The anatomy and physiology of the ferret is different than cats or dogs. Gastrointestinal disease has is usually manifested by diarrhea, weight loss, and anorexia. The role of Helicobacter mustelae has been studied as a model for gastrointestinal disease in other species. The hedgehog and sugar glider are essentially insectivore/omnivores but have the simple stomach and intestinal tract more similar to those of carnivores. The Virginia opossum's gastrointestinal tract has served as a model for omnivorous marsupials. Gastrointestinal disease in the insectivore/omnivores is one of the most common reasons for presentation in the exotic pet practice of these species.

. Etiologies of gastrointestinal disease. Diarrhea is most common clinical sign in ferrets. 15-18
. Medications used as adjunctive therapy of gastroenteritis. 17,18

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2006 Proceedings 29

Anatomy and Physiology of the Gastrointestinal

System of the Ferret and Selected Exotic Carnivores

Cathy A. Johnson-Delaney, DVM, Dipl ABVP (Avian)

Session #125

Affiliation: From Eastside Avian & Exotic Animal Medical Center, PLLC, 13603 100th Ave NE, Kirkland, WA

98034, USA and Bird & Exotic Clinic of Seattle, 4019 Aurora Ave N, Seattle, WA 98103, USA.

Abstract: The anatomy and physiology of the ferret is different than cats or dogs. Gastrointestinal disease

has is usually manifested by diarrhea, weight loss, and anorexia. The role of Helicobacter mustelae has

been studied as a model for gastrointestinal disease in other species. The hedgehog and sugar glider are

essentially insectivore/omnivores but have the simple stomach and intestinal tract more similar to those of

carnivores. The Virginia opossum's gastrointestinal tract has served as a model for omnivorous marsupials.

Gastrointestinal disease in the insectivore/omnivores is one of the most common reasons for presentation

in the exotic pet practice of these species.

Introduction

Several of our common non-traditional companion pets have a "carnivore" type of gastrointestinal tract, although

the actual diet may consist largely of insects rather than meat. The gastrointestinal tract of the domestic ferret,

Mustela putorius furo, has been studied extensively as a model for several human gastrointestinal tract diseases,

including spontaneous gastric and duodenal ulcers, gastro-esophageal reflux, gastric carcinoma and lymphoma,

the lack of acid mucosubstances similar to humans, and Helicobacter mustelae infection. Hedgehogs (Atelerix

albiventris) are classified as insectivores, but most are omnivorous/carnivorous and opportunistic, including

consumption of carrion. Sugar gliders (Petaurus breviceps ) have a simple gastrointestinal tract with the exception

of a large cecum, which is used for gum fermentation.

The Ferret

The ferret has a short transit time, 148–219 minutes when fed a meat-based diet. The digestive system is under

vagal and sacral innervation. The tract is spontaneously active even under anesthesia. Motility can be moderated

with atropine. The stomach spontaneously produces acids and proteolytic enzymes. Histamine and vagal stimulation

provoke more secretions.1

Gut closure for antibody absorption occurs in kits between 28 and 42 days of age. Ferrets can absorb beta

carotene and convert it to retinoic acid. Carbohydrases and proteolytic activity take place distally in the jejunum

rather than more proximally in the duodenum.1

Stomach

The ferret has a simple stomach, similar in shape to that of the dog. There is prominent vasculature of the stomach

as well as a prominent lymph node lying in the lesser curvature. It is innervated by parasympathetic fibers from the

vagus nerve and sympathetic fibers via the celiacomesenteric plexus. The stomach has considerable storage capacity

(100 ml of milk in 10 minutes in an adult). Some 80% of a meal is stored in the proximal stomach.1

Association of Avian Veterinarians

30

The lower esophageal sphincter (LES) and the mechanisms of gastro-esophageal reflux in the ferret are being

used as an animal model.2,3 Transient LES relaxation is the mechanism and is unassociated with swallowing in

the ferret, just as in the human.4 Gastric infusions of glucose, lipid, and gas are all effective in provoking gastro-

esophageal reflux in the ferret. Lipid and glucose stimulate acid secretion.4 The fundus of the stomach and the

LES are coinnervated by vagal preganglionic motor neurons as these sections work in tandem: the LES must

relax to accommodate food during ingestion or preceding emesis. The antrum of the stomach provides mixing and

propulsion of contents for gastric emptying and are innervated by neurons responding to differing

neurotransmitters.5–9 The ferret is used as an emetic model to test anti-emetics. Serotonin successfully blocks

cisplatin at 10 mg/kg emesis.10 An anti-emetic pursued in the ferret model has been delta9-tetrahydrocannabinol

(D9 -THC), the cannabinoid that is anti-emetic in humans. Ferrets have the Cannabinoid1 receptor in the dorsal

motor vagal nucleus, with cell bodies in the area postrema, nucleus tractus solitarius, and nodose ganglion. This

receptor mediates the anti-emetic action of cannabinoids.11,12 The cannabinoid D9 -THC was found to cause

gastro-esophageal reflux due to the relaxation of the lower esophageal sphincter. This effect may have implications

in the treatment of gastro-esophageal reflux and other upper gastrointestinal disorders.12

The ferret stomach also secretes acid in response to histamine, pentagastrin, and calcium. There is a low

concentration of free histamine in the stomach. The ferret lacks the histamine-forming enzyme (L-histidine

decarboxylase) in the stomach, although histamine-destroying activity is present. Histamine also stimulates secretion

of proteolytic enzymes. Histamine H2 receptor antagonists abolish the acid secretion response to exogenous

histamine or exogenous stimulation with pentagastrin. Atropine only reduces acid secretion by 30%.1

Gastrin is secreted in the gastric antrum and duodenum. Hypoglycemia induced by insulin produces a sustained

stimulation of acid secretion.1 This is particularly relevant to ferrets with insulinomas: therapy needs to include

medications that decrease acid secretion.

