Structure and function of adrenal gland and pathophysiology of HAC Flashcards
Label the adrenal glands and associated structures
Describe the synthesis of steroid hormones
Begins with cholesterol
Cholesterol converted into pregnenolone by P-450 side-chain cleavage enzyme
Pregnenolone converted into different corticoids according to zone of adrenal cortex
Describe the control of glucocorticoid release
CRH from hypothalamus down axons to portal capillary bed
CRH causes corticotrophin cells in ant. pit to make and release ACTH
ACTH travels in circulation to adrenal glands to stimulate synthesis of glucocorticoids
How is ACTH formed?
Synthesised from POMC (pro-opiomelanocortin)
POMC undergoes series of post translation modifications before it is cleaves into various polypeptides
Describe the physiology of of glucocorticoids
Travel in blood bound to plasma proteins
Bind to specific cell membrane or cytosolic receptors at their target
Receptor-steroid complex is transported to nucleus => altered gene expression
What are the actions of glucocorticoids?
‘Stress’ hormone:
- stimulates gluconeogenesis
- stimulates glycogenolysis
- Causes proteolysis
- Promotes lipolysis
- Cortisol in chronic stress - increase in blood glucose
What is the action of glucocorticoids on fat?
mobilisation from peripheral stores
What is the action of glucocorticoids in muscle?
catabolism
What is the action of glucocorticoids in the liver?
gluconeogenesis
antagonise insuline
What is the action of glucocorticoids on the kidney?
increased GFR
block ADH action
What is action of glucocorticoids on the skin?
Follicular atrophy
Sebaceous gland atrophy
Break down collagen
=> thinner skin
What is the action of glucocorticoids on bone?
Reduce calcium levels
Osteopaenia (Reduced bone density)
What is the action of glucocorticoids on the brain?
hunger
thirst
What is the action of glucocorticoids on the immune system
Release neutrophils from marginated pool
Down regulates immune responses
Describe the control of mineralocorticoid release
Main stimulus for aldosterone release = low BP (RAAS)
High serum potassium stimulates release
ACTH has minor role
What is the function of aldosterone
Regulation of BP
Acts on distal tubule and collecting duct to increase reabsorption of Na, Cl and water
Stimulates the secretion of K+ into tubular lumen
What is the function of androgens
Stimulate or control the development and maintenance of male characteristics by binding to androgen receptors
Precursors for all oestrogens
What is HAC?
Hyperadrenocorticism/Cushing’s Disease
Excessive production of steroid hormones, especially glucocorticoids, from the adrenal cortex
What is hypoadrenocorticism?
Addison’s disease
under secretion of glucocorticoids and mineralocorticoids from the adrenal cortex
What are the 2 forms of HAC?
Pituitary dependent (PDH):
- most common
- excess ACTH secretion => bilateral adrenal hyperplasia
Adrenal dependent (ADH):
- less common
- adenomas or carcinomas
What are the 2 forms of PDH (pituitary dependent HAC)
Microadenomas:
- <10mm
- majority of cases
Macroadenomas:
- >10mm
- slow growing
- can produce neurological signs
Describe ADH (adrenal dependent HAC)
Unilateral adrenal enlargement and atrophy of contralateral side as compensation
Independent of ACTH control
ACTH conc low or undetectable so normal gland atrophies as it is not stimulated
Describe the signalment for PDH and ADH
ADH - more common in larger or older dogs
PDH - more common in middle-aged dogs, poodles, daschunds and small terriers
Females slightly more at risk of ADH
No sex predisposition for PDH
What are the clinical signs of HAC?
PU/DP
Abdominal enlargement
Polyphagia
Skin changes
Hepatomegaly
Muscle wasting/weakness
Pot bells
Lethargy
Repro changes - decrease fertility
