Intestinal Pathology

Villus Atrophy

A common Pathological change in intestineResults in malabsorption of nutrientsTwo categories

Intestine with apparently normal or hypertrophic crypts, associated with atrophy of villi to various degrees

Gut with some evidence of damage to the proliferative compartment and variable villus atrophy.

A. The first type occur in two formsPrimary increase in rate of loss of epithelium from

villus surface e.g. coronaviral and rotaviral infection, coccidia, some enteroinvasive bacteria, clostridial toxins, transient ischemia

Villus contract and become stubbyCompensatory expansion of the proliferative

compartment in crypts permits complete recoveryMicroscopic appearance vary depending upon

extent of cellular loss and regeneration Exfoliation into the gut, villi short/bluntSubsequently, the atrophic villi are covered by

poorly differentiated,low columnar, cuboidal or squamous cells.

Fusion of lateral surfaces of villi Erosion in sever cases,

Atrophy of villi and hypertrophy of crypts is also associated with chronic or persistent processes e.g. nematode parasitism, chronic coccidial infection, giardiasis, Johne's disease and histoplasmosis

T-cell activity(No, IL-12, TNF) seems to be associated with villus atrophy of this type in parasitisms

Immune reactions in the gut are associated with increased epithelial cell proliferation but cells not fully differentiated

Hypertrophy of crypts is the early and outstanding change in this lesion

B. Hypertrophy of crypts is the early and outstanding change in this lesion

Sequel to insults that cause necrosis of cells in crypts, or impair their mitotic capacity.

Agents causing this lesion has the capacity to damage dividing cells

These was also termed as Radi0mimetic as radian was the first known agent to cause this lesion

Other causes include cancer chemotherapeutic agents, T-2 mycotoxin, and pyrrolizidine alkaloids, BVD, Rinderpest

Microscopically: Damage e.g. apoptotic cells and neutrophils will be evident in the crypts before the villus atrophy

In severe necrosis, remaining cells become flattened to maintain integrity of crypt lining

The surface sloughing continues at normal rate though regenerative process is poor

Villi will eventually become atrophiedsquamous epithelial cells derived from

surviving crypts may cover the surface or surface will be eroded

Epithelial turnover in the cecum and colon is fundamentally similar to that in the small intestine, though villi are not present on the surface.

Lesions in the large bowel presumed to be associated with increased epithelial turnover include alterations in both surface and glandular epithelium.

E.g. number of goblet cells on the surface and in theupper portion of glands is often diminished, and

epithelium in these areas appears poorly differentiated

proliferative compartment in the gland may hypertrophy, causing glands to elongate and dilate.

Diarrhea

Presence of water in feces in relative excess in proportion to fecal dry matter

Severe electrolyte depletion, acid-base imbalance, and dehydration

Small-bowel diarrhea is classed as "secretory, malabsorptive,"or "effusive.

Secretory diarrhea result from derangement of normal secretory and absorptive mechanisms. Vibrio cholerae and Escherichia coli, Salmonella serotypes,

Yersinia enterocolitica, Shigella, and Campylobacter jejuniToxin-stimulate cAMP which shuts down sodium

chloride cotransport and stimulated chloride secretion

Resultantly more water flow from small bowel to colon

Malabsorptive diarrhea is exemplified by the osmotic retention of water in the gut lumen by poorly absorbed magnesium sulfate

Malabsorption commonly results from villus atrophy, no matter what the cause

Electrolyte and nutrient solute, malabsorbed along with osmotically associated water.

Increased permeability of the mucosa may contribute to diarrhea by permitting increased retrograde movement of solute and fluid from

the lateral intercellular space to the lumen, or by facilitating transudation of tissue fluid

Portal hypertension, right-sided heart failure, hypoalbuminemia , and expansion of plasma volume

Large-bowel diarrhea is due to a reduction in the innate capability of the colon to absorb the solute and fluid presented by the more proximal

bowel.Malabsorbed nutrients excess carbohydrate transfer from

small to large bowel result in colon osmotic overload and lead to diarrhea

Intestinal obstruction

Clinically acute obstruction involves the upper or middle small intestine

Chronic blockage usually involves the ileum and large bowel.

