HP Relationships And Biofeedback Pt. 2 Flashcards
What are mineralocorticoids?
Secreted from?
Function?
Aldosterone
From zona glomerulosa of adrenal cortex
Regulates salt and volume homeostasis
What are glucocorticoids?
Secreted from?
Function?
Cortisol
Form zona Fasciculata of adrenal cortex
longer acting stress response steroid hormone, regulates glucose utilization, immune and inflammatory homeostasis
What does the zona fasciulata and zona reticularis both secrete?
Glucocorticoids
Androgens
What are catelcholamines?
Where are they secreted from?
Function?
NE and E
Medulla’s chromaffin cells
Rapid responder to stress
(i.e. hypoglycemia, exercise)
What are the hypothalamic hormones released in the HP-Adrenal axis?
CRH
Corticotropin releasing hormone
What are the pituitary hormones released in the HP-Adrenal axis?
ACTH
What is ACTH derived from?
What does it share a precursor with?
From post-translational processing of POMC (proopiomelanocortin)
Melanin
What hormones does the adrenal cortex release in the HP-Adrenal axis?
Cortisol (Zona Glom.)
Mineralocorticoid (Zona F and R)
Androgens (Zona F and R)
What regulates teh HP-Adrenal axis?
Cortisol will feedback and INHIBIT pituitary and hypothalamus
What is the stimulus for CRH (Corticotropin releasing hormone) from the Hypothalamus?
- emotional stress (fear)
- physical stress (surgery)
- metabolic stress (hypoglycemia)
- infection and inflammation via cytokines
- Circadian rhythm
What 3 things will cortisol feedback and inhibit?
ACTH @ pituitary
CRH @ hypothalmus
Cytokines (in infections and inflammation)
What kind of loop does cortisol act in?
Long loop negative feedback
What are the actions of cortisol on the
Immune system?
Liver?
Muscle?
Adipose tissue?
◦ Immune system —> immune suppression
◦ Liver —> gluconeogenesis
◦ Muscle —> protein catabolism
◦ Adipose tissue —> lipolysis
When is secretion of cortisol highest?
Lowest?
Highest in early morning
Lowest in late evening
What will exogenous glucocorticoid drugs do?
mimic cortisol actions
- longer acting stress response steroid hormone
- regulates glucose utilization
- immune and inflammatory homeostasis
What can administration of an excess of exogenous glucocorticoid drugs do?
Atrophy adrenal cells that produce cortisol
Show symptoms of XS cortisol (Cushing’s)
What are examples of synthetic glucocorticoids?
Prednisone
Methylprednisone
Dexamethasone
If there is increased ACTH levels, what will happen to your skin?
Hyperpigmentation due to acth acting on alpha-MSH and inducing melanin synthesis
What is primary hypercortisolism?
How will levels of Cortisol CRH ACTH Change?
Xs production of cortisol by adrenal cortex
Cortisol: high
CRH: low (cortisol acts back)
ACTH: Low (cortisol acts back)
What is secondary hypercortisolism?
How will levels of Cortisol CRH ACTH Change?
Xs production of cortisol by defect @ pituitary gland
Cortisol: high
CRH: low (cortisol acts back)
ACTH: high (defect @ pituitary)
What is Primary deficiency of cortisol?
How will levels of Cortisol CRH ACTH Change?
Deficiency @ adrenal cortex
Cortisol: low
CRH: high (no cortisol to act back)
ACTH: high (no cortisol to act back)
What is secondary deficiency of Cortisol?
How will levels of Cortisol CRH ACTH Change?
Deficiency of cortisol bc of defect @pituitary gland
Cortisol: low
CRH: high (bc no cortisol to act back)
Pituitary: low (bc problem @ pituitary)
How will steroid administration of glucocorticoids change levels of
Cortisol
CRH
ACTH
Cortisol: low
CRH: low
ACTH: low
No need to produce naturally when provided synthetically
What changes in the HP-adrenal axis would an
Adrenal tumor secreting cortisol cause?
Increased cortisol
Lower ACTH and CRH (bc of feedback)
What changes in the HP-axis will occur from an ectopic ACTH secreting tumor?
Exogenous ACTH: high
Cortisol: high
Endogenous ACTH: low
CRH: low
What is Cushing DISEASE?
HYPERcortisolism with HIGH ACTH bc of pituitary adenoma
What are the symptoms of Cushing’s?
!!• Rounding in of face = moon face !!• Excess fat on back of neck = buffalo hump !!• Excess weight gain in abdomen !!• Dark red or purple stretch marks • Osteoporosis !!• Easy bruising, hypertension • Hirsuitism (bc androgens also made) • Acne • Etc.
What is the test for Cushing’s syndrome?
Dexamethasone suppression test
Will administer synthetic glucocorticoid @ low dose
Positive: no acth suppression
What will a HIGH dose of Dexamethasone suppression test tell you?
