Download MBBS Adrenal Cortex Lecture PPT

ADRENAL CORTEX
Anatomy of Adrenal gland

? The 2 adrenal gland wt. about 4gm lies at the

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superior pole of the two kidney.

? Each gland composed of two distinct parts ,

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the adrenal medulla, and the adrenal cortex.

? Adrenal medulla secretes Catecholamines

and Adrenal cortex steroid hormones.

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? Blood supply by superior, middle and inferior

adrenal arteries

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Histology and Develpoment

? The adrenal cortex in adult comprises 3

distinct zone:

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? Zona glomerulosa(outermost), 15%

? Zona fasciculata(middle zone),50%

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? Zona reticularis(innermost zone),7%

? The adrenocortical cells contains abundant

lipids, especially in outer portion of zona fasci

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culata.
Section of Adrenal gland showing

medulla & zones of cortex

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Contd.

? Fetal adrenal gland begins developing 3-4 wks of gestation

? At 6-8wks ,there is rapid enlargement of adrenal gland.

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? Cells of cortex differentiate to form `fetal zone' and an

outer layer called definitive zone

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? Fetal zone is capable of synthesizing steroids at 8-10 wks.

? At birth : Fetal cortex, 80% of the gland with 20% true

cortex.

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? Within 1 months after birth: fetal cortex 50% and adrenal

medulla increases in size.

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? ACTH regulates growth and development of adrenal gland
Adrenal cortex

? Secretes two major hormones

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:mineralocorticoids and glucocorticoids, and

small amounts of sex steroids especially

androgenic hormones.

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Structure of Adrenocortical hormones

? The hormones of adrenal cortex are

derivatives of cholesterol.

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? Contains Cyclopentanoperhydre

phenanthrene nucleus like cholesterol, bile

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acid ,vit.D, ovarian and testicular steroid
Contd.

? Gonadal and adrenocortical steroids are of 3

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types: C21,C19,C18 steroids

? The adrenal cortex secretes primarily C21 &C19

steroids.

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? C19 steroids have keto group at position 17 ,so

called 17-ketosteroid,they have androgenic

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activity.

? C21 steroid have hydroxyl group at position 17 in

addition to side chain , hence called 17-

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hydroxysteroid.have both moneralocorticoid and

glucocorticoid activity.
Basic structure of adrenocortical and

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gonadal hormone
Steroid Biosynthesis

? The precursor of all steroids is cholesterol.

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? Some is synthesized, but most are taken up

from LDL in the circulation.

? LDL receptors are especially abundant in

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adrenocortial cells.

? ACTH facilitates cortisol synthesis by

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activating enzyme cholesterol ester hydrolase.

Synthesis of mineralocorticoids

? Mineralocorticoids are formed in zona

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glomerulosa of adrenal cortex.

? The conversion of cholesterol to pregnenolone is

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stimulated by ACTH and angiotensin II.

? Aldosterone synthesis is limited to this zone b'coz

aldosterone synthase is found only in cells of

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zona glomerulosa.

? Zona glomerulosa lacks enzyme 17-hydroxylase,

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hence glucocorticoids and sex steroid are not

formed here.
Cholesterol

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ACTH,ANG II

Pregnenolone

Progesterone

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Deoxycorticosterone

Corticosterone

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Aldosterone synthase,

18-Hydroxycorticosterone

Ald . synthase

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Aldosterone
Function of mineralocorticoid-

Aldosterone

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? Aldosterone is very potent and accounts for

about 90% of mineralocorticoid activity.

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? Deoxycorticosterone is 1/30 as potent as

aldosterone ,but very small quantity secreted..

? Aldosterone increases renal tubular

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reabsorbtion of Na+ and secretion of K+

especially in the principal cells (P cells)of

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collecting tubules, and lesser extent in DT and

collecting ducts.
Functions of aldosterone

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? 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

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?Excretion of K+ and through renal tubules

? Secretion of H+ into renal tubules.

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?Also es Na+ reabsorbtion from sweat ,

Saliva , and contents of colon.
MOA Of Aldosterone

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? Like other steroids. Aldosterone binds to

cytoplasmic receptor.

? HR complex moves to nucleus.

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? Transcription of mRNA.

? production of proteins that alter cell functions.

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Contd.

Aldosterone stimulated proteins leads to:
Genomic actions like
? es activity of ENaCs (epithelial Na+ channels),a

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rapid action.

