A Ratty Story - University of Georgia College of Veterinary Medicine

Transcription

Cara Pillitteri, DVM
Resident, Anatomic Pathology
Department of Pathobiology
College of Veterinary Medicine
University of Tennessee - Knoxville
Permission granted only for viewing on SEVPAC website

Adult intact male
Zucker rat

Part of a research
protocol

One of eight rats
submitted for
evaluation
www.criver.com

8/8 rats underweight to
emaciated

8/8 kyphosis

4/8 submandibular
swelling

1/8 corneal/conjunctival
keratinization
www.criver.com
200X image of salivary gland
100X Image of salivary gland
40X image of salivary gland

Marked chronic
diffuse
pyogranulomatous
sialoadenitis with
ductular squamous
metaplasia,
keratinization , and
intralesional mixed
bacteria
Culture
› 1000 colonies Escherichia coli
› >200 colonies Gram negative
nonfermentative rod (Acinetobacter or
Stenotrophomonas)
› >100 colonies Gram positive anaerobic
rod (Actinomyces-like)
http://wineserver.ucdavis.edu
Vision
› Rhodopsin
Metabolism
› Lipid
› Bone
Resistance
infection
to
› Intestinal barrier
Anti-inflammatory
› Neutrophil inhibition
Growth
› Growth factor
receptors
› Tumor suppressor
genes
www.interestinglife.info
Early lesions
› Glandular epithelial cell
atrophy
› Interstitial edema and
fibroplasia
› Decreased salivary
secretion
Decreased
growth
factor receptors
Neutrophilic
and
bacterial invasion of
salivary ducts
Decreased
flow

salivary
Decreased neutrophilic
inhibition
Later lesions
› Ductular squamous
metaplasia and
keratinization
x Occlusion & rupture
Unclear pathogenesis
› Increased basal cell
proliferation
› Decreased differentiation
signals
› Alterations in biochemical
milieu
Corneal/Conjunctival
keratinization
Unclear pathogenesis
› Increased basal cell
proliferation
› Decreased
differentiation signals
› Alterations in
biochemical milieu

Thyroid gland
Parathyroid glands
Anterior pituitary
Harderian glands
Lacrimal glands
Seminiferous tubules
Prostate gland
Seminal vesicles
Coagulating gland
Exocrine pancreas
Brunner’s glands
Sebaceous glands

Harderian glands
Lacrimal glands
Meibomian glands
Upper respiratory
epithelium
Olfactory
epithelium
Trachea
Bronchi
Gastric epithelium*
Pancreatic ducts

Renal pelvis
Ureter
Urinary Bladder
Seminiferous tubules
Prostate
Seminal vesicles
Coagulating gland
Oviduct
Uterus
Vagina
Respiratory
› Hyperplasia of the olfactory epithelium
› Thickened alveolar BM
› Impaired type II pneumocyte
differentiation
› Interstitial pneumonia
Cardiovascular
› Focal myofiber degeneration
Alimentary
› Lingual ulcers*
› Taste bud hyperkeratosis
› Esophageal hyperkeratosis*
› Decreased duodenal goblet cell numbers
› Increased Lactobacillus and Escherichia
coli

Hepatic
› Hepatocellular vacuolation
Special Senses
› Retinal degeneration (photoreceptor)
Hematopoietic
› Splenic and thymic lymphoid depletion
› Hyperkeratosis of Hassall’s corpuscles
Skeletal
› Kyphosis*
Emaciation*
›
›
›
›
Decreased intestinal absorptive capacity
Appetite suppression
Increased fatty acid oxidation
Lack of dietary palatability
Secondary
bacterial infection
Shelley Newman, DVM, DVSc,
DACVP
Dee Stephenson
Sharon Schlosshen
Michelle Hill
David Durtschi
Obtained
›
from diet
Retinol esters and Carotenoids (βCarotene)
Transported
to liver in chylomicrons
› Bind hepatocellular apolipoprotein E
receptor
May
be esterified for hepatic storage
Stored
retinol released in to circulation
› Carried by hepatocellular Retinol Binding
Protein
Uptake
by other cell types
› Cell-specific Retinol Binding Proteins
Hepatocellular
Retinol Binding Protein
released back in to circulation
Eye
› Oxidized to all-trans retinaldehyde
› Isomerized to 11-cis retinaldehyde
www.taekwondotigers.com

Other tissues
› Oxidized to all-trans retinaldehyde
x Alcohol dehydrogenases
x Short-chain dehydrogenase/reductases
x Cytochrome P450s
› Further oxidized to all-trans retinoic acid
x Aldehyde dehydrogenases
› Some isomerized to 9-cis retinoic acid
Vision
› 11-cis retinal associates with 7
transmembrane rod protein Ærhodopsin
› Photon reaching rods isomerize 11-cis
retinal to all-trans retinal
› All-trans retinal dissociates
› Conformational change in opsin
Growth
› All-trans retinoic acid binds to Retinoic
Acid Receptors (RAR)
› RAR forms heterodimer with Retinoic X
Receptor (RXR)
› RAR-RXR activates Retinoic Acid
Response Elements (RARE) in promoter
regions
x Growth factor receptors
x Tumor suppressor genes
Resistance to Infection
› Strengthens intestinal barrier
x Promotes goblet cell differentiation
x Promotes defensin production
x Suppresses expression of TLRs 2 and 5
Metabolism
› 9-cis retinoic acid activates RXR
› RXR forms heterodimers with PPARs and
Vitamin D receptors
RXR-PPARs
› Fatty acid
oxidation in
adipose and
muscle
RXR-Vitamin
receptors
D
› Osteoclasia
› Osteoblast
secretory activity
› Adipogenesis
› Lipoprotein
metabolism
Anti-inflammatory
› Inhibits neutrophil superoxide production
› Inhibits release of neutrophilic lysozomal
enzymes
› Decreases synthesis of LTB4

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