Adrenal cortex, structure, function ,hormones and their clinical significance for MBBS students

1. ADRENOCORTICAL
HORMONES
Dr Prafull H Turerao.
Department of Physiology
D.Y.Patil Medical College, Kolhapur

2. Functional Anatomy of Adrenal Glands
• Two adrenal glands situated one on either side at upper
pole of kidney hence called suprarenal gland
• Each weighs 5gm consist of two part outer adrenal cortex
and inner adrenal medulla.
• Adrenal cortex consist of three layers
- zona glomerulosa,
- zona fasciculata and
- zona reticularis
• Adrenal medulla is made up off chromaffin cells
• Adrenal gland is supplied by superior, middle and inferior
branches of suprarenal artery and drained single central
vein

5. Hormones of Adrenal Cortex
• Glucocorticoids – Include cortisol and corticosterone
have widespread effect on glucose and protein
metabolism
• Mineralocorticoids – Aldosterone is chief
mineralocorticoid It regulates sodium balance and ECF in
the body
• Adrenal sex steroids – These include DHEA and its
sulphate ester

6. Glucocorticoids
• Synthesis - Largely in zona fasciculata
• Plasma levels – Cortisol – 14, Corticosterone -1,
Aldosterone – 0.009, DHEA – 115
• Transport – Two forms bound (90%) and free (15%).Most
physiological action is done by free form
• Excretion – About 70% of conjugated steroids are
excreted in urine about 20% in faeces

10. Action of Glucocorticoids
• Action - Like other steroid hormones, glucocorticoids act
through effect of gene expression by binding with receptor
called glucocorticoid receptor
• Metabolic effect
• Effect on Carbohydrate metabolism - Anti insulin effect
which leads to hyperglycaemia

14. • Glucocorticoids increase rate of glucose production from
non carbohydrates by as much as 6-10 fold leading to
increased gluconeogenesis
• Decreased utilization of glucose in peripheral tissues.
Inhibit glucose uptake by muscle, skin, bone, adipose
tissue but brain, liver and erythrocytes are spared

15. • Effects on protein metabolism are
• Catabolic – Enhances release of amino acids by
proteolysis in skeletal muscle
• Antianabolic – Inhibit the de novo synthesis of protein
• In liver glucocorticoids increase the synthesis of enzyme
involved in production of hepatic proteins, plasma proteins
and glycogen

16. • Effect on fat metabolism – Lipolytic effect of cortisol
itself is slight it is necessary for other lipolytic agents like
epinephrine, growth hormone etc.
• Glucocorticoids increase differentiation of adipose tissue
and stimulate lipogenesis. Lipogenic effect varies in
different regions of the body.

17. • Effects on electrolyte and water metabolism-
glucocorticoids control distribution of body water and
electrolytes by their opposing actions. Retention of
sodium and water by aldosterone like activity the
glucocorticoids increase sodium and chloride retention
and excretion by kidney.
• Promotion of diuresis by increasing the inactivation of
ADH by liver and by antagonising the action of ADH at the
level distal convoluted tubules of kidney.

18. • Physiological actions on various organs and systems
• Effects on muscle
• Contractility and work performance of skeletal and cardiac
muscle are maintained by cortisol.
• Decrease in muscle mass and strength is caused by
excess of cortisol

19. • Effects on bone – Increase in bone resorption by
increasing activity of osteoclasts and collagenase enzyme
• Inhibition of bone formation by decreasing collagen
synthesis, inhibiting formation of mature osteoblasts,
increase rate of apoptosis and osteoblasts, impending
calcium absorption from intestinal tract by antagonizing
action of Vit D3, increasing calcium excretion in urine

20. • Effects on connective tissue – Cortisol decrease
collagen synthesis producing thereby thinning of the skin
and thinning of wall of capillaries
• Effects on vascular system – cortisol is essential in
maintaining normal blood pressure by sustaining
myocardial performance, enhancing the vasopressor
effect, decreasing production of vasodilator
prostaglandins, maintaining normal blood volume by
decreasing permeability of vascular endothelium

21. • Effects on GFR - By increasing glomerular flow, rapid
excretion of water flow, rapid excretion of water load,
increase in calcium and excretion
• Effects on central nervous system - GR are present in
various parts of brain especially the limbic system.
Through these receptors glucocorticoids modulate
excitability behaviour and mood.
• Effect on blood cells and lymphatic organs - Excess of
glucocorticoids leads to eosinopenia and basopenia,
lymphopenia, neutrophilia, polycythemia, thrombocytosis

22. • Anti inflammatory and antiallergic effects-
• Not produced physiologically.
• Only produced by large doses when given therapeutically
and are called pharmacological actions of glucocorticoids.
• Cortisol inhibits activity of phospholipase A2
• Stabilize lysosomal membrane
• Inhibits migration of circulating leucocytes
• Leukotriene and collagen formation
• Anti immunity effect - Cortisol inhibits both cellular and
humoral immunity

23. • Role of glucocorticoids in foetal life - Maturation of
CNS, retina and skin in utero, maturation of lungs
immediately after birth, maturation of GIT
• Role of glucocorticoid in stress - Various stresses can
be tolerated by increased secretion.

