes of the vomiting.
infection with Pythium spp. Urinalysis is useful to Occasionally, severe intestinal disease caused by
rule out nongastrointestinal causes of vomiting trichuriasis or by bacterial enterocolitis will mimic
such as renal failure and diabetic ketoacidosis. hypoadrenocorticism, causing a syndrome of vomit-
Vomiting of short duration does not change ing and diarrhea and hyponatremia-hyperkalemia
fluid, electrolyte, or acid-base balance, whereas pro- that is typical of hypoadrenocorticism.
164 CHAPTER 5 DISEASES OF THE STOMACH
B
CHAPTER 5 DISEASES OF THE STOMACH 165
masses, ulceration, or evidence of delayed gastric spheres. The primary function of the large spheres
emptying can usually be identified. Filling the is to detect GI tract obstruction, whereas the
stomach with air to provide negative contrast can smaller spheres provide a quantitative measure of
help to identify foreign bodies, gastric wall masses, gastric emptying rate and intestinal transit time of
or deep ulcers. Positive contrast gastrography using food. The rate of gastric emptying is calculated by
premixed barium sulfate is more reliable. Barium determining the percentage of markers that remain
should be given by stomach tube to the fasted in the stomach after a standard period of time and
patient; recommended doses are 4 to 6 ml/lb for comparing that percentage with reference ranges
small dogs and cats and 2 to 4 ml/lb for large dogs. provided by the manufacturer. Various radio-
Ventrodorsal, right lateral, and left lateral radio- graphic patterns showing selective movement or
graphs should be taken within 5 minutes of giv- retention of small versus large spheres or patterns
ing the barium and repeated in 20 to 30 minutes. that show a bunching of spheres are also used to
Liquid barium should be observed in the duode- identify and localize specific problems such as par-
num within 5 to 20 minutes, and the stomach tial obstruction. Use of these spheres is a practical
should be nearly empty within 3 hours. If barium diagnostic tool to evaluate gastric emptying of
does not enter the duodenum within 30 minutes, solids in dogs and cats. Patients with chronic vom-
or if the stomach remains barium filled with no iting, particularly those with chronic postprandial
evidence of peristalsis, a gastric motility disorder vomiting, recurrent bloating, or suspected radiolu-
or gastric outflow obstruction should be suspected cent foreign body, or patients with anorexia of
(Figure 5-3, A). The presence of a persistently nar- unknown cause are good candidates for a gastric
rowed stream of barium at the pylorus is suggestive motility study using BIPS.
of pyloric obstruction from hypertrophy, neopla- Gastric emptying of solids can also be evaluated
sia, or inflammatory disease (Figure 5-3, B and C). using fluoroscopy to observe movement of barium
Atropine, aminopentamide, ketamine, and xylazine mixed with food into the doudenum. Nuclear
will significantly slow gastric emptying, giving the scintigraphy is used to evaluate gastric emptying of
false impression of gastric outlet obstruction. If a liquids versus solids. These techniques are obvi-
tranquilizer is needed, acepromazine is recom- ously limited in availability to referral institutions,
mended. (See Chapter 2 for details on GI contrast whereas use of BIPS is practical for most veteri-
radiography.) nary practices. Ultrasonography has limited use in
Liquid barium contrast radiographs are most evaluating the stomach wall for abnormalities
useful to detect gross abnormalities of the gastric because of interference from air in the gastric
mucosa. This technique, however, is an insensitive lumen. Filling the stomach with water via gas-
indicator of gastric emptying of a meal when a tric tube helps to eliminate this problem and
functional gastric motility disorder or partial improves sonographic visualization of the gastric
obstruction in the stomach or bowel is suspected. wall. (See Chapter 2 for a discussion on GI ultra-
This limitation, in addition to the difficulty sonography.)
encountered in administering barium by orogas-
tric tube, the need for multiple radiographs to be
taken at specific times, the risk of barium aspira- Endoscopy
tion, and the inaccuracies in interpretation of Gastroduodenoscopy (Figure 5-4, A and B; see
results have led to the development of a new color plate) is the most useful method available for
method to evaluate GI motility. the diagnosis of gastric disease because it allows
Barium-impregnated polyethylene spheres direct visualization and biopsy of the surface of the
(BIPS)* are commercially available radiopaque stomach and duodenum. Small lesions not
markers that are given orally to quantitatively detected by radiographs can usually be seen with
measure the gastric emptying rate and intes- an endoscope, foreign bodies can be removed, and
tinal transit time of food. Diagnostic sets of BIPS biopsy specimens can be obtained. Because histo-
consist of multiple (30 1.5-mm spheres and 10 logic lesions can be present in a normal-appearing
5.0-mm spheres) contained within gelatin capsules stomach or duodenum, multiple biopsy specimens
that dissolve in the stomach and release the should always be obtained, even if the gross
appearance is normal. If endoscopy is not available,
exploratory surgery must be done to remove
*
Medical ID Systems Inc., Grand Rapids, MI, 49512. foreign bodies and to obtain biopsy specimens.
166 CHAPTER 5 DISEASES OF THE STOMACH
FIGURE 5-3 Delayed gastric emptying. A, Right lateral recumbent radiograph of a 5-year-old, 16-lb
female/spayed (F/S) Chihuahua-mix with chronic intermittent vomiting caused by antral pyloric hypertrophy. The
stomach is distended with liquid barium, most of which is retained in the stomach 5 hours after administration.
B, Ventrodorsal radiograph showing a narrowed pyloric antrum. Filling defects (arrows) caused by antral
hypertrophy were consistent throughout the series of radiographs. C, Close-up ventrodorsal view of the pyloric
region. Hemispheric filling defects (black arrows) protruding into the lumen cause an annular stricture of the pyloric
sphincter. A faint narrow stream of barium (beak sign) (white arrows) can be seen passing through the partially
obstructed pylorus into the duodenum. D, Endoscopic appearance of the pylorus showing circumferential
thickening and bulging of a masslike lesion of the pylorus. The pylorus was rigid, and the endoscope could not be
passed into the duodenum. Endoscopic biopsy revealed mild lymphocytic-plasmacytic gastritis and mucosal
hyperplasia. A Y-U antral advancement flap pyloroplasty was done, and excisional biopsy confirmed the presence of
hypertrophic gastropathy.
A B
FIGURE 5-4 Normal stomach. A, Endoscopic appearance of a normal stomach. The smooth, pale-pink rugal folds
of the greater curvature of the gastric body gradually become more linear distally at the junction with the pyloric
antrum. The incisura angularis appears as a curved fold located at the 12 to 3 o’clock position. B, Appearance of a
normal pyloric antrum (foreground) and pylorus (upper left). The antral mucosa is smooth, pale pink, and without
rugal folds. The closed pyloric orifice is located at the center of the converging mucosal folds. (See color plate.)
barrier function. Reduced blood flow to the gastric those not controlled with acid-suppressing drugs
mucosa impairs epithelial cell renewal. Endogenous alone can be treated with octreotide (Sandostatin),
vasoconstrictive catecholamines and corticosteroids an antisecretory drug that inhibits gastrin secretion.
that are secreted in response to hypotension further
potentiate ulcer formation, as will the administration
of exogenous corticosteroids. All critically ill patients, Medical Management
especially those with severe trauma, major surgery, organ Treatment of acute gastritis, erosions, and ulcera-
failure, or sepsis, should be considered likely candidates tion requires elimination of predisposing causes
for development of ulcers. and symptomatic-supportive therapy to enhance
Mast cell tumors (MCT), pancreatic gastrin- mucosal defenses (Box 5-5). In general, fluids are
secreting tumors (gastrinomas), and pancreatic given to prevent dehydration and to maintain
polypeptide-secreting tumors can cause severe mucosal perfusion. Oral intake should be stopped
gastritis and significant GEU. MCTs, even those until vomiting resolves. Parenteral or enteral nutri-
benign-looking subcutaneous lumps that at first tion should be given to patients in poor nutri-
glance appear to be nothing more than a lipoma, tional condition (see Chapter 12), and blood
can release excessive amounts of histamine that transfusion is given to patients with severe anemia
stimulate hypersecretion of gastric acid, which and evidence of ongoing GI bleeding. Surgical
subsequently damages the gastric and duodenal treatment is indicated when uncontrolled hemor-
mucosa. Most dogs with MCT do not have clini- rhage or perforation is suspected.
cal signs of GEU at the time of diagnosis. Drugs used for nonspecific medical manage-
However, surgical manipulation or aggressive pal- ment of gastritis and GEU include H2-receptor
pation can cause massive mast cell degranulation antagonists, proton pump inhibitors, cytopro-
and release of histamine. Corticosteroids, which tective agents, and prostaglandin analogues (Table
are sometimes used to treat MCT, can further pre- 5-4) and antiemetics (Table 5-5). The drugs listed
dispose to GEU and occasionally cause gastric in Table 5-4 were developed primarily for the
perforation. treatment of gastric ulcer disease. However, they
Gastrinomas are small pancreatic tumors that are very useful to treat a broad variety of disorders,
secrete large amounts of gastrin, a trophic hor- including esophagitis, gastritis, and GI bleeding, as
mone that stimulates growth of gastric mucosa and well as GEU. Suppression of gastric acid promotes
secretion of excessive gastric acid. Severe gastro- healing of damaged mucosa and diminishes the
esophageal reflux, esophagitis, esophageal ulcera- proteolytic effects of gastric pepsin, which is most
tion, chronic gastritis, duodenitis, and proximal active in an acid environment. Cytoprotectants
duodenal ulceration will typically occur. Gastri- and prostaglandin analogues strengthen mucosal
noma should be considered in any adult dog that defenses. Promotility drugs reduce gastro-
has chronic vomiting, weight loss, diarrhea, esophageal and enterogastric reflux and help to
melena, and/or signs of esophagitis. Increased fast- control vomiting. Antiemetic therapies are
ing concentration of serum gastrin is diagnostic. designed to diminish either the humoral or neural
Other causes of increased gastrin concentration pathways of the vomiting and are recommended
that must be considered when interpreting serum for short-term use to provide patient comfort and
gastrin results include renal failure and conditions to reduce fluid and electrolyte losses.
that cause chronic gastric distention. In addition,
treatment with proton pump inhibitors (e.g., Antisecretory Drugs. Histamine, gastrin, and
omeprazole, lansoprazole) that have potent acid- acetylcholine stimulate the gastric parietal cell to
suppressing effects will cause increased gastrin pro- secrete acid; simultaneous stimulation by all three
duction because of the lack of negative feedback causes maximal acid secretion. H2-receptor antag-
of acid on gastrin-secreting cells in the pyloric onists competitively and reversibly bind to H2-
antrum. Treatment for gastrinoma requires tumor receptors on acid-producing gastric parietal cells
removal (partial pancreatectomy), which can be to block the acid-stimulating effects of histamine
curative if no metastasis has occurred. Medical man- and to render the cell less responsive to stimulation
agement requires use of the proton pump by acetylcholine and gastrin. Because these drugs
inhibitors such as omeprazole to maximally sup- are competitive inhibitors, they suppress but do
press acid secretion and control symptoms. Therapy not eliminate gastric secretion. The H2-receptor
is indefinite. Patients with metastatic disease and antagonists cimetidine, ranitidine, nizatidine, and
CHAPTER 5 DISEASES OF THE STOMACH 171
<2.0 80
2.0-2.5 60
2.5-3.0 40
3.0-3.5 30
famotidine are useful to treat gastritis and GEU in promote gastric emptying, which is helpful in con-
dogs and cats. All are effective and differ primarily trolling vomiting for patients with gastritis, and to
in acid-suppressing potency, frequency of dosing, decrease gastroesophageal and enterogastric reflux.
and in prokinetic effects. Cimetidine is the least Because of the dual prokinetic and acid suppression
potent and must be given three to four times daily effects of ranitidine, this drug is a good first-choice
to achieve adequate acid suppression. Ranitidine H2-receptor antagonist. The reported incidence of
and nizatidine both have about 5 times the side effects from H2-receptor antagonists is low, and
potency of cimetidine. Ranitidine must be given use of these drugs is safe in both dogs and cats.
twice daily, whereas nizatidine needs to be Cimetidine can cause vomiting, diarrhea, and
given only once daily. Famotidine is the most depression in dogs and cats. Because cimetidine and
potent H2-receptor antagonist, being approxi- ranitidine inhibit the same hepatic enzymes that
mately 20 times more potent that cimetidine, and metabolize drugs such as theophylline and warfarin,
requires only once-daily dosing. these drugs should not be given concurrently.
In addition to blocking acid secretion, ranitidine
and nizatidine have a prokinetic effect on the GI Proton Pump Inhibitors
tract. Both drugs increase acetylcholine, the primary Benzimidazole drugs such as omeprazole and lan-
stimulatory neurotransmitter of GI smooth muscle, soprazole block the hydrogen-potassium adenosine-
by inhibiting acetylcholinesterase. The effects are to triphosphatase (ATPase) enzyme of the gastric
TABLE 5-4 Drugs Used in the Treatment of Gastritis and Gastrointestinal Ulcer Disease
Suggested
172 CHAPTER 5
Generic Name Mechanism Product (Mfr) Dosage How Supplied Side Effects
H2 Receptor Decrease acid
Antagonists secretion
Cimetidine Tagamet 2.5-5.0 mg/lb q6h PO, IV, IM Tablet 200 mg Inhibition of hepatic
DISEASES
Liquid 60 mg/ml
Injection 150 mg/ml
Ranitidine Zantac 1.0 mg/lb q8-12h PO, IV, IM, SQ Tablet 150 mg Similar to cimetidine, but to
STOMACH
Prokinetic
Drugs
Metoclopramide Enhances gastric emptying; Reglan (Robins) 0.15-0.25 mg/lb q8h PO, SQ Tablet 5 mg Hyperactivity, constipation
antiemetic 0.5-1 mg/lb q24h IV 10 mg
Liquid 1 mg/ml
Injection 5 mg/ml
Erythromycin Accelerates gastric emptying Erythromycin 0.25-0.5 mg/lb q8h PO
of solids
H2-receptor Enhances gastric emptying Zantac 0.25-0.5 mg/lb q8h PO
DISEASES
CRTZ, Chemoreceptor trigger zone; SQ, subcutaneously; IM, intramuscularly; PO, orally; IV, intravenously.
parietal cell to profoundly and irreversibly inhibit Proton pump inhibitors are recommended for the
gastric acid secretion. Because these drugs block treatment of severe esophagitis and GEU that has
the final step of hydrogen ion secretion, they not responded to therapy with H2-receptor antag-
prevent secretion of gastric acid stimulated by onists and sucralfate. They are recommended as
histamine, acetylcholine, and gastrin. These the drugs of choice for treatment of patients with
drugs noncompetitively block the proton pump hypersecretion of gastric acid that occurs with
and therefore are much more potent than the MCT and gastrinoma. Omeprazole and lansopra-
H2-receptor antagonists. Proton pump inhibitors zole are similar in potency, are given once daily,
accumulate in the parietal cell and increase with cause no clinical, hematologic, or biochemical
each dose until acid secretion is almost totally abnormalities, and are safe to use in cats and dogs.
inhibited after the fifth dose. Because of this delay
in gastric acid suppression, H2-receptor antagonists Sucralfate
should be used concurrently with proton pump Sucralfate is a sulfated disaccharide–aluminum
inhibitors for the first 3 to 4 days of treatment in hydroxide complex that accelerates gastric
patients where rapid acid suppression is needed. mucosal healing by adhering to mucosal erosions
CHAPTER 5 DISEASES OF THE STOMACH 175
and ulcers to provide a barrier to acid penetra- receptors in the chemoreceptor trigger zone
tion. Sucralfate inactivates pepsin and adsorbs (CRTZ) of the medulla to inhibit vomiting induced
gastric-damaging bile acids refluxed from the duo- by drugs, toxins, metabolic disease, and acid-base
denum. Sucralfate also stimulates endogenous imbalances. Because serotonin receptors predomi-
prostaglandin synthesis in the gastric mucosa, nate in the CRTZ of the cat, metoclopramide does
resulting in increased secretion of mucus and bicar- not appear to be as effective as a centrally acting
bonate and accelerated ulcer healing. Sucralfate is antiemetic in the cat as in the dog. The prokinetic
effective at acidic to near neutral pH and can there- effect of metoclopramide is mediated through stim-
fore be used concurrently with antisecretory drugs ulation of serotonergic 5-HT4 receptors on GI
such as H2-receptor antagonists or proton pump smooth muscle to improve coordination of antral,
inhibitors. However, because sucralfate can adsorb pyloric, and duodenal contractions. The primary
other orally administered drugs, it should not be prokinetic effects are to accelerate gastric emptying
given within 2 hours of other oral drugs. Sucralfate of liquids and to decrease duodenogastric reflux,
is recommended for the treatment of esophagitis, whereas gastric emptying time of solids does not
gastritis, and gastric ulcer of any cause in dogs and appear to be shortened.
cats. Its safety is well established, with constipation Metoclopramide is more effective as a centrally
being the only reported side effect. acting antiemetic than it is as a prokinetic drug. It is
best used to control vomiting caused by nonspecific
Synthetic Prostaglandins gastritis, uremia, and chemotherapy. The peripheral
Synthetic prostaglandin analogues such as miso- effects of metoclopramide to prevent gastric stasis
prostol have been developed that impart protection and duodenogastric reflux, and to inhibit retrograde
to gastric mucosa in a manner similar to endoge- peristalsis that precedes vomiting, further help to
nous prostaglandins. Misoprostol stimulates gastric diminish the severity of vomiting. Metoclopramide
mucus secretion, increases bicarbonate secretion, is administered parenterally to the vomiting patient
increases gastric mucosal blood flow, and inhibits at 0.1 to 0.25 mg/lb body weight every 8 hours.
gastric acid secretion. Because most NSAIDs Constant intravenous infusion of 0.5 to 1.0 mg/lb
inhibit the production of endogenous prostaglan- body weight per 24 hours is usually more effective
dins, treatment with misoprostol helps to prevent to initially control vomiting, particularly in patients
gastric ulceration in patients in which chronic with severe vomiting. Metoclopramide should not
NSAIDs are used to control inflammation and pain be used if gastric outlet obstruction or GI perfora-
from degenerative joint disease. Clinical studies of tion is suspected or if the patient has a seizure dis-
human and canine arthritic patients have shown order. Some patients are very sensitive to the effects
misoprostol to be effective in preventing NSAID- of this drug and will actually have increased vomit-
induced gastric hemorrhage, erosion, or ulceration. ing, presumably caused by excessive gastric contrac-
Diarrhea, vomiting, and transient abdominal dis- tions. Central effects of metoclopramide can also cause
comfort are potential side effects, particularly if behavioral changes in some patients, ranging from lethargy
used above the recommended dosage range of 1 to in some to hyperactivity and agitated behavior in others.
1.5 µg/lb every 12 hours. No adverse hematologic These effects can occur at recommended dosages
or biochemical effects have been reported with the and occur most frequently in cats. Pacing, vocaliza-
use of misoprostol in dogs; similar information in tion, aggressive or agitated behavior, chewing at an
cats is lacking. Misoprostol will cause abortions and intravenous catheter, and excessive panting are signs
should not be used in pregnant patients. that should alert the clinician to sensitivity to or
overdosage of metoclopramide. Side effects usually
Prokinetic Drugs resolve when the drug is discontinued. However, if
Prokinetic drugs have no direct healing effect on central nervous system (CNS) signs are severe, treat-
gastric erosion or ulcer. However, these drugs ment with diphenhydramine (Benadryl) at 1 to 2
improve gastric emptying and decrease enterogastric mg/lb intravenously will effectively reverse the side
reflux, thereby helping to prevent damage to the effects without altering promotility effects of the
gastric mucosa from refluxed bile acids and pancre- drug. Because metoclopramide is excreted by the
atic enzymes. Metoclopramide is especially effective kidneys, the dosage should be reduced by 50% in
because it has both central antiemetic and peripheral patients with renal failure.
gastric prokinetic effects. The antiemetic effect is Cisapride is a serotonergic agonist that binds
mediated through antagonism of dopaminergic D2 to 5-HT4 receptors on enteric postganglionic
176 CHAPTER 5 DISEASES OF THE STOMACH
cal biopsy. Laboratory abnormalities that might findings of gastritis. H. felis, H. heilmannii, and
occur are nonspecific and include anemia, leuko- H. pylori are the most common types found in cats.
cytosis, eosinophilia, and hypoproteinemia. Survey The reported prevalence of gastric Helicobacter
radiographs help to identify gastric foreign bodies infection is high in clinically normal dogs and
but seldom identify primary gastric lesions. cats, as well as in dogs and cats with signs of gas-
Contrast radiographs may show a thickened gastric tritis. In our hospital approximately 50% of dogs
wall, mucosal ulceration, mass lesions, or evidence and cats that have had gastroscopy to determine
of delayed gastric emptying. the cause of chronic vomiting are infected with
Helicobacter.
Specific Causes of Chronic Gastritis Despite the high incidence of infection, most
Helicobacter-associated Gastritis dogs and cats infected with Helicobacter are not symp-
Spiral bacteria of the genus Helicobacter infect the tomatic for gastritis. However, some infected animals
stomachs of many mammalian hosts, including are symptomatic, a situation similar to that observed
humans, dogs, and cats. These gram-negative spiral in humans. These observations pose the obvious
organisms characteristically produce urease, an question, Does infection cause disease? Most evidence
enzyme that helps these organisms to adapt to the indicates that certain Helicobacter spp. do cause dis-
gastric environment and can be used diagnostically ease, although the incidence of disease is much lower
to confirm infection. In humans, infection with than the incidence of infection. A few anecdotal
Helicobacter pylori has been shown to be the pri- reports exist that describe resolution of Helicobacter-
mary cause of chronic gastritis and of gastric and associated clinical gastritis following treatment with
duodenal ulcer disease and has been identified as a various combinations of antimicrobial-antacid ther-
predisposing cause of gastric carcinoma and apy. These reports are limited by having small
mucosal lymphoma. Several species of Helicobacter numbers of patients, by lack of biopsy-confirmed
are commonly found in the stomachs of dogs and resolution of gastritis, and by lack of clinical con-
cats, and although the entire clinical significance of trols. Perhaps the most compelling evidence of
Helicobacter infection in these species is not known, cause and effect is in a study of 100 animals (62
evidence indicates that infection is a cause of dogs and 38 cats) with clinical signs of gastritis.
chronic gastritis in dogs and cats. Helicobacter spp. were found in 63 animals (43 dogs
Helicobacter heilmannii, Helicobacter felis, Helicobacter and 20 cats), 62 of which had histologically con-
bizzozeronii, and Helicobacter salomonis are the most firmed gastritis. Treatment of infected animals
common types found in dogs, having been identi- with antibiotics plus antacids was associated with
fied in clinically normal dogs, as well as in dogs with resolution of clinical signs in more than 90% of the
clinical signs of chronic gastritis and with histologic affected animals. Of 19 animals in which biopsy
178 CHAPTER 5 DISEASES OF THE STOMACH
was performed after treatment, 14 were negative designed to noninvasively detect infected patients
for organisms and histologic gastritis had resolved and to monitor treatment efficacy. Limited clinical
in all. Other studies of experimental infection in application indicates that this test might eventually
dogs and cats have confirmed that Helicobacter be useful in dogs and cats. Measurement of
spp. can induce a lymphocytic gastritis in these humoral IgG to H. pylori is a sensitive, specific, and
species. In our hospital, many patients evaluated noninvasive method of diagnosis in humans.
for clinical signs of gastritis have biopsy-confirmed Naturally and experimentally infected dogs and
Helicobacter infection associated with lymphocytic cats also produce antibody titers; however, a sero-
gastritis, where no other cause for the gastritis logic test has not been available for use in dogs and
or clinical signs can be found. Symptoms and his- cats. Most species of Helicobacter are very difficult
tologic disease have resolved in most, but not to culture, and this method is not recommended
all, following combination antibiotic-antacid for diagnosis. Electron microscopy, polymerase
therapy. chain reaction, and in situ hybridization are tech-
Diagnosis of Helicobacter infection is confirmed by niques used to identify species and subspecies.
gastric cytologic findings or results of biopsy. Cytologic Endoscopic appearance of suspected Helicobacter-
analysis of gastric mucosal biopsy impression associated gastritis is variable, ranging from a normal-
smears stained with new methylene blue is a sen- appearing mucosa to mucosal hyperemia to
sitive test to confirm presence of Helicobacter punctate erosions. Some patients will have a diffuse
organisms. Cytologic findings obtained by endo- nodular gastritis with a raised follicular appearance
scopic brush of the gastric mucosa are less sensi- (Figure 5-7; see color plate) caused by accumula-
tive. Routine hematoxylin and eosin (H&E) stain tions of lymphocytes. Histologic findings associated
histopathologic study is usually adequate to iden- with Helicobacter in humans, dogs, and cats vary in
tify the organisms in gastric biopsy specimens. Use severity from mild vacuolization of surface epithe-
of a silver stain (e.g., Warthin-Starry stain) is best, lium to lymphocytic-plasmacytic or neutrophilic
especially to identify organisms located in the mucosal inflammation. Lymphoid nodules occur in
deeper areas in the gastric glands and mucosa. more severely affected patients. Infected dogs and
Biopsy specimens obtained by endoscopy can cats that have mild histologic gastritis are often non-
be rapidly tested for urease production by placing symptomatic, whereas those with moderate to
the biopsy sample in a medium containing urea severe histologic gastritis are symptomatic.
and a pH indicator. Urease-producing Helicobacter Uncertainty regarding the pathogenicity of
organisms in the specimen convert urea to ammo- Helicobacter infection in dogs and cats raises another
nia, causing a color change in the medium. fundamental question for the clinician: Should
Commercial test kits are used routinely in humans Helicobacter infection be treated? Based on cur-
to rapidly screen endoscopic biopsy samples for rent information and clinical experience, a logical
Helicobacter (CLO Test*). These tests are sensitive approach to this question is to first rule out other
and specific for Helicobacter and work well to causes of chronic vomiting. Anthelmintic treat-
detect infection in dogs and cats. In our hospital, ment for gastric nematodes (refer to the discussion
gastric biopsy specimens from all dogs and cats of parasitic gastritis), followed by a complete blood
undergoing gastroscopic examination for vomiting count (CBC), biochemical profile, urinalysis, and
are screened for the presence of urea-producing abdominal radiographs, should be done initially.
organisms using this type of test, in addition to Endoscopic biopsy to confirm the presence of
doing cytologic studies of gastric biopsy specimens both Helicobacter infection and gastritis should
or mucosal brushings. If cytologic examination then be considered. In our hospital, treatment
reveals the presence of spiral organisms and the for Helicobacter is recommended for dogs and cats
urea test is positive, treatment for Helicobacter is in which biopsy has confirmed the presence of
started pending histopathologic results. If no other Helicobacter-associated gastritis for which no other
cause of vomiting is revealed by histopathologic cause of the clinical signs can be identified. For
studies, treatment for Helicobacter is continued for symptomatic patients in which endoscopy is not
at least 14 days. (See the following discussion.) an option, the question that frequently arises
Urease production by Helicobacter spp. is also the is, Should the patient be treated empirically for
basis for the carbon-14 breath test, which was Helicobacter-associated gastritis? This issue is debat-
able. If the patient is not systemically ill and is not
*
Trimed Specialties, Lenexa, Kan. losing weight, and if metabolic causes of chronic
CHAPTER 5 DISEASES OF THE STOMACH 179
with chronic vomiting where the only abnormality appearance. Diffuse superficial gastritis is characterized
found was a single parasite attached to the gastric by mucosal infiltrate with lymphocytes and plasma
mucosa. Treatment for these parasites has resolved cells, often involving full thickness of the mucosa.
the clinical signs. Adult worms are easily identified Atrophic gastritis is characterized by severe inflamma-
as 1- to 4-cm-long nematodes in the fundus or tory infiltrate with reduced mucosal parenchyma and
antrum, but the smaller larvae are difficult to visu- loss of gastric glands and prominent fibrosis.
alize. Some parasitized animals have gastric erosions Hypertrophic gastritis is characterized by diffuse or
and moderate lymphocytic-plasmacytic or eosino- focal mucosal hypertrophy with variable inflamma-
philic gastritis. Because nonendoscopic diagnosis is tory infiltrate and fibrosis (see discussion of pyloric
difficult, it is advisable to treat chronically vomiting mucosal hypertrophy). Plasmacytic-lymphocytic
dogs and cats that are not systemically ill for gastric gastritis usually occurs as part of the more diffuse
parasites before recommending extensive diagnostic syndrome of IBD and likely has a similar etiopatho-
tests and endoscopy. Treatment with a single dose genesis. A permeability defect in the gastric mucosal
of pyrantel pamoate (2.3 mg/lb orally) eliminates barrier, possibly caused by dietary sensitivity, drug-
Physaloptera from dogs, whereas cats require two induced damage, or infection, might allow abnormal
doses (2.3 mg/lb) given 3 weeks apart. Treatment absorption of luminal antigens into the mucosa,
for Ollulanus is uncertain; however, fenbendazole thereby initiating an immune-mediated response.
(4.5 mg/lb every 24 hours for 2 days) appears to be Clinical, laboratory, and radiographic findings are
effective in cats. nonspecific, and diagnosis is based on results of
Chronic Gastritis of Unknown Cause biopsy. Severe lymphocytic infiltrate can sometimes
Lymphocytic-plasmacytic gastritis is a common his- be difficult to distinguish from gastric lymphoma,
tologic diagnosis characterized by gastric mucosal particularly when evaluating small endoscopic
infiltrate with lymphocytes and plasma cells, but biopsy specimens. Treatment is essentially sympto-
without evidence of an underlying cause. Three matic, centering on dietary protein change coupled
types have been described based on histologic with immunosuppressive therapy (Box 5-6).
PROTECTANTS AZATHIOPRINE
Sucralfate is well tolerated long term and enhances Use if response to steroids is inadequate or as adjunct to
healing of gastric mucosa; it should be used when- steroids in severe lymphocytic-plasmacytic disease;
ever hematemesis or melena is observed. rarely needed to control eosinophilic gastroenteritis.
Dose: 0.5 mg/lb once daily for 2 weeks, followed by
PROKINETICS alternate-day therapy.
Metoclopramide or cisapride may be helpful in Alternate-day treatment with azathioprine-prednisone
decreasing chronic vomiting and can be used for long-term maintenance.
indefinitely. Monitor CBC for neutropenia or thrombocytopenia
every 2 weeks for first month of therapy and
ANTIBIOTICS monthly thereafter. Decrease dose or discontinue
If Helicobacter-associated gastritis is suspected. drug if evidence of bone marrow suppression occurs.
Corticosteroids
Generally not used unless histologic diagnosis has
confirmed lymphocytic-plasmacytic or eosinophilic
CHAPTER 5 DISEASES OF THE STOMACH 181
ium more accurately estimates gastric emptying More accurate techniques to evaluate gastric
time of solids. Interpretation of both types of con- motility are limited to hospitals with nuclear med-
trast studies is subjective, and results of both can vary icine and GI motility laboratory facilities.
significantly in normal animals. Fluoroscopic exam- Scintigraphic studies using radioactive tracers
ination improves accuracy of interpretation by mixed with food is the method of choice for
allowing visualization of sequential changes in the measuring gastric emptying time. Electrogastro-
shape of the stomach and pylorus and of movement grams can also be done and are useful to detect
of contrast through the pylorus. Liquid barium abnormal patterns of gastric motility such as
should begin to enter the duodenum within tachygastria and bradygastria.
15 minutes after administration, and gastric empty- Functional gastric motility disorders are charac-
ing of liquid should be complete within 1 to 4 terized by delayed gastric emptying in the absence
hours. Complete gastric emptying of a barium meal of morphologic lesions. Partial obstruction caused
should occur within 8 hours but might not be com- by restrictive or infiltrating mural diseases of the
plete in some normal dogs until 15 hours after feed- pylorus, such as muscular hypertrophy, neoplasia,
ing. If most of the liquid barium is retained in the or granulomatous diseases, produces annular nar-
stomach after 4 hours, if liquid barium is present in rowing of the pyloric canal. Barium may only fill
the stomach longer than 12 hours, or if a large the narrow entrance to the pylorus, resulting in a
amount of a barium meal is retained longer than 8 thin stream of barium often referred to as having
to 10 hours, delayed gastric emptying is present. a “beaklike” appearance (see Figure 5-3, C ); this
An alternative method to barium studies for is a common finding with antral pyloric hypertro-
evaluation of gastric emptying is the use of phy. Polyplike filling defects can be caused by
radiopaque BIPS. BIPS are given with a canned- mucosal hypertrophy, inflammatory granuloma,
food meal consisting of approximately 25% of the neoplasia, or foreign body.
daily caloric intake. Abdominal radiographs should Once delayed gastric emptying has been con-
then be taken at 4- to 6-hour intervals over the firmed, additional diagnostic procedures such as
next 12 to 24 hours. The percentage of BIPS that ultrasonography, endoscopy, or exploratory sur-
have left the patient’s stomach is compared with a gery are necessary to determine if an obstructive
standard curve for normal gastric emptying that is lesion is present. Ultrasonography is useful to
provided by the manufacturer.When radiographic detect foreign bodies, mural thickening, and
gastric-emptying studies are done, it is important masses not detected by radiographs. Endoscopy
to remember that fear and anxiety from physical and mucosal biopsies are useful in diagnosing
restraint often cause a transient delay of gastric chronic gastritis, IBD, neoplasia, or foreign body.
emptying. More importantly, potent anticholiner- Surgical examination and biopsy should be con-
gic drugs such as aminopentamide (Centrine) can sidered if the cause of delayed gastric emptying is
delay gastric emptying for several hours. Because uncertain. Full-thickness gastric biopsy allows
aminopentamide can cause profound and prolonged gas- examination of muscle and nerve plexuses not
tric stasis and ileus, which sometimes worsens the emesis included in endoscopic pinch biopsy specimens
and diarrhea that it was intended to resolve, it is not rec- that usually extend only into the submucosa.
ommended for antiemetic therapy. Surgery provides an opportunity for resection of
184 CHAPTER 5 DISEASES OF THE STOMACH
masses and for procedures to relieve gastric outlet some patients require a feeding schedule of small
obstruction. frequent meals and treatment with metoclo-
pramide to enhance gastric emptying.
Specific Syndromes of Delayed
Gastric Emptying Primary Gastric Motility
Antral pyloric hypertrophy syndrome, also referred Disorders
to as pyloric stenosis and chronic hypertrophic Delayed gastric emptying can be caused by abnor-
pyloric gastropathy (CHPG), occurs either as a mally slow gastric contraction (bradygastria),
congenital condition or more frequently as an rapid rhythm (tachygastria), or irregular rhythm
acquired disorder (Table 5-8). Young to middle- (dysrhythmia), conditions thought to be caused
age male brachycephalic breeds, particularly box- by abnormal gastric pacemaker activity. Brady-
ers, Boston terriers, Lhasa apsos, and Maltese, gastria causes infrequent gastric contraction,
Pekingese, and shih tzu dogs, are most commonly whereas tachygastria can cause reversed propagation
affected. Clinical and radiographic signs of delayed of motor activity, which prevents normal emptying.
gastric emptying with intermittent gastric dilata- Gastric dysrhythmias have been observed to occur
tion and episodes of projectile vomiting are often normally in healthy dogs during fasting, whereas
observed. Physical examination and laboratory find- feeding will abolish the dysrhythmia. Animals
ings are usually normal. Contrast radiographs often symptomatic for gastric dysrhythmias are presented
reveal a distended stomach with delayed gastric emp- for signs of post prandial abdominal discomfort,
tying of contrast material and an abrupt narrow- bloating, or chronic vomiting. Diagnosis requires
ing of the pyloric canal with only a narrow stream documentation of gastric retention and elimination
of barium passing through (see Figure 5-3, C ). of obstructive and metabolic causes of delayed gas-
Endoscopic examination usually reveals a thick- tric emptying (Figure 5-8; see color plate).
ened pyloric mucosa that sometimes appears as a Measurement of gastric electrical activity is diag-
protuberant mass, often with mucosal erosions (see nostic but is limited to referral institutions.
Figure 5-3, D). Histologically the mucosa is thick- Treatment relies on a combination of dietary
ened with edema and hyperplasia, and the muscu- changes and prokinetic drugs to improve gastric
laris is usually hypertrophied. emptying (Box 5-8). Surgical procedures are gen-
Treatment requires pyloroplasty with submu- erally not successful to improve gastric emptying
cosal resection to remove thickened mucosal folds for patients with primary functional gastric motil-
to reestablish gastric outflow. Y-U antral advance- ity disorders. Liquified or blenderized diets are
ment flap pyloroplasty is the most effective useful to try because liquids empty from the stom-
method of reestablishing gastric outflow while ach more rapidly than solids. Because fats and pro-
preserving normal pyloric function. Prognosis is teins delay gastric emptying, diets low in fat and
generally good following pyloroplasty, although protein and high in carbohydrates should be tried
used primarily to inhibit gastric acid secretion. bassets, bulldogs, miniature poodles, dachshunds,
These drugs also stimulate GI motility by inhibiting and Pekingese are affected. GDV is rare in cats.
acetylcholinesterase activity, thereby increasing the GDV occurs in animals ranging in age from
amount of acetylcholine available to bind to smooth 2 months to 15 years, with a mean of about
muscle muscarinic receptors. The result is primarily 6 years. No sex predilection has been identified.
stimulation of gastric emptying, with some increase No single cause of GDV has been identified;
in small intestinal and colonic motility. however, several risk factors are thought to be of
The choice of which prokinetic drug to use importance for the development of this condition.
first depends in part on whether an underlying Deep-chested breeds of dogs appear to have an
cause has been identified. For example, ranitidine increased potential for rotational instability of the
and nizatidine are useful in the treatment of gastric stomach, in part because of laxity of hepatoduode-
motility disorders associated with gastric ulcerative nal and hepatogastric ligaments. Large-volume
or inflammatory diseases where both acid sup- intake of food and water causes chronic gastric
pression and stimulation of gastric emptying are distention that can potentially impair gastric emp-
beneficial. Metabolic causes of delayed gastric tying. Exercise with a distended stomach, particu-
emptying such as uremia or diabetic ketoacidosis, larly in deep-chested dogs, might subsequently
where central stimulation of vomiting might also cause the stomach to become displaced and result
occur, and gastric hypomotility following surgery in volvulus. Dietary composition, particularly
for GDV tend to respond well to treatment with feeding dry-food diets, has also been suggested as
metoclopramide. If an underlying abnormality a contributing factor to GDV; however, a direct
cannot be identified, the choice of treatment is relationship has not been established. The inci-
trial and error. In general, cisapride (if available) dence of GDV was reported to decline when dry
should be tried initially, with erythromycin being food was dampened before feeding, presumably
a second choice. Metoclopramide and ranitidine preventing swelling of dry food with water in the
or nizatidine are considered if inadequate response stomach. Aerophagia from rapid eating, hyperven-
is achieved with the initial treatment. tilation, and esophageal motility abnormalities
Clinical experience indicates that several days of have also been associated with recurrent GDV.
treatment are often required before a clinical Impaired eructation may result from an anatomi-
response is observed. Some patients with functional cally or functionally abnormal gastroesophageal
dysrhythmias that respond to prokinetic drugs may junction (GEJ) in deep-chested dogs. The oblique
require treatment indefinitely, perhaps at lower or angle of the GEJ may become exaggerated, espe-
less frequent dosing than the standard recommen- cially if the stomach is distended following a large
dations, whereas other patients might eventually be meal, preventing normal eructation.
weaned off therapy. To determine if a lower drug
dose is adequate requires individualized treatment
for each patient. A suggested protocol is to first Pathophysiology of Gastric
decrease the frequency of dosing (e.g., if a drug is Dilatation-Volvulus
being given three times a day, decrease to two times GDV traps ingesta, fluid, and gas in the stomach,
a day; if being given two times a day, decrease to which rapidly causes extreme increase of intragas-
every day). If clinical signs are adequately controlled tric pressure. A cascade of life-threatening effects
for several days, alternate-day treatment can then be develops that, if not corrected rapidly and aggres-
tried. If signs are still controlled, discontinuing the sively, will cause death. The most immediate effect
drug should be considered. If the signs reoccur, is impedance of gastric blood flow by increased
treatment must be resumed, and the lowest possible intragastric pressure, gastric wall edema, vasocon-
effective dose is used on a longer-term basis. striction, and thrombosis. Gastric ulceration, necro-
sis, and perforation develop rapidly. As the stomach
GASTRIC DILATATION- enlarges, respiratory tidal volume and cardiac
venous return from the viscera decrease, resulting in
VOLVULUS SYNDROME impaired respiration, acidosis, and decreased cardiac
Acute GDV occurs most frequently in large-breed output. Malposition of the spleen results in splenic
dogs, particularly Great Danes, German shepherds, congestion, thrombosis, and necrosis. Ischemic vis-
Irish setters, Saint Bernards, and Doberman pin- cera release endotoxins that further contribute
schers. Occasionally smaller-breed dogs such as to hepatic, renal, pancreatic, and cardiac damage.
CHAPTER 5 DISEASES OF THE STOMACH 187
Vascular collapse, disseminated intravascular coagu- graphic findings and gastric decompression.
lation (DIC), and sepsis occur. Treatment by gas- Clinical features of GDV are listed in Table 5-9.
tric deflation and derotation and by the rapid The most characteristic clinical signs are an acute
administration of fluids, although very necessary, onset of retching, but without vomiting, rapidly
can have further detrimental effects on the developing abdominal distention and tympany,
patient. Reperfusion injury and release of endo- and depression. Some animals are reluctant to
toxins and cardiodepressant factors, hemodilu- stand, whereas others are recumbent. Rapid and
tion, and metabolic acidosis further contribute to weak pulses, prolonged capillary refill time, and
metabolic dysfunction and cardiovascular com- pale, congested, or cyanotic mucous membranes
promise. are indicative of cardiovascular failure. Cardiac
The metabolic consequences of GDV are vari- arrhythmia is usually present or develops soon
able but can be severe, depending on the duration after presentation. Arrhythmias are usually ven-
of the problem. Acid-base and electrolyte imbal- tricular in origin and range from intermittent ven-
ances may initially be absent but usually develop tricular premature conductions to ventricular
during treatment. Frequent monitoring of these tachycardia; supraventricular arrhythmias such as
parameters is necessary until the patient is stabi- atrial fibrillation occur occasionally.
lized. Metabolic acidosis occurs commonly in the Radiographs taken following initiation of fluid
GDV patient from decreased circulating blood vol- therapy and decompression are necessary to deter-
ume, arterial hypoxemia, and lactic acidosis. mine if volvulus is present. Radiographic determi-
Metabolic alkalosis, caused by fluid sequestration in nation of the location of the pylorus is the key
the stomach and by loss of gastric H+, Cl–, and K+, feature to differentiate gastric dilation from gastric
occurs less frequently. Hyperventilation can cause volvulus. This is best accomplished by comparing
respiratory alkalosis, whereas hypoventilation from left and right lateral recumbent views (see Figure
gastric distention can interfere with diaphragmatic 5-2). Gastric volvulus usually results in displace-
function and cause respiratory acidosis. Electrolyte ment of the pylorus dorsally and to the left, creat-
abnormalities occur less frequently than acid-base ing a shelflike partition of soft tissue that appears to
imbalances, with hypokalemia being the most compartmentalize the stomach. With the pylorus
common. shifted to the left and the patient in left lateral
Presumptive diagnosis of GDV is made on the recumbency, the pylorus fills with fluid and gas fills
basis of clinical findings and is confirmed by radio- the rest of the stomach. However, when the patient
is in right recumbency, gas fills the pyloric portion cal repositioning of the stomach and gastropexy.
and fluid shifts to the fundus or body of the stom- Concurrent therapy for electrolyte imbalances,
ach. The finding that the pylorus fills with fluid arrhythmias, and DIC are necessary. Box 5-9 pro-
when in the left lateral recumbent position and fills vides guidelines for the emergency treatment of
with gas when in the right lateral recumbent the patient with GDV.
position indicates that the pylorus has rotated to
the left. The presence of abdominal fluid is Initial Stabilization
suggestive of peritonitis or hemorrhage, and air Fluid therapy should be started immediately.
in the abdominal space indicates that perforation A balanced crystalloid such as lactated Ringer’s
has occurred. Megaesophagus is a common solution should be given intravenously (25 ml/lb)
finding. within the first 15 minutes to reestablish cardiac
output; an additional 25 ml/lb is then given over
Treatment the next 30 to 45 minutes. After this initial bolus,
Successful treatment begins with rapid fluid ther- a colloid such as hetastarch should be given at a
apy and gastric decompression, followed by surgi- dose of 5 ml/lb as a slow intravenous bolus over
10 to 15 minutes. Depending on patient response, procedure; either mask induction using an inhalant
crystalloid fluid should be resumed at a rate of anesthetic or use of a short-acting injectable anes-
10 to 20 ml/lb/hr for the next 2 hours and then thetic is sufficient. Once decompression has been
decreased to 5 to 10 ml/lb/hr. Pulse quality, capil- achieved, an oral-gastric tube can usually be placed
lary refill, central venous pressure, and urinary out- to facilitate ongoing patient stabilization.
put should be used as a guide for continued fluid
needs. The packed cell volume and plasma total Surgical Correction
protein concentration should be monitored hourly As soon as the clinical condition has been stabi-
to avoid hemodilution (total plasma protein con- lized, surgery should be done to reposition and
centration should not decrease to less than stabilize the stomach (Box 5-10). The optimal
3.5 g/dl). Following gastric decompression, the time for surgery to occur is variable, depending on
fluid rate can usually be decreased to 5 ml/lb/hr, patient condition and response to initial therapy.
depending on patient stability. Hetastarch can be In general, surgery should not be delayed beyond
repeated within 6 to 12 hours if needed to main- the initial period of time required for stabilization.
tain perfusion. If the plasma protein concentration If gastric contents are noted to contain digested
decreases to less than 3.5 g/dl, a plasma transfusion blood suggestive of gastric ulceration and/or
(10 ml/lb) should be given. necrosis, if there is radiographic evidence of perfo-
Gastric decompression must be accomplished ration or peritonitis, if decompression cannot be
immediately, occurring as soon as intravenous fluid achieved, or if decompression is difficult to main-
therapy has begun. Decompression is achieved tain, surgery should not be delayed for more than
either by passage of a stomach tube or by gastric 1 or 2 hours. If the patient responds well to initial
trocarization. Trocarization is easier and better therapy and decompression is sustained, surgery
tolerated by the patient than gastric intubation; can be delayed for 12 to 24 hours if necessary.
rarely does it cause peritonitis. A 16-gauge 2-inch In this circumstance decompression must be main-
needle or 14- to 16-gauge over-the-needle catheter tained by nasogastric or pharyngostomy tubes,
is used to trocarize the stomach on the left side at gastrostomy, or repeated orogastric intubation.
the site of maximal distention. Partial decompres- Spontaneous repositioning of the stomach occurs
sion in this manner often facilitates passage of a infrequently following decompression. In this cir-
large-bore orogastric tube for more complete cumstance surgery can be delayed or may not be
decompression and for gastric lavage. Once a gas- necessary.
tric tube is passed, gastric contents should be A gastropexy should be done to prevent recur-
removed. If possible, the tube should be left in rence of volvulus. A recent study determined that
place while radiographs are taken. If the stomach 55% of dogs that did not have gastropexy following
tube is difficult to pass, attempts should be made to surgery had a recurrence, compared with 4% recur-
pass the tube while holding the patient in an rence for dogs that did have gastropexy. Median
upright or sitting position. Gently shaking the survival time was 188 days for dogs not having gas-
patient while in the upright position may help. tropexy, compared with 547 days for dogs that did
Forcing the tube can cause esophageal or gastric have a gastropexy. Several types of gastropexy done
perforation. Inability to pass the tube does not neces- through laparotomy have been described and
sarily mean that volvulus is present, nor does the ability include incisional gastropexy, circumcostal gas-
to pass the tube mean that volvulus is not present. tropexy, belt-loop gastropexy, and tube gastropexy.
Gastric decompression can also be achieved by The benefit of doing a prophylactic gastropexy to
gastrostomy, usually done under sedation and local prevent GDV in a dog that is conformationally or
anesthesia. This is a temporary procedure that genetically predisposed has not been scientifically
fixes the stomach caudal to the right costal arch proven. It is logical, however, that gastropexy would
but does not return the stomach to normal posi- be of benefit to prevent a first episode of GDV in
tion. It is indicated for patient stabilization if a gas- such patients, as well as for patients in which an
tric tube cannot be placed or if the patient needs episode of GDV was managed medically. A rapid
several days of stabilization before surgical reposi- laparoscopic gastropexy technique that provides a
tioning and gastropexy. As an alternative, gastric strong fibrous adhesion between the stomach and
decompression can be done using an endoscope if abdominal wall has recently been described that
passage of an orogastric tube has not been success- could be used for this purpose, thereby eliminating
ful. The patient must be anesthetized for this the need for laparotomy.
190 CHAPTER 5 DISEASES OF THE STOMACH
Medical Management (Box 5-11) therapy can be started during initial therapy and
Antibiotics should be given to dogs with GDV continued for 7 to 10 days. If gastric mucosal dam-
because shock, mucosal damage, and portal hyper- age has been severe, omeprazole should be used as
tension predispose to sepsis. Antibiotics should soon as oral medication can be tolerated because it
be effective against gram-positive, gram-negative, is a more potent gastric antisecretory drug.
and anaerobic organisms. A combination of ampi-
cillin (10 mg/lb intravenously) and enrofloxacin
(2.5 mg/lb intramuscularly) is a good choice. Management of Complications
Second-generation cephalosporins (e.g., cefox- Cardiac arrhythmias, DIC, and GI motility disor-
itin 10 mg/lb every 8 hours intravenously) or ders are common complications occurring during
trimethroprim-sulfa antibiotics are reasonable alter- the acute and convalescent phases of disease.
natives. Corticosteroids may be beneficial for the Cardiac arrhythmias can occur at the time of pres-
initial management of shock to improve capillary entation but may not develop until as long as
blood flow, to decrease capillary permeability, to 72 hours after onset of GDV. Continuous electro-
reduce intestinal absorption of endotoxin, and to cardiographic (ECG) monitoring is required from
inhibit tissue-damaging phospholipases. Short- presentation until the dog is discharged from
term, high-dose therapy is recommended; pred- the hospital. Ventricular premature contractions
nisolone sodium succinate (20 mg/lb intravenously, (VPCs), paroxysmal ventricular contractions, and
given every 1 to 3 hours as needed) or dexametha- ventricular tachycardia are common. Correction
sone sodium phosphate (5 mg/lb intravenously, of acid-base, electrolyte (especially potassium), and
given every 3 to 6 hours as needed) is recom- fluid balance is the first step in control of arrhyth-
mended to treat shock. H2-receptor antagonists can mias. Antiarrhythmic therapy is indicated if ven-
be given to help diminish gastric ulceration. This tricular tachycardia with a heart rate of 150 beats
CHAPTER 5 DISEASES OF THE STOMACH 191
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44:1512, 1983. action of omeprazole: a survey of its inhibitory actions
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testinal neoplasms, Vet Pathol 14:447, 1997. Walter MC, Matthiesen DT: Acquired antral pyloric
Pennick DG et al.: Ultrasonographic evaluation of gas- hypertrophy in the dog, Vet Clin North Am 23:547,
trointestinal diseases in small animals, Vet Radiol 1993.
Ultrasound 31(30):134, 1990. Zerbe CA et al.: Pancreatic polypeptide and insulin-
Rawlings CA et al.: A rapid and strong laparoscopic- secreting tumor in a dog with duodenal ulcers and
assisted gastropexy in dogs, Am J Vet Res 62(6):871, 2001. hypertrophic gastritis, J Vet Intern Med 3:178, 1989.
A B
FIGURE 5-4 Normal stomach. A, Endoscopic appearance of a normal stomach.The smooth, pale-pink rugal
folds of the greater curvature of the gastric body gradually become more linear distally at the junction with the
pyloric antrum.The incisura angularis appears as a curved fold located at the 12 to 3 o’clock position. B, Appearance
of a normal pyloric antrum (foreground) and pylorus (upper left).The antral mucosa is smooth, pale pink, and without
rugal folds.The closed pyloric orifice is located at the center of the converging mucosal folds.
FIGURE 5-6 NSAID-induced gastric ulcer. A, Gastric ulcer in pyloric antrum of a 5-year-old Welsh corgi that
had been treated for back pain with ibuprofen (325 mg every day for 5 days).The dog had an acute onset of
vomiting and an episode of melena on the day of presentation. B, Healing gastric ulcer in the same patient after 7
days of treatment with omeprazole (0.3 mg/lb every day).
A B
FIGURE 5-7 Helicobacter gastritis. A, Endoscopic view of the gastric body and incisura angularis in a
3-year-old English bulldog with chronic intermittent vomiting. Raised nodules, some with a central reddened
craterlike appearance, were present throughout the body and antrum. B, Endoscopic view of the pyloric antrum
from the same dog showing a diffusely nodular mucosa.The pylorus is seen distally in the center of the image.
Biopsy revealed the nodules to be accumulations of lymphocytes. Urease-positive Helicobacter organisms were
present on the surface musosa and extending into the gastric pits. Clinical signs resolved after treatment with
omeprazole (0.3 mg/lb every day) in combination with amoxicillin (10 mg/lb 2 times a day) for 14 days.
FIGURE 5-8 Gastric retention of food particles and FIGURE 5-9 Malignant gastric ulcer located on the
bile-colored fluid in a 12-year-old miniature poodle incisura angularis (1 to 3 o’clock position in the field
with clinical signs of intermittent vomiting, of view) in a 13-year-old Weimaraner with a 2-month
regurgitation, inappetence, and bloating.The dog had history of chronic vomiting and weight loss.The dog
no food or water for 14 hours before endoscopy. had hypochromic microcytic anemia.The raised edges
Results of gastric mucosal biopsies were normal, and and central crater of the ulcer were very firm and
the dog was diagnosed with primary (idiopathic) required that multiple biopsy specimens be obtained
gastric motility disorder. Clinical signs improved, but from each of several sites to ensure adequate depth of
did not resolve, when the dog was treated with tissue was obtained. Histopathologic findings
cisapride and dietary management (small meals, fat- confirmed gastric adenocarcinoma.
restricted food).
6
ACUTE MEDICAL
DISEASES OF THE
SMALL INTESTINE
Andrew Triolo
Michael R. Lappin
195
196 CHAPTER 6 ACUTE MEDICAL DISEASES OF THE SMALL INTESTINE
Chloride follows passively inward along an electrical sorption, and abnormal intestinal motility. The best
gradient established by inward sodium transport. understood stimuli in humans are bacterial entero-
Bicarbonate is rapidly absorbed in the jejunum by toxins resulting in secretory diarrhea. Bacteria
active transport or is neutralized by hydrogen ions, such as Escherichia coli and Vibrio, Clostridium, and
generating water and carbon dioxide. In the ileum, Staphylococcus spp. induce intestinal secretion by
chloride absorption and bicarbonate absorption are increasing intracellular concentrations of cyclic
coupled, such that bicarbonate moves out in adenosine nucleotides. Acute diarrhea in patients
exchange for inward transport of chloride. As a that eat spoiled food (garbage enteritis) may be
result, pH and bicarbonate concentration increase in from ingestion of preformed enterotoxins. Dietary
the distal small bowel; fluid losses originating there fatty acids and bile acids also stimulate intestinal
are more likely to cause metabolic acidosis than are secretion, as do certain GI hormones and intestinal
losses from the proximal small intestine. obstruction.
Intestinal secretion involves the net efflux of an Malabsorptive diarrhea results from mucosal or
isotonic solution of water and electrolytes. This is an submucosal diseases that impair absorption by
important mechanism of fluid loss and may induce either the small or the large intestine. Diseases of
severe diarrhea. Intestinal secretion can be triggered the intestinal mucosa may directly impair sodium
by a number of stimuli, including bacterial entero- resorption, thereby inhibiting water resorption
toxins, malabsorbed substances such as unconjugated and inducing diarrhea. Poorly absorbed dietary
bile acids and fatty acids, certain drugs, and mechan- substances (e.g., complex carbohydrates such as
ical obstruction of the small bowel. sucralfate) also may interfere with water resorption
Abnormal intestinal motility also may induce by altering osmotic gradients. Some products of
diarrhea and fluid losses, although the relationships maldigestion, such as bile acids, may directly
between intestinal motility, secretion, and absorp- inhibit sodium transport in the colon and also
tion are generally poorly understood. induce diarrhea.
Diarrhea results from either impaired absorp- Intestinal mucosal damage results in generalized
tion or excessive solute (including exudation) transudation of water and electrolytes, as well as
secretion. Increased osmolality within the intes- plasma proteins and blood, when injury is severe.
tinal lumen results in net water loss as well. Normal mechanisms for sodium transport also are
Diarrhea usually results in loss of fluids isotonic to disrupted. These mechanisms (combined secre-
plasma. The major solutes in diarrhea fluid are tory and malabsorptive diarrhea) are thought to be
sodium, chloride, organic anions, and potassium. largely responsible for diarrhea that develops in
In most instances the primary body deficits due to acute small intestinal diseases characterized by
diarrhea are in sodium and water. Loss of isotonic severe, bloody diarrhea. Examples include acute
fluid decreases circulating plasma volume and may viral enteritis and canine hemorrhagic gastroen-
in severe instances (e.g., parvoviral enteritis) pre- teritis.
cipitate hypovolemic shock. Because isotonic It is likely that altered intestinal motility plays
fluids are lost, serum electrolyte concentrations a role in the pathogenesis of acute diarrhea,
usually remain normal initially. During diarrheal although the mechanisms and prevalence in ani-
diseases the most important source of potassium mals are poorly understood. Segmental contrac-
loss is via urine, mediated by aldosterone released tions of the intestines are reduced with most
in response to extracellular fluid volume deple- causes of diarrhea, leading to hypomotile gut.
tion. When diarrhea is severe and/or prolonged, For this reason, drugs that reduce intestinal
significant amounts of potassium also may be lost motility, such as anticholinergic agents, are not
via feces. Mild metabolic acidosis and hypokalemia recommended for symptomatic treatment of
are the most common acid-base and electrolyte acute diarrhea.
alterations observed in patients with acute small Diseases resulting in acute diarrhea can be
intestinal disease and diarrhea. grouped into primary (diseases of the intestine) or
secondary (diseases outside the intestine with diar-
rhea as a sequela) causes (Box 6-1). The most com-
Causes of Diarrhea mon primary diseases are parasites, infectious diseases,
Acute diarrheas can be grouped by mechanism or ingestion of toxins, and obstruction. Secondary diar-
disease. The most common mechanisms include rheas are less common causes of acute diarrhea and
abnormal fluid secretion (primarily sodium), malab- are discussed in other chapters.
CHAPTER 6 ACUTE MEDICAL DISEASES OF THE SMALL INTESTINE 197
BACTERIA PROTOZOANS
Bacterial cholangiohepatitis (S) Balantidium coli (ciliate; L)
Bacterial overgrowth (S) Cryptosporidium spp. (coccidian; S)
Bacterial peritonitis (S) Giardia spp. (flagellate; S)
Campylobacter jejuni (S, M, L) Isospora spp. (coccidian; L)
Clostridium perfringens (M, L) Entamoeba (amoeba; L)
Enterotoxigenic E. coli (S, M) Pentatrichomonas (flagellate; L)
Helicobacter spp. (V)
Salmonella spp. (S, M, L) MISCELLANEOUS
Prototheca (algae; L)
Histoplasma (fungal; L)
Neorickettsia spp. (rickettsia; S)
color, consistency). Occasionally parasites may be of Toxoplasma gondii and C. parvum. Giardia cysts
noted. are distorted by sugar centrifugation but can still
Due to the high prevalence of parasitic and be easily identified. Fecal sedimentation will
infectious diseases associated with acute diarrhea, recover most cysts and ova but will also contain
fecal testing is mandatory. To adequately assess debris. This technique is superior to flotation pro-
patients for infectious causes of diarrhea, a direct cedures for the documentation of fluke eggs. Some
smear, fecal flotation, fecal cytologic study, and parasites such as Trichuris spp. and Giardia spp. are
Cryptosporidium parvum screening test should be shed intermittently and so can be occult.
performed. Performing two to three fecal flotations over 5 to
7 days will increase sensitivity of detection of these
parasites. Feces should be refrigerated, not frozen,
Direct Smear. Liquid feces or feces that until assayed for parasites. If a fecal sample is to be
contains large quantities of mucus should be sent to a diagnostic laboratory for further analysis
microscopically examined immediately for the and will not be evaluated for parasites within 48
presence of protozoal trophozoites, including hours, it should be preserved. Polyvinyl alcohol,
those of Giardia spp., Pentatrichomonas hominis, Merthiolate-iodine-formalin, and 10% formalin
Balantidium coli, and Entamoeba histolytica. A direct preservation can be used. Because of routine avail-
saline smear can be made to potentiate observation ability, 10% formalin is commonly used; add 1 part
of these motile organisms. The amount of mucus feces to 9 parts formalin and mix well.
and feces required to cover the head of a pin is
mixed thoroughly with one drop of 0.9% NaCl.
Following application of a coverslip, the smear is Stained Smear. A thin smear of feces
evaluated for motile organisms by examining it should be made from all dogs or cats with large or
under × 100 magnification. Use of fresh feces gives small bowel diarrhea. Material should be collected
the highest yield of positive results. by rectal swab if possible to increase chances of
finding white blood cells. A cotton swab is gently
introduced 3 to 4 cm through the anus into the
Fecal Flotation. Cysts, oocysts, and ova in terminal rectum, directed to the wall of the rec-
feces can be concentrated to increase sensitivity of tum, and gently rotated several times. Placing a
detection. Most ova, oocysts, and cysts are easily drop of 0.9% NaCl on the cotton swab will facil-
identified after zinc sulfate centrifugal flotation. itate passage through the anus of cats but not
This procedure is considered by many to be opti- adversely affect cell structure. The cotton swab is
mal for the demonstration of protozoan cysts, in gently rolled on a microscope slide multiple times
particular Giardia spp., and so is a good choice to give areas with varying thickness. Following air
for a routine flotation technique in practice drying, a slide should be stained with Diff-Quik or
(Figure 6-1). Sugar centrifugation can be used for Wright’s or Giemsa stain. The slide should be
routine parasite evaluation and may be superior to examined for white blood cells and bacteria mor-
many techniques for the demonstration of oocysts phologically consistent with Campylobacter jejuni or
Clostridium perfringens (Figure 6-2). Presence of
neutrophils on rectal cytologic examination can
suggest inflammation induced by Salmonella spp.,
Ca. jejuni, or C. perfringens; fecal culture is indi-
cated in these cases (see the following section).
Histoplasma capsulatum or Prototheca may be
observed in the cytoplasm of mononuclear cells.
Methylene blue in acetate buffer (pH 3.6) stains
trophozoites of the enteric protozoans. Iodine
stains and acid methyl green are also used for the
demonstration of protozoans. Acid-fast staining of
a fecal smear is one of the C. parvum screening
procedures that should be performed in dogs or
cats with diarrhea. C. parvum is the only enteric
FIGURE 6-1 Giardia cysts. organism of approximately 4 to 6 µm in diameter
CHAPTER 6 ACUTE MEDICAL DISEASES OF THE SMALL INTESTINE 199
*
Remel, Lenexa, Kan.
†
Becton Dickinson Microbiology Systems, Franklin
Lakes, N.J.
‡
Diagnostic Laboratory, Colorado State University,
College of Veterinary Medicine and Biomedical
FIGURE 6-3 Cryptosporidium parvum oocysts. Sciences, Fort Collins, Colo.
200 CHAPTER 6 ACUTE MEDICAL DISEASES OF THE SMALL INTESTINE
physical examination findings. However, history severe that an intravenous catheter cannot be
and signalment can help aid in ranking differential placed, fluids should be given initially using
diagnoses. For example, viral enteritis and diarrhea intraosseous administration. Subcutaneous admin-
due to parasitism is most common in puppies and istration of fluids has unpredictable absorption and
kittens from crowded environments. Diagnostic is too slow to be useful in replacing large-volume
testing is usually necessary to make a definitive deficits in hypovolemic, hypotensive patients.
diagnosis. In most cases the therapeutic plan for Jugular catheters are preferred over peripheral
many patients with acute medical diseases of catheters in most cases; blood samples can be
the small intestine and severe diarrhea is initially drawn, the catheters can be maintained for up to 5
handled in a similar manner. days, the catheters are rarely affected by position
changes, there is reduced risk for phlebitis, and
there is the potential to measure central venous
Fluid and Electrolyte pressure to aid in monitoring fluid therapy.
Imbalances Fluids are initially administered rapidly
In cases with acute GI disturbances, of immediate (approximately 5 to 10 ml/lb over 30 to 60 min-
concern is correction of fluid and electrolyte utes, then the infusion rate is slowed) in patients
imbalances. In most instances patients are pre- with clinical hypovolemic shock (weak femoral
sumed to have lost sufficient isotonic fluids to pulse pressure, tachycardia, delayed capillary refill
become dehydrated. Restoration of normal circu- time, tacky mucous membranes). For more pro-
lating fluid volume is an immediate priority, both longed fluid administration, fluid needs for 24
to prevent renal functional impairment and to hours are calculated, and the total volume is
minimize further GI injury. Even if clinical evi- divided into three equal amounts, each to be
dence of dehydration is not apparent, patients administered every 8 hours. An infusion pump is
are assumed to be at least 5% dehydrated. Fluid optimal for constant-rate fluid infusion to patients
administration is calculated on the basis of the for- of any size to avoid overhydration.
mula in Box 6-3. The fluid of choice for initial volume replace-
In dehydrated patients fluids should always be ment is either a buffered crystalloid solution such
administered intravenously. If dehydration is so as lactated Ringer’s solution or Normosol-R or
0.9% saline solution. Both supply sodium and
chloride in adequate amounts. Also, lactated
BOX 6-3 Fluid Calculations for Use Ringer’s solution and Normosol-R are mildly
With Acute Gastrointes- alkalinizing (the buffer supplies bicarbonate) and
may be beneficial in patients with metabolic aci-
tinal Diseases dosis, especially patients with severe diarrhea. The
REPLACEMENT OF LOSSES buffer sources in Normosol-R are acetate and glu-
Dehydration (%) × body weight (kg) × 10 = ml conate. There has been a trend toward using glu-
fluid to be administered over 18 to 24 hours conate and acetate because they do not require
hepatic metabolism and they do not contribute to
MAINTENANCE NEEDS lactate levels. Administration of hypertonic solu-
30 ml/lb/day tions (e.g., 5% dextrose in lactated Ringer’s solu-
tion) has been advocated because hypertonic
ONGOING LOSSES
fluids, by shifting water from the intracellular to
Estimate continuing losses via vomiting and/or
diarrhea (overestimate if in doubt) and replace the extracellular compartment, may expand the
every 8 hours extravascular fluid compartment more than do
isotonic fluids. Fluids without high sodium con-
SAMPLE CALCULATION centrations (e.g., 2.5% dextrose in water or 2.5%
25-kg dog, 5% dehydrated, losing 200 ml of stool dextrose in 0.45% saline) should be avoided
every 8 hours because of the failure to replenish the sodium
Replacement of losses: 1250 ml deficit, which may decrease circulating fluid vol-
Maintenance needs: 1500 ml ume.
Ongoing losses: 600 ml Adequacy of fluid replacement therapy can be
Total volume to be administered over 24 hours:
easily and accurately evaluated by serial measure-
3350 ml, or 1117 ml every 8 hours
ment of body weight relative to body weight on
CHAPTER 6 ACUTE MEDICAL DISEASES OF THE SMALL INTESTINE 201
entry. Body weight should increase over the first ops more readily in young patients because of their
24 hours by at least the calculated fluid deficit small hepatic glucose reserves. In these patients,
(dehydration); 500 ml of water weighs 1 lb. Fluid glucose administration (typically as a 5% solution)
administration rate should be increased if body may produce a dramatic response. The caloric con-
weight begins to drop and should be decreased if tent of a 5% dextrose solution is far less than the
body weight increases excessively (more than 5% patient’s requirements but nonetheless seems to be
to 10% of calculated normal weight). Other helpful in alleviating some of the adverse effects of
parameters for assessing adequacy of fluid replace- sepsis. Glucose supplementation is begun either at
ment therapy include serial measurement of the outset or early in the course of fluid therapy in
hematocrit and plasma protein concentration, esti- patients with severe enteritis. It is recommended
mation of pulse pressure, capillary refill time, and that glucose levels be evaluated every 8 to 12
mucous membrane texture. hours during the period of intensive therapy.
Early potassium supplementation is critical for Blood glucose levels in normal patients on a 5%
optimum management of dogs and cats with dextrose drip should range from approximately
severe gastroenteritis and volume depletion, 130 to 180 mg/dl. A patient on a 5% dextrose
because depletion of body potassium stores devel- infusion with a low-normal glucose level is prob-
ops rapidly. Routine potassium supplementation ably significantly hypoglycemic and may be septic.
should begin before hypokalemia is detected Additional glucose (e.g., 7.5% infusion or intra-
because serum potassium content represents only a venous bolus [0.5 ml of 25% dextrose per pound])
small fraction of total body potassium stores. and other treatments for sepsis (see later section in
Adverse consequences of hypokalemia are numer- this chapter on acute viral enteritis) may be indi-
ous and include decreased GI motility, decreased cated. Bicarbonate administration is rarely indi-
cardiac output, hypotension, skeletal muscle weak- cated and in most instances is contraindicated by
ness, and general malaise and inappetence. Cats the added risks of iatrogenic hypernatremia,
seem particularly likely to develop hypokalemia hyperosmolality, and alkalosis. Metabolic acidosis
during periods of GI fluid loss and fluid replace- usually corrects rapidly after volume deficit
ment therapy, and they should be supplemented replacement.
early and aggressively. Empirical supplementation
of potassium is begun at 20 to 40 mEq/L of fluids
administered; cats should receive at least 40 Nonspecific Treatment
mEq/L. Daily measurement of serum potassium is of Diarrhea
recommended to facilitate maintenance of normal Many episodes of acute diarrhea are of viral or
concentration. If at all possible, serum potassium bacterial origin, are self-limiting, and generally do
concentration should be determined before initiat- not require specific therapy. Patients should not
ing supplementation. For example, although receive solid foods for at least 24 to 48 hours but
patients with adrenocortical insufficiency and should still be allowed access to liquids, because
advanced oliguric renal failure often develop GI intestinal absorptive functions are usually intact.
disease, they should not receive potassium because Electrolyte-containing solutions may be useful as
they are often hyperkalemic. These two important sources for oral fluid replacement in patients
disorders may be detected, and inappropriate without severe GI disease and large fluid losses.
potassium supplementation avoided, by determi- Suitable electrolyte replacement solutions include
nation of serum electrolyte and urea nitrogen lev- Enterolyte or Gatorade. Alternatively, a replace-
els. A rapid and reasonably reliable screening test ment solution can be formulated using guidelines
for identifying life-threatening hyperkalemia early developed by the World Health Organization: each
is an electrocardiogram. Typical early electrocar- liter of replacement solution should contain 120
diographic changes include tall, peaked T waves, mEq sodium, 25 mEq potassium, 48 mEq sodium
loss of P waves, and wide QRS complexes. bicarbonate, and 1.1 g glucose.
Glucose administration is particularly beneficial Antidiarrheal agents are occasionally indicated
in treating septic patients, especially dogs with par- for the treatment of idiopathic, acute diarrhea of
voviral enteritis and severe diarrhea. Sepsis results nonbacterial origin (fecal cytologic findings are
in a number of disturbances in glucose metabolism noninflammatory; see earlier section on diag-
that are often manifested clinically by develop- nostic considerations), especially diarrhea caused
ment of hypoglycemia. Hypoglycemia also devel- by dietary changes. Narcotics, generally considered
202 CHAPTER 6 ACUTE MEDICAL DISEASES OF THE SMALL INTESTINE
the most effective antidiarrheal agents, act by diagnostic work-up. Injectable drugs are usually
increasing segmental contractions of the small needed, and their use is therefore restricted to in-
and large intestine. Recommended narcotics for hospital patients.
short-term treatment of acute diarrhea (Table 6-1) Chlorpromazine (Thorazine) is preferred as the
include paregoric, diphenoxylate (Lomotil), or initial agent because it has a wide safety margin
loperamide (Imodium). Diphenoxylate is con- and is a potent antiemetic, acting on the emetic
traindicated in patients with severe underlying center, chemoreceptor trigger zone, and peripheral
hepatic disease. Neither diphenoxylate nor lo- chemoreceptors (see Table 6-1). In addition, chlor-
peramide should be used in patients with viral promazine is thought to function as a calcium chan-
enteritis, because delayed intestinal motility may nel antagonist, thereby decreasing cyclic adenosine
predispose to the development of sepsis. In addi- monophosphate concentration in intestinal epithe-
tion, these agents have been shown to prolong lial cells. The result is decreased intestinal epithelial
illness in humans with salmonellosis, shigellosis, cell secretion, especially when excess secretion is
and campylobacteriosis by interfering with normal mediated by enterotoxins. Chlorpromazine is also
immune clearance mechanisms. excellent for alleviating some of the discomfort
Salicylate-containing drugs, such as bismuth caused by nausea. Chlorpromazine may precipitate
subsalicylate (Pepto-Bismol), may be beneficial for hypotension in dehydrated patients and should
treatment of prostaglandin-mediated diarrhea. therefore not be given before fluid replacement in
Intestinal adsorbents such as kaolin pectate are volume-depleted patients.
generally of limited usefulness and must be admin- Metoclopramide (Reglan) given subcutaneously
istered in high doses. or as a constant intravenous infusion (see Table 6-1)
Antiemetic medication may be indicated for exerts antiemetic activity in the chemoreceptor
treatment of patients with persistent vomiting. trigger zone of the dog and increases gastric emp-
However, these agents should not be administered tying in dogs and cats. Adverse effects from meto-
to patients that are vomiting as a result of intestinal clopramide in dogs and cats are uncommon,
obstruction or before completing an adequate consisting largely of excessive excitement. Severe,
protracted vomiting that does not respond well to syndrome associated with feline leukemia virus
either chlorpromazine or metoclopramide should (FeLV) and feline immunodeficiency virus (FIV)
prompt consideration of possible intestinal obstruc- enteritis cause acute diarrhea in some cats. Feline
tion or pancreatitis and additional diagnostic evalu- panleukopenia is caused by a parvovirus closely
ation before continuing prolonged antiemetic related to canine parvovirus, and the intestinal
therapy. lesions are similar. In contrast to dogs, many
Ondansetron (Zofran) is a potent antiemetic parvovirus-infected cats have vomiting without
drug that is frequently effective in reducing severe diarrhea.
and frequent vomiting. It has been used in human Clinical outcome following exposure to par-
cancer patients undergoing therapy with cisplatin, voviruses depends largely on the degree of prior
a drug that frequently causes nausea and severe maternal immunity, virus strain, host immune
vomiting. Ondansetron acts as a selective antago- responses, and infecting dose of virus. Onset of
nist of serotonin 5HT3 receptors (a principal signs is usually within 3 to 5 days of exposure.
mediator of the emetic reflex). It is also effective in Small intestinal disease results from intestinal
decreasing the frequency of vomiting in patients mucosal injury that induces a combination of secre-
with severe parvoviral enteritis and should be used tory and malabsorptive diarrhea. Sepsis occurs
when chlorpromazine and metoclopramide do commonly in both dogs and cats with parvoviral
not provide adequate control. As the nausea and enteritis as a result of absorption of preformed bac-
vomiting are controlled, a state of increased com- terial toxins, as well as intact bacteria, across the
fort seems to prevail. At this time the primary lim- damaged intestinal epithelium. Bacteremia is more
itation for ondansetron is expense. It is strongly likely to occur in severely leukopenic patients.
recommended, however, that all hospitals that treat
dogs and cats stock at least one bottle of Diagnosis. Acute onset of vomiting, fever,
ondansetron so that it will be readily available for diarrhea (often bloody), and leukopenia (variable
use in patients that have intractable vomiting. finding) in a previously unvaccinated dog is con-
sistent with parvovirus infection. Parvovirus anti-
gen can be detected in feces by enzyme-linked
MANAGEMENT immunosorbent assay (ELISA),* but results can be
OF SPECIFIC ACUTE falsely negative based on timing of the infection or
SMALL INTESTINAL can be falsely positive due to modified live vaccine
DISEASES administration. Coronavirus usually induces
milder disease, and leukopenia, if present, is gener-
Acute Viral Enteritis ally less severe than in parvovirus infection.
General Considerations. The viral causes of Diagnosis of viral enteritis from organisms other
acute small intestinal disease in dogs include par- than parvovirus can be confirmed by fecal electron
voviruses 1 and 2, canine distemper virus, coro- microscopy.
navirus, astrovirus, and rotavirus (see Box Feline panleukopenia is tentatively diagnosed in
6-2). Disease due to coronavirus, astrovirus, and a young, previously unvaccinated cat with initial
rotavirus infection is rare. The disease caused by acute onset of vomiting and fever that progresses to
parvovirus in dogs (destruction of intestinal crypt bloody diarrhea and leukopenia (especially neu-
epithelium, lymphocyte depletion, neutropenia) is tropenia) within 24 to 48 hours. Diagnosis is con-
much more severe that that caused by coronavirus firmed by fecal electron microscopy or paired
(destruction of tips of intestinal villi).The severity serology. A primary differential diagnosis for dogs and
of disease associated with parvovirus infection of cats exhibiting findings consistent with parvoviral infec-
dogs is subjectively greater in some breeds, such tion is salmonellosis.
as Doberman pinschers, rottweilers, and pit bull
terriers. These breeds may have an inherited Treatment. Fluid losses, potassium deficits, and
immunodeficiency, but this has not been proved hypoglycemia should be corrected as described. In
conclusively to date. Coronavirus is generally asso- patients with signs of advanced sepsis, short-term
ciated with disease only in very young puppies. administration of a glucose-insulin-potassium mix-
In cats, panleukopenia virus and enteric coro- ture (3 g glucose/1 unit regular insulin/0.5 mEq
navirus are the two most common viral causes of
*
intestinal disease. However, the panleukopenia-like Synbiotics and IDEXX.
204 CHAPTER 6 ACUTE MEDICAL DISEASES OF THE SMALL INTESTINE
potassium chloride/kg, to be infused over 4 to treatment is administered for short periods of time
5 hours) may be warranted. If possible, once-daily (usually until the white blood cell count returns to
measurement of serum electrolyte concentrations normal); follow-up treatment with orally adminis-
and blood glucose monitoring at least twice daily tered antibiotics is not indicated. Leukocyte
are recommended while the patient remains criti- rebound is a favorable sign and usually indicates
cally ill. Both food and water are withheld for at that the patient will recover.
least the first 48 to 72 hours of treatment and Flunixin meglumine (Banamine) has been
are usually not reinstituted until vomiting and shown experimentally to increase survival of dogs
diarrhea have subsided. Small amounts of water after endotoxin administration and has been rec-
(or water plus electrolytes) are offered first over a ommended for treatment of dogs with sepsis due
24-hour period and, if well tolerated, are followed to parvoviral enteritis. Because of potential for gas-
by small meals of solid, easily digestible, bland food tric injury, only a single dose for emergency man-
over the next several days. agement of sepsis in dogs should be used.
Broad-spectrum antibiotics are indicated for In some parvovirus patients with severe
treatment of dogs and cats with severe gastroen- leukopenia, recombinant granulocyte colony-
teritis (especially those with hemorrhagic diar- stimulating factor (Neupogen) has been shown to
rhea), particularly if clinical findings consistent be effective in increasing white blood cell counts.
with sepsis are detected. However, routine use of However, use of these products has not correlated
antimicrobial therapy in all patients with acute to increased survival or decreased morbidity. Thus
viral enteritis is not indicated, because many with granulocyte colony-stimulating factor may not be
milder disease can be effectively managed without indicated for treatment of parvoviral enteritis.
antibiotics, thus avoiding the unnecessary expense Passive immunotherapy with serum or plasma
and risk their use entails. Studies have shown that from hyperimmune dogs or cats may lessen the
bacteremia is most likely to occur in patients with morbidity of acute viral enteritis, especially par-
enteritis and concurrent severe leukopenia, and it vovirus. Administration of antiparvovirus antibody
is these patients that are most likely to benefit from in this fashion may lessen viremia. Use of fresh
antimicrobial therapy. Bacteremia occurs uncom- plasma has the added advantage of potentiating
monly in patients with acute enteritis and normal opsonization of bacteria by fibronectin. On day 1
white blood cell counts. of hospitalization, 0.5 ml/lb of hyperimmune
The GI tract has a rich normal flora, and so serum or plasma should be given intravenously,
broad-spectrum coverage is necessary to cover for subcutaneously, or intramuscularly. Vaccinated
both aerobic bacteria (especially E. coli) and facul- blood donor animals or survivors of parvovirus
tative anaerobic bacteria (especially Bacteroides and infection are excellent donors. Red blood cells
Clostridium). Adequate coverage for both types of should not be administered unless needed.
bacteria can usually be attained by administration Hypoproteinemia often develops rapidly in
of a penicillin or first-generation cephalosporin patients with severe diarrhea and serious small
parenterally. Addition of an aminoglycoside or intestinal injury. As a consequence, plasma oncotic
quinolone is indicated for treatment of severely pressure drops and fluid losses via the bowel are
septic patients. Maintenance of normal blood vol- accelerated. Plasma or hetastarch should be used
ume is essential when using aminoglycoside antibi- to help restore normal oncotic pressure (see Table
otics, and patients should be monitored carefully by 6-1). Plasma has the advantage of supplying pas-
means of a daily urinalysis for signs of possible sive immunotherapy. Sufficient plasma is adminis-
aminoglycoside-induced nephrotoxicity. Once- tered to increase total protein concentration to at
daily aminoglycoside protocols should be used, and least the low-normal range. An in-line filter is
this drug class should not be administered until used to remove particulate material during plasma
hypovolemia and hypokalemia have been resolved. infusion.
Development of proteinuria or urine casts is often
the first warning of renal injury; aminoglycoside Sequelae. Intestinal intussusception is the most
treatment should be discontinued at this point. serious sequela that may develop during treatment
Cefoxitin, a second-generation cephalosporin, pro- for viral gastroenteritis. Altered intestinal motility
vides single-agent broad-spectrum coverage for is implicated. Careful abdominal palpation for the
patients with severe sepsis and avoids the potential presence of an abdominal mass should be per-
toxicity of aminoglycocides. In general, antibiotic formed daily. Persistent vomiting after apparent
CHAPTER 6 ACUTE MEDICAL DISEASES OF THE SMALL INTESTINE 205
clinical recovery should prompt a careful search with the short-term oocyst shedding period (gen-
for intussusception. Abdominal radiographs, ultra- erally less than 14 days).
sound, or contrast studies may be necessary to diag-
nose intussusception. Other potential complications Diagnosis. All dogs and cats with acute vomit-
include bacterial embolization and metastatic ing or diarrhea should be evaluated for parasites
abscessation (joints, subcutis, kidney) and intra- (see diagnosis section). Diagnosis of helminth
venous catheter infection. Catheters should be infections is based on demonstration of ova after
maintained in a sterile manner under a bandage that fecal flotation. Ova detection can be used to doc-
completely covers the catheter, and catheters should ument cestode infection, but proglottid detection
be rotated to a different vein every 72 hours (up to occurs most commonly (D. caninum and Taenia
5 days for jugular catheters). spp.). Trophozoites of protozoans are best demon-
strated by wet mounts performed on fresh feces.
For parasites that are commonly occult, such as
Gastrointestinal Parasitism Trichuris vulpis, Giardia, and Cryptosporidium spp.,
General Considerations. Parasitism is com- performance of multiple fecal evaluations
mon in dogs and cats, and, depending on the improves sensitivity. Physaloptera and Ollulanus
parasite, can occur regardless of age, breed, or sex. rarely shed eggs in feces and frequently are diag-
Although outdoor animals are more likely to be nosed only by endoscopy or therapeutic trials.
parasitized than indoor animals, indoor animals Giardia can be found in duodenal aspirates of dogs
can be exposed to some parasites from transmis- but lives in the distal small intestine of cats.
sion by transport hosts such as rodents, flies, and Antigen ELISA is being assessed as a diagnostic aid
cockroaches. Predominant clinical signs of disease for giardiasis and cryptosporidiosis (see diagnosis
vary by the parasite (see Box 6-2), but most can section).
induce vomiting and diarrhea.
The most common helminth parasites causing Treatment. There are multiple antiparasite drugs
GI tract disease in dogs and cats are listed in Box that can be effective (Table 6-2). Anthelmintics such
6-2. Toxocara spp., Toxascaris leonina, Ollulanus tri- as pyrantel pamoate should be routinely adminis-
cuspis, and Physaloptera are generally found in the tered to all puppies and kittens on initial examina-
upper GI tract and are commonly associated with tion and again 2 to 3 weeks later because of
vomiting. The hookworms Ancylostoma spp. and zoonotic health risks. In heartworm endemic areas,
Uncinaria stenocephala are found in the intestines use of preventatives that also control helminths is
and cause diarrhea and significant blood loss, par- indicated. Because T. vulpis infection is commonly
ticularly in small dogs or cats. Trichuris spp. live in occult, all dogs with large bowel diarrhea with no
the large intestine and cecum and can result in obvious cause should be given fenbendazole or
large bowel diarrhea. Dipylidium caninum, Taenia other anthelmintic with activity against T. vulpis.
spp., and Echinococcus spp. are the most common Praziquantel is one drug with activity against the
cestodes that infect small animals. Dogs and cats three major canine tapeworms. Fenbendazole can be
are infected with D. caninum after ingesting effective for the treatment of Taenia spp. infection.
infected fleas and with Taenia spp. and Echinococcus Entamoeba, Giardia, Balantidium, and Pentatrichomonas
spp. by carnivorism. Clinical signs are minimal but generally respond clinically to metronidazole, but
may include failure to thrive. Pentatrichomonas and Giardia may not be cleared
The most common protozoal agents potentially from the GI tract. Fenbendazole, albendazole, paro-
causing GI tract disease in dogs and cats are Giardia momycin, and febantel-pyrantel-praziquantel (dogs)
spp., Cryptosporidium spp., Isospora spp., and are alternate anti-Giardia drugs. If Giardia infection
Pentatrichomonas (see Box 6-2). Giardiasis and alone is suspected, fenbendazole is superior to
cryptosporidiosis most commonly induce small metronidazole. Albendazole has been associated with
bowel diarrhea; Isospora spp. and P. hominis are most neutropenia in dogs and cats, and so fenbendazole
commonly associated with mixed or large bowel appears to be safer. Addition of insoluble fiber to the
diarrhea. Isospora spp. infection usually causes dis- diet may aid in the control of giardiasis. Sequential
ease only in puppies and kittens. Only cats com- administration of clindamycin followed by tylosin
plete the coccidian life cycle of T. gondii; oocysts in blocked oocyst shedding and resolved diarrhea in
dog feces are from the ingestion of cat feces. This one cat with chronic, clinical cryptosporidiosis.
parasite rarely induces diarrhea and is only associated Tylosin alone was apparently successful in blocking
TABLE 6-2 Drugs Commonly Used in the Management of Parasitic
Diseases Associated With Acute Gastrointestinal Disease
Organism/Generic Drug Name Common Canine Dosage Common Feline Dosage
Balantidium coli
Metronidazole 4.5-11 mg/lb PO q12h for 8 days NA
Tetracycline 11 mg/lb PO q8h for 7-10 days NA
Cryptosporidium parvum
Azithromycin 2.5-5 mg/lb PO q12h for 5-7 days 3-7 mg/lb PO q12h for 5-7 days
Paromomycin 75 mg/lb PO q12h for 5 days 75 mg/lb PO q12h for 5 days
Tylosin 4.5 mg/lb PO q8-12h for 21 days 4.5 mg/lb PO q8-12h for 21 days
(administer in capsules for cats)
Isospora spp.
