Editors

Kishore Phadke Martin Bitzan

Department of Pediatric Nephrology Division of Pediatric Nephrology
Childrens Kidney Care Center Montreal Childrens Hospital
St. Johns Medical College Hospital McGill University
Bangalore, KA Montreal, QC
India Canada

Paul Goodyer
Division of Pediatric Nephrology
Montreal Childrens Hospital
McGill University
Montreal, QC
Canada

ISBN 978-3-642-12482-2 ISBN 978-3-642-12483-9 (eBook)

DOI 10.1007/978-3-642-12483-9
Springer Heidelberg New York Dordrecht London
Library of Congress Control Number: 2013948392

Springer-Verlag Berlin Heidelberg 2014

This work is subject to copyright. All rights are reserved by the Publisher, whether the whole or part of
the material is concerned, specically the rights of translation, reprinting, reuse of illustrations, recita-
tion, broadcasting, reproduction on microlms or in any other physical way, and transmission or infor-
mation storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar
methodology now known or hereafter developed. Exempted from this legal reservation are brief excerpts
in connection with reviews or scholarly analysis or material supplied specically for the purpose of being
entered and executed on a computer system, for exclusive use by the purchaser of the work. Duplication
of this publication or parts thereof is permitted only under the provisions of the Copyright Law of the
Publishers location, in its current version, and permission for use must always be obtained from Springer.
Permissions for use may be obtained through RightsLink at the Copyright Clearance Center. Violations
are liable to prosecution under the respective Copyright Law.
The use of general descriptive names, registered names, trademarks, service marks, etc. in this publica-
tion does not imply, even in the absence of a specic statement, that such names are exempt from the
relevant protective laws and regulations and therefore free for general use.
While the advice and information in this book are believed to be true and accurate at the date of publica-
tion, neither the authors nor the editors nor the publisher can accept any legal responsibility for any errors
or omissions that may be made. The publisher makes no warranty, express or implied, with respect to the
material contained herein.

Printed on acid-free paper

Springer is part of Springer Science+Business Media (www.springer.com)

2 Fluids, Electrolytes, and AcidBase Disorders 83

2.2 Sodium and Water Balance

2.2.1 Sodium Handling and Dysnatremias

Dysnatremias are one of the common electrolyte abnormalities seen in children. They
usually result from disorders of water metabolism. It is the brain that suffers from all
the consequences of alteration in water metabolism. In hyponatremia, there is an
inability of the kidney to generate dilute urine and excrete free water. It may also be
due to excessive salt losses. Hyponatremia is an independent predictor of mortality in
a critically ill child. It is also a signicant risk factor for sensorineural hearing loss and
cerebral palsy. Hospital-acquired hyponatremia may be iatrogenic and in large part are
due to the administration of hypotonic uids to sick children who may have elevated
arginine vasopressin levels. In hypernatremia, there is a net decit of water in relation
to sodium. It may be caused by water loss, sodium gain, or a combination of both.

2.2.1.1 Renal Handling of Sodium

Sodium, the major extracellular cation in the body is freely ltered and then reab-
sorbed, but not secreted. More than 99 % of the ltered sodium is reabsorbed.
Most sodium reabsorption occurs in the proximal tubule. Nearly 60 % is reab-
sorbed at the proximal tubule, 3040 % at thick ascending limb of loop of Henle
and 510 % actively at the distal tubule.
Sodium reabsorption is driven by the 3Na+/2K+ ATPase enzyme in the three
tubular segments mentioned above.
The main factors that regulate sodium reabsorption and excretion are extracellu-
lar volume status, delivery of sodium to the distal tubule, and aldosterone levels.

2.2.2 Hyponatremia

Hyponatremia is dened as serum Na+ <135 mEq/l. Mild hyponatremia (serum Na+
<135 mEq/l) occurs in 25 % of hospitalized children, while moderate hyponatremia
(Serum Na+ <130 mEq/l) is seen in 1 % of hospitalized children.

2.2.2.1 Applied Physiology

Development of hyponatremia typically requires a relative excess of free water in
conjunction with an underlying condition that impairs the ability to excrete free
water. Rarely, excess ingestion of free water or excess loss of urinary sodium causes
hyponatremia. Excretion of free water will be impaired when there is either:
A marked reduction in glomerular ltration rate (acute or chronic renal failure)
Renal hypoperfusion (diarrhea, vomiting, cardiac failure, nephrotic syndrome)
Arginine vasopressin (AVP) excess (SIAD, mutations in AQP2 receptors)
Hyponatremia may result from increased non-osmotic AVP production.
84 A. Vasudevan and K. Phadke

2.2.2.2 Etiology

1. Hypovolemic hyponatremia
Extrarenal losses:
Gastrointestinal vomiting, diarrhea
Transcutaneous excessive sweating, cystic brosis
Third-space losses burns, trauma, septic shock
Renal losses:
Diuretics
Tubulointerstitial diseases medullary cystic disease, polycystic kidney disease
Tubular: proximal RTA, Bartter syndrome
Polyuric phase of AKI, post-obstructive diuresis
Prematurity
Mineralocorticoid deciency
Pseudohypoaldosteronism
Cerebral salt wasting
2. Euvolemic hyponatremia
SIAD
Glucocorticoid deciency
Hypothyroidism
Psychogenic polydipsia
Drugs (increased ADH release) desmopressin, carbamazepine, chlorpropamide,
vincristine, haloperidol, cyclophosphamide
3. Hypervolemic hyponatremia (increase in effective circulating volume or increased salt
and water retention)
Nephrotic syndrome
Renal failure (acute/chronic)
Congestive cardiac failure
Cirrhosis of liver

2.2.2.3 Clinical Features

The symptoms depend not only on the level of sodium but also on the rapidity of
development (acute versus chronic).
Sometimes, children present with symptoms of primary disease and recognition
of hyponatremia may be incidental.
The primary symptoms of hyponatremia are mostly due to cerebral edema, and
the severity of neurologic symptoms correlates well with the rapidity and sever-
ity of the drop in serum sodium:
Early or mild hyponatremia headache, nausea and vomiting, lethargy, con-
fusion, agitation, and gait disturbances
Advanced or severe hyponatremia seizures, coma, non-cardiogenic pulmo-
nary edema, papilledema, and rarely cardiac arrhythmias
Signs of dehydration may be exaggerated in presence of hypovolemic hyponatremia.
Asymptomatic chronic hyponatremia in preterm neonates is associated with poor
growth and development and sensorineural hearing loss.
2 Fluids, Electrolytes, and AcidBase Disorders 85

