JPC SYSTEMIC PATHOLOGY

DIGESTIVE SYSTEM

September 2024

D-M09

 

Signalment (JPC #1851823): Adult white leghorn chicken

 

HISTORY: None.

 

HISTOPATHOLOGIC DESCRIPTION: Esophagus: Diffusely, submucosal glands are markedly ectatic, dilated up to 1.0mm, 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 necrotic heterophils, cellular and karyorrhectic debris, and multifocal areas of deeply basophilic granular, fragmented material (mineral). Within the lamina propria and surrounding glands, there are multifocal aggregates of numerous lymphocytes with fewer plasma cells, macrophages, and heterophils. The mucosal epithelium is diffusely hyperplastic and characterized by prominent rete ridges, acanthosis, intracellular edema, and prominent intercellular bridging (intercellular edema).

 

MORPHOLOGIC DIAGNOSIS: Esophagus: Mucous gland squamous metaplasia and ectasia, diffuse, severe, with moderate chronic peri-glandular esophagitis, mucosal epithelial hyperplasia, and mineralization, white leghorn chicken, avian.

 

CAUSE: Vitamin A deficiency (Hypovitaminosis A)

 

GENERAL DISCUSSION:

• Hypovitaminosis A is a nutritional disease (i.e. dietary insufficiency)
• Dietary vitamin A originates from plant (carotenoids) or animal (retinyl esters) sources; converted to retinal, retinol, retinoic acid (retinoids); diets composed of cereals, seeds, and captive raised insects are often deficient (backyard flocks)
• Vitamin A is fat soluble (vitamins A, D, E & K); stored in hepatic stellate cells (Ito cells) of liver
• Important in cellular growth and differentiation (controls epithelial differentiation), visual processes, and reproduction

• In birds, 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; generally manifests as hyperkeratosis of oral cavity, conjunctiva, nasal lacrimal duct, upper alimentary tract, and respiratory tract
• 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
• Most poultry rations contain alfalfa meal or new yellow corn (excellent sources of provitamin A carotenoids)

• Stored corn (old), seeds, and cereal grains are often deficient; rancid fat in diet can be deleterious on vitamin A's availability

• Hepatic stellate cells (HSCs, also known as Ito cells) function in storage and homeostasis of Vitamin A 

 

PATHOGENESIS:

• Secondary to dietary deficiency, decreased intestinal absorption, liver disease, or toxicities (chlorinated naphthalene toxicity in cattle)
• Predisposes birds to secondary bacterial/fungal infections

 

Vitamin A deficiency effects:

Epithelial differentiation:

• The role of Vitamin A in epithelial differentiation is unclear; cutaneous lesions are squamous epithelial hyperkeratosis and squamous metaplasia of secretory epithelia (i.e. glandular epithelium)
• 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

 

Vision:

• 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 retinal and rhodopsin (photoreceptor atrophy affecting outer segments, specifically rods), since it must be replaced daily; results in “night blindness”

 

Growth:

• 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 > abnormal odonotoblastic differentiation and spatial organization > enamel hypoplasia and hypermineralization, vascularized dentin (osteodentin) and retarded or failed tooth eruption
• Teratogenic: Varied lesions among different species, variability may be due to stage of skeletal growth and severity of deficiency

 

CNS: 

• 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

 

Reproduction:

• 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
• Oversupplementation is teratogenic

 

Immune function:

• 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; unthriftyness, decreased egg production, decreased hatchability, and embryonic mortality observed; individuals in a flock may have conjunctivitis and sinusitis with mucoid or caseous exudate in the conjunctival sac; owners often report "the birds have a cold"
• Chicks and poults: Initially anorexia, growth retardation, then drowsiness, mild ataxia, and increased mortality; birds usually die before development of eye lesions but if survive >1wk, eyelids become inflamed and can be adhered with caseous material present in nostrils and eyes
• Birds hatched from layers with low vitamin A will have very low vitamin A reserves and will quickly develop hypovitaminosis A if placed on deficient ration after hatching
• Azotemia: Chronic Vitamin A deficiency also damages renal tubules, sporadically causes visceral gout

 

TYPICAL GROSS FINDINGS:

• Chicks and poults: Conjunctivitis; eyelids adhered by exudate; excessive urates in ureters, collecting ducts, and bursa 
• Adult chickens and turkeys: Small white nodules (1-3 mm) often with a central depression in nasal passages, mouth, pharynx, esophagus, and crop
• Seromucoid watery masses fill turbinates and may cause facial swelling; 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, bursal atrophy, corneal opacity, blunting of choanal papilla (psittacines) 

 

TYPICAL LIGHT MICROSCOPIC FINDINGS:

• Dilation of submucosal glands; replacement of glandular epithelium with squamous metaplasia
• 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)

 

ADDITIONAL DIAGNOSTIC TESTS:

 

DIFFERENTIAL DIAGNOSIS:

Oral and esophageal 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
• Esophageal mucosal hyperplasia: Flamingos raising chicks produce and feed young an opaque substance, crop milk; histologically, esophageal mucosa of parent birds (both male and female) is markedly hyperplastic and these cells slough into the lumen

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:

 

COMPARATIVE PATHOLOGY:

Lesions of hypovitaminosis A in other species:

• Mammals: Testicular atrophy/degeneration 
• Dogs: Hyperkeratosis of sebaceous gland ducts; vitamin A-responsive dermatosis (Cocker spaniel); deafness prominent sign in puppies from changes in internal auditory meatus; implicated in urolithiasis
• Pigs: Renal dysplasia, incoordination; posterior paresis; squamous metaplasia in the urinary bladder (1-2mm light-yellow nodules); very susceptible to teratogenic effects; cutaneous lesions - follicular hyperkeratosis
• Cattle, swine, sheep, and goats:
  • Pathognomonic lesion in cattle: 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 and pigs, stenosis of the optic foramina > compression > atrophy of optic nerve > blindness
  • Uncommon non-infectious cause of abortion and stillbirth (Kim, J Vet Diagn Invest, 2024)
• Cats: 
  • 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, follicular orthokeratotic hyperkeratosis, and alopecia
• Guinea pigs and rats: Irregular dentin formation and enamel hypoplasia
• 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; obstruction of large colleting ducts in kidneys, resulting in renal and visceral gout and secondary tubulonephritis; respiratory disease; retention of sloughed keratin within glandular ostia in lingual glands of crocodiles
• Amphibians: Anurans and caudates fed insect based diets (captive reared insects lack significant preformed vitamin A vs. the plant based carotenoids found in wild insects); affected toads initially described as having "short tongue syndrome" due to difficulty prehending prey, but had no gross lesions; squamous metaplasia of mucus producing glands or ciliated epithelium of oral mucosa, esophagus, cloaca, and urinary tract 
• Fish: Poor growth; ascites; edema; exophthalmos; hemorrhagic kidneys

 

REFERENCES:

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