superior pole of the two kidney.
? Each gland composed of two distinct parts ,
--- Content provided by FirstRanker.com ---
the adrenal medulla, and the adrenal cortex.? Adrenal medulla secretes Catecholamines
and Adrenal cortex steroid hormones.
--- Content provided by FirstRanker.com ---
? Blood supply by superior, middle and inferior
adrenal arteries
--- Content provided by FirstRanker.com ---
Histology and Develpoment? The adrenal cortex in adult comprises 3
distinct zone:
--- Content provided by FirstRanker.com ---
? Zona glomerulosa(outermost), 15%
? Zona fasciculata(middle zone),50%
--- Content provided by FirstRanker.com ---
? Zona reticularis(innermost zone),7%? The adrenocortical cells contains abundant
lipids, especially in outer portion of zona fasci
--- Content provided by FirstRanker.com ---
culata.
Section of Adrenal gland showing
medulla & zones of cortex
--- Content provided by FirstRanker.com ---
Contd.? Fetal adrenal gland begins developing 3-4 wks of gestation
? At 6-8wks ,there is rapid enlargement of adrenal gland.
--- Content provided by FirstRanker.com ---
? Cells of cortex differentiate to form `fetal zone' and an
outer layer called definitive zone
--- Content provided by FirstRanker.com ---
? Fetal zone is capable of synthesizing steroids at 8-10 wks.? At birth : Fetal cortex, 80% of the gland with 20% true
cortex.
--- Content provided by FirstRanker.com ---
? Within 1 months after birth: fetal cortex 50% and adrenal
medulla increases in size.
--- Content provided by FirstRanker.com ---
? ACTH regulates growth and development of adrenal glandAdrenal cortex
? Secretes two major hormones
--- Content provided by FirstRanker.com ---
:mineralocorticoids and glucocorticoids, andsmall amounts of sex steroids especially
androgenic hormones.
--- Content provided by FirstRanker.com ---
Structure of Adrenocortical hormones? The hormones of adrenal cortex are
derivatives of cholesterol.
--- Content provided by FirstRanker.com ---
? Contains Cyclopentanoperhydre
phenanthrene nucleus like cholesterol, bile
--- Content provided by FirstRanker.com ---
acid ,vit.D, ovarian and testicular steroidContd.
? Gonadal and adrenocortical steroids are of 3
--- Content provided by FirstRanker.com ---
types: C21,C19,C18 steroids? The adrenal cortex secretes primarily C21 &C19
steroids.
--- Content provided by FirstRanker.com ---
? C19 steroids have keto group at position 17 ,so
called 17-ketosteroid,they have androgenic
--- Content provided by FirstRanker.com ---
activity.? C21 steroid have hydroxyl group at position 17 in
addition to side chain , hence called 17-
--- Content provided by FirstRanker.com ---
hydroxysteroid.have both moneralocorticoid and
glucocorticoid activity.
Basic structure of adrenocortical and
--- Content provided by FirstRanker.com ---
gonadal hormone
Steroid Biosynthesis
? The precursor of all steroids is cholesterol.
--- Content provided by FirstRanker.com ---
? Some is synthesized, but most are taken upfrom LDL in the circulation.
? LDL receptors are especially abundant in
--- Content provided by FirstRanker.com ---
adrenocortial cells.
? ACTH facilitates cortisol synthesis by
--- Content provided by FirstRanker.com ---
activating enzyme cholesterol ester hydrolase.Synthesis of mineralocorticoids
? Mineralocorticoids are formed in zona
--- Content provided by FirstRanker.com ---
glomerulosa of adrenal cortex.
? The conversion of cholesterol to pregnenolone is
--- Content provided by FirstRanker.com ---
stimulated by ACTH and angiotensin II.? Aldosterone synthesis is limited to this zone b'coz
aldosterone synthase is found only in cells of
--- Content provided by FirstRanker.com ---
zona glomerulosa.
? Zona glomerulosa lacks enzyme 17-hydroxylase,
--- Content provided by FirstRanker.com ---
hence glucocorticoids and sex steroid are notformed here.
