The horse shifts her weight back onto her hindquarters. Her forefeet, curved and creasing into a gross distortion of the polished, tough hoof capsules of her previous life, practically paddle the air to avoid that moment of pain when they must make contact with the earth and bear weight. Everything that was once so easy is now impossibly hard. The mare’s jaw is perpetually clamped, her eyes ever narrowed and her expression withdrawn, from the effort of managing her life now that pain is her master.
Founder, the ultimate and awful outcome of uncontrolled laminitis, brings this picture of misery to you. At some point, possibly years before, a catastrophic event occurred within the mare’s forefeet. It was of such magnitude that it dissolved the fundamental union of sensitive and insensitive laminae upon which equine mobility is based. Throughout the mare’s lifetime, the hoof wall had grown and adapted to its workload.
Then the catastrophic occurred, and many of the sensitive laminae, particularly those down the front of the hoof, let go of their attachments to the horny hoof wall. And that was that. Without medical and mechanical intervention, the mare would shuffle in pain for the rest of her days. It might have been worse: All the laminae in the forefeet could have let loose to drop her coffin bone through the sole, or all four feet could have failed her instead of just the two.
What, exactly, is the catastrophic event responsible for all this suffering? If only we knew for sure. For all the research and clinical efforts expended on protecting horses from the ravages of this cruel condition, the origin and development of laminitis continue to be more speculation than certainty.
Yes, laminitis means “inflammation of the laminae”; yes, oxygen deprivation in the foot tissues is what produces such pain and the resulting gait abnormalities; yes, mechanical forces sunder the weakened hoof connections. By medicating and managing laminitic horses to control these factors, we’re able to halt and sometimes reverse the destruction before chronic founder occurs.
Yet being able to identify and counteract the consequences of laminitis is not the same as understanding the progress of the disease from its earliest cause(s) through the “cascade” of events occurring within the hoof. The destructive process is already far advanced–as much as 48 hours in the making–before the horse shows obvious lameness.
Only recently has scientific technology allowed researchers to venture into the borderland between living and dead tissue to discover how laminitis undermines the hoof foundation. Among the most active explorers of the “silent” period at the start of the laminitic process is Christopher Pollitt, BVCs, PhD, of the University of Queensland, Australia. In 1994, Pollitt pinpointed the site of the critical breakdown in the lamellar union. Since then, he has delved further into the chemistry and metabolism of the afflicted digit to discover what appear to be key triggering factors in the development and progress of laminitis.
A Common Cause
How can so many different conditions–including overeating of grain and grass, retained placenta, corticosteroid reaction and excess fat circulating in the blood–end up having the same structural effect on horses’ feet, of all places? It must be a circulatory cause, the conventional wisdom has declared for years, with either constricted vessels locking out the essential flow, or sluggish circulation allowing blood to pool in the feet. Or perhaps it’s tiny blood clots blocking the small capillaries or maybe a suffocating flood of inflammatory fluids choking the tissues within the unexpandable hoof wall. One way or the other, the circulatory theory goes, oxygen deprivation has started the destructive events.
Pollitt’s more recent studies point to deprivation of a different kind: The hoof tissues fail because they can’t utilize glucose, the body’s carbohydrate-derived fuel. This probable common cause is supported by laboratory tests in which samples of normal hoof were nourished in a variety of media, then tested to see how the bonds between sensitive and insensitive laminae were affected. In every case, the hoof material that “fed” on a mix containing glucose remained firmly together, while samples maintained in physiologic saline–an analog of the fundamental body fluid-pulled apart within 36 hours of immersion.
Tissue behavior in laboratory dishes may not be an exact duplicate of what goes on in living horse bodies, but Pollitt believes the metabolic disruption accompanying acute medical conditions supports glucose unavailability as the common cause in laminitis cases. Major gut shutdowns, severe diarrhea, uterine sepsis and other such life-threatening conditions put the body’s metabolism in a code-red state intended to muster and direct healing forces to the endangered system. One mechanism is to cut back on glucose availability to the outlying tissues (and there’s nothing more outlying on horses than their feet) so the injured organs can be fully supplied with energy for recovery and repair.
