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Physiology of the Adrenal Gland <ul><li>Adrenal cortex </li></ul><ul><li>Anatomy review </li></ul><ul><li>Synthesis of cor...
The adrenal glands are situated at the upper poles of each kidney and consist of an outer cortex surrounding a central med...
Adrenal cortex <ul><li>Has three histological zones </li></ul><ul><li>1. Zona glomerulosa  (produces  aldosterone , minera...
<ul><li>Synthesis of corticosteroids </li></ul>Zona glomeruloza Pregnenolone Progesterone 11-Deoxycortico sterone Corticos...
<ul><li>Glucocorticoids </li></ul><ul><li>-  cortisol  ~ 96% is bound to corticosteroid- </li></ul><ul><li>binding globuli...
Effects of glucocorticoids <ul><li>Metabolic effects </li></ul><ul><li>- anti-insulin </li></ul><ul><li>- stimulate glucon...
<ul><li>Antigrowth effects : </li></ul><ul><li>-  growth hormone and its action on somatic growth </li></ul><ul><li>- caus...
Effects of mineralocorticoid <ul><li>Is essential for life </li></ul><ul><li>Aldosterone exerts ~95% of  mineralocorticoid...
Hypothalamic-hypophyseal-adrenal axis (control system) <ul><li>CRF ( hypothalamus )  ACTH ( adenohypophysis )  </li></ul><...
Higher brain centers  Hormonal Limbic system Hypothalamus Pituitary CRF Adrenal ACTH ACTH Stress Diurnal rhythm Cortisol -...
Renin-angiotensin-aldosterone (control system) <ul><li>Renin , a proteolytic enzyme, secreted by juxtaglomerular cells (JG...
 
Clinical <ul><li>Addison’s disease  (due to destruction of adrenal gland – autoimmune disease/ </li></ul><ul><li>tuberculo...
<ul><li>Cushing’s syndrome  – results from excess glucocorticoid activity/hypercortisolism </li></ul><ul><li>May be caused...
Adrenal Medullary Hormones <ul><li>Cells in the adrenal medulla synthesize and secrete  </li></ul><ul><li>epinephrine  and...
 
Synthesis and Secretion of Catecholamines Synthesis of catecholamines begins with the amino acid tyrosine, which is taken ...
Adrenergic Receptors and Mechanism of Action <ul><li>The physiologic effects of epinephrine and norepinephrine are initiat...
Complex physiologic responses result from adrenal medullary stimulation because there are multiple receptor types which ar...
Physiologic Effects of Medullary Hormones In general, circulating  epinephrine  and  norepinephrine  released from the adr...
 
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19. adrenal glands

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Transcript of "19. adrenal glands"

  1. 1. Physiology of the Adrenal Gland <ul><li>Adrenal cortex </li></ul><ul><li>Anatomy review </li></ul><ul><li>Synthesis of corticosteroids </li></ul><ul><li>Glucocorticoids </li></ul><ul><li>Mineralocorticoids </li></ul><ul><li>Controlling system </li></ul><ul><li>Renin-angiotensin system </li></ul><ul><li>Adrenal medulla and its hormones </li></ul><ul><li>-Synthesis and secretion </li></ul><ul><li>-Adrenergic receptors </li></ul><ul><li>-Physiologic effects </li></ul>
  2. 2. The adrenal glands are situated at the upper poles of each kidney and consist of an outer cortex surrounding a central medulla
  3. 3. Adrenal cortex <ul><li>Has three histological zones </li></ul><ul><li>1. Zona glomerulosa (produces aldosterone , mineralocorticoid) </li></ul><ul><li>2. Zona fasciculata and </li></ul><ul><li>3. Zona reticularis (both produce glucocorticoids, cortisol and corticosterone ) + </li></ul><ul><li>androgens ( DHEA, DHEA sulfate ) </li></ul><ul><li>21 carbon atom compounds </li></ul><ul><li>- mineralocorticoid (aldosterone) </li></ul><ul><li>affects Na & K metabolism </li></ul><ul><li>- glucocorticoids (cortisol & </li></ul><ul><li>corticosterone) affect carbohydrate </li></ul><ul><li>and protein metabolism </li></ul><ul><li>19 carbon atoms </li></ul><ul><li>- adrenal androgenes </li></ul>
