1. Adrenal cortex II

2. Functional zonation Zona glomerulosa –Mienralocorticoid secretion only No 17a-hydroxylase Tissue-specific expression of 11beta- hydroxylase (CYP11B2) Zona fasciculata –Glucocorticoids production Difference in promoter that activates 11beta- hydroxylase (CYP11B1)

3. Adrenal stroidogenesis Cholesterol –LDL from circulation Receptor-mediated endocytosis –Uptake regulated by StAR Regulated by cAMP Process –Mostly identical to gonadal steroidogenesis –Almost exclusively uses delta-4 pathway

5. Secretion of mienraocorticoid Aldosterone –Secreted by zona glomerulosa –Regulates salt uptake Water balance Regulated by kidneys –Renin-angiotensin system

6. Renin-angiotensin system Angiotensin II –Cleaved from angiotensin I –8 AA in length Angiontensin I –Cleaved from angiotensinogen Renin –Secreted from juxtaglomerular cells in kidneys

7. Secretion of renin –In response to hypovolumia (loss of blood volume) –In response to increased blood osmolarity

8. Secretion of renin –Baroreceptor hypothesis Part of mechanism regulating arterial blood pressure –Stretching of afferent arterioles (detected by baroreceptors) –Macula dense theory Mediated by chemoreceptors –Distal tubular epithelium –Urinary sodium concentrations

9. Juxtaglumerular apparatus –JG cells plus macula densa cells

10. Role of the CNS Secretion of renin –Under autonomic nervous system control –Increased in response to sympathetic nerve stimulation Binding of norepinephrine to beta receptor –Increased production of cAMP

11. Angiotensin II Vasoconstrictor –Constriction of afferent and efferent atrerioles Regulation of blood pressure Regulation of glomerular filtration rate Angiotensin III –Cleaved from angiotensin II Stimulates secretion of aldosterone without altering blood pressure

12. Local regulation of aldosterone secretion Adrenal renin-angiotensin system –Found in zona glomerulosa –Changes in response to intake of Na and K

13. Kellikrenin-kinin system Kinin –Part of plasma protein –Cleaved from kininogen Kallikrenins Glandular kallikrenins –Found in many glands Regulate production of kinins within the specific tissue

14. Production of kinins within the kidney –Lysolbradykinin Converted to bradykinin –Bradykinin Induces renal vascular smooth muscle relaxation

15. Role of kallikinins in kidneys –Production of renin from prorenin –Production of bradykinin Kininase II –Production of angiotensin II Inactivation of bradykinin

16. Production of angiotensin II and bradykinin by the same pathway –Vasoconstrictor and vasodilator –Elevation of blood pressure without altering blood flow Action of bradykinin restricted to renal vascular bed Normal blood flow to kidney while elevating systemic arterial pressure

17. Function of aldosterone Regulation of Na homeostasis –Regulation of fluid volume within the body Water absorption Sodium/potassium homeostasis –Increased Na reabsorption Distal tubules of kidney GI tract Salivary gland Sweat gland

18. Renal reabsorption of Na –Alters concentrations of K and H –Nephron Increased Na reabsorption Concomitant loss of K –Increased H release by tubules –Mediation of aldosterone action Distal tubules Increased blood Na concentrations

19. Renal reabsorption of Na –Mediation of aldosterone action Distal tubules Increased blood Na concentrations monitored by the JG cells –Decreased renin secretion –Decreased aldosterone secretion Increased blood K concentrations –Increased aldosterone secretion

20. Mechanism of action Transfer of Na –Entry of Na to the cells from fluid via mucosal surface –Release of Na into the interstitial fluid through serosal membrane

21. Effects of aldosterone –Increased protein synthesis Argumentation of Na transport –Increased Na pump activity –Increased metabolism (ATP synthesis) –Increased permeability

22. Receptors –Binds equally well with glucocorticoids Requires additional mechanism for specificity –Conversion of cortisol to corticosterone by 11  - hydroxisteroid dehydrogenane

23. Disorders Glucocorticoid secretion disorders –Hypoadrenalism Addison’s desease –Caused by destruction/atrophy of the gland –Weakness, increased pigmentation, weight loss –Hypotension, salt craving, hypoglycemia –increased pigmentation caused by increased ACTH secretion

24. Disorders Glucocorticoid secretion disorders –Hypercortisolism Cushing’s desease Caused by tumors in adrenal gland (primary) –Pituitary tumor (excess secretion of ACTH, secondary) Symptoms –Central obesity, hypertension, glucose intolerance, hirsutism, osteoporosis, polyuria, and polydipsia –Steroid diabetes

25. Disorders Aldosterone secretion disorders –Conn’s syndrome Hypersecretion caused primarily by the tumor Excess excretion of K and H –Serum alkalosis and neuropathy Increased water retention –Increased Na reabsorption –Increased blood pressure