Fluid and Electrolytes

Chrisitne S. Caringal. MD, DPPS, DPSN, DPNSP

FUNCTIONS OF KIDNEY

Regulation of Water and Electrolyte

Balance

The balance concept states that our bodies are in balance

for any substance when the inputs and outputs of that
substance are matched.

Maintains balance of water by regulating the amount of

urine

Excrete minerals in variable rate to match input

Excretion of Metabolic Waste

End products of metabolic processes serve no function

and are harmful at high concentration.

Includes: 1) Urea (from protein)

2) Uric acid (from nucleic acid)
3) Creatinine (from muscle creatine)
4) End products of hemoglobin breakdown
5) Metabolite of various hormones

Excretion of Bioactive Substances (Hormones and Many

Foreign Substances, Specifically) Drugs that Affect Body
Functions

Drug dosage are based on how fast the y are excreted to

ensure that appropriate body level is achieved

Regulation of Arterial Blood Pressure

Blood pressure depends on blood volume, and the

kidneys maintenance of sodium and water balance
achieves regulation of blood volume.

Kidneys also generates vasoactive substances that

regulate smooth muscle in the peripheral vasculature

Regulation of Red Blood Cell Production

Erythropoietin stimulates the
bone marrow to increase its production of erythrocytes.

Regulation of Vitamin D Production

The active form of vitamin D (1,25-dihydroxyvitamin D3) is

actually made in the kidneys, and its rate of synthesis is
regulated by hormones that control calcium and
phosphate balance.

Gluconeogenenesis

During prolonged fasting

SODIUM
mETABOLISM

Sodium

Dominant cation of the ECF

Principal determinant of extracellular osmolality

Necessary for the maintenance of intravascular volume.

Distribution of Sodium in the Body

Increased
Extracellular
Sodium
Conc

Decreased
Intracellular
Sodium Con

Energy for
the
movement of
substances
into the cell

Sodium
Intake

Sodium
Excretion

Sodium and Water Balance

Increased Sodium Concentration

Increased Plasma Osmolality

Increased thirst
Increased ADH secretion
Renal water conservation and normal
sodium concentration

Hyponatremia

Total
Serum
Sodium

Serum Sodium
Concentration
Total
Body
Water

Pseudohyponatremia

laboratory artifact that is present when the

plasma contains very high concentrations of
protein or lipid

does not occur if a direct ion-selective electrode

determines the sodium concentration

Pseudohyponatremia
Normal serum
osmolality

True Hyponatremia
Low serum
osmolality

Causes of Hyponatremia
Hyperosmolality
Hypovolemic Hyponatremia
Euvolemic Hyponatremia
Hypervolemic Hyponatremia

Hyperosmolality

water moves down its osmotic gradient from the

intracellular space into the extracellular space,
diluting the sodium concentration

do not have symptoms of hyponatremia

When the etiology of the hyperosmolality

resolves, water moves back into the cells and the
sodium concentration increases to its "true"
value.

Hyperosmolality
Hyperglycemia

Osmotic diuresis

Mannitol

Postobstructive diuresis

Gastrointestinal (emesis, diarrhea)

Polyuric phase of ATN

Skin (sweating or burns)

Juvenile nephronophthisis

Third space losses

Autosomal recessive polycystic kidney

disease

Absent aldosterone (e.g., 21-hydroxylase

deficiency

Tubulointerstitial nephritis

Pseudohypoaldosteronism type I

Obstructive uropathy

Urinary tract obstruction and/or urinary

tract infection

Cerebral salt wasting

Thiazide or loop diuretics

Proximal (Type II) RTA

Hypovolemic Hyponatremia

combination of sodium loss and water retention to

compensate for the volume depletion

The volume depletion stimulates ADH synthesis, resulting

in renal water retention in the collecting duct.

The volume depletion decreases the GFR and enhances

water reabsorption in the proximal tubule, which reduces
water delivery to the collecting duct.

Hypovolemic Hyponatremia

develops if the patient receives hypotonic fluid

In diseases with volume depletion due to extrarenal

sodium loss, the urine sodium should be low (<10 mEq/L)
as part of the renal response to maintain the intravascular
volume.

Diseases with both extrarenal sodium losses and renal

losses:
1) adrenal insufficiency
2) pseudohypoaldosteronism

Hypovolemic Hyponatremia

Extrarenal losses
Renal losses

Iatrogenic (i.e.,
excess hypotonic
intravenous fluids)
Swimming lessons
Tap water enema

Child abuse
Psychogenic
polydipsia

Diluted formula
Beer potomania

Hypervolemic Hyponatremia

an excess of total body water and sodium but the

increase in water is greater than the increase in sodium

sodium concentration decreases because water intake

exceeds sodium intake, and ADH prevents the normal
loss of excess water.

low urine sodium concentration (<10 mEq/L) and an

excess of both water and sodium

Hypervolemic Hyponatremia

Exception: patient with renal failure and hyponatremia

expanded intravascular volume and hyponatremia ---suppress ADH production

Water cannot be excreted because very little urine is

being made.