Intestine

The ferret intestine consists of 3 sections. Villi and goblet cells are present in all sections. The duodenum is the

proximal segment. The duodenum is innervated by vagal preganglionic parasympathic neurons originating in the

dorsal motor nucleus of the vagal nerve in the brainstem.13 The major duodenal papilla contains the common

opening for the bile and pancreatic ducts. This is located about 3 cm from the pylorus. The minor papilla may be

absent. Brunner's glands are present in the submucosa of duodenum proximal to bile duct. The glands produce

only neutral mucosubstances, as in humans.1

The jejunal and ileal segments cannot be distinguished and may be referred to as the "jejunoileum" that ends at

the ascending colon. The small intestine is innervated by the vagus nerve and the sympathetic trunks arise from

the celiac and cranial mesenteric plexus.1

Motility is affected by the hormones secretin, PZ-CCK (pancreozymin-cholecystokinin), an unidentified

vasoconstrictor, VIP, and substance P. VIP inhibits jejunal motor activity due to vagal simulation while substance

P excites activity. Both increase water secretion by jejunal epithelium. The muscular layer has a higher concentration

of these hormones than the epithelium. Jejunal motility mediated by hormones is not blocked by atropine. 5-

hydroxytryptamine (5-HT3 ) and synthetic serotonin receptor agonists induce large contraction and defecation.

The basal colonic motility pattern was not changed, and the large contractions can be blocked with a receptor

antagonist. The implications of this model are for testing pharmaceuticals for constipation without undesired

changes in gut motility patterns.14 Cervical (mechanical) vagus stimulation will affect motility. This has significant

implications for the clinician who may manipulate the neck and thorax during intubation and inadvertently stimulate

the vagus nerve and intestinal motility at the beginning of surgery.

2006 Proceedings 31

The large intestine is composed of the colon and rectum. There is no cecum and no ileocolic junction. The junction

is inferred by the presence of the anastomoses of the jejunal artery with the ileocolic artery. The colon consists of

the ascending, transverse, and decending colon, with the largest being the decending. The colon is innervated by

autonomic fibers from the vagus, cranial, and caudal mesenteric plexus.1

There are tubular glands and goblet cells in the colon. These secrete sulfated mucosubstances. The motility of the

colon resembles that of a dog ileum. Motility is vagus-dependent and mediated by cholinergic and noncholinergic

fibers. Sacral innervation is excitatory. Retroperistalsis begins in the colon which may be the genesis of vomiting

in the ferret.1

Exocrine pancreas and biliary system

The exocrine pancreas and biliary system are also under vagal stimulation. There is a trophic relationship with

capillary connections between the islets and the exocrine pancreatic tissue. A bile salt-dependent lipase is produced.

The adult jill mammary tissue is high in this enzyme. Ferret milk has activity 10–20 times higher than human milk.

If lipase elevations are present in the blood, consider pancreatic inflammation or disease.1

The gallbladder contracts in response to cholecystokinin. Cholecystokinin is found throughout the gastrointestinal

tract. This contraction inhibits gastric emptying and stimulates small intestine and colonic motiity. The contractile

response directly effects smooth muscles and/or neurons, which furthers intestinal motility.1

Diseases of the Gastrointestinal Tract

Ferrets are used as animal models for emesis as they have a low tolerance for many chemicals and the vagal

reflex is strong, with a simple stomach for propulsion. They are also used as models of Helicobacter gastritis,

gastric carcinoma, pyloric and intestinal ulceration, inflammatory bowel disease, colitis, and gastrointestinal neoplasia.

As Helicobacter mustelae is endemic in most of the commercially-produced pet ferrets, the ferret is set up for

gastrointestinal disease from this etiologic agent alone. In addition, ferrets are prone to stress-induced gastrointestinal

ulcers with hemorrhage and hypermotility. All of the above conditions may result in varying degrees of diarrhea:

acute, chronic or intermittent; with or without visible hemorrhage, and with or without secondary bacterial or viral

involvement. Table 1 lists gastrointestinal diseases of ferrets. Table 2 lists treatments published for H mustelae .

Table 3 lists adjunctive therapies for gastroenteritis. A detailed history is needed to determine a course of action.

This includes volume, color, consistency, frequency, and duration the clients have seen diarrhea. The source of

the ferret, including breeder, may play a significant role in the priority of etiologies. Other information should

include how long the ferret has been in the household, whether other ferrets and pets are present, as well as

human family members–are any symptomatic with diarrhea? The type of litter used and sanitation program may

be of importance. Diet including treats fed, toys available, and incidental environmental information (such as

access to showers or sinks) should be recorded. Ferrets are notorious for licking soaps, chewing on stuffing dug

out of furniture, and chewing shoes and shoe liners, and even perfume or shampoo bottles. Correlation with

activity should also be figured into the evaluation. For example, does it occur round the clock or is it only after

intense playtime? Does it only occur after the vacuum cleaner is run near the ferret's cage? Tenesmus or

vocalization, or accompanying borborygmus or flatulence should be recorded. Teeth grinding may indicate pain,

and anorexia may be a sequellae to the pain. A full dental examination should also be done as severe dental

disease may be part of the clinical presentation.

A physical examination of the ferret should be thorough and include auscultation of the abdomen and examination

of the anal area. A fecal examination should include floatation and direct smear of fresh material, as well as

Association of Avian Veterinarians

32

staining to look at bacterial levels and presence of blood cells. A rectal culture and cytology may be indicated.