2.2.2.4 Evaluation

Serum electrolytes
Spot urinary sodium and potassium
Serum osmolality
Urine osmolality
Renal function tests
Serum uric acid and ureaa
Arterial blood gas
TSH and cortisol levels
a
Important supportive information in differentiating between syndrome of
inappropriate antidiuresis (SIAD) and cerebral salt wasting (CSW)

2.2.2.5 Approach to Hyponatremia

Rule out pseudohyponatremia:- normal plasma osmolaity

Rule out hyperglycemia@/mannitol administration: - high plasma
osmolality

True hyponatremia (plasma osmolality-low)

Assess volume status

Hypovolemia Hypervolemic
Euvolemia
(deficit of total body water and (decrease in effective
larger deficitof total body sodium) circulating volume)

Spot urine Na+ >20 Spot urine Na+ Spot urine Na+

<20 >20 <20

>20
SIAD,
Hypothyroidism,
Glucocorticoid AKI Nephrotic
deficiency Diuretics, Vomiting
ATN, CKD syndrome,
Diarrhoea
RTA, Cardiac
Third spacing
Aldosterone failure,
deficiency, Cirrhosis of
Cerebral salt liver
wasting

*Hyperproteinemia and hyperlipidemia can produce spuriously low serum sodium values (pseudo-
hyponatremia) if it is measured by ame emission spectrophotometer. Readings obtained by ion-
selective electrode method may not have an effect on lipid or protein levels in the serum. @A rise
in serum glucose by 100 mg/dl (5.55 mmol/l) more than baseline of 100 mg/dl will decrease serum
Na+ by 1.6 mEq/l (1.6 mmol/l). SIAD syndrome of inappropriate antidiuresis, ATN acute tubular
necrosis, RTA, renal tubular acidosis, AKI acute kidney injury, CKD chronic kidney disease; spot
urine values are in mEq/l (mmol/l in SI units)
86 A. Vasudevan and K. Phadke

2.2.2.6 Treatment
It is important to ensure that the patient has associated hypoosmolality. The treat-
ment of hypertonic and pseudohyponatremia is directed at the underlying
disorder.
While treating hyponatremia, three factors should be taken into consideration:
severity and duration of hyponatremia, neurological symptoms, and volume
status of the child.
Asymptomatic hyponatremia is usually chronic (>48 h duration), while symp-
tomatic hyponatremia is acute (<48 h duration).
If the child is in shock or volume depleted, treat with isotonic saline in sufcient
amounts to restore the intravascular volume before correcting serum sodium.
Acute hyponatremia, especially those with hyponatremic encephalopathy,
requires early recognition and treatment (see box).
Children with chronic hyponatremia are at signicant risk for developing cerebral
pontine demyelination, if hyponatremia is treated aggressively.
Asymptomatic hyponatremia (chronic hyponatremia) should be corrected
gradually, and recommended safe limits for the correction of hyponatremia is
<10 mmol/l in 24 h or <20 mmol/l in 48 h (see box).

Management of Symptomatic Hyponatremia

Goal: 56 mmol/l increase in serum sodium (SNa) in rst 12 h.
End point: Resolution of neurological symptoms or acute rise in SNa of 5 mmol/l in rst
46 h.
Dosage: 2 ml/kg of 3 % NaCl over 10 min (maximum 100 ml). Repeat bolus 12 times
as needed until symptoms improve.
Monitoring: SNa q 24 h, signs of uid overload, urine output, acid base status,
correction in rst 48 h should not exceed 1520 mmol/l.

Management of Asymptomatic Hyponatremia (Chronichyponatremia)

Treat the underlying cause
Fluid restriction ( to 2/3 maintenance uids/day)
Oral salt supplementation
Furosemide (to increase free water loss) + 0.45 % normal saline (to replace sodium loss
in the urine)
Demeclocycline
V2-receptor antagonists (vaptans) could be used to treat euvolemic or hypervolemic
hyponatremia that do not respond to uid restriction.
2 Fluids, Electrolytes, and AcidBase Disorders 87

Formulae to Calculate no of Mmol of Na Necessary to Achieve the Desired

Change in Serum Sodium (SNa) Concentration
1. (0.6) body weight in kg (desired Na present Na) commonly used method
infusate Na - current serum Na
2. Change in serum Na =
TBW + 1
(NicholasMadias formula which estimates change in S Na with 1 l of infusate)

2.2.2.7 Case Example for Correction of Hyponatremia

An infant weighing 10 kg with symptomatic hyponatremia (SNa:120 mmol/l), the goal

is to increase SNa to 125 mmol/l over a period of 12 h.
Step 1: Assess the volume status: if the child is hypovolemic, treat with isotonic saline in
sufcient amounts to restore the intravascular volume.
Step 2: Calculate the rise in sodium required using the formulae and the optimal rate.
Formula 1
Number of mmol of Na+ required increasing serum Na to 125 mmol/l
= 0.6 10 (125 120) = 6 5 = 30 mmol.
1 ml of 3 % NaCl = 0.5 mmol of Na+, so to give 30 mmol of Na, 60 ml of 3 % NaCl
should be given over a period of 12 h (i.e., 3060 ml/h).
Formula 2
By applying the NicholasMadias formula, if we use 3 % NaCl (513 mmol/l) for
correction,
513 (infusate Na + ) - 120
Change in SNa =
(0.6 10 ) + 1
513 - 120
= = 56 mmol
6 +1
That means 1 l of 3 % NaCl will increase the serum Na concentration by 56 mmol/l.
Thus, in order to increase the SNa+ concentration by 5 mmol/l, dividing the target. Na
(5 mmol/l) by the change in SNa+ obtained by this formula (56 mmol/l), 0.089 l, i.e.,
89 ml (5/56) over a period of 2 h or 40 ml/h of 3 % NaCl is required.
Step 3: Once symptom-free, hyponatremia can be corrected more slowly over a period
of 48 h with a goal of not to increase the serum Na+ concentration by more than
1020 mmol/l over 2448 h by using the same formulae.
88 A. Vasudevan and K. Phadke

