Endocrinopathic laminitis Flashcards
What three things occur during laminitis?
- elongation of secondary epidermal laminae- primarily due to stretching small increase in cell proliferation
- increased mitosis
- increased apoptosis
What is the link between IGF-1 and laminitis?
- lamellar epithelial cells have IGF-1 receptors
- IGF-1 receptors are stimulated by high concentrations of insulin
- therefore hyperinsulinaemia may abnormally stimulate lamellar epithelial growth
- elongate SEL’s therefore weakening lamellar cohesion
What stimulates corticotroph secretion?
It is stimulated by corticotroph releasing factor from the hypothalamus
What controls the secretion of melanotrophs?
- melanotrophs secrete autonomously
- controlled by inhibitory dopaminergic neurones from the hypothalamus
What are the clinical features of PPID
- associated with aging
- associated with laminitis
- excessive drinking and urination
- muscle catabolism
What three conditions are associated with insulin dysregulation?
- Equine metabolic syndrome
- PPID/ Equine Cushings
- Exogenous glucocorticoid administration
What three risk factors relate to endocrinopathic laminitis?
- Obesity
- Cardiovascular changes
- Adipose dysregulation
What would you notice in the tests for Equine Metabolic syndrome?
- High Insulin
- High Triglyceride
- High leptin in adipokines
- Adiponectin is low
What peptide do both Corticotrophs and Melanotrophs synthesise?
241-amino-acid peptide propiolipomelanocortin/ POMC
What three ways is POMC cleaved?
◦ Prohormone convertase 1/3 (PC 1/3)
◦ Prohormone convertase 2 (PC2)
◦ Carboxypeptidase E (CPE)
What is corticotroph secretion stimulated by?
Cortciotroph Releasing factor from the hypothalamus and therefore carried to the pituitary via the blood
How are melanotrophs secreted?
they secrete autonomously and are controlled by inhibitory dopaminergic neurones from the hypothalamus
What is the primary causal event in development of PPID?
Oxidative damage to the inhibitory dopaminergic neurones
What are the Clinical Defining features of PPID?
- Aging
- Susceptability to laminitis
- Abnormal hair growth
- excessive drinking/ urination
- susceptability to infections
- muscle catabolism
What are the metabolic defining features of PPID?
- Increased production of POMC-derived peptides
- insulin dysregulation
- insulin resistance
- hyperinsulinaemia
- hypertriglycerideamia
Name three POMC peptides that would be high on a PPID lab test
- ACTH
- a-MSH
- B-endorphin
What happens between insulin and the MAP kinase pathway?
Insulin resistance affects the PI3 kinase pathway, so insulin overstimulates the MAP kinase pathway therefore cellular growth/ differentiation occurs
What are the equine metabolic syndrome risk factors for endocrinopathic laminitis?
- Insulin dysregulation
- Obesity
- Cardiovascular changes
- Adipose dysregulation
What are the clinical features of equine metabolci syndrome?
- Susceptability to laminitis
- Obesity/ Generalised and/or regional
What are the metabolci features of equine metabolic syndrome?
- Hyperinsulinaemia
- insulin resiatnce
- hypertriglyceridaemia
What most likely causes the metabolic features of Equine metabolic syndrome?
- Genetic factors
- obesity
- inactivity
- diet high in non-structural carbohydrates
What are the predominant cell types in Equine anterior pituitary anatomy?
- Corticotrophs
- Melanotropes
they both synthesise propiolipomelanocortin POMC
How are melanotrophs secreted?
They are secreted autonomously and are controlled by inhibitory dopaminergic neurones from the hypothalamus
What is the primary causal event in development of PPID?
oxidative damage to inhibitory dopaminergic neurones
- releases the pars intermedia from inhibition
* causes increased secretion
What are the grades of PPID?
- normal- normal
- mild hypertrophy- normal age effects
- marked hypertrophy- mild PPID
- microadenoma- moderate PPID
- macroadenoma- marked PPID