Blood work should include lipase, which has been shown to be elevated in many cases of inflammatory bowel

disease. Anemia is not an uncommon finding and may indicate gastrointestinal hemorrhage. Fecal occult blood

can be tested; however, the ferret should be placed on a diet that does not contain meat for at least 24–36 hours

prior to testing as normal ferret foods contain meat and blood products that result in positive test results. Radiographs

including a contrast study are frequently useful. Ultrasonography can be used to look at motility of the stomach,

including the pyloric area. Ultrasonography of the abdomen may also find other pathologic conditions. Endoscopy

is useful for examination of the stomach, pylorus and colon. Endoscopy can also be used abdominally. Biopsies

can be taken endoscopically or via laparotomy. A PCR test for gastric Helicobacter mustelae is available from

Research Associates Laboratory, R.A.L., Inc, Dallas, TX, USA (www.vetdna.com). The author uses a sterile

length of infusion set tubing measured for the particular ferret. Using a sterile hemostat, the culturette swab can

be inserted into the tubing and pushed in until it is firmly seated. The tube is then passed into the sedated ferret's

stomach and the stomach manually massaged around the culturette.15-18

Inflammatory bowel disease (usually lymphoplastic) probably has multiple causes and may have an underlying

genetic component, particularly considering its progression to neoplasia in many ferrets. Food allergies have yet

to be explored other than some clinical trials in some cases to alternate protein feline diets. The grain carbohydrates

used in commercial food formulations may be a problem: allergy testing as done in dogs and cats should be

pursued. Immunomodulating medications such as prednisone (prednisone USP, Roxane Laboratories, Columbus,

OH, USA), azathioprine (Imuran, GlaxoSmithKline, Research Triangle Park, NC, USA), and metronidazole

(Metronidazole USP, Watson Laboratories, Inc, Corona, CA, USA) have been used based on therapies for other

species. Table 3 lists dosages.

Although H mustelae is found in most adult ferrets, it is not always implicated in clinical gastritis or ulcers. It does

play a role as an opportunist and exacerbates ulceration of the stomach and intestines. It appears to play a role in

the development of gastric neoplasia, and it may play a role in inflammatory bowel disease and colitis. As H

mustelae is a model for human H pylori infection, further improvements in clinical implications, diagnosis, and

treatment will be forthcoming.

In summary, the ferret gastrointestinal tract is designed to be excitatory, have rapid motility, and be highly secretory.

Exogenous stressors and chemical and neurologic stimulations further increase motility and secretion. During any

hypoglycemic episode, the clinician needs to be aware of the pancreatic and gastric physiology and treat the

nausea and secretions in addition to the hypoglycemia. It may also be prudent to administer medication to inhibit

acid secretions prior to surgeries and in any stressed, ill ferrets.

2006 Proceedings 33

Table 1. Etiologies of gastrointestinal disease. Diarrhea is most common clinical sign in ferrets.

15–18

Disease Diagnosis Treatment Age grouping

Bacterial, primary or

secondary

1. Helicobacter mustelae

2. Lawsoni/Desulfovibrio

3. Campylobacter jejuni

Culture and Sensitivity

1. Helicobacter PCR,

histopathology

2. Biopsy and

Histopathology

3. Culture difficult,

human labs

Appropriate

antimicrobial therapy,

adjunctive

Any. #2 –

usually younger

Bacterial, uncommon

Mycobacteriosis Histopathology

PCR Zoonotic risks? > 2 years

Viral:

1. Ferret Enteric

Coronavirus (FEVC)

2. Rotavirus

3. Canine Distemper Virus

Coronavirus isolation

PCR

PCR

PCR

Supportive care #1. Any, usually

following

stressful event,

ferret gathering

#2. baby,

weanlings

#3. Ferrets who

did not complete

their baby series

of vax

Coccidiosis

Giardiasis Fecal floatation, direct

smear Anti-coccidial drugs Usually < 1 year

Inflammatory bowel disease Histopathology Some suggest anti-

inflammatory drugs;

caution in ferrets with

possible Helicobacter

Usually > 2

years, history of

intermittent

diarrhea

Gastrointestinal neoplasia Histopathology Surgical excision

Chemotherapy Usually > 3

years

Foreign body ingestion PE, radiographs,

exploratory surgery Surgery Usually < 2

years

Stress-medical or

psychological History

Detection of underlying

medical condition

Correction of

underlying medical

disorder or

psychological stress

Any

Idiopathic megaesophagus Radiology Unrewarding Any

Association of Avian Veterinarians

34

Table 2. Treatment regimens for Helicobacter mustelae based on clinical trials.

17,18

Effective combinations Unsuccessful medications

Amoxicillin (30 mg/kg q8h X 21–28d;

Metronidazole (20 mg/kg q8h X 21–28d;

bismuth subsalicylate (7.5 mg/kg q8h X 21–

28d)

Amoxicillin alone. May not be effective at

q12h even in combinations

Metronidazole alone. May not be effective with

Amoxi if given at 12-h intervals

Chloramphenicol alone

Enrofloxacin alone

Enrofloxacin (8.5 mg/kg/day divided q12h) X

14d; bismuth subcitrate* (12 mg/kg divided

q12h) X 14d

Tetracycline

Bismuth subsalicylate alone

Omeprazole and amoxicillin

Clarithromycin (12.5 mg/kg q12h X 14d

Ranitidine bismuth citrate*(24 mg/kg q12h X

14d)

Omeprazole alone

Clarithromycin (12.5 mg/kg q8h X 14d;

Ranitidine bismuth citrate* (24 mg/kg q8h X

14d) This is also a published dosage.

* not commercially available in the US, can be compounded

Sources:

Amoxicillin: Amoxil, GlaxoSmithKline, Research Triangle Park, NC, USA

Metronidazole USP: Watson Laboratories, Inc, Corona, CA, USA

Bismuth subsalicylate: Pepto-Bismol, Proctor & Gamble, Cinncinati, OH, USA

Enrofloxacin: Baytril, Bayer, West Haven, CT, USA

Clarithromycin: Biaxin, Abbott Laboratories, Abbott Park, IL, USA

Omeprazole: Prilosec, AstraZeneca Pharmaceuticals LP, Wilmington, DE, USA

2006 Proceedings 35

Table 3. Medications used as adjunctive therapy of gastroenteritis.

17,18

Drug Dosage Comments

Azathioprine 0.9 mg/kg PO q24– 72h Used in IBD if other tx

ineffective.

