Indeed, researchers are closer than ever to understanding each type of laminitis, but it’s still a difficult disease to predict and treat, said van Eps in his update on the pathophysiology of laminitis at the 2016 British Equine Veterinary Association Congress, held in Birmingham, U.K., in the fall.
“It’s a bit akin to a train wreck (and) trying to work out where the penny was on the track,” said van Eps, “and a lot of times when we look at laminitis, that’s what we’re trying to do.”
Van Eps is probably best known for scientifically validating foot-cooling with cryotherapy to prevent and treat laminitis. At the time of his presentation, he was studying laminitis at the University of Queensland in Australia, but he joined faculty at the University of Pennsylvania late in 2016.
He started by giving congress attendees an anatomy refresher. “The (coffin) bone is essentially suspended within the hoof capsule by lamellar tissue,” he said. “There about 600 primary dermal lamellae on the bone side, and they interdigitate with 600 primary epidermal lamellae, which span the entire hoof wall, and right into the bars of either side.”
These lamellae branch about 200 more times, he explained, until they give the horse’s foot about a meter-square of attachment surface area for optimal strength.
“Without those it’s about .006 meters squared, which is the situation in the cow,” he said. “The cow does not have secondary lamellae. It relies more on the digital cushion” to support the weight of the animal. (This is all fine and well for an animal that isn’t a high-performance athlete, but not so much for the horse.)
The basal cells in the secondary lamellae don’t have a primary blood supply, but they’re very metabolically active. In fact, more glucose extraction occurs in the horse’s hoof than in his head. “That probably gives insight into the importance of the foot vs. the brain in the horse.”
So, why all the glucose? The lamellar basal cells attach to a surface called the basement membrane, anchored by structures called hemidesmosomes found at the base of the cells that make up the inner hoof capsule lining (epidermal basal cells).
“Their only job is really just to hang on,” said van Eps, which takes a lot of energy, “so they consume glucose in order to just maintain their attachments (including the hemidesmosomes). Yet, there’s nowhere to store glycogen in the foot, so they reply on constant delivery of glucose from the blood supply.”
A rich vascular network in the foot makes it excellent for delivering glucose and absorbing shock, but “there aren’t really any valves per se and no muscle,” he said, “so the foot of the horse really relies on the pumping action (of movement) and the expansion and contraction of the hoof in order to keep blood from congesting … (and to keep) delivering it back up the limb.”
Ultimately, he said, the blood flow to (and away from) the foot’s lamellae “is in careful balance and can be upset by many different factors, including weight bearing and load cycling—this might be the most important factor in supporting-limb laminitis.“
Technically, the laminitis lesion is a failure of the apparatus suspending the coffin bone within the hoof capsule. The position of the bone changes, and sometimes that results in the weight of the horse driving it to or through the sole. It might also disrupt the surrounding blood vessels as it shifts.
The three major causes of laminitis include:
- Systemic disease (sepsis) causing acute laminitis;
- Hyperinsulinemia as a part of endocrinopathy; and
- Excessive weight bearing on a limb, as in supporting-limb laminitis.
There is one other cause—road founder, or “traumatic” laminitis—but this is not seen very frequently anymore with fewer horses working for long distances on hard surfaces.
“The overall end result is similar,” he said, “we get morphological derangement of the tissue, it loses its strength, the bone’s no longer suspended within the hoof, and we get proliferation and expansion of the epidermal tissue, which is (called) the lamellar wedge, and pain, which is the most important thing from our clinical standpoint.”
How severe the damage is depends on the initial insult, the speed of the progression, and the mechanical factors at play.
“We’ve learned that the pathology is a little bit different if you’re looking at the acute septic cases (such as a mare with retained placenta), where there is a lot of that basement membrane separation (‘pulling off like fingers of a glove’), and the insulin-type cases, where we tend to get more lengthening, proliferation of cells; it’s a slower process and there’s definitely some different results,” said van Eps.
Van Eps stressed that the significance of mechanical disruption cannot be underestimated. “If it’s severe enough and widespread enough, then the whole thing just lets go,” he said. “That’s the classic sinker … the bone sinks in the hoof capsule and we get mass separation, bleeding, inflammation, and these ones rarely survive.”
However, he said, “if it’s a milder insult, then it’s amazing how quickly this basement membrane gets repopulated with basal cells as part of the initial repair process.”
The Persistent Lamellar Wedge
Indeed, the delicate architecture of the lamellae can repair in many cases, but it simply doesn’t have the organization and strength of the original tissue. “These changes are generally considered irreversible; once it happens, it’s not going back,” he said. “The big thing is we’ve lost that nice 1-meter-square of attachment and so that horse or pony is never going to have that same strength in the foot again.
Part of the repair process after acute laminitis includes “variable exuberant proliferation and expansion of the epidermal tissue,” also known as the “lamellar wedge.”
“These cells … are kind of a one-trick pony,” he said. “If they get damaged, if they get stressed, if they get unhappy, they proliferate and keratinize, and that’s what causes this lamellar wedge, which is like an epidermal scar. And this lamellar wedge has consequences for our management, because it’s generally what’s inhibiting us from returning the bone to the normal position within the hoof capsule or returning the hoof capsule to the normal position on the bone, whichever way you look at it.”
Changing the position of the coffin bone also changes the orientation of the hoof horn papillae of the coronet band, with abnormal and apparently slow growth at the dorsal/toe region in horses with chronic laminitis as a consequence.
Inflammation, ischemia (inadequate blood supply), and increased pressure between the coffin bone and the sole might all contribute to pain in laminitis cases.
As if pain from damage itself weren’t enough, nerves sometimes take over in producing pain signals even though the actual insult might be long past. “There’s definitely a component of neuropathic pain,” with laminitis he said, “There are physical and molecular changes consistent with that.”
In sum, there might be three distinct forms of laminitis, but they all result in a disorganization of tissue and mechanical changes that cause varying degrees of pain and dysfunction in horses and ponies and often vastly different outcomes in terms of survival, quality of life, and ongoing use.
“Much progress has been made in unlocking the events and processes that cause laminitis,” he said, “and these discoveries are what is leading to better preventative and management strategies for different types of laminitis. Laminitis research relies mostly on private donations for funding, so I would encourage anyone interested in helping to either contact a funding group such as the Grayson Jockey Club Research Foundation or an active researcher directly.”