  4. 4. <ul><li>Synthesis of corticosteroids </li></ul>Zona glomeruloza Pregnenolone Progesterone 11-Deoxycortico sterone Corticosterone Aldosterone Angiotensin II (18-OH Corticosterone) (2) (3) (4) (5) Cholesterol Pregnenolone Progesterone 11-Deoxycorticosterone Corticosterone 17-OH Pregnenolone DHEA Androstene- dione (2) (1) 17-OH Progesterone (2) 11-Deoxy-cortisol Cortisol (3) (4) (2) (3) (4) Zona fasciculata and zona reticularis Hormone synthesis in the adrenal cortex. The zona glomerulosa can not convert corticosterone to cortisol. 1-5 indicate the enzymes responsible for hormone synthesis: 1) 17 α-hydroxylase (lacking in zona glomerulosa); 2) 3 β-dehydrogenase; 3) 21 β-hydroxylase; 4) 11 β-hydroxylase; 5) corticosterone methyloxidase
  5. 5. <ul><li>Glucocorticoids </li></ul><ul><li>- cortisol ~ 96% is bound to corticosteroid- </li></ul><ul><li>binding globulin (CBG) or transcortin </li></ul><ul><li>- a minor degree of binding to albumin </li></ul><ul><li>- ~ 4% is free ( biologically active ) </li></ul><ul><li>- corticosterone (secreted 1/10th amount </li></ul><ul><li>of cortisol) </li></ul><ul><li>Plasma level follows circadian rhythm: </li></ul><ul><li>- highest between 4.00 – 8.00 am </li></ul><ul><li>- levels secondary to variation in ACTH and circadian rhythm of CRF </li></ul>
  6. 6. Effects of glucocorticoids <ul><li>Metabolic effects </li></ul><ul><li>- anti-insulin </li></ul><ul><li>- stimulate gluconeogenesis plasma glucose </li></ul><ul><li>- plasma amino acid levels </li></ul><ul><li>- lipolysis which causes truncal obesity </li></ul><ul><li>Renal effect: </li></ul><ul><li>- maintain GFR (glomerular filtration rate) and RPF (renal plasma flow) </li></ul><ul><li>Gastric effects: </li></ul><ul><li>- gastric flow and acid secretion </li></ul><ul><li>- mucosal cell proliferation </li></ul><ul><li>Vascular effect: </li></ul><ul><li>- Cortisol catecholamine synthesis </li></ul>
  7. 7. <ul><li>Antigrowth effects : </li></ul><ul><li>- growth hormone and its action on somatic growth </li></ul><ul><li>- cause muscle atrophy and muscle weakness </li></ul><ul><li>- Ca absorption from the gut </li></ul><ul><li>- collagen formation osteoporosis and delayed wound healing </li></ul><ul><li>Anti-inflammatory and anti-allergic effects: </li></ul><ul><li>- capillary permeability </li></ul><ul><li>- leucocyte migration </li></ul><ul><li>- number of lymphocytes, monocytes, eosinophils, basophils and histamine </li></ul><ul><li>release </li></ul><ul><li>- number of neutrophils, erythrocytes and platelets </li></ul><ul><li>Stress adaptation: </li></ul><ul><li>- activates the hypothalamic-hypophyseal-adrenal axis </li></ul><ul><li>- has some mineralocorticoid action – retain Na and water </li></ul><ul><li>- exerts negative feedback effect at the level of CRF and ACTH secretion </li></ul>
  8. 8. Effects of mineralocorticoid <ul><li>Is essential for life </li></ul><ul><li>Aldosterone exerts ~95% of mineralocorticoid effect </li></ul><ul><li>The majority of aldosterone remains bound: </li></ul><ul><li>- to albumin </li></ul><ul><li>- the rest is bound to CBG </li></ul><ul><li>Na retention by: </li></ul><ul><li>- absorption of Na in distal and collecting tubules of nephrons </li></ul><ul><li>- sweat glands </li></ul><ul><li>- salivary glands and </li></ul><ul><li>- GI mucosa </li></ul><ul><li>K elimination </li></ul><ul><li>Maintains ECF (extracellular fluid volume) </li></ul>
