‫بسم ا الرحمن‬
‫الرحيم‬

‫”رب اشرح لي صدري‬
‫ويسر لي أمري‬
‫واحلل عقدة من لساني‬
‫يفقهوا قولي“‬
WATER AND SODIUM
DISORDERS
The Concept of Balance
and Steady Stat
 Hydrogen

ion (acid-base) balance
 Potassium, calcium, phosphorous,
magnesium, e...
Potassium Balance (3.5-5.0 mEq)
Water
Balance
Daily filtration:
Water 180 Lt
Sodium 25000 mEq
Total Body Water (sex & age)
Total Body Sodium 50 meq/Kg
Compartments
Ions Distribution
95%

98%
Concepts of:
1- FS forces
2- Diffusion
3- Osmosis
↑Serum Sodium↓

CNS Symptoms
AVP-Receptor Subtypes
Receptor
Subtype

Site of Action

Pharmacologic Effects

V1A

Vascular smooth muscle
Platelets
Lymph...
CV Symp & signs
Volume disorders

Water disorders
CRITERIA FOR DIAGNOSIS OF SIADH
(Syndrome of Inappropriate ADH secretion)

 Hyposmolar

hyponatremia

 Euvolemia
 Urine...
Plasma AVP (pg/mL)

Plasma AVP Is Elevated in Patients
With SIADH
11
10
9
8
7
6
5
4
3
2
1
0

Normal
range

230

240

250

...
COMMON DISORDERS
ASSOCIATED WITH SIADH
 Malignancy

Lung, duodenum, pancreas, lymphoma
 Pulmonary

disorders

Infectio...
DRUGS ASSOCIATED WITH
HYPONATREMIA
 ADH

analogs
 enhance ADH release
Chlorpropamide, nicotine, tegretol,
narcotics, cl...
TREATMENT OF
HYPONATREMIA
Depends on the following conditions
 Patient volume status
 The degree of hyponatremia
 The s...
Osmotic Demyelination
Syndrome Can Be a
Consequence of Inappropriate
Management
of Hyponatremia 
SODIUM & WATER
DISORDERS

Definitions

Hypernatremia & hyponatremia (135-145)
Hypervolemia & hypovolemia (50 meq/Kg)
Hy...
PSEUDOHYPONATREMIA
ISOTONIC HYPONATREMIA

SERUM Na+ = 140 meq/L
SOLIDS 7%

140/930

Serum Osmolality=
2Na+urea+glucose

SE...
Calculated Serum Osmolality=
2Na+urea+glucose
Measured Serum Osmolality=
(Nl: 280-290 mOsm/l
Normal Serum Osm Gap (Measure...
Salt and Water Rules (I)
Regulation of the plasma sodium and of
extracellular volume involve separate pathways
 The plasm...
Salt and Water Rules (II)
 All patients will tend to return to a steady state
in which intake equals excretion
 The maxi...
The Concept of Normal Steady State
Isotonic (pure) Hypovolemia
Most Common form of hypovolemia
Occurs when fluids and electrolytes are lost in
even (proporti...
Hypertonic Dehydration
Second most common type of hypovolemia

Occurs when water loss from ECF is greater than solute
loss...
Hypotonic Hypovolemia
Relatively Uncommon - Loss of more solute
(usually sodium) than water.

Hypotonic hypovolemia causes...
Fluids can be described as being from
three categories
- Isotonic: Fluid has the same osmolarity as
plasma
Normal Saline (...
Isotonic
infusion

• Ringer’s acetate
• Ringer’s lactate
• Normal saline
Replace acute/
abnormal
loss

increases ECF

ICF
...
Hypotonic
infusion

• 5% dextrose

Replace Normal
loss (IWL + urine)

increases ICF > ECF

ICF
660 ml

ISF
255 ml

Plasma
...
Volume
CV

ECF=1/3

Water
CNS

ICF=2/3

Na

Na

Na

IO

K

K

K

K

K

Na

Na

Na

O

K

K

K

K

K

Na

Na

Na

IO

K

K
...
Osmotic Pressure
Relation of volume and
osmotic force

H2 O
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

N...
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
...
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
...
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 (ORTHOSTA...
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

...
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
...
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
...
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
...
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 HYPONATREMI...
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 HYPONATREMI...
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

Ure...
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
...
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
G...
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
...
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

+

H2O

SIA...
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 ...
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
...
Diagnostic Algorithm for Hyponatremia
Assessment of volume status
Hypovolemia
• Total body water ↓
• Total body Na+ ↓↓

U[...
(Adrogue-Madias) FORMULA

∆ Na = (infusate Na (+K) – actual Na)
TBW* + 1

*TBW = 0.5 X body wt (Kg)
TREATMENT OF
HYPONATREMIA
70 year old male, serum Na = 110 ?
TBW = 70 * 0.6 = 42 liters
Excess water = 42 - (110/120* 42) ...
Aquaresis
 Aquaresis is defined as the solute-free excretion
of water by the kidney
 Because electrolytes represent a ma...
VAPRISOL®
(conivaptan hydrochloride injection)
 Vaprisol is indicated for the treatment of euvolemic
hyponatremia (eg, SI...
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 ...
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 ...
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 HYPERNATREMI...
CAUSES OF
DIABETES INSIPIDUS
 Central

