Download - Toxicopathology of Git
![Page 1: Toxicopathology of Git](https://reader036.vdocuments.net/reader036/viewer/2022081412/544e46f0b1af9f23638b4c6d/html5/thumbnails/1.jpg)
Toxicopathology of
gastrointestinal tract
Submitted with respect to:Submitted with respect to:Dr. D. J. GhodasaraDr. D. J. GhodasaraAssociate ProfessorAssociate ProfessorDepartment of Veterinary Pathology
Submitted by:Mukesh kumarMukesh kumarM.V.Sc (2M.V.Sc (2ndnd Semester) Semester)
![Page 2: Toxicopathology of Git](https://reader036.vdocuments.net/reader036/viewer/2022081412/544e46f0b1af9f23638b4c6d/html5/thumbnails/2.jpg)
Normal structure of GIT
• Mouth cavity
• Pharynx
• Oesophagus
• Stomach– Ruminant
– Non ruminant
• Small intestine– Duodenum
– Jejunum
– Ileum
• Large intestine– Caecum
– Colon
– Rectum
![Page 3: Toxicopathology of Git](https://reader036.vdocuments.net/reader036/viewer/2022081412/544e46f0b1af9f23638b4c6d/html5/thumbnails/3.jpg)
Normal structure of Small Intestine
![Page 4: Toxicopathology of Git](https://reader036.vdocuments.net/reader036/viewer/2022081412/544e46f0b1af9f23638b4c6d/html5/thumbnails/4.jpg)
Normal structure of Rectum
![Page 5: Toxicopathology of Git](https://reader036.vdocuments.net/reader036/viewer/2022081412/544e46f0b1af9f23638b4c6d/html5/thumbnails/5.jpg)
Drug associated with esophageal injury
• Antibiotics(doxycycline,tetrecycline,clindamycin)
• NSAIDs
• Emprolium bromide
• Ferrous sulfate
• Potassium chloride(slow release)
• Quinidine
![Page 6: Toxicopathology of Git](https://reader036.vdocuments.net/reader036/viewer/2022081412/544e46f0b1af9f23638b4c6d/html5/thumbnails/6.jpg)
Drug associated with gastric lesions
• NSAIDs
• Antibiotics
• Iron
• Corticosteroids
• Colchicines
• Proton pump inhibitors(omperazole)
![Page 7: Toxicopathology of Git](https://reader036.vdocuments.net/reader036/viewer/2022081412/544e46f0b1af9f23638b4c6d/html5/thumbnails/7.jpg)
Drug associated with small intestinal lesions
• NSAIDs- mefenamic acid, indomethacine, ibuprofen, diclofenac potassium chloride
• Cytotoxic agents- colchicine, methotrexate,5-FU, vincristine
• Antibiotics- neomycin, penicillins, cyclosporins
• Progestional steroids
• Clofazimine (granulomatous enteritis)
![Page 8: Toxicopathology of Git](https://reader036.vdocuments.net/reader036/viewer/2022081412/544e46f0b1af9f23638b4c6d/html5/thumbnails/8.jpg)
Drug associated with large intestinal lesions
• Melanosis coli-Antraquinone laxatives- colitis(inflammation) presence of neutrophiles
• Penicillamine, methyldopa,indomethcin suppostories,(colitis)
• Gold salts, methyl dopa, & NSAIDs(colitic lesions)
• Cyclosporins
• Rantidine
• Antibiotics (clindamycin and lincomycin, cephalosporins, ampicillins)
• Pseudomembranous colitis(antibiotics chlorpropamide)
• Anticoagulants- haemorrhage
• Oral contraceptives, estrogen- arterial or venous thrombosis with ischaemia
![Page 9: Toxicopathology of Git](https://reader036.vdocuments.net/reader036/viewer/2022081412/544e46f0b1af9f23638b4c6d/html5/thumbnails/9.jpg)
Main alteration due to drug toxicity
• Epithelial hyperplasia
• Erosions/ulcers
• Villous atrophy/stunting• Tumours of GIT
• Caecal enlargement• Lymphangiectasis • Accumulation enteropathies
• Miscellaneous changes in intestine
![Page 10: Toxicopathology of Git](https://reader036.vdocuments.net/reader036/viewer/2022081412/544e46f0b1af9f23638b4c6d/html5/thumbnails/10.jpg)
Epithelial hyperplasiaEpithelial hyperplasia
• Generally found in stomach
• Occurs in response to irritant drugs
• It is a protective mechanism against loss of surface structure.