2.2.3 Syndrome of Inappropriate Antidiuresis

Syndrome of inappropriate antidiuresis (SIAD) is characterized by clinical euv-

olemia, low plasma osmolality, and inappropriately concentrated urine, with nor-
mal renal, adrenal, and thyroid function.
The term SIAD has replaced syndrome of inappropriate antidiuretic hormone
secretion (SIADH) because not all patients with the syndrome have inappropri-
ately elevated circulating levels of arginine vasopressin (ADH).
The degree of water retention that leads to hyponatremia is determined by both
the uid intake and the severity of the impairment in water excretion.
ADH regulation is impaired in SIAD, and four different patterns have been
described.
Type A unregulated release of ADH that varies widely with no relation to
the plasma osmolality.
Type B constant release of ADH with little or no variation in ADH levels.
Type C resetting of the osmostat, plasma sodium concentration is normally
regulated at a lower level (between 125 and 135 mmol/l).
Type D ADH level is undetectable and is secondary to activating mutations
in V2 vasopressin receptor.
In SIAD, there is an initial phase of water retention and hyponatremia followed
by partial escape from antidiuresis.

2.2.3.1 Diagnostic Criteria (Bartter and Schwartz 1967)

Essential criteria
Hyponatremia(serum Na <135 mmol/l)
Decrease extracellular uid effective osmolality (<270 mOsm/kg H2O)
Inappropriate urinary concentration (>100 mOsm/kg H2O)
Clinical euvolemia
Elevated urinary Na (>20 mmol/l) concentration under conditions of normal salt and
water intake
Absence of adrenal, thyroid, pituitary, or renal insufciency or diuretic use
Supplemental criteria
Plasma vasopressin level inappropriately elevated relative to plasma osmolality
(Any detectable AVP level when serum osmolality is <270 mOsm/kg H2O itself
denotes inappropriate elevation.)
Abnormal water load test inability to excrete at least 90 % of a 20 ml/kg water load
in 4 h and/or failure to dilute urine osmolality to <100 mOsm/kg H2O
No signicant correction of serum sodium with volume expansion but improvement
after uid restriction
2 Fluids, Electrolytes, and AcidBase Disorders 89

2.2.3.2 Etiology

CNS disorders infection, trauma, hypoxic ischemic encephalopathy, GuillainBarre

syndrome, cerebral malformations, intracranial hemorrhage, and malignancy
(primary or secondary)
Pulmonary disorders infections, malignancy, cystic brosis, and positive pressure
ventilation
Postsurgery anesthetic or premedication induced, abdominal, cardiothoracic and
neurosurgery procedures, pain
Drugs desmopressin, carbamazepine, chlorpropamide, vincristine, haloperidol,
cyclophosphamide
Miscellaneous acute intermittent porphyria, leukemia, lymphoma

2.2.3.3 Evaluation and Differential Diagnosis

SIAD may be difcult to distinguish from cerebral salt wasting (CSW), a syndrome
characterized by hyponatremia and extracellular uid depletion due to inappropriate
urinary sodium wasting in patients with intracranial bleeding or following neurosur-
gical procedures. It is postulated that unregulated release of brain natriuretic peptide
(BNP) results in impaired renal tubular sodium reabsorption. CSW tends to be tran-
sient and usually resolves within 34 weeks.
The primary feature that differentiates cerebral salt wasting from SIAD is extra-
cellular uid volume depletion, but clinical assessment of volume status is impre-
cise (Table 2.6).
It is important to distinguish SIAD from CSW because uid restriction is the
mainstay of treatment in SIAD while volume repletion with isotonic saline is the
denitive treatment in CSW.

Table 2.6 Differentiating SIAD CSW

between SIAD and CSW Sodium Low Low
(cerebral salt wasting)
Body water Increased Decreased
Serum urea Decreased Increased
Serum uric acid Decreased Increased
Serum osmolality <280 mOsm/l Decreased
Urine osmolality >500 mOsm/l Increased
Urine to serum >1 >1
osmolality ratio
Urine output Low High
Urine Na Increased Increased
concentration
90 A. Vasudevan and K. Phadke

2.2.3.4 Treatment
Correct the underlying cause.
Fluid restriction with appropriate sodium-containing uids to avoid worsening of
hyponatremia is the mainstay of therapy. Fluid restriction to less than 2/3 of main-
tenance and decreased to maintenance or lower if no improvement in 46 h.
Use 0.45 sodium chloride solution with 5 % dextrose, if intravenous uids are
indicated.
Severe symptomatic patients with SIAD often initially require administration of
3 % NaCl.
The use of furosemide with 0.45 or 0.9 N sodium chloride solution to replace
urinary losses of sodium can be successful in some children.
Demeclocycline may be used in those who do not respond to uid restriction.
The dose in children >8 years is 612 mg/kg/day divided into 23 doses orally.
However, it has unpredictable renal clearance, and onset of the response varies
and ranges between 5 and 8 days.
Osmotic diuretics like urea have been used in adults with refractory SIAD, but
safety and efcacy in children has not been established.
The efcacy and safety of vasopressin receptor antagonists (tolvaptan, conivap-
tan) in children has not been established.

2.2.4 Hypernatremia

Hypernatremia, dened as serum Na+ >145 mmol/l, always represents a hypertonic

state.
The ability to release ADH (AVP) and intact thirst mechanism are two mecha-
nisms by which hypernatremia or increased effective blood osmolality is prevented in
a normal child. In hypernatremia, there is a net decit of water in relation to sodium,
and it may be caused by water loss or sodium gain or a combination of both.

2.2.4.1 Etiology

1. Water decit in excess of sodium (clinically dehydrated)

Diarrhea, emesis/nasogastric tube suction, burns
2. Free water decit (clinically dehydrated/normal hydration)
Central diabetes insipidus (CDI) may be partial or complete; Hereditary: autosomal
dominant
Acquired: trauma, craniopharyngioma, postsurgical, radiation
Nephrogenic diabetes insipidus (NDI) hereditary: X-linked dominant, autosomal
recessive; acquired: hypercalcemia, hypokalemia, tubulointerstitial nephritis,
obstructive uropathy, amphotericin B, demeclocycline
Inadequate intake ineffective breast feeding, lack of thirst (adipsia)
Increased insensible water loss preterm newborns on radiant warmer/phototherapy,
excessive sweating
2 Fluids, Electrolytes, and AcidBase Disorders 91

3. Sodium excess (clinically normal hydration/mild hypervolemia)

Improperly mixed formula or rehydration solutions
Excessive sodium bicarbonate administration
Hypertonic saline enema
Primary hyperaldosteronism

2.2.4.2 Clinical Features

Hypernatremic dehydration increased thirst, poor skin turgor, dry mucus mem-
branes, and doughy feel of abdomen are observed in a child with hypernatremic
dehydration. Signs and symptoms of dehydration may be masked because of bet-
ter preservation of intravascular volume.
CNS symptoms high-pitched cry, irritability, hyperpnea, and increase in mus-
cle tone; eventually progress to seizures, coma, and death.