DI

Idiopathic, posttraumatic, tumors,
infection, granuloma, histocytosis
 Nephr...
WATER-DEPRIVATION TEST
Urine Osm. & Plasma AVP &
deprivation
deprivation

Urine Osm.
After AVP

Normal

> 800

> 2 pg/ml

...
TREATMENT OF
HYPERNATREMIA
 Goal

is to restore normal volume &
osmolality
 Slow correction over 48 hours
 H2O deficit ...
Tonicity disorders v2
Tonicity disorders v2
Tonicity disorders v2
Tonicity disorders v2
Tonicity disorders v2
Tonicity disorders v2
Tonicity disorders v2
Tonicity disorders v2
Tonicity disorders v2
Tonicity disorders v2
Tonicity disorders v2
Tonicity disorders v2
Tonicity disorders v2
Tonicity disorders v2
Tonicity disorders v2
Tonicity disorders v2
Tonicity disorders v2
Tonicity disorders v2
Tonicity disorders v2
Tonicity disorders v2
Tonicity disorders v2
Tonicity disorders v2
Tonicity disorders v2
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Water and sodium disorders

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Tonicity disorders v2

  1. 1. ‫بسم ا الرحمن‬ ‫الرحيم‬ ‫”رب اشرح لي صدري‬ ‫ويسر لي أمري‬ ‫واحلل عقدة من لساني‬ ‫يفقهوا قولي“‬
  2. 2. WATER AND SODIUM DISORDERS
  3. 3. 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
  4. 4. Potassium Balance (3.5-5.0 mEq)
  5. 5. Water Balance Daily filtration: Water 180 Lt Sodium 25000 mEq
  6. 6. Total Body Water (sex & age) Total Body Sodium 50 meq/Kg
  7. 7. Compartments Ions Distribution 95% 98%
  8. 8. Concepts of: 1- FS forces 2- Diffusion 3- Osmosis
  9. 9. ↑Serum Sodium↓ CNS Symptoms
  10. 10. AVP-Receptor Subtypes Receptor Subtype Site of Action Pharmacologic Effects V1A Vascular smooth muscle Platelets Lymphocytes and monocytes Hepatocytes Vasoconstriction Platelet aggregation Coagulation factor release Glycogenolysis V1B Anterior pituitary ACTH and β-endorphin release V2 Renal collecting duct cells Free water absorption
  11. 11. CV Symp & signs
  12. 12. Volume disorders Water disorders
  13. 13. 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
  14. 14. Plasma AVP (pg/mL) Plasma AVP Is Elevated in Patients With SIADH 11 10 9 8 7 6 5 4 3 2 1 0 Normal range 230 240 250 260 270 280 290 Plasma Osmolality (mOsm/kg) 300 310
  15. 15. COMMON DISORDERS ASSOCIATED WITH SIADH  Malignancy Lung, duodenum, pancreas, lymphoma  Pulmonary disorders Infection, respiratory failure, IPPB  CNS disorders Infection, trauma, sol, CVA, psychosis
  16. 16. 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
  17. 17. TREATMENT OF HYPONATREMIA Depends on the following conditions  Patient volume status  The degree of hyponatremia  The severity of symptoms  The duration of hyposmolality
  18. 18. Osmotic Demyelination Syndrome Can Be a Consequence of Inappropriate Management of Hyponatremia 
  19. 19. SODIUM & WATER DISORDERS Definitions Hypernatremia & hyponatremia (135-145) 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)
  20. 20. PSEUDOHYPONATREMIA ISOTONIC HYPONATREMIA SERUM Na+ = 140 meq/L SOLIDS 7% 140/930 Serum Osmolality= 2Na+urea+glucose SERUM Na+ = 130 meq/L SOLIDS 14% HYPERLIPIDEMIA H2O 93% HYPERPROTEINEMIA H2O 86% Measured>Calculated 140/930 = 151/1000 = 130/860 WATER 7% 10/70 OSMOLALITY: MEASURES SOLUTE PER UNIT PLASMA WATER 130/860
  21. 21. Calculated Serum Osmolality= 2Na+urea+glucose Measured Serum Osmolality= (Nl: 280-290 mOsm/l Normal Serum Osm Gap (MeasuredCalculated)= (-14 to +10)
  22. 22. 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 
  23. 23. 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
  24. 24. The Concept of Normal Steady State
  25. 25. Isotonic (pure) Hypovolemia Most Common form of hypovolemia Occurs when fluids and electrolytes are lost in even (proportionate) amounts There are no intercellular fluid shifts in isotonic dehydration (EC fluid disorder) Common Causes diuretic therapy excessive vomiting excessive urine loss hemorrhage decreased fluid intake
  26. 26. Hypertonic Dehydration Second most common type of hypovolemia Occurs when water loss from ECF is greater than solute loss (disproportionate disorder) (EC and IC disorder): Causes: hyperventilation, pure water loss with high fevers, and watery diarrhea Diabetic Ketoacidosis and Diabetes Insipidus Iatrogenic Causes prolonged NPO
  27. 27. Hypotonic Hypovolemia Relatively Uncommon - Loss of more solute (usually sodium) than water. Hypotonic hypovolemia 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 - Headache and Confusion. Seen in Heat Stroke
