AdrenocorticalHormones.pptx physiology 1styear mbbs

Adreno

1. Objectives ■ Name the three catecholamines secreted by the adrenal medulla and summarize their biosynthesis, metabolism, and function. ■ List the stimuli that increase adrenal medullary secretion. ■ Differentiate between C 18 , C 19 , and C 21 steroids and give examples of each. ■ Outline the steps involved in steroid biosynthesis in the adrenal cortex. ■ Name the plasma proteins that bind adrenocortical steroids and discuss their physiologic role. ■ Name the major site of adrenocortical hormone metabolism and the principal metabolites produced from glucocorticoids , adrenal androgens, and aldosterone . ■ Describe the mechanisms by which glucocorticoids and aldosterone produce changes in cellular function.

2. ■ List and briefly describe the physiologic and pharmacologic effects of glucocorticoids . ■ Contrast the physiologic and pathologic effects of adrenal androgens ■ Describe the mechanisms that regulate secretion of glucocorticoids and adrenal sex hormones. ■ List the actions of aldosterone and describe the mechanisms that regulate aldosterone secretion. ■ Describe the main features of the diseases caused by excess or deficiency of each of the hormones of the adrenal gland.

3. Four factors are known to play essential roles in the regulation of aldosterone . In the probable order of their importance, they are as follows Increased potassium ion concentration in the extracellular fluid greatly increases aldosterone secretion. Increased angiotensin II concentration in the extracellular fluid also greatly increases aldosterone secretion. Increased sodium ion concentration in the extracellular fluid very slightly decreases aldosterone secretion. ACTH from the anterior pituitary gland is necessary for aldosterone secretion but has little effect in controlling the rate of secretion in most physiological conditions.

4. CHAPTER SUMMARY ■ The adrenal gland consists of the adrenal medulla that secretes dopamine and the catecholamines epinephrine and norepinephrine , and the adrenal cortex that secretes steroid hormones. ■ Norepinephrine and epinephrine act on two classes of receptors, α- and β- adrenergic receptors, and exert metabolic effects that include glycogenolysis in liver and skeletal muscle, mobilization of FFA, increased plasma lactate, and stimulation of the metabolic rate. ■ The hormones of the adrenal cortex are derivatives of cholesterol and include the mineralocorticoid aldosterone , the glucocorticoids cortisol and corticosterone , and the androgens dehydroepiandrosterone (DHEA) and androstenedione .

5. ■ Androgens are the hormones that exert masculinizing effects, and they promote protein anabolism and growth. The adrenal androgen androstenedione is converted to testosterone and to estrogens (aromatized) in fat and other peripheral tissues. This is an important source of estrogens in men and postmenopausal women. ■ The mineralocorticoid aldosterone has effects on Na + and K + excretion and glucocorticoids aff ect glucose and protein metabolism. ■ Glucocorticoid secretion is dependent on ACTH from the anterior pituitary and is increased by stress. Angiotensin II increases the secretion of aldosterone .

6. ADRENAL GLAND

7. Adrenal glands Consist of 2 distinct organs – - outer adrenal cortex – secrete steroid hormones Essential for life ( adrenalectomy - ↓ aldosterone→fatal hypovolumic shock) inner adrenal medulla – secrete adrenalin, Noradrenalin Not Essential for life Cortical tissue is more than medullary Fetal adrenal gland is larger. By 3 rd year 3 distinct zones are found in adrenal cortex

8. Adrenal cortex – histologically 3 layers 1) zona glomerulosa - 5-6 layers of small compact cells, thin, secrete mineralocorticoids – aldosterone , deoxycortisone 2) zona fasciculata – columns of cells arranged in columns - secrete glucocorticoids – cortisol , corticosterol 3) zona reticularis – network of large cells – secrete sex hormones (androgens and estrogens)

9. Cross – sectional view of the adrenal gland

10. All cells have high conc. of cholesterol from which adrenocortical hormones are synthesized Synthesis – synthesis of different hormones depend upon presence or absence of particular enzymes. If 3- β -OH- dehydrogenase – mineralocorticoid If 17- α - hydroxylase - glucocrticoids

