Equine Endocrinopathies Flashcards
insulin regulation obesity and the metabolic syndrome (1), endocrinopathic laminitis (2),
How is insulin synthesised
initially preproinsulin from beta-cells
signal peptide is removed to leave proinsulin
C-peptide is removed to leave insulin (made up of A and B peptides)
What does insulin do ? ( 3x actions)
- glucose “gatekeeper”
- inspires liver, fat and resting muscle (“insulin sensitive tissues”) to take up glucose - metabolic effects
- stimulates glycogen synthesis
- stimulates FA uptake and triglyceride synthesis
- stimulates cellular AA uptake
( in turn, inhibits glycogenolysis, gluconeogenesis, lipolysis and proteolysis) - other effects
- increases K+ uptake
- increases Na+ resorption in the kidney
- stimulates gastric acid secretion
- vascular effects
Define obesity
excessive adiposity to a degree that results in a negative health effect
How do we measure obesity ?
in the lab with tests or in practice by weighing body mass and calculating the BMI (weight/height^2).
also BCS and cresty neck score in horses
Define bioimpedance
a weak electric current flows through the body and the voltage is measured to calculate impedance (resistance and reactance)
this works because lean tissue is a good conductor where fat is a poor conductor
Define hydrometry
give a set dose of deuterium oxide (D2O) and measure the saliva
total body water = dose / concentration in saliva
body fat % = 100-(%TBW/0.732)
How can insulin resistance be a survival advantage to individuals in a harsh/variable environment ?
conservation of glucose for vital organs (CNS, heart, etc…)
mobilisation of energy stores
Define laminitis
elongation of secondary epidermal lamellae, primarily due to stretching but also partially due to an increase in cell proliferation.
How is insulin involved in laminitis ?
insulin activates 2 metabolic pathways ..
1. PI3 kinase (metabolic and vasodilation)
2. MAP kinase (growth and vasoconstriction)
What happens in the event of insulin resistance (laminitis wise)
PI3 kinase pathway is affected, and the compensatory mechanism overstimulates the MAP kinase pathway.
it may lead to dysregulation of lamellar epithelial cell growth, but these cells do not have insulin receptors, so it cannot be the main cause of laminitis.
How are IGF-1 and insulin related, and how does this affect laminitis ?
IGF-1 is synthesised by the liver and mediates GH effects, stimulating cell growth and regeneration.
lamellar epithelial cells do not have insulin receptors, but they do have IGF-1 receptors, which can be stimulated by high levels of insulin (-> proliferation of lamellar epithelial cells)
Define equine metabolic syndrome
a collection of risk factors for endocrinopathic laminitis, including insulin dysregulation, obesity CV changes and adipose dysregulation.
What are the CS of EMS
susceptibility to laminitis
obesity (general and/or regional)
What are the metabolic features of EMS ?
insulin dysregulation
obesity, inactivity and diet
How do you diagnose endocrinopathic laminitis ?
insulin dysregulation can be tested for in blood concentrations (especially postprandially). You may also see high triglyceride levels
Define PPID
pituitary pars intermedia dysfunction
What is the primary causal event of PPID ?
oxidative damage to inhibitory dopaminergic neurones, which releases the pars intermedia from inhibition and leads to excessive GH and other hormone release
Describe PPID histopathologic grading system
Grade 1 = normal
Grade 2 = mild hypertrophy / hyperplasia, may be normal if older animal
Grade 3 = marked hypertrophy / hyperplasia (mild PPID?)
Grade 4 = ^ + microadenoma (moderate PPID)
Grade 5 = ^ + macroadenoma (marked PPID)
What are the CS of PPID
susceptibility to laminitis
abnormal hair growth
excessive drinking and urination
susceptibility to infections
muscle catabolism
(we don’t know what causes these!)
How do we diagnose PPID ?
blood test :
high POMC-derived peptides especially ACTH
high insulin with normal glucose
common also to inject insulin and measure the effect it has on glucose levels
What are the 2 major lipoproteins ?
chylomicrons (large, rich in triglyceride, transport exogenous lipid into tissues, dietary)
VLDLs (synthesised by the liver, 2nd largest, 2nd richest, transport endogenous lipid to tissues, adipose)
What happens during fasting to lipid metabolism ?
- triglycerides in fat stores are broken down into glycerol and 3 NEFAs, which are released into the bloodstream
- liver takes up NEFAs from the blood and uses them for energy
OR 2. NEFA converted into triglycerides, ATP and ketones - triglycerides incorporated into VLDL, which is secreted into plasma
- tissues extract NEFAs from the VLDLs
- all remnants return to the liver
Define hyperlipaemia in horses and give CS and causes
plasma TG >5mmol/L
CS :
- sick
- inappetant
- plasma is opaque
causes :
- pregnancy/lactation/poor diet
- secondary following disease
- insulin resistance
Define hypertriglyceridaemia
plasma TG level greater than normal, but plasma is normal and the animal is not sick or inappetant