Hypervolemic Hyponatremia
third spacing of
fluid or poor
cardiac function

decrease in the
effective blood
volume

Kidney:
aldosterone and
other intrarenal
mechanisms,
retains sodium

regulatory systems
of the body sense
this decrease

ADH causes renal

water retention

Hypervolemic Hyponatremia

Congestive heart failure

Cirrhosis
Nephrotic syndrome
Renal failure
Capillary leak due to sepsis
Hypoalbuminemia due to gastrointestinal
disease

Euvolemic Hyponatremia

an excess of total body water and a slight decrease in

total body sodium

increase in weight --- technically overloaded

Clinically, they appear normal or have subtle signs of fluid

overload.

Euvolemic Hyponatremia

Syndrome of inappropriate
antidiuretic hormone
Desmopressin acetate
Glucocorticoid deficiency
Hypothyroidism
Water intoxication

Brain swelling

Because the intracellular space then has a higher

osmolality, water inevitably moves from the extracellular
space to the intracellular space to maintain osmotic
equilibrium.
The increase in intracellular water causes cells to swell.
Acute, severe hyponatremia can cause brainstem
herniation and apnea; respiratory support is often
necessary
brain swelling can be significantly obviated if the
hyponatremia develops gradually.

Treatment

Treat the etiology

monitoring and avoidance of an overly quick

normalization of the serum sodium concentration

Patient with severe symptoms, no matter the etiology,

should be given a bolus of hypertonic saline to produce a
small, rapid increase in the serum sodium.

Treatment (Euvolemic Hyponatremia)

Intravenous hypertonic saline rapidly increases the serum

sodium, and the effect on serum osmolality leads to a
decrease in brain edema.

Each milliliter of 3% sodium chloride increases the serum

sodium by approximately 1 mEq/L

Treatment (Hypovolemic
Hyponatremia)

hypovolemic hyponatremia -- deficiency in sodium and

may have a deficiency in water.

The cornerstone of therapy is to replace the sodium

deficit and any water deficit that is present.

The first step in any dehydrated patient is to restore the

intravascular volume with isotonic saline.

Treatment (Hypervolemic
Hyponatremia)

Administration of sodium leads to worsening volume

overload and edema

cornerstone of therapy: water and sodium restriction

(because these patients are overloaded)

Diuretics may be helpful by causing excretion of both

sodium and water.

Central Pontine Myelinosis

produces neurologic symptoms, including confusion,

agitation, flaccid or spastic quadriparesis, and death

usually characteristic pathologic and radiologic changes in

the brain, especially in the pons

more common in patients who are treated for chronic

hyponatremia

Central Pontine Myelinosis

Pathophysiogy: reduced intracellular osmolality that is an

adaptive mechanism for chronic hyponatremia makes
brain cells susceptible to dehydration during rapid
correction of the hyponatremia

avoid correcting the serum sodium by more than 12

mEq/L each day

Hypernatremia

Water
deficit
Water and
Sodium
deficit

Sodium
Excess

Hypernatremia

Sodium Excess
Improperly mixed formula

Premature infants

Excess sodium bicarbonate

Radiant warmers

Ingestion of seawater or sodium

chloride

Phototherapy

Intentional salt poisoning (child abuse

or Mnchhausen syndrome by proxy)

Ineffective breast-feeding

Intravenous hypertonic saline

Child neglect or abuse

Hyperaldosteronism

Adipsia (lack of thirst)

Water Deficit
Nephrogenic diabetes

Burns

Central diabetes insipidus

Increased insensible losses

Excessive sweating
Osmotic diuretics (e.g.,
mannitol)
Diabetes mellitus
Chronic kidney disease (e.g.,
dysplasia and obstructive
uropathy)
Polyuric phase of acute tubular
necrosis
Postobstructive diuresis

Inadequate intake

Diarrhea

Emesis/Nasogastric suction
Osmotic cathartics (e.g.,
lactulose)

Water and Sodium Deficit

Gastrointestinal losses
Cutaneous losses
Renal losses

Clinical Manifestations of
Hypernatremia
Dehydration--- doughy skin
Central nervous system symptoms
--- severity proportional to the degree of
hypernatremia
Increased thirst
Hyperglycemia
Hypoglycemia

Brain Hemorrhagemost devastating

complication of hypernatremia

Increased
Extracellular
Osmolality

Water moves out

of brain cells

Decrease brain
volume

Seizures and
coma

Tearing of
intracerebal veins
and bridging
nlood vessels

Brain moves away

from the skull and
meninges

Other sequelae

Central pontine demyelination

Extrapontine myelinosis

Thrombotic complicatio

Treatment

Goal: to decrease the serum sodium by less than 12

mEq/L every 24 hr, a rate of 0.5 mEq/L/hr.