11. Cholesterol in blood LDL receptors cholesterol in Adrenocortical cells pregnanolone Cholesterol desmolase Corticosteroid hormones and their synthesis Zona glomerulosa – mineralocorticoids Zona fasciculata - glucocorticoids Zona reticularis - sex homones

12. Zona glomerulosa – Progesterone Aldosterone Deoxycortisone Pregnanolone Aldosterone synthetase 3- β -OH- dehydrogenase

13. Zona fasciculata & reticularis – 17- α - hydroxy -Progesterone DHEA cortisol Pregnanolone Aldosterone synthetase 17- α - hydroxylase β - hydroxylase Androstenedione Testosterone estradiol aromatase If β - hydroxylase absent

14. Mineralocorticoids - Aldosterone Deoxycorticosone cortisol The main mineralocorticoid is aldosterone while there are some endogenous hormones which have a mineralocorticoid function.

15. Transport in blood - bound to plasma protein – 90% transcortin ( α -globulin) & 6% albumin –Acts as reserve 4% in free form -active. Metabolized in liver to glucuronides (bile salts) Excreted in bile and urine.

16. Actions of aldosterone – On renal tubules – DCT and P cells of collecting duct. Increases reabsorption of Na + associated with H 2 O and secretion of K + & H + . - Regulates only 3% of total Na + absorption which is very imp. For maintaining Na + balance in body. Mechanism of action – activation of Na + - K + ATPase at the basal membrane cause entry of Na + through apical membrane.

17. At pH 7.4 Na + reabsorption is coupled with K + secretion. In acidosis instead of K + H + are secreted. 2. Aldosterone stimulates absorption of Na + & secretion of K + in large intestine, salivary gland and sweat glands. Aldosterone escape - ↑ aldosterone →ECF volume by 10-15% → ↑BP → pressure diuresis Also causes secretion of ANP → ↑ excretion of Na along with H2O →no effect of aldosterone

18. Regulation of aldosterone secretion- ↑K+ conc. In ECF 1. Action directly on cells of z.glomerulosa ↑ synthesis of aldosterone ↑ excretion of K+

19. 2. Renin-angiotensin mechanism - ↓ECF vol. or low Na+ ↓ BP Stimulation of JG cells Secretion of renin liver angiotensinogen Angiotensin I Angiotensin II Adrenal cortex Aldosterone Na+ & H2O reabsorption lung

20. 3. ACTH has mild effect Abnormal secretion – Hypersecretion – Conn’s syndrome – aldosteronism – leads to hypernatrimia , ↑BV, hypertension, hypokalaemia – muscular paralysis, alkalosis. Deficiency of aldosterone – loss of H2O & Na+ in urine - ↓blood volume and ↓BP. ↓K+ excretion causes hyperkalaemia & acidosis

21. Glucocorticoids Source Chemistry Synthesis – in mitochondria & ER Natural glucocorticoids – cortisol , corticosterone Synthetic – cortisol prednisolone dexamethazone It is usually referred to as the “stress hormone” as it is involved in response to stress and anxiety

22. Transport in blood - bound to plasma protein – 90% transcortin ( α -globulin) & 6% albumin –Acts as reserve 4% in free form -active. Metabolized in liver to glucuronides (bile salts) Excreted in bile and urine.

23. Ant. Pit. Adrenal cortex Paraventricular nucleus Median eminance CRH ACTH Unbound cortisol corticotropes Gluconeogenesis Mobilization of a.a . % FFA Stabilization of lysosomes Relieves stress Regulation of glucocorticoids 1.

24. 2. Diurnal variation –maximum in the morning, minimum at mid night 3. Increases sharply in response to stress ACTH –secreted by corticotrops in ant. Pit. 1. CRH by paraventricular nucleus in response to stress 4.