Trimethoprim-sulfonamide 6-13 mg/lb PO q12h for 5 days 6 mg/lb PO q12h for 5 days
Sulfadimethoxine 22-25 mg/lb PO daily for 5-20 days 22-25 mg/lb PO daily for 5-20 days
Furazolidone 3-9 mg/lb PO q12-24h for 5 days 3-9 mg/lb PO q12-24h for 5 days
Amprolium 300-400 mg PO daily for 5 days 60-100 mg daily for 5 days
Paromomycin 75 mg/lb PO q12h for 5 days 75 mg/lb PO q12h for 5 days
Giardia
Metronidazole 4.5-11 mg/lb PO q12h for 8 days 4.5-11 mg/lb PO q12h for 8 days
Fenbendazole 22 mg/lb PO q24h for 3-7 days 22 mg/lb PO q24h for 3-7 days
Furazolidone 1.8 mg/lb PO q12h for 7 days 1.8 mg/lb PO q12h for 7 days
Paromomycin 75 mg/lb PO q12h for 5 days 75 mg/lb PO q12h for 5 days
Praziquantel, pyrantel, and PO daily for 3 days NA
febantel
Pentatrichomonas hominis
Metronidazole 4.5-11 mg/lb PO q12h for 8 days 4.5-11 mg/lb PO q12h for 8 days
Paromomycin 75 mg/lb PO q12h for 5 days 75 mg/lb PO q12h for 5 days
Toxoplasma gondii
Azithromycin 2.5-5 mg/lb PO q12h for 5-7 days 3-7 mg/lb PO q12h for 5-7 days
Clindamycin hydrochloride 5.5 mg/lb PO, IM q12h for 28 days 5.5 mg/lb PO, IM q12h for 28 days
Clarithromycin 2.5-5 mg/lb PO q12h for 7 days 2.5-5 mg/lb PO q12h for 7 days
Pyrimethamine 0.1-0.25 mg/lb PO q24h for 28 days Usually not used due to toxicity
Trimethoprim-sulfonamide 6.5 mg/lb PO q12h for 28 days 6.5 mg/lb PO q12h for 28 days
Doxycycline 2.5-5 mg/lb PO q12h for 4 weeks 2.5-5 mg/lb q12h PO for 4 weeks
(caution regarding potential for
esophageal stricture formation in
cats, see Chapter 4)
Ascarids
Dichlorvos 5 mg/lb PO once 5 mg/lb PO once
Febantel 5 mg/lb PO q24h for 3 days 5 mg/lb PO q24h for 3 days
Pyrantel pamoate 2.2 mg/lb PO once 2-7 mg/lb PO once
Fenbendazole 25 mg/lb PO once NA
Hookworms
Dichlorvos 5 mg/lb PO once 5 mg/lb PO once
Febantel 5 mg/lb PO q24h for 3 days 5 mg/lb PO q24h for 3 days
Pyrantel pamoate 2.2 mg/lb PO once 2-7 mg/lb PO once
Fenbendazole 25 mg/lb PO once NA
Dipylidium caninum
Epsiprantel 2.5 mg/lb PO, repeat in 3 weeks 1.25 mg/lb PO, repeat in 3 weeks
Praziquantel 2-6 mg/lb PO, SQ, repeat in 2-6 mg/lb PO, SQ, repeat in
3 weeks 3 weeks
Taenia pisiformis
Epsiprantel 2.5 mg/lb PO, repeat in 3 weeks 1.25 mg/lb PO, repeat in 3 weeks
Praziquantel 2-6 mg/lb PO, SQ, repeat in 3 weeks 2-6 mg/lb PO, SQ, repeat in
3 weeks
Echinococcus
Epsiprantel 2.5 mg/lb PO, repeat in 3 weeks 1.25 mg/lb PO, repeat in 3 weeks
Praziquantel 2-6 mg/lb PO, SQ, repeat in 3 weeks 2-6 mg/lb PO, SQ, repeat in 3
weeks
oocyst shedding in 12 other dogs or cats with should be maintained. Giardia, Cryptosporidium,
diarrhea. Paromomycin,* an orally administered Entamoeba, Balantidium, and Pentatrichomonas
aminoglycoside, has effect against Pentatrichomonas, should be considered potentially zoonotic. Not all
Cryptosporidium, and Giardia but has been associated Giardia or C. parvum isolates cross-infect other
with acute renal failure in cats with hemorrhagic species, but this cannot be determined by micro-
diarrhea. The T. gondii oocyst shedding period in scopic examination. Cats have not been shown to
cats can be shortened by administration of clin- be infected by Balantidium and are unlikely to give
damycin. Clinical signs from Isospora spp. generally Entamoeba to people because it is rare in cats and
respond to the administration of sulfadimethoxine; cats are unlikely to form cysts.
alternatives include other sulfas, clindamycin, and
paromomycin. Drugs used to treat Isospora spp. are
static, and so cysts may still be seen after treatment. Acute Bacterial Gastroenteritis
General Considerations. The most com-
Sequelae. Severe blood loss anemia may occur monly recognized primary bacterial pathogens of
from hookworm infestation. Some intestinal para- the GI tract of dogs and cats include Salmonella
sites such as Giardia or Cryptosporidium may be dif- spp., C. jejuni, C. perfringens, Helicobacter spp., and
ficult to clear. In addition, chronic vomiting or enterotoxigenic E. coli. Each agent can cause vom-
diarrhea from secondary inflammatory cell infil- iting; all but Helicobacter spp. are commonly associ-
trates into the GI tract may occur (see other sec- ated with the clinical signs of large, small, or mixed
tions). Some parasitic infections are zoonotic. bowel diarrhea. C. perfringens–associated disease
Visceral larva migrans can occur in humans fol- appears to be less common in cats than in dogs.
lowing infection by Toxocara spp. eggs. Follow- Each of the bacterial infections can be associated
ing human ingestion of infectious eggs, larvae with contaminated environments, direct contact
penetrate the intestinal wall and migrate through with infected animals, or potentially ingestion of
the tissues, leading to eosinophilic granulomatous infected prey species. Salmonellosis and campy-
reactions involving the skin, lungs, central nervous lobacteriosis are commonly associated with inges-
system, and eyes. Ocular larva migrans most com- tion of undercooked poultry products. It is
monly involves the retina and can cause reduced also possible that each of the organisms could be
vision, strabismus, uveitis, and endophthalmitis. carried by healthy animals only to overgrow
Cutaneous larva migrans in humans can be and induce disease because of other stimuli such
induced with infection by all three species of as stress, diet change, or antimicrobial therapy.
hookworms infecting dogs and cats in the United Salmonellosis is commonly associated with poly-
States. Larvae are released from eggs passed into systemic clinical signs such as fever, as well as
the environment in feces; infectious larvae infect neutropenia, in the sepsis stage of infection.
humans by skin penetration. Larval migration Approximately 50% of the cats with salmonellosis
results in the development of an erythematous, are seen for evaluation of fever without GI tract
pruritic cutaneous tunnel. Occasionally larvae will disease signs; the owner may report a recent his-
reach the lungs and cornea. Ancylostoma caninum tory of songbird ingestion. Campylobacteriosis is
also causes eosinophilic enteritis in humans. most common in puppies and kittens, and the
Transmission of small animal cestodes to humans organism is less likely to cause polysystemic signs
occurs following ingestion of the intermediate than salmonellosis. Small animals can also be
host (flea, Dipylidium) or by the ingestion of eggs infected by other potential bacterial pathogens
(Echinococcus). Dipylidium infection is most com- such as Shigella and Yersinia enterocolitica but seem
mon in children and can lead to diarrhea and pru- to be relatively resistant to disease induced by
ritus ani. Following human ingestion of eggs, these organisms.
Echinococcus enters the portal circulation and
spreads throughout the liver and other tissues, Diagnosis. Helicobacteriosis is diagnosed clini-
causing hydatid disease. Prevention and/or control cally by the combination of demonstration of
is primarily by use of taeniacides and sanitation spirochetes by cytologic or histologic studies, pos-
procedures. To lessen human risks, dogs and cats itive urease test results, presence of inflammation,
should not be allowed to hunt and flea control exclusion of other causes of inflammation, and
response to treatment (see Chapter 5). Presence of
*
Parke-Davis, Morris Plains, N.J. large numbers of neutrophils on rectal cytologic
208 CHAPTER 6 ACUTE MEDICAL DISEASES OF THE SMALL INTESTINE
Treatment. Supportive care and nonspecific Diagnosis. Diagnosis is based on the presence
therapy as discussed for acute viral diseases should of significant hemoconcentration (packed cell vol-
be given as indicated. Holding the patient off ume may approach 70% to 80%), with little to no
food for 24 hours may speed resolution of clinical increase in total protein concentration, in a small
disease. C. perfringens generally responds to treat- dog with typical clinical signs. Hypovolemia is
ment with ampicillin, amoxicillin, tylosin, or thought to account for the increase in hematocrit,
metronidazole. The drug of choice for campy- whereas gut losses of serum proteins serve to pre-
lobacteriosis is erythromycin; alternative drugs are vent a corresponding increase in serum total pro-
tetracyclines, chloramphenicol, and potentially tein concentration.
tylosin. Salmonellosis should be treated only
parenterally because of rapid resistance that Treatment. Early, aggressive replacement of
occurs following oral administration of antibiotics. fluid volume deficits is critical to successful man-
Appropriate antibiotics for the treatment of salmo- agement of dogs with HGE. Either normal saline
nellosis include chloramphenicol, trimethoprim- or lactated Ringer’s solution (9 to 18 ml/lb) is
sulfonamide, and amoxicillin; quinolones are infused rapidly intravenously over 1 to 2 hours,
effective but should be reserved for resistant infec- followed by slower infusion of a sufficient volume
tions. Helicobacter spp. infection is usually treated of fluids to correct dehydration, replace ongoing
with the combination of metronidazole and tetra- losses, and provide for maintenance needs (see pre-
cycline or amoxicillin and metronidazole with vious discussion of fluid therapy) over the next
acid reduction therapy (e.g., omeprazole, famoti- 24 hours. Electrolyte concentration and body
dine). Clarithromycin can be effective and can be weight should be monitored closely during treat-
used once daily in cats. ment. To date, evidence has not been presented to
indicate that administration of antibiotics is bene-
Sequelae. Chronic gastritis is associated with ficial, although patients with evidence of severe
Helicobacter spp. infection in some cases. It is pos- leukopenia or presence of a left shift on complete
sible that some chronic diarrheas are associated blood count should probably receive antibiotic
with bacterial infections. There appears to be treatment. Antiemetic drugs may be warranted if
minimal zoonotic risk associated with Helicobacter vomiting is severe or prolonged.
infections of small animals. However, dogs and
cats infected with Salmonella and Campylobacter Sequelae. Coagulation abnormalities, especially
will shed the organisms into the human environ- thrombocytopenia, may develop but are usually
ment for a period of time after acute infection. reversed once fluid deficits are corrected.
Thus feces of these patients should be handled Recovery typically occurs rapidly over 24 to
carefully. 48 hours, and residual effects from HGE are rare.
CHAPTER 6 ACUTE MEDICAL DISEASES OF THE SMALL INTESTINE 209
functional impairment (hypovolemia). Outcome have perforated or that have undergone ischemic
after correction of bowel obstruction depends injury may be helpful in enhancing intestinal heal-
largely on whether complications occur (sepsis, ing and guarding against bowel leakage.
peritonitis, bowel perforation, and acute renal fail-
ure). Sequelae. Complications after intestinal sur-
gery, although generally uncommon, include peri-
Diagnosis. Abdominal palpation and radio- tonitis, stricture formation, abscessation, formation
graphic evaluation are the two primary methods of of adhesions, and malabsorption syndromes fol-
diagnosis of obstruction. Survey abdominal radio- lowing resection of large segments of small bowel.
graphs are obtained first, and if evidence of obstruc-
tion is observed (see Chapter 2), contrast material REFERENCES
(e.g., liquid barium or barium-impregnated
polyethylene spheres [BIPS]) may be adminis- Bornay-Llinares FJ et al.: Identification of Cryptosporidium
felis in a cow by morphologic and molecular methods,
tered to enhance visualization of possible obstruc-
Appl Environ Microbiol 65:1455, 1999.
tive lesions and to evaluate intestinal motility. Cubeddu LX et al.: Efficacy of ondansetron and the role
Abdominocentesis and cytologic evaluation of any of serotonin in cisplatin-induced nausea and vomiting,
fluid obtained also may be helpful in determining N Engl J Med 322:810, 1990.
whether bowel leakage and subsequent peritonitis Hill S et al.: Prevalence of enteric zoonoses in cats, J Am
have occurred. Vet Med Assoc 216:687, 2000.
Lappin MR, Calpin JP: Laboratory diagnosis of
Treatment. If acute small intestinal obstruction is protozoal infections. In Greene CE, ed: Infectious dis-
diagnosed, immediate surgery is nearly always indicated, eases of the dog and cat, ed 2, Philadelphia, 1998, WB
because delay in surgical correction of an obstructing Saunders.
lesion may lead to further ischemic injury and possible Marks SL et al.: Evaluation of methods to diagnose
Clostridium perfringens–associated diarrhea in dogs,
intestinal necrosis and perforation. Thorough abdomi-
J Am Vet Med Assoc 214(3):357, 1999.
nal exploration is done at the time of surgery, even Macintire DK et al.:Treatment of dogs naturally infected
if an obvious lesion is initially identified. If a lesion with canine parvovirus with lyophilized canine IgG.
cannot be identified grossly, intestinal biopsy (at ACVIM Proceedings, June 10, 1999, Chicago.
least jejunum and ileum) is warranted, because Obradovich JE et al.: Evaluation of recombinant canine
certain intestinal infectious or inflammatory dis- granulocyte colony-stimulating factor as an inducer of
eases may induce signs that mimic intestinal granulopoeisis, J Vet Intern Med 5:75, 1991.
obstruction. If bowel perforation with severe peri- Pieniazek NJ et al.: New Cryptosporidium genotypes in
tonitis has developed, delayed body wall closure HIV-infected persons, Emerg Infect Dis 5:444, 1999.
with sterile open packing of the abdomen may be Rewerts JM et al.: Recombinant human granulocyte
used to facilitate drainage. The abdomen is closed colony-stimulating factor for treatment of puppies
with neutropenia secondary to canine parvovirus
after several cycles of abdominal lavage and when
infection [see comments], J Am Vet Med Assoc 213:991,
the infection appears to be under control (usually 1998.
1 to 2 days). If there is any question as to bowel Sargent KD et al.: Morphological and genetic charac-
viability at the time of initial exploratory lapa- terisation of Cryptosporidium oocysts from domestic
rotomy, a second laparotomy 24 hours later may be cats, Vet Parasitol 77:221, 1998.
indicated to better assess intestinal viability. Serosal Triolo AJ: Clinical use of hypertonic saline. ACVIM
patching of bowel segments (especially colon) that Proceedings, June 10, 1999, Chicago.
C H A P T E R
7
CHRONIC
DISEASES OF THE
SMALL INTESTINE
Todd R.Tams
Chronic disorders of the small intestine in dogs disease usually disrupts normal function of the
and cats are frequently encountered in clinical small intestine and results in vomiting and/or
practice. A majority of these disorders can be suc- diarrhea, and weight loss.
cessfully managed. It is urged, however, that clini-
cians pursue early meaningful diagnostic evaluation
on patients that have chronic symptoms (lasting
more than 2 to 4 weeks) because some disorders, CLINICAL SIGNS OF
if not treated appropriately, can result in severe SMALL INTESTINAL
malabsorptive disease and death. In the interim
some patients with chronic disorders are lethargic,
DISEASE
inappetent, and sometimes uncomfortable (e.g., The most common clinical signs associated with
intestinal cramping and pain may be present). Owner chronic small intestinal disease are diarrhea and
frustration also escalates when symptoms persist weight loss. Vomiting is common in inflamma-
with little or no improvement. Early diagnostic eval- tory disorders, and intermittent inappetence, list-
uation and correct therapeutic intervention alleviate lessness, borborygmus, flatulence, trembling, and
many problems. signs of abdominal pain are also important symp-
In the dog and cat the primary function of the toms. Signs of abdominal pain may be subtle and
small intestine is to assimilate nutrients by the not obvious to the owner. In association with
processes of digestion and absorption. Important marked hypoproteinemia resulting from infiltra-
motility functions include rhythmic segmentation tive intestinal diseases (protein-losing enteropa-
to slow the passage of contents through the tube thy), signs may include pitting subcutaneous edema,
and peristalsis to move contents continuously in ascites, or dyspnea associated with hydrothorax.
an aboral direction. The movement of contents Colonic disorders are a common cause of diar-
through the small intestine is the net effect of rhea. Diarrhea of large intestinal origin should be
these two important types of motility. Intestinal differentiated clinically from small intestinal causes
211
212 CHAPTER 7 CHRONIC DISEASES OF THE SMALL INTESTINE
because work-up and treatment often differ (see syndrome, and intestinal neoplasia. The diagnostic
Chapter 8). approach to the problem of chronic diarrhea was
reviewed in Chapter 1. The diagnosis and treat-
ment of each individual disorder are presented
CLASSIFICATION here.
Malabsorption syndrome includes chronic enter-
opathies that cause a generalized failure of diges-
tion and absorption, resulting in diarrhea and
CHRONIC GIARDIASIS
weight loss. Some common causes include diffuse Giardia as a cause of acute diarrhea was discussed
chronic inflammatory bowel disease (IBD) in Chapter 6. Diarrhea is the most common clin-
(lymphocytic-plasmacytic enteritis, eosinophilic ical sign in symptomatic dogs and cats. Until a
enteritis, granulomatous enteritis), lymphangiecta- diagnosis is made and adequate therapy instituted,
sia, lymphosarcoma, idiopathic villous atrophy, and Giardia may cause intermittent or chronic ongo-
histoplasmosis. Malabsorption may occur second- ing diarrhea. In some practice areas Giardia is the
ary to bacterial overgrowth, parasitic infections most common parasitic cause of diarrhea. Other
such as giardiasis, and massive bowel resection. signs may include weight loss and unthriftiness.
Protein-losing enteropathy refers to a group of Occasionally vomiting may be the predominant
disorders characterized by excessive loss of serum sign.
proteins into the intestinal tract. Blood chemistry Giardia has proven to be a difficult problem
profiles reveal proportionately equal depressions of both to diagnose definitively and to treat suc-
albumin and globulin concentrations, often with a cessfully. For example, despite adequate treatment
total protein of less than 5.5 g/dl. Hypoproteinemia regimens using both metronidazole (Flagyl) and
results from either decreased production or increased quinacrine (Atabrine) in the past, some dogs in
loss of protein. Hypoproteinemia due to chronic our practice remained infected and symptomatic.
liver disease is characterized by primary hypoalbu- It should be recognized that there may be one or
minemia, resulting from decreased production of several concurrent intestinal disorders (e.g., intes-
albumin. In protein-losing nephropathies there is a tinal bacterial overgrowth, IBD) that complicate
primary hypoalbuminemia, due to increased loss of resolution of clinical signs. In some cases, even
albumin. Macroglobulins are generally not lost until though Giardia is present, it may not be a signifi-
disease is severe and glomerular membranes become cant pathogen. Some other process then may be
porous. In contrast, protein loss from the GI tract responsible for the clinical abnormalities.
generally involves loss of all fractions at an equal rate, Individual host immunity factors also play an
regardless of molecular size. important role in infection control. Deficiency of
The most common causes of protein-losing secretory IgA has been shown to be a factor in
enteropathy (PLE) in the dog include moderate persistent Giardia infection in humans, and the
to severe lymphocytic-plasmacytic enteritis, lym- same may be true for animals. A competent cell-
phangiectasia, diffuse intestinal lymphosarcoma, and mediated immune system is required to resist
histoplasmosis. Pythiosis causes severe intestinal infection. Also, immunosuppressive doses of cor-
inflammation and protein loss and is generally seen ticosteroids can cause recrudescence of Giardia infec-
in dogs living in the Gulf Coast states, although it tions in dogs and other species. Noting the
has been recognized in other southern states as prevalence of IBD in dogs and cats and the fre-
well (see later discussion on pythiosis). Chronic quent use of corticosteroids to treat the syndrome,
parasitism, including giardiasis, can also result in every effort should be made to identify the pres-
intestinal protein loss. Subnormal protein levels in ence of Giardia and to ensure that adequate treat-
cats due to GI disease are not commonly recog- ment be administered in patients that are also
nized. Among this group, lymphosarcoma and being treated for IBD (either empirically or
severe IBD are the most common causes. because a definitive diagnosis has been made).
This chapter presents diagnostic and detailed In dogs, diarrhea may begin as early as 5 days
treatment information for some of the most after exposure to infection.The life cycle of Giardia
important and challenging chronic small intestinal is direct, and the prepatent period lasts between
disorders seen in clinical practice. These include 1 and 2 weeks. Giardia occurs in both trophozoite
chronic giardiasis, IBD, intestinal bacterial over- and cyst forms. Trophozoites attach to the brush
growth, lymphangiectasia, pythiosis, short bowel border of the villous epithelium of the small intes-
CHAPTER 7 CHRONIC DISEASES OF THE SMALL INTESTINE 213
tine. The cyst form is infective. Trophozoites may absence of a concave disk, a single nucleus, and the
also be passed, especially with diarrheic stools, but presence of an undulating membrane. Identification
they are incapable of causing infection and soon die. of Giardia trophozoites is diagnostic, but their
absence in fecal samples does not rule out giardiasis.
Many studies have now shown that zinc sulfate
Diagnosis concentration, with centrifugation is the most reli-
As described in Chapter 6, standard diagnostic able test available for demonstration of Giardia
tests used in any practice setting should include cysts in a fecal sample. The test can be done in any
fresh saline fecal smears and zinc sulfate flotation. practice setting, or fecal samples can be submitted
Trophozoites are more likely to be found in loose to a commercial laboratory for detailed evaluation.
stools, whereas cysts are more often found in semi- The technique is described in Box 7-1. Zinc sul-
formed or formed stools. fate concentration is also a very effective method
A fresh saline smear is made by mixing a for identifying nematode eggs in feces. It is there-
drop of feces with a drop of saline on a glass slide. A fore now used as the standard test for screening for
coverslip is applied, and the preparation is examined intestinal parasites in some academic and private
immediately under ×40 magnification. Tropho- practices. Studies have shown that approximately
zoites are pear shaped and have a characteristic 70% of Giardia-positive dogs can be identified on
concave ventral disk. They demonstrate wobbly a single zinc sulfate centrifugal flotation test (as
motion, similar to a falling leaf. A drop of Lugol’s opposed to approximately 40% of dogs after three
solution of iodine on the edge of the coverslip separate saline smear preparations).
enhances the morphologic features of the organisms Slides should be examined within 10 minutes
and makes them easier to find. The iodine kills the of preparation because the cysts may begin to
parasite, so its motion is no longer seen if this pro- shrink. Because animals shed Giardia on an inter-
cedure is used. Differentiation of trichomonads mittent basis, it is recommended that a series of
from Giardia is based on a different motion pattern zinc sulfate concentration tests be run over 3 to
(more forward motion with trichomonads), the 5 days to maximize chances of accurately diagnosing
From Barr SC, Bowman DD: Giardiasis in dogs and cats, Compend Contin Educ Pract Vet 16:605, 1994; from Zajac AM: Giardiasis,
Compend Contin Educ Pract Vet 14:606, 1992.
214 CHAPTER 7 CHRONIC DISEASES OF THE SMALL INTESTINE
or ruling out Giardia in patients with chronic diar- quinacrine was often used. It was also used in cats.
rhea. Diagnostic efficiency increases to 95% when Although quinacrine has been shown to be more
three zinc sulfate examinations are conducted over effective than metronidazole, it frequently causes
3 to 5 days. A positive result on any of the tests side effects, including lethargy, anorexia, and vom-
warrants treatment for Giardia. iting. Quinacrine is no longer available. More
Whether or not any other diagnostic work-up recently it was shown that albendazole (Valbazen)
is suspended until a therapeutic response is deter- is highly effective in controlling Giardia and that
mined depends on the patient’s clinical situation. it has a high safety factor. However, it was later
If it is likely that some other disorder is more found that albendazole can cause leukopenia and
responsible for the patient’s overall condition (e.g., lethargy, and so its use in dogs and cats is no
severe protein-losing enteropathy and significant longer recommended. Fenbendazole (Panacur),
weight loss that would be highly unlikely to well known for its effectiveness against a variety
occur solely from a Giardia infection), Giardia of intestinal parasites, is very effective, as is feban-
might be considered a concurrent but less impor- tel (in the combination product Drontal Plus,
tant problem. When evaluating a patient for a which includes febantel, praziquantel, and pyrantel
chronic GI disorder, the clinician must focus on pamoate).
finding the most significant problem. Sometimes Metronidazole is still a useful drug for treating
a particular diagnostic “lead” is pursued too long Giardia, and it has the added advantage of having
while the patient’s overall condition continues to antibacterial as well as antiinflammatory proper-
decline. ties. In situations in which it is unclear whether
Other diagnostic tests for Giardia include an diarrhea is due to giardiasis, bacterial overgrowth,
enzyme-linked immunosorbent assay (ELISA) for or mild IBD, metronidazole is an excellent choice,
Giardia antigen in feces, a direct immunofluores- especially when an owner requests empiric therapy
cent assay, duodenal aspiration under endoscopic rather than definitive diagnostic testing. Metro-
guidance, and the peroral string test. nidazole is only approximately 70% effective in
The fecal ELISA detects Giardia antigen that is eliminating Giardia from dogs, however; so if a
produced by dividing trophozoites. The test is positive diagnosis is made, fenbendazole or feban-
very sensitive in humans and reportedly detects tel represents a better choice. Potential side effects
30% more cases of Giardia than does zinc sulfate. of metronidazole include anorexia, vomiting, and
Studies in dogs, however, have shown that the neurologic problems (ataxia, vestibular problems,
ELISA appears to be less sensitive than a series of seizures). In my experience these side effects are
zinc sulfate centrifugal flotation tests. It may be a not common. They are more likely to occur when
little more sensitive than a single zinc sulfate test. the anti-Giardia dose is used (12 to 15 mg/lb
Keep in mind, however, the quality of the test orally every 12 hours for 5 to 7 days). The total dose
being run and the accuracy of microscopic inter- per day should not exceed 30 mg/lb. A lower dose (5
pretation in the hands of an inexperienced to 10 mg/lb every 12 hours) is used in treatment
observer. This is a common problem area in small of intestinal bacterial overgrowth and IBD. Side
animal hospital laboratories. One advantage of the effects are infrequent at this dose. In the past if a 5-
ELISA is that, because it detects antigen in the to 7-day course of metronidazole failed to elimi-
feces, it avoids the problem of intermittent cyst nate Giardia, a longer follow-up course (10 to 14
excretion in the feces. This test can be run either days) was often used. With the availability of fen-
in-house or at a commercial laboratory. In human bendazole and febantel, it is recommended that
medicine the recognized “gold standard” for diag- one of these drugs be used instead in this situation.
nosis of Giardia is to run both a Giardia antigen Metronidazole is suspected of being teratogenic
test and a zinc sulfate assay. This is now a com- and should therefore not be administered to preg-
monly used approach in veterinary medicine as nant patients. Fenbendazole is recommended in
well. this situation.
Fenbendazole has also been shown to be effec-
tive in eliminating Giardia. The same dose that is
Treatment used to treat roundworms, hookworms, whip-
For many years the primary treatment for Giardia worms, and the tapeworm Taenia pisiformis
in dogs and cats involved metronidazole. For dogs (22 mg/lb orally once daily for 3 to 5 consecutive
in which metronidazole proved ineffective, days) is used to treat Giardia. Fenbendazole has a
CHAPTER 7 CHRONIC DISEASES OF THE SMALL INTESTINE 215
proven record for being very safe and is thought rinse as previously described before being placed
not to have any teratogenic effects. Therefore fen- in the environment.
bendazole would be the drug of choice for treat- In home environment situations bathing the
ment of Giardia in pregnant animals. Fenbendazole patient at the conclusion of drug therapy may also
is now the preferred treatment for Giardia in cats be helpful. Patients may be reinfected with cysts
(Drontal Plus is approved for use only in dogs). that are in the hair coat or the environment. Bath-
Drontal Plus is now recognized as an excellent ing will help remove cysts that could be licked
drug for treatment of Giardia, as well as nematodes from the hair coat by the patient and help reduce
and tapeworms. This product includes febantel in the chances of reinfection.
addition to praziquantel and pyrantel pamoate.
Febantel is the drug component that treats Giardia. Zoonotic Potential. Zoonotic potential defi-
Febantel is metabolized into fenbendazole and nitely exists with Giardia. Children may be espe-
oxyfenbendazole after oral administration. Drontal cially at risk due to their proclivity for playing in
Plus is administered once daily for 3 to 5 consec- grass and soil areas where cysts may be present.
utive days in dogs for treatment of Giardia. They also are more likely to put their fingers or
Oral furazolidone has proven to be an effective hands in their mouths, and this can occur anytime
drug for treating Giardia in cats at a dose of after they have had direct contact with an animal’s
2 mg/lb orally twice daily for 5 to 10 days. hair coat, including in the perineal area. This is
Furazolidone causes vomiting and/or diarrhea in why it is so important for veterinarians to perform
some cats. It should not be used in pregnant quality laboratory tests to investigate companion
queens. animals for parasitic infections, including Giardia,
In addition to use of pharmacotherapy to on a routine basis whenever there are children in
eradicate Giardia, it is important to consider envi- contact with family pets. When both animals and
ronmental control to minimize chances of reinfec- humans living in the same environment become
tion, especially in kennel or cattery situations. infected, a common source of infection rather than
Cysts that are present in a cool, wet environment direct transmission must also be considered.
can remain infective for a period. Cages and runs The question whether patients that are asymp-
should be thoroughly cleaned of all solid fecal tomatic carriers of Giardia should be treated is
material. Steam cleaning and treatment with a often asked. Giardia cysts have been found in many
quaternary ammonium compound are both very patients with well-formed feces. Giardia is clearly
effective measures for killing cysts. Allowing time not pathogenic in some patients, whereas in others
for thorough drying is important to desiccate any it causes significant enteritis. Because the public
remaining cysts. Finally, patients should be bathed health considerations must still be considered, it is
before they are returned to the kennel area to strongly recommended that all patients with fecal
wash out any cysts that may be present in the hair samples that contain Giardia be treated and then
coat. In kennel or cattery environments where retested to ensure that the infection has been
Giardia is recognized as a significant problem an cleared.
additional step that can be undertaken is to use a
quaternary ammonium compound topically. The
hair in the perineal and perianal regions can be Vaccination
washed with a quaternary ammonium compound In 1999 a new vaccine was released for control of
once the shampoo has been rinsed out. These Giardia. The vaccine is a killed product containing
compounds do not seem to cause any significant chemically inactivated trophozoites. Efficacy stud-
skin irritation as long as they are left on for no ies showed that vaccinated dogs were less severely
more than 3 to 5 minutes and then thoroughly affected clinically and shed cysts for a shorter time
rinsed out and allowed to dry. These compounds following challenge with infective cysts, compared
can inactivate Giardia cysts within 1 minute at with nonvaccinated dogs. In addition, chronic
room temperature. In addition, a second 5-day giardiasis resolved after dogs were vaccinated
course of treatment for Giardia is administered to with this product. In these studies clinical signs of
ensure that each animal is parasite free before infection were less severe by 21 to 35 days after
being returned to the kennel or cattery. Any new- vaccination, and cysts were no longer detected in
comers are treated with fenbendazole or Drontal the feces by 21 to 70 days. This is not expected to
Plus (dogs) and a topical quaternary ammonium be a “core” vaccine (i.e., recommended for annual
216 CHAPTER 7 CHRONIC DISEASES OF THE SMALL INTESTINE
was commonly limited to such tests as fecal exami- result of these experiences, I have had the oppor-
nation for parasites, fecal cultures, hematologic stud- tunity to study the various clinical manifestations
ies, and survey and contrast radiography, or in some of IBD in quite a large number of cats and dogs.
cases simply fecal tests and a series of empiric phar- The information that follows represents a compi-
maceutical maneuvers. Now, however, an under- lation of my experiences as a clinician along with
standing of the absolute importance of histologic observations of other specialists in gastroenterol-
evaluation of GI tissues in patients whose symptoms ogy who have also managed a significant number
are not readily explained by routine tests and dietary of cases.
trials is thankfully well entrenched in our thinking. We are in the midst of an exciting era of
Indeed, IBD is a diagnosis that can be made only by research in the field of the various inflammatory
biopsy specimen analysis. I suspect that in the past bowel disorders. It must be realized, however, that
many patients with what was described as “nonspe- despite our ever-increasing knowledge in this area
cific enteritis” may actually have had some type of in both the human and the veterinary fields, we
IBD.Without specific treatment, many patients with are still at the frontier.We have much to learn!
chronic vomiting and/or diarrhea with subsequent
wasting disease were euthanized or died prematurely
as a result of “unknown causes.” Terminology and Pathogenesis
My personal experience parallels that of other The term inflammatory bowel disease describes a
veterinary gastroenterologists working in the early group of chronic intestinal disorders that are
1980s. Beginning in 1980 as pediatric-sized endo- characterized by a diffuse infiltration within the
scopes became more readily available and as we lamina propria by various populations of inflam-
gained the necessary skills to routinely guide an matory cells, including lymphocytes, plasma cells,
endoscope through the pylorus and into the duo- eosinophils, neutrophils, and macrophages. The
denum of cats and dogs, we rapidly became more most commonly identified idiopathic inflamma-
capable of obtaining GI tissue samples both more tory bowel disorders in cats are lymphocytic-
safely (endoscopy is less invasive than exploratory plasmacytic enteritis, benign lymphocytic enteritis
surgery, with procurement of full-thickness biopsy (an apparently distinct disorder from intestinal lym-
specimens) and more readily (owners are much phosarcoma), and lymphocytic-plasmacytic colitis.
more likely to allow endoscopy than they are to Two different classifications of eosinophilic IBD
approve a laparotomy). Once it became apparent have been identified in cats: eosinophilic enteritis
that significant inflammatory bowel changes were and hypereosinophilic syndrome.
present in a number of patients with GI symptoms Eosinophilic enteritis is characterized by diffuse
(especially vomiting and/or diarrhea), it followed or focal infiltration of inflammatory cells that are
that procurement of gastric and intestinal biopsy almost entirely eosinophils into one or more layers
samples should be strongly recommended in any of the alimentary tract. The stomach, small intes-
patient with chronic (lasting as little as 4 weeks) tine, and colon may all be involved in some cases
unexplained signs. Indeed, the more we looked, (eosinophilic gastroenterocolitis). Eosinophilic
the more we found. enteritis in cats is similar in clinical manifestations
On a personal note, I have had the good for- and response to treatment (very favorable) to the
tune to have worked at two large high-caseload same condition in dogs.
institutions (Angell Memorial Animal Hospital in Hypereosinophilic syndrome is a severe type of
Boston and the VCA West Los Angeles Animal IBD in cats that involves massive infiltration of
Hospital) in urban areas where a majority of ani- eosinophils in the alimentary tract and other parts
mal owners tend to demonstrate a strong desire to of the body. Dramatic bowel thickening often
provide the best medical care that they can for results.
their pets. Many of our owners have embraced the The eosinophilic disorders are not seen very
idea of reaching a definitive diagnosis as early as commonly in cats. Of the two, hypereosinophilic
possible. With the availability of endoscopy, we syndrome is less common and more life threatening.
have been able to recommend and perform GI Occasionally, mixed populations of inflammatory
biopsies much earlier on the “chronicity curve” of cells (e.g., lymphocytic-plasmacytic-eosinophilic,
disease. Our patients and their owners have no lymphocytic-eosinophilic) are identified. Inflamma-
doubt benefited greatly from this approach. As a tory disease may be localized to the small intestine
218 CHAPTER 7 CHRONIC DISEASES OF THE SMALL INTESTINE
(enteritis), specific areas of the small intestine clear, the most commonly speculated causes in-
(e.g., duodenitis, ileitis), or colon (colitis). Although clude defective mucosal immune responses, changes
some cats have generalized intestinal involvement in mucosal permeability, dietary influences, and
(enterocolitis), many cats with IBD have only small intestinal microorganisms.
intestinal disease. Recently research in human medicine has
In dogs the most common types of focused on a possible autoimmune response in the
IBD are lymphocytic-plasmacytic enteritis and pathogenesis of IBD. It has been proposed that
lymphocytic-plasmacytic colitis. Pure lymphocytic there may be a specific immune response against
enteritis is rarely identified in dogs. Eosinophilic an antigen expressed on the patient’s own cells,
enteritis is occasionally seen, but definitely not as particularly on intestinal epithelial cells. In this the-
commonly as was once speculated. ory the patient mounts an appropriate immune
It is essential that the clinician understand that response against some luminal antigen (e.g., dietary
identifying an increase in inflammatory cells on or microbial). However, because of similarities
intestinal biopsy specimen analysis does not auto- between proteins on the epithelial cells and the
matically warrant a diagnosis of IBD. Inflammatory luminal antigens, the patient’s immune system also
cells may be present in increased numbers simply as attacks the epithelial cells. The immune response
a normal response to a variety of inciting factors. may be directed specifically at the epithelial cell.
Potential underlying causes include hyperthy- A defect in immunoregulation may be involved in
roidism (thyrotoxicosis may generate an inflamma- this process (i.e., in individuals with IBD there
tory response); various infectious agents, including may be a failure to suppress the inflammatory
bacteria, viruses, and parasites (including Giardia); response). Thus, as a result of failure of normal
food antigens; presence of a foreign body; and GI suppressor mechanisms, there may be a prolonged
neoplasia, which may be associated with a blanket and vigorous response to some normal luminal
of inflammatory cells surrounding neoplastic cells antigens.
(e.g., this may occur with lymphosarcoma). Although theories abound, there is still no
It is my impression that tissue samples that are defined cause for IBD. Active research in both
characterized by moderate to severe inflammation the human and the animal fields for pathogenic
represent true idiopathic disease in a majority of mechanisms continues.
cases. Specimens that reveal only mild inflam-
mation, however, could be consistent with either
mild idiopathic IBD or any number of underlying Patient Profile
disorders. It is the clinician’s responsibility to inves- Although IBD most commonly occurs in middle-
tigate thoroughly (see section on diagnosis) for age to older cats and dogs, it has occasionally been
underlying causes, whenever possible, before set- diagnosed in patients as young as 4 months. The
tling on a final diagnosis of idiopathic IBD. By tak- predominant clinical sign in young cats with IBD
ing this approach, we will most certainly better tends to be diarrhea, whereas in young dogs I have
serve both our patients (by definitively diag- found vomiting to be the more predominant sign.
nosing and specifically treating any underlying Attempts to perform intestinal biopsies on young
disorders) and our combined efforts in more accu- patients are made only after meticulous effort
rately defining the diverse group of inflammatory is taken to rule out intestinal parasites (includ-
bowel disorders. The term IBD is used here to describe ing Giardia and Cryptosporidium), infectious agents
a chronic disorder in which no specific cause can be (including viruses and bacteria, including Campylo-
determined. bacter, Salmonella, and Shigella), adverse food reac-
The definitive cause of IBD, despite years of tions, and metabolic derangements. No breed or
major research in humans and some recent work sex predilections have been identified in animals
in animals, remains unknown. It is likely that a with IBD.
cytopathic immunologic response results in the
bowel from chronic antigenic challenge. It appears
that immune activation in IBD is largely confined History and Clinical Signs
to the GI tract, so the search for the “antigenic One of the most common clinical signs observed
trigger” has focused on the intestinal lumen. in patients with idiopathic small intestinal IBD
Although the specific inciting factor or factors for is vomiting. Vomiting is a common presenting
these host hypersensitivity responses are still un- complaint seen in clinical practice, and clinicians
CHAPTER 7 CHRONIC DISEASES OF THE SMALL INTESTINE 219
should give careful attention to patterns observed nonspecific symptomatic treatment. The first step
by the owner. In inflammatory bowel disorders, in diagnosis of a disorder characterized by diarrhea
vomiting is most often recognized as an intermit- is to decide whether the process is principally
tent occurrence for weeks, months, or years. Often affecting small or large intestine or both. This
as the disorder progresses, there is an increased helps determine the direction of further work-up
frequency of vomiting and other clinical signs, and is done by combining information from his-
which leads the owner to seek veterinary attention. tory, physical examination, and stool characteris-
Alternatively, an occasional patient with even mod- tics (frequency, volume, consistency, odor, color,
erate to severe inflammatory changes on biopsy composition).
specimen analysis may be presented with clinical Small bowel diarrhea is most often character-
signs limited to an acute onset of vomiting and ized by large quantities of soft-formed, bulky, or
lethargy, with no past history of GI signs. watery stool. Steatorrhea may be evident, and
Vomiting episodes are usually associated with more chronic cases are often accompanied by
retching, are nonprojectile, and may produce clear weight loss and listlessness. In contrast, diarrhea of
fluid, bile, or foam.Vomiting of food, either fresh large bowel origin most often has a loose, stringy
or partially digested, is sometimes observed. In consistency due to increased mucus content, and
patients with concurrent gastric hypomotility that intermittent streaks of fresh blood may be present.
is either idiopathic or secondary to chronic gas- Owners are often not aware of the presence of
tritis or IBD, vomiting of undigested food may blood. Other signs include increased frequency of
occur many hours after eating. Blood is rarely attempts to defecate (cat owners may misinterpret
present. Hematemesis may indicate concurrent this as attempts to urinate), defecating in abnormal
gastric involvement (e.g., erosions, foreign body, places, and hiding (cats). Cats with large intestinal
gastritis, neoplasia) or superficial erosive changes in inflammation sometimes begin defecating outside
the proximal small intestine. the litter box. Dogs sometimes demonstrate a sense
Vomiting in IBD can occur at variable times of urgency to defecate.
after eating. Many patients with mild IBD go If the disease is limited to the large intestine,
about their daily routine showing no untoward most patients remain active and alert, have a normal
effects from any of the vomiting episodes. The appetite, and do not lose weight. Some patients have
vomiting and associated nonspecific signs may be both small and large intestinal disease, with similar
cyclical in nature. Clinical signs may be evident on histologic changes, yet only small intestine or large
one or several days and then spontaneously disap- intestine signs predominate. If biopsy specimens are to be
pear, indicating that untreated IBD runs a course obtained in chronic diarrhea cases, obtaining tissue samples
often characterized by exacerbations and remis- from both small and large intestine is strongly recom-
sions. Successes therefore should not automatically mended. Treatment for only small or large intestinal
be attributed to the symptomatic treatment that is disease is not likely to result in complete resolution
often given in these cases (nothing by mouth, of signs if generalized involvement is present.
bland diets, antiemetics). It is owing to this cyclic In some cats with chronic IBD, diarrhea does
nature that some patients with IBD are not pre- not occur until some stressful episode (e.g., change
sented until signs are more frequent or severe. If a in environment, queening) causes an exacerbation
pattern of intermittent vomiting in a cat causes of clinical signs. In these cases of acute diarrhea,
owner concern, a work-up to determine its cause initial testing is naturally directed toward ruling
should be undertaken, even if it is not a long- out dietary indiscretions, parasites, foreign bodies,
standing clinical sign.Without question, IBD is one and infectious agents (e.g., Campylobacter). Often
of the leading differentials of chronic vomiting in no definitive diagnosis can be made, and feed-
cats and dogs. ing trials and empirical treatment fail to effect last-
In my experience the second most common ing resolution of the diarrhea. Further work-up
sign observed in feline IBD is diarrhea. It may be involving intestinal biopsy in these cases may
the most common sign in dogs. Diarrhea may be reveal chronic moderate to severe inflammatory
the sole clinical sign or may occur in conjunction bowel changes. A review of the history again may
with intermittent vomiting. Diarrhea may be surprisingly not show any past occurrence
acute or chronic, but most cases are evaluated of vomiting or diarrhea. Diarrhea, once apparent,
because of chronic diarrhea that is responsive or usually does not resolve until specific treatment for
only temporarily responsive to diet changes or IBD is instituted in these cases.
220 CHAPTER 7 CHRONIC DISEASES OF THE SMALL INTESTINE
In addition to vomiting and diarrhea, other instituted early rather than later, when more inten-
clinical signs that may be observed in IBD include sive therapy might be needed.
changes in attitude or activity, altered appetite,
and weight loss. Many patients tend to be more
depressed during periods of increased vomiting. Diagnosis
As with the sign of vomiting, these activity-level The differential diagnosis for IBD is listed in Box
changes are often cyclic. In some cats with chronic 7-3.A definitive diagnosis of IBD can only be made
diarrhea, listless behavior is the predominant atti- based on intestinal biopsy specimen analysis. Other
tude. An owner may describe decreased tenden- tests are run to evaluate the overall health status of
cies to play, decreased interest in surroundings, and the patient and to rule out other disorders.
more frequent hiding or sitting near heating units Recommended baseline tests include a complete
for long periods of time. blood count, complete biochemical profile, uri-
Appetite changes in cats with IBD vary from nalysis, and fecal examinations for parasites and in
decreased to complete anorexia to ravenousness. cats a serum thyroxine (T4) test and tests for feline
Inappetence seems to occur more commonly in leukemia virus antigen and feline immunodeficiency
cats that have vomiting as the primary clinical sign virus antibody.
and usually occurs during exacerbations of clinical Baseline test results frequently are normal
signs. In some cats, anorexia is the primary clini- or negative, but abnormalities that may be identi-
cal sign and vomiting or diarrhea is not observed fied include mild nonregenerative anemia (anemia
until later or not at all. The three leading differen- of chronic inflammatory disease); leukocytosis
tial diagnoses for a cat with a ravenous appetite, (20,000 to 50,000 cells/µl) without a left shift (sug-
diarrhea, and weight loss are IBD, hyperthy- gests active chronic inflammatory disease); eosino-
roidism, and exocrine pancreatic insufficiency (an philia (mild to dramatic increase) in some cats
uncommon disorder in cats). I have also seen cats and dogs with eosinophilic enteritis and in all cats
with chronic low-grade lymphocytic lymphoma with hypereosinophilic syndrome; and hypopro-
of the small intestine exhibit identical clinical signs teinemia (increased loss of protein through a dam-
(Box 7-2). Dogs with IBD tend to have a normal aged intestinal lining) or mild hyperproteinemia
to decreased appetite, depending on the degree (due to increased globulin fraction in idiopathic
of disease that is present. One notable excep-
tion is that Chinese shar-peis with IBD frequently
have an increased to ravenous appetite (see further
information about shar-peis later in this chapter).
The clinical course of IBD in many dogs and BOX 7-3 Differential Diagnosis of
cats, at least fairly early in the course, is character- Disorders Resembling
ized by unpredictable exacerbations and remis- Inflammatory Bowel
sions. This makes accurate assessment of disease Disease in Dogs and Cats
burden difficult. It is important that an early assess-
ment be made for patients that demonstrate GI Chronic giardiasis
symptoms so that the best course of therapy can be Hyperthyroidism (cats)
Dietary sensitivity (e.g., food allergy or intolerance)
Bacterial overgrowth
Clostridium perfringens enterotoxicosis
BOX 7-2 Differential Diagnosis Lymphangiectasia (dogs)
of Disorders Causing Lymphoma
Pythiosis
Chronic Diarrhea, Functional bowel disorder (e.g., irritable bowel
Weight Loss, and syndrome)
Ravenous Appetite Histoplasmosis
in Cats Exocrine pancreatic insufficiency
Feline infectious peritonitis (gastrointestinal involve-
Hyperthyroidism ment)
Inflammatory bowel disease Adenocarcinoma
Intestinal lymphoma Stagnant loop (secondary intestinal obstruction)
Exocrine pancreatic insufficiency (e.g., adenocarcinoma, mesenteric adhesions)
CHAPTER 7 CHRONIC DISEASES OF THE SMALL INTESTINE 221
IBD or feline infectious peritonitis with intestinal Testing for hyperthyroidism may include running
involvement). a free T4 by equilibrium dialysis or a thyroid hor-
Hypoproteinemia (total protein less than 6.0 mone (T3) suppression test in cats with clinical
g/dl, with albumin and globulin fractions propor- signs suggestive of hyperthyroidism but that have a
tionately decreased) occurs much less commonly baseline T4 level in the high normal range.
in cats with IBD than in dogs and usually indicates Interestingly, thyrotoxicosis can cause inflamma-
moderate to severe intestinal involvement when it tory changes in the intestinal tract, and this may
is identified in a cat with IBD. A work-up should explain why some cats with hyperthyroidism have
be expedited to determine the cause. The most vomiting or diarrhea. These changes often resolve
common cause of hypoproteinemia in cats with a after treatment for hyperthyroidism is instituted.
total protein level less than 5.0 g/dl in my case Failure of vomiting or diarrhea to resolve, how-
series is intestinal lymphoma. The most common ever, within 4 to 6 weeks of institution of treat-
cause of PLE in dogs is lymphocytic-plasmacytic ment for hyperthyroidism suggests the possibility
enteritis. of ongoing inflammatory disease or some other
Fecal α1-protease inhibitor (Fα1-PI) is an assay disorder that likely requires primary therapy.
that will help detect evidence of excessive intes- I have observed cats with moderate to severe
tinal protein loss in dogs before hypoproteinemia lymphocytic-plasmacytic enteritis or lymphocytic
develops. α1-PI is a plasma glycoprotein. It is not enteritis that were also hyperthyroid. Intestinal
present in the intestinal lumen above trace back- biopsy specimens were obtained from these patients
ground concentrations unless there is abnormal after treatment for hyperthyroidism effectively
transmucosal loss of plasma, lymph, or intracellular decreased serum thyroid hormone concentrations
fluid as a result of GI disease. Fα1-PI can reach into the normal range but had little effect in
abnormal concentrations before there is enough resolving ongoing GI symptoms (generally prima-
protein loss from the intestine to cause panhy- rily vomiting and/or diarrhea, although in several
poproteinemia. α1-PI is excreted in the stool with cats the predominant sign was inappetence). It has
minimal loss of its immunoreactivity, because it is been my impression that cats with such significant
largely resistant to degradation in the intestinal degrees of inflammation have both hyperthy-
lumen by virtue of its inhibitory activity. roidism and idiopathic IBD rather than a single
This assay is useful in dogs with chronic diar- problem.
rhea that have normal or slightly decreased serum It is also recommended that all dogs and cats
protein levels, as a screening tool for evidence of exhibiting chronic signs of GI disease have the
the presence of a potentially severe PLE disorder. serum cobalamin concentration measured. Several
The assay is available at the GI laboratory at Texas studies have demonstrated that some patients with
A&M University.* Contact the laboratory for spe- GI disease have a significant deficiency of tissue-
cial fecal sample submission tubes. Samples are level cobalamin. This is particularly important in
submitted frozen. The level of Fα1-PI in healthy any case in which there has already been a subop-
dogs has been determined to be no more than timal response to previous therapy, because supple-
5.7 µg/g. Values as high as 53.2 µg/g have been mentation with cobalamin may be helpful to such
observed in dogs with PLE sufficiently severe to patients. Clinical signs of cobalamin deficiency
cause panhypoproteinemia.Values in the range of include chronic wasting or failure to thrive,
6.0 to 15.0 µg/g have been observed in dogs with lethargy, and diarrhea. Subnormal cobalamin levels
PLE not sufficiently severe to cause panhypopro- may result from intestinal mucosal disease, reduced
teinemia. intrinsic factor availability, or bacterial competition.
Hyperthyroidism should always be ruled out in Cobalamin therapy in patients with subnormal lev-
any cat older than 5 years of age that has manifest els may be an important key to improved weight
unexplained GI signs. Hyperthyroidism is occa- gain and a decrease in signs such as vomiting and
sionally diagnosed in cats younger than 5 years of diarrhea. Dose recommendations are described in
age, so this possibility should always be considered. the treatment section for IBD.
Patients with chronic diarrhea should also
*
GI Laboratory at Texas A&M University, College of be thoroughly evaluated for intestinal parasites,
Veterinary Medicine,TAMU 4474, College Station, including Giardia and Cryptosporidium, and Clostri-
TX 77843-4474;Telephone: (979) 862-2861; dium perfringens enterotoxicosis (CPE). A panel of
www.cvm.tamu.edu/gilab. fecal tests is run, including zinc sulfate centrifugal
222 CHAPTER 7 CHRONIC DISEASES OF THE SMALL INTESTINE
flotation, Giardia antigen test, C. perfringens entero- the proximal jejunum in cats), and colon can be
toxin assay, and Cryptosporidium indirect fluorescent thoroughly evaluated. In many cats, ileum samples
antibody test. Dogs and cats with IBD may have can be obtained blindly, with the endoscope tip
multiple GI disorders concurrently, and it is impor- situated in the ascending colon or at the junction
tant that each problem be identified so that the of the transverse and ascending colon. In most
most comprehensive treatment regimen can be dogs larger than 8 to 10 lb, a pediatric-sized endo-
instituted. Dogs should also be tested for intestinal scope can be advanced into the ileum. A total of
bacterial overgrowth (described later in this chap- 8 to 10 small bowel biopsy specimens are usually
ter). obtained at endoscopy, depending on the gross
Survey abdominal radiographs and barium appearance of the mucosa. Biopsies of proximal
contrast study results are often unremarkable. small intestine, as well as stomach, should always be
Because cost containment is so often an important done in patients with chronic vomiting that are
factor in clinical practice, barium series are often undergoing endoscopy. It is not uncommon for
not performed unless clinical signs or abdominal cats and dogs with inflammatory changes involv-
palpation findings (e.g., obstruction) indicate that ing only the small intestine to be presented with
this procedure should be done. In many cases, signs limited to chronic intermittent vomiting.
money is best spent on baseline tests and intestinal If only gastric biopsy samples are obtained, the
biopsies. Abnormal findings that may be identified diagnosis may be missed.
on a barium series include diffuse mucosal irregu- The gross appearance of the mucosa in IBD
larities or spicular small intestinal mucosal changes can range from normal (primarily cream to
and thickened bowel segments. Positive findings slightly pink in color) to mildly erythemic to vary-
do not provide a definitive diagnosis; rather, they ing degrees of mucosal irregularity (Figure 7-1).
confirm the need for direct examination and Mucosal irregularity may appear as fissures or
biopsy of the affected areas. Radiographs can also resemble a cobblestone texture in more advanced
suggest false-positive findings. cases (Figure 7-2). Focal erosions may also be
Intestinal biopsies can be performed either observed. The mucosa may be friable and may
under endoscopic control or by exploratory lapa- bleed from direct contact with the endoscope tip
rotomy.Among the many advantages of endoscopy as it is advanced. Endoscopic biopsy techniques
are that it is relatively quick and noninvasive. useful in the small intestine have been described in
Multiple biopsy samples can be obtained, and the detail elsewhere. Biopsy samples vary in size. They
stomach, proximal small intestine (and frequently are often small when the intestinal mucosa is
A B
FIGURE 7-1 A, Endoscopic photograph of normal duodenal mucosa in a dog. Normal small intestinal mucosa is
primarily cream to slightly pink in cats and pinkish white to light red in dogs.The mucosa often appears slightly
irregular or velvety as a result of its makeup of digitate villi. B, Mild mucosal irregularity, increased graininess, and
patchy erosive mucosal changes in a dog with moderate lymphocytic-plasmacytic enteritis.There was a history of
chronic intermittent vomiting that had recently become more frequent.
CHAPTER 7 CHRONIC DISEASES OF THE SMALL INTESTINE 223
distortion of glands or crypts. There may also be raised many questions about the significance of
mild villous blunting. “Severe” IBD is manifest by certain findings. Part of the basis for the confusion
architectural distortion of the mucosa, marked vil- is that little information is available regarding nor-
lous blunting, marked separation of glands or mal cellularity of the lamina propria or normal vil-
crypts, necrosis, and fibrosis. Studies are ongoing to lus length in dogs and cats of different breeds and
further define the criteria for various degrees of ages, that eat different diets, that live under differ-
IBD. ent conditions, and so on. This then makes it dif-
Severe cases of lymphocytic-plasmacytic ficult to clearly define and describe various degrees
enteritis or lymphocytic enteritis can be difficult of normal and abnormal intestinal histologic find-
to differentiate histologically from lymphoma, ings. One pathologist’s interpretation may be quite
especially in cats, when endoscopic-sized biopsy different from that of another. The difficulty
samples are evaluated. There are serious implica- becomes somewhat greater when inadequate
tions as to what type of therapy to prescribe in endoscopic samples (too small or damaged) are
such cases. Changes that tend to suggest lym- submitted or when a pathologist is inexperienced
phoma include absolute uniformity of the lym- or disinterested in evaluating other than full-
phocyte population, mitotic cells, pleomorphism, thickness intestinal samples. It is therefore recom-
and attendant ablation of villous arches. Areas of mended that clinicians select their pathologists
necrosis may be present. Overlying mixed inflam- carefully and that consistent efforts be made to
matory cell infiltrates may make it difficult to dif- obtain the best-quality tissue samples. There are
ferentiate benign from malignant disease. If a veterinary pathologists who specialize in GI tissue
diagnosis is unclear from evaluation of endoscopic pathology, just as there are specialists in derma-
biopsy samples, it may be necessary to repeat the tologic pathology. Most pathologists are eager
procedure to obtain more samples (generally 2 to to discuss cases with clinicians, and indeed this
4 weeks later) or to obtain full-thickness intestinal opportunity to compare observations is an invalu-
samples at laparotomy. Use of immunohistochem- able means of making the best use of the available
ical staining techniques may also be helpful. information for determining a patient’s treatment
Histologic differentiation of IBD and lymphoma is and prognosis. In some situations it may be best to
summarized in Table 7-1. obtain a second or third opinion before deciding
A major, and probably underappreciated, prob- on a final diagnosis.
lem related to interpretation of pathologic findings In recent years investigators have begun some
by clinicians is the lack of uniformity with which very important work centered on developing spe-
pathologists assess intestinal biopsy specimens. cific criteria for histologic grading of various
Variability in the histologic assessment of the gen- inflammatory bowel disorders in small animals. In
eral group of inflammatory bowel disorders has one study it was shown that there can be
substantial interobserver variation among patholo- tion of clinical signs. In one study, which evaluated
gists when evaluating the same intestinal histologic 55 cats with various GI symptoms, of which vom-
sections. Biopsy specimen interpretation can be iting and diarrhea were the most common signs,
notoriously subjective from one pathologist to the 16 cats (29%) were classified as food sensitive based
next. Most clinicians are well aware of the impor- on response to feeding of a novel protein source
tance of obtaining intestinal biopsy specimens (either chicken or lamb in this particular study).
from patients with signs that may be consistent Resolution of GI signs occurred fairly quickly in
with intestinal disease. As we go forward we need these cats, and then signs recurred once the origi-
to focus more on two important areas, namely, we nal diet was reintroduced. All of the cats with food
need more consistency among pathologists regard- sensitivity had inflammation, identified on endo-
ing how different pathologists interpret the same scopic biopsy specimens, in at least one region of
tissue specimens, and there is a need for some cor- their intestinal tract. Gastric mucosal biopsy spec-
relation between the pathologist’s description of imens were abnormal in 66% of the food-sensitive
the tissue and the clinical state of the patient. cats, and duodenal samples were abnormal in 50%.
We need to know whether or not a clinically This study provides further confirmation of the
significant disorder exists in a particular tissue, importance of dietary therapy in cats with inflam-
because in some instances a pathologist may inter- matory GI disorders. Clearly, long-term control of
pret a sample as being abnormal, suggesting the IBD with minimal drug administration may be
presence of intestinal disease, and yet the patient aided by specific dietary management. However,
may be known to have no signs that correlate with some cats will be only temporarily responsive or
these findings. only minimally responsive to careful dietary manip-
Variation in the interpretation of intestinal ulations. Therefore some cats with mild disease will
biopsy specimens among pathologists has also require some form of pharmacologic therapy in
been described in human medicine, in which addition to dietary manipulation. Most cats with
there are also sometimes blatant differences in moderate to severe IBD will require pharmaco-
diagnostic criteria. It is certainly acknowledged logic therapy, and this is started in conjunction
that histologic evaluation of the digestive tract is with dietary therapy as soon as a diagnosis is
difficult. Continued collaboration between clini- made.
cians and pathologists is essential if we hope to There is no single diet that can be universally
develop a more accurate and predictable set of cri- recommended for management of IBD in cats.
teria for consistent interpretation of intestinal The diet must be chosen based on the dietary his-
biopsy samples. tory, and then an assessment has to be made as to
how well the affected patient embraces the rec-
ommended diet. Adjustments may need to be
Treatment made over time. We now have the advantage of
It is important that the clinician formulate a treat- having a wide variety of very palatable commercial
ment protocol based on a correlation of clinical diets available, and using commercial diets, com-
course, laboratory and gross findings, and histo- pared with home-prepared diets, reduces concern
logic findings rather than relying on histologic about dietary imbalances significantly. Using com-
changes alone. Although treatment principles for mercial diets is also much more convenient for
cats and dogs with IBD are similar, drug selection owners.
and dosage regimens vary between these two In general the first step is to select a diet with a
species in some situations. For the sake of clarity, novel protein source, that is, something the animal
treatment recommendations for cats and dogs are has not been fed before (e.g., duck, venison, lamb,
discussed separately. rabbit, whitefish, turkey). The effects of this diet
should be assessed over a 3- to 4-week period for
Cats therapeutic response and palatability. If there is not
Dietary Therapy a satisfactory response to the first diet and the cat’s
Because dietary allergens may play a role in the condition remains very stable, then an alternate
cause of IBD, specific dietary therapy may be ben- diet can be tried, or, alternatively, drug ther-
eficial. Dietary therapy is instituted at the outset apy can be instituted at this point as well. Most
for all cats with IBD, and in cats with mild IBD, owners are anxious for prompt resolution of their
dietary therapy alone may be sufficient for resolu- pet’s clinical signs, and so I usually try to make a
226 CHAPTER 7 CHRONIC DISEASES OF THE SMALL INTESTINE
determination as to whether ongoing strict dietary several palatable and effective diets can be identi-
trials will be practical or not. fied that will be well tolerated over time.
Many of the commercially available therapeutic Pharmacologic Therapy for Cats
diets have been enriched with omega-3 fatty acids. With IBD
Altering the dietary ratio of omega-6 to omega-3 Corticosteroids are the cornerstone of pharmaco-
polyunsaturated fatty acids may affect the inflam- logic therapy for idiopathic inflammatory bowel
matory response of IBD. Omega-3 fatty acids disorders. Mild to moderate cases often respond
competitively inhibit formation of prostaglandins to prednisone or prednisolone at a starting dose
and leukotrienes derived from arachidonic acid, of 0.5 to 1 mg/lb divided twice daily for 2 to
resulting in decreased concentrations of proin- 4 weeks, followed by a gradual decline in 50%
flammatory fatty acid metabolites. It remains increments at 2-week intervals. Cats with inflam-
unclear, however, if dietary supplementation with matory changes graded as mild usually respond
fatty acids is truly beneficial. quite well to the lower dose, and alternate-day or
Hydrolyzed protein diets have become available every-third-day treatment can often be achieved
for dietary therapy. The theory is that because by 2 to 3 months. In many but not all cats with
these diets contain no intact proteins, only pep- mild disease, treatment can be discontinued alto-
tides of sizes ranging from 6,000 to 15,000 dal- gether by 3 to 6 months.
tons, which are proposed to be nonantigenic, no If biopsy specimen analysis reveals disease that
adverse reaction to the diet will occur. It is still is moderate to severe, a dose of 1 to 2 mg/lb
possible, however, for an antigenic response to one divided twice daily is used for the first 4 weeks or
of the epitomes of the peptides to occur. Further until clinical signs resolve. Some clinicians feel that
investigation is needed; however, these diets cer- better bioavailability will be achieved in cats with
tainly do represent an attractive option for feeding use of prednisolone rather than prednisone.
to some patients with dietary sensitivities or true Therefore for more severe cases it may be best to
food allergy. prescribe prednisolone specifically. This dose of
Recent studies conducted in dogs and cats have corticosteroid is generally very well tolerated in
shown that cell mediated immunity declines with cats. In these cases a dose of 0.5 to 1 mg/lb/day
age. Dietary supplementation with vitamin E may be necessary long-term (months to years) to
appears to enhance this function. Other potential maintain clinical remission. Use of combination
benefits of vitamin E include reduction of oxida- drug therapy (e.g., prednisolone and metronida-
tive damage and correction of a deficiency of vita- zole, or prednisolone and azathioprine) may also
min E that may naturally occur in animals with be required at the outset to control clinical signs
severe GI disease. Therefore it may be beneficial and prevent progression of the disease. Cats with
to provide vitamin E supplementation for dogs hypoproteinemia and histologic changes graded as
and cats with moderate to severe IBD. At this time severe often respond quite well when an aggressive
it is still unclear what dose of vitamin E is best for therapeutic course is undertaken. Dexamethasone
antioxidant effects in the GI tract. A dose of 100 IU (0.15 to 0.25 mg/lb orally every 24 hours) may be
per 10 lb per day is suggested. useful in cats that are poorly responsive to
For cats with concurrent large bowel disease increased doses of prednisolone.
and symptoms, fiber supplementation may be It has been my experience that young cats (less
helpful. Beneficial effects of fiber supplementation than 5 years of age) with IBD often do not need
include improved fecal character, improved to be treated as long as do many middle-age to
colonic motility, binding of potential colonic irri- older cats.This may be due in part to the fact that
tants, and production of beneficial short-chain by the time older cats are diagnosed, the disease is
fatty acids that positively influence large intestinal often long-standing and often of a moderate to
structure and function. severe degree. Earlier diagnosis of these older cats
Once the disease has been in remission for 6 or in conjunction with appropriate therapy will likely
more months, adjustments in the type of foods provide a better opportunity for lower daily or
offered can be attempted, based on owner and alternate-day dosage levels to be successful in
patient preferences. New ingredients should be maintaining control. I have found that many
added one at a time, and the owner should observe older cats with moderately severe to severe IBD
for any adverse effects. If any adverse effects occur, require prednisone or prednisolone at 1 mg/lb/
the offending ingredients are removed. Usually day for life for adequate control of all symptoms
CHAPTER 7 CHRONIC DISEASES OF THE SMALL INTESTINE 227
related to IBD. Combination drug therapy may Therapeutic results with budesonide have been
also be required (see subsequent information). promising in humans with Crohn’s disease, col-
Many clinicians who treat empirically for sus- lagenous colitis and lymphocytic colitis, ulcerative
pected IBD often use inadequate dosages of cor- colitis, either when administered as a retention
ticosteroids (initial dose either not high enough enema or in oral form, and primary biliary cirrho-
or tapered too early). The importance of evaluating sis. Budesonide has been used by some veterinary
biopsy samples, including periodic follow-up biopsy clinicians in recent years to treat IBD in dogs and
specimens in some cases, to best tailor a treatment pro- cats. Dosage recommendations vary. In humans, a
gram cannot be overemphasized. range of 6 to 9 mg per day has been used during
Methylprednisolone acetate (Depo-Medrol) initial therapy. The following general recommen-
can be used as sole treatment for cats with mild to dations have been made for dogs and cats. In gen-
moderate IBD or as adjunctive therapy when oral eral, budesonide is administered to cats and small
prednisolone and/or metronidazole are used as the dogs at 1 mg once per day. It has been used at
primary treatment and flare-ups of clinical signs higher doses (3 mg per small dog or cat per day),
occur. Consistent control of clinical signs in cats but the lower dose is frequently effective. Large
with moderate to severe IBD is more difficult to dogs receive 3 mg twice daily initially, and the
maintain when methylprednisolone acetate is used dosage is later tapered to 3 mg once daily, and then
alone, however. It is recommended that sole use to alternate day administration for longer term
of methylprednisolone acetate be reserved for sit- use.
uations in which the owner is unable to consis- Budesonide can be used in combination with
tently administer tablet or liquid preparations orally. other drugs. Since cats tolerate corticosteroids very
Initially 20 mg is given subcutaneously or intra- well, there is little indication to use budesonide as
muscularly and is repeated at 2-week intervals for a primary therapy for IBD. However, this may be
two to three doses. Injections are then given every a very attractive option for use in diabetic cats that
4 to 6 weeks or as needed for control. also have IBD.
Budesonide is a glucocorticoid that represents a Potential adverse effects include PU/PD, when
new alternative for management of IBD in dogs budesonide is used at the high end of the dose
and cats, especially in severe cases that have proven range, and GI ulceration. These reactions have
to be refractory to prednisolone, metronidazole, been observed in some human patients. These
azathioprine, and dietary management; or that are problems would be more likely to occur in dogs
intolerant of the corticosteroids discussed previ- than in cats. It appears to be very safe when used
ously. Budesonide is a new and recently approved at the levels listed above.
corticosteroid for use in humans. It is one of a When combination therapy is indicated,
group of novel corticosteroids that have been in metronidazole is usually the first choice to be
development for use in humans in an attempt used in conjunction with prednisolone. It can
to make available alternative preparations that also be used as sole treatment in some cases (e.g.,
will help limit toxicity associated with corticos- in the unusual event that a cat cannot tolerate
teroid use. Others include fluticasone propi- corticosteroids, or if their use is contraindicated).
onate, tixocortol pivalate, and beclomethasone Metronidazole’s mechanism of action includes an
dipropionate. antiprotozoal effect, inhibition of cell-mediated
Budesonide undergoes high first pass metabo- immune responses, and anaerobic antibacterial
lism in the liver, and 90% is converted into activity. A dosage of 5 to 10 mg/lb twice daily is
metabolites with low corticosteroid activity. It used for IBD. Ideally at least several months of
has minimal systemic availability. The potential metronidazole therapy is given once it is started. In
for typical corticosteroid side effects is signifi- some cats with severe disease, long-term consecu-
cantly reduced as a result of decreased bioavail- tive use (months to years) or 1- to 2-month cycles
ability and the resulting limited systemic exposure, of treatment may be required.
which makes this a particularly attractive drug Side effects of metronidazole at this low dose
for use in humans and animals that are poorly are uncommon in cats. Adverse reactions that have
tolerant of other corticosteroids. Budesonide been observed include primarily GI (inappetence,
also has a high receptor-binding affinity in the nausea, and occasionally vomiting and/or diar-
mucosa. It has been referred to as a “locally acting” rhea) and neurologic (ataxia, seizures, disorienta-
corticosteroid. tion) problems. In my experience, neurologic side
228 CHAPTER 7 CHRONIC DISEASES OF THE SMALL INTESTINE
effects are very rare when the dose range recom- including immunoblasts, is inhibited, and there is
mended here is used, for whatever duration (weeks interference with cellular function. Azathioprine
to months to years). I have observed two cats that is usually used in cats only when the previously
were treated with prednisone and metronidazole discussed therapeutic measures fail to control the
(5 mg/lb twice a day in one, and 7 mg/lb twice a disease.The most important side effect of azathio-
day in the other) for IBD that developed rear limb prine in cats is bone marrow suppression.
ataxia within 3 to 4 days of the start of therapy. In I use a maximum starting dose of azathioprine
both cases the metronidazole was discontinued in cats of 0.15 to 0.23 mg/lb once every other
within 24 hours and the ataxia completely day. At this low dose, side effects are very uncom-
resolved within 2 to 4 days. Metronidazole was not mon in my experience, but I have seen one cat
reinstituted in either cat. develop significant pancytopenia within 4 weeks
The most troublesome problem that the of the start of therapy. The cat gradually recovered
owners of my patients have encountered with after immediate cessation of azathioprine. One
metronidazole is excessive salivation after pill blood transfusion was required. Alternatively, if
administration in cats. Metronidazole is known to clinical signs of IBD do not resolve on the initial
have a sharp, unpleasant metallic taste. Most cats azathioprine dose, the dose can gradually be
are given half to one quarter of a 250-mg tablet increased if there is no evidence of bone marrow
per dose, and the taste of broken sections is appar- suppression. Because of lag effect, beneficial thera-
ently quite bitter. Salivation does not occur when peutic results from azathioprine are often not
the medication is administered directly to the back apparent until 3 to 4 weeks after treatment is
of the mouth and quickly swallowed. If, however, started. Azathioprine is generally used for 3 to
the pill is retained in the oral cavity for even the 9 months or longer in cats. A majority of cats with
shortest time, the battle is most likely lost! IBD do not require azathioprine treatment.
Recompounding metronidazole into a tasty sus- A complete blood count and platelet count
pension form often makes the task of administer- should be run to monitor for anemia, leukopenia,
ing metronidazole much easier. and thrombocytopenia before the start of therapy
Metronidazole has shown evidence of carcino- with azathioprine and at 3- to 4-week intervals for
genic activity in studies involving chronic oral the first 2 months, and then once every 2 months.
administration in mice and rats. There are reports Significant side effects are most often identified
of humans with Crohn’s disease who have been during the first 3 to 6 weeks of treatment. There is
treated with high doses of metronidazole for pro- usually no physical evidence of early azathioprine
longed periods of time and in whom breast or oral toxicity in cats. Mild leukopenia (e.g., 3000 to
cancer subsequently developed. A cause-and- 4000 cells/µl) is usually the first abnormality that
effect relationship has not been established. To date is identified. Azathioprine is currently available
I am aware of no cases of GI or mammary cancer only as 50-mg tablets. Because it is too difficult to
that have occurred in dogs or cats in conjunction break azathioprine into a consistent fragment size
with metronidazole use. I consider it to be a safe for cats, it should always be recompounded into an
drug for prolonged use (months to years) in oral suspension form for administration to cats. A
patients with chronic disorders for which long- major advantage of administering azathioprine in
term therapy is required. this manner is that any required increase in dosage
If remission cannot be maintained with use of can be done very accurately. If azathioprine is well
corticosteroids and metronidazole, azathioprine tolerated and there has been inadequate clinical
(Imuran) should be added to the treatment regi- improvement, the dosage can be increased from
men. There is no need to reduce the prednisolone 0.15 mg/lb to 0.2 mg/lb to 0.25 mg/lb every
dose in cats when azathioprine is used in conjunc- 48 hours.
tion. It may not be necessary to continue metro- Another immunosuppressive drug that is used
nidazole after completion of the first 4 weeks of in some cats with severe IBD is chlorambucil
azathioprine therapy. This decision is best made (Leukeran). Some clinicians use chlorambucil as an
on an individual case basis. Azathioprine is a alternative to azathioprine (they are not used in
potent immunosuppressive drug. It is metabolized conjunction). Chlorambucil is an alkylating agent.
to 6-mercaptopurine, its active metabolite, which Alkylating agents alter DNA synthesis and inhibit
functions to interfere with antigenic triggering of rapidly proliferating cells. Chlorambucil is admin-
lymphocytes. Replication of rapidly dividing cells, istered initially at 0.05 to 0.1 mg/lb/day in
CHAPTER 7 CHRONIC DISEASES OF THE SMALL INTESTINE 229
conjunction with prednisolone at 1 mg/lb/day. ulins, lactoferrin, and other immune factors,
The small pill size of chlorambucil (2 mg) allows and stimulation of repair of intestinal membranes
for easy dosing. Most cats receive one-half tablet at the cellular level through actions of epithelial
(1 mg) per day. Various dosage schedules for cats growth factors. There may also be an enhanced
have been published. An alternate schedule is effect of assimilation of nutrients.
0.07 to 0.15 mg/lb every 72 hours. Toxicities are Currently colostrum can be considered as an
uncommon in cats but may include anorexia, alternative therapeutic option for animals with IBD
vomiting, and diarrhea, but these problems gener- that are poorly responsive to conventional medica-
ally resolve rapidly when chlorambucil is reduced tions and dietary trials. Colostrum has been effec-
from daily to every-other-day administration. Bone tive in improving the stool consistency of some
marrow suppression is possible but uncommon animals with chronic diarrhea caused by IBD.
and is mild and rapidly reversible when it does Results in human trials have been promising, and
occur. Once the desired clinical response is use of colostral-derived preparations may become
achieved, chlorambucil is gradually tapered over more prevalent in the next several years. Studies
several months while prednisolone is continued as are needed to help determine the most effective
the primary maintenance drug. dose.Various preparations are currently available in
Colostrum is currently recognized as an emerg- health food stores.
ing therapy for various inflammatory disorders in Cats with hypereosinophilic syndrome should be
human medicine. Some patients with infectious treated aggressively as soon as a diagnosis is estab-
diarrhea caused by Cryptosporidium parvum lished. Prednisolone (1.5 to 2 mg/lb divided twice
have also benefited from bovine colostrum a day for 2 to 4 weeks, then reduced to a mainte-
immunoglobulin concentrate. Animal studies have nance dose of 1 to 1.5 mg/lb/day), metronidazole,
shown promise, and so colostrum also represents a and azathioprine should be used in conjunction.
potential alternative therapy for various disease Contrary to early reports that characterize this
conditions in animal patients. Colostrum is particu- severe eosinophilic enteritis syndrome as very
larly rich in immunoglobulins, antimicrobial pep- poorly responsive to treatment, early aggressive
tides (e.g., lactoferrin and lactoperoxidase), and therapy can help achieve a state of remission in
other bioactive molecules, including growth fac- some patients that can last for months to several
tors. Recent studies have suggested that the pep- years or more. Cats with eosinophilic enteritis, which
tide growth factors in colostrum might provide is a much milder disease than hypereosinophilic
novel treatment options for a variety of GI condi- syndrome, generally respond well to corticos-
tions, as well as other disorders. The growth fac- teroids alone (follow guidelines for treatment of
tors in colostrum include insulinlike growth factor mild to moderate IBD).
I and II (IGF-1 and IGF-2), epithelial growth fac- Antibacterial therapy can be quite beneficial in
tor (EGF), transforming growth factors A and B some situations, most notably for treatment of
(TGFs A and B), growth hormone (GH), fibroblast patients that are suspected of having a bacterial
growth factor (FGF), and platelet derived growth cause or component of IBD and CPE. Indications
factor (PDGF). Bovine colostrum is an excellent for use of antibiotics include histologic changes
source of growth factors and immunoglobulins, that include presence of neutrophils or evidence of
and it will most likely be the main source for ther- crypt abscesses or poor initial response to antiin-
apeutic supplies of colostrum, since it is readily flammatory therapy. Intestinal bacterial problems
available in large supplies, as opposed to human occur more commonly in dogs than in cats.
colostrum. The growth factors in bovine CPE can cause intermittent or chronic diarrhea
colostrum reportedly boost cell and tissue growth (see Chapter 8). Definitive diagnosis requires
by stimulating DNA and RNA formation, and identification of C. perfringens enterotoxin in fresh
also assist in repairing and replacing cell structures. feces (assay available at commercial laboratories).
Other beneficial effects include increases in T cell Amoxicillin, metronidazole, and tylosin appear to
numbers. Antiaging effects are currently under be the most effective antibiotics for treatment
investigation in humans. of CPE. Occasionally only tylosin is effective
Proposed mechanisms of action for colostrum (¹⁄₁₆ tsp Tylan Soluble powder administered in cap-
in IBD include inhibition or prevention of repro- sule form twice a day for cats). Cats generally will
duction of pathogenic invaders and protection not eat food to which tylosin powder has been
against toxins through the action of immunoglob- added. Antibiotics used most commonly for
230 CHAPTER 7 CHRONIC DISEASES OF THE SMALL INTESTINE
bacteria-related intestinal problems in cats include 2. Failure to use ancillary medications (metro-
amoxicillin, metronidazole, enrofloxacin, and nidazole, azathioprine, chlorambucil) in cases
trimethoprim-sulfa. in which disease is moderate to severe
Usually a 2- to 4-week course of antibacterial 3. Failure to recognize and treat a concurrent
therapy is adequate (adjunctive treatment in cases condition (e.g., gastric hypomotility disor-
in which the inflammatory disease is considered der that may either be secondary to IBD
most significant). In cats with IBD that experience or idiopathic in nature, hyperthyroidism,
intermittent flare-ups of diarrhea, the most com- parasitism [e.g., Giardia, Cryptosporidium],
monly successful therapeutic maneuvers are use of CPE)
antibiotics for 2 to 3 weeks at a time or use of more 4. Poor owner compliance
aggressive antiinflammatory measures. Because 5. Treatment for only small intestinal inflam-
metronidazole has both antibacterial and anti- matory disease when colitis is present as well
inflammatory activity, it is an excellent choice for (colitis that might respond better to sul-
use in cats in which symptoms are not well con- fasalazine than to corticosteroids or metro-
trolled by corticosteroids alone. Metronidazole is nidazole)
often used in these situations for several months or 6. Failure to recognize and treat low body
more at a time. cobalamin levels (measure serum cobalamin)
Some cats with concurrent IBD and colitis 7. Failure to identify an effective diet
may show minimal or no clinical signs of colitis.
Initiation of treatment specific for colitis (sulfa-
salazine [Azulfidine] at 5 to 7 mg/lb two times Management of Dogs With IBD
daily for 7 to 10 days at a time and increased Specific treatment recommendations for dogs with
dietary fiber) may result in dramatic improvement IBD are as follows. Corticosteroids are the initial
in cats with enterocolitis. It is interesting to note, treatment of choice for lymphocytic-plasmacytic
however, that cats with colitis generally demon- and eosinophilic enteritis. Mild to moderate
strate a much better response to corticosteroids cases (as determined by clinical signs, normal
than do dogs. Therefore sulfasalazine is used much protein levels, and degree of inflammatory cell
less commonly in cats that in dogs. infiltrate on biopsy specimens) often respond to
As described earlier, significant tissue-level cobal- prednisone at a dose of 0.25 to 0.75 mg/lb divided
amin deficiency is present in some patients with GI twice daily for 2 to 4 weeks, followed by a gradual
disease. This is usually secondary to reduced cobal- decrease in 50% increments at 2-week intervals.
amin absorptive capacity.Therapy involves adminis- Alternate-day or every-third-day treatment can
tering injectable cobalamin at the following often be reached by 2 to 3 months. Occasionally
schedule for cats: 250 µg subcutaneously once a treatment can be discontinued altogether by 3 to
week for 6 weeks, then every 2 weeks for the next 6 months.
six doses, then once monthly. Most generic cobal- Moderate to severe cases and any case in which
amin preparations contain 1 mg/ml (1000 µg/ml). the total protein is less than 5.5 g/dl should be
It is important to note that multivitamin and B- treated more aggressively using an initial pred-
complex injectable formulations contain signifi- nisone dose of 1 mg/lb/day for 2 to 4 weeks
cantly lower concentration of cobalamin and they before an attempt is made to decrease the dose.
also cause pain when injected. Therefore it is rec- Dogs in this category often require long-term
ommended that these preparations not be used for therapy (months to years) on an every-other-day
cobalamin supplementation. Unless the intestinal or every-third-day basis to maintain remission.
disease is totally resolved, long-term and perhaps Use of combination drug therapy (prednisone and
lifelong supplementation with cobalamin may be metronidazole) in these cases at the outset is rec-
necessary. The frequency of injections on a long- ommended to improve chances of controlling
term basis is determined by regular measurement of clinical signs more quickly and to prevent progres-
serum cobalamin concentration. sion of the disease.
Poor responses to treatment of cats with IBD If significantly bothersome side effects are
usually result from the following: caused by prednisone (e.g., severe polyuria/
polydipsia, panting, lethargy), either oral dexa-
1. Inadequate initial or long-term mainte- methasone or budesonide can be used instead.
nance corticosteroid dosage Budesonide is a new oral corticosteroid that was
CHAPTER 7 CHRONIC DISEASES OF THE SMALL INTESTINE 231
described earlier in the section on management of other-day basis. If it is not possible to discontinue
IBD in cats. Its use should be considered in any medication altogether owing to recurrence of
case where conventional corticosteroids may be symptoms when no medication is given, con-
problematic, for example, where side effects are trol can be maintained with prednisone and/or
very significant or in diabetic animals or those metronidazole given on an alternate-day basis. If
with Cushing’s disease that also require manage- both drugs are used, I often recommend giving
ment for IBD. In general, budesonide is adminis- prednisone on one day and metronidazole on the
tered to small dogs at 1 mg once per day. It has alternate day. Occasionally in dogs with moderate
been used at higher doses (3 mg per small dog per to severe IBD or in a case in which both IBD
day), but the lower dose is frequently effective. and chronic bacterial overgrowth are present, it is
Large dogs receive 3 mg twice daily initially, and necessary to continue metronidazole on a long-
the dosage is later tapered to 3 mg once daily, and term (months to years) basis (5 to 7 mg/lb twice
then to alternate day administration for longer daily). I have observed no instances of significant
term use. In some dogs, dexamethasone is much complications when this protocol has been used.
better tolerated than prednisone and side effects Dogs with marked hypoproteinemia (total
are minimal or nonexistent. If prednisone side protein less than 4.5 g/dl) caused by severe
effects are judged to be severe, it is generally dis- lymphocytic-plasmacytic enteritis often respond
continued for 12 to 36 hours to allow for adequate well when an aggressive therapeutic course is
metabolism and clearance. Prednisone may then undertaken (prednisone, metronidazole, and aza-
be reintroduced at 25% to 50% of the previous thioprine used in combination). This aggressive
dose, or, alternatively, dexamethasone can be insti- approach has led to control of clinical signs and
tuted at a conservative level (0.005 to 0.01 return to a total protein level of greater than
mg/lb/day orally). Some dog breeds are very sensi- 6.0 g/dl (by 2 to 4 months) in a number of cases.
tive to steroids and are poorly tolerant of prednisone One exception to this approach in my experience
doses over 0.5 to 0.75 mg/lb/day. Arctic breeds and is that patients with hypoproteinemia resulting
rottweilers are often in this category. from eosinophilic enteritis often respond well to
As was discussed in the section on treatment of corticosteroids alone.
cats with IBD, metronidazole has both antibacte- Combination drug therapy is used early in
rial and antiinflammatory effects. It is very useful severe cases or if a side effect to one drug requires
in treatment of IBD in dogs, as well as in cats. that it be used at a lower dose. If corticosteroids are
Metronidazole is administered at 5 to 10 mg/lb poorly tolerated (e.g., excessive polyuria/polydip-
two times daily. A major advantage of using com- sia, listlessness, panting, inappetence associated
bination therapy is that the corticosteroid dose can with steroid hepatopathy) or if corticosteroids and
usually be decreased from the high initial dose in metronidazole are unable to achieve remission,
a timely manner, thus decreasing the likelihood of azathioprine should be added to the regimen.
significant corticosteroid-related side effects. Azathioprine is started early in the course for cases
Also, I have successfully managed on a long-term of lymphocytic-plasmacytic enteritis that cause a
basis canine patients with mild to moderate protein-losing enteropathy and result in a total
lymphocytic-plasmacytic enteritis that were intol- protein level less than 4.5 g/dl.
erant to corticosteroids on metronidazole alone. The canine dose of azathioprine is 1 mg/lb/day
When prednisone and metronidazole are used (note significant difference in dose between cats
in combination, the dosage level of each drug is [0.15 mg/lb once every other day] and dogs). If
generally gradually decreased as the patient’s con- azathioprine is used at the outset, the prednisone
dition improves and laboratory parameters (espe- dose is decreased by 50% from 1 mg/lb/day after
cially protein levels and white blood cell count) 3 to 4 weeks or based on clinical improvement
return to normal. Corticosteroids are decreased (i.e., remission of signs and increase in protein lev-
gradually for several months before any reduction els) and degree of tolerance of this dose of pred-
is made on the metronidazole dose. If there has nisone. Subsequent decreases in the prednisone
been an excellent response, it is possible that dose can usually be made at monthly intervals
metronidazole can be discontinued after several until an alternate-day schedule is reached. If
months. Alternatively, if chronic therapy is azathioprine is started in any type of IBD case
required, metronidazole can often be administered because of significant corticosteroid side effects,
on a once-daily basis and eventually on an every- the prednisone is initially decreased by 50% to
232 CHAPTER 7 CHRONIC DISEASES OF THE SMALL INTESTINE
75% but is not stopped completely unless absolu- fully discontinued as early as 6 months to 1 year.
tely necessary because loss of remission might In others, lifelong treatment is required.
result. Cobalamin deficiency and associated clinical
Azathioprine is generally used for 3 to 9 months signs were described in the section on IBD in cats.
in dogs. Once adequate control is achieved, the For dogs that are thought to be deficient in cobal-
daily dose is decreased by 50%, and subsequently amin, supplementation is as follows: dogs up to
alternate-day therapy is used. Side effects are 10 lb, 250 µg per injection; 10 to 30 lb, 500 µg per
uncommon in dogs but may include anorexia, injection; and over 30 lb, 1000 µg per injection. As
jaundice (hepatic damage), poor hair growth, and with cats, injections are administered once weekly
bone marrow suppression. In addition, it is sus- for 6 weeks, then every 2 weeks for six doses, and
pected that azathioprine has the potential to induce then once monthly. The incidence of low tissue
pancreatitis (this is an uncommon occurrence, cobalamin levels in dogs with chronic intestinal
however, in my experience). A complete blood disease is not known, but it is recommended
count should be run to monitor for evidence of that dogs with a history of chronic GI disease be
anemia or leukopenia at 3-week intervals for the investigated for this possibility by running serum
first 2 months and then once every several months. cobalamin assays.
Routine monitoring also includes periodic (once Dietary Therapy
every 4 to 6 weeks initially) evaluation of hepatic In some patients with mild lymphocytic-plasmacytic
enzyme levels (increases may be due to corticos- enteritis or eosinophilic enteritis, dietary modifi-
teroids and occasionally azathioprine) and protein cation may lead to partial or complete resolution
levels. of clinical signs and even improvement in histo-
Colostrum, which is currently recognized as a logic lesions. In others, dietary therapy may be an
potential new adjunctive therapy for IBD patients important adjunct to pharmacotherapy in the
that do not respond fully to more conventional control of clinical signs related to chronic IBD. It
therapies, was described in the section on manage- is also possible that dietary management used on a
ment of IBD in cats. There may be indications for long-term basis will effectively help maintain con-
use of colostrum in dogs as well. Therapeutic tri- trol once drug therapy is discontinued. Potential
als in dogs are needed to determine whether or benefits of dietary therapy include reduction of
not this is a useful option to consider. hypersensitivity reactions to dietary antigens, alter-
IBD that is initially graded as moderate to ation of bowel motility, and effects on composition
severe can usually be managed quite successfully of the bowel flora and mucosal morphology and
and can be maintained in remission but not often function.
cured. Sometimes follow-up biopsy specimen Dietary therapy for IBD may involve use of a
analyses in severe cases reveal only slight to mod- strict elimination diet or a balanced commercial
erate histologic resolution of inflammatory infil- diet that contains minimal additives. In most cases,
trates despite excellent clinical control even on diets that are highly digestible and have low
lower drug doses. Alternatively, dramatic histo- residue work best for small intestinal disease. If a
logic resolution has been noted in other cases. decision is made to manage a patient initially with
Treatment decisions (e.g., can treatment be dis- dietary therapy alone, the dietary trial should be
continued completely?) ideally are based on a conducted for a minimum of 3 to 4 weeks. Some
thorough review of clinical response to date (con- patients require 6 weeks or more before clinical
trol of clinical signs, levels of medication required, improvement occurs. If biopsy results reveal mod-
and resolution of hypoproteinemia if it was ini- erate to severe IBD and/or if there is any degree
tially present) and follow-up endoscopic biopsy of patient compromise, pharmacotherapy should
specimen information. be included in the treatment regimen along with
As a general clinical rule of thumb, an attempt dietary management. In my experience, patients
can be made to discontinue therapy after 2 to with this degree of disease rarely respond to
3 months of successful control on twice-weekly dietary manipulation alone.
medication. If signs recur, medication is resumed Diets that often work well include those that
on a daily basis for 7 to 14 days before a gradual supply a single source of protein to which the
reduction program is started. In some dogs with patient has not previously been exposed (i.e.,
severe lymphocytic-plasmacytic enteropathy and “novel” proteins). These may include lamb, rab-
marked hypoproteinemia, therapy can be success- bit, venison, duck, whitefish, or low-fat cottage
CHAPTER 7 CHRONIC DISEASES OF THE SMALL INTESTINE 233
cheese. A single digestible carbohydrate such as tion of fat and the fat-soluble vitamin K. Both cats
boiled rice should be added to home-prepared experienced a sudden onset of bleeding. In one
diets. Many of the premium commercial diets now there was an acute intraabdominal bleeding
include optimum levels of omega-6 and omega-3 episode, whereas in the other there was sponta-
fatty acids. These agents may be useful in reduc- neous and extensive subcutaneous hemorrhage.
ing inflammation in the intestine. Dividing feed- Both cats had marked lymphocytic-plasmacytic
ings into two to three meals per day will help enteritis with villous atrophy.
maximize dietary assimilation. Spontaneous bleeding is an infrequent but
well-documented complication of intestinal mal-
absorption in humans. The acquired hemorrhagic
Unusual Complications in diathesis is characterized as a hypoprothrombine-
Patients With Inflammatory mic disorder secondary to malabsorption of vita-
Bowel Disease min K. The fact that this occurs infrequently in
Several complications associated with IBD or its patients with malabsorption is probably attributa-
treatment have been reported. These include the ble to absorption of bacterially derived vitamin K2
potential for IBD to progress to lymphoma, hem- from the ileum and colon.
orrhagic diathesis secondary to intestinal malab- Treatment involves subcutaneous injections of
sorption of fat and the fat-soluble vitamin K, and vitamin K (oral administration should be avoided
toxoplasmosis in cats on immunosuppressive ther- because the active absorption of vitamin K from the
apy for treatment of IBD. duodenum is unpredictable in patients with malab-
sorption). Its use is also indicated before surgery
Lymphoma. It has been recognized in cats, when abnormal clotting is detected. Chronic main-
dogs, and humans that IBD can progress to lym- tenance therapy (oral vitamin K) may also be
phoma. In one report, three of nine cats with required. Dietary fat requirements of patients with
lymphocytic-plasmacytic gastroenteritis confirmed malabsorption should be met by short- or medium-
by full-thickness biopsy, diagnosed during a 1-year chain saturated fatty acids, because absorption of
period, subsequently developed GI lymphoma 9 to vitamin K is reduced by progressively longer chain
18 months after the initial diagnosis. Clinical signs fatty acids and greater degrees of unsaturation.
initially resolved in all cats in response to manage-
ment with hypoallergenic diets but later recurred Toxoplasmosis. Intensive immunosuppressive
in the three cats with lymphoma. therapy for IBD can potentiate reactivation of latent
To date the progression has been found overall infections. Toxoplasmosis was reported in two cats
to be an uncommon occurrence. No one type of that were initially diagnosed with and treated for
IBD is recognized as more likely than others to IBD. Toxoplasma gondii was found on follow-up
progress to lymphoma. It has occurred in cats with biopsy (full thickness) of the intestine in one cat 9
an original diagnosis of lymphocytic enteritis, weeks after endoscopic biopsy specimens had
lymphocytic-plasmacytic enteritis, or lympho- revealed severe lymphocytic-plasmacytic gastroen-
cytic-plasmacytic-eosinophilic enteritis. teritis. Treatment had included prednisone,
In my four feline cases in which progression metronidazole, and azathioprine. Both cats had
occurred, initially there was excellent control of serologic evidence of active toxoplasmosis. In cats
the inflammatory bowel disorder with conven- treated with azathioprine, it is hypothesized that
tional treatment. All four cats required chronic active toxoplasmosis was attributable to reactivation
medication to control clinical signs, and at a range of a prior infection, resulting from the immunosup-
of 1 to 3 years, clinical remission was lost. Follow- pressive effects of prednisolone and azathioprine.
up histologic evaluation is recommended in Both cats had no signs of illness other than GI tract
patients with IBD if previous treatment is no disease (diarrhea, weight loss). Recent coincidental
longer successful in controlling clinical signs in infection was considered highly unlikely because
order to detect and treat lymphoma as early as both cats were kept strictly indoors and were fed
possible. controlled diets.
