Laminitis and founder are two words in the lexicon of the horse that are guaranteed to elicit a definite response, whether it is a painful memory for a horse owner, a recurring anxiety for a breeder, a shoeing dilemma for a farrier, a complex prognosis for a veterinarian, or an enigma for a researcher. Laminitis and founder have dashed horses' athletic careers on the rocks, compromised the longevity and productivity of broodmares, and even cost the horse world its most beloved celebrity, racehorse and sire Secretariat.
Despite the complexity of the disease itself and its possible longterm effects on the horse, the fact that dumbfounds owners and trainers when told they have a laminitic horse is that the veterinary community still does not know exactly what causes laminitis, or what happens in the horse's foot when the disease strikes.
"Tiny fibers hold the hoof wall to the coffin bone," practitioners patiently tell their clients outside the stall, "and when the horse has laminitis, the fibers just let go in places. If it's bad enough, the coffin bone falls away from the hoof wall. It sort of rotates, and the tip can go right through the sole of the foot if the damage is bad enough." By then, an owner's face is colorless, but the response is usually predictable, "You mean, veterinarians don't know what causes this? You can't tell me if my horse is going to be a cripple...or not?" The frustration is universal, on both sides.
A leading researcher trying to solve the laminitis mystery is Christopher Pollitt, BVSc, PhD, of the University of Queensland in Australia. Pollitt's landmark textbook, The Color Atlas of the Horse's Foot, published in 1995, established him as a world leader in the hybrid field that he calls "equine foot science," an area where farriers and veterinarians work together to medically and mechanically restore or enhance a horse's soundness. Pollitt's personal area of research is the inner workings of the foot, and he pins his hopes for a future laminitis prevention program on understanding both the normal and laminitic foot.
In the most basic terms, a laminitic horse has suffered a systemic "insult," which can be any sort of traumatic physiological event, such as retained placenta in mares, carbohydrate overload, stress, kidney or colic episodes, and so on. By whatever mechanism, the disease condition secondarily damages the bond between the hoof wall and the primary bone of the foot, known as P3 (third phalanx, distal phalanx, and coffin bone are all terms that refer to the same bone).
For years, the term for this damage was "stretching" of the two-part connective tissue called the lamella. One set, the insensitive (epidermal, or outer) lamellae, is connected to the hoof wall. The second set, the sensitive (dermal, or inner) lamellae, is connected to the bone. They link together "like a hand in a glove," according to Pollitt, and suspend the distal phalanx in an enclosing capsule shell of hoof wall, which the bone never touches.
The lamellae in a horse's foot are not dissimilar to the lamellae that attach a human fingernail or toenail to the digit. There, however, similarity ends; the horse's lamellae are part of a much more complex system, since the hoof wall to which the lamellae attach is used as a weight-bearing structure. Interestingly, horses' lamellae have tiny, secondary branches, making a tight fit; cows and sheep have only primary, or "single-arm," lamellae, although they do still suffer from a type of laminitis.
To understand how--and even if--the lamellae stretch, break, collapse, or disintegrate during laminitis, Pollitt and his co-workers at the Australian Equine Laminitis Research Unit studied 13 pairs of Standardbred horses' feet, using a scanning electron microscope and forearmed with the knowledge that German researchers had recently counted 600 lamellae in an average horse's foot.
Pollitt's Standardbreds averaged only 550 lamellae per hoof, perhaps because the Germans might have used the much larger feet of warmblood horses, which would require more lamellae for a larger circumference. An interesting anecdotal statistic from Pollitt's work is that, of the pairs of feet, no left and right feet of the same horse ever had the same lamellar count. One foot always had approximately 30 more lamellae than its paired foot.
Pollitt also studied the lamellar composition of fetal horses, and found that a fetus at six months of gestation also had 550 lamellae, but with an equal number between left and right feet.
Pollitt went on measuring the components of the inner hoof wall. He found that the greatest height of a lamella was 5 cm.; he worked on "mapping" the perimeter of the lamellae and calculated lengths at the different areas of the hoof wall (actually, the lamellae continue around the perimeter of the hoof wall and take a sharp turn at the heels, continuing as "bar lamellae," attaching the rim-like bars of the heel to the sole).
Pollitt was fascinated to find that the lamellae were lined by a thin, unbroken sheet of structural material that partitioned the dermis (inner, sensitive lamellae) from the epidermis (hoof wall, insensitive lamellae). This basement membrane is an active tissue that coordinates important biological processes between the vascular dermis and the avascular epidermal regions of the foot and organizes the cytoskeletal framework of the epidermal cells. It influences the exchange of nutrients, macromolecules, and growth-regulating factors of the ever-growing hoof wall. Since the horse's hoof withstands incredible biomechanical loads, the basement membrane, being attached to the wall, must have remarkable properties of strength and resilience, Pollitt theorized. He set out to perform a histochemical analysis of the basement membrane he had isolated.
