Tonicity disorders
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Hypernatremia and hyponatremia for medical students, tonicity, volume and water disorders including syndrome of inappropriate ADH secretion and diabetes insipidus.
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Tonicity disorders
- 1. بسم ا الرحمن الرحيم ”رب اشرح لي صدري ويسر لي أمري واحلل عقدة من لساني يفقهوا قولي“
- 2. WATER AND SODIUM DISORDERS
- 3. Tonicity Disorders Outline : Water and sodium BALANCE and distribution The differences and the relation between water and volume disorders The concept of equilibrium (balance) and steady state Clinical presentation of water and volume disorders Outline of management Diuretics and fluid therapy
- 4. The Concept of Balance and Steady Stat Hydrogen ion (acid-base) balance Potassium, calcium, phosphorous, magnesium, etc… Water balance Sodium and volume balance Energy (calories) balance
- 6. Potassium Balance (3.5-5.0 mEq)
- 7. Water Balance Daily filtration: Water 180 Lt Sodium 25000 mEq
- 8. Positive vs negative balance Negative Balance state Positive
- 9. Total Body Water (sex & age) Total Body Sodium 50 meq/Kg
- 11. Compartments Ions Distribution 95% 98%
- 12. Concepts of: 1- FS forces 2- Diffusion 3- Osmosis
- 14. Tonic and non-tonic regulation of water balance
- 15. AVP-Receptor Subtypes Receptor Site of Action Pharmacologic Effects Subtype Vascular smooth muscle Vasoconstriction Platelets Platelet aggregation V1A Lymphocytes and monocytes Coagulation factor release Hepatocytes Glycogenolysis V1B Anterior pituitary ACTH and β-endorphin release Renal collecting duct Free water absorption V2 cells
- 17. CV Symp & signs
- 18. Volume disorders Water disorders
- 19. SODIUM & WATER DISORDERS Definitions Hypernatremia & hyponatremia (135-145 meq/l) Hypervolemia & hypovolemia (50 meq/Kg) Hypovolemia vs. dehydration Proportionate and disproportionate disorder Hyperosmolar & hypertonic (urea vs. glucose) Pseudohyponatremia (Isotonic hyponatremia) Translocation hyponatremia (Hypertonic) Acute vs. chronic (48 hrs)
- 23. 27 gram Na hypertonic (Osm 924) H2O Osm 308 Cl 4.5 gram Na hypotonic (Osm 77) Isotonic
- 24. PSEUDOHYPONATREMIA ISOTONIC HYPONATREMIA SERUM Na+ = 140 meq/L SERUM Na+ = 130 meq/L SOLIDS 7% Serum Osmolality= SOLIDS 2Na+urea+glucose 14% HYPERLIPIDEMIA 140/930 130/860 H2O HYPERPROTEINEMIA H2O 93% 86% Measured>Calculated 140/930 = 151/1000 = 130/860 WATER 7% 10/70 OSMOLALITY: MEASURES SOLUTE PER UNIT PLASMA WATER
- 26. + Hyper SIADH N DI Hypo - - +
- 27. Volume vs. Water Disorders
- 28. Salt and Water Rules (I) Regulation of the plasma sodium and of extracellular volume involve separate pathways The plasma sodium is regulated by changes in water excretion (ADH) and water intake (thirst) Hyponatremia is usually due to inability to excrete water, mostly due to persistent ADH Symptoms of hyponatremia (acute) are due to cerebral edema (decreased plasma osmolality) Chronic hyponatremia is usually asymptomatic, (loss of CNS osmolytes). Avoid rapid correction
- 29. Salt and Water Rules (II) All patients will tend to return to a steady state in which intake equals excretion The maximal diuretic effect is seen with the first dose, counterregulatory factors then stimulated Chronic diuretic use is associated with a steady state at lower volume and potassium levels The ability to markedly increase water, sodium, potassium, and bicarbonate excretion means that chronic accumulation of these substances requires an impairment in urinary excretion
