Working to Understand Equine Laminitis
Equine laminitis can be a devastating result of many different disease processes in the horse, including sepsis and endocrinopathies. The two primary types of endocrinopathic laminitis are equine metabolic syndrome (EMS, seen most often in the obese horse), and Cushing's syndrome (also known as pituitary pars intermedia disorder) in older horses (characterized by high levels of circulating steroids produced by a pituitary tumor). Interestingly, the "target" tissue in the horse for sepsis, equine metabolic syndrome, and Cushing's syndrome is the digital laminae.
Most likely the main reason the digital laminae are the primary target is because no other soft tissue structure injury or dysfunction will result in the collapse of the musculoskeletal system of the animal; the laminar basal epithelial cells are exposed to incredible forces (supporting the entire weight of the horse).
Septic conditions in the horse that can lead to laminitis include gastrointestinal disease (surgical lesions, diarrhea/enteritis from infectious agents, or carbohydrate overload), retained placenta in the post-foaling broodmare leading to a uterine infection, pleuropneumonia, and any other infection in which enough tissue is compromised to result in systemic effects. In most of these cases, toxins absorbed from Gram-negative bacteria thought to be responsible for systemic problems, such as laminitis. Bacterial infections from other types of organisms can also result in laminitis. Most progress has been made in studying sepsis-related laminitis, as most experimental models for laminitis mimic this condition.
Systemic inflammation leading to inflammatory injury to the laminar tissue has been reported in sepsis-related laminitis in horses. In the laminae, this injury is characterized by adhesion and migration of circulating white blood cells out of the blood vessels into the laminar tissue. This is accompanied by massive increases in expression of inflammatory proteins such as cytokines (a 10-fold to more than 2,000 fold increase in expression) and cyclooxygenase-2 (COX-2, the enzyme targeted by non-steroidal anti-inflammatory drugs such as phenylbutazone or flunixin). These events most likely cause injury to the laminar basal epithelial cells, leading to disruption of their critical cellular events, including adhesion to the underlying matrix. The matrix itself can also be injured by the release of matrix-degrading enzymes by leukocytes, epithelial cells, and other cell types in the laminae.
EMS, which includes pasture-associated laminitis, is now the most common type of laminitis reported by veterinarians. Although the animals affected are commonly obese, animals in "show shape" that are not overtly obese also succumb to EMS-related laminitis. A consistent factor in the horse or pony with EMS is insulin resistance, with the animals usually exhibiting increased circulating insulin concentrations. It has been suspected that laminar injury in EMS was from an inflammatory event as discovered in sepsis-related laminitis. However, recently presented data indicate that the high circulating insulin concentration itself can induce laminitis with limited evidence of inflammation in the laminae.
The other type of endocrinopathic laminitis, equine Cushing syndrome (ECS), could have a pathophysiologic mechanism similar to that of EMS, as ECS horses similarly have high levels of circulating insulin. However, it is possible that the glucocorticoids (any group of steroid hormones involved in metabolism) could be playing a role in disruption of the cell biology of the laminar keratinocytes (cells that form keratin) in ECS.
The pathophysiology of supporting limb laminitis, the type suffered by 2006 Kentucky Derby winner Barbaro, is the type of laminitis about which we presently have the least knowledge. With this type, excessive weight bearing (usually due to an injury on the opposite limb) results in laminar failure. The recent interest supporting limb laminitis has resulted in several studies being funded by equine foundations. Hopefully, these studies will further elucidate the pathologic mechanisms (and thus therapeutic targets) for this equally devastating form of laminitis.
Laminitis is likely the end product of a diverse array of disease processes that lead to disruption and failure of a highly evolved cell type that is exquisitely sensitive to injury--the laminar basal epithelial cell.
CONTACT: James Belknap, DVM, MS, PhD, Dipl. ACVS, 614/292-6661, firstname.lastname@example.org, The Ohio State University College of Veterinary Medicine, Columbus, Ohio
This is an excerpt from Equine Disease Quarterly, funded by underwriters at Lloyd's, London, brokers, and their Kentucky agents.
Disclaimer: Seek the advice of a qualified veterinarian before proceeding with any diagnosis, treatment, or therapy.
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