• Failure in hyperplasia results in erosions and ulcers.
• It some time also occur due to accumulation of a drugs in epithilium.
![Page 11: Toxicopathology of Git](https://reader036.vdocuments.net/reader036/viewer/2022081412/544e46f0b1af9f23638b4c6d/html5/thumbnails/11.jpg)
Hexenal toxicity in rat(fore stomach)(A) Control: no significant lesions(B) 10 mg/kg of hexenal: minimal mucosal hyperplasia. (C) 30 mg/kg of hexenal: mild mucosal hyperplasia with hyperkeratosis. (D) 100 mg/kg of hexenal: severe diffuse mucosal hyperplasia with hyperkeratosis.
![Page 12: Toxicopathology of Git](https://reader036.vdocuments.net/reader036/viewer/2022081412/544e46f0b1af9f23638b4c6d/html5/thumbnails/12.jpg)
(A) Control: no significant lesions. (B) 50 mg/kg of hexenal: no significant lesions. (C) 200 mg/kg of hexenal: necrosis with loss of the epithelium and vesicle formation. (D) 500 mg/kg of hexenal: diffuse coagulative necrosis of the epithelium.
![Page 13: Toxicopathology of Git](https://reader036.vdocuments.net/reader036/viewer/2022081412/544e46f0b1af9f23638b4c6d/html5/thumbnails/13.jpg)
Erosions/ulcersErosions/ulcers
• Common in stomach due to low PH condition
• These are seen generally due to NSAID toxicity.
• Mechanism-
• Alters blood flow inhibit cyclooxygenase reduce synthesis of prostaglandins loss of barrier function cell damage neutophils influx bacterial invasion erosion inflammation ulcer
![Page 14: Toxicopathology of Git](https://reader036.vdocuments.net/reader036/viewer/2022081412/544e46f0b1af9f23638b4c6d/html5/thumbnails/14.jpg)
![Page 15: Toxicopathology of Git](https://reader036.vdocuments.net/reader036/viewer/2022081412/544e46f0b1af9f23638b4c6d/html5/thumbnails/15.jpg)
Iodomethacine induced ulcer in GIT
![Page 16: Toxicopathology of Git](https://reader036.vdocuments.net/reader036/viewer/2022081412/544e46f0b1af9f23638b4c6d/html5/thumbnails/16.jpg)
Histology of small bowel biopsy showing oedematous lamina propria containing patchy mixed inflammatory cell infiltrate with focal erosion of the surface epithelium. Mucosal and submucosal
granulomata are also seen
![Page 17: Toxicopathology of Git](https://reader036.vdocuments.net/reader036/viewer/2022081412/544e46f0b1af9f23638b4c6d/html5/thumbnails/17.jpg)
Microscopically, the ulcer here is sharply demarcated, with normal gastric mucosa on the left falling away into a deep ulcer whose base contains infamed, necrotic debris. An arterial branch at the ulcer base is eroded and bleeding.
![Page 18: Toxicopathology of Git](https://reader036.vdocuments.net/reader036/viewer/2022081412/544e46f0b1af9f23638b4c6d/html5/thumbnails/18.jpg)
Villous atrophy/stunting Villous atrophy/stunting
• Reduction in size and height of villi.
• Increased loss, degeneration and apoptosis of enterocytes occur.
• Inhibition of mitosis of crypt cells results in reduced and arrested replacements in crypts.
• This may also leads to chronic inflammatory condition.
![Page 19: Toxicopathology of Git](https://reader036.vdocuments.net/reader036/viewer/2022081412/544e46f0b1af9f23638b4c6d/html5/thumbnails/19.jpg)
![Page 20: Toxicopathology of Git](https://reader036.vdocuments.net/reader036/viewer/2022081412/544e46f0b1af9f23638b4c6d/html5/thumbnails/20.jpg)
![Page 21: Toxicopathology of Git](https://reader036.vdocuments.net/reader036/viewer/2022081412/544e46f0b1af9f23638b4c6d/html5/thumbnails/21.jpg)
Duodenal biopsy showing mild and moderate villous atrophy. A mild grade of villous atrophy (red arrow) is adjacent to an area of
moderate villous atrophy (black arrow).
