the structure and function of the adrenal glands and pathophysiology of HAC Flashcards
where is the adrenal gland located ad decribe their appearance
- next to the kidneys within the retroperitoneal space
- cranial aspect of the kidneys
- elongated and are often asymmetrical being moulded around the neighbouring vessels
- size varies (juveniles are larger than adults)
describe the anatomy of the adrenal cortex
- constitues 80-90% of gland
- 3 zones: outisde to inside: zona glomerulosa, fasciculate and reticularis
what do the 3 zones of the adrenal cortex produces respectively
inside to outside:
1. zona glomerulosa = mineralcorticoids
2. zona fasciculate = glucocorticoids
3. zona reticularis = androgens
describe the adrenal medulla
- only 10-20% of gland
- neuroendocrine tissue
- has sympathetic ganglion cells
- secretes catecholamines
what does the adrenal medulla secrete
catecholamines
- adrenaline
- noradrenaline
discuss the synthesis of steroid hormones
- synthesis of all steroid hormones begins with cholesterol
- cholesterol is converted into pregnenolone by P-450 side chain cleavage enzyme (rate limiting step is activated by ACTH)
- pregnenolone is converted into different corticoids according to the zone: glomerulosa = aldosterone, fasciculata = glucocorticoids, reticularis = androgens
what are glucocorticoids and give an example
example: cortisol
- metabolises glucose
- synthesized in the adrenal cortex
- steroidal structure
how is the release of glucocorticoids controlled
- CRH is transported from the hypothalamus down axons to the portal capillary bed
- CRH causes corticotropom cells in the anterior pituitary to make and release ACTH
- ACTH travels through the systemic circulation to the adrenal glands where it stimulates synthesis of glucocorticoids (predominanatly cortisol)
discuss the importance of POMC in relation to ACTH
- ACTCH is synthesized from pro-opiomelanocortin (POMC)
- POMC undergoes a series of post translation modifications before it is proteolytically cleaved to yield various polypeptides with varying physiological actions
discuss the physiology of glucocorticoids
- once released, glucocorticoids are transported in the blood, 90% bound to plasma proteins
- they bind to specific cell membrane or cytosolic receptors at their target
- these receptor-steroid complex is then trasnported to the nucleus
- resulting in altered gene expression
how do glucocorticoids act
- they are stress hormones
- stimulate gluconeogenesis
- stimulate glycogenolysis
- causes proteolysis
- promotes lipolysis
what are the actions of glucocorticoids on fat
mobilisation from peripheral stores
what are the actions of glucocorticoids on muscle
catabolism
what are the actions of glucocorticoids on the liver
- gluconeogenesis
- antagonise insulin
what are the actions of glucocorticoids on the kidneys
- increased GFR
- blocks ADH action
what are the actions of glucocorticoids on skin
- follicular atrophy
- sebaceous gland atrophy
what are the actions of glucocorticoids on bone
- reduces calcium levels
- osteopaenia
what are the actions of glucocorticoids on the brain
- hunger
- thirst
what are the actions of glucocorticoids on the immune system
- release neutrophils from marginated pool
- down regulates immune response (T cell function and recruitment/B cell activation
what are mineralcorticoids and give an example
example: aldosterone
- a class of steroid hormone characterised by their effects on salt and water balance. the name derives from their involvement in retention of sodium and mineral
how is the release of mineralcorticoid controlled
- main stimulus for aldosterone release is low blood pressure (RAAS)
- high serum potassium also stimulates release
- role of ACTH only minor
what is the function of aldosterone
- plays a central role in the regulation of BP
- acts on cells of distal tubule and collecting duct to increase reabsorption of Na, Cl and hence water
- stimulates the secretion of K+ into the tubular lumen
what are androgens
- steroid hormones
- stimulate or control the development and maintenance of male characteristics by binding to androgen receptors
- androgens are precursors for all oestrogens
- most important androgens are: testosterone, dihydrotestosterone, dehydroepiandrosterone and androstenedione
what is hyperadrenocoricism
- a condition that can develop in all domestic species and is characterised by the excessive production of steroid hormones, especiall glucocorticoids, from the adrenal cortex
- clinical signs therefore relate to abnormal circulating concentrations of steroid hormones
- often called cushings disease
discuss canine HAC and its prevalence
- can be either spontaneous or iatrogenic (caused by tx)
- spontaneous has 2 forms: pituitary dependent and drenal depedent
- pituitary dependent = 80-90% of cases
- in PDH, excess ACTH secretion results in bilateral adrenal hyperplasia
- adrenal dependent = 10-20% of cases (either adenoma or carcinoma)
- independent of pituitary control
discuss PD HAC pathology
- most arise from pars distalis, less from pars intermedia
- normal negative feedback mechanism fails (tumour ignores feedback and keeps stimulating ACTH production)
Discuss AD HAC pathology
- unilateral adrenal enlargement which causes atrophy of contralateral side
- independent of ACTH control
- ACTH concentration low or undetectable (because high levels of cortisol circ so pituiatary doesnt need to produce)
- approx 50% will be calcified regardless of tumour type (due to interaction btwn calcium and cortisol)
discuss the common signalment of a dog with HAC
- ADH in older dogs (11-12) PDH in middle aged (7-9)
- poodles, dachshunds and small terriers predisposed to PDH
- larger breeds appear more at risk for ADH
- no sex predisposition for PDH, females slightly more at risk for ADH
describe the clinical signs of HAC and when they are most commonly seen
- more common in small breed dogs
- onset usually insidious and disguised as “aging”
- may be initially intermittent
- can occasionally develop rapidly
- affects multiple organs (liver, muscle, bone, kidneys, immune system, repro, etc)
Clinical signs:
- PU/PD
- Abdominal enlargement
- polyphagic
- skin changes
- hepatomegaly
- muscle wasting/weakness
- lethargy/exercise intolerance/panting
- repro changes
list reasons for PU/PD in cushinoid dogs and relate them to the physiology
- PD secondary to PU
- antagonism of ADH, increased GFR and inhibition of ADH release
list reasons for abdominal enlargement in cushingoid dogs and relate them to physiology
- pot belly appearnace
- re distribution of fat into the abdomen due to breakdown of fat caused by increased cortisol
- hepatic enlargement
- wasting and weakness of abdominal muscles (protein breakdown)
- makes palpation of abdo easier
list reasons for cuchingoid dogs having skin changes and relate them to the physiology
- bilaterally symmetrical alopecia due to inhibitory effects of steroids on anagen phase of hair growth
- thin skin and reduced elasticity with prominent abdominal veins due to protein catabolism and loss of SQ fat
- excessive scale and comedones
- slow wound healing due to inhibition of fibroblast proliferation and collagen synthesis
what response woul you expect in a healthy dog if you injected them with ACTH
increase cortisol
what would you expect to happen in a healthy dog if you injected them with glucocorticoids
decreased cortisol and ACTH production
how is HAC treated
- vetoryl (trilostane)
- adrenalectomy or hypophysectomy (requires hormone replacement
d
discuss feline HAC
- uncommon
- cats are more resistant to the effects of glucocorticoids
- signalment = middle aged to older cats
- most due to PDH
- clinical signs same as in dogs
