pathophysiology

1. Disorders of water and electrolyte metabolism Yu-Hong Jia, Ph.D Pathophysiological department Dalian medical university

14. 3. Body fluid composition

15. Body Fluid Compartments

21. Osmosis When a bottle bottomed with a semi-permeable membrane is filled with 3% salt solution and put into a glass of water, the water in the glass will move into the bottle, this phenomenon is call osmosis. Osmosis make the salt solution rising and solution stops rising when weight of column equals osmotic pressure.

24. fewer same more Particle concentration compared with intracellular fluid Swell & burst no alteration wrinkle or shrivel Response of cell placed in solution 0.45% NaCl 0.9% NaCl 3% NaCl Distilled water 5% glucose 20% glucose Representative solution <280 280-310 >310 Osmolality (mmol/L) hypotonic isotonic hypertonic

31. The vascular organ of the lamina terminalis (OVLT) contains osmoreceptive neurons – also the subfornical organ (SFO) and the median preoptic n. (MnPO) Osmoreceptors stimulate AVP secretion and thirst These cells project to the paraventricular nuclei ( PVN) and supraoptic nuclei ( SON) to produce AVP secretion

33. Thirst is inhibited by decreased plasma osmolality (OVLT receptors) and by increased blood pressure (hypervolemia) Thirst is triggered by increased plasma osmolality (OVLT receptors) , decreased plasma volume, and increased plasma Ang Ⅱ which is caused by decreased plasam volume. (angiotensin II in SFO). Thirst precisely regulate the volume and osmolality of ECF

35. Two Kinds of Thirst

37. The signal pathway following V2 receptor stimulation by ADH AC: adenylate cyclase; BLM: basolateral membrane; AM: apical membrane; V2: vasopressin receptor; PKA: protein kinase A tubule

39. ADH is more sensitive to the change of osmotic pressure. 1-2% change of osmotic pressure will change the production of ADH. At first, when blood volume is not markedly decrease, ADH will not be increased. When blood volume is decreased >10%, ADH will be increased At this time, the decrease of blood volume may be life-threatening. ADH released BP/Blood volume + Stretch receptor + Plasma osmotic pressure + Osmoreceptor + Plasma osmotic pressure - Osmoreceptor - ? maintenance of body fluid volume has priority over maintenance of body fluid osmolality.

41. Mechanism of aldosterone effect Principal cells

42. The renin-angiotensin-aldosterone system Renin Ang Ⅰ Ang Ⅱ Adrenal gland

45. Atrial Natriuretic Peptide (ANP) (causes afferent arterial vasodilation and relaxes mesangial cells) (inhibits sympathetic output from cardiovascular center)

46. NPR-A/B Mediates ANP Functional Effects NPR-C is Clearance Mechanism Levin et al., NEJM (1998) 339:321-328 Action of atrial natriuretic peptide at target cells PDE: phosphodiesterase

50. Ⅲ . Disorders of water and sodium metabolism

55. Classification of disorders of water and sodium metabolism ECF volume Hypervolemia Normovolemia Hypovolemia Disorders of water metabolism with normal serum sodium concentration Hypovolemic hyponatremia (Hypotonic dehydration) Isotonic dehydration Hypovolemic hypernatremia (Hypertonic dehydration) Normal Hypervolemic hyponatremia (Water intoxication) Edema Hyponatremia Hypernatremia Dehydration : an excessive loss of body fluid. Serum sodium concentration Normovolemic hyponatremia (SIADH, Rest osmostat) Normovolemic hypernatremia (Upward resetting of hypothalamus osmolar set-point) Hypervolemic hypernatremia (Sodium intoxication) (<130mmol/L) (130-150mmol/L) (>150mmol/L)

58. Diabetes Insipidus Central diabetes insipidus is characterized by decreased secretion of antidiuretic hormone (ADH) that results in polyuria and polydipsia by diminishing the patient's ability to concentrate urine. Nephrogenic diabetes insipidus is characterized by a decrease in the ability to concentrate urine due to a resistance to ADH action in the kidney.

59. Osmotic diuresis Increased blood glucose ↑ Glomerular filtration of glucose ↑ Osmotic pressure of renal tubular fluid ↓ Water reabsorption Osmotic diuresis H 2 O reabsorption ↑ glucose filtration Osmotic diuresis ↑ Osmolality -

62. Principles of Therapy: Treating the primary disease Supplying 5%-10% Glucose Adding a small amount of NaCl solution Adding K + properly

67. Principles of Therapy: Treating the primary disease Supplying 5%Glocose normal saline or 0.9% NaCl solution

70. Isotonic dyhydration Hypertonic dehydration Hypotonic dehydration Insensible water loss Treated inappropriately with pure water

77. Alterations of metabolism and function hyponatremia-> water shifting into cells-> brain cell edema-> CNS dysfunction

81. Effects of hypernatremia on the brain. Brain shrinkage within minutes of development of hypertonicity.Rapid adaptation in few hrs. Rapid correction results in cerebral edema

82. Effects of hyponatremia on the brain and adaptive responses. Brain swelling occurs in minutes of developing hypotonicity, Partial restoration in hrs, normalization of brain vol in days. Overly aggressive correction of Na can lead to irreversible brain damage

88. Classification of disorders of water and sodium metabolism ECF volume Hypervolemia Normovolemia Hypovolemia Disorders of water & sodium metabolism with normal serum sodium concentration Hypotonic dehydration Isotonic dehydration Hypertonic dehydration Normal Water intoxication Edema Hyponatremia Hypernatremia Dehydration : an excessive loss of body fluid. Serum sodium concentration SIADH Rest osmostat Upward resetting of hypothalamus osmolar set-point Sodium intoxication (<130mmol/L) (130-150mmol/L) (>150mmol/L)