Immunosuppressive

Famotidine 0.25-0.5 mg/kg PO, IM, IV

q24h Histamine antagonist;

available over the counter;

decreases gastric acid;

provides pain relief. Oral OTC

can be crushed, mixed with

flavor gel, palatable

Metronidazole 50 mg/kg PO q24h IBD, some

immunosuppressive effects

Omeprazole 0.7 mg/kg PO q24h Protein pump inhibitor, short-

term usage only

Prednisone 1-2.5 mg/kg PO q24h Anti-inflammatory. Used in

eosinophilic gastroenteritis,

IBD, palliative in LSA

Ranitidine USP 24 mg/kg PO q8h X 14d Histamine inhibitor; decreases

gastric acid; provides pain

relief. Tablet form available

over the counter, must be

compounded as human

formulation unpalatable

Sucralfate 25 mg/kg PO q8h Coats esophageal and gastric

mucosa, local effect only.

Syrup palatable

Sources:

Azathioprine: Imuran, GlaxoSmithKline, Research Triangle Park, NC, USA

Famotidine: Famotidine tablets USP, Zenith Goldine Pharmaceuticals, Inc, Miami, FL, USA

Metronidazole: Metronidazole USP, Watson Laboratories, Inc, Corona, CA, USA

Omeprazole: Prilosec, AstraZeneca Pharmaceuticals LP, Wilmington, DE, USA

Prednisone: Prednisone USP, Roxane Laboratories, Columbus, OH, USA

Ranitidine USP: Ranitidine Tablet USP, Perrigo Co, Allegan, MI, USA

Sucralfate: Carafate Aventis Pharmaceuticals, Inc, Kansas City, MO, USA

Association of Avian Veterinarians

36

The Hedgehog

The African pygmy hedgehog's (Atelerix albiventris) gastrointestinal system is similar to most carnivore

gastrointestinal tracts. It has a simple stomach, and a smooth non-complex colon. It does not have a cecum and

has a poorly defined ileo-colonic junction. Gut transit time in one study was reported as 12–16 hours.19

Disease etiologies and clinical manifestations of disease are similar to those of other carnivores. Treatment with

oral medications may be more difficult in those that are not used to having the owner manipulate its head and

mouth. Salmonella serotype Tilene has been identified from pet hedgehogs in the United States. Table 4 lists

diseases, diagnoses, and therapies of gastrointestinal disease in pet hedgehogs. A complete workup with hematology,

serum chemistries, imaging, and fecal parasite examination are recommended for any hedgehog presenting with

gastrointestinal disease. Diagnostics listed in Table 4 are specific to those etiologies.

Table 4. Gastrointestinal diseases of pet hedgehogs.20

Etiology Signs Diagnostics Treatments

Salmonella sp, other

bacteria Clinically

asymptomatic or

diarrhea, weight loss,

anorexia, dehydration,

lethargy, death

Fecal culture and

sensitivity, Salmonella

special media

Salmonella: supportive care

primarily, discuss zoonotic

potential. Other bacterial: per

sensitivity; supportive care

Candidiasis,

alimentary Weight loss,

depression, blood in

stool

Fecal cytology and

culture and sensitivity Appropriate antifungal per

sensitivity, supportive care,

decrease sugars in diet?

Cryptosporidiosis of

ileum, jejunum, colon Severe enteritis,

wasting, death Fecal cytology, biopsy,

histology No effective treatment.

Endoparasites Unthriftiness,

diarrhea Fecal floatation,

wetmount, history of

exposure to wild-

caught hedgehogs

Antihelminthics per parasite

identified. Not seen much

anymore with captive reared

Obstructions (foreign

bodies) Vomiting, diarrhea,

non-specific weight

loss, abdominal pain,

lethargy, acute

collapse

Radiology, contrast

needed sometimes,

laparotomy,

exploratory

Surgical enterotomy or

gastrotomy as indicated.

Analgesics

Non-specific enteritis,

gastrointestinal

inflammation,

ulcerations

Tenesmus, diarrhea,

melena or frank

blood, anorexia,

weight loss, lethargy,

dehydration

Radiology, contrast,

ultrasonography,

laparotomy, biopsy

Non-specific, antibiotics,

supportive,

antiinflammatories,

gastrointestinal protectives

Diet-induced Diarrhea History of treat foods,

milk, diet changes Discontinue offending foods,

stabilize diet, symptomatic

antidiarrheals

Neoplasia Diarrhea, weight loss,

unthriftiness, non-

specific pain, lethargy

Imaging, laparotomy

with biopsy Palliative or can try neoplasia

therapies as in felids for

specific diagnosis

2006 Proceedings 37

The Sugar Glider and Virginia Opossum

The sugar glider is considered an omnivore, although its gastrointestinal morphology and dentition share features

with carnivorous mammals. Teeth have limited shearing action and can only compress insects, not break them

down into small pieces like a true carnivore. They can extract the hemolymph and soft tissues of insects through

compression, then discard the exoskeleton. An interesting functional difference between eutherians and marsupials

concern the Brunner's glands of the duodenum. In eutherians, Brunner's glands are usually confined to the

submucosa and the ducts empty into intestinal crypts of Lieberkuhn. In American marsupials, they drain into large

mucosal depressions that are surrounded by more glands. In Australian marsupials, the ducts empty directly into

the duodenal lumen. No Australian marsupial carnivore has a cecum. The sugar glider has a well-developed

cecum, needed for the fermentation of ingested gums and a short colon. Otherwise, their gastrointestinal tract is

similar to the Virginia opossum. There are will developed salivary glands that include large mandibular and

smaller parotid and sublingual glands. The distal esophagus mucosa has raised transverse rugae. The stomach is

simple and rather globular in form. The gastric mucosa is mostly fundic glands. There are some pyloric glands,

and there is a narrow zone of cardiac glands at the cardiac sphincter. Eneteroendocrine cells, along with endocrine

cells in the pancreas control digestive functions. Secretions include gastric acid, gastrin, gastric-inhibitory polypeptide,

secretin, cholecystokinin, and pancreozymin.21

The small intestine is about 3 times the length of the large intestine. The mesenteric attachments to the colon are

loose. Just distal to the pylorus is the "collar" of Brunner's glands in the submucosa. These secrete alkaline fluid

and mucus.21

Gastrointestinal disease in omnivorous/insectivorous marsupials clinically presents most frequently with diarrhea

and some degree of anorexia, weight loss, dehydration, lethargy, and collapse. Vomiting may be seen in predominantly

upper gastrointestinal illnesses. Bacterial, protozoal, and toxic etiologies have been found. Malnutrition or dietary

changes may also play a role. Diagnostics and treatments follow regimens similar to that of other essentially

carnivorous mammals.