![Page 22: Toxicopathology of Git](https://reader036.vdocuments.net/reader036/viewer/2022081412/544e46f0b1af9f23638b4c6d/html5/thumbnails/22.jpg)
Tumours of GIT• Intestinal carcinogens
– di methyl hydrazine, iron containing compounds are colon carcinogens.
– Carrageenans produce colonic polyps and adenocarcinomas.
– Synthetic steroids produce duodenal invasive carcinomas.
– Folpet produce carcinomas and hyperplastic changes
sequential changes occurs during origin of tumours:-
Goblet cell hyperplasia mucosal hyperplasia atypical mucosal hyperplasia adenomas adenocarcinomas
![Page 23: Toxicopathology of Git](https://reader036.vdocuments.net/reader036/viewer/2022081412/544e46f0b1af9f23638b4c6d/html5/thumbnails/23.jpg)
![Page 24: Toxicopathology of Git](https://reader036.vdocuments.net/reader036/viewer/2022081412/544e46f0b1af9f23638b4c6d/html5/thumbnails/24.jpg)
![Page 25: Toxicopathology of Git](https://reader036.vdocuments.net/reader036/viewer/2022081412/544e46f0b1af9f23638b4c6d/html5/thumbnails/25.jpg)
Villous atrophy (arrows) along with hyperplasia of the crypts (arrow heads), producing an appearance with features of ileal and colonic mucosa.
![Page 26: Toxicopathology of Git](https://reader036.vdocuments.net/reader036/viewer/2022081412/544e46f0b1af9f23638b4c6d/html5/thumbnails/26.jpg)
A) Tubular adenoma with high-grade dysplasia. (B) Tubular adenoma with high-grade dysplasia. (C) Tubular adenoma with adjacent colonic metaplasia (D)
Nuclear staining in the dysplastic ileal epithelium
![Page 27: Toxicopathology of Git](https://reader036.vdocuments.net/reader036/viewer/2022081412/544e46f0b1af9f23638b4c6d/html5/thumbnails/27.jpg)
![Page 28: Toxicopathology of Git](https://reader036.vdocuments.net/reader036/viewer/2022081412/544e46f0b1af9f23638b4c6d/html5/thumbnails/28.jpg)
![Page 29: Toxicopathology of Git](https://reader036.vdocuments.net/reader036/viewer/2022081412/544e46f0b1af9f23638b4c6d/html5/thumbnails/29.jpg)
![Page 30: Toxicopathology of Git](https://reader036.vdocuments.net/reader036/viewer/2022081412/544e46f0b1af9f23638b4c6d/html5/thumbnails/30.jpg)
Squamous cell papilloma (top panel) and squamous cell carcinoma in rats with invasion into submucosa and muscularis mucosa(bottom
panel)
![Page 31: Toxicopathology of Git](https://reader036.vdocuments.net/reader036/viewer/2022081412/544e46f0b1af9f23638b4c6d/html5/thumbnails/31.jpg)
Malignant neuroendocrine tumor
![Page 32: Toxicopathology of Git](https://reader036.vdocuments.net/reader036/viewer/2022081412/544e46f0b1af9f23638b4c6d/html5/thumbnails/32.jpg)
Sections of stomach from mice (A and B) The mucosa was severely hyperplastic demonstrating branching tortuous glands, (C and D) inflammatory foci associated with
dysplasia. (E, white arrow) Numerous mitotic and apoptotic profiles (E, black arrow) were observed. (F) A proportion of the blood vessels contained thrombotic clots. (G) Numerous
epithelial cells demonstrate nuclear atypia as well as significant nuclear stratification.
![Page 33: Toxicopathology of Git](https://reader036.vdocuments.net/reader036/viewer/2022081412/544e46f0b1af9f23638b4c6d/html5/thumbnails/33.jpg)
Cecal carcinoma observed in the o-nitrotoluene carcinogenicity study in mice .
![Page 34: Toxicopathology of Git](https://reader036.vdocuments.net/reader036/viewer/2022081412/544e46f0b1af9f23638b4c6d/html5/thumbnails/34.jpg)
Large intestinal adenoma (top panel) and adenocarcinoma (bottom panel) observed in the bromo dichloromethane carcinogenicity study in rats.