- 30. The Concept of Normal Steady State
- 32. Isotonic Dehydration (Pure Hypovolemia) Most Common form of Dehydration Occurs when fluids and electrolytes are lost in even amounts There are no intercellular fluid shifts in isotonic dehydration Common Causes diuretic therapy excessive vomiting excessive urine loss hemorrhage decreased fluid intake
- 33. Hypertonic Hypovolemia Second most common type of dehydration Occurs when water loss from ECF is greater than solute loss: hyperventilation, pure water loss with high fevers, and watery diarrhea Diabetic Ketoacidosis and Diabetes Insipidus Iatrogenic Causes prolonged NPO
- 34. Hypotonic Hypovolemia Relatively Uncommon - Loss of more solute (usually sodium) than water. Hypotonic Dehydration causes fluid to shift from the blood stream into the cells, leading to decreased vascular volume and eventual shock Seen in Heat Exhaustion Increased cellular swelling -causes increased intracranial pressure - H/A and Confusion. Seen in Heat Stroke
- 35. Fluids can be described as being from three categories - Isotonic: Fluid has the same osmolarity as plasma Normal Saline (N/S or 0.9% NaCl), Ringers Acetate(RA), Ringer’s lactate (RL) - Hypotonic: Fluid has fewer solutes than plasma Water, 1/2 N/S (0.45% NaCl), and D5W (5% dextrose in water) after the sugar is used up - Hypertonic : Fluid has more solutes than plasma 5 % Dextrose in Normal Saline (D5 N/S),
- 37. Isotonic • Ringer’s acetate infusion • Ringer’s lactate • Normal saline Replace acute/ increases ECF abnormal loss ICF ISF Plasma 800 ml 200 ml
- 38. Hypotonic infusion • 5% dextrose Replace Normal increases ICF > ECF loss (IWL + urine) ICF ISF Plasma 660 ml 255 ml 85 ml
- 39. Volume Water CV ECF=1/3 ICF=2/3 CNS Na Na Na IO K K K K K Na Na Na O K K K K K Na Na Na IO K K K K K Na Na Na Na Na Na Na Na Na Na H2O Sodium Isotonic Hypertonic Hypotonic
- 40. Osmotic Pressure Relation of volume and osmotic force H2 O
- 41. ECF=1/3 ICF=2/3 Na Na Na IO K K K K K Na Na Na IO K K K K K Na Na Na IO K K K K K + Na Na Na Na Na Na Isotonic
- 42. ECF=1/3 ICF=2/3 Na Na Na Na Na IO K K K K K Na Na Na Na Na IO K K K K K Na Na Na Na Na IO K K K K K SIGNS: INTRAVASCULAR: HTN, S3 GALLOP, ELEVATED JVP, HEPATIC CONGESTION INTERSTITIAL: DEPENDENT PITTING EDEMA, PULMONARY RALES THIRD SPACE: ASCITIS, PLEURAL EFFUSION HYPERVOLEMIA
- 48. ECF=1/3 ICF=2/3 Na Na Na IO K K K K K Na Na Na IO K K K K K Na Na Na IO K K K K K - Na Na Na Na Na Na Isotonic
- 49. ECF=1/3 ICF=2/3 Na IO K K K K K Na IO K K K K K Na IO K K K K K SIGNS: INTRAVASCULAR: MILD (ORTHOSTATIC CHANGE IN BP & PULSE, FLAT JVP) SEVERE (HYPOTENSION, SHOCK) INTERSTITIAL: DIMINISHED SKIN TURGOR TRANSCELLULAR: DRY MOUTH AND MM. DIMINISHED OCULAR PRESSURE HYPOVOLEMIA
- 50. ECF=1/3 ICF=2/3 Na Na Na O K K K K K Na Na Na O K K K K K Na Na Na O K K K K K + Na Na Na Na NY nursery catastrophe Na Na Sodium
- 51. ECF=1/3 ICF=2/3 Na Na Na Na Na O K K K K K Na Na Na Na Na O K K K K K Na Na Na Na Na O K K K K K CNS SYMPTOMS & SIGNS OF HYPERNATREMIA: LETHARGY, IRRITABILITY, SPASTICITY, CONFUSION, STUPOR, COMA FOCAL NEUROLOGIC DEFICITS INTENSE THIRST, EMESIS, FEVER, LABORED RESPIRATION HYPERVOLEMIC HYPERNATREMIA ACUTE
- 52. ECF=1/3 ICF=2/3 Na Na Na Na Na K K K K K Na Na Na Na Na K K K K K Na Na Na Na Na K K K K K HYPERVOLEMIC HYPERNATREMIA CHRONIC (48 HOURS)
