Friday, June 29, 2012

Equine Laminitis Update: Belknap's Summary of Basic Facts

Laminitis terminology suggested by Dr Belknap in this article
A laminitis word cloud made from the words in this article. A lot of words and a lot of ideas circulate the world when it comes to preventing, treating and /or understanding laminitis. But what do we really know?
Laminitis: what does that word mean to you? Do you think you know all about it, or does hearing the very word have you shaking your head over all we just don't know.

The recent--and some would say long overdue--expansion in laminitis research has spawned a generation of geeks who can speak the lingo and conject about the future. Their ideas are exciting--but what do we really know about laminitis, and how much more do we know that a year ago, or ten years ago? 

Is it possible to find a cure for something you don't understand?

Dr. James Belknap, a leading laminitis researcher, recently wrote this succinct summary of what laminitis is, based on the few facts he and his researcher allies know to be the foundation of the disease. 

It's not far off to say that what he describes here is the laminitis base camp. Research expeditions head out from here. Sherpas lead the way, but it is one step at a time and sometimes bad weather forces an expedition back to the base just when the summit is in sight. Everyone wants to stand at the summit, on top of the world. Getting there has not been easy, but here's what the tents at base camp are built upon.

Laminitis is not a disease of the foot as much as a disease of the horse--yet the foot has a delicate structure--what Dr. Belknap calls "target tissue"--that is incredibly sensitive to changes from the many triggers. And the target tissue gets bullseyed more often than we'd like.

From Dr. Belknap:

Equine laminitis can be a devastating result of many different disease processes in the horse, including, most commonly, sepsis and endocrinopathies. The two primary types of endocrinopathic laminitis are equine metabolic syndrome (seen most often in the obese horse), and Cushing’s syndrome 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 in species injury/dysfunction will result in the entire 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).

Laminitis researcher James Belknap from Fran Jurga's Hoof Blog/Hoofcare Publishing
Dr. James Belknap is a leading researcher in the pathophysiology of laminitis. He is a professor at
 The Ohio State University College of Veterinary Medicine's Galbreath Equine Center.

1. Laminitis related to septic conditions

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 are thought to be responsible for the systemic problems such as laminitis. However, 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 > 2,000 fold increase in expression) and cyclooxygenase-2 (COX -2, the enzyme which is targeted by non-steroidal antiinflammatory drugs such as phenylbutazone or flunixin).

Plastinated equine hoof specimen demonstrating laminitis damage Christoph von Horst and Hoofcare Publishing
Research attempts to sort out not only what happens, but when it happens,
to cause the horse's hoof to experience the freefall of chronic laminitis,
Plastinated hoof tissue courtesy of HC Biovision/Dr Christoph von Horst

2. Laminitis related to Equine Metabolic Syndrome and Equine Cushing Syndrome

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 may also be injured by the release of matrix-degrading enzymes by leukocytes, epithelial cells, and other cell types in the laminae.

Equine metabolic syndrome (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), may 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 (GCs) may be playing a role in disruption of the cell biology of the laminar keratinocytes in ECS.

3. Laminitis related to weightbearing (“supporting limb laminitis”)

The pathophysiology of supporting limb laminitis, the type suffered by Barbaro, is the type of laminitis about which we presently have the least knowledge. With this type, excessive weight bearing (usually due to a painful 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. Thus, 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.

James Belknap, DVM, PhD, DACVS is Professor of Veterinary Clinical Sciences from The Ohio State University Galbreath Equine Center and a leading researcher in the pathophysiology of laminitis. He shared this succinct summary of the current knowledge based on the types of laminitis via the Equine Disease Quarterly of the University of Kentucky’s Gluck Equine Research Center.

Equine Hoof Wall Anatomy Lisa Lancaster Hoofcare Publishing
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