Acknowledgments: The author thanks Dr. Angela Lennox, Ernie Coliazzi, the Washington Ferret Rescue &

Shelter ferrets and volunteers, and the Farscape Kids.

References

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2. Staunton E, Smid SD, Dent J, Blackshaw LA. Triggering of transient LES relaxations in ferrets: role of sympathetic

pathways and effects of baclofen. Am J Physiol Gastrointest Liver Physiol. 2000;279:G157–G162.

3. Blackshaw LA, Staunton E, Lehmann A, Dent J. Inhibition of transient LES relaxations and reflux in ferrets

by GABA receptor agonists. Am J Physiol Gastrointest Liver Physiol. 1999;277:G867–G874.

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5. Hyland NP, Abrahams TP, Fuchs K, et al. Organization and neurochemistry of vagal preganglionic neurons

innervating the lower esophageal sphincter in ferrets. J Comp Neurol. 2001;430:222–234.

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6. Smid SD, Young RL, Cooper NJ, Blackshaw LA. GABAB R expressed on vagal afferent neurons inhibit

gastric mechanosensitivity in ferret proximal stomach. Am J Physiol Gastrointest Liver Physiol.

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ferret lower oesophageal sphincter. Auton Neurosci. 2000;86:30–36.

8. Abrahams TP, Partosoedarso ER, Hornby PJ. Lower oesophageal sphincter relaxation evoked by stimulation

of dorsal motor nucleus of the vagus in ferrets. Neurogastroenterol Motil. 2002;14:295–304.

9. Page AJ, Blackshaw LA. An in vitro study of the properties of vagal afferent fibres innervating the ferret

oesophagus and stomach. J Physiol. 1998;512(Pt3):907–916.

10. Rudd JA, Cheng CH, Naylor RJ. Serotonin-independent model of cisplatin-induced emesis in the ferret. Jpn

J Pharmacol. 1998;78:253–260.

11. Van Sickle MD, Oland LD, HoW, et al. Cannabinoids inhibit emesis through CB1 receptors in the brain of

the ferret. Gastroenterology. 2001;121:767–774.

12. Partosoedarso ER, Abrahams TP, Scullion RT, et al. Cannabinoid1 receptor in the dorsal vagal complex

modulates lower oesophageal sphincter relaxation in ferrets. J Physiol . 2003;550(1):149–158.

13. Odekunle A,Chinnah TI. Brainstem origin of duodenal vagal preganglionic parasympathetic neurons. A WGA-

HRP study in the ferret (Mustela putorius furo) human model. West Indian Med J. 2003;52:267–272.

14. Nagakura Y, Kiso T, Miyata K, et al. The effect of the selective 5-HT3 receptor agonist on ferret gut

motility. Life Sciences. 2002;71:1313–1319.

15. Lennox AM. Working up mystery anemia in ferrets. Exotic DVM. 2004;6(3):22–26.

16. Johnson-Delaney CA. A clinician's perspective on ferret diarrhea. Exotic DVM. 2004;6(3):27–28.

17. Lennox AM. Gastrointestinal diseases of the ferret. Vet Clin North Am Exotic Anim Pract. 2005;8:213–226.

18. Johnson-Delaney CA. The ferret gastrointestinal tract and Helicobcter mustelae infection. Vet Clin North

Am Exotic Anim Pract. 2005;8:197–212.

19. Reeve N. Hedgehogs . London, UK: T & A D Poyser Ltd; 1994.

20. Ivey E, Carpenter JW. African hedgehogs. In Quesenberry KE, Carpenter JW eds. Ferrets, Rabbits &

Rodents Clinical Medicine and Surgery. 2nd ed. St. Louis, MO: Saunders; 2004:339–353.

21. Hume I. Marsupial Nutrition . Melbourne, Vic, Aus: Cambridge University Press; 1999.

... There is a paucity of information relating to the histology of the gastrointestinal tract of marsupials in general. Portions of the gastrointestinal tract have been examined in the koala (Phascolarctos cinereus) (Hanger and Heath 1994), the stomach in macropods (Langer et al. 1980), intestinal glands in a range of marsupials (Krause 1972(Krause , 1973Takagi et al. 1990) including the sugar glider (Petaurus breviceps) (Johnson-Delaney 2006), the Julia Creek dunnart (Sminthopsis douglasi) (Hume et al. 2000), and the ground cuscus (Phalanger gymnotis) (Hume et al. 1997). The gastrointestinal tract has been examined for many eutherians, including the domestic ferret (Mustela putorius furo), the African pygmy hedgehog (Atelerix albiventris), the rabbit (Orycotolagus cuniculus) and rodents (Grandi et al. 2006;Johnson-Delaney 2006;Kotze et al. 2006). ...

... Portions of the gastrointestinal tract have been examined in the koala (Phascolarctos cinereus) (Hanger and Heath 1994), the stomach in macropods (Langer et al. 1980), intestinal glands in a range of marsupials (Krause 1972(Krause , 1973Takagi et al. 1990) including the sugar glider (Petaurus breviceps) (Johnson-Delaney 2006), the Julia Creek dunnart (Sminthopsis douglasi) (Hume et al. 2000), and the ground cuscus (Phalanger gymnotis) (Hume et al. 1997). The gastrointestinal tract has been examined for many eutherians, including the domestic ferret (Mustela putorius furo), the African pygmy hedgehog (Atelerix albiventris), the rabbit (Orycotolagus cuniculus) and rodents (Grandi et al. 2006;Johnson-Delaney 2006;Kotze et al. 2006). In none of the marsupial or eutherian species, even those with similar diets to peramelids, has folding of the villi in the small intestine into a zig-zag formation been reported. ...

