JPC SYSTEMIC PATHOLOGY
Signalment (AFIP #1851823): Adult white leghorn chicken
HISTOPATHOLOGIC DESCRIPTION: Esophagus: Diffusely, the submucosal glands are markedly ectatic, dilated up to 2 mm, and the glandular epithelium is replaced by gradually keratinizing stratified squamous epithelium (squamous metaplasia). The lumina are variably occluded or expanded by eosinophilic lamellations of keratin, admixed with few degenerate heterophils, necrotic debris, and multifocal areas of a deeply basophilic granular, fragmented material (mineral). Multifocally, within the lamina propria and surrounding glands, there are aggregates of predominantly lymphocytes with fewer plasma cells, macrophages and heterophils. Diffusely, mucosal epithelium is mildly hyperplastic characterized by prominent rete ridges, acanthosis, intracellular edema and prominent intercellular bridges.
MORPHOLOGIC DIAGNOSIS: Esophagus: Mucous gland squamous metaplasia and ectasia, diffuse, severe, with moderate chronic periglandular esophagitis, mucosal epithelial hyperplasia and mineralization, white leghorn chicken, avian.
CAUSE: Vitamin A deficiency (Hypovitaminosis A)
- In poultry, Vitamin A is essential for optimal growth, vision and integrity of mucous membranes
- Epithelial linings composed of mucous membranes (i.e. alimentary, urinary, genital, and respiratory systems) are most often affected
- Primarily a disease of young (1-7 week-old) birds, but reported in all species
- Outbreaks usually occur in small, backyard flocks with poor ration formulation
- Vitamin A is one of four fat soluble vitamins (also D, E & K) and has multiple functions:
- Vision: Retinal derivative a component of visual pigments in retinal sensory cells
- Vitamin A as retinoic acid functions in:
- Morphogenesis during embryonic development
- Maintenance of epithelial cells
- Bone growth (stimulates osteoclasts for remodeling)
- Dietary Vitamin A originates from plant (carotenoids) or animal (retinyl esters) sources; converted to retinal, retinol, retinoic acid
- Vitamin A is stored in Ito cells in the liver; hepatic stellate cells (HSCs) function in storage and homeostasis of Vitamin A
- The role of Vitamin A in epithelial differentiation is unclear; cutaneous lesions are squamous epithelial hyperkeratosis and squamous metaplasia of secretory epithelia
- Vitamin A deficiency > impaired epithelial differentiation > reduction in mucus-secreting cells > squamous epithelial metaplasia (of respiratory and genitourinary epithelium) > hyperkeratosis
- Decreased synthesis of some glycoproteins and immunoglobulins by intestinal mucosa > impaired local immunity
- In the retina, the protein opsin combines with 11-cis-retinal, a retinal derivative, to form rhodopsin (visual pigment), the direct recipient of light energy during night vision; vitamin A deficiency causes rapid depletion of retina and rhodopsin (photoreceptor atrophy affecting outer segments, specifically rods), since it must be replaced daily; results in “night blindness”
- Vitamin A deficiency has been shown to decrease BMP2, collagen α1 type 1, and osteocalcin expression in bone
- Odontodystrophies: Vitamin A deficiency > altered ameloblast differentiation and reduced ability to organize > odonotoblastic differentiation and spatial organization abnormal > enamel hypoplasia and hypermineralization, vascularized dentin (osteodentin) and retarded or failed tooth eruption
- Teratogenic: Varied lesions, among different species, may be due to stage of skeletal growth and severity of deficiency
- Vitamin A deficiency > stimulatory effect on osteoclastic activity > defective remodeling of membranous bone, inadequate resorption of endosteal bone > asynchrony between developing CNS and bones of skull and spinal column > failure of cranial cavity to enlarge to sufficiently accommodate the brain, cranial nerves and spinal cord > neurologic signs
- Defect in bones of caudal fossa: Cerebellar herniation through foramen magnum
- Vitamin A deficiency > arrest of spermatogenesis at the spermatid phase in all species, especially in cattle, rats, and chickens
- Abnormal estrous cycles, congenital anomalies (including congenital and neonatal hydrocephalus in cattle), and fetal resorption
- Thought to stimulate T-cells directly through 14-hydroxyretinol
- During infection retinol-binding protein synthesis is down regulated (negative acute phase protein), decreasing availability of Vitamin A
TYPICAL CLINICAL FINDINGS:
- Adult chickens and turkeys: Signs and lesions usually develop in 2-5 months depending on amount stored in the liver and other tissues
- Chicks and poults: Cessation of growth, hunched-up posture, emaciation, lethargy, mild ataxia, swollen eyelids with a mucoid oculonasal discharge
- Laying hens: Decreased egg production with increased incidence of blood spots, emaciation, weakness, ruffled feathers
- Azotemia: Chronic Vitamin A deficiency also damages renal tubules
TYPICAL GROSS FINDINGS:
- Small white nodules (1-3 mm) often with a central depression in nasal passages, mouth, esophagus, pharynx and often into the crop
- Seromucoid watery masses fill turbinates and may cause facial swelling; the paranasal sinuses, trachea and bronchi may be lined by a delicate pseudomembrane
- Other lesions: Bone deformities, keratinization of the tongue, hyperkeratosis and hyperplasia of esophageal epithelium, corneal opacity
TYPICAL LIGHT MICROSCOPIC FINDINGS:
- Dilation of submucosal glands; replacement of glandular epithelium with squamous metaplasia
- Squamous metaplasia of parotid glands in cattle
- Atrophy and deciliation of respiratory cells +/- necrosis (early lesion in avian species)
