Endocrine Physiology The Adrenal Gland 1

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Endocrine PhysiologyThe Adrenal Gland1
Dr. Khalid AlrRegaiey
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Adrenal (Suprarenal) Glands

• Adrenal glands paired, pyramid-shaped organs
  atop the kidneys
• Weigh 6-10 g.
• Structurally and functionally, they are two
  glands in one
• Adrenal cortex (80-90) glandular tissue derived
  from embryonic mesoderm
• Adrenal medulla (10-20) formed from neural
  ectoderm, can be considered a modified
  sympathetic ganglion

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Adrenal Cortex

• Synthesizes and releases steroid hormones
  (corticosteroids)
• Different corticosteroids are produced in each of
  the three layers
• Zona glomerulosa mineralocorticoids (mainly
  aldosterone)
• Zona fasciculata glucocorticoids Androgens
  (mainly cortisol and corticosterone)
• Zona reticularis gonadocorticoids
  glucocorticoids (mainly dehydroepiandrosterone
  DHEA)

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Adrenal Cortex
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HPA Axis
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Steroid Hormones Structure
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Steroid Hormones Synthesis

• Steroids are derivatives of cholesterol
• Cholesterol is from the lipid droplets in
  cortical cells (cholesterol esters in LDL)
• Removed cholesterol is replenished by cholesterol
  in LDL in blood or synthesized from acetate

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Steroid Hormones Synthesis (Cont.)

• Steroid hormones are synthesized and secreted on
  demand (not stored)
• The first and rate-limiting step in the synthesis
  of all steroid hormones is conversion of
  cholesterol to pregnenolone by the enzyme
  cholesterol dismolase (aka cholesterol side chain
  cleavage (SCC) enzyme
• Newly synthesized steroid hormones are rapidly
  secreted from the cell
• Following secretion, all steroids bind to some
  extent to plasma proteins CBG and albumin

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Steroidogenesis
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Genetic Defects in Adrenal Steroidogenesis

• Congenital adrenal hyperplasia

ACTH
?Adrenal hyperplasia
cortisol

• 21-hydroxylase (P450c21) deficiency
• cortisol, corticosterone, and aldosterone
  deficiency
• ACTH Adrenal hypertrophy and high
  amounts of androgen
• Virilization of female (masculanization)

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Congenital Adrenal Hyperplasia 21ß- Hydroxylase
Deficiency
17, 20 Lyase (P450 c17)
17a-Hydroxylase (P450 c17)
Cholesterol
ACTH
Cholesterol desmolase (P450 scc)
Pregnenolone
17-Hydroxypregnenolone
Dehydroepiandrosterone
3b-Hydroxysteroid dehydrogenase
17-Hydroxyprogesterone
Progesterone
Androstenedione
21b-Hydroxylase (P450 c21)
11-Deoxycortisol
11-Deoxycorticosterone
Testosterone
11b-Hydroxylase (P450 c11)
Estradiol
Cortisol
Corticosterone
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Congenital Adrenal Hyperplasia 11ß- Hydroxylase
Deficiency
17, 20 Lyase (P450 c17)
17a-Hydroxylase (P450 c17)
Cholesterol
ACTH
Cholesterol desmolase (P450 scc)
17-Hydroxypregnenolone
Pregnenolone
Dehydroepiandrosterone
3b-Hydroxysteroid dehydrogenase
Progesterone
17-Hydroxyprogesterone
Androstenedione
21b-Hydroxylase (P450 c21)
11-Deoxycortisol
11-Deoxycorticosterone
Testosterone
11b-Hydroxylase (P450 c11)
Estradiol
Corticosterone
Cortisol
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Steroid Hormones Action
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Mineralocorticoids

• Synthesized in zona glomerulosa
• Regulate the electrolyte concentrations of
  extracellular fluids
• Aldosterone most important mineralocorticoid
• Maintains Na balance by reducing excretion of
  sodium from the body

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Mineralocorticoids Aldosterone

• A steroid hormone.
• Essential for life.
• Responsible for regulating Na reabsorption in
  the distal tubule and the cortical collecting
  duct
• Target cells are called principal (P) cell.
• It also affects Na reabsorption by sweat,
  salivary and intestinal cells.

