Laminitis Flashcards
Define Endocrinopathic Laminitis?
Laminitis from hormonal influences rather than pro-inflammatory or intestinal conditions
What are the two main risk factors for endocrinopathic laminitis?
1. Glucocorticoid associated
- Iatrogenic corticosteroids administration (incase horse on long courses of corticosteroids that can cause laminitis)
- PPID
2. Insulin resistance associated
- EMS
Discuss Glucocorticoid-associated laminitis?
Maybe attributed to corticosteroid induced IR
IATROGENIC
Triamcinolone (used for treatment of inflam condition orthopaedic system)
- Hyperglycaemia for 3-6 days after 1 dose
Dexamethasone (3 weeks at 0.08mg/kg EOD)
- Increase 10x basal insulin and IR
Relationship between corticosteroids and laminitis is historical and difficult to conclusively demonstrate
PPID
Induces hyperadrenocorticism
Increased cortisol production resulting in IR
Horses with very high insulin are more likely to develop laminitis and survive <2 years than those with moderate elevations or normal insulin
What factors trigger endocrinopathic laminits?
Insulin
Endotoxaemia
What factors predispose to endocrinopathic laminitis?
Obesity
Breed
Insulin dysregulation
PPID
What factors exacerbate endocrinopathic laminitis?
Progression of obesity
Diet rich in starches and sugars
Progression of PPID
What is the evidence of the role of hyperinsulinaemia in endocrinopathic laminitis?
Hyperinsulinaemia raises the risk of pasture-associated laminitis in ponies
Laminitis has been experimentally induced by infusing insulin intravenously (hyperinsulinaemia)
Discuss what the consequences of hyperinsulinaemia are on vasodilation?
Increases perfusion to the lamellar tissue
Increase glucose delivery to hoof tissues
- Glucotoxicity
Advanced glycation end products
Important role in diabetic angiopathy in humans
Might affect lamellar blood vessels and result in laminitis
How does insulin effect vascular dynamics?
How are vascular dynamics effected by hyperinsulinaemia?
What happens to vascular dynamics with insulin resistance?
Slow vasodilation occurs in response to insulin through increased synthesis of nitric oxide (NO) by endothelial cells (Muniyappa et al. 2007). However, insulin also promotes vasoconstriction by stimulating endothelin-1 (ET-1) synthesis and activating the sympathetic nervous system. Under normal conditions, the opposing actions of NO (vasodilation) and ET-1 (vasoconstriction) are in balance because both arms of the insulin signalling cascade are active; activation of the insulin receptor therefore stimulates 2 different signalling pathways within the vascular endothelial cell. Nitric oxide is secreted when the phosphatidylinositol 3-kinase (PI3K) pathway is activated, whereas activation of the mitogen-activated protein kinase (MAPK) pathway leads to release of ET-1 (Muniyappa et al. 2008). Both the vasodilatory effects of insulin and insulin-dependent stimulation of glucose uptake are mediated by PI3K and this pathway becomes disrupted when IR develops. Consequently, vasoconstriction is promoted in insulin resistant animals because only the MAPK pathway remains fully functional
Also low adiponectin is associated with IR mediated inhibition of vasodilation
What does Adiponectin do?
regulates glucose metabolism and fatty acid oxidation and activity decreases with IR
What do the inflammatory mediaters released from adipose tissue do?
Describe the progression of obesity to hyperinsulinamia and endocrinopathic laminitis?
Describe obesity EMS progression?