European settlement has had a dramatic impact on the distribution and abundance of peramelid (bandicoot and bilby) marsupials. Predation and competition from introduced species and altered habitat have been implicated in their decline or extinction. Bandicoots and bilbies inhabit a broad range of habitats in Australia. Research on the distribution, morphology, gastrointestinal histology, lactation, metabolism and nutritional physiology of extant peramelid species has increased in the last few decades. This paper provides a review that encompasses recent nutritional-based research. Peramelid research is mostly limited to only three species - Isoodon macrourus, Perameles nasuta and Macrotis lagotis - which prevents effective comparisons between species. Peramelids are broadly classified as omnivores and possess relatively uncomplicated gastrointestinal tracts. The caecum is the region of greatest diversity among species. The relatively large caecum of Chaeropus ecaudatus supports the theory that this species may have been the only herbivorous peramelid. The caecum of M. lagotis is less pronounced than other species and is continuous with the proximal colon. M. lagotis also has a longer total colon length, which aids water conservation to ensure survival in an arid environment. Temperate-zone species such as I. macrourus, I. obesulus and P. nasuta are more similar to each other with respect to gastrointestinal morphology than either C. ecaudatus or M. lagotis. Additional research on the morphometrics of the gastrointestinal tracts of P. gunnii, P. bougainville, P. eremiana, M. leucura and I. auratus would enable further comparisons to determine whether differences are a result of geographic distribution, habitat preference or variation between genera and/or individual species. Currently, histological information of the gastrointestinal tract is limited to the small intestine of P. nasuta and I. macrourus. The histology of the small intestine of the weaned juvenile I. macrourus more closely resembles that of P. nasuta pouch young than P. nasuta adults. The younger bandicoots possessed villi whereas in the adult P. nasuta and I. macrourus villi were arranged in a zig-zag formation. The reason for the zig-zag formation of the villi and the function it may serve remains unclear. Detailed nutritional research on captive M. lagotis, I. mac:I-aunts and P. nasuta indicate that the two temperate-zone species I. macrourus and P. nasuta - are more similar to each other than to the arid-dwelling M. lagotis. Detailed nutritional studies are required on all species, both free-living and captive. Experimental diets do not always accurately reflect a natural diet, which means that results from captive studies may not reflect the situation for free-living animals. The hindgut of peramelids is the main region for retention of digesta, and presumably where microbial digestion occurs. However, no studies have been undertaken to examine the microflora of the gastrointestinal tract of bandicoots or the bilby. As captive husbandry is an important tool in conservation management, it should also improve their successful maintenance in captivity by the provision of diets that better meet their nutritional requirements.

... This same lack of microbial flora means that carbohydrates are digested poorly and fiber not at all. The dental formula of the ferret is 2 (I 3/3 C1/1 P3/3 M1/2) ¼ 34 [2,3]. ...

... Although the anthelmintic, ivermectin, may be administered to ferrets with eosinophilic gastroenteritis, prednisone seems to be the mainstay of treatment for both conditions. Other medications that have been tried include azathioprine and metronidazole [2,3]. ...

  • Christal Pollock

Common emergency conditions seen in the ferret include insulinoma, cardiomyopathy, and urethral obstruction. When developing a diagnostic and therapeutic plan, the ferret veterinarian must seek a balance between species-specific information and information extrapolated from cat and dog medicine. The therapeutic plan must always include close and careful monitoring. Significant changes in the status of these small patients can occur extremely quickly in the course of providing basic supportive care, such as intravenous fluids or supplemental heat.

... The ferret's rapid gastrointestinal (GI) transit time, measured in domestic ferrets as 2 hr for small intestinal transit and 148-219 min for total GI transit, allowed for collection of samples in the morning to be representative of the previous evening's diet. 4,18 In this study, feces taken the morning after a meat-based diet was consumed, versus a whole-prey diet, had a significantly higher spore-former count and higher frequency of yeast. This finding speaks to the interplay of diet and the gut microenvironment and microflora. ...

The black-footed ferret (Mustela nigripes) is an endangered mustelid native to North America. Gastroenteritis is a documented cause of morbidity and mortality in managed individuals, particularly by infectious agents. Fecal cytology is an inexpensive and rapid test that can help guide clinical management strategies for animals with enteritis; however, normal parameters have not been established in black-footed ferrets. The objective of this study was to characterize fecal cytological findings of 50 fecal samples from 18 black-footed ferrets that received two different diet types (ground meat versus whole prey) and that were visibly judged to be normal or abnormal. This study also tested for the presence of Clostridium perfringens enterotoxin by enzyme-linked immunosorbent assay in all abnormal and a subset of normal fecal samples. Significantly higher spore-forming bacteria and yeast prevalence were present in normal feces from individuals following the meat-based compared with the whole-prey diet. Samples from individuals with abnormal feces had significantly more spore-forming bacteria than normal feces, regardless of diet. Normal feces had higher diplococci and spore-forming bacteria compared with domestic canine and feline standards. A single abnormal fecal sample was positive for enterotoxin and originated from the only animal requiring treatment. Results indicate that low numbers of spore-forming bacteria can be found in fecal samples from clinically normal black-footed ferrets. Fecal cytology shows significantly increased spore-formers in clinically abnormal ferrets and in clinically normal ferrets following a ground meat-based diet.

  • Lindsey E. Bullen

Although the companion animal population is predominantly canine and feline, the popularity of domesticated small mammals (or pocket pets) has been steadily increasing. As a result, ferrets, rabbits, and rodents can be expected to present for veterinary evaluation. Many common medical problems in pocket pets are often associated with poor husbandry and/or inappropriate nutrition and are thus responsive to nutritional therapies. Although this article touches on minor background information and husbandry, the primary foci are the basic nutritional needs of, and common nutrition-responsive diseases in, pocket pets. Detailed husbandry needs are beyond the scope of this article.

