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Disorders of  water and electrolyte  metabolism Yu-Hong Jia, Ph.D Pathophysiological department Dalian medical university
[object Object],[object Object],[object Object],[object Object]
[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],Solutes  – dissolved particles
Disorders of water and electrolyte metabolism ,[object Object],[object Object],[object Object],[object Object],[object Object],Be familiar with and grasp the pathogenesis and changing rule of water and electrolyte disturbance is important for clinical work.
[object Object],[object Object],[object Object],[object Object],[object Object]
Ⅰ.  Body fluid and electrolyte balance ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
1. Body fluid volume ,[object Object],[object Object],[object Object],[object Object]
 
Why women have less water than men if they are the same weight? ,[object Object]
2. Body fluid distribution ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
 
[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
[object Object],[object Object],[object Object],[object Object]
3. Body fluid composition
Body Fluid Compartments
 
3. Body fluid composition ,[object Object],[object Object],? ? Na +   Cl -   HCO 3 - Extracellular fluid K +  Mg 2+  PO 4 3- Intracellular fluid Cation  Anion
[object Object],[object Object],[object Object],[object Object],[object Object]
 
4. Body fluid osmolality ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
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.
[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
[object Object],[object Object],[object Object],[object Object],[object Object],Because water can move freely through cell membrane and blood capillary wall, so there is no osmotic disequilibrium among different fluid compartment
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
 
[object Object],[object Object],[object Object],Method of water transport? Water  transport Simple diffusion ? Intracellular fluid Interstitial fluid Lipid cell Water  Water channel bilayer
[object Object],[object Object],Aquaporin discovery
Aquaporins,AQPs ,[object Object],[object Object],[object Object],Peter Agre Roderick MacKinnon   2003 Chemistry Nobel Prize Water Channels
Ⅱ.  Mechanism for regulating body fluid and electrolyte balance ,[object Object],[object Object],[object Object],[object Object],[object Object]
[object Object],[object Object],[object Object],[object Object],THIRST 1. The sensation of thirst
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
The regulation of thirsty reaction ,[object Object],[object Object],[object Object]
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
 
Two Kinds of Thirst
2.  Antidiuretic hormone(ADH) ,[object Object],[object Object],[object Object],[object Object],[object Object]
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
ADH feedback regulation mechanism ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
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.
3. Aldosterone ,[object Object],[object Object],[object Object],[object Object],[object Object]
Mechanism of aldosterone effect Principal cells
The renin-angiotensin-aldosterone system Renin  Ang Ⅰ Ang Ⅱ Adrenal gland
4. The natriuretic peptide family ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Atrial Natriuretic Peptide: Release ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Atrial Natriuretic Peptide (ANP) (causes afferent arterial vasodilation and relaxes mesangial cells) (inhibits sympathetic output from cardiovascular center)
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
5. The guanylin family ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
[object Object],↑RAAS ↑ Uroguanylin released from GI Sodium oral intake Renal excretion of Sodium  Sodium balance Increased  decreased - +
[object Object]
Ⅲ . Disorders of water and sodium metabolism
Water Steady State ,[object Object],disorders To eliminate waste produced by metabolism, at least 500ml of urine must be excreted everyday.
[object Object]
 