25. Actions of cortisol – required to have normal long life in spite of physical & mental stress. Metabolic actions – Carbohydrate -↑BSL through gluconeogenesis , glycogen storage in liver, ↓utilization except brain – adrenalin diabetes Protein metabolism –catabolic hormone except in liver, ↑ a.a . level ↑ synthesis in liver Lipid metabolism – lipolysis , ↑FFA, Electrolytes –effect same as mineralocorticoid

26. Other actions – Resistance to stress -Helps to cope with the stress –by mobilizing fats & protein Anti inflammatory action and immuno supressive action – Antiallergic response Cortisol ↓number of eosinophils & lymphocytes ↑production of RBC, Platelets and neutrophils

27. f. Gastric effects -↑gastric acid secretion & ↓proliferation of gastric mucosal cells g.Vascular effect –permissive action –increases vascular response to noradrenaline and help in maintainance of BP. Psychomotor response – high levels cause irritability, insomnia, depression Action on bone - ↓Ca++ absorption from gutand inhibit mitosis of fibroblast, break down of collagen- all lead to osteoporosis

28. Disorders of cortisol ( 1) Cushing syndrome – A hormone disorder caused by high levels of cortisol in the blood . It may be caused by ; ( 1 ) Taking glucocorticoid drugs . ( 2 ) Tumors in cortisol secreting cells . ( 3 ) Tumors in ACTH secreting cells – in ant. Pituitary (Cushing’s disease) or in Lungs .

29. Symptoms ( 1 ) Rapid weight gain – central obesity with thinning of limbs Moon face, Buffalo hump,Pendulum abdomen (2) Muscle weakness (3) hirsutism and acne (4) Hyperglycemia (5) immunosupression (6) purple striae (7) Osteoporosis (8) Hypertension. (9) poor wound healing (10) thin skin and hair (11) atherosclerosis Cushing syndrome can be treated by surgery .

30. Central obasity Pendular abdomen Gymacomastia Thinning of extremiti es Moon shaped face

31. Hirsutism Acne

32. Purple stria

33. Buffalo hump

34. ( 2 ) Addison’s disease - hypoadrenalism Deficiency in cortisol level in the blood . Causes – primary atrophy of adrenal cortex invasion by Cancer sudden discontinuation of steroids after prolonged treatment -suppression of ACTH Clincal picture related to ↓ aldosterone , ↓ cortisol , ↑ACTH; ↓ECF volume High potassium levels in the blood – tired Low blood pressure . Low blood sugar succeptibility to infections and stress Mild acidosis Full body weakness Melanin pigmentation due to ↑ ACTH.

35. Adrenogenital syndrome –excess secretion of androgens Musculizing effect in females – virilism -growth of beard, deep voice -baldness, musculine distribution of hairon body, growth of clitoris, thick skin In males – prepubertal - early puberty, rapid growth of sex organs In adults – difficult to diagnose

36. Adrenal Gland-Suprarenal glands

37. Adrenal medulla Only autonomic effector organ without two neuron sympathetic innervation . Sympathetic ganglion where postganglionic neurons have lost their axons and become secretory cells – chromaffin cells or pheochromocytes . Along with whole sympathetic system these hormones prepare the body for “ fight or flight ” response during emergency

38. Synthesis of catacholamines Tyrosine hydroxylase Decarboxylation DOPA decarboxylase dopamine hydroxylase dopamine hydroxylase PNMT –(induced by glucocorticoids ) Hydroxylation In cytoplasm Hydroxylation In vesicles Methylation In cytoplasm In vesicles

39. Storage in cells – Dopamine, Norepinephrine and Epinephrine bound to ATP and a protein called chromogranin A are packaged in granulated vesicles. Release of hormones – preganglionic neuron → release of A Ch → acts on cation channels → entry of Ca ++ → exocytosis of granules containing catecholamines , Half life in circulation is 2 mins .

