Kamala Kannan Stomach in Preclinical Toxicology · Kamala Kannan_Stomach in Preclinical...
Transcript of Kamala Kannan Stomach in Preclinical Toxicology · Kamala Kannan_Stomach in Preclinical...
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STOMACH IN PRECLINICAL TOXICOLOGY
Dr. K. Kamala
Pathology
Advinus, Bangalore
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Disclaimer
The ideas and thoughts expressed
in this presentation are purely that
of the presenter and do not
necessarily reflect the thinking of
the organization or represented by
the presenter.
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Anatomy
Rat
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Anatomy
Mouse
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Trimming Guidelines
1: Forestomach (FS), gastric fundus (GF), antrum (A), pylorus (P).
2: Forestomach (FS), gastric fundus (GF)
3: Optional section - fundus
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1: Forestomach (FS), gastric fundus (GF), antrum (A), pylorus (P).
Trimming Guidelines
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2: Forestomach (FS), gastric fundus (GF)
Trimming Guidelines
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3: Optional section - fundus
Trimming Guidelines
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Histology Comparisons
Rat Mouse
A
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Histology Comparisons
Rabbit Dog
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Commonly Affected Regions
ü In the decreasing order
ü Non glandular stomach in rats-frequency more
ü Glandular stomach in mice
ü Non glandular stomach in mice
ü Glandular stomach in rats
ü Dogs
ü Rabbits
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Common Factors
Influencing Stomach Findings
üGavage/feeding studies
üFeed Quality/texture , contamination
üDuration of exposure
üSpecies difference
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Gross Lesions
Non-glandular mucosa, white, focus
Glandular mucosa-raised focus
Glandular mucosa, Ulcer
Non glandular - Mass
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Recording Gross Lesions
üFoci-depressed/white/raised
üDiscolouration
üMucosal thickening
üThinning of mucosa
üDistension
üTexture of contents
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Gross & Micro Correlation
ØFoci
ØDiscoloration
ØDistended stomach
ØMucosal Thickening
ØAdhesions
ØMasses/nodular growth
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Common Microscopic
Lesions- Short Term Studiesü Dilated/distended glands
ü Vacuolar changes/degeneration-non
glandular stomach-limiting ridge
ü Inflammation-glandular mucosa/submucosa
ü Submucosal leukocytic infiltration
ü Epithelial degeneration-eosinophilic
droplets in fundic mucosa—HE, PAS
ü Epithelial hyperplasia
ü Ectopic pancreas/keratin cyst
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Common Induced Lesions-
Short Term Studies- Rat
üNon glandular-epithelial hyperplasia,
mucosal necrosis/erosion/ulceration
üGlandular-individual cell
necrosis/epithelial degeneration/mucosal
necrosis/ulceration
üMineralization
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Disturbances of growthDilated/Distended Glands - Rat
4x
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Disturbances of growth
20x
Dilated/Distended Glands - Rat
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Disturbances of growthEpithelial Cell Vacuolation-
Limiting Ridge- Rat
10x4x
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Disturbances of growthHyperkeratosis –
Non-glandular - Mouse
10x
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Disturbances of growthMucosal Necrosis/Ulcer –
Non-glandular - Mouse
10x
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Disturbances of growthMucosal Necrosis/Ulcer -
Non-glandular - Mouse
20x
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Disturbances of growthUlcer/Epithelial Hyperplasia-
Non-glandular - Rat
4x
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Disturbances of growthUlcer/Epithelial Hyperplasia-
Non-glandular - Rat
10x
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Epithelial Hyperplasia/Ulcer- non
Glandular
ØHMG Co-A inhibitors
Ø Irritant potential of test substance
ØNot related to pharmacodynamic
properties of test substance
ØLong stasis of test substance
ØStress/starvation
ØBiochemical changes- BUN/Urea
ØHematology changes- altered
leukocyte count
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Disturbances of growthUlcer- Glandular Stomach–
Rat
10x
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Disturbances of growthUlcer-Glandular stomach –
Rat
20x
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Disturbances of growthMucosal Necrosis and
Pigmentation – Glandular - Rat
4x
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Ulcer-glandular stomach
• Non seroidal anti-inflammatory drugs
• Stress
• High doses of ACE inhibitors
• Biochemical changes
• Hematology changes- associated
hemorrhage
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Leukocytic Infiltration
Glandular Stomach - Rat
20x
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Disturbances of growthEpithelial degeneration
Glandular Stomach - Rat
20x
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Disturbances of growthEpithelial degeneration
Glandular Stomach - Rat
20x
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Epithelial degeneration
Glandular Stomach - Rat
20x
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20x
Epithelial degeneration
Glandular Stomach - Rat
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100x
Epithelial degeneration
Glandular Stomach - Rat
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100x
Epithelial degeneration
Glandular Stomach - Rat
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Epithelial Degeneration
üCommon in feeding studies
üAllergic gastritis
üEosinophilic gastritis
üEosinophilic droplets/ capillaries
ü Industrial chemicals
üNot observed with Pharmaceutical
compounds
üEnzyme preparations-fermentation
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Epithelial Degeneration
Associated/primary changes
• Non glandular epithelial hyperplasia
• Lekocytic infiltration
• Edema in submucosa
• Foveolar epithelial hyperplasia
• Increased mucosal thickness- fundic
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Disturbances of growthEpithelial Hyperplasia
Glandular Stomach - Rat
10x
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Disturbances of growthEpithelial Hyperplasia
Glandular Stomach - Mouse
10x
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Epithelial Hyperplasia-
Glandular stomach
ØCommon in aged mice
ØRats- discrete lesion and the incidence
rat is low, basophilic cells
ØMice-to differentiate for the
dilated/distended glands
ØTo differentiate adenoma/glandular
polyp
ØGastric acid inhibitors, H2 antagonists
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Disturbances of growthMineralization
Glandular Stomach - Rat
10x
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Disturbances of growthMineralization
Glandular Stomach - Rat
20x
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Mineralization-
Glandular stomach
üMetastatic calcium salt deposits
üKidney injury and parathyroid
hyperplasia
üDystrophic
üAssociated changes
üConfirmation of metastatic mineral
deposits
üBasement membrane of blood vessels
üTyrosine kinase inhibitors(fibroblast
growth factor inhibitor)
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Disturbances of growthVasculitis/Perivasculitis -
Serosa - Rat
4x
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Disturbances of growthVasculitis/Perivasculitis -
Serosa - Rat
20x
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Disturbances of growthSquamous Cell Carcinoma -
Non-glandular - Mouse
4x
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Disturbances of growthSquamous Cell Carcinoma -
Non-glandular - Mouse
20x
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Disturbances of growthSquamous Cell Carcinoma –
Mouse
10x
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Disturbances of growthSquamous Cell Carcinoma –
Mouse
10x
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Disturbances of growthHistiocytic Sarcoma
Mouse
10x
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Disturbances of growthHistiocytic Sarcoma
Mouse
40x
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Disturbances of growthArtifact/Erosion -
Glandular Stomach - Rat
10x
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Disturbances of growthArtifact-
Glandular Stomach - Rat
10x
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Artifact-
Glandular Stomach - Rat
10x
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