Experience from these two cases indicates that
Hemorrhagic Diathesis. One report de- toxoplasmosis should be considered in cats with
scribed two cats with hemorrhagic diathesis that IBD if signs of illness (i.e., GI type of signs) occur
was thought to be related to a chronic malabsorp- during treatment with immunosuppressive drugs.
234 CHAPTER 7 CHRONIC DISEASES OF THE SMALL INTESTINE
Recurrent signs of IBD may actually not be due to are rarely found in the proximal small intestine of
failure of the current treatment regimen. Diagnosis the dog, whereas in cats there may be up to 105 to
of toxoplasmosis is based on serologic documenta- 108 bacteria per milliliter of fluid, commonly includ-
tion of active toxoplasmosis (IgM titers should be ing obligate anaerobic bacteria such as Bacteroides,
done because they may permit earlier diagnosis Eubacterium, and Fusobacterium. In cats Pasteurella spp.
than is possible with IgG titers) and response to are the most common bacteria isolated.
an anti-Toxoplasma drug (clindamycin is recom- The pathophysiology of SIBO is very complex
mended). Treatment for IBD is continued as and is related to both the effects of proliferation of
needed. bacteria in the intestinal lumen and direct damage
to enterocytes. Potential mechanisms include
direct injurious effects on brush border enzymes
SMALL INTESTINAL and carrier proteins, secretion of enterotoxins,
BACTERIAL deconjugation of bile acids, hydroxylation of fatty
acids, and competition for nutrients.
OVERGROWTH The most common clinical signs of SIBO are
Small intestinal bacterial overgrowth (SIBO) is a diarrhea and weight loss.Vomiting, flatulence, and
syndrome in which there are excessive numbers of anorexia may also occur. Diarrhea is usually of
bacteria (more than 105 organisms per milliliter small bowel type of consistency and may be
of intestinal contents) in the duodenum and watery to soft formed and malodorous. Stools may
jejunum in a fasting state.This overproliferation of also be lighter in color than normal, but this is a
microflora can result in malabsorption and diar- nonspecific sign. Blood and mucus are usually not
rhea. SIBO is well recognized in dogs and humans, present (if they are, a large bowel disorder of any
but there are no reports of SIBO in cats. type should be considered). Other clinical signs that
The normal small intestinal microflora consists might be present occur as a result of a primary
of a small but stable population of aerobic and fac- disorder (e.g., ravenous appetite associated with
ultative anaerobic bacteria. Population size is influ- exocrine pancreatic insufficiency, decreased appetite,
enced by factors such as the host’s immune system, frequent vomiting, and lethargy associated with
bacterial interactions, dietary composition, and the obstruction).
action of normal mechanisms that help to limit
bacterial overgrowth (secretion of gastric acid, the
dynamic process of intestinal motility and contin- Diagnosis
uous aborad flow of ingesta, and antibacterial fac- Establishing a definitive diagnosis of SIBO is diffi-
tors in pancreatic juice). Causes of overgrowth of cult in a private-practice setting. Ideally, quantitative
bacteria may include anatomic factors such as duodenal fluid cultures should be done to deter-
obstruction (e.g., partial stricture, presence of a mine if SIBO is present. This is difficult to do
mass), segmental hypomotility, conditions associ- properly and is also expensive. Aliquots of duode-
ated with decreased secretion of gastric acid, intes- nal fluid need to be obtained either at laparotomy
tinal mucosal disease, immunodeficiency states, or by using a sterilized endoscope to obtain sam-
and concurrent exocrine pancreatic insufficiency, ples from the small intestine. A positive response
or it may result from some unidentifiable cause. to antibiotics (e.g., amoxicillin, metronidazole,
A state of immunodeficiency may be one of the tetracycline, tylosin) for 2 to 4 weeks can be used
reasons that SIBO might be more commonly as a presumptive diagnosis of SIBO.
diagnosed in German shepherds and shar-peis than The best screening tests for use in private
in other breeds. These breeds appear to have a practice involve serum analysis of fasting cobal-
higher incidence of IgA deficiency. The most amin (vitamin B12) and folate levels, although
common problems in dogs with IgA deficiency these tests are not regarded as very sensitive,
are recurrent infections and atopic dermatitis. The because many affected dogs do not have abnor-
infections associated with IgA deficiency are gen- mal test results. Abnormalities that suggest
erally not severe or life threatening, and treatment SIBO include elevated folate levels (due to
is symptomatic. increased production by abnormal microflora)
Although any species of bacteria may be found, and decreased cobalamin levels (due to utiliza-
Escherichia coli, enterococci, and lactobacilli are tion by microflora). It is not common for this
more common in dogs. Obligate anaerobic species combination of results to be found. In many
CHAPTER 7 CHRONIC DISEASES OF THE SMALL INTESTINE 235
patients only one of the two tests is abnormal. weeks to many months. Some patients require
In patients with SIBO that is not present in con- intermittent treatment. Sometimes once-daily
junction with exocrine pancreatic insufficiency, antibiotic administration is adequate in patients
elevated folate level is found in approximately that require long-term therapy. Any identifiable
50% of the cases, and decreased cobalamin level causes should be removed (e.g., surgical removal of
alone in about 25% of cases. These tests should blind or stagnant loops of bowel). Antibiotics that
be considered in any patient that has chronic have broad-spectrum effect that includes anaerobic
diarrhea, including those with exocrine pancre- bacteria are selected (amoxicillin, metronidazole,
atic insufficiency (these dogs commonly have tetracycline, and tylosin are good choices). If there
SIBO). Cobalamin levels that are below the con- is a rapid response to therapy, an attempt to dis-
trol range may also be consistent with disease continue antibiotic administration can be made
affecting the distal small intestine (cobalamin is after 2 to 3 weeks.
absorbed only in the last 25% of the distal small If long-term antibiotic administration seems to
intestine). Folate levels below the control range be necessary, my preference is usually to use either
may indicate infiltrative disease affecting the metronidazole or tylosin powder. The recom-
proximal small intestine (folate is absorbed in mended dose of tylosin is 5 to 10 mg/lb orally
the proximal small intestine only). every 12 hours mixed with food. Tylosin powder
A new test for SIBO is serum unconju- has a bitter taste, and some dogs will accept it bet-
gated cholic acid (SUCA). Many of the species ter if it is mixed in the food initially in very small
of bacteria that increase in number in SIBO have the amounts.
capacity to unconjugate bile acids. Unlike the con- It is emphasized that concurrent problems may
jugated bile acids that are normally present in the be present with SIBO, and even if the bacterial
small intestinal lumen, bile acids that are unconju- overgrowth is adequately treated, an underlying
gated diffuse across the intestinal mucosa into the disorder not yet diagnosed and managed may itself
blood. In dogs, SUCA values greater than 72 nm/L cause persistence of clinical signs.
are suggestive of bacterial overgrowth or disturbance
of the normal flora of the upper small intestine. The
SUCA test is currently available at the Texas A&M CHRONIC
University GI Lab. ENTEROPATHY
The sample should be shipped overnight on
ice, ideally on the same day on which the sample
IN SHAR-PEIS
is obtained. Dogs should be fasted for 12 hours Shar-peis with chronic diarrhea frequently have
before sampling. When testing for SIBO, it is rec- PLE due to moderate to severe IBD, and some also
ommended that serum for cobalamin, folate, and likely have intestinal bacterial overgrowth as well.
SUCA assays should be run concurrently. Trypsin- Typical signs in shar-peis often include persistent
like immunoreactivity (TLI) assay should be done diarrhea weeks to months in duration, weight loss,
as well if pancreatic exocrine insufficiency has not and an increased to ravenous appetite. There is
already been ruled out. almost always evidence of small bowel diarrhea,
It is not uncommon for a dog with IBD to but in some dogs large intestinal signs such as
have SIBO as well. Intestinal biopsy speci- hematochezia, mucoid feces, and dyschezia are
mens from patients with SIBO are normal or may evident as well. I have seen shar-peis that con-
show minimal morphologic mucosal changes. currently have vomiting that is due to gastric
Minor changes may include mild atrophy of hypomotility, and occasionally reflux esophagitis
villi and a slight increase in inflammatory cells. is diagnosed as well, based on endoscopic findings
If intestinal biopsy samples in a dog or cat of esophageal lesions. Energy level often remains
with chronic diarrhea are normal or exhibit only normal or nearly normal until the disease is
mild changes, the presence of SIBO should defi- severe.
nitely be considered. The prognosis for successful clinical control of
symptoms is excellent as long as a definitive diag-
nosis is made before the disease becomes too
Treatment severe. Clinicians are reminded that although a
Treatment of SIBO involves use of selected antibi- great majority of shar-peis with chronic diarrhea
otics, and treatment time may vary from several have IBD and some also likely have SIBO, an
236 CHAPTER 7 CHRONIC DISEASES OF THE SMALL INTESTINE
least several factors involved concurrently. Possible mined if antibiotics should be continued on a
factors include the following: long-term or intermittent basis.
severe form of IBD that is thought to result from nosis, although some affected dogs can be main-
a genetic disorder of immune regulation. There is tained for a period of years with careful monitor-
an intense infiltration of lymphocytes and plasma ing and ongoing therapy.Affected dogs should not
cells in the intestinal mucosa. Other changes often be bred.
include gastric rugal hypertrophy, lymphocytic
gastritis and/or gastric mucosal atrophy, blunting
and widening of intestinal villi, and mild dilation
LYMPHANGIECTASIA
of lacteals. Intestinal lymphangiectasia is a chronic protein-
The disorder is often progressive in nature. losing enteropathy of dogs that results in malab-
Clinical signs may tend to be intermittent for a sorption. It is characterized by obstruction and
period of time before they worsen and become dysfunction of the intestinal lymphatic network.
more persistent. GI signs may be exacerbated by Lymphatic obstruction leads to stasis of chyle
episodes of “stress,” such as traveling, boarding, or within dilated lacteals and lymphatics of the bowel
other medical disorders. Clinical signs usually wall and mesentery. Lymphatic hypertension results,
include small intestinal diarrhea, which may become and overdistended lacteals release intestinal lymph
intractable, vomiting, and/or inappetence. Weight into the intestinal lumen either by extravasation or
loss can become significant as the disease pro- by rupture, resulting in loss of protein, lymphocytes,
gresses. Ulcerative dermatitis of the pinnae occa- and chylomicrons. Although proteins may be
sionally occurs in conjunction with this disease. digested and resorbed to some extent, loss in patients
Most affected basenjis demonstrate clinical signs with a significant degree of lymphatic obstruction
by 3 to 4 years of age. eventually exceeds the normal recovery mechanism,
Basenji enteropathy is commonly associated and hypoproteinemia results.
with hypoalbuminemia and hyperglobulinemia, At the time of presentation, dogs with lym-
especially in advanced cases. Neutrophilic leuko- phangiectasia frequently have marked hypopro-
cytosis and mild nonregenerative anemia are com- teinemia. Prominent clinical consequences include
monly present as well. Early in the disease course, body cavity effusions (ascites, hydrothorax) and
basenji enteropathy may mimic other forms of IBD dependent pitting edema of the subcutis and limbs.
(e.g., mild symptoms, no significant laboratory In addition to hypoproteinemia, leakage of fat
abnormalities). (chylomicrons) from the lacteals may cause inflam-
As the disease becomes more advanced, signs mation and granuloma formation in the intes-
and laboratory parameters are characteristic; how- tinal wall, which may further exacerbate lymphatic
ever, clinicians should be aware that other forms of obstruction.
intestinal disease, such as lymphoma, lymphangiec- Potential causes of lymphatic obstruction
tasia, or histoplasmosis, may be present, and the include congenital malformation of the lymphatic
symptoms of any of these diseases can mimic system; infiltration or obstruction due to an inflam-
basenji enteropathy. Therefore it is always best to matory, fibrosing, or neoplastic process; obstruction
confirm the diagnosis by doing intestinal biopsies of lymph flow through the thoracic duct; and peri-
before instituting aggressive immunosuppressive carditis or congestive heart failure. Generalized
therapy. inflammatory disease of the intestinal lymphatic
Treatment of basenji enteropathy is based on network is probably the most common factor in
control of the inflammatory bowel component pathogenesis of the disease. The cause of this
(see guidelines for treatment of IBD in dogs inflammation is undetermined in most cases. Most
described earlier in this chapter), management of dogs with lymphangiectasia also have mild to
intestinal bacterial overgrowth if it is present, and moderate lymphocytic-plasmacytic infiltration in
feeding a controlled or hypoallergenic diet. the lamina propria. The fact that patients with
Because the disease is often progressive, basenjis lymphangiectasia often respond better when cor-
with this disorder should be carefully monitored. ticosteroids are included in the treatment regimen
Over time, treatment may need to include combi- adds credence to the theory that an inflamma-
nation immunosuppressive drugs and use of long- tory process is involved in the pathogenesis of the
term antibiotics (e.g., metronidazole, tylosin). If disease.
there is evidence of gastric hypomotility, a pro- Lymphangiectasia is not commonly encoun-
motility drug (metoclopramide or cisapride) is also tered in clinical practice. Of the diseases that cause
used. Most basenjis die within 2 to 3 years of diag- protein-losing enteropathy, IBD (especially severe
CHAPTER 7 CHRONIC DISEASES OF THE SMALL INTESTINE 239
lymphocytic-plasmacytic enteritis) is by far the is reviewed (a “stress” leukogram also includes neu-
most common. Although some dogs with lym- trophilia and eosinopenia).
phangiectasia respond well to treatment, this dis- Lymphangiectasia must be differentiated from
ease is not as consistently responsive to therapy as other protein-losing enteropathies and from non-
is IBD. Breed predilections for intestinal lym- intestinal causes of hypoproteinemia (primarily
phangiectasia are not documented, but there seems liver and kidney disease). If hypoproteinemia occurs
to be an increased incidence in Yorkshire terriers, in association with kidney and liver disease, it is
soft-coated wheaten terriers, lundehunds, and rot- usually primarily due to a decrease in the albumin
tweilers. Lymphangiectasia should be a leading fraction (impaired synthesis in liver disease and
consideration if hypoproteinemia is detected in increased loss through the glomeruli in protein-
any of these breeds. losing glomerulonephropathy). Liver function test-
ing (e.g., serum bile acids assay) and urine protein
determinations (e.g., urine protein-creatinine
Clinical Signs ratio) are very useful in evaluating for presence of
The most common clinical manifestations of lym- liver and kidney disease.
phangiectasia are diarrhea and weight loss. It is Intestinal biopsy specimens can be obtained at
important to note, however, that some dogs do not either endoscopy or surgery. Endoscopy offers a safer
have diarrhea until the disease process is advanced, approach to obtaining small bowel biopsy samples in
or there may be no incidence of diarrhea at all. protein-losing enteropathy cases in which there is
Initial presentation may be directly related to signs concern that full-thickness biopsy sites may heal
associated with significant hypoalbuminemia and slowly. This is an especially important consideration
the effects of reduced colloidal osmotic pressure, in patients with a total protein level less than
including peripheral edema, ascites, and increased 3.5 g/dl. Lymphangiectasia has a characteristic histo-
respiratory rate and/or distress secondary to logic appearance. The severity of lesions is usually
hydrothorax. The onset of clinical signs may be graded as mild, moderate, or severe. Lymphangitis
acute (less than 21 days in 10 of 17 dogs in one may be present as well. Concurrent inflammatory cell
reported case series) or chronic (greater than infiltrates are usually found on histologic examination.
21 days in 7 of 17 dogs). In some cases pronounced gross changes can
When present, diarrhea is usually watery to be seen at endoscopy (white “cottony” appearance
semisolid in consistency. It may be persistent or or multifocal white granular foci of the mucosa,
intermittent. Vomiting may be observed in dogs occasional presence of pooled mucoid lymph fluid
with lymphangiectasia (11 of 17 dogs in one case in the intestinal lumen). Occasionally a diagnosis
series). Progressive weight loss is common. of lymphangiectasia is missed if only the descend-
ing duodenum is examined and sampled during
biopsy. In dogs with hypoproteinemia associated
Diagnosis with chronic diarrhea, it is best to examine both
A definitive diagnosis of lymphangiectasia is made upper (duodenum, and jejunum if it can be
only on intestinal biopsy specimen analysis. The reached) and lower small intestine (the ileum can
index of suspicion is heightened when the follow- be entered after traversing the colon) to obtain
ing test results are identified: samples from as many areas as possible. This
● Panhypoproteinemia (often between 2.5 and approach maximizes the likelihood that represen-
5.0 g/dl total protein at the time of diagno- tative biopsy samples will be obtained.
sis, with albumin frequently in the range of Gross lesions that may be observed at lapa-
0.8 to 1.6 g/dl) rotomy include a prominent weblike network of
● Absolute lymphopenia (found in approxi- dilated milky-white lymphatic channels; small
mately 70% of cases and due to loss of lym- yellow-white granulomas (lipogranulomas) adja-
phocytes into the gut lumen) cent to lymphatics; patchy, foamy white deposits
on the serosa; and diffuse intestinal thickening. As
● Hypocholesterolemia
is the case any time full-thickness intestinal biopsy
● Hypocalcemia
samples are obtained from a hypoproteinemic
Lymphopenia is also a common hematologic patient, serosal patch grafting and nonabsorable
finding in “stressed” patients however, and this fac- suture material should be used to minimize
tor should not be overlooked when the hemogram chances of dehiscence and peritonitis.
240 CHAPTER 7 CHRONIC DISEASES OF THE SMALL INTESTINE
I have found that it is very difficult to diagnose Absorption of long-chain triglycerides from the
lymphangiectasia in rottweilers endoscopically. diet stimulates an increase in intestinal lymph flow,
This is primarily because lesions in this breed are thus promoting further engorgement of intestinal
frequently most prominent in the jejunum, an lacteals and subsequent loss of more protein. Fat
area of the small intestine that is difficult to reach restriction helps decrease lymphatic hypertension
in large-breed dogs with an endoscope. Typical by decreasing lymph flow and aids in controlling
clinical signs in rottweilers include weight loss, diarrhea, presumably by reducing steatorrhea.
chronic intermittent diarrhea, decreased appetite, Initially a home-prepared diet that includes
and occasionally peripheral edema. There is usu- nonfat or low-fat cottage cheese as the primary
ally significant hypoproteinemia (often ranging protein source and carbohydrate sources such as
from 2.8 to 4.0 g/dl). The lymphocyte count is boiled rice, potatoes, and pasta is fed (one part cot-
frequently but not always low. Biopsy speci- tage cheese and three parts carbohydrate source).
mens from duodenum and ileum often reveal only White turkey and potatoes is a formulation that
mild lymphocytic-plasmacytic enteritis in rottweil- also works well for some dogs. Yogurt can also
ers with lymphangiectasia. This mild degree of be used as a source of protein. Diets should be
inflammatory infiltrate is not enough to explain supplemented with a fat-soluble vitamin.
the degree of hypoproteinemia and clinical signs One of the greatest difficulties encountered in
that are often present, and this finding certainly managing dogs with lymphangiectasia is that some
should raise suspicions that a more significant tend to be inappetent, even when corticosteroids
process is involved. are included in the treatment regimen. Owners
If a disorder that is consistent with the clinical should be encouraged to try a variety of low-fat
presentation is diagnosed at endoscopy (e.g., mod- foods until they find something that the dog
erate to severe IBD), treatment for that disorder will eat. Sometimes breakfast cereals are readily
should be instituted. If there is suspicion that a dis- ingested. Persistent coaxing may be required.
ease other than what was diagnosed at endoscopy Once a dog with lymphangiectasia begins to eat
is present, ideally exploratory surgery should be well, there is often noticeable clinical improve-
done next to evaluate the serosa and mesentery for ment and the prognosis gradually begins to
gross evidence of lymphangiectasia and to obtain improve. For example, removal of ascitic fluid from
full-thickness intestinal biopsy samples. If the dog a significantly distended abdomen may promote a
is judged to be a poor surgical candidate, treatment return to a normal appetite. An appetite stimu-
for lymphangiectasia and IBD should be insti- lant such as cyproheptadine is sometimes effec-
tuted. The prognosis for reasonable control in tive. Frequent divided feedings should be provided
rottweilers is guarded to fair. The prognosis is bet- initially.
ter if the dog eats enough of the prescribed diet to As improvement in overall condition occurs
effect weight gain. (increase in weight, resolution of diarrhea if it was
present, increase in serum protein levels), commer-
cial foods can be added gradually on a trial basis.
Treatment Some clinicians elect to feed commercial diets at
The cornerstone of treatment for lymphangiecta- the outset of therapy. Special commercial diets
sia is dietary management. Corticosteroids are such as Innovative Veterinary Diets (IVD) Select
used to reduce the intestinal inflammation that is Care Canine Sensitive formula, IVD Vegetarian
often present. As is true any time there is a chronic Diet, Iams Low Residue (Iams Food Co), and
enteropathy, an effort is made to investigate as Prescription Diet i/d and/or w/d (Hill’s Pet
thoroughly as possible for other disorders that may Products) can be tried. One significant disadvan-
be present at the same time. For example, I have tage of feeding low-fat calorie-restricted diets such
treated dogs with lymphangiectasia that concur- as Prescription Diet r/d in dogs with lymphan-
rently had CPE and intestinal parasites. Bacterial giectasia is that when this type of food is used as
overgrowth should always be considered as well. the primary diet, it is difficult to meet the patient’s
Response to treatment is best when all disorders total energy requirements. Palatability can also be
are adequately treated. a problem. Some dogs do best when fed a combi-
The ideal diet for lymphangiectasia should nation of home-prepared and commercial foods.
contain minimal fat (long-chain triglycerides) and Long-term dietary management is required in
provide an ample quantity of high-quality protein. most cases.
CHAPTER 7 CHRONIC DISEASES OF THE SMALL INTESTINE 241
Most dogs with lymphangiectasia benefit from misnamed phycomycosis (outdated name that should
corticosteroid therapy. Prednisone is administered no longer be used).
at 1 to 1.5 mg/lb daily for 2 to 4 weeks and then Historically, definitive diagnosis of pythiosis
gradually decreased to a maintenance level of and zygomycosis has been difficult because of the
0.1 to 0.2 mg/lb every other day. If there is an challenges inherent in obtaining a culture-based
excellent response to dietary management and confirmation of these organisms. Therefore a pre-
corticosteroids, the corticosteroids can often be sumptive diagnosis has often been made (i.e.,“sus-
discontinued after 3 to 6 months’ total treatment pected pythiosis”) based on histopathologic
time. findings. Newer tests are now available that are
If there is poor weight gain despite adequate making specific diagnosis somewhat easier.
food intake, it is sometimes beneficial to supple- Clinical signs include chronic intractable diar-
ment the diet with medium-chain triglycerides rhea and vomiting, loss of appetite, depression, and
(MCT Oil). Medium-chain triglycerides are chronic weight loss. The diarrhea may become
hydrolyzed more rapidly and efficiently than long- bloody due to intestinal necrosis and ulceration.
chain triglycerides and are absorbed directly into Extensive granulomatous reaction may cause pal-
the portal system, thus bypassing the diseased lym- pable enteromesenteric masses to develop. There
phatics. The primary purpose of supplementing may eventually be spread to other abdominal
the diet with medium-chain triglycerides is to sup- viscera.
ply extra calories. MCT Oil contains 8 kcal/ml. Baseline laboratory tests may reveal mild to mod-
The recommended dose is 0.5 to 1 ml/lb mixed erate nonregenerative anemia, neutrophilic leukocy-
in food. Because most dogs (and humans!) do not tosis, and panhypoproteinemia. Survey abdominal
like the taste of MCT Oil, gradual introduction radiography may reveal a mass effect, and barium
and thorough mixing in the food are recom- contrast radiography may identify an area of
mended. I do not routinely recommend using obstruction. Abdominal ultrasonography can iden-
MCT Oil with dogs other than those that I feel tify intestinal thickening and lymphadenopathy.
will significantly benefit from its use. Rectal scraping cytologic analysis may reveal organ-
isms as may a fecal culture. Historically diagnosis
has been dependent on histologic identification of
PYTHIOSIS characteristic hyphae in biopsy samples of stomach,
Pythiosis is a severe and often fatal cause of intestine, or abdominal lymph nodes. Diagnostic
chronic GI or cutaneous disease in dogs living tissue samples are best obtained surgically, because
mostly in tropical or subtropical climates. In the endoscopic biopsy techniques do not reliably har-
United States most cases are seen in the Gulf Coast vest adequate tissue in all cases for diagnosis of
region, but it has been seen as far north as southern pythiosis. Extensive tissue reaction may be evident
Indiana, Missouri, Kentucky, and North Carolina. at laparotomy, and this should not be mistaken for
There are also rare cases in cats that involve neoplasia. It is best to obtain tissues and await a his-
mostly invasive subcutaneous lesions. Pythiosis is tologic diagnosis rather than making assumptions
caused by the aquatic oomycete Pythium insidio- based on visual inspection alone.
sum. The infective stage of P. insidiosum is The clinical faculty at Louisiana State University
thought to be the zoospore, which is released has extensive experience in diagnosis and manage-
into warm water environments. Infection is ment of pythiosis and zygomycosis, and some prom-
caused either through encystment in the skin or ising new tests have recently been developed in
through ingestion. GI pythiosis causes severe their laboratory. These include polymerase chain
segmental transmural thickening of the GI tract reaction (PCR)-based assays and serologic analysis.
with variable mucosal ulceration and mesenteric There is now a PCR test available for identification
lymphadenopathy. of P. insidiosum. This assay can be applied to DNA
There are other fungal agents of the class extracted either from cultured isolates or from
Zygomycetes that can cause severe intestinal and appropriately preserved infected tissue samples. The
skin disease. It is difficult to differentiate some of test will reliably differentiate P. insidiosum from other
the agents, however, and so the general term Pythium species. A new highly specific and sensitive
zygomycosis is often used. Dogs with zygomycosis mycelial antigen-based ELISA assay for the detec-
oftentimes are undifferentiated from those cases tion of anti–P. insidiosum antibodies is also now
with pythiosis. These infections were formerly available for use on samples from both dogs and
242 CHAPTER 7 CHRONIC DISEASES OF THE SMALL INTESTINE
cats. This test provides an excellent means for mak- vascular thrombosis, loss of blood supply due to
ing an early, noninvasive diagnosis and also provides injury, and intestinal neoplasia. Clinical mani-
an excellent means for monitoring response to festations of short bowel syndrome persist when the
therapy. This is especially important with regard to remaining intestine is unable to undergo adequate
the GI form of the disease because, unlike skin compensatory changes. SIBO may also become
lesions, the lesions cannot be visually monitored by a significant complicating factor, especially if the
the owner. ileocolic valve is removed.
Affected patients usually have unrelenting small
bowel diarrhea and progressive weight loss in the
Treatment face of a ravenous appetite. It should be noted,
The treatment of choice for pythiosis is aggressive however, that not all patients that lose a large
surgical removal of lesions. Complete resection amount of small intestine have signs of short bowel
provides the best chance for long-term cure. For syndrome. It is not always the amount of bowel
intestinal lesions the goal is to resect infected tis- loss that determines whether or not a patient will
sues with 4- to 6-cm margins. Postoperative med- be affected. The response to bowel loss is often
ical management is also necessary, because there is unpredictable. Clinically, sometimes a patient will
always a chance for local recurrence. Medical do surprisingly well when it was anticipated that
management using itraconazole either with or the prognosis would be poor, and in other cases a
without terbinafine is recommended for a period patient will do unexpectedly poorly. Several impor-
of 2 to 4 months after surgery. Drug cost is a sig- tant factors are involved in determining clinical
nificant concern for some owners. If medical man- course. These include the following:
agement cannot be afforded, then ELISA serologic 1. Status of the ileocolic valve (symptoms are
analysis is recommended at several-month inter- consistently worse if the valve is lost)
vals for up to a year after surgery to monitor for 2. The extent and site of bowel resection
evidence of recurrence. 3. The functional capacity of the remaining
Medical management alone is often unreward- bowel and other digestive organs
ing, but this is the only choice in patients that 4. The degree of adaptation that subsequently
have diffuse nonresectable disease. The internal occurs in the remaining small and large
medicine service at Louisiana State University intestine
has reported that in recent years about 15% of
their cases of pythiosis in dogs have responded The ileocolic valve is important for preventing
to either itraconazole at 5 mg/lb every 24 hours SIBO, and it may also play an important role in
for 3 to 6 months or amphotericin B lipid com- slowing small intestinal transit time.
plex (Abelcet) 1 to 1.5 mg/lb administered intra- Maldigestion and malabsorption are prominent
venously over several hours every other day to a features of short bowel syndrome. Factors causing
cumulative dose of 11 to 12.5 mg/lb. The drugs malabsorption include decreased absorptive sur-
can also be used in combination, or, alternatively, face area; reduced transit time, which results in
itraconazole and terbinafine (2.5 to 5 mg/lb per inadequate intestinal mucosa–nutrient contact
24 hours) can be used in combination. Com- time; decreased bile salt reabsorption, especially if
bination has been shown to achieve a better the ileum is lost, resulting in decreased fat absorp-
response overall, although the prognosis still tion; and decreased fatty acid absorption, which
remains very guarded. results in impairment of colonic water absorption.
Maldigestion results from decreased nutrient
SHORT BOWEL contact time with digestive enzymes; deficiency of
cholecystokinin and secretin in patients with signif-
SYNDROME icant resection of duodenum and jejunum, which
Short bowel syndrome refers to the clinical con- subsequently causes decreased release of pancreatic
sequences of massive small bowel resection, with or and biliary exocrine secretions; and loss of impor-
without some additional loss of large intestine. tant mucosal brush border digestive enzymes, which
Short bowel syndrome frequently results when 75% follows massive bowel resection. Gastric acid hyper-
or more of the small intestine is resected. Reasons secretion may also occur after massive small bowel
for massive bowel resection include intussusception, resection, for unknown reasons. Consequences of
intestinal infarction secondary to strangulation or acid hypersecretion may include inactivation of
CHAPTER 7 CHRONIC DISEASES OF THE SMALL INTESTINE 243
pancreatic lipase and increased osmolarity in the factor of diarrhea and should be controlled with
small intestinal lumen. H2-receptor antagonists (e.g., famotidine). Intestinal
The degree of adaptation that occurs in the bacterial overgrowth is managed with antibiotics
small intestine is an important factor in determin- (metronidazole and amoxicillin or enrofloxacin are
ing whether or not a patient will be able to often used initially; metronidazole and/or tylosin
recover sufficiently to maintain adequate fluid bal- are often used if long-term antibiotics are required).
ance and body weight. Over time following mas- It is sometimes useful to provide pancreatic enzyme
sive bowel resection, compensatory changes that replacement therapy (e.g., Pancrezyme). If diar-
increase the absorptive surface of the remaining rhea is persistently watery, an antidiarrheal agent
intestine occur. The fact that it takes time for com- such as loperamide is used. The dose for dogs is
pensation to occur is an important clinical point, 0.05 to 0.1 mg/lb orally two to three times daily.
because it is important that a decision resulting in Loperamide can be used in cats at 0.025 to 0.04
too early euthanasia of a patient not be made too mg/lb every 12 hours. In some patients, it may
hastily. These include increased bowel diameter, be necessary to use loperamide on a long-term
lengthening of villi, and crypt enlargement to basis.
maximize the number of mucosal cells per unit If the treatments listed above are not considered
length of gut. One of the most important factors reasonably effective, several other maneuvers can be
in promoting adaptation is the presence of intralu- tried. Research work published in Japan in 1992
minal nutrients (long-chain triglycerides or long- suggested that ursodeoxycholate (UDCA) is bene-
chain free fatty acids have been shown to have the ficial in some dogs with short bowel syndrome.
greatest trophic effect, but any nutrient may pro- The study involved resection of 75% of the small
mote a stimulatory effect). Pancreaticobiliary secre- intestine in healthy beagle dogs followed by separa-
tions, GI and other hormones, and prostaglandin E2 tion of the dogs into one of three treatment groups:
also play a role in stimulating bowel adaptation. 1. 300 mg UDCA plus 0.375 µg of vitamin D3
Corticosteroids probably do not have any significant every other day
effect on promoting bowel adaptation. 2. 0.375 µg vitamin D3 every other day
3. Control group, no drug therapy
Clinical Signs Dogs medicated with UDCA experienced sig-
In patients that have undergone extensive resection, nificant improvements in body weight, fecal char-
persistent diarrhea that is often watery in nature is acteristics, and overall nutritional status. The
the predominant early sign. Dehydration and elec- beneficial effect of UDCA may be in prolongation
trolyte deficiencies can readily occur. Postoperative of intestinal transit time. Other investigators have
treatment is directed at preventing these factors also found that UDCA has an inhibitory effect on
from becoming significant. Malabsorption predom- GI smooth muscle.
inates during the ensuing weeks, and major weight Finally, use of a hydrophilic laxative may help
loss and nutritional deficiencies develop. Later, as decrease fluidity of the existing bowel content and
intestinal adaptation begins to occur, body weight increase fecal bulk. Among the compounds that
frequently stabilizes, although at levels that are may be tried are methylcellulose (Citrucel), psyl-
mildly to moderately below preresection levels. lium (Metamucil, Siblin), Karaya gum, and calcium
Diarrhea and steatorrhea persist in most patients. In polycarbophil (Fiberall, Fiber Con). Calcium poly-
some patients, especially those that have lost the carbophil reportedly absorbs 60 to 100 times its
ileocolic valve, steatorrhea and malabsorption con- weight in water.
tinue to be severe and the prognosis for stabilization The ideal form of nutritional support during
becomes very poor. the early postoperative period is total parenteral
nutrition (TPN) (see Chapter 12). TPN is rou-
tinely used in humans with short bowel syndrome
Treatment to maintain caloric intake, electrolyte balance, and
The primary goal of medical therapy for patients acid-base balance for as long as 1 to 2 months of
with short bowel syndrome involves providing the initial phase of therapy. This is not feasible in
adequate nutritional support and controlling diar- most veterinary patients.
rhea through use of antidiarrheal agents. Gastric Partial parenteral nutrition can also be used to
acid hypersecretion can be an important causative help provide adequate early nutritional support.
244 CHAPTER 7 CHRONIC DISEASES OF THE SMALL INTESTINE
ProcalAmine (McGaw, Inc) is a protein-sparing mizing the amount of intestine that will need to
product that is very convenient for use in clini- be removed.
cal practice because no mixing or additives are
required. It is a combination of 3% amino acids, NEOPLASIA OF THE
3% glycerol, and electrolytes. If infused at mainte-
nance rates (30 ml/lb/day), this product provides
SMALL INTESTINE
approximately 20% of a patient’s caloric needs and Neoplasia of the small intestine is discussed in
0.6 to 0.9 g/lb/day of protein. ProcalAmine con- detail in Chapter 11. A summary is provided here.
tains inadequate sodium (35 mEq/L) and chloride Tumors of the small intestine occur uncom-
(41 mEq/L) for total maintenance requirements. monly. GI neoplasms account for approximately
Addition of 65 ml of 7.2% hypertonic saline to a 2% of all canine and feline neoplasms. Intestinal
liter of ProcalAmine increases electrolyte levels neoplasms of dogs and cats are usually malignant.
sufficiently (sodium, 115 mEq/L). ProcalAmine Although neoplasia is uncommon overall, in cats
does contain adequate potassium (24 mEq/L). intestinal lymphoma is now diagnosed with
A peripheral vein can be used. ProcalAmine is increased frequency. This is important to recognize
hypertonic, and the catheter site should be because cats with intestinal lymphoma, especially
watched carefully for any evidence of phlebitis. the type now referred to as chronic low-grade
Catheters are not left in place any longer than 60 lymphocytic lymphoma, often respond well to
to 72 hours. chemotherapy if the diagnosis is made relatively
Limited oral intake is instituted as soon as pos- early in the disease course. The most common
sible after surgery to begin stimulation of intestinal malignant neoplasms of the intestinal tract are
adaptation. Elemental or polymeric diets are often lymphoma and adenocarcinoma. Other tumors
fed in the initial phase. Long-term feeding involves affecting the intestinal tract include mast cell
diets that are low in fat and highly digestible. Small tumor, fibrosarcoma, leiomyoma, leiomyosarcoma,
amounts should be fed frequently (three to four undifferentiated sarcoma, carcinoids, plasmacy-
meals per day).Vitamin B12 (cobalamin) as well as toma, and neurolemmoma.
fat-soluble vitamins should be supplemented Most dogs with intestinal neoplasia are middle-
indefinitely. age or older (7 years or more). A majority of dogs
If intestinal adaptation occurs, a stable body with lymphoma and adenocarcinoma are males.
weight and a reasonable stool consistency can be There is no apparent sex predilection in cats with
maintained on a long-term basis. Some patients, intestinal neoplasia. Siamese cats appear to be at
however, never stabilize despite all treatment efforts greater risk for developing adenocarcinoma of the
and careful dietary manipulation, and their progno- intestine.
sis becomes poor. The prognosis seems to be better in The most common clinical signs of intestinal
patients that are aggressively managed in the early stages. neoplasia are weight loss, vomiting, diarrhea, and
Because it can be very difficult to predict accu- lethargy. Inappetence is often apparent as the dis-
rately how well a patient with short bowel syn- ease advances. Other signs may include melena,
drome will respond to therapy, every effort should hematemesis, anemia, fever, icterus, and abdominal
be made to maintain treatment for a reasonable effusion. Although clinical signs in most patients
period of time before euthanasia is recommended. are slowly progressive, dogs with intestinal adeno-
Careful consideration about how much bowel carcinoma are occasionally presented because of
will be resected should be given at the time of sur- acute signs that may mimic intestinal obstruction
gery. Prevention of situations that may end with (e.g., acute frequent vomiting, anorexia, lethargy).
development of short bowel syndrome begins Physical examination may reveal pallor, cachexia,
with avoiding unnecessarily extensive resection of thickened intestinal loops, an isolated intestinal
small intestine, considering conservative resection mass, intraabdominal lymphadenopathy, dilated
of ischemic bowel with the option of follow-up intestinal loops, organomegaly (liver, spleen),
surgery if necessary, and making every effort to abdominal effusion, and peripheral edema (most
leave the duodenum and ileocolic valve intact. often due to hypoproteinemia associated with dif-
Early diagnosis and timely surgical intervention fuse intestinal lymphoma).
in situations that might end up requiring intes- Hematologic and biochemical parameters are
tinal resection are extremely important in mini- often normal, although anemia (anemia of chronic
CHAPTER 7 CHRONIC DISEASES OF THE SMALL INTESTINE 245
disease or anemia consistent with blood loss) and fuse or focal) can be reliably diagnosed in a major-
hypoproteinemia may be present. Hypoproteinemia ity (approximately 90%) of dogs and cats when
may be due to either blood loss into the intestine proper biopsy instrumentation and technique are
or diffuse infiltrative intestinal disease. Neutrophilic used. Mass lesions can be very reliably diagnosed
leukocytosis and elevated hepatic enzymes may also (samples should be obtained as deeply as possible).
be present. Laparotomy offers the advantage of thorough
Useful procedures in evaluating patients for evi- exploration of the abdomen with biopsy and pos-
dence of intestinal neoplasia include survey radiog- sibly complete excision of involved areas.
raphy, ultrasonography, and endoscopy. Pulmonary Intestinal lymphoma in cats and dogs will be
metastases are rarely detected on thoracic radiog- discussed here, and the reader is referred to
raphy in patients with small intestinal neopla- Chapter 11 for a more detailed discussion of neo-
sia. Survey abdominal radiographs may reveal a plasia of the small intestine. Intestinal lymphoma
soft tissue opacity consistent with a mass or lym- is discussed here as well because clinically it can
phadenopathy, or signs of intestinal obstruction. appear very similar to IBD in cats.
Contrast radiography can be helpful for delineat-
ing regions of significant mucosal irregularity,
luminal narrowing, and intramural thickening. Lymphoma
Narrowing of the lumen is commonly seen with In cats chronic low-grade lymphocytic lymphoma
carcinoma, which has a tendency to be annu- can be very similar to IBD in the way it manifests
lar (Figure 7-3). Annular indicates that there is itself clinically. It can only be differentiated based
360-degree constriction. Intramural disease usually on biopsy specimen analysis. Because cats with
produces radiographic signs of thickening, rigidity chronic low-grade lymphocytic lymphoma often
of the wall, and narrowing of the lumen. have a reasonably good prognosis when indicated
Abdominal ultrasonography is useful for defin- treatment is administered, it is incumbent on vet-
ing abdominal mass lesions (e.g., confirming pres- erinarians to make the correct diagnosis early in
ence of a mass effect, delineating intestinal versus the disease course, rather than later, when it may
lymph node involvement, examining for hepatic be more difficult to successfully manage the
involvement). patient.
A definitive diagnosis of intestinal neoplasia can The GI tract is a common site of extranodal
be made only on histologic examination of biopsy lymphoma in dogs and cats. In cats intestinal lym-
material. Biopsy specimens are most commonly phoma is caused by feline leukemia virus, although
obtained via either endoscopy or exploratory lapa- as few as 12% to 30% have been reported to be
rotomy. Percutaneous fine-needle aspiration under viremic. However, more recent studies using PCR
either ultrasound or laparoscopic guidance can be methods suggest that the incidence of feline
used in selected cases in which the involved area leukemia virus in lymphoma may be as high as
can be isolated and stabilized for needle insertion. 63%. The cause in dogs is unknown. GI lym-
Endoscopy is particularly useful for examining and phoma reportedly arises from B lymphocytes of
procuring biopsy samples from the duodenum and the gut-associated lymphoid tissue (GALT) in
terminal ileum. Intestinal lymphoma (either dif- most cases in dogs and cats.
needle aspiration of a mass may yield sufficient stain for the other lymphocyte type. An alternative
material to make a definitive diagnosis. approach is to proceed to obtaining full-thickness
Endoscopy is a very safe and reliable means of intestinal biopsy samples if it is not clear from eval-
diagnosing diffuse intestinal lymphoma in cats. Small uation of endoscopic samples what disease process
intestinal masses are not often accessible to endo- is present.
scopic evaluation, however; if present, exploratory Lymphocytic-plasmacytic gastroenteritis may
surgery is recommended. As previously stated, constitute a prelymphomatous disorder (see dis-
aspiration cytologic analysis of a mass may pro- cussion earlier in this chapter in the section on
vide a diagnosis, but surgery is still recommended feline IBD). In my experience, however, eventual
for detailed evaluation and resection of an intes- transition from benign to malignant disease is
tinal mass, where feasible, if there is concern that rare.
the mass may cause significant luminal obstruc- There are few detailed reports in the literature
tion. Mass resection also provides effective tumor of treatment response among cats with GI lym-
debulking before chemotherapy. Full-thickness phoma. One recent report described diagnosis and
intestinal biopsies and mass resection should be management of 67 cats with GI lymphoma. In this
done with careful surgical technique, because dehis- series the histologic grade was determined to be
cence of the suture line may occur. Nonabsorbable lymphocytic in 75% of cases (50 cats) and lym-
suture should be used. phoblastic in 25% of cases (17 cats). Several thera-
If endoscopy is done, as much of the small peutic protocols have been described. Two of
intestine as possible is examined. In many cats the these are discussed here. Multiagent chemotherapy
tip of the endoscope can be extended to the is recommended for all affected cats. Survival times
jejunum. Proper instrumentation and biopsy tech- in excess of 12 to 18 months are not unusual. In
nique are essential for making a definitive diagno- some cats the response is somewhat shorter (3 to
sis of lymphoma on endoscopic biopsy specimen 6 months). The prognosis for longer survival
analysis. Gross appearance varies from normal to time is much better if the diagnosis is made before
variable degrees of mucosal irregularity. Erosions clinical signs become chronic and debilitation
or ulcerative changes are occasionally present. As results. The protocol that I have used most often
was discussed in the section on IBD, it is some- is described in Table 7-2. This protocol uses
times difficult for a pathologist to differentiate dif- cyclophosphamide, vincristine (Oncovin), and
fuse intestinal lymphoma from IBD. This is prednisolone (COP). It can be easily managed
especially true when severe lymphocytic enteritis in any practice setting. An alternate protocol
is present. Immunoperoxidase studies to assess the that was used in the series of 67 cats used mostly
clonality of the lymphoid population are often prednisolone and chlorambucil. (See guidelines that
helpful in confirming whether or not lymphoma follow.)
is present. Pathologists can request that these COP Protocol. Vincristine is administered
special stains be done at an academic institution intravenously at a dose of 0.75 mg/m2 once weekly
if they are not available at their own laboratory. for 4 consecutive weeks and then once every 3
T-cell and B-cell stains often show presence of vir- weeks. The initial doses are often decreased by
tually 100% of either T lymphocytes or B lympho- approximately 25% for cats that are inappetent or
cytes in lymphoma cases, with a virtually negative debilitated. If well tolerated, the dose can then be
gradually increased. Care is taken to ensure that dration is a problem, owners are taught how to
none of the vincristine is given extravascularly. The administer subcutaneous fluids at home (e.g.,
average volume that is administered is quite low lactated Ringer’s solution, 100 to 150 ml every
(0.1 to 0.15 ml for many cats, using a vincristine 24 hours to 48 hours, based on the individual
concentration of 1 mg/ml). Cyclophosphamide cat’s needs). Injections of B-complex vitamins are
is given orally at a single dose of 225 mg/m2 sometimes helpful as well.
every 3 weeks (50-mg tablets are used, with dose Rarely, chemotherapy can be discontinued after
adjusted to the nearest 25 mg on the low side of 1 year. This is done only if follow-up endoscopic
the calculated dose). Prednisolone is given orally intestinal biopsy samples indicate that there is
at 1 mg/lb/day. Although cyclophosphamide and no remaining lymphoma. Most cats remain on
vincristine can be given on the same day, I often treatment for the rest of their lives. If chemother-
prefer to have the owner administer the cyclophos- apy is poorly tolerated and reduced dosages and
phamide 2 to 3 days after the vincristine. This increased intervals between treatment times are
allows a little recovery time between treatments. unsuccessful in adequately decreasing side effects,
A complete blood count is done several times chemotherapy should be suspended. Prednisolone
during the first month and then every 3 weeks to should be continued, however, because it may
be sure that adequate granulocytes are present help maintain remission for a period of time.
before treatment. At least 3000 granulocytes/µl L-Asparaginase can also be used if cyclophos-
must be present before cyclophosphamide is phamide and vincristine are poorly tolerated.
given. If the granulocyte count drops to less than Doxorubicin (Adriamycin) can also be used in cats.
1000/ µl 5 to 7 days after cyclophosphamide, the Prednisone and Chlorambucil for Lym-
dose for subsequent treatments is reduced by 25%. phocytic Lymphoma. Lymphocytic lymphoma
The highest nontoxic dose is most likely to result may also be treated with prednisone (or pred-
in the greatest tumor cell kill. nisolone) at 10 mg/day orally and chlorambucil
The COP protocol is generally well tolerated, (Leukeran) at a dosage of 15 mg/m2 orally once
although side effects may occur and dosage or per day for 4 days, repeated every 3 weeks.
interval adjustments may be necessary. Side effects Many cats go into remission for a number of
of COP in cats may include anorexia, vomiting, months. Cyclophosphamide can be used for “res-
lethargy, and severe tissue irritation if any vin- cue” (225 mg/m2 every 21 days). Adverse reac-
cristine is given extravascularly. Also, the hair coat tions on this protocol are rare but may include
may become thinner, but complete hair loss does vomiting, diarrhea, anorexia, and leukopenia.
not occur. Cats do tend to lose whiskers. Cats Monitoring includes running a complete blood
should be carefully observed for sepsis, especially count on days 10 and 21 of the first 3-week cycle.
during the induction phase. Prophylactic antibi- If there is no neutropenia (less than 3,000/µl),
otics are not indicated, but any infections that the same dosage of chlorambucil is continued.
occur should be treated aggressively. Subsequently a complete blood count is obtained
Advantages of this protocol include hospital on the tenth day on every second or third cycle
visits at only 3-week intervals after the first thereafter.
4 weeks, lower cost to the owner, and a treatment
interval that allows recovery of normal cells Canine Lymphoma
between treatments. I would like to emphasize GI lymphomas occur less commonly in dogs than
that with careful monitoring and use of a dosage in cats. The GI tract may be involved as either a
schedule that is tailored to each individual cat, primary or a secondary site. GI lymphoma appears
few problems are encountered. It is my general to be somewhat more common in males than in
practice to encourage owners of most cats with females.
GI lymphoma to pursue treatment that includes Clinical signs commonly include vomiting,
chemotherapy. diarrhea, decreased appetite, weight loss, and
Nutritional and metabolic support is also lethargy. Signs are usually slowly progressive
important. If inappetence is a problem, cyprohep- and poorly responsive to symptomatic therapy.
tadine can be administered as an appetite stimu- Hematologic findings include anemia and panhy-
lant (1 to 2 mg orally every 12 to 24 hours) on an poproteinemia, especially in dogs with diffuse
as needed basis (long-term if necessary). If there is intestinal lymphoma. Lymphoma must be consid-
concurrent renal disease with azotemia or if dehy- ered in any dog with hypoproteinemia that occurs
CHAPTER 7 CHRONIC DISEASES OF THE SMALL INTESTINE 249
in conjunction with GI signs (IBD, lymphangiec- achieved. Clinical experience indicates that dogs
tasia, and histoplasmosis are the main disorders to with diffuse intestinal lymphoma have a worse
rule out). prognosis than those with localized disease. Further
Endoscopy has been very reliable for diagnos- information can be found in Chapter 11.
ing diffuse intestinal lymphoma in dogs in my
experience. As opposed to cats, dogs rarely have
the nearly pure lymphocytic form of IBD; there-
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by intestinal disease. After complete colonoscopy, a lymphoma in 20 dogs: a retrospective study, J Vet Intern
pediatric endoscope can be advanced through the Med 3:73, 1989.
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German AJ, Hall EJ, Day MJ: Immune cell populations
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adequate-size samples. Every effort is made to caused by Cryptosporidium parvum with oral bovine
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inflammation commonly occurs in conjunction ments in canine pythiosis. Proceedings of the twenti-
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Grooters AM et al.: Development and evaluation of an
infiltration was present adjacent to or occasionally enzyme-linked immunosorbent assay for the serodiag-
distant from the neoplastic foci in 8 of 15 dogs nosis of pythiosis in dogs, J Vet Intern Med 16:142, 2002.
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region between neoplastic and nonneoplastic tis- bowel resection on metabolism of bile acids and vita-
sue was not sharply demarcated, and often an min D3 and gastrin release in dogs, Tohoku J Exp Med
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Jergens AE et al.: Cytologic examination of exfoliative
of IBD that was diagnosed via endoscopy. It may
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be that the poor treatment response is due to lym- gastrointestinal tract disease in dogs and cats, J Am Vet
phoma that has not yet been identified. Med Assoc 213:1755, 1998.
Treatment involves multiple-agent chemother- Krecic MR: Feline IBD: diagnostic challenges, treatment,
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Kull PA et al.: Clinical, clinicopathologic, radiographic, Strombeck DR, Guilford WG: Maldigestion, malab-
and ultrasonographic characteristics of intestinal lym- sorption, bacterial overgrowth, and proteinlosing
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Med Assoc 219:197, 2001. Small animal gastroenterology, Davis, Calif, 1990,
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MJ, ed: Disease mechanisms in small animal surgery, Louis, 1999, Mosby.
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Playford RJ, Macdonald CE, Johnson WS: Colostrum and icosis in dogs. In Bonagura JB, Kirk RW, eds: Current
milk-derived peptide growth factors for the treatment veterinary therapy XI, Philadelphia, 1992,WB Saunders.
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Rhodes KH: Feline immunomodulators. In Bonagura Personal communication,1999.
JB, Kirk RW, eds: Current veterinary therapy XII, Willard MD: Disorders of the intestinal tract. In Nelson
Philadelphia, 1995,WB Saunders. RW, Couto CG, eds: Essentials of small animal inter-
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C H A P T E R
8
DISEASES OF THE
LARGE INTESTINE
Robert G. Sherding
The large intestine comprises the cecum, colon, contractions (both dogs and cats) mix and delay
rectum, and anal canal. In the carnivores such as passage of the bowel contents, thereby promoting
the dog and cat, the colon is relatively small and optimal absorption, whereas peristaltic contrac-
the cecum is only a vestigial component. In the tions (mass movements) propel the bowel contents
ventrodorsal plane, the colon has the shape of a downstream, eventually resulting in defecation.
question mark and is anatomically subdivided into Defecation is a well-controlled act involving the
a short proximal ascending colon with ileocolic colon, rectum, and anus under nervous system
and cecocolic junctions or sphincters, a middle control.
transverse colon, and a long descending colon that In general, most diseases of the colon are man-
is continuous with the rectum and anal canal. ifested as either diarrhea or constipation, and thus
The two principal functions of the colon are colonic diseases are categorized as such for the
(1) the absorption of electrolytes and water from purposes of discussion in this chapter. Perforation
the luminal content and (2) the temporary storage and volvulus of the colon are rare causes of an
and periodic elimination of the resulting feces. acute abdominal distress presentation. Diseases in
Absorption is mostly a function of the proximal or near the anus generally cause dyschezia, often
colon, whereas storage is mostly a function of the accompanied by constipation and sometimes fecal
rectum and distal colon. The principal function of incontinence.
the anus is to maintain fecal continence between
defecations.
Colonic mucosal cells actively absorb sodium DISEASES OF THE
and chloride; water follows passively. Within the COLON WITH
colonic mucosa, tubular glands called the crypts of DIARRHEA AS THE
Lieberkühn contain numerous mucus-secreting
goblet cells. The circular and longitudinal muscle
PRINCIPAL SIGN
layers of the colon are responsible for the normal Diarrhea is the most common sign associated with
motility and “tone” of the colon, under the influ- colonic disease in the dog and cat. Inflammatory
ence of intrinsic and extrinsic innervation and gas- diseases (colitis), which may be dietary, traumatic,
trointestinal (GI) hormones. Retrograde peristaltic parasitic, infectious, immune, or idiopathic, are the
contractions (cats only) and phasic segmentation most important causes of large bowel diarrhea.
251
252 CHAPTER 8 DISEASES OF THE LARGE INTESTINE
Other causes include neoplastic (lymphoma, may be caused by urgency and inability to control
adenocarcinoma), obstructive (intussusception, urges to defecate. The owner may also notice
volvulus), and functional (irritable bowel syn- straining (tenesmus) as the patient remains in a
drome) disorders. The principal causes and cate- squatting posture for an extended period of time
gories of large bowel diarrhea are summarized in after defecation or makes repeated attempts to
Box 8-1. defecate within a period of a few minutes. These
attempts may produce little or no feces, or some-
times a small amount of feces composed almost
Clinical Signs of Large Bowel entirely of mucus, exudate, and blood.
Diarrhea Because many colonic diseases are associated
The first step in the recognition and diagnosis of with mucosal injury, inflammation, or ulceration,
large bowel diarrhea is the anatomic localization of abnormal fecal constituents are frequently found
the disease process to the colon based on the eval- in large bowel diarrhea. These include (1) fresh
uation of the patient’s defecation pattern and fecal red blood (hematochezia), which originates from
characteristics (frequency, volume, consistency, sites of erosion or ulceration; (2) mucus, which
color, odor, and composition). Large bowel diar- originates from the abundant goblet cells in the
rhea is characterized by frequent urges to defecate colon that respond to mucosal injury by an out-
(usually greater than three times normal fre- pouring of mucus; and (3) exudate (leukocytes),
quency), with each defecation producing small which originates from sites of inflammation. Blood
quantities of feces that often contain excessive may coat the feces, streaks of blood may be mixed
mucus and sometimes fresh red blood. Urgency, within the feces, or drops of blood may be passed at
resulting from irritability or inflammation of the the end of defecation. Excessive mucus may give
distal colon, causes frequent premature expulsions the feces a glistening or jellylike appearance.
of small quantities of feces that would otherwise Exudates are detected by the positive identification
be insufficient to trigger the defecation reflex. In of fecal leukocytes on conventional cytology stains.
addition, lapses in house training (“accidents”) These abnormal constituents—red blood, mucus,
FIP, Feline infectious peritonitis; FeLV, feline leukemia virus; FIV, feline immunodeficiency virus; PAS, periodic
acid–Schiff.
CHAPTER 8 DISEASES OF THE LARGE INTESTINE 253
and leukocytes—are localizing signs indicative of are nonspecific. An effort should be made to iden-
colonic disease. tify underlying extraintestinal diseases that may be
Because the principal function of the colon is a cause or consequence of diarrhea. The colon and
absorption of water and electrolytes rather than rectum should be thoroughly examined by palpa-
digestion and absorption of nutrients, nutrient tion, and if abnormalities are identified, additional
malabsorption and steatorrhea are absent in large diagnostic studies, such as colonoscopy, radiography,
bowel diarrhea. Thus dramatic weight loss and or ultrasonography, are usually indicated. For exam-
wasting are unlikely if the patient is eating, and the ple, abdominal palpation of the colon (and small
daily fecal output (volume or weight of feces) is intestines as well) may reveal masses, thickenings,
usually only minimally increased. This contrasts intussusception, distention, fecal impaction, pain, or
with the substantial increase in fecal output of associated changes in abdominal lymph nodes and
dogs with small intestinal disease. The characteris- other abdominal organs. Digital palpation of the
tics of small bowel diarrhea are discussed in rectum may reveal foreign objects, intramural or
Chapter 1. Diffuse diseases of the GI tract may extramural masses, strictures, or abnormalities of
produce concurrent small and large bowel signs mucosal texture. In addition, the fecal material
and sometimes gastric signs as well. It has been obtained on the palpation glove can be inspected
estimated that vomiting is an associated sign in for abrasive particles (such as bone chips), blood, or
about 30% of patients with colitis. mucus. Fecal material also can be examined micro-
scopically for parasites and inflammatory cells and
submitted for culture if indicated.
Diagnostic Approach for Large
Bowel Diarrhea Consideration of Dietary, Parasitic,
Diarrhea as a clinical sign is relatively nonspecific; and Infectious Causes
however, once it is localized to a disorder of the Before hospitalizing a patient with large bowel
large bowel, a logical diagnostic approach can be diarrhea for an in-depth diagnostic work-up, the
followed. Specific treatment or intervention is possibilities of dietary, parasitic, or infectious causes
usually necessary, and this generally requires either should initially be considered. Ingestion of abrasive
a specific diagnosis or at least a histopathologic materials such as bones or chew toys can injure the
characterization. Initial evaluations should be rectocolonic mucosa, producing abrasive colitis
aimed at diagnosis of dietary, parasitic, and infec- and signs of diarrhea and hematochezia that typi-
tious causes of diarrhea. This should include mul- cally last 2 to 3 days. The diagnosis can usually be
tiple fecal examinations for whipworm ova and made from a thorough dietary history and inspec-
protozoa, therapeutic deworming trials (fenbenda- tion of the feces for abrasive particles.
zole, 22 mg/lb orally daily for 3 days), fecal exam- Acute nonspecific large bowel diarrhea often
inations for Clostridium perfringens spores and toxin, resolves with restriction of food intake for 24 to
and a 4-week dietary trial using a highly digestible 48 hours followed by gradual resumption of feed-
commercial or homemade GI diet alone and with ing using a bland digestible diet. Chronic nonspe-
fiber added (psyllium). If diarrhea persists and the cific diet-responsive diarrhea can be resolved in
cause is not apparent, the next phase of diagnostic many cases by strict feeding of a balanced, highly
evaluations should include a complete blood digestible diet using one of the commercially
count (CBC), serum chemistry profile, urinalysis, available “GI diets,” such as Low Residue Formula
additional fecal examinations for infectious agents (Iams), Select Care Sensitive (IVD), Prescription
(cytologic examination, toxin assay, cultures), and i/d (Hill’s), EN (Purina), or Low Fat (Waltham),
abdominal imaging (radiography and ultrasonog- or using a comparable homemade diet following
raphy). Finally, complete colonoscopic examina- published recipes. In dogs if diarrhea persists after
tion and biopsy are performed. The various a 4-week feeding trial, then add fermentable solu-
diagnostic procedures for animals with large bowel ble fiber in the form of psyllium (Metamucil, 1 to
diarrhea are summarized in Table 8-1. 3 tbsp/day) or oat bran (1 to 3 tbsp/day) to deter-
mine if the patient has fiber-responsive large
Physical Examination bowel diarrhea.
A complete physical examination may reveal In dogs, whipworms are the most common cause
important clues about the severity, nature, and cause of colitis in many practice areas and should be ruled
of diarrhea, although in many patients the findings out by fecal flotation or, if occult infection is
254 CHAPTER 8 DISEASES OF THE LARGE INTESTINE
suspected, by a therapeutic trial of an effective (more than five spores per high-power oil immer-
anthelmintic such as fenbendazole (Panacur). sion field) with a “safety pin” or “tennis racket”
Hookworms can also cause colitis. Although less configuration in fecal cytologic preparations
common, protozoan causes of colitis (e.g., Tricho- stained with Diff-Quik; however, fecal assays for
monas) can be detected rapidly by examination of C. perfringens enterotoxin are probably a more reli-
saline fecal smears for the presence of motile able means of diagnosing clostridial diarrhea (see
trophozoites. In warm, humid regions endemic section on C. perfringens).
for Strongyloides tumefaciens in cats (e.g., parts of Histoplasmosis is an important cause of chronic
the southern United States), sedimentation or colitis in areas endemic for this mycotic infection.
Baermann techniques can be used to identify larvae The diagnosis is usually based on either positive
in the feces. serologic study (immunodiffusion or complement
Campylobacter, Salmonella, and C. perfringens are fixation) or identification of the organisms in
becoming recognized as important bacterial causes exfoliative cytology specimens from rectocolonic
of enterocolitis. Campylobacter and Salmonella can mucosa. Sabouraud’s medium can be used to cul-
be diagnosed by specialized fecal cultures. Such ture feces for Histoplasma and other fungi or for
cultures are particularly indicated when examina- Prototheca, a rare cause of colitis, but culture growth
tion of fecal cytologic preparations reveals the is slow (up to 2 weeks) and the isolation rate is low.
presence of numerous fecal leukocytes or when
there is an outbreak of diarrhea in groups of animals. Hematology and Serum Biochemistry
C. perfringens enterotoxigenic diarrhea is suggested In addition to fecal examinations, the initial data-
by the presence of large numbers of endospores base for undiagnosed chronic large bowel diarrhea
CHAPTER 8 DISEASES OF THE LARGE INTESTINE 255
should include a complete hemogram (CBC) and uniformly. The mucosa should be nonfriable, thin
serum biochemistry profile. Significant CBC find- enough that the submucosal vessels are visible, and
ings may include (1) anemia, which could result free of ulcers, thickened folds, masses, or strictures.
from enteric blood loss or depressed erythropoiesis Cultures, exfoliative cytology specimens, and bi-
due to chronic disease; (2) eosinophilia, which opsy specimens of the colonic mucosa are easily
could suggest parasitism, eosinophilic enterocolitis, obtained through the instrument.
or sometimes other inflammatory or neoplastic There are occasions when colonoscopy cannot
intestinal diseases; (3) regenerative neutrophilia, be used to evaluate adequately or to perform deep
which could suggest bowel inflammation (partic- enough biopsies of lesions in the proximal colon,
ularly involving the deeper layers), necrosis, or especially when deep inflammatory or neoplastic
neoplasia; and (4) degenerative or toxic neutrope- lesions involve the region of the ileocecocolic
nia, which could suggest overwhelming sepsis or junction. Under these circumstances, examination
endotoxemia, such as occurs with bowel ischemia, and biopsy by laparotomy are required for accurate
necrosis, or perforation. diagnosis.
A serum biochemistry profile and urinalysis
should be considered to identify metabolic or Radiography and
extraintestinal disorders that could cause or result Ultrasonography
from diarrhea. For example, underlying systemic Plain abdominal radiography is indicated for de-
diseases that can cause diarrhea may be detected, tection of foreign material in the colon, intestinal
such as renal failure (increased levels of blood urea masses, intussusception, or an abnormal gas-fluid
nitrogen and creatinine), pancreatitis (increased pattern that would suggest obstruction or volvulus.
amylase and lipase levels), liver disease (e.g., abnor- Barium enema contrast radiography is useful in
mal serum liver enzymes levels), or hypoadreno- selected cases of large bowel diarrhea for detection
corticism (hyperkalemia and hyponatremia). In of ileocolonic intussusceptions, cecal inversions,
addition, serum chemistry findings can be used to neoplasms, polyps, strictures, colonic displacement,
evaluate potential complications of large bowel colonic shortening, and chronic inflammatory
diarrhea, such as dehydration, electrolyte abnor- lesions. Some of these lesions can also be detected
malities, and hypoproteinemia. Because of the in the latter phases of an upper GI barium contrast
high incidence of hyperthyroidism in cats older radiographic series; however, the lower bowel is
than 5 years of age and because this disorder is generally evaluated better by a barium enema
occasionally manifested as unexplained diarrhea, study. (See Chapter 2 for a more detailed discussion
cats in this age-group with diarrhea should have a of contrast radiography.) However, it must be
screening serum thyroxine (T4) level measured. emphasized that if flexible fiberoptic colonoscopy
is available, it is generally preferred over barium
Colonoscopy and Biopsy radiography for evaluation of the proximal colon
Most cases of chronic large bowel diarrhea in because it is easier to perform and yields more
which extraintestinal, dietary, parasitic, and infec- definitive diagnostic information.
tious causes have been excluded require colono- Abdominal ultrasonography can be a useful
scopic examination and mucosal biopsy for diagnostic aid in selected cases of unexplained
definitive diagnosis or accurate characterization of diarrhea for noninvasively defining intestinal and
the disease. Colonoscopy allows direct visualiza- other abdominal or perirectal masses, for diagnosis
tion of the lumen of the colon, sampling of lumi- of intussusceptions, and for evaluating the mesen-
nal content, and directed forceps biopsy of the teric lymph nodes, pancreas, liver, and prostate (see
mucosa. Suitable rigid colonoscopes are relatively Chapter 2).
inexpensive and easy to use. Because colonic dis-
eases are often diffuse, examination of the descend- Therapeutic Trials
ing colon with a rigid instrument is sufficient for Therapeutic trials can sometimes support a tentative
diagnosis in many patients. However, when lesions diagnosis when accompanied by other supportive
are located predominantly in the ascending or clinical evidence. For example, occult whipworm
transverse colon, areas that are inaccessible with a infection is often diagnosed circumstantially by
rigid colonoscope, a flexible fiberoptic colonoscope rapid resolution of signs in response to fenbenda-
must be used. The normal colonic mucosa through zole therapy. In some patients, nonspecific diet-
a colonoscope appears pale pink and reflects light responsive large bowel diarrhea is resolved by
256 CHAPTER 8 DISEASES OF THE LARGE INTESTINE
feeding a highly digestible diet or a diet supple- diagnostic findings, minimal abnormalities on
mented with fiber as described previously in this colonoscopy, and responsiveness to supplementa-
section. Similarly, the response to trial-and-error tion of a digestible diet with fermentable soluble
test diets plays an important role in establishing fiber in the form of psyllium (Metamucil, 1 to 3
dietary hypersensitivity as a cause of lymphocytic- tbsp/day) or oat bran (1 to 3 tbsp/day). Some of
plasmacytic colitis. these patients may actually have so-called irritable
bowel syndrome (see later section). Fermentable
soluble fiber is fermented by colonic bacteria to
Abrasive Colitis short-chain fatty acids (SCFAs) that provide an
Ingested bone particles, pieces of chew toys, or other energy source for colonic epithelium, protect against
indigestible abrasive foreign materials (stones, hair, mucosal injury, and acidify bowel contents, which
plants, wood, cloth, carpeting, foil, plastic), when may reduce proliferation and sporulation of
incorporated into the fecal mass, may cause abrasive enteropathogenic bacteria such as C. perfringens.
colitis because of a traumatizing sandpaper-like effect Fiber also has other beneficial effects on fecal
on the rectocolonic mucosa during transit. Abrasive water content, fecal bulk, and colonic myoelectrical
injury is usually transient and self-limiting after 2 to function.
3 days, although repeated episodes in patients that Novel protein diets are used in diagnostic trials
have frequent dietary indiscretions may mimic other and treatment for chronic colitis related to dietary
causes of chronic intermittent colitis. Dietary his- hypersensitivity. This is discussed in the section on
tory and examination of the feces for abrasive parti- lymphocytic-plasmacytic colitis.
cles are usually sufficient to establish the diagnosis.
Management is based on eliminating the source of
ingested abrasive material. Parasitic Colitis
Whipworm Colitis
Whipworm (Trichuris vulpis) infection is a com-
Diet-Responsive and Fiber-
mon cause of acute, chronic, or intermittent signs
Responsive Large Bowel of large bowel diarrhea in dogs in many practice
Diarrhea areas. The adult nematode has a predilection for
These conditions are characterized by chronic the proximal colon and cecum, where its distinc-
nonspecific large bowel diarrhea. The diagnosis is tive thread like head end or “whip” firmly embeds
based on a complete absence of abnormal findings deep within the mucosa to feed on blood and tis-
on diagnostic evaluations, minimal abnormalities sue fluids, thereby resulting in colitis and typhlitis.
on colonoscopy, and complete response to dietary Whipworms infect dogs of all ages. Although
manipulation. A 4-week feeding trial of a new there may be minimal clinical signs in light infes-
diet is usually adequate to determine response. tations, trichuriasis frequently causes mucoid large
Some of these patients respond simply to feeding bowel type of diarrhea with urgency and some-
of a balanced, highly digestible diet (i.e., moderate times hematochezia. Because of these signs, whip-
to restricted fat level with digestible protein and worm infection is often mistaken for other, more
carbohydrate) using one of the commercially serious forms of colitis or colonic neoplasia. In
available “GI diets,” such as Low Residue Formula addition, a condition of pseudohypoadrenocorti-
(Iams), Select Care Sensitive (IVD), Prescription cism characterized by hyperkalemia and hypona-
i/d (Hill’s), EN (Purina), or Low Fat (Waltham), or tremia in the presence of normal adrenal function
using a comparable homemade diet. One example has been associated with severe whipworm diar-
of a homemade diet combines turkey, rice, and saf- rhea in several dogs. The feline whipworms,
flower oil. Other acceptable recipes for homemade Trichuris campanula and Trichuris serrata, are consid-
“GI diets” are published elsewhere. The advantage ered to be very rare and usually are not associated
of a highly digestible diet would be less undigested with clinical signs.
“residue” presented to the colon from the small Whipworm infections occur by ingestion of
intestines. This helps to prevent unabsorbed fat infective ova, and the life cycle is direct. The
from reaching the colon, where it can be metabo- prepatent period is approximately 3 months.
lized to hydroxy fatty acids that produce diarrhea. Because ova may survive and remain infectious in
In dogs the diagnosis of fiber-responsive large the environment for 4 to 5 years, contaminated
bowel diarrhea is based on an absence of abnormal ground is probably the major reservoir of infection.
CHAPTER 8 DISEASES OF THE LARGE INTESTINE 257
Definitive diagnosis of whipworm infection Young dogs are most often affected, and the
necessitates identification of the characteristic diagnosis is usually readily established by identifi-
brown, bipolar-operculated, football-shaped ova cation of the characteristic hookworm ova by rou-
by routine fecal flotation. Repeated fecal examina- tine fecal flotation. Eosinophilia is a common
tions may be necessary to identify ova because of ancillary finding on CBC.
the unusually long prepatent period and also There are many anthelmintics that are effective
because it is not uncommon for active infection to for eradicating hookworms, including the standard
be characterized by prolonged periods when ova recommended dosages (4.5 mg/lb for patients
are not shed in the feces. It is estimated that up to under 5 lb; 2.25 mg/lb for patients over 5 lb) of
50% of dogs presenting with whipworm diarrhea pyrantel pamoate (Nemex), fenbendazole, or
have ova-negative or so-called occult infections. febantel. Most heartworm preventatives also con-
Alternative means of diagnosis are directly by trol hookworms.
colonoscopic observation of adult whipworms in
the bowel lumen or indirectly by observing reso- Strongyloides Colitis
lution of signs in response to a therapeutic trial of S. tumefaciens is a tiny nematode parasite of cats in
an effective anthelmintic. warm, humid tropical regions such as the Gulf
Whipworms are treated with fenbendazole (22 region of the United States. The adult parasites
mg/lb orally for 3 consecutive days). Treatment burrow within the mucosa of the large intestine.
should be routinely repeated at 3 weeks and 3 Infection is usually asymptomatic, but in some cats
months because whipworms are difficult to eradi- the parasite causes peculiar tumorlike, white, 2- to
cate. In refractory cases, a 5-day course of fenben- 3-mm nodular proliferations in the colonic
dazole is recommended. Febantel is an alternative mucosa and submucosa that are associated with
treatment for whipworms. Regular use of milbe- signs of chronic diarrhea and debilitation.
mycin (Interceptor, Sentinel) for heartworm Ova that contain first-stage Strongyloides larvae
prevention also helps to control whipworm infec- can be identified in feces by flotation techniques,
tions. Because whipworm ova survive so well in and free larvae may be identified by direct micro-
the environment, frequent reinfection is a com- scopic examination of feces or by a Baermann tech-
mon problem. Therefore feces should be collected nique. In addition, the diagnosis can be established
and disposed of properly whenever possible. In by colonoscopic observation and biopsy of the
dogs with frequent access to ground that has been mucosal nodules, which are filled with adult worms.
heavily contaminated with whipworm ova, a com- Strongyloidiasis can be treated with a 5-day
mon situation in many public parks and backyards, course of fenbendazole (23 mg/lb/day orally).
reinfection is so frequent that retreatment every 2
to 3 months may be necessary. It is virtually Protozoan Colitis
impossible to eradicate the parasite from infected Pentatrichomonas hominis, Entamoeba histolytica, and
ground; however, concrete runs can be disinfected Balantidium coli are large bowel protozoal parasites
with dilute sodium hypochlorite solution or by that are occasionally associated with colitis and
flaming. large bowel diarrhea in animals. In addition,
Rarely trichuriasis has been associated with Giardia, which is primarily a small bowel parasite
severe transmural granulomatous typhlitis, which (see Chapter 6), has been associated with bloody-
may be palpable as a tender right midab- mucoid large bowel diarrhea on very rare occa-
dominal mass. This lesion may be refractory to sions. All of these protozoa are responsive to
anthelmintics and require typhlectomy. treatment with metronidazole (Flagyl).
Trichomoniasis
Hookworm Colitis Trichomonas spp. are motile, pear-shaped, flagellated
Although the common canine hookworm, protozoa that inhabit the colon and cecum of dogs
Ancylostoma caninum, is primarily a small intestinal and cats and have been found in both normal and
parasite, it occasionally parasitizes the colon in diarrheic feces. The pathogenicity of these proto-
large numbers. Hookworms embed their mouth- zoa in dogs has not been conclusively estab-
parts in the mucosa to suck blood, leaving bleed- lished, but massive numbers of trichomonads are
ing punctiform ulcers as they “graze.” When they sometimes found in diarrheic feces of puppies and
involve the colon, they produce a bloody mucoid are especially associated with unsanitary over-
diarrhea characteristic of colitis. crowded kennel conditions and coinfection with
258 CHAPTER 8 DISEASES OF THE LARGE INTESTINE
other parasites. Tritrichomonas foetus has recently dogs. Rural dogs in contact with swine feces are
been identified as a frequent cause of chronic large most at risk for the disease. Humans can also be
intestinal diarrhea in young cats, especially cats infected. Dogs with balantidiasis are usually coin-
confined in crowded cattery conditions. The diar- fected with whipworms, and thus it has been sug-
rhea may wax and wane, may be malodorous, and gested that whipworm-induced damage to the
may contain blood or mucus. The diagnosis of colonic mucosa may be a predisposing factor. The
trichomoniasis is based on identification in saline diagnosis is based on identification of extremely
fecal smears or in fecal culture (Modified large (40-80 × 25-45 µm), oval, brown, rapidly
Diamond’s Media or InPouch TF kit) of motile, swimming ciliated trophozoites with prominent
pear-shaped, flagellated trophozoites with charac- macronuclei in saline smears of fresh feces or
teristic wavelike motion of an undulating mem- on identification of protozoal cysts in zinc sul-
brane and a constant erratic turning and rolling fate or sedimentation preparations of feces.As with
motion. Feces for detecting trichomonads should Entamoeba and Giardia, the trophozoite stage of
be taken directly from the rectum or examined Balantidium can be seen in diarrheic feces, whereas
within minutes of defecation, while trophozoites cysts are more likely to be found in formed
are still motile. Trichomonads lack a cyst stage. feces. Balantidiasis is treated with metronidazole
Fecal polymerase chain reaction (PCR) testing has (10 to 15 mg/lb orally twice a day for 5 to
also been used in cats. Trichomonas are extremely 10 days).
difficult to eradicate in cats. Numerous antibiotic
agents have been evaluated without success.
Treatment can reduce the number of organisms Viral Colitis
and improve clinical signs, but it usually does not The colon may be significantly involved in gener-
eliminate the infection. The patient should also be alized viral infections of the intestinal tract. Lesions
evaluated and treated for concurrent infection of acute colitis are especially common in parvovi-
with other parasites and enteropathogens. Proper ral infections of both the dog and the cat. In addi-
sanitation measures should be instituted to control tion, the colon may be involved in some of the
infection in animals housed in groups. multisystemic viral diseases. For example, in dogs
Amebic Colitis the epitheliotropic attack of canine distemper
E. histolytica, primarily a human pathogen, may virus may involve the colon, whereas cats infected
rarely cause amebic colitis in dogs and cats. with feline leukemia virus (FeLV), feline immu-
Amebic invasion of the colonic mucosa and sub- nodeficiency virus (FIV), or feline infectious peri-
mucosa results in ulceration and signs of bloody- tonitis (FIP) virus sometimes have diarrhea
mucoid large bowel diarrhea with tenesmus. associated with enterocolitis that varies from
Diarrhea is usually severe and may simulate other necrotizing to ulcerative to pyogranulomatous.
forms of chronic colitis or is manifested as an acute (See Chapter 6 for further discussion of viral
dysentery. Both forms of Entamoeba, the tropho- infections of the GI tract.)
zoite and cyst, are infectious for animals. Infection
is most likely acquired from ingestion of food or
water contaminated with human feces, such as Bacterial Colitis
drinking from polluted water sources (free- Invasive enteropathogenic bacteria primarily invade
roaming animals) or toilets (house pets). The diag- the colon and distal small bowel, where the mucosal
nosis is based on identification of ameboid damage they cause leads to inflammation, exuda-
trophozoites with pseudopodial movement in tion, mucus secretion, and bleeding. Thus typical
saline smears of fresh diarrheic feces, amebiccysts signs of large bowel diarrhea and hematochezia are
in zinc sulfate flotation of formed feces, or tropho- characteristic of these infections. Bacterial entero-
zoites in colon biopsy specimens. Amebic colitis toxins may also play a role in the pathogenesis of
responds to metronidazole (12 to 15 mg/lb orally diarrhea. Although the clinical importance of the
two times a day for 5 to 10 days) or furazolidone various enteropathogenic bacteria in animals has
(1 mg/lb orally three times a day for 7 days). not yet been fully defined, Salmonella sp.,
Balantidiasis Campylobacter jejuni, Yersinia sp., Bacillus piliformis,
B. coli, a ciliated protozoan that primarily infects and Clostridium sp. may be associated with colitis
swine, is a rare cause of chronic ulcerative colitis in and large bowel diarrhea in dogs and cats.
CHAPTER 8 DISEASES OF THE LARGE INTESTINE 259
Definitive diagnosis of Tyzzer’s disease is diffi- Increased frequency is common, and tenesmus
cult because B. piliformis cannot be cultured on may be seen. In dogs enterotoxigenic C. perfringens
artificial media. Instead, mouse inoculation or has also been associated with a syndrome of acute
embryonated egg culture techniques must be used hemorrhagic gastroenteritis (HGE) accompanied
to isolate the organisms. Most cases have been by severe hemoconcentration. Infection can also
diagnosed at necropsy by the histologic identifica- cause diarrhea in groups of animals confined
tion of typical-appearing bundles of intracellular together and nosocomial outbreaks in hospitalized
filamentous bacilli at the margins of necrotic foci patients. Clostridial diarrhea is usually self-limiting
within liver and intestinal lesions with special after a few days, but in some patients diarrhea can
stains such as methenamine silver, Giemsa, or persist chronically for weeks to months. Some
periodic acid–Schiff (PAS). patients have recurrent episodes of diarrhea.
Diagnosis
Clostridial Diarrhea Routine hematologic and serum chemistry evalu-
Enterotoxigenic C. perfringens is an important ations are usually normal in patients with clos-
cause of acute and chronic large bowel diarrhea in tridial diarrhea. Colonoscopy is not routinely
dogs and cats. In addition, Clostridium difficile, the necessary in these cases, but endoscopic findings
primary cause of antibiotic-associated pseudom- are usually nonspecific (diffuse hyperemia,
embranous colitis in humans, is also found in dogs increased friability, fresh bleeding, and increased
and cats and may occasionally be associated with mucus). Biopsy results range from minimal abnor-
diarrhea. malities to catarrhal, lymphocytic-plasmacytic, or
Diarrhea Associated With Clostridium suppurative colitis.
Perfringens A definitive diagnostic test for C. perfringens–
C. perfringens is a large anaerobic gram-positive induced diarrhea is lacking. Further work is
bacillus that normally exists in the intestinal tract needed to determine the role of CPE in canine
of most dogs and cats. Enterotoxin-producing and feline diarrhea and to define the optimal diag-
strains of C. perfringens can be associated with nostic parameters for clostridial diarrhea. Fecal
nonspecific episodes of diarrhea, acute hemor- spore counts in stained fecal smears are commonly
rhagic diarrhea, chronic or recurrent diarrhea, and used for routine cage-side screening; however,
outbreaks of diarrhea in animal groups. These studies have not shown a correlation between
bacteria normally reside in the bowel in the veg- spore counts and positive assays for CPE or a cor-
etative form, but they can release their toxin dur- relation between either of these diagnostic proce-
ing sporulation endogenously within the bowel dures and the presence or absence of diarrhea. In
or exogenously in contaminated food. The cpe humans, fecal assays for CPE are considered more
gene that regulates production of C. perfringens accurate than spore counts; however, the commer-
enterotoxin (CPE) is up-regulated by factors that cially available CPE assays used in humans need to
activate sporulation; thus the presence of clos- be validated for dogs and cats. In principle, CPE
tridial endospores in feces or food has been sug- assays should be valid across species.
gested as an indirect marker for the presence of The identification of more than five clostridial
CPE.Whether derived endogenously or ingested, endospores per oil immersion field (identified by
CPE causes diarrhea by binding to intestinal their “safety-pin” appearance with Diff-Quik or
epithelium and causing increased permeability, Wright’s staining, see Chapter 6) is considered by
hypersecretion, and cell damage (cytotoxicity). many to be presumptive evidence for a diagnosis
Endogenous sporulation and the production of of enterotoxigenic diarrhea caused by C. perfrin-
CPE can be associated with alteration of the gens. Clostridial spores are generally larger than
intraluminal environment caused by sudden other bacilli found in feces. Malachite green can
changes in diet, antibiotic administration, alkaline be used as a special stain for endospores. Fecal
conditions, immunosuppression, inflammatory leukocytes also may be present. Unfortunately,
bowel disease (IBD), or concurrent intestinal the appearance or absence of clostridial spores in
infections. the feces does not correlate well with CPE
Clinical Signs assays or signs; thus it might be advisable to take
Enterotoxigenic C. perfringens infection is associ- into account spore counts, CPE assays, and clini-
ated with large bowel diarrhea that varies from cal information before making a diagnosis of
watery to soft and may contain mucus or blood. clostridial diarrhea.
262 CHAPTER 8 DISEASES OF THE LARGE INTESTINE
Commercial fecal assays for C. perfringens its toxin have been isolated from normal dogs and
enterotoxin are available in kit form as either an cats and from a few patients with mild diarrhea;
enzyme-linked immunosorbent assay (ELISA) or however, this organism does not appear to be sig-
reverse passive latex agglutination (RPLA Kit).* nificant as an enteropathogen in dogs and cats.
The ELISA assay is recommended as easier to use C. difficile can be cultured using selective medium;
and interpret than the RPLA assay, and possibly however, infection can be established more rapidly
more sensitive. It is recommended that fresh feces by fecal PCR assay for the toxin gene or by latex
be used whenever possible and transported with- agglutination assay of feces for toxin.
out delay to the laboratory in prechilled diluent at
4˚ C (but freezing should be avoided). Assays for
CPE are generally considered to be more specific Mycotic Colitis
than fecal spore counts. Histoplasma Colitis
Cultures are not helpful because C. perfringens Histoplasma capsulatum, a dimorphic soilborne fun-
are normally found in the feces of most normal gus endemic to regions bordering the Mississippi
dogs and cats, and cultures do not reliably distin- River and its tributaries, primarily causes pul-
guish toxigenic and nontoxigenic strains. Assays monary and macrophage-monocyte system infec-
using molecular probes and polymerase chain tion and occasionally intestinal tract infection.
reaction are currently being evaluated as improved Widespread dissemination to virtually any tissue
diagnostic procedures for enterotoxigenic C. per- or organ system also can occur. The intestinal
fringens. form of histoplasmosis occurs most often in young
Treatment dogs and cats and is characterized by extensive
Diarrhea caused by enterotoxigenic C. perfringens transmural granulomatous inflammation of the
can be effectively treated with ampicillin (10 mg/lb bowel with mucosal ulceration and involvement of
orally every 8 hours), amoxicillin-clavulanate (6 to associated lymph nodes. The macrophages in
12.5 mg/lb orally every 12 hours), tylosin (10 to 20 these lesions contain Histoplasma organisms.
mg/lb orally every 12 hours), or clindamycin (2.5 Intestinal histoplasmosis may be manifested as
to 5 mg/lb orally every 12 hours) for 5 to 7 days. either small or large bowel diarrhea, or a combi-
Metronidazole (5 to 10 mg/lb orally every 12 nation of both when the disease is diffuse. Small
hours) can also be effective but seems to work less bowel involvement is characterized by malabsorp-
consistently. Clostridial diarrhea is usually self- tion syndrome and sometimes protein-losing
limiting or responsive to antibiotics in 2 to 3 days; enteropathy (see Chapter 7). When the colon is
however, chronic or recurrent clostridial diarrhea affected, severe bloody-mucoid large bowel diar-
may require long-term antibiotics (e.g., tylosin rhea and tenesmus are seen. The disease is usually
once daily or every other day) and a fiber- chronic, and associated signs may include fever,
supplemented diet to prevent relapses. Commercial pallor, inappetence, lethargy, and progressive
fiber-containing diets or regular diets supple- weight loss. Abdominal palpation may reveal dif-
mented with psyllium (Metamucil; dogs: 1 to 2 fuse thickening of the colon or small intestines,
tbsp/day) may help to reduce bacterial prolifera- focal tumorlike (granulomatous) thickenings in
tion and sporulation because fiber is fermented to the intestinal tract or mesentery, mesenteric lym-
SCFAs that acidify bowel contents. Alkaline rather phadenopathy, or abdominal effusions. When the
than acid conditions are most favorable for C. per- rectum is involved, mucosal proliferations may be
fringens. In addition, SCFAs nourish colonic detected by digital palpation. Physical examination
epithelium and protect against injury. may also detect other extraintestinal sites of
Diarrhea Associated With Clostridium dissemination (e.g., liver, spleen, or eyes).