40. Transport in blood – In plasma 70% of catecholamines are in conjugated with sulphates which is inactive form. Mechanism of action – catecholamines combine with receptors on cell membrane → conformational changes in membrane protein Changes in permeability for ions Effect on activity of enzymes

41. Types of receptors – based on their pharmacological properties – α receptors – α 1 , & α 2 – excitatory except on intestinal movements β receptors – β 1 , & β 2 – inhibitory but excitatory on myocardium β 3: Norepinephrine acts only on α receptors where as Epinephrine acts on both α receptors & β receptors

42. Second messengers – α 1 – IP 3 , Ca ++ , protein kinase C α 2 – G i protein, ↓ cAMP & protein kinase A activity β 1 & β 2 – adenylyl cyclase & cAMP Inactivation of circulating hormones – they are metabolizes predominantly in liver and kidney by enzymes –MAO and COMT to form metanephrine and vanillylmandelic acid (VMA)

43. Actions

44. Effects of catecholamines metabolic effects – β receptors increased blood glucose level - glycogenolysis in liver and muscle - gluconeogenesis – increased lactates - decreased insulin secretion Lipolysis – by activation of hormone sensitive lipase increased FFA Increased metabolic rate due to increased body temp. and metabolism of lactates

45. 2. Systemic effects – a. overall vasoconstriction – α receptors b. vasodilation of muscle vessels – β 2 c. iris dilation – contraction of dilator pupillae – α d. relaxation of intestinal muscles – α e. constriction of sphincters – α f. Cardioacceleration - β 1 g. increased force of contraction of myocardium – β 1 h. bronchodilator – β 2 i . relaxation of bladder muscle – β 2 3. Increased alertness 4. ↑secretion of glucagon and ↓ secretion of insulin 5 ↑ serum K + levels

46. Receptors Signal transduction Location Actions α 1 IP 3 , Ca ++ , protein kinase C Iris Radial Muscle General circulation GIT Urinary bladder Skin Uterus Liver Salivary glands Sex organs(male) Contraction (Dilatation of pupil) Vasoconstriction Decreases motility Sphincters contraction Piloerection Contraction Glycogenolysis Thick viscous secretion Ejaculation α 2 G i protein, cAMP & protein kinase A Blood vessels GIT, Pancreas Vasoconstrictuion Decreases motility Inhibition of Insulin,glucogon secretion

47. Receptors Signal transduction Location Actions β 1 cAMP Heart Kidney Increase in conduction,contraction Renin Secretion β 2 cAMP Ciliary muscle, Heart, Skeletal ,coronary circultn Lungs, GIT liver, Spleen (capsule), Pancreas, Skeletal muscle, Detrusor muscle Relaxation conduction,contraction Dilatation Relaxation(dilatation) Decreases motility Glycogenolysis Relaxation Stimulation of Insulin , Glucogon secretion Increased Contractility, Relaxation β 3 cAMP Adipose tissue Lipolysis

48. Applied – “Adrenal medulla is not essential for life” Hyposecretion – no clinical features 2. Pheochromocytoma – benign tumor causing excess secretion of NE . causes hypertension, orthostatic hypotension. Pt. suffers from headache, palpitations, sweating, blurred vision, Increased urinary excretion of hormones and their metabolites Treatment – removal of tumor

49. Regulation of secretion- Low levels of secretion during basal conditions –contributes to sympathetic tone Decreased secretion during sleep Increased secretion when symp . stimulation as a part of ‘alarm reaction’. It caters help to body for coping up with emergencies such as hypoglycemia, hypovolumia , severe exercise, surgery, pain, hypotension – fight or flight response Selective secretion – Anger aggressive states with familiar situations- NE Anxiety,theatening situations - E

50. α receptors β receptors Inhibition of insulin glycogenolysis ↑ glucogon ↑ ACTH Adipose tissue In liver gluconeogenesis ↑ B S L ↑ blood ketones Ketones ↑ lactates in blood ↑ gl-6-phosphate In muscle ↑ lipolysis ↑ glycolysis ↑ cortisol ↑ FFA

51. ADRENAL GLAND

52. ADRENAL CORTEX Zona Glomerulosa Zona Fasciculata Zona Reticularis Medulla Secrete Mineralocorticoids Secrete Glucocorticoids & sex steroids Secrete sex steroids & Glucocorticoids Catecholamines