26. Regulation of Glucocorticoid Secretion
• The glucocorticoid secretion is regulated by hypothalamic
anterior pituitary adrenal cortex axis which exerts its effect
through Corticotropin releasing hormone CRH,
Adrenocorticotropic hormone (ACTH) and Glucocorticoid
negative feedback effect
• Role of Corticotrophin releasing hormone is secreted by
parvo ventricular nucleus of hypothalamus. CRH reaches
the anterior pituitary through hypothalamic hypophyseal
portal system acts by cAMP mechanism through CRH
receptors.

27. Control of CRH secretion - Stressful Stimuli e.g. Pain,
anaesthesia, surgery, haemorrhage which ultimately
increase cortisol secretion
Circadian rhythm - CRH secretion and thus ACTH and
Cortisol secretion show circadian rhythm.
ACTH acts on hypothalamus to reduce secretion of ACTH
by short loop negative feedback mechanism
Glucocorticoids exert long loop feedback effect on CRH
secretion.

29. • Actions of CRH - Stimulation of synthesis and release of
ACTH by acting on corticotrophs. Other actions of CRH
related to or independent to ACTH include central arousal,
increase in blood pressure, diminution of reproductive
function by decreasing synthesis of gonadotrophin
releasing hormone and gonadotrophins, decrease in
feeding activity and growth, stimulation of release of
cytokines in immune cells.

30. ACTH
• ACTH formation from anterior pituitary initially causes
formation of preprohormone which is a large protein
molecule which contains ACTH, MSH, beta-lipoprotein
and beta endorphin.
• Under normal conditions only ACTH is secreted and
others are not secreted in large enough quantities to have
any effect on the body.

31. • Role of adrenocorticotropic hormone - Secreted by
corticotrophs. Acts by combining with ACTH receptors to
activate cAMP
• Actions of ACTH
• Actions on adrenal cortex- ACTH primarily concerned with
growth and function of adrenal cortex
• Extra adrenal actions of ACTH occur only with very high
level.

32. • Regulation of ACTH secretion – Hypothalamic control is
through CRH
• Diurnal variations is due to CRH release. Biological clock
is located in limbic system
• Pulsatile release of ACTH also due to CRH. Upto 3 pulses
per hour. Each pulse lasts 20 min. Release of ACTH in
response to stress is mediated by CRH and ADH
• Brain natriuretic peptide inhibit ACTH

36. Applied aspects
• Therapeutic administration of exogenous glucocorticoid
for long duration supress CRH and ACTH secretion. As
long as dosage continues the absence of glucocorticoids
is not noted. But sudden stoppage may cause acute
adrenal deficiency.
• Dexamethasone Suppression test - This test is used to
check response of hypothalamus pituitary adrenocortical
axis. Administration of Dexamethasone inhibits ACTH and
Cortisol secretion when HPA axis is normal

37. Cushing's Syndrome
• Cushing's syndrome – Group of clinical condition due to
excessive level of glucocorticoids
• It is can be divided into 2 types
• ACTH dependent – More common type (80%). Causes
include hyperactivity of pituitary, Ectopic ACTH secretion,
hypothalamic disorder of hypothalamus
• ACTH independent – Less common (20%). Adrenal
origin (Adenoma, Carcinoma), Iatrogenic.

38. Clinical Features
• Truncal obesity
• Moon face
• Purple striae
• Muscle weakness sodium and water retention
• Hyperglycaemia
• Hirsutism
• Susceptibility to infection, osteoporosis and peptic
ulceration
• Psychological emotional and personality changes

40. Tests for Cushing's syndrome
• Plasma cortisol level – Cortisol level is raised and there is
loss of diurnal pattern.
• Dexamethasone suppression test – The test is not able
supress plasma cortisol level.
• 24 hour free urinary cortisol – Free cortisol levels are
raised

41. Mineralocorticoids
• Mineralocorticoids include Aldosterone. It is the chief
mineralocorticoid, Deoxycorticosterone DOC and 18-
hydroxy-deoxycorticosterone 18-OH-DOC is secreted in
small amount and has some mineralocorticoid activity.
• Synthesis – Aldosterone is synthesized exclusively by
zona glomerulosa.
• Transport – 40% in free form and 60% in bound form.
Weakly bound to specific aldosterone binding globulin to
transcortin and albumin. Metabolized in liver.