Difficile Histoplasmosis should be suspected in young
A severe form of pseudomembranous colitis in patients in endemic areas with chronic intractable
humans is caused by colonic overgrowth of diarrhea. The results of diagnostics are variable but
cytotoxin-producing C. difficile, usually subsequent may reveal nonregenerative anemia, regenerative
to suppression of the normal flora by antimicro- neutrophilia, monocytosis, and hypoproteinemia.
bials or anticancer agents. Toxigenic C. difficile and Contrast radiography may demonstrate an irregu-
lar mucosal pattern indicative of a diffuse infiltra-
tive lesion. Ultrasonography may reveal diffuse or
*Oxoid, Unipath, Ogdensberg, NY. focal thickening of the colon with associated lym-
CHAPTER 8 DISEASES OF THE LARGE INTESTINE 263
phadenopathy. Colonoscopy usually reveals severe dogs, and it is characterized by extensive necrotiz-
granulomatous ulcerative colitis. Definitive diag- ing transmural granulomatous inflammation of the
nosis depends on identification of Histoplasma bowel. The lesions may result in tumorlike thick-
organisms in cytologic preparations (rectal mucosal ening of the affected segment of the GI tract. The
smears, colonic biopsy impressions, aspirates of stomach, small intestines, and mesentery are most
lymph nodes or abdominal masses), colonoscopic often affected; however, the colon is occasionally
biopsy specimens, or cultures of feces or affected involved and may result in chronic bloody-mucoid
tissues on Sabouraud’s medium. In addition, sero- large bowel diarrhea.
logic tests (immunodiffusion, complement fixa- The antemortem diagnosis of any of these intes-
tion) that detect anti-Histoplasma antibodies can be tinal mycoses is difficult, usually requiring histo-
used to establish a presumptive diagnosis; however, logic identification of the fungi in colonic biopsy
reliability of these tests is questionable because specimens. The branching hyphae of Aspergillus sp.
false-negative results are frequent. or the sparsely septate hyphae of Pythium sp. and
Histoplasma colitis is progressive without treat- Zygomycetes are best demonstrated in tissue spec-
ment. Oral itraconazole (2.5 mg/lb orally every 12 imens by Gridley’s or methenamine silver stains.
hours) is the treatment of choice for histoplasmo- Candida may form yeastlike cells or septate mycelia
sis. Ketoconazole (5 mg/lb every 12 hours with (pseudohyphae), which can be seen with fungal
food) can also be used as a more economical alter- stains or Gram stain (gram-positive). Feces or
native, but it has less consistent efficacy and greater biopsy specimens can be cultured on Sabouraud’s
risk of side effects. Treatment with either of these medium for fungi, but this is slow and often
antifungal drugs is continued for at least 2 to 3 unrewarding.
months beyond remission, usually for a total of 4 Most cases of intestinal aspergillosis and can-
to 6 months, while monitoring for hepatotoxicity. didiasis have been diagnosed at necropsy; thus
For symptomatic relief of colonic inflammation and information on which to base treatment is limited.
tenesmus, 5-aminosalicylates (5-ASA) (e.g., sul- Treatment with oral itraconazole is suggested.
fasalazine, olsalazine, mesalamine) can be adminis- Successful treatment of pythiosis is rare; thus the
tered as described later under treatment of prognosis must be considered poor.When feasible,
idiopathic IBD. surgical excision of the severely involved segments
of bowel with follow-up therapy using oral itra-
Other Mycoses conazole or intravenous (IV) lipid-complexed
Other than histoplasmosis, mycotic infections of amphotericin B is suggested.
the colon are rare; however, opportunistic fungi
sometimes invade devitalized tissue (such as
mucosa traumatized by passage of a foreign body) Protothecal Colitis
or infect young patients already compromised by Prototheca sp. are ubiquitous unicellular algae that
predisposing factors such as immunodeficiency, may rarely colonize the lamina propria and sub-
malnutrition, preexisting debilitating illnesses mucosa of the intestinal tract of dogs and cause
(such as parasitism or parvovirus), or prolonged severe necrotizing or ulcerating enterocolitis.
therapy with antimicrobials or corticosteroids. These algae appear to have a predilection for ini-
Opportunistic fungi can infect any portion of the tially invading the colon, resulting in signs of
intestinal tract of the dog and cat, and they include chronic large bowel diarrhea with hematochezia.
Candida albicans, Aspergillus sp., Pythium sp., and Typically the protothecal organisms then dissemi-
various fungi of the Zygomycetes class. nate widely throughout the body and most fre-
Both Aspergillus and Candida cause chronic quently involve other visceral organs, the eyes, and
diarrhea with mucosal ulceration and necrotizing the central nervous system (CNS). Only a cuta-
lesions that extend into the deeper layers of the neous form has been described in cats.
bowel wall. Pseudomembrane formation and vas- Colonoscopy reveals thickened, corrugated
cular invasion by hyphae have been seen in cats mucosal folds, and the mucosa may be friable or
with aspergillosis. ulcerated. Prototheca organisms can be identified in
The term pythiosis is often used to designate GI feces, cytologic preparations (Wright’s or Gram
infections caused by Pythium sp. and Zygomycetes. stain), and biopsy specimens (Gomori’s or PAS
Pythiosis is most prevalent in the Gulf region of stain) as clusters of endosporulated ovoid struc-
the United States, especially in young large-breed tures (5 to 16 µm in length). Prototheca can also be
264 CHAPTER 8 DISEASES OF THE LARGE INTESTINE
cultured on Sabouraud’s cycloheximide-free dex- from parasitic and infectious causes of colitis. Even
trose medium. Successful treatment of systemic though the cause of IBD is unknown, dietary
protothecosis in animals is rare. A combination of manipulation and medical treatment are often
IV lipid-complexed amphotericin B with either effective in controlling the disease.
itraconazole, ketoconazole, or tetracycline is
suggested. Lymphocytic-Plasmacytic Colitis
The most common form of IBD in both dogs and
cats is characterized by diffuse infiltration of the
Chronic Idiopathic Colitis lamina propria by lymphocytes and plasma cells in
(Inflammatory Bowel Disease) association with mucosal damage and abnor-
The terms chronic idiopathic colitis and inflammatory malities of mucosal epithelium and permeability.
bowel disease (IBD) are generally used interchange- Idiopathic lymphocytic-plasmacytic IBD is gener-
ably to refer to a diverse group of chronic disorders ally considered to be the most common finding in
characterized by diffuse infiltration of the colonic dogs and cats evaluated for chronic vomiting and
mucosa and sometimes submucosa with inflam- diarrhea. The stomach, small intestines, and colon
matory cells. The types of colitis are classified may be involved separately or together. This dis-
histopathologically on the basis of the predominant cussion will focus on lymphocytic-plasmacytic
infiltrating cells as lymphocytic-plasmacytic colitis, colitis; the reader is referred to other chapters in
eosinophilic colitis, neutrophilic colitis, granuloma- this book for further information regarding IBD
tous colitis, and histiocytic ulcerative colitis. Thus of the stomach and small intestine.
definitive diagnosis depends on colonoscopic Etiology
biopsy in conjunction with establishing the idio- The etiology of lymphocytic-plasmacytic IBD is
pathic nature of the condition. Sometimes there is unknown, but genetic, dietary, bacterial, immuno-
a mixture of inflammatory cells in the lesion that logic, and mucosal permeability factors have been
makes classification difficult. The most common suggested to play a role. The disease involves either
form of IBD in dogs and cats is lymphocytic- a primary disorder of the intestinal immune system
plasmacytic colitis. In some animals with IBD, infil- or its regulation, or immune responses that occur
trative lesions may also involve the small intestines secondary to mucosal injury and permeability.
and/or stomach. It is unclear whether these are Chronic inflammation of the bowel may become
variants of the same disease process or not. Chronic self-perpetuating when loss of mucosal integrity
idiopathic inflammatory diseases of the stomach and increased permeability allow bacterial or
and small bowel are discussed in Chapter 5 and dietary proteins to enter the lamina propria,
7, respectively. where they incite further immune reaction and
The etiology of colitis (IBD) in dogs and cats is inflammation.
not determined in most cases, but genetic, dietary, In some cases this lesion can be associated
bacterial, immunologic, and mucosal permeability with dietary hypersensitivity, enteric pathogens,
factors have been implicated. The pathogenesis or lymphoma. Some patients with lesions of
may involve altered mucosal permeability and a lymphocytic-plasmacytic enterocolitis respond to
hypersensitivity response to antigens derived from protein elimination diets or antibiotics such as
food, intestinal bacteria, or the intestine itself. This metronidazole or tylosin; however, in most
may result either from a primary disorder of the patients lymphocytic-plasmacytic colitis is idio-
intestinal immune system or its regulation or from pathic.
immune events that occur secondary to mucosal Clinical Signs
injury and permeability. It has been suggested that The most frequent presenting clinical signs of
chronic inflammation of the bowel becomes self- lymphocytic-plasmacytic IBD are vomiting, diar-
perpetuating when loss of mucosal integrity allows rhea, and weight loss. The signs vary with the
bacterial or dietary proteins to enter the lamina regions of the GI tract that are involved and the
propria, where they act as antigens (or cross-react severity of mucosal infiltration and damage. The
with self-antigens) that incite ongoing immune- typical historical pattern is one of GI problems
mediated recruitment of inflammatory cells. that wax and wane over periods ranging from a
Most animals with IBD involving predomi- few weeks to several years. Animals of all ages are
nantly the colon have chronic or recurrent large susceptible. Chronic intermittent vomiting is the
bowel diarrhea; thus IBD must be differentiated most frequent sign of lymphocytic-plasmacytic
CHAPTER 8 DISEASES OF THE LARGE INTESTINE 265
IBD in cats. Colitis usually causes large bowel diar- mild-to-moderate elevations of serum liver enzymes
rhea characterized by increased frequency of defe- (especially alanine aminotransferase), which in some
cation, urgency, tenesmus, increased fecal mucus, cases is due to associated cholangiohepatitis and/or
and hematochezia. Fecal consistency varies. Inter- pancreatitis. Hypoproteinemia related to protein-
mittent hematochezia without diarrhea may be losing enteropathy sometimes is noted in dogs
the only sign of IBD. A change in defecation with small intestinal involvement but is rare in
habits or loss of litter training without diarrhea can cats.
also occur. Physical examination is usually unre- Radiography and Ultrasonography
markable, except for cachexia in severe cases. In most cases radiographic and ultrasonographic
Intestinal loops can occasionally be palpably thick- findings are unremarkable and do not aid in diag-
ened and firm when the small intestine is nosis. Some patients have a nonspecific finding of
involved. The literature reports some patients with fluid- and gas-distended bowel loops on plain
concurrent food allergic dermatopathy, but this abdominal radiography. Barium-contrast radiogra-
has been extremely rare in my experience. phy occasionally demonstrates diffuse mucosal
Diagnosis irregularity, and ultrasonography may reveal intes-
Precise criteria for the diagnosis of idiopathic tinal thickening, but these are nonspecific find-
lymphocytic-plasmacytic colitis have not yet been ings that merely suggest an infiltrative lesion. In
established. In general the clinical criteria for diag- selected cases contrast radiography and ultrasonog-
nosis are (1) chronic signs of colonic disease, raphy can be helpful nonetheless, because they
(2) characteristic mucosal lesions of IBD in colono- may discover an unexpected diagnosis other than
scopic biopsy specimens, (3) failure to respond to IBD, for example, pancreatitis, hepatobiliary dis-
dietary trials, and (4) exclusion of known causes of ease, or intestinal tumors, polyps, granulomas, or
chronic inflammation of the intestinal tract based on malformations (e.g., diverticulum, short colon).
thorough diagnostic evaluation. This last criterion Endoscopic Examination
emphasizes that IBD is a diagnosis of exclusion and In patients with GI disease, the spectrum of clini-
not a catch-all label to be used as a substitute for cal signs usually suggests the most appropriate
diagnostic evaluation. Because lymphocytic-plasma- region of the GI tract for endoscopic examination.
cytic inflammation is a nonspecific lesion, only a In IBD, however, signs do not always correlate
thorough diagnostic work-up can establish that it is with the region of greatest cellular infiltra-
truly idiopathic and not merely an inflammatory tion, especially in cats. It is not uncommon to
response to an undiagnosed condition. find significant involvement of the colon in cats
A well-planned diagnostic approach could include that present for vomiting. Conversely, cats with
routine fecal examinations (for parasites, C. perfrin- hematochezia or other colonic signs may have
gens spores, Campylobacter, and fecal leukocytes), unexpected gastroduodenal lesions. Therefore it
a therapeutic trial of fenbendazole for occult whip- may be advisable in many cases to obtain biopsy
worm infection, elimination dietary trials, routine specimens from the stomach, duodenum, jejunum
screening for extraintestinal disease (CBC, serum (if possible), colon, and ileum (if the ileocolic
chemistry profile, urinalysis, retrovirus tests in cats, sphincter can be navigated during colonoscopy).
and baseline serum T4 level in cats over 5 years of Endoscopically the mucosa in colitis may
age), abdominal imaging (radiography, ultrasonogra- appear to be normal or it may have any of the
phy), and colonoscopy with biopsy under anesthesia. following abnormalities: erythema, petechiae,
Laboratory Evaluations increased mucus, increased friability, increased
Routine hematologic and serum biochem- surface granularity, decreased visibility of the
ical parameters are normal in most patients with submucosal vessels, thickened or increased folds,
lymphocytic-plasmacytic colitis; however, some erosions/ulcers, or decreased distensibility. The
are found to have mild nonspecific laboratory mucosal lesions may be apparent only microscop-
abnormalities such as mild anemia, stress leuko- ically; thus a normal endoscopic appearance does
gram (mature neutrophilia, lymphopenia), stress not rule out IBD, and multiple biopsy specimens
hyperglycemia, mild hypoproteinemia (hypoal- should be taken even if there are no endoscopi-
buminemia, hypoglobulinemia, or both), and cally visible abnormalities.
hypokalemia. Unexplained thrombocytopenia has Mucosal Histopathologic Examination
been observed occasionally. Eosinophilia is occa- The histopathologic lesion of lymphocytic-
sionally found in cats. Cats with IBD often have plasmacytic IBD is characterized by diffuse
266 CHAPTER 8 DISEASES OF THE LARGE INTESTINE
infiltration of the lamina propria with mature lym- be substituted for more convenience for long-
phocytes and plasma cells in association with term management.
mucosal damage. In some cases the inflammation A cooperative and patient owner is required for
is mostly lymphocytic; in others the infiltrate also a successful elimination diet trial. A minimum of
contains a mixture of other types of inflammatory 3 to 4 weeks should be allowed for initial response
cells (neutrophils, eosinophils, macrophages). The to an elimination diet. If no improvement has
cellular infiltrate is usually confined to the mucosa occurred during this time, then dietary hypersen-
but occasionally may extend to the submucosa. sitivity is unlikely and medical therapy should
Additional findings indicative of mucosal damage be instituted. If some improvement has been
include architectural distortion, fibrosis, and observed, then the trial should continue, because it
epithelial abnormalities (hyperplasia, degeneration, may require 6 to 10 weeks before improvement is
necrosis, erosion, ulceration, glandular dilation, loss complete.
of globlet cells). Pathologists may differ in their If there is a substantial improvement with the
interpretation of endoscopic biopsy specimens and elimination diet, then the patient can be rechal-
in their definition of how many lymphocytes and lenged with its original diet. Recurrence of clinical
plasma cells within the lamina propria are too signs confirms dietary intolerance or hypersensitiv-
many. Infiltrates assessed to be minimal or mild by ity. In addition, once remission is restored with the
an inexperienced pathologist may not be truly controlled diet, the patient can then be challenged
abnormal. For definitive diagnosis of lymphocytic- sequentially with individual dietary components to
plasmacytic colitis there must be abnormal infiltra- identify the specific offenders. To do this, individual
tion of lymphocytes and plasma cells, as well as components of the original diet are added one at a
evidence of mucosal damage.Various grading sys- time to the controlled diet while the patient is in
tems have been proposed, but these have not cor- remission.With each challenge the patient is moni-
related well with clinical disease activity. A severe tored for recurrence of signs for 7 to 10 days. If signs
infiltration of lymphocytes that extends beyond recur, then that substance is implicated as an
the mucosa into the submucosa and muscularis offender.
should raise the suspicion of early lymphoma After several weeks of remission of the con-
mimicking IBD, and further diagnostics should be trolled diet, some patients can be returned to their
recommended. original diet and remain asymptomatic; but in
Evaluation for Dietary Hypersensitivity most cases specially formulated or hypoallergenic
Dietary hypersensitivity or food allergy is an diets may need to be continued indefinitely to pre-
immunologically mediated adverse reaction to a vent relapse. If there is no response to dietary man-
protein component in food. A well-controlled agement within 4 to 6 weeks, the patient can be
dietary trial using a protein elimination diet is the returned to its original diet and medical therapy
basis for diagnosis of dietary hypersensitivity as a instituted.
cause of IBD. The diet is changed to a well- Treatment
defined, additive-free, highly digestible diet that Well-controlled therapeutic trials for chronic coli-
contains a single source of protein not found in tis in animals are lacking; thus treatment is largely
the patient’s normal diet. Intake of all other foods empirical and based on clinical experience.
or sources of antigen must be completely elimi- Because dietary hypersensitivity, parasites (see
nated throughout the feeding trial, including table previous section), and bacterial enteropathogens
scraps, treats, and flavored medications such as vita- (see previous section) may cause lymphocytic-
min supplements. The goal is to feed a single pro- plasmacytic colitis, it is appropriate to first consider
tein source to which the patient is not yet evaluation and treatment for these possibilities. In
sensitized. Although many commercial hypoaller- most cases of lymphocytic-plasmacytic colitis an
genic diets are available (see the section on treat- underlying cause cannot be identified and the most
ment), home-prepared single-protein diets are effective treatment is an antiinflammatory regi-
preferred for diagnostic testing purposes. Examples men of either a corticosteroid or mesalamine (5-
of novel protein sources not likely found in the aminosalicylate derivative) combined with dietary
patient’s regular diet might include turkey, duck, modification (e.g., novel protein diet or fiber-
lamb, rabbit, venison, fish, or soybean (tofu). Once enriched diet). If diet and antiinflammatory drugs
dietary hypersensitivity is confirmed with a home- fail to control the disease, metronidazole is added
prepared diet, commercial hypoallergenic diets can for its antibacterial and immunomodulatory prop-
CHAPTER 8 DISEASES OF THE LARGE INTESTINE 267
erties. Metronidazole can also be used as a single has many beneficial effects on colonic function
drug to induce or maintain remission in less severe and helps to keep enteropathogens in check.
cases. For the most refractory cases a cytotoxic Colonic bacteria metabolize fermentable fiber to
immunosuppressive agent such as azathioprine is SCFAs that nourish colonic epithelium and pro-
added to the corticosteroid regimen. tect against mucosal injury. Adjustment of the lev-
Dietary Therapy els of omega-6 and omega-3 fatty acids in the diet
Various strategies for dietary modification have has been proposed to manage bowel inflammation
been used for treatment of chronic colitis, includ- through decreasing inflammatory mediators,
ing novel protein diets, fiber-enriched diets, and although evidence for this is lacking.
diets with adjusted omega-6 and omega-3 fatty Corticosteroids
acid levels. In some patients with IBD, dietary Oral prednisolone is the most consistently effective
modification produces a complete or partial res- medical therapy (dogs: 0.5 to 1 mg/lb/day; cats: 1
olution of the signs and sometimes regression of to 2 mg/lb/day or 5 mg total dose every 12 hours)
the lesions. Potential explanations for a beneficial for inducing remission of idiopathic lymphocytic-
response to dietary modification include the plasmacytic colitis. Clinical improvement using this
effects of the diet on bowel motility, composition dosage should be noted within 1 to 2 weeks. After
of the microflora, mucosal structure and func- 2 weeks of remission, the dosage is tapered in 2-
tion, and exposure to foodborne antigens or to 4-week increments to the lowest effective
additives. alternate-day dosage. In cats that are too difficult to
The treatment of IBD associated with dietary medicate orally, periodic injections of methylpred-
hypersensitivity is based on the controlled feeding nisolone acetate (20 mg intramuscularly or subcu-
of a well-defined, additive-free, highly digestible taneously every 2 to 4 weeks) may be substituted
diet that contains a single source of protein not for oral treatment, or dermal preparations formu-
found in the patient’s normal diet (i.e., a novel lated by a compounding pharmacist may be
protein to which the patient is not yet sensitized). applied topically. Corticosteroid therapy may be
Home-prepared diets (turkey, duck, lamb, rabbit, discontinued on a trial basis after 6 to 12 weeks of
venison, whitefish, or tofu) are most suitable for remission; however, continuous alternate-day ther-
diagnostic testing purposes (see previous section apy is often required to prevent relapse. In refrac-
on diagnosis); however, if the home-prepared diet tory cases metronidazole or mesalamine (see
suggests diet-responsive disease, then a commercial following sections) should be added to the pred-
“hypoallergenic” novel protein diet can be substi- nisolone regimen. If this fails to control the disease,
tuted and is more convenient and balanced for then the combination of azathioprine (see later
long-term feeding. Many commercial diets that section) and prednisolone may be more effective in
contain novel protein sources are now marketed achieving remission of the disease.
for dietary hypersensitivity. A relapse rate of 5-Aminosalicylic Acid
approximately 15% to 20% is to be expected when Derivatives of 5-ASA, also known as
switching from a home-prepared to a commercial mesalamine, exert an antiinflammatory effect in
hypoallergenic diet. For long-term feeding of a colitis through local inhibition of mucosal
home-prepared diet, recipes for balanced diets leukotrienes and prostaglandins. Many gastroen-
containing novel protein sources can be found in terologists regard these as the initial drugs of
standard veterinary therapy and nutrition text- choice for treatment of colitis, particularly in
books, or various reliable websites under supervi- dogs. Orally administered 5-ASA derivatives are
sion of Diplomates of the American College of designed to be minimally absorbed during pas-
Veterinary Nutrition. sage through the small intestine so that they
In cases in which hypoallergenic novel protein reach the colon. These drugs should be used
diets have not been effective, other dietary adjust- cautiously in cats because some salicylate
ments may be beneficial as an adjunct to medical absorption occurs and cats metabolize salicylates
therapy for IBD. This includes fiber supplementa- very slowly.
tion (psyllium, bran, canned pumpkin) of the reg- In sulfasalazine (Azulfidine), 5-ASA is com-
ular diet or switching to a commercial diet bined with sulfapyridine by an azo bond that pre-
enriched with fermentable fiber (e.g., beet pulp) vents significant absorption of the drug so that
marketed for improving colonic function and 75% of it reaches the colon, where colonic bacte-
ameliorating diarrhea in patients with colitis. Fiber ria split the bond and release the 5-ASA for its
268 CHAPTER 8 DISEASES OF THE LARGE INTESTINE
ANTIBIOTICS
Metronidazole Flagyl (Searle) Tab: 250 mg, 500 mg 5-7 mg/lb PO q8-12h
Tylosin|| Tylan Soluble (Elanco) Powder D: 10-20 mg/lb PO q12h
FIBER SUPPLEMENT
Psyllium Metamucil (Procter & Powder D: 1-3 tbsp/day (in food)
Gamble) C: 1-3 tsp/day (in food)
identified by digital rectal palpation when this area such as histoplasmosis, pythiosis, and mycobacte-
is involved. riosis. In cats FIP coronavirus can occasionally
Diagnosis cause pyogranulomatous colitis manifesting as a
Regional granulomatous colitis must be differen- large tumorlike mass. Barium contrast radiogra-
tiated from intestinal neoplasia and from infec- phy or ultrasonography of the ileum and colon
tious causes of pyogranulomatous bowel lesions, may delineate a thickened or stenosed segment of
CHAPTER 8 DISEASES OF THE LARGE INTESTINE 271
bowel. A routine CBC may reveal eosinophilia, The disease is treated with olsalazine or sul-
neutrophilia, or monocytosis. Panhypoproteinemia fasalazine, prednisone, azathioprine, and metronida-
due to chronic intestinal bleeding and protein loss zole in single-agent or combination regimens as
may be found in some patients. described for lymphocytic-plasmacytic colitis (see
Definitive diagnosis of granulomatous colitis Table 8-2); however, lifetime therapy is needed and
depends on biopsy by colonoscopy or lapa- the prognosis for effective control of the disease is
rotomy. Colonoscopic findings include thickened poor. In general these dogs seem to have less diar-
and corrugated folds, proliferative mucosal masses, rhea on a highly digestible diet than on a high-fiber
ulceration, loss of distensibility, and partial obstruc- diet.
tion. The key histopathologic feature is trans- There have been isolated case reports of histio-
mural granulomatous inflammation. Fibrosis and cytic colitis in a cat and a French bulldog, but it is
aggregates of epithelioid cells, giant cells, and not known if these represent the same disease as
eosinophils are often found deep in the lesion. occurs in boxers.
Deep ulceration is common. Whenever granulo-
matous lesions are found in the bowel, infectious
causes should be ruled out with special stains that Colitis Associated With
identify fungi and acid-fast organisms. In cats Pancreatitis
polymerase chain reaction assay for detection Necrotizing hemorrhagic colitis occurs occasion-
of coronavirus in biopsy specimens should be ally in dogs with acute pancreatitis. It is presumed
considered. that because the transverse colon lies adjacent to
Treatment the inflamed pancreas, it can sometimes become
Medical treatment of regional granulomatous coli- secondarily involved in the local inflammatory and
tis is based on the use of antiinflammatory and vascular-compromising processes in that region of
immunosuppressive agents such as olsalazine or the abdominal cavity.
sulfasalazine, prednisone, azathioprine, and metro- The diagnosis is based on colonoscopic demon-
nidazole, as described for treatment of lymphocytic- stration of lesions of colitis in the transverse colon
plasmacytic colitis (see Table 8-2). If the degree of in a patient that has laboratory, radiographic,
thickening and cicatrization of the affected segment and ultrasonographic evidence of pancreatitis.
of bowel is producing severe stenosis and oblitera- Olsalazine, sulfasalazine, or metronidazole can be
tion of the lumen, surgical excision of the lesion added to the treatment regimen for pancreatitis, but
may be necessary. Surgery should be followed by corticosteroids should be avoided in acute
long-term medical therapy for 6 to 8 weeks or pancreatitis.
longer to prevent recurrence of the lesion at the
surgical site. The prognosis is guarded.
Cecocolonic Intussusception
Histiocytic Ulcerative Colitis (Cecal Inversion)
Histiocytic ulcerative colitis is a chronic idiopathic Cecocolonic intussusception results in invagination
IBD of young boxer dogs characterized by infiltra- of the cecum into the lumen of the colon, where
tion of the lamina propria and submucosa of the mucosa of the inverted cecum then becomes
the colon by distinctive histiocytes engorged congested, inflamed, hemorrhagic, and ulcerated.
with deposits that stain positive with PAS stain. Whipworm infection has been suggested as a pre-
A mixture of other types of inflammatory cells disposing cause. With partial ileocolonic obstruc-
also is found in the lesion, and there is usually severe tion, chronic or intermittent bloody-mucoid
mucosal ulceration. Affected boxers generally diarrhea is usually the presenting sign; thus cecal
develop a severe unresponsive bloody-mucoid large inversion can often mimic colitis or colonic neo-
bowel diarrhea before 2 years of age. Colonoscopy plasia. When cecal inversion causes complete ileo-
reveals diffuse severe mucosal inflammation with colic obstruction, the signs are acute depression,
corrugation, ulceration, bleeding, and thickened anorexia, vomiting, and dehydration.
folds. Weight loss and moderate hypoproteinemia The inverted cecum can sometimes be palpated
may occur in dogs with long-standing disease. The as a firm, painful, right cranial abdominal mass, but
diagnosis is based on the known breed predisposi- usually the diagnosis is made by identification of
tion and the presence of numerous PAS-positive the inverted cecum during colonoscopic examina-
histiocytes in a colonoscopic biopsy specimen. tion of the proximal colon by ultrasonography or
272 CHAPTER 8 DISEASES OF THE LARGE INTESTINE
copiously lavaged, and the septic peritonitis is treated (1) ingested foreign material, (2) environmental
vigorously postoperatively. The prognosis for sur- factors, (3) painful anorectal or orthopedic condi-
vival from colonic perforation is guarded to poor. tions, (4) anorectal or colonic obstruction, (5) neu-
romuscular diseases, (6) fluid and electrolyte
disturbances, and (7) drug-related effects.
Volvulus of the Colon Ingested foreign material such as indigestible
Torsion or volvulus of the colon results in com- fibrous material (especially hair in cats from their
plete distal bowel obstruction, rapidly progressive grooming behavior) or abrasives (especially bones
ischemic necrosis of the bowel, eventual septic in dogs) may become incorporated into the fecal
peritonitis, and finally death from septic shock; mass and result in the formation of hard fecal
thus early recognition and immediate surgical impactions that are difficult or painful to evacuate
intervention are necessary. This is a rare condition from the colon.
in dogs and cats. When it occurs, the signs are Environmental factors that are not conducive
those of acute abdominal distress with pain, vom- to defecation or that vary from the daily routine to
iting, raspberry jam–like hemorrhagic diarrhea, which the patient is accustomed may cause the
and acute collapse. Radiographs generally reveal a patient to inhibit the urge to defecate, leading to
gas-distended lower bowel, which, taken together constipation. This occurs, for example, when a
with the clinical signs, is indication to proceed patient is placed in strange surroundings such as a
with emergency laparotomy. Measures to treat kennel or veterinary hospital or when the patient’s
hypovolemic and septic shock also should be daily outdoor exercise routine is changed. Indoor
initiated immediately. cats will often suppress the urge to defecate
when their litter box is too dirty or there is terri-
CONSTIPATION AND torial competition with other cats in the house-
hold.
DYSCHEZIA Painful defecation caused by anorectal diseases
Constipation is a clinical sign characterized by (e.g., anal sacculitis or perianal fistulae; see section
absent, infrequent, or difficult defecation associ- on anorectal disease) or by orthopedic disorders that
ated with retention of feces within the colon and limit positioning for defecation (e.g., disorders of
rectum.When feces are retained in the colon for a pelvis, spine, or hips) can result in voluntary inhibi-
prolonged period of time, the mucosa continues to tion of defecation and lead to constipation.
absorb water from the fecal mass, which gradually Rectocolonic obstructions that mechanically
results in impacted feces that become progressively impede passage of feces may occur from intralumi-
harder and drier. Obstipation is a condition of nal causes, such as foreign bodies, perineal hernia, or
intractable constipation in which the colon and stenosing neoplastic or inflammatory lesions (i.e.,
rectum become so impacted with excessively hard strictures), and from extraluminal causes, such as
feces that defecation cannot occur. Megacolon is a prostatic enlargement, paraprostatic cysts, compres-
term that refers to a disorder (not a sign) in which sive pelvic fractures, perianal tumors, or pseudoco-
the colon becomes extremely dilated and hypo- prostasis (feces matted to the hair of the perianal
motile, usually irreversibly so, and it is an impor- area).
tant cause of chronic constipation/obstipation in Neuromuscular disorders may lead to constipa-
cats. tion by interfering with colonic innervation,
Dyschezia, a clinical sign often associated with colonic smooth muscle function, or simply the abil-
constipation, is defined as difficult or painful evac- ity of the patient to assume the normal defecation
uation of feces from the rectum and is usually stance—for example, disease or injury of the lum-
associated with lesions in or near the anal region. bosacral spinal cord (e.g., canine intervertebral disk
Tenesmus is a clinical sign characterized by inef- disease), spinal deformity (as occurs in Manx cats),
fective or painful straining to defecate; thus it usu- endocrine disease (hypothyroidism), or dysautono-
ally accompanies dyschezia. mia, a progressively fatal autonomic polyneuropathy
of young cats. When innervation of the anus is
also impaired, fecal incontinence may be an associ-
Etiology ated clinical sign. The pathogenesis of idiopathic
Underlying causes or predisposing factors for megacolon appears to involve smooth muscle dys-
constipation are listed in Table 8-3 and include function. Studies have demonstrated decreased
CHAPTER 8 DISEASES OF THE LARGE INTESTINE 275
be predisposing causes of constipation; and imaging pelvic canal structures and the lum-
(5) enlargement of the prostate that may be an bosacral spine.
underlying cause of constipation.
Additional specialized diagnostic studies may
be indicated in selected patients.When intralumi- Treatment
nal obstructive lesions are suspected, barium Mild constipation resolves spontaneously or is
enema contrast radiography (see Chapter 2) or treated on an outpatient basis by dietary adjust-
colonoscopy (see Chapter 3) may be used after the ment and oral or suppository laxatives. Severe
retained feces have been evacuated to evaluate the constipation is treated initially by evacuation of
lumen of the colon. Myelographic and electrodi- impacted feces from the colon by means of ene-
agnostic evaluations of the lumbosacral spinal cord mas and/or manual extraction along with correc-
and spinal nerves should be considered in patients tion of complicating dehydration and electrolyte
with evidence of impaired anorectal innervation. imbalances. Follow-up therapy is aimed at elimi-
When prostatic disease or paraprostatic cysts are nating or controlling any of the underlying causes
suspected to be the cause of constipation, further of constipation that are identified from Table 8-3
evaluations might include caudal abdominal ultra- and at preventing recurrences by means of dietary
sound examination, contrast cystourethrography, adjustments and laxative therapy (Table 8-4).
and cytology/culture studies of the prostate. Surgical correction is required for obstructing neo-
Computed tomography (CT) and magnetic reso- plasms and strictures and many anorectal disorders.
nance imaging (MRI) scans can be useful for Finally, long-term management of megacolon or
Lubricant Laxatives
White petrolatum Laxatone (Evsco) 1-5 ml daily PO
Emollient Laxatives
Docusate sodium Colace (Shire) Dog: 50-200 mg daily PO
Cat: 50 mg daily PO
Docusate calcium Surfak (Geneva) Dog: 100-240 mg daily PO
Cat: 50-100 mg daily PO
Saline Laxatives
Magnesium hydroxide Phillips’ Milk of Magnesia (Glenbrook) Dog: 2-8 tablets daily PO
Osmotic Laxatives
Lactose Milk Add to diet to effect
Lactulose Duphalac (Reid Rowell); Cephulac 0.25-0.5 ml/lb PO, q8-12h
(Merrell Dow)
Polyethylene glycol and Colyte (Schwarz); Golytely (Braintree) 12-20 ml/lb PO repeated
electrolytes‡ in 2-4h (for bowel prep)
Stimulant Laxatives
Bisacodyl Dulcolax (Boehringer Ingelheim) Dog: 5-20 mg daily PO
Cat: 5 mg daily PO
Continued
278 CHAPTER 8 DISEASES OF THE LARGE INTESTINE
Rectal Suppositories
Glycerin Various 1-3 pediatric suppositories
Docusate sodium Colace (Shire) 1-3 pediatric suppositories
Bisacodyl Dulcolax (Boehringer Ingelheim) 1-3 pediatric suppositories
*
Ancillary treatment measures:
1. Regular grooming to prevent ingestion of loose hair (especially cats).
2. Prevent ingestion of abrasive foreign materials.
3. Provide fresh drinking water.
4. Provide clean litter for cats.
5. Encourage regular exercise.
†
For severe recurrent or refractory cases: total or subtotal colectomy.
‡
Used mainly to prepare the colon for radiography or endoscopy.
§
Should not be used in cats or small dogs.
recurrent obstipation that is unresponsive to medical enterally. The colon is then evacuated manually
therapy in the cat may involve colectomy surgery. under general anesthesia with a combination of
colonic irrigation with warm isotonic saline as an
Initial Relief of Constipation enema solution to soften the impacted feces and
Simple constipation with mild to moderate extraction of retained fecal masses by gentle trans-
impaction of feces and without accompanying sys- abdominal manipulation to milk the feces into
temic signs (depression, vomiting, dehydration) the distal rectum for digital extraction or removal
can often be managed on an outpatient basis using with sponge or whelping forceps. To avoid exces-
dietary adjustment, measures to increase water sive bowel trauma in patients with extensive
intake, and oral laxatives. Oral laxatives can be pre- fecal impaction, it may be advisable to evacuate
scribed as discussed later in this chapter and the the colon manually in stages over a period of 2 to
animal reevaluated in 48 hours. To promote initial 3 days.
evacuation of the distal colon when impaction is Enema Solutions
not severe, one to three pediatric suppositories Enema solutions can be used to soften hard,
consisting of docusate sodium, bisacodyl, or glyc- impacted feces and promote evacuation. The
erin also can be used or a therapeutic enema can enema solutions should be warmed prior to instil-
be administered. lation, and the calculated dose administered slowly
In severe constipation/obstipation, fluid and so as not to induce vomiting. The following are
electrolyte balance should initially be restored par- commonly used enema solutions:
CHAPTER 8 DISEASES OF THE LARGE INTESTINE 279
Osmotic Laxatives. These consist of poorly by stimulating colonic smooth muscle, increasing
absorbed disaccharides (such as lactose or lactu- the physiologic release of acetylcholine from post-
lose), ions (such as magnesium hydroxide, magne- ganglionic nerve endings of the myenteric plexus,
sium citrate), or inert osmotic agents (polyethylene and acting as a 5-HT4-serotonergic agonist. These
glycol) that osmotically retain water in the bowel actions lead to improved propulsive motor activity
lumen to produce soft or fluid feces. A mild of the esophagus, the stomach, and the small and
osmotic laxative effect can be produced in some large intestines. Cisapride is a highly effective lax-
patients by the addition of milk (lactose) to the ative for both cats (0.5 mg/lb every 8 hours
diet in a quantity that exceeds the digestive capac- or 0.7 mg/lb every 12 hours orally) and dogs
ity of small intestinal lactase. The nonabsorbable (0.25 to 0.5 mg/lb every 8 to 12 hours orally) (see
disaccharide lactulose (Duphalac, Cephulac, 0.25 Table 8-4). It can be administered alone or com-
to 0.5 ml/lb orally three times a day) is an excel- bined with stool-softening measures such as a fiber-
lent choice as a safe and effective all-purpose lax- augmented diet or lactulose. Cisapride is the most
ative for short- or long-term use in both dogs and effective medical therapy for megacolon in cats.
cats. Unabsorbed dissacharides such as lactulose are The colon in cats with megacolon may even
fermented by colonic bacteria to lactic acid and resume normal diameter radiographically under
other organic anions, thereby producing an treatment with cisapride. Unfortunately, megacolon
osmotic catharsis and acidification of the colon. commonly becomes refractory to cisapride after
The dosage of lactulose needs to be adjusted to several months of therapy, necessitating increasing
effect. If the dosage is too high, abdominal dis- the dosage to 1 mg/lb every 8 hours or higher.
comfort, flatulence, and diarrhea may occur. These Eventually after several months to years, many cats
side effects resolve with lowering the dosage. with megacolon become completely refractory to
Magnesium hydroxide is available as an over- cisapride and require colectomy.
the-counter drug (Phillips’ Milk of Magnesia). Cisapride is contraindicated in the presence of
Magnesium is contraindicated in renal failure. GI obstruction or perforation. It is ineffective if
Magnesium citrate and polyethylene glycol– used with anticholinergics. Side effects are uncom-
electrolyte solutions (Colyte, GoLYTELY) are mon, but nausea, vomiting, diarrhea, flatulence, and
available commercially for preparation of the abdominal discomfort are occasionally reported.
colon for endoscopy, but the large oral doses Cisapride appears very safe for long-term use in
required are too impractical for therapeutic use. animals; however, it is no longer approved for use
Stimulant Laxatives. These increase propul- in humans in the United States because of its asso-
sive motility of the bowel by a variety of mecha- ciation with serious arrhythmias. This side effect
nisms. They are generally contraindicated in the has not been a problem in animals. Cisapride can
presence of an obstructive lesion and are less be obtained in the United States from compound-
appropriate for long-term use than other cate- ing pharmacies for animal use.
gories of laxatives. A useful stimulant laxative for Ranitidine (Zantac) and nizatidine (Axid) are
the dog and cat is bisacodyl (Dulcolax, daily dose H2-receptor antagonists that also stimulate GI
of 5 mg for cats and small dogs, 10 mg for and colonic motility at standard dosages (see Table
medium-sized dogs, and 15 to 20 mg for large 8-4). They increase acetylcholine by inhibiting
dogs), which works by stimulating colonic smooth synaptic acetylcholinesterase. These are not as
muscle and the myenteric plexus. Although bene- potent as cisapride as promotility agents; however,
ficial on a short-term basis in conjunction with they may be useful when a mild laxative effect is
measures to soften the feces, long-term use of needed.
bisacodyl may damage the myenteric plexus.
Castor oil, another stimulant laxative, is hydrolyzed Colectomy
in the intestines to ricinoleic acid, which stimu- For megacolon and severe recurrent constipa-
lates colonic motility and secretion. Castor oil is tion/obstipation that is unresponsive to medical
not very useful for outpatient treatment because of management, especially in cats, subtotal colectomy
poor patient acceptance, but it can be used effec- is the most effective method of treatment. This
tively in hospitalized patients to prepare the bowel procedure involves the removal of 95% or more of
for radiographic or endoscopic procedures. the colon. In cats with obstipation from pelvic
Promotility Therapy. Cisapride (Propulsid) is fracture malunion, pelvic osteotomy or recon-
a benzamide derivative that promotes GI motility structive surgery can allow return of normal
CHAPTER 8 DISEASES OF THE LARGE INTESTINE 281
colonic function if obstipation has been a problem straining that produces recurrence of the prolapse.
for less than 6 months; otherwise, subtotal colec- Amputation is performed when the prolapsed tis-
tomy is recommended. After subtotal colectomy, sue is nonviable. For recurrent prolapse, a prophy-
diarrhea and frequent defecation are common; lactic colopexy should be considered. Successful
however, bowel function gradually improves dur- management requires identification and treatment
ing the 2 to 4 weeks following surgery in most of the underlying cause; thus the anus, rectum,
cats. In dogs, diarrhea, frequent defecation, hema- intestines, and urogenital tract should be evaluated
tochezia, and tenesmus often persist after colon by palpation, urinalysis, fecal examinations, proc-
removal. toscopy, and radiographic studies as deemed
appropriate.
ANORECTAL DISEASES
The presenting signs of anorectal disease may Perineal Hernia
include any of the following: dyschezia, hema- Perineal hernia occurs when weakness of the
tochezia, constipation, anal discomfort (licking, pelvic diaphragm muscles fails to support the rec-
scooting), ribbonlike feces, fecal incontinence, anal tal wall, resulting in persistent rectal distention
discharge, foul perianal odor, matting of perianal and impaired defecation. The pathogenesis of the
hair, and perianal dermatitis. Physical examination weakened pelvic diaphragm is poorly under-
establishes the diagnosis of anorectal disease in stood. Older male dogs are almost exclusively
most cases. In many of these disorders, surgery is affected, although perineal hernia has also been
required for effective treatment. reported in cats. The hernia usually contains out-
pouched rectum and can be either unilateral or
bilateral; unilateral hernias are predominantly
Anorectal Prolapse right-sided. The rectal defects associated with
Anorectal prolapse is usually a consequence of perineal hernia have been classified as (1) saccu-
an underlying disorder that produces persistent lation, when unilateral loss of support allows
straining; thus it is associated with (1) intestinal expansion of the rectal wall to one side; (2) dila-
diseases that cause diarrhea and tenesmus, tion, when bilateral loss of support allows gener-
(2) anorectal diseases that cause dyschezia, alized distention of the rectum; (3) deviation or
(3) lower urinary tract and prostatic diseases that flexure, when the rectum curves or bends to one
cause stranguria, and (4) dystocia. Partial prolapse side within the hernia sac; and (4) diverticulum,
involves only the rectal mucosa and appears as a when there is an outpouching of mucosa through
red, swollen, donut-shaped ring of prolapsed a defect in the rectal wall. The hernia sac may
mucosa. Complete prolapse involves all layers of also contain retroperitoneal fat, prostate gland, or
the rectal wall and appears as an edematous rarely abdominal organs such as the urinary
cylindric-shaped mass. The prolapsed tissue may bladder.
be viable (pink or red and moist) or necrotic The clinical signs of perineal hernia include
(blackened and dry). A thermometer or finger constipation, obstipation, dyschezia, and tenesmus.
should be inserted in the space between the pro- Stranguria may occur with herniation of the uri-
lapsed tissue and the anal sphincter to probe for a nary bladder and associated urethral obstruction.
cul-de-sac. If there is none and resistance is not The diagnosis is based on palpation of a reducible
met, the prolapsed tissue is an intussusception of swelling ventrolateral to the anus and rectal palpa-
ileum or colon rather than an anorectal prolapse. tion of the weakened pelvic diaphragm and rectal
Management of anorectal prolapse involves dilation.
both repair of the prolapse and treatment of the Initial treatment is aimed at evacuating retained
underlying cause. Minor prolapses in which the feces from the rectum as described in the section
tissue is viable are treated by reduction and med- on constipation and dyschezia. Urethral catheteri-
ical therapy to reduce tenesmus and prevent repro- zation or cystocentesis also may be necessary ini-
lapse, such as an anticholinergic-antispasmodic tially to relieve urinary obstruction. In some dogs
drug, hydrocortisone retention enema, mesalamine with perineal hernia, normal defecations can be
enema, or mild sedation. See Table 8-2 for dosages. maintained by laxative therapy and stool-softening
A temporary (2 to 3 days) anal purse-string suture diets (see Table 8-4); however, perineal hernior-
may be required in patients with persistent rhaphy surgery combined with castration provides
282 CHAPTER 8 DISEASES OF THE LARGE INTESTINE
the best, longer-lasting results in most cases. Even contraction of the anal sphincter, leading to more
with surgery, the recurrence rate is fairly high. pain. Digital palpation of the rectum is vigorously
resented, and the anal sphincter muscle feels hyper-
trophied and tightly contracted in spasm. Even
Anorectal Foreign Bodies visually the external sphincter muscle appears
and Fecoliths hypertrophied. Most affected dogs have been
Ingested foreign bodies such as bones, toys, sticks, or German shepherds of temperamental disposition.
sewing needles can sometimes pass unobtrusively To attribute dyschezia to anal spasm, it is important
through the GI tract and become lodged transversely to rule out structural causes of dyschezia (such as
within the rectum or at the anal sphincter. In addi- anal sac disease and perianal fistulae) and to exclude
tion, foreign objects are occasionally inserted into anal stricture (stenosis) by thorough rectal examina-
the anus of an animal by a malicious or deranged tion under anesthesia. Conservative treatment
person. Older cats are sometimes presented for involving anal sac evacuation, topical analgesics,
inability to pass a firm lump of feces (fecolith) that antispasmodic-sedative drugs, and stool softeners
lodges in the anal canal between the internal and the has not been very successful; thus resection of one
external sphincter. Whenever a foreign body or or both anal branches of the pudendal nerve has
fecolith is lodged in the anal canal or rectum, defe- been required for palliation in most dogs. Fecal
cation becomes painful or impossible and signs of incontinence is often a postoperative problem.
dyschezia, tenesmus, and secondary fecal impaction
occur.
Most anorectal foreign bodies and fecoliths can Congenital Defects of the Anus
be detected and removed by rectal palpation, and Rectum
although sedation or anesthesia is often necessary. Imperforate Anus and Rectal Agenesis
In some cases a proctoscope may facilitate foreign Imperforate anus and rectal agenesis are uncom-
body extraction. There are two potentially serious mon congenital malformations of cloacal develop-
complications of anorectal foreign bodies: rectal ment that result in an absence of a patent anal
laceration, resulting in retroperitoneal cellulitis, opening for defecation. Consequently, within days
and anorectal stricture. or weeks of birth the affected puppy or kitten
shows signs of abdominal distention and discom-
fort, tenesmus, restlessness, vomiting, and loss of
Anorectal Stricture (Stenosis) appetite. The diagnosis is established by absence of
Strictures of the anus or rectum may result from an anal opening. The variations in the malforma-
the trauma caused by passage of sharp foreign bod- tion range from an imperforate anal mem-
ies (especially bones), from postsurgical scarring brane covering the anal opening (atresia ani) to
after anorectal surgery, and from the chronic varying degrees of rectal agenesis (rectal atresia),
inflammation of anal sac disease, perianal fistulae, in which the rectum ends in a blind pouch at
or proctitis. Anorectal strictures cause dyschezia, some distance cranial to the anus. The terminal
tenesmus, hematochezia, and secondary constipa- end of the rectum can be delineated radiographi-
tion. The stricture can usually be identified by cally by the intraluminal air when a lateral ra-
digital rectal palpation, proctoscopy, or barium diograph is exposed with the patient’s hind end
enema contrast radiography. Surgical correction is slightly elevated. In some patients, imperforate
usually required. anus is associated with genitourinary defects such
as rectovaginal fistula.
The treatment for atresia ani is surgical opening
Anal Spasm and removal of the retained anal membrane, usu-
Some authors report a rare form of severe ally producing favorable results. For rectal atresia,
dyschezia, in which the anal sphincter appears to surgical correction is more difficult and requires
contract in spasm when the patient attempts to combined abdominal surgery and rectal pull-
defecate; the patient may cry out in pain, move through; thus the prognosis is guarded.
about frantically before stopping to make another
attempt to defecate, turn and stare at its hindquar- Rectovaginal Fistula
ters, and appear extremely anxious. A cycle seems Rectovaginal fistula is a rare congenital malforma-
to occur of painful defecation, leading to defensive tion of females characterized by passage of fecal
CHAPTER 8 DISEASES OF THE LARGE INTESTINE 283
material from the vaginal opening. In many cases Anal sac abscess is usually unilateral and charac-
there also is an imperforate anus. Persistent fecal terized by marked distention of the sac with pus,
incontinence through the vagina leads to perivulvar cellulitis of surrounding tissues, erythema of the
dermatitis. Colonic distention usually occurs once overlying skin, and fever. Abscessed anal sacs may
the puppy or kitten begins eating solid food. The rupture through the adjacent skin, producing a
defect can be surgically corrected, but the progno- draining fistulous tract.
sis is guarded. Other related anorectal anomalies that Treatment of anal sac impaction and anal sac-
are very rare include rectovestibular fistula, anovagi- culitis by manual evacuation of the sac contents to
nal cleft, and rectourethral fistula. reestablish drainage may be all that is required in
many patients. Follow-up examination and
expression of the anal sacs again in 1 to 2 weeks
Anal Sac Disease are advisable. A high-fiber diet may help to pre-
Disorders of the anal sacs are the most common vent recurrences. For recurrence of impaction or
problem of the anal area in small animals, espe- sacculitis, irrigation with povidone-iodine solu-
cially in dogs. Anal sac disease has been classified tion with a lacrimal needle and instillation of an
into impaction, inflammation (sacculitis), infec- antibiotic (e.g., an otic or ophthalmic antibiotic
tion, abscess, and rupture. These probably repre- ointment) into the sac may be helpful, along with
sent a continuum such that impacted anal sacs follow-up expression of the sacs every 3 to 4 days.
tend to become inflamed and infected, which may Culture and sensitivity testing of the sac contents
then lead to abscessation and finally to rupture or also should be considered for patients with trou-
fistulation. All breeds of dogs can be affected. Anal blesome recurrences. Anal sac abscesses are
sac disease is uncommon in cats and usually drained, irrigated with povidone-iodine solution,
involves only impaction. and treated with systemic antibiotics. Recurrent
The specific cause of anal sac disease is poorly anal sacculitis or abscess is treated by surgical exci-
understood. It is believed to be associated with sion of the sacs. Chemical cautery and cryosurgery
conditions that promote inadequate emptying of also have been used as alternatives to surgical excision
the sacs, which should normally occur during for ablation of the sacs.
defecation when feces of normal consistency are
forced through a normally functioning anal
sphincter. It is therefore the abnormal retention of Perianal Fistulae
anal sac secretions that leads to the impaction- Perianal fistulae is a chronic progressive disease
inflammation-infection cycle. characterized by deep ulcerating fistulous tracts
The most frequent clinical signs of anal sac dis- and suppuration in the perianal tissues. The dis-
ease are related to anal discomfort and include ease occurs primarily in the German shepherd,
scooting the hind end on the floor, tenesmus, and although it has been reported sporadically in Irish
licking and biting the anal area, perineum, or base setters, Labrador retrievers, and various other
of the tail. Chewing and licking may result in areas breeds. The proposed pathogenesis involves infec-
of self-inflicted (pyotraumatic) dermatitis. In addi- tion and abscessation of the various glandular ele-
tion, tail chasing, malodorous perianal drainage, ments in and around the anus as promoted by the
and change in temperament may be noted. moist contaminated environment of the area and a
The diagnosis of anal sac disease is based on broad-based, low-slung tail conformation.
historical signs and examination of the anal Dogs with perianal fistulae usually have signs
sacs.The anal sacs are best examined by palpation of anal discomfort (licking the anal area, scoot-
with a gloved index finger inserted in the rectum ing, dyschezia, tenesmus) along with any of
and a thumb compressed against the skin ventro- the following: hematochezia, constipation, fecal
lateral to the anus. Impaction is usually bilateral incontinence, or foul-smelling purulent perianal
and indicated by sacs that are distended, mildly discharge. Examination of the perianal area estab-
painful on palpation, and not readily expressed. lishes the diagnosis. The fistulas usually first appear
The impacted contents are usually thick and pasty as small draining puncture holes in the perianal
and dark brown or grayish brown. Anal sacculitis skin with inflammation and hyperpigmentation of
is associated with moderate to severe pain on the surrounding skin. These small tracts then
palpation, and the sacs contain a thinner-than- enlarge and coalesce to form large, interconnect-
normal, yellowish or blood-tinged purulent fluid. ing fistulas and areas of ulceration and granulation
284 CHAPTER 8 DISEASES OF THE LARGE INTESTINE
tissue. The fistulous tracts may extend deep into Perianal Dermatitis
the perirectal tissues, and the anal sacs may also be Anal irritation, a common consequence of anal sac
infected or ruptured. Histopathologically, there is disease and other anorectal disorders, often causes
hidradenitis, chronic necrotizing pyogranuloma- licking and biting at the anal area, which may lead
tous inflammation of skin and hair follicles, to perianal dermatitis. Any pruritic skin condition,
cellulitis, necrosis, and fibrosis. most notably fleas, also may cause local dermatitis in
Surgery is the traditional method of treatment this area. Finally, the mucocutaneous junction
for perianal fistulae. Numerous surgical tech- where the perianal skin and anal mucosa join may
niques have been advocated, including varying be severely inflamed and ulcerated similarly to other
degrees of excision and debridement of diseased mucocutaneous junctions of the body in any of the
tissue, chemical cautery and electrocautery, and systemic mucocutaneous dermatologic disorders
cryosurgery. It is advisable to tailor the aggressive- such as pemphigus vulgaris, bullous pemphigoid,
ness of the technique to the extensiveness of the systemic lupus, candidiasis, and cutaneous drug
lesions and to preserve as much normal tissue and eruption. Eosinophilic granuloma complex of cats
anal function as possible. Postoperative complica- also may involve the perianal region. Perianal der-
tions such as fecal incontinence, anal stenosis, and matitis itself can often be treated topically, but the
recurrence of the lesions can lead to an unaccept- key is to recognize that it is usually secondary to
able outcome. Recent studies have shown that some other anorectal or dermatologic disorder that
medical therapy using cyclosporine (Sandimmune, must be identified and treated.
0.8 mg to 1.4 mg/lb orally every 12 hours) pro-
duces a high rate of healing within 16 weeks,
although the recurrence rate is 40%, necessitating Anal and Perianal Tumors
additional treatment or surgery. In general, early The most common tumor of the anal region is the
diagnosis and medical or surgical intervention perianal (circumanal) gland adenoma of dogs.
allows a less radical excision than is required These androgen-dependent tumors occur most
in advanced disease, which in turn means less often in older intact male dogs, and they usually
risk of postoperative complications and a better appear as small, firm, well-circumscribed nodules
prognosis. in the skin surrounding the anus. Perianal gland
adenomas may be incidental findings unassociated
with clinical signs or they may cause anal irritation
Pseudocoprostasis with scooting and licking at the anal area. In addi-
Pseudocoprostasis is a condition of obstruction of tion, they sometimes ulcerate and periodically
the anal opening when the surrounding hair bleed. The treatment of choice is excisional or
becomes densely matted with feces. It occurs most cryosurgical removal and adjunctive castration
often in long-haired breeds of dogs and cats, espe- because of their hormone dependency. Castration
cially during bouts of diarrhea. The anal obstruc- alone can produce regression of these tumors;
tion leads to anal irritation, inability to pass feces, however, excisional biopsy at the time of castration
and constipation. The patient is usually restless and is the only way to rule out malignancy. Estrogens
attempts to bite or lick at the anal region. The also are inhibitory for perianal gland adenomas;
owner may complain of an unexplained foul odor however, they cannot be recommended for pro-
from the patient. In addition, the matted hair often longed use because of their myelotoxic effects.
results in an underlying dermatitis and in warm Other benign tumors of the anal area are rare but
weather attracts flies that may produce a maggot include lipoma and leiomyoma.
infestation (myiasis) of the anal area. Examination The two most important anal malignancies are
of the anal region is sufficient for diagnosis. For the perianal (circumanal) gland adenocarcinoma
treatment the hair mats are clipped away and the and the apocrine gland (anal sac, anal gland) ade-
underlying irritated skin is cleansed and treated nocarcinoma. Perianal gland adenocarcinomas
topically. Once the obstructing hair mats are occur most often in older male dogs and may
removed, defecation should occur normally; how- resemble an ulcerated perianal gland adenoma,
ever, if the patient has severe colonic impaction of except they are locally invasive and may cause
feces, measures to evacuate the colon, as discussed diffuse thickening of surrounding tissues. They
in the Constipation and Dyschezia section may be eventually metastasize to regional lymph nodes
required. (sublumbar) and beyond. Their appearance can
CHAPTER 8 DISEASES OF THE LARGE INTESTINE 285
also be confused with a perianal fistula lesion or a Hasler AH, Washabau RJ: Cisapride stimulates contrac-
ruptured anal sac. Apocrine gland adenocarcino- tion of idiopathic megacolonic smooth muscle in cats,
mas arise in the anal sac and most often affect J Vet Intern Med 11:313, 1997.
older spayed female dogs. They are unique in that Jergens AE: Inflammatory bowel disease: current per-
spectives, Vet Clin North Am 22(2):501, 1999.
they can be an ectopic source of parathyroid hor-
Jergens AE et al.: Idiopathic inflammatory bowel disease
mone–like protein; thus even very small apocrine
in dogs and cats: 84 cases (1987-1990), J Am Vet Med
adenocarcinoma nodules often produce a hyper- Assoc 201:1603, 1992.
calcemia of malignancy syndrome with polyuria Johnson SE: Canine eosinophilic gastroenteritis, Semin
and polydipsia. Other malignant tumors of the Vet Med Surg 7:145, 1992.
anal region include squamous cell carcinoma, Leib MS: Chronic colitis in dogs. In Bonagura JD, ed:
melanoma, and mast cell neoplasia. Kirk’s current veterinary therapy XIII, Philadelphia, 2000,
For potentially malignant lesions of the perianal WB Saunders.
area, excisional biopsy is the diagnostic procedure of Leib MS et al.: Plasmacytic lymphocytic colitis in the
choice. Thoracic and abdominal radiography and dog, Semin Vet Med Surg 4:241, 1989.
abdominal ultrasonography of the sublumbar region Marks SL, Fascetti AJ: Nutritional management of
diarrheal diseases. In: Bonagura JD, ed: Kirk’s current vet-
are indicated to evaluate for metastasis. Early exci-
erinary therapy XIII, Philadelphia, 2000,WB Saunders.
sion of malignant tumors of the anal region can be
Marks SL et al.: Evaluation of methods to diagnose
effective, but once extensive local invasion or Clostridium perfringens–associated diarrhea in dogs, J Am
regional lymph node metastasis has occurred, the Vet Med Assoc 214:357, 1999.
prognosis for a cure is poor. Repeated partial exci- Mathews KA, Sukhiani HR: Randomized controlled
sions, radiation therapy, cryosurgery, and chemother- trial of cyclosporine for treatment of perianal fistulas
apy have been used for palliative therapy of in dogs, J Am Vet Med Assoc 211:1249, 1997.
inoperative malignancies of the anal region. Nelson RW, Dimperio ME, Long GG: Lymphocytic-
plasmacytic colitis in the cat, J Am Vet Med Assoc
184:1133, 1984.
REFERENCES Nelson RW, Stookey LJ, Kazacos E: Nutritional man-
agement of idiopathic chronic colitis in the dog, J Vet
Dennis JS, Kruger JM, Mullaney TP: Lymphocytic/plas- Intern Med 2:133, 1988.
macytic colitis in cats: 14 cases (1985-1990), J Am Vet Roth L et al.: A grading system for lymphocytic plas-
Med Assoc 202:313, 1993. macytic colitis in dogs, J Vet Diagn Invest 2:257, 1990.
Dibartola SP et al.: Regional enteritis in two dogs, J Am Sherding RG: Diseases of the intestines. In Sherding
Vet Med Assoc 181:904, 1982. RG, ed: The cat: diseases and clinical management New
Gookin JL et al.: Diarrhea associated with trichomoni- York, 1994, Churchill Livingstone.
asis in cats, J Am Vet Med Assoc 215:1450, 1999. Simpson JW, Maskell IE, Markwell PJ: Use of a restricted
Guilford WG: Idiopathic inflammatory bowel diseases. antigen diet in the management of idiopathic canine
In Guilford WG et al., eds: Strombeck’s small animal colitis, J Small Anim Pract 35:233, 1994.
gastroenterology ed. 3, Philadelphia, 1996,WB Saunders. Washabau RJ, Holt D: Feline constipation and idiopathic
Guilford WG et al.: Food sensitivity in cats with chronic megacolon. In Bonagura JD, ed: Kirk’s current veterinary
idiopathic gastrointestinal problems, J Vet Intern Med therapy XIII, Philadelphia, 2000,WB Saunders.
15:7, 2001. Washabau RJ, Sammarco J: Effect of cisapride on feline
Hall EJ: Dietary sensitivity. In Bonagura JD, ed: Kirk’s colonic smooth muscle function, Am J Vet Res 57:541,
current veterinary therapy XIII, Philadelphia, 2000, WB 1996.
Saunders. Washabau RJ, Stalis IH: Alterations in colonic smooth
Hall EJ et al.: Histiocytic ulcerative colitis in boxer dogs muscle function in cats affected with idiopathic mega-
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C H A P T E R
9
DISEASES OF THE
LIVER AND
HEPATOBILIARY
SYSTEM
Keith P. Richter
286
CHAPTER 9 DISEASES OF THE LIVER AND HEPATOBILIARY SYSTEM 287
including the PIVKA test. Patients with coagu- hepatic clearance of gastrin and increased gastrin
lopathies are no more likely to bleed than patients release stimulated by elevated bile acid concentra-
without coagulopathies. In most cases of sig- tions), which causes an increase in gastric acid pro-
nificant bleeding following hepatic biopsy, there duction. In addition, DIC can lead to abnormal GI
are technical problems. In my experience, the mucosal microcirculation due to microthrombi
rapidity of bleeding and/or necropsy examina- formation, thus decreasing the ability of the
tion suggest that a large vessel has been damaged mucosa to withstand injury. One of the conse-
rather than hemorrhage being due to persistent quences of GI hemorrhage is exacerbation of
oozing from needle biopsy sites. The exception to hepatic encephalopathy because blood is a sub-
this is that patients with disseminated intravascular strate for ammonia production in the large intes-
coagulation (DIC) often have significant hem- tine. In addition, GI hemorrhage can result in
orrhage regardless of biopsy technique used. partial depletion of clotting factors, and, when
Controlled studies in veterinary patients will be reduced further by hepatic biopsy, massive or
necessary to make final conclusions regarding prolonged bleeding can result.
postbiopsy hemorrhage in the patient with a coag- When evaluating patients with hepatic disease
ulopathy. for hemostatic abnormalities, the clinician must be
DIC is the most common coagulopathy occur- aware of the relative insensitivity of clotting times.
ring with hepatic disease in my experience and These times are prolonged only when coagulation factors
the one most likely to result in hemorrhage fol- are reduced to 30% of normal. In addition, multiple
lowing hepatic biopsy. Thrombosis and hemor- defects may be present, some of which are not
rhage are both potential sequellae of DIC. DIC detected by routine coagulation tests, such as
can result from decreased hepatic synthesis of abnormal platelet function and excessive fibrinol-
antithrombin III, decreased clearance of activated ysis. Sudden demand for clotting factors, as would
clotting factors, and increased release of tissue occur following hepatic biopsy or laparotomy, may
thromboplastin associated with massive hepatic precipitate massive or prolonged hemorrhage in a
destruction. These mechanisms may be further patient with normal coagulation test results.
complicated by events leading to excess fibrinoly- Because the exact nature of the defect is often
sis. The latter situation can occur from excessive unknown or multifactorial, treatment with fresh
activity of the fibrinolytic enzyme plasmin (occur- whole blood collected in a plastic blood collection
ring because of increased plasminogen activator bag (to preserve platelet activity and prevent acti-
and decreased antiplasmin concentrations). The vation of factor XII) is usually indicated to treat
net result of excessive fibrinolysis is the formation these patients. If possible, efforts such as this should
of fibrin degradation products (FDPs), which have be taken before hepatic biopsy to correct a known
potent anticoagulant effects and are not cleared coagulopathy.
efficiently by a diseased liver. Laboratory test
results suggesting the presence of DIC include
prolongation of prothrombin, partial thrombo- Ammonia Metabolism
plastin, and thrombin times, thrombocytopenia, Ammonia has long been considered one of the
elevated FDPs, hypofibrinogenemia, and schisto- most important encephalopathic toxins in patients
cytosis. with hepatic disease. The most important source
Abnormal platelet function can also occur with of ammonia is the large intestine, where intralu-
hepatic disease. These defects may be evaluated by minal bacteria convert proteins and other
platelet aggregation studies, but these studies are nitrogen-containing compounds to ammonia.
not routinely performed in clinical patients Once the ammonia is absorbed into the portal
because of the lack of equipment availability. circulation, the liver normally extracts most of it,
Platelet function defects may explain bleeding ten- converting it to urea via the urea cycle. Hepatic
dencies in patients with normal coagulation tests. failure results in increased blood ammonia and
Platelet function can be estimated by evaluating decreased blood urea nitrogen (BUN) concentra-
toenail or lip bleeding time. tions.
Spontaneous hemorrhage is unusual with Gram-negative enteric bacteria are quantita-
hepatic disease with the exception of gastrointesti- tively the most important organisms for convert-
nal (GI) hemorrhage. The latter can result from ing nitrogenous substrates to ammonia, although
increased gastrin concentration (due to decreased certain anaerobes are also capable of synthesizing
CHAPTER 9 DISEASES OF THE LIVER AND HEPATOBILIARY SYSTEM 291
ammonia. Dietary proteins are the most important and defecation and appear no longer housebroken.
substrate for ammonia production, but other sub- Signs can progress to include seizures, severe
strates such as urea (which freely diffuses from the dementia, and coma. The severity of these signs
systemic circulation into the colon), sloughed often wax and wane, sometimes in response to
intestinal epithelial cells, and GI hemorrhage are feeding, but do not always correlate with the
also quantitatively important. Therefore reduction severity of the hepatic lesion.
of these substrates and of large intestinal bacterial
numbers will have a beneficial effect on ammonia Etiology of Hepatic Encephalopathy
absorption. Treatment measures used to decrease Several factors have been implicated in contribut-
ammonia absorption are discussed in the section ing to hepatic encephalopathy. Most of these fac-
on management of hepatic disease. tors relate to an accumulation of neurotoxic
Portal blood in the dog normally contains substances that have not been metabolized prop-
approximately 350 µg/dl of ammonia (and about erly by the liver, including ammonia, benzodi-
double this in the cat because of the higher azepine-like substances, amino acids, mercaptans,
dietary protein content of this species). The liver and fatty acids. Other causes include changes in
is normally able to extract approximately 85% of the blood-brain barrier, abnormal neurotransmit-
this, resulting in a systemic venous ammonia con- ter balance, abnormal cerebral metabolism, and
centration of approximately 50 µg/dl (± 30 metabolic abnormalities.
µg/dl). Because the liver has a large capacity for There is experimental and clinical evidence
ammonia removal, there must be considerable that hepatic encephalopathy is multifactorial. The
hepatic dysfunction or abnormal portal circula- concentrations of ammonia, mercaptans, and free
tion to raise systemic plasma concentrations. The fatty acids necessary to produce coma individually
normal liver can tolerate up to twice the normal are much higher than when more than one or all
ammonia load. This degree of tolerance can be a are elevated. Both mercaptans and free fatty acids
sensitive indicator of hepatic function and is will increase ammonia concentration. Likewise
used clinically when performing the ammonia hyperammonemia will contribute to amino acid
tolerance test. imbalances. In addition to the synergistic effects of
encephalopathic toxins, metabolic derangements aug-
ment these effects. These changes include azotemia,
Hepatic Encephalopathy hypoxia, electrolyte imbalances, hypoglycemia, tranquil-
Hepatic encephalopathy is defined as a clinical ization, alkalosis, and hypovolemia. Patients with these
syndrome characterized by abnormal mental sta- derangements are more likely to develop encephalopathy,
tus occurring in patients with severe hepatic and correction of these derangements will significantly
insufficiency. This can result from primary hepa- improve the encephalopathic state. For example, the
tocellular disease or from portosystemic shunting hypokalemia that frequently accompanies hepatic
of blood away from the liver. Clinical signs in failure is one of the most common metabolic
patients with this condition include a wide vari- derangements that contribute to depression and
ety of behavioral changes, ranging from only anorexia.With potassium supplementation there is
mild depression and anorexia to coma. Many often dramatic clinical improvement in appetite
signs are nonspecific and can be seen with a and attitude. Factors that can precipitate meta-
wide variety of unrelated disorders.These include bolic changes that lead to encephalopathy include
depression, anorexia, vomiting, diarrhea, polydip- increased dietary protein intake, GI hemor-
sia, and polyuria. Neurologic signs are also com- rhage, diuretic administration, sedative adminis-
mon. These signs are variable and often cannot be tration, uremia, infection, constipation, large
localized to a specific anatomic lesion. When this intestinal bacterial overgrowth, and methionine
occurs, or when the nature of the neurologic administration.
abnormalities vary with time, hepatic encephalopa- The importance of synergistic effects and mul-
thy should be considered as a cause. The most tiple interactions of encephalopathic factors help
common neurologic manifestation is decreased explain the different clinical presentations and
mentation and responsiveness. Often patients will severity of encephalopathy with varying blood
appear confused, have compulsive pacing and concentrations of encephalopathic toxins. It also
wandering, and appear transiently blind. Some explains the occurrence of encephalopathy in the
patients will have abnormal patterns of urination absence of a striking abnormality in any single
292 CHAPTER 9 DISEASES OF THE LIVER AND HEPATOBILIARY SYSTEM
factor, including ammonia concentration. The renal salt and water retention before the develop-
therapeutic manipulations of all these factors repre- ment of ascites, thus expanding the circulating
sent the cornerstone of symptomatic management plasma volume and contributing to the develop-
of hepatic encephalopathy. These will be discussed ment of portal hypertension. Eventually portal
in the section on management of hepatic disease. hypertension leads to the development of ascites,
with hypoalbuminemia continuing to perpetuate
it. Factors that may initiate renal salt and water
Ascites and Portal retention include increased sensitivity to aldos-
Hypertension terone and failure to release or respond to natri-
Ascites (the accumulation of free fluid in the peri- uretic hormone in response to an expanded
toneal cavity) is a common sign of hepatic disease circulating plasma volume. The latter situation
and occurs as a result of chronic portal hyperten- results in the inability to excrete a salt and water
sion, hypoalbuminemia, and increased renal salt load in response to volume expansion. In addition,
and water retention. The development of ascites the normal negative feedback system that governs
occurs when there is an alteration of Starling’s the renin-angiotensin-aldosterone system does not
forces, including increased venous or lymphatic shut off and reduce aldosterone secretion in the
hydrostatic pressure, decreased capillary oncotic presence of portal hypertension and ascites. This is
pressure, increased vascular permeability, and because the high concentrations of aldosterone do
increased intraperitoneal oncotic pressure. not return effective circulating plasma volume to
Portal hypertension is one of the most impor- normal in the presence of ascites, despite the
tant factors leading to the development of ascites retention of sodium. Because of these mecha-
in patients with hepatic disease. Portal hyperten- nisms, therapeutic interventions for managing
sion can be caused by increased total portal blood ascites include salt restriction and inhibition of the
flow; increased resistance to portal, intrahepatic, or renin-angiotensin-aldosterone axis with drugs
posthepatic blood flow; or a combination of these such as spironolactone, enalapril, and benazepril.
changes. The most common cause of portal This will be discussed in the section on manage-
hypertension is cirrhosis, resulting in increased ment of hepatic diseases.
resistance in sinusoidal vessels caused by swelling The presence of ascites acts to increase albu-
of hepatocytes or fibrosis around sinusoids causing min’s volume of distribution, which lowers
postsinusoidal outflow block. The combination of blood albumin concentration. This lowers plasma
increased portal pressure and blood flow causes an oncotic pressure and exacerbates the formation of
increase in hepatic lymph formation.When this is ascitic fluid. The presence of portal hypertension
excessive, ascites results. Another common effect is necessary for the development of ascites and
of chronic portal hypertension is the development leakage of albumin into the abdominal cavity. In
of acquired portosystemic shunts. Unlike congeni- this setting, ascites is present when plasma albumin
tal portosystemic shunts, acquired shunts are usu- concentrations are higher than when ascites can be
ally multiple, extremely tortuous, and variable in attributed to hypoalbuminemia alone. With nor-
their location. mal portal pressure, plasma albumin concentration
It was formerly thought that portal hyperten- must be below approximately 1.5 g/dl to result in
sion and hypoalbuminemia initiate ascites forma- ascites, as occurs with GI or renal protein loss.
tion. This results in decreased effective circulating When this occurs, subcutaneous edema often
plasma volume. The compensatory response to predominates over ascites.
this is renal conservation of fluid and electrolytes,
mediated by changes in renal blood flow, glomeru-
lar filtration rate, and activation of the renin- Other Metabolic Abnormalities
angiotensin-aldosterone axis. This retention of salt Carbohydrate Metabolism
and water perpetuates the problem by leading to The liver plays a central role in carbohydrate
increased splanchnic lymph and portal blood flow. metabolism. It is the primary organ for glucose
However, more recent evidence contradicts this storage (converting glucose by glycogenic
theory and suggests that the renal mechanisms enzymes) and also provides glucose during fasting
leading to retention of water and electrolytes are (through glycogenolysis). When there are inade-
the primary initiating events in the formation of quate stores of glycogen, as might occur with
ascites with hepatic disease. In this setting there is hepatic disease, the glucose need is supplied
CHAPTER 9 DISEASES OF THE LIVER AND HEPATOBILIARY SYSTEM 293
through catabolism of muscle proteins to amino drug metabolism and clearance. In addition, drugs
acids and conversion to glucose via gluconeogenic that are highly protein bound can have increased
pathways. This causes muscle wasting and increases biologic effects when there is hypoalbuminemia
the nitrogen load and aggravates hyperammone- associated with hepatic disease. In this setting there
mia. Because of the importance of gluconeogene- is less albumin to bind to the drug and therefore
sis in the liver for maintaining blood glucose more unbound (active) drug to exert its effects.
concentrations, complete hepatectomy rapidly Therefore drugs that undergo hepatic clearance
results in death from hypoglycemia. or that are highly protein bound should be admin-
Hepatic failure can result in either preprandial istered with caution in patients with hepatic
hypoglycemia or postprandial hyperglycemia. Loss failure.
of approximately 70% of the hepatic mass may cause Many hormones are metabolized by the
fasting hypoglycemia because of inadequate glyco- liver and can be abnormally elevated with hepatic
gen storage and gluconeogenesis. Additional causes disease. The more important hormones to have
of hypoglycemia include congenital deficiency of prolonged clearance are the steroid hormones,
glycogen-metabolizing enzymes (as occurs with including cortisol, estrogens, androgens, and pro-
glycogen storage diseases), tumor hypoglycemia, and gesterones. As with many drugs, the degree of
portosystemic shunts (associated with decreased protein binding and therefore the concentra-
hepatic mass and lack of tropic portal blood to the tion of unbound, active hormone can be altered
liver). In patients with hypoglycemia associated with with hypoalbuminemic states. Other hormones
hepatic disease, it is usually easy to get the blood that undergo altered metabolism in patients
glucose concentration into the normal range with with hepatic disease include insulin, glucagon,
intravenous glucose supplementation, in contrast to thyroxine, pituitary hormones, gastrin, and
patients with insulin-producing tumors in which it aldosterone. Many of these alterations were dis-
can be very difficult to get the blood glucose con- cussed in reference to their specific physiologic
centration into the normal range despite aggressive effects.
intravenous glucose administration.
Causes of postprandial hyperglycemia with
hepatic disease include deficient hepatic enzymes Reticuloendothelial System
to handle the carbohydrate load, leading to inade- Function
quate glycogenesis, and increased plasma concen- The reticuloendothelial system (RES) removes
tration of glucocorticoids (because of decreased toxic or foreign substances, cellular debris, bacte-
hepatic clearance). ria, drugs, and endotoxins from the blood.
The hepatic RES is more important than that in
Fibrinogen the rest of the body for appropriate processing of
Fibrinogen is a protein that is synthesized by the these materials. Primary hepatocellular disease
liver. Synthesis of fibrinogen is diminished only or portosystemic shunting (either congenital or
in the late stages of severe hepatic failure. Other acquired) can cause failure of the hepatic RES.
factors are usually more important in determin- With hepatic disease other tissues with RES activ-
ing fibrinogen concentration than the rate of ity can only partially compensate for the dimin-
hepatic synthesis. Factors that will more com- ished hepatic RES function. Deficiencies of
monly lead to decreased fibrinogen concentra- specific roles of the hepatic RES function can lead
tion include increased fibrinogen consumption, to characteristic changes that other RES tissues
as occurs with DIC or primary fibrinolysis. cannot compensate for. The liver is directly
Factors that result in increased fibrinogen con- responsible for clearing absorbed GI products,
centration include inflammatory diseases (involv- because they pass through the liver before gaining
ing or not involving the liver) and major surgery. access to the systemic circulation. These products
In this setting there is increased synthesis and include intestinal bacteria, endotoxins, and GI
release by the hepatocyte. mucosal antigens. The effects of decreased clear-
ance of GI products can be the systemic access of
Drug and Hormone Metabolism bacteria or their toxins, resulting in potential sepsis
The microsomal enzyme system of the liver is and/or endotoxemia. In addition, there can be
important for drug and hormone metabolism. positive bacterial growth from hepatic biopsy
Hepatic failure can result in abnormally delayed specimens even when the underlying cause of
294 CHAPTER 9 DISEASES OF THE LIVER AND HEPATOBILIARY SYSTEM
TABLE 9-1 Serum Hepatic Enzyme Activities and Chemistry Values in Various Disease States
SALT SAST ALP GGT Total Bilirubin BUN Glucose Albumin Bile Acids
Chronic active hepatitis ++–+++ ++–+++ +–+++ +–+++ N–+++ Dec–N Dec–N Dec–N +–+++
Steroid hepatopathy N–++ N–++ ++–+++ +–+++ N N N–+ N N–+
Feline cholangiohepatitis +–+++ +–++ N–++ N–++ N–+++ N N N N–+++
Feline hepatic lipidosis +–+++ +–+++ +–+++ +–++ +–+++ N N N N–+++
Primary hepatic neoplasia +–+++ +–+++ +–+++ +–+++ N–+++ N Dec–N N N–+++
Metastatic neoplasia N–++ N–++ N–++ N–++ N–++ N Dec–N N +–+++
Portosystemic shunt N–+ N–+ N–+ N–+ N Dec–N Dec–N Dec–N +–+++
Cirrhosis N–++ N–++ N–++ N–++ N–+++ Dec–N Dec–N Dec–N ++–+++
Hepatic necrosis ++–+++ ++–+++ +–+++ +–+++ N–++ N N N N–+++
Bile duct obstruction +–+++ +–++ +++ +++ ++–+++ N N N +–+++
DISEASES OF THE LIVER AND HEPATOBILIARY SYSTEM
SALT, Serum alanine aminotransferase; SAST, serum aspartate aminotransferase; ALP, serum alkaline phosphatase; GGT, gamma glutamyl transpeptidase; BUN, blood urea nitrogen; + mild increase;
++, moderate increase; +++, severe increase; Dec, decrease; N, normal.
CHAPTER 9 DISEASES OF THE LIVER AND HEPATOBILIARY SYSTEM 297
bile acids are synthesized in the liver as a result of artifactually increases the serum bile acid measure-
cholesterol metabolism and secreted into bile. ment determined by the enzymatic method but
Feeding is a normal stimulus for bile acid secre- artifactually decreases the measurement when
tion. Bile acids enter the intestine and undergo an determined by the RIA method. Moderate to
efficient enterohepatic circulation following active marked hemolysis artifactually decreases the
absorption from the ileum. Once absorbed, they serum bile acid value determined by the enzy-
are removed from the portal circulation by the matic method but probably does not affect the
liver and reexcreted into bile. During a typical measurement determined by the RIA method.
meal, the total bile acid pool is recycled two to Bilirubin has little effect on the measurement
three times through this enterohepatic pathway. of bile acid concentration unless the serum
Only small amounts of bile acids are lost in the bilirubin concentration is greater than 5 mg/dl,
feces. Normally the liver synthesizes enough bile in which case there may be a small (less than
acids to compensate for fecal losses, which are 20%) decrease in measurement at low bile acid
minimal with respect to the total bile acid pool. concentrations. If there is hyperbilirubinemia due
Although bile acid formation depends on hepatic to hepatic disease, measurement of serum bile
synthesis, the liver reserve capacity for this is never acids is not indicated.
exceeded because of the small amounts needed for Bile acid measurements have certain advan-
physiologic purposes. Thus measurement of bile tages over other tests of hepatic function. They
acid concentration is a reliable test even in do not require the administration of exogenous
end-stage liver disease. compounds (such as sulfobromophthalein [BSP]
Abnormal hepatic function, biliary excretion, and indocyanine green [ICG] dyes and oral
or portal circulation can interrupt the normal ammonium chloride) or meticulous sample
enterohepatic circulation and thus lead to an handling (as is required for plasma ammonia
increase in serum bile acid concentration. This determination).
occurs with many hepatobiliary diseases.When the The indications for measuring serum bile acid
liver parenchyma is diseased, the abnormal uptake, concentrations include the identification of occult
conjugation, and secretion of bile acids result in hepatic disease when enzyme determinations are
decreased extraction from the portal circulation normal (as can occur with portosystemic shunts,
and lead to increased systemic concentrations. cirrhosis, and metastatic hepatic neoplasia), evalua-
With intrahepatic or posthepatic cholestasis, bile tion for the possibility of a portosystemic shunt in
acids diffuse from bile into the systemic circula- patients with suggestive symptomatology, monitor-
tion in a manner similar to that of bilirubin. ing of hepatobiliary function to assess progression
With portosystemic shunting (either congenital or of hepatic disease, and identification of abnor-
acquired), the enterohepatic circulation is directly mal hepatic function in patients in which enzyme
interrupted and bile acids fail to be extracted by activity elevations may be due to extrahepatic
the bypassed liver. In this setting, hepatic synthesis causes.
of bile acids continues in order to maintain a nor- To maximize the diagnostic information from
mal bile acid pool. This can result in tremendous total serum bile acid measurement, both a 12-hour
increases in systemic concentrations, especially fasting and a 2-hour postprandial sample should
following feeding. be obtained. In general it is recommended that
Both solid-phase radioimmunoassay (RIA) and a normal-size meal be fed. However, minimum
direct enzymatic spectrophotometric methods of amounts of food that should be consumed have
bile acid determinations have been validated for been established. Patients weighing 10 lb or less
the dog and cat. These methods have made serum should be fed a minimum of 2 tsp, and those over
bile acid determinations a routine part of evaluat- 10 lb, 2 tbsp. Foods that are high in protein and fat
ing hepatic function. In my laboratory, normal should be fed because they most consistently chal-
fasting concentrations are approximately 2.5 lenge the bile acid enterohepatic circulation at the
µmol/L in the dog, and 1.5 µmol/L in the cat. 2-hour postprandial level.
Two-hour postprandial concentrations rise to If inappetence is a problem, it may be necessary
approximately 8.5 µmol/L in the dog and cat. to force-feed the patient. For cats, special steps
Serum is stable for measurement for several days at to avoid anorexigenic stimuli may be necessary
room temperature. Several artifacts can affect bile (e.g., offer food in a quiet environment away from
acid measurement. Moderate to marked lipemia dogs, have the owner hand feed in a private area).
298 CHAPTER 9 DISEASES OF THE LIVER AND HEPATOBILIARY SYSTEM
Warming the food may help coax an inappetent when postprandial bile acid concentrations are
cat to eat. measured in conjunction with the preprandial
In patients with encephalopathic tendencies, sample.
where there is concern about feeding high-protein In summary, serum bile acid concentrations are
foods, a low-protein meal may be fed. If vomiting a sensitive and specific indicator of hepatobiliary
is a problem and its frequency precludes feeding, function and hepatoportal circulation and are a
initial testing is limited to a fasting sample. If the clinically useful tool in the diagnosis of these
result is above normal, then a significant hepatic disorders. Serum bile acid concentrations are espe-
disorder remains a consideration. However, if the cially valuable in anicteric hepatic disease. They
fasting sample is normal, liver disease cannot be are more conveniently measured than blood
ruled out. ammonia concentration because specimen han-
Several studies have shown serum bile acid dling is routine. They are more sensitive than BSP
measurements to be a sensitive and specific indica- retention and do not require the injection of a for-
tor of hepatic function in the dog and cat. In eign compound (which is becoming increasingly
dogs, fasting serum bile acid concentrations are more difficult to obtain). In my laboratory, when
significantly increased with congenital portosys- postprandial concentrations exceed 30 to 40
temic shunts, glucocorticoid-induced hepatopathy, µmol/L in the dog and 20 to 30 µmol/L in the
hepatic neoplasia, hepatitis, cholestasis, hepatic cat, further diagnostic efforts, such as hepatic
necrosis, and cirrhosis. Of these diseases, dogs with biopsy, are warranted.
glucocorticoid-induced hepatopathy have the Plasma Ammonia and the Ammonia
lowest increase in concentration of serum bile Tolerance Test
acids. Therefore marked increase in elevations Because ammonia is metabolized primarily in the
(i.e., greater than 75 to 100 µmol/L) are unlikely liver, blood ammonia concentration represents a
to be caused by glucocorticoid-induced hepatopa- sensitive test of hepatic function. Ammonia is pro-
thy. Although serum bile acid concentrations are a duced from bacterial action in the colon on sub-
sensitive indicator of hepatic function, they do not strates such as dietary proteins, sloughed intestinal
distinguish the cause of the disease process. The epithelial cells, and urea, which freely diffuses into
magnitude of elevation in serum bile acid concen- the colon from the plasma. Once absorbed into
trations is weakly correlated with histologic sever- the portal circulation, ammonia is extracted by the
ity. Furthermore, dogs with intestinal disease and liver and converted to urea through the urea cycle
normal hepatic function have normal serum bile enzyme pathway. Normally this extraction process
acid concentrations. This is important in cases of is very efficient, with only a small amount of
“reactive hepatopathy” associated with intestinal ammonia escaping into the systemic circulation.
or pancreatic disease. The determination of 2- The concentration of ammonia in the portal vein
hour postprandial concentrations further increases is approximately 350 µg/dl in the dog (and
the sensitivity of this test in most diseases and approximately 700 µg/dl in the cat), whereas the
should be done routinely in conjunction with the normal concentration in the systemic circulation
preprandial sample. is approximately 20 to 120 µg/dl. When there is
In cats the measurement of fasting serum bile abnormal hepatocyte function or abnormal por-
acids concentrations has a specificity approaching tal circulation (as would occur with portosys-
100%. Bile acid concentration is also the most sen- temic shunting), the liver cannot efficiently
sitive test for most feline hepatic diseases, although extract portal ammonia and systemic plasma levels
it only approaches 60% to 70%. The value of increase.
serum bile acids for detecting hepatic disease is Increasing the demand on the liver by increas-
also increased when combined with standard bio- ing portal vein ammonia concentration can
chemical tests, and visa versa. As in dogs, the mag- increase the sensitivity of plasma ammonia con-
nitude of elevation does not help in the differential centration in detecting abnormal hepatic function.
diagnosis of hepatobiliary disease. This can be done by measuring ammonia concen-
In detecting portosystemic shunts, serum bile tration in the postprandial state or by administer-
acid concentrations have the best diagnostic accu- ing an oral or rectal ammonia load. The latter
racy compared with conventional biochemical provocative test is known as the oral ammonia tol-
tests and BSP excretion and sensitivity equal to the erance test. The test is performed by taking a rest-
ammonia tolerance test. The accuracy is improved ing plasma ammonia sample, then administering
CHAPTER 9 DISEASES OF THE LIVER AND HEPATOBILIARY SYSTEM 299
oral ammonium chloride (NH4Cl) at a dosage of tosystemic shunts, in assessing hepatic function in
45 mg/lb body weight, with a maximum dose of 3 anicteric hepatic disease (especially when hepatic
g. Ammonium chloride is available from most enzyme activities may be normal), and in assessing
chemical reagent suppliers or as the main ingredi- the role of ammonia (and therefore hepatic func-
ent of some urinary acidifiers. It is dissolved in 20 tion) in patients with encephalopathic signs. The
to 50 ml tap water and administered via orogastric test is as sensitive as measuring serum bile acid
tube, then flushed with 20 ml water. Alternatively, concentrations in assessing hepatic function and
it can be administered in empty gelatin capsules. more sensitive than measuring BSP excretion.
A plasma sample is then obtained 30 minutes later The ammonia tolerance test has been shown to be
for ammonia measurement. A rectal ammonia tol- virtually 100% sensitive in detecting portosystemic
erance test has been described. This is performed shunts, whereas approximately 10% of dogs with
by administering 1 ml/lb body weight of a 5% congenital portosystemic shunts can have normal
solution of NH4Cl following cleansing enemas. resting ammonia concentrations or normal BSP
A plasma sample is then obtained 20 to 40 minutes retention. Its main limitation is the need for
later. Theoretically, rectal administration has the meticulous sample handling and the need for the
advantage that vomiting of the orally administered determination to be performed soon after obtain-
solution is not a problem. However, in my experi- ing the sample. In addition, it requires the admin-
ence, vomiting following oral NH4Cl administra- istration of an exogenous compound (NH4Cl),
tion is rarely a clinical problem, especially when which in rare instances can worsen encephalopathy
the solution is diluted with water as described and induce hepatic coma. If the latter complica-
above, and does not invalidate the test if it occurs. tion is anticipated, a resting ammonia deter-
Often the cause of vomiting is hyperammonemia, mination can be performed first, and the need and
and therefore ammonia measurements are diag- safety of NH4Cl administration can then be
nostic of hepatic failure. In normal patients, there determined.
should be little or no increment in plasma ammo-
nia concentration following administration of Serum Hepatic Enzyme Activities
ammonium chloride (less than 32% increase). The routine use of measuring serum hepatic
Sample handling is critical for plasma ammonia enzyme activities as an indication of hepatic dis-
determinations. It is important that the venipunc- ease has been made possible by automated bio-
ture be rapid and atraumatic. Prolonged stasis of chemistry profiles. It must be pointed out that
blood can result in ammonia generation. When enzyme activities do not reflect hepatic function.
the sample is obtained, it must be placed in an They reflect either the integrity of the hepatocyte mem-
ammonia-free heparinized tube and immediately brane or the patency of the biliary system. Severe
placed in an ice bath, then centrifuged as soon as hepatic dysfunction can occur in the face of nor-
possible (within 30 minutes). Red blood cells elab- mal enzyme activities, whereas hepatic function
orate ammonia (they contain two to three times as may be near normal despite marked increases in
much ammonia as plasma), and, when the sample serum enzyme activities. Therefore the limitations
is not separated in a prompt manner, falsely ele- and usefulness of hepatic enzymes must be appre-
vated concentrations will result. Likewise, hemoly- ciated. Loss of intracellular enzymes (with the
sis will result in a falsely increased ammonia exception of certain proteases) does not lead to
concentration. Ideally the sample should be abnormal function or clinical signs but can be a
assayed for ammonia as soon as possible (within 2 useful laboratory test for diagnostic purposes. The
hours) to eliminate artifacts, because the ammonia enzymes that leak into plasma following increased
concentration can increase or decrease with stor- hepatocellular membrane permeability include
age and thus yield unpredictable and unreliable ALT, AST, SDH, LDH, and OCT. Enzyme activi-
results. Ammonia concentration may increase ties that increase with biliary obstruction include
because of deamination of proteins such as gluta- ALP, GGT, and 5⬘-nucleotidase.
mine, breakdown of adenyl pyrophosphate and/or Serum Alanine Aminotransferase
adenylic acid, or hydrolysis of other ammonio- Serum alanine aminotransferase (SALT; formerly
genic substances. Plasma ammonia may decrease serum glutamic-pyruvic transaminase [SGPT]) is
during storage because of vaporous loss. the most liver-specific enzyme in the dog and the
The main clinical usefulness of the ammonia cat. It is used to detect hepatocyte membrane
tolerance test is in detecting patients with por- damage and necrosis. This enzyme is found only
300 CHAPTER 9 DISEASES OF THE LIVER AND HEPATOBILIARY SYSTEM
lipid accumulation, neoplastic infiltration) result- Therefore even mild elevations of serum ALP activity in
ing in intrahepatic cholestasis (see Table 9-1). the cat are indicative of marked hepatobiliary disease.