53. HORMONES OF ADRENAL CORTEX : MINERALOCORTICOIDS: 1. Aldosterone 2. Deoxycorticosterone GLUCOCORTICOIDS: 1. Cortisol 2. Corticosterone SEX STEROIDS: 1. Dehydroepiandrosterone 2. Androsterone

54. BINDING OF ADRENOCORTICAL HORMONES: PLASMA PROTEIN BINDING: 1. Transcortin binding – 80% of Glucocorticoids 50-60% Mineralocorticoids 2. Albumin – 10-15% of Glucocorticoids Small amounts of Sex steroids

55. GLUCOCORTICOIDS : REGULATION OF SECRETION: 1. ROLE OF ACTH: a. Circadian rhythm - b. Response to stress - 2. GLUCOCORTICOID FEEDBACK:

56. a. Circadian rhythm - 4pm 6pm 4am 6am Midnight Noon 11-OXysteroids ( μ g/dl) 25 5 15 Time:

57. 2. GLUCOCORTICOID FEEDBACK: HYPOTHALAMUS CRH ACTH CORTISOL ANTERIOR PITUITARY ( Corticotrophs ) + ADRENAL CORTEX − − − Circadian regulation NTS Emotion (Limbic system) STRESS Pain ( Nociceptive pathway)

58. GCR HSP GCR GC HSP Nucleus MECHANISM OF ACTION: G R E Transcription of mRNA Transcription of mRNA Gene expression Cell membrane

59. FUNCTIONS OF GLUCOCORTICOIDS 1. EFFECTS ON INTERMEDIARY METABOLISM: 2. PERMISSIVE ACTIONS OF CORTISOL: 3. EFFECTS ON CVS: 4. EFFECTS ON CNS: 5. EFFECTS ON MUSCULOSKELETAL SYSTEM: 6. EFFECTS ON CONNECTIVE TISSUE: 7. EFFECTS ON KIDNEY & WATER METABOLISM:

60. 8. EFFECTS ON FETUS: 9. EFFECTS ON BLOOD CELLS: 10. EFFECTS ON INFLAMMMATION: 11. EFFECTS ON ALLERGY: 12. EFFECTS ON IMMUNE SYSTEM: 13. EFFECTS ON GIT: 14. EFFECTS ON ENDOCRINE FUNCTION: 15. ROLE IN STRESS: Contd :

61. A. ON CARBOHYDRATE METABOLISM: i . Stimulates hepatic gluconeogenesis – ii. Increases secretion of Glycogenolytic hormones – iii. Anti-insulin effect – B. ON PROTEIN METABOLISM: i . Facilitates – ii. Inhibits synthesis of – iii. Mobilizes muscle protein for – Overall effect – 1. EFFECTS ON INTERMEDIARY METABOLISM :

62. Contd : C. ON FAT METABOLISM: Causes Lipolysis – During fasting – D. ON FOOD INTAKE & FAT DISTRIBUTION: i . Increases – by stimulating- ii. Stimulates – iii. Stimulates lipogenesis – iv. Stimulates synthesis of – OVERALL EFFECT ON METABOLISM : 1) DIABETOGENIC, 2) ANTIINSULIN-EFFECT & 3) KETOGENIC

63. SUMMARY OF METABOLIC ACTIONS OF CORTISOL: CORTISOL ANTI-INSULIN, PRODIABETOGENIC & KETOGENIC Gluconeogenesis Glycogenolysis Ketogenesis Plasma Glucose & Ketone bodies Glycogenolysis Anti-insulin effect Proteolysis Amino acid & glucose release Lipolysis FFA & glycerol release Plasma FFA & glucose Glucagon & Epinephrine release Glycogenolysis Plasma glucose NPY release food intake Obesity & insulin resistance

64. 2. PERMISSIVE ACTIONS OF CORTISOL : DEFINITION: 1. Vasopressor & bronchodilator actions of – CATECHOLAMINES 2. Calorigenic effects of – GLUCAGON & CATECHOLAMINES 3. Lipolytic effects of – CATECHOLAMINES 4. During puberty development of - MAMMARY GLAND 5. During fetal life development of - HEPATIC ENZYMES 6. In fetal lung synthesis, maturation of - SURFACTANT 7. Development of bacterial flora & enzymes in - INTESTINE

