A review of recent advances and current hypotheses on the pathogenesis of acute laminitis

Abstract

SummaryWith the increasing number of studies being published on the different experimental models used to induce and study acute laminitis, the pathophysiological events associated with these various models (i.e. starch overload, oligofructose overload, black walnut extract and hyperinsulinaemia) can be compared more realistically. Within this review, the mechanisms for metabolic vs. inflammatory laminitis are discussed, and the question of how pasture laminitis may fit into any of the proposed mechanisms is addressed.

A prospective cohort study of digital cushion and corium thickness. Part 2: Does thinning of the digital cushion and corium lead to lameness and claw horn disruption lesions?

“…Historically, subacute ruminal acidosis has also been thought to weaken the suspensory apparatus through laminitis, yet this theory has been disregarded by many researchers as the primary cause of most CHDL (Mulling and Greenough, 2006;Vermunt, 2007;Bicalho and Oikonomou, 2013). In equine lameness, recent advances in laminitis research have identified multiple pathogenic mechanisms behind the disease process (Katz and Bailey, 2012), and in one mechanism hyperinsulinemia affects the integrity of the suspensory apparatus in vivo, causing noninflammatory changes in and distension of laminar morphology; the term laminitis is even being replaced with laminopathy to reflect noninflammatory changes within the laminae early in the disease process. This occurs in the absence of gastrointestinal involvement, systemic illness, or inflammatory infiltration into laminae (Asplin et al, 2007), and carbohydrate overload appears not to be implicated in all equine laminitis mechanisms (de Laat et al, 2010;de Laat et al, 2012;Selim et al, 2015).…”

Insulin resistance in the horse: a review

“…It was thought that chronic hyperinsulinemia-related glucotoxicity, hypoperfusion, elevated release of reactive oxygen species or haemodynamic changes lead finally to MMP activation and cause insulin-induced laminitis (De Laat et al 2011;Katz & Bailey 2012). The research on insulin-induced laminitis proved that during the developmental and acute stage of laminitis, the expression of the genes coding for MMP-2 was not triggered.…”

“…The dynamic balance between the degradation and synthesis of collagen in the extracellular matrix in physiological conditions is sustained by the cooperation of matrix metalloproteinases (MMP) and their tissue inhibitors (tissue inhibitors of metalloproteinases). The unregulated activity of MMP, particularly MMP-2 and MMP-9, which are responsible for type IV collagen degradation, may lead to hoof tissue damage -the destruction of basement membrane -and consequently, to distal phalangeal attachment apparatus damage (Orsini et al 2009;Huntington et al 2010;De Laat et al 2011;Katz & Bailey 2012). The production and later activation of MMPs are observed during local or systemic inflammatory states, ischaemia, or as a result of bacterial toxins' presence.…”

Histologic and inflammatory lamellar changes in horses with oligofructose-induced laminitis treated with a CXCR1/2 antagonist

“…A strong correlation between microstructural damage and the severity of clinical signs was established (Pollitt 1996). Dermal-epidermal junction collapse is common in laminitis of numerous etiologies, but the initial event triggering the structural failure remains poorly understood (Katz & Bailey 2012). Multiple studies propose resident leukocyte activation in the lamella and leukocytic infiltration from the bloodstream, associated with systemic inflammatory response syndrome (SIRS), as probable mechanisms that initiate structural failure (Black et al 2006, Hurley et al 2006, Loftus et al 2007, Stewart et al 2009, Faleiros et al 2009b, Faleiros et al 2011a.…”