Diseases that are periportal in location tend to The magnitude of increase in serum ALP activity
cause more marked increases in serum ALP activ- is most marked with feline hepatic lipidosis, almost
ity than centrilobular disorders, because they tend always exceeding the magnitude of increase in
to affect bile flow through canaliculi more. serum GGT activity in this syndrome. Other dis-
In addition to the isoenzyme induced by biliary eases in the cat that result in increased serum ALP
obstruction, there is also a steroid-induced isoen- activity include hepatic malignant lymphoma,
zyme of ALP. Although this isoenzyme is also pro- feline cholangiohepatitis complex, bile duct
duced in the liver, it is a separate entity from that obstruction, and hyperthyroidism.
induced by biliary obstruction. The dog is very Gamma Glutamyltranspeptidase
sensitive to the effects of glucocorticoids in this GGT measurement is now available on chemistry
regard as opposed to the cat. A single injection of profiles from many commercial laboratories. Its
a glucocorticoid can increase the serum activity of serum activity increases with biliary stasis and
the steroid-induced isoenzyme of ALP. This steroid hepatopathy. In most cases the activity of
increase in activity can last for several weeks with serum GGT parallels that of serum ALP and its
short-acting preparations and for several months measurement is of only occasional value in the dog
with long-acting preparations. The magnitude of and cat. There is GGT activity in liver, kidney,
increase depends on the dose administered, dura- pancreas, and intestine; however, the half-life of the
tion, route, and individual sensitivity. In addition, hepatic isoenzyme is the only one long enough to
dogs with spontaneous hyperadrenocorticism account for significant serum activity. Therefore
(Cushing’s syndrome) usually have marked elevated serum GGT activity is specific for hepa-
increases in serum ALP activity. Assays are now tobiliary disease or hepatic induction from drugs.
available to readily distinguish the isoenzyme As with serum ALP, elevations are most marked
induced by biliary obstruction from the steroid- with biliary obstruction, but activity can also
induced isoenzyme. These assays generally report increase with primary hepatocellular disease if it
the percentage of total ALP activity that is results in intrahepatic cholestasis. The serum activ-
accounted for by the steroid-induced isoenzyme. ity of GGT may increase earlier in biliary disease
However, this is not a reliable test to distinguish than ALP activity. In addition, there is also marked
patients with steroid hepatopathy from those with elevation in serum GGT activity with glucocorti-
other hepatopathies because the serum activity of coid administration or spontaneous hyperadreno-
the steroid-induced isoenzyme of ALP is variably corticism. Other drugs (such as anticonvulsants)
increased with many types of hepatic diseases and will also increase serum GGT activity.
nonhepatic illness. Alternatively, hepatic biopsy In the cat, serum GGT activity has a higher
specimen analysis in dogs readily distinguishes sensitivity but lower specificity than serum ALP
steroid-induced hepatopathy from primary hepa- activity for detection of hepatobiliary disease. Only
tobiliary disease of other causes. in feline hepatic lipidosis does the magnitude of increase
Certain drugs will also induce increases in in serum ALP activity generally exceed that of serum
serum ALP activity. The most common drugs to GGT activity. In the dog, serum GGT activity is
have this effect are glucocorticoids, barbiturates, generally more specific but less sensitive than serum
and anticonvulsant drugs, including phenobarbital, ALP activity for the detection of hepatobiliary dis-
primidone, and phenytoin. These drugs will result ease. Thus serum GGT activity has a higher positive
in increased serum ALP activity, with or without predictive value, whereas ALP activity has a higher
morphologic changes in the liver or alterations in negative predictive value for evaluating hepatobil-
hepatic function (as documented with hepatic iary disease. The diagnostic performance is best
function tests). when both enzyme activities are evaluated together.
Unlike the dog, the activity of ALP is much lower in In general, serum GGT activity is less influenced by
feline serum. This is because the half-life is much nonhepatic diseases or enzyme-inducing drugs.
shorter in the cat (6 hours versus 3 days) and less
feline ALP is produced secondary to biliary Other Biochemical Tests
obstruction than in the dog because the feline liver Many of the tests routinely obtained on automated
contains only one third the concentration of ALP serum biochemistry profiles give information
per gram of liver that the canine liver contains. regarding hepatic function, including determina-
302 CHAPTER 9 DISEASES OF THE LIVER AND HEPATOBILIARY SYSTEM
tions of bilirubin, albumin, BUN, and glucose (see ing the hematocrit (to rule out hemolysis) and
Table 9-1). ultrasonography, laparoscopy, cholecystography,
Serum and Urine Bilirubin and laparotomy (to distinguish intrahepatic from
Hepatobiliary excretion of bilirubin requires ade- posthepatic causes).
quate uptake, conjugation, and secretion by the In general, serum bilirubin concentration
hepatocyte, as well as a patent biliary system. increases most markedly with extrahepatic biliary
There must be considerable hepatocellular disease obstruction. Hepatocellular diseases that may result
or increase in the bilirubin load (hemolysis) to in cholestasis and therefore hyperbilirubinemia
result in hyperbilirubinemia, because the liver’s include chronic active hepatitis, certain cases
reserve capacity for bilirubin processing is up to of primary neoplasia, feline cholangiohepatitis,
30 times the normal bilirubin load. Conjugated feline hepatic lipidosis, and cirrhosis (see Table
bilirubin is water soluble and readily excreted by 9-1). Other hepatic disorders that generally have
the kidneys. The dog has a very low renal thresh- normal serum bilirubin concentration include
old for bilirubin excretion; thus the finding of +1 portosystemic shunts, hepatic necrosis, steroid
to +3 bilirubinuria in a concentrated sample is hepatopathy, and metastatic neoplasia (see Table
normal. Therefore the concentration of bilirubin 9-1). In general, disorders involving the periportal
in the urine increases before that of the serum. areas are most likely to result in increased bilirubin
Thus the serum bilirubin concentration is an concentration.
insensitive indicator of hepatocellular disease, and Serum Albumin
serum concentrations are not increased until there Albumin represents approximately 25% of the pro-
is marked decrease in hepatic function. Therefore teins synthesized by the liver. Because albumin has
slight elevations in serum bilirubin concentration a relatively high priority for synthesis, severe hepa-
are significant, suggesting hepatobiliary disease. tocellular disease must exist before serum albumin
The exception to this is with artifactual increases concentration falls. Hypoalbuminemia resulting
in serum bilirubin concentration, as would occur from hepatic disease suggests chronic dysfunction.
with lipemia or hemolysis. If there is not signifi- Because the serum half-life of albumin is 7 to
cant bilirubinuria associated with a serum biliru- 21 days (depending on the disease state and
bin concentration greater than normal, artifact the serum concentration), there must be pro-
should be considered. The cat has a high renal longed hepatic disease before serum concentration
threshold for bilirubin excretion, and any bilirubin decreases. In addition to lack of production occur-
in the urine is abnormal.When serum bilirubin is ring with hepatic disease, albumin concentra-
in the normal range (anicteric hepatic disease), tion can drop from protein-calorie malnutrition
other tests of hepatic function discussed earlier (sometimes associated with an extremely low pro-
are needed for detection, such as serum bile acid tein diet, often used in the therapeutic manage-
or blood ammonia measurements. However, when ment of hepatic disease) and from an increased
serum bilirubin concentration is elevated, there is no need volume of distribution due to ascites, resulting in a
to run additional function tests if hemolysis can be dilutional effect on serum albumin concentration.
excluded. In this setting, bilirubin represents an accurate Although serum albumin concentration is an
and specific indicator of hepatic function. insensitive and nonspecific test of hepatic func-
Increased serum total bilirubin concentration tion, hypoalbuminemia may be the only change on a
can result from prehepatic (hemolysis), intrahe- serum biochemistry profile in certain cases of hepatic fail-
patic (primary hepatocellular disease), or posthe- ure (such as cirrhosis and portosystemic shunts), and its
patic (biliary obstruction) causes. The relative presence may justify specific hepatic function tests (e.g.,
amounts of conjugated or unconjugated bilirubin serum bile acid assay), which may subsequently identify
are variable with all three general categories of hepatic failure. In one study the presence of hypoal-
hyperbilirubinemia because secondary events can buminemia in dogs with chronic hepatitis was a
change the relative concentrations of the two predictor of shorter survival time.
forms. Therefore their measurement does not aid Blood Urea Nitrogen
the clinician in localizing the nature of the lesion. A low BUN concentration may indicate chronic
The magnitude of increase in serum bilirubin hepatic disease. The liver manufactures urea by
concentration also is not helpful in localizing the extracting portal vein ammonia and converting it
nature of the lesion. Other methods of localizing to urea through the urea cycle enzyme pathway.
the cause of hyperbilirubinemia include measur- With hepatic failure this process fails, and BUN
CHAPTER 9 DISEASES OF THE LIVER AND HEPATOBILIARY SYSTEM 303
Technique
BOX 9-7 Causes of Radiographic
General anesthesia or heavy sedation is required
Signs of Increased for splenoportography. The spleen is localized
Hepatic Size by transabdominal palpation, or ultrasound or
Neoplasia (primary or metastatic) laparoscopy can be used to aid in needle place-
Congestion (right-sided heart failure) ment. Approximately 0.25 to 0.5 ml/lb body
Fatty infiltration weight of an iodinated radiographic contrast
Diffuse inflammation media is injected directly into the splenic pulp at
Hyperadrenocorticism the rate of 1 to 2 ml/sec. Radiographs are taken
Storage diseases immediately and approximately 10 seconds after
Abscess the end of the injection.
Hepatic or biliary cyst Cranial Mesenteric Arterial Portography
Liver lobe torsion
Cranial mesenteric arterial portography is an
Puppies and kittens (normal)
excellent method of evaluating the entire portal
Deep inspiration (normal)
system and evaluating hepatic blood flow. The
technique is less invasive than operative mesenteric
portography; however, it requires fluoroscopy,
addition, the residual portovenous flow into the serial films, and special injection equipment.
liver can be assessed for prognostic importance. If a
portosystemic shunt is identified, surgical correc-
tion may be performed during the same anesthetic Ultrasonographic Evaluation
procedure. of the Liver
Technique Ultrasonography is now widely used to evaluate
Intraoperative mesenteric portography is a tech- the liver because it is ideally suited for soft tissue
nique that can readily be performed in general imaging. It gives specific information regard-
practice, because no special equipment is needed. ing structural abnormalities in the liver and can
A mesenteric or jejunal vein is catheterized at readily distinguish fluid-filled structures from
laparotomy. A vessel that can eventually be sacri- solid soft tissue structures, including visualization
ficed is selected, and as large a catheter as possible of the gallbladder, hepatic vessels, and adjacent
is used. Once the catheter is secured, an intra- parenchyma. Hepatic ultrasonography is discussed
venous extension set is attached and the abdomen in Chapter 2. Also see the References for addi-
temporarily closed (with the extension set exiting tional information regarding basic principles of
through the abdominal wall). A total of 0.25 to ultrasound and the ultrasonographic appearance of
0.5 ml/lb body weight of an iodinated ra- the liver.
diographic contrast media is injected as rapidly as The main reasons I use ultrasonography to
possible through the extension set. A radiograph is evaluate hepatic disease are to distinguish focal
obtained just at the end of the injection. Unless a from diffuse disease (and thus help determine an
portable radiographic unit is available, it is usually appropriate biopsy method) and to distinguish
easiest to perform the laparotomy on the x-ray intrahepatic causes of cholestasis from extrahepatic
table.With portosystemic shunting, contrast media causes of cholestasis (the former being a poten-
passes directly into the systemic venous circulation tially medically treatable problem, the latter a
and bypasses the liver. If the caudal extent of the surgically treatable problem). Additional indica-
shunt is cranial to T13, it is probably an intrahe- tions for an ultrasound evaluation of the liver
patic shunt; if it is caudal to T13, it is probably an include any abnormality in hepatic function, size,
extrahepatic shunt. or radiodensity. Diffuse changes in hepatic
Percutaneous Splenoportography echogenicity (compared with falciform fat, the
The indications for percutaneous splenoportogra- renal cortex, and spleen) may suggest certain
phy are similar to those described for intraopera- hepatic diseases. Diffuse hyperechogenicity is seen
tive mesenteric portography. Splenoportography with fatty change, steroid hepatopathy, fibrosis, and
often yields a lesser quality study but has the cirrhosis. Hypoechogenicity is seen with passive
advantage of not requiring a laparotomy. This congestion, lymphoma, and suppurative hepatitis.
is especially important in a hypoalbuminemic Ultrasonography can also be a useful method to
patient that is at risk for wound dehiscence. obtain a biopsy specimen of the liver, because it
CHAPTER 9 DISEASES OF THE LIVER AND HEPATOBILIARY SYSTEM 305
passage of the bolus (60 seconds) as the radiocol- In patients with persistently abnormal serum hepatic
loid is cleared from the circulation by the spleen enzyme activities, efforts to rule out nonhepatic
and liver. There is subsequent gradual increase in causes of enzyme elevations should be made first,
activity in the liver, reflecting uptake of the radio- such as hyperadrenocorticism, diabetes mellitus,
colloid. In dogs with portosystemic shunts, there is congestive heart failure, and feline hyperthy-
increasing activity in the lungs after the initial pas- roidism. In an asymptomatic patient, when
sage of the bolus, indicating pulmonary uptake. increased hepatic enzyme activities are detected
The rate of hepatic uptake is considerably less than on routine biochemical profiles, I generally assess
that seen in normal dogs. Unfortunately, there are hepatic function with serum bile acid measure-
many indeterminate and false-positive results with ments. If these are not grossly elevated, the bio-
this method compared with transcolonic adminis- chemistry profile is repeated in 4 to 6 weeks. If
tration of the radioisotope. In normal cats, extra- there is a persistent increase in hepatic enzyme
hepatic uptake in the lungs occurs, preventing activity at this time, hepatic biopsy is justified.
adequate images of the liver. Abnormal hepatic size of unknown cause
(either microhepatica or hepatomegaly) is another
indication for hepatic biopsy. If hepatomegaly is
Hepatic Biopsy present, efforts must be made to rule out nonhe-
Hepatic biopsy specimen analysis is the only way patic causes, such as hyperadrenocorticism, diabetes
to accurately diagnose and classify hepatic disease. mellitus, and congestive heart failure. Even in the
Biochemical tests, radiographs, and ultrasonogra- presence of these disorders, it might be clinically
phy determine that hepatic disease exists. None of indicated to assess hepatic involvement in these
these tests accurately determines the cause or multisystem diseases with hepatic biopsy specimen
appropriate treatment or predicts prognosis (with analysis. In many cases of hepatomegaly (with
the exception of angiography or scintigraphy for either diffuse or focal enlargement), the purpose of
detecting portosystemic shunts). Recent advances the biopsy is to confirm suspected neoplasia.
in biopsy methods and in noninvasive imaging of Recent advances in chemotherapy have made this
the liver have made hepatic biopsy a routine and an important step in proper management.
essential tool in the diagnosis and management of Finally, hepatic biopsy specimen analysis is
patients with hepatic disease. Many types of important to document the progression of disease.
hepatic diseases are treatable, and a definitive diag- Often multiple or serial biopsies are necessary to
nosis allows the clinician to make appropriate document remission (as in certain cases of chronic
clinical decisions with regard to specific treat- active hepatitis [CAH] or hepatic malignant lym-
ment, rather than just supportive care. Hepatic phoma) and therefore determine appropriate
biopsy specimen analysis helps determine treatment.
whether the abnormality is (1) reversible or irre-
versible, (2) progressive or static, (3) primary Precautions
hepatic or secondary, (4) treated with specific Most contraindications to hepatic biopsy are rela-
therapy or only with supportive therapy and tive contraindications and depend on the biopsy
whether there is a need for follow-up biopsy method.When these factors are present, the clini-
posttreatment. cian must weigh the potential benefits of obtain-
ing the biopsy (i.e., a definitive diagnosis and the
Indications opportunity to begin rational specific therapy)
The most common indication for performing with the risks of the complications that could
hepatic biopsy is abnormal hepatic function potentially occur. However, with experience and
and/or increased serum hepatic enzyme activities knowledge of various methods of hepatic biopsy,
of unknown origin. This is usually identified by these risks can be minimized.
hepatic function tests (such as serum bile acids or The most common contraindication to hepatic
blood ammonia measurements) and serum bio- biopsy is a coagulopathy. Determining the nature of
chemical profile findings obtained in patients the coagulopathy is important in minimizing
showing signs compatible with hepatic disease or its influence. The most common coagulopathy asso-
in routine preanesthetic blood work. If clinical ciated with hepatic disease is DIC. When DIC is
illness is attributed to hepatic disease, a biopsy is present, knowledge of the underlying disease is
warranted. essential in long-term management, and thus
CHAPTER 9 DISEASES OF THE LIVER AND HEPATOBILIARY SYSTEM 307
obtaining the biopsy is essential. In this setting I Finally, hepatic abscess, cyst, or vascular tumors
recommend high volumes of intravenous fluids to are contraindications to percutaneous biopsy
maintain tissue perfusion in the face of micro- methods. Unfortunately, it is usually not known
thrombi, platelet function inhibition with aspirin to that these are present until it is too late, unless an
minimize the hypercoagulable state, and a transfu- imaging modality such as ultrasonography or
sion with fresh crossmatched whole blood collected laparoscopy is available.
in a plastic collection bag (glass activates factor XII)
with 125 units of heparin added per 500 ml of blood Prebiopsy Considerations
to activate antithrombin III (to minimize the hyper- Appropriate biochemical and hepatic function
coagulable state). Methods of obtaining the biopsy tests must be performed to assess the need for the
that require a minimal incision yet allow control of biopsy and identify concurrent disease. Once the
bleeding, such as laparoscopy-guided or the keyhole need for hepatic biopsy is determined, several con-
method, are preferred. siderations must be made. History, physical exami-
When there are prolonged clotting times unac- nation, laboratory, and ancillary findings deter-
companied by DIC, there may be decreased clot- mine the overall health status of the patient. This
ting factor synthesis or vitamin K deficiency. is important in deciding an appropriate anesthetic
Vitamin K administration may be helpful in cer- regime. Certain biopsy methods require minimal
tain situations. In one report vitamin K adminis- to no sedation (blind percutaneous or ultrasound-
tration improved PIVKA times in 10 of 23 dogs guided), some require short general anesthetics
with hepatic disease and normalized PIVKA times (keyhole or laparoscopy-guided), whereas others
in 12 of 48 cats. It has been my experience that require a long general anesthetic (laparotomy). In
bleeding following hepatic biopsy does not corre- addition, patients with extremely low serum albu-
late with coagulation tests, including the PIVKA min concentration are at greater risk for wound
test. Patients with coagulopathies are no more dehiscence and therefore biopsy is more appropri-
likely to bleed than patients without coagu- ately performed with percutaneous methods.
lopathies. In most cases of significant bleeding Abdominal radiographs are helpful to assess
following hepatic biopsy, there are technical prob- hepatic size. This information is useful to narrow
lems. In my experience the rapidity of bleeding the list of differential diagnoses and also to help plan
and/or necropsy examination suggest that a large the biopsy approach. For example, with microhep-
vessel has been damaged rather than hemorrhage atica the transthoracic percutaneous approach may
being due to persistent oozing from needle biopsy be preferred over the transabdominal percuta-
sites. The exception to this is that patients with neous approach and laparoscopy-guided biopsy
DIC often have significant hemorrhage regardless may be preferred over ultrasound-guided biopsy.
of technique. Controlled studies in veterinary The reverse is true with hepatomegaly. Thoracic
patients will be necessary to make final conclu- radiographs are helpful to rule out metastatic
sions regarding postbiopsy hemorrhage in the neoplasia.
patient with a coagulopathy. Coagulation profiles should be performed
An unstable patient that cannot be safely anes- before hepatic biopsy because of the multitude of
thetized is another relative contraindication for abnormalities possible with hepatic disease.
performing a liver biopsy. In these patients blind These were discussed in detail in the section on
percutaneous or ultrasound-guided biopsy meth- pathophysiologic derangements occurring with
ods may be considered because these can often be hepatic disease. Ideally PIVKA time, prothrombin
done with minimal or no sedation. time, partial thromboplastin time, platelet count,
Complete biliary obstruction with dilation and fibrin degradation product determinations
of intrahepatic bile ducts is a contraindication should be made before hepatic biopsy. If there are
described in humans because of the potential for significant cost and time concerns, a less accept-
bile peritonitis. Theoretically this occurs because able alternative is the measurement of activated
there is increased intraductal pressure, and there- clotting time and toenail bleeding time. The for-
fore inadvertent duct rupture following biopsy mer test assesses the intrinsic and common
results in bile leaking into the abdominal cavity. In clotting pathways but is only abnormal when
my experience, however, this complication has not clotting factor activity drops below 10% of
been recognized in cases when percutaneous biopsy normal (whereas partial thromboplastin time is
was performed in animals with biliary obstruction. abnormal when clotting factor activity drops
308 CHAPTER 9 DISEASES OF THE LIVER AND HEPATOBILIARY SYSTEM
below 30% of normal). The management of Semiautomated cutting needles include the
coagulopathies when obtaining hepatic biopsy Vet-Core needle (Cook). Semiautomatic needles
was discussed in the section on precautions for require manual thrusting of the internal obturator
hepatic biopsy. (containing the biopsy tray or specimen notch)
Because chemical restraint is sometimes neces- into the organ, followed by an automatic thrusting
sary to insure a safe procedure, the patient should of the outer cutting sheath by the spring-loaded
be clipped before sedation. For general anesthesia I mechanism. These needles have some of the
prefer isoflurane or sevoflurane induction by face advantages of the completely automatic needles
mask or induction chamber. If an injectable anes- and have the additional advantages of having more
thetic is desired, I prefer the combination of keta- control over final needle position and being lighter
mine and diazepam. Although oxymorphone with a smaller handle. These characteristics also
provides adequate restraint and can be reversed if make these needles well suited to computed
necessary, excessive panting often occurs, which tomography (CT) guidance because the handle
interferes with the biopsy procedure and therefore can be let free by the operator for intraprocedural
is not recommended. scanning without the weight of the handle causing
the needle to move. In addition, the tip of the nee-
Biopsy Methods dle can be precisely localized before the outer cut-
The five basic methods of obtaining a hepatic ting sheath is “fired.” The older manual cutting
biopsy are blind percutaneous, keyhole technique, ultra- needles (Tru-Cut or ABC needles) offer no advan-
sound-guided, laparoscopy-guided, and laparotomy tages over these newer needles.
biopsy. Each method has certain advantages and Aspiration needles are generally used to obtain
disadvantages. Knowledge of these, as well as prac- smaller samples that would be suitable for cyto-
tice and expertise in each respective method, allow logic preparations (rather than histopathologic
the clinician to select the most appropriate and preparations), or for Menghini and Westcott nee-
safest method to obtain hepatic tissue. dles, used to obtain small samples for histopatho-
Blind Percutaneous Biopsy logic examination (see below). These needles are
The advantages of blind percutaneous biopsy are also well suited to obtain samples of fluid, such as
that it is very rapid, requires minimal sedation, and intraparenchymal cysts and gallbladder puncture.
is low cost. Disadvantages of this method are that Usually these are smaller-gauge needles (20 to 22
there is the potential for inadvertent trauma to gauge) and therefore tend to be less traumatic.
other organs, focal lesions may be missed, and Aspiration needles employ suction to obtain fluid
detection of bleeding may be delayed. or cut the core of tissue. The Menghini needle is
Equipment especially suited for transthoracic hepatic biopsy
Various biopsy needles can be used for percuta- but can be used for transabdominal techniques as
neous biopsy. In general, newer automated needles well. The tip of the needle is slightly oblique and
are preferred. These are spring-loaded needles that convex and cuts a core of tissue when suction is
are similar in style to manual Tru-Cut (Baxter) or applied as the needle is rapidly thrust into the liver
ABC (Monoject) needles. Automated needles can and immediately withdrawn. The intrahepatic
be completely automatic or semiautomatic. phase should last just a fraction of a second. A slid-
Automated cutting needles include the Monopty ing screw acts as a depth gauge and prevents the
(Bard), ASAP (Microvasive), and Biopty (Bard) needle from entering too deeply into the
needles. Completely automatic needles thrust the parenchyma. For the Westcott needle, suction is
inner obturator (containing the biopsy tray or used to draw tissue into a specimen notch at the
specimen notch) followed by the outer cutting distal end. Gentle back-and-forth movement
sheath into the organ in a fraction of a second. allows a core of tissue to be cut.
These needles can easily be operated with one Transthoracic Technique
hand. Because the action is so quick, there is min- Because of the short intrahepatic phase, the
imal displacement of the organ, a shorter intra- transthoracic technique is especially suitable for
parenchymal phase, and much more reliable yield patients in which sedation is too risky or unde-
of tissue. This allows the biopsy of the organ to be sirable and in patients with microhepatica, in which
performed with minimal manual mobilization, the transabdominal technique may be difficult.
allows a smaller diameter needle to be used, and The patient is given corn oil orally (1 ml/lb
allows a lighter degree of sedation. body weight) to cause the gallbladder to contract
CHAPTER 9 DISEASES OF THE LIVER AND HEPATOBILIARY SYSTEM 309
and thus minimize the risk of inadvertent puncture. given corn oil orally (2 ml/kg body weight) to
A Menghini needle is used to obtain the biopsy cause the gallbladder to contract and thus reduce
specimen. The patient is placed in left lateral the risk of inadvertent puncture. I prefer to use
recumbency, and the right hemithorax clipped and automated cutting type of needles such as the
surgically prepared. A local anesthetic is injected Monopty or ASAP needles. The patient is placed
subcutaneously at the needle puncture site: just in right dorsal oblique recumbency at a 45-degree
dorsal to the costochondral junction of the fifth angle. In this position the stomach falls down
through seventh intercostal space (depending on the toward the right side. A large area around the
size of the patient and distance to the diaphragm). xiphoid cartilage is clipped and surgically pre-
Using a No. 11 blade, a skin incision is made to pre- pared. A local anesthetic is injected subcuta-
vent dulling of the biopsy needle.With the stylet of neously at the needle entry site: just caudal and to
the Menghini needle in place, the needle is the left of the xiphoid cartilage, in the middle of
“popped” into the pleural space and then directed the “V” formed by the xiphoid cartilage and the
caudally and parallel to the rib cage until it contacts rib cage. If the needle enters too far cranially, it
the diaphragm (respiratory movements will be felt). may inadvertently enter the thoracic cavity. If
Care is taken to avoid lacerating the intercostal ves- there is hepatomegaly, the entry site is moved cau-
sels that lie along the caudal aspect of each rib. dally as appropriate for the hepatic size. The skin is
Upon making contact with the diaphragm, the nee- incised with a No. 11 blade to prevent dulling of
dle depth gauge is slid to within approximately the biopsy needle. The biopsy needle is inserted
1.5 cm of the skin so that the depth of penetration and advanced just through the body wall and
into the liver is limited to this distance.The stylet is aimed in a craniolateral direction towards the left
then removed and quickly replaced with a 12-ml shoulder. The needle should be advanced during
syringe filled with 5 to 6 ml of sterile saline. inspiration. The liver should be very close to the
Negative pressure corresponding to approximately body wall, and the needle need not be advanced
3 ml of fluid volume is produced by drawing on the very far. Penetration of the liver is often not felt.
plunger. At the peak of expiration, the needle is The most common error using this technique is
rapidly thrust into the liver (with the distance lim- inserting the needle too far and going completely
ited by the depth gauge) and immediately with- through the liver. Once the liver is entered the
drawn from the patient in one swift motion, biopsy needle is operated to cut the sample. This is
maintaining negative pressure throughout. This done during peak inspiration. The needle is
entire step (i.e., the intrahepatic phase) should last removed after each attempt. The core of hepatic
only a split second. The core of hepatic tissue tissue should be resting within the specimen notch
should rest within the fluid in the syringe or in the of the needle. If the initial attempt fails to obtain
needle. The plunger is removed and the contents hepatic tissue, the needle is redirected based
poured into culture broth, onto a slide for impression on perceived location of the liver, body conforma-
cytologyic study, and/or into a jar containing 10% tion (i.e., deep chested), and direction of previ-
formalin. The patient is then immediately turned ous attempts. Tissue is carefully removed with a
onto its right side for approximately 5 minutes to 25-gauge needle and placed into culture broth,
allow the weight of the liver to control hemorrhage. onto a slide for impression cytologic study, and/or
Possible complications with this technique into 10% formalin. The patient is immediately
include gallbladder puncture (and possible bile placed in sternal recumbency to allow the weight
peritonitis and pleuritis), pneumothorax, and of the liver to control hemorrhage.
excessive bleeding. In patients with firm fibrotic Possible complications of this technique include
livers, this technique may not yield a suitable sam- puncture of the stomach, gallbladder rupture (and
ple. In this situation a cutting type of needle used possible bile peritonitis), puncture of the dia-
with a transabdominal approach may be successful. phragm and lung (and possible pneumothorax),
Transabdominal Technique (Blind) and excessive bleeding.
The transabdominal technique is especially useful Keyhole Technique
when the size of the liver is normal or large. It has The keyhole technique offers the advantages of
a longer intrahepatic phase than the transthoracic providing more guidance of the needle than blind
technique if a cutting type of needle is used, and percutaneous biopsy, being relatively rapid, and
therefore a higher degree of sedation may be nec- being low cost. Disadvantages of this method
essary in an uncooperative patient. The patient is include the requirement for more sedation com-
310 CHAPTER 9 DISEASES OF THE LIVER AND HEPATOBILIARY SYSTEM
pared with blind percutaneous biopsy, the possibil- focal liver biopsy the location of the lesion will
ity of causing inadvertent trauma to other organs, determine the position of the scan head and nee-
the possibility that focal lesions may be missed, and dle path. For diffuse lesions the transducer is usu-
the possibility that detection of bleeding may be ally placed just caudal and to the left of the
delayed. This technique is especially suitable for xiphoid and aimed at the left medial or lateral
individuals who lack the experience to perform a lobes. In patients with extremely small livers, it
blind percutaneous biopsy. may be difficult to adequately visualize the needle
The keyhole technique and equipment are without stomach gas interfering. In this case plac-
similar to that described for the blind transabdom- ing the patient in a 45-degree right ventral
inal percutaneous biopsy. Under a general anes- oblique position often helps reduce interference
thetic a small incision into the abdominal cavity is from the stomach. Otherwise the patient is usually
made just caudal to the site of needle introduction. placed in dorsal recumbency for most procedures.
A gloved finger is inserted into the abdomen to A rubber trough or V tray assists in positioning. In
palpate the liver and stabilize it for biopsy. The addition, if the patient is under gas general anes-
needle is inserted through the same incision or thesia, an assistant compresses the rebreathing bag
through a separate incision just cranial to the first to hold the patient in deep inspiration. This
incision. The finger then guides the needle into moves the diaphragm and liver caudally to
the liver, and the biopsy specimen is cut. I prefer improve visualization. If a lesion cannot be seen
an automated cutting needle for this technique due to overlying gas or bone, changing patient or
because it can be operated with one hand, whereas transducer position usually allows adequate visu-
the Tru-Cut needle would require an assistant to alization.
operate the needle. Complications are similar The area to be scanned, including the needle
to those described for blind percutaneous biopsy. entry site, is surgically prepared. The ultrasound
Ultrasound-Guided Biopsy transducer is covered with sterile plastic wrap (or
Ultrasound-guided biopsy offers the advantage of a sterile glove) after a small amount of coupling
providing more guidance to the needle than is gel is placed on the transducer surface. A biopsy
possible with blind percutaneous biopsy, is rela- guide may be used if desired, allowing accurate
tively rapid, and requires minimal sedation. placement of the needle in the same plane as the
Because intraparenchymal lesions can be visual- scan. However, it is sometimes desirable to have
ized, biopsy of them can be selectively performed. the needle enter in a different plane due to over-
In addition, other intrahepatic structures such as lying structures in the plane of the scan, in which
the gallbladder and portal vessels can be avoided. case a biopsy guide cannot be used. Biopsy guides
Disadvantages of ultrasound-guided biopsy in- also limit the angle of insertion of the needle, and
clude the requirement for expensive equipment the entry site is usually 2 to 3 cm from the scan
and that detection of bleeding may be delayed. As head. Therefore for superficial lesions or those in
with other biopsy methods, success is operator- the center of the scan, a biopsy guide should not
dependant. Ultrasound-guided biopsy is easier be used. Furthermore, when the needle is in a
when the liver is normal or large in size. When rigid biopsy guide, inadvertent trauma to the
there is microhepatica, overlying gas in the stom- organ may result if the patient moves or takes a
ach often makes visualization of the liver difficult. deep breath.
In this setting, laparoscopy would offer a more A small amount of sterile coupling gel or
appropriate image-guided biopsy method. water-soluble lubricant is placed on the skin, and
Technique the ultrasound examination is repeated to verify
Most dogs require minimal sedation for ultra- the needle path. A small stab incision is made in
sound-guided biopsy. I use a low dose of ketamine the skin at the needle insertion site. Automated
for cats (10 to 20 mg intravenously) or isoflurane needles are generally preferred because they can
or sevoflurane administered by face mask. A care- be easily operated with one hand. Therefore the
ful ultrasound examination is performed before needle must be loaded before entry into the
biopsy. This allows planning of the procedure abdomen. While one hand maneuvers the trans-
based on the type of echo pattern, size of the ducer, the other hand advances the needle into the
lesion, proximity to other organs, proximity to organ under direct ultrasound visualization. If the
blood vessels, determination of cystic or solid tis- needle tip cannot be seen, gentle movement of the
sue, and determination of the needle path. For transducer should allow visualization. To allow
CHAPTER 9 DISEASES OF THE LIVER AND HEPATOBILIARY SYSTEM 311
distinction of the needle from other echogenic perform a complete laparoscopic examination and
structures in the image, the needle can be gently obtain multiple biopsy specimens in 10 to 15
moved in and out. Ideally this should be minimal minutes in most cases, and because there is only a
and just enough to move the organ within the 1.0-cm incision, there is much less risk for wound
abdominal cavity rather than moving the needle dehiscence. Disadvantages of laparoscopy are the
within the organ. If a spinal needle is used, mov- requirement for a general anesthetic and the need
ing the stylet in and out of the stationary nee- for expensive equipment. Details of the equip-
dle increases the echogenicity and visualization ment and techniques for performing laparoscopy
of the needle tip without creating tissue trauma. are found in Chapter 3.
Occasionally the needle cannot be visualized. Potential complications of the procedure
Indirect evidence of organ puncture can be used, include those related to a general anesthetic,
including movement of the organ or visualization excessive bleeding, overdistention of the abdomen
of motion at the organ border. The needle is with gas, air embolism, and a tension pneumotho-
directed so the trajectory will avoid other struc- rax if the diaphragm is inadvertently punc-
tures when it is fired. Care must be taken to pre- tured (as abdominal gas enters the thoracic
vent going too deep with the needle, or it will be cavity). In my experience these complications are
seen to penetrate the diaphragm and enter the extremely rare.
thoracic cavity. Once the biopsy specimen is Laparotomy Biopsy
obtained, the needle is removed. The core of liver Advantages of a laparotomy biopsy include the abil-
should be resting within the specimen notch of ity to view the entire abdominal cavity and to treat
the needle. A 25-gauge needle is then carefully disease when surgically correctable. Therefore
used to transfer the tissue into culture broth, onto one can visualize and select the biopsy site. If
a slide for impression cytologic study, and/or into there is excessive hemorrhage, it can be controlled.
10% formalin. The number of biopsy specimens However, if there is a known coagulopathy, lapa-
obtained will depend on the coagulation status of rotomy is not advised because of the size of the inci-
the patient, types of diagnostic tests planned, and sion and therefore high potential for additional
adequacy of tissue retrieved. After completion of bleeding. In this setting laparoscopy is the preferred
the procedure, an ultrasound examination is per- method for obtaining the biopsy specimen.
formed to check for excessive hemorrhage. Laparotomy offers the additional advantage of being
External digital pressure or an abdominal com- able to obtain large biopsy specimens. Disadvantages
pression wrap may be used to control hemor- of laparotomy biopsy include the requirement for a
rhage. Possible complications of this technique are long general anesthetic and therefore more risk to
similar to those described above for the blind the patient. In addition, there may be poor wound
transabdominal percutaneous biopsy. healing if severe hypoalbuminemia is present and
Laparoscopy-Guided Biopsy therefore increased risk for dehiscence.
The main advantage of laparoscopy-guided The techniques to obtain hepatic tissue at
biopsy is the ability to visualize the liver, biliary laparotomy are beyond the scope of this chapter.
tree, and other abdominal organs. With experi- The reader is referred to surgical textbooks for
ence the gallbladder can be examined, palpated further information on this subject.
with a blunt probe, and the bile duct traced to its
entry into the duodenum. In this manner it can Postbiopsy Monitoring
be determined whether there is a common bile The most important complication to monitor for
duct or cystic duct obstruction. In addition, following hepatic biopsy is excessive hemorrhage
because focal lesions on the liver can be directly and subsequent hypovolemic shock. Hematocrit
visualized, an appropriate biopsy site can be and total solid measurements are an unreliable
selected, and other intrahepatic structures such as means of identification of hemorrhage, because
the gallbladder and portal vessels can be avoided. several hours are necessary for extravascular fluid
Hemorrhage can be observed and, when exces- redistribution to occur following acute bleeding
sive, controlled with direct compression with a and therefore changes in hematocrit are delayed.
blunt probe over the biopsy site, with electro- By the time the hematocrit drops, it might be
cautery, or with application of gel foam. too late to begin a life-saving blood transfusion.
Compared with laparotomy, there is much less Therefore clinical monitoring, including assessing
anesthetic time.With experience the operator can mucous membrane color and capillary refill time,
312 CHAPTER 9 DISEASES OF THE LIVER AND HEPATOBILIARY SYSTEM
certain antiparasitic drugs (mebendazole, thia- looked for and that not all cases of chronic hepatitis are
cetarsamide). Finally, metabolic abnormalities such “steroid-responsive” or “autoimmune.”
as copper-storage diseases can result in hepatic When an underlying cause for chronic hepatitis
inflammation. The histologic appearance of all cannot be identified, a pathogenesis similar to that
these entities can be very similar. Therefore the described for humans (Figure 9-1) may have
clinician must be aware of the many factors merit. Briefly, it is proposed that immunologic
that can lead to hepatic inflammation and thor- factors lead to the perpetuation of inflamma-
oughly evaluate the patient to manage the disorder tion following hepatocyte damage caused by
appropriately. any agent. Following hepatocyte injury, there is a
release of hepatic antigens previously not exposed
Chronic Active Hepatitis, Chronic to the systemic immune system (hidden from
Hepatitis immune surveillance). This results in an influx of
CAH is defined as an idiopathic active inflamma- inflammatory cells (primarily lymphocytes and
tory disease of the liver that is chronic in duration. plasma cells), which cause antibody-mediated and
The term has been applied to a proposed specific complement-mediated cytotoxicity. This results in
disease analogous to the disease in humans of the further hepatocyte injury, and this vicious cycle is
same name or to a description of the pathologic perpetuated by these immunologic events and
process that results in the histologic appearance occurs long after the initial insult is gone. At first
characterized by chronic ongoing inflammation. the reaction occurs near the portal triads, but
Some clinicians believe that the disorder is not a eventually it extends beyond the limiting plate of
specific disease but rather a general reaction by the hepatocytes (the single-cell–thick layer of hepato-
liver to any injury, with the histologic pattern cytes surrounding the portal triad) into the hepatic
one of nonspecific inflammation as a response lobule. This eventually results in necrosis and
to any insult. Others believe that the clinical fea- bridging fibrosis (inflammation and fibrosis extend-
tures, histologic pattern, and response to immune- ing between adjacent portal areas). When the nor-
modulating drugs are similar enough to the disease mal hepatic architecture is lost and the fibrotic
in humans to warrant the name as a true disease process becomes diffuse, it is termed cirrhosis.
entity. Whether these events occur in the dog as has been
Several distinct clinical entities can result in proposed in humans, and whether the syndrome
chronic hepatitis, including copper-storage dis- seen in dogs is analogous to CAH in human
eases (Bedlington terrier, West Highland white beings, is unknown.
terrier, Skye terrier, and possibly the Doberman Clinical Features of Chronic Active
pinscher), infectious diseases (viral hepatitis, lep- Hepatitis in Dogs
tospirosis), drugs (anticonvulsants), or idiopathic CAH is represented in approximately 5% to 16%
causes. This discussion will focus primarily on of dogs undergoing hepatic biopsy in one study.
idiopathic causes, although it must be emphasized The disease occurs primarily in middle-age dogs
that diseases with a known underlying cause must be (average 6 years), with the majority (greater than
Fibrosis/cirrhosis
Damaged hepatocyte
Inflammatory process
extends into parenchyma Liver antigens released
75%) occurring in females. There is a marked pre- death, and the presence of bridging fibrosis was the
disposition in Doberman pinschers, with virtually histologic change most predictive of shorter sur-
all cases (greater than 95%) occurring in females vival time in dogs surviving more than 1 week.
of this breed. Because of the finding of marked Radiographic findings vary with the severity of
copper accumulation in the livers of affected the disease. Abnormal findings include microhe-
Doberman pinschers, it is unclear if the disease patica (usually associated with terminal cirrhosis),
seen in this breed is the same as that occurring in ascites (associated with portal hypertension and
other breeds. However, copper is normally hypoalbuminemia), and, in those cases that
excreted in the bile, and it accumulates in hepato- undergo angiographic evaluation, there are multi-
cytes with any cholestatic disorder. The finding of ple acquired tortuous portosystemic shunts indica-
high hepatic copper concentrations in two tive of chronic portal hypertension.
Doberman pinschers with subacute hepatitis (i.e., The histologic appearance is not unique to
without evidence of cholestasis) suggests the possi- CAH but can be seen in other inflamma-
bility of a primary copper-storage disease. For the tory hepatic diseases. Therefore other inflam-
purposes of this discussion, however, the disease matory diseases must be eliminated to suggest the
seen in the Doberman pinscher breed will be con- diagnosis of CAH. Histologic features include
sidered with that seen as idiopathic CAH in other piecemeal necrosis, bridging necrosis, and active
breeds because the clinical features are similar. cirrhosis. Piecemeal necrosis refers to a specific
There is also a breed predisposition in American pattern that is typical of CAH and characterized
cocker spaniels. by periportal necrosis and inflammation occurring
Clinical signs of CAH include those typical of in an irregular fashion surrounding islands of nor-
chronic hepatic disease, such as polyuria, polydip- mal hepatocytes. The majority of inflammatory
sia, weight loss, anorexia, icterus, ascites, abnormal cells are lymphocytes and plasma cells, although
bleeding tendency, depression, disorientation, and there are lesser numbers of neutrophils and
seizures. Some patients have a short fulminant macrophages. Accompanying features include bile
clinical course and die within a short period of duct hyperplasia, bile stasis, and regenerative nod-
showing clinical signs. Others are presented with ules. Eventually there is deposition of fibrous tissue
progressive signs of hepatic disease, although signs as a sequela to the inflammation and necrosis,
often wax and wane. A third group of dogs is eventually connecting adjacent portal triads
asymptomatic when presented, with the disease (bridging necrosis and fibrosis). When normal
identified from biochemical screening and subse- hepatic architecture is lost and the fibrotic process
quent hepatic biopsy specimen analysis. becomes diffuse, it is termed cirrhosis. In most
Abnormal laboratory findings include in- Doberman pinschers that have been evaluated,
creased serum activity of all hepatic enzymes copper stains are strongly positive and quantitative
(including ALT, AST, ALP, and GGT) in virtually measurements of hepatic copper concentration are
all dogs. Most dogs (approximately 75%) have high. Other breeds have not been studied as exten-
increased serum total bilirubin concentration sively for the presence of hepatic copper; however,
(mild to marked), and many (approximately 50%) I have seen several cases in other breeds with high
are hypoalbuminemic. Abnormalities in other hepatic copper concentrations histologically. The
chemistry values are inconsistent. Hepatic function gross appearance of the liver can be normal in
tests (serum bile acids and plasma ammonia con- early cases. As the disease progresses, the liver
centrations) are usually abnormal. Clotting times becomes shrunken, loses its normal lobular pat-
may be abnormal. These test results generally tern, becomes discolored (brown, red, and yellow
reflect the severity of the disease and stage in mottling), and the surface becomes irregular.
which it is detected. In one large series of dogs Eventually the surface becomes coarsely nodular
reported with chronic hepatitis from any cause, in texture, reflecting regenerative nodules occur-
low serum glucose concentration and prolonged ring in a setting of terminal cirrhosis.
prothrombin time were the best predictors of early Treatment of Chronic Active Hepatitis
death (within 1 week of presentation). In dogs sur- in Dogs
viving more than 1 week, hypoalbuminemia was The treatment of CAH in dogs remains specula-
the laboratory change most predictive of shorter tive because controlled clinical trials with large
survival time. The degree and severity of necrosis numbers of dogs have not been performed. The
and fibrosis were accurate predictors of early necroinflammatory response is usually progressive,
316 CHAPTER 9 DISEASES OF THE LIVER AND HEPATOBILIARY SYSTEM
and most dogs do not go into spontaneous remis- Likewise, azathioprine is tapered to an alternate-
sion. If cirrhosis is present, the likelihood of suc- day dosage schedule (at the original dose). I gener-
cessfully managing the case is low. Therefore the ally taper prednisone first and do not taper
prognosis is poor in severe cases, and most of these azathioprine until the dose of prednisone is low.
dogs die within several weeks to months despite This is because azathioprine is generally associated
appropriate treatment. This emphasizes the need for with fewer side effects and is better tolerated.
early detection. A complete blood count (CBC) and platelet count
There are three basic goals in treating dogs with should be obtained 3 and 6 weeks after starting
CAH: azathioprine and every 2 months thereafter to
1. To arrest inflammation look for potential myelosuppression. If this is
2. To correct nutritional imbalances and treat detected, azathioprine should either be tapered or
hepatic encephalopathy with dietary manage- discontinued depending on the magnitude of the
ment cytopenia. During the tapering process, patients
3. To resolve fibrosis are monitored with serum biochemistry profiles
for relapses. Often it is difficult to differentiate the
Arresting Inflammation effect of prednisone on serum hepatic enzyme
Though there are no controlled trials using gluco- activities (especially ALP activity) from the effect
corticoids to treat dogs with CAH, many clinicians of the disease process on serum enzyme activities.
have had success using them as part of the thera- In this setting, clinical judgment is used to deter-
peutic regimen. In a large study of Doberman pin- mine if prednisone should continue to be tapered.
schers with CAH, however, there was little benefit Serial bile acid assays and serum bilirubin and
seen with prednisone alone. In another study of albumin concentrations also can be used to moni-
chronic hepatitis in various breeds, dogs surviving tor the patient. If hepatic inflammation is being
more than 1 week that were treated with pred- adequately controlled by azathioprine, the enzyme
nisone had improved survival compared with dogs activities will decrease as prednisone is tapered.
not treated with prednisone. However, the vari- Eventually prednisone is discontinued, and later
eties of hepatic diseases treated and lack of a azathioprine is discontinued.
prospective control group limit the validity of In cases with cholestasis the use of the hydro-
conclusions of that study. Studies in humans show choleretic drug ursodeoxycholic acid (ursodiol;
that the combination of low-dose glucocorticoids Actigall or Urso) may be helpful. Ursodeoxycholic
and azathioprine (Imuran) is as efficacious as high- acid is a naturally occurring dihydroxylated
dose glucocorticoids alone and has fewer side hydrophilic bile acid found in small quantities in
effects. Because of these observations, the combi- normal human bile and in larger quantities in the
nation may be justified in dogs. I have had more bile of certain species of bears. One of its uses is
success using a combination of prednisone and for dissolution of radiolucent gallstones. The pro-
azathioprine than prednisone alone. posed mechanism of action is that it alters the
On a theoretical basis, prednisolone is preferred composition of bile, changing it from cholesterol-
over prednisone in treating dogs with hepatic dis- precipitating to cholesterol-solubilizing and dis-
ease because the latter drug requires hepatic con- persing cholesterol as liquid crystals in the bile,
version to the former (active) drug. However, thus solubilizing the gallstones. In humans, urso-
studies in humans with CAH have shown the two diol dissolves gallstones at the rate of approximately
drugs to have equal efficacy and reach similar 1 mm/month and works best on radiolucent, non-
blood levels of the active form. Similar studies have calcified gallstones less than 20 mm in diameter.
not been performed in the dog, although I have Side effects are rare (diarrhea), and there is no
found no difference between prednisolone and influence on either serum total cholesterol or
prednisone in treating dogs with hepatic disease. triglyceride concentrations.
The recommended starting dosage of pred- The exact mechanisms of its beneficial effects
nisone is 0.5 to 1 mg/lb body weight per day. The in inflammatory hepatic diseases remain contro-
starting dosage of azathioprine is 50 mg/m2 body versial. It is believed that there is a favorable
surface area once daily. Once clinical remission is change in the bile acid pool, rendering retained
achieved (usually 3 to 4 weeks), the dose of pred- endogenous bile acids less toxic by changing the
nisone is gradually tapered to a low maintenance bile acid pool from the more toxic hydrophobic
dose (approximately 0.2 mg/lb body weight). bile acids to less toxic hydrophilic bile acids. It is
CHAPTER 9 DISEASES OF THE LIVER AND HEPATOBILIARY SYSTEM 317
also thought that ursodeoxycholic acid has antiin- twice a day. Bile acids are required for fat-soluble
flammatory, immunomodulatory, and choleretic vitamin E absorption, and, because they may be
effects (promoting bile flow and decreasing viscos- reduced with liver disease, a water-soluble formu-
ity of bile). The latter mechanism is believed to be lation should be used. This type of formulation is
mediated through the cholehepatic shunting available at most health food stores.
hypothesis. This proposes that ursodeoxycholate is S-adenosylmethionine (SAMe) is a molecule
converted to ursodeoxycholic acid through addi- synthesized by all cells and is critical to intermedi-
tion of a hydrogen ion originating from carbonic ary metabolism. It is especially important in the
acid. This leaves a bicarbonate ion to act as an liver, where much of the body’s intermediary
osmotic draw for water to decrease viscosity and metabolism occurs. SAMe is derived from the
promote bile flow. Ursodeoxycholic acid has been amino acid methionine and initiates three major
used in the management of chronic hepatic dis- biochemical pathways (transmethylation, transsul-
eases in humans, including CAH, primary biliary furation, and aminopropylation). These pathways
cirrhosis, and primary sclerosing cholangitis. are involved with major anabolic and catabolic
Significant improvement in symptoms, laboratory reactions that influence steroid hormone effects,
parameters, and survival has been reported in carnitine synthesis, drug metabolism and detoxifi-
many patients undergoing treatment for these cation, and hepatocyte and red blood cell mem-
diseases. brane function. In addition, SAMe is involved in
I have used ursodeoxycholic acid, either alone detoxification of toxins and protection against
or in combination with other drugs, in patients oxidative injury. The latter effect is in large part
with various cholestatic diseases (including dogs mediated through glutathione, a metabolite of
with CAH and cats with cholangiohepatitis). The SAMe through the transsulfuration pathway of
drug is very well tolerated, and in some cases the metabolism. Glutathione depletion has been docu-
response can be dramatic. Use of ursodeoxycholic mented in approximately 45% of canine and feline
acid should be considered as either primary or hepatopathies.With glutathione depletion, oxidative
adjunctive (in combination with immunosuppres- injury is more likely to result in membrane damage
sive or antiinflammatory drugs) treatment in and toxin accumulation, resulting in hepatocellular
patients with chronic liver diseases. It may be the injury and death. It has been speculated that this
only effective drug in patients in which glucocor- could be minimized by supplementation with
ticoid therapy or other immunosuppressive drug SAMe. Furthermore, SAMe has aminopropylation
therapy is contraindicated or ineffective. Ursode- metabolites that contribute to antiinflammatory
oxycholic acid is also a powerful choleretic agent effects.
that can be used to treat sludged bile and SAMe is available as a “nutraceutical” that has
cholelithiasis. The drug is supplied in 300-mg been studied experimentally and clinically in a
capsules and more recently in 250-mg tablets. A variety of species. Oral use became possible when
safe and effective dose is 6 to 7 mg/lb/day, admin- a stable oral salt in an enteric-coated tablet was
istered either once daily or divided twice a day. developed. Nutramax Laboratories, Inc, currently
The drug should be given with food. Studies need markets it under the trade name Denosyl SD4.
to be performed to substantiate its efficacy and Several studies have shown the product to be safe
dosage in the dog and cat. in a variety of species, including dogs and cats.
Vitamin E therapy is also recommended in Potential indications for usage in dogs and cats
many types of hepatic diseases, including CAH. include hepatic necrosis, inflammatory disorders,
Oxidative injury to the liver is now well recog- cholestasis, drug-induced hepatotoxicity, copper
nized in several types of inflammatory processes. storage hepatopathy, and metabolic disorders such
Free radicals are generated in chronic hepatitis by as glucocorticoid-induced hepatopathy and idio-
the injurious effects of certain drugs, toxins, or pathic feline hepatic lipidosis. In these disorders
immunologic injury. These free radicals can dam- administration of SAMe is meant to help mini-
age cellular macromolecules via lipid peroxidation mize oxidative injury, protect against free radical
and thus participate in cellular injury and play an damage, protect against the deleterious effect of
important role in initiating and/or perpetuating retained bile acids, enhance bile flow, stabilize
hepatic injury.Vitamin E reduces oxidant injury to hepatocellular membranes, decrease inflamma-
hepatic tissue by providing protection from free tion, and aid in detoxification of endotoxins
radicals.Vitamin E is used at a dosage of 7 units/lb and other substances absorbed from the portal
318 CHAPTER 9 DISEASES OF THE LIVER AND HEPATOBILIARY SYSTEM
circulation. Since SAMe has such a diverse spec- rect vitamin and mineral deficiencies. Feeding a
trum of effects, it may be helpful in a diverse group controlled diet will also reduce the production and
of hepatopathies. The currently recommended absorption of toxins from the small intestine,
dose is 9 mg/lb divided twice daily for dogs and potential antigens that can worsen CAH. These
90 mg (per cat) once daily for cats. It is rapidly therapeutic efforts are similar to those used to
absorbed and is best administered on an empty manage any case of hepatic disease symptomati-
stomach to maximize absorption. The drug can be cally. These are discussed in detail in the section
safely administered with other drugs used to treat on management of hepatic disease.
hepatic diseases without toxicity or compromising In cases where there is excess hepatic copper
effects of other drugs, including ursodeoxycholic documented by special copper stains or quantita-
acid. Controlled studies are needed to substantiate tive hepatic copper measurement, efforts must
these recommendations and to determine which be made to minimize hepatic copper concentra-
disorders are most likely to benefit from SAMe tion. Drugs such as penicillamine (Cuprimine)
administration. and trientine (Syprine) are useful chelators of
The optimal duration of treatment is unknown hepatic copper (enhancing urinary excretion).
and can be quite variable. The decision to discon- Supplementation with vitamin C (ascorbic acid)
tinue medication should ideally be based on will also increase copper excretion in the urine.
follow-up hepatic biopsy specimen analysis. If there Supplementation with zinc acetate, gluconate, or
is evidence of ongoing inflammation, therapy sulfate will limit intestinal copper absorption and
should be continued. In the absence of follow-up deposition in the liver, as well as remove copper
hepatic biopsy specimen analysis, the decision to from the liver. These drugs will be discussed in
discontinue treatment may be arbitrary but should detail in the section on copper-storage diseases.
be based on clinical and biochemical information. Resolving Fibrosis
Patients should be monitored at least monthly for Because fibrosis is a common sequela to CAH and
relapses at first. Some patients require long-term its severity an accurate predictor of early death and
(years), low-dose therapy (e.g., prednisone every shorter survival times in those surviving the initial
48 to 72 hours) to maintain remission. 1 week postdiagnosis period, its management is an
Possible sources of sepsis should be examined important part of managing cases of CAH. The
for while these immunosuppressive drugs are drug of choice to decrease further fibrotic deposi-
being administered. This includes a culture of the tion and to dissolve existing fibrous tissue in the
original hepatic biopsy specimen, because it is not liver is colchicine. There are several studies in
uncommon to grow bacteria as a secondary event humans with alcoholic, posthepatitic, and primary
in cases of hepatic failure due to abnormal hepatic biliary cirrhosis that show colchicine to have ben-
reticuloendothelial cell function. Urinary tract eficial effects clinically, biochemically, histologi-
infections are also common in dogs receiving cally, and on survival. Colchicine has been used
prednisone and azathioprine. with success in cases of chronic hepatitis with
It must be emphasized that there are no long- fibrosis or cirrhosis in dogs. Controlled trials are
term controlled studies to support these recom- needed to further substantiate these clinical obser-
mendations in treating dogs with CAH. Such vations.
studies are needed and should help clarify the The mechanism by which colchicine benefits
most appropriate treatment. Because Doberman patients with chronic hepatitis with cirrhosis is
pinschers are at increased risk of developing CAH, unclear, although it has antifibrotic and antiinflam-
I recommend that a serum chemistry profile be matory effects. Its antifibrotic effects are primarily
performed every 6 to 12 months to screen for due to inhibition of microtubule assembly within
CAH in this breed so that treatment can be insti- cells by binding to the protein tubulin (thus inter-
tuted before the development of clinical signs. fering with collagen synthesis and secretion) and
Certainly owners who wish to provide the very by stimulating collagenase activity (thus enhanc-
best care should be given this option early in their ing breakdown of existing collagen). Colchicine
pet’s life. also interferes with the transcellular movement of
Dietary Treatment and Correction collagen, reduces activity of hepatic collagen-
of Nutritional Imbalances processing enzymes, and inhibits proliferation
Goals of dietary therapy are to minimize hyperam- of fibroblasts. Thus colchicine inhibits collagen
monemia, correct amino acid imbalances, and cor- production and increases collagenase-mediated
CHAPTER 9 DISEASES OF THE LIVER AND HEPATOBILIARY SYSTEM 319
cats are febrile. Clinical signs are often acute in mal lobular architecture). There may be accentu-
onset, although some cats with the nonsuppurative ated lobular markings giving a reticulated appear-
form can have chronic illness. Despite these trends ance (reflecting the prominent portal infiltrate).
in presentation, none of these features reliably dis- Treatment
tinguishes the suppurative from the nonsuppura- If an underlying associated disease is identified, this
tive form of cholangiohepatitis. should be aggressively treated. For example, in
Laboratory findings include a marked increase cases of bile duct obstruction, surgical correction is
in SALT activity, moderate increases in serum ALP usually necessary. This may involve biliary decom-
and GGT activity, and usually hyperbilirubinemia. pression if the obstruction can be relieved or
Concurrent bilirubinuria is also seen. Some cats rerouting of the bile duct through a cholecystoen-
have a mild nonregenerative anemia consistent terostomy. Concurrent inflammatory bowel dis-
with anemia of chronic disease. Ultrasound find- ease or pancreatitis should also be considered.
ings are nonspecific but may identify underlying In cases of lymphocytic-plasmacytic cholangio-
diseases such as pancreatitis and extrahepatic bile hepatitis, glucocorticoids are the drug of choice.
duct obstruction. Prednisolone (preferred over prednisone in cats
Definitive diagnosis depends on histologic due to the possibility of improved bioavailability of
examination of hepatic biopsy tissue. Cytologic prednisolone in some cats) is instituted at a dosage
examination is usually not reliable for establishing of 1 to 2 mg/lb body weight twice a day for at
the diagnosis. The disease is characterized by dif- least 1 month and subsequently tapered over 2 to
fuse involvement of the liver, so random-location 3 months when there is biochemical and clinical
hepatic biopsy is adequate for obtaining represen- remission. If there is positive growth on culture of
tative tissue. There is usually a prominent infiltrate hepatic biopsy tissue, an appropriate antibiotic is
of lymphocytes and plasma cells, lymphocytes given concurrently. Metronidazole (Flagyl) may
alone, or predominantly neutrophils in the portal also be a useful adjunct to treatment due to its
triads (depending on the form of the disease). immune modulatory effects. It is administered at a
Portal triad fibrosis, bile duct proliferation, and slightly reduced dosage of 3.5 mg/lb two to three
centrilobular accumulation of bile with bile casts times a day because it undergoes hepatic metabo-
in canalicular areas is also frequently present. Septa lism.
of fibrous tissue with a variable lymphocytic infil- In cats that are refractory to the above immuno-
trate often link portal tracts and form circum- suppressive regimen or with the sclerosing form
scribed nodules of hepatocytes. It has been (biliary cirrhosis), low-dose pulse oral methotrex-
suggested that the disease can progress to biliary ate in combination with prednisolone, metronida-
cirrhosis characterized by bridging portal fibrosis, zole, SAMe, and ursodeoxycholic acid is used. A
bile duct proliferation and hyperplasia, and nodu- total dose of 0.13 mg methotrexate is given at 12-
lar regeneration with minimal inflammation. hour intervals for a total of three doses over a 24-
Aerobic and anaerobic culture of hepatic tissue hour period. If this dose is well tolerated at 7-day
with or without bile (obtained via cholecystocen- intervals (based on hematologic and clinical evalu-
tesis) should be obtained. Culture is often positive, ation) and there is no biochemical improvement,
although it is not always clear if this is a primary or the first morning dose is doubled to 0.26 mg.
secondary event. In cats with suppurative cholan- Some cats need the dosage interval extended to
giohepatitis, the most common organisms cultured every 10 days because of GI side effects.
(in descending order of prevalence) are E. coli, Treatment of the suppurative form of feline
Staphylococcus, α-hemolytic streptococcus, Bacillus, cholangiohepatitis involves use of an appropriate
Actinomyces, Bacteroides, Enterococcus, Enterobacter, and antibiotic based on culture results of hepatic
Clostridia. Prior treatment with antibiotics may biopsy specimens. If culture results are negative,
result in false-negative cultures. amoxicillin–clavulanic acid (7 mg/lb body weight
The liver in cats with cholangiohepatitis may three times a day) or a quinolone antibiotic is usu-
appear large with rounded margins. The surface is ally a good choice. Metronidazole is effective
often irregular and nodular, although it may also against anaerobes and can be combined with
be smooth depending on the degree of nodular the antibiotics mentioned above at a dosage of
regeneration. The color is often a mottled red and 3.5 mg/lb body weight two to three times a
brown with the normal lobular pattern being day. Duration of therapy often ranges from 2 to
completely lost (reflecting distortion of the nor- 6 months. In many cases there is only a transient
CHAPTER 9 DISEASES OF THE LIVER AND HEPATOBILIARY SYSTEM 321
response to antibiotic administration and subse- to substantiate its efficacy and dosage in the dog
quent concurrent glucocorticoid administration and cat. The use of SAMe also appears helpful for
is often necessary. Clinical judgment is used in this disease. See section on CAH for detailed
this situation to determine when glucocorticoids description of this drug.
should be started. Some cases, however, are wors- Specific dietary management is generally not
ened by glucocorticoid administration, emphasiz- critical to a successful outcome; however, nutri-
ing the need for hepatic biopsy. Glucocorticoids tional support may be necessary. It is more impor-
therefore should only be given for the suppurative tant that the affected cat eat any balanced diet than
form as a last resort when antibiotics have failed. any specific diet. A protein-restricted diet is rarely
In virtually all cases without extrahepatic necessary in cats. In most cases, response to therapy
bile duct obstruction, the use of the hydroc- is rapid and tube feeding is not necessary. If there is
holeretic drug ursodeoxycholic acid (ursodiol; prolonged anorexia, nutritional support should be
Actigall or Urso) may be helpful (see discussion of provided by using an enteral feeding tube (percu-
ursodeoxycholic acid in section on chronic active taneous endoscopic gastrostomy [PEG] tube,
hepatitis). Ursodeoxycholic acid is a naturally esophagostomy tube, or nasoesophageal tube). Use
occurring dihydroxylated hydrophilic bile acid of feeding tubes is described in Chapter 12.
found in small quantities in normal human bile Vitamin E therapy is also recommended in
and in larger quantities in the bile of certain many types of hepatic diseases, including feline
species of bears. The exact mechanisms of its ben- cholangiohepatitis. Oxidative injury to the liver is
eficial effects in inflammatory hepatic diseases now well recognized in several types of inflamma-
remain controversial. It is believed that there is a tory processes. Free radicals are generated in
favorable change in the bile acid pool, rendering chronic hepatitis by the injurious effects of certain
retained endogenous bile acids less toxic by chang- drugs or toxins or by immunologic injury. These
ing the bile acid pool from the more toxic free radicals can damage cellular macromolecules
hydrophobic bile acids to less toxic hydrophilic via lipid peroxidation and thus participate in cellu-
bile acids. It is also believed that ursodeoxycholic lar injury and play an important role in initiating
acid has antiinflammatory and immunomodula- and/or perpetuating hepatic injury. Vitamin E
tory effects. Ursodeoxycholic acid has been used reduces oxidant injury to hepatic tissue by provid-
in the management of chronic hepatic diseases in ing protection from free radicals.Vitamin E is used
humans, including CAH, primary biliary cirrhosis, at a dosage of 100 to 200 units/day. Because bile
and primary sclerosing cholangitis. Significant acids are required for fat-soluble vitamin E absorp-
improvement in symptoms and laboratory param- tion and may be reduced with liver disease, a
eters has been reported in many patients undergo- water-soluble formulation should be used. This
ing treatment for these diseases. type of formulation is available at most health food
I have used ursodeoxycholic acid, either alone stores.
or in combination with other drugs, in patients The prognosis is fair to good unless the disease
with various cholestatic diseases (including dogs is histologically advanced. Many patients respond
with CAH and cats with cholangiohepatitis). The dramatically to glucocorticoid administration, and
drug is very well tolerated, and in some cases the most can eventually be weaned off medication.
response can be dramatic. Use of ursodeoxycholic However, some cats will relapse and need ongoing
acid in feline cholangiohepatitis complex should or intermittent treatment. Some cats require pred-
be considered as adjunctive (in combination with nisolone at a dosage of 0.5 to 0.7 mg/lb/day on a
immunosuppressive or antiinflammatory drugs or long-term basis (months to years) for successful
antibiotics) with any of the histologic forms of the control of the disease process. Fortunately, the
disease. Ursodeoxycholic acid is also a powerful long-term side effects of glucocorticoid adminis-
choleretic agent that can be used to treat sludged tration are minimal in the cat.
bile and cholelithiasis. The recommended dose is
6 to 7 mg/lb/day, administered either once daily Hepatic Necrosis and Toxic
or divided twice a day. The newer 250-mg tablet Hepatopathies
form of the drug (Urso) has made dosing more Hepatic necrosis often leads to acute hepatic fail-
convenient. The drug has minimal side effects, and ure. Because the hepatocyte is exposed to an
in my experience it may dramatically improve extensive portal and systemic venous circulation, it
therapeutic benefit. Studies need to be performed is susceptible to injury by a variety of etiologic
322 CHAPTER 9 DISEASES OF THE LIVER AND HEPATOBILIARY SYSTEM
agents. Hepatic necrosis can occur secondary to abnormalities include hypoglycemia and abnormal
other hepatic processes such as inflammation or clotting parameters. Hepatic function tests such
neoplasia, can be associated with known hepato- as serum bile acids and plasma ammonia con-
toxins, or can occur when no other cause is centration are often normal unless there is mas-
known. Causes of hepatic necrosis are listed in sive hepatic necrosis and hyperbilirubinemia.
Box 9-11. Laboratory abnormalities usually overlap those of
Clinical Features other diseases such as CAH and primary hepatic
Clinical signs of hepatic necrosis depend on the neoplasia.
degree of severity. Many patients are asympto- Histologic findings reflect the degree of hepatic
matic, with disease detected only by biochemical necrosis. The pattern of necrosis is differentiated
screening (such as many cases of hepatic trauma), from that seen in CAH by its location within lob-
whereas other cases have acute fulminant hepatic ules, by the appearance of neutrophils that enter to
failure. In the latter instance, affected patients range phagocytize cellular debris, and by the absence of
from profoundly depressed to comatose, with the lymphocytes and plasma cells as the predominant
degree of hepatic encephalopathy depending on the inflammatory cells.
cause and severity. Vomiting, anorexia, and fever Treatment involves withdrawal of known hepa-
are often seen. Icterus is often seen when there is totoxins or treatment of underlying conditions
periportal involvement. The presence of coagu- listed in Box 9-11 that are associated with hepatic
lopathies such as DIC reflect the degree of severity necrosis. Efforts must be made to look for
and usually manifest with GI bleeding, hema- these disorders associated with hepatic necrosis.
temesis, ecchymoses, and excessive bleeding at Additional treatment measures are aimed at pro-
venipuncture sites. viding optimum conditions for hepatic regenera-
Laboratory findings include profound increases tion and preventing secondary complications of
in SALT and SAST activity. Increased SALT activ- hepatic disease. These measures are discussed in
ity correlates with histologic findings only in the detail in the section on management of hepatic
initial period of hepatocellular injury, after which disease.
serum enzyme activity may persist or decline in
the following days despite the persistence of Approach to Nonspecific Increases
extensive necrosis. The activities of serum ALP in Hepatic Enzyme Activities
and GGT and serum bilirubin concentration Many patients will be detected as having
are variable and reflect the degree of cholestasis. increased serum activities of hepatic enzymes on
The degree of clinical severity is often poorly routine biochemical screening or when presented
correlated with measurements. Other variable with clinical illness. The clinician must try to
determine if an underlying nonhepatic cause is
present, including endocrinopathies (hyper-
adrenocorticism, diabetes mellitus, and hyperthy-
BOX 9-11 Causes of Hepatic roidism) and those disorders listed in Box 9-11. If
Necrosis no obvious underlying cause exists, the clinician
must determine whether clinical signs can be
Chemicals
attributed to hepatic disease. If these signs are
Drugs
Aflatoxins serious enough to cause illness, further work-up
Septicemia with hepatic function tests (bile acids or blood
Pancreatitis ammonia concentration), ultrasound examina-
Inflammatory bowel disease tion, and/or hepatic biopsy is warranted. If clini-
Viral agents cal signs are absent or mild, a baseline hepatic
Inflammatory hepatic disease (CAH) function test (generally serum bile acids assay) is
Systemic hypoxia run and is used as a monitoring parameter. Unless
Anemia hepatic function is significantly abnormal, a
Ischemic injury repeat chemistry profile and hepatic function test
Excessive copper storage
are run in 4 to 8 weeks. If these tests are persis-
Heartworm-associated (postcaval syndrome)
Trauma
tently abnormal, hepatic imaging and biopsy are
warranted, even in patients that remain clinically
CAH, Chronic active hepatitis. normal.
CHAPTER 9 DISEASES OF THE LIVER AND HEPATOBILIARY SYSTEM 323
hepatic failure. If these tests are abnormal, hepatic relationship to developing hepatic toxicosis. Of the
biopsy or decreasing the dosage of the anticonvul- 21 dogs, 13 were Labrador retrievers. Dogs ranged
sant may be warranted. from 4 to 15 years old (mean, 9.4 years). Carprofen
Two distinct forms of hepatotoxic injury are was administered for alleviation of signs of muscu-
related to anticonvulsant drug treatment. One loskeletal pain in all dogs. The amount of carpro-
form is characterized by the development of clini- fen administered ranged from 0.71 to 1.41 mg/lb
cal signs after extended periods of treatment. of body weight (mean, 1.06 mg/lb) orally every
Histologic findings include diffuse fibrosis, nodular 12 hours. The duration of treatment ranged from
regeneration, and various amounts of necrosis, lipi- 3 to 180 days (mean, 31 days). Clinical signs of
dosis, and inflammation that eventually lead to toxicosis were noticed for 18 dogs between 5 and
macronodular cirrhosis. The second form of 30 days (mean and median, 19 days) after initiation
hepatotoxic injury is metabolic hepatic failure of carprofen. Two dogs received carprofen for
with intrahepatic cholestasis that is distinct in his- 60 and 180 days before developing clinical signs.
torical, clinical, and histologic features from One dog received the drug for 54 days and did not
those associated with cirrhosis. There is a conspic- have clinical signs of toxicosis. The drug was dis-
uous absence of a necroinflammatory response continued after discovery of hepatic necrosis on a
versus other forms of drug toxicity or acquired biopsy specimen obtained for evaluation of possi-
canine hepatic disease unrelated to drug adminis- ble metastatic cancer in this dog. All Labrador
tration. retrievers developed clinical signs at an interval of
The prognosis is poor when histologic lesions 14 or more days after initiation of carprofen
are severe and hepatic failure has occurred. administration (mean and median, 20 days). One
Treatment involves withdrawal of anticonvulsant of these dogs received carprofen for only 3 days,
drugs if possible or use of alternative anticonvul- but clinical abnormalities developed 18 days after
sant drugs such as potassium bromide. There are the first dose.
no hepatotoxic effects associated with potassium Clinical signs associated with toxicosis were
bromide. There is no indication for the use of predominantly anorexia (17 dogs) and vomiting
glucocorticoids unless there is an active inflamma- (16 dogs). Other signs noticed less frequently were
tory component. The use of colchicine might be lethargy, diarrhea, polyuria, polydipsia, and hema-
indicated if fibrosis is a prominent feature (see turia. Physical examination revealed icterus in
section on chronic active hepatitis). The use of 15 dogs and ascites in 1 dog. The most common
ursodeoxycholic acid may also be indicated due to laboratory abnormalities were increases in serum
the presence of a significant cholestatic compo- activities of ALT (21 of 21 dogs), AST (14 of
nent in most cases. The use of SAMe may also be 15 dogs),ALP (20 of 21 dogs), and serum bilirubin
helpful. It should be emphasized that caution should be concentration (18 of 21 dogs). Hypoalbuminemia
used when attributing abnormal hepatic function and was seen in only 4 of 21 dogs. In addition, urinal-
hepatic failure to anticonvulsant administration because yses were performed in 9 dogs. In 7 dogs evidence
the incidence of this problem is low. Other laboratory and of renal disease was present (including isosthenuria
ancillary tests, including hepatic biopsy specimen analy- with azotemia, glucosuria, proteinuria, and evi-
sis, may well be justified in these patients. dence of epithelial cells and granular casts).
Carprofen Toxicity Hemogram, radiographic and ultrasonographic
Carprofen (Rimadyl) is a commonly used non- abnormalities were minimal. Histopathologic eval-
steroidal antiinflammatory drug (NSAID) to treat uation (performed in 18 of 21 dogs) revealed vary-
canine osteoarthritis (degenerative joint disease). ing degrees of vacuolar change, ballooning
It is estimated that the incidence of severe hepato- degeneration, necrosis of hepatocytes, bridging
toxic reactions from carprofen is 1.4 dogs per fibrosis, mixed-cellular inflammation, and accumu-
10,000. In one report 21 dogs were described to lation of bile pigment.
have hepatocellular toxicosis associated with Fifteen of the dogs were treated. Of these dogs,
administration of carprofen. At the time of the 12 were hospitalized. These 12 dogs received
report, over 500,000 dogs had received carprofen. intravenous fluids and antibiotics. Drugs used to
No dog in this report had evidence of a previous manage GI signs included histamine H2-receptor
significant hepatopathy or medical problems pre- antagonists, metoclopramide, sucralfate, and miso-
disposing to a hepatopathy. Various other drugs prostol. Three dogs were given ursodeoxycholic
were given to some dogs, with no apparent acid for 14 to 60 days.
CHAPTER 9 DISEASES OF THE LIVER AND HEPATOBILIARY SYSTEM 325
Four dogs died or were euthanized within 3 to drug intolerance and instructed to immediately
5 days after initial examination. One dog with discontinue the drug if these signs develop.
severe hepatic and renal failure also had perfora- Mebendazole-Induced Hepatic Disease
tion of the GI tract and diffuse intestinal ulcers Mebendazole (Telmintic) is an anthelmintic drug
documented during necropsy. It is unknown that is useful for its effects against ascarids, hook-
whether the GI tract ulcers and subsequent per- worms, and whipworms. Though generally con-
foration were directly attributable to carprofen sidered to be a safe drug, acute hepatic necrosis
use or indirectly attributable to hypoperfusion, associated with mebendazole administration to
ischemia, or uremia. The other 17 dogs fully dogs has been reported. In addition to this report,
recovered from drug-induced hepatic disease. All 45 additional cases of adverse drug reactions asso-
13 Labrador retrievers recovered from the hepatic ciated with mebendazole administration have
injury. The mortality rate for the other breeds was been reported to the U.S. Food and Drug
50%. For surviving dogs, vomiting resolved 1 to Administration. Based on these reports and exten-
5 days after supportive care was instituted and sive safety studies in normal animals and in
carprofen was discontinued. Inappetence was the induced hepatic disease, it is unclear whether
primary persistent clinical sign, which resolved 6 mebendazole is an intrinsic (predictable) or idio-
to 20 days after carprofen was discontinued. syncratic hepatotoxin. The fact that toxicity is of
Carprofen administration was discontinued but low incidence, difficult to reproduce experimen-
was repeatedly reinstituted and discontinued dur- tally, and apparently not dose related suggests that
ing a 1-month period for 1 dog. Clinical signs mebendazole is an idiosyncratic toxin, whereas the
resolved after discontinuance and reappeared in presence of toxicity in several members of one
association with drug administration. Laboratory kennel suggests that mebendazole is an intrinsic
evaluations were performed on all surviving dogs hepatotoxin.
3 to 4 weeks after onset of clinical signs. All dogs Regardless of the mechanism of toxicity, I
were markedly improved with regard to hepatic recommend that mebendazole not be used.
variables. Values determined 3 months after diag- Safer and more effective anthelmintics with a sim-
nosis of the toxic condition for 8 dogs were within ilar antiparasitic spectrum such as fenbendazole
reference ranges or only slightly increased. Fifteen (Panacur) or febantel (Drontol Plus) are recom-
of 17 surviving dogs were healthy 60 days after mended.
the episode of toxicosis. The other 2 dogs had
unrelated problems. Copper-Storage Hepatopathy
The results of this study suggest that the drug Pathophysiology
reaction to carprofen is idiosyncratic and host- The abnormal accumulation of copper in hepato-
dependent in nature. Progression of the condition cytes as a result of a metabolic defect in cop-
did not appear to correlate with the dose of per metabolism has been documented in the
carprofen, magnitude of hepatic enzyme activities, Bedlington terrier, West Highland white terrier,
or histopathologic severity of hepatic lesions. It is Skye terrier, and possibly the Doberman pinscher
also noteworthy that renal lesions were detected in breed. These disorders are similar (but not identi-
a number of dogs, a well-documented side effect cal) to Wilson’s disease in humans. Once excessive
of other NSAIDs. Although prescreening hemato- copper accumulates in hepatocytes, it results in
logic and serum biochemical analyses may not progressive hepatocyte destruction. The disease in
yield results that can be used to predict dogs that these breeds must be distinguished from other
will have adverse reactions to carprofen, evaluation causes of secondary hepatic copper accumulation.
of renal and hepatic function before administra- Copper is normally excreted through the biliary
tion of the drug is recommended. Dogs with renal tract. Therefore copper can accumulate in the
and hepatobiliary abnormalities may be poor can- liver with any cholestatic disorder, including
didates to receive this drug, or extra caution CAH or cirrhosis. In dogs with a primary copper-
should be used if carprofen is to be used in these storage disease, copper accumulates in the liver
dogs. In addition, serum biochemistry analysis before the development of hepatic damage or
should be obtained approximately 3 to 4 weeks cholestasis.
after starting carprofen to detect patients with Once copper is ingested, 40% to 60% is pas-
developing hepatic or renal disease. Owners sively absorbed in the proximal small intestine,
should be informed of the clinical signs of with the remainder lost in the feces. Some
326 CHAPTER 9 DISEASES OF THE LIVER AND HEPATOBILIARY SYSTEM
ingested copper is bound to the copper transport age a West Highland white terrier has reached its
protein, metallothionein. This portion is lost in upper limit of excess copper, and some dogs with
the feces. Unbound copper is absorbed from the excess hepatic copper will return to normal by
intestine and enters the portal circulation, where it 1 year of age. In the Skye terrier excessive copper
is bound to albumin and another copper transport accumulation in the liver appears to be related to
protein, transcuprein. Copper is then transported cholestasis, thought to result from a disorder of
to the liver. Within hepatocytes, copper is bound intracellular bile metabolism and abnormal bile
to cytosolic metallothionein and stored in lyso- secretion.
somes. Copper can then undergo two fates: it can Although Wilson’s disease in humans is similar
be excreted in bile or bound to the copper trans- to the disease in affected Bedlington terriers, there
port protein ceruloplasmin for transport to are several important differences. Wilson’s disease
peripheral tissues. Of these steps, the most impor- often leads to copper accumulation and subse-
tant step that regulates copper homeostasis is bil- quent damage in other tissues, including the brain.
iary excretion. In dogs with abnormal copper These manifestations are not seen in the dog. In
storage, copper accumulates within the lysosomes addition, the concentration of ceruloplasmin in
of hepatocytes. While in the lysosomes, copper is humans with Wilson’s disease is low, whereas the
innocuous. Once the lysosomal storage capacity is concentration of unbound copper is variable but
exhausted, copper breaks into the cytoplasm, may be high. In affected Bedlington terriers,
where it is toxic to the hepatocytes. Excessive serum copper and ceruloplasmin concentrations
hepatic copper can alter hepatic membrane per- are normal.
meability and interfere with normal hepatocyte Clinical Features
transport of proteins and triglycerides, and eventu- The disease is an autosomal recessive inherited
ally these hepatocytes undergo cellular lysis and defect. In studies in which large numbers of
necrosis. This can result in massive release of cop- Bedlington terriers have been screened by liver
per from damaged hepatocytes, which when taken biopsy for abnormal copper storage, approximately
up in the circulation can lead to a hemolytic crisis. 50% to 80% of dogs have been affected. Recent
In Bedlington terriers the disease is an auto- genetic studies by VetGen, LLC, suggest that only
somal recessive disorder. The specific defect in 30% of Bedlington terriers tested are homozygous
copper metabolism is thought to be excessive cop- clear of the disease, 39% are homozygous affected,
per binding by an abnormal metallothionein in and the remainder (31%) are heterozygous
the liver, which sequesters copper in the liver carriers.
(lysosomes) and reduces biliary excretion. The The copper-storage disease of Bedlington ter-
excess copper accumulation can be detected as riers can be categorized into three general groups.
early as 6 months of age and progresses with time. In the first group, affected dogs are usually young
It is unclear whether a subset of Doberman pin- adults. They have a short, fulminant course of
schers with CAH have a primary copper-storage acute hepatic necrosis and failure with a high mor-
disease or whether the abnormal hepatic copper tality rate. These dogs are usually icteric, anorectic,
concentration is secondary to the cholestasis asso- and vomiting, and they may undergo a hemolytic
ciated with the active hepatitis. One report, how- crisis because of copper toxicity from rapid lysis of
ever, documented increased hepatic copper hepatocytes. Most dogs die despite supportive
concentrations in two Doberman pinschers with measures. Sometimes a stressful event such as
subacute hepatitis in which cholestasis was not whelping or showing precipitates the onset of
present histologically, leading to the speculation signs.
that a genetic defect in copper metabolism might In the second group, affected dogs are usually
be the primary cause of hepatic inflammatory dis- middle-age or older. There is usually an insidious
ease in some Doberman pinschers. The disease in deterioration of their general condition, charac-
West Highland white terriers differs from the terized by chronic weight loss, anorexia, intermit-
copper-storage disease in Bedlington terriers by tent vomiting, and a general unthriftiness. On
comparatively lower concentrations of hepatic presentation many dogs have hallmarks of chronic
copper.West Highland white terriers can generally end-stage hepatic disease, including icterus and
tolerate up to 2000 µg/g (ppm) of copper. West ascites.
Highland white terriers rarely accumulate excess In the third group, affected dogs are asympto-
copper throughout their lifetime. By 6 months of matic and the disease is detected by biochemical
CHAPTER 9 DISEASES OF THE LIVER AND HEPATOBILIARY SYSTEM 327
screening (usually with increased SALT activity) nodular surface, with regenerative nodules reflect-
and documented by hepatic biopsy specimen ing end-stage liver disease.
analysis. It is thought that dogs in this group repre- Recently VetGen, LLC, began offering a
sent a prestage of the first two groups. In affected genetic test for copper toxicosis of the Bedlington
dogs of all groups, hepatic copper concentration terrier breed. This test uses a linked marker that
can be elevated as early as a few months of age. has two alleles, or marker types, called 1 and 2. It
Progressive increases in copper concentration usu- was found that over 90% of dogs that were 1/1
ally occur until 5 to 6 years of age (if the patient marker type were homozygous normal (clear of
survives), at which time levels slowly decline, the disease) and over 90% of dogs that were
although they never completely return to normal. affected with the disease were 2/2 marker type.
The most consistent laboratory abnormality is Most 1/2 dogs are carriers with the 2 allele usually
increased SALT activity, usually occurring once associated with the copper toxicosis disease allele.
hepatic injury has taken place. The SALT activity The finding of such a strong genetic disequilib-
usually correlates with the severity of the disease rium allows this to be potentially a valuable test. In
histologically, although enzyme depletion may interpreting the results, if the dog is a 1/1, it is
occur with terminal cirrhosis. Serum ALP activity more than 90% likely that it is homozygous nor-
and serum bilirubin concentration are variable, mal (clear of disease). If the dog is a 2/2, it is 72%
reflecting the degree of cholestasis. A presumptive likely that it is affected (over 90% of affected dogs
diagnosis should be considered in any Bedlington are 2/2, but 72% of 2/2 are affected; 24% are car-
terrier with increased SALT activity, although the riers). If the dog is a 1/2,VetGen data indicate the
disease needs to be confirmed with hepatic biopsy dog has a 95% chance of being a carrier. This test
specimen analysis. It must be pointed out that a may be helpful in making recommendations to
normal SALT level does not rule out the disease, breeders. If only 1/1 and 1/2 dogs are chosen for
and Bedlington terriers get other forms of hepatic breeding, the 2 gene could be eliminated in subse-
disease. quent generations. However, breeders should still allow
The diagnosis is confirmed with quantitative liver biopsy specimens to be obtained in 1/1 dogs to be
measurements of hepatic copper from hepatic used for breeding for the near to intermediate future
biopsy specimens. Normal hepatic copper con- because it is currently the only way to detect the small
centrations range from 91 to 377 µg/g (ppm) of number of affected dogs associated with the 1 allele.
liver on a dry weight basis, although there is VetGen provides a collection kit for DNA using a
marked variability among dogs of various breeds. soft cheek brush. This test can be completed
Formalin-fixed hepatic tissue is suitable for quan- before puppies are purchased at an early age.*
titative measurement. Dogs having values above Treatment
this range are considered affected, and most Early detection is essential. Therefore, because of
affected dogs have hepatic concentrations from 5 the high incidence in the breed, it is strongly rec-
to 50 times above normal. The disease can also be ommended that Bedlington terriers undergo bio-
documented by histochemical staining for copper chemical screening two to three times per year.
with rubeanic acid, Timm’s, rhodanine, or orcein Ideally a liver biopsy should be performed at
stains (most pathologists use rubeanic acid). In 1 year of age. Once a positive diagnosis is estab-
affected livers, granules of copper can be seen with lished, treatment depends on the stage of the dis-
these stains and are qualitatively estimated. The ease. In affected dogs, specific therapy involves the
measurement of copper-64 excreted in stool fol- administration of drugs that chelate copper and
lowing intravenous injection has also been advo- increase urinary excretion, as well as efforts to
cated as a noninvasive method of detecting decrease copper absorption. Traditionally, the drug
affected dogs. Histologic findings vary from nor- of choice has been D-Penicillamine (Cuprimine).
mal (with the exception of excess copper accumu- The recommended dosage for dogs is 4.5 to
lation) to varying severities of chronic hepatitis. 7 mg/lb two times a day. The drug should ideally
The disease progresses from focal hepatitis and be given before meals to maximize its effect. In
necrosis to features identical to those described for this manner, penicillamine will remove approxi-
CAH. Eventually the disease progresses to micro- mately 1000 µg/g (ppm) of copper per year. When
nodular and macronodular cirrhosis. The gross
appearance of the liver reflects the histologic *
VetGen can be contacted at (800) 483-8436 (3728
severity, ranging from normal to a fine or coarse Plaza Dr, Suite 1, Ann Arbor, MI 48108).