- Bone lesions: Decreased endosteal and periosteal osteoblasts > impaired bone growth, bone remodeling and thin cortex; marked retardation and suppression of endochondral bone growth, reduced proliferating zone (young chicks and ducks)
- Oral lesions
- Fowl pox (avian poxvirus): Raised nodules with necrotic centers in oropharynx and esophagus
- Trichomoniasis (Trichomonas gallinae): Caseous proliferative lesions in buccal cavity, pharynx, esophagus, crop, especially in pigeons and raptors
- Thrush (Candida albicans): Crop mucosa is thickened with white circular, raised plaques
- Mucoid oronasal discharge and facial swelling
- Infectious coryza (Avibacterium paragallinarum): Profuse nasal discharge (“wet beak”)
- Infectious bronchitis (coronavirus): Swollen sinuses, catarrhal nasal and ocular discharge, caseous exudate in lower trachea and bronchi
- Neurologic signs:
- Ataxia in severe deficiency may resemble Vitamin E deficiency; differentiation is by histologic examination of the brain (Vitamin E deficiency causes encephalomalacia)
Vitamin A deficiency:
- The pathogenesis of skeletal lesions in vitamin A defeciency associated with defective bone remodeling likely associated with decreased osteoclast activity (vitamin A is stimulatory for osteoclasts)
- Asynchronous development between CNS and bones of skull and spinal column resulting in neurologic signs
- Vitamin A deficiency during pregnancy has been associated with increased risk of congential ano-rectal malformation in several species, possibly due to improper development of enteric nervous system
- Vitamin A defeciency and excess are BOTH teratogenic; swine and large felids are very susceptible; abortions and stillbirth in addition to a variety of other lesions occur
- Cause of testicular atrophy/degeneration in mammals and rodents
- Reptiles: Common in turtles and tortoises, rare in snakes; squamous metaplasia of respiratory and digestive mucous membranes; bilaterally swollen conjunctiva and tympanic membranes from metaplasia of orbital gland epithelium; respiratory disease
- Dogs: Hyperkeratosis of sebaceous gland ducts; vitamin A-responsive dermatosis (Cocker spaniel); deafness prominent sign in puppies from changes in internal auditory meatus
- Pigs: Renal dysplasia, incoordination; posterior paresis; squamous metaplasia in the urinary bladder (1-2mm light-yellow nodules); blindness caused by narrow optic foramina and compression of optic nerves; very susceptible to teratogenic effects; cutaneous lesions - follicular hyperkeratosis
- Cattle, swine, sheep, and goats:
- Pathognomonic lesion in cattle is squamous metaplasia of the parotid gland
- Common in cattle and pigs fed supplemented rations of grain and/or old hay
- Hyperkeratosis and hyperplasia of esophageal epithelium (herbivores); hyperkeratosis of ruminal epithelium (calves)
- Night blindness; edema in brisket and limbs; excessive lacrimation; neurologic disorders; increased cerebral spinal fluid pressure; corneal changes; skeletal abnormalities; reproductive disorders (infertility and abortion, particularly in swine); scaling, crusting, faded hair, orthokeratotic dermatitis
- In calves stenosis of the optic foramina > compression > atrophy of optic nerve > blindness
- Experimental (rare) loss of vision; ocular exudate; weakness; incoordination; bronchopneumonia; subpleural pulmonary cysts lined with squamous epithelium; corneal ulceration; squamous metaplasia of the conjunctiva, salivary glands, uterus, and respiratory tract; cutaneous lesions - scaling, follicular plugging, follicluar orthokeratotic hyperkeratosis and alopecia
- Leukoencephalomyelopathy has been reported in cats fed long term diet of gamma-irradiated dry diet (irradiation destroys vitamin A content in food)
- Large and young captive felids: Neurologic lesions associated with osteodystrophy of skull bones, especially tentorium cerebelli and herniation of cerebellar vermis
- Fish: Poor growth; ascites; edema; exophthalmos; hemorrhagic kidneys
- Guinea pigs and rats: There is inadequate differentiation and organization of odontoblasts leading to irregular dentin formation and enamel hypoplasia
- Suspected hypovitaminosis A – associated salt gland adenitis in Northern Rockhopper penguins (Eudyptes moseleyi) reported in recent literature
Vitamin A toxicity:
- Both Vitamin A deficiency & toxicity are teratogenic
- Physeal lesions associated with reduced chondrocyte proliferation and reduced size of hypertrophic chondrocytes, resulting in narrowing of growth plates
- Osteoporosis associated with decreased numbers of osteoblasts and reduced osteoid seams; most severe in cortical bone and some membranous bones of skull
- “Hyena disease” in calves (dwarfism) due to premature closure of growth plates which causes underdevelopment of caudal body structures;
- Focal closure of growth plates is basis for gross lesions of toxicity associated with single, large doses of Vitamin A
- Osteophyte formation (exostoses), often extensive at cervical vertebrae (deforming cervical spondylosis) typically seen in cats >2Y age; hallmark syndrome from chronic toxicity in fed beef livers
- Oral & dental lesions in cats associated with hypermobility and loss of incisor teeth even in the face of normal dietary calcium
- Ectopic mineralization of internal organs in rats, rabbits and dogs
- Decreased CSF pressure in cattle, pigs and dogs; associated with thinning of fibrous cap of arachnoid granulations in calves
- Alopecia & dermatitis in horses
- Peliosis-like changes in liver, joint hemorrhage and hair loss in humans
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