Electrolyte and Acid-Base

Disorders

 The fetus has very high TBW, which

gradually decreases to approximately
75% of birthweight for a term infant.
Premature infants have higher TBW
than term infants.
During the 1st yr of life, TBW
decreases to approximately 60% of
body weight and basically remains at
this level until puberty

Fluid Compartments
TBW is divided between 2 main
compartments: intracellular fluid (ICF) and
extracellular fluid (ECF).
In the fetus and newborn, the ECF volume
is larger than the ICF volume.
By 1yr of age, the ratio of the ICF volume
to the ECF volume approaches adult
levels. The ECF volume is approximately
20-25% of body weight, and the ICF
volume is approximately 30-40% of body
weight, close to twice the ECF volume

Compartments of total
body water, expressed
as percentages of body
weight, in an older child

Web Figure 52-3 The concentrations of the major cations

and anions in the intracellular space and the plasma,
expressed in mEq/L.

The plasma osmolality is normally 285295mOsm/kg.

Glucose and urea normally contribute little
to the plasma osmolality;. multiplication of
the sodium value by 2 provides an
approximation of the osmolality.

 Urea is not confined to the extracellular

space because it readily crosses the
cell membrane and its intracellular
concentration approximately equals its
extracellular concentration.
Whereas an elevated sodium
concentration causes a shift of water
from the intracellular space, with
uremia, there is no osmolar gradient
between the 2 compartments and,
consequently, no movement of water.

 The only exception is during

hemodialysis, when the decrease in
extracellular urea is so rapid that the
intracellular urea does not have time
to equilibrate. This may lead to the
disequilibrium syndrome, in which
water shifts into brain cells,
potentially causing severe symptoms.

 Ethanol, because it freely crosses cell

membranes, is another ineffective osmole. The
effective osmolality can be calculated as follows:

effective osmolality = 2Na +

Glucose/18
The effective osmolality (also called the tonicity)
determines the osmotic force that is mediating
the shift of water between the ECF and the ICF.

 Hyperglycemia causes an increase in the plasma

osmolality because it is not in equilibrium with the
intracellular space.
During hyperglycemia there is a shift of water from
the intracellular space to the extracellular space.
This is clinically important in children with
hyperglycemia during diabetic ketoacidosis.
The shift of water causes dilution of the sodium in
the extracellular space, causing hyponatremia
despite an elevated plasma osmolality.

 Corrected Sodium
= Measured sodium + (((Serum glucose - 100)/100) x
1.6)

where [Na]measured = sodium concentration measured by

the clinical laboratory and [Na]corrected = corrected
sodium concentration (the sodium concentration if the
glucose concentration were normal and its
accompanying water moved back into the cells). The
[Na]corrected is the more reliable indicator of the patient's
true ratio of total body sodium to TBW, the normal
determinant of the sodium concentration.

 Normally, the measured osmolality and the

calculated osmolality are within 10mOsm/kg.
However, there are some clinical situations in which
this does not occur.
The presence of unmeasured osmoles causes the
measured osmolality to be significantly elevated in
comparison with the calculated osmolality. This
difference is the osmolal gap, which is present
when the measured osmolality exceeds the
calculated osmolality by >10mOsm/kg.

 Examples of unmeasured osmoles include

ethanol, ethylene glycol, methanol, and
mannitol. These substances increase the
measured osmolality but are not part of the
equation for calculating osmolality.
The presence of an osmolal gap is a clinical
clue to the presence of unmeasured osmoles
and may be diagnostically useful when there
is clinical suspicion of poisoning with
methanol or ethylene glycol.

 Pseudohyponatremia is a second situation in

which there is discordance between the measured
osmolality and the calculated osmolality.
It occurs in patients with large amounts of lipids
and proteins in the body.
In such situations, the plasma osmolality is normal
despite the presence of pseudohyponatremia,
because the method for measuring osmolality is
not appreciably influenced by the percentage of
serum that is composed of lipids and proteins.
Pseudohyponatremia is diagnosed by the
finding of a normal measured plasma
osmolality despite hyponatremia.

 Whereas many children with high

plasma osmolality are dehydrated
as seen with hypernatremic
dehydration or diabetic ketoacidosis
high osmolality does not always
equate with dehydration.
A child with salt poisoning or
uremia has an elevated plasma
osmolality but may be volume
overloaded.

Regulation of osmolality and volume

Osmoreceptors in the hypothalamus
sense the plasma osmolality.
An elevated effective osmolality
leads to secretion of antidiuretic
hormone (ADH) by neurons in the
supraoptic and paraventricular nuclei
in the hypothalamus.

 The axons of these neurons

terminate in the posterior pituitary.
Circulating ADH binds to its V2
receptors in the collecting duct cells
of the kidney, and, via the generation
of cyclic adenosine monophosphate,
causes insertion of water channels
(aquaporin-2) into the renal
collecting ducts.