The cause of Cushing’s syndrome
- drop in ACTH = pituitary adenoma
- no change = non-pituitary adenoma
What can cause Cushing syndrome? (Excess cortisol)
Exogenous glucocorticoid adminstration
Pseudo Cushing’s
Cushing’s DISEASE
adrenal adenoma/carcinoma
Ectopic ACTH or CRH secreting tumors
What is pseudo Cushing’s syndrome caused by?
Depression, anxiety, acute/chronic illness, alcoholism
All stressors that could cause release of CRH and increase cortisol
How will acth levels change in Cushing syndrome caused by a
Pituitary tumor?
High
How will acth levels change in Cushing syndrome caused by a
Adrenal tumor?
Lower than normal
How will acth levels change in Cushing syndrome caused by a
Ectopic acth secreting tumor?
Higher than normal
What is Addison’s disease?
Primary Adrenal insufficiency
Low in aldosterone and cortisol, yet HIGH ACTH
What are the symptoms of Addisons?
• Hyperpigmentation ◦ excess ACTH —> MC1R—> increase melanin production • Weakness • Weight loss • Hypotension • Hyponatremia (low Na)
What are the causes of Addison’s disease?
• Autoimmune disease • Adrenal hemorrhage ◦ Waterhouse-Friedrichsen syndrome ◦ hemorrhage from anticoagulant treatment • infection ◦ Tuberculosis ◦ N. Meningitis is • tumor metastasis to adrenal gland
What is Waterhouse-Friedrichsen syndrome?
What can Waterhouse-friedrichsen cause?
‣ Adrenal hemorrhage secondary to N. Meningitis is
Can cause Addison’s disease
What is low/nonexistent in Addison’s disease?
High?
Low: cortisol and aldosterone
Non-existent: renin-angiotensin-aldosterone axis
High = ACTH
What is the test for Addison’s disease?
• Cosyntropin (synthetic ACTH) stimulation test
Cortisol = less than 18 ug/dL
If ACTH = elevated = pirmary
If ACTH = low/normal = secondary/tertiary Adrenal insufficiency
What is the treatment for Addison’s?
Steroid replacement for life
Cortisol replaced w/ corticosteroid
(Aldosterone replaced w/ mineralcorticoid)
What is secondary adrenal insufficiency?
How does it differ from primary?
How will tx differ?
Low production of cortisol because of NO ACTH
Renin-angiotensin-aldosterone axis still exists
Cortisol replacement needed but not mineralocorticoid (aldosterone) replacement
What regulates the secretion of aldosterone?
Where is it secreted from?
Angiotensin II from renin-angiotensin system
Zona glomerulosa
What activates the renin-angiotensin system?
What will this then go and activate?
‣ Activated by decrease in Na or by increase in K == Decrease in BP
Angiotensin —> aldosterone
What is the primary action of aldosterone?
Renal sodium reabsorption to INCREASE BP
How does aldosterone increase BP?
‣ 1. Aldosterone combines w/ a cytoplasmic receptors
‣ 2. Hormone receptor complex initiates transcription in teh nucleus
‣ 3. Translation and protein synthesis makes new protein channels and pumps
‣ 4. Aldosterone induced proteins modulate existing channels and pumps
‣ 5. Result = increased Na reabsorption and K+ secretions—> increased BP
What is primary HYPERaldosteronism?
Excess release of aldosterone bc defect @ adrenal cortex
What is COnn’s syndrome?
Tx?
Adenoma in adrenal cortex causes Primary HYPERaldosteronism
Surgery
What is bilateral adrenal hyperplasia?
Tx?
Can cause HYPERaldosteronism
Spironolactone
What are the symptoms of PRIMARY HYPERaldosteronism?
Hypertension (too much Na reabsorption)
HYPOkalemia (too much K secretion)
Low plasma renin
What is secondary HYPERaldosteronism?
Excess aldosterone production bc of excess renin secretion by juxtaglomerular cells in kidney
How is Hyperaldosternoism detected?
Ratio of Plasma aldosterone contention to plasma renin activity ratio
ratio > 20
PAC >15
= primary aldosteronism
What is hypoaldosternoism?
Inadequate release of aldosterone due to defects in aldosterone synthesis or destruction of adrenal cortex
How are steroid hormones produced?
Cholesterol —> Cholesterol desmolase —> Pregnenolone
How is aldosteron produced?
Pregnenolone —3b—> Progesterone —21–> DOC —11–> Corticosterone —18–> 18-OH Corticosterone —18-oxidase—>
Aldosterone
How is cortisol produced?
Pregnenolone —3b—>
Progesterone —17–>
17-OH Progesterone —21–>
11-Deoxycortisol —11–>
Cortisol
What is DOC?
A weak mineralocorticoid (aldosterone)
How are androgens produced?
Pregnenolone —3b—>
Progesterone —17, 20 —> Dehydroepiandrosterone (DHEA) —3B—>
Androstenedione
What is the function of 11-beta-HSD2?