- 55. ECF=1/3 ICF=2/3 Na Na Na IO K K K K K Na Na Na IO K K K K K Na Na Na IO K K K K K - Na Na Na Na Na Na Sodium
- 56. ECF=1/3 ICF=2/3 Na IO K K K K K Na IO K K K K K Na IO K K K K K CNS SYMPTOMS & SIGNS OF HYPONATREMIA: ASYMPTOMATIC GI: ANOREXIA CNS: LETHARGY, HEADACHE, CONFUSION, STUPOR, SEIZURES, COMA HYPOVOLEMIC HYPONATREMIA ACUTE
- 57. ECF=1/3 ICF=2/3 Na IO K K K K K IO Na IO K K K K K IO Na IO K K K K K IO HYPOVOLEMIC HYPONATREMIA CHRONIC (48 HOURS)
- 62. ECF=1/3 ICF=2/3 Na Na Na IO K K K K K Na Na Na IO K K K K K Na Na Na IO K K K K K + Urea Urea Urea Urea Urea Urea UREA
- 63. ECF=1/3 ICF=2/3 Na Na Na IO K K K K K Urea Urea Na Na Na IO K K K K K Urea Urea Na Na Na IO K K K K K Urea Urea HYPEROSMOLAR ISOTONIC STATE (CRF)
- 64. ECF=1/3 ICF=2/3 Na Na Na IO K K K K K Na Na Na IO K K K K K Na Na Na IO K K K K K + Glu Glu Glu GLUCOSE
- 65. ECF=1/3 ICF=2/3 Glu Na Na Na IO K K K K K Glu Na Na Na IO K K K K K Glu Na Na Na IO K K K K K HYPEROSMOLAR HYPERTONIC STATE
- 66. ECF=1/3 ICF=2/3 Na Na Na IO K K K K K Na Na Na IO K K K K K Na Na Na IO K K K K K + SIADH HYPOTHYROID AND HYPOADRENALISM PREGNANCY PAIN, EMOTIONAL STRESS, POST SURGERY DRUGS THIAZIDE PSYCOGENIC, PRIMARY POLYDIPSIA H2O
- 67. ECF=1/3 ICF=2/3 Na Na Na IO K K K K K Na Na Na IO K K K K K Na Na Na IO K K K K K ISOVOLEMIC HYPONATREMIA ACUTE
- 68. ECF=1/3 ICF=2/3 Na Na Na IO K K K K K IO Na Na Na IO K K K K K IO Na Na Na IO K K K K K IO ISOVOLEMIC HYPONATREMIA CHRONIC (48 HOURS)
- 69. CRITERIA FOR DIAGNOSIS OF SIADH (Syndrome of Inappropriate ADH secretion) Hyposmolar hyponatremia Euvolemia Urine osmolality >100 (urine not maximally diluted) Normal renal, cardiac, hepatic, and endocrine function Absence of diuretics & stress Urine sodium > 20 mEq/l, low serum UA
- 70. Plasma AVP Is Elevated in Patients With SIADH 11 10 Plasma AVP (pg/mL) 9 8 7 Normal 6 range 5 4 3 2 1 0 230 240 250 260 270 280 290 300 310 Plasma Osmolality (mOsm/kg)
- 71. COMMON DISORDERS ASSOCIATED WITH SIADH Malignancy Lung, duodenum, pancreas, lymphoma Pulmonary disorders Infection, respiratory failure, IPPB CNS disorders Infection, trauma, sol, CVA, psychosis
- 72. DRUGS ASSOCIATED WITH HYPONATREMIA ADH analogs enhance ADH release Chlorpropamide, nicotine, tegretol, narcotics, clofibrate, antipsychotic Potentiate ADH renal action NSAID, chlorpropamide, cytoxan Unknown mechanisms Haloperidol, amitriptyline
- 73. TREATMENT OF HYPONATREMIA Depends on the following conditions Patient volume status The degree of hyponatremia The severity of symptoms The duration of hyposmolality
- 74. Osmotic Demyelination Syndrome Can Be a Consequence of Inappropriate Management of Hyponatremia
- 75. Diagnostic Algorithm for Hyponatremia Assessment of volume status Hypovolemia Euvolemia (no edema) Hypervolemia • Total body water ↓ • Total body water ↑ • Total body water ↑↑ • Total body Na+ ↓↓ • Total body Na+ ↔ • Total body Na+ ↑ U[Na+] >20 mEq/L U[Na+] <20 mEq/L U[Na+]>20 mEq/L U[Na+] >20 mEq/L U[Na+] <20 mEq/L Renal losses Extrarenal losses Glucocorticoid Acute or chronic Nephrotic syndrome Diuretic excess Vomiting deficiency renal failure Cirrhosis Mineralocorticoid deficiency Diarrhea Hypothyroidism Cardiac failure Salt-losing deficiency Third spacing of fluids Syndrome of Bicarbonaturia with renal Burns inappropriate tubal acidosis and Pancreatitis metabolic alkalosis Trauma ADH secretion Ketonuria - Drug-induced Osmotic diuresis - Stress Legend: ↑ increase; ↑↑ greater increase; ↓ decrease; ↓↓ greater decrease; ↔ no change.