May be the sequel to a physical blockage of the lumen resulting from stenosis, obturation

(occlusion) by an intraluminal mass, or extrinsic compressionFailure of the intestinal circular smooth muscle

to contract blocks the peristaltic wave, causing functional obstruction, or pseudo-obstruction

Proximal to the point of obstruction there is accumulation of fluid and gas.

Intestinal distension associated with water and electrolyte sequestration into the lumen

Dehydration and circulatory collpase may occur

Stenosis and obturotion

Acquired stenosis occur due to intramural abscesses, intramural hematomas neoplasms and scarring following ulceration

Foreign bodies of all kinds are commonly foundMay act as a nucleus for enterolith Sharp impacted pointed foreign may cause pressure

necrosis with ulceration and possibly perforationEnteroliths were common in the colon of horses

(magnesium ammonium phosphate) Phytobezoars or phytotrichobezoars occur in colon

of horses

Foreign body obstruction

Small intestinal obstruction may be caused by parasites e.g. pigs and foals infested with large numbers of ascarids.

Impaction of the colon, by feces in dogs and cats, and by digesta, fibrous foreign material, sand, or feces in horses, is not uncommon

Impaction of the cecum or colon in horses may be precipitated by water deprivation, a change of diet from something soft and lush to hay or chaff, or poor dentition

Tumors, abscesses, peritonitis, and fibrous adhesions may cause extrinsic obstruction

Functional obstruction Paralytic ileus following rough handling during

surgery, or peritonitisIt is the result of neurogenic reflexes that

interfere with control of the inhibitory neurons of the myenteric plexus

Continual tonic discharge by these neurons inhibits contraction of circular smooth muscle and prevents

peristalsis.

The intestines are distended with a mixture of gas and fluid, and the wall is flaccid

Pseudo-obstruction, a clinical syndrome may result from segmental or diffuse neuromuscular dysfunction in the gut

Megacolon in Clydesdale foals, in association with hypoganglionosis of the myenteric plexus, has been reported

Gras, s sickness in horses common in those 3-6 years of age

In the acute disease, there is progressively severe tympany, swallowing is avoided, and saliva drools freely

The esophageal wall is sometimes edematous, and the mucosa may show longitudinal bands of congestion and ulceration

stomach is distended with alkaline mucinous fluidExcess fluid in the small intestine. Large intestine

is impacted with dry contents

Degenerative lesions e.g. subtle chromatolysis, nuclear eccentricity, and neuronal necrosis,

The formation of perineuronal eosinophilic axonal spheroids in many autonomic ganglia

Central neuropathy has also been reported

Idiopathic inflammatory bowel disease

mainly dogs, but less commonly cattle, cats, and horses

Associated with malabsorption and/or plasma loss into the gut

Also called as Lymphocyticplasmacytic enteritis, filled-villi syndrome, or eosinophilic gastroenteritis.

Difficult to diagnose as there is no landmark for histological lesions

Histologic abnormalities are grouped under three

broad headings: changes in mucosal architecture reflecting active or recent epithelial abnormality increased numbers of proprial leukocytes fibrosis within the lamina propria

Cardinal finding in small intestine is abnormally intense infiltrates of well-differentiated

lymphocytes and plasma cells, and sometimes eosinophils, in the lamina propria of villi, between crypts and perhaps in the submucosa

These cells are normally present in the intestine as well

A layer of plasma cells, lypmhocytes, eosinophils or neutrophils more than 4 cell thickness in deep mucosa is abnormal

