WATER AND SODIUM 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 disorders Outline of management Diuretics and fluid therapy

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%

FS forces Diffusion Osmosis

AVP-Receptor Subtypes
Receptor Subtype
V1A V1B V2 Site of Action
Vascular smooth muscle Platelets Lymphocytes and monocytes Hepatocytes Anterior pituitary Renal collecting duct cells

Pharmacologic Effects
Vasoconstriction Platelet aggregation Coagulation factor release Glycogenolysis ACTH and -endorphin release Free water absorption

Serum Sodium

CNS Symptoms

CV Symp & signs

Volume disorders

Water disorders

SODIUM & WATER DISORDERS

Definitions
Hypernatremia & hyponatremia (135-145) Hypervolemia & hypovolemia (50 meq/Kg) Proportionate and disproportionate disorder Hyperosmolar & hypertonic (urea vs. glucose) Pseudohyponatremia (Isotonic hyponatremia) Translocation hyponatremia (Hypertonic) Acute vs. chronic (48 hrs)

H2O
Osm 308

27 gram Na hypertonic (Osm 924)

Cl

Isotonic

4.5 gram Na hypotonic (Osm 77)

PSEUDOHYPONATREMIA
ISOTONIC HYPONATREMIA
SERUM Na+ = 140 meq/L SOLIDS 7%

Serum Osmolality= 2Na+urea+glucose

HYPERLIPIDEMIA

SERUM Na+ = 130 meq/L SOLIDS 14%

140/930

H2O
93%

HYPERPROTEINEMIA

H2O
86%

130/860

Measured>Calculated 140/930 = 151/1000 = 130/860

WATER 7%

10/70

OSMOLALITY: MEASURES SOLUTE PER UNIT PLASMA WATER

Calculated Serum Osmolality= 2Na+urea+glucose Measured Serum Osmolality= (Nl: 280-290 mOsm/l
Normal Serum Osm Gap (MeasuredCalculated)= (-14 to +10)

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

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

Steady state

Isotonic Dehydration
(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

Hypertonic Dehydration
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

Hypotonic Dehydration
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

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), Ringers 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), 3% saline solution, D5 in RL.

Isotonic infusion

Ringers acetate Ringers lactate Normal saline

Replace acute/ abnormal loss

increases ECF

ICF

ISF

Plasma

800 ml

200 ml

Hypotonic infusion
increases ICF > ECF

5% dextrose

Replace Normal loss (IWL + urine)

ICF
660 ml

ISF
255 ml

Plasma
85 ml

Volume CV
Na
Na

ECF=1/3 Na
Na

ICF=2/3 Na
Na

Water CNS
K
K

IO
O

K
K

K
K

K
K

K
K

Na

Na

Na

IO

Na

Na

Na

Na
Na H2O Sodium

Na
Na Isotonic

Na
Na Hypertonic Na Hypotonic

Osmotic Pressure
Relation of volume and osmotic force

H2O

ECF=1/3 Na Na Na Na Na Na Na Na Na IO IO IO K K K

ICF=2/3 K K K K K K K K K K K K

+
Na
Na

Na
Na

Na

Na

Isotonic

ECF=1/3 Na
Na

ICF=2/3 Na
Na

Na
Na

Na
Na

Na
Na

IO
IO

K
K

K
K

K
K

K
K

K
K

Na

Na

Na

Na

Na

IO

SIGNS:
INTRAVASCULAR: HTN, S3 GALLOP, ELEVATED JVP, HEPATIC CONGESTION INTERSTITIAL: DEPENDENT PITTING EDEMA, PULMONARY RALES THIRD SPACE: ASCITIS, PLEURAL EFFUSION

HYPERVOLEMIA

ECF=1/3 Na
Na Na

ICF=2/3 Na
Na Na

Na
Na Na

IO
IO IO

K
K K

K
K K

K
K K

K
K K

K
K K

Na
Na

Na
Na

Na

Na

Isotonic

ECF=1/3 Na Na Na IO IO IO K K K

ICF=2/3 K K K K K K K 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

ECF=1/3 Na Na Na O K

ICF=2/3 K K K K

Na
Na

Na
Na

Na
Na

O
O

K
K

K
K

K
K

K
K

K
K

+
Na Na Na Na Na Na

NY nursery catastrophe

Sodium

ECF=1/3 Na
Na Na

ICF=2/3 Na
Na Na

Na
Na Na

Na
Na Na

Na
Na Na

O
O O

K
K K

K
K K

K
K K

K
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

ECF=1/3 Na Na Na Na Na K K

ICF=2/3 K K K

Na
Na

Na
Na

Na
Na

Na
Na

Na
Na

K
K

K
K

K
K

K
K

K
K

HYPERVOLEMIC HYPERNATREMIA CHRONIC (48 HOURS)

ECF=1/3 Na Na Na Na Na Na Na Na Na IO IO IO K K K

ICF=2/3 K K K K K K K K K K K K

Na Na Na Na Na Na

Sodium

ECF=1/3 Na Na Na IO IO IO K K K

ICF=2/3 K K K K K K K K K K K K

CNS SYMPTOMS & SIGNS OF HYPONATREMIA:

ASYMPTOMATIC GI: ANOREXIA CNS: LETHARGY, HEADACHE, CONFUSION, STUPOR, SEIZURES, COMA

HYPOVOLEMIC HYPONATREMIA ACUTE

ECF=1/3
Na Na Na IO IO IO K K K

ICF=2/3
K K K K K K K K K K K K IO IO IO

HYPOVOLEMIC HYPONATREMIA CHRONIC (48 HOURS)

ECF=1/3 Na Na Na IO K

ICF=2/3 K K K K

Na
Na

Na
Na

Na
Na

IO
IO

K
K

K
K

K
K

K
K

K
K

+
Urea Urea Urea Urea Urea Urea

UREA

ECF=1/3 Na
Urea Urea

ICF=2/3 Na Na IO IO K K K K K K K K K K
Urea Urea Urea Urea

Na Na

Na

Na

Na

Na

IO

HYPEROSMOLAR ISOTONIC STATE (CRF)

ECF=1/3 Na Na Na IO K

ICF=2/3 K K K K

Na
Na

Na
Na

Na
Na

IO
IO

K
K

K
K

K
K

K
K

K
K

+
Glu Glu Glu

GLUCOSE

ECF=1/3
Glu Glu Glu

ICF=2/3 Na Na Na IO IO IO K K K K K K K K K K K K K K K

Na Na Na

Na Na Na

HYPEROSMOLAR HYPERTONIC STATE

ECF=1/3 Na Na Na IO K

ICF=2/3 K K K K

Na
Na

Na
Na

Na
Na

IO
IO

K
K

K
K

K
K

K
K

K
K

+
SIADH HYPOTHYROID AND HYPOADRENALISM PREGNANCY PAIN, EMOTIONAL STRESS, POST SURGERY DRUGS THIAZIDE PSYCOGENIC, PRIMARY POLYDIPSIA

H2O

ECF=1/3 Na Na Na Na Na Na Na Na Na IO IO IO K K K K K K

ICF=2/3 K K K K K K K K K

ISOVOLEMIC HYPONATREMIA ACUTE

ECF=1/3 Na Na Na Na Na Na Na Na Na IO IO IO K K K K K K

ICF=2/3 K K K K K K K K K

IO IO

IO

ISOVOLEMIC HYPONATREMIA CHRONIC (48 HOURS)

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

Plasma AVP Is Elevated in Patients With SIADH

11 10 9 8 7 6 5 4 3 2 1 0 230 240 250 260 270 280 290

Plasma AVP (pg/mL)

Normal range

300

310

Plasma Osmolality (mOsm/kg)

COMMON DISORDERS ASSOCIATED WITH SIADH

Malignancy

Lung, duodenum, pancreas, lymphoma

Pulmonary
CNS

disorders

Infection, respiratory failure, IPPB

disorders

Infection, trauma, sol, CVA, psychosis

DRUGS ASSOCIATED WITH HYPONATREMIA

ADH

analogs enhance ADH release

Chlorpropamide, nicotine, tegretol, narcotics, clofibrate, antipsychotic
Potentiate Unknown

ADH renal action mechanisms

NSAID, chlorpropamide, cytoxan

Haloperidol, amitriptyline

TREATMENT OF HYPONATREMIA
Depends on the following conditions Patient volume status The degree of hyponatremia The severity of symptoms The duration of hyposmolality

Osmotic Demyelination Syndrome Can Be a Consequence of Inappropriate Management of Hyponatremia

Diagnostic Algorithm for Hyponatremia

Assessment of volume status
Hypovolemia Total body water Total body Na+

Euvolemia (no edema) Total body water Total body Na+

U[Na+]>20 mEq/L

Hypervolemia Total body water Total body Na+

U[Na+] <20 mEq/L

U[Na+] >20 mEq/L

U[Na+] <20 mEq/L

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

Extrarenal losses Vomiting Diarrhea Third spacing of fluids Burns Pancreatitis Trauma

Glucocorticoid deficiency Hypothyroidism Syndrome of inappropriate ADH secretion - Drug-induced - Stress

Acute or chronic renal failure

Nephrotic syndrome Cirrhosis Cardiac failure

Legend: increase; greater increase; decrease; greater decrease; no change.

(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) = 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

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)

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)

ECF=1/3 Na Na Na IO K

ICF=2/3 K K K K

Na
Na

Na
Na

Na
Na

IO
IO

K
K

K
K

K
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

ECF=1/3 Na Na Na IO K

ICF=2/3 K K K K

Na Na

Na Na

Na Na

IO IO

K K

K K

K K

K K

K K

ISOVOLEMIC HYPERNATREMIA ACUTE

ECF=1/3

ICF=2/3

Na
Na Na

Na
Na Na

Na
Na Na

K
K K

K
K K

K
K K

K
K K

K
K K

ISOVOLEMIC HYPERNATREMIA CHRONIC (48 HOURS)

CAUSES OF DIABETES INSIPIDUS

Central

DI

Idiopathic, posttraumatic, tumors, infection, granuloma, histocytosis

Nephrogenic

DI

Congenital Acquired
Hypercalcemia, hypokalemia, drugs, renal cystic and interstitial diseases