One of Pollitt's first tests was a periodic silver methenamine (PASM) stain; it isolated the basement membrane as a fine black line under his microscope. Slides of the PASM stain show the basement membrane meandering the edges of the lamellae like an aerial view of a perimeter fence separating livestock from hazardous creek embankments. Instantly, Pollitt noticed that the secondary epidermal (insensitive hoof wall) lamellae (SEL) had rounded tips, and that the secondary dermal lamellae (sensitive inner, SDL) were tapered, beautifully illustrating the "hand in glove" analogy, but with an interesting thin black line between.
PASM is used to identify collagen components of organic material; Pollitt's PASM stain showed collagen of type IV in the basement membrane. A companion PAS (periodic acid-Schiff) test of the membrane exposed the non-collagenous carbohydrate-containing components of the basement membrane, revealing the glycoproteins laminin, fibronectin, nidogen, and amyloid P component, the sulfated entactin, and heparin sulfate proteoglycan.
The basement membrane is, therefore, a complex latticework of both collagen and glycoprotein molecules; the next step was to go deeper inside this fascinating structure, which seems to be a dynamic, constantly remodeling river of life through the connective tissue.
The transmission electron microscope (TEM) revealed more information about the basement membrane's capacity for strength and resiliency. Pollitt found that the lamellae's extensions were denser at the SEL tips, and that many anchoring fibrils and double basement membranes could be found at the SDL tips. The images revealed that the basement membrane is the actual location of the attachment between hoof and bone.
Next, Pollitt removed cytoplasm and nuclei of the hoof lamellae with a detergent/enzyme treatment, and lifted the basement membrane free of the epidermis, finding the membrane to be smooth, with only a few folds and wrinkles.
Pollitt also examined the resulting exposed SEL basal cells, finding that, after the enzyme detergent treatment, they lacked cytoplasm, cell membranes, and nuclei, revealing the relatively rigid matrix of keratinized material (non-cellular protein).
Understanding normal lamellar function and attachment was key to knowing what questions to ask about the structural failure that is the most severe result of laminitis.
Basement Membrane and Laminitis
Pollitt found a close correlation between the histological changes in the early stages of laminitis and the clinical signs. Using mid-dorsal hoof wall samples from horses undergoing laminitic distress, Pollitt again used the PASM stain, and found that the early insult of laminitis initiates a loss of collagen in the basement membrane. He noted disintegration of the basement membrane, like the knockdown of sections of a perimeter fenceline in a windstorm. Disintegration of the basement membrane and failure of the epidermal cell attachment occurred early on; the weakened basement membrane allowed a collapse of the lamellar architecture.
Scanning electron microscopy studies confirmed the basement membrane damage in the histology slides; leukocytes (white blood cells) were attracted to the damaged lamellae early in the onset of laminitis. The images showed the basement membrane to be torn and distorted. The normally smooth surface of the basement membrane was tattered, and in places, it was possible to see through to the collagen fibers.
As the laminitis "episode" begins, lamellar lesions in the basement membrane occur rapidly. Separation of the entire circumference of the inner hoof wall (a condition known as a "sinker" type of laminitis) can occur within 48 hours of ingestion of a carbohydrate overload in a test horse.
Theories involving the role of a vascular mechanism (arteriovenous anastomoses, or "AV shunts") and ischaemia (lack of oxygen delivered to the tissues) have been put forward by researchers, including Pollitt in earlier research. They identified activity in the foot's AV shunts and pondered their role in the onset of laminitis. He now feels that the vascular components of laminitis in the foot are occurring on a parallel or possibly secondary relationship to the chemical damage to the basement membrane.
Pollitt's extensive tests of the thermoregulatory function of the AV shunts indicate that a temperature change in the foot would need to be identified to isolate the vascular theory as the primary "cause" of lamellar damage. Pollitt's test horses have shown that while laminitis is developing, blood flow to the foot is at its maximum. Also, a horse which sloughs a hoof within 24 hours of the onset of laminitis would not have time for vascular devastation.
How is the Basement Membrane Affected?
The next avenue for Pollitt to explore was the possibility of an enzymatic autodegradation of the basement membrane, which he calls the "meltdown" and feels could initiate laminitis. Performing in vitro experiments with tissue-cultured (TC) hoof explants, Pollitt finds that in a "normal" medium of TC, the basement membrane and epidermis survive intact for five days. When connective tissue enzyme activator is added to the tissue-cultured medium, the basement membrane detaches from the epidermal lamellae within 36 hours.