  • John A Rudd John A Rudd
  • Celine H.K. Cheng
  • R J Naylor

para-Chlorophenylalanine (PCPA, 100-200 mg/kg) was used as a pharmacological tool to characterize the 5-hydroxytryptamine (5-HT) involvement in the emesis occurring 24 hr after the administration of cisplatin (10 mg/kg) in the ferret. PCPA was effective to antagonize the initial 8 hr period of retching and vomiting, but potentiated the emesis that occurred during the remaining 8- to 24-hr observation period. Tissue samples removed from the brainstem at 24 hr post injection of cisplatin alone revealed an elevation of 5-HT, dopamine and homovanillic acid that was antagonized by the injection of PCPA. Cisplatin also induced increases in the urinary levels of 5-hydroxyindoleacetic acid that was similarly antagonized by PCPA. Results are discussed in terms of the relevance of 5-HT to the model of cisplatin (10 mg/kg)-induced emesis in the ferret compared to the problem of acute and delayed emesis in man. The residual or delayed phase of cisplatin-induced emesis may involve a 5-HT-independent mechanism.

Transient lower oesophageal sphincter (LOS) relaxation is the major mechanism of gastro-oesophageal reflux in humans - an event unassociated with swallowing. Mechanisms involved in triggering transient LOS relaxation are poorly understood, and their further study requires a small animal model. In this study we aimed to establish methods for prolonged ambulant oesophageal manometry in ferrets, and to determine motor events associated with reflux episodes and their triggering by different gastric nutrient loads. Forty-two studies were performed on nine ferrets with chronic cervical oesophagostomies, through which a manometric assembly was introduced and secured to a collar, which incorporated a microphone for detection of swallows. The assembly included a gastric feeding channel, one gastric and four oesophageal manometric sideholes, a 2.5-cm-long LOS sleeve sensor, and an oesophageal pH electrode. Intragastric infusions were given over 2 min, the first after a 30-min control recording period, and in 29/42 studies, a second infusion was given 60 min later. Infusions were either 25 mL 10% dextrose solution, pH 3.5 (22 studies), 25 mL triglyceride emulsion (Intralipid) pH 3.5 (11 studies), or 25 mt air (nine studies). Episodes of oesophageal acidification were absent before gastric infusions. After infusion, 2.1 +/- 0.2 episodes occurred over the first 30 min. After glucose infusion, 15/18 acidification episodes (83%) occurred during transient LOS relaxation, and 3/18 (17%) occurred after gradual (< 1 mmHg sec(-1)) downward drifts in basal LOSP to < 2 mmHg. After lipid infusion two acidification episodes occurred, both during transient LOS relaxation. Mean duration of transient LOS relaxation was 8.0 +/- 0.4 sec. All infusions increased occurrence of transient LOS relaxation to a similar extent, each of which ended with primary peristalsis. We conclude that gastric infusion of glucose, lipid and gas are all effective in provoking gastro-oesophageal reflux in ferrets. Reflux occurs through similar mechanisms to those seen in humans, i.e. increased triggering of transient LOS relaxation. The conscious ferret is therefore an appropriate model for future studies of manipulation of mechanisms giving rise to gastrooesophageal reflux.

  • K.E. Quesenberry
  • J.W. Carpenter

A concise guide to the care of small mammals, Ferrets, Rabbits, and Rodents: Clinical Medicine and Surgery covers the conditions seen most often in veterinary practice. The book emphasizes preventive medicine along with topics including disease management, ophthalmology, dentistry, and zoonosis. More than 400 illustrations demonstrate key concepts related to radiographic interpretation, relevant anatomy, and diagnostic, surgical, and therapeutic techniques. Now in full color, this edition adds coverage of more surgical procedures and expands coverage of zoonotic disease. From editors Katherine Quesenberry and James W. Carpenter, along with a team of expert contributors, the "Pink Book" provides an authoritative, single source of information that is hard to find elsewhere.

• A novel preparation of the oesophagus with attached vagus nerve from the ferret maintained in vitro was used to study the properties of single vagal afferent nerve fibres with identified receptive fields. • Recordings were made from three types of gastro-oesophageal vagal afferent fibres that were classified on the basis of their sensitivity to mechanical stimulation. There were those responding to mucosal stroking (mucosal receptors), to circular tension (tension receptors) and those responding to mucosal stroking and circular tension, which we have termed tension/mucosal (TM) receptors. • The conduction velocities for mucosal, TM and tension receptor fibres were 6.38 ± 1.22 m s−1 ( n= 22 ), 6.20 ± 1.49 m s−1 ( n= 13 ) and 5.33 ± 0.86 m s−1 ( n= 22 ), respectively. • Receptive fields of afferents showed random topographical distribution by fibre type and conduction velocity. They were found mainly distal but also occasionally proximal to the point of vagal dissection. • Twenty-eight per cent of mucosal, 63 % of TM and 43 % of tension receptors responded to one or more drugs or chemical stimuli applied to the receptive field. • In conclusion, this experimental preparation provides evidence for the existence of three types of oesophageal vagal afferent fibre, namely mucosal, tension and the newly identified tension/mucosal receptors.

  • L. Ashley Blackshaw L. Ashley Blackshaw
  • Esther Staunton
  • Anders Lehmann
  • J Dent

Transient lower esophageal sphincter (LES) relaxation is the major mechanism of gastroesophageal reflux. This study uses an established ferret model to evaluate GABA(B) receptor agonists' ability to reduce triggering of transient LES relaxations. One hundred sixty manometric/pH studies were performed on 18 conscious ferrets. In untreated animals, intragastric infusion of 25 ml glucose (pH 3.5) led to 2.0 +/- 0.6 reflux episodes over the first 30 min. Twenty-nine of forty-seven reflux episodes occurred during transient LES relaxation, and 18 occurred after downward drifts (<1 mmHg/s) in basal LES pressure. The GABA(B) receptor agonists baclofen (7 micromol/kg ip), CGP-44532, and SKF-97541 (both ED(50) <0.3 micromol/kg) reduced reflux episodes and transient LES relaxations. The putative peripherally selective GABA(B) receptor agonist 3-aminopropylphosphinic acid (80-240 micromol/kg) was ineffective, as was the GABA(A) receptor agonist muscimol (5 micromol/kg). Baclofen's inhibition of transient LES relaxations and reflux was unaffected by low-affinity GABA(B) receptor antagonists CGP-35348 and CGP-36742 at 100 micromol/kg but was reversed by higher-affinity CGP-54626 and CGP-62349 (0.7 micromol/kg) or by CGP-36742 at 200 micromol/kg. Therefore, GABA(B) receptor inhibition of reflux shows complex pharmacology. Our and other data indicate the therapeutic potential for these drugs.

