Chapter 2

1. Chapter 2 Disorders of Water & Electrolyte Metabolism(Ⅰ)

3. 2.1 Disorders of Water & Sodium Metablism

4. Normal water & Sodium Metabolism • Distribution of body fluid(BF) • Electrolyte in BF • Osmolality of BF • Functions and balance of water • Functions of electrolyte • Balance of sodium • Volume & Osmolality regulation of BF

5. Distribution of body fluid(BF) ICF 40% BF 60% plasma 5% ECF 20% Interstitial fluid 15%

8. Electrolyte in BF K Na Na Cl Na Cl HPO4 HCO3 HCO3 HPO4 HCO3 HPO4 Ca SO4 SO4 SO4 K K 有机酸 Mg Pr 有机酸 Ca Mg Ca Mg Pr plasma Interstitial fluid ICF

10. Osmolality of BF • Directly related to the concentration of solutes in the solution • The higher the solute concentration, the greater the osmotic pressure and the greater the tendency of water to move into the solution • Normal OPP＝ cation(151) ＋ anion(139) • ＋ nonelectrolyte (10) • ＝300mmol/L(280 ～310mmol/L)

12. Functions and balance of water • Essential for metabolism • Necessary for temperature regulation • lubrication

13. Water balance

14. Functions of electrolyte • Maintain the osmosis and acid-base balance of BF • Ions carry electric current( action potentials) • Involved in metabolism and physiologic activities

15. Sodium (Na +) • creates osmotic pressure of ECF • most abundant cation in ECF • essential for electrical activity of neurons and muscle cells

16. Sodium balance • N=135-145 mmol/L • aldosterone (from adrenal cortex) increases plasma sodium (Na +) concentrations by increasing rate of Na + reabsorption in the distal convoluted tubules and collecting ducts

17. Volume & Osmolality regulation of BF variation of BF vol ADH aldosterone ANP Thirst center Thirst center ADH aldosterone variation of OPP

19. Regulation of Water Intake • Thirst mechanism involves: - osmotic pressure of ECF - thirst center in the hypothalamus of brain • as water is lost, osmotic pressure of ECF increases • osmoreceptors are stimulated by change and hypothalamus causes person to feel thirsty and seek water

21. Factors affecting the release of ADH.

22. Aldosterone Release: the Renin-Angiotensin Pathway

23. Effects of aldosteron

24. other modifiers • atrial natriuretic peptide (ANP) • ↓renin secretion • ↓aldosteron secretion • Anti-vasoconstriction effect ofAng • Anti sodium-retention effect ofaldo

25. Factors affecting release of Atrial Natriuretic Peptide.

26. Regulating effects of ANP _ 1. increased GFR 2. decreased Na+ reabs. in proximal tubule 3. inhib. Na+ reabs. by collecting duct ANP or ANF

27. other modifiers • Channel Proteins • Some act as a passive pore to allow diffusion of water and some other molecules • Does not require energy • Aquaporins (AQPs）AQP 0-9

28. Peter Agre • BA in Chemistry 1970 Augsburg College • MD 1974 from Johns Hopkins University School of Medicine • 1974 – 75 Postdoctoral Fellowship Johns Hopkins Dept of Pharamacology

29. Aquaporin is a water channel that increases a membrane’s permeability to water

30. AQP-2mediate water retention

31. Vesicles move to and fuse with apical membrane H2O H2O H2O H2O ADP H2O ATP H2O PKA H2O (active) H2O cAMP cAMP cAMP cAMP Vasopressin cAMP ATP PKA (inactive) Kidney Distal Tubule Cell Aquaporin-2 Phosphorylated aquaporin-2 in vesicles bound to microtubular subunits Basolateral membrane Adenylyl cyclase Gs protein Apical membrane Cytoplasm V2 vasopressin receptor Protein Kinase A Pathway Nephrogenic Diabetes Insipidus: defective receptor causes ADH resistance

32. Classification of H2O & Na metabolism disorders hypovolemic hyponatremia low normal high [ Na+ ] hypervolemic hyponatremia Isovolemic hyponatremia hypovolemic hypernatremia low normal high hypervolemic hypernatremia ECF Isovolemic hypernatremia Isotonic dehydration Edema

33. hyponatremia serum sodium＜130 mmol/L • hypovolemic hyponatremia • hypervolemic hyponatremia • Isovolemic hyponatremia

34. hypovolemic hyponatremic (hypotonic dehydration) Definition Causes & mechanism Effects Principles of therapy

35. Definition sodium loss > water loss serum sodium＜130 mmol/L OPP＜ 280mmol/L

36. Causes & mechanism • renal loss • ex-renal loss Diuretics Adrenal insufficiency Renal disease renal tubule acidosis GI tract Third space Skin Renal reabsorb Of H2ONa↓

37. circulatory failure　shock Bl vol↓ aldo↑→ UNa↓ ADH ↑→oliguria interstitial fluid↓→sign of dehydration OPP ECF Thirst ↓ →water intake↓ ADH ↓ → oliguria ICF →ECF↓ Effects • Caused by renal factors，UNa↑

38. Principles of therapy • Treat underlying cause • Restoration the vol of ECF • Treat complication

39. hypervolemic hyponatremia （water intoxication） Definition Causes & mechanism Effects Principles of therapy

40. Definition serum sodium＜130 mmol/L OPP＜ 280mmol/L water retention total sodium : normal or ↑

41. Causes & mechanism • Water intake↑ • Water loss↓ hydroposia↑ GI absorb↑ overtransfusion acute renal failure Oversecretion of ADH Fear、 pain blood loss、shock injury

43. Effects Thirst ↓ →water take↓ ADH ↓ →polyuriaUNa↓ ICF ↑ cellular edema→CNSdisorder OPP

44. Principles of therapy • Treat underlying cause • Restoration water intake • hypertonic saline • diuretics

45. Isovolemic hyponatremia Definition Causes & mechanism Effects Principles of therapy

46. Definition serum sodium＜130 mmol/L OPP＜ 280mmol/L Bl vol: normal or ↑slightly

47. Causes & mechanism • Syndrome of inappropriate secretion of ADH(SIADH) • Malignant tumors Bronchogenic/pancreatic/duodenal/ureter/thymus • CNSdisorders Encephalitis/meningitis/brain abscess/head trauma/ cerebrovascular accident • Pulmonary disorders Pneumonia/pulmonary abscess/tuberculosis/pulmonary fungal infection/ cytic fibrosis

48. Causes & mechanism • UNa↑ Bl vol↑→ANP↑→Na reabsorb↓→UNa↑ ↓ Keep normal ECFvol←ICF↑←ECF OPP↓

49. OPP Thirst ↓ →water intake↓ ICF ↑ cellular edema→CNSdisorders Effects

50. Principles of therapy • Treat underlying cause • Restoration water intake • hypertonic saline • diuretics