- 76. (Adrogue-Madias) FORMULA ∆ Na = (infusate Na (+K) – actual Na) TBW* + 1 *TBW = 0.5 X body wt (Kg)
- 77. TREATMENT OF HYPONATREMIA 70 year old male, serum Na = 110 ? TBW = 70 * 0.6 = 42 liters Excess water = 42 - (110/120* 42) = 3.5 L 110 = TBC/TBW TBC = 42 * 110 = 4620 Over 2h he received 200 ml NaCl 3%, and excreted 1000 ml urine (Na+K=70+30) TBW = 42 - 0.8 = 41.2 , Na=4620/41.2 = 112
- 78. Aquaresis Aquaresis is defined as the solute-free excretion of water by the kidney Because electrolytes represent a major component of urine solutes, aquaresis is also electrolyte- sparing Measured by increases in EWC and is calculated from the urine volume and from the plasma and urine [Na+] and [K+] Typically accompanied by increased urine output and reduced urine osmolality Distinguished from diuresis (increased urine output accompanied by electrolyte excretion)
- 79. VAPRISOL® (conivaptan hydrochloride injection) Vaprisol is indicated for the treatment of euvolemic hyponatremia (eg, SIADH, or in the setting of hypothyroidism, adrenal insufficiency, pulmonary disorders, etc) in hospitalized patients Vaprisol is also indicated for the treatment of hypervolemic hyponatremia in hospitalized patients Not indicated for the treatment of congestive heart failure (effectiveness and safety have not been established in these patients)
- 80. ECF=1/3 ICF=2/3 Na Na Na IO K K K K K Na Na Na IO K K K K K Na Na Na IO K K K K K - RENAL LOSS (DI) EXTRA RENAL (RESP., DERMAL) INABILITY TO GAIN ACCESS TO FLUIDS HYPODIPSIA, ADIPSIA RESET OSMOSTST (ESSENTIAL HYPERNATREMIA) H2O
- 81. ECF=1/3 ICF=2/3 Na Na Na IO K K K K K Na Na Na IO K K K K K Na Na Na IO K K K K K ISOVOLEMIC HYPERNATREMIA ACUTE
- 82. ECF=1/3 ICF=2/3 Na Na Na K K K K K Na Na Na K K K K K Na Na Na K K K K K ISOVOLEMIC HYPERNATREMIA CHRONIC (48 HOURS)
- 83. CAUSES OF DIABETES INSIPIDUS Central DI Idiopathic, posttraumatic, tumors, infection, granuloma, histocytosis Nephrogenic DI Congenital Acquired » Hypercalcemia, hypokalemia, drugs, renal cystic and interstitial diseases
- 84. WATER-DEPRIVATION TEST Urine Osm. & Plasma AVP & Urine Osm. deprivation deprivation After AVP Normal > 800 > 2 pg/ml little or no ∆ Complete <300 undetectable great central DI increase Partial central 300-800 <1.5 pg/ml >10% DI increase Nephrogenic <300-800 >5 pg/ml little or no ∆ DI Primary >500 <5 pg/ml little or no ∆ polydipsia
- 85. TREATMENT OF HYPERNATREMIA Goal is to restore normal volume & osmolality Slow correction over 48 hours H2O deficit = 0.6 * Wt * (P Na/140 -1) Replace concomitant continuous losses Treat the cause of hypernatremia
- 87. ECF=1/3 ICF=2/3 Na Na Na IO K K K K K Na Na Na IO K K K K K Na Na Na IO K K K K K + EXTRARENAL (CHF, CIRRHOSIS) RENAL (NEPHROSIS, ARF, CRF) Na Na Na Hypotonic
- 88. Approach to polyuria Urine Osmolality (U osm) < 250 mOsm/kg H20 > 250 mOsm/kg H20 Water diuresis Osmotic diuresis
- 89. Adrogue H & Madias N. NEJM 2000; 342,1581.