328 CHAPTER 9 DISEASES OF THE LIVER AND HEPATOBILIARY SYSTEM
given with meals the efficacy decreases by approx- is relatively slow. For this reason dogs with severe
imately half. Common side effects include or fulminant hepatitis secondary to copper accu-
anorexia and vomiting. Further dividing the mulation are not candidates for zinc therapy alone.
dosage into three to four daily doses and/or For these patients zinc is commonly combined
administering it with food often minimizes these with a chelating agent such as trientine. One study
signs. Unfortunately, these side effects may be demonstrated marked improvement in hepatitis
intolerable in some dogs and necessitate discontin- and hepatic copper concentrations in three
uation of the drug. It usually takes several years for Bedlington terriers and three West Highland white
hepatic copper concentrations to decrease to nor- terriers treated with zinc acetate as the sole decop-
mal, and therapy must be continued for life. In pering agent. The advantages of zinc for treatment
addition to chelating copper, D-Penicillamine has include efficacy, low cost, and minimal side effects.
antifibrotic properties, stabilizes lysosomes, and has With any of the above types of zinc supplements,
immune-modulating effects that might also be of it is important to measure serum zinc levels. The
benefit in managing this disease. goal is to achieve plasma zinc concentrations of
More recently tetramine cupruretic agents 200 to 600 µg/dl. After a 3- to 6-month loading
(2,2,2-tetramine; 2,3,2-tetramine) have been eval- period, the dose is decreased to approximately half
uated and have been shown to be effective decop- of the original dose. Serum zinc levels are then
pering agents, lowering hepatic copper and measured every 4 to 6 months. If the serum con-
increasing urinary excretion. These drugs are also centration drops below 150 µg/dl, the dose is
better tolerated than D-Penicillamine. Trientine increased to the original dose. To be effective, zinc
(Syprine; 2,2,2-tetramine) is my drug of choice. It must be given separately from food by at least
has cupruretic effects similar to those of D-Penicil- 1 hour because some food constituents such as
lamine (i.e., removing approximately 1000 µg/g phytates can bind zinc and diminish its efficacy. If
[ppm] of copper per year), although it may attack zinc causes vomiting, it may be mixed in a table-
a different copper pool. The recommended dose spoon of tuna fish (in oil) to minimize nausea.
is 7 to 14 mg/lb two times a day. Side effects are Vitamin C also might be useful because it
minimal in dogs compared with those caused by decreases copper absorption and increases copper
D-Penicillamine. Trientine is often used first or in excretion in the urine. In addition, dogs with
patients that experience side effects with D-Penicil- hepatic insufficiency are deficient in ascorbic acid.
lamine. Trientine is not always readily available, Ideally vitamin C should be given with meals.
but many pharmacists will order it or it can be The recommended dosage is 12 mg/lb/day. Dogs
ordered directly from the manufacturer (Merck). should also be fed a diet low in copper concentra-
2,3,2-Tetramine is an experimental drug that has tion. Some commercial diets low in copper
been shown to be a potent copper chelator. It is include Hill’s Prescription Diet l/d, Purina Fit &
not yet commercially available. Trim, Purina HiPro,Wayne, ANF, Pedigree, Nutro
Additional measures to reduce hepatic copper Natural Choice, and Precise. Diets high in copper
concentrations include supplementing the diet include Iams Eukanuba, Science Diet, and Blue
with zinc (0.7 to 1.15 mg/lb zinc gluconate three Seal Natural. Homemade diets that do not contain
times a day, 0.3 mg/lb zinc sulfate three times a excess copper should include meats, poultry, fish,
day, or 100 mg elemental zinc as zinc acetate two and dairy products. Foods with excessive copper
times a day). Zinc induces increased concentration should be excluded from the diet. These include
of intestinal metallothionein, which then binds eggs, liver, shellfish, organ meats, beans/legumes,
ingested copper to intestinal epithelial cells, thus mushrooms, chocolate, nuts, and cereals. Mineral
preventing copper absorption. As these cells are supplements containing copper should also be
sloughed, copper is subsequently lost in the feces. avoided. Other treatment measures are supportive
In addition, zinc will enhance removal of copper and symptomatic. These are discussed in detail in
from hepatocytes. Zinc lowers hepatic cop- the section on management of hepatic disease.
per indirectly by affecting multiple areas of copper
equilibria and by displacing copper in target tis- Infectious Inflammatory Diseases
sues. Zinc also induces hepatic metallothionein, Primary infections involving the liver are rare
which will then bind to and sequester excessive causes of hepatitis in dogs and cats. It is not
copper into an innocuous form compared with uncommon, however, to culture bacteria as a sec-
free copper. The rate of removal of hepatic copper ondary event in noninfectious hepatic diseases due
CHAPTER 9 DISEASES OF THE LIVER AND HEPATOBILIARY SYSTEM 329
4. Major solitary portal-azygous shunt dietary substrates; however, this finding seldom
5. Portal-azygous shunt with discontinuation of occurs in most cases.
the prerenal segment of the caudal vena cava The most common clinical signs are chronic
6. Left gastric vein to caudal vena cava depression, retarded growth, and weight loss. Most
7. The development of intrahepatic arterioportal dogs are stunted in appearance and “poor doers.”
fistula. Additional clinical signs include chronic GI signs
(vomiting, diarrhea), anorexia, polydipsia/polyuria,
Approximately one fourth of congenital por- and neurologic signs. It is often the neuro-
tosystemic shunts are intrahepatic in both dogs and logic signs that are most suggestive of a shunt,
cats, with most associated with a patent ductus and approximately 90% of cases have some degree
venosus. Single extrahepatic shunts, with a major of neurologic dysfunction related to hepatic
solitary portal–caudal vena caval shunt being the encephalopathy. Neurologic signs are often variable
most common, constitute 50% of portosystemic and wax and wane over time, including depression,
shunts. Most intrahepatic shunts are found in incoordination, behavioral changes (often aggres-
large-breed dogs (Doberman pinscher, golden sive), amaurotic blindness, seizures, dementia, and
retriever, Labrador retriever, Irish setter, Samoyed, stupor. An additional abnormality is intolerance of
and Irish wolfhound), whereas most extrahepatic anesthetic agents (often seen during routine neu-
shunts are seen in small-breed dogs (miniature tering in the first year of life). Any young patient
schnauzer,Yorkshire terrier, miniature poodle, and that has persistence of any of these signs (especially
dachshund). Dogs with intrahepatic shunts may neurologic or behavior changes) should be sus-
develop clinical signs at an earlier age than dogs pected of having a portosystemic shunt. In the cat,
with extrahepatic shunts, possibly due to a larger ptyalism is a common sign, as are central nervous system
volume of blood flow through intrahepatic shunts. (CNS) and GI signs. Any young cat with ptyalism
Approximately 2% of portosystemic shunts seen in and/or CNS signs should be evaluated for the presence of
small animals occur in cats. a portosystemic shunt.
The severity of clinical signs depends on the Laboratory Findings
volume and location of the shunt. Clinical signs Routine hemograms and serum chemistry profiles
result from impairment of hepatic function, lead- may be normal. Often there will be a mild nonre-
ing to hepatic encephalopathy. The most impor- generative microcytic anemia, and target cells may
tant factors that lead to encephalopathy are the be seen. Most patients have conspicuously normal
accumulation of blood ammonia and other gut- (or mildly increased) serum hepatic enzyme activ-
associated encephalopathic toxins that are nor- ities despite hepatic failure. This is because the
mally metabolized and cleared by the liver. With principal lesion is one of atrophy and lack of por-
portosystemic shunting, ammonia and other tox- tal blood supply. Cholestasis and hepatocellular
ins increase in the blood, leading to encephalopa- necrosis and leakage are not features of this disease.
thy. In addition, increased benzodiazepine-like Approximately 50% of patients will have mild
substances and amino acid derangements hypoalbuminemia (reflecting decreased albumin
(increased aromatic amino acids) occur with por- synthesis or increased volume of albumin distribu-
tosystemic shunts, contributing to encephalo- tion if ascites is present), and many patients (70%)
pathic signs. have decreased BUN concentrations (reflecting
Clinical Signs decreased synthesis from ammonia). Virtually all
Most cases are diagnosed in patients less than patients have normal serum bilirubin concentra-
1 year of age; however, there have been cases in tions. A fasting hypoglycemia may be seen.
patients as old as 10 years at the time of diagnosis. Because many of these changes are nonspecific,
There is no sex predilection. Clinical signs in hepatic function tests must be performed to docu-
patients with portosystemic shunts are highly vari- ment hepatic failure. Serum bile acid measure-
able. Because of the diverse nature of signs, the cli- ments and the ammonia tolerance test are the
nician must maintain a high index of suspicion in most sensitive tests to detect the presence of a por-
any young patient with unexplained signs compat- tosystemic shunt, being abnormal virtually 100%
ible with a shunt to avoid missing the diagnosis. of the time.
Clinical signs often change throughout the day or Approximately one third to half of dogs with
week. There may be an exacerbation of signs after portosystemic shunts have ammonium biurate
feeding, reflecting ammonia generation from crystals in the urine. These form because of the
332 CHAPTER 9 DISEASES OF THE LIVER AND HEPATOBILIARY SYSTEM
increased concentration of uric acid in the urine as then performed later (2 to 4 weeks or longer) to
a result of decreased hepatic conversion to allan- correct the shunt. I prefer the latter approach in
toin and increased urine concentration of ammo- small patients that are under anesthesia for a long
nia associated with hyperammonemia. When the time for the angiogram because of the poten-
urine is acidic and supersaturated with these sub- tial for hypothermia and prolonged anesthetic
strates, crystallization and precipitation can occur. recovery.
In addition to crystals in the urine, calculi can Portosystemic shunts can also be identified
form in the kidney or less commonly in the blad- with ultrasonographic guidance or nuclear scintig-
der. These stones usually are composed of ammo- raphy (see section on nuclear scintigraphy to eval-
nium acid urate or uric acid. Often the presence of uate the liver). If the latter diagnostic method is
renal calculi is an important clue that a portosys- used, mesenteric portography may still be neces-
temic shunt is present in a young patient. If calculi sary to locate the shunt if it is not readily seen
are removed and crystallographic analysis identifies during exploratory laparotomy.
that uric acid stones are present, the patient should Pathologic Findings
be evaluated for the presence of a portosystemic Histopathologic findings in patients with portosys-
shunt. temic shunts include diffuse hepatic atrophy, lobular
Radiographic Findings collapse, and proliferation of small hepatic arterioles.
The most reliable methods of confirming the pres- Atrophy is characterized by close proximity of the
ence of a portosystemic shunt are contrast radiog- portal triads, compressed hepatic cords, and incon-
raphy and nuclear scintigraphy. Plain radiographic spicuous portal veins. These findings are usually
findings are usually indicative of microhepatica, diagnostic of a congenital vascular anomaly, and
best determined by upright angulation of the hepatic biopsy specimen analysis represents another
stomach on a lateral projection. Because puppies method (in addition to radiographic findings) to
and kittens normally have large livers relative to obtain a diagnosis. However, these changes may be
their body size, this finding should increase the difficult to distinguish from portal vein hypoplasia
index of suspicion of a portosystemic shunt. The without a macroscopic shunt (formerly known as
diagnosis can then be confirmed by evaluating hepatic microvascular dysplasia; see section starting
hepatic blood flow with contrast radiography or on p. 334). The latter disorder has clinical and
nuclear scintigraphy. histopathologic features of a portosystemic shunt but
There are several techniques to evaluate hepatic has normal findings on mesenteric portography
blood flow, including intraoperative mesenteric and/or nuclear scintigraphy. Degenerative changes
portography, percutaneous splenoportography, in the brain suggestive of hepatic encephalopathy
and cranial mesenteric arterial portography. Intra- include leukopolymicrocavitation at the gray-white
operative mesenteric portography is the most matter junction, spongiform degeneration, and
practical technique to be applied in general prac- cortical necrosis.
tice. In addition to identifying the shunt, mesenteric Surgical Treatment
portography can also assess the residual portovenous The treatment of choice for single portosystemic
flow into the liver for prognostic importance. shunts is surgical ligation, because long-term
Following an injection into a mesenteric or jejunal medical management is palliative rather than cura-
vein, radiographic contrast medium normally flows tive. Before surgical intervention, medical manage-
into the portal vein and arborizes into the liver. In ment may be necessary to stabilize the patient.
patients with a portosystemic shunt, contrast Emergency treatment of hepatic encephalopathy
medium will bypass the liver and be seen in the includes cleansing enemas, oral antibiotics or lac-
caudal vena cava or azygous vein. If the caudal tulose administration (see section on management
extent of the shunt is cranial to T13, it is probably of acute hepatic failure). Surgical correction of
an intrahepatic shunt, whereas if the caudal extent multiple portosystemic shunts is usually not suc-
of the shunt is caudal to T13, it is probably an cessful because underlying portal hypertension
extrahepatic shunt. Once a shunt is identified on and hepatic pathologic abnormalities persist. (See
the angiographic study, one can proceed with sur- the References or surgical textbooks for detailed
gical correction during the same surgical proce- descriptions of surgical techniques.)
dure. Alternatively, the patient can be allowed to As a general rule small-breed dogs have extra-
recover from the anesthetic procedure used to hepatic shunts and large-breed dogs have intrahe-
obtain the angiogram and a second procedure is patic shunts. Single extrahepatic shunts are usually
CHAPTER 9 DISEASES OF THE LIVER AND HEPATOBILIARY SYSTEM 333
readily identified at surgery and can thus be iso- The constrictors come in various inner diameters
lated and attenuated or occluded (depending on (3.5, 5.0, or 6.0 mm) so that they can be used on
portal pressure). Surgical manipulation of intra- various-sized shunt vessels. The constrictor is
hepatic shunts is much more difficult, whereas made of hygroscopic casein material that is
extrahepatic shunt ligation is more adaptable to porous, surrounded by a metal outer ring. As the
general practice. Most extrahepatic shunts are porous material is gradually saturated with peri-
found terminating in the caudal vena cava toneal fluid, it expands. Because the outer metal
between the left phrenicoabdominal and renal ring prevents outward expansion, there is inward
veins. expansion, gradually occluding the central hole,
Once the shunt vessel is isolated, correction can which has the shunt vessel in it. In this manner
be made by gradual occlusion using an ameroid the shunt is gradually occluded, usually over a
constrictor (see below) or by occlusion with period of 4 to 8 weeks. Because there is gradual
cellophane banding on suture material. If suture is occlusion, there is no need to measure portal
used, portal pressures must be measured to deter- pressures. As the shunt is occluded the hepatic
mine whether complete occlusion is possible. This vasculature becomes more perfused, thus acting to
is readily done by placing a 3a or 5 Fr feeding prevent portal hypertension. In general there is
tube into a mesenteric vein and threading it into complete occlusion of single extrahepatic shunts
the portal vein. This is then connected to a saline using the ameroid constrictor in approximately
manometer to measure pressure, with the zero 80% to 90% of cases.
level standardized at the level of the femoral trian- Manipulation of intrahepatic shunts is techni-
gle or heart. Normal portal pressure is 10 to 15 cm cally more difficult. Several techniques have been
H2O (8 to 12 mm Hg), and most patients have described for attenuation of intrahepatic shunts.
normal or decreased portal pressure before shunt See the References and surgical literature for
manipulation. If a shunt is completely ligated, fatal details. If possible, the shunt can be isolated before
acute portal hypertension can develop. This results its entry into the liver or as it leaves the liver
from splanchnic congestion and stasis of blood, before entering the caudal vena cava. Otherwise
with the rapid development of endotoxic shock. the shunt is looked for by incising the prehepatic
During shunt attenuation with a silk suture, portal vena cava after occluding hepatic and vena caval
pressure should not exceed 20 to 23 cm H2O blood flow and located by noting the abnormal
(18 to 21 mm Hg) or 11 cm H2O (8 mm Hg) irregular margins of the shunt vessel as it enters the
above baseline. The silk ligature is placed as close vena cava from the inside. Alternatively, the shunt
to the vena cava as possible and gradually tight- can be located by a transportal approach follow-
ened while measuring portal pressure. Observing ing vascular occlusion. If the shunt cannot be
splanchnic viscera for signs of stasis, including occluded completely without causing portal
blanching of the bowel, hypermotility of the small hypertension, a novel approach has been described
bowel, and distended and pulsating jejunal arteries that involves complete intrahepatic shunt closure
is also important. Monitoring central venous pres- along with the surgical creation of a portacaval
sure may also be helpful to predict the presence of shunt using an external jugular vein graft. An
portal hypertension. With increased portal resis- ameroid constrictor is placed around the graft to
tance and decreased portal venous flow, central permit its gradual closure.
venous pressure drops because of decreased venous Dogs that have mild to moderate portal hyper-
return and splanchnic venous pooling. tension (20 to 23 cm H2O) following shunt
To avoid the need to measure portal venous manipulation usually have normal portal pressure
pressure and still allow complete occlusion of the within several weeks of surgery. These dogs often
shunt, attenuation can be accomplished with an have ascites secondary to the transient portal
ameroid constrictor.* This is a device that is hypertension, which disappears in 1 to 3 weeks as
shaped like a miniature donut that has a small portal pressure drops. Often the silk ligature used
opening allowing it to be placed around the to partially occlude a shunt will cause a reaction
shunt. It can be subsequently locked to prevent its that results in gradual complete occlusion of the
removal after placement around the shunt vessel. shunt over time.
A biopsy of the liver is always performed for
histopathologic evaluation and occasionally for
*
Research Instruments and Mfg, Corvallis, Ore. bacterial culture. If there are cystic or renal calculi
334 CHAPTER 9 DISEASES OF THE LIVER AND HEPATOBILIARY SYSTEM
concurrent with the portosystemic shunt, they can could be performed for complete shunt closure. In
be removed during the procedure for shunt cor- one study 50% of dogs undergoing partial shunt
rection if the patient is stable and the anesthetic closure developed complications associated with
time is not excessive. Otherwise a second surgery continued or renewed portosystemic shunting in a
is performed several weeks later to remove the uri- 4-year follow-up period despite excellent short-
nary calculi. A follow-up mesenteric portogram term results. This suggests that a second surgery
and hepatic biopsy can be performed at this time should be considered in these dogs.
to evaluate the shunt correction. Prognosis
Postoperative monitoring is important to The prognosis for medical management of con-
detect signs of severe portal hypertension, includ- genital portosystemic shunts is poor. Most patients
ing abdominal pain, hemorrhagic diarrhea, and have progressive hepatic atrophy, and eventually
endotoxic shock leading to death. Fortunately, the signs of hepatic encephalopathy become refractory
use of an ameroid constrictor or intraoperative to medical management. Occasionally a patient
monitoring of portal pressure makes this an will live to an old age (with or without medical
unusual complication. Hypoglycemia may occur if therapy), although later in life such patients often
the patient is not eating, necessitating intravenous have urate urinary calculi or signs of hepatic
glucose supplementation. Intravenous crystalloids encephalopathy. These cases are uncommon,
or colloids (if there is significant hypoalbumine- however.
mia) are essential in the immediate postoperative The prognosis for single extrahepatic shunts
period. Status epilepticus and generalized motor with surgical correction is excellent, unless severe
seizures can occur following shunt attenuation. portal hypertension persists (which is unusual).
These are usually first observed 3 days postopera- Clinical improvement is often seen shortly after
tively. The etiology of the seizures is unknown, surgical correction. Hepatic biopsy specimen
but one theory is that there may be stimulation of analysis obtained several months after surgical cor-
brain receptors for benzodiazepines associated rection may be normal if there is no concurrent
with the presence of the shunt. Following ligation portal vein hypoplasia. The results of surgical liga-
of the shunt, seizures may result from withdrawal tion of extrahepatic portosystemic shunts in cats
of benzodiazepine-like substances (documented to seem to be worse than in dogs, with only approxi-
be present in portal blood of dogs with portosys- mately 50% to 60% of cats having a favorable
temic shunts) following shunt ligation. The prog- outcome.
nosis is poor in my experience despite control of The prognosis for intrahepatic shunts is more
status epilepticus. The role of prophylactic anti- guarded due to the technical difficulties of the
convulsant drugs such as potassium bromide needs surgical correction and inability to completely
to be defined. attenuate the shunt without developing portal
Medical management of chronic hepatic dis- hypertension. Success depends in large part on the
ease should continue as needed to manage signs of skill and experience of the surgeon.
encephalopathy; however, most patients are
asymptomatic shortly after surgical shunt correc- Portal Vein Hypoplasia Without
tion. Patients should be evaluated 1, 3, and a Macroscopic Shunt (Formerly
6 months after surgery with serum biochemical Hepatic Microvascular Dysplasia)
and hepatic function tests (e.g., bile acids assay). Portal vein hypoplasia without a macroscopic
Persistent abnormal function suggests incomplete shunt (formerly referred to as HMD) refers to a
shunt closure, concurrent portal vein hypoplasia, microscopic pathologic malformation of the
or the development of multiple extrahepatic hepatic microvasculature. It is characterized by
shunts if portal hypertension results. If an ameroid small intrahepatic portal vessels, portal endothelial
constrictor or partial ligation is used to attenuate hyperplasia, portal vein dilation, random juvenile
the shunt, nuclear scintigraphy (or mesenteric por- intralobular blood vessels, and central venous mural
tography) is performed 2 to 3 months after surgery hypertrophy and fibrosis. It is thought that these
to evaluate for complete closure. If there is evi- lesions allow abnormal communication between
dence of incomplete shunt closure, nuclear scintig- portal and systemic circulation. It is important to
raphy is repeated 4 to 5 months following surgery. note that portal vein hypoplasia can occur as an
If there is still evidence of incomplete closure and isolated disease or in conjunction with macro-
the patient is still symptomatic, a second surgery scopic portosystemic shunts. In one large study
CHAPTER 9 DISEASES OF THE LIVER AND HEPATOBILIARY SYSTEM 335
58% of dogs and 87% of cats with portal vein (iatrogenic administration) amounts of glucocorti-
hypoplasia also had concurrent congenital por- coids. It represents one of the most common
tosystemic shunts. Dogs and cats with portal vein causes of increased serum hepatic enzyme activi-
hypoplasia can have clinical signs similar to those of ties and the most common diagnosis on hepa-
portosystemic shunts, including neurologic and GI tic biopsy specimen analysis in dogs. Steroid
abnormalities, as well as urate urolithiasis. Portal hepatopathy occurs only rarely in the cat. The
hypertension does not usually develop in dogs and etiology of changes in the liver induced by gluco-
cats with portal vein hypoplasia. corticoids is unknown. The likelihood that an
Breeds of dogs affected with portal vein individual patient will develop steroid hepatopathy
hypoplasia are similar to those with congenital following glucocorticoid administration is variable
portosystemic shunts, including Yorkshire and and depends on individual sensitivity, type, route,
Cairn terriers (a hereditary mechanism has been and duration of administration of the glucocorti-
described in this breed). Reports of dogs with por- coid. Some patients show minimal changes in
tal vein hypoplasia suggest that clinical signs and serum hepatic enzyme activities and morphologic
clinicopathologic features are similar to those of changes in the liver even after chronic glucocorti-
portosystemic shunts, although often not as severe. coid administration, whereas other patients have
A recent study of 42 cases comparing dogs with increased serum hepatic enzyme activities and
portal vein hypoplasia alone and dogs with portal morphologic changes that persist for weeks after a
vein hypoplasia concurrent with portosystemic single dose of a glucocorticoid. Changes can persist
shunts revealed that dogs with portal vein for several months after a single injection of a long-
hypoplasia alone were older and had higher values acting glucocorticoid or after chronic administra-
for mean corpuscular volume (MCV) and serum tion of oral glucocorticoids. Changes can also
total protein, albumin, creatinine, cholesterol, occur after topical or ocular administration of glu-
BUN, and blood glucose concentrations. In addi- cocorticoids.
tion, dogs with portal vein hypoplasia alone had Clinical Findings
lower preprandial and postprandial bile acid con- Clinical signs of steroid hepatopathy range from
centrations. The most discriminating variables for asymptomatic to those associated with glucocorti-
the two groups were postprandial bile acid con- coid excess. These signs include polyuria, polydip-
centrations, MCV, and serum albumin and choles- sia, polyphagia, endocrine alopecia, distended
terol concentrations. However, there is a large abdomen, and lethargy. There are usually no signs
overlap in values, suggesting that patients with pre- specifically related to hepatic failure with the
senting clinical findings of a congenital vascular exception of lethargy in severe cases. Hepatomegaly
anomaly must undergo an imaging study (nuclear is often identified on abdominal palpation and on
scintigraphy or mesenteric portography) to detect abdominal radiographs.
patients with macroscopic portosystemic shunts, Laboratory Findings
because these are amenable to surgical therapy. There are usually mild to moderate increases in
Further definition of portal vein hypoplasia SALT and SAST activities, and marked increases in
requires hepatic biopsy. A surgical wedge biopsy serum ALP and GGT activities in dogs with steroid
or laparoscopic “spoon” biopsy is preferred hepatopathy. These increases are variable. Occasi-
because they provide more hepatic lobules for onally the magnitude of elevation in serum activi-
evaluation. ties of the transaminases (ALT and AST) exceeds
Treatment for portal vein hypoplasia is sup- the magnitude of elevations of serum ALP and
portive because there is no macroscopic shunt to GGT activities. Serum albumin and bilirubin con-
attenuate. Dietary measures and agents used to centrations are usually normal (when these are
treat hepatic encephalopathy are described in the abnormal, other causes should be looked for). Often
section on management of chronic hepatic dis- the laboratory abnormalities seen with primary
ease. Many dogs remain asymptomatic with nonhyperbilirubinemic hepatobiliary disease and
dietary therapy alone, although the prognosis is with steroid hepatopathy are similar. The presence
variable. of increased serum bilirubin concentration virtually
eliminates steroid hepatopathy from the differential
Steroid Hepatopathy diagnosis of primary hepatobiliary disease.
Steroid hepatopathy can result from excessive The increase in serum ALP activity is attrib-
endogenous (hyperadrenocorticism) or exogenous uted to an isoenzyme that is different from that
336 CHAPTER 9 DISEASES OF THE LIVER AND HEPATOBILIARY SYSTEM
associated with production of orotic acid precur- concentration, resulting in clinical manifestations
sors. However, attempts to produce hepatic lipido- such as hemolytic anemia. Radiographs usually
sis in cats with orotic acid administration were reveal normal hepatic size or hepatomegaly.
unsuccessful, and urine orotic acid concentrations Ultrasonographic Findings
are normal in cats with hepatic lipidosis.Vitamin Ultrasonographic findings are almost always
B12 deficiency has also been speculated to be asso- abnormal in feline hepatic lipidosis. Findings
ciated with hepatic lipidosis. In one description of include overall increased echogenicity of hepatic
96 cats with hepatic lipidosis, vitamin B12 defi- parenchyma compared with falciform fat. In one
ciency was not documented. In that series, inspec- study this finding was seen in 100% of cats with
tion of plasma and urine for unusual fatty acids hepatic lipidosis. However, other studies have also
reflecting site-specific impaired mitochondrial found this relationship in diseases other than
oxidation did not reveal unique moieties, suggest- hepatic lipidosis, making this a nonspecific finding.
ing no obvious defect in a particular mitochon- In addition, there is increased beam attenuation by
drial enzyme. the liver, and borders of hepatic vessels are difficult
Clinical Features to visualize. Other underlying disorders, such as
As mentioned earlier, most cats with hepatic lipi- pancreatitis, may also be detected with an ultra-
dosis are obese. There is usually a period of sound examination.
anorexia followed by signs typical of hepatic fail- Pathologic Findings
ure. In some cases a known illness, stressful event The diagnosis of feline idiopathic hepatic lipidosis
(e.g., boarding, travel), or diet change may cause is based on histologic findings and the absence of
the initial period of anorexia. In most cases, how- other concurrent diseases that are known to cause
ever, no initiating cause is known. When hepatic lipid accumulation in the liver (see Box 9-13).
lipidosis occurs, clinical signs include inappetence, Typical histopathologic features are a diffuse lobu-
weight loss, vomiting, and jaundice. Physical lar fatty infiltration within individual hepatocytes.
examination findings include obesity with evi- The lipid accumulation is usually macrovesicular
dence of dorsal muscle wasting, jaundice, and in nature, although it can be microvesicular in
possible hepatomegaly. some cats. Usually there is evidence of intrahepatic
Laboratory and Radiographic Findings cholestasis. The diagnosis can often be made by
Laboratory findings include marked elevations in analysis of fine needle aspiration of the liver or
serum hepatic enzyme activities, especially ALP impression smear made of hepatic biopsy speci-
and to a lesser extent the transaminases (SALT, mens. Cytologic features include vacuolated hepa-
SAST). Because the half-life of ALP is very short in tocytes with minimal inflammation. However,
the cat (6 hours), activity of this enzyme is only cytologic examination cannot exclude the pres-
increased in the serum with severe hepatobiliary ence of concurrent diseases such as cholangiohep-
disease. In hepatic lipidosis the activity of ALP is usually atitis and lymphoma.
markedly elevated and often higher than in any other Grossly the liver in cats with hepatic lipidosis is
form of hepatic disease in cats. Hepatic lipidosis is also usually large, friable, and has slightly rounded mar-
the most common hepatobiliary disease in the cat gins with a smooth surface. The color is usually
to result in a magnitude of increased ALP activity yellow with an accentuated lobular pattern.
exceeding that of serum GGT activity. Serum Treatment
total bilirubin concentration is usually increased If precipitating causes of the anorexia can be iden-
and reflects the degree of intrahepatic cholestasis. tified, they should be addressed. These include
Coagulation abnormalities (especially elevated environmental influences such as diet changes and
PIVKA times) are also common, occurring in boarding. If concurrent diseases are identified, such
almost 50% of cats in one study. However, overt as cholangiohepatitis, inflammatory bowel disease,
bleeding (including from hepatic biopsy sites) is or pancreatitis, they should be treated.
rare in my experience. Hypokalemia was present in The goal of treatment is to reverse the meta-
25% to 30% of affected cats and was found to be a bolic changes that resulted in mobilization of free
negative prognostic factor. Postprandial serum bile fatty acids occurring during starvation. This is
acid concentrations are almost always abnormally usually accomplished with aggressive force-
elevated. Hypophosphatemia was present in 10% to feeding. In mild cases, methods to stimulate volun-
15% of cats in one report. Oral alimentation may tary oral intake may be effective. Heating food and
result in a further decline in serum phosphorus adding seasoning and salt substitutes to food may
CHAPTER 9 DISEASES OF THE LIVER AND HEPATOBILIARY SYSTEM 339
be helpful. However, tube feeding seems to be weight at any feeding. Attempts are made to grad-
necessary in most cases. This is best accomplished ually increase the feeding volume to maintenance
with a PEG tube (No. 18 to 20 Fr), esophagos- over the first 3 to 5 days.
tomy tube (No. 18 to 20 Fr), or nasoesophageal Antiemetics may be necessary to prevent
tube (No. 5 Fr). My preference is to place a PEG vomiting during the first few days (or longer) of
tube in most cases, often when the cat is under treatment in many cases. The drug of choice is
general anesthesia for the hepatic biopsy proce- metoclopramide (Reglan). This is given at a
dure if analysis of an impression smear of the dosage of 2.5 to 5 mg 30 minutes before feeding.
biopsy sample is suggestive of hepatic lipidosis. In most cases it works when given through the
This avoids the stress of a second anesthetic proce- feeding tube (a liquid form is available for this
dure. However, there are some cats that are clearly purpose). Occasionally subcutaneous administra-
not stable enough to undergo an anesthetic proce- tion or constant intravenous infusion may be
dure for placement of a feeding tube. In these necessary. Other strategies to control vomiting
cases, cats often never recover completely from the include the addition of other antiemetics such as
procedure. In these patients it is usually much safer prochlorperazine (Compazine), chlorpromazine,
to obtain a biopsy specimen under local anesthesia or ondansetron. Other strategies are to adminis-
or to rely on cytologic analysis of a fine needle ter a liquid enteral formula (CliniCare) by con-
aspirate. This is then followed by placement of a stant infusion or to decrease the amount of water
nasoesophageal tube with the cat awake. This added to the cat food gruel to decrease the vol-
allows administration of a liquid nutritional for- ume administered and still provide the same
mula (such as CliniCare [Pet-Ag]) on a temporary amount of calories. When diluted with one part
basis. Constant administration with an infusion water to two parts food, the gruel contains
pump or gravity flow (versus bolus feeding) is also 1.0 kcal/ml.
helpful if vomiting is a problem during the initial Various dietary supplements have been proposed
few days of treatment. These cats often have elec- to be helpful in treating cats with idiopathic hepatic
trolyte disturbances such as hypokalemia and lipidosis. Carnitine supplementation seems to
should also be stabilized with appropriate intra- improve survival rates and shorten recovery times.
venous fluids (non–lactate-containing fluids sup- In one report (n = 57) supplementation with
plemented with potassium chloride or potassium L-carnitine (250 to 500 mg/day) was advocated
phosphate).When the cat is more stable, a PEG or based on the possibility that there is a relative carni-
esophagostomy tube is then placed for long-term tine deficiency. Compared with historical controls,
use at home. These large-bore tubes are preferred cats that received L-carnitine had a recovery rate of
because they are more comfortable to the cat than 81% compared with a recovery rate of 37% in cats
nasoesophageal tubes and allow the owner to feed that did not receive L-carnitine. Cats that received
blended cat food at home. L-carnitine and gastrostomy tube feedings had
The total calorie intake should be 28 to a recovery rate of 89% (cats that did not receive L-
36 kcal/lb body weight per day. If a large-bore carnitine but had gastrostomy tube feedings had
tube is used, a balanced commercial cat food gruel a recovery rate of 29%). In this report, taurine sup-
(e.g., Hills Feline p/d [674 kcal per can] or c/d plementation (250 to 500 mg/day) was also advo-
[604 kcal per can]) can be used as the feeding solu- cated because many cats with hepatic lipidosis have
tion. These are generally diluted 1:1 with water, decreased serum taurine concentrations. Taurine is
to make a gruel containing approximately important because this amino acid is used for oblig-
0.75 kcal/ml. They can also be diluted 1:2 with atory bile acid conjugation in the cat and may mod-
water to make a gruel containing approximately ify the injurious potential of retained bile acids and
1.0 kcal/ml. Restricted protein diets are not indi- increase their renal excretion. Thiamine should also
cated unless there are overt signs of hepatic be provided (100 mg by injection or orally two
encephalopathy present (such as ptyalism). Initially times a day for 3 days) if there is evidence of thi-
feeding is started at one half the calculated amount amine deficiency (ventral neck flexion).Vitamin E
for the first 24 to 48 hours. The calculated daily may be helpful to minimize oxidative hepatic
requirement is divided into four to six feedings per injury. SAMe administration (9 mg/lb/day) may
day initially. Eventually most cats tolerate the nec- also help speed recovery. Vitamin K supplementa-
essary volume in three to four feedings per day. tion is used if overt bleeding is detected or sus-
The volume should not exceed 14 ml/lb body pected. If there is prolonged recovery (rare),
340 CHAPTER 9 DISEASES OF THE LIVER AND HEPATOBILIARY SYSTEM
from intrahepatic disease. Following injection created. Clinical signs include depression, fever,
of 99mTc-diisopropyl iminodiacetic acid (di- and vomiting. Empirical antibiotic administration
sofenin) into patients with unobstructed biliary is usually effective in controlling these episodes.
tracts, there is nuclear activity in the intestine
within 3 hours. There is failure to visualize the Cholelithiasis and Choledocholithiasis
intestine with nuclear imaging by 3 hours in Etiology
patients with biliary obstruction. In one study, this Choleliths are rare in dogs and cats, and the etiol-
method was 83% sensitive and 94% specific (91% ogy is unknown. Most theories implicate bile sta-
accurate) in diagnosing extrahepatic biliary sis, infection, and changes in bile composition.
obstruction. Finally, hepatic biopsy often suggests Choleliths in dogs and cats have been reported
the presence of extrahepatic biliary obstruction. to contain primarily cholesterol and bilirubin.
Treatment Relative percentages of these components are vari-
Treatment of bile duct obstruction depends on able, and mixed stones often occur. Additional
the underlying etiology (see Box 9-1). In most components include calcium, magnesium, and
cases, specific medical therapy is not possible and oxalates. If choleliths are analyzed by methods used
symptomatic care or surgery is necessary. Approxi- for cystic calculi, cholesterol and bilirubin contents
mately 80% of patients with pancreatitis that will not be determined.
results in bile duct obstruction will eventually Clinical Findings
resume normal bile flow without surgical inter- Cholelithiasis is usually asymptomatic unless
vention if given appropriate supportive care and associated with cholecystitis or obstruction of
enough time. In these cases obstruction is probably bile flow. In one report approximately 75%
associated with acute edema and inflammation of choleliths were discovered at necropsy and were
around the bile duct.When this resolves, bile duct not associated with clinical signs. When clinical
patency returns. Therefore if pancreatitis is sus- signs are present, they are often intermittent.When
pected as the cause of biliary obstruction, support- cholecystitis is present, there is often fever, abdom-
ive care is warranted in the initial period. If there is inal pain, and vomiting. When bile duct or cystic
no biochemical or clinical improvement within duct obstruction occurs, jaundice and other signs
2 weeks, patency is unlikely to spontaneously of extrahepatic biliary obstruction are seen.
occur and surgical intervention is warranted. Physical examination findings usually reflect the
During this period, nutritional support with degree of abdominal pain and jaundice.
jejunostomy tube feeding or total parenteral nutri- Laboratory findings may be normal or similar
tion (TPN) may be required. There is no specific to those seen with extrahepatic biliary obstruc-
medical therapy for bile duct obstruction caused tion, including increased serum activities of
by pancreatitis. hepatic enzymes and bilirubin concentration.
Surgical treatment is usually necessary for most Radiographic findings depend on whether
other causes of bile duct obstruction. Surgery is choleliths are calcified. In most cases there is not
intended to establish patency of the extrahepatic enough calcium in the stones to make them
biliary system with the intestine. The procedure radiopaque. However, when they are calcified, they
used depends on the location of the obstruction, are seen in the area of the gallbladder or rarely in
the degree of distention of the common bile duct the area of the common bile duct. Ultrasonog-
and gallbladder, the presence of concurrent chole- raphy is the modality of choice in detecting
cystitis, and the underlying disease. The most choleliths, because the gallbladder is readily seen
common procedures performed are cholecystoje- on an ultrasonographic examination. Choleliths
junostomy or cholecystoduodenostomy. If the appear as a hyperechoic area with a hypoechoic
gallbladder is infected and the common bile duct acoustic shadow. It can also be determined by
is large enough, a cholecystectomy and choledo- ultrasonography whether there is gallbladder and
choenterostomy is indicated. A detailed descrip- biliary duct distention. A thickened gallbladder
tion of these procedures is beyond the scope of wall with inspissated bile suggests the presence of
this chapter. The reader is referred to the surgi- cholecystitis.
cal literature for more information. Recurrent Treatment
cholangitis and/or cholecystitis can be sequelae Surgical intervention is usually the treatment of
to biliary-enteric anastomoses; however, this is sel- choice unless the patient is asymptomatic. Usually
dom a clinical problem if a large enough stoma is the procedure of choice is cholecystectomy, espe-
342 CHAPTER 9 DISEASES OF THE LIVER AND HEPATOBILIARY SYSTEM
cially if there is concurrent cholecystitis. An alter- biliary duct distention, cholelithiasis, thickening of
native is cholecystotomy and stone removal. If the gallbladder wall, and inspissated bile.
there is common bile duct obstruction that cannot Treatment
be relieved, a cholecystoenterostomy or choledo- In mild cases treatment involves an appropriate
choenterostomy will be necessary. At surgery bile antibiotic based on results of bile culture. In these
should be cultured aerobically and anaerobically, so patients the prognosis is fair. In severe cases,
an appropriate antibiotic can be administered to including those with necrotizing or emphysema-
manage concurrent cholangitis and cholecystitis. tous cholecystitis, the treatment of choice is chole-
Additional therapeutic methods used to manage cystectomy. In many cases the gallbladder is
choleliths in humans include endoscopic removal, ruptured at the time of surgery. In this situation
chemical dissolution, and extracorporeal shock cholecystectomy and exploration of the abdomen
wave lithotripsy. These methods have not been for stones that escaped the gallbladder are required.
evaluated in small animals. A high-protein, low- Patency of the bile duct must be established and
cholesterol diet might be helpful to prevent recur- treated appropriately with diversion procedures if
rences. necessary. In cases without gallbladder rupture, it
is still advisable to remove the gallbladder because
Cholecystitis it will be easier to treat the infection if the source is
Etiology removed. Aerobic and anaerobic cultures of bile,
Cholecystitis is rare in the dog and cat. Predisposing calculi, and the gallbladder wall are mandatory to
factors include cholelithiasis, bile stasis, ascending determine appropriate antimicrobial therapy.
biliary tract infection, and bacteremia with second- Pending culture results, a combination of an
ary cholangitis and cholecystitis. Cholecystitis is aminoglycoside or quinolone and ampicillin is
most commonly associated with complete or par- recommended. In one large study the most com-
tial bile duct obstruction. Necrotizing cholecystitis mon bacteria isolated were E. coli. Other bacteria
often results in either chronic or acute gallbladder cultured included Klebsiella sp., Clostridium sp., and
rupture with secondary bile peritonitis. Pseudomonas sp. Aggressive fluid support is also
Clinical Findings mandatory.
In mild cases, signs may be intermittent and Prognosis
include vomiting, fever, and abdominal pain. In The prognosis is guarded to poor in severe cases.
acute necrotizing cholecystitis, signs include vom- Early diagnosis and surgical intervention is the key
iting, anorexia, abdominal pain, and fever. Many of for successful therapy. Death is usually attributed
these patients will show signs of shock, including to sepsis, shock, peritonitis, and stress of anesthesia.
increased heart rate, pale mucous membranes, poor Therefore patients that show signs compatible with
capillary refill, and weak pulses. When gallbladder cholecystitis should have the diagnosis aggressively
rupture occurs, signs of bile and septic peritonitis pursued with serial abdominal paracentesis, ultra-
will result. sonography, peritoneal lavage, abdominal radiogra-
Laboratory findings in severe cases include a phy, and serial hemograms. When the diagnosis is
neutrophilic leukocytosis with a left shift, hypopro- suggested, surgical exploration should not be
teinemia, hypoglycemia, and increased BUN con- delayed.
centration. These changes are associated with sepsis
and endotoxic shock. In addition, there are usually
increased serum hepatic enzyme activities and Hepatic Neoplasia
increased serum bilirubin concentration if there is Incidence
biliary obstruction. Abdominal paracentesis may The liver is frequently affected with primary or
reveal evidence of septic or bile peritonitis. metastatic neoplasia. Primary tumors account for
Radiographic findings include decreased 0.6% to 1.3% of all neoplasms in the dog.
abdominal detail if there is leakage of bile and Metastatic tumors occur at least twice as fre-
peritonitis. If choleliths are present, they may quently as primary tumors. Hepatic neoplasia
be seen radiographically if they are calcified. occurs less frequently in the cat with the excep-
Some cases have gas in the gallbladder (emphysema- tion of malignant lymphoma and myeloprolifera-
tous cholecystitis) if there is a gas-forming organism tive diseases. The prevalence of hepatic neoplasia
involved (usually Clostridium spp. or E. coli). in the cat is 1.5% to 2.3%. The most common pri-
Ultrasonographic findings include gallbladder and mary hepatic neoplasms in the dog in order of
CHAPTER 9 DISEASES OF THE LIVER AND HEPATOBILIARY SYSTEM 343
frequency are hepatoma, hepatocellular carci- currently untreatable, usually rapidly progressive,
noma, cholangiocarcinoma (bile duct carcinoma), and highly metastatic and have a grave prognosis.
fibroma, fibrosarcoma, hemangioma/heman- Metastatic tumors are only treatable with
giosarcoma, leiomyoma, osteosarcoma, and hamar- chemotherapy. Lymphoma is the most respon-
toma. The most common metastatic tumors in the sive tumor to chemotherapy. Various protocols
dog that involve the liver are lymphoma and have been described, and most consist of various
hemangiosarcoma. Other important primary sites combinations of prednisone, cyclophosphamide
are the mammary glands, adrenal gland, pancreas, (Cytoxan), vincristine (Oncovin), doxorubicin
bowel, bone, lung, and thyroid gland. Metastasis to (Adriamycin), and L-asparaginase (Elspar). The
the liver can occur via the portal vein, hepatic reader is referred to veterinary oncology literature
artery, lymphatics, or by direct extension. Spread for details of these protocols. The prognosis with
from the portal circulation is most common. In hepatic involvement is similar to that of multicen-
the cat, malignant lymphoma and myeloprolifera- tric involvement. In cats with well-differentiated
tive diseases are the most common metastatic lymphocytic lymphoma of the liver, the prognosis
tumors. Nonhematopoietic hepatic neoplasms in is better in my experience, with survival times
cats include benign bile duct adenomas, bile duct usually between 1.5 and 2 years or longer when
adenocarcinomas, and hepatocellular carcinoma. treated with a combination of prednisone and
Most hepatic tumors, with the exception of lym- chlorambucil (Leukeran). Hemangiosarcoma can
phoma, are seen in older patients. Hepatic neopla- also be palliated with chemotherapy (using
sia is reviewed in detail in Chapter 11. doxorubicin plus dacarbazine, or the combination
of vincristine, doxorubicin, and cyclophospha-
Clinical Signs mide). In humans hepatic arterial infusions of
Clinical signs of hepatic neoplasia depend on the chemotherapeutic agents or embolization agents
extent of involvement. In many cases of primary (such as iodinated poppyseed oil) using a pump
neoplasia, especially hepatic adenomas and adeno- delivery system or via angiography procedures are
carcinomas, signs are not seen until the tumor is more efficacious than systemic administration for
very advanced. When symptomatic, patients show certain tumors, allowing higher regional drug
signs typical of other hepatic diseases, including concentrations. These methods have not been
anorexia, lethargy, vomiting, polyuria, and poly- evaluated extensively in small animals.
dipsia. If there is involvement of the biliary system
by direct involvement (cholangiocarcinoma) or by MANAGEMENT OF
impingement of an extrahepatic bile duct, jaun-
dice may be seen. In many cases hepatomegaly can
HEPATIC DISEASE
be detected on physical examination. Clinical signs Many types of hepatic disease are managed with
of metastatic neoplasia involving the liver tend to specific treatment modalities. Examples of disor-
be more severe earlier in the disease, because more ders with specific treatments are listed in Table 9-2.
of the liver is usually affected. In addition to signs In addition to specific treatment, many patients
typical of hepatic failure, patients may also show with hepatic disease require general supportive
signs typical of their primary tumor location. care to manage the acute and chronic aspects of
the derangements seen with hepatic failure. This
Treatment and Prognosis discussion will concern therapeutic efforts com-
The treatment of hepatic neoplasia depends on the mon to the management of hepatic disease in gen-
type of tumor and extent of involvement. Hepa- eral. Refer to the discussion of specific hepatic
tomas and hepatocellular carcinomas grow very diseases for appropriate specific therapy.
slowly and are often localized to a single lobe of the
liver. They are often amenable to surgical resection
and have good long-term prognosis. Up to 75% of Management of Acute Hepatic
the liver can be resected without significant hepatic Failure
dysfunction, and regeneration usually occurs within The cornerstone of treating acute hepatic failure
6 to 8 weeks. Less commonly, hepatocellular carci- includes elimination of the inciting cause (such as
nomas are nodular or diffuse. In these cases the drugs or toxins), providing optimal conditions for
prognosis is poor. Cholangiocarcinomas are usually hepatic regeneration, preventing complications,
widespread and either massive or diffuse. They are and reversing derangements that occur with
344 CHAPTER 9 DISEASES OF THE LIVER AND HEPATOBILIARY SYSTEM
hepatic failure. The important derangements that immediately. In general the fluid of choice is half-
may be seen include dehydration and hypovolemia, strength saline (0.45%) with 2.5% dextrose, sup-
hepatic encephalopathy, hypoglycemia, acid-base plemented with potassium chloride. Potassium
and electrolyte abnormalities, coagulopathies, gas- chloride should be added at the rate of 30 mEq/L
tric ulceration, sepsis, and endotoxemia. of fluids until serum potassium concentration is
known, at which time the concentration can be
Dehydration, Hypovolemia, and adjusted. Ringer’s solution or normal saline (0.9%)
Electrolyte Disturbances are acceptable alternatives, but their higher sodium
Many patients with severe hepatic disease have content makes them less desirable because many
vomiting, diarrhea, and anorexia. Therefore dehy- patients with hepatic disease have excessive
dration can readily occur. In addition, patients sodium retention and their administration can
with ascites already are using all of their circula- exacerbate ascites. Lactated Ringer’s solution
tory reserve function to maintain intravascular should be avoided because lactate must be con-
volume and tissue perfusion.When additional fluid verted to bicarbonate in the liver. Care must also
losses (such as vomiting or diarrhea) occur, hypo- be taken not to administer fluids too aggressively
volemic shock can result. In addition to volume because patients with hepatic disease cannot effi-
depletion, these patients frequently have elec- ciently excrete a salt and water load in response to
trolyte and acid-base disturbances. Patients with volume expansion, thus exacerbating ascites and
hepatic disease frequently have hypokalemia in portal hypertension. Diuretics such as furosemide
addition to total body potassium depletion. should be given with caution because these can
In addition to other deleterious effects, hypo- exacerbate hypovolemia, prerenal azotemia,
kalemia contributes greatly to the severity of hypokalemia, and metabolic alkalosis.
hepatic encephalopathy. Often potassium supple-
mentation makes an enormous difference in the Acute Hepatic Encephalopathy
treatment of these patients. The most common The approach to managing acute hepatic
acid-base disturbance with hepatic disease is alka- encephalopathy involves reducing the formation
losis, although other disturbances can be seen. If and absorption of encephalopathic toxins from the
prerenal azotemia occurs, excess urea will diffuse intestinal tract, avoidance of drugs that exacerbate
into the colon, where it becomes a substrate for encephalopathy (e.g., tranquilizers, anticonvul-
ammonia production and thus worsens enceph- sants, anesthetics), controlling GI hemorrhage, and
alopathy. Appropriate fluid therapy will minimize appropriate dietary management. Factors that pre-
this deleterious effect. cipitate metabolic changes that can lead to
To manage these derangements, aggressive encephalopathy are listed in Box 9-14. These
intravenous fluid therapy is often needed. The factors must be avoided or treated if possible.
fluid of choice may be determined by measure- Decreasing Encephalopathic Toxins
ment of serum electrolyte and arterial blood The therapeutic efforts designed to reduce forma-
gas levels. If arterial blood testing is not available, tion and absorption of encephalopathic toxins are
the serum bicarbonate concentration can be esti- primarily directed towards reducing ammonia
mated from the serum total CO2 concentration. absorption, although other encephalopathic toxins
However, these values are usually not available are also important, including benzodiazepine-like
CHAPTER 9 DISEASES OF THE LIVER AND HEPATOBILIARY SYSTEM 345
had the fewest problems with meperidine Another drug that might have potential for
(Demerol). This drug is used at a lower dose than managing GI ulceration is misoprostol (Cytotec), a
in patients with normal hepatic function. synthetic prostaglandin E1 analogue. It has been
Controlling Gastrointestinal Hemorrhage approved for use in humans and has also under-
GI hemorrhage must also be controlled. Patients gone clinical evaluation in veterinary medicine as
with hepatic disease are prone to GI hemorrhage a prophylactic agent for NSAID-induced ulcers. It
because gastrin concentration may be increased acts by stabilizing the protective mucous layer in
(due to decreased hepatic clearance and increased the stomach, increases epithelial cell turnover, and
secretion stimulated by excess bile acids), resulting inhibits gastric acid secretion. I have used it on a
in gastric hyperacidity, and because microthrombi limited basis at a dosage of 1 to 2.5 µg/lb body
in the mucosal microcirculation (if DIC is present) weight orally three to four times a day in the dog.
result in inability to handle back-diffused hydro- Therapeutic trials are needed to further define its
gen ions. In addition, patients with hepatic disease role in managing GI hemorrhage in animals with
often have coagulopathies that exacerbate any hepatic disease.
bleeding tendency. The result of GI hemorrhage is It is important to note that blood transfusion
increased ammonia production because blood is should be avoided unless absolutely necessary. Red
a substrate for bacterial conversion to ammonia blood cells have a high ammonia content, and,
(100 ml of blood yields 15 to 20 g of protein). In once blood is stored, ammonia is released. Storage
addition, GI hemorrhage leads to hypovolemia, of blood for 1 day results in the elaboration of
shock, and hypoxia. These effects also exacerbate 170 µg ammonia per 100 ml blood; after 4 days,
encephalopathy as discussed above. 330 µg per 100 ml; and after 21 days, 900 µg per
A bland diet with minimal residue is helpful to 100 ml. It is not uncommon to see clinical deteri-
minimize potential inflammation in the bowel. In oration shortly after blood is administered to
addition, specific drug therapy is indicated, includ- patients with hepatic failure. If blood administra-
ing drugs that inhibit gastric acid secretion. The tion is necessary, freshly collected blood must be
drugs of choice are histamine H2-receptor antago- used. Ideally plastic blood collection bags should
nists. These drugs include ranitidine (Zantac), be used because platelets stick to glass and glass
famotidine (Pepcid), and cimetidine (Tagamet). I activates factor XII and can exacerbate DIC.
prefer using ranitidine parenterally at a dosage of Dietary Management
1.0 mg/lb body weight two times a day subcuta- Dietary management is important in the acute and
neously or intramuscularly in the acute stages, chronic stages of hepatic failure. In the acute
whereas the drug can be administered orally at the stages, food restriction is important to mini-
same dosage and frequency for chronic mainte- mize dietary substrates for ammonia production
nance. For cats oral famotidine (2.5 mg one to two in the colon. Most encephalopathic patients are
times a day) is the best choice. The dose of cime- anorectic, so this is not a problem. Once acute
tidine is 2.5 mg/lb body weight four times a day encephalopathy is controlled, dietary management
intravenously, subcutaneously, intramuscularly, or is important. This involves protein restriction,
orally. small frequent meals, and the careful selection
I also frequently combine ranitidine with of ingredients in the diet. These factors will be
sucralfate (Carafate). The latter drug has local pro- discussed in detail in the section on management
tective effects at sites of GI erosions or ulcers. It of chronic hepatic disease.
forms a complex with proteins in the ulcer crater
and provides a barrier to the penetration of gastric Hypoglycemia
acid. In addition, recent evidence has demon- Many patients with severe hepatic failure are
strated it to have protective effects for normal gas- hypoglycemic because of inadequate gluco-
tric mucosa by stimulating the production of neogenic enzymes and depletion of glycogen
the protective prostaglandin E1 and by stimulat- stores. Hypoglycemia can significantly worsen
ing normal epithelial cell turnover (a protective hepatic encephalopathy in addition to its other
effect). Sucralfate is given at a dosage of 0.5 to deleterious effects. It has been shown that hypo-
1.0 g orally three to four times a day. It has a very glycemia is an accurate predictor of early death in
wide safety margin because it is not absorbed. The patients with hepatitis. Glucose supplementa-
dose for cats is 0.25 g orally three to four times tion will correct hypoglycemia, prevent cata-
a day. bolic processes, and may lower CNS and blood
CHAPTER 9 DISEASES OF THE LIVER AND HEPATOBILIARY SYSTEM 347
ascites. Therefore a low-sodium diet is recom- treatment of chronic active hepatitis for a detailed
mended (see Box 9-15). discussion of these drugs.
Lipotrophic agents that contain methio-
nine should not be administered. This amino acid is Ascites
a precursor to mercaptans, a group of potent Ascites can be an important complication of
encephalopathic toxins. Methionine administration chronic hepatic disease. See the section on patho-
can significantly worsen signs of encephalopathy. physiologic derangements occurring with hepatic
Therefore lipotrophic drugs containing methio- disease for a detailed discussion of the pathogene-
nine have no place in the management of hepatic sis of ascites.
disease and are contraindicated. Emergency treatment of ascites is rarely neces-
Summary of Nutritional Management sary. Occasionally, however, the volume of ascitic
In summary, the nutritional management of fluid is high enough to result in respiratory distress
chronic hepatic disease should include the follow- because of compression of the diaphragm, limiting
ing considerations: inspiratory efforts. In these patients, paracentesis
1. Calories from protein should be moderately may be helpful. The only other reasons to with-
restricted, and ingredients that are of high bio- draw fluid from the abdominal cavity are to make
logic value and highly digestible should be it easier to perform percutaneous hepatic biopsy,
used. laparoscopy, abdominal radiographs, and for diag-
2. Protein sources with high branched-chain/aro- nostic fluid analysis and cytologic examination.
matic amino acid ratios are preferred. Cottage Otherwise, paracentesis is of no therapeutic value.
cheese is an ideal protein source in this regard. The risks of paracentesis are hypovolemic shock,
3. A palatable energy-dense diet in amounts suffi- iatrogenic infection, protein depletion, and perfo-
cient to meet energy needs is necessary to ration of abdominal viscera. Patients with ascites
avoid negative energy balance. are already using their maximum cardiac and cir-
4. Carbohydrates supply most nonprotein calories culatory reserve to maintain tissue perfusion.
but should be from highly digestible sources. When a large volume of fluid is rapidly removed,
5. Sodium and copper should be restricted. fluid shifts from the intravascular to extravascular
6. Supplementation with zinc, ascorbic acid, and a compartment and can precipitate hypovolemic
salt- and copper-free vitamin-mineral supple- shock. Although this is rare in my experience, it is
ment may be helpful. recommended that if paracentesis is necessary, fluid
7. These considerations must be present in a should be withdrawn slowly and intravenous fluid
highly digestible, low-residue diet and should support should be available if necessary.
be fed in small, frequent meals. Dietary salt restriction, diuretics, and aldosterone-
inhibiting drugs are used in the long-term control
of ascites. Diuretics should be administered with
Other Drugs to Manage Chronic caution to avoid dehydration. Patients with
Hepatic Encephalopathy hepatic failure are already using their maximum
As previously discussed, lactulose is effective in circulatory and cardiac reserve to maintain perfu-
decreasing ammonia absorption by decreasing sion when ascites is present. Because one of the
colonic bacterial numbers and lowering colonic main causes of sodium retention in patients with
pH. For chronic administration, lactulose is given hepatic disease is excessive aldosterone activity,
at an initial dosage of 0.5 ml/lb body weight three aldosterone-inhibiting drugs are used first. I rec-
times a day. The dosage is titrated to yield two to ommend spironolactone at a dosage of 0.5 mg/lb
three loose to slightly liquid bowel movements per body weight two times a day initially. If this dose
day. Oral antibiotics will also decrease ammonia is ineffective, it is doubled to 1 mg/lb body
absorption by decreasing colonic bacterial num- weight two times a day. Spironolactone will also
bers. not exacerbate hypokalemia. Loop diuretics such
as furosemide (Lasix) are also effective. Furosemide
Inflammation and Fibrosis should be used with caution because it can cause
The presence of active inflammation and fibrosis excessive urinary fluid loss that will result in hypo-
in patients with hepatic disease may justify the use volemia before it improves ascites and also exacer-
of glucocorticoids and antifibrotic drugs such as bate hypokalemia and alkalosis. Furosemide is used
colchicine and D-Penicillamine. See the section on at a dosage of 0.5 to 1 mg/lb body weight two to
CHAPTER 9 DISEASES OF THE LIVER AND HEPATOBILIARY SYSTEM 351
three times a day. Serum electrolytes must be Center SA et al.: Bile acid concentrations in the diagno-
measured periodically in addition to clinical sis of hepatobiliary disease in the cat, J Am Vet Med
assessment. Assoc 189:891, 1986.
If ascites persists, enalapril or benazepril is Center SA: Hepatic lipidosis in the cat. Proceedings of
the fourth annual Veterinary Medicine Forum,
added at a dosage of 0.125 to 0.25 mg/lb one to
American College of Veterinary Internal Medicine,
two times a day. These drugs are angiotensin-
Washington, DC, 13, 1986.
converting enzyme (ACE) inhibitors that decrease Center SA: S-adenosylmethionine (SAMe): an antioxi-
activity of the renin-angiotensin-aldosterone sys- dant and anti-inflammatory nutraceutical. Proceedings
tem. Dietary salt restriction is of prime importance of the eighteenth American College of Veterinary
to minimize sodium retention. Appropriate low- Internal Medicine Forum; 2000, 550-552.
salt diets include those listed in Box 9-15, in the Center SA: S-adenosylmethionine (SAMe), glutathione
References, and Prescription Diet 1/d (Hill’s Pet (GSH), & Vitamin B12 rescue therapy in cats with
Products). hepatic lipidosis. Proceedings of the seventh Inter-
national Veterinary Emergency and Critical Care
Symposium (IVECCS); 2000, 230-235.
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in dogs with hepatic tumors, J Am Vet Med Assoc Philadelphia, 1983,WB Saunders.
199:735, 1991. Taboada J, Meyer DJ: Cholestasis associated with extra-
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C H A P T E R
10
DISEASES OF THE
PANCREAS
Kenneth W. Simpson
Disease of the exocrine pancreas is most often a acterized by fibrosis and low-grade mononuclear
consequence of inflammation, which may be acute inflammation and may be a sequela of recurrent
or chronic, or a reduction in pancreatic mass and acute pancreatitis or a subclinical disease process
exocrine secretion. Neoplasia is less common and that may present as diabetes mellitus or exocrine
is discussed in Chapter 11. pancreatic insufficiency (EPI).
353
354 CHAPTER 10 DISEASES OF THE PANCREAS
FIGURE 10-1
Schematic diagram of the
progression of acute
pancreatitis. (From
Simpson KW, Lamb CR:
Acute pancreatitis in the
dog, In Practice: J Vet
Postgrad Clin Study
17:328, 1995.)
IV, Intravenous; CCK, cholecystokinin; GDV, gastric dilatation volvulus; FIP, feline infectious peritonitis.
pancreatic necrosis in humans is associated with per- C1-IA C1-IA, ATIII, a2M, a-AT
sistent trypsinogen activation, so it may be the abil-
ity of the pancreas to limit trypsinogen activation
Complement Kinin
that stops edematous pancreatitis from progressing
to necrotizing pancreatitis. Contact
Pancreatic hyperstimulation may also be of
direct relevance to naturally occurring pancreati- Factor 12
tis in dogs and cats. CCK is normally released by
cells in the duodenum in response to intraluminal
fat and amino acids and coordinates and stimulates Coagulation Fibrinolysis
pancreatic secretion and gallbladder contraction
during digestion. It is possible that high-fat diets
exert their effects via the excessive release of
CCK and that hypercalcemia, organophosphates, ATIII, a2M, a-AT C1-IA, a2M, a-AT
and high levels of circulating glucocorticoids also
facilitate or cause pancreatic hyperstimulation; FIGURE 10-2 The complex interactions of the
however, this is not proven. complement, kinin, fibrinolytic, and coagulation
pathways following activation of factor XII by contact
Often pancreatic inflammation is a self-limiting
or trypsin. Inhibitors are shown in italics. ATIII,
process, but in some patients reduced pancreatic
Antithrombin III; a2M, alpha2-macroglobulin; a-AT,
blood flow and leukocyte and platelet migration alpha1-antitrypsin; C1-1A, complement fragment
into the inflamed pancreas may cause progression C1-1A. (Modified from Lasson A:Acute pancreatitis in
to pancreatic necrosis. Secondary infection may man: a clinical and biochemical study of
arise by bacterial translocation from the intestine. pathophysiology and treatment, Scand J Gastroenterol
Release of active pancreatic enzymes and inflam- 99:1, 1984.)
matory mediators from the inflamed pancreas,
such as tumor necrosis factor-α (TNF-α), inter-
leukin-1 (IL-1), and phospholipid platelet activat- Clinical Findings
ing factor (PAF), amplifies the severity of pancreatic Signalment and History
inflammation and adversely affects the function Dogs. Middle-age to old dogs (more than 5
of many organs (systemic inflammatory response). years of age) that are overweight appear to be at
Derangement in fluid, electrolyte, and acid- higher risk. Miniature schnauzers, Yorkshire and
base balance also results (Figures 10-2 and 10-3). Silky terriers, nonsporting breeds, and perhaps
It is the development of multisystemic abnormali- miniature poodles may be at increased risk of
ties that separates mild from severe, potentially fatal developing pancreatitis. There is no clear sex
pancreatitis. predisposition. Endocrinopathies such as hypothy-
Further study of the cellular mechanisms gov- roidism, diabetes mellitus, and hyperadrenocortic-
erning enzyme secretion and activation, leukocyte ism may also be risk factors.The history may reveal a
and platelet recruitment to the pancreas, bacterial recent episode of dietary indiscretion or drug
translocation, and the development of the systemic administration. Common clinical signs include
inflammatory response in pancreatitis will hope- lethargy, anorexia, hunched stance, vomiting (with
fully provide information that will be useful in or without blood), diarrhea (with or without
treating acute pancreatitis in the patient population blood), increased respiratory rate, and enlarged
in the future. abdomen. Some dogs have a history of icterus pre-
ceded by vomiting.
Cats. Acute pancreatitis has been reported in
Diagnosis cats from 4 weeks to 18 years of age. Domestic short
There is currently no single specific test for pan- and long hair cats are most commonly affected.
creatitis in dogs and cats, and diagnosis is based on Siamese cats have been overrepresented in some
a combination of compatible clinical, clinico- series. No sex bias has been demonstrated. A small
pathologic, and imaging findings. Laparoscopic number of cases have been associated with trauma,
or surgical biopsy may be required to confirm a Toxoplasma gondii, pancreatic and liver flukes, feline
diagnosis and to distinguish inflammation from infectious peritonitis (FIP), and lipodystrophy.
neoplasia. Usually there are no obvious associated factors.
356 CHAPTER 10 DISEASES OF THE PANCREAS
Inciting event
Acute pancreatitis
IL-6
IL-8
TNF NO
IL-1 PAF
IL-10
IL-2
Oxygen free radicals
Hepatic Hypo-
Shock DIC
dysfunction tension
FIGURE 10-3 Inflammatory mediators in acute pancreatitis. Regardless of the inciting event (e.g., alcohol or
gallstones), many poorly understood intracellular events lead to the development of acute pancreatitis.The
progression of pancreatitis depends on several inflammatory mediators (interleukin [IL]-1, tumor necrosis factor
[TNF], and platelet activating factor [PAF] are believed to be the most important). Other mediators (e.g., IL-6, IL-8,
and nitric oxide [NO]) are produced, but they are markers of disease severity or regulatory proteins and are not
mediators of disease progression. IL-1,TNF, and PAF stimulate the production of each other and mediate distant
organ dysfunction such as adult respiratory distress syndrome (ARDS), hepatic dysfunction, shock, and death. DIC,
disseminated intravascular coagulation; ATN, acute tubular necrosis. (From Denham W, Norman J:The potential role
of therapeutic cytokine manipulation in acute pancreatitis, Surg Clin North Am 79:767, 1999.)
The most common clinical findings in cats a third of cats in some clinical series and in cats with
with acute pancreatitis are lethargy, anorexia, and experimental and trauma-induced pancreatitis.
weight loss. Vomiting, diarrhea, constipation,
icterus, dehydration, ascites, and dyspnea are more Diagnostic Approach and Differential
variably present. Vomiting is not as prominent a Diagnosis
sign of pancreatitis in cats as it is in dogs. Polyuria Dogs. The differential diagnosis of acute pan-
and polydipsia have been encountered in some creatitis in dogs is usually centered around the
cats with diabetes mellitus and pancreatitis. The problems of vomiting and abdominal pain (Box
duration of clinical signs until presentation varies 10-1).
from less than 3 days to 12 weeks. In vomiting dogs the initial approach is to dis-
Physical Examination tinguish self-limiting from more severe causes of
Dogs. Physical findings in dogs with acute pan- vomiting on the basis of physical findings and a
creatitis are highly variable and range from depres- minimum database (e.g., packed cell volume, total
sion, to mild dehydration with signs of abdominal protein, blood urea nitrogen [BUN; e.g.,Azostick],
pain, to acute abdominal crisis with shock (tachy- urinalysis, plasma concentrations of sodium and
cardia, prolonged capillary refill time, tacky potassium).Where vomiting is associated with sys-
mucous membranes, hypothermia), petechiation, temic signs of illness, or is persistent, the clinician
icterus, and ascites. An abdominal mass is palpated has to differentiate metabolic, polysystemic, infec-
in some dogs. tious, toxic, and neurologic causes from intraab-
Cats. In cats dehydration and hypothermia have dominal causes. This is usually achieved on the
been most commonly observed. Icterus may also be basis of combined historical and clinical findings
present. Abdominal pain is infrequently elicited. coupled with a minimum database and the evalua-
The presence of a palpable cranial abdominal mass tion of hematology and serum chemistry profile,
or abdominal pain has been reported in a quarter to urinalysis, and abdominal radiography. Measurement
CHAPTER 10 DISEASES OF THE PANCREAS 357
CAUSES OF VOMITING
Intraabdominal
Gastric
Gastritis, ulceration, neoplasia, outflow obstruction, foreign bodies, motility/functional disorders
Intestinal
Inflammatory bowel disease, neoplasia, foreign bodies, intussusception, torsion, rupture, bacterial overgrowth,
functional disorders
Non-Gastrointestinal (Non-GI)
Pancreas: pancreatitis, pancreatic neoplasia
Liver: cholangiohepatitis, biliary obstruction
Genitourinary: pyometra, nephritis, nephrolithiasis,
Urinary: obstruction, prostatitis
Peritonitis
Metabolic/Endocrine
Uremia, hypoadrenocorticism, diabetic ketoacidosis, hepatic encephalopathy, hypercalcemia, septicemia
Drugs
Digoxin, erythromycin, chemotherapy, apomorphine, xylazine
Toxins
Strychnine, ethylene glycol, lead
Dietary
Indiscretion, intolerance, allergy
Neurologic
Vestibular disease, encephalitis, neoplasia, raised intracranial pressure
Infectious
Distemper, parvovirus, infectious canine hepatitis, leptospirosis, Salmonella
of serum amylase or lipase activity is often reported sonography, and paracentesis. Concurrently, sup-
on routine serum chemistry profiles. Additional portive treatment is provided on the basis of physi-
procedures such as ultrasonography, abdominal para- cal findings and a minimum database while awaiting
centesis, or pancreatic lipase immunoreactivity (PLI) the results of hematology, serum chemistry profile,
assay are usually performed on the basis of these ini- and urinalysis findings. Abdominal pain can arise from
tial test results and help to distinguish pancreatitis any intraabdominal structure. Musculoskeletal disorders
from other intraabdominal causes of vomiting. such as discospondylitis and prolapsed disks can be hard to
Where abdominal pain is the major finding, distinguish from abdominal causes of pain.
localizing abnormalities such as abdominal disten- It is of note that diarrhea, which was bloody in
tion are rapidly pursued with radiography, ultra- some cases, was a more frequent sign than vomiting
358 CHAPTER 10 DISEASES OF THE PANCREAS
in dogs with experimental acute pancreatitis. Acute help to detect pancreatitic inflammation. Pancreatic
pancreatitis and its complications (infection, pseudo- biopsy is required to achieve a definitive diagnosis.
cyst or abscess formation) should also be considered
in the differential diagnosis of icterus and pyrexia. Clinicopathologic Findings
Some dogs with pancreatitis exhibit few localizing Hematology
clinical signs. Diagnosis in these patients requires a Dogs. Hematologic findings are highly vari-
high index of suspicion and use of versatile diagnostic able, ranging from mild neutrophilia and slightly
tests such as ultrasonography. increased hematocrit, through marked leukocyto-
Cats. In cats, lethargy, anorexia, and weight loss sis with a left shift, to thrombocytopenia, anemia,
are the usual presenting complaints.Where encoun- and leukopenia with a degenerative left shift. If
tered, localizing signs or findings such as vomiting, thrombocytopenia is detected, blood clotting tests
icterus, diarrhea, abdominal pain, abdominal mass, (one stage prothrombin time [OSPT], activated
polyuria, or polydipsia should be pursued. Because partial thromboplastin time [APTT], fibrin degra-
the antemortem diagnosis of acute pancreatitis is dation products [FDP or D-dimer]) are performed
rarely made, its overall significance as a cause of to determine if the patient has disseminated
these problems is unclear at this time. intravascular coagulation (DIC). Where available,
Where vomiting is present, it is approached by the measurement of antithrombin III is useful in
pursuing localizing findings such as abdominal the early diagnosis of DIC.
pain or masses and by ruling out infectious, para- Cats. A mild anemia that may be nonregen-
sitic, metabolic, and gastrointestinal (GI) causes. erative and a leukocytosis that is usually not
Hyperthyroidism should be ruled out in older cats accompanied by a left shift are the most common
by determination of serum total thyroxine (T4) findings in cats with pancreatitis.
concentration. Elevated levels of hepatic enzymes, Serum Biochemistry
hyperbilirubinemia, hyperglycemia, and glucosuria Dogs. Serum biochemical abnormalities are
are frequently encountered in cats with acute pan- variable and include azotemia (prerenal and renal),
creatitis, so pancreatitis should be strongly consid- increased levels of liver enzymes (alanine amino-
ered in these cats. transferase [ALT], aspartate aminotransferase [AST],
The diagnostic approach to feline icterus is first alkaline phosphatase [AP]), hyperbilirubinemia,
to rule out prehepatic causes and then to pursue lipemia, hyperglycemia, hypoproteinemia, hypocal-
hepatic or posthepatic causes. The association of cemia, metabolic acidosis, and variable alter-
acute pancreatitis and hepatic lipidosis of increased ations (usually decreased) in sodium, potassium, and
mortality, cholangiohepatitis, and inflammatory chloride.
bowel disease has been demonstrated in some Cats. Increased levels of ALT, AP, bilirubin,
studies. A high index of suspicion should be cholesterol, and glucose and hypokalemia and
adopted for pancreatitis in cats with hepatic, bil- hypocalcemia are most common. Azotemia is
iary, or intestinal disease. Cats with a confirmed variably present.
diagnosis of hepatic lipidosis and that have a peri- Urinalysis
toneal effusion should also be strongly suspected of Urinalysis enables azotemia to be characterized
having pancreatitis. as renal or prerenal. Transient proteinuria occurs
Pancreatitis may be the cause of diabetes melli- in some dogs with acute pancreatitis, possibly as
tus in some cats, but the true association between a consequence of pancreatic enzyme-mediated
these diseases is unclear. One study suggests that glomerular damage. The absence of white cell
cats with pancreatitis and diabetes mellitus are very casts or bacteria helps to rule out pyelonephritis as
sensitive to insulin. Transient euglycemia and a cause of abdominal pain. The presence of glu-
reduced insulin requirements after removal of a cosuria or ketonuria should prompt consideration
pancreatic abscess suggest that pancreatic inflam- of diabetes mellitus.
mation or infection can exacerbate diabetes melli- Pancreas-Specific Enzymes
tus in cats. Transient diabetes mellitus has also Classically elevations in serum amylase and lipase
been reported in a cat that was suspected of having activity have been used as indicators of pancreatic
pancreatitis. inflammation in dogs. However, these tests are not
Where a high index of suspicion for pancre- very accurate because dogs with nonpancreatic
atitis is present, ultrasonography and enzymology disorders may have elevated enzyme activities.
(assay of feline PLI) should initially be employed to This may occur because both amylase and lipase
CHAPTER 10 DISEASES OF THE PANCREAS 359
are normally present in other organs and their pancreatic histologic findings in cats with inflamma-
serum activities may increase with nonpancreatic tory bowel disease or lymphoma (Table 10-2). The
disorders, including intestinal obstruction (amy- reason for this is unclear. Nonpancreatic diseases
lase), corticosteroid administration (lipase), and such as renal disease and possibly corticosteroids may
renal disease (both enzymes). Dogs with con- increase circulating TLI in cats.
firmed pancreatitis may also have normal amylase At the present time it seems fair to conclude
and lipase activity. For example, in two recent case that the TLI assay is highly accurate for differenti-
series of dogs with histologically confirmed pan- ating EPI from small intestinal disease. It appears
creatitis, lipase was normal in 28 dogs (61%) and less accurate in detecting pancreatitis. This is not
amylase was normal in 31 dogs (47%). This may surprising because pancreatitis is a very dynamic
be due to exhaustion of enzymes, thrombosis of disease, which may influence the synthesis, secre-
pancreatic vessels, the presence of inhibitors, tion, elimination, and activity of circulating marker
alterations in activity, and perhaps increased clear- enzymes such as TLI. The tissue specificity of
ance. In cats it seems fair to state that measuring total TLI makes it an attractive alternative to amylase
amylase and lipase activity is of no utility for diagnosing and lipase activity tests in dogs, and it is presently
pancreatitis. the only useful indicator in the cat. The recent
These limitations have stimulated the develop- development of assays that measure pancreas spe-
ment of assays for enzymes considered pancreatic in cific lipase in dogs and cats (cPLI and f PLI) has
origin. TLI is one candidate. This species-specific yielded promising initial results in helping to diag-
immunoassay measures circulating trypsinogen in nose pancreatic inflammation and may in time
healthy individuals and trypsinogen and trypsin in prove to be a useful diagnostic aid.
those with pancreatitis.
In dogs, circulating TLI is abolished by pancre- Radiography
atectomy and extremely low concentrations occur Radiographic findings in cats and dogs with acute
in EPI. Experimental and clinical studies have pancreatitis may include loss of serosal detail,
documented high concentrations of TLI in dogs increased opacity in the right cranial quadrant of
with acute pancreatitis. TLI is therefore consid- the abdomen, displacement of the duodenum ven-
ered a useful indicator of pancreatic mass and trally and/or to the right, dilated hypomotile duo-
potentially inflammation. Nonpancreatic diseases denum, and caudal displacement of the transverse
such as renal disease and possibly corticosteroids large intestine (see Chapter 2). Punctate calcifica-
may increase circulating TLI. It is important to tion is occasionally identified in dogs with long-
note that the utility of TLI assay for the diagnosis standing pancreatitis; it indicates saponification of
of spontaneous pancreatitis in dogs has not been mesenteric fat around the pancreas.
thoroughly evaluated, and I have observed both Although radiographic signs often are absent
normal and subnormal concentrations in dogs and are nonspecific, radiography remains a useful
with pancreatitis. diagnostic method for pancreatitis largely because
A TLI test has also been developed for cats. Cats it may enable detection of other abnormalities that
with EPI and some cats with spontaneous pan- can cause similar signs (e.g., gastric foreign body or
creatitis have abnormal concentrations of TLI. intestinal obstruction). Radiography is a logical
Increased application of this test indicates that high first-choice imaging modality for patients with
TLI concentrations may occur in the face of normal vomiting or abdominal pain. Negative or equivo-
Modified from Simpson KW et al.: Subnormal concentrations of serum cobalamin (vitamin B12) in cats with gastrointestinal
disease, J Vet Intern Med (submitted).
360 CHAPTER 10 DISEASES OF THE PANCREAS
cal radiographic findings may be followed up with dict the severity of acute pancreatitis. The pres-
ultrasonography or an upper GI contrast study. ence of shock or abnormalities such as oliguria,
Thoracic radiographs may enable the detection azotemia, icterus, markedly elevated levels of
of pleural fluid, edema, or pnemonia, which has transaminases, hypocalcemia, hypoglycemia, hypo-
been associated with pancreatitis in dogs and cats. proteinemia, acidosis, leukocytosis, falling hemat-
ocrit, thrombocytopenia, and DIC should be
Ultrasonography considered likely indicators of severe pancreatitis
The use of ultrasound for detecting pancreatic in the dog and cat.
lesions is perhaps one of the most significant The measurement of components of the systemic
advances in the diagnosis of acute pancreatitis in inflammatory response such as TNF-α, C-reactive
dogs and cats. Ultrasonographic findings include protein, and IL-6 may also yield information about
enlarged, hypoechoic pancreas, cavitary lesions the severity of pancreatitis in dogs and cats and in
such as abscess or pseudocyst, dilated pancreatic the future might lead to the administration of
duct, swollen hypomotile duodenum, biliary dila- specific antagonists of this response.
tion, and peritoneal fluid. A recent study of dogs Indicators that are potentially useful in the
with fatal acute pancreatitis indicated that ultra- diagnosis and prognosis of pancreatitis include
sound supported a diagnosis of pancreatitis in 23 assay of trypsinogen activation peptide (TAP),
of 34 dogs. Findings in cats are also encourag- trypsin complexed with inhibitors, and phospholi-
ing (Figure 10-4, see Table 10-2) but emphasize pase A2. TAP has been shown to accurately pre-
that a normal ultrasound examination may be pres- dict severity in humans with pancreatitis. This
ent in approximately 60% of cats with pancreatitis. peptide is released when trypsinogen, a pancreas-
The clinician should also be careful to consider specific enzyme, is converted to its active form and
differential diagnoses other than pancreatitis, for rapidly accumulates in the urine and plasma of
example, pancreatic neoplasia, pancreatic edema dogs and cats with experimental acute pancreatitis.
(associated with hypoproteinemia or portal hyper- Phospholipase A2 is elevated in dogs with severe
tension), and enlarged peripancreatic structures, pancreatitis. Further validation of these markers is
which can have an ultrasonographic appearance required before clinical application.
identical to pancreatitis. Fine-needle aspirates of Morphologic assessment of severity is accom-
cavitary lesions may be useful to distinguish plished in humans by use of contrast-enhanced
abscess from pseudocyst. computed tomography (CE-CT). Where lack
of pancreatic perfusion is encountered (i.e., necro-
Abdominal Paracentesis sis), fine-needle aspiration is used to distinguish
Examination of peritoneal fluid may aid the detec- infected from sterile necrosis. Substantially reduced
tion of various causes of acute abdominal signs such mortality has been achieved by the detection and
as pancreatitis, GI perforation, or ruptured bile duct. surgical treatment of humans with infected necro-
The accumulation of fluid in the abdomen or the sis. The lack of availability of CT has restricted
pleural cavity has been variably encountered in cats veterinary application to date, but a recent study of
with acute pancreatitis. Effusion in the abdomen or cats with pancreatitis failed to demonstrate any
chest was present in 17 of 40 cats in one study, in benefit of CE-CT. Where a diagnosis of infected
the abdomen of 5 of 5 cats with hepatic lipidosis necrosis is being considered, the relative accessibil-
and pancreatitis, and in the abdomen of 2 of 8 cats ity of the canine and feline pancreas to ultrasound-
in another. guided needle aspiration holds the potential of the
adoption of a similar approach.
Prognostic Indicators
Stratifying the severity of pancreatitis is useful Treatment
when deciding how aggressive to be with medical Medical treatment is based on maintaining or
and nutritional support and in offering a progno- restoring adequate tissue perfusion, limiting bacte-
sis. Severe pancreatitis requires aggressive support rial translocation, and inhibiting inflammatory
and carries a guarded prognosis, whereas mild mediators and pancreatic enzymes. Surgical treat-
pancreatitis often responds to short-term sympto- ment consists principally of restoring biliary out-
matic therapy and has a good prognosis. Clinical flow, removing infected necrotic pancreatic tissue,
and clinicopathologic criteria can be used to pre- or coping with sequelae such as pseudocysts. No
CHAPTER 10 DISEASES OF THE PANCREAS 361
FIGURE 10-4 Ultrasonographic and gross findings in four cats with pancreatitis. A, A hypoechoic mass (arrow)
visualized in the right cranial abdomen corresponded to an abscess in the right limb of the pancreas. B, A large
mass of complex echogenicity (arrows) detected in the right cranial abdominal quadrant was consistent with acute
necrotizing pancreatitis with saponification of fat detected at surgery. C, A cystic mass (p) with distal acoustic
enhancement (open arrow) was identified in the region of the left pancreatic lobe. Necropsy confirmed biliary
obstruction and cystic dilation of the pancreatic duct secondary to pancreatitis. D, A hypoechoic structure (small
arrows) medial to the duodenum (large arrow) and ventral to the cranial pole of the right kidney (k) was confirmed at
necropsy to be an inflamed pancreas. (From Simpson KW et al.:Antemortem diagnosis of pancreatitis in 4 cats,
J Small Anim Pract 35:93, 1994.)
362 CHAPTER 10 DISEASES OF THE PANCREAS
studies have critically evaluated treatment modali- considered to be effective enough. Ondansetron
ties in dogs or cats with naturally occurring pan- is administered at 0.05 mg/lb slowly intravenously
creatitis. two to three times a day.
Prophylactic broad-spectrum antibiotics (e.g.,
Initial Management amoxicillin with or without enrofloxacin, depend-
The initial medical management of dogs and cats ing on severity) may be warranted in patients with
with acute pancreatitis is invariably initiated before shock, fever, diabetes mellitus, or evidence of
a diagnosis is confirmed and is based on the pre- breakdowm of the GI barrier.
senting clinical findings and the results of an initial Analgesia is an important aspect of caring for
database. Where dehydration or hypovolemia are patients with pancreatitis. It can be provided using
encountered, these are supported with intravenous injectable opioids such as buprenorphine (0.0023
fluid therapy. Lactated Ringer’s solution or 0.9% to 0.0045 mg/lb subcutaneously every 6 to 12
NaCl are common first choices. Potassium and hours), oxymorphone (0.023 to 0.05 mg/lb in
glucose should be supplemented where necessary. cats, 0.05 to 0.1 mg/lb in dogs intramuscularly or
The type of fluid should be tailored on the basis of subcutaneously every 1 to 3 hours), or morphine
electrolyte and pH measurements to restore nor- (0.05 to 0.2 mg/lb in cats subcutaneously or intra-
mal electrolyte levels and acid-base balance. For muscularly, 0.2 to 0.5 mg/lb in dogs subcuta-
example, dogs with a history of vomiting that are neously or intramuscularly every 6 hours). It may
mildly dehydrated are usually given crystalloids be necessary to administer low-dose sedation with
such as lactated Ringer’s solution at a rate that will acepromazine (0.005 mg/lb intramuscularly) to
provide maintenance and replace both deficits and patients that become dysphoric after opioids. It
ongoing losses over a 24-hour period. Dogs with should be borne in mind that buprenorphine is a
signs of shock require more aggressive support. partial agonist and may antagonize the administra-
The volume deficit can be replaced with crystal- tion of more potent analgesics in patients with severe
loids at an initial rate of 30 to 45 ml/lb/hr, then pain. A transdermal fentanyl patch (Duragesic)
tailored to maintain tissue perfusion and hydration. applied to a clipped, clean area of skin is a good way
Plasma (10 ml/lb intravenously) or colloids of providing a longer duration of analgesia in dogs
(e.g., degraded gelatin or hetastarch at 5 to (5 to 30 lb, 25 µg/hr patch; 30-60 lb, 50 µg/hr
10 ml/lb/day intravenously) may be indicated in patch; 60 to 120 lb, 75 µg/hr; every 72 hours) and
the presence of hypoproteinemia or shock. cats (25 µg/hr patch every 118 hours). Adequate
Colloids such as dextran 70 and hetastarch may fentanyl levels are not attained for between 6 and
also have antithrombotic effects that help maintain 48 hours after application (it takes somewhat
the microcirculation. longer in some dogs than in cats), so another anal-
Insulin therapy is initiated in diabetic patients. gesic should be administered in the short term
Stress hyperglycemia has to be differentiated from (morphine, oxymorphone). In cats effective levels
diabetes mellitus in cats. are reached by 6 to 12 hours and in some by 3 to
Where vomiting is a problem, oral intake is 4 hours. It is emphasized that each patient should
restricted, and antiemetics (metoclopramide or be treated as an individual. Careful monitoring for
chlorpromazine) and gastric acid reduction with ongoing signs of pain is very important, and some
an H2-receptor antagonist (e.g., famotidine at patients will require more aggressive analgesic
0.25 mg/lb intravenously twice a day) are pre- therapy than others. Without question, however,
scribed when vomiting is persistent or severe. analgesic therapy is warranted in patients that have
Patients with persistent or severe vomiting are at acute pancreatitis. Nonsteroidal analgesics are gen-
risk for development of esophagitis (see Chapter 4). erally not used in patients with acute pancreatitis
H2-receptor antagonist therapy will help in man- because of concerns for GI ulceration, renal fail-
agement of both esophageal and gastric erosive ure, and potential hepatotoxicity.
conditions. Chlorpromazine is an excellent
antiemetic drug that helps provide mild sedation Steroids in Cats With Pancreatitis, and
along with its effects of reducing nausea and vom- Management of Concurrent Diseases
iting. Ondansetron (Zofran) is a potent antiemetic The high frequency of intercurrent hepatic and
drug that may be more effective in controlling intestinal disease in cats with pancreatitis must be
severe and frequent vomiting in dogs and cats taken into consideration when formulating a
when chlorpromazine or metoclopramide is not treatment plan. Treatment with amoxicillin and
CHAPTER 10 DISEASES OF THE PANCREAS 363
metronidazole should be initiated if cholangio- patients are not presented until 24 to 48 hours
hepatitis is present. Dietary support is broadly sim- after the onset of pancreatitis. Support for this
ilar in hepatic lipidosis and pancreatitis, though hypothesis is provided by the efficacy of somato-
jejunostomy tube feeding may be theoretically statin and gabexate mesilate in reducing pancreati-
indicated in the latter. The principal dilemma tis in humans undergoing elective procedures,
arises in cats with pancreatitis and inflammatory such as endoscopic retrograde cholecystopancre-
bowel disease. Should corticosteroids be used? In atography, that are associated with pancreatitis.
my experience the use of corticosteroids in cats The lack of success with inhibiting the progres-
with pancreatitis and inflammatory bowel disease sion of spontaneous pancreatitis has led to
has enabled resolution of diarrhea and weight gain increased emphasis on damage limitation: amelio-
without exacerbating pancreatitis. Subnormal rating the effects of inflammatory mediators or
cobalamin concentrations are frequently present pancreatic enzymes on the patient and maintaining
in cats with pancreatitis and GI disease, and cobal- pancreatic perfusion.
amin should be supplemented parenterally (1 mg Coagulation abnormalities should be pursued,
subcutaneously every 14 days). There is a possibil- and treatment with parenteral vitamin K can be
ity of adverse effects of chemotherapeutic agents, assessed. If a coagulopathy (e.g., DIC) or hypopro-
such as methotrexate and chlorambucil, in the treat- teinemia is present, or if the patient’s condition is
ment of cats with pancreatitis and intestinal lym- deteriorating, fresh frozen plasma (5 to 10 ml/lb)
phoma or sclerosing cholangitis. Serum folate level may be beneficial in alleviating the coagulopathy
should be evaluated before initiating chemother- and hypoproteinemia and restoring a more normal
apy and supplemental folic acid administered if protease-antiprotease balance. The administration
indicated. of heparin (35 to 70 IU/lb three times a day) may
be potentially useful in ameliorating DIC, promot-
Specific Therapy ing adequate microcirculation in the pancreas, and
Once a diagnosis of pancreatitis is confirmed, clearing lipemic serum. In experimental pancreati-
potentially more specific therapy can be employed. tis, isovolemic rehydration with dextran has also
The majority of dogs with acute pancreatitis respond been shown to promote pancreatic microcircu-
to fluid therapy and nothing by mouth for 48 lation in dogs. A dopamine infusion had a pro-
hours. Hence, specific therapy is usually reserved for tective effect when administered to cats within
dogs that do not respond to fluid therapy or those 12 hours of induction of experimental pancreati-
with signs of multiorgan system involvement or tis. Therapy to abrogate the systemic inflamma-
DIC. Pancreatitis in cats seems to be more chroni- tory response with antagonists of PAF (e.g.,
cally active and severe than in dogs; thus cats with a lexipafant), IL-1, and TNF-α holds promise for
confirmed diagnosis of pancreatitis generally need the future.
more support than the majority of dogs. Oral pancreatic enzyme extracts have been
The specific treatment of pancreatitis has reported to reduce pain in humans with chronic
evolved along two lines: pancreatitis, though this is controversial. They are
1. Stopping further pancreatitis from occur- less likely to be effective in dogs because they do
ring not appear to have a protease-mediated negative
2. Limiting the local and systemic conse- feedback system.
quences of pancreatitis
Dietary Management
Therapies aimed at inhibiting pancreatic secretion Our ability to make precise recommendations for
(e.g., glucagon, somatostatin) or the intracellular dietary management of acute pancreatitis is limited
activation of proteases (e.g., gabexate mesilate), by the absence of controlled studies of the dietary
which have been of benefit in ameliorating the management of this syndrome.
severity of experimental pancreatitis, have shown Dogs. In dogs suspected of having acute pan-
little benefit in the treatment of patients with creatitis, oral intake is usually withheld for the
spontaneous pancreatitis. This lack of success is initial 48 hours and then gradually reintroduced
probably related to the timing of therapy in relation if tolerated. The rationale for giving nothing
to the development of pancreatitis. Experimental by mouth even when vomiting is absent is to “rest
therapy is usually initiated before or shortly after the pancreas” by decreasing pancreatic stimulation.
the induction of pancreatitis, whereas most clinical Because fats and amino acids are potent stimulators
364 CHAPTER 10 DISEASES OF THE PANCREAS
of pancreatic enzyme secretion, their effects are liquid diet distal to the duodenum and TPN are
initially avoided by feeding a diet high in carbohy- other solutions to providing balanced nutrition
drate and then gradually increasing fat and pro- and minimizing pancreatic secretion that may
tein content during the recovery period (the first prove useful in refractory cases.
and second weeks after the onset). Continued fat
restriction is usually recommended for dogs that
have had pancreatitis and is based on clinical and Patient Monitoring
experimental observations that suggest an associa- Patients with suspected or confirmed pancreatitis
tion between high-fat meals, hyperlipidemia, and a should be carefully monitored to enable early
“high plane” of nutrition and pancreatitis. The detection of shock or other systemic abnormali-
protein content of the diet may also be important ties. Minimal monitoring for stable patients
because dogs fed a choline-deficient ethionine- includes regular assessment of vital signs and fluid
supplemented diet or a protein-restricted high-fat and electrolyte balance. In those with systemic
diet develop pancreatitis. abnormalities, monitoring should be more aggres-
Alternative strategies of minimizing pancreatic sive and may include vital signs, weight, hemat-
stimulation include total parenteral nutrition ocrit, total protein concentration, fluid intake and
(TPN) and feeding distal to the CCK-releasing output, blood pressure (central venous and arte-
part of the intestine via a jejunostomy tube, but rial), levels of electrolytes and glucose, acid-base
these options are usually reserved for dogs with status, platelets, and coagulation status. Monitoring
persistent vomiting or severe pancreatitis. Recent amylase, lipase, or TLI on an intermittent sequen-
studies in humans indicate that acute pancreatitis tial basis may also help to support resolution or
may be exacerbated by the early administration of progression of pancreatic inflammation.
