The document provides information on the embryology, anatomy, histology, physiology and functions of the adrenal glands. It discusses that the adrenal cortex and medulla develop from different embryonic origins and produce different hormones. The adrenal cortex consists of three zones that secrete mineralocorticoids, glucocorticoids and sex steroids. The adrenal medulla produces catecholamines. The hormones regulate sodium balance, stress response, growth and sexual development.
4. Embryology
• It is composed of 2 endocrine glands. Outer
cortex and inner medulla; each with distinct
embryologic, anatomic, histologic, and
secretory gland.
5. Adrenal cortex:
• Originate from mesodermal tissue near the
gonads on the Adrenogenital ridge.
• Around the 5th week
• Cortex divided into
– Thin definitive cortex:
• persist after birth to form adult cortex over first 03 years of
life.
– Thicker and inner fetal cortex:
• Produce adrenal steroids by 8th week of gestation.
• Involution (decrease in weight) after birth in 3rd postpartum.
• Ectopic adrenocortical tissue may be found in the
ovaries, spermatic cord, and testes
6. Adrenal medulla
• Ectodermal origin and
• Arises from neural crest 5th-6th WOG.
• Neural crest cells migrate to the paraaortic and
paravertebral areas and toward the medial aspect of
the developing cortex to form the medulla.
• Most extra-adrenal neural tissue regresses but may
persist at several sites.
– Adrenal medullary tissue also may be found in neck,
urinary bladder and para-aortic regions
• Some factors for adrenal development: IGF2; GIP;
dosage sensitve, sex reserve adrenal hypoplasia
(DAX1) gene.
7.
8. Anatomy
• Each kidney is caped by adrenal gland
• 2 Glands; Each 4 -5g.
• Right pyramidal.
• Left crescent shaped.
• Enclosed within Gerota’s( perirenal fascia)
• Composed of cortex and medulla.
• The adrenals are among the most highly perfused
organs in the body, receiving 2000 mL/kg/min of
blood, after only the kidney and thyroid.
13. Artery supply: 03 arteries
– Superior adrenal arteries derived from inferior
Phrenic artery
– Middle adrenal arteries derived from the aorta itself
– Inferior adrenal arteries derived from the renal
artery.
• Note: arteries divide into about 50 arterioles to form rich plexus
beneath glandular capsule require careful dissection and ligation
during adrenalectomy.
Lymphatics:
• The lymphatic vessels accompany the suprarenal vein and drain
into the lumbar lymph nodes.
14. Venous drainage:
– Right adrenal vein: short and drains into IVC
– Left adrenal vein: longer and empties into Lt
renal vein.
• Accessory vein:
– Rt side in 5-10% cases and drains into Rt. hepatic
or rt. renal vein.
– Lt accessory vein drains directly into lt. renal vein.
15. Histology
The adrenal cortex
• About 80% to 90% of the gland’s volume
• Appears yellow due to its high lipid content.
• Divided into three zones—the
– Zona glomerulosa: outer area, consist of small cell and produce
mineralocorticoid hormone and aldosterone
– Zona fasciculate: made up larger cell, appear foamy due to
multiple lipid inclusions. Produce glucocorticoid
– Zona reticularis cells are smaller. Secrete adrenal androgens
16. Adrenal medulla:
• Reddish-brown in color
• Constitutes up to 10% to 20%
of the gland’s volume
• The cells of the adrenal medulla
are arranged in cords and are
polyhedral in shape.
• Referred to as chromaffin cells
because they stain specifically
with chromium salts.
18. • Adrenal cortex produce steroid hormones,
• Cholesterol being precursor are generally
derived from plasma or synthesized in adrenal
cortex
19. Mineralocorticoids
• Major mineralcorticoids are 11- deoxycorticosterone
(DOC), and cortisol
• Aldosterone secretion is regulated primarily by the
renin-angiotensin system.
– Renin release from juxtaglomerular cells are stimulated by
• Decreased renal blood flow,
• Decreased plasma sodium,
• Increased sympathetic tone
• Angiotensin II, not only a potent vasoconstrictor, but also leads to
increased aldosterone synthesis and release.
• Stimulator of aldosterone synthesis
– Hyperkalemia (potent,)
– whereas ACTH, pituitary pro-opiomelanocortin, and
antidiuretic hormone are weak stimulators.
20. Kinetics
• Secreted at a rate of 50 to 250 μg/d (depending on sodium intake)
• Circulates in plasma
– Chiefly as a complex with albumin.
• Small amounts of the hormone bind to corticosteroid-binding globulin, and
– Circulates in a free form approximately 30% to 50% of secreted
aldosterone.
• Half-life of only 15 to 20 minutes.
• Excretion: rapidly cleared via the liver and kidney.
– A small quantity of free aldosterone also is excreted in the urine also.
• Mechanism of action: Mineralocorticoids cross the cell membrane
and bind to cytosolic receptors. The receptor-ligand complex
subsequently is transported into the nucleus where it induces the
transcription and translation of specific genes.
