Page 209 - Veterinary Immunology, 10th Edition

triggered by carbohydrate (starch and oligofructose) overload;
VetBooks.ir black walnut poisoning, or by sepsis. All of these forms of laminitis

may have a final common pathway.
In most mammals with sepsis, as described above, internal

organs such as liver or lung are damaged as a result of a cytokine
storm, and this results in organ failure. In the horse, in contrast, it is
suggested that the epidermal laminae within the hoof are the
vulnerable organs. (The laminar tissue is formed by the

interdigitations between the dermis and epidermis formed by the
basement membrane.) Infections that trigger laminitis may
therefore include pleuropneumonia, endometritis, and
gastrointestinal injury. In the latter case, this may be due to

enterocolitis and severe colic, especially when associated with
dysbiosis of the colonic microbiota as a result of carbohydrate
overload. Massive death of Gram-negative bacteria releases large
amounts of lipopolysaccharide, resulting in destruction of the

epithelial barrier, Gram-negative sepsis, and endotoxemia. While
endotoxin alone cannot induce laminitis, other molecules escaping
from the damaged gut probably play a role. The complex mixture
of PAMPs and DAMPs escaping from the colon, presumably acting

through PRRs, trigger acute laminar inflammation. Endothelial
cells, epidermal cells, and macrophages release COX-2 and ROS, as
well as IL-1β and IL-6, and many different chemokines. They also
trigger leukocyte infiltration and activation. The resulting acute

inflammation within the lamina upregulates matrix and secreted
metalloproteases within the hoof. These degrade the proteoglycans
in the basement membrane of the lamellae as well as collagen in the
intercellular matrix. This leads to basement membrane disruption

and the separation of the epidermal and dermal laminar tissue. The
separation may also be due to downregulation of epithelial cell
adherence proteins such as integrins and to a loss of
hemidesmosomes, oxidative injury, and excessive apoptosis.

Treatment includes prolonged cooling of the foot to reduce blood
flow and exudation, pain management, and mechanical support for
the damaged hoof. If lamellar damage is not controlled, the disease
may become chronic, leading to rotation of the third phalanx, coffin
bone remodeling, dropped sole, and development of a lamellar

wedge.

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