Adrenal gland physio (Wong)
Terms in this set (84)
what are the 3 classes of reproductive steroids?
what is the most abundant androgen?
what is the most abundant estrogen?
what is the most abundant progestin?
how is the adrenal gland functionally divided?
a larger adrenal cortex region
and an inner adrenal medulla region
what is the adrenal medulla considered as?
a modified sympathetic ganglion => secretes
) into blood in response to preganglionic sympathetic stimulation
what are the 3 zones of the adrenal cortex? and what do they secrete?
Zona glomerulosa => mineralcorticoids
Zona fasciculata => glucocorticoides
Zona reticularis => androgens
steroid hormone biosynthesis
steroid hormone secretion
steroid hormone transport
steroid hormone metabolism
biochemical inactivation => half life: 20-90 min
steroid hormone mechanism
intracellular membrane receptor
hypothalamic-anterior pituitary => CRH/ACTH
what are the functions of glucocorticoids?
energy metabolism (catabolic)
what adrenal steroid is responsible for the majority of the physiological activities associated with glucocorticoids?
what is the net effect of glucocorticoids on metabolism?
mobilizes energy substrate stores
increase muscle protein catabolism => increase plasma glucose and gluconeogenesis
decrease tissue glucose uptake => increase plasma glucose
increase adipose tissue lipolysis => increase plasma glucose and gluconeogenesis
when are glucocorticoids released?
during long-term metabolic stress => starvation
what is the main function of glucocorticoids on inflammation?
glucocorticoids suppress processes causing inflammation => decreased pain, swelling, redness, heat, autoimmunity
what is essential for survival?
the rise in glucocorticoid secretion in response to stress => the absence of glucocorticoids results in
what is stress defined as?
any number of noxious stimuli that results in an increase in ACTH
what maintains the balance between CRH and ACTH throughout the day?
circadian rhythm through higher brain centers
when are cortisol levels the lowest?
in the late evening = 8PM-3AM
when are cortisol levels the highest?
early morning = 5-8AM
what is the relationship of glucocorticoids and the circadian rhythm?
basal levels vary according to an intrinsic circadian rhythm, the appearance of circadian pulses are
independent of sleep
(because they appear whether asleep or awake), but the timing of the circadian peaks can be
by altering the
(i.e. night shift)
clinical symptoms and physical features that occur as a consequence of chronic glucocorticoid excess (hyperglucocorticoidism)
what is the most common cause of Cushing's syndrome?
Cushing's disease due to an unregulatble anterior pituitary tumor that secretes excessive ACTH, which stimulates cortisol hypersecretion
what are the lab values of cushing's disease due to ant. pituitary tumor (secondary hyperglucocorticoidism)?
what are the lab values of primary hyperglucocorticoidism?
what are the lab values of excess exogenous GC (secondary hyperglucocorticoidism)?
low [cortisol] (endogenous)
what are the symptoms of Cushing's syndrome?
muscle weakness and loss (due to increased protein catabolism)
red cheeks, moon facies, acne
poor wound healing, infection, bruisability
osteoporosis, bone loss
increased appetite, hyperglycemia
what causes fat accumulation in Cushing's syndrome?
increased appetite stimulated by low CRH level due to feedback inhibition => hyperglycemia due to increased eating and gluconeogenesis => hyperinsulinemia => insulin resistance => insulin insensitivity -- chronically, adrenal diabetes may develop
what are the effects of excess cortisol in Cushing's syndrome?
Acne and Hirutism => due to hyperandrogenism
Amenorrhea and infertility in women
decreased libido in men
what are the effects of anti-inflammatory abnormalities in Cushing's syndrome?
weakened inflammatory response
poor wound healing
what is addison's disease?
what causes addison's disease?
adrenal gland destruction (TB or cancer)
atrophy (autoimmune disease)
what are the lab values of addison's disease?
low [cortical hormone]
what are the symptoms of addison's disease?
opposite of cushing's
what are the mineralcorticoid deficiencies in addison's disease?
what is a common feature of Addison's and why?
because ACTH is synthesized as a common peptide (proopiomelanocortin (POMC)) that encodes Melanocyte stimulating hormone (MSH) => unevenly distributed melanin
what are the net effects of aldosterone?
increased Na+ reabsorption
increased K+ and H+ secretion
increased ECF volume (because H2O passively follows Na+)
what does aldosterone primarily act on?
late distal tubules and cortical collecting ducts of the nephron
what is the mechanism of action of aldosterone?
aldosterone diffuses into the cell and binds to intracellular cytoplasmic receptors the aldosterone-receptor complex (AR) migrates to the nucleus where it affects DNA transcription => proteins stimulate renal Na+ reabsorption
how does aldosterone outcompete cortisol for mineralcorticoid receptors?