 This produces increased permeability

to water, permitting resorption of
water into the hypertonic renal
medulla.
The end result is that the urine
concentration increases and water
excretion decreases.

 The regulation of ADH secretion is tightly linked to

plasma osmolality, responses being detectable with a
1% change in the osmolality.
ADH secretion virtually disappears when the plasma
osmolality is low, allowing excretion of maximally
dilute urine.
The consequent loss of free water (water without
sodium) corrects the plasma osmolality. ADH
secretion is not an all-or-nothing response; there is a
graded adjustment as the osmolality changes.

 Production of concentrated urine under the control

of ADH requires a hypertonic renal medulla. The
countercurrent multiplier, produced by the loop of
Henle and the vasa recta, generates this
hypertonicity.
ADH stimulates sodium transport in the loop of
Henle, helping to maintain this gradient when
water retention is necessary.
Water intake is regulated by hypothalamic
osmoreceptors, although these are different from
the osmoreceptors that determine ADH secretion.
These hypothalamic osmoreceptors, by linking to
the cerebral cortex, stimulate thirst when the
serum osmolality increases. Thirst occurs with a

 When volume depletion is present, both ADH

secretion and thirst are stimulated, regardless
of the plasma osmolality.
angiotensin II, which is increased during
volume depletion, is known to stimulate thirst.
In the syndrome of inappropriate
antidiuretic hormone (SIADH), ADH
continues to be produced despite a low plasma
osmolality. In the presence of ADH, urinary
dilution does not occur, and sufficient water is
not excreted

 The minimum urine osmolality is

approximately 30-50mOsm/kg.
This places an upper limit on the kidney's
ability to excrete water; sufficient solute
must be present to permit water loss.
Volume depletion is an extremely important
cause of decreased water loss by the kidney
despite a low plasma osmolality. This
appropriate secretion of ADH occurs
because volume depletion takes precedence
over the osmolality in the regulation of ADH.

 The normal response to increased plasma

osmolality is conservation of water by the
kidney.
In central diabetes insipidus, this does not
occur because of an absence of ADH secretion.
Patients with nephrogenic diabetes
insipidus have an inability to respond to ADH
and produce dilute urine despite an increase in
plasma osmolality

 The maximum urine osmolality is about

1,200mOsm/kg. The obligatory solute losses
dictate the minimum volume of urine that must be
produced, even when maximally concentrated.
Obligatory water losses increase in patients with
high salt intake or high urea losses, as may occur
after relief of a urinary obstruction or during
recovery from acute tubular necrosis.
An increase in urinary solute and, consequently,
water losses occurs with an osmotic diuresis,
which occurs classically from glycosuria in diabetes
mellitus as well as iatrogenically after mannitol
administration. There are developmental changes
in the kidney's ability to concentrate the urine.

 The maximum urine osmolality in a

newborn, especially a premature
newborn, is less than that in an older
infant or child. This limits the ability to
conserve water and makes such a
patient more vulnerable to
hypernatremic dehydration.
Very high fluid intake, as seen with
psychogenic polydipsia, can dilute
the high osmolality in the renal
medulla, which is necessary for
maximal urinary concentration. I

 If fluid intake is restricted in patients with this condition,

there may be some impairment in the kidney's ability to
concentrate the urine, although this defect corrects
after a few days without polydipsia.
This may also occur during the initial treatment of
central diabetes insipidus with desmopressin acetate;
the renal medulla takes time to achieve its normal
maximum osmolality. Loop diuretics, such as
furosemide, by inhibiting sodium resorption in the
ascending limb of the loop of Henle, decrease medullary
hypertonicity, preventing excretion of maximally
concentrated urine.

Regulation of Volume
Because sodium is the principal extracellular cation and it is
restricted to the ECF, adequate body sodium is necessary for
maintenance of intravascular volume.
The principal extracellular anion, chloride, is also necessary, but
for simplicity, sodium balance is considered the main regulator of
volume status because body content of sodium and that of
chloride usually change proportionally, given the need for equal
numbers of cations and anions.
In some situations, chloride depletion is considered the dominant
derangement causing volume depletion (metabolic alkalosis with
volume depletion). In other situations, such as volume depletion
with metabolic acidosis, sodium depletion may exceed chloride
depletion.

 The kidney determines sodium balance because there

is little homeostatic control of sodium intake, even
though salt craving does occasionally occur, typically in
children with chronic renal salt loss.
The kidney regulates sodium balance by altering the
percentage of filtered sodium that is resorbed along the
nephron.
Normally, the kidney excretes <1% of the sodium
filtered at the glomerulus. In the absence of disease,
extrarenal losses and urinary output match intake, with
the kidney having the capacity to adapt to large
variations in sodium intake.
When necessary, urinary sodium excretion can be
reduced to virtually undetectable levels or increased
dramatically.