21. • Function:
– Mainly to increase sodium reabsorption and
potassium and hydrogen ion excretion at the
level of the renal distal convoluted tubule.
– Less commonly, aldosterone increases sodium
absorption in salivary glands and GI mucosal
surfaces.
22. Glucocorticoids:
• Cortisol, major glucocorticoids
• Regulated by ACTH secreted by the anterior pituitary,
which, in turn.
• 39-amino-acid protein, which is derived by cleavage from a larger
precursor, pro-opiomelanocortin.
• Has trophic action for the adrenal glands.
• Secretion may be stimulated by pain, stress, hypoxia, hypothermia,
trauma, and hypoglycemia.
• Secretion fluctuates, peaking in the morning and reaching nadir
levels in the late afternoon.
• Shows a diurnal variation in the secretion of cortisol,
– Peak cortisol excretion also occurring in the early morning
and
– Declining during the day to its lowest levels in the evening.
23. Kinetics
• Circulation in plasma
– Bound primarily to corticosteroid-binding globulin (75%) and albumin
(15%).
– Approximately 10% of circulating freely and is the biologically active
component.
• Half-life : 60 to 90 minutes
– Determined by the extent of binding and rate of inactivation.
• Converted to di- and tetrahydrocortisol and cortisone metabolites in
the liver and the kidney.
• Excretion: The majority (95%) of cortisol and cortisone metabolites
are conjugated with glucuronic acid in the liver, thus facilitating their
renal excretion.
– A small amount of unmetabolized cortisol is excreted unchanged in the
urine
24. Mechanism of action:
• Glucocorticoid hormones enter the cell and bind
cytosolic steroid receptors. The activated receptor-
ligand complex is then transported to the nucleus
where it stimulates the transcription of specific
target genes via a “zinc finger” DNA binding
element.
• Cortisol also binds the mineralocorticoid
receptor with an affinity similar to aldosterone.
• However, the specificity of mineralocorticoid action
is maintained by the production of 11β-
hydroxysteroid dehydrogenase, an enzyme that
inactivates cortisol to cortisone in the kidney
25.
26. Sex Steroids:
• Adrenal androgens are produced in the zona
fasciculata and reticularis from 17-
hydroxypregnenolone in response to ACTH
stimulation.
• They include
– Dehydroepiandrosterone (DHEA) and its sulfated
counterpart (DHEAS),
– Androstenedione, and
– Small amounts of testosterone and estrogen.
27. • Adrenal androgens are weakly bound to
plasma albumin.
• They exert their effects
– Major effects by peripheral conversion to the
more potent testosterone and dihydrotestosterone ,
– Also have weak intrinsic androgen activity.
• Androgen metabolites are conjugated as
glucuronides or sulfates.
• Excreted in the urine.
28. • Function:
– During fetal development, adrenal androgens
promote the formation of male genitalia.
– In normal adult males, the contribution of adrenal
androgens is minimal;
– They are responsible for the development of
secondary sexual characteristics at puberty.
– Adrenal androgen excess leads to
• Precocious puberty in boys and
• Virilization, acne, and hirsutism in girls and women.
30. • Catecholamine hormones: Epinephrine,
norepinephrine, and dopamine
• Produced in
• In the central and sympathetic nervous system
• The adrenal medulla.
• The substrate, tyrosine, is converted to catecholamines via a
series of steps
• Phenylethanolamine N-methyltransferase, which converts
norepinephrine to epinephrine, is only present in the
adrenal medulla and the organ of Zuckerkandl.
– Chromogranins: When catecholamines are stored in
granules in combination with other neuropeptides, ATP,
calcium, magnesium, and water-soluble proteins called
Chromogranins.
31. Secretion stimulated by
• Various stress stimulus.
• And mediated by the release of acetylcholine at preganglionic nerve
terminals.
– In circulation: are bound to albumin and other proteins.
– Excretion: Catecholamines are cleared by several
mechanisms including
• Reuptake by sympathetic nerve endings,
• Peripheral inactivation by catechol O-methyltransferase and
monoamine oxidase, and
• Direct excretion by the kidneys.
•
– Metabolism:
• Takes place primarily in the liver and kidneys.
• Leads to the formation of metabolites such as metanephrines,
normetanephrines, and VMA.
• which may undergo further glucuronidation or sulfation
before being excreted in the urine
32. Metabolism:
• Takes place primarily in the liver and kidneys.
• Leads to the formation of metabolites such as
metanephrines, normetanephrines, and VMA.
• which may undergo further glucuronidation or
sulfation before being excreted in the urine
33. Mechanism of action:
– Adrenergic receptors are transmembrane-spanning
molecules that are coupled to G proteins.
– Subdivided into α and β subtypes.
• The receptor affinities for
• α receptors are—epinephrine > norepinephrine>>
isoproterenol;
• β1 receptors—isoproterenol > epinephrine =
norepinephrine; ands
• β2 receptors—isoproterenol > epinephrine >>
norepinephrine.
•