converts cortisol to cortisone, which is not recognized by MR
what happens if a person is 11beta-HSD2 deficient?
pseudohyperaldosteronism => hypertension and hypokalemia
how is aldosterone regulated?
via renin-angiotensin pathway
low blood pressure/volume, stimulates renin release from kidneys (juxtoglomerular apparatus), this activates angiotensinogen => angiotensin I, which is activated to angiotensin II, which stimulates aldosterone release from the adrenal cortex => increase in bp/volume
adrenal destruction, addison's disease
lack of aldosteronism is
if left untreated due to hypotension, which causes circulatory insufficiency that leads to shock
what is the most common cause of primary hyperaldosteronism?
what is seen clinically in primary hypoaldosteronism?
what is the treatment of primary hypoaldosteronism?
what is seen clinically in primary hyperaldosteronism?
what is the treatment of primary hyperaldosteronism?
what is the principle mineralcorticoid?
what is the principle adrenal androgen?
what are the steroid hormone biosynthesis pathways?
what is steroid hormone biosynthesis dependent on?
cytochrome P450 enzymes
what enzyme does the glomerulosa region lack?
: the glomerulosa layer is unable to synthesize glucocorticoid or androgen hormones and is restricted to the biosynthesis of mineralcorticoid pathway products =
what are the labs seen in 17-OH hydroxylase deficiency?
what is the presentation of 17-OH hydroxylase deficiency?
XY: pseudohermaphfoditism (ambiguous genitalia, undescended testes)
XX: lack secondary sexual development
what enzymes do fasciulata and reticularis pathways lack?
18-OH hydroxylase: neither layer can synthesize mineralcorticoids, they can each
biosynthesize both glucocorticoid and androgen steroids
what are the dominant enzymes in the fasciculata region? what is the major secretion product?
17-OH and 21-OH hydroxylase, cortisol
what is the primary product of the reticularis region? how is it different from the fasciculata region?
21-OH hydroxylase is very weak, so it does not typically synthesize significant amounts of glucocorticoids
what is the reticularis layer thought to be?
an inner layer of degenerating fasciculata cells
what is the general rule of thumb for p450 enzyme deficiency disorders?
steroid intermediates will become
and accumulate in
what is the importance of overlapping actions of steroid hormones?
aldosterone deficiency = excess corticosterone => increased reabsorption of Na+ because corticosterone binds to the same receptor as aldosterone (possessing some mineralcorticoid qualities), so pt exhibits symptoms of hyperaldosteronism (
HTN and hypokalemia
), but has
lack of aldosterone production and an excess of mineralcorticoid intermediates => shunted into the androgen pathway causing an excess DHEA
HTN = 11-deoxycorticosterone accumulation
abnormal sex development of fetuses= excess DHEA
21-OH deficiency pathophysiology
- glucocorticoids (cortisol) => increase in ACTH to try to make more (can cause adrenal cortex hypertrophy)
- mineralcorticoids (aldosterone)
what is the clinical presentation of 21-OH deficiency?
Females: masculinization (virilization)
Males: precocious puberty
presents in infancy = salt wasting
presents in childhood = precocious puberty
what is the treatment of 21-OH deficiency?
exogenous steroid replacement
what are the secretory cells of the adrenal medulla?
, considered modified
postganglionic sympathetic neurons
because they arise from neuroectoderm and receive efferent input from sympathetic spinal neurons and secrete catecholamiens
which amino acid are catecholamines derived from?
what is the major secreted product from the adrenal medulla?
modification = short half-life: seconds-minutes
G-protein coupled membrane receptor
how are catecholamines transported in the blood?
70% are conjugated to sulfate
what is the plasma concentration of norepi compared to epi?
2-8x greater than epinephrine due to significant "leakage" into the venous system from nerve endings and large amount of norepi is released during stimulation
how is adrenal catecholamine secretion initiated?
by Ach release from preganglionic axons innervating chromaffin cells => depolarization causes influx of Ca2+ through voltage gated channels, which triggers
of cellular storage granules
what is the net effect of epinephrine on metabolism?
increase plasma glucose
what is the most common cause of primary hyposecretion of adrenal medulla? why is it rare?
because there is autonomic compensation
what are the symptoms of primary hyposecretion of catecholamines?
maybe depressed cardiac functions
what is the most common cause of primary hypersecretion of catecholamines?
medullary tumor = *pheochromocytoma
what are the symptoms of primary hypersecretion of catecholamines?
increased heart contractility, HTN, tachycardia, anxiety