[object Object]
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)
1. Hypovolemic hypernatremia ,[object Object],Hypertonic dehydration Concept:  Characteristics: ,[object Object],[object Object],[object Object]
Etiology and pathogenesis ,[object Object],[object Object],(1).  Water intake (2).  Water loss ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],i.e. diarrhea and vomitting i.e. ↑environmental and body temperature i.e. diabetes insipidus, Osmotic diuresis ↓ ↑
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.
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 -
Alterations of metabolism and function ,[object Object],↑ Ingestion of water 2. Hyperosmolality of ECF -> stimulate secretion of ADH -> ↑ renal tubular reabsorption of water  ->  decrease of urinary volume & increase of urinary concentration 3. Hyperosmolality of ECF ->water shift from intracellular to extracellular compartment The relative volume change of ICF, interstitial fluid and plasma. -> cell dehydration and shrinkage ↑ ECF volume ↓ ECF osmolality ↑ ECF volume ↓ ECF osmolality ↑ ECF volume ↓ ECF osmolality ICF Interstitial fluid plasma
[object Object],Alterations of metabolism and function (continued) ↑ ADH ->H 2 O reabsorption increase ↑ Urinary sodium Late state, decrease of blood volume ->increase of ADS -> Na +  reabsorption increase ->↓urinary sodium 5. Brain cell dehydration-> CNS dyfunction, such as  twitching, somnolence, coma 6. hypovolemia-> reduced blood pressure, elevation in body temperature
Principles of Therapy: Treating the primary disease Supplying 5%-10% Glucose Adding a small amount of NaCl solution Adding K +  properly
2. Hypovolemic hyponatremia ,[object Object],Hypotonic dehydration Concept:  Characteristics: ,[object Object],[object Object],[object Object]
Etiology and pathogenesis ,[object Object],[object Object],[object Object],[object Object],1. Loss of sodium  via kidney ,[object Object],[object Object],[object Object],[object Object],2. Loss of sodium via extra-kidney furosemide->inhibit Na+ reabsorption by Henle’s loop ascending branch -> ↓ ADS -> ↓renal Na +  reabsorption Chronic interstitial nephritis -> impairment of medullary interstitium and dysfunction of Henle’s loop ->↑urinary Na +  excretion A decrease in H +  excretion in the collecting duct causes the dysfunction of H + -Na +  exchange -> ↑urinary sodium excretion Vomitting, diarrhea Serious perspiration, burn peritonitis->ascites
Alterations of metabolism and function ,[object Object],2. Early stage, hypoosmolality of ECF -> inhibit secretion of ADH -> ↓ renal tubular reabsorption of water  ->  polyuria and & urinary dilution late stage, blood volume seriouly decreased ->↑ADH -> oliguria 3. Hypoosmolality of ECF ->water shift from extracellular to intracellular compartment -> ECF volume further decrease The relative volume change of ICF, interstitial fluid and plasma. ICF Interstitial fluid plasma Decrease skin turgor, postural hypotension, tachycardia, shock
[object Object],Alterations of metabolism and function (continued) If sodium loss via extra-kidney, decrease of blood volume ->increase of ADS -> Na +  reabsorption increase ->↓urinary sodium 4. Water movement into cells  ->  Brain cell swelling->  CNS  dyfunction , such as  nausea, vomiting, twitching, confusion, lethargy, stupor and coma.
Principles of Therapy: Treating the primary disease Supplying 5%Glocose normal saline or 0.9% NaCl solution
3. Isotonic dehydration ,[object Object],Concept:  Characteristics: ,[object Object],[object Object],[object Object]
[object Object],[object Object],[object Object],[object Object]
Isotonic dyhydration Hypertonic dehydration Hypotonic dehydration Insensible water loss Treated inappropriately with pure water
4. Hypervolemic hyponatremia ,[object Object],[object Object],Concept:  Characteristics: ,[object Object],[object Object]
Etiology and pathogenesis (1).  Excessive water intake (2).  Decreased Water loss ,[object Object],[object Object],[object Object],[object Object],[object Object],Over retention of hypotonic fluid in the body In general, water intoxication mostly occurred in patient with acute renal failure and infused inappropriately at the same time. which exceed the ability of renal excretion of water
Alterations of metabolism and function ,[object Object],[object Object],water movement into cells cell swelling  Signs and symptoms of brain cell swelling Elevated blood pressure, blood dilution
5. normovolemic hyponatremia ,[object Object],Concept:  Characteristics: ,[object Object],[object Object]
Etiology and pathogenesis ,[object Object],[object Object],[object Object],1. syndrome of inapproriate ADH secrection (SIADH) 2. reset osmostat syndrome.
SIADH ,[object Object],SIADH->↑ADH ->↑renal reabsorption of water  ECF volume expansion ↑ GFR ↓ Reabsorption of sodium at proximal tubule ↑  ANP ↓ ADS natriuresis ↑ Water excretion slight - diluted serum sodium
Alterations of metabolism and function hyponatremia-> water shifting into cells-> brain cell edema-> CNS dysfunction
6. hypervolemic hyperatremia ,[object Object],Concept:  causes: ,[object Object],[object Object],Alterations of metabolism and function: ,[object Object],[object Object]
7. normovolemic hypernatremia ,[object Object],Characteristics: Etiology and pathogenesis: Osmoreceptor insensitive to osmotic stimulus Only osmotic pressure is obviously higher than normal level  Baroreceptor, stretchreceptor Change of blood volume or pressure Hypothalamus disease abnormal normal Normal: >150mmol/L Abnormal: >160mmol/L 150-160mmol/L [Na + ] upward resetting of osmolar set-point Thirst,  ADH secretion hypernatremia normovolemia
 
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
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
Application Problem 1 ,[object Object]
Answer to Problem 1 ,[object Object]
MILLIEQUIVALENT (mEq) ,[object Object],[object Object],[object Object],[object Object]
Electrochemical Equivalence  ,[object Object],[object Object],[object Object],[object Object],[object Object]
Osmotic Concentration ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],e.g. 1 M NaCl = 2 M Glu in Osm/L
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)

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Body Fluid And Electrolyte Balance

  • 1. Disorders of water and electrolyte metabolism Yu-Hong Jia, Ph.D Pathophysiological department Dalian medical university
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  • 11.  
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  • 13.
  • 14. 3. Body fluid composition
  • 16.  
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  • 19.  
  • 20.
  • 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.
  • 22.
  • 23.
  • 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
  • 25.  
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  • 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
  • 32.
  • 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
  • 34.  
  • 35. Two Kinds of Thirst
  • 36.
  • 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
  • 38.
  • 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.
  • 40.
  • 41. Mechanism of aldosterone effect Principal cells
  • 42. The renin-angiotensin-aldosterone system Renin Ang Ⅰ Ang Ⅱ Adrenal gland
  • 43.
  • 44.
  • 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
  • 47.
  • 48.
  • 49.
  • 50. Ⅲ . Disorders of water and sodium metabolism
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  • 52.
  • 53.  
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  • 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)
  • 56.
  • 57.
  • 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 -
  • 60.
  • 61.
  • 62. Principles of Therapy: Treating the primary disease Supplying 5%-10% Glucose Adding a small amount of NaCl solution Adding K + properly
  • 63.
  • 64.
  • 65.
  • 66.
  • 67. Principles of Therapy: Treating the primary disease Supplying 5%Glocose normal saline or 0.9% NaCl solution
  • 68.
  • 69.
  • 70. Isotonic dyhydration Hypertonic dehydration Hypotonic dehydration Insensible water loss Treated inappropriately with pure water
  • 71.
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  • 76.
  • 77. Alterations of metabolism and function hyponatremia-> water shifting into cells-> brain cell edema-> CNS dysfunction
  • 78.
  • 79.
  • 80.  
  • 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
  • 83.
  • 84.
  • 85.
  • 86.
  • 87.
  • 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)