TPN (before 5 days) and that enteral nutrition, Ultrasound-guided fine-needle aspiration of
administered via a nasojejunostomy tube, can atten- the pancreas may enable infected pancreatic necro-
uate the systemic inflammatory response and may sis to be detected. Ultrasonography may also enable
decrease complications. Feeding tube placement is detection of delayed consequences of acute pancre-
discussed in Chapter 12. atitis such as pancreatic abscessation, pseudocyst
Cats. In contrast to dogs, where vomiting and formation, and biliary obstruction.
abdominal pain predominate, pancreatitis in cats is
usually associated with anorexia and weight loss.
The presence of anorexia and weight loss in cats Surgical Intervention
with pancreatitis may be a significant contributing Surgery is potentially indicated to remove devi-
factor to their poor prognosis. Prolonged fasting talized tissue in patients with infected pancreatic
(more than 3 days) to avoid pancreatic stimulation necrosis and to investigate and relieve persistent
may only serve to compound malnutrition. The biliary obstruction. The removal or drainage of
clinician is faced with the dilemma of having to abscesses is another indication for surgery. Resection
provide nutritional support to prevent or reverse or surgical drainage of pancreatic pseudocysts is
malnutrition and hepatic lipidosis and fasting the not always necessary because these can resolve
patient to prevent pancreatic stimulation.The sur- spontaneously or following percutaneous drainage.
gical or endoscopic placement of a gastrostomy or Pancreatitis that is recurrent or is unresponsive
esophagostomy tube may circumvent anorexia to treatment may also require surgery to confirm a
where vomiting is not a problem. Current dogma diagnosis and to exclude pancreatic cancer.
suggests that a diet that limits pancreatic stimula- Surgery has often been necessary to confirm an
tion and provides adequate nutrients should be antemortem diagnosis of acute pancreatitis in cats.
fed. However, this ideal may be difficult to achieve The increased application of ultrasonography and
because cats are physiologically adapted to diets measurement of TLI has led to a reduced depend-
that are high in fat and protein, and most balanced ency on surgery in cats with high TLI and sono-
cat foods contain between 30% and 60% fat on an graphic abnormalities. However, it should be
energy basis. I have had success when feeding stressed that cats with pancreatitis often have con-
commercial maintenance or intestinal diets comitant abnormalities in other organ systems
through a gastrostomy tube. (e.g., liver and intestine), and biopsy of these
As discussed above, the endoscopic or surgical organs and the pancreas may be indicated to opti-
placement of a jejunostomy tube and feeding a mize diagnosis and treatment. Transient eu-
CHAPTER 10 DISEASES OF THE PANCREAS 365
of these abnormalities is unclear. The marked test) for the diagnosis of EPI have been largely
maldigestion of nutrients in EPI may lead to the superseded by the development of an assay that
development of protein-calorie malnutrition, which determines the concentration of TLI in serum.
can further compromise residual pancreatic function, Serum TLI is considered to be derived solely
intestinal absorption, and metabolic homeostasis. from the pancreas and can be used as an indicator
of pancreatic mass or inflammation. In dogs and
cats with EPI caused by atrophy or chronic inflam-
Diagnosis mation, the amount of TLI that leaks from the pan-
A diagnosis of EPI is usually made on the basis of creas into the circulation is reduced and a subnormal
compatible historical and clinical findings and by TLI concentration can be demonstrated. Healthy
ruling out infectious, parasitic, metabolic, and ana- dogs usually have a fasting (overnight fast) TLI con-
tomic causes of small bowel diarrhea and demon- centration greater than 5.0 µg/L, whereas dogs with
strating a subnormal circulating concentration of EPI caused by reduced pancreatic mass have fasting
TLI (species-specific TLI: less than 2.5 µg/L in dogs, concentrations less than 2.5 µg/L. Preliminary infor-
less than 8 µg/L in cats). mation in cats suggests that healthy cats have a fast-
ing TLI concentration greater than 17 µg/L,
Clinical Findings whereas cats with EPI have fasting concentrations
Dogs and cats with EPI usually have a history of less than 8 µg/L. When the TLI concentration
chronic small bowel diarrhea (large volume, cow- is between 2.5 and 5.0 µg/L in dogs and 8 and
pat consistency) and weight loss (mild to extreme), 17 µg/L in cats, the patient may be normal or may
which is often associated with a ravenous appetite. have partial EPI and the test should be repeated after
Poor hair coat and marked muscle loss are observed ensuring adequate fasting. Patients with persistently
in some patients. Although pancreatic acinar atro- intermediate TLI concentrations are likely to have
phy is prevalent in young German shepherd dogs, partial EPI that may progress to complete EPI.
it is important to note that many other breeds are The BT-PABA test and fecal azocaesin digest test
affected by EPI.Young dogs diagnosed with EPI are are likely to be the best means of diagnosing EPI
usually suspected to have pancreatic acinar atrophy, that is secondary to the destruction of pancreatic
whereas older dogs and cats with EPI probably have enzymes by hypersecretion of gastric acid.
a higher incidence of chronic pancreatitis.
with EPI fed maintenance diets and those fed and/or evaluate pancreatic function by measuring
modified diets. fecal proteolytic activity.
Highly digestible fat-restricted diets are theo-
retically attractive due to the limited digestive Inadequate Enzyme Supplementation
capabilities of patients with EPI. Clinical studies in Ensure that the enzyme supplement being admin-
dogs have shown highly digestible diets to be ben- istered is appropriate (non–enteric-coated pow-
eficial in reducing fecal volume, borborygmi, and der), current, and being fed at the correct dose.
flatulence but have no clear effects on fecal consis- A new batch, change of preparation, or increased
tency, appetite, or coprophagy. Studies in dogs with amounts may produce a response. In dogs if
experimental EPI suggest that it is fat digestibility, a response is not being achieved with a dose of
rather than the amount of fat, that is impor- 0.2 g/lb of non–enteric-coated powdered extract
tant and have demonstrated an inverse correla- or 1.4 g/lb body weight per meal whole pancreas,
tion between fat digestibility and fecal water consider other reasons for treatment failure. Some
content. However, further controlled trials are dogs and cats develop aversions to the enzyme
necessary to determine if feeding a fat-restricted supplement, and raw pancreas may have to be used
highly digestible diet is warranted on a routine if attempts to disguise the taste are unsuccessful.
basis. Fat-restricted, highly digestible diets may be Rarely some dogs develop a stomatitis related to
useful in the treatment of dogs with EPI that show the enzyme supplement.
poor weight gain in response to initial treatment
with enzyme therapy and a maintenance diet. Hyperacidity
Dietary supplementation with medium-chain Lipase is the most acid-sensitive enzyme, and its
triglyceride oil (2 to 4 ml per meal) may also be activity may be enhanced by decreasing gastric
beneficial in these patients. acid secretion. In dogs a treatment trial with ci-
metidine (2.5 to 5 mg/lb orally two times a day)
Vitamin Supplementation may reveal whether the enzyme supplement is
Cobalamin deficiency can have a myriad of effects being inactivated. This problem has not been
on the body, so the provision of supplementary studied in cats with EPI.
cobalamin (cyanocobalamin, vitamin B12) is pru-
dent. It has recently emerged that dogs and cats do Antibiotic-Responsive
not have the capacity to store large quantities of Diarrhea/”Bacterial Overgrowth”
cobalamin in their bodies and can become rapidly Small intestinal bacterial overgrowth has been
depleted when normal homeostasis is disrupted by diagnosed in dogs with EPI when a cut-off value
EPI or intestinal disease. Studies in dogs indicate that greater than 5 (log 10 colony-forming units
the parenteral administration of a single dose of [CFUs] per milliliter) of duodenal juice is applied.
cyanocobalamin (1 mg subcutaneously) is enough to The bacterial flora of dogs with EPI created by
prevent recurrence of metabolic abnormalities for pancreatic duct ligation increases after the induc-
up to 1 month. Cats may require supplementation tion of EPI but returns towards baseline after sup-
every 2 weeks to maintain normal serum concentra- plementation with pancreatic enzymes. These
tions of cobalamin. Dogs with EPI may also have observations suggest that increases in bacterial
to be supplemented with Vitamin E (400 to 500 numbers in EPI are a consequence of increased
IU orally once a day for 1 month). A vitamin substrate availability secondary to EPI. The bacte-
K–responsive coagulopathy has been reported in cats rial counts in this experimental study (6.4 [log 10
with EPI, and it seems sensible to examine the vita- CFUs per milliliter]) were within the range for
min K status of dogs with EPI that have laboratory healthy dogs, and antimicrobials were not needed
evidence of a coagulopathy. to control clinical signs. Most dogs with sponta-
neous EPI respond to treatment with enzyme sup-
plementation and do not require antibiotics.
Treatment Failures However, some dogs need and respond to antibi-
Confirm EPI otic therapy. In those dogs it is likely that the bal-
Review the patient’s history, physical examination, ance between intestinal damage and repair is
and laboratory findings to ensure that EPI is a altered by EPI: increased degradation of microvil-
likely cause of the diarrhea. If the TLI test results lar enzymes by the increased (relatively) bacterial
do not fit the patient, then resubmit the test flora versus decreased degradation by pancreatic
368 CHAPTER 10 DISEASES OF THE PANCREAS
enzymes in the face of decreased synthesis of Wiberg ME, Saari SAM, Westermarck E: Exocrine pan-
microvillar enzymes. creatic atrophy in German shepherd dogs and rough-
The abnormal flora cannot be predicted accu- coated collies: an end result of lymphocytic pancreatitis,
rately by serum concentrations of cobalamin Vet Pathol 36:530, 1999.
and folate, so a trial with an antibiotic such as oxy- Diagnosis and Treatment of Acute
tetracycline (9 mg/lb orally two times a day for
Pancreatitis
28 days) may be undertaken in dogs that are unre-
Akol KG et al.: Acute pancreatitis in cats with hepatic
sponsive to enzyme and dietary manipulation.
lipidosis, J Vet Intern Med 7:205, 1993.
Antibiotic-responsive diarrhea has not been Bruner JM et al.: High feline trypsin-like immunoreac-
reported in cats with EPI. tivity in a cat with pancreatitis and hepatic lipidosis,
J Am Vet Med Assoc 210:1757, 1997.
Small Intestinal Disease Hess RS et al.: Clinical, clinicopathologic, radiographic,
Some dogs and cats with EPI have small intestinal and ultrasonographic abnormalities in dogs with fatal
disease causing malabsorption despite adequate acute pancreatitis: 70 cases (1986-1995), J Am Vet Med
enzyme supplementation. Results of routine hema- Assoc 213:665, 1998.
tologic and biochemical studies are almost always Hess RS et al.: Evaluation of risk factors for fatal acute
normal in uncomplicated EPI, so abnormalities pancreatitis in dogs, J Am Vet Med Assoc 214:46, 1999.
such as hypoproteinemia (which may indicate a Hill RC, Van Winkle TJ: Acute necrotizing and acute
suppurative pancreatitis in the cat: a retrospective study
protein-losing enteropathy) should be pursued.
of 40 cases (1976-1989), J Vet Intern Med 7:25, 1993.
Dogs and cats with EPI that respond poorly to the Johnson SE: Fluid therapy for gastrointestinal, pancre-
above treatment modifications and have no evi- atic, and hepatic disease. In DiBartola SP, (ed): Fluid
dence of extraintestinal disorders usually require therapy in small animal practice, Philadelphia, 1992,
further investigation of the small intestine. Further WB Saunders.
evaluation that should be considered includes Karanjia ND et al.: Assay of trypsinogen activation in
checking the serum folate level, ultrasound, and the cat experimental model of pancreatitis, Pancreas
endoscopy with intestinal biopsy. 8:189, 1993.
Kitchell BE et al.: Clinical and pathologic changes in
experimentally induced acute pancreatitis in cats, Am
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North Am 79:767, 1999. tion on serum trypsin-like immunoreactivity in
Karne S, Gorelick FS: Etiopathogenesis of acute pancre- healthy dogs, Am J Vet Res 60:1357, 1999.
atitis, Surg Clin North Am 79:699, 1999. Macintire DK:The acute abdomen: differential diagno-
Ruaux CG et al.:Tumor necrosis factor-alpha at presen- sis and management, Semin Vet Med Surg (Small Anim)
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atitis, Vet Immunol Immunopathol 72:369, 1999. Murtaugh RJ: Acute pancreatitis: diagnostic dilemmas,
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Simpson KW et al.: Cholecystokinin-8 induces edema- ulin and trypsin-like immunoreactivity are poor indi-
tous pancreatitis in dogs which is associated with a cators of clinical severity in spontaneous canine acute
short burst of trypsinogen activation, Dig Dis Sci pancreatitis, Res Vet Sci 67:83, 1999.
40:2152, 1995. Salisbury SK et al.: Pancreatic abscess in dogs: six cases
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between inflammatory hepatic disease and inflamma- Saunders HM: Ultrasonography of the pancreas. In
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C H A P T E R
11
ONCOLOGIC
DISEASES OF THE
DIGESTIVE
SYSTEM
Nicole F. Leibman
Victoria S. Larson
Gregory K. Ogilvie
Exciting advances have been made in the diagno- cancer is a disease that has an emotional impact for
sis and treatment of tumors of the gastrointestinal all people involved.Therefore the myths associated
(GI) tract.Without a doubt, as our knowledge base with cancer must first be dispelled through appro-
expands regarding diagnostic techniques and the priate education, then the veterinary health care
biologic behavior of neoplastic disease, so do our team can proceed to meet the nonmedical needs
options for methods of diagnosis and treatment. of the client, along with the medical needs of the
Perhaps just as important is our general awareness patient. The next step, which is predicated on the
that cancer medicine has a tremendous emotional success of these first two steps, is to provide com-
impact on everyone involved, including the own- passionate care to enhance quality of life first and
ers and the entire veterinary health care team. length of life second. Quality of life can be
When approaching the dog or cat with cancer, we enhanced in part by meeting all the needs of the
must be cognizant that the myths and mispercep- patient, including providing adequate pain and
tions that our clients and the veterinary health care nausea control and meeting the patient’s changing
team carry with them can alter judgment and nutritional needs. Fully understanding the cancer
bring us to false conclusions about the manage- we are facing can enhance both length and quality
ment of the disease. Similarly, we must realize that of life. This understanding is best achieved by first,
although the veterinary health care team is key in obtaining a tissue sample from the disease in question
providing medical and surgical care for the patient, (making an accurate tissue diagnosis); second, determining
370
CHAPTER 11 ONCOLOGIC DISEASES OF THE DIGESTIVE SYSTEM 371
the extent of the disease (staging the cancer); and third, Specific oral tumors in dogs and cats, the stag-
assessing the condition of the patient. ing of these tumors, and their treatment options
are discussed below.
ORAL TUMORS
Oral tumors represent 6% of all neoplasms in the CANINE EPULIDES
dog and are the fourth most common neoplasm in
dogs. Cancer of the mouth and pharynx occurs Background
more frequently in dogs than in cats. Male dogs Greater than 40% of all oral tumors are of dental
may be at greater risk for developing an oral tumor or periodontal origin. There are three types of
than female dogs. Most oral tumors occur in geri- epulides: fibromatous epulides, ossifying epulides,
atric patients. Malignant melanomas, nontonsillar squa- and acanthomatous epulides. All arise from the
mous cell carcinomas, and fibrosarcomas are the three most periodontal ligament; therefore they are intimately
common oral tumors in dogs. Squamous cell carcinoma related to the dental arcade. Fibromatous epulides
occurs anywhere in the oral cavity and is by far the most and ossifying epulides are benign, whereas acan-
common oral tumor that occurs in the cat. Metastasis thomatous epulides may act aggressively by destroy-
due to oral tumors is rare with the exception of ing bone and surrounding tissue. Other terms that
melanomas, high-grade sarcomas, and tonsillar have been used to describe acanthomatous epulis
squamous cell carcinomas in both the dog and cat. include adamantinoma and ameloblastoma, although
Before obtaining a biopsy specimen or attempt- ameloblastoma may be a distinct tumor seen in
ing surgical resection of an oral tumor, the clinini- young dogs. Most of these tumors are considered
cian should confirm the general good health of all benign, although acanthomatous epulides can be
dogs and cats with a complete blood count, bio- locally aggressive.
chemical profile, total thyroxine (T4 ) level, and uri- Epulides affect both sexes at equal rates. Although
nalysis.Thoracic radiographs should be obtained to most affected dogs are middle-age, the age range
rule out macroscopic pulmonary metastases. Fine- is wide. Epulides have been documented in dogs
detail radiographs of the affected area may provide as young as 1 year and as old as 15 years of age.
information on the aggressiveness of the tumor. Although boxers may be predisposed to developing
Any local lymphadenopathy should be further gingival hyperplasia, this breed does not seem to be
investigated by fine-needle aspiration or biopsy at excessive risk for developing epulides.
performed at the same time as tumor biopsy. In a
small percentage of cases, tumor metastasis can be
demonstrated in lymph nodes that are not enlarged. Clinical Parameters
Therefore the recommendation is to aspirate and Dogs with epulides often have malodorous breath,
potentially perform a biopsy of the regional lymph facial swelling, or a lump on the gums. Fibromat-
nodes in every case. The parotid and medial ous and ossifying epulides are slow-growing,
retropharyngeal lymph nodes should be evaluated. discrete masses that rarely exceed 2 cm in diame-
A fine-needle aspirate may in fact provide useful ter.They are firm gingival tumors covered by oral
information regarding metastatic disease secondary epithelium.They may be single or multiple but are
to malignant oral tumors.The surgical approach for always discrete and located near teeth. Ossifying
lymph node staging of oral and maxillofacial neo- epulis differs from fibromatous only in osteoid
plasms in dogs has been described. production.
The first surgical excision is the most likely to Acanthomatous epulis is a more rapidly pro-
result in tumor control; therefore appropriate plan- gressive tumor that has a high epithelial compo-
ning is essential.The tumor should not be scraped nent and infiltrates readily into bone. It is usually
or peeled from underlying bone, as recurrence found in the mandible but may also occur in the
is certain and the tumor bed will be enlarged. maxilla.
A definitive aggressive first surgery, such as max-
illectomy or mandibulectomy, should be per-
formed in cases where the tumor involves bone. Clinical Work-up
Prompt diagnosis followed by aggressive treatment On first presentation, epulides may look like other
often results in improved survival and local tumor oral tumors; therefore a biopsy of the tumor, aspirates
control. or biopsies of regional lymph nodes, radiographs of
372 CHAPTER 11 ONCOLOGIC DISEASES OF THE DIGESTIVE SYSTEM
the affected bone, chest radiographs, and blood effects of orthovoltage radiation are osteonecrosis
work are warranted. Fibromatous and ossifying and malignant transformation of the original
epulides are not invasive; therefore high-detail epulis at the site of radiation. Malignant trans-
radiographs of the affected bone are unlikely to formation occurred in 7 dogs at a median of
identify changes in bone. Such radiographs may be 47 months after radiation therapy. One can rea-
helpful in assessing the degree of the specific bony sonably hypothesize that some of these tumors
destruction caused by acanthomatous epulides. may have been initially misdiagnosed as epulides.
In one series of 39 dogs with acanthomatous In another series of 37 dogs with acanthomatous
epulis, radiographic changes in bone were prima- epulis, progression-free survival for 3 years was
rily osteolytic in 23 dogs and osteoblastic in only 80% after cobalt-60 radiation therapy.These dogs
8 dogs. More than 50% of the bone must be were treated with megavoltage radiation to a total
replaced by tumor before lysis is evident radio- of 48 Gy delivered over 4 weeks on an alternate-
graphically; therefore radiographs should not be day schedule of 4-Gy fractions. Most of the
relied on for surgical margins. Computed tomog- tumors recurred within the field rather than at
raphy (CT) may assist in delineating the mar- the margins. Malignant tumor formation at the
gins of tumor involvement more accurately. site of previously irradiated acanthomatous
Technetium-99m nuclide scans tend to overes- epulides was reported as a complication in 4 of
timate tumor margins by imaging peripheral 32 dogs treated in one study.
reactive bone. In one dog an acanthomatous epulis regrew
6 weeks after receiving 50 Gy of orthovoltage
radiation therapy. This dog had almost complete
Therapeutic Approach regression of the tumor after 10 doses of
Local gingival excision of an epulis is unlikely to doxorubicin (30 mg/m2 intravenously every 3
be curative for most cases.These tumors arise from weeks) and cyclophosphamide (50 mg/m2 orally
the periodontal ligament and can recur from sub- daily for 4 days every week) and had stable disease
gingival tumor tissue. Surgery can be curative if for at least 20 months after starting chemotherapy.
surgical margins include the affected tooth root, In one study four dogs with acanthomatous
as with mandibulectomy or maxillectomy. If nor- epulides were given bleomycin intralesionally.The
mal bone is included in a wide surgical excision, dose given was 5 mg weekly. Tumors disappeared
the procedure should be curative. With larger within 3 to 10 weeks, and no adverse effects were
tumors, however, tumor-free margins may be diffi- noted. No tumor recurrence was noted for these
cult to obtain. In a series of 37 dogs treated with dogs.
surgery for acanthomatous epulis, there was just When considering therapy for acanthomatous
1 local recurrence and all dogs were alive at 1 year. epulis, the age of the patient should be considered.
Cryosurgery has been used for treatment of In younger dogs, surgery may be offered as the
epulides, but it is difficult to penetrate bone using treatment of choice owing to the risk, albeit low,
this modality and therefore recurrence is com- of radiation-induced tumorigenesis. For geriatric
mon. Cryotherapy should not be used if it will dogs, radiation-induced malignant transformation
delay more definitive treatments. may be less of a concern due to the protracted
Radiation therapy is a very effective treat- course of this phenomenon. Alternatively, radia-
ment for acanthomatous epulis. In one report of tion can be considered for the first course option
39 dogs that received between 20 and 70 Gy of with a reasonable probability of being successful
orthovoltage radiation therapy on a Monday, with surgery for the second option, should radia-
Wednesday, Friday schedule, 27 of the dogs had a tion fail.
complete remission. The majority (30 of 39) Ameloblastomas have been reported in young
received 35 to 50 Gy. Twelve dogs did not have dogs. These tumors also arise from odontogenic
a complete regression of visible tumor. Regrowth tissue, but they are distinct from acanthomatous
occurred in only 3 dogs at 8, 18, and 24 months epulides. Two dogs younger than 1 year of age
after radiation. Two of these dogs had tumors with ameloblastoma were treated with surgery;
that responded to reirradiation. Overall sur- tumors recurred in both dogs within 6 months.
vival ranged from 1 month to 102 months, with a A second surgery resulted in a cure for one of
median of 37 months. These dogs did not have these dogs, with no recurrence 105 months after
surgery before radiation therapy. Possible adverse surgery.
CHAPTER 11 ONCOLOGIC DISEASES OF THE DIGESTIVE SYSTEM 373
Background
In one study fibromatous epulis was the third most ORAL MALIGNANT
common feline oral tumor, accounting for 29 of MELANOMA IN DOGS
371 oral tumors (7.8%). Epulides occur in middle-
age to older cats. Fibroameloblastoma is a rare Background
tumor that typically affects cats younger than 1 year Melanoma is the most common oral malignancy
of age.These tumors are different from the epulides found in the dog. Unlike cutaneous melanomas, which
in that they histologically resemble embry- are often benign, melanomas of the oral cavity in dogs are
onic connective tissue of the dental pulp. These very aggressive and commonly metastasize to local lymph
tumors are benign and grow by expansion rather nodes and lungs. Oral melanomas are often poorly
than invasion. Complete surgical excision can be responsive to conventional therapy.Although some
challenging with large tumors. oral melanomas may appear histologically benign,
these tumors may behave very aggressively. Oral
malignant melanomas are most common in poo-
Clinical Parameters dles, dachshunds, Scottish terriers, golden retriev-
Cats with oral tumors, including odontogenic ers, standard and miniature schnauzers, Doberman
tumors, often have malodorous breath, dysphagia, pinschers, and Irish and Gordon setters.
anorexia, oral bleeding, ptyalism, and, in advanced In three studies totaling 193 dogs with oral
cases, facial deformity.Weight loss may be a common melanoma, there were 94 male and 99 female
concurrent problem. dogs.This is a disease of old dogs. In one study the
median age of affected dogs was 11 years; ages
ranged from 4 to 16 years.
Clinical Work-up
Cats with oral tumors should have a biopsy per-
formed, as well as blood work, thoracic ra- Clinical Parameters
diographs, evaluation of regional lymph nodes Most oral melanomas originate in the gingiva, but
via aspiration or biopsy, and fine-detail intraoral these tumors can also arise from the palatine,
radiographs of the affected area. Thoracic labial, and buccal mucosa.
radiographs rarely show evidence of metastasis Clients may present dogs for an oral mass or
from feline odontogenic tumors because of their more frequently for persistent halitosis, bleeding
typically benign behavior but should be per- from the mouth, and (occasionally) dysphagia.
formed as part of a thorough staging scheme for Tumors may be quite large, ranging in volume up
oral tumors. to 64 cm3 in one study. Although masses are fre-
quently pigmented, amelanotic tumors can occur.
Oral melanomas are friable and invasive within the
Therapeutic Approach soft tissues of the mouth.
The treatment of choice for feline fibroameloblas-
tomas is surgical excision. One must remove a
“cuff ” of normal bone around the tumor, which Clinical Work-up
requires removal of part of the mandible or maxilla Dogs with oral tumors of any type should be
in most cases. Surgery can be curative if adequate staged using blood work, radiographs of the lesion,
surgical margins are obtained. Seven cats with a metastasis evaluation of the thorax, and cytologic
fibroameloblastoma were treated with surgery or histopathologic examination of the lesion and
in one report; one had recurrence of the tumor regional lymph nodes. The metastatic rate is very
42 months later. Four cats had complete tumor high for oral melanoma, but the time to metastasis
control 6, 7, 24, and 36 months after surgery. One varies. At diagnosis, fine-needle aspiration of the
cat had tumor recurrence and was tumor-free mandibular lymph nodes (both ipsilateral and con-
5 years after a second surgery.The seventh cat was tralateral), as well as any enlarged node, should be
lost to follow-up.There is no known published lit- performed for cytologic examination. It is impor-
erature on treatment for fibromatous epulis in cats, tant to remember that nodes that are palpably
374 CHAPTER 11 ONCOLOGIC DISEASES OF THE DIGESTIVE SYSTEM
within normal parameters can still demonstrate that tumors of the rostral mandible and the caudal
metastatic disease.The surgical approach for lymph maxilla had longer remissions and survival after
node evaluation has been previously published. In surgery.Another study found longer survival times
one study, only 5 (12%) of 41 dogs had metastatic for dogs with tumors that had fewer than three
disease in regional lymph nodes at the time of mitotic figures per high-power field.
diagnosis. Aspiration cytologic findings that are
suspicious should be confirmed by surgical biopsy.
Thoracic radiographs may indicate pulmonary Therapeutic Approach
metastasis at the time of diagnosis. Pulmonary Surgery is the treatment of choice for oral melanoma
metastasis, however, frequently occurs late in the and should consist of mandibulectomy or maxillec-
course of the disease or may be a micrometasta- tomy. Radiation has a role in local tumor control.
sis at the time of diagnosis and therefore unde- Chemotherapy with platinum compounds, perhaps
tectable by radiography. In one study, only 3 (7%) combined with liposome-encapsulated muramyl-
of 41 dogs had evidence of pulmonary metastasis tripeptide-phosphatidylethanolamine (L-MTP-PE,
at diagnosis, but at the time of death, metastatic not yet commercially available) immunotherapy,
rate for this tumor approximated 80%. Melanoma may offer the best adjunctive treatment for metastatic
may also spread systemically, and metastasis has disease.
been reported to kidney, myocardium, brain, and Although metastatic rate with oral melanoma is
other sites. high, metastases frequently are not observed until
Metastasis due to melanoma probably occurs late in the course of disease, occasionally more
early in the course of this disease (during clinical than 1 year after local therapy. Most dogs therefore
stages I and II, indicating small, localized disease); are euthanized because of progression or recur-
however, metastases are often not detected until rence of local disease. Surgery should be aggressive
long after the primary melanoma is resected. The from the outset; it may prolong survival and pro-
growth rate of metastases may vary, and it is this vide palliation. Aggressive local therapy should
variation, rather than the time that metastasis include resection of underlying bone. In one early
occurs, that determines survival time. study 34 of 49 dogs had local recurrence of tumor,
Some investigators have found that the World and 33 dogs developed metastases.The recurrence
Health Organization (WHO) staging system pro- rate of 84% probably reflects the less aggressive
vides prognostic information, but an alternative nature of the surgery, because more recent studies
staging system has been proposed that includes the reported local recurrence rates of less than 15% for
WHO criteria and also uses the mitotic index from melanomas treated by mandibulectomy to 48% for
histopathologic results and location within the oral tumors treated by maxillectomy. Both mandibulec-
cavity. This staging system also offers prognostic tomy and maxillectomy are tolerated well by dogs,
information. with median hospitalization times ranging from
Current recommendations for staging oral 2 days for simple excision to 8 days for total hemi-
melanoma therefore include a complete blood mandibulectomy. Eighty-five percent of owners in
count, biochemical profile, urinalysis, lymph node one study who decided to treat their dogs with
evaluation by cytologic examination or biopsy, tho- mandibulectomy or maxillectomy were very satis-
racic radiographs, and tumor measurements, as well fied with the outcome. In three studies, dogs
as anatomic location and evaluation of mitotic treated with aggressive surgery had a median sur-
index as determined by histopathologic findings. vival time of 7.3 to 9.1 months, compared with
seven dogs that did not have surgery and sur-
vived a median of 2 months. Mandibulectomy or
Prognostic Factors maxillectomy should be the first surgery used to treat
Some studies have demonstrated significantly oral melanoma in dogs. Less aggressive surgeries do not
longer survival for dogs with stage I (small) tumors prolong survival and make subsequent surgery more
(median, 511 days) than for dogs with stage II or difficult.
III tumors (median, 164 days) (Table 11-1). Small Surgical excision was used to treat five dogs with
melanomas were also associated with longer sur- melanoma of the tongue and achieved local control
vival times in another study. in three dogs, with survival times ranging from
One study found that the location of the tumor 3 months to 45 months (median, 19 months). Only
was not prognostic, but two other studies indicated one dog developed metastases.
CHAPTER 11 ONCOLOGIC DISEASES OF THE DIGESTIVE SYSTEM 375
T: PRIMARY TUMOR
T1 Tumor in situ or ≤2 cm maximum diameter (volume ≤8 cm3)
T2 Tumor 2-4 cm maximum diameter (volume 8-64 cm3)
T3 Tumor >4 cm maximum diameter (volume >64 cm3)
MITOTIC INDEX
(a) ≤3 per high power field
(b) >3 per high power field
Oral cavity or oropharyngeal location
(1) Rostral mandible/caudal maxilla
(2) Other
STAGE GROUPING
T N M
I T1a1 N0 M0
II T1a2, any T1b,T2a1 N0 M0
Any T N1 M0
III T2a2, any T2b or T3 N0 M0
Any T N2 M0
Any T Any N M1
Within 6 months of surgery the majority of teletherapy. Five dogs had local recurrence. One
patients will have developed metastatic disease. dog had regional lymph node metastasis, and 14
However, metastases may not be visible for longer developed distant metastasis. Dogs with rostrally
than 1 year after surgery. After metastases develop, located tumors and dogs with smaller tumors had
dogs may still survive for an extended period of longer remissions. Median progression-free sur-
time, depending on the growth rate. Dogs may tol- vival was estimated to be 14 months. In another
erate pulmonary metastatic disease with very little study, dogs were treated with 48 Gy over 4 weeks
apparent effect on their quality of life. on an alternate-day schedule with 4-Gy fractions.
Radiation therapy has been used and certainly In 8% of the dogs, severe acute reactions were rec-
has a role in the treatment of melanoma, particu- ognized (tumors other than melanoma were also
larly for small tumors. In one study 33 dogs with included).After completion of radiation, dogs with
melanoma were treated with 48 Gy of 60Co malignant melanoma in this study were 2.6 times
376 CHAPTER 11 ONCOLOGIC DISEASES OF THE DIGESTIVE SYSTEM
more likely than dogs with squamous cell carcinoma macrophages, which enhances the antibody response.
to develop tumor progression. Dogs with larger or Improved survival over surgery alone has been
more invasive tumors had a worse prognosis. In reported when oral melanoma was treated with a
another study 36 dogs with oral melanomas were combination of surgery and C. parvum. Immuno-
treated with 36 Gy given in four fractions of 9 Gy therapy with C. parvum was found to benefit dogs
at 7-day intervals. In 25 of the 36 dogs, com- with small tumors (stage I). L-MTP-PE, a more spe-
plete remission was achieved and median survival cific macrophage activator, improves survival in dogs
for these dogs was 37 weeks. None of the dogs in treated after surgery for oral melanoma, with a
this study suffered severe acute effects, and most died median survival of 346 days. L-MTP-PE was admin-
of metastatic disease. Local control of oral melanoma istered to 24 dogs after surgery, and 26 dogs received
(53% complete response) has been achieved with a placebo. Only 8 (33%) of the L-MTP-PE dogs
coarse fractionation using three 8-Gy fractions. had died at an interim analysis, whereas 14 (54%) of
A review of the literature would lead to the the placebo group had died.
conclusion that chemotherapy has demonstrated Granulocyte-macrophage colony-stimulating
very little effect on survival times in dogs with oral factor (GM-CSF) transfected vaccines using autolo-
melanoma. Drugs such as dacarbazine (DTIC) gous tumor cells have been used in dogs with
(1000 mg/m2 intravenously every 3 weeks), melanoma. Direct intratumoral injection of GTM-
doxorubicin (30 mg/m2 intravenously every 3 CSG plasmid DNA induced partial or complete
weeks), and melphalan (0.23 mg/lb intravenously tumor regression and prolonged survival times
every 4 weeks) have not had repeatable success. compared with historical controls.
Platinum compounds may be more efficacious;
cisplatin (60 mg/m2 intravenously every 3 weeks)
provided partial response for a dog with metastatic ORAL MELANOMA IN
disease, and carboplatin (300 mg/m2 intravenously CATS
every 3 weeks) appears to have some efficacy,
although the response rate is still probably less than Background
30%. Intralesional chemotherapy with cisplatin in Oral melanoma is very rare in cats.They occur in
purified bovine collagen matrix material has been older cats with no apparent sex or breed predispo-
used successfully to treat oral melanomas. Dogs sition.
were treated with an average of 20 mg of cisplatin
delivered over an average of 5.2 treatments. Dogs
with complete responses had a mean survival of Clinical Parameters
54 weeks, whereas those having a partial response Cats with oral melanoma show signs of drool-
had a mean survival of 14 weeks. ing and facial swelling. Tumors occur in the gin-
Immunotherapy has a role in treating melanoma giva, palate, and mandible. These tumors may be
in many species. Cimetidine, which appears to have pigmented.
an immunomodulating effect by inhibition of
suppressor T cells, has been shown to cause regres-
sion of melanoma in some horses, although its role Clinical Work-up
in the treatment of the disease in dogs is not Any oral tumor requires staging by blood work,
defined. Immunotherapy with interleukin-2 has radiographs, and local lymph node evaluation.
been beneficial in treating humans with melanoma. Metastasis of oral melanoma in cats is common,
Combined with tumor necrosis factor, this treat- although it sometimes is late to occur.
ment might be useful for dogs. This combination
was administered to 13 dogs with measurable oral
melanoma. Five dogs showed reduction in tumor Therapeutic Approach
size, although only two had durable responses. Three cats with oral melanomas were treated with
One of these dogs had a complete remission for surgical excision. All three died as a result of
more than 3 years. metastatic disease within 5 months of surgery.
Immunotherapy with heat-inactivated Coryne- Oral melanoma is an aggressive neoplasm, and,
bacterium parvum (0.045 mg/lb intravenously per without therapy adjunctive to surgery, a poor
week) was used as an adjunct to surgery in 42 dogs. prognosis should be given. Radiation therapy
C. parvum activates and increases production of has been shown to be effective in controlling
CHAPTER 11 ONCOLOGIC DISEASES OF THE DIGESTIVE SYSTEM 377
Prognostic Factors
One study reported that dogs with maxillary
FIGURE 11-1 An intraoperative biopsy of a 7-week-
old puppy with dramatic osteolysis of the underlying
tumors had a longer average response to radiation
mandible due to an oral papillary squamous cell therapy (12 months) than did dogs with mandibular
carcinoma. Radiation therapy resulted in a cure. She (3.4 months) or soft tissue tumors (1.8 months).
died 13 years later of unrelated causes. Oral papillary Eight dogs that were younger than 6 years of age
squamous cell carcinoma is a curable disease by either lived for a median of 58 months after radiation;
surgery or radiation therapy. older dogs lived for a median of 6 months. Dogs
378 CHAPTER 11 ONCOLOGIC DISEASES OF THE DIGESTIVE SYSTEM
with rostrally located tumors live longer than dogs or for dogs with tumors that have tumor-present margins
with caudal tumors, whereas dogs with tumors on surgical histopathologic examination. One dog
that extend both rostrally and caudally have signif- treated in this way had no evidence of disease
icantly shorter survival times. Therefore larger 16 months after treatment.
tumors with larger radiation fields are associ- Squamous cell carcinoma of the tongue is a more
ated with shorter survival. Megavoltage radiation aggressive tumor than gingival squamous cell carcinoma.
therapy in dogs with nontonsillar squamous cell Metastatic disease in this location often determines
carcinoma was associated with shorter median sur- survival. Unless wide surgical margins are obtained,
vival in dogs older than 9 years of age compared recurrence is common. Complete removal of the
with younger dogs (median survival, 315 versus tongue is indicated in some cases and, surprisingly,
1080 days, respectively). dogs adapt to this well. In one study five dogs with
small tumors were treated with surgery alone and
had a median survival time of 8 months.Three of
Therapeutic Approach these dogs had local recurrence.
Rostral gingival squamous cell carcinoma has a Recurrence of tongue tumors is also com-
generally low metastatic rate, which makes this mon after radiation therapy. Larger tumors in
malignancy a good candidate for local therapies 10 dogs were treated with radiation therapy, and
such as surgery and radiation. Aggressive sur- the dogs survived for a median of 4 months; 9 of
gery is necessary to obtain adequate surgical mar- 10 dogs had recurrence. The 1 dog that received
gins. Maxillectomy and mandibulectomy have radiation after surgery survived 26 months with
been used to treat this tumor. From several dif- no recurrence.
ferent reports, median survival ranged from 9 to A combined modality approach for larger tumors
18 months. Recurrence was more frequent than of the tongue seems warranted for local control,
metastasis after surgery. Incomplete surgical resection is although metastasis occurs in approximately 50%
commonly associated with recurrence, which emphasizes of the cases. Chemotherapy, with or without radia-
the importance of early diagnosis and obtaining wide sur- tion, should be considered for these tumors as an
gical margins by mandibulectomy or maxillectomy at the adjuvant to surgery. Chemotherapeutic agents that
first surgery. Adjunctive radiation therapy may also have been reported to be of some help in these cases
be useful. include cisplatin, carboplatin, mitoxantrone, and
In 33 dogs, orthovoltage radiation therapy piroxicam.
without surgery was used to treat oral squamous Papillary squamous cell carcinoma in young
cell carcinoma to a total dose of approximately dogs is an aggressive disease. Conservative surgery
40 Gy. Overall average survival was approximately alone is unlikely to be curative because of the high
14 months; however, the size and location of the rate of bone involvement and the young age of the
tumor, as well as the age of dog, influenced these patient. Radiation therapy has a good success rate,
figures. Recurrence was noted in 15 dogs, metasta- although disruption of normal bone growth in
sis in 3, and serious complications (e.g., bone young dogs may produce facial malformations.
necrosis) from radiation in 2 dogs. In another study Radiation therapy to a total dose of 40 Gy was
39 dogs with squamous cell carcinoma were used to treat three puppies with this disease.There
treated with 48 Gy of 60Co teletherapy delivered was no evidence of disease in any dog 10, 32, and
over 4 weeks on an alternate-day basis. Twelve 39 months after treatment.
dogs had local recurrence, 1 dog developed metas- Chemotherapy is rarely indicated for rostral gin-
tases to regional lymph nodes, and 2 dogs had gival squamous cell carcinoma in dogs due to the
distant metastases. Dogs with rostrally located low metastatic rate for this tumor. Chemotherapy
tumors and dogs with smaller tumors had longer may be indicated for squamous cell carcinoma of
remissions. Median progression-free survival was the tongue, tonsil, and caudal location of the mouth
approximately 13.6 months. In another study dogs because of the high metastatic rate of such tumors.
with nontonsillar squamous cell carcinoma had a Subcutaneous bleomycin treatment, as well as
median survival of 450 days after megavoltage doxorubicin, cyclophosphamide, and chlorambucil
radiation therapy. treatment, failed to induce responses in two dogs
Surgery combined with radiation gives the best control with oral squamous cell carcinoma. Cisplatin has
for gingival squamous cell carcinoma, and postsurgical caused responses in dogs with metastatic subungual
radiation should be considered for dogs with large tumors squamous cell carcinoma; however, no responses
CHAPTER 11 ONCOLOGIC DISEASES OF THE DIGESTIVE SYSTEM 379
occurred in five dogs with oral squamous cell carci- may confirm metastatic carcinoma, in addition to a
noma (including one tongue and one tonsillar complete blood count, biochemical profile, urinal-
tumor). In another report, cisplatin caused a partial ysis, and skull, thoracic, and abdominal radiographs
response in three of five dogs with oral squamous or ultrasound. Occasionally dogs with this disease
cell carcinoma for 2, 10, and 15 weeks, respectively. may be seen for a cervical swelling, and upon oral
Cisplatin or carboplatin has yet to be fully evaluated examination a tonsillar swelling is noted. If no
for oral squamous cell carcinoma; however, it may diagnosis can be reached, biopsy of the tonsil and
be useful in combination therapy for this disease. the regional lymph node is warranted. Thoracic
Mitoxantrone (5 to 6 mg/m2 every 3 weeks) caused radiographs should be taken, although metastasis
responses in four (45%) of nine dogs with squamous is unlikely to be seen at the time of diagnosis.
cell carcinoma of various sites, including the oral If treatment is undertaken, radiographs should
cavity, for between 6 and 21 weeks. Mitoxantrone be repeated at regular intervals to screen for metas-
chemotherapy in combination with surgery was tasis. In view of the high reported rate of intraab-
effective in controlling squamous cell carcinoma of dominal metastases in one study, abdominal
the tongue in dogs in another study. radiographs and ultrasonography should be per-
Oral piroxicam (0.14 mg/lb once daily) may be formed before any definitive treatment.Abdominal
helpful in alleviating clinical symptoms and in imaging may also be useful for monitoring the
tumor control.Toxicities associated with the use of patient for metastases after treatment.
this drug include GI and renal.A biochemical pro- Tonsillar squamous cell carcinoma commonly
file should be performed before the use of this metastasizes to the local lymph nodes. In one study
drug, and if clinical signs associated with GI upset all 22 dogs had lymphadenopathy, as well as infil-
occur, the drug should be discontinued. trative primary tumors, at the time of diagnosis.
Despite early spread to the lymph nodes, pul-
monary metastases are rarely noted at diagnosis.
TONSILLAR After treatment 9 (33%) of 27 dogs had evi-
dence of distant metastases. In two earlier studies
SQUAMOUS CELL 77 (85%) of 91 dogs with tonsillar squamous cell
CARCINOMA IN DOGS carcinoma had metastasis to regional lymph nodes
at necropsy. Systemic metastases were less com-
Background mon; they occurred in the lung, spleen, liver, and
Tonsillar squamous cell carcinoma is a more thyroid gland. In a smaller group of dogs, metasta-
aggressive tumor than either gingival or lingual sis to the spleen and liver occurred more often
squamous cell carcinoma.The median age of dogs than to the lungs.
with this disease is 9 to 11 years.There appears to
be a male predisposition. No breed predisposition
has been described. Occasionally, tonsillar squamous Therapeutic Approach
cell carcinoma may occur bilaterally. Surgery alone is rarely effective in the treatment of
tonsillar squamous cell carcinoma due to a high
metastatic rate, which manifests early in the course
Clinical Parameters of the disease. A combination of surgery and radi-
Dogs with tonsillar squamous cell carcinoma usually ation provided good local control at radiation
present with dysphagia, anorexia, and pain. Owners doses of 35 Gy to 42.5 Gy; six of eight dogs
may have noticed a cervical swelling, which is showed a complete response, and one dog showed
usually lymph node metastasis rather than pri- a partial response. Recurrence was seen in only
mary tumor. Most dogs have shown these signs two of the seven responding dogs, although
for 1 month or less, although some dogs may show metastatic disease to the spleen, liver, bone, and
signs for up to 3 months before presentation. lungs was seen or suspected in all seven. Sur-
vival ranged from 44 to 631 days, with a median
of 109 days.
Clinical Work-up In another study, dogs were treated with a com-
All dogs with oral tumors should have a thorough bination of surgery, orthovoltage radiation therapy,
examination of both tonsils and aspiration cyto- and chemotherapy that alternated doxorubicin
logic examination of the local lymph nodes, which (30 mg/m2 intravenously every 3 weeks) with cis-
380 CHAPTER 11 ONCOLOGIC DISEASES OF THE DIGESTIVE SYSTEM
ORAL SQUAMOUS
FIGURE 11-2 Squamous cell carcinoma is the most
CELL CARCINOMA common oral tumor in the cat and one of the three
IN CATS most common oral tumors in the dog. Bone
involvement can suggest a more favorable outcome.
Background This 12-year-old spayed female cat had a
Neoplasia of the oral cavity represents 10% of all mandibulectomy, followed by radiation therapy and
mitoxantrone chemotherapy.An esophageal feeding
tumors diagnosed in cats, and approximately 90%
tube was placed during this therapy and removed
of these are malignant. Squamous cell carcinoma is the 2 weeks after radiation therapy was discontinued. Her
most common oral tumor in cats (Figure 11-2). This tumor was controlled for 18 months, when metastases
tumor accounts for approximately 60% of all oral were identified. Quality of life was excellent, according
tumors. The average age of a cat with this disease to her caregivers.
is 11 to 12 years of age; however, cats as young as
3 years of age may be affected. No gender or breed
predilection has been noted. sent with dysphagia, halitosis, anorexia, nasal dis-
Most oral squamous cell carcinomas in cats occur at charge, sneezing, pawing at the mouth, changes in
the base of the tongue and involve the frenulum (Figure eating habits, oral hypersensitivity, loose teeth,
11-3). This area should be routinely examined in weight loss, and drooling of ropelike saliva. In
older cats, especially when they are anesthetized some cats a small mass is found initially in con-
for dental or any other procedure that requires junction with a thorough oral examination during
sedation or anesthesia. Some speculation has led to anesthesia for routine dentistry. There may be no
the thought that extensive grooming habits of the symptoms whatsoever at this early stage. In the early
cat possibly cause the species to contact carcino- stages, differentiating squamous cell carcinoma from gin-
gens on its hair coat, thereby predisposing the gival proliferation and dental disease may be difficult, so
tongue to development of neoplasia. a biopsy should be performed on any oral mass in an
older cat, even in absence of the above symptoms.
The mandible and maxilla are equally distrib-
Clinical Parameters uted as far as frequency of site that is affected.
Cats with oral squamous cell carcinoma most Bone invasion is common with gingival tumors.
commonly present for a mass or facial asymmetry. Some squamous cell carcinomas arise primarily
Squamous cell carcinomas are characterized by within the mandible, causing enlargement of the jaw
mucosal ulceration, necrosis, and severe suppura- as a result of bony proliferation.These tumors should
tive inflammation. Cats with this tumor may pre- be differentiated from deep-seated osteomyelitis
CHAPTER 11 ONCOLOGIC DISEASES OF THE DIGESTIVE SYSTEM 381
Therapeutic Approach
In five cats with squamous cell carcinoma of
the mandible, resection alone was not very suc-
cessful in maintaining a remission. Recurrence
occurred in four cats within 5 to 12 months of
surgery despite aggressive surgical technique.
These tumors were all large (between 2 and 4 cm
in diameter), and all invaded bone. In another
study, surgery alone resulted in a median survival
FIGURE 11-3 Sublingual squamous cell carcinoma is of 6 weeks for seven cats. Small tumors, particu-
a difficult tumor to treat; however, most patients can be larly those located rostrally on the mandible, may
made more comfortable with good analgesia and be more amenable to complete surgical excision.
nutritional support, such as assisted tube feeding.
Radiation therapy used alone for the treatment
Piroxicam (Feldene) is a nonsteroidal antiinflammatory
of this disease has also not been rewarding.
agent and potent analgesic and has been reported to
have anticancer effects against selected tumor types. Radiation therapy (orthovoltage, 52 Gy) was used
Although its efficacy against sublingual squamous cell to treat 11 cats with oral squamous cell carcinoma.
carcinoma has yet to be documented in the dog and Treatment included ethanidazole, which is a
cat, it is one treatment option for patients that have hypoxic cell sensitizer that was injected intratu-
normal renal function. morally. Eight cats were evaluated for response.
Four died from complications of therapy, which
generated by severe dental disease and from other included tissue necrosis and ischemia of the
malignant tumors, such as osteosarcoma. tongue, between 45 and 341 days after radiation
(median, 114 days). The other 4 cats had tumor
recurrence at 125 to 331 days after radiation
Clinical Work-up (median, 170 days). No cats were alive 1 year after
Staging of any cat with an oral tumor should be treatment. Overall median survival was 132 days. In
performed as previously described in the dog. another study, radiation alone or in combination
High-detail radiography of the skull provides with chemotherapy or with hyperthermia resulted
information on bony lysis caused by gingival in a median survival of 10 weeks for 45 cats.
tumors.As stated previously, however, radiographic Combination treatment, with mandibulectomy
appearance of lysis does not occur until more than followed by external beam radiation to a dose of
50% of the bone has been demineralized; therefore 40 Gy to 45 Gy starting 10 to 15 days after sur-
radiography is a poor indicator of tumor margins. gery, has demonstrated more success. Six of seven
Biopsy is required for definitive diagnosis and cats had tumor recurrence between 3 and 36
should be considered in any old cat with severe months after treatment (median, 12.5 months).
gingival disease. Common differential diagnoses One cat died but showed no evidence of disease
include eosinophilic granuloma and fibrosarcoma. 14 months after completing radiation therapy.
Metastasis is rare, although mandibular lymph Placement of a gastrostomy tube by endoscopy
nodes may be involved and should be evaluated by or an esophagostomy tube at the time of surgery
cytologic or histopathologic examination. may prolong survival and definitely facilitates
Although lymphadenopathy is usually assumed to nutritional supplementation in cats undergoing
signal possible metastatic disease, two studies found surgery or radiation therapy for oral squamous cell
that less than 50% of cats with enlarged lymph carcinoma (Figure 11-4). The tube allows enteral
nodes had histologic evidence of metastatic dis- feeding of the cat during recovery while allowing
ease. Lymph node metastasis was seen in 8 of 59 the mouth to heal. Gastrostomy tubes can remain
cats in these two studies. Metastatic disease may in place after surgery until the cat is able to eat
occur late in the course of the disease, or perhaps normally. Placement of gastrostomy tubes and rec-
metastases are slow to progress.This is further sup- ommendations for providing enteral nutrition are
ported by 1 cat that had no evidence of metastatic described in Chapter 12.
382 CHAPTER 11 ONCOLOGIC DISEASES OF THE DIGESTIVE SYSTEM
ORAL FIBROSARCOMA
IN DOGS
Background
The third most common oral malignancy in the
dog is fibrosarcoma.These tumors generally occur
in older dogs; however, these tumors may occur in
young dogs more commonly than melanoma or
squamous cell carcinoma.The average age of dogs
with oral fibrosarcoma is 7 years, although these
tumors have been reported in dogs as young as
6 months of age. There does not seem to be any
breed predilection, although 4 of 10 affected dogs in
FIGURE 11-4 Esophageal and gastric assisted tube one study were golden retrievers.There is an appar-
feeding are two vital tools for enhancing quality and ent male predilection for developing oral fibrosar-
length of life in dogs and cats with tumors of the coma, although this is not consistent in all studies.
gastrointestinal system. Fluid therapy, medical therapy,
and nutritional support can all be achieved through
these tubes.They are easy to place and maintain.This Clinical Parameters
cat is being fed via an esophagostomy tube. (Photo
courtesy Dr. K.L. Mitchener.) Fibrosarcomas are just as likely to arise from the
maxilla as from the mandible. These tumors most
commonly originate from the gingival tissue.
Tumors are usually large, with diameters of greater
Because lack of success has often been experi- than 4 cm. Dogs may be asymptomatic, or they
enced with other treatment modalities, trials with may have ptyalism, anorexia, oral bleeding, and
chemotherapeutic agents have been attempted. facial deformity.
Mitoxantrone at doses up to 6.5 mg/m2 intra-
venously every 3 weeks caused 1 complete remis-
sion and 3 partial remissions for 21 to 60 days in Clinical Work-up
32 cats. In another study, 7 cats received mito- Dogs with any oral tumor should be staged using
xantrone (5 mg/m2 intravenously every 3 weeks) blood work, thoracic radiographs, lymph node
during and following megavoltage radiation ther- evaluation, and fine-detail skull radiographs.
apy. Radiation was delivered as a “shrinking field,” Fibrosarcomas frequently invade bone and may
whereby the tumor and mandibular lymph node extend much farther than is obvious by external
received 39.6 to 46.2 Gy, the mandible received viewing. In addition, all soft tissue sarcomas have
49.5 to 51 Gy, and the gross tumor received 59.4 “tendrils” of tumor cells that extend deep into
to 61.2 Gy in daily 3-Gy fractions. The median normal surrounding tissues, making complete
survival for these cats was 180 days.Thirty percent excision very difficult without wide margins.
of the cats were alive 1 year after radiation therapy. Before surgery, particularly when the tumor
Complete remission has been reported in 2 cats involves maxilla, high-detail skull radiographs or a
with squamous cell carcinoma after treatment with CT scan should be obtained to gain a better
carboplatin. Oral piroxicam therapy (0.14 mg/lb appreciation of tumor borders. Due to the fact that
orally every other day) may be of benefit for clini- radiographs usually underestimate tumor margins,
cal symptoms and as an antineoplastic agent. CT scanning is a more accurate method of assess-
The best therapy for oral squamous cell carci- ing fibrosarcoma margins. A CT scan provides a
noma in cats has not been determined. A combina- spatial assessment of the tumor that may be useful
tion of surgery, radiation therapy, and chemotherapy for planning surgery, as well as either presurgical or
probably offers the best chance of success. Pre- postsurgical radiation therapy. CT scanning may
operative radiation and chemotherapy may cause also indicate whether complete surgical removal is
CHAPTER 11 ONCOLOGIC DISEASES OF THE DIGESTIVE SYSTEM 383
impossible, thereby protecting the patient from a In one study, pretreatment with 50 to 56 Gy
poorly planned procedure. of radiation seemed to improve control rates,
Occasionally a tumor may be termed a although few dogs were involved in this study.
fibroma, which implies that the process is benign. Control of fibrosarcoma improves only at high
Fibromas of the oral cavity should be treated as doses of 50 Gy or more. Of 17 dogs treated with
aggressively as fibrosarcomas. A recent report 40.0 to 54.5 Gy of orthovoltage, 4 died during
described 25 dogs with tumors that were histolog- or soon after radiation therapy. Survival times in
ically labeled as either fibromas, nodular fasciitis, or the remaining 13 dogs ranged from 2 months to
granulation tissue. Although all of these lesions more than 27 months, with a median survival of
were considered benign, they invaded bone and 6 months. Tumors recurred in 12 dogs at a mean
metastasized in 5 of the dogs. Bony invasion time of 3.9 months after radiation was complete.
should be interpreted as a sign of malignancy In another study, radiation therapy without sur-
regardless of the pathology report. gery was able to control tumor growth in 3 of
Fibrosarcoma is rarely metastatic at the time of 13 dogs. Megavoltage radiation may be more effi-
diagnosis. However, mandibular lymph nodes cacious than orthovoltage in controlling oral
should be palpated and always subjected to fine- fibrosarcomas. Twenty-eight dogs with fibrosar-
needle aspiration or biopsy.Young dogs apparently coma were treated with 48 Gy of 60Co teletherapy.
have more aggressive tumors than old dogs. In eight Nine dogs had local recurrence as the first cause of
series totaling 107 dogs, metastasis was reported in failure, and 4 dogs developed distant metastasis as
23 (21%) dogs. In most cases metastasis was to the first cause of failure. Dogs with rostrally located
regional lymph nodes; it is rare for oral fibrosarcoma tumors and dogs with smaller tumors had longer
to metastasize to lungs. Thoracic radiographs remissions. Median progression-free survival was
should, however, be performed before definitive estimated to be 26.2 months. Clinical stage was
surgery. Metastases often appear many months after important in predicting time to failure. Radiation
surgery, and it is possible that earlier reports with alone, or combined with hyperthermia, results in a
less effective therapies may have underestimated the median survival of over 18 months for biologically
metastatic rate, because dogs died from inadequate high-grade, histologically low-grade, fibrosarcomas.
local tumor control before metastasis occurred. When used in combination with radiation, inter-
stitial hyperthermia provides better local control
rates than those achieved by radiation alone. Ten
Therapeutic Approach dogs that received between 32 and 48 Gy of ortho-
Complete surgical excision is the treatment of voltage also received interstitial hyperthermia to a
choice for fibrosarcoma of the oral cavity. Tumor- temperature of either 50˚ C or 43˚ C for 30 seconds.
present margins lead to rapid recurrence. Radical Complete remissions were obtained in 9 of 10 dogs,
surgical techniques such as maxillectomy and and overall median survival was 12.9 months,
mandibulectomy are well tolerated by dogs and which is comparable to survival times for dogs that
are necessary to obtain adequate surgical margins. In undergo surgery. Tumors recurred in 4 dogs
five series, totaling 54 dogs treated for oral fibrosar- between 38 days and 378 days after radiation.
coma with aggressive surgery, the median survival Complications of this combined modality include
was 12 months and ranged from 1.5 weeks to 33 fistula formation and sepsis following tissue necrosis.
months. Early and aggressive management of maxil- Chemotherapy has had little application in the
lary and mandibular fibrosarcoma in large purebred treatment of oral cavity fibrosarcomas, although
dogs with histologically low-grade yet biologically doxorubicin has been noted occasionally to pro-
high-grade tumors should be a standard approach. duce objective responses in soft tissue sarcomas.
Even after mandibulectomy or maxillectomy, Low doses of doxorubicin (10 mg/m2 intra-
local recurrence was a problem in 20 of 54 dogs venously every 7 days) appear to act as a “radiation
(37%). Tumor recurrence varied with each study, sensitizer” and improve tumor response at lower
however, from 20% to nearly 60% and occurred radiation therapy dosages.
soon after surgery in studies with the highest rates Intratumoral injections of cisplatin and bovine
of recurrence. In 3 dogs in one study, recurrence collagen matrix were given every week during a
was treated by a second surgery (2 dogs) or surgery 48-Gy course of 60Co teletherapy to five dogs with
plus radiation therapy (1 dog) for second remissions oral fibrosarcoma. Complete remission was seen in
of 2 months, 15 months, and 2 years, respectively. three dogs, and partial remission was seen in one
384 CHAPTER 11 ONCOLOGIC DISEASES OF THE DIGESTIVE SYSTEM
dog, for a median duration of 14 weeks.There was Oral piroxicam (0.14 mg/lb every other day) may
tumor recurrence in three of these dogs. In these be of benefit in these cats.
and other dogs treated with radiochemotherapy, Because of the encouraging results of radia-
recurrences often took place at the periphery of the tion therapy in cats with other soft tissue sarco-
chemotherapy site but still within the radiation mas (including fibrosarcoma), this modality in
field, implying that the combination is synergistic or combination with surgery may offer the best
additive in its effect on the tumor. chance of tumor control in cats, as it does in dogs.
The treatment of choice for oral fibrosarcoma Doxorubicin or carboplatin have been employed
probably involves combined surgery and radiation with variable results.
therapy to dosages that exceed 50 Gy. Intralesional
chemotherapy is investigational but may improve
tumor control. LESS COMMON ORAL
TUMORS IN THE DOG
ORAL FIBROSARCOMA Other reported oral malignancies in the dog
IN CATS include osteosarcomas (Figure 11-5), intraosseous
carcinomas, neurofibrosarcomas, anaplastic sarco-
Background mas, chondrosarcomas, myxosarcomas, invasive
The second most common oral tumor in cats is nasal tumors, mast cell tumors, hemangiosarcomas,
fibrosarcoma.There is no obvious breed or gender lymphomas, and transmissible venereal tumors.
predilection. Fibrosarcoma is most common in old In one report the overall 1-year survival rate for
cats that average 10 years of age. dogs with mandibular osteosarcomas treated with
combination modalities was 53%. Dogs treated
Clinical Parameters
Feline fibrosarcoma is found mostly in the oral
gingivae but has no obvious site predilection.The
lesion may be ulcerated, causing halitosis and
drooling, and is difficult to distinguish clinically
from squamous cell carcinoma.
Clinical Work-up
Staging procedures should be performed as dis-
cussed for squamous cell carcinoma. Fibrosarcomas
cause tissue destruction and occasionally invade
bone or muscle. On histopathologic examination
these fibrosarcomas often have a high mitotic
index; however, metastatic potential appears low.
Therapeutic Approach
Two cats were treated with hemimandibulec-
tomy or premaxillectomy and were free of dis-
ease 11.5 months and 24 months after surgery,
respectively. In another two cats treated with FIGURE 11-5 This 5-year-old male Rhodesian
hemimandibulectomy, one cat had recurrence in Ridgeback had a maxillectomy to include the orbit and
2 months, and one cat failed to eat and was eutha- eye for an oral osteosarcoma, followed by radiation
nized. A gastrostomy tube should be placed in all therapy to the surgery area beginning 1 week after
surgery. Chemotherapy with cisplatin and doxorubicin
cats undergoing oral surgery.
was continued after radiation was completed.At the
Vincristine (0.5 mg/m2 intravenously per week)
time of this picture, several months after the
caused complete regression of an oral fibrosarcoma completion of radiation therapy, he was free of disease
in one cat when treated for 30 weeks. Other and absolutely asymptomatic for any adverse effects of
chemotherapy for this tumor has not been de- therapy.This case is a good example of how many
scribed, although doxorubicin reportedly causes modes of cancer therapy can be used in concert to
regression of fibrosarcoma at other sites in cats. benefit the patient and control or cure the disease.
CHAPTER 11 ONCOLOGIC DISEASES OF THE DIGESTIVE SYSTEM 385
with surgery alone had a 1-year survival rate of metastasis 12, 25, and 40 months after treatment.
71%. Histologic grade was demonstrated to be Radiation therapy should be considered as an
important for survival. adjunct to surgery for salivary gland tumors. In
another group of dogs treated with either surgery,
surgery and radiation, or surgery and chemother-
SALIVARY GLAND apy, the median survival was 550 days. The dogs
TUMORS IN DOGS that were treated with surgery and chemotherapy
had shorter survival times than the other two
Background groups. Presumably these dogs had more progres-
Salivary gland tumors are usually seen in older sive disease and hence were treated with chemo-
dogs with no obvious gender predilection. Poodles therapy. In another study six dogs with salivary
are at higher risk for developing this disease than gland adenocarcinoma were treated with surgery
other breeds. alone, and median survival was 74 days with a
Carcinomas are the most common tumor type, range of 42 to 300 days. All of the dogs in this
although salivary glands are occasionally invaded report died of pulmonary metastases.
by fibrosarcomas or mast cell tumors. Enlargement
of the salivary gland in a dog is more likely to be
an inflammatory process than a tumor. SALIVARY GLAND
TUMORS IN CATS
Clinical Parameters Background
Patients most commonly have a swelling or mass in Most salivary gland tumors are carcinomas. In con-
the neck; however, signs may also include anorexia, trast to dogs, enlargement of a salivary gland in cats is
dysphagia, and pain on opening the mouth. more likely to signal a tumor than inflammation or any
other condition. The median age of affected cats is
10 years, and there is no gender predilection.
Clinical Work-up Siamese cats are at higher risk for developing
The clinical work-up for salivary gland tumors salivary gland tumors; 7 (26%) of 27 cats were
should include a complete blood count, biochemical Siamese in one survey.
profile, T4 levels, urinalysis, and cytologic evaluation
of the tumor. Local lymph node metastasis may
occur; therefore lymph nodes should always have a
biopsy or a fine-needle aspiration. Although pul- Clinical Parameters
monary metastases are rare, thoracic radiographs Cats usually have a mass in the cervical region,
should always be performed as part of a thorough which may be accompanied by other signs, such as
staging scheme. In one study only 8% of the dogs anorexia, dysphagia, and salivation due to second-
had metastatic disease at time of diagnosis. ary infections and ulceration.
The mandibular glands were more likely to be
affected than the parotid glands. In many cases,
tumor was dispersed throughout the salivary tissue Clinical Work-up
in the submucosa of the oral cavity, tongue, and Most reported cats have regional lymph node
oropharynx. Surgical excisional biopsy is war- metastases, and one cat developed lung metastases
ranted for localized tumors; however, more diffuse 5 months after surgery. Careful palpation of
tumors may require incisional biopsy before a regional lymph nodes followed by fine-needle
definitive procedure. aspiration or biopsy of enlarged nodes, as well as
blood work, urinalysis, and thoracic radiographs,
should precede any definitive treatment for these
Therapeutic Approach tumors. In one study, median survival for cats with
Surgical excision in two dogs resulted in local this disease was 516 days. Staging was not shown
recurrence within 6 months. One of these dogs to be prognostic in cats, and a low mitotic index
and two other dogs received 45 Gy of orthovolt- was associated with a poorer prognosis.There was
age radiation to the surgical site, and none of the no difference in surgery alone versus surgery with
three dogs had developed local recurrence or chemotherapy or surgery with radiation.
386 CHAPTER 11 ONCOLOGIC DISEASES OF THE DIGESTIVE SYSTEM
Clinical Work-up
Gastric adenocarcinomas often involve a large
area of the stomach wall, making them unre-
sectable. These tumors arise in the mucosa, but
most extend to or through the serosa. Ulceration
is common and often deep and craterlike, causing
hematemesis or melena. Contrast radiography,
particularly with fluoroscopy, may give indications
of gastric tumor, but these indications are rarely
definitive. Endoscopy can determine the location
of most tumors, except when neoplasia is diffusely
infiltrative, and may reveal tumor ulceration
(Figure 11-6). Although endoscopy can be defini-
tive, it can also be inconclusive. Multiple endo-
scopic biopsy specimens should be obtained, and
deep biopsy specimens should be taken if the
mucosa is not obviously involved (Figure 11-7).
Endoscopy is ideal for evaluating the stomach
itself, but ultrasonography should be used to assess FIGURE 11-6 Endoscopic view of a gastric
epigastric lymph nodes and other abdominal vis- carcinoma resulting in a mild “cobblestone” effect to
cera for evidence of metastasis. Ultrasonography the mucosal surface. Note the ulcers in the upper
or laparoscopy can also be used to define the bor- right-hand portion of the image.This dog’s only
ders of localized tumors and to identify ulcera- clinical sign was intermittent vomiting.A partial
tions and diffuse infiltration. In one report the use gastrectomy was performed, and the vomiting and
endoscopic abnormalities resolved. (Photo courtesy
of ultrasonography in the diagnosis of canine gas-
Dr. David Twedt.)
tric neoplasia was evaluated prospectively in a
series of six cases that were subsequently con-
firmed as having adenocarcinoma by cytologic or
histologic examination or both.These investigators nar, or solid) are less common than diffuse types
found that gastric neoplasia was associated with (e.g., undifferentiated or glandular). No differences
mural thickening, loss of normal wall sonographic in biologic behavior have been ascribed to these
layers, and altered motility. Ultrasound findings were different tumor types. All gastric adenocarcinomas are
consistent with tumor localization obtained by aggressive malignancies.
other diagnostic methods that were employed.
Fine-needle aspirations of the masses were success-
ful in two out of three cases in which they were Therapeutic Approach
performed. Ultrasound-guided microcore biopsy The advanced stage of gastric adenocarcinomas at
can have a high diagnostic sensitivity. When the diagnosis, their diffuse nature, and their high rate
aforementioned modalities are unsuitable, of metastasis usually make surgery unsuccessful.
exploratory laparotomy or laparoscopy can be Most tumors are too large or invasive for complete
used to obtain biopsy specimens from affected resection. Wide resection often requires gastro-
sites. A therapeutic excisional biopsy may be pos- duodenostomy (Billroth type I procedure); how-
sible for small localized tumors via exploratory ever, most dogs die within 4 months of surgery
laparotomy; however, incisional biopsy should be from local recurrence and metastases. Earlier diag-
performed on larger tumors. nosis occasionally allows successful surgical resec-
Gastric adenocarcinoma often metastasizes, tion and long-term freedom from recurrence and
particularly to perigastric lymph nodes and vis- metastasis. There is a report of long-term sur-
cera. Extension of gastric adenocarcinoma through vival after total gastrectomy for gastric adenocarci-
the serosa creates an intense scirrhous reaction in noma in a dog. In this dog the esophagus was
the mesentery and omentum, which may cause anastomosed to a remnant of the antrum, leav-
ascites. ing the pylorus intact, and a splenopexy was
Histology of gastric adenocarcinomas varies, performed. Another long-term survival case is
and “intestinal” types of tumors (e.g., papillary, aci- illustrated in Chapter 1 (see pp. 22-33).
388 CHAPTER 11 ONCOLOGIC DISEASES OF THE DIGESTIVE SYSTEM
A B
FIGURE 11-7 Gastric adenocarcinoma in a dog. A, Lower gastric body with an area of superficial ulceration seen
in the lower field. B, Close-up view of a mass in the midgastric body.The mass was rigid and had a very dense wall
(suggestive of neoplasia). Biopsy of masses such as this one should be performed as deeply as possible. If only
superficial tissue is obtained, the endoscopist may fail to retrieve neoplastic cells.The first four attempts to perform a
biopsy of the mass yielded very small tissue samples, but on the fifth attempt the biopsy instrument advanced inside
the mass.A number of large tissue samples were then obtained, and the diagnosis of adenocarcinoma was confirmed.
Biopsy samples were also obtained from the ulcerated area shown in A. (Courtesy Dr.Todd R.Tams. From Tams
TR, ed: Small animal endoscopy, ed 2, St. Louis, 1999, Mosby.)
Photodynamic therapy with rhodamine dye phoma to chemotherapy are surprisingly good
was not successful in treating an unresectable despite previous reports, especially if they are small
tumor. Results of chemotherapy for adenocarci- cell lymphomas.
noma have not been reported.
A technique using gastrotomy and submucosal
resection was evaluated for removal of leiomyomas INTESTINAL TUMORS
and other benign masses from the cardiac region of IN DOGS
the stomach.There were no postoperative compli-
cations in the six dogs that underwent the proce- Background
dure, and excision was incomplete in two of the In dogs, adenocarcinomas are the most com-
dogs. mon tumor in the intestine and the stomach.
Leiomyosarcomas are less common than adenocar-
cinoma and occur more frequently in the intestine
STOMACH TUMORS than in the stomach (Figure 11-9). Intestinal
IN CATS leiomyomas are uncommon. All reported cecal
tumors have been of smooth muscle origin
Stomach tumors are rare in cats. Most that do occur (i.e., leiomyosarcoma or leiomyoma). Epithelial and
are lymphoma (Figure 11-8). Adenocarcinomas smooth muscle tumors both occur in other areas of
and leiomyosarcomas are rare. Gastric thickening is the intestinal tract. Lymphoma may be found any-
common in cats with gastric lymphoma and is often where within the GI tract but is usually associated
substantial enough to be detected on palpation. with systemic disease. In one study of 144 dogs with
Ultrasound-guided biopsy or fine-needle aspiration lymphoma, 6.9% had GI involvement.
facilitates diagnosis. Endoscopic biopsy is useful in Intestinal tumors generally occur in older dogs.
superficial lesions but is not as helpful for submu- The median age is 11 to 12 years, although the aver-
cosal lymphoma. Most are detectable via endoscopy age age of dogs with lymphoma is younger. There
(given proper endoscopic biopsy instrumenta- are no obvious breed predilections. Males are more
tion and good technique). Lymphoma is rarely con- frequently affected by intestinal tumors than females,
fined to the stomach and is best treated with although this trend is most marked for adenocarci-
chemotherapy. Responses of cats with GI lym- noma and is less obvious for smooth muscle tumors.
CHAPTER 11 ONCOLOGIC DISEASES OF THE DIGESTIVE SYSTEM 389
Endoscopy can be used to obtain biopsy speci- does not usually metastasize; metastases occur in
mens, which may provide a definitive diagnosis for less than 30% of affected dogs, often long after
duodenal or colonic and rectal tumors; however, definitive surgery. Metastasis of colorectal adeno-
multiple biopsy specimens should be taken, carcinoma is considerably less common.There was
because lesions deep to the mucosa may escape no evidence of metastasis in 78 dogs with this
detection, and tumors that create ulcerated lesions disease even after long survival times following
may be obscured by inflammatory changes (Figure surgery.
11-10). In one study, endoscopic biopsy of intes- Carcinoid is a term used to describe intestinal
tinal lymphoma was confounded by the presence tumors of neuroendocrine derivation that may be
of inflammatory infiltrates in nearly 50% of the hormonally active. Of five reported intestinal car-
dogs. Endoscopy of the entire large bowel is par- cinoids, all had metastases to regional lymph nodes
ticularly important when a distal rectal tumor is and liver at the time of diagnosis and there were
palpated, because dogs may have additional proximal additional sites of metastasis in two dogs.
lesions that could otherwise remain undetected and
continue to cause clinical signs after surgery. Biopsy
of small intestinal tumors often requires exploratory Prognostic Factors
laparotomy, but biopsy of rectal tumors may be per- In one study of colorectal adenocarcinomas, dogs
formed via proctoscopy or by prolapsing the rectum with annular tumors had the shortest average sur-
manually or with stay sutures. vival (1.6 months). Dogs with tumors that com-
Metastasis is more commonly described for prised multiple “cobblestone” nodules had an
intestinal adenocarcinoma than for leiomyosar- average survival of 12 months. Dogs with a single
coma, and the most common sites of metastasis are pedunculated polyp had the longest survival
the regional lymph nodes. In 22 (71%) of 31 dogs (32 months) after surgery. These prognostic fac-
with small intestine adenocarcinoma, there was tors are probably related to the ease with which
evidence of metastases to regional lymph nodes. In complete surgical excision may be performed.
contrast, metastasis occurred to liver and lung in In one group of dogs with adenomatous polyps
only four (13%) of these 31 dogs. Leiomyosarcoma or carcinoma in situ of the colon and rectum,
malignant transformation was documented in 18%
of the cases. Higher rates of recurrence and malig-
nant transformation occurred in dogs with multi-
ple masses or diffuse disease and in dogs initially
diagnosed with carcinoma in situ.
Diffuse intestinal lymphoma carries a poor
prognosis in dogs. Prognostic factors for GI
lymphoma are those that have been previously
described for multicentric lymphoma.
Therapeutic Approach
There is little information regarding survival after
surgical resection of small intestinal adenocarcino-
mas. Four dogs with small intestinal tumors that
had not metastasized at the time of surgery had
survival times of 3 days, 6 months (two dogs), and
2 years. In another study five dogs with surgically
treated cancer of the small intestine had an average
FIGURE 11-10 Colonic carcinoma of a 7-year-old survival of 55 days. In another study, dogs with
castrated male dog with a 5-week history of straining
surgically treated epithelial tumors had a mean
to defecate. Results of blood work, abdominal and
chest radiographs, and abdominal ultrasound were survival of 6.9 months and local recurrence was
normal. Colonoscopy was used to obtain a diagnosis of the cause of death in all dogs. In one study,
colonic carcinoma. Resection of the colon resulted in dogs with large intestinal adenocarcinoma treated
control of this tumor for 24 months. (Courtesy only with fecal softeners had a mean survival of
Dr. David Twedt.) 15 months.
CHAPTER 11 ONCOLOGIC DISEASES OF THE DIGESTIVE SYSTEM 391
Surgical excision of intestinal or cecal leiomyosar- For the dog the longest remission and survival
coma carries a better prognosis. Thirteen (57%) of 23 times have been reported with the University of
dogs with leiomyosarcoma survived the perioperative Wisconsin-Madison protocol noted in Table 11-5.
period and had median survivals of 8 to 13 months This protocol is complex but gratifying because of
(ranging from 2 months to 7 years). Only 3 of these consistently improved responses.The University of
13 dogs developed metastases. One dog had evidence Wisconsin-Madison short canine lymphoma pro-
of metastasis at the time of surgery and without expla- tocol appears in Table 11-4. Diffuse GI canine
nation survived 3 years without adjuvant therapy. lymphoma is associated with a variable response to
Cecal rupture may occur and lead to death in some chemotherapy, although solitary or nodular lym-
dogs as a result of peritonitis. Perioperative mortality phoma does respond better.
was 60% in 10 dogs in one study. Four dogs survived
for 19 months, 28 months, 36 months, and 48
months. Two of these dogs died due to recurrence INTESTINAL TUMORS
(28 months) or metastases (36 months). IN CATS
The median survival after surgical resection of
colorectal leiomyoma was 26 months. Only one of Background
five affected dogs died from tumor-related causes. Adenocarcinoma is by far the most common non-
Colorectal adenocarcinomas have a low rate of hematopoietic tumor of the intestinal tract in cats;
metastasis, and treated dogs may have long survival sarcomas are rarely described. Intestinal adenocar-
times following diagnosis. Of multiple treatment cinoma is more common in cats than in dogs.The
modalities, local excision gave the longest average majority of intestinal adenocarcinomas occur in
survival (22 months) with the lowest complica- the small intestine of affected cats. The ileum or
tion rate. Recurrence after local excision of a soli- jejunum is most often affected, whereas the duo-
tary mass occurred in 11 (52%) of 21 dogs. In denum is rarely involved. Adenocarcinoma of the
contrast, radical surgical excision of annular colo- large intestine is less common and usually involves
rectal adenocarcinoma resulted in wound dehis- the colon, although the cecum and rarely rectum
cence and septic peritonitis in all four dogs treated. may be affected.
Cryosurgery prolonged survival in 11 dogs Intestinal adenocarcinoma primarily affects old
with colorectal adenocarcinoma (average survival of 24 cats; the mean age of affected cats is 10 to 11 years,
months). Recurrence was similar to that after local although they may be as young as 2 years of age.
excision; however, additional complications, including The vast majority of affected cats are Siamese,
stricture (5 of 11 dogs), rectal prolapse, and perineal which constitute 152 (68%) of 225 reported cases.
hernia followed treatment. Other techniques, such as Other purebreds are rarely affected. In one study
electrocoagulation and neodymium: yttrium-alu- all 22 adenocarcinomas of the large intestine
minum-garnet (Nd:YAG) laser-assisted surgery, pro- occurred in domestic short hairs, although no
vide control similar to that of local excision. other study addressed this association. Cats with
Radiation therapy using a single high dose colonic adenocarcinoma typically are older, with a
(15 Gy to 25 Gy) of orthovoltage teletherapy may mean age of 16 years.There seems to be no gender
provide reasonable control for recurrent distal rec- predilection for intestinal adenocarcinoma with the
tal adenocarcinomas. In six dogs, median tumor exception of one report in which male cats pre-
control duration was 6 months and no complica- dominated. Feline leukemia virus (FeLV) is unlikely
tions were reported. One dog treated with radia- to play a role in this disease. Only two studies
tion therapy suffered a rectal perforation and died reported the FeLV status of affected cats; all 28 cats
from peritonitis 2 months after treatment. studied tested negative for FeLV antigenemia.
Results of chemotherapy have not been reported Although benign tumors of the intestinal
for intestinal tumors in dogs. Doxorubicin has been tract are rare and the duodenum is not usually
suggested by some as a good adjunctive therapy. Few affected, 18 cats with adenomatous polyps of the
data exist quantitating its efficacy. duodenum have been described. Signalment was
Surgery is indicated in obstructive intestinal lym- similar to that in cats with adenocarcinoma in
phoma or when bowel perforation has occurred. that older, primarily Oriental-breed cats
Chemotherapy protocols for lymphoma can be are most often affected. The cats in this study
employed as adjuvant therapy or as the major form were predominantly castrated males. Most cats
of therapy in diffuse disease (Tables 11-2 to 11-5). were tested for FeLV and feline immuno-
392 CHAPTER 11 ONCOLOGIC DISEASES OF THE DIGESTIVE SYSTEM
SINGLE-AGENT THERAPY
Mitoxantrone Dogs, cats 44 41 30 127
Epirubicin Dogs 35 82 74 143
Idarubicin Cats 13 — — —
Actinomycin D Dogs, cats 12 85 70 42
Doxorubicin Dogs 21 85 76 190
COMBINATION THERAPY
LVPCD Dogs 55 91 84 252
CVP Dogs — 89 75 180
CVPD Dogs 46 87 83 210
VLCM Dogs 147 94 — 140
VLCMP Cats 103 82 62 —
CVP Cats 38 94 79 321
VCM Cats 62 — 52 112
L, L-Asparaginase; V, vincristine; P, prednisone; C, cyclophosphamide; D, doxorubicin; M, methotrexate.
*
From Ogilvie GK: Chemotherapy. In Withrow SJ, MacEwen EG, eds: Small animal clinical oncology, Philadelphia, 1996,
WB Saunders.
deficiency virus (FIV), and all had negative anorexia. Some cats actually have increased appetite
results. All polyps occurred within 1 cm of the because of poor absorption of nutrients through
pylorus. the tumor of the intestinal tract. Most cats have a
For colonic neoplasia in particular, one study palpable abdominal mass. The World Health
found that adenocarcinoma followed by lym- Organization’s classification scheme for lymphoma
phoma, mast cell disease, and neuroendocrine car- appears in Table 11-6.
cinoma were the most common tumors found in The most frequent presenting signs in cats with
this location. intestinal adenocarcinoma reflect involvement of
the proximal small intestine. In decreasing order of
frequency, vomiting, weight loss, and anorexia pre-
Clinical Parameters dominate. Hematochezia is occasionally described
The most common presenting clinical signs for cats in cats with colonic or rectal tumors. Clinical signs
with alimentary lymphoma are as follows: vomit- often have been present for a considerable time
ing, diarrhea, and interestingly a large portion of (median, 2 months, but up to 2 years). Cats with
cats will present with only weight loss and tumors involving more proximal intestinal tract tend
CHAPTER 11 ONCOLOGIC DISEASES OF THE DIGESTIVE SYSTEM 393
CYCLE 2
If in complete remission at week 9, continue treatment at 2-week intervals alternating vincristine 0.7 mg/m2 IV,
chlorambucil (Leukeran) 1.4 mg/kg PO, vincristine 0.7 mg/m2, and methotrexate 0.8 mg/kg IV. Doxorubicin
30 mg/m2 is substituted for every second methotrexate treatment.This cycle continues through week 25.
CYCLE 3
If in complete remission at week 25, continue treatment sequence outlined in Cycle 2, but now at 3-week
intervals.This cycle continues through week 51.
CYCLE 4
If in complete remission at week 51, continue with treatment sequence outlined in Cycle 2, but now at 4-week
intervals. Doxorubicin is no longer substituted for methotrexate.All treatment is discontinued at week 156.
thickness biopsy specimens may be necessary for a with stage III and IV disease and 2.6 months for
definitive diagnosis. those in stage V.
In one series 65% of cats with intestinal mast Cats that are positive for the FeLV antigen have
cell tumors had metastases to regional lymph shorter survival times, but viral status does not
nodes, spleen, liver, lung, or bone marrow. influence response to therapy. In another study,
Anemia in cats with lymphoma is common but response to therapy, FeLV status, and clinical sub-
is usually low grade and characterized as normo- stage were predictive of outcome. FeLV-negative
cytic and normochromic, which is compatible with cats that achieve a complete response following
anemia of chronic disease. Occasionally a moderate induction therapy are likely to have durable
to severe anemia may be present due to GI blood (greater than 6 months) responses, particularly
loss secondary to lymphoma. Anemia is rarely a when doxorubicin is included in the chemother-
consequence of bone marrow involvement. Lym- apy protocol.
phocytosis requires evaluation of lymphocyte
morphology and could indicate bone marrow
involvement and a worse prognosis for remission. Therapeutic Approach
Complete response rates to chemotherapy are Nutritional support is a crucial prerequisite for the
as follows: stage I (93%), stage II (48%), stage III successful management of intestinal tumors.
(52%), stage IV (42%), and stage V (58%). Cats with Whenever chemotherapy or surgery is indicated,
stage I and II disease have median survival times of assisted tube feeding with esophageal, gastrostomy,
7.6 months compared with 3.2 months for cats or jejunostomy tubes is a must.
396 CHAPTER 11 ONCOLOGIC DISEASES OF THE DIGESTIVE SYSTEM
Resection of the intestinal mass is the only enced by extent of GI involvement, sex, FeLV status,
reported primary treatment for intestinal adeno- hematocrit, serum total protein concentration, and
carcinoma in cats, and there is only one report of a clinical stage. Response to therapy is probably the
cat that was treated with adjuvant therapy.That cat single most important prognostic factor for cats with
received levamisole (2.3 mg/lb orally 3 days per GI lymphoma.
week) for 2 months and lived 28 months before In another study 14 cats with alimentary lym-
developing widespread metastases. The contribu- phoma were treated with vincristine, cyclophos-
tion of this treatment to survival is doubtful, phamide, and methotrexate. The protocol was
because similar long survival times have been as follows: week 1, vincristine (0.01 mg/lb)
reported following surgery alone. Early studies administered intravenously; week 2, cyclophos-
that included some cats that died periopera- phamide (4.5 mg/lb) administered intravenously;
tively had median survival times of 5 weeks and week 3, vincristine, same as week 1; week 4,
10 weeks, respectively; however, both studies methotrexate (0.36 mg/lb) administered intra-
included some cats that lived for 2 years. In more venously. The median survival of these cats was
recent studies the average survival ranged from 2.75 months.
6 to 15 months and some cats lived more than In a different study 21 cats with alimentary lym-
4 years.These figures are significant because seven phoma were treated with combination chemo-
cats with confirmed lymph node metastasis at the therapy consisting of prednisolone, L-asparaginase,
time of surgery lived for an average of 12 months, vincristine, cyclophosphamide, doxorubicin, and
and two cats with carcinomatosis lived 4.5 and methotrexate (see protocol at end of this sec-
28 months. The finding of metastatic disease at surgery tion). Median survival for these cats was 40 weeks,
should not be a disincentive to treat cats surgically for and overall median duration of first remission was
intestinal adenocarcinoma. 20 weeks. The only significant prognostic factor
Resection of duodenal adenomatous polyps is associated with duration of first remission was
predictably associated with a good surgical out- whether cats had a complete response following
come, although anorexia is a postoperative com- induction chemotherapy. Duration of first remission
plication in more than half of feline patients. was significantly associated with survival time. Cats
Chemotherapy is the mainstay of treatment for cats tolerated this protocol well.
with alimentary lymphoma. Generally cats with lym- In another study 38 cats with lymphoma were
phocytic lymphoma do substantially better than treated with induction COP chemotherapy. After
cats with large or intermediate lymphoblastic lym- induction, cats were randomized to receive either
phoma. Single agents that have been used include maintenance COP chemotherapy or single-agent
prednisolone, cyclophosphamide, and chlorambu- doxorubicin. The median remission duration for
cil.Varying responses have been seen with the use the cats continuing on COP chemotherapy was
of each of these drugs, and in one report a cat 83 days, which was significantly shorter than the
had a complete response to cyclophosphamide for median remission for the cats that received
14 months. The use of vincristine alone has pro- doxorubicin as maintenance, which was 281 days.
duced long-term responses. L-Asparaginase, idaru- Therefore doxorubicin should be considered an
bicin, and mitoxantrone have been used with efficacious agent for the maintenance treatment of
varying responses. cats with lymphoma. It is, however, a drug that is
Combination chemotherapy, for example, the poor at inducing a complete remission.There was
cyclophosphamide, vincristine, prednisone (CVP) minimal toxicity noted in the cats in this report. It
protocol (see Table 11-3), still provides the basis for should be noted that the dose of prednisolone
most chemotherapy protocols for feline lymphoma. used in this study was 40 mg/m2 daily and the
In one study, median survival of 27 cats with doxorubicin dose used was 25 mg/m2 every
alimentary lymphoma treated with vincristine (0.75 3 weeks. The other drug dosages used are as
mg/m2 intravenously weekly for 4 weeks, then printed above.
every 3 weeks thereafter), cyclophosphamide (300 Finally, another study involved 67 cats with GI
mg/m2 orally every 3 weeks), and prednisolone (0.9 lymphoma that were treated with chemotherapy.
mg/lb/day) was 50 days. Although most cats Twenty-nine cats with lymphocytic lymphoma
responded poorly to chemotherapy, 9 cats achieved a were treated with chlorambucil and prednisolone.
complete remission. Survival times were not influ- The chlorambucil dosage we use is the total cumu-
CHAPTER 11 ONCOLOGIC DISEASES OF THE DIGESTIVE SYSTEM 397
Abdominal ultrasonography should be performed critical tumor mass, because even dogs with metas-
in addition to routine abdominal and thoracic tases may not show recurrence of hypercalcemia
radiographs, because abdominal metastases are until those metastases become large.
much more common than thoracic. Complications of surgery reflect the difficulties
Paraneoplastic hypercalcemia is common in encountered in any surgical procedure involving
dogs with apocrine gland adenocarcinoma of the the perineal area. Fecal incontinence can follow
anal sacs and may occur in both males and females. surgery in up to 20% of dogs and may be perma-
In one study, serum calcium was elevated in 25% nent.Wound infection can occur and cause sepsis.
of the affected dogs to an average of 14.6 mg/dl. Local recurrence is a problem with some dogs,
In another study 90% of dogs with anal sac adeno- and others develop recurrence in the regional
carcinoma had elevated serum calcium levels, to an lymph nodes. If the sublumbar nodes are enlarged
average of 16.1 mg/dl. Hypophosphatemia occurred at diagnosis, it may be possible to remove them
concurrently with hypercalcemia in some but not surgically; however, tumor-invaded nodes are fre-
all of the affected dogs. quently friable and invade around the vessels and
This neoplasm is highly malignant and metasta- nerves in this area.The nodes were well-encapsulated
sizes early in the course of the disease to the sub- in 80% of dogs treated surgically in one study, but
lumbar and iliac lymph nodes. In one study they were also well vascularized; thus the surgeon
approximately 50% of the dogs developed lymph should be prepared to encounter bleeding. In this
node metastases; in two other studies 94% of the study, complications during lymph node surgery
dogs had metastases to the above-mentioned sites. caused the death of one third of the dogs; almost
Abdominal radiographs are useful in identifying one third of the survivors developed transient uri-
sublumbar lymphadenopathy, but ultrasonography nary incontinence, presumably as a result of neu-
may be more accurate than radiographs or digital rologic trauma. Overall, 6 of 27 dogs died within
rectal palpation in disclosing the extent of lymph 2 weeks after undergoing surgery for removal of
node involvement. either the primary tumor or its metastases. Median
Less frequent sites of metastasis are the lungs, survival for the remaining dogs was 8.3 months;
which may show a nodular or diffuse pattern ra- the range of survival was 6 weeks to 39 months.
diographically, and (rarely) the lumbar vertebrae, Five dogs were still alive at 14 months after sur-
liver, and kidneys. Metastasis may occur when the gery. This moderate success rate was corroborated
primary tumor is very small, and clinical signs in another study in which 50% of the dogs died
relating to the primary tumor may not be obvious. between 2 and 22 months after surgery, with an
average survival of 8.8 months. In another report
the median survival of dogs with this disease
Prognostic Factors treated with surgery alone was 295 days.
