Adrenal Cortex Flashcards
Describe the parent molecule that all adrenal steroids are derived.
Cholesterol; Is modified by enzymes to make other steroid hormones
List the major actions of glucocorticoids
You don’t want lots of glucocorticoids floating around all of the time. Rise in glucocorticoids during periods of reduced food availability will help maintain serum glucose concentrations for CNS function at the expense of fat and protein; CNS only uses glucose Physiological function of glucocorticoids: Metabolic: Glucose “sparing – promotes gluconeogenesis, Stimulates lipolysis, Promotes protein degradation, Stimulates glycogen formation, Inhibits glucose uptake by many tissues, Catabolic for most tissues Response to stress Immune- Potent anti-inflammatory role (used clinically), Immunosuppression (at higher doses), Potential for infections Blood- Increases neutrophils, decrease lymphocytes Skeletal- Can promote bone breakdown, Inhibits vitamin D
List stimuli that alter ACTH secretion
cortisol inhibits secretion of CRH and ACTH; CRH stimulates the production of ACTH
Describe the actions of aldosterone on ion metabolism
not regulated by the pituitary; promotes Na retention and K elimination, involved in water retention and H ion elimination
Describe with diagrams the regulatory system that controls the secretion rate of aldosterone
Describe with diagrams the regulatory system that controls the secretion rate of cortisol
List the major symptoms of Cushing’s disease in the dog
PU/PD, hyperphagia, abdominal enlargement (pendulous), alopecia, muscle weakness, lethargy
Describe the effect of ACTH on the adrenal cortex
acts on the 2 inner zones, promotes the secretion of glucocorticoids (cortisol/corticosterone)
Describe the mechanism of ACTH action
acts via cAMP, negative feedback system loop
Describe the role glucorticoids play in regulating ACTH secretion
negative feedback loop, high levels of cortisol suppress CRH/ACTH production
Name two species where cortisol is the most critical glucocorticoid
cats, horses
Name two species where corticosterone is the most critical glucocorticoid
rats, mice
Name a species where both cortisol and corticosterone are major glucocorticoids
dogs
Describe why administration of synthetic glucocorticoid causes atrophy of the adrenal zones that normally make glucocorticoid
exogenous cortisol in system, decrease CRH/ACTH (feedback), decrease endogenous cortisol secretion, atrophy of cells
Describe why a hypoglucocorticoid state frequently results following cessation of exogenous glucocorticoid treatment
atrophy of cells, ACTH stimulation of endogenous cortisol not as effective
Define and describe iatrogenic Cushing’s.
Clinical caused by treatment of other disorders by high doses of cortisol; ex.- use of glucocorticoids in immune suppression can lead to a short term Cushnoid state
Explain what sex steroids are produced by the adrenal cortex
Zona reticularis- DHEA: primary androgen; androstenedione
Explain the actions of sex steroids produced by the adrenal cortex
DHEA/androstenedione- development of secondary sex characteristics at puberty; serve as substrates for production of estrogens; may play role in preventing degenerative changes in ageing
Describe why production of high levels of adrenal steroids sometimes leads to estrogenic effect
Because they can serve as substrates for the production of estrogens
Describe the effect of glucocorticoids on the immune system
high doses can cause immunosuppression
- inhibits inflammation/T-lymphocytes production
Understand the mechanism of action and principle toxicities of the adrenolytic drug o,p’-DDD (mitotane) and appropriate approaches to its use for the treatment of hyperadrenocorticism
selective necrosis of inner zone cells (mechanism unknown); used in treatment of secondary or PDH (pituitary-dependent hyperadrenocorticism)
DHEA
primary androgen, sex steroid produce by the adrenal gland (zona reticularis)
androstenedione
sex steroid produced by the adrenal gland (zona reticularis)
glucocorticoid
cortisol/corticosterone; produced by adrenal gland; diurnal variation, can be influenced by stress
mineralocorticoid
produced by the adrenal gland in the zona glomerulosa/articuate; not regulated by the pituitary; promotes Na retention, K elimination, water retention, H ion elimination
zona glomerulosa
produces mineralcorticoids, not regulated by the pituitary gland
(salt)
zona fasiculata
produces glucocorticoids (cortisol/corticosterone); acted on by ACTH from pituitary
(sugar)
zona reticularis
produces sex steroids (DHEA/androstenedione); acted on by ACTH from pituitary
(sex)
corticosterone
only glucocorticoid in birds, rats, mice
dogs have both corticosterone and cortisol
T cells
T cell production is inhibited by high doses of glucocorticoids if given at an immunosuppressive dose
compare/contrast long and short term stress
long term stress: adrenal cortex; leads to retention of sodium and water by kidneys, increased blood volume and blood pressure, proteins and fats converted to glucose or broken down for energy, increased blood sugar, suppression of immune system
short term stress: adrenal medulla; release of catecholamines; increased HR, BP, liver converts glycogen to glucose and releases glucose to the blod, dilation of bronchioles, increased metabolic rate, changed blood flow
Cushing’s syndrome
Hyperadrenocorticism
Diagnosis- ACTH challenge (suppressed in primary, elevated in secondary)
Primary- tumor; tumor removal
Secondary- PDH; treatment- mitotane, selective destruction of cells
symptoms- PU/PD, pendulous abdomen, hyperphagia, lethargy, muscle weakness
Addison’s disease
Hypoadrenocorticism
Primary (most common)- includes changes in Na and K values as well; treat with glucocorticoids and mineralcorticoids
Secondary- can be natural or iatrogenic; diagnose with ACTH stim test; treat with glucocorticoids
Symptoms- weight loss, lethargy, hypovolemia
ACTH challenge
159-161
iatrogenic
clinically caused; ex.- Primary hypoadrenocorticism
hydrocortisone
short-acting glucocorticoid, weak, common in OTC topicals
prednisone/prednisolone
intermediate acting, 4x more potent that hydrocortisone; has glucocorticoid and mineralcorticoid affects
(oral)
dexamethasone
long acting, only glucocorticoid effects; 25-30x more potent than hydrocortisone
(injection)
adrenolytic
inhibiting the action of the adrenergic nerves, or the response to epinephrine
Lysodren
used in chemotherapy of adrenal tumors in hyperadrenocorticism
