AP Adrenal Flashcards
Describe the hormones secreted by adrenal cortex.
The adrenal gland secretes steroid hormones such as cortisol and aldosterone. It also makes precursors that can be converted to sex steroids (androgen, estrogen). A different part of the adrenal gland makes adrenaline (epinephrine).
Anatomy of adrenal gland
Adrenal glands are paired organs located in the retroperitoneal area near the superior poles of the kidneys
Structure & Function of Adrenal Gland
Cortex: Comprises 80% of gland and is derived from mesoderm
Medulla; Comprises of 20% of gland and is derived from ectoderm
Adrenal Medulla
¢Functionally related to sympathetic nervous system
¢Chromaffin cells (neuroendocrine cells) in adrenal medulla secretes catecholamines like epinephrine & norepinephrine into blood on sympathetic stimulation
¢Effects of secreted epinephrine & norepinephrine mimic sympathetic stimulation
¢More widespread effect than direct sympathetic stimulation
¢Influences all organs & tissues of body
¢Epinephrine stimulates cardiac output & metabolic activity throughout body
¢Norepinephrine promotes vasoconstriction & dilates pupils of eyes
Adrenal Medulla…cont’d
-Catecholamines
- ¢Derived from tyrosine (non essential amino acid)
- Phenylalanine → Tyrosine → Dopamine → Norepinephrine → Epinephrine
¢Pheochromocytoma
- Catecholamine-secreting tumor that arises from chromaffin cells of the adrenal medulla
Adrenal Cortex
Corticosteroids
Corticosteroids
¢Mineralocorticoids
Zona glomerulosa
Affects electrolytes of ECF like sodium and potassium
Aldosterone
¢Glucocorticoids
Zona fasciculata
Increase blood glucose concentrations
Cortisol
¢Androgens
Zona reticularis
Similar to testosterone
Dihydroepiandrosterone
Synthesis of Adrenocortical Hormones
¢Cholesterol enters adrenal cortex cells in form of low-density lipoproteins (LDL)
¢ACTH stimulates uptake of LDL & liberation of cholesterol
¢ACTH & angiotensin II stimulate conversion of cholesterol to pregnenolone
- Rate-limiting step in synthesis of adrenocorticosteroids
Transport of Corticosteroids in Blood
¢Cortisol largely (90–95%) bound to plasma proteins in blood
- Cortisol-binding globulin plays primary role
- Binding prolongs lifetime in plasma (t½ = 60–90 min
¢Aldosterone less extensively (-60%) bound to plasma proteins in blood
- Shorter lifetime in plasma (t½ . 20 min)
¢Cortisol & aldosterone metabolized primarily in liver
- Metabolites excreted partially in bile (-25%) & remainder by kidneys (-75%)
Aldosterone
- Critical role in regulation of electrolytes (K+, Na+ & Cl–) in extracellular fluids
- Absence of aldosterone leads to
- ↑ K+, ↓ Na+ & ↓ Cl– in plasma
- Marked reductions in blood & extracellular fluid volumes & cardiac output
- Fatal condition unless mineralocorticoid administered
Functions of Aldosterone
-Aldosterone triggers Na+ reabsorption & K+ secretion by renal tubular epithelial cells
- Predominant effect on principal cells of collecting tubules
- EXCESS of aldosterone : HYPOKALEMIA
- TOO LITTLE of aldosterone: HYPERKALEMIA
- Results in conservation of Na+ in extracellular fluid & enhanced urinary K+ excretion
- ↑ Na+ reabsorption leads to ↑ water reabsorption
Signaling Mechanism for Aldosteron
- High lipophilicity of aldosterone allows ready diffusion into cell
- Activation of the mineralocorticoid receptor (MR) by aldosterone can be antagonized with spironolactone, a MR antagonist.
- ENaC - epithelial sodium channel proteins
- ¢help maintain Na-K homeostasis together with Na-K pump
Regulation of Aldosterone Secretion
Renin Angiotensin: Angiotensin II causes marked ↑ in aldosterone secretion
Potassium: High levels of K+ induces marked ↑ in aldosterone secretion
Major glucocorticoid:
Cortisol, known also as hydrocortisone.
Small but significant amount of glucocorticoid activity is provided by corticosterone.
