JPC SYSTEMIC PATHOLOGY
Signalment (JPC #2314370): A young guinea pig
HISTORY: This guinea pig was fed autoclaved commercial rabbit food for a period of 6 weeks prior to death.
HISTOPATHOLOGIC DESCRIPTION: Stifle joint (femur, tibia and patella): The femoral and tibial physeal growth plate cartilage is diffusely irregular and thinned, characterized by shortening, loss and disorganization of chondrocyte columns with a poorly discernible zone of hypertrophy and thin resting zone. In the areas of the primary spongiosa there are numerous spicules of cartilage lined by decreased numbers of osteoblasts with no discernible osteoid production (scorbutic lattice) that extend into the metaphyses. Multifocally there are coalescing microfractures of the scorbutic lattice often surrounded by hemorrhage and fibrin. Multifocally within the medullary cavity of both the femur and tibia there are reduced amounts of epiphyseal and metaphyseal trabecular bone, as well as thinning of both the cortical bone (osteopenia). Multifocally within the tibial metaphyseal medullary cavity, hematopoietic elements are replaced by loosely arranged mesenchymal cells (myelofibrosis) and hemorrhage. Hemorrhage frequently separates and elevates the periosteum from the cortex and extends into the adjacent periarticular connective tissue and skeletal muscle.
MORPHOLOGIC DIAGNOSIS: Tibia; femur: Failure of endochondral ossification, with scorbutic lattice formation, osteopenia, microfractures and subperiosteal and periarticular hemorrhage, guinea pig (Cavia poricellus), rodent.
ETIOLOGIC DIAGNOSIS: Scorbutic osteoarthropathy
CAUSE: Hypovitaminosis C/Ascorbic acid deficiency
- Most mammals synthesize ascorbic acid (Vitamin C) from glucose via glucuronic & gulonic acid
- Humans, nonhuman primates (except some prosimians), guinea pigs, Indian fruit bats, several species of birds (red-vented bulbul bird, northern shrike, Indian pistrel), cetaceans and fish (channel catfish, trout, salmon, most aquarium fish) lack the enzyme L-gulonolactone oxidase, which is required for L-gulonolactone conversion to L-ascorbic acid
- Ascorbic acid is required by fibroblasts, odontoblasts, and osteoblasts for the formation of collagen, dentin, and osteoid
- Hallmarks of scurvy are capillary hemorrhage and lack of bone deposition
- Disease is most severe in young, growing animals
- Guinea pigs with prenatal vitamin C deficiency serve as a model of human Lissencephaly type II
- Severity of changes depends on degree of dietary insufficiency
- Ascorbic acid (vitamin C) is required for hydroxylation of proline and lysine, essential in the formation of collagen's helical structure, rigidity and strength
- Lack L-gulonolactone oxidase AND decreased dietary vitamin C> decreased hydroxylation of proline/lysine> decreased deposition of collagen and decreased cross linking of fibrillar collagen (types 1-5)> decreased amounts of collagen and weak cartilage; decreased osteoid (microfractures); increased blood vessel fragility with hemorrhage (usually periarticular because most collagen turnover & blood vessels are epiphyseal/metaphyseal); loose attachment of periosteum to bone/tooth loss
- Anemia results from a combination of hemorrhage and interference with folate metabolism and iron absorption
- Focal myocardial necrosis sometimes occurs, resulting in sudden death
- Other functions of ascorbic acid:
- Catabolism of cholesterol to bile acids
- Macrophage migration and granulocyte phagocytosis
- Cofactor of dopamine beta-oxidase, which converts dopamine to noradrenaline
- Folate metabolism
- Iron absorption
TYPICAL CLINICAL FINDINGS:
- Joint pain, reluctance to move, lameness, muscle wasting, scruffy haircoat, anorexia, and delayed healing of skin wounds
- Radiographic lesions:
- Dense metaphyseal line (collapsed fragile spicules of mineralized cartilage)
- Submetaphyseal translucent zone
- Epiphyseal fractures
- Subclinical form in guinea pigs:
- Anorexia, weight loss, diarrhea and death
- Bone lesions only evident histologically