- 90. ECF=1/3 ICF=2/3 Na Na Na Na IO K K K K K Na Na Na Na IO K K K K K Na Na Na Na IO K K K K K HYPERVOLEMIC HYPONATREMIA ACUTE
- 91. ECF=1/3 ICF=2/3 Na Na Na Na IO K K K K K IO Na Na Na Na IO K K K K K IO Na Na Na Na IO K K K K K IO HYPERVOLEMIC HYPONATREMIA CHRONIC (48 HOURS)
- 92. ECF=1/3 ICF=2/3 Na Na Na IO K K K K K Na Na Na IO K K K K K Na Na Na IO K K K K K - RENAL LOSSES OSMOTIC DIURESIS LOOP DIURETICS POST OBSTRUCTIVE DIURESIS INTRINSIC RENAL DISEASE EXTRARENAL LOSSES Na Na Na GI (V,D,F) DERMAL (SWEATING, BURN) Hypotonic
- 93. ECF=1/3 ICF=2/3 Na Na IO K K K K K Na Na IO K K K K K Na Na IO K K K K K HYPOVOLEMIC HYPERNATREMIA ACUTE
- 94. ECF=1/3 ICF=2/3 Na Na K K K K K Na Na K K K K K Na Na K K K K K HYPOVOLEMIC HYPERNATREMIA CHRONIC (48 HOURS)
- 95. ECF=1/3 ICF=2/3 Na Na Na IO K K K K K Na Na Na IO K K K K K Na Na Na IO K K K K K + Na Na Na HYPERTONIC SALINE ADMINISTRATION Na Na Na SODIUM BICARBONATE HYPERTONIC FEEDING MINERALOCORTICOID EXCESS Na Na Na Hypertonic
- 96. ECF=1/3 ICF=2/3 Na Na Na Na Na Na IO K K K K K Na Na Na Na Na Na IO K K K K K Na Na Na Na Na Na IO K K K K K HYPERVOLEMIC HYPERNATREMIA ACUTE
- 97. ECF=1/3 ICF=2/3 Na Na Na Na Na Na K K K K K Na Na Na Na Na Na K K K K K Na Na Na Na Na Na K K K K K HYPERVOLEMIC HYPERNATREMIA CHRONIC (48 HOURS)
- 98. ECF=1/3 ICF=2/3 Na Na Na IO K K K K K Na Na Na IO K K K K K Na Na Na IO K K K K K - RENAL LOSSES OSMOTIC DIURESIS Na Na Na DIURETICS SALT LOOSING NEPHRITIS MINERALOCORTICOID DEFICIENCY Na Na Na EXTRARENAL GI (D,V,F) Na Na Na THIRD SPACE PANCREATITIS Hypertonic PERITONITIS, OBSTRUCTION
- 99. ECF=1/3 ICF=2/3 IO K K K K K IO K K K K K IO K K K K K HYPOVOLEMIC HYPONATREMIA ACUTE
- 100. ECF=1/3 ICF=2/3 IO K K K K K IO IO K K K K K IO IO K K K K K IO HYPOVOLEMIC HYPONATREMIA CHRONIC (48 HOURS)
- 101. ASSESSMENT OF ECF VOLUME STATUS H&P LABORATORY STUDIES CXR MEASUREMENT OF CENTRAL PRESSURES
- 102. Assessment of Hyponatremia Serum Osmolality (R/O Pseudo) Volume status (Iso, hype, or hypo) Urine Osmolality (not maximally diluted) Urine sodium <10 or >20
- 103. Assessment of Hypernatremia Volume status Hypervolemia (restrict salt and use diuretics), may use water and hypoosmolar Hypovolemia (hydrate with hypo or isotonic) Euovolemia (R/O Diabetes Insipidus)
- 105. Proposed mechanisms for the production of CSW Syndrome BNP, ANP Ouabain Like Adrenomedulina Dendraspis NP