2.2.4.3 Evaluation
The kidneys normal response to hypernatremia is excretion of a minimal amount of
maximally concentrated urine. If urine osmolality is >600 mOsm/kg in a child with
hypernatremia, suspect extrarenal hypotonic uid losses (e.g., vomiting, diarrhea,
burns). Isotonic urine osmolality may be observed with diuretics.
CT scan or MRI of brain is suggested in all patients with severe hypernatremia.

Serum osmolality
Urine osmolality
Serum electrolytes
Renal function tests
Arterial blood gas
Spot urinary sodium and potassium
CT/MRI imaging of brain

2.2.4.4 Treatment
Identify and treat the underlying cause.
Stabilize hypovolemic children who have unstable vital signs with isotonic saline
before correcting free water decits.
Correct free water decit/sodium excess by calculating the free water decit and
replacing water or by calculating the required rate of sodium reduction for the
chosen infusate (see box).
Free water decits can be replaced either orally or intravenously depending on
the childs status.
Do not decrease serum sodium level by more than 0.5 mmol/l/h or 12 mmol/l/day.
Hyperglycemia may also accompany hypernatremia. Insulin treatment is not
recommended because it may increase brain idiogenic osmoles content.
92 A. Vasudevan and K. Phadke

Hypocalcemia is common; addition of calcium gluconate to rehydration uid is

often indicated.
Dialysis if conservative measures fail.
If child develop seizures during correction (suggestive of rapidly falling S. Na),
give 3 % NaCl (46 ml/kg over 30 min).

2.2.4.5 Approach to Hypernatremia

Approach to hypernatremia

Hydration status

Dehydration Hypervolemia

Urine output > 3 ml/kg/h, Urine output: low

Urine sp.gravity (SG) <
1.005,
Urine osm:<800 mOsm/kg
Urine Na variable
Urine SG>1.020
Urine osm: Urine output: N/
Urine Na: > 20 mEq/l
>800 mOsm/kg.
Urine Na <20 mmol/L Urine osm: variable
(More readily occurs when
GFR is low)

Diarrhoea
Water deprivation test Inadequate intake
(also,see Sect. 1.5) Increased insensible water loss
Excessive oral/iv intake
Hypertonic saline enemas
Primary
hyperaldosteronism

Disease Urine osmolality Plasma AVP Increase in urine osmolality

with water after dehydration after exogenous AVP
deprivation administration at one hour
Complete Low (<300) Undetectable >10 % increase in Uosm
CDI
Partial CDI Same or low (300 <1.5 pg/ml >50 % increase in Uosm
800)
NDI Same or low >5 pg/ml No increase
Primary Increase (800 <5 pg/ml Little or no increase
polydypsia 1400)
2 Fluids, Electrolytes, and AcidBase Disorders 93

Formulae to Calculate Desired Rate of Drop in Sodium

1. 1.5 times the maintenance intravenous (IV) uid is given at a constant rate over the
time for correction. 0.45 % DNS is the preferred uid for children.
2. Volume of uid to be administered over 48 h = 2 maintenance uid + calculated total
body free water decit.
Free water decit: total body water total body water at the time of hypernatremia
TBWD weight (kg)normal serum Na TBWD weight (kg)
normal serum Na TBWD weight (kg )
TBWD weight (kg ) -
Current serum Na
TBWD = total body water distribution =>0.6 for children and 0.7 in case of infants
The free water decit calculated by this formula is equivalent to 4 ml/kg for each
mmol > the expected Na+.
infusate Na - current serum Na
3. Change in serum Na =
TBW + 1
(Nicholas Madias formula which estimates change in S Na with 1 l of infusate)

2.2.4.6 Case Example for Correction of Hypernatremia

An infant weighing 10 kg presents with symptomatic hypernatremia

(serum Na 170 mmol/l).
Sodium correction based on the various methods is shown below:
Step 1: Restoration of intravascular volume if there is evidence of shock
Step 2: Calculation of desired rate of SNa drop and uid requirements
Formula 1:
Amount of fluid to be given
over next 24 h = 1.5 maintenance IV fluid
= 1.5 1, 000 = 1,500 / 24
= 62.5 ml/h 0.45% DNS to be given.
Formula 2:
According to the formula, the free water decit will be
150 0.6 10 900
0.6 10 - = 6- = 6 - 5.3 = 0.7 l = 700 ml
170 170
The volume of uid required to be given over 48 h will be 2 1,000 ml (maintenance
uid) + 700 ml (calculated decit) = 2,800 ml over 48 h, i.e., 1,400 ml/24 h, i.e., 58 ml/h.
So, the child needs to be given 0.45 % DNS at 58 ml/h for correction of hypernatremia.
94 A. Vasudevan and K. Phadke

Formula 3:
By applying NicolasMadias formula, if we use 0.45 % DNS for correction,

change in SNa =
( )
77 infusate Na + - 170 (SNa )
=
-93
= -13
(0.6 10 ) + 1 7
That means 1 l of 0.45 % NS will lower the SNa+ concentration by 13 mmol/l.
So, to reduce the SNa+ concentration by 10 mmol/l over next 24 h, 770 ml of 0.45 %
DNS 1,000 10/13 to be given in addition to the maintenance iv uids.
Maintenance iv uid = 1,000 ml (100 ml/kg, i.e., 1,000 ml), total 1,770 ml of 0.45 %
DNS at 73 ml/h
Step 3: Replacement of ongoing losses as they occur
Diarrhea => replace with D5 1/4 NS + 15 mmol/l NaHCO3 +20 mmol/l of KCl;
replace stool ml/ml every 16 h.
Vomiting/Nasogastric tube losses => D51/2 NS + 10 mmol/l of KCL, replace output
ml/ml
Step 4: Frequent monitoring and management of complications
If child develop seizures during correction (suggestive of rapidly falling S. Na), give
3 % NaCl (46 ml/kg)

