Download 10-The Adrenal gland- Aldosterone 01-02-2016

Endocrine Physiology
The Adrenal Gland 1
Dr.Mouaadh abdelkarim
Assistant Professor of Physiology
Department of Physiology
2nd floor
Email: [email protected]
Tel: 0114671606
Adrenal (Suprarenal) Glands
• Adrenal glands are paired,
Cortex
Medulla
pyramid-shaped organs at the
top of 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
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)
Adrenal Gland
Guyton and Hall
Adrenal Cortex
Salt
Sugar
Sex
Guyton and Hall
HPA Axis
Guyton and Hall
Steroid Hormones: Structure
Guyton and Hall
Steroid Hormones Synthesis
• Steroids are derivatives of cholesterol
• Cholesterol is from the lipid droplets
in cortical cells
• Removed cholesterol is replenished by cholesterol
in LDL in blood or synthesized from acetate
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 (cholesterol side chain cleavage enzyme
(SCC))
• Newly synthesized steroid hormones are rapidly
secreted from the cell
• Following secretion, all steroids bind to some
extent to plasma proteins: CBG (corticosteroid
binding globulin) and albumin
Steroidogenesis: Steroidogenesis entails processes by which cholesterol is converted to
biologically active steroid hormones
Genetic Defects in Adrenal Steroidogenesis
• Congenital adrenal hyperplasias: Congenital adrenal
hyperplasia (CAH) are any of several autosomal recessive diseases resulting
from mutations of genes for enzymes mediating the biochemical steps of production
of cortisol from cholesterol by the adrenal glands (steroidogenesis).
cortisol
ACTH
ِAdrenal hyperplasia
Congenital adrenal hyperplasias
• 21-hydroxylase (P450c21) deficiency:
cortisol, corticosterone, and aldosterone
deficiency
*ACTH
Adrenal hypertrophy and high
amounts of androgen
* Virilization of female (masculanization)
Steroid Hormones: Action
Guyton and Hall
Hormones of adrenal cortex
production
mg/day
concentr.
ng/ml
activity
MINERAL.
activity
GLUCO.
aldosterone
0.05-0.15
0.15
90%
deoxycorticosterone
0.6
0.15
1/15
corticosterone
1-4
2-4
1/50
4%
cortisol
8-25
40-180
1/400
95%
DHEA
7-15
5
1- Cortisol is at 1000 fold higher
concentrations than aldosterone
2- Corticosterone >>>>aldosterone
3- Cortisol binds well to the mineralocorticoid
receptor
Mineralocorticoids:
Aldosterone
• A steroid hormone.
• Essential for life.
• Synthesized in zona glomerulosa
• 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.
Mineralocorticoids:
Aldosterone
• Aldosterone secretion is stimulated by:
• Decreasing blood volume or pressure (reninangeotensin system).
• Rising blood levels of K+
• Low blood Na+
• ACTH
Aldosterone synthesis
• Voltage-sensitive calcium channels open and the intracellular calcium
concentration increases—activating calcium calmodulin kinase.
• Calcium channel blockers inhibit aldosterone synthesis.
• Aldosterone levels fluctuate diurnally—
highest concentration being at 8 AM, lowest
at 11 PM, in parallel to cortisol rhythms.
The Four Mechanisms of Aldosterone Secretion
• Renin-angiotensin mechanism – kidneys release
renin, which stimulates angiotensin II that in
turn stimulates aldosterone release
• Plasma concentration of potassium and sodium–
directly influences the zona glomerulosa cells
• ACTH – causes small increases of aldosterone
during stress
• Atrial natriuretic peptide (ANP) – inhibits activity
of the zona glomerulosa
The Four Mechanisms of Aldosterone Secretion
Guyton and Hall
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
• Expands ECF volume
•
Aldosterone binds to the mineralocorticoid receptor in
target cells and affects transcriptional changes typical of
steroid hormone action.
•
The kidney is the major site of mineralocorticoid activity.
Aldosterone: Role in diseases
• Complete failure to secrete aldosterone leads to
death (dehydration, low blood volume).
• Hyperaldosterone states: Contribute to
hypertension associated with increased blood
volume.
Overproduction of aldosterone
• primary causes, ie. Conn’s syndrome
• adenoma, nodular hyperplasia of zona
glomerulosa
• secondary
• cirrhosis, ascites, nephrotic syndrome
• symptoms, signs
• headache, hypokalemia causing muscle
weakness, hypernatremia, hypervolemia,
nocturnal polyuria, hand cramping
J winker
Overproduction of aldosterone
• treatment
• surgical for adenoma
• Spironolactone
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