The Adrenal Glands Part 1

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The Adrenal GlandsPart 1

• ERM Lecture
• 4/ 2007
• Steven Chessler M.D., Ph.D.

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• Anatomy of the adrenal glands
• Hypothalamic Pituitary Adrenal Axis
• Renin-angiotensin system
• Steroid hormones
• Congenital adrenal hyperplasia (CAH)
• Adrenal disorders
• Adrenal hyperfunction (Cushings syndrome)
• Adrenal insufficiency (Addisons disease and
  others)
• Pheochromocytoma (adrenal medulla)

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The Adrenal Glands
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Adrenal Cross Section
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Zones of the Adrenal Cortex
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Adrenal Zonation and Vasculature
-blood flow -steroid gradient
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Overview Hypothalamic-Pituitary-Adrenal (HPA)
Axis
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PROCESSING OF POMC IN THE PITUITARY ACTH (and
MSH, beta-endorphin)
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Addisons Disease effect of MSH activity
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The HPA Axis and the Stress Response

• Glucocorticoids trigger the release of sugar from
  body stores to provide quick energy for fight or
  flight.
• Injected into the brain in animals, CRH causes
  arousal and behavioral changes suggesting fear or
  emotional distress.
• Beta-endorphin (like ACTH a part of POMC)
  partially antagonizes these responses.

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• My mind sent a message to my hypothalamus, and
  told it to release the hormone CRF into the short
  vessels connecting my hypothalamus and pituitary
  gland.
• The CRF inspired my pituitary gland to dump the
  hormone ACTH into my bloodstream. My pituitary
  had been making and storing ACTH for just such an
  occasion.
• And some of the ACTH in my bloodstream reached
  the outer shell of my adrenal gland, which had
  been making glucocorticoids for emergencies.
  My adrenal gland added the glucocorticoids to my
  bloodstream. They went all over my body,
  changing glycogen into glucose. Glucose was
  muscle food. It would help me fight like a
  wildcat or run like a deer.
• -Kurt Vonegut, Jr., Breakfast of Champions

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Adrenal medulla also participates in stress
response
Adrenal Gland Glomerulosa Fasciculata Reticularis
Medulla
1. Efferent sympathetic inflow 2. Cortisol-rich
blood ? epinephrine release
Kidney
BDA
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Cortisol and epinephrine (adrenaline)

• Fight or flight hormones
• Secretion increased 4-5 fold with marked
  stress -emotional or physical
• Catabolic
• Support/ defend blood pressure
• Supply energy, e.g. glucose fatty
  acids -usually at the expense of anabolic
  processes, e.g. protein synthesis, fuel
  storage and growth

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Source of plasma catecholamines

• Norepinephrine
• Almost all from sympathetic nerve fibers
• Epinephrine
• Almost all from adrenal medulla (85)

BDA
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Physiological Effects of Glucocorticoids
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The Hypothamic-Pituitary-Adrenal Axis
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• Anatomy of the adrenal glands
• Hypothalamic Pituitary Adrenal Axis
• Renin-angiotensin-aldosterone system
  (Kidney-Adrenal Axis)
• Steroid hormones
• Congenital adrenal hyperplasia (CAH)
• Adrenal disorders
• Adrenal hyperfunction
• Adrenal insufficiency
• Pheochromocytoma (adrenal medulla)

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Components of RAA axis

• Renin
• Acts to start cascade
• Angiotensin (II)
• Aldosterone

BDA
(slide by Brad Anawalt, M.D.)
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Function of R-A-A axis

• Responds to changes in blood pressure sensed at
  the kidney
• ? body Na content and blood volume
• K homeostasis

(slide by Brad Anawalt, M.D.)
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Glomeruli
(Modified from Ham AW. Histology. Philadelphia
JB Lippincott, 1969. by A. Dubrow and L.
Desimone)
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Glomeruli
Renal sympathetic nerves
U
JG cells
Efferent arteriole
Afferent arteriole
(slide by Brad Anawalt, M.D.)
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Stimulators of Renin Release

• ? sympathetic/adrenergic activity
• ? renal perfusion pressure
• ? serum K
• ? urinary lumen Na , macula densa

(B. Anawalt, M.D.)
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Angiotensin II increases blood pressure

• vasoconstriction
• - (direct effect on BP)
• aldosterone
• - (indirect effect on BP)

BDA
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Aldosterone
BDA
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Renin-Angiotensin-Aldosterone Axis
?
blood volume UNa near macula densa
BDA
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Summary function of R-A-A axis

• Initiate cascade to defend blood pressure
• (renin)
• ? body Na content and blood volume
• (aldosterone)
• ? arterial BP
• (aldosterone angiotensin II )
• K homeostasis
• (aldosterone)

(slide by Brad Anawalt, M.D.)
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11b-Hydroxysteroid Dehydrogenase in
Aldosterone-Sensitive Tissues Modulation of
Cortisol Levels
11bHSD2

• Cortisol binds mineralacortidoid receptor
• Impaired 11bHSD2 apparent mineralacorticoid
  excess -example licorice
• Synthetic glucorticoids lower mineralacorticoid
  activity

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• Anatomy of the adrenal glands
• Hypothalamic Pituitary Adrenal Axis
• Renin-angiotensin system
• Steroid hormone biosynthesis
• Congenital adrenal hyperplasia (CAH)
• Adrenal disorders
• Adrenal hyperfunction (Cushings syndrome)
• Adrenal insufficiency (Addisons disease and
  others)
• Pheochromocytoma (adrenal medulla)

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CAH 21-Hydroxylase Deficiency
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CAH 21-Hydroxylase Deficiency

• Salt-Wasting - severe hypotension often present
  from birth due to mineralocorticoid deficiency.
• Simple virilizing form less severe
  mineralocoritcoid deficiency.
• Nonclassical, late childhood and adult-onset
  form - Presents as androgen excess in females.
  May resemble Polycyctic Ovarian
  Syndrome. -hirsutism, acne, menstrual
  irregularity.

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Ambiguous Genitalia in Congenital Adrenal
Hyperplasia
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Neonatal Screening
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ACTH Stimulation test for 21-Hydroxylase
deficiency
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• Anatomy of the adrenal glands
• Hypothalamic Pituitary Adrenal Axis
• Renin-angiotensin system
• Steroid hormones
• Congenital adrenal hyperplasia (CAH)
• NEXT SESSION
• Adrenal disorders
• Adrenal hyperfunction (Cushings syndrome)
• Adrenal insufficiency (Addisons disease and
  others)
• Pheochromocytoma (adrenal medulla)