2.3 Disorders of Potassium Homeostasis

2.3.1 Potassium Balance

Potassium is the major intracellular cation. Ninety-eight percent of the potassium in

the body is within cells, primarily in skeletal muscles and to a lesser extent in liver.
The maintenance of distribution of potassium across cells is largely dependent on the
activity of the sodium pump (Na+ K+ ATPase). The ratio of intracellular and extracel-
lular potassium is the primary determinant of the resting membrane potential. All of
the excitable cells (muscle cells, nerve cells) rely upon this resting membrane poten-
tial or K+ gradient to set their basal voltage for their function. Hence, there are
profound clinical effects whenever this K+ gradient gets disturbed.
The three components for defense against abnormalities in potassium balance
are:
Shift K+ in and out of cells
Excretion by the kidney
Excretion into the GI tract

2.3.1.1 Renal Handling of Potassium

Cortical Collecting Duct
There are two main regulators of potassium secretion in the cortical collecting
duct:
2 Fluids, Electrolytes, and AcidBase Disorders 95

Mineralocorticoid activity
A combination of high mineralocorticoid and high distal delivery of sodium
results in high K+ secretion and hypokalemia, seen in aldosterone-secreting tumor.
A combination of low mineralocorticoid and low distal delivery of sodium leads
to low K+ secretion and hyperkalemia, classically seen in Addisons disease.
Distal delivery of sodium
A diuretic that works proximal to the cortical collecting duct causes an increase
in distal delivery of sodium; a lot of that sodium goes out in the urine and causes
volume depletion. The volume depletion then leads to an increase in mineralo-
corticoids leading to increased K+ secretion, resulting in hypokalemia. In acute
glomerulonephritis, there is volume expansion and decreased distal delivery of
sodium due to decreased GFR. This suppresses mineralocorticoids secretion
causing hyperkalemia.

Medullary Collecting Duct

The potassium absorption occurs via H+ K+ ATPase.
It may contribute to hypokalemia in the condition of hypokalemic distal RTA,
where defect in hydrogen secretion causes defective K+ reabsorption.

2.3.1.2 Urinary Indices Used in Evaluation of Disorders

of Potassium Homeostasis
Assessing renal K+ excretion is an important step in evaluation of hypokalemia
or hyperkalemia.
The 24-h urine and/or spot urine have been used to assess renal K+ excretion rate.
However, 24-h urine collection is often difcult in children and is prone to errors
because of inaccuracies in timing and collection.
Four spot urine indices of renal potassium excretion are commonly used:
Spot urine K+ concentration: Value <15 mmol/l in presence of hypokalemia
suggests appropriate renal conservation, while >15 mmol/l suggests renal
wasting of potassium.
Urine potassium/creatinine (K+/Cr) ratio: Values less than 1.5 suggest renal
conservation of potassium during hypokalemia. However, the ratio can vary
with age, renal failure, and muscle mass and hence should be interpreted
with caution.
Fractional excretion of K+ (FeK+): It measures the amount of ltered potas-
sium that is excreted in urine. Normally, it is less than 3 %.
FeK+ = urinary potassium/serum potassium serum creatinine/urinary
creatinine e100
96 A. Vasudevan and K. Phadke

Potassium excretion in normal infants is slightly higher than in older children and
adults. Among normal infants, mean FEK = 12.2 % (range 527 %); values above
27 % indicate potassium wasting (Rodrigues-Soriano Ped Nephrol 1990).
Transtubular potassium gradient (TTKG): The transtubular potassium gradi-
ent (TTKG) is used to assess renal potassium secretion by the cortical collect-
ing duct, indirectly assessing aldosterone activity in patients who have
hypo- or hyperkalemia. For details, refer to Sect. 1.5.

2.3.2 Hypokalemia

Serum potassium concentration <3.5 mmol/l is dened as hypokalemia.

2.3.2.1 Applied Physiology

Hypokalemia is typically due to increased aldosterone activity or increased delivery
of sodium to distal tubules of loop of Henle. Hypokalemia seen with vomiting and
prolonged nasogastric suction is not due to increased losses from GI but is due to
increased urinary potassium loss secondary to intravascular volume depletion and
metabolic alkalosis which result in secondary hyperaldosteronism.

2.3.2.2 Etiology

Spurious hypokalemia: (Abnormal white blood cells take up potassium from

extracellular compartment when stored at room temperature)
Leukemia
Redistribution: (Movement of potassium from extracellular to intracellular
compartment)
Aldosterone, beta-adrenergic agonists, hypokalemic periodic paralysis, alkalosis,
exogenous insulin, hyperthyroidism
Extrarenal losses:
Excessive sweating, diarrhea, burns, stula and ostomies, short bowel syndrome,
malabsorption syndromes
Renal loss:
Drugs: thiazide and loop diuretics, carbenicillin, Amphotericin B
Hormones: aldosterone, cortisol
Magnesium depletion: aminoglycosides, cisplatin
Intrinsic renal defect: Bartter syndrome, Gitelmans syndrome, Liddles syndrome
Bicarbonaturia: metabolic alkalosis, proximal renal tubular acidosis
2 Fluids, Electrolytes, and AcidBase Disorders 97

2.3.2.3 Clinical Features

Mild hypokalemia is often asymptomatic.
Patients with more severe hypokalemia (serum K+ <3 mmol/l) present with gen-
eralized weakness, fatigue, and constipation.
Severe hypokalemia can precipitate rhabdomyolysis and impair urinary concen-
trating mechanism. It can also cause life-threatening cardiac arrhythmias and
respiratory paralysis due to weakness of respiratory muscles.
Moderate and severe hypokalemia can induce electrocardiographic changes,
including a prominent U wave, a attened T wave, low ST segment, and a wid-
ened QRS complex.

