Download MBBS (Bachelor of Medicine and Bachelor of Surgery) Latest Adrenal Cortex Lecture PPT
ADRENAL CORTEX
Anatomy of Adrenal gland
? The 2 adrenal gland wt. about 4gm lies at the
superior pole of the two kidney.
? Each gland composed of two distinct parts ,
the adrenal medulla, and the adrenal cortex.
? Adrenal medulla secretes Catecholamines
and Adrenal cortex steroid hormones.
? Blood supply by superior, middle and inferior
adrenal arteries
Histology and Develpoment
? The adrenal cortex in adult comprises 3
distinct zone:
? Zona glomerulosa(outermost), 15%
? Zona fasciculata(middle zone),50%
? Zona reticularis(innermost zone),7%
? The adrenocortical cells contains abundant
lipids, especially in outer portion of zona fasci
culata.
Section of Adrenal gland showing
medulla & zones of cortex
Contd.
? Fetal adrenal gland begins developing 3-4 wks of gestation
? At 6-8wks ,there is rapid enlargement of adrenal gland.
? Cells of cortex differentiate to form `fetal zone' and an
outer layer called definitive zone
? Fetal zone is capable of synthesizing steroids at 8-10 wks.
? At birth : Fetal cortex, 80% of the gland with 20% true
cortex.
? Within 1 months after birth: fetal cortex 50% and adrenal
medulla increases in size.
? ACTH regulates growth and development of adrenal gland
Adrenal cortex
? Secretes two major hormones
:mineralocorticoids and glucocorticoids, and
small amounts of sex steroids especially
androgenic hormones.
Structure of Adrenocortical hormones
? The hormones of adrenal cortex are
derivatives of cholesterol.
? Contains Cyclopentanoperhydre
phenanthrene nucleus like cholesterol, bile
acid ,vit.D, ovarian and testicular steroid
Contd.
? Gonadal and adrenocortical steroids are of 3
types: C21,C19,C18 steroids
? The adrenal cortex secretes primarily C21 &C19
steroids.
? C19 steroids have keto group at position 17 ,so
called 17-ketosteroid,they have androgenic
activity.
? C21 steroid have hydroxyl group at position 17 in
addition to side chain , hence called 17-
hydroxysteroid.have both moneralocorticoid and
glucocorticoid activity.
Basic structure of adrenocortical and
gonadal hormone
Steroid Biosynthesis
? The precursor of all steroids is cholesterol.
? Some is synthesized, but most are taken up
from LDL in the circulation.
? LDL receptors are especially abundant in
adrenocortial cells.
? ACTH facilitates cortisol synthesis by
activating enzyme cholesterol ester hydrolase.
Synthesis of mineralocorticoids
? Mineralocorticoids are formed in zona
glomerulosa of adrenal cortex.
? The conversion of cholesterol to pregnenolone is
stimulated by ACTH and angiotensin II.
? Aldosterone synthesis is limited to this zone b'coz
aldosterone synthase is found only in cells of
zona glomerulosa.
? Zona glomerulosa lacks enzyme 17-hydroxylase,
hence glucocorticoids and sex steroid are not
formed here.
Cholesterol
ACTH,ANG II
Pregnenolone
Progesterone
Deoxycorticosterone
Corticosterone
Aldosterone synthase,
18-Hydroxycorticosterone
Ald . synthase
Aldosterone
Function of mineralocorticoid-
Aldosterone
? Aldosterone is very potent and accounts for
about 90% of mineralocorticoid activity.
? Deoxycorticosterone is 1/30 as potent as
aldosterone ,but very small quantity secreted..
? Aldosterone increases renal tubular
reabsorbtion of Na+ and secretion of K+
especially in the principal cells (P cells)of
collecting tubules, and lesser extent in DT and
collecting ducts.
Functions of aldosterone
? Aldosterone is very essential for life.
? It maintains the osmolarity and volume of ECF.
? Main function of aldosterone are:
?Reabsorbtion of Na+ from renal tubules
?Excretion of K+ and through renal tubules
? Secretion of H+ into renal tubules.
?Also es Na+ reabsorbtion from sweat ,
Saliva , and contents of colon.
MOA Of Aldosterone
? Like other steroids. Aldosterone binds to
cytoplasmic receptor.
? HR complex moves to nucleus.
? Transcription of mRNA.
? production of proteins that alter cell functions.
Contd.