Activation of gastric vagal mechanoreceptors by distention is thought to be the trigger for transient lower esophageal sphincter relaxations (TLESR), which lead to gastroesophageal reflux. The contribution of higher-threshold gastric splanchnic mechanoreceptors is uninvestigated. GABA(B) receptor agonists, including baclofen, potently reduce triggering of TLESR by low-level gastric distention. We aimed to determine first whether this effect of baclofen is maintained at high-level distention and second the role of splanchnic pathways in triggering TLESR. Micromanometric/pH studies in conscious ferrets showed that intragastric glucose infusion (25 ml) increased triggering of TLESR and reflux. Both were significantly reduced by baclofen (7 micromol/kg ip) (P < 0.05). When 40 ml of air was added to the glucose infusion, more TLESR occurred than with glucose alone (P < 0.01). These were also reduced by baclofen (P < 0.001). TLESR after glucose/air infusion were assessed before and after splanchnectomy (2-4, 9-11, and 23-25 days), which revealed no change. Baclofen inhibits TLESR after both low- and high-level gastric distention. Splanchnic pathways do not contribute to increased triggering of TLESR by high-level gastric distention.

The motor control of the lower esophageal sphincter (LES) is critical for normal swallowing and emesis, as well as for the prevention of gastroesophageal reflux. However, there are surprisingly few data on the central organization and neurochemistry of LES-projecting preganglionic neurons. There are no such data in ferrets, which are increasingly being used to study LES relaxation. Therefore, we determined the location of preganglionic neurons innervating the ferret LES, with special attention to their relationship with gastric fundus-projecting neurons. The neurochemistry of LES-projecting neurons was also investigated using two markers of "nontraditional" neurotransmitters in vagal preganglionic neurons, nitric oxide synthase (NOS), and dopamine (tyrosine hydroxylase: TH). Injection of cholera toxin B subunit (CTB)-horseradish peroxidase (HRP) into the muscular wall of the LES-labeled profiles throughout the rostrocaudal extent of the dorsal motor nucleus of the vagus (DMN) The relative numbers of profiles in three regions of the DMN from caudal to rostral are, 43 +/- 5, 67 +/- 11, and 113 +/- 30). A similar rostrocaudal distribution occurred after injection into the gastric fundus. When CTB conjugated with different fluorescent tags was injected into the LES and fundus both labels were noted in 56 +/- 3% of LES-labeled profiles overall. This finding suggests an extensive coinnervation of both regions by vagal motor neurons. There were significantly fewer LES-labeled profiles that innervated the antrum (16 +/- 9%). In the rostral DMN, 15 +/- 4% of LES-projecting neurons also contained NADPH-diaphorase activity; however, TH immunoreactivity was never identified in LES-projecting neurons. This finding suggests that NO, but not catecholamine (probably dopamine), is synthesized by a population of LES-projecting neurons. We conclude that there are striking similarities between LES- and fundic-projecting preganglionic neurons in terms of their organization in the DMN, presence of NOS activity and absence of TH immunoreactivity. Coinnervation of the LES and gastric fundus is logical, because the LES has similar functions to the fundus, which relaxes to accommodate food during ingestion and preceding emesis, but has quite different functions from the antrum, which provides mixing and propulsion of contents for gastric emptying. The presence of NOS in some LES-projecting neurons may contribute to LES relaxation, as it does in the case of fundic relaxation. The neurologic linkage of vagal fundic and LES relaxation may have clinical relevance, because it helps explain why motor disorders of the LES and fundus frequently occur together.

In the present study we aimed to discretely characterise ganglionic and neuroeffector transmission to the ferret lower oesophageal sphincter (LOS) using a novel preparation of LOS muscle with intact vagal innervation in conjunction with isolated LOS muscle strips. In this way we could compare vagally mediated LOS relaxation with that of enteric inhibitory motorneurones which were directly stimulated. Preparations of LOS muscle, with or without attached vagus nerves, were dissected from adult ferrets and maintained under preload in organ baths, where LOS muscle developed spontaneous tone. LOS relaxations in response to vagal stimulation (0.5-5 Hz, 30 V) were recorded, alone and following pretreatment with tetrodotoxin (TTX), hexamethonium (Hex), Hex and atropine and NG-nitro-L-arginine (L-NNA). Direct activation of enteric inhibitory motorneurones was performed via electrical field stimulation (EFS). Vagal stimulation elicited frequency-dependent relaxations of the LOS that were abolished by tetrodotoxin (1 microM) and markedly reduced following L-NNA pretreatment (100 microM), but unaltered following pretreatment with the selective VIP or PACAP receptor antagonists VIP (10-28) or PACAP (6-38), respectively (each at 5 microM). The potent NOS inhibitor S-methyl-L-thiocitrulline (100 microM) inhibited LOS relaxation to the same degree at 5 Hz. Hex alone (500 microM) reduced maximal relaxation by 50%; in combination with atropine (2 microM), relaxation was almost abolished. In isolated LOS muscle strips, neither VIP (10-28) nor PACAP (6-38) altered EFS-induced relaxation. Taken together, these results suggest ganglionic neurotransmission to the ferret LOS occurs mainly through a combination of nicotinic and muscarinic receptors and utilises nitroxidergic enteric inhibitory motorneurones to relax the LOS. Moreover, LOS relaxation due to direct activation of inhibitory motorneurones also utilises primarily nitric oxide and other as yet undefined neurotransmitters. Neither VIP nor PACAP are involved in vagally mediated or direct enteric neuronally stimulated LOS relaxation in the ferret.