The most important component of correcting moderate

or severe hypernatremia is frequent monitoring of the
serum sodium so that fluid therapy can be adjusted to
provide adequate correction, neither too slow nor too
fast.

Treatment of Hypernatremic
Dehydration

first priority is restoration of intravascular volume with

isotonic fluid

Normal saline > lactated Ringer solution

-- the lower sodium concentration of the lactated
Ringer solution can cause the serum sodium to decrease
too rapiidly

Water deficit
= Body weight x 0.6 (1-145/Actual serum Na)
Treat underlying cause

Determinants of the rate of decrease

in sodium concentration

Serum concentration of the fluid

Rate of fluid administration

Continuous water losses

Rapid Correction of Hypernatremia

Rapid decrease in sodium
Movement of water from serum
into brain cells to equalize
osmolality

BRAIN SWELLING

Treatment of Brain edema

administration of hypotonic fluid should be

stopped

infusion of 3% saline

POTASSIUM
METABOLISM

Potassium Distribution

Intracellular

Extracellular

approximately 150
mEq/L, is much
higher than the
plasma concentration

Bone: majority

Muscle: majority
(directly
proportional)

Plasma: 1%

Factors increasing intracellular

potassium

Na-K ATPase

Insulin

Metabolic alkalosis

-adrenergic agnist

Factors decreasing intracellular

potassium

-adrenergic agonist

Exercise

Mannitol infusion (Increase plasma osmolality)

Functions of Potassium

electrical responsiveness of nerve and muscle

cells, and for the contractility of cardiac, skeletal,
and smooth muscle (Action Potential)

maintaining cell volume because of its important

contribution to intracellular osmolality

HYPERKALEMIA

Hyperkalemia

Most

alarming electrolyte
abnormalities due to
potential lethal arrythmias

Fictitious Hyperkalemia

very common in children because of the difficulties in

obtaining blood specimens.

due to hemolysis during phlebotomy

can be the result of prolonged tourniquet application or

fist clinching, which cause local potassium release from
muscle.

Causes of Hyperkalemia

Spurious Laboratory Value

Increased Intake
Transcelullar Shift
Decreased Excretion

Spurious Laboratory Value

Hemolysis
Tissue ischemia during blood
drawing
Thrombocytosis
Leukocytosis

Increased Intake

Intravenous or Oral
Blood Transfusion

Transcellular Shifts

Analyze plasma instead of serum

It is important to analyze the sample promptly to avoid

potassium release from cells.

This occurs if the sample is stored in the cold, whereas

room temperature storage can lead to cellular uptake of
potassium and spurious hypokalemia

Transcellular Shifts
Acidemia
Rhabdomyolysis
Tumor lysis syndrome
Tissue necrosis
Hemolysis/hematomas/GI
bleeding
Succinylcholine
Digitalis intoxication

Fluoride intoxication
Beta-adrenergic blockers
Exercise
Hyperosmolality
Insulin deficiency
Malignant hyperthermia
Hyperkalemic periodic
paralysis

Transcellular Shifts
Acquired Addison disease

Urinary tract obstruction

21-hydroxylase deficiency
3-hydroxysteroid
dehydrogenase deficiency
Lipoid congenital adrenal
hyperplasia
Adrenal hypoplasia congenita
Aldosterone synthase
deficiency
Adrenoleukodystrophy

Sickle cell disease

Kidney transplant
Lupus nephritis

Transcellular Shifts

Angiotensin-converting enzyme
inhibitors
Angiotensin II blockers
Potassium-sparing diuretics
Cyclosporin
Nonsteroidal anti-inflammatories
Trimethoprim

Decreased Excretion

Renal failure
Primary adrenal disease
Hyporeninemic hypoaldosteronism
Renal tubular disease
Medications

Clinical Manifestations

Usually preceeded by cardiac toxicity

paresthesias

weakness

tingling

Cardiac Toxicity

Peak T waves
Increased PR interval

Flattening of P wave
Widening of QRS complex
Ventricular fibrillation

Transtubular Potassium Gradient

(TTKG)

Useful method to evaluate renal response to

hyperkalemia

K(urine)/K(plasma)x (plasma osmolality/urine osmolality)

ranging from 5-15

TTKG >10 ---normal renal excretion of potassium

TTKG < 8 ---defect in renal potassium excretion, which is

(lack of aldosterone or an inability to respond to
aldosterone)

Treatment

stop all sources of additional potassium (oral and

intravenous)

Washed red blood cells can be used for patients who

require blood transfusions

Two basic goals:

(1) to stabilize the heart to prevent life-threatening
arrhythmias
(2) to remove potassium from the body

Treatment (preventing arrhythmias)

Calcium -- stabilizes the cell membrane of heart cells,

preventing arrhythmias. It is given over a few minutes
intravenously and its action is almost immediate.