65. 3. EFFECTS ON CVS : ON HEART: ON BLOOD VESSELS: 4. EFFECTS ON CNS : ON SLEEP – ON MOOD – ON MEMORY – 5. EFFECTS ON CONNECTIVE TISSUE : ON COLLAGEN SYNTHESIS

66. 6. EFFECTS ON MUSCULOSKELETAL SYSTEM ON MUSCLE: ON BONE: 7. EFFECTS ON KIDNEY & WATER BALANCE : ON GFR: 8. EFFECTS ON FETUS : ON CNS: ON LUNGS: ON GIT:

67. 9. EFFECTS ON BLOOD CELLS : ON LEUCOCYTES – Leucocytosis Lymphocytopenia Eosinopenia ON RBC – ON PLATELETS –

68. 10. EFFECTS ON INFLAMMATION : INFLAMMATORY RESPONSES – 1. Dilation of capillaries 2. Increased capillary permeability 3. Granulocyte migration 4. Killing of organism MEDIATORS OF INFLAMMATION: a. Prostaglandins, b. Thromboxanes , c. Leukotrienes , d. Kinins , e. Histamine, f. Serotonin, g. Lymphokines , h. EDR & i . Platelet activating factor Mechanism of Anti-inflammatory actions :

69. CORTISOL Synthesis of Lipocortins Inhibition of Phospholipase A2 Release of Arachidonic acid Inflammatory mediators Stabilization of Lysosomal membrane Release of Proteolytic enzymes No Proteolytic damage Inflammatory injury Histamine release Vasodilation Capillary permeability blood flow; No Swelling & flare Inhibition of mast cell PREVENTION OF INFLAMMATION 1 3 2

70. CORTISOL On Leucocytes 4 Chemotaxis Phagocytosis Leucocyte activity 5 Production of I k B α ( Cytoplasmic protein) NF K B (Nuclear factor) Remains attached to I k B α Inactivation of NF K B Inhibition of Gene Transcription Formation of inflammatory chemicals PREVENTION OF INFLAMMATION

71. 11. EFFECTS ON ALLERGY : ANTI-ALLERGIC EFFECTS: 1. Cortisol inhibits degranulation of – 2. It prevents growth of – 12. EFFECTS ON IMMUNE SYSTEM : IMMUNOSUPPRESIVE EFFECTS: Influences more on cellular immunity – IMMUNOSUPPRESIVE MECHANISM -

72. IMMUNOSUPPRESIVE MECHANISM :

73. CORTISOL Apoptosis of T cells Destroys: T cells (Thymus) B & T cells (lymph node) Inhibits transformation of monocyte to macrophage CELLULAR IMMUNITY ↓ Circulating T cells ↓ NF K B activity of T cells ↓ Lymphocyte Migration & cytokine production ↓ Circulating T & B cells ↓ IL2 production from T cells ↓ Humoral immunity ↓ IL2 & γ IFN from macrophage General suppression of immunity

74. CORTISOL INDICATIONS & CONTRAINDICATIONS : INDICATIONS: Inflammatory diseases – Prevention of transplant rejection – Prevention of fibroblastic growth – CONTRAINDICATIONS: Acute infection –

75. 13. EFFECTS ON GIT : 1. Cortisol stimulates secretion of – 2. It decreases absorption of – 14. EFFECTS ON ENDOCRINE FUNCTION : Inhibits secretion of – 15. ROLE IN STRESS : Essential for Catecholamines to – a. Exert their FFA mobilizing action b. Maintenance of vascular reactivity

76. ROLE OF CORTISOL IN STRESS : STRESS HYPOTHALAMUS: CRH ANTERIOR PITUITARY: ACTH ADRENAL CORTEX: CORTISOL FFA RELEASE VASCULAR REACTIVITY MAINTENANCE OF BLOOD VOLUME & BLOOD PRESSURE CALORIE SUPPLY