In one study, hypercalcemic dogs had a median Chemotherapy might be promising as adjuvant
survival of 6 months after surgical excision of the therapy for this tumor, but relatively little has been
tumor, compared with 11.5 months for normocal- reported.Three dogs treated with doxorubicin and
cemic dogs. Dogs with metastases detected at sur- cyclophosphamide, either alone or in combination
gery predictably had shorter median survival with prednisolone, vincristine, and L-asparaginase
times (6 months) than did dogs without metastases (for concurrent lymphoma), had survival times of
(15.5 months). 1, 2, and 14 months. Another tumor did not re-
spond to treatment with melphalan and cyclophos-
phamide. Anecdotally cisplatin has caused complete
Therapeutic Approach regression of metastatic lesions in some dogs with
Ideally, hypercalcemia should be controlled before this disease. Recent investigations suggest that sur-
and during definitive therapy. Surgical excision gical excision of the primary tumor and sublum-
of the primary tumor is often difficult because of bar lymph nodes followed by intraoperative and
the large size of these tumors and their invasive external beam radiation therapy combined with
growth characteristics. Local recurrence occurs in chemotherapy (e.g., doxorubicin) provides clinical
approximately 25% of dogs. Even with incomplete remission times of more than 1 year. In another
surgical excision, however, most dogs that are report, dogs with this disease were treated with
hypercalcemic become normocalcemic after sur- several different chemotherapeutic agents and
gery. Hypercalcemia presumably reflects some median survival was 245 days.
CHAPTER 11 ONCOLOGIC DISEASES OF THE DIGESTIVE SYSTEM 399
son, hepatic aspiration or biopsy is commonly in only 2 of 13 dogs with hepatocellular carci-
required to make a definitive diagnosis. Prebiopsy noma and bile duct carcinoma. Large, solitary
evaluations should include a review of the patient’s hepatocellular carcinomas are less likely to metas-
overall status, risk for hemorrhage or impaired tasize than are multiple lesions.Thirteen of 14 dogs
wound healing, and liver size. A very ill patient (93%) with multiple or diffuse lesions had metasta-
may not be a good anesthetic candidate, in which sis, whereas 11 of 30 dogs (37%) with solitary liver
case less-invasive biopsy techniques with the use of masses had evidence of metastasis. The size of a
local anesthetic would be a better choice. A coag- liver mass has little influence on prognosis,
ulation profile including prothrombin time (PT), although it is speculated that large lesions that
partial thromboplastin time (PTT), fibrin degrada- have not led to the demise of the patient are more
tion products (FDPs), fibrinogen content, and likely to behave in a less aggressive fashion. Further,
platelet count should identify those patients at the degree of invasion and presence of metastasis
increased risk for hemorrhage. At a minimum, are more likely to be prognostic indicators than
packed cell volume (PCV), total solids (TS), esti- size. Predictably dogs with solitary liver tumors are
mate of platelet count, buccal mucosa bleeding probably the best candidates for surgical resection
time (BMBT), and activated clotting time (ACT) and control of disease, whereas dogs with multiple
should be performed. lesions have a less favorable prognosis.
Techniques for obtaining neoplastic material
include fine-needle aspiration (percutaneous, blind), Treatment
keyhole biopsy (percutaneous, blind), ultrasound- Up to 75% of the liver can be resected with negli-
guided fine-needle aspiration or biopsy, transtho- gible compromise to liver function, and complete
racic biopsy, laparoscopic biopsy, or exploratory regeneration occurs within 6 to 8 weeks. Several
celiotomy. See the References for hepatic aspiration techniques are described in the literature, includ-
and biopsy techniques. One study found a poor cor- ing partial lobectomy, complete lobectomy, and
relation between cytologic and histologic findings partial hepatectomy. The most commonly used
for liver disease, with an agreement of only 44% for procedures are partial and complete lobectomies.
hepatic tumors in particular. Ultrasound-guided For benign liver masses—such as hepatocellular
biopsy with a 14-gauge Tru-Cut biopsy instrument adenoma, cholangioma, fibroma, and bile duct cys-
usually provides a definitive diagnosis and is the pro- tadenoma—surgical excision has the greatest
cedure of choice for diffuse lesions, zonal lesions potential for definitively controlling disease.
that involve all hepatic lobules or acini, or focal Surgery is also the treatment of choice for dogs
lesions defined by ultrasound. However, with lesions with hepatocellular carcinoma that involves one
other than those mentioned, wedge liver biopsy or two liver lobes (Figure 11-12). In a report of
samples taken during laparotomy provide the 18 dogs with solitary hepatocellular carcinoma,
pathologist with the best specimen for evaluation 16 were resected with single lobectomies and 2 by
and allow the surgeon to examine the liver during partial hepatectomy. At the time of publication
the procedure as well. in that study, 8 dogs had died with a mean sur-
Staging of liver tumors should be performed vival time of 306 days (range, 1 to 548 days), and
with chest radiographs and abdominal ultrasound 10 dogs were still alive with a mean survival time
to detect hepatic lymphadenopathy, other organ of 377 days (range, 195 to 1025 days).
involvement, or lesions in multiple lobes. Of The success of treatment for other types of
49 dogs with hepatocellular carcinoma, 30 (61%) hepatic neoplasms is less defined. In a report of
were initially diagnosed to have a solitary mass in two dogs with bile duct carcinoma and adenocar-
only one liver lobe, but 24 of the 30 (80%) actually cinoma treated with partial hepatectomy, both
had lesions in other lobes.A solitary liver mass was dogs had survival times of 6 months. A hepatic
the most common presenting sign for hepatocel- mesenchymoma treated by excision recurred
lular carcinoma in other studies. Regardless of 4 months after surgery in another dog.
histologic type, metastasis is common for liver It is unknown whether chemotherapy is valuable
tumors. In a study of 57 dogs with liver tumors, as an adjunctive treatment; however, many drugs
metastasis to the regional lymph nodes (14 dogs), have been used (5-fluorouracil [5-FU], cisplatin,
lungs (14 dogs), or peritoneal surfaces (7 dogs) actinomycin D, and mitoxantrone). Occasional
occurred in 35 (61%) cases. In another study, responses have been seen with doxorubicin in
spread to the lungs was less common and occurred humans with hepatocellular carcinoma.
CHAPTER 11 ONCOLOGIC DISEASES OF THE DIGESTIVE SYSTEM 401
nonhematopoietic liver tumors found 57 intra- the cases, whereas the majority (7 of 9 [78%]) of
hepatic bile duct tumors, of which 34 (60%) were bile duct carcinomas were widespread throughout
benign. Hepatocellular carcinoma is less common the liver. Metastasis to the peritoneal surfaces,
in cats than in dogs and accounted for 25% of pri- hepatic lymph nodes, and lungs is commonly
mary feline liver tumors. Tumors of the extrahe- encountered with malignant bile duct tumors in
patic bile duct (9 of 107) or gallbladder (4 of 107) cats; less common sites include thoracic lymph
are usually malignant. Most cats affected with bile nodes, diaphragm, spleen, urinary bladder, GI tract,
duct tumors are middle-age, ranging upward in and bone. Malignant transformation from benign
age from 6 years. In a series of 21 cats with liver to malignant lesions has also been reported. Of
tumors, affected animals were older than 10 years 18 cats with hepatocellular carcinoma, however,
of age. Sex predilection for bile duct tumors has only 5 (28%) had evidence of metastasis to the
not been resolved, because one study found male hepatic lymph nodes, lung, or spleen.
cats to be overrepresented, whereas another found Aspiration or biopsy (and prebiopsy evaluation)
the opposite to be true. In both studies, bile duct should be performed as outlined in the section on
tumors were more common in domestic short primary liver tumors in dogs.As is the case in dogs,
hairs than in Siamese. The median age of cats cytologic evaluation from fine-needle aspiration
affected with hepatocellular carcinoma is 11 years, has only a 44% correlation with histopathologic
and males are more commonly affected (11 of findings and should be interpreted with caution.
17 [65%]).As is the case with biliary tumors, hepa- In the case of cystadenomas, aspiration of cystic
tocellular carcinomas also affect domestic short fluid characteristically produces a yellow to color-
hairs more frequently. FeLV does not seem to play less transudate with a specific gravity of 1.001 to
a role in nonhematopoietic liver tumors. Hepatic 1.008 and protein concentration less than 2 gm/dl,
myelolipoma, an uncommon tumor consisting of with the most common cell type being a macro-
adipose tissue and bone marrow elements, has phage. Although this finding is not diagnostic
been associated with diaphragmatic hernias in cats for hepatobiliary cystadenomas, it will permit
and may be associated with chronic hypoxia or one to rule out abscesses, hematomas, and parasitic
trauma to the liver. cysts.
FIGURE 11-13 Biliary cystic hyperplasia in a 15-year-old cat.The cat was asymptomatic, and results of a complete
blood count and biochemical profile were normal. A, Lateral and, B, ventrodorsal survey abdominal radiographs
showing marked hepatomegaly and displacement of the stomach dorsally and to the left. C and D, Appearance of
the liver at laparotomy. Multiple (polycystic) hepatic cysts were present throughout the liver.Treatment involved
removal of two liver lobes to decrease the size of the liver.The polycystic disorder appears to be inheritable and runs
a benign course in affected patients. (Courtesy Dr.Todd R.Tams.)
treatment of dogs with primary hepatic tumors. for these tumors are similar to that which is
Doxorubicin and 5-FU have been recommended described in the section on tumors of the GI tract.
by some; however, efficacy is unknown.
Metastatic Liver Tumors in Cats
Hematopoietic Liver Tumors Background
in Cats Metastatic liver disease is less common in the cat.
Background Although no specific tumor type is overrepre-
Lymphoma is the most common hematopoietic sented, the most common metastatic tumor types
tumor with liver involvement in the cat, followed include pancreatic carcinoma, intestinal carci-
by a variety of myeloproliferative neoplasias and noma, and renal carcinoma.
mast cell tumors.
Clinical Parameters, Work-up,
Clinical Parameters, Work-up, and Treatment
and Treatment Clinical signs for metastatic disease are usually a
Clinical signs result from the infiltration and dis- result of disruption of liver function. The clinical
ruption of liver function. Diagnosis and treatment work-up should be the same as that described for
404 CHAPTER 11 ONCOLOGIC DISEASES OF THE DIGESTIVE SYSTEM
primary liver cancer. However, treatment will dif- carcinoma where panniculitis, subcutaneous
fer between tumor types and is usually directed at swelling, and shifting leg lameness were clinically
palliation rather than curative intent. apparent for months. Blood work revealed
marked elevations in levels of serum lipase and
Exocrine Pancreas Tumors amylase in one of these cases, although no evi-
in Dogs dence of pancreatitis was seen. Hematologic
Background abnormalities associated with pancreatic carci-
Exocrine pancreatic tumors are uncommon.These noma may include elevated serum amylase and
tumors do not show a sex predilection and occur lipase levels; lipase levels of 25 times greater than
in older dogs. Cocker spaniels may be overrepre- normal are most likely to be diagnostic for
sented, because this breed was seen in 3 of 14 cases exocrine pancreatic carcinoma.
reported in one study. Another series found that Ultrasonography can be useful in detecting a
only spaniel breeds were affected in the cases pancreatic mass if the pancreas can be visualized
reported.The most common histologic type is car- despite shadowing from gas-filled GI structures.
cinoma arising from the ductal epithelium, with This will also permit evaluation of the liver for
adenocarcinoma—which arises from the acinar metastases, although definitive diagnosis requires
cell—being the second most common. biopsy.
The WHO staging scheme is as follows: Abdominal ultrasound infrequently detects a mass
on the pancreas, but other organ metastases and/or
Stage I (T1 N0 M0) Tumor confined to
mesenteric lymphadenopathy may be evident.The
pancreas only
diagnosis of insulinoma is based on demonstration
Stage II (T1 N1 M0) Tumor in pancreas and
of hyperinsulinemia in the face of hypoglycemia.
regional lymph nodes
There are several means by which one can achieve
Stage III (T1 N0-1 M1) Tumor in pancreas,
this, including the insulin-glucose, glucose-insulin,
lymph nodes, and
and amended insulin-glucose ratios. For the most
distant metastatic
part these ratios are not considered diagnostic
sites (most
because they are associated with a high number
commonly the liver)
of false-positive results. For this reason, perform-
Clinical Parameters ing a paired insulin and glucose test is considered
Clinical signs of insulinomas include seizures, col- to be the most reliable method of diagnosing an
lapse, generalized or caudal weakness, lethargy, insulinoma.This test is further described below.
ataxia, muscle fasciculations, bizarre behavior, One study describes the use of chromogranin
polyphagia, exercise intolerance, shaking/trem- A (CgA) and neuron-specific enolase (NSE) as a
bling, polyuria/polydipsia, and weight gain. These marker for cannine and feline pancreatic islet cell
clinical signs can be explained by hyperinsuline- tumors.The study found these assays to be sensitive
mia with resultant hypoglycemia and release of in detecting tumors of neuroendocrine origin.
counter-regulatory hormones (catecholamines Another report describes the use of fructosamine
and glucagon in the early phase and cortisol and measurement, which may be helpful in conjunction
growth hormones in the later phase of disease). with insulin measurement in diagnosing an insuli-
Because of the patient’s ability to adjust to a chronic noma. Provocative testing has been described in the
state of hypoglycemia, signs of hypoglycemia literature. Such tests include glucagon tolerance,
are often not seen, even with extremely low glucose tolerance, tolbutamide tolerance, L-leucine,
blood glucose levels.The rate of decrease in blood oral glucose tolerance, epinephrine tolerance, and
glucose, as well as the duration of hypoglycemia, the calcium infusion test. These tests use the
is considered important in the development of administration of potentially dangerous substances
clinical signs. and are expensive, time consuming, and most
There are two types of presenting clinical signs: importantly not as accurate as the paired insulin-
neuroglycopenic (seizures, weakness, ataxia, and glucose tests.
lethargy) and sympathetic (behavioral changes, Preferred Test Protocol. Most dogs will become
shaking/trembling, and muscle fasciculations). hypoglycemic within 8 to 10 hours of fasting.
Neurologic signs are due to the reliance of the Dogs should be fed at 5:00 PM, 8:30 PM, and mid-
central nervous system on diffusion for glucose night, then fasted thereafter. Blood glucose should
uptake (which is predictably low in periods of be monitored starting at 8:00 AM the next morn-
hypoglycemia) and its inability to utilize other ing. When serum glucose is 60 mg/dl, serum
forms of energy, such as fatty acids and ketone should be saved for insulin levels. This test will
bodies. The sympathetic signs are related to an detect hyperinsulinemia in approximately 77% of
increased discharge of counter-regulatory hor- patients.The remaining 23% will show insulin lev-
mones.There is no correlation between the sever- els in the normal range, which is highly suggestive
ity of clinical signs and the stage of disease, for but not diagnostic of insulinoma, and the test
however. should be repeated.
Clinical Work-up Treatment
Basic blood work and urinalysis, chest and abdom- Surgical resection is the treatment of choice for insuli-
inal radiographs, and abdominal ultrasound should noma. Both lobes of the pancreas are affected with
be performed to diagnose and stage dogs with sus- equal frequency, with the body of the pancreas
pected insulinomas, to rule out other causes of affected less commonly. In a study of 39 dogs with
hypoglycemia, and to evaluate for the presence insulinoma comparing surgical to medical treat-
of any concurrent disease. Blood work, urinaly- ment, 26 underwent exploratory celiotomy and
sis, and radiographs are usually unremarkable in partial pancreatectomy and the median survival
the patient with insulinoma, with the exception of was 381 days (range, 20 to 1758 days). Thirteen
hypoglycemia and, rarely, elevated liver enzymes. were treated medically and had a median survival
406 CHAPTER 11 ONCOLOGIC DISEASES OF THE DIGESTIVE SYSTEM
of 74 days (range, 8 to 508 days). Twelve of the have recurrence of clinical signs earlier. More
13 dogs (92%) died or were euthanized because of than 80% of dogs in stage III have recurrence of
clinical signs resulting from hypoglycemia. disease at 1 year.There is little doubt that surgery
Medical Management. Medical management should be recommended for patients with sus-
should be approached in a stepwise fashion. pect insulinomas and that many patients require
Initially a reduction in exercise and concomitant concurrent medical management.
dietary changes (frequent small feedings contain-
ing high protein and complex carbohydrates) is Glucagonoma
employed. Prednisolone can be introduced as signs Background
of hypoglycemia worsen. Prednisolone has antiin- A rare tumor of the pancreatic alpha-islet cells,
sulin and hyperglycemic effects starting at a dose glucagon-secreting tumors have been described in
of 0.11 mg/lb (orally twice daily); the dose can be the dog in a number of case reports. A review of
increased as needed up to 0.5 mg/lb (orally twice the characteristic syndrome, referred to as gluca-
daily) when iatrogenic Cushing’s disease becomes gonoma syndrome, cites no sex predilection.
a risk. Clinical Parameters and Work-up
Diazoxide has several beneficial effects in the Clinical signs described in the literature include
treatment of insulinomas. It inhibits cell uptake of skin lesions, referred to as superficial necrolytic
glucose, blocks calcium entry into beta cells, cat- dermatitis (SND) or metabolic epidermal necrosis
alyzes the breakdown of glycogen to glucose, (MEN).These lesions are characterized by mild to
and enhances glucose synthesis.The initial dose is marked hyperkeratosis and fissuring of the foot-
2.3 mg/lb (orally twice daily), which may be pads, erythema, and crusting plaques on the oral
increased to 13.6 mg/lb (orally twice daily) if cavity, muzzle, limbs, abdomen, and genital areas.
required to control signs of hypoglycemia. Potential Staging for glucagonoma should include basic
side effects include GI toxicity (vomiting, diarrhea, blood work, urinalysis, and thoracic and abdominal
inappetence), hyperglycemia, diabetes, myelosup- imaging. Biochemical abnormalities are variable
pression, and hypernatremia. Hydrochlorothiazide and may include hyperglycemia, elevated liver
(0.9 to 1.8 mg/lb, orally once daily) can be added enzyme levels, and nonregenerative anemia. A case
to potentiate the effects of diazoxide. report on one dog found hyperglucagonemia, hyper-
Octreotide acetate (somatostatin) can be given insulinemia, and hypoaminoacidemia. Ultrasound
at 10 to 20 µg subcutaneously two to three times findings are usually unremarkable, although a pan-
daily. Its efficacy is variable in the small subset of creatic mass was suggested in one of seven dogs
patients treated to date. Calcium channel blockers reported.
may be useful. Alloxan (29.5 mg/lb intravenously Treatment
with concurrent fluid therapy) has been Surgical excision is the treatment of choice.
described in a small number of dogs. Metastasis is common to the liver (three of four
Streptozotocin, a nitrosurea compound, has also dogs [75%]) and/or mesenteric lymph node (one
been reported in two dogs but is extremely of four dogs [25%]). However, survival and resolu-
nephrotoxic, can be hepatotoxic, and should be tion of disease is reported in one case. The major
considered as a rescue agent only. Similarly, dox- postoperative surgical complication in reported
orubicin and streptozotocin, carboplatin, cases was bile duct obstruction and pancreatitis.
cyclophosphamide, tubercidin and mithramycin Medical management includes symptomatic
have all been used in humans, but with variable therapy with intravenous amino acid administra-
effects, and there is no data on canine patients to tion. A 10% solution of crystalline amino acid solu-
date. Radiation therapy has not been reported in tion, approximately 11.4 ml/lb of body weight, is
dogs. The prognosis for long-term control of administered over 6 to 8 hours and repeated every
insulinoma in the dog is grave in those with 7 to 10 days. Oral nutritional support with a high-
metastatic disease, although the short-term con- quality protein diet should also be instituted.
trol is good.Young dogs and those with very high Supplementation with egg yolks (three to six
serum insulin concentrations have shorter sur- daily), zinc, essential fatty acids, and prednisone
vival times. In one study the overall survival for have also been described. Somatostatin analogues
dogs undergoing surgery for insulinoma was 10 have been used in humans and have resulted in
to 14 months. Dogs in stages I and II tend to have remissions, although these drugs have not been
similar survival times, although dogs in stage II evaluated in dogs.
CHAPTER 11 ONCOLOGIC DISEASES OF THE DIGESTIVE SYSTEM 407
Ultrasonography can sometimes detect a soft glucose, as well as the duration of hypoglycemia, is
tissue density in the cranial abdomen, but deter- considered important in the development of clinical
mining whether the mass arises from the pancreas signs.
can be difficult. There may be effusion in the There are two types of presenting clinical
abdomen that can be aspirated, but this rarely pro- signs: neuroglycopenic (seizures, weakness, ataxia,
vides a diagnosis because pancreatic carcinomas do and lethargy) and sympathetic (behavioral changes,
not readily exfoliate into the peritoneum. This shaking/trembling, and muscle fasciculations).
tumor can metastasize anywhere, but liver and The neurologic signs are due to the reliance of
intraabdominal nodes are commonly involved. the central nervous system on diffusion for glu-
cose uptake (which is predictably low in periods
Treatment of hypoglycemia) and its inability to utilize other
Because diagnosis is usually made by exploratory forms of energy such as fatty acids and ketone
laparotomy, if the patient is in good general bodies. The sympathetic signs are related to an
health and there is no evidence of metastasis, an increased discharge of counter-regulatory
attempt at surgical resection can be considered. hormones.
However, due to the highly malignant nature of Clinical Work-up
this tumor (81% metastasis at the time of diagno- Basic blood work and urinalysis, chest and
sis), complete surgical excision is rarely achieved. abdominal radiographs, and abdominal ultra-
Chemotherapy and radiation therapy have not sound should be performed to diagnose and stage
been reported to be efficacious in pancreatic cats with suspected insulinomas and to rule out
neoplasia. other causes of hypoglycemia. Blood work, uri-
nalysis, and radiographs are usually unremarkable.
Abdominal ultrasound infrequently detects a
Endocrine Pancreas Tumors mass on the pancreas, but other organ metastases
in Cats and/or mesenteric lymphadenopathy may be evi-
Insulinoma (Beta Cell Tumor, Islet dent. The diagnosis of insulinoma is based on
Cell Tumor) demonstration of hyperinsulinemia in the face of
Background hypoglycemia. There are several means by which
Insulinoma is rare in the cat. It is a functional secret- one can achieve this, including the insulin-
ing tumor that arises from the islet cells in the glucose, glucose-insulin, and amended insulin-
endocrine pancreas. In addition to the secretion of glucose ratios. For the most part these ratios are
insulin and its precursors, insulinomas are now not considered diagnostic because they are asso-
known to secrete pancreatic polypeptide, somato- ciated with a high number of false-positive
statin, glucagon, serotonin, gastrin, and corticotropin. results. For this reason, performing a paired
Insulinomas are considered slow growing, are most insulin and glucose test is considered to be the
commonly carcinomas, and often present late in most reliable method of diagnosing an insuli-
the course of disease with signs attributable to the noma. This test is further described in the earler
resultant hypoglycemia. Insulinomas occur in section on endocrine pancreas tumors in the dog.
older cats. However, it should be noted that the radioim-
Clinical Parameters munoassay for insulin has not been validated in
Clinical signs most commonly seen in cats are cats and so should be interpreted with caution.
seizures, cutaneous twitching that progresses to One study describes the use of CgA and NSE
muscle tremors, generalized ataxia, and focal as a marker for canine and feline pancreatic islet
tremors of the facial and appendicular muscula- cell tumors and found these assays to be sensi-
ture. These clinical signs can be explained by tive in detecting tumors of neuroendocrine ori-
hyperinsulinemia with resultant hypoglycemia and gin. One report in the dog states that the use of
release of counter-regulatory hormones (cate- fructosamine measurement may be helpful, in
cholamines and glucagon in the early phase and conjunction with insulin measurement, in diag-
cortisol and growth hormones in the later phase of nosing an insulinoma. Provocative testing has been
disease). Because of the patient’s ability to adjust to described in the literature. Such tests include
a chronic state of hypoglycemia, signs of hypo- glucagon tolerance, glucose tolerance, tolbutamide
glycemia are often not seen, even with extremely low tolerance, L-leucine, oral glucose tolerance, epi-
blood glucose levels. The rate of decrease in blood nephrine tolerance, and the calcium infusion test.
CHAPTER 11 ONCOLOGIC DISEASES OF THE DIGESTIVE SYSTEM 409
These tests use the administration of potentially Medical management for glucagonoma syn-
dangerous substances and are expensive, time con- drome has been described in the dog. For specifics,
suming, and most importantly not as accurate as see the section on endocrine pancreas tumors in
the paired insulin-glucose tests. the dog.
The metastatic behavior of insulinoma in the
cat is unknown. Of three cases, only one had his- Gastrinoma
tologic confirmation. This mass was solitary and Background
well encapsulated. No metastases were detected A rare tumor of the pancreatic islets, gastrinomas
grossly. However, this patient developed hypo- secrete gastrin and result in hypertrophic gastritis
glycemia 7 months later, suggestive of incomplete and subsequent peptic ulcers. This syndrome is
surgical excision and recurrence or a metastatic referred to as Zollinger-Ellison syndrome.
lesion. Clinical Parameters and Work-up
Treatment Clinical signs of gastrinomas include chronic vom-
Minimal information is available for treatment of iting and weight loss, which is related to the
insulinoma in the cat. However, in a stable patient hypersecretion of gastrin and consequent ulcera-
with no evidence of metastasis, surgical resection tion. The clinical work-up should include basic
can be attempted. blood work, urinalysis, and abdominal and tho-
Medical management has not been described racic imaging. Diagnosis involves the measurement
for the management of insulinoma in the cat. For a of serum gastrin, demonstration of gastric hyper-
discussion of appropriate drugs for use in the dog, trophy and ulceration, and increased secretion of
see the section on endocrine pancreas tumors in gastric acid. Provocative testing with secretin or
the dog. calcium is usually only indicated when gastrin lev-
els are minimally elevated. A novel method of
Glucagonoma diagnosis described is the use of somatostatin-
Background receptor scintigraphy.
Rare tumors of the pancreatic alpha cells, Treatment
glucagon-secreting tumors have been described in Although the course of gastrinomas tends to be
two cats. The typical lesions that are concomitant chronic, early surgical resection can be attempted.
with a glucagonoma are SND or MEN and are Medical management is symptomatic and includes
characteristic of glucagonoma syndrome. an H2-receptor antagonist or omeprazole, and
Clinical Parameters and Work-up octreotide acetate. Ulcer therapy is described in
Clinical signs described in the literature include detail in Chapter 5.
skin lesions and blood work abnormalities. In the
cat, skin lesions are characterized by erythema Pancreatic Polypeptidoma (Vasoactive
and crusting plaques on the limbs, abdomen, and Intestinal Peptidoma,
genital areas. A complete staging scheme should Somatostatinoma)
include basic blood work, urinalysis, and abdom- This tumor is not reported in the cat.
inal and thoracic imaging. In one tumor evalu-
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C H A P T E R
12
ENTERAL AND
PARENTERAL
NUTRITION
Howard B. Seim III
Joseph W. Bartges
416
CHAPTER 12 ENTERAL AND PARENTERAL NUTRITION 417
ENTERAL
NUTRITIONAL
SUPPORT
From Cerra FB: How nutrition changes what getting sick
Enteral nutritional support is a practical, safe, easy,
means, J Parenter Enteral Nutr 14:164S, 1990. economic, physiologic, and well-tolerated tech-
NC, No change; –, decrease; +, increase. nique with minimal morbidity; however, it requires
418 CHAPTER 12 ENTERAL AND PARENTERAL NUTRITION
Contraindications Oral
Enteral nutritional support may be contraindi- As a general rule, oral feeding is the method of
cated in several situations. Patients with adynamic choice if adequate amounts of nutrients can be
ileus, small bowel obstruction, severe intrinsic consumed to meet the patient’s protein and calorie
small bowel disease (e.g., inflammatory bowel dis- needs. Several techniques have been used to suc-
ease, diffuse intestinal lymphosarcoma), persistent cessfully coax a patient to eat. Sending the patient
vomiting or diarrhea, or severe malabsorption home if the disease state permits and if owners are
should have nutrients delivered by routes other capable of managing the patient may prove suc-
than the GI tract. In addition, patients at risk for cessful. Petting and vocal reassurance is also helpful
aspiration pneumonia (e.g., stupor or coma) in stimulating patients to eat; however, it is time
should not be fed via the GI tract. consuming (Figure 12-2). Highly palatable foods
or food coverings (e.g., gravy) may stimulate
appetite; adding water to food increases palatabil-
ROUTES OF ity for dogs (Figure 12-3).Warming foods to near
ADMINISTRATION but not above body temperature (e.g., with a
microwave oven) will increase aroma and palata-
As a general rule, the closer one comes to the oral bility. Nutrition may also be provided by syringe
route of food intake and digestion, the more effi- feeding, but the diet must be semiliquid in consis-
cient is the assimilation and digestion of nutrients tency and there is a risk of aspiration pneumonia
and the greater the flexibility in formula composi- (Figure 12-4). Drugs may be used successfully to
tion. Conversely, the further aboral one gets, the stimulate appetite sometimes; however, if they do
less efficient is the assimilation and digestion of not work immediately, then more aggressive forms
nutrients and the greater the care that must be of nutritional support should be considered. A list
taken when choosing formula composition. of drugs and their recommended dosages are given
Route of administration also dictates feeding tube in Table 12-3.
420 CHAPTER 12 ENTERAL AND PARENTERAL NUTRITION
Orogastric Tube
Passing a feeding tube through the mouth into the
distal esophagus or stomach is technically easy to
FIGURE 12-3 Using a variety of diets or highly do; however, it is usually stressful to adult dogs and
palatable foods may stimulate appetite. cats (Figure 12-5). It is often used to provide
nutrition to orphaned puppies and kittens. A 5 Fr
Appetite stimulant drugs are generally not ade- infant feeding tube can be used for orphans
quate in promoting replacement of a patient’s weighing less than 300 g, an 8 to 10 Fr infant feed-
caloric needs; however, they may provide the stim- ing tube can be used for orphans weighing over
ulus necessary for the patient to resume eating. 300 g, or an appropriate-size, soft, male urethral
Appetite stimulants are contraindicated in patients catheter may be used. An appropriate size syringe
suffering from severe malnutrition or in those should be used to avoid disconnecting the syringe
patients that cannot tolerate the medication. from the feeding tube to refill it while feeding and
Diazepam should be used cautiously in patients to prevent administering formula too rapidly.
with preexisting liver disease because its use has Once weekly the feeding tube should be clearly
been associated with inducing hepatocellular marked to indicate the depth of insertion to ensure
necrosis. Glucocorticoids stimulate appetite; how- gastric delivery; that is, the distance from the last rib
ever, they are catabolic and induce diuresis and to the tip of the nose can be measured and marked
hepatic lipid accumulation. Megestrol acetate may off on the feeding tube as a guide.To insert an oro-
induce diabetes mellitus, adrenal suppression, and gastric feeding tube in a neonatal puppy or kitten,
mammary neoplasia in cats. None of these drugs the clinician passes the feeding tube through the
work consistently, and none have been evaluated mouth into the stomach. The feeding tube must
in a controlled manner. be in the GI tract and not the respiratory tract
CHAPTER 12 ENTERAL AND PARENTERAL NUTRITION 421
TABLE 12-3 Appetite Stimulants That Can Be Used in Cats (C) and
Dogs (D)
Agent Dose Route Frequency Species
Diazepam 0.5-1 mg/lb PO As needed C
0.05-0.1 mg/lb PO As needed D
0.025-0.05 mg/lb IV As needed C, D
0.5-2.0 mg IV As needed C
Oxazepam 0.15-0.2 mg/lb PO As needed C, D
2-2.5 mg PO As needed C
Flurazepam 0.05-0.1 mg/lb PO As needed C
0.05-0.25 mg/lb PO As needed D
Chlordiazepoxide 2 mg PO As needed C
Cyproheptadine 2 mg PO q8-12h C
Prednisone 0.125-0.25 mg/lb PO q48h C, D
Boldenone undecylenate 5 mg IM/SQ q7d C
Nandrolone decanoate 10 mg IM q7d C
2.5 mg/lb IM q7d D
(maximum 200 mg)
Stanozolol 1-2 mg PO q12h C, D
25-50 mg IM q7d C, D
Megestrol acetate 0.5 mg/lb PO q24h D
B vitamins 1 ml/L fluids IV CRI C, D
Cobalamin 0.25 mg/lb SQ q24h C
0.5 mg/lb SQ q24h D
Elemental zinc 0.5 mg/lb PO q24h C, D
Potassium 0.25-0.5 mEq KCl/lb PO q12h C, D
3 mEq K gluconate PO q6-8h C, D
Interferon alfa-2b 3-30 IU PO q12h C
PO, Orally; IV, intravenously; IM, intramuscularly; SQ, subcutaneously; CRI, constant rate infusion.
before feeding; it can often be palpated in the cer- into the respiratory tract, bubbles will appear in
vical esophagus. If an obstruction is felt while pass- the water as the neonate breathes. If the tube is
ing the tube before reaching the mark, the tube is properly placed, then the neonate may be fed.
in the trachea. After inserting the feeding tube to When feeding, the clinician fills a syringe with
the premeasured mark, the clinician places the warm formula and fits it to the feeding tube, being
flared end of the tube in a glass of water and careful to expel any air in the tube or syringe, then
observes for bubbles while the neonate breathes. If aspirates back on the tube to make sure there is no
the feeding tube has been inadvertently inserted residual formula remaining from the previous
feeding.When certain that the tube is in the stom-
ach, the clinician slowly administers the formula
over a couple of minutes to allow sufficient time
for slow filling of the stomach. Regurgitation of
formula rarely occurs, but if it does, the feeding
tube is withdrawn and feeding is interrupted until
the next scheduled meal.
Nasoesophageal/Nasogastric
Tube
Nasoesophageal tube placement is an easy, effec-
tive, and efficient means of providing enteral
FIGURE 12-5 Orogastric feeding tube placement in nutritional support (Figure 12-6). The availability
an adult cat. of small-bore, soft polyvinyl and Silastic feeding
422 CHAPTER 12 ENTERAL AND PARENTERAL NUTRITION
FIGURE 12-6 Use of a nasoesophageal feeding tube Tube Placement—Cat. The clinician places
in an adult dog. the tube in the ventromedial aspect of the external
nares (Figure 12-7, C ) and passes it in a caudoven-
tubes (i.e., 3.5 to 5 Fr) and low-viscosity, nutri- tral medial direction into the nasal cavity (Figure
tionally complete liquid diet formulations and 12-7, D). The tube will generally “drop” into the
patient tolerance of tube placement have made oropharynx and stimulate a swallowing reflex.
nasoesophageal tube placement a popular avenue When the patient swallows, the clinician flexes
for feeding malnourished patients. Nasoesophageal the patient’s head to facilitate passage of the tube
tube placement is indicated in any conscious into the esophagus and passes the tube to the
patient with protein-calorie malnutrition that will predetermined mark.
not undergo oral, pharyngeal, esophageal, gastric,
or biliary tract surgery. Tube Placement—Dog. The clinician iden-
tifies the prominent alar fold and directs the tube
Technique. Local nasal anesthesia, sedation, or from a ventrolateral location in the external nares
light general anesthesia may be necessary for to a caudoventral and medial direction as it enters
placement of a nasoesophageal tube in dogs and the nasal cavity. When the tube is introduced
cats. In the majority of cases, topical anesthetic is 0.5 to 1 cm inside the nostril, the clinician feels it
all that is necessary for proper tube placement. In contact the median septum at the floor of the nasal
cats the clinician places 0.5 to 1 ml of 0.5% cavity. At this moment the clinician pushes the
proparacaine hydrochloride (topical local anes- external nares dorsally to facilitate opening the ven-
thetic) or in dogs the clinician places 1 to 2 ml of tral meatus, elevates the proximal end of the tube,
0.5% proparacaine or 2% lidocaine into the nasal and continues to advance the tube (Figure 12-8).
cavity and tilts the head up to encourage the local Once the tube is inserted an additional 3 to 5 cm,
anesthetic to coat the nasal mucosa (Figure 12-7, the clinician discontinues pushing the nares dor-
A). Application of local anesthetic is repeated to sally. The clinician flexes the patient’s head while
ensure adequate anesthesia of the nasal mucous continuing to insert the tube to facilitate passage
membrane. If the patient will not tolerate nasal through the nasopharynx into the esophagus and
intubation (i.e., if excess stress is required to place inserts the tube to the predetermined measurement
the nasoesophageal tube, particularly with debili- mark.
tated cats), light sedation or a light plane of anes-
thesia is induced. Confirming Esophageal Placement.
The clinician confirms esophageal placement by
Tube. An appropriate-size polyvinyl chloride injecting 3 to 5 ml of sterile saline through the
feeding tube is selected. For cats a 5 Fr, 91-cm tube. If a cough is elicited, the tube is removed and
tube works best. For dogs between 4.5 and 22 lb, a replaced. Alternately, the clinician places 6 to 12
5 Fr, 91-cm tube is best, and an 8 Fr, 91-cm tube is ml of air in the tube and auscultates for borboryg-
best for dogs greater than 22 lb.The clinician esti- mus at the xiphoid to confirm tube placement.
mates the length of tube to be placed in the Esophageal placement can also be confirmed by
esophagus or stomach by placing the tube from taking a lateral thoracic radiograph. If the patient
CHAPTER 12 ENTERAL AND PARENTERAL NUTRITION 423
A C
B D
FIGURE 12-7 Nasoesophageal tube placement. A, Instillation of topical anesthetic into the nasal cavity.
B, Estimation of length of tube to be inserted in the patient. C, The feeding tube is inserted into the ventromedial
aspect of the nares. D, The feeding tube is inserted through the ventral meatus and nasopharynx into the esophagus.
NP, Nasopharynx: NV, nasal vestibule; CS, cartilaginous septum; M, maxilla; DM, dorsal meatus; MM, middle
meatus: EC, ethmoidal conchae; VNC, ventral nasal concha; DNC, dorsal nasal concha; AF, alar fold. (D from
Crowe DT Jr: Clinical use of an indwelling nasogastric tube for enteral nutrition and fluid therapy in the dog and
cat, J Am Anim Hosp Assoc 22:675, 1986.)
requires general anesthesia, tube placement can be Tube Management. The clinician should
determined visually. place a column of water in the tube and cap it
with an infusion cap, three-way stopcock, or
Securing the Tube to the Patient. Once Christmas tree adapter when not in use; this pre-
the tube is properly inserted, the clinician should vents intake of air, reflux of esophageal contents,
suture it to the nose and head to ensure that it will and occlusion of the tube by diet. Nasoesophageal
not be removed by the patient.The tube is secured tubes can be left in place for several weeks, are well
to the lateral aspect of the nose with the preplaced tolerated, and are easily removed; the patient can
butterfly tape and the zygomatic arch using 3-0 drink and swallow around the tube; and repeated
nylon suture (see Figure 12-6).An encircling suture orogastric intubation is prevented.
and Chinese finger-trap friction suture (Figure 12-9,
A and B) or cyanoacrylate glue may be used also. Complications. Patients tolerate nasoesophageal
Although there may be concern about stimulating feeding tubes fairly well; however, several complica-
a feline’s whiskers using this placement, clinical tions may occur. Premature removal is a common
experience has not found this to be a problem. An occurrence, particularly if the tube is irritating.
Elizabethan collar should be used until it is deter- Other complications include rhinitis, dacryocystitis,
mined if the patient will tolerate the presence of esophageal reflux, vomiting, aspiration pneumonia,
the tube. Many cats tolerate a nasoesophageal tube and obstruction of the tube. In addition, patients
without an Elizabethan collar. may vomit or regurgitate the tube and inhale the
424 CHAPTER 12 ENTERAL AND PARENTERAL NUTRITION
Esophagostomy Tube
Esophagostomy tube feeding is indicated in
anorexic patients with disorders of the oral cavity
or pharynx or anorexic patients with a functional
GI tract distal to the esophagus (Figure 12-12).
Esophagostomy tube placement is contraindicated
in patients with a primary or secondary esophageal
FIGURE 12-10 A pharyngostomy feeding tube in an disorder (e.g., esophageal stricture, following
adult male West Highland white terrier. esophageal foreign body removal or esophageal
surgery, esophagitis, megaesophagus).
the intrapharyngeal ostium and laryngopharynx is
identified; this is the proper location for the Tube Placement. Patients should be placed
pharyngostomy tube exit (Figure 12-11, B). under general anesthesia and the trachea intu-
Enough pressure is gently applied to the lateral bated. The patient is placed in right lateral recum-
pharyngeal wall to create an externally visible bency with left side uppermost. The tube can be
bulge. An Eld device or large curved forceps (e.g., placed on either the right or left side of the mid-
Carmalt or Doyen) should be used to maintain the cervical region; however, the esophagus lies
bulge. A 1- to 2-cm skin incision is made over the slightly left of midline, making left-sided place-
bulge, and curved forceps are used to bluntly dissect ment more desirable. The clinician aseptically pre-
subcutaneous tissue, pharyngeal muscle, and pha- pares a 4-cm-square area along the left lateral
ryngeal mucosa until the forceps become visible. midcervical area. The neck is slightly extended
If an Eld device is used, see esophagostomy tube and the mouth held open with a mouth speculum.
placement for technique.The clinician uses forceps The clinician premeasures and marks a 14 to 24 Fr
to grasp the tip of the pharyngostomy tube and polyvinyl chloride or Silastic feeding tube (i.e., 20
pull it through the incision, into the oral cavity, to 24 Fr for dogs and 14 to 18 Fr for cats) from the
and out of the mouth.The tip of the tube is rein- level of the midcervical region (i.e., exit point of
426 CHAPTER 12 ENTERAL AND PARENTERAL NUTRITION
FIGURE 12-11 Pharyngostomy tube placement. A, Anatomic location for tube placement in the lateral
pharyngeal wall.The white circle indicates the appropriate site for tube placement. (From Crowe DT Jr, Downs
MO: Pharyngostomy complications in dogs and cats and recommended technical modifications: experimental and
clinical investigations, JAAHA 22:493, 1986.) B, Top: Improper placement of the tube exiting cranial to the
epihyoid cartilage results in interference with function of the epiglottis and hyoid apparatus. Bottom: Proper
placement of the tube exiting caudal to the hyoid apparatus. (From Crowe DT Jr: Nutrition in critical patients:
administering the support therapies, Vet Med 84:162, February 1989.) C, The tip of the feeding tube exiting the oral
cavity is grasped with forceps and directed into the esophagus.
feeding tube) to the level of the seventh or eighth cutaneous gastrostomy feeding tube placement
intercostal space, ensuring thoracic esophageal device (Eld device), and the second involves using
placement. The clinician enlarges the two lateral long curved forceps similar to pharyngostomy
openings of the feeding tube or cuts off the distal tube placement except caudal to the larynx.
rounded end of the feeding tube to encourage
smoother flow of blended diets. There are two Eld Gastrostomy Feeding Tube Place-
techniques that can be used to place esophagos- ment Device Technique. An Eld device can
tomy tubes: one method involves using an Eld per- be used to place an esophagostomy feeding tube.
CHAPTER 12 ENTERAL AND PARENTERAL NUTRITION 427
A1
A2 A3
FIGURE 12-13 A, Esophagostomy tube placement: Eld PGFT applicator. 1,The applicator is passed through the
oral cavity into the mid to proximal esophagus.A small skin incision is made in the lateral cervical region over the
tip of the applicator. 2 and 3, Photographs illustrating these steps.
Continued
428 CHAPTER 12 ENTERAL AND PARENTERAL NUTRITION
B1 C1
C2
B2
C3
grasped with the forceps, and the forceps are involves using a stylet or hemostat to advance the
retracted into the oral cavity. distal tip of the catheter into the esophagus, and
the second involves inserting a stylet down the
Redirection of Tube. With either method, shaft of the feeding tube. In the dog the clinician
using the Eld device or using curved forceps, the places a stylet through one of the side holes of the
distal end of the tube exits the oral cavity and the feeding tube and against its tip.The feeding tube is
flared end of the feeding tube exits the midcervi- lubricated and advanced into the esophagus until
cal esophagus.The next step is to redirect the dis- the entire oral portion of the tube disappears.The
tal end of the feeding tube so that it terminates in clinician gently retracts the stylet from the oral cav-
the thoracic esophagus. There are two methods ity, being careful to ensure its release from the feed-
that the clinician can use to accomplish this: one ing tube (Figure 12-15, A and B). In the cat the
430 CHAPTER 12 ENTERAL AND PARENTERAL NUTRITION
Gastrostomy Tube
Tube gastrostomy is indicated in anorexic patients
with a functional GI tract distal to the esophagus
or patients undergoing operations of the oral cav-
ity, larynx, pharynx, or esophagus (Figure 12-18).
Gastrostomy tube placement is contraindicated in
patients with primary gastric disease (e.g., gastritis,
gastric ulceration, gastric neoplasia) or disorders
Technique
Percutaneous Without Visualization
Placement of gastrostomy tubes with visualization
is advised when possible because direct visualiza-
tion is associated with potentially fewer complica-
tions; however, gastrostomy feeding tubes can be
placed safely without visualization.
Stomach Tube Technique
A gastrostomy tube placement device can be pre-
pared by purchasing a length of vinyl or stainless
steel tubing from a hardware store (Figure 12-19,
A). The length of the tubing is determined by
FIGURE 12-18 Percutaneous endoscopically placed measuring the distance from the nasal planum to
gastrostomy feeding tube in an adult cat with the iliac crest and adding 15 cm.The outer diame-
idiopathic hepatic lipidosis. ter of the tube ranges from 1.2 cm (patients
weighing less than 25 lb) to 2.5 cm for dogs
weighing more than 55 lb.The distal tip of a stain-
causing uncontrolled vomiting and in comatose less steel tube can be flared and deflected 45
patients. Advantages of gastrostomy tube feeding degrees to the long axis of the tube to help displace
include ease of tube placement, patient tolerance, the body wall laterally. The patient is anesthetized
use of large-bore feeding tubes, ease of tube care and positioned in right lateral recumbency. The
and feeding by the owner, and the fact that oral lubricated tube is passed through the mouth and
feeding can commence while the tube is in place. into the stomach. The tube is advanced until the
Disadvantages of gastrostomy tube feeding include end of the tube displaces the stomach laterally.
the following: use of specialized equipment may Positioning the patient with its head over the edge
be necessary (e.g., endoscope, special tube place- of the table and lowering the proximal end of the
ment instruments), general anesthesia is required, tube will facilitate identifying the tube tip through
feeding cannot be initiated the first 12 hours after the body wall (Figure 12-19, B).A stab skin incision
tube placement, and, depending upon placement is made over the distal end of the tube, and a 14-
technique, tubes must remain in place for a mini- gauge hypodermic needle or an over-the-needle
mum of 7 to 14 days before removal (in order to intravenous catheter is introduced percutaneously
encourage adhesion formation between stomach into the lumen of the tube while holding the dis-
and abdominal wall). tal tip of the tube between two fingers. Proper
positioning of the catheter is confirmed by mov-
Tube Placement. Gastrostomy feeding tubes ing the hub from side to side and feeling the
may be placed without visualization (using the catheter tip strike the inside of the tube. A guide
stomach tube technique, Eld feeding tube placement wire prepared from a monofilament banjo string
device, or Cook feeding tube placement device) or or cerclage wire is threaded through the needle or
with visualization (using endoscopy or surgery). catheter, into the tube, and out of the mouth of
Gastrostomy tubes placed surgically may be done the patient (Figure 12-19, C and D).The tube and
with or without gastropexy. Gastrostomy tubes are catheter are removed, and the wire is attached to a
usually placed under general anesthesia with the gastrostomy tube, which is secured (Figure 12-19,
patient positioned in right lateral recumbency. For E ). Securing the gastrostomy feeding tube to the
all techniques except placement through a midline wire is accomplished by cutting off the flared end
laparotomy, the left paralumbar fossa is clipped and of the mushroom-tipped catheter (Figure 12-19,
prepared aseptically. Drapes are not necessary unless F ). An intravenous catheter or 5-ml pipette tip is
a surgical approach is used. Gastrostomy feeding fed over the wire at the oral cavity.Two V-shaped
tubes should exit the left lateral abdominal wall notches are then cut opposite each other at the
approximately 1 to 2 cm caudal to the costochondral proximal end of the gastrostomy tube.The feeding
arch and approximately one third of the way dorsal tube is tied to the wire, and the notched end of the
from the ventral abdominal wall.This results in the feeding tube is planted firmly in the flared end of
tube being located along the gastric fundus cranial the intravenous catheter or pipette tip.The feeding
to the spleen and caudal to the liver. tube and catheter/pipette tip are lubricated.A long
CHAPTER 12 ENTERAL AND PARENTERAL NUTRITION 433
B C
FIGURE 12-19 Gastrostomy tube placement without visualization: stomach tube. A, Equipment required to insert
a gastrostomy feeding tube without visualization using a stomach tube.The stomach tube may be hard plastic or
metal.A length of wire is also necessary for placement. B, The stomach tube is inserted through the oral cavity and
esophagus into the stomach.The end of the tip in the stomach is palpated through the abdominal wall. C, An
intravenous catheter has been inserted through a small skin incision into the lumen of the stomach tube, and a wire
has been inserted into the catheter and lumen of the stomach tube. (A-C courtesy Dr.T. Glaus, Switzerland.)
Continued
piece of fishing line or Vetafil is placed through the Placement of a gastrostomy feeding tube using the
side holes of the mushroom end of the feeding Eld device is performed in a manner similar to
tube; this suture should not be tied.This provides a using the device to place an esophagostomy tube.
means to recover the feeding tube should prob- The patient is anesthetized and placed in right lat-
lems arise. The tube is then pulled through the eral recumbency; the tube will exit the left lateral
esophagus,into the stomach,and through the abdom- abdominal wall in the paralumbar fossa. The Eld
inal wall by placing tension on the wire at the device is passed through the oral cavity, down the
abdominal wall exit site (Figure 12-19, G and H). esophagus, and into the stomach. Gentle downward
The skin incision may need to be enlarged to pressure is applied to the handle to facilitate iden-
facilitate passage of the feeding tube through the tification of the distal end of the Eld device in the
body wall and skin (Figure 12-19, I ). The mush- stomach (Figure 12-20, B).When the distal end of
room tip should be palpable through the body the Eld device is positioned properly in the left
wall. The mushroom tip should not be pulled paralumbar fossa, a small stab skin incision is made
through the body wall. Once the feeding tube is over the distal end. Then the spring-loaded
secured, the suture placed through the side holes plunger is pushed (Figure 12-20, C), resulting in
of the mushroom tip is removed by pulling on one the sharp point being thrust through the gastric
end of the suture. and abdominal wall. A piece of suture (such as
Eld Feeding Tube Device Vetafil) or monofilament fishing line is inserted
Gastrostomy feeding tubes may be placed nonvisu- through the hole in the pointed tip of the distal
ally using a device that facilitates placement. One end of the Eld device (Figure 12-20, D), and the
device is the Eld percutaneous gastrostomy feeding distal end is retracted into the outer sheath. The
tube applicator (Eld device) (Figure 12-20, A). entire device is removed, pulling the suture or
434 CHAPTER 12 ENTERAL AND PARENTERAL NUTRITION
E F
FIGURE 12-19, cont’d D, Schematic illustrating passage of the wire through the intravenous catheter and
lumen of the stomach tube. E, The stomach tube is removed, but the wire is left in place.The wire now enters the
lateral abdominal wall, passes through the stomach and esophagus, and exits the oral cavity. F, A tapered catheter is
inserted on the end of the wire that exits the oral cavity, and the feeding tube is attached to the wire. (E and F
courtesy Dr.T. Glaus, Switzerland.)
fishing line in an antegrade direction. This results tip is fed over the wire at the oral cavity. Two V-
in an end of the suture or fishing line exiting the shaped notches are then cut opposite each other at
oral cavity and the other end exiting the left the proximal end of the gastrostomy tube. The
abdominal wall. The gastrostomy tube is then feeding tube is tied to the suture, and the notched
secured to the suture exiting the oral cavity end of the feeding tube is planted firmly in the
(Figure 12-20, E). Securing the gastrostomy feed- flared end of the intravenous catheter or pipette
ing tube to the suture is accomplished by cutting tip. The feeding tube and catheter/pipette tip are
off the flared end of the mushroom-tipped lubricated. A long piece of fishing line or Vetafil is
catheter. An intravenous catheter or 5-ml pipette placed through the side holes of the mushroom
CHAPTER 12 ENTERAL AND PARENTERAL NUTRITION 435
G H
FIGURE 12-19, cont’d G, Tension is applied to the end of the wire that exits the lateral abdominal wall. H, The
feeding tube is pulled into the oral cavity, esophagus, and stomach. I, The lateral abdominal wall skin incision is
enlarged, and the feeding tube is exteriorized. (G-I courtesy Dr.T. Glaus, Switzerland.)
end of the feeding tube; this suture should not be distal end of the Cook device is angled and flared,
tied.This provides a means to recover the feeding and this end is palpated in the left paralumbar
tube should problems arise.The tube is then pulled fossa. A stab skin incision is made over the flared
through the esophagus, into the stomach, and end of the Cook device (Figure 12-23, B), and the
through the abdominal wall by placing tension on application needle is passed through the stab incision
the suture at the abdominal wall exit site.The skin and body wall into the lumen of the Cook device
incision may need to be enlarged to facilitate pas- (Figure 12-23, C). Correct insertion of the needle
sage of the feeding tube through the body wall
and skin. The mushroom tip should be palpable
through the body wall.The mushroom tip should
not be pulled through the body wall. Once the
feeding tube is secured, the suture placed through
the side holes of the mushroom tip is removed by
pulling on one end of the suture.
Cook Feeding Tube Placement Device
Use of a Cook feeding tube placement device
(Cook device) is another technique for placing
gastrostomy feeding tubes without visualization
(Figure 12-21). The patient is anesthetized and
placed in right lateral recumbency (Figure 12-22).
The tube will exit in the left paralumbar fossa, and
that area is aseptically prepared. The Cook device FIGURE 12-20 A, Gastrostomy tube placement
is passed through the oral cavity, down the esoph- without visualization: Eld percutaneous gastrostomy
agus, and into the stomach (Figure 12-23, A).The feeding tube (PGFT) applicator.
Continued
436 CHAPTER 12 ENTERAL AND PARENTERAL NUTRITION
FIGURE 12-20, cont’d B, The applicator is inserted through the oral cavity and esophagus into the stomach.
The tip of the tube is palpated through the lateral abdominal wall. C, When the spring-loaded plunger is depressed,
a sharp, pointed end is exposed at the distal tip of the applicator. (B modified from JorVet Eld gastrostomy tube
applicator manual, Jorgensen Laboratories, Loveland, Colo.)
is verified by tapping the needle against the inner end of the feeding tube is inserted on the ribbed
wall of the lumen of the Cook device. If the flared end of the tapered insertion device (Figure 12-23,
end of the Cook device cannot be palpated in the G ). The insertion device has a threaded end,
gastric lumen or if the spleen appears to be overly- which is attached to the threaded end of the wire
ing the end, a three-way stopcock can be attached exiting the mouth (Figure 12-23, H). A long piece
to the proximal end of the Cook device and air of fishing line or Vetafil is placed through the side
can be injected to distend the stomach (Figure 12- holes of the mushroom end of the feeding tube; this
23, D). A threaded wire supplied with the Cook suture should not be tied.This provides a means to
device is inserted through the needle so that it recover the feeding tube should problems arise.The
exits the proximal end of the Cook device where insertion device and feeding tube are lubricated,
it exits the oral cavity (Figure 12-23, E ).The wire and the tube is then pulled through the esophagus,
is fed so that the threaded end is inserted and exits into the stomach, and through the abdominal wall
at the mouth (Figure 12-23, F ).The Cook device by placing tension on the wire at the abdominal
is then removed. The flared end of a mushroom- wall exit site (Figure 12-23, I ). The mushroom tip
tipped feeding tube is cut off, and the remaining should not be pulled through the body wall (Figure
CHAPTER 12 ENTERAL AND PARENTERAL NUTRITION 437
FIGURE 12-20, cont’d D, The sharp, pointed, distal tip of the applicator is thrust through the stomach and
lateral abdominal wall.A piece of suture is threaded through the hole in the tip, and the tip is retracted into the body
of the applicator. E, The applicator and attached suture are removed.The feeding tube is attached to the suture.
(D modified from and E from JorVet Eld gastrostomy tube applicator manual, Jorgensen Laboratories, Loveland, Colo.)
438 CHAPTER 12 ENTERAL AND PARENTERAL NUTRITION
oblique muscle. This muscle is dissected in the sutures are placed in the exposed stomach wall to
direction of its fibers to expose the transversus ensure that it will not fall back into the abdominal
abdominus muscle.The clinician dissects this mus- cavity. The orogastric tube can now be removed
cle in the direction of its fibers and penetrates the from the stomach. A purse-string suture is placed
peritoneum to expose the wall of the stomach in the stomach wall around the proposed tube
over the tube, being careful not to enter the lumen entry point using 3-0 Maxon.The clinician uses a
of the stomach. One or two 3-0 Maxon stay No. 11 scalpel blade to enter the stomach, places a
A D
C F
FIGURE 12-23 Gastrostomy tube placement without visualization: Cook feeding tube insertion device. A, The
device is inserted through the oral cavity and esophagus into the stomach. B, A small skin incision is made over the
left paralumbar fossa. C, The tip of the device located in the stomach is positioned under the skin incision, and
the needle is inserted through the lateral abdominal wall and stomach wall into the lumen of the device.
D, A three-way stopcock can be attached to the end of the device for stomach insufflation. E, The threaded wire is
inserted through the needle into the lumen of the device until it is visualized at the end of the device inserted into
the oral cavity. F, The wire extends from the left lateral abdominal wall through the stomach and esophagus, and
exits the oral cavity. (A-F courtesy Dr. R. Bright, Colorado.)
Continued
440 CHAPTER 12 ENTERAL AND PARENTERAL NUTRITION
G I
H J
FIGURE 12-23, cont’d G, The flared end of the mushroom-tipped feeding tube is removed, and the remaining
end of the feeding tube is attached to the ribbed end of the tapered insertion device. H, The tapered insertion
device with the mushroom-tipped feeding tube is attached to the threaded end of the wire that exits the oral cavity.
I, The wire is retracted through the abdominal wall, pulling the feeding tube through the oral cavity and esophagus
into the stomach. J, The tapered insertion device aids in pulling the feeding tube through the stomach and lateral
abdominal wall. (G courtesy Dr. R. Bright, Colorado.)
20 to 24 Fr Foley catheter 3 to 4 cm into its lasting seal between the stomach wall and body
lumen, and inflates the bulb. The purse-string wall, and confirmation of proper tube placement is
suture is secured around the Foley catheter to cre- performed during placement. Feeding tubes can be
ate an airtight and watertight seal. Gentle traction safely removed at any time after placement. A dis-
is placed on the Foley catheter to bring its bulb advantage of this technique is the difficulty of pal-
against the stomach wall and the stomach wall pating the orogastric feeding tube in the flank of
against the abdominal wall. Four or five simple obese patients. Also it requires a surgical and thus
interrupted sutures of 3-0 Maxon are placed from more invasive approach to placing a feeding tube.
the stomach wall to the body wall to provide a Surgical Placement Through a Midline
firm gastropexy to the abdominal wall. The clini- Laparotomy
cian closes subcutaneous tissues and skin around The patient is aseptically prepared for a midline
the exiting Foley catheter and secures the catheter celiotomy. From a ventral midline laparotomy
to the skin with a Chinese finger-trap friction approach, the distal end of a 20 Fr Foley or Pezzer
suture of No. 1 Novofil (Figure 12-26, A-C). catheter is brought into the abdominal cavity
Advantages and Disadvantages. Advantages of through a stab incision in the left body wall. The
the surgical technique include the following: the ventral surface of the stomach is exteriorized, a
tube is easily placed, the stomach is easily found in purse-string suture is placed in the body of the
an anoretic patient, tube placement is quick, no stomach equidistant between the lesser and greater
special equipment is needed to place the tube (i.e., curvature, and a stab incision is made in the center
endoscope or feeding tube placement device), sur- of the purse-string suture with a No. 11 scalpel
gical gastropexy ensures an immediate and long- blade. The distal end of the feeding catheter is
CHAPTER 12 ENTERAL AND PARENTERAL NUTRITION 441
FIGURE 12-24 Gastrostomy tube placement: percutaneous endoscopic placement. A, With the dog in right lateral
recumbency, the endoscope is inserted into the stomach and the stomach is distended with air. B, An over-the-
needle catheter or hypodermic needle is placed transabdominally into the stomach lumen adjacent to the tip of the
endoscope. C, Close-up of an endoscopic snare grasping a 2-inch catheter after the stylet has been removed. (A and
C from Tams TR: Small animal endoscopy, ed 2, St. Louis, 1999, Mosby. B from Bright RM, Burrows CF:
Percutaneous endoscopic tube gastronomy in dogs, Am J Vet Res 49[5]: 629, 1988.) Continued
placed in the lumen of the stomach, and the purse- abdominal wall, creating an early permanent gas-
string suture is tightened around the catheter. tropexy. The major disadvantage is the need to
The bulb (i.e., Foley) is inflated with saline, and perform a laparotomy to place the tube.This tech-
gentle traction is placed on the catheter to bring the nique is generally performed when exploratory
body of the stomach in close apposition to the left laparotomy is required for diagnosis or treatment
body wall. The stomach wall is sutured to of the patient’s primary disorder.
the abdominal wall with four or five 3-0 Maxon
sutures to provide an early permanent gastropexy. Complications of Gastrostomy
The feeding tube is secured to the skin with a Feeding Tubes
Chinese finger-trap friction suture of No. 1 Potential complications of gastrostomy feeding
Novofil. The abdomen is closed routinely (Figure tubes relate to mechanical, GI, and metabolic
12-27). complications. The most severe complication of
Advantages and Disadvantages. The advantage gastrostomy tube placement is early removal with
of gastrostomy tube placement via laparotomy is leakage of gastric contents into the abdominal
the ability to suture the stomach wall to the cavity and subsequent generalized peritonitis.
442 CHAPTER 12 ENTERAL AND PARENTERAL NUTRITION
lateral recumbency, passes the endoscope through gastrostomy tube, and the duodenal tube stylet is
the pylorus and into the duodenum, advances the slowly removed (Figure 12-30, F).
biopsy forceps to their full length, and releases the
catheter (Figure 12-30, D). The biopsy forceps are Advantages and Disadvantages. The
replaced in the biopsy port, and the endoscope is advantage of this technique is placement of an
slowly removed (Figure 12-30, E). The duodenal enteral feeding tube without the need of lapa-
feeding tube is secured to the gastrostomy tube by rotomy. Disadvantages include difficulty placing the
seating the flanged end of the duodenal tube in the tube in the duodenum, difficult placement in
444 CHAPTER 12 ENTERAL AND PARENTERAL NUTRITION
G2
H I
patients weighing less than 40 lb, migration of the radiographic assessment for tube placement con-
tube from the duodenum, mechanical obstruction of firmation.This technique is technically demanding
the tube (e.g., kinking), specialized instrumentation and is recommended only for veterinarians
necessary for placement, and the necessity of experienced in endoscopy.
CHAPTER 12 ENTERAL AND PARENTERAL NUTRITION 445
Stomach
wall
A exteriorized
through grid
incision
Purse-string
suture
Tube
in
stomach
C
Stab
incision
FIGURE 12-25 Percutaneous gastrostomy tube placement with gastropexy (cont’d in Figure 12-26). A, Pass a large-
bore, stiff plastic stomach tube into the stomach. Palpate the end of the tube at the flank. B, Grasp the tube and move it
to a point 2 to 3 cm caudal to the thirteenth rib and 2 to 3 cm distal to the transverse processes of the lumbar
vertebrae. Secure the tube with thumb and finger, make an incision through the skin and subcutaneous tissue, and
bluntly dissect the abdominal muscles to expose the gastric wall over the tube. C, Place a purse-string suture in the
gastric wall around the tube and puncture the wall with a scalpel blade. (From Fossum et al.: Small animal surgery, ed 2,
St. Louis, 2002, Mosby.)
Purse-string
A suture
tightened
Pexy
suture
C Chinese
finger-trap friction
suture
FIGURE 12-26 Percutaneous gastrostomy tube placement with gastropexy (cont’d from Figure 12-25). A, Place
the Foley or Pezzer catheter into the lumen of the stomach and into the tube. B, Tighten the purse-string suture,
remove the stomach tube, inflate the bulb of the Foley catheter, and suture the gastric wall to the abdominal wall.
C, Note the proper tube placement of the inflated Foley catheter, the gastropexy, and the Chinese finger-trap
friction suture to secure the tube in place. (From Fossum et al.: Small animal surgery, ed 2, St. Louis, 2002, Mosby.)
one end can be conveniently capped or a red rub- to 12 inches of the tube is passed aborally in the
ber feeding tube is recommended.The distal tip of lumen of the jejunum.The exiting portion of the
the feeding tube is brought into the abdominal tube is laid in the 1- to 1.5-cm seromuscular inci-
cavity through a 2- to 3-mm stab incision on the sion, and the tube is sutured in this “tunnel” by
right or left body wall using a No. 11 scalpel blade. inverting the seromuscular layer over the tube
The clinician selects a segment of small intestine, with three or four interrupted Cushing sutures of
identifies the normal direction of flow of ingesta 4-0 Maxon (Figure 12-32, A-C).The tube exit site
(i.e., oral to aboral), and ensures the selected seg- of the jejunum is sutured to the exit site at the
ment can be easily mobilized to the feeding tube body wall with four to five simple interrupted
entrance location on the body wall.A 1- to 1.5-cm sutures of 4-0 Maxon to provide a permanent
linear incision is made through the seromuscular enteropexy.The exiting feeding tube is secured to
layers of the antimesenteric border of the selected abdominal skin using a Chinese finger-trap fric-
jejunal segment. A 10-gauge hypodermic needle tion suture of 2-0 Novofil.The clinician should be
or the point of a No. 11 scalpel blade is used, and careful not to occlude the lumen of the tube when
the lumen of the jejunum is entered at the most placing the finger-trap suture (Figure 12-33, A-C).
aboral end of the incision. The distal end of the The feeding tube exit site should be incorporated
feeding tube is placed through the incision, and 10 into a body bandage to prevent premature removal
CHAPTER 12 ENTERAL AND PARENTERAL NUTRITION 447
Gastrostomy-Enterostomy Tube
Combination
Occasionally patients may require placement of
gastrostomy and enterostomy feeding tubes
(Figure 12-34).This combination of tubes is gen-
erally indicated for patients that present with vom-
iting as a major part of the history. These patients
cannot initially be fed via a gastrostomy feeding
B
tube immediately postoperatively. Therefore an
enterostomy tube is placed and recommended for
the initial feeding. A gastrostomy tube is also
placed and used if the patient is still anorexic when
the vomiting resolves.
A B
FIGURE 12-29 Low-profile gastrostomy tube placement. A, A stoma-measuring device placed into a
gastrocutaneous fistula and withdrawn until the tip lies gently against the mucosa of the stomach. Circumferential
lines indicate three depths (1.5, 2.6, and 4.3 cm) that correspond with the shaft length of the feeding tube. B, An
obturator being advanced inward until the disk back apposes the base of the low-profile gastrostomy feeding tube.
This elongates the mushroom tip, facilitating placement into the stomach. (Modified from Bright RM et al.: Use of
a low-profile gastrostomy device for administering nutrients in two dogs, J Am Vet Med Assoc 207[9]:1184, 1995.)
enterostomy feeding) is passed through the gastros- the difficulty in passing the enterostomy tube in
tomy tube so that it exits from its distal end. Before the small intestine. Care and patience is needed
gastric placement of the gastrostomy tube, the exit- to encourage the small 5 Fr feeding tube to pass
ing portion of the 5 Fr feeding tube is placed into through the pylorus and into the small intestine.
the stomach lumen through the gastrotomy inci-
sion and manipulated into the duodenum and Complications. The major complication asso-
passed into the proximal jejunum. Once the ciated with combination gastrostomy-enterostomy
enterostomy tube is placed 10 to 12 inches into the tube placement is gastrostomy tube occlusion with
small intestine, the gastrostomy tube is placed into diet fed in the enterostomy tube. Occasionally diet
the gastrotomy incision and secured as described placed in the enterostomy tube will occlude the
above in gastrostomy tube placement via laparo- gastrostomy tube. It is important to encourage
tomy. The jejunostomy tube is secured to the gas- careful management of the enterostomy tube so
trostomy tube to prevent tube migration. that diet does not enter the gastrostomy tube.
FIGURE 12-30 Percutaneous gastroduodenostomy tube placement. A, Ventrodorsal view of the abdomen of a
dog, depicting the location of the percutaneous endoscopic gastrostomy (PEG) tube (1) and the percutaneous
gastroduodenostomy (PEGD) tube (2).The tip of the PEGD tube is at the caudal duodenal flexure. B, With the
dog in right lateral recumbency, the enteral tube is pushed into the PEG tube after shortening the PEG tube and
infusing it with 2.5 ml of water-soluble lubricant. C, Endoscopic view of the gastric fundus.The enteral tube is
identified after pushing it through the cut end of the PEG tube (arrows).The suture is grasped with a standard
biopsy instrument (large arrowhead). D, Endoscopic view of the duodenum.The dog is placed in left lateral
recumbency to facilitate pyloric intubation.The endoscope is advanced aborally as far as possible.The biopsy
forceps are advanced until moderate resistance is felt, then the suture is released.The biopsy forceps (large arrow)
are retracted, leaving the enteral tube (small arrowheads) in the duodenum. E, Endoscopic view of the pylorus
(large arrowheads).The endoscope is gently retracted from the pylorus, while the enteral tube stylet (thin arrows)
remains in place. F, Endoscopic view of the pyloric antrum.The endoscope is withdrawn from the stomach,
while the remaining length of the enteral tube is pushed into the stomach and the stylet is removed, leaving the
enteral tube in place. Arrows indicate where the enteral tube exits the pylorus. (From McCrackin MA et al.:
Endoscopic placement of a percutaneous gastroduodenostomy feeding tube in dogs, J Am Vet Med Assoc
203[6]:792, 1993.)
and milliliters of water required by the animal is of resting energy requirements or some fraction of
calculated. maintenance energy requirements. In addition,
energy requirements may be calculated using a lin-
ear or exponential formula. These formulas are
Energy Requirements presented in Table 12-4.
There are several ways to estimate the amount of Although estimates overlap in patients weigh-
calories required by a patient. Illness energy ing between approximately 2 and 20 kg (5 to 45 lb),
requirements may be estimated by using a multiple in larger dogs the linear formula often overestimates
450 CHAPTER 12 ENTERAL AND PARENTERAL NUTRITION
Puncture in submucosa/mucosa
Oral
Aboral
Interrupted
B Cushing Oral
suture
Aboral
Tunnel
C
Oral
Aboral
Cross
section
FIGURE 12-32 Placement of an enterostomy tube. A, Make a 1- to 1.5-cm linear incision in the seromuscular
layers of the antimesenteric border of the selected jejunal segment; use the tip of a scalpel blade to puncture a hole
in the aboral aspect of the seromuscular incision. B and C, Place the distal end of the feeding tube through the
incision; lay the exiting portion of the tube in the 1- to 1.5-cm seromuscular incision and construct a “tunnel” by
inverting the seromuscular layer over the tube with three or four Cushing sutures of 4-0 absorbable material. (From
Fossum et al.: Small animal surgery, ed 2, St. Louis, 2002, Mosby.)
452 CHAPTER 12 ENTERAL AND PARENTERAL NUTRITION
Needle
Jejunum
Catheter
Aboral Oral A
FIGURE 12-33 A, The catheter is exteriorized through a separate stab incision in the body wall. B and C, The
jejunum is attached to the peritoneum with three to four simple interrupted sutures of 3-0 or 4-0 absorbable suture
material. (From Fossum et al.: Small animal surgery, ed 2, St. Louis, 2002, Mosby.)
CHAPTER 12 ENTERAL AND PARENTERAL NUTRITION 453
METHODS OF
PROVIDING
NUTRITION
ENTERALLY
FIGURE 12-34 Combination of enterostomy feeding Feeding Into the Stomach
tube (red rubber feeding tube in foreground) and When feeding into the stomach (i.e., oral, nasogas-
gastrostomy feeding tube (mushroom-tipped feeding tric/nasoesophageal, esophagostomy, pharyngostomy,
tube in background) in an adult male West Highland or gastrostomy), the quantity of diet fed is deter-
white terrier with acute pancreatitis and hiatal hernia. mined by the patient’s stomach capacity. In normal
dogs and cats, stomach capacity is approximately
70% to 85% water. Normal daily fluid requirements 80 ml of fluid per kilogram of body weight.
are approximately equal to daily caloric require- However, anorexic patients can accommodate only
ments. Patients affected with diseases associated with 30 to 40 ml of fluid or liquid diet per kilogram of
excessive fluid losses (e.g., polyuria, diarrhea, vomit- body weight when feeding begins. A gradual
ing, and third spacing of fluids) require more than increase in volume over a 2- to 3-day period will
calculated normal fluid amounts.Abrupt changes in generally allow the stomach to accommodate larger
body weight usually reflect hydration status; there- volumes of nutrients. A minimum of three feedings
fore fluid intake can be adjusted to maintain body daily should be used; however, if vomiting and
weight. Fluid requirements should be met as part of abdominal distention occur, the volume should be
nutritional support.A general recommendation is to reduced and the number of feedings per day
mix water and canned diet in a 1:1 ratio to meet increased.When using 5 Fr or smaller feeding tubes
maintenance energy requirements for most patients. (i.e., nasoesophageal or nasogastric tubes), only liq-
uid diets may be administered. When using 8 Fr
feeding tubes, convalescent diets with a homoge-
Vitamins and Minerals neous consistency may be used if diluted. When
Little is known about vitamin and mineral status in using larger-bore feeding tubes, blended canned
critically ill patients, although deficiencies have diets may be used (Figure 12-35). The volume of
been observed in veterinary medicine. One study food administered per feeding is determined by the
in humans indicated that micronutrient deficiency caloric requirements and the consistency of the
was common (64% of 284 patients examined) in a gruel.To calculate the amount of food to administer,
wide variety of illnesses. Use of well-balanced the clinician divides the energy requirements of the
diets should provide adequate amounts of micro- patient by the caloric density of the food. Although
nutrients, especially when pet foods are used. the amount of water administered using canned
Human enteral products may not provide ade- products can be calculated by multiplying the vol-
quate amounts. Oversupplementation should be ume of food to be administered by the moisture
FIGURE 12-35 Blended canned diets can be Transition From Tube Feeding
administered through large-bore feeding tubes.
to Oral Feeding
When the patient begins to eat voluntarily or is
content of the diet, an alternative is to mix 1 part able to eat voluntarily, the clinician should con-
food with 1 part water.This usually exceeds the daily sider making a transition from tube feeding to oral
fluid requirements of the patient. Although starter feeding. This should be done over several days. If
regimens have been recommended (e.g., feeding one the tube is not interfering with oral consumption
third of calories on day 1, two thirds of calories on of food, the clinician should leave it in for a few
day 2, and full caloric intake on day 3), we recom- extra days to use if the patient is not consuming
mend feeding full caloric intake on day 1. It is nec- enough diet or if the patient stops eating again.
essary to feed the total amount of diet and water
divided over 6 to 8 feedings on day 1, however. On General Complications of Tube
day 2, the volume of administered diet per feeding
Feeding
can be increased and the frequency of feedings can
be decreased to four to six times. On day 3, the Three types of complications can occur during the
number of feedings can usually be decreased to 3. course of enteral nutritional support: mechanical,
GI, and metabolic.
B C
FIGURE 12-36 A, Survey lateral abdominal radiograph of an adult cat with a mushroom-tipped percutaneous
endoscopic gastrostomy feeding tube. B, Survey ventrodorsal abdominal radiograph of the adult cat in A.
C, Ventrodorsal abdominal radiograph of an adult cat with a mushroom-tipped percutaneous endoscopic
gastrostomy feeding tube. Diluted iodinated contrast medium has been injected into the tube, which is positioned
on the left abdominal wall. Contrast fills the stomach and has entered the small intestine.
acids, a carbohydrate source in the form of dex- milliliter, 16.5 mg calcium chloride per milliliter,
trose, a lipid source in the form of long-chain fatty 74.6 mg potassium chloride per milliliter, 25.4 mg
acids, electrolytes, minerals, trace elements, and magnesium chloride hexahydrate per milliliter,
vitamins (Figure 12-38). Amino acids are com- and 121 mg sodium acetate per milliliter) and
monly supplied as an 8.5% solution with or with- potassium phosphate (224 mg of monobasic potas-
out electrolytes (4.25% to 10% solutions are sium phosphate per milliliter and 236 mg dibasic
available), dextrose is commonly supplied as a 50% potassium phosphate per milliliter) may be added
solution, and lipids are commonly supplied as a as a source of phosphate. Vitamins and trace ele-
20% emulsion (10% solutions are also available). If ments are also available for use.We routinely use a
electrolytes are not contained in the amino acid B-vitamin complex in the parenteral solution
solution, an electrolyte solution designed for use (1 ml/L of TPN). Vitamin K cannot be given
with parenteral nutrition can be used (TPN elec- intravenously and is administered subcutaneously
trolytes providing 16.1 mg sodium chloride per at 0.25 mg/lb once a week.
CHAPTER 12 ENTERAL AND PARENTERAL NUTRITION 457
catheter or lines, occlusion of the lines or catheter, clinical signs of mineral or trace element deficien-
or using a bottle of parenteral solution for too cies were not apparent. In that study 46% of cases
long. There are several metabolic complications experienced mechanical problems (e.g., break in
that can occur and have been described; however, infusion line or catheter dysfunction), 16% devel-
the most common ones are hypoglycemia, hyper- oped clinical sepsis, and metabolic complications
glycemia, hyperlipidemia, metabolic acidosis, and (e.g., glucose, lipid, protein, electrolyte, or acid-
potassium imbalances. Fortunately, these are not base imbalances) occurred in approximately 50%
usually severe. As mentioned before, trace element of the cases but did not result in clinical problems.
and/or mineral deficiency may occur. In one study Mechanical and septic complications can be mini-
of dogs and cats receiving TPN for 1 to 14 days, mized by practicing aseptic technique when
placing the intravenous access line and by careful Carnevale JM et al.: Nutritional assessment: guidelines
handling of the infusion system. Monitoring to selecting patients for nutritional support, Comp
serum biochemical parameters and adjusting the Cont Educ Pract Vet 13:255, 1991.
TPN rate or formulation as needed may minimize Cerra FB: How nutrition intervention changes what get-
ting sick means, J Parenter Enteral Nutr 14:164S, 1990.
metabolic complications.
Crowe DT: Nutritional support for the seriously ill or
injured patient: an overview, J Vet Emerg Crit Care 1:1,
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Abood SK, Buffington CA: Use of nasogastric tubes: in dogs and cats and recommended technical modifi-
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Philadelphia, 1992,WB Saunders. Fulton RBJ, Dennis JS: Blind percutaneous placement
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Medicine, 1986. Rawlings CA: Percutaneous placement of a midcervical
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INDEX
A Adrenocorticotropic hormone (ACTH)
Abdomen stimulation test
distention of, 44-45, 161-162 in megaesophagus, 124
evaluation of, in vomiting, 15, 20 in vomiting, 17, 163
gas in, 67f Adynamic ileus, ultrasonography of, 76
pain/discomfort in, 44-45 Aerophagia, 44. See also Flatulence.
differential diagnosis of, 357, 358 Air embolism, laparoscopy and, 117
palpation of Alanine aminotransferase, 294, 296t, 299-300
in diarrhea, 34 Albendazole, in Giardia infection, 214
in fecal incontinence, 47 Albumin, 289, 296t, 302
in vomiting, 15 Alkaline phosphatase, 294, 296t, 300-301
Abscess Alkalosis, metabolic
anal sac, 283 in gastric dilatation-volvulus syndrome, 187
hepatic, 87f, 88f with parenteral nutrition, 461t
Acanthomatous epulis, 371-372 Amebic colitis, 258
Acetylcholine receptor antibody titer Ameloblastoma, 371-373
in dysphagia, 5 Amikacin, 202t
in megaesophagus, 124, 132 Amino acids, in liver failure, 347-348
Acidosis, metabolic Aminoglycosides, in megaesophagus-associated
in gastric dilatation-volvulus syndrome, 187 pneumonia, 130
with parenteral nutrition, 460t 5-Aminosalicylic acid
Adamantinoma, 371-373 in idiopathic colitis, 270t
Adenocarcinoma in lymphocytic-plasmacytic colitis, 267-268
anal sac, 397-399 Amitriptyline, in irritable bowel syndrome, 273
apocrine gland, 285 Ammonia, 290-291, 298-299
gastric, 192-193 Ammonia tolerance test, 298-299
biopsy of, 103, 104f Amphotericin B, in pythiosis, 242
endoscopy in, 22-23, 22f, 23f, 192, 192f, 387, Ampicillin, 202t
388f Amprolium, 206t
ultrasonography of, 77f Amylase, in pancreatitis, 358-359
intestinal, 77f, 272 Anal reflex, in fecal incontinence, 47
pancreatic, 95f Anal sacs
perianal, 284-285 adenocarcinoma of, 397-399
S-Adenosylmethionine, in chronic hepatitis, 317-318 clinical features of, 397-398
prognosis for, 398
Page numbers followed by f indicate figures; t, tables; b, treatment of, 398-399
boxes. inflammation-infection of, 283
463
464 INDEX
Anal tone, in fecal incontinence, 47 Aortic arch, right, persistent, 134-136, 135f
Analgesia, in pancreatitis, 362 Apocrine gland, adenocarcinoma of, 285
Ancylostoma spp. infection, 205-207, 206t, 257 Apomorphine, in coprophagy, 25
Anemia, in lymphoma, 395 Appetite. See also Diet; Nutrition.
Anesthesia in diarrhea, 30t, 34
esophageal stricture and, 7 in inflammatory bowel disease, 220
gastroesophageal reflux disease and, 139-140, Appetite stimulants, 420, 421t
143 Arrhythmias, in gastric dilatation-volvulus
lower esophageal sphincter effects of, 138 syndrome, 190-191
Angiography, of portal venous system, 71-72, 71f Ascarid infection, 206t
Angiotensin-converting enzyme inhibitors, in Ascites
liver disease, 351 in hepatic disease, 292, 295
Anorectum, 281-285 in intestinal tumors, 394
agenesis of, 282 laparoscopy and, 117
dermatitis of, 284 Aspartate aminotransferase, 294, 296t, 300
fistula of, 283-284 Aspergillus infection, 263
foreign bodies in, 282 Aspiration pneumonia, in megaesophagus, 129,
hair mat obstruction of, 283 130
inflammation-infection of, 283 Astrovirus infection, 203-205
persistent distention of, 281-282 Attitude changes, in inflammatory bowel disease,
prolapse of, 281 220
spasm of, 282 Azathioprine
stricture of, 282 in canine inflammatory bowel disease,
tumors of, 284-285 231-232
Anorexia, 2t. See also Nutrition; Starvation. in chronic gastritis of unknown cause, 180b,
Anthelmintics, 205-207 181
Antibiotics in chronic hepatitis, 316
in bacterial colitis, 258-262 in feline inflammatory bowel disease, 228
in feline cholangiohepatitis, 320-321 in idiopathic colitis, 270t
in feline inflammatory bowel disease, 229-230 in lymphocytic-plasmacytic colitis, 268
in gastric dilatation-volvulus syndrome, 190 in myasthenia gravis, 133
in hepatic encephalopathy, 345 Azithromycin, 206t
in hepatobiliary infection, 329-330
in liver failure, 346, 347 B
in megaesophagus, 124, 125, 130 Bacillus piliformis infection, 260-261
in small intestine bacterial overgrowth, 235 Bacterial overgrowth, 39-40, 234-235
in viral enteritis, 204 in exocrine pancreatic insufficiency, 367-368
Antibody test in German shepherd dogs, 236-237
in heartworm, 18 Balantidium coli infection, 206t, 257, 258
in Helicobacter infection, 178 Balloon catheter dilation, in esophageal strictures,
Antidiarrheal agents, 201-202, 202t 147-149, 147f, 148f, 150f
Antiemetic agents, 174t, 202-203 Basenjiis, lymphocytic-plasmacytic enteritis of,
in feline hepatic lipidosis, 339 237-238
Antinuclear antibody, in megaesophagus, 125 Bedlington terriers, copper-storage disease of,
Antiparasite agents, 205-207 325-328
Antral pyloric hypertrophy syndrome, 166f, 184, Behavior modification, in coprophagy, 25
184t Benazepril, in hepatic disease, 351
Anus. See also Anal sacs;Anorectum. Bentiromide (BP-PABA) test, in exocrine
atresia of, 282 pancreatic insufficiency, 38
congenital defects of, 282-283 Beta cell tumor
imperforate, 282 canine, 404-406
spasm of, 282 feline, 408-409
tumors of, 284-285 Bile, in vomitus, 12
INDEX 465
Narcotics, in acute diarrhea, 201-202, 202t Ollulanus tricuspis infection, 179-180, 205-207
Nasoesophageal tube, 421-424, 422f vomiting in, 19, 19f
complications of, 423-424 Olsalazine
diets for, 453-454, 454f in idiopathic colitis, 270t
in cat, 422, 423f in lymphocytic-plasmacytic colitis,
in dog, 422, 424f 268
management of, 423 Omega-3 fatty acids, in feline inflammatory
placement confirmation of, 422-423 bowel disease, 226
suture for, 423, 424f Omeprazole
technique of, 422, 423f in acute gastritis, 171, 172t, 174
tube for, 422 in gastric erosive-ulcerative disease, 171, 172t,
Nasogastric tube. See Nasoesophageal tube. 174
Nasopharynx, 51, 52f in gastroesophageal reflux disease, 142
Nausea. See also Vomiting. Ondansetron, 174t, 202t, 203
grass ingestion and, 23-24, 24f Opiates, in fecal incontinence treatment, 47-48
Necrosis, hepatic, 296t, 321-322, 322b Opioids, in pancreatitis, 362
Neonety, 25 Oropharyngeal dysphagia, 3-5, 3b
Neoplasia. See Tumors. Oropharynx, 51, 52f
Neo-stigmine, in myasthenia gravis, 133 Osteosarcoma, 384, 384f
Neurologic examination, in fecal incontinence, 47 Oxazepam, for appetite stimulation, 421t
Neuron-specific enolase, 405, 408
Neutrophilic colitis, 269 P
Nifedipine, in megaesophagus, 128 Palate, soft, 52f
Nizatidine Pancreas, 353-368
in acute gastritis, 170-171, 172t anatomy of, 72-74, 87, 91, 91f
in constipation, 278t, 280 biopsy of, 111, 112f, 116
in delayed gastric emptying, 186 carcinoma of, 95f, 404, 407-408
in gastric erosive-ulcerative disease, 170-171, endocrine tumors of
172t canine, 404-407
in gastroesophageal reflux disease, 142 feline, 408-409
Nonsteroidal antiinflammatory drugs, in gastric exocrine insufficiency of, 365-368. See also
erosion-ulceration, 167-168, 169f Exocrine pancreatic insufficiency.
Nutrition, 416-462. See also Enteral nutrition; exocrine tumors of
Parenteral nutrition. canine, 404
energy requirements for, 449-450, 453t feline, 407-408
fluid requirements for, 450, 453 hyperplasia of, 94f
goals of, 416, 417t inflammation of. See Pancreatitis.
in short bowel syndrome, 243-244 laparoscopic evaluation of, 111, 111f, 116
indications for, 416-417, 418t pseudocyst of, 95
mineral requirements for, 453 radiology of, 72-74, 73f, 74f
protein requirements for, 450 inflammation on, 73, 73f, 74f, 359-360
vitamin requirements for, 453 normal, 72-73
resection of, 405-406
O tumors of, 404-409
Obesity, 418t endocrine, 404-407, 408-409
Obstipation, 2t, 48-49, 48f, 49f, 274. See also exocrine, 404, 407-408
Constipation. in gastric erosion-ulceration, 170
Octreotide acetate, in insulinoma, 406 ultrasonography of, 87
Ocular larva migrans, 207 inflammation on, 91-95, 91f, 92f, 93f, 94f,
Odor 360, 361f
of breath, 25, 31t mass on, 95, 95f
of vomitus, 13 Pancreatic acinar atrophy, in pancreatic
Odynophagia, 2t insufficiency, 365, 365b
480 INDEX