 Urinary sodium excretion is regulated by both

intrarenal and extrarenal mechanisms.
The most important determinant of renal sodium
excretion is the volume status of the child; it is
the effective intravascular volume that influences
urinary sodium excretion.
The effective intravascular volume is the volume
status that is sensed by the body's regulatory
mechanisms.
Heart failure is a state of volume overload, but
the effective intravascular volume is low because
poor cardiac function prevents adequate
perfusion of the kidneys and other organs.
This fact explains the avid renal sodium retention
that is often present in patients with heart failure.

 Sodium resorption occurs throughout the nephron.

Whereas the majority of filtered sodium is resorbed
in the proximal tubule and the loop of Henle, the
distal tubule and the collecting duct are the main
sites for precise regulation of sodium balance.
Approximately 65% of the filtered sodium is
reclaimed in the proximal tubule, which is the major
site for resorption of bicarbonate, glucose,
phosphate, amino acids, and other substances that
are filtered by the glomerulus.
The transport of all these substances is linked to
sodium resorption by cotransporters, or a sodiumhydrogen exchanger in the case of bicarbonate.

 This link is clinically important for bicarbonate and

phosphate because their resorption parallels
sodium resorption.

In patients with metabolic alkalosis and

volume depletion, correction of the metabolic
alkalosis requires urinary loss of bicarbonate, but
the volume depletion stimulates sodium and
bicarbonate retention, preventing correction of the
alkalosis.

 Volume expansion causes increased urinary losses of

phosphate, even when there is phosphate depletion.
Resorption of uric acid and urea occurs in the proximal
tubule and increases when sodium retention increases.
This arrangement accounts for the elevated uric acid
and BUN measurements that often accompany
dehydration, which is a stimulus for sodium retention
in the proximal tubule. The cells of the proximal tubule
are permeable to water; thus, water resorption in this
segment parallels sodium resorption.

 The loop of Henle is, in terms of absolute

amount, the 2nd most important site of sodium
resorption along the nephron.
The Na+,K+,2Cl cotransporter on the luminal
side of the membrane reclaims filtered sodium
and chloride, whereas most of the potassium is
recycled back into the lumen.
This is the transporter that is inhibited by
furosemide and other loop diuretics, which are
highly effective at increasing sodium excretion.

 The ascending limb of the loop of Henle is not permeable

to water, permitting sodium retention without water.
ADH stimulates sodium retention in this segment; this
arrangement helps create a more hypertonic medulla,
which maximizes water conservation when ADH acts in
the medullary collecting duct.
Because loop diuretics inhibit sodium retention in this
segment, their use causes a less hypertonic medulla,
preventing excretion of maximally concentrated urine in
the presence of ADH.

 Sodium retention in the distal tubule is mediated by

the thiazide-sensitive Na+,Cl cotransporter.
This segment of the nephron is relatively impermeable
to water, and along with sodium and chloride retention,
the distal tubule is important for delivery of fluid with a
low sodium concentration to the collecting duct.
This allows for excretion of water without sodium in
patients who stop secreting ADH because of low
plasma osmolality.
Thiazide diuretics, by inhibiting sodium and chloride
retention in this segment, prevent the excretion of
water without electrolytespartially explaining the
severe hyponatremia that occasionally develops in
patients receiving chronic thiazide diuretics.

 The collecting duct, the final segment of the nephron, is

important for the regulation of excretion of water,
potassium, acid, and sodium.
Even though the amount of sodium resorbed in this
segment is less than in any other segment, this is the
critical site for the regulation of sodium balance.
Sodium resorption occurs via a sodium channel that is
regulated by aldosterone.
When these channels are open under the influence of
aldosterone, almost all of the sodium can be resorbed.
The uptake of sodium creates a negative charge in the
lumen of the collecting duct, which facilitates the
secretion of potassium and hydrogen ions.

 The potassium-sparing diuretics amiloride and

triamterene block these sodium channels, and the
inhibition of sodium uptake decreases potassium
excretion.
The potassium-sparing diuretic spironolactone blocks
the binding of aldosterone to its receptor; thus, it
indirectly decreases the activity of the sodium
channels.
The collecting duct is important for the regulation of
water balance because it responds to ADH by inserting
water channels that increase the permeability to
water, and the hypertonicity of the renal medulla
allows for maximal concentration of the urine.

 A number of systems are involved in the regulation

of renal sodium excretion. The amount of sodium
filtered at the glomerulus is directly proportional to
the GFR.
If sodium resorption in the nephron were constant,
complete resorption of sodium with a small decrease
in the GFR and significant renal sodium wasting with
a small increase would result.
This does not occur, however, because sodium
resorption in the nephron is proportional to sodium
delivery, a principle called glomerular tubular
balance.