? Slower effect is that it increases the synthesis of

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ENaCs , by ing the mRNA activity for synthesis of

proteins.

? es insertion of these channels on cell membrane.

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? Gene activated by aldostrone is sgk gene ,a serine-

threonine protein kinase.

? Non-Genomic Actions: mediated by IP3

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? Nongenomic actions occurs rapidly.

? It es activity of Na+K+exchangers,which

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Increases intracellular accumulation of Na+
What is Aldosterone escape

phenomenon ?

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? When there is aldosterone excessive

secretion the ECF expands due to Na+ and

water retention , but when the ECF expansion

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passes a certain point ,Na+ excretion is

usually ed inspite of continued action of

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mineralocorticoids on renal tubules.
Mechanism

? Mineralocorticoid/aldosterone excess.

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? ECF expansion(due to Na+ & water retension).

? BP rises leading to distention of atria.

? Secretion of ANP(atrial natriuretic peptide).

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? ANP causes profound natriuresis and diuresis.
Contd.

? ECF returns back to normal.

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?Due to this phenomenon edema is not

produced by mineralocorticoids in normal

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individual and in patients of

hyperaldosteronism.
Regulation of Aldosterone Secretion

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? Aldosterone secretion is regulated mainly by

3 important stimuli:

1. ACTH

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2. Angiotensin II

3. Plasma K+ conc.

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RAAS system
RAAS system

? Angiotensinogen

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Renin(JGA)

Angiotensin

ACE(lungs)

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Angiotensin II

Adrenal cortex

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Aldosterone

Na+ and water retention,es ECF volume
ACTH

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? Cells of zona glomerulosa have ACTH

receptors.

? ACTH mediates aldosterone secretion by

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cAMP& Protein kinase.

? Effect of ACTH on aldosterone secretion is

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temporary , aldosterone secretion declines

even if ACTH secretion is elevated ,due to

decrease renin secretion.

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Plasma K+ Conc.

? Plasma K+ level need increase only 1meq/L to

stimulate aldosterone secretion.

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? Like angiotensin II, K+ stimulates the conversion

of cholesterol pregnenolone ,&

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deoxycortecosteronealdosterone.
? ECF K+ Activate voltage gated Ca channel

cytosolic Ca

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aldosterone secretion
Dysfunction Of Aldosterone

Primary
? Hypersecretion

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Secondary
Primary Hyperaldosteronism
? The cause of excess aldosterone secretion is

due to adrenal disease : Adrenal adenoma

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? Adrenal hyperplasia

?Adrenal carcinoma
Conn's Syndrome

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? Major cause of primary hyperaldosteronism.
? Occurs due to the tumor(adenoma) of zona

glomerulosa of adrenal cortex.

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? Clinical features: Hypertension

? Muscle weakness

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? Polyuria

? Edema is absent

? Hypokalemia

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? Hypernatremia
? Low renin level

? Metabolic alkalosis

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Secondary Hyperaldosteronism

? ed aldosterone secretion is due to activation

of RAAS .

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? Occurs in cirrhosis, heart failure, nephrosis,

renin secreting tumor.

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? renin in plasma.
? Edema is a usual feature.
Hyposecretion of Aldosterone

Addison's disease/Primary Adrenal Insufficiency

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? Occurs due to autoimmune inflammation of

adrenal gland, tuberculosis.

? Deficiency of mineralocorticoids occurs.Leading

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to hyponatremia , hyperkalemia, ECF,

metabolic acidosis, cardiac output,BP.

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? Also there is glucocorticoid deficiency, so patient

is unable to maintain blood glucose conc.

Contd.

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? Circulating ACTH levels are elevated, leading to

melanin deposition , so there is pigmentation of

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palm creases, lips ,gums etc.

? Untreated patient may die in 4days-2wks.
? Treatment: Mineralocorticoid & Glucocorticoids

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replacement.

?Addisonian Crisis : Glucocorticoid level does not

during stress in addison's disease patients e.g.;

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trauma, surgery etc leading to severe debility.


Contd.

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? Secondary adrenal insufficiency: caused

by pituitary disease and decrease ACTH

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secretion.

? Tertiary adrenal insufficiency : caused by

hypothalamic disorders disrupting CRH

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release.

? Pseudohypoaldosteronism : produced when

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there is resistence to action of aldosteronism.