Research on the role of endotoxemia has shown that it causes macrophages to release cytokines, which circulate in the blood of horses with severe gastrointestinal diseases and some of which can induce the production of collagenase (an enzyme that catalyzes the destruction of collagen). This could cause a dramatic change in the shape of secondary epidermal lamellae. White blood cells present at the disaster site dissolve collagen by enzymatic action and destroy the basement membrane even more; excess white blood cells form pus and cause abscesses to break out on the coronary band.
At the same time, proteinases (enzymes that break down proteins) might be produced in excess within the foot, carried from a disfunctioning colon, uterus, or lungs via the horse's vascular system. Since proteinases are already in abundant supply in the foot, a vasodilated foot would receive a large, critical overdose of these factors, compromising local enzyme inhibitor production and blood enzyme inhibitors and cause neutrophils to degranulate, resulting in liberation of collagenase IV and free radicals of oxygen.
In the course of laminitis, the basement membrane disintegrates until the primary epidermal lamellae separate from the primary dermal lamellae. The horse does not exhibit clinical signs of pain in the foot until a critical mass of the lamellae fail, and blood pressure rises. When pain becomes apparent, irreversible pathology to the lamellar anatomy already exists. Only the growth of a completely new lamellar bed from the coronary band down will ensure a sound, integral hoof wall-P3 bond. Damaged lamellae do not have the capacity to be repaired or to "reattach."
In conclusion, Pollitt's quiet work in Australia has given the world a system for evaluating laminitis and its effect on the horse's foot. Histopathological diagnosis of laminitis requires staining of the basement membrane and evaluation of its condition; Pollitt has developed a laminitis grading system based on basement membrane pathology.
Basement Membrane in Other Research
Pathology to the basement membrane, similar to that of laminitis, exists in the diagnosis of malignant cancer. Pollitt theorizes that anti-cancer drugs might be useful one day in preventing or "blocking" damage to the basement membrane of the horse's foot. The destructive enzyme collagenase has recently been shown to correlate strongly with the degree of malignancy and invasiveness of lethal human tumors such as malignant melanoma (skin cancer), breast cancer, and colon cancer. In cancer, however, the enzyme also destroys normal tissue, facilitating the spread of the cancer throughout the body.
Working with pharmacologists at the University of Queensland, Pollitt is studying the possible use of a human drug that blocks the enzyme in cancer patients to see if it might be effective in preventing laminitis. Possible applications for horses might include identification of "at-risk" horses which might develop laminitis secondary to another condition. Pollitt believes that a patch containing this human drug placed above the coronet could be effective, or possibly an injection or cream applied to the coronet.
Pollitt warns that these types of applications would need to be administered early in the developmental process of laminitis, perhaps during episodes of colic, diarrhea, or uterine infection. Once laminitis has affected the foot, such treatments would be less effective.
While all of Pollitt's speculations are based on observation and evaluation of horses in laboratory conditions in a sophisticated university veterinary hospital, the implications for horses in the "real world" are obvious. Pollitt cautions against unbridled optimism for a "cure" for laminitis in the near future. Until we understand more about the difference between normal and laminitic hoof wall attachments, prognosis and treatment will be as challenging as ever.
The best advice Pollitt said he could give practitioners working on acute laminitis cases was blocking the inflammation mechanism aggressively and early, and he suggested the use of massive fluid therapy, non-steroidal anti-inflammatory drugs, hyperimmune plasma, and free-radical scavengers such as dimethyl sulfoxide (DMSO).
Therapy aids recommended by Pollitt include a frog-support heart bar system and packing the foot in ice. Use of any frog support device should be preceded by careful trimming of the frog to find its true point, and affixing the frog support accordingly to a point just behind the point of the frog and leaving the perimeter of the frog exposed. Recessed or atrophied frogs may required a shim on the heart bar to make contact the entire length of the tongue. When laminitis has actually occurred, a radiographic study of the foot is essential to achieve correct positioning of the heart bar shoe.
In conclusion, Pollitt warns that laminitis is every bit the equal to colic for classification as a medical emergency in the horse.
About the Author
Fran Jurga is the publisher of Hoofcare & Lameness, The Journal of Equine Foot Science, based in Gloucester, Mass., and Hoofcare Online, an electronic newsletter accessible at www.hoofcare.com. Her work also includes promoting lameness-related research and information for practical use by farriers, veterinarians, and horse owners. Jurga authored Understanding The Equine Foot, published by Eclipse Press and available at www.exclusivelyequine.com or by calling 800/582-5604.
POLL: University Equine Hospitals