77. HYPERSECRETION OF ADRENAL CORTICAL HORMONES HYPERSECRETION OF GLUCOCORTICOIDS: CUSHING’S SYNDROME HYPERSECRETION OF ANDROGEN SECRETION: ADRENOGENITAL SYNDROME HYPOSECRETION OF GLUCOCORTICOIDS: ADDISON’S DISEASE

78. CUSHING’S SYNDROME CAUSES:

79. FEATURES: 1. Centripetal obesity & overweight: 2. Moon face: 3. Hypertension: 4. Reddish purple striae : 5. Ecchymoses : 6. Proximal myopathy : 7. Poor wound healing: 8. Osteoporosis: 9. Hyperglycemia:

80. Pendulous abdomen Fat pads Moon face Striae Poor muscle development Poor wound healing

81. ADRENOGENITAL SYNDROME Cause: Features: 1. Hirsuitism 2. Small breasts 3. Receding hairline 4. Heavy arms & legs 5. Male escuticheon 6. Androgenic flush 7. Enlarged clitoris

82. Hirsuitism Small breasts Receding hairline Heavy arms & legs Male escutcheon Androgenic flush Enlarged clitoris

83. ADDISON’S DISEASE : ETIOLOGY: CLINICAL FEATURES: 1. Loss of weight & fatigability – 2. Pigmentation of skin – 3. Hypotension – 4. Eosinophilia – DIAGNOSIS: TREATMENT:

84. MINERALOCORTICOIDS REGUALTION OF ALDOSTERONE: Important stimuli – Renin - Angiotensin - Aldosterone mechanism - Enzymes required: 3. Angiotensin converting enzyme (ACE) 1. Angiotensin II 2. ACTH 3. Plasma K + concentration 1. ANGIOTENSIN II: 2. Angiotensinogen , 1. Renin , Angiotensin receptors - AT1 & AT2 2. ACTH: Receptors – Glomerulosa cells

85. ANGIOTENSINOGEN ANGIOTENSIN I RENIN ANGIOTENSIN II ACE AMINOPEPTIDASE ANGIOTENSIN III STIMULATES ALDOSTERONE SYNTHEISIS STIMULATES ALDOSTERONE SYNTHEISIS

86. Conditions that increase aldosterone secretion – Hemorrhage, Hypovolemia , Hyponatremia , Standing , Anxiety & Physical trauma Secondary hyperaldosteronism : Congestive heart failure, Cirrhosis of liver & Nephritic syndrome Conditions that decrease aldosterone secretion – Hypokalemia & Hypernatremia ECF volume,

87. MECHANISM OF ACTION: GENOMIC ACTION – NON-GENOMIC ACTION – PHYSIOLOGICAL ACTIONS: Electrolyte & water balance – Mechanisms- ALDOSTERONE ESCAPE PHENOMENON:

88. HYPERSECRETION : PRIMARY HYPERALDOSTERONISM – SECONDARY HYPERALDOSTERONISM – HYPOSECRETION : SEX STEROIDS CONTROL – FUNCTIONS –

89. ADRENAL MEDULLA HORMONES: 1. EPINEPHRINE 2. NOREPINEPHRINE 3. DOPAMINE REGULATION OF SECRETION: MECHANISM OF ACTION: Cell membrane receptors –

90. PHYSIOLOGICAL ACTIONS: I. ON INTERMEDIARY METABOLISM: a. Carbohydrate metabolism – Net effect: b. Fat metabolism – Prodiabetogenic & Proketogenic c. On Thermogenesis – d. Fight or fight response – II. EFFECTS ON CVS:

91. III. ON GIT: IV. ON RS: V. ON EYE: VI. ON ENDOCRINE ORGANS: Stimulate ADH Secretion Increased Renin secretion Stimulate Thyroid Hormone secretion Promote conversion of T 4 to T 3 VII. On KIDNEYS:

92. APPLIED : CLINICAL USES OF CATECHOLAMINES – 1. Agonists – Nasal decongestant Apetite inhibitor 2. Antagonists – Treatment of Hypertension Treatment of Hyperthyroidism PHEOCHROMOCYTOMA: Cause – Features –