Acute
Skeletal muscle weakness involving limbs, trunk, and respiratory muscles
Smooth muscle weakness: paralytic ileus and gastric dilatation
Cardiac arrhythmia: premature ventricular contractions, sinus bradycardia
Ventricular tachycardia or brillation
Atrioventricular block
Rhabdomyolysis
Chronic
Growth failure
Tubulointerstitial and cystic changes
Polyuria
Metabolic alkalosis
Impaired glucose tolerance

2.3.2.4 Evaluation

Serum potassium, sodium and chloride

EKG (see Fig. 2.4)
Serum magnesium, calcium, phosphorous, alkaline phosphatase
Blood urea/serum creatinine
Urine potassium, urine creatinine
Arterial blood gas
Plasma and urine osmolality to estimate transtubular potassium gradient
98 A. Vasudevan and K. Phadke

ECG changes in hypokalemia

V1 V4

V2 V5

V3 V6

Fig. 2.3 EKG changes of hypokalemia: Sinus rhythm. Normal axis. Narrow QRS complex. ST
depression V3V5. Apparent prolonged QT interval. T-waves unseparable from giant U-waves
seen V26 (Webster A et al. Emerg Med J 2002; 19:7477)
2 Fluids, Electrolytes, and AcidBase Disorders 99

2.3.2.5 Approach to Hypokalemia

K+ < 3.5 mEq/l

Exclude spurious and transcellular K+shift

Life threatening emergency (arrhythmias, respiratory

paralysis)

Yes

Treat immediately
No

Spot urine K+

<15 mmol/l >15 mmol/l

Acute onset of weakness Renal losses

(See below)

Yes No

Familial or ABG
sporadic PP
hyperthyroidism

Metabolic acidosis Normal Metabolic alkalosis

Diarrhoea Low intake Former use of diuretics

Enteric fistula PEM
Burns Cation exchange resin use in CKD

Laxative abuse

PP periodic paralysis, PEM protein energy malnutrition, ABG arterial blood gas, CKD chronic
kidney disease
100 A. Vasudevan and K. Phadke

2.3.2.6 Approach to Hypokalemia Due to Increased Renal Losses

Renal loss
(Spot urine K > 15 mmol/l)

ABG

Metabolic acidosis Metabolic alkalosis Normal

Distal RTA, Recovering phase of ATN,

proximal RTA, post obstructive diuresis,
drugs (Amphotericin B, Blood pressure hypomagnesemia,
carbonic anhydrase inhibitors), drugs (aminoglycosides,
diabetic ketoacidosis, cisplatin)
ureterosigmoidostomy

Hypertensive Normal

Measure PRA and PA Urine Cl

<20 mmol/l >20 mmol/l

High PA Both low Both high
Low PRA Vomiting Bartters syndrome
Nasogastric suction Gitelmans syndrome
PHA, LS, RAS, Congenital chloride diarrhea Diuretics
AME, COA, Posthypercapnic alkalosis
Adrenal CS,
tumour, RST
CAH
GRA

RTA renal tubular acidosis, ATN acute tubular necrosis, PRA plasma renin activity, PA plasma aldos-
terone, PHA primary hyperaldosteronism, LS Liddles syndrome, AME apparent mineralocorticoid
excess, CS Cushings syndrome, CAH congenital adrenal hyperplasia, RAS renal artery stenosis, COA
coarctation of aorta, RST renin-secreting tumor, GRA glucocorticoid remediable aldosteronism
2 Fluids, Electrolytes, and AcidBase Disorders 101

2.3.2.7 Treatment of Hypokalemia

Symptomatic Hypokalemia
Management in emergencies (EKG changes, respiratory paralysis)
The initial aim of therapy is to raise serum potassium to a safe range (>3 mEq/l).
Potassium chloride (KCl) as intravenous bolus dose (given in 12 min) at a dose
calculated as: [3 measured K+ body weight 0.04] followed by an infusion at
rate of 0.015 mEq/kg/min.
Concentration of K+ in IV uid should not exceed 60 mmol/l while giving through
peripheral line, 80 mmol/l via central line, and should not be mixed with dextrose
solution.
The infusion should also not contain HCO3 because this might aggravate the
degree of hypokalemia by increasing redistribution of K+ from extracellular uid
space into intracellular space.
Caution should be exercised in children with hypokalemia due to increased shift
K+ into cells as aggressive KCl therapy may be associated with a potential risk of
rebound hyperkalemia, due to K+ rapidly released from cells when the K+ shift
resolves.
Hypokalemia needs to be corrected prior to correcting metabolic acidosis.
Concomitant magnesium deciency may exacerbate hypokalemia and render it
refractory to treatment with K+ supplementation.
Cardiac monitoring and a central venous catheter are essential for aggressive
treatment.

Management in Nonemergent Situations

The infusion rate of potassium chloride should not exceed 0.51 mEq/kg/h and
should be replaced by oral or nasogastric supplementation of potassium chloride
(13 mmol/kg in divided doses) as soon as the child starts taking orally, titrating
with serum K levels.

Asymptomatic Hypokalemia
The mainstay of therapy is oral potassium supplementation (34 mmol/Kg/
day).
Dietary supplementation with foods having high potassium content like coconut
water, banana, citrus fruits, and potatoes should be encouraged.
Potassium-sparing diuretics (spironolactone, amiloride) may be used in children
on loop diuretics to counteract diuretic-induced hypokalemia.
Treatment of underlying cause.

Formulations of Potassium Salts Available in the Market

Potassium chloride (20 % KCl 1 ml = 2 mmol) It is most commonly preferred.
Potassium citrate (1 ml = 2 mmol) Useful in children with renal tubular acidosis.
Potassium phosphate (94 mg PO4 and 4.4 mmol K+/ml) Useful in children who
also have hypophosphatemia (diabetic ketoacidosis, children on continuous renal
replacement therapy).
102 A. Vasudevan and K. Phadke

2.3.3 Hyperkalemia

Hyperkalemia is dened as serum concentration of K+ > 6 mmol/l in newborn and

>5.5 mmol/l in older children.