  9. 9. Hypothalamic-hypophyseal-adrenal axis (control system) <ul><li>CRF ( hypothalamus ) ACTH ( adenohypophysis ) </li></ul><ul><li>adrenal cortex (ZG & ZF) Cortisol </li></ul><ul><li>Cortisol CRF ACTH cortisol (negative </li></ul><ul><li>feedback) </li></ul><ul><li>CRH-ACTH axis is activated by: </li></ul><ul><li>- severe trauma - hemorrhage </li></ul><ul><li>- burns - heavy exercise </li></ul><ul><li>- pyrogens - infection and fever </li></ul><ul><li>- hypoglycemia - chemical intoxication </li></ul><ul><li>- histamine - pain </li></ul><ul><li>- electrical shock - surgery </li></ul><ul><li>- anxiety - cold exposure </li></ul><ul><li>Level of “free” cortisol acts on anterior pituitary and hypothalamus </li></ul><ul><li>by negative feedback </li></ul>
  10. 10. Higher brain centers Hormonal Limbic system Hypothalamus Pituitary CRF Adrenal ACTH ACTH Stress Diurnal rhythm Cortisol - - negative feedback Mineralocorticoids Androgens/Estrogens The hypothalamic-pituitary-adrenal axis
  11. 11. Renin-angiotensin-aldosterone (control system) <ul><li>Renin , a proteolytic enzyme, secreted by juxtaglomerular cells (JG) of the </li></ul><ul><li>juxtaglomerular apparatus (JGA) </li></ul><ul><li>Baroreceptors and chemoreceptors of JGA are sensitive to: </li></ul><ul><li>- hypovolemia renin </li></ul><ul><li>- concentration of Na renin </li></ul><ul><li>The renin-angiotensin system is also stimulated by: </li></ul><ul><li>- sympathetic nervous system renin </li></ul><ul><li>Hypotension renin </li></ul><ul><li>Aldosterone secretion is controlled by: ECF volume BP or Na </li></ul><ul><li>renin (JGA) angiotensin (plasma) angiotensin I </li></ul><ul><li>angiotensin II aldosterone (zona glomerulosa) [“converting enzyme” </li></ul><ul><li>converts ANG I to ANG II] </li></ul><ul><li>K adrenal zona glomerulosa aldosterone </li></ul>
  12. 13. Clinical <ul><li>Addison’s disease (due to destruction of adrenal gland – autoimmune disease/ </li></ul><ul><li>tuberculosis) – primary hypoadrenalism </li></ul><ul><li>ACTH melanocyte activity pigmentation of the skin + buccal mucosa </li></ul><ul><li>Secondary hypoadrenalism is due to: ACTH (pituitary damage) </li></ul><ul><li>Features: </li></ul><ul><li>- weakness - anorexia </li></ul><ul><li>- loss of weight - abdominal pain </li></ul><ul><li>- loss of Na and water dehydration - hypercalcemia </li></ul><ul><li>- hypotension - hyperkalemia metabolic acidosis </li></ul><ul><li>- postural dizziness - anemia </li></ul><ul><li>- hypoglycemia - lymphocytosis </li></ul><ul><li>- vomiting - eosinophilia </li></ul><ul><li>- diarrhea </li></ul>
  13. 14. <ul><li>Cushing’s syndrome – results from excess glucocorticoid activity/hypercortisolism </li></ul><ul><li>May be caused by </li></ul><ul><li>- ACTH </li></ul><ul><li>- glococorticoid secreting tumor and stunted growth </li></ul><ul><li>Features: </li></ul><ul><li>In children: arrested puberty and stunted growth </li></ul><ul><li>In adults: </li></ul><ul><li>- truncal obesity - hirsutism ( androgens) </li></ul><ul><li>- moon face - hypertension </li></ul><ul><li>- think skin striae - altered mentation </li></ul><ul><li>- acne - proximal muscle weakness </li></ul><ul><li>- menstrual irregularity - osteoporosis </li></ul><ul><li>- increased appetite - decreased libido </li></ul><ul><li>- diabetes mellitus - poor wound healing </li></ul><ul><li>Mineralocorticoid excess (primary hyperaldosteronism/Conn’s syndrom) </li></ul><ul><li>Features: </li></ul><ul><li>- hypertension - headache </li></ul><ul><li>- hypokalemia metabolic alkalosis - tateny </li></ul><ul><li>- fatigue - polyuria and polydipsia </li></ul><ul><li>- nocturia - escape phenomenon prevents edema </li></ul><ul><li>- muscle weakness </li></ul>
  14. 15. Adrenal Medullary Hormones <ul><li>Cells in the adrenal medulla synthesize and secrete </li></ul><ul><li>epinephrine and norepinephrine . </li></ul><ul><li>The ratio of these two catecholamines </li></ul><ul><li>differs considerably among species: </li></ul><ul><li>in humans, cats and chickens, roughly 80, 60 and 30% of the </li></ul><ul><li>catecholamine output is epinephrine. </li></ul><ul><li>Following release into blood, these hormones bind adrenergic </li></ul><ul><li>receptors on target cells, where they induce essentially the same </li></ul><ul><li>effects as direct sympathetic nervous stimulation </li></ul>