 The renin-angiotensin system is an important

regulator of renal sodium excretion.
The juxtaglomerular apparatus produces renin in
response to decreased effective intravascular
volume. Specific stimuli for renin release are
decreased perfusion pressure in the afferent
arteriole of the glomerulus, decreased delivery
of sodium to the distal nephron, and 1adrenergic agonists, which increase in response
to intravascular volume depletion.
Renin, a proteolytic enzyme, cleaves
angiotensinogen, producing angiotensin I.
Angiotensin-converting enzyme (ACE) converts
angiotensin I into angiotensin II.

 The actions of angiotensin II include direct stimulation of

the proximal tubule to increase sodium resorption and
stimulation of the adrenal gland to increase aldosterone
secretion.
Through its actions in the distal nephronspecifically, the
late distal convoluted tubule and the collecting duct
aldosterone increases sodium resorption.
Aldosterone also stimulates potassium excretion,
increasing urinary losses.
Along with decreasing urinary loss of sodium, angiotensin
II acts as a vasoconstrictor, which helps maintain
adequate blood pressure in the presence of volume
depletion.

 Volume expansion stimulates the synthesis

of atrial natriuretic peptide, which is
produced by the atria in response to atrial
wall distention.
Along with increasing the GFR, atrial
natriuretic peptide inhibits sodium
resorption in the medullary portion of the
collecting duct, facilitating an increase in
urinary sodium excretion.

 Volume overload occurs when sodium

intake exceeds output.
In children with kidney failure, there is
an impaired ability to excrete sodium.
This impairment tends to be proportional
to the decrease in the GFR, although in
some kidney diseases, such as renal
dysplasia and juvenile nephronophthisis,
damaged tubules cause significant
sodium loss until the GFR is quite low.
In general, as the GFR decreases,
restriction of sodium intake becomes
increasingly necessary..

 The GFR is low at birth, limiting a newborn's

ability to excrete a sodium load.
In other situations, there is a loss of the
appropriate regulation of renal sodium excretion.
This loss occurs in patients with excessive
aldosterone, as is seen in primary
hyperaldosteronism or renal artery stenosis,
wherein excess renin production leads to high
aldosterone levels.
In acute glomerulonephritis, even without
significantly reduced GFR, the normal intrarenal
mechanisms that regulate sodium excretion
malfunction, causing excessive renal retention of
sodium and volume overload.

 Renal retention of sodium occurs during

volume depletion, but this appropriate
response causes the severe excess in total
body sodium that is present in heart failure,
liver failure, nephrotic syndrome, and other
causes of hypoalbuminemia.
In these diseases, the effective intravascular
volume is decreased, causing the kidney and
the various regulatory systems to respond,
leading to renal sodium retention and edema
formation.

 Volume depletion usually occurs when

sodium losses exceed intake.
The most common etiology in children is
gastroenteritis. Excessive losses of sodium may
also occur from the skin in children with burns,
in sweat from patients with cystic fibrosis, or
after vigorous exercise.
Inadequate intake of sodium is uncommon
except in neglect, in famine, or with an
inappropriate choice of liquid diet in a child
who cannot take solids.

 Urinary sodium wasting may occur in a range of renal

diseases, from renal dysplasia to tubular disorders,
such as Bartter syndrome.
The neonate, especially if premature, has a mild
impairment in the ability to conserve sodium.
Iatrogenic renal sodium wasting takes place during
diuretic therapy. Renal sodium loss occurs as a result
of derangement in the normal regulatory systems.
An absence of aldosterone, seen most commonly in
children with congenital adrenal hyperplasia due
to 21-hydroxylase deficiency, causes sodium wasting.

 Isolated disorders of water balance can affect volume

status and sodium balance.
Because the cell membrane is permeable to water,
changes in TBW influence both the extracellular
volume and the intracellular volume.
In isolated water loss, as occurs in diabetes insipidus,
the impact is greater on the intracellular space
because of its higher volume compared with the
extracellular space.
This is why, in comparison with other types of
dehydration, hypernatremic dehydration has less
impact on plasma volume; most of the fluid loss
comes from the intracellular space.

 Yet, significant water loss eventually affects intravascular

volume and will stimulate renal sodium retention, even if
total body sodium content is normal.
Similarly, with acute water intoxication or SIADH, there is
an excess of TBW, but most is in the intracellular space.
However, there is some effect on the intravascular
volume, which causes renal excretion of sodium.
Children with SIADH or water intoxication have high urine
sodium concentrations, despite hyponatremia.
This finding reinforces the concept that there are
independent control systems for water and sodium, yet
the 2 systems interact when pathophysiologic processes
dictate, and control of effective intravascular volume
always takes precedence over control of osmolality.