43. Actions of Aldosterone
• Primary actions – Effects on renal tubules. Aldosterone
acts on late distal tubules and collecting ducts causing
sodium absorption and potassium and H+ excretion.
Ammonium and magnesium excretion also increases
• Mechanism of action – Aldosterone acts by increasing
aldosterone induced protein AIP synthesis. AIP increases
membrane permeability, number of thiazide sensitive
NaCl co transporter, increase in content of Na+ K+
ATPase, increase in the Krebs's cycle enzyme activity and
phospholipase activity

44. • Effect on sweat glands, salivary glands and colon –
Sweat and salivary gland secretes large amount of
sodium chloride.
• Aldosterone decreases loss of Na+ and Cl- in sweat.
• Aldosterone stimulates sodium reabsorption from colon
while enhancing potassium excretion.

45. • Secondary effects of aldosterone –
• Effect on plasma potassium concentration – decrease in
plasma K+ level may occur in aldosterone excess due to
increased urinary excretion of K+ (Hypokalaemia). In
aldosterone deficiency hyperkalaemia occurs.
• Effect on plasma sodium level – Hypernatremia may
occur due to increased Na+ absorption in aldosterone
excess

46. • Aldosterone escape – A mentioned above in
hyperaldosteronism or when aldosterone is administered
for several days to normal individuals the increased
sodium and water absorption by renal tubules leads to
increase in ECF volume and hypertension. However after
10-15% increase in ECF there occur pressure diuresis i.e.
excretion of sodium and water in urine is increased in
spite of continued action of aldosterone. This
phenomenon is called aldosterone escape.

47. Regulation of Aldosterone Secretion
• Aldosterone secretion is controlled by following factors –
• Renin angiotensin system – The secretion of
aldosterone is influenced by changes in circulating fluid
volume. Kidney increases secretion of aldosterone when
ECF volume is decreased and vice versa
• Conditions associated with decreased ECF are
- Sodium deprivation
- Haemorrhage
- Upright posture
- Acute diuresis

48. • Steps involved in secretion of aldosterone by renin
angiotensin system are –
• Decrease in ECF volume leads to decreases in renal
arterial blood flow
• Decrease in renal perfusion causes JG cells to secrete
renin

49. • Renin catalyses the conversion of angiotensinogen to
angiotensin I. It is converted to angiotensin II by ACE.
• Angiotensin II increases secretion of aldosterone.
Aldosterone may be increased by 4-8 fold by renin
angiotensin system
• Factors which affect aldosterone secretion is sympathetic
neural activity, local prostaglandin and Atrial natriuretic
peptide ANP

50. • Plasma potassium concentration – There exists a vital
negative feedback relationship between plasma
potassium concentration and aldosterone secretion i.e.
increase in plasma potassium level causes increase in
plasma aldosterone level and decrease in plasma
potassium concentration lowers aldosterone secretion
• Role of ACTH – Direct stimulating effect of ACTH on
aldosterone secretion is mild and transient. ACTH also
stimulates secretion of deoxycortisone (18-OH-DC) which
has mild mineralocorticoid activity.

53. • Hyperaldosteronism - It refers to over production of
hormone aldosterone.
• Primary Hyperaldosteronism (Conn’s disease) –
Occurs due to tumour or hyperplasia of zona glomerulosa
• Secondary hyperaldosteronism – Occurs due to some
extra adrenal cause, which stimulates renin angiotensin
aldosterone system e.g. cirrhosis of liver, nephrotic
syndrome
• Clinical features – sodium and water retention,
Hypokalaemia and metabolic alkalosis

54. Summary
• Functional Anatomy of Adrenal Glands
• Hormones of Adrenal Cortex
• Glucocorticoids- Synthesis, action and regulation
• HPA Axis
• Mineralocorticoid- Synthesis, action and regulation
• Applied Aspects

55. References
• Textbook of Medical Physiology – Guyton And Hall 13th
Edition
• Textbook of Physiology – A K Jain 6th Edition
• Medical Physiology For Undergraduate Students – Indu
Khurana 1st Edition
• www.webmd.com
• Wikipedia.com
• Net Source for pictures & etc.