Adrenal Gland Flashcards
blood goes from out to in of the adrenal gland.. what does that tell you about bathing in the medulla?
cortisol bathes the medulla
Zona fasciculate and zona reticularis can do what?
Zona reticularis releases what?
they both can release androgens and glucocorticoids.
DHEA –> sex androgens.
of the medulla, what’s the main product of the two?
epinephrine, not NE.
What stimulates catecholamines production?
ACh
Where does the medulla come from? cortex?
neural crest
mesoderm
pathway of HPA axis for cortisol?
what is the negative feedbacks?
Hypothalamus releases CRH –> gets to the AP activating corticotrophs releasing ACTH –> targets the adrenal gland –> creates cortisol and androgens
Cortisol will negatively regulate the Anterior pituitary (ACTH) and negatively regulate hypothalamus (CRH)
cortisol and the liver (think of the name of cortisol)
cortisol on muscle?
cortisol on adipose?
cortisol and the immune system?
Cortisol is a glucocorticoid, raising blood glucose levels at the level of the liver, promoting GNG! (glucagon like actions, anti insulin actions)
promote muscle degradation to generate acids
promote adipose tissue breakdown to produce more fatty acids
immune suppression
What is the main stimulus CRH from the hypothalamus?
Physical/Psychological Stress (exercise being physical) and Circadian Rhythm (SCN)
Cortisol secretion is happening most at what time?
what kind of manner?
pulsatile manner, and highest secretions are around when you wake up.
whenever you order lab tests, you need to know when cortisol is elevated and the ranges.
for the most part, boost is happening mostly around 8 early in the morning (20mg/dL).
Exogenous cortisol therapy?
what does it do to the system? (include the axis)
what if we measure glucocorticoids?
what about the target tissue?
most potent glucocorticoid?
we can put in synthetic / analog glucocorticoids that are given.
when they’re given, it’ll be a negative feedback mechanism decreasing CRH, decreasing ACTH.
cortisol will be decreased because of ACTH.
higher levels of glucocorticoids.
target tissue will be up taking it more!
most potent is dexamethasone, least is prednisone
What happens if you down regulate ACTH on Aldosterone?
changes in ACTH will not affect chronic change in aldosterone (remember that’s the RAAS pathway)..
angiotensin 2 from renin and elevated potassium are what stimulating it.
ACTH is a weak stimulator but not crucial
main stimulus of aldosterone? (3)
Angiotensin 2 from renin
and elevated potassium, decreased Na in the blood.
where is renin coming from? what makes this structure make it?
pathway?
what happens when we have the angiotensin 2?
KIDNEY
low BP –> the kidney –> makes renin –> makes Angiotensin 1 (using angiotensinogen from the liver)–> ACE converts it to angiotensin 2
angiotensin 2 goes to the cortex –> release aldosterone –> increase water/Na absorption –> increases BP!
frequent bruising with slow healing, backaches, excessive sweating, rapid weight gain..
face looks swollen compared to her body. sounds depressed, arms and legs are thin
low ACTH but high cortisol secretion
Cushing syndrome –> moon face / buffalo hump
hypercholesterol levels
abnormal glucose test and Cushing’s syndrome?
if you have an abnormal test, you would have insulin resistance because we normally have a hyper secretion of glucose due to cortisol levels being up
how do you know that Cushing’s syndrome isn’t from the pituitary gland?
there wouldn’t be a hyper excretion of ACTH, it would be lower because of the cortisol levels. so it has to be an adenoma in the adrenal gland.
for someone with Cushing’s syndrome, what’s the point of the dexamethasone test?
Inhibits ACTH so you know it’s not from the anterior pituitary and that it’s from the adrenal gland.
Cushing syndrome typical presentation?
what happens with the upper body?
face?
back?
what about their skin morphology?
Truncal obesity Moon face Buffalo Hump (supraclavicular inflammation) Easy bruising Hypertension
What is the low dose of dexamethasone?
low dose –> differentiating patients who have Cushing syndrome or not –> if you don’t have ACTH suppression would indicate CS.
test isn’t specific for telling you where the ACTH is coming from!!
High dose of dexamethasone?
what is it telling the difference between?
what is going to happen with a high dose?
distinguishes patients with Cushing disease (disease = pituitary tumor)
pituitary secreting ACTH-secreting tumor from CS caused by a non-pituitary ACTH tumor)
you’re differentiating from something in a pituitary tumor vs changes in ACTH that are coming from an ectopic tumor.
high dose will lead to a PARTIAL SUPPRESSION of the pituitary tumor but do NOTHING for ectopic
low dose there wouldn’t be any suppression.
Cortisol.. why is it causing enlargement of the trunk and abdomen?
adipose distribution in visceral obesity
Fat mobilization is leading that fat to areas of the periphery to the center.
Cortisol on elevation in plasma glucose?
hypertension and high levels of cortisol
Easy Bruising?
breakdown of glycogen and increased GNG
cortisol excess –> weak mineralocorticoid activity that affects the individual leading to hypertension
easy bruising is due to thin skin from breaking down the muscle!
How does glucocorticoid affect bone formation?
what can it lead to?
it tips the system to bone resorption and not formation when having high levels of glucocorticoid.
so lowering the mass of bones and leading to osteoporosis
Cushing’s syndrome vs disease?
Cushing syndrome is an ADRENAL TUMOR secreting cortisol.
this will lower the CRH and ACTH levels
Cushing’s Disease is a pituitary tumor –> high levels of ACTH to high so high cortisol.. it’s going to negative regulate CRH but do nothing on the pituitary gland ACTH because it can’t block it when it’s hyper secreting
What happens during an ectopic ACTH secreting tumor? (on the axis)
it’ll tell the cortisol to go up
it’ll lower ACTH and CRH levels
What happens with a glucocorticoid excess through exogenous drugs?
lower CRH, lower ACTH, lower cortisol secretion
all three are lower
rapid heartbeat, shakiness, sweating and fainting, HYPERPIGMENTATION . weakness, fatigue, lightheadedness. she thinks she has hypoglycemia.
Na = low, K+ = high glucose = low
what level of cortisol do you expect?
what do you think ACTH levels are going to be?
what disease is it?
Low cortisol
elevated ACTH
Addison’s disease.
Conn’s syndrome?
primary hyperaldosterone syndrome
How is the HPA axis altered in Addison’s disease
lowers the amount of cortisol and lowers the amount of aldosterone, so you’re going to expect super high CRH and ACTH
Where is hyperpigmentation coming from for Addison’s patients? explain the pathway
what does aldosterone do? explain the pathway
high ACTH –> produced by the POMC –> depending on how it’s cleaved you get ACTH and other multiple fragments.. some of the fragments are a different form of a-MSH, which creates melanin!!!
aldosterone binds to the distal nephron, increasing transcription for ENaC and Na/K ATPase.. overall effect is the promote the reabsorption of sodium and secretion of potassium!
How is primary adrenal insufficiency distinct from secondary adrenal insufficiency?
primary adrenal insufficiency usually presents with hyperpigmentation
How does synthetic ACTH stimulation test works?
applies when trying to discriminate if it’s primary insufficiency or not.
you measure cortisol at 8AM.. if you have more than 15 microgram you can rule out adrenal insufficiency.
if it’s 3-15 or less than 3.. we stimulate with COSYNTROPIN (synthetic ACTH)
if the adrenal gland makes more to more than 18, it rules out primary adrenal insufficiency because that would mean that it’s functional.
if we have a person that still isn’t responding to ACTH, now we’re measuring ACTH levels directly… so in primary adrenal insufficiency we would have no cortisol so ACTH levels would be high.
if it was low/normal, it’s secondary or tertiary AI
after levels of that have been checked and we have elevated levels –> Primary AI
primary adrenal insufficiency? what is being depressed?
Renin levels?
adrenal gland isn’t working.. it won’t make cortisol, it won’t make aldosterone.
renin will be up
secondary adrenal insufficiency?
what would you expect for ACTH? Cortisol? Aldosterone?
Pituitary is screwed
Aldosterone will be normal (RAAS works separately)
Cortisol will be lowered.
What infections can affect and destroy the adrenal gland
Tuberculosis, Meningitis
Hyperaldosteronism? (2 types)
where do you find secondary? primary?
Primary hyperaldosteronism –> excessive secretion of aldosterone due to an adenoma in the adrenal cortex (CONNS SYNDROME)
Secondary hyperaldosteronism –> excessive renin secretion by the juxtaglomerular cells in the kidney
Hypoaldosteronism?
destruction of the adrenal cortex
defect in synthesis (congenital hyperplasia)
inadequate RAAS axis
What is the Plasma Aldosterone Concentration (PAC) to plasma renin activity (PRA) test?
for primary hyperaldosteronism
high aldosterone will give you high Na (hypertension) and Low K (hypokalemia).
High PAC, low PRA
girl has blood pressure that is high.
clitoral enlargement, labial fusion, scant pubic hair
slightly elevated sodium, low potassium, chloride and bicarb normal *HYPERTENSIVE
what enzyme is associated with this condition?
11B-hydroxylase
baby with ambiguous genitalia, dangerously hypertensive, fused labia, large and masculinized clitoris?
HYPOTENSIVE
21B-hydroxylase
for congenital adrenal hyperplasia. ACTH is going to be elevated which is signaled by low level of cortisol
Cholesterol pathway. when we inhibit 17a-hydroxylase, what is going to be favored?
more aldosterone.
low androgens, low cortisol
Cholesterol pathway. when we inhibit 21-hydroxylase, what is going to be favored?
impair aldosterone (hypotensive), impair cortisol
so high androgen (biliarization)
Cholesterol pathway. when we inhibit 11B-hydroxylase, what is going to be favored?
aldosterone effected (DOC effected but in excess is giving you symptoms that are associated with excessive mineralocorticoid activity) cortisol effected
Metanephrine and normetanephrine levels, high catecholamine production
what’s most consistent?
what’s the disease?
catecholamine production from an adrenal tumor in the MEDULLA
pheochromocytoma –> chromatin cells of the adrenal medulla.
over secretion is going to be acting on adrenergic and beta adrenergic receptors.. it stimulates both.
pathway of creating epinephrine from tyrosine?
Tyrosine + ACh (via tyrosine hydroxylase) –> DOPA –> Dopamine + ACh –> Norepinephrine + CORTISOL –> Epinephrine
cortisol is going to increase the PNMT enzyme activity to create more epinephrine.
Conversion of tyrosine to dopamine happens where?
in the cytosol
Dopamine goes into the chromaffin cell and then is changed to NE.
NE is shoved back into the cytosol to be changed by cortisol.
Epinephrine goes BACK into the chromatin and goes into the Chromogranin.
What two enzymes in the creation of epinephrine from tyrosine are susceptible to Ach (sympathetic) stimulation?
what does cortisol act on?
Tyrosine hydroxylase (tyrosine to DOPA)
Dopamine B-Hydroxylase (Dopamine to NE)
changing NE to E
What two things are needed to degrade catecholamines?
COMT
MAO
Short term stress is by what?
long term is by what?
catecholamines
glucocorticoids mostly