Villi may be normal to severely atrophic Surface epithelium relatively normal, mucous

metaplastic or low columnar to cuboidalCrypts may be hypertrophic and lined by numerous

goblet cellsEdema of the lamina propria and dilation of lacteals

Idiopathic mucosal colitis

the colonic manifestation of chronic inflammatory bowel disease, and the commonest form of colitis

recognized in dogsEtiologically nonspecificChronic or chronic-active lymphocytic-plasmacytic or

eosinophilic mucosal inflammation.Mild acute mucosal colitis is characterized by

congestion of superficial capillaries and venules, and proprial edema

Neutrophils infiltrate the superficial lamina propria around vessels, lymphocytes and plasma cells relatively normal, but increase in mononuclear and eosinophils

Greater severity of the lesion is reflected in attenuation and exfoliation of surface epithelium, and the development of microerosions on

the mucosal surfaceEtiopathogenesis of idiopathic inflammatory

bowel disease is not understood in any animal species

However loss of tolerance to dietary antigen or antigens produced by the enteric microflora may be implicated.

Eosinophilic enteritis in cats and horses

Part of hypereosinophilic syndrome in middle to old aged cats

Diarrhea, sometimes bloody, vomition, loss of appetite, and loss of condition

Grossly: Intestinal thickening, hepato- and splenomegaly, and enlarged mesenteric lymph nodes and circulating eosinophilia, tan nodularities on the kidneys

Microscopically: well differentiated eosinophilic infiltration which may be transmural

Lymph nodes have hyperplastic follicles and many mature eosinophils in sinusoids

In horses, it is part of multisystemic epitheliotropic syndrome

Associated with eosinophilic granulomatous pancreatitis and eosinophilic dermatitis

Animals have weight loss, diarrhea hypoalbuminemia

Mucosal and sometimes transmural thickening may occur in any part of the alimentary tract

Esophageal and gastric squamous mucosa is hyperkeratotic

Folded mucosaMicroscopically: Diffuse infiltration of the mucosa,

submucosa, and deeper layers of the enteric wall by eosinophils, mast cells, macrophages, lymphocytes and some plasma cells.

Moderate to severe villus atrophy, fibroplasia in the lamina propria, and hypertrophy of the muscularis mucosae

Caseous foci in the mucosa and submucosa consist of central masses of eosinophils, sometimes surrounded by macrophages, giant cells, and occasionally fibrous tissue.

Villus atrophy

Eosinophilic interstitial infiltrates and granulomas in the biliary and pancreatic ducts, pancreas, salivary

glands, capsule, and outer cortex of enlarged firm mesenteric lymph nodes, and near portal tracts in the liver

Granulomatous enteritis

Chronic inflammatory infiltrates, including aggregates of histiocytes, and perhaps giant cells, in the lamina propria

submucosa is usually edematous, and lymphatics are prominent.

Affected lymph nodes are hyperplastic, usually with prominent sinus histiocytosis.

Johne's disease, other intestinal mycobacterioses, and Histoplasma enteritis are specific examples

Transmural granulomatous enteritis is occasionally seen in dogs and cats

Generally segmental and perhaps discontinuous

in distributionAffect lower ileum, colon, and draining lymph nodes.Marked necrosis in the centers of granulomas

and considerable fibrosis. Fibrosis

Idiopathic granulomatous enteritis as a cause of wasting and protein- losing enteropathy is most commonly seen as a sporadic problem in horses.

Usually small intestineCachectic animals with edema of depend partsMesenteric lymph nodes are usually enlarged, edematous,

with mottled firm gray areas, fibrotic nodules or caseous fociMicroscopic lesion may be patchy, regional, or diffuse, and it

may be mucosal, or transmural,Villi are mildly to markedly atrophic with hypertrophy of

cryptsEpithelium normal to low columnar/cuboidal, lamina propria

is edematous with histiocytes

Typhlocolitis in dogs

Diarrhea, frequent, small in volume, mucoid or bloody, and often accompanied by tenesmus.

Severe acute necrotizing colitis and typhlitis, leading to ulceration and perforation associated with Glucocorticoid therapy, functional adrenal cortical

tumors, and with trauma or surgery involving the spinal cord.