2.3.3.1 Etiology

Pseudohyperkalemia: Hemolysis
Severe leukocytosis/thrombocytosis
Redistribution: Hyperglycemia
Acidosis due to nonorganic acids
Excess intake: Potassium supplements
Impaired renal secretion:
Chronic kidney disease
Primary decrease/resistance in mineralocorticoid activity
Tubulointerstitial disease, Addisons disease, Type IV RTA
Primary decrease in sodium delivery
Oliguric acute kidney injury
Acute glomerulonephritis
Gordons syndrome
Abnormal cortical collecting duct
Pseudohypoaldosteronism type 1
Tubulointerstitial nephritis
Obstruction
Drugs: Spironolactone, amiloride, triamterene
Trimethoprim, pentamidine
NSAIDs, COX2 inhibitors
Cyclosporine, tacrolimus
ACEI, ARBs, heparin
RTA renal tubular acidosis, ACEI angiotensin-converting enzyme inhibitor, ARB angiotensin
receptor blockers, NSAIDs nonsteroidal anti-inammatory drugs, COX2: cyclooxygenase
2 Fluids, Electrolytes, and AcidBase Disorders 103

2.3.3.2 Clinical Features

Acute: Cardiac standstill

Neuromuscular weakness
Chronic: Asymptomatic
ECG Findings: Diminished to absent p waves
Tall peaked t waves
Widened QRS complex
Sine wave pattern of QRS widening

2.3.3.3 Evaluation

EKG (see Fig. 2.5)

Serum bicarbonate
Serum sodium, potassium, chloride
Serum creatinine
Urine spot potassium
Transtubular potassium gradient: TTKG

The ECG changes as hyperkalaemia develops

a b c d

Fig. 2.4 The EKG changes as hyperkalaemia develops. (a) A normal complex. (b) Loss of
P-waves, tenting of the T-waves. (c) Broadening of the QRS complex. (d) Sine wave appearance
(Webster A et al. Emerg Med J 2002; 19:7477)
104 A. Vasudevan and K. Phadke

2.3.3.4 Approach to Hyperkalemia

Hyperkalemia

Pseudo hyperkalemia True hyperkalemia Transcellular shift

Leukemia
Stored blood
GFR
Hemolysed blood

GFR = <15 ml/ml/1.73 m2 GFR >15 ml/ml/1.73 m2

AKI Estimate aldosterone and

CKD renin

Normal or high Low

rennin, Low aldosterone, aldosterone,
aldosterone normal/ high renin lowrenin

Potassium sparing diuretics, Diabetic nephropathy,

Pseudohypoaldosteronism, Primary Interstitial nephritis,
Type IV RTA, hypoaldosteronism, Obstructive uropathy,
Obstructive uropathy Congenital adrenal Cyclosporin,
hyperplasia, Tacrolimus,
Addisons disease, NSAIDS
ACEI and ARBs adrenergic and
calcium channel
blockers

GFR glomerular ltration rate, AKI acute kidney injury, CKD chronic kidney disease, RTA renal
tubular acidosis, ACEI angiotensin-converting enzyme inhibitor, ARB angiotensin receptor block-
ers, NSAIDs nonsteroidal anti-inammatory drugs

2.3.3.5 Treatment
Immediate Treatment (Also See Chap. 8)
Eliminate potassium from diet and uids and discontinue drugs causing
hyperkalemia.
Calcium gluconate (10 % solution) 1 ml/kg/dose diluted in saline over 10 min
under cardiac monitoring. (The onset of action is within 23 min and the effect
lasts for 1 h.)
Sodium bicarbonate 12 mmol/kg IV over 10 min.
Insulin bolus dose at 0.1 unit/kg with 5 % dextrose at 2 ml/kg over 30 min
or
Insulin infusion of 5 % dextrose 12 ml/kg/h with regular insulin 0.1 U/kg/h. The
insulin glucose infusion causes cellular shifts of potassium which occur by
30 min and lasts for 24 h.
2 Fluids, Electrolytes, and AcidBase Disorders 105

Potassium binders sodium or calcium polystyrene sulfonate 1 g/kg/dose every

46 h, with 20 % sorbitol orally or mixed with 250 ml of water as retention enema.
Peritoneal dialysis or hemodialysis potassium content of dialysate could be
zero or 12 mmol/l against a normal content of 34 mmol/l.

Long-Term Treatment
Measure aldosterone levels, and if they are low treat with udrocortisone. If the
levels are normal, treat with a diuretic.
Assess the volume status. If the volume is low, treat with udrocortisone, and if
the patient is volume expanded, treat with a diuretic.

2.4 Calcium, Phosphate and Magnesium

2.4.1 Calcium Disturbances

2.4.1.1 Calcium Metabolism

Introduction
Calcium (Ca) exists in three forms in plasma: calcium bound to protein, predomi-
nantly albumin (40 %); ionized calcium (48 %); and calcium that is complexed with
anions like phosphate, citrate, and bicarbonate (12 %). A change in serum albumin
of 10 g/l causes a change in serum calcium in the same direction by 0.8 mg/dl (0.2
mmol/l). Calcium stores depend on dietary Ca intake, absorption of Ca from the GI
tract, and renal Ca excretion.

Renal Handling of Calcium

Bone, intestine, and kidney are key organs involved in Ca homeostasis and is
regulated principally by parathyroid hormone (PTH) and 1, 25 dihydroxyvitamin
D (1, 25(OH)2D), and to a lesser extent by calcitonin.
Sixty percent of plasma calcium is freely ltered at the glomerulus. Seventy
percent of this is passively reabsorbed at the proximal tubule, 20 % at thick
ascending limb of loop of Henle by the transepithelial electrochemical gradient
created by sodium reabsorption, 510 % actively at the distal tubule by calcium
channels TRPV5, and 5 % in the collecting tubules via TRPV6.

2.4.1.2 Hypocalcemia
Denition
Preterm newborn serum calcium <7 mg/dl (1.75 mmol/l) or ionized calcium
<1 mmol/l
Term newborn serum calcium <8 mg/dl (2 mmol/l) or ionized calcium <1.1
mmol/l
Children serum calcium <8.5 mg/dl (2.12 mmol/l) or ionized calcium <50 % of
serum calcium
106 A. Vasudevan and K. Phadke