Hormones, including insulin, glucagons, cortisol and adrenaline, orchestrate the complex manufacture and distribution plans for glucose and other nutrients. As Pollitt sees it, the reactions of laboratory samples suggest that hoof tissue does rely on glucose for essential nourishment and that rapid withdrawal of local glucose supplies during major body-wide upsets starts the cascade of destructive events in the laminae.
Hoof tissue is not solely reliant on glucose for its variability. The tissue samples supplied with glucose really sucked down that energy source for the first two days in the dish, but the longer they remained in the “soup,” the less glucose they consumed and the more they derived their energy from other ingredients–probably the amino acids in the mix.
Pollitt observes that glucose deprivation of the laboratory samples caused lamellar separation within 36 hours, which corresponds to the usual real-life “incubation” period of 24 to 56 hours between the triggering event and the first signs of laminitic lameness. Because the laboratory samples did adapt to a different energy source, it appears that living horses also probably accommodate to shifts in glucose availability that happen more gradually than the code-red reactions to grain overloads and other such immediate threats to metabolic stability.
Pollitt’s landmark research in 1994 identified the site of lamellar failure as the basement membrane that covers the thin, pleated soft tissues that join the coffin bone to the hoof. This exceedingly fine membrane underlies every kind of surface and gland tissue in the body, including the skin, the intestinal lining, the uterine endometrium and the hoof’s sensitive laminae. It acts rather like a placenta, conveying nourishment to the basal cells that produce and maintain the surface layer of tissue. Because nerves do not serve the basement membrane, the membrane’s failure goes “unreported,” and only subsequent tissue damage in nearby nerve-served areas will raise a pained cry.
In the ordinary course of epidermal injury, skin layers may separate, but the essential connection of the deepest (“basal”) cell layer remains. When you get a blister, for instance, friction destroys the connection between the surface cells and the basal cells, and the space fills with fluid. You also are conscious of the tissue loss because of that nagging burning pain. But because the basal cells and the basement membrane are still glued together and functioning, healing and regrowth begin rapidly and end with a fully attached new surface layer.
In laminitis, patches of basement membrane detach entirely from the basal cells, and before long, the sensitive laminae, attached by these no-longer-nourished basal cells, begin to deform and let go of their corresponding insensitive laminae.
Pollitt continued his investigation of the separation process by staining samples of lamellar tissue, a process that reveals under microscopic examination whether the cellular structure is normal or if the tissue even remains at all. In samples of laminitic hoof harvested 48 hours after carbohydrate overload, the structural failure begins with areas of basement membrane coming “unzipped” from the basal layer and forming loose strands in the connective tissue adjoining the laminae. As the condition progresses, the basement membrane deteriorates further and finally disappears, leaving those lamellar areas–most often down the front of the hoof–with no access to healing materials.
Pollitt hypothesizes that the signal to separate is generated within the basal layer, because the seemingly healthy basement membrane remains attached for the moment to the corium between it and the coffin bone. The basal layer, too, peels off as a single viable layer–until the loss of nourishment takes its toll. If the chemical instrument of dissolution were coming in via the bloodstream, the basement membrane would be likely to feel the ill effect first. Instead, signals for dissolving the specific adhesion molecules fastening the two layers together must come from the local area. Colic, diarrhea, asthma and autoimmune diseases of the skin and other epithelial tissues can produce the same widespread separation and sloughing of superficial tissue.
The Wrecking Crew
Continuous orderly sloughing of epidermal tissue is a normal event. In fact, good health depends on this key function for growth and adaptation. Inside and out, all body surfaces are continually losing and replacing dead cells; reproduction depends on the ability of the uterus to shed its lining and clear out the placenta after a birth.