Cholesterol
--- Content provided by FirstRanker.com ---
ACTH,ANG IIPregnenolone
Progesterone
--- Content provided by FirstRanker.com ---
Deoxycorticosterone
Corticosterone
--- Content provided by FirstRanker.com ---
Aldosterone synthase,18-Hydroxycorticosterone
Ald . synthase
--- Content provided by FirstRanker.com ---
Aldosterone
Function of mineralocorticoid-
Aldosterone
--- Content provided by FirstRanker.com ---
? Aldosterone is very potent and accounts for
about 90% of mineralocorticoid activity.
--- Content provided by FirstRanker.com ---
? Deoxycorticosterone is 1/30 as potent asaldosterone ,but very small quantity secreted..
? Aldosterone increases renal tubular
--- Content provided by FirstRanker.com ---
reabsorbtion of Na+ and secretion of K+
especially in the principal cells (P cells)of
--- Content provided by FirstRanker.com ---
collecting tubules, and lesser extent in DT andcollecting ducts.
Functions of aldosterone
--- Content provided by FirstRanker.com ---
? 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
--- Content provided by FirstRanker.com ---
?Excretion of K+ and through renal tubules
? Secretion of H+ into renal tubules.
--- Content provided by FirstRanker.com ---
?Also es Na+ reabsorbtion from sweat ,Saliva , and contents of colon.
MOA Of Aldosterone
--- Content provided by FirstRanker.com ---
? Like other steroids. Aldosterone binds tocytoplasmic receptor.
? HR complex moves to nucleus.
--- Content provided by FirstRanker.com ---
? Transcription of mRNA.
? production of proteins that alter cell functions.
--- Content provided by FirstRanker.com ---
Contd.Aldosterone stimulated proteins leads to:
Genomic actions like
? es activity of ENaCs (epithelial Na+ channels),a
--- Content provided by FirstRanker.com ---
rapid action.
? Slower effect is that it increases the synthesis of
--- Content provided by FirstRanker.com ---
ENaCs , by ing the mRNA activity for synthesis ofproteins.
? es insertion of these channels on cell membrane.
--- Content provided by FirstRanker.com ---
? Gene activated by aldostrone is sgk gene ,a serine-threonine protein kinase.
? Non-Genomic Actions: mediated by IP3
--- Content provided by FirstRanker.com ---
? Nongenomic actions occurs rapidly.
? It es activity of Na+K+exchangers,which
--- Content provided by FirstRanker.com ---
Increases intracellular accumulation of Na+What is Aldosterone escape
phenomenon ?
--- Content provided by FirstRanker.com ---
? When there is aldosterone excessivesecretion the ECF expands due to Na+ and
water retention , but when the ECF expansion
--- Content provided by FirstRanker.com ---
passes a certain point ,Na+ excretion is
usually ed inspite of continued action of
--- Content provided by FirstRanker.com ---
mineralocorticoids on renal tubules.Mechanism
? Mineralocorticoid/aldosterone excess.
--- Content provided by FirstRanker.com ---
? ECF expansion(due to Na+ & water retension).? BP rises leading to distention of atria.
? Secretion of ANP(atrial natriuretic peptide).
--- Content provided by FirstRanker.com ---
? ANP causes profound natriuresis and diuresis.
Contd.
? ECF returns back to normal.
--- Content provided by FirstRanker.com ---
?Due to this phenomenon edema is not
produced by mineralocorticoids in normal
--- Content provided by FirstRanker.com ---
individual and in patients ofhyperaldosteronism.
Regulation of Aldosterone Secretion
--- Content provided by FirstRanker.com ---
? Aldosterone secretion is regulated mainly by3 important stimuli:
1. ACTH
--- Content provided by FirstRanker.com ---
2. Angiotensin II
3. Plasma K+ conc.
--- Content provided by FirstRanker.com ---
RAAS systemRAAS system
? Angiotensinogen
--- Content provided by FirstRanker.com ---
Renin(JGA)Angiotensin
ACE(lungs)
--- Content provided by FirstRanker.com ---
Angiotensin II
Adrenal cortex
--- Content provided by FirstRanker.com ---
AldosteroneNa+ and water retention,es ECF volume
ACTH
--- Content provided by FirstRanker.com ---
? Cells of zona glomerulosa have ACTHreceptors.