TYPICAL GROSS FINDINGS:
- Periarticular hemorrhage; gingival swelling, hemorrhage, erosion, ulceration, tooth loss
- Swollen joints/enlarged costochondral junctions (scorbutic lattice)
TYPICAL LIGHT MICROSCOPIC FINDINGS:
- Initially, dilation of metaphyseal vessels
- Thin physis with irregular columnization & hypertrophy of physeal cartilage
- Most characteristic lesions are in metaphysis- naked (lacking osteoid deposition) spicules of calcified cartilage (“scorbutic lattice”) derived from zone of provisional calcification in the growth plate; reduced or absent deposition of osteoid on this cartilage framework
- Decreased numbers of osteoblasts
- Microfractures of the trabeculae and metaphyseal hemorrhage
- Proliferation of mesenchymal cells in the medullary cavity (displacing hematopoietic cells) loosely arranged with interspersed aggregates of eosinophilic material
- Decreased osteoclasts, with reduced matrix remodeling
- Resorption of dentin, derangement of odontoblasts in teeth and fibrosis of the pulp during the early stages of the disease
- Cortices of long bones may be thin with periosteal and subperiosteal hemorrhages present
- Rickets: Abnormal endochondral ossification from inadequate mineral deposition; soft and pliable bones with enlarged costochondral junctions; thickened and disordered zone of hypertrophied cartilage cells in the physis, defective calcification, failure of normal cartilage degeneration and deposition of excess osteoid in the metaphysis
- Osteoporosis/Osteopenia: Reduced bone mass with thin, porous cortices; reduced number, size and connectivity of bony trabeculae
- Osteogenesis imperfecta: Defect in type 1 collagen synthesis resulting in decreased bone production; lack of cortical bone and thin, loosely spaced trabeculae of unmodelled bone with retention of cartilage cores; multiple fractures
- Humans, most nonhuman primates (except some prosimians), Indian fruit bats, several bird species (e.g. red-vented bulbul bird, northern shrike, Indian pipstrels) and fish species (channel catfish, trout, salmon, most aquarium fish) lack the enzyme L-gulonolactone oxidase and cannot synthesize ascorbic acid
- Squirrel monkeys
- Pericranial hemorrhage resulting in large hematomas that become surrounded by a thin rim of bone (cephalohematoma) in affected young animals (predominant lesion)
- Long bones: Metaphyseal fibrosis, premature epiphyseal closure and reduced cartilage cellularity
- Oral lesions have not been seen in this species
- Rhesus macaques: Metaphyseal fractures with periosteal hemorrhage within long bones
- Pigs: Autosomal recessive mutation involving L-gulonolactone oxidase; normal until 2-3 weeks post-weaning (milk is high in ascorbic acid); classic scorbutic lesions, though more severe than other species; subperiosteal accumulations of clotted blood around shafts of effected bones
- ODS rats (Osteogenic Disorder Shionogi): od/od homozygotes lack L-gulonolactone oxidase and develop scurvy
- Fish: Develop lordosis, scoliosis, hemorrhage and depigmentation
- There are several reports of bats with hypovitaminosis C.
- Barthold SW, Griffey SM, Percy DH. Pathology of Laboratory Rodents and Rabbits. 4th ed. Ames, IA: Blackwell Publishing; 2016: 239-241.
- Capo I, Hinic N, Lalosevic D, et al. Vitamin C depletion in prenatal guinea pigs as a model of lissencephaly type II. Vet Pathol. 2015;52(6):1263-1271.
- Craig LE, Dittmer KE, Thompson KG. Bones and joints. In: Maxie MG, ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals. Vol 1. 6th ed. St. Louis, MO: Elsevier; 2016:83-84.
- Kumar V, Abbas AK, Aster JC. Environmental and nutritional diseases. In: Robbins and Cotran Pathologic Basis of Disease. 9th Philadelphia, PA: Saunders Elsevier; 2015:442-443.
- Pritzker KPH, Kessler MJ. Arthritis, Muscle, Adipose Tissue, and Bone Diseases of Nonhuman Primates. In: Abee CR, Mansfield K, Tardif S, Morris T, eds. Nonhuman Primates in Biomedical Research: Diseases. Vol 2, 2nd San Diego, CA: Elsevier Inc; 2012:660-661.