Mineralocorticoids

Liver [Ref Molecular and cellular pediatric endocrinology By Stuart Handwerger p219; http://en.wikipedia.orgAviki/Mineralocorticoid_receptor%5D

Mineralcorticoid receptors are expressed at high levels in renal distal tubules and cortical collectiong ducts and in other mineralocorticoid target tissues such as salivary glands and the colon. It is also found in multiple sites in the brain (hippocampus), myocardium, peripheral vasculature, brown adipose tissue and sweat glands. Mineralcorticoid receptors are located mainly in the cytoplasm.

Primary mineralocorticoid excess [Ref: Harrison 16^th/e p. 268]

• Mineralocorticoid excess increases net acid excretion, this leads to metabolic alkalosis.

Also know

• The plasma potassium concentration changes with serum pH.
• If pH decreases the excess 1-1^. tends to enter the body’s cells in exchange for K’ and plasma [1C7 increases.
• If the pH increases (alkalosis) IP tends to leave cells and enters bloodstream to partly compensate for the alkalosis.
• In exchange for H, K- enters the cells and results in decreased plasma [K’] hypokalemic alkalosis.

This is the complete list of metabolic alkalosis the list given in answer 32 is not complete.

Bartter’s syndrome, thiazide diuretic therapy and recurrent vomiting results in metabolic alkalois. Mineralocorticoid deficiency results in metabolic acidosis.

Ref: Harrisons principles of internal medicine, 18th edition, Page: 369.

Hypokalemia is a feature of Gitelman’s syndrome

• Primary and secondary hyperaldosteronism
• Malignant hypertension
• Renin secreting tumors
• Renal artery stenosis
• Hypovolemia
• Bartter’s syndrome

• Liddle’s syndrome
• 11 beta dehydrogenase-2 deficiency

Mineralocorticoid receptors are expressed in many tissues, such as the kidney, colon, heart, central nervous system (hippocampus), brown adipose tissue and sweat glands. It is not present in liver.

Ref: Barrett K.E., Barman S.M., Boitano S., Brooks H.L. (2012). Chapter 20. The Adrenal Medulla & Adrenal Cortex. In K.E. Barrett, S.M. Barman, S. Boitano, H.L. Brooks (Eds), Ganong’s Review of Medical Physiology, 24e. 

D i.e. Liver

D i.e. 11 13 hydroxysteroid dehydrogenase

Apparent mineralocorticoid excess is d/t inhibition or absence of /V hydroxysteroid dehydrogenase type 2Q AME syndrome & 11 HSD type 2

• Invitro (in lab), the mineralocorticoid receptor has much higher affinity for glucocorticoids than the glucocorticoid receptor does, & glucocorticoids are present in large amount in body (vivo). But binding of glucocorticoids to mineralocorticoid receptor (& so production of mineralcorticoid effects by glucocorticoids) is prevented by presence of 11 3 hydroxyl steroid dehydrogenase tye 2 enzyme in mineralocorticoid sensitive tissues. This enzyme leaves aldosterone untouched, but converts cortisol to cortisone & corticosterone to its 11 oxy derivatives. These 11 oxy derivatives do not bind to receptor.
• If 11 hydroxysteroid dehydrogenase type 2 is congenitally absent or inhibited by prolonged ingestion of licorice (containing glycyrrhetinic), cortisol has marked mineralocorticoid effects resulting in apparent mineralocorticoid excess (AME syndrome.
• Patient with AME have clinical picture of hyper aldosteronism because cortisol is acting on their mineralo corticoid

receptors, & their plasma aldosterone levels and plasma rennin activity is low.

C i.e. Dexamethasone

Ans. is ‘a’ i.e., Spironolactone

Ans. is ‘c’ i.e. Mineralocorticoid antagonist

• Spirinolactone is mineralocorticoid (aldosterone) antagonist. It opposes the action of Aldosterone without requiring access to the tubular lumen. Spirinolactone (as well as aldosterone) act from the interstitial side.

Ans. is ‘c’ i.e., Triamcinolone

o Zero mineralocorticoid activity –^—> Triamcinolone, Paramethasone, Dexamethasone, Betamethasone

o Mineralocorticoid with zero glucocorticoid activity —> DOCA (Deoxycorticoisterone acetate)

o Most potent glucocorticoid – Betametasone

o Least potent glucocorticoid – Cortisone

o Maximum mineralocorticoid activity – Aldosterone

• Maximum glucocorticoid activity – Dexamethosone & Betametasone

Ans. is ‘a’ i.e., Aldosterone

o Glucocorticoid with max. mineralocorticoid activity —> Hydrocortisone (cortisol) o Glucocorticoid with min. glucocorticoid activity -4 Hydrocortisone

o Glucocorticoid with no mineralocorticoid activity —> Betamethasone, Paramethasone, Dexamethasone, Triamcinolone.

o Mineralocorticlid with no glucocorticoid activity DOCA

o Maximum mineralocorticoid activity —> Aldosterone.

o Maximum glucorticoid activity -4 dexamethasone, Betamethasone.

Ans. is ‘c’ i.e., DOCA

Mineralocroticoid with no glucocorticoid activity —> Desoxycorticosterone acetate (DOCA)..

Ans. is ‘c’ i.e., Methylprednisolone

Mineralocorticoid activity of given options in decreasing order : Aldosterone (3000) > DOCA (100) > Hydrocortisone (1) > Methylprednisolone (0-5).

Ans. is ‘a’ i.e, Fludrocortisone

Ans. is ‘a’ i.e., Pregnenolone

Ans. is ‘a’ i.e., Spironolactone 

Ans. is ‘c’ i.e., Methylprednisolone