? ACTH mediates aldosterone secretion by
--- Content provided by FirstRanker.com ---
cAMP& Protein kinase.
? Effect of ACTH on aldosterone secretion is
--- Content provided by FirstRanker.com ---
temporary , aldosterone secretion declineseven if ACTH secretion is elevated ,due to
decrease renin secretion.
--- Content provided by FirstRanker.com ---
Plasma K+ Conc.? Plasma K+ level need increase only 1meq/L to
stimulate aldosterone secretion.
--- Content provided by FirstRanker.com ---
? Like angiotensin II, K+ stimulates the conversion
of cholesterol pregnenolone ,&
--- Content provided by FirstRanker.com ---
deoxycortecosteronealdosterone.? ECF K+ Activate voltage gated Ca channel
cytosolic Ca
--- Content provided by FirstRanker.com ---
aldosterone secretionDysfunction Of Aldosterone
Primary
? Hypersecretion
--- Content provided by FirstRanker.com ---
SecondaryPrimary Hyperaldosteronism
? The cause of excess aldosterone secretion is
due to adrenal disease : Adrenal adenoma
--- Content provided by FirstRanker.com ---
? Adrenal hyperplasia
?Adrenal carcinoma
Conn's Syndrome
--- Content provided by FirstRanker.com ---
? Major cause of primary hyperaldosteronism.
? Occurs due to the tumor(adenoma) of zona
glomerulosa of adrenal cortex.
--- Content provided by FirstRanker.com ---
? Clinical features: Hypertension
? Muscle weakness
--- Content provided by FirstRanker.com ---
? Polyuria? Edema is absent
? Hypokalemia
--- Content provided by FirstRanker.com ---
? Hypernatremia
? Low renin level
? Metabolic alkalosis
--- Content provided by FirstRanker.com ---
Secondary Hyperaldosteronism? ed aldosterone secretion is due to activation
of RAAS .
--- Content provided by FirstRanker.com ---
? Occurs in cirrhosis, heart failure, nephrosis,
renin secreting tumor.
--- Content provided by FirstRanker.com ---
? renin in plasma.? Edema is a usual feature.
Hyposecretion of Aldosterone
Addison's disease/Primary Adrenal Insufficiency
--- Content provided by FirstRanker.com ---
? Occurs due to autoimmune inflammation ofadrenal gland, tuberculosis.
? Deficiency of mineralocorticoids occurs.Leading
--- Content provided by FirstRanker.com ---
to hyponatremia , hyperkalemia, ECF,
metabolic acidosis, cardiac output,BP.
--- Content provided by FirstRanker.com ---
? Also there is glucocorticoid deficiency, so patientis unable to maintain blood glucose conc.
Contd.
--- Content provided by FirstRanker.com ---
? Circulating ACTH levels are elevated, leading to
melanin deposition , so there is pigmentation of
--- Content provided by FirstRanker.com ---
palm creases, lips ,gums etc.? Untreated patient may die in 4days-2wks.
? Treatment: Mineralocorticoid & Glucocorticoids
--- Content provided by FirstRanker.com ---
replacement.?Addisonian Crisis : Glucocorticoid level does not
during stress in addison's disease patients e.g.;
--- Content provided by FirstRanker.com ---
trauma, surgery etc leading to severe debility.
Contd.
--- Content provided by FirstRanker.com ---
? Secondary adrenal insufficiency: caused
by pituitary disease and decrease ACTH
--- Content provided by FirstRanker.com ---
secretion.? Tertiary adrenal insufficiency : caused by
hypothalamic disorders disrupting CRH
--- Content provided by FirstRanker.com ---
release.
? Pseudohypoaldosteronism : produced when
--- Content provided by FirstRanker.com ---
there is resistence to action of aldosteronism.