Effects of CORTISOL on Carbohydrate Metabolism
-STIMULATION OF GLUCONEOGENESIS IN LIVER
- Increased expression of enzymes for gluconeogenesis plays major role
- Mobilization of amino acids from extrahepatic tissues
DECREASED GLUCOSE UTILIZATION BY CELLS
- Results in ↑ blood glucose & secretion of insulin
- May cause “adrenal diabetes” due to impaired action of insulin
Effects of cortisol on protein metabolism
¢Cortisol ↓ protein synthesis & ↑ protein catabolism in muscle & many tissues EXCEPT IN LIVER
Effects of cortisol on fat metabolism
-Cortisol ↑ mobilization of fatty acids from adipocytes
Fatty acids used in preference to glucose as energy source
Cortisol plays key role in resisting
stress & inflammation
¢Stress triggers ↑ ACTH secretion by pituitary & ↑ cortisolsecretion by adrenals
¢Multiple mechanisms contribute to cortisol’s ability to suppress inflammation
- Stabilization of lysosomal membranes in inflammatory cells
- ↓ permeability of blood capillaries
- ↓ chemotaxis of leukocytes into inflamed area & ↓ phagocytosis
- ¢Mediated by ↓ production of prostaglandins & leukotrienes
- Suppression of immune system & ↓ expansion of T lymphocyte clones
- Suppression of fever & ↓ vasodilaton
¢Cortisol may also enhance repair & healing of damaged tissues
Regulation of Cortisol Secretion
ACTH acts on GPCR to stimulate of adenylyl cyclase; ↑ cAMP stimulates conversion of cholesterol to pregnenolone; pregnenolone → cortisol
Pathophysiology of Adrenal Medulla
Pheochromocytoma
¢Neoplasms of the chromaffin cells of the adrenal medulla
¢These tumors secrete excessive amounts of epinephrine, norepinephrine, or both
¢Most common presenting feature of pheochromocytoma is hypertension
Pathophysiology of Adrenal Cortex
Hyperadrenalism
- Characterized by excess cortisol secretion, also known as Cushing’s syndrome
- Primary cause is usually excess ACTH secretion from anterior pituitary
- Can arise from tumor in adrenal cortex, ectopic tumor or excess CRH secretion
- Major symptoms of Cushing’s syndrome due to changes in fat & protein metabolism
Cushing’s Syndrome
¢Symptoms
- Extra fat deposition in upper abdomen & thorax (“buffalo torso”)
- Edematous appearance of face (“moon face”)
- Gradual weight gain
- Severe muscle weakness
- Osteoporosis
- ¢↓ osteoblast function and Ca2+ absorption; ↑ bone resorption
- Suppressed immune function
- Surgery & pharmacological antagonism (drugs that inhibit steroidogenesis) provide treatment options
- Ketoconozole and Mitotane can both block cortisol biosynthesis and are indicated for Cushing’s syndrome
Pathophysiology of Adrenal Cortex
Hypoadrenalism
- Also known as Addison’s disease
- Atrophy or injury of adrenal cortices leads to adrenal insufficiency
- Autoimmune process responsible in most cases (-80%)
- Can occasionally arise secondary to impaired function of anterior pituitary
- Disease characterized by reduced production of aldosterone & cortisol
- Symptoms characterized by these deficiencies
- Most patients also show excessive melanin pigmentation (due to excess ACTH – absence of negative inhibition)
Diagnosis of Addison’s Disease
-ACTH Stimulation test
Administration of 250 μg of synthetic ACTH (cosyntropin) intravenously or intramuscularly and monitor elevation of cortisol level
No elevation in cortisol is a positive indicator of Addison’s disease
Hyperaldosteronism
Conn’s Syndrome
- Tumor in zona glomerulosa
- The most important effects are hypokalemia, hypertension, mild metabolic alkalosis, slight ↑ in ECF volume and blood volume
- Occasional periods of muscle paralysis caused by the hypokalemia
- Treatment options include surgical removal of tumor or pharmacological antagonism (for mineralocorticoid receptor with spironolactone
Hypoaldosteronism causes
- Causes: destruction of adrenocortical tissue, defects in the synthesis of aldosterone or inadequate stimulation of aldosterone secretion
- Characterized by Na+ loss (hyponatremia), hypovolemia, hypotension, hyperkalemia and metabolic acidosis
- Mineralocorticoid replacement therapy
Adrenogenital Syndrome
¢Excessive quantities of androgens → intense masculinizing effects
¢Females: development of male secondary sexual characteristics
¢Rapid development of male sexual organs in prepubertalmales (pseudopuberty) but little effect in mature males