Aldosterone stimulated proteins leads to:
Genomic actions like
? es activity of ENaCs (epithelial Na+ channels),a
rapid action.
? Slower effect is that it increases the synthesis of
ENaCs , by ing the mRNA activity for synthesis of
proteins.
? es insertion of these channels on cell membrane.
? Gene activated by aldostrone is sgk gene ,a serine-
threonine protein kinase.
? Non-Genomic Actions: mediated by IP3
? Nongenomic actions occurs rapidly.
? It es activity of Na+K+exchangers,which
Increases intracellular accumulation of Na+
What is Aldosterone escape
phenomenon ?
? When there is aldosterone excessive
secretion the ECF expands due to Na+ and
water retention , but when the ECF expansion
passes a certain point ,Na+ excretion is
usually ed inspite of continued action of
mineralocorticoids on renal tubules.
Mechanism
? Mineralocorticoid/aldosterone excess.
? ECF expansion(due to Na+ & water retension).
? BP rises leading to distention of atria.
? Secretion of ANP(atrial natriuretic peptide).
? ANP causes profound natriuresis and diuresis.
Contd.
? ECF returns back to normal.
?Due to this phenomenon edema is not
produced by mineralocorticoids in normal
individual and in patients of
hyperaldosteronism.
Regulation of Aldosterone Secretion
? Aldosterone secretion is regulated mainly by
3 important stimuli:
1. ACTH
2. Angiotensin II
3. Plasma K+ conc.
RAAS system
RAAS system
? Angiotensinogen
Renin(JGA)
Angiotensin
ACE(lungs)
Angiotensin II
Adrenal cortex
Aldosterone
Na+ and water retention,es ECF volume
ACTH
? Cells of zona glomerulosa have ACTH
receptors.
? ACTH mediates aldosterone secretion by
cAMP& Protein kinase.
? Effect of ACTH on aldosterone secretion is
temporary , aldosterone secretion declines
even if ACTH secretion is elevated ,due to
decrease renin secretion.
Plasma K+ Conc.
? Plasma K+ level need increase only 1meq/L to
stimulate aldosterone secretion.
? Like angiotensin II, K+ stimulates the conversion
of cholesterol pregnenolone ,&
deoxycortecosteronealdosterone.
? ECF K+ Activate voltage gated Ca channel
cytosolic Ca
aldosterone secretion
Dysfunction Of Aldosterone
Primary
? Hypersecretion
Secondary
Primary Hyperaldosteronism
? The cause of excess aldosterone secretion is
due to adrenal disease : Adrenal adenoma
? Adrenal hyperplasia
?Adrenal carcinoma
Conn's Syndrome
? Major cause of primary hyperaldosteronism.
? Occurs due to the tumor(adenoma) of zona
glomerulosa of adrenal cortex.
? Clinical features: Hypertension
? Muscle weakness
? Polyuria
? Edema is absent
? Hypokalemia
? Hypernatremia
? Low renin level
? Metabolic alkalosis
Secondary Hyperaldosteronism
? ed aldosterone secretion is due to activation
of RAAS .
? Occurs in cirrhosis, heart failure, nephrosis,
renin secreting tumor.
? renin in plasma.
? Edema is a usual feature.
Hyposecretion of Aldosterone
Addison's disease/Primary Adrenal Insufficiency
? Occurs due to autoimmune inflammation of
adrenal gland, tuberculosis.
? Deficiency of mineralocorticoids occurs.Leading
to hyponatremia , hyperkalemia, ECF,
metabolic acidosis, cardiac output,BP.
? Also there is glucocorticoid deficiency, so patient
is unable to maintain blood glucose conc.
Contd.
? Circulating ACTH levels are elevated, leading to
melanin deposition , so there is pigmentation of
palm creases, lips ,gums etc.
? Untreated patient may die in 4days-2wks.
? Treatment: Mineralocorticoid & Glucocorticoids
replacement.
?Addisonian Crisis : Glucocorticoid level does not
during stress in addison's disease patients e.g.;
trauma, surgery etc leading to severe debility.
Contd.
? Secondary adrenal insufficiency: caused
by pituitary disease and decrease ACTH
secretion.
? Tertiary adrenal insufficiency : caused by
hypothalamic disorders disrupting CRH
release.
? Pseudohypoaldosteronism : produced when
there is resistence to action of aldosteronism.
This post was last modified on 30 November 2021