Etiology

Vitamin D deciency or impaired metabolism

Nutritional vitamin D deciency, vitamin D-dependent rickets, bone mineral disease
of CKD
Hypoparathyroidism
DiGeorge syndrome (22q11 deletion), CHARGE association, HDR association, HRD
syndrome, KCS syndrome,
X-linked, autosomal or recessive hypoparathyroidism
PTH gene mutations
Calcium sensing receptor (CASR) abnormality gain of function mutations or
antibodies to the receptors
Hypomagnesemia
Neck surgery/post-parathyroidectomy
Mitochondrial diseases (MELAS, KearnsSayre syndrome)
Others thalassemia, Wilsons disease, iodine 131 therapy
Resistance to PTH
Pseudohypoparathyroidism type IA, IB, II
Redistribution of plasma calcium
Tumor lysis syndrome
Hyperphosphatemia
Hungry bone syndrome
Acute pancreatitis
Poor calcium intake
Parenteral nutrition
Presence of dietary calcium chelators
Malabsorption
Others
Septic shock
Drugs furosemide, steroids, phenytoin, phenobarbitone, rifampicin
Massive blood transfusions
CHARGE coloboma, heart anomaly, choanal atresia, mental retardation, genital hypoplasia,
and ear anomalies, HDR hypoparathyroidism, deafness, and renal dysplasia, HRD hypopara-
thyroidism, mental and growth retardation, and dysmorphic features, KCS KennyCaffey
syndrome, MELAS mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes,
CKD chronic kidney disease

Clinical Features (See Table 2.10)

Hypocalcemia may often be asymptomatic. In children with symptoms, the signs
and symptoms are related to the severity and duration of hypocalcemia. Acute
hypocalcemia often results in symptoms due to neuromuscular irritability or car-
diac arrhythmias.
Tetany and seizures are more common in children with acute hypocalcemia.
Rickets, candidiasis, cataracts, skin and dental changes, and extrapyramidal abnor-
malities are usually seen with chronic hypocalcemia and hypoparathyroidism.
2 Fluids, Electrolytes, and AcidBase Disorders 107

Table 2.10 Clinical features of hypocalcemia

Acute
Neuromuscular irritability
Paresthesias of lips, extremities (ngers and toes)
Tetany
Laryngeal stridor, apnea in neonates
Seizures
Cardiac
Congestive cardiac failure
Arrhythmias
ECG: prolonged QT interval, heart block
Chronic
Candidiasis, subcapsular cataracts, basal ganglia calcications, extrapyramidal symptoms,
enamel hypoplasia, papilledema
Features of rickets
Latent signs
Signs of Chvostek and Trousseau

Eliciting Signs of Chvostek and Trousseau

Chvosteks Sign
A sphygmomanometer cuff is inated above systolic pressure and maintained for
3 min. A positive sign is exion of the wrist and metacarpophalangeal joints and
extension of the interphalangeal joints and adduction of the ngers due to carpope-
dal spasms.

Trousseaus Sign
Tap gently and repeatedly with a forenger on the lateral cheek over the course of
the facial nerve 0.51.0 cm below the zygomatic process and 2 cm anterior to the
earlobe. A positive sign is twitching of the corner of the mouth on the ipsilateral side
due to contractions of the circumoral muscles.

Evaluation of Hypocalcemia

Serum ionized calcium, phosphate, and magnesium

Serum albumin
Serum alkaline phosphatase
Serum electrolytes, creatinine
Arterial blood gases
Plasma 25-hydroxyvitamin D (25 OH D)
108 A. Vasudevan and K. Phadke

Serum intact parathyroid hormone

Urine analysis
pH, glucose, protein
Calcium/creatinine ratio
Fractional excretion of phosphate
ECG for prolonged QT interval
X-ray of wrist or knee
Renal ultrasound for nephrocalcinosis
Maternal vit D3 levels
1, 25 dihydroxy D3 level
Auto antibody screen for autoimmune polyendocrinopathy
Genetic studies (22q11 deletion, CASR mutations)

Approach to Hypocalcemia

Hypocalcemia

Serum phosphate

Low High

Vitamin D deficiency Parathyroid

(will also have high PTH) hormone

High Low/normal

Pseudo Urine calcium :

hypoparathyroidism creatinine ratio

Low Normal/High
25 OH D levels

Low Normal /High

True CASR gain of
hypoparathyroidism# function
mutations
Vitamin D 1, 25 dihydroxy
deficiency D3 levels

Low High

Vitamin D Vitamin D
dependent rickets dependent rickets
Type I Type II
2 Fluids, Electrolytes, and AcidBase Disorders 109

Treatment
Symptomatic hypocalcemia
Elemental calcium at 100200 mg per kg (12 ml/kg/dose of 10 % calcium glu-
conate diluted to twice the volume in dextrose; maximum dose 10 ml/dose) is
given intravenously under cardiac monitoring at a rate of not more than 100 mg/
min. Do not mix IV calcium with NaHCO3.The same dose is then repeated every
68 h. Once the symptoms have resolved, oral supplements can be initiated at
50100 mg/kg/day of elemental calcium in 34 divided doses.
While administering the intravenous dose, ensure patency of the venous access
as calcium extravasations can cause tissue necrosis. The intravenous infusion
should be immediately discontinued if there is a gradual decrease or sudden
slowing of heart rate.
Asymptomatic hypocalcemia
Oral supplements can be initiated at 50100 mg/kg/day of elemental calcium in
34 divided doses.
Treatment of underlying cause of hypocalcemia
For example, vitamin D deciency should be treated with ergocalciferol (D2) or
cholecalciferol (D3) (see Sect. 2.4.3). Hypomagnesemia if present should be
treated (see Sect. 2.4.4). Vitamin D analogue (1a-hydroxyvitamin D
(alphacalcidol) or 1, 25(OH)2D3 (calcitriol)) in a dose of 2550 ng/kg/day helps
in increasing intestinal calcium absorption in hypoparathyroidism or pseudohy-
poparathyroidism. Management of vitamin D-dependent rickets type I and II has
been described in Sect. 2.4.3

2.4.1.3 Hypercalcemia
Denition
Hypercalcemia is dened as serum calcium >12 mg/dl (>3 mmol/l). Severe hyper-
calcemia is dened as serum calcium >15 mg/dl (3.75 mmol/l).

Etiology

Hyperparathyroidism
Primary adenoma, multiple endocrine neoplasia, calcium-sensing receptor mutation
(loss of function)
Secondary and tertiary hyperparathyroidism (e.g., chronic kidney disease)
Excess vitamin D
Hypervitaminosis D
Sarcoidosis
Granulomatous diseases (Wegeners, Crohns disease)
Cat scratch disease
Tuberculosis
Factors releasing calcium from bone
Thyrotoxicosis
Immobilization
110 A. Vasudevan and K. Phadke

Low turnover renal osteodystrophy on vitamin D

Malignancy