  15. 17. Synthesis and Secretion of Catecholamines Synthesis of catecholamines begins with the amino acid tyrosine, which is taken up by chromaffin cells in the medulla and converted to norepinephrine and epinephrine through the following steps: Norepinephine and epinephrine are stored in electron-dense granules which also contain ATP and several neuropeptides. Secretion of these hormones is stimulated by acetylcholine release from preganglionic sympathetic fibers innervating the medulla. Many types of &quot;stresses &quot; stimulate such secretion, including exercise , hypoglycemia and trauma . Following secretion into blood, the catecholamines bind loosely to and are carried in the circulation by albumin and perhaps other serum proteins .
  16. 18. Adrenergic Receptors and Mechanism of Action <ul><li>The physiologic effects of epinephrine and norepinephrine are initiated by their </li></ul><ul><li>binding to adrenergic receptors on the surface of target cells. </li></ul><ul><li>These receptors are prototypical examples of seven-pass transmembrane proteins </li></ul><ul><li>that are coupled to G proteins which stimulate or inhibit intracellular signalling </li></ul><ul><li>pathways. </li></ul>
  17. 19. Complex physiologic responses result from adrenal medullary stimulation because there are multiple receptor types which are differentially expressed in different tissues and cells. The alpha and beta adrenergic receptors and their subtypes were originally defined by differential binding of various agonists and antagnonists and, more recently, by analysis of molecular clones. Receptor Effectively Binds Effect of Ligand Binding Alpha 1 Epinephrine, Norepinphrine Increased free calcium Alpha 2 Epinephrine, Norepinphrine Decreased cyclic AMP Beta 1 Epinephrine, Norepinphrine Increased cyclic AMP Beta 2 Epinephrine Increased cyclic AMP
  18. 20. Physiologic Effects of Medullary Hormones In general, circulating epinephrine and norepinephrine released from the adrenal medulla have the same effects on target organs as direct stimulation by sympathetic nerves , although their effect is longer lasting . <ul><li>Increased rate and force of contraction of the heart muscle: this is predominantly </li></ul><ul><li>an effect of epinephrine acting through beta receptors . </li></ul><ul><li>Constriction of blood vessels: norepinephrine , in particular, causes widespread </li></ul><ul><li>vasoconstriction, resulting in increased resistance and hence arterial blood pressure. </li></ul><ul><li>Dilation of bronchioles: assists in pulmonary ventilation. </li></ul><ul><li>Stimulation of lipolysis in fat cells: this provides fatty acids for energy production </li></ul><ul><li>in many tissues and aids in conservation of dwindling reserves of blood glucose. </li></ul><ul><li>Increased metabolic rate: oxygen consumption and heat production increase </li></ul><ul><li>throughout the body in response to epinephrine . Medullary hormones also promote </li></ul><ul><li>breakdown of glycogen in skeletal muscle to provide glucose for energy production. </li></ul><ul><li>Dilation of the pupils . </li></ul><ul><li>Inhibition of certain &quot;non-essential&quot; processes: an example is inhibition of </li></ul><ul><li>gastrointestinal secretion and motor activity. </li></ul>Common stimuli for secretion of adrenomedullary hormones include exercise , hypoglycemia , hemorrhage and emotional distress .
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