Stimulates synthesis of more Na/K-ATPase pumps.
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Aldosterone contin.

• Aldosterone exerts the 90 of the
  mineralocorticoid activity.
• Cortisol also have mineralocorticoid activity,
  but only 1/400th that of aldosterone.
• - Secreted by Zona glomerulosa.

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Corticosteroids Their Relative Glucocorticoid
Mineralocorticoid Activities Compared to Cortisol
Average Plasma Concentration (free and
bound, µg/100 ml)
Average Amount Secreted (mg/24 hr)
Glucocorticoid Activity
Mineralocorticoid Activity
1 15.0 3000 100 __
1.0 0.8 __ __ 125
1 0.3 0.3 0.2 __ 0.7 4 5 30 10
15 3 0.15 0.2 20 __ __ __ __ __
12 0.4 0.006 0.006 175 __ __ __ __ __
Steroids Adrenal Steroids Cortisol Corticost
erone Aldosterone Deoxycorticosterone Dehydropiand
rosterone Synthetic Steroids Cortisone Prednisolon
e Methylprednisone Dexamethasone 9a-fluorocortisol
Table 77-1, Guyton Hall
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Aldosterone Actions

• Maintains extracellular fluid volume by
  conserving body sodium. Aldosterone stimulates
  sodium potassium transport in sweat glands,
  salivary glands, intestinal epithelial cells.

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Actions of Aldosterone

• Stimulates sodium reabsorption by distal tubule
  and collecting duct of the nephron and promotes
  potassium and hydrogen ion excretion
• Increases transcription of Na/K pump
• Increases the expression of apical Na channels
  and an Na/K/Cl cotransporter
• By osmosis, water is also retained which expands
  ECF volume

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Aldosterone Actions

• Aldosterone stimulates the active secretion of
  potassium from the tubular cell into the urine.
• Most potassium that is excreted daily results
  from distal tubular secretion.
• Hence aldosterone is critical for disposal of
  daily dietary potassium load at normal plasma
  potassium concentrations.
• Stimulates secretion of H by the kidney.

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Regulation of Aldosterone Release
1. Increased potassium ion concentration in the
extracellular fluid greatly increases
aldosterone secretion. 2. Increased activity
of the renin-angiotensin system (increased levels
of angiotensin II) also greatly increases
aldosterone secretion. 3. Increased sodium ion
concentration in the extracellular fluid very
slightly decreases aldosterone secretion. 4.
ACTH from the anterior pituitary gland is
necessary for aldosterone secretion but has
little effect in controlling the rate of
secretion.
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Regulation of Aldosterone Release
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Renin-angiotensin-aldosterone system

• Principal factor controlling Ang II levels is
  renin release.
• Decreased circulating volume stimulates renin
  release via
• - Decreased BP (symp effects on JGA).
• Decreased NaCl at macula densa (NaCl sensor)
• - Decreased renal perfusion pressure (renal
  baroreceptor)

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Hypoalsosteronism

• Lack of aldosterone
• Increased sodium, chloride, water loss
• Decrease ECF volume
• Hyperkalemia
• Mild acidosis
• Plasma sodium decreases and may lead to
  circulatory collapse. Decrease cardiac output
  shock - death within 4 days to a 2 weeks if not
  treated.
• Cardiac toxicity

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Hyperaldosteronism

• Hyperaldosteronism can be caused by
• Primary overproduction of aldosterone in
  conditions such as Conns syndrome.
• Conditions of low cardiac output are also known
  to stimulate synthesis of aldosterone.
• Both conditions result in sustained hypertension.
  

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Clinical features of Hyperaldosteronism

• Hypertension.
• Hypokalemia
• Nocturnal polyuria polydipsia
• Increased tubular (intercalated cells) hydrogen
  ion secretion, with resultant mild alkalosis.
• Neuromuscular manifestations
• weakness, paresthesia
• intermittent paralysis

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Overproduction of aldosterone

• treatment
• surgical for adenoma
• medical with Spironolactone