Uremia may also cause necrotic ulcerative colitis Trichuris vulpis, Entamoeba histolytica

Ulcerative, granulomatous transmural colitis by histoplasrnosis.

Leishmaniasis may also cause colitis with heavy mucosal macrophage infiltration

Canine coronavirus may also cause damage to colon

Campylobacter jejuni in some cases

Histiocytic ulcerative colitis is a distinctive histologic syndrome, recognized in Boxers and French Bulldog.

A chronic transmural ulcerative colitis characterized

by the presence of large numbers of macrophages

containingperiodic acid-Schiff-positive granules, in the deep mucosa and submucosa, and in lymph nodes

usually under 2 years of ageGrossly, the colon is variably thickened, folded,

and perhaps dilated and shortened

Patchy punctate red ulcers to more extensive irregular circular or linear lesions

Goblet cells disappear from the surface and glands.Microerosion of epithelium in the upper glands and

on the surface, neutrophilsMacrophages with phagocytic debris in mucosa and

with PAS positive material in deep lamina propriaCecum is also involved Exact cause unknown, various microbes postulatedDefect in lysosomal function in some boxer dogs

Colitis in cats

Colitis in cats is uncommon.Idiopathic mucosal colitis, similar to that described in

dogsTritrichomonas foetus, associated with persistent large

bowel diarrhea and idiopathic mucosal colitis in cats under 1 year age

Feline panleukopenia virus causes colonic lesions in about half the cases.

Mycotic colitis is occasionally seen in cats as a hemorrhagic ulcerative colitis by Candida,

zygomycetes, or AspergillusClostridium piliforme caused mild mucosal colitis in

several kittens

Transmural acute ulcerative colitis, with a heavy infiltrate of neutrophils, is the hallmark of Salmonella Typhimurium

AnaerobiospiriUum, associated with colitis in cats

Typhlocolitis in horses

Clostridial: animal is dehydrated, subcutaneous and serosal petechial hemorrhage

Dark blood with poor clottingLarge bowel, which is distended, with

abnormally fluid content.Serosa of the cecum and large colon may

appear cyanoticMucosa, submucosa edematousMucosa may appear brown and necrotic with

focal fibrinohemorrhagic exudate

Microscopically: superficial or full-thickness necrosis of the mucosa, dilation and perhaps thrombosis of small mucosal and submucosal venules

hemorrhage and edema in the mucosa, and the submucosa

Dilated lymphaticsSome neutrophilsClostridium pegringens type A, C. difficile Antibiotic therapy, stress, feed change

Subacute and chronic diarrhea in horses almost always involves the large intestine

Salmonella typhlocolitis must be suspected in such cases.

Potomac horse fever is associated with congestion and ulceration of the mucosa of the large bowel, and enlargement of mesenteric lymph nodes.

Diarrhea up to 10 daysRhodococcus equi in foals : Suppurative ulcers

involving lymphoid tissue in the typhlocolic mucosa, and cecal and colic lymphadenitis,

strongyles

Ischemic mucosal lesions due to arterial thromboembolism and slow flow lead to chronic diarrhea , cachexia due to persistent ulceration of the cecum or colon

NSAID’s has also been reported to cause cecum and colon ulceration

NSAID induced enterocolitis

Typhlocolitis in ruminants

Acute to subacute fibrinohemorrhagic typhlocolitis include salmonellosis, bovine viral diarrhea, Rinderpest coccidiosis adenoviral infection, winter dysentery (coronavirus).

Arsenic, other heavy metals, and oak or acorn poisoning may also cause hemorrhagic typhlocolitis and dysentery

Granulomatous typhlocolitis associated with chronic diarrhea and wasting may occur in Johne's disease

In sheep, hemorrhagic typhlocolitis may be present in animals with bluetongue and peste des petits ruminants

Salmonellosis may cause fibrinohemorrhagic enteritis in lambs and pregnant ewes

Coccidiosis may be implicated in hemorrhagic ileotyphlocolitis in lambs and kidsC. perfingens type D in goats