Laminitis

Question 1

Define Endocrinopathic Laminitis?

Answer 1

Laminitis from hormonal influences rather than pro-inflammatory or intestinal conditions

Question 2

What are the two main risk factors for endocrinopathic laminitis?

Answer 2

1. Glucocorticoid associated

• Iatrogenic corticosteroids administration (incase horse on long courses of corticosteroids that can cause laminitis)
• PPID

2. Insulin resistance associated

• EMS

Question 3

Discuss Glucocorticoid-associated laminitis?

Answer 3

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

Question 4

What factors trigger endocrinopathic laminits?

Answer 4

Insulin

Endotoxaemia

Question 5

What factors predispose to endocrinopathic laminitis?

Answer 5

Obesity

Breed

Insulin dysregulation

PPID

Question 6

What factors exacerbate endocrinopathic laminitis?

Answer 6

Progression of obesity

Diet rich in starches and sugars

Progression of PPID

Question 7

What is the evidence of the role of hyperinsulinaemia in endocrinopathic laminitis?

Answer 7

Hyperinsulinaemia raises the risk of pasture-associated laminitis in ponies

Laminitis has been experimentally induced by infusing insulin intravenously (hyperinsulinaemia)

Question 8

Discuss what the consequences of hyperinsulinaemia are on vasodilation?

Answer 8

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

Question 9

How does insulin effect vascular dynamics?

Answer 9

Question 10

How are vascular dynamics effected by hyperinsulinaemia?

Answer 10

Question 11

What happens to vascular dynamics with insulin resistance?

Answer 11

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

Question 12

What does Adiponectin do?

Answer 12

regulates glucose metabolism and fatty acid oxidation and activity decreases with IR

Question 13

What do the inflammatory mediaters released from adipose tissue do?

Answer 13

Question 14

Describe the progression of obesity to hyperinsulinamia and endocrinopathic laminitis?

Answer 14

Question 15

Describe obesity EMS progression?

Answer 15

Question 16

How does carbohydrate overload exacerbate endocrinopathic laminitis?

Answer 16

• Excessive, sudden carbohydrate consumption triggers a systemic inflammatory response
• Elevated plasma endotoxin concentrations in 85% of horses after carbohydrate overload to induce laminitis
• SIRS detected in horses after oligofructose administered to induce laminitis

Question 18

Matrix metalloproteinases (MMP) are involved in lamellar tissue physiological matrix turn-over. MMP activity is increased by?

Answer 18

• Endotoxaemia
• Hypoperfusion (vasoconstriction)
• Leukocyte activation/margination in laminar blood vessels

Greater amount of MMP in fore than hind feet why it happens more in front feet.

1. Degradation of the extracellular matrix
2. Matrix cannot maintain shape or tensile strength
3. Laminae stretch and tear, causing separation at dermal/epidermal junction

Question 19

Draw a flow diagram of endocrinopathic laminitis and it’s theorised causes?

Answer 19

Question 20

What are the final steps to laminitis?

Answer 20

Question 21

How do you make a diagnosis of endocrinopathic laminitis?

Answer 21

1. History

Carbohydrate overload

PPID, EMS

2.Physical exam

PPID vs EMS

3. Orthopaedic exam + Radiography

OBEL grading

4. Endocrine testing

PPID

IR

Question 22

How can endocrinopathic laminitis be managed?

Answer 22

Predisposition

• Manage/treat obesity and insulin resistance
• Treat PPID
• Consistent farrier care

Exacerbation

• Regulate starch/sugar intake and total calories
• Monitor for PPID

Triggers

• Avoid sudden changes in feeding practices
• Gradual introduction to new pastures
• Treat endotoxemia and systemic inflammation

Question 23

What should you do to treat a horse during acute laminitis?

Answer 23

• Treat underlying condition (PPID, EMS)
• Absolute box rest until sound and beyond
  
  • Deep (1 foot), soft bedding
• NSAIDs
  
  • Flunixin
  • Phenylbutazone
• Cryotherapy
  
  • Maintain limb temperature to 4°C (8°C acceptable) for 72h distally form carpus/knee
  • Start as soon as possible, ideally before onset of endotoxaemia
• ACUTE LAMINITIS ONLY:
  
  • Lowers metabolic rate of lamellar tissue
  • Reduces impact of vasoconstriction
  • Decreased cytokine production
  • Reduce MMP activity (enzymes cant work at lower temp)
• Remedial farriery
  
  • Every 6 weeks
  • Consider farrier with extensive experience with laminitis

Question 24

What is the long term management of endocrinopathic laminitis?

Answer 24

Goals

Manage obesity

Stop sugars in the grass from exacerbating hyperinsulinemia

Strategies

Short turnout (< 1 hour)

Grazing muzzles

Strip grazing (electric fence)