The Pathogenesis of Equine Pasture-Associated Laminitis

Final Common Pathway to Digital Failure

The link between the gastrointestinal tract and the foot remains unclear. The final common pathway to digit failure and breakdown of the bond between the dermal and epidermal laminae seems to within the dermis and epidermis involve activation of matrix metalloproteinase (MMP) enzymes. These enzymes allow the sensitive and insensitive laminae to slide over each other during normal equine hoof growth. They may be produced by keratinocytes, fibroblasts, endothelial cells present within the dermis and epidermis or produced by migrating neutrophils. Triggering mechanisms for digital failure might include increased enzyme expression, downregulation of their natural inhibitors and release of MMP activators. There are three theories regarding how excessive activity of MMPs is triggered and how it is linked to consumption of carbohydrate, namely 1) bacteria-derived exotoxins that activate MMPs; 2) gutderived products that trigger dermal inflammation leading to MMP activation; 3) gut-derived products that trigger vascular disturbances leading to vasoconstriction and ischaemia-reperfusion injury, part of which involves MMP activation. There is evidence to support and refute all three theories.

Bacterial Exotoxins

It is suggested that there is a period of increased digital perfusion that exposes the laminae to concentrations of blood borne factors sufficient to trigger excessive MMP activity. The exact nature of these blood borne factors remains unclear, but a bacterial toxin produced following rapid proliferation of Streptococcal species within the hindgut secondary to excess carbohydrate consumption is implicated.

Dermal inflammation

It is suggested that there is a systemic inflammtory syndrome resulting from events within the gut, possibly through the release of factors such as endotoxin and resultant upregulation of inflammatory cytokines. Activation of MMPs as part of the inflammatory response could contribute to the pathophysiology of laminitis. [...]