the structure and function of the adrenal glands and pathophysiology of HAC Flashcards
(36 cards)
1
Q
where is the adrenal gland located ad decribe their appearance
A
- 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)
2
Q
describe the anatomy of the adrenal cortex
A
- constitues 80-90% of gland
- 3 zones: outisde to inside: zona glomerulosa, fasciculate and reticularis
3
Q
what do the 3 zones of the adrenal cortex produces respectively
A
inside to outside:
1. zona glomerulosa = mineralcorticoids
2. zona fasciculate = glucocorticoids
3. zona reticularis = androgens
4
Q
describe the adrenal medulla
A
- only 10-20% of gland
- neuroendocrine tissue
- has sympathetic ganglion cells
- secretes catecholamines
5
Q
what does the adrenal medulla secrete
A
catecholamines
- adrenaline
- noradrenaline
6
Q
discuss the synthesis of steroid hormones
A
- 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
7
Q
what are glucocorticoids and give an example
A
example: cortisol
- metabolises glucose
- synthesized in the adrenal cortex
- steroidal structure
8
Q
how is the release of glucocorticoids controlled
A
- 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)
9
Q
discuss the importance of POMC in relation to ACTH
A
- 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
10
Q
discuss the physiology of glucocorticoids
A
- 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
11
Q
how do glucocorticoids act
A
- they are stress hormones
- stimulate gluconeogenesis
- stimulate glycogenolysis
- causes proteolysis
- promotes lipolysis
12
Q
what are the actions of glucocorticoids on fat
A
mobilisation from peripheral stores
13
Q
what are the actions of glucocorticoids on muscle
A
catabolism
14
Q
what are the actions of glucocorticoids on the liver
A
- gluconeogenesis
- antagonise insulin
15
Q
what are the actions of glucocorticoids on the kidneys
A
- increased GFR
- blocks ADH action
16
Q
what are the actions of glucocorticoids on skin
A
- follicular atrophy
- sebaceous gland atrophy
17
Q
what are the actions of glucocorticoids on bone
A
- reduces calcium levels
- osteopaenia
18
Q
what are the actions of glucocorticoids on the brain
A
- hunger
- thirst
19
Q
what are the actions of glucocorticoids on the immune system
A
- release neutrophils from marginated pool
- down regulates immune response (T cell function and recruitment/B cell activation
20
Q
what are mineralcorticoids and give an example
A
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
21
Q
how is the release of mineralcorticoid controlled
A
- main stimulus for aldosterone release is low blood pressure (RAAS)
- high serum potassium also stimulates release
- role of ACTH only minor
22
Q
what is the function of aldosterone
A
- 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
23
Q
what are androgens
A
- 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
24
Q
what is hyperadrenocoricism
A
- 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
25
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
26
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)
27
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)
28
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
29
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
30
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
31
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
32
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
33
what response woul you expect in a healthy dog if you injected them with ACTH
increase cortisol
34
what would you expect to happen in a healthy dog if you injected them with glucocorticoids
decreased cortisol and ACTH production
35
how is HAC treated
- vetoryl (trilostane)
- adrenalectomy or hypophysectomy (requires hormone replacement
36
# 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