![Page 35: Toxicopathology of Git](https://reader036.vdocuments.net/reader036/viewer/2022081412/544e46f0b1af9f23638b4c6d/html5/thumbnails/35.jpg)
Caecal enlargement
• It seen in alcohol, sugar, and antibiotics toxicity
• It is due to disturbance in microflora.
• Results in damage and distention by opportunistic pathogens.
![Page 36: Toxicopathology of Git](https://reader036.vdocuments.net/reader036/viewer/2022081412/544e46f0b1af9f23638b4c6d/html5/thumbnails/36.jpg)
![Page 37: Toxicopathology of Git](https://reader036.vdocuments.net/reader036/viewer/2022081412/544e46f0b1af9f23638b4c6d/html5/thumbnails/37.jpg)
Lymphangiectasis
• Dilated lacteals/lymphatic found in lamina propria can extend up to the lymphatic sinuses of mesenteric lymph node.
• Generally occurs in toxicity which are related with protein loses.
![Page 38: Toxicopathology of Git](https://reader036.vdocuments.net/reader036/viewer/2022081412/544e46f0b1af9f23638b4c6d/html5/thumbnails/38.jpg)
The large white areas within the intestinal microvillus shown.
![Page 39: Toxicopathology of Git](https://reader036.vdocuments.net/reader036/viewer/2022081412/544e46f0b1af9f23638b4c6d/html5/thumbnails/39.jpg)
Duodenal lymphangiectasia, Dilated lymphatic vessels in the apical part of duodenal villi
![Page 40: Toxicopathology of Git](https://reader036.vdocuments.net/reader036/viewer/2022081412/544e46f0b1af9f23638b4c6d/html5/thumbnails/40.jpg)
Accumulation enteropathies
• Ingested products are accumulated within enterocytes, lamina propria, or within macrophages.
• Such accumulation results in foreign body reaction.
• E.g. puromycin, ethionine, tetracyclins, cholesterol rich/fatty diets, detergents, pigmented dyes, plant extracts etc.
![Page 41: Toxicopathology of Git](https://reader036.vdocuments.net/reader036/viewer/2022081412/544e46f0b1af9f23638b4c6d/html5/thumbnails/41.jpg)
Aggregation of macrophage-containing pigment in the lamina propia of the colon.
![Page 42: Toxicopathology of Git](https://reader036.vdocuments.net/reader036/viewer/2022081412/544e46f0b1af9f23638b4c6d/html5/thumbnails/42.jpg)
Section of rectum showing macrophages after feeding cholesterol rich diet
![Page 43: Toxicopathology of Git](https://reader036.vdocuments.net/reader036/viewer/2022081412/544e46f0b1af9f23638b4c6d/html5/thumbnails/43.jpg)
![Page 44: Toxicopathology of Git](https://reader036.vdocuments.net/reader036/viewer/2022081412/544e46f0b1af9f23638b4c6d/html5/thumbnails/44.jpg)
![Page 45: Toxicopathology of Git](https://reader036.vdocuments.net/reader036/viewer/2022081412/544e46f0b1af9f23638b4c6d/html5/thumbnails/45.jpg)
Miscellaneous changes in intestine
• Intussusceptions- seen due to increased peristalsis. E.g. alpha adrenergic agents
• Vacuolation of brunner’s gland- beta blocker, atenolol toxicity
• Degeneration of brunner’s gland-VEGF’s
• Hypertrophy & dilation of brunner’s gland-GLP-1 antagonist
• No. of goblet cell increase- prolactin inhibitors
![Page 46: Toxicopathology of Git](https://reader036.vdocuments.net/reader036/viewer/2022081412/544e46f0b1af9f23638b4c6d/html5/thumbnails/46.jpg)
![Page 47: Toxicopathology of Git](https://reader036.vdocuments.net/reader036/viewer/2022081412/544e46f0b1af9f23638b4c6d/html5/thumbnails/47.jpg)
Photomicrograph of Brunner's gland hyperplasia shows lobular proliferation of Brunner's glands, some of which are cystically
dilated. The overlying mucosa exhibits duodenitis.
![Page 48: Toxicopathology of Git](https://reader036.vdocuments.net/reader036/viewer/2022081412/544e46f0b1af9f23638b4c6d/html5/thumbnails/48.jpg)