Bicarbonate -- causes potassium to move intracellularly,

lowering the plasma potassium.

Insulin

Nebulized albuterol (2 agonist)

Treatment (Potassium removal)

Loop diuretic for non-anuric patients only

Sodium polystyrene sulfonate (Kayexalate) -- an exchange

resin that is given either rectally or orally. Sodium in the
resin is exchanged for body potassium and the potassiumcontaining resin is then excreted from the body.

Treatment (potassium removal)

Dialysis
-- severe renal failure
-- high rate of endogenous potassium release as is
sometimes present with tumor lysis syndrome or
rhabdomyolysis
-- Hemodialysis rapidly lowers plasma potassium
levels.
-- Peritoneal dialysis is not nearly as quick or reliable,
even though it is usually adequate as long as the acute
problem can be managed with medications and the
endogenous release of potassium is not extremely high.

HYPOKALEMIA

Spurious Hypokalemia

in patients with leukemia and very elevated white blood

cell counts if plasma for analysis is left at room
temperature, permitting the white cells to take up
potassium from the plasma.

Causes

Transcellular Shifts
Decrease Intake

Renal Losses
Non-renal Losses

Transcellualr shifts

Alkalemia
Insulin
-adrenergic agonists
Drugs/toxins (theophylline, barium,
toluene)
Hypokalemic periodic paralysis

Decreased Intake

Anorexia nervosa
Bulimia
Laxative or diuretic abuse

Extrarenal Losses
Diarrhea
Laxative abuse

Sweating
Distal renal tubular acidosis
(RTA)
Proximal RTA
Ureterosigmoidostomy
Diabetic ketoacidosis

Tubular toxins: amphotericin,

cisplatin, aminoglycosides
Interstitial nephritis
Diuretic phase of acute tubular
necrosis
Postobstructive diuresis
Hypomagnesemia
High urine anions (e.g.,
penicillin or penicillin derivatives)

Extrarenal Losses
Emesis nasogastric suction

Adrenal adenoma or hyperplasia

Chloride losing diarrhea

Glucocorticoid-remedial
aldosteronism

Cystic fibrosis

Renovascular disease

Low chloride formula

Renin-secreting tumor

Posthypercapnia

17-hydroxylase deficiency

Previous loop or thiazide diuretic use

11-hydroxylase deficiency

Gitelman syndrome

Cushing syndrome

Bartter syndrome (MIM 602023)

11-hydroxysteroid dehydrogenase
deficiency

Loop and thiazide diuretics

Licorice ingestion
Liddle syndrome

Extrarenal Losses

Low urine chloride

High urine chloride and normal
blood pressure
High urine chloride and high
blood pressure

Renal Losses

With metabolic acidosis

Without specific acid-base
disturbance
With metabolic alkalosis

Cardiac complications

Flattened T wave
Depressed ST segment
Appearance of U wave

Clinical Manifestations

skeletal muscle include muscle weakness and cramps

Paralysis is a possible complication, at levels less than 2.5

mEq/L. This usually starts with the legs, followed by the
arms. Respiratory paralysis may require mechanical
ventilation

Rhabdomyolysis increased with exercise

Slows gastrointestinal motility

Clinical Manifestations

impairs bladder function -- urinary retention

polyuria and polydipsia by two mechanisms: primary

polydipsia and impaired urinary concentrating ability,

stimulates renal ammonia production, which is clinically

significant if hepatic failure is present because the liver
cannot metabolize the ammonia
--- worsen hepatic encephalopathy

Distuinguishing Renal from nonrenal

losses

24-hour urine collection

spot potassium/creatine ratio

fractional excretion of potassium,

calculation of the TTKG

-- most widely used approach in children
-- >4: excessive urinary loss of potassium

Treatment

Oral supplementation is safer than IV but less rapid.

The dose of intravenous potassium is 0.5-1 mEq/kg,

usually given over 1 hr.

Potassium chloride is the usual choice for

supplementation, although the presence of concurrent
electrolyte abnormalities may dictate other options.

Patients with acidosis and hypokalemia can receive

potassium acetate or potassium citrate.

Treatment

For patients with excessive urinary losses, potassiumsparing diuretics are effective, but they need to be used
cautiously in patients with renal insufficiency.

If hypokalemia, metabolic alkalosis, and volume depletions

are present (e.g., with gastric losses), then restoration of
intravascular volume with adequate chloride will decrease
urinary potassium losses.

Disease-specific therapy is effective in many of the genetic

tubular disorders.