JPC SYSTEMIC PATHOLOGY
DIGESTIVE SYSTEM
September 2021
D-M21 (NP)

 

SIGNALMENT (JPC #3134054): A six-month old, spayed-female, Labrador retriever

 

HISTORY: One month prior to euthanasia the dog presented with bilateral dropped eyelids and mild prolapse of both third eyelids. This was followed by vomiting and diarrhea. Complete blood count, clinical chemistry, thoracic radiographs and blood lead data were within normal limits. A barium study of the gastrointestinal tract revealed a dilated, non-motile, stomach and small intestine. A clonic-tonic head motion was noted.

 

MICROSCOPIC DESCRIPTION: Small and large intestines: Within the muscularis interna and externa of the tunica muscularis, within the myenteric (Auerbach’s) plexi, and to a much lesser extent the submucosal (Meissner’s) plexi, there are multifocal to coalescing, variably dense aggregates of lymphocytes, plasma cells, and fewer macrophages admixed with small amounts of basophilic to eosinophilic karryorhectic debris, small amounts of basophilic granular material (mineral), and increased clear space.  The inflammatory infiltrates separate smooth muscle fibers that are often either shrunken (atrophic), swollen with vacuolated sarcoplasm (degenerate), or shrunken with pyknotic nuclei (necrotic). The inflammatory infiltrates frequently surround neurons of the myenteric plexi. Neurons within the myenteric and submucosal plexi are decreased in density, and remaining neurons frequently have peripheralized Nissl substance and increased central pallor (central chromatolysis).  The gut-associated lymphoid tissue (GALT) of the large intestine contains few peripheral macrophages with intracytoplasmick, golden brown, non-light polarizing pigment (hemosiderin). The serosa is moderately expanded by clear space (edema).

 

Stomach: The stomach is similarly affected to a much lesser degree, with approximately 30% of the tunica muscularis infiltrated by multifocal aggregates of lymphocytes, plasma cells, and fewer macrophages that separate smooth muscle fibers.

 

MORPHOLOGIC DIAGNOSIS: Stomach, small intestine, large intestine, tunica muscularis: Leiomyositis, lymphoplasmacytic, multifocal to coalescing, marked, with smooth muscle necrosis, atrophy, and loss, and myenteric plexitis and degeneration, Labrador Retriever, canine.

 

CONDITION: Intestinal pseudo-obstruction

 

GENERAL DISCUSSION:

• Described mostly in dogs where there is impaired intestinal motility with clinical signs of obstruction but no physical occlusion of the intestinal lumen is present
• Humans: pseudo-obstruction is considered a result of failed nervous and muscular components of the intestine
• Inflammation/fibrosis affects myenteric plexi or tunica muscularis

 

PATHOGENESIS:

• Pathogenesis is unknown
• Dogs: predominantly T-lymphocyte rich infiltration of the tunica muscularis leading to fibrosis

 

TYPICAL CLINICAL FINDINGS:

• Identical to true physical obstruction: vomiting, regurgitation, diarrhea
• Anorexia, weight loss

 

TYPICAL GROSS FINDINGS:

• Flaccid and dilated intestines

 

TYPICAL LIGHT MICROSCOPIC FINDINGS:

• Fibrosis and mononuclear infiltration of the tunica muscularis
  • Myofiber degeneration and necrosis
  • Fibrotic areas are centered on regions of myofiber loss
• Neuronal loss or ganglioneuritis

 

ADDITIONAL DIAGNOSTIC TESTS:

• Radiography: marked gastric distension with dilated small intestines

 

DIFFERENTIAL DIAGNOSIS:

• Intestinal sclerosis (intestinal smooth muscle disease)
  • Resembles systemic sclerosis or scleroderma in humans
• Adynamic ileus:
  • Often preceded by abdominal surgery (post operative ileus), especially following rough handling or trauma to intestines
  • Other causes: parvoviral enteritis, pancreatitis, peritonitis, hypokalemia
  • Due to neurogenic reflexes interfering with control of inhibitory neurons of myenteric plexus, with continual tonic discharge inhibitin contraction of circular smooth muscle and prevention of peristalsis

 

COMPARATIVE PATHOLOGY:

• Dogs, cats, and horses: Pyloric stenosis
  • Congenital or acquired; results in delayed gastric emptying
  • Limited functional information on congenital form, though an analogous condition in humans is associated with lack of interstitial cells of Cajal
  • Hypertrophy of pyloric smooth muscle reported in some dogs and Siamese cats
• Cats:
  • Dysautonomia, also known as Key-Gaskell syndrome
  • Affects cats under 3 years of age; pathogenesis unknown
  • Alimentary signs include salivation, megaesophagus, constipation, ileal impaction, and diarrhea; signs suggest disordered motility
  • Nerve involvement:
  • Cranial: III, V, VII, XII
  • Ventral horns of the spinal gray matter
  • Dorsal root ganglia
  • Distinct ultrastructural appearance:
  • autophagocytic vacuoles, dilated cisternae, complex stacks of smooth endoplasmic reticulum
• Horses:
  • Grass sickness: young horses of Europe, southern South America, rarely United States
  • Most often occurs in the spring season
  • Suspected cause: Clostridium botulinum type C and/or type C neurotoxin
  • Acute presentation as colic, tympany, and drooling with rapid progresson and nearly always fatal, usually within 7 days (note: a chronic form manifesting as colic of >7 days also exists)
  • Histology: neuronal degeneration of intestinal (myenteric or submucosal plexi) and extraintestinal ganglia; minimal inflammation
  • Cytologic examination of cranial cervical ganglion scrapings was recently described as a reliable method for rapid postmortem diagnosis (Piccinelli, Vet Pathol. 2019)
  • Megacolon of Clydesdale foals: hypoganglionosis of the myenteric plexus
  • 4-9 month old foals in United States and Australia; pathogenesis unknown; timing of clinical onset suggests acquired condition although common breed suggests genetic basis
  • Equine congential colonic aganglionosis: white foals
  • Loss of function mutation of endothelin receptor type B
  • Histology: absence of myenteric plexi in the ileum, cecum, colon
• Sheep:
  • Abomasal dilation and emptying defect; characterized by an impacted, dilated abomasum
  • May be a form of acquired dysautonomia; neuronal necrosis in celiac and mesenteric ganglia are consistent with neurotoxicosis but cause is unknown
  • Suffolk and Hampshire sheep affected
• Avians:
  • Proventricular Dilatation Disease (PDD) (N-V20): also known as neuropathic gastric dilatation, myenteric gangioneuritis, and splanchnic neuropathy; affects psittacines; caused by Avian bornavirus
    • Complete ileus of the digestive tract; flaccidity and dilation of any portion of the gastrointestinal tract, but most commonly affected portions are the proventriculus, ventriculus, and crop
    • Histology: lymphoplasmacytic infiltrate of myenteric plexus
  • Other infectious causes of proventricular dilation: clostridial infections, gastric mycobacteriosis, fungal gastritis, coelomitis, and ulcerative or erosive gastritis
  • Lead poisoning: common cause of proventricular dilation in geese 

 

REFERENCES:

1. Cooper BJ, Valentine BA. Muscle and tendon. In: Maxie MG, ed. Jubb, Kennedy and Palmer’s Pathology of Domestic Animals, Vol 1, 6th ed. St. Louis, USA: Elsevier; 2016:227-228.
2. Gelberg HB. Alimentary system and the peritoneum, omentum, mesentery, and peritoneal cavity. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 6th ed. St. Louis, MO: Elsevier; 2017:333,361-362,370.
3. Hall EJ, Day MJ. Diseases of the small intestine. In: Ettinger SJ, Feldman EC, Cote, E. eds. Textbook of Veterinary Internal Medicine: Diseases of the Dog and Cat. Vol 2. 8th ed. St. Louis, MO: Elsevier; 2017:1562-1563.

4. Harvey AM, Hall EJ, Day MJ, Moore AH, Battersby IA, Tasker S. Chronic intestinal pseudo-obstruction in a cat caused by visceral myopathy. J Vet Intern Med. 2005;19:111-114.
5. Johnson CS, Fales-Williams AJ, Reimer SB, Lotsikas PJ, Haynes JS. Fibrosing gastrointestinal leiomyositis as a cause of chronic intestinal pseudo-obstruction in an 8-month-old dog. Vet Pathol. 2007;44(1):106-109.
6. Miller AD, Zachary JF. Nervous system. In: McGavin MD, Zachary JF, eds. Pathologic Basis of Veterinary Disease. 6th ed. St. Louis, MO: Elsevier; 2017:900-901.
7. Piccinelli C, Jago R, Milne E. Ganglion Cytology: A Novel Rapid Method for the Diagnosis of Equine Dysautonomia. Vet Pathol. 2019;56(2):244-247.
8. Schmidt RE, Reavill DR, Phalen DN. Gastrointestinal system and pancreas. In: Pathology of Pet and Aviary Birds. 2nd ed. Ames, IA: John Wiley & Sons, Inc.; 2015:69.
9. Uzal FA, Plattner BL, Hostetter JM. Alimentary system. In: Maxie MG, ed. Jubb, Kennedy and Palmer’s Pathology of Domestic Animals. Vol 2. 6th ed. St. Louis, MO: Elsevier Saunders; 2015:77-78.
10. Zacuto AC, Pesavento PA, Hill S, McAlister A, Rosenthal K, Cherbinsky O, Marks SL. Intestinal leiomyositis: a cause of chronic intestinal pseudo-obstruction in 6 dogs. J Vet Intern Med. 2016 Jan-Feb;30(1):132-140.

Click the slide to view.

---