  28. 28. 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),
  29. 29. Isotonic infusion • Ringer’s acetate • Ringer’s lactate • Normal saline Replace acute/ abnormal loss increases ECF ICF ISF Plasma 800 ml 200 ml
  30. 30. Hypotonic infusion • 5% dextrose Replace Normal loss (IWL + urine) increases ICF > ECF ICF 660 ml ISF 255 ml Plasma 85 ml
  31. 31. Volume CV ECF=1/3 Water CNS ICF=2/3 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 H2O Na Na Na Na Sodium Isotonic Hypertonic Hypotonic
  32. 32. Osmotic Pressure Relation of volume and osmotic force H2 O
  33. 33. 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
  34. 34. 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 (PURE) HYPERVOLEMIA
  35. 35. 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
  36. 36. 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 (PURE) HYPOVOLEMIA
  37. 37. 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 Na Na Sodium NewYork nursery catastrophe
  38. 38. 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 Mixed Disorder HYPERVOLEMIC HYPERNATREMIA ACUTE
  39. 39. 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)
  40. 40. 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
  41. 41. 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: SHOCK GI: ANOREXIA CNS: LETHARGY, HEADACHE, CONFUSION, STUPOR, SEIZURES, COMA Mixed Disorder HYPOVOLEMIC HYPONATREMIA ACUTE
  42. 42. 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)
  43. 43. 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
  44. 44. 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 HYPEROSMOLAR ISOTONIC STATE (CRF) Urea
  45. 45. 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
  46. 46. 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
  47. 47. 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 + H2O SIADH HYPOTHYROID AND HYPOADRENALISM PREGNANCY PAIN, EMOTIONAL STRESS, POST SURGERY DRUGS THIAZIDE PSYCOGENIC, PRIMARY POLYDIPSIA
  48. 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 ISOVOLEMIC HYPONATREMIA ACUTE Pure Disorder
  49. 49. 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)
  50. 50. Diagnostic Algorithm for Hyponatremia Assessment of volume status Hypovolemia • Total body water ↓ • Total body Na+ ↓↓ U[Na+] >20 mEq/L Renal losses Diuretic excess Mineralocorticoid deficiency Salt-losing deficiency Bicarbonaturia with renal tubal acidosis and metabolic alkalosis Ketonuria Osmotic diuresis U[Na+] <20 mEq/L Extrarenal losses Vomiting Diarrhea Third spacing of fluids Burns Pancreatitis Trauma Euvolemia (no edema) • Total body water ↑ • Total body Na+ ↔ U[Na+]>20 mEq/L Glucocorticoid deficiency Hypothyroidism Syndrome of inappropriate ADH secretion - Drug-induced - Stress Hypervolemia • Total body water ↑↑ • Total body Na+ ↑ U[Na+] >20 mEq/L Acute or chronic renal failure Legend: ↑ increase; ↑↑ greater increase; ↓ decrease; ↓↓ greater decrease; ↔ no change. U[Na+] <20 mEq/L Nephrotic syndrome Cirrhosis Cardiac failure
  51. 51. (Adrogue-Madias) FORMULA ∆ Na = (infusate Na (+K) – actual Na) TBW* + 1 *TBW = 0.5 X body wt (Kg)
  52. 52. 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
  53. 53. 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 electrolytesparing  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)
  54. 54. 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)
  55. 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 RENAL LOSS (DI) EXTRA RENAL (RESP., DERMAL) INABILITY TO GAIN ACCESS TO FLUIDS HYPODIPSIA, ADIPSIA RESET OSMOSTST (ESSENTIAL HYPERNATREMIA) H2O
  56. 56. 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
  57. 57. 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)
  58. 58. CAUSES OF DIABETES INSIPIDUS  Central DI Idiopathic, posttraumatic, tumors, infection, granuloma, histocytosis  Nephrogenic DI Congenital Acquired » Hypercalcemia, hypokalemia, drugs, renal cystic and interstitial diseases
  59. 59. WATER-DEPRIVATION TEST Urine Osm. & Plasma AVP & deprivation deprivation Urine Osm. After AVP Normal > 800 > 2 pg/ml little or no ∆ Complete central DI Partial central DI Nephrogenic DI Primary polydipsia <300 undetectable 300-800 <1.5 pg/ml <300-800 >5 pg/ml great increase >10% increase little or no ∆ >500 <5 pg/ml little or no ∆
  60. 60. 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

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