The same basic biochemical action is responsible for both the normal physiological processes and the pathologies such as laminitis. One of the agents of this necessary process are the matrix metalloprotenases (MMPs), substances found throughout body tissues that, when activated by other substances, destroy the protein matrix that serves as cellular scaffolding to give tissues their appropriate shapes. As their scientific name indicates, these chemicals contain metals, and the zinc-bearing variety tears down matrix so it can be replaced during growth and remodeling of various body parts. It also has been identified as one of the agents used by malignant tumors to invade and replace adjacent healthy tissue.
In testing the role of MMPs in the degradation of lamellar attachments, Pollitt subjected nonlaminitic hoof samples and samples from acutely laminitic horses’ hooves to a variety of laboratory tests. The laminitic samples showed a dramatic increase in MMPs within 48 hours of carbohydrate overload. Interestingly, the forefeet samples of these laminitic horses contained a greater excess of MMPs compared to their hind-feet samples, which, Pollitt suggests, may explain why laminitis is considerably more common in front than in back. Even more intriguing is the possibility that the slow-down in glucose-utilization can be an activating switch for the MMP wrecking crew to break down the lamellar bonds.
So how does circulation play in this scheme of structural collapse? Very importantly, but as Pollitt interprets the circulatory role at the onset of laminitis, it’s not at all a matter of insufficiency. Starting at zero hour with horses experiencing carbohydrate overload, Pollitt monitored hoof temperature as a gauge of the amount of blood flow entering the hoof. The horses were stabled in consistently cool (50-degree Fahrenheit) surroundings to ensure that, at the start their hooves would be uniformly cool and that an temperature changes would be the result of the amount of blood flow into the foot. Many other vital signs were monitored throughout the 48-hour observation period as well.
Circulation to the equine digit involves a complex dual system in which the capillary network, as controlled by local need, slowly suffuses the laminae with nutrients and oxygen. The fast arterial system for controlling the foot’s surface temperature uses a shunting system that can U-turn the blood at the lamellar level when “ordered” by the temperature-regulating center of the brain. Both blockage of the capillaries and shunting of blood away from the laminae have been proposed as characteristic of the laminitic state, but those models have been based on horses who have already passed the “silent” stage and begun showing typical clinical signs of laminitis.
In Pollitt’s early-onset studies, the six horses who developed laminitis experienced a marked increase in blood flow after the carbohydrate overload, as indicated by a significant increase in hoof temperature. Nonlaminitic horses did not experience increased hoof temperature even though they shared all the other physical effects of carbohydrate overdosing. In the earliest stages, then, the circulatory role appears to be one of flooding the laminae with blood via dilated vessels and supplying all the wrong blood-borne factors at the time when they are most vulnerable, triggering lamellar separation.
Later, after the first 48 hours and when the cascade of destruction is well under way, inflammatory fluids build, lamellar capillaries are destroyed and probably causes the oxygen-starved tissues to cry out in pain. But from the onset of laminitis through the first silent hours, the trend is for more blood to flow into the foot, and this is a situation where more is not at all better. Among Pollitt’s experimental horses, the ones who escaped laminitis were the ones whose digital circulation remained constricted, as expressed in continuously cool hoof temperatures, to block out the toxic brew.
Laminitis is certainly better understood today than it was at the beginning of this decade, but it’s hardly a solved puzzle. Yet Pollitt’s recent research provides hopeful indications for possible testing and early treatment to stop laminitis before the lamellar bonds break:
- Preventive strategies may be possible based on manipulating the metabolic factors associated with glucose utilization.
- Hoof temperature might serve as a reliable indicator of impending laminitis.
- An MMP inhibitor called Batimastat that proved effective experimentally may halt lamellar separation.
- Management of the circulation to restrict blood flow to the digit immediately following a potential triggering event could protect the laminae.
- For all the horses stricken with the misery of lamellar failure, modern technology is finally allowing researchers to disclose the early “quiet” causes of a complex condition with a terribly obvious outcome.
This article originally appeared in the October 1999 issue of EQUUS magazine.