What can inhibit it??
Protects mineralocorticoid receptor from activation by cortisol
Inhibited by black licorice
How will enzyme deficiencies in steroid biosynthesis pathways ALL present?
Enlargement of adrenal glands (adrenal hyperplasia)
Bc of increased ACTh stimulation and low cortisol = no negative feedback
How will an enzyme deficiency of
17alpha present?
High aldosterone HIGH BP (See above) LOW K (see above) Low cortisol Low sex hormones
Low androstenedione (precursor to androgens)
Males - in descending testes
Females - lack of secondary sexual development
How will an enzyme deficiency of
21-beta present?
LOW aldosterone
—> low BP
—> high K
High sex hormones
Low cortisol
Increased renin activity (trying to get BP up)
Increased 17-hydroxy-progesterone (step in cortisol production that requires 21 next)
Salt wasting in infants
Precocious puberty
Virilization
-what is the most common enzyme deficiency in the steroid biosynthesis pathway?
21-beta
How will an enzyme deficiency of
11-beta present?
Affects all pathways
Low aldosterone
HIGH DOC (precursor to aldosterone)
—> HIGH BP
—> LOW K
Low cortisol
High sex hormones
Decreased renin activity (bc BP is high)
Virilization
How much Epinephrine is produced c0mpared to norepinephrine?
E: 80%
NE: 20%
What is the synthesis of catecholamines under?
2 things
Sympathetic activity
CRH-ACTH-Cortisol axis
How does cortisol control the synthesis of Catecholamines?
Cortisol upregulates PNMT enzyme that causes NE—> E
What is the synthesis pathway for catelcholamines?
- hydroxylation of Tyrosine by tyrosine hydroxylase
◦ Produces DOPA - DOPA —> DA (via Aromatic amino acid de Carboxylase - AADC)
- DA transported into secretory vesicle (chromaffin granule)
- DA —> NE (via Dopamine beta-hydroxylase - DBH) INSIDE CELL
• Most of the NE diffuses out by facilitated transport - NE —> E (via methylation by PNMT)
OUTSIDE CELL - E transported back into granule by VMATS (Vesicular monoamine transporters)
What is the rate limiting step of catelcholamine synthesis?
Step 1.
Tyrosine —tyrosine hydroxylase —> DOPA
How are molecules of E and NE stored?
in Chromaffin granule w/ ATP, Ca, and chromogranin proteins
What are chromogranins?
multimolecule complexes
‣ Decrease osmotic burden of storing E w/in chromaffin granules
What can circulating chromogranins be used as a marker for?
sympathetic paragnglion derived tumor (paragangliomas)
What signals for secretion of catelcholamines?
Sympathetic innervation via ACh
How long do catelcholamines act for?
~10 secodns
How are NE and E degraded?
Via COMT or MAO
If NE or E are degraded by MAO, what are the next steps?
Makes them into dihydroxymandelic acid
—> COMT —> Vanyllylmandelic acid in urine
If E gets degraded by COMT, what is its byproduct?
Metanephrine
—> MAO —> Vanillylmandelic acid in urine
If NE gets degraded by COMT, what is its byproduct?
Normetanephrine
—> MAO —> Vanillylmandelic acid in urine
What can be measured in urine to asses catelcholamine production?
Vanillylmandelic acid
What can elevated levels of metabolic byproducts and catecholamines diagnose?
Pheochromocytoma
What are the actions of epinephrine?
What receptor does it prefer?
◦ Reponder to stress
‣ I.e. hypoglycemia/exercise
◦ influences energy metabolism and cardiac output
-increases lipolysis, Ca Lori genesis, insulin secretion, glucagon secretion, muscle potassium uptake, cardiac contractility, heart rate, conduction velocity,
Decrease BP, glucose utilization
◦ Higher affinity for Beta -2 receptor
What receptors does NE prefer?
Actions?
Higher affinity for alpha receptors and beta 3 receptors
Increase gluconeogenesis, glycogenolysis, cardiac contractility, arteriolar vasoconstriction, blood pressure, sphincter contract
Decrease insulin secretion
What is pheochromocytoma?
Tumor of chromaffin cells that secrete xs catelcholamines
Most tumors = benign, unilateral adrenal tumors
What can pheochromocytoma cause?
Hypertension
Headaches
Palpitation
Sweating
Due to catelcholamines stimulating both alpha and beta adrenergic receptors
How does short term stress act on the HP-Adrenal axis?
Sympathetic innervation —> medulla Will secrete catecholamines
Increasing BP, HR, glycogenolysis, metabolic rate
Dilation of bronchioles, reduced blood flow to digestive system
How does long term stress act on the HP-Adrenal axis?
ACTH —> Adrenal cortex
Release of steroid hormones
Aldosterone: raises BP by retaining Na and H20
Cortisol: proteins and fat broken down for energy, increase in blood glucose, suppression of immune system (cytokines)