WATER-DEPRIVATION TEST
Urine Osm. & Plasma AVP & deprivation deprivation Urine Osm. After AVP

Normal Complete central DI Partial central DI Nephrogenic DI Primary polydipsia

> 800 <300 300-800 <300-800 >500

> 2 pg/ml undetectable <1.5 pg/ml >5 pg/ml <5 pg/ml

little or no great increase >10% increase little or no little or no

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

ECF=1/3 Na Na Na Na Na Na IO IO K K

ICF=2/3 K K K K K K K K

Na

Na

Na

IO

+
EXTRARENAL (CHF, CIRRHOSIS) RENAL (NEPHROSIS, ARF, CRF)

Na

Na

Na

Hypotonic

Approach to polyuria
Urine Osmolality (U osm)
< 250 mOsm/kg H20 > 250 mOsm/kg H20

Water diuresis

Osmotic diuresis

Adrogue H & Madias N. NEJM

2000; 342,1581.

ECF=1/3
Na Na Na Na Na Na Na Na Na Na Na Na IO IO IO K K K K K K

ICF=2/3
K K K K K K K K K

HYPERVOLEMIC HYPONATREMIA ACUTE

ECF=1/3
Na Na Na Na Na Na Na Na Na Na Na Na IO IO IO K K K K K K

ICF=2/3
K K K K K K K K K IO IO IO

HYPERVOLEMIC HYPONATREMIA CHRONIC (48 HOURS)

ECF=1/3 Na Na Na Na Na Na Na Na Na IO IO IO K K K

ICF=2/3 K K K K K K K K K K K K

Na Na Na
RENAL LOSSES OSMOTIC DIURESIS LOOP DIURETICS POST OBSTRUCTIVE DIURESIS INTRINSIC RENAL DISEASE EXTRARENAL LOSSES GI (V,D,F) DERMAL (SWEATING, BURN)

Hypotonic

ECF=1/3
Na Na Na Na Na Na IO IO IO K K K

ICF=2/3
K K K K K K K K K K K K

HYPOVOLEMIC HYPERNATREMIA ACUTE

ECF=1/3 Na Na Na Na Na Na K K K K K K

ICF=2/3 K K K K K K K K K

HYPOVOLEMIC HYPERNATREMIA CHRONIC (48 HOURS)

ECF=1/3 Na Na Na Na Na Na Na Na Na IO IO IO K K K

ICF=2/3 K K K K K K K K K K K K

+
Na Na Na Na Na Na Na Na Na
HYPERTONIC SALINE ADMINISTRATION SODIUM BICARBONATE HYPERTONIC FEEDING MINERALOCORTICOID EXCESS

Hypertonic

ECF=1/3
Na Na Na Na Na Na Na Na Na Na Na Na IO IO K K

ICF=2/3
K K K K K K K K

Na

Na

Na

Na

Na

Na

IO

HYPERVOLEMIC HYPERNATREMIA ACUTE

ECF=1/3 Na Na Na Na Na Na Na Na Na Na Na Na K K K K

ICF=2/3 K K K K K K

Na

Na

Na

Na

Na

Na

HYPERVOLEMIC HYPERNATREMIA CHRONIC (48 HOURS)

ECF=1/3 Na Na Na IO K

ICF=2/3 K K K K

Na
Na

Na
Na

Na
Na

IO
IO

K
K

K
K

K
K

K
K

K
K

Na Na Na Na Na Na

Na

Na

Na

Hypertonic

RENAL LOSSES OSMOTIC DIURESIS DIURETICS SALT LOOSING NEPHRITIS MINERALOCORTICOID DEFICIENCY EXTRARENAL GI (D,V,F) THIRD SPACE PANCREATITIS PERITONITIS, OBSTRUCTION

ECF=1/3 IO IO IO K K K K K K

ICF=2/3 K K K K K K K K K

HYPOVOLEMIC HYPONATREMIA ACUTE

ECF=1/3 IO IO IO K K K K K K

ICF=2/3 K K K K K K K K K

IO

IO
IO

HYPOVOLEMIC HYPONATREMIA CHRONIC (48 HOURS)

ASSESSMENT OF ECF VOLUME STATUS

H

&P LABORATORY STUDIES CXR MEASUREMENT OF CENTRAL PRESSURES

Assessment of Hyponatremia
Serum

Osmolality (R/O Pseudo) Volume status (Iso, hype, or hypo) Urine Osmolality (not maximally diluted) Urine sodium <10 or >20

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)

Approach to Hyponatremia

Approach to Hypernatremia

Proposed mechanisms for the production of CSW Syndrome

BNP, ANP Ouabain Like Adrenomedulina Dendraspis NP

Electrolyte solutions
Plasma Isotonic solutions 308 273

Hypotonic solutions

290

278 278

290

Normal saline

Ringers acetate/ lactate

D5

KAEN 3B*

* KAEN 3B : contains 50 mmol Na+, 20 mmol K+, 50 mmol Cl-, 20 mmol lactate, 27 g dextrose per L.