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THE ADRENAL GLAND. Dr. Ayisha Qureshi Assistant Professor, MBBS, Mphil. THE ADRENAL GLANDS. 2 in number Each weighs about 4 gms . They are located above the upper pole of each kidney in the retroperitoneal space. Each adrenal is composed of 2 distinct parts: - Adrenal cortex
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THE ADRENAL GLAND Dr. Ayisha Qureshi Assistant Professor, MBBS, Mphil
THE ADRENAL GLANDS 2 in number Each weighs about 4 gms. They are located above the upper pole of each kidney in the retroperitoneal space. Each adrenal is composed of 2 distinct parts: - Adrenal cortex - Adrenal medulla Embryologically, the cortex is derived from the mesoderm whereas the medulla is derived from the neural crest cells that migrate into the developing cortex.
Each Adrenal Gland consists of a STEROID-SECRETING CORTEX and a CATECHOLAMINE-SECRETING MEDULLA. On the basis of their primary action, the adrenal steroids (the adrenocortical hormones) can be categorized into: Mineralocorticoids Glucocorticoids Sex Hormones esp. Androgens
What happens when there is a deficiency of the enzyme 21 α-Hydroxylase Deficiency? From the last slide we can predict that deficiency of this enzyme will lead to inadequate production of both glucocorticoid and mineralocorticoid hormones. Affected infants are ill with symptoms of: • Mineralocoroticoid deficiency. • Glucocorticoid deficiency. Congenital defects in the enzymes lead to deficient cortisol secretion and the syndrome of congenital adrenal hyperplasia. The hyperplasia is due to increased ACTH secretion. All the precursor molecules are converted into Androgens which leads to “virilization” of the infant which means more male characteristics which will be more apparent in the female child. (detail with the pathophysiological disorders.)
Receptor Types & Specificity Each of the adrenocortical steroid hormones binds with a receptor specific for it within the cytoplasm of the hormone’s target cells: • MR- Mineralocorticoid Receptor: binds a mineralocorticoid. • GR- Glucocorticoid Receptor: binds a glucocorticoid. • AR- Androgen Receptor: binds dehydroepiandrosterone. As is true of all steroid hormones, each hormone-receptor complex moves to the nucleus and binds with a complementary hormone-response elementin DNA, namely the mineralocorticoid response element, glucocorticoid response element, and androgen response element. This binding initiates specific gene transcription leading to synthesis of new proteins that carry out the effects of the hormone.
Relative Potency of Natural & Synthetic steroidsAldosterone's mineralocorticoid activity is about 3000 times greater than that of cortisol, but the plasma concentration of cortisol is nearly 2000 times that of aldosterone.
ALDOSTERONE Is a mineralocorticoid so called because of its effect on the minerals (Na & K) of the body.
In the target organ, when Aldosterone complexes with MR, it causes increased transcription of mRNAs. This increases protein synthesis which alters cell function.
POINT TO REMEMBER: ACTH from the Anterior pituitary is necessary for Aldosterone secretion but has little effect in controlling the rate of secretion!
DOES ANY OTHER ADRENOCORTICAL HORMONE HAVE MINERALOCORTICOID ACTIVITY? IF SO, THEN WHY DO THEY NOT EXERT THEIR EFFECT THROUGH THE MR (MINERALOCORTICOID RECEPTOR)?
WHAT WILL HAPPEN IF THERE ARE NO MINERALOCORTICOIDS BEING PRODUCED IN THE BODY?
Total loss of adrenocortical secretion usually causes death within 3 days to 2 weeks unless the person receives extensive salt therapy or injections of mineralocorticoids. Without mineralocorticoids: • Potassium ion concentration of the extracellular fluid rises markedly. • Sodium and chloride are rapidly lost from the body. • Total extracellular fluid volume and blood volume become greatly reduced. • The person soon develops diminished cardiac output, which progresses to a shock like state, followed by death. This entire sequence can be prevented by the administration of aldosterone or some other mineralocorticoid. Therefore, the mineralocorticoids are said to be the acute "lifesaving" portion of the adrenocortical hormones.
Aldosterone Escape Excess Aldosterone secretion ↓ Na & water retention ↓ Increased blood volume ↓ Pressure Natriuresis & Pressure Diuresis ↓ Salt & water excretion returns to normal ↓ This is called Aldosterone Escape
Question: • What is Pressure Natriuresis & Pressure Diuresis? • A rise in arterial blood pressure causes increased excretion of both salt (Pressure Natriuresis) and water (Pressure Diuresis). This is due to the secretion of ANP from the atrial muscles of the heart.
Cortisol is a Glucocorticoid so called because of its effect on glucose levels in the plasm. • It is also a derivative of cholesterol. • About 99% cortisol binds to the plasma proteins esp. a globulin called Cortisol Binding Globulin (CBG) or Transcortin. • Because most of the cortisol is in bound form, thus, it has a relatively long half-life of 60-90 minutes.
BIOSYNTHESIS of CORTISOL Cholesterol ↓cholesterol desmolase Pregnenolone ↓17-α- hydroxylase 17-hydroxypregnenolone ↓3-β-hydroxydsteroid dehydrogenase Progesterone →17-hydroxyprogesterone ↓21-β-hydroxylase 11- deoxycortisol ↓11-β-hydroxylase cortisol
How does Cortisol help in resolution of healing? • Blocks early stages of inflammation preventing it from starting • If inflammation already started then it causes its rapid resolution & hastens healing. • Blocks the inflammatory response to allergic reactions. • Cortisol stabilizes the lysosomal membranes as a primary effect. • Cortisol decreases the permeability of the capillaries as a secondary effect. • Cortisol decreases both migration of White blood cells & phagocytosis of the damaged cells in the inflamed area. • Cortisol suppresses the immune system, esp. decreasing the lymphocyte reproduction. • Cortisol reduces fever as it decreases the release of interleukin-2.
Immunosuppressive Effects: Role in Autoimmune diseases • Certain diseases respond well to cortisol given as “steroids”: • Rheumatoid arthritis • Rheumatic fever • Acute Glomerulonephritis All these diseases are characterized by severe local inflammation and the harmful effects are caused by the inflammation itself and not by the disease. When cortisol is given, then the inflammation subsides within 24 hours. This prevention of the damaging effects of the inflammation alone can be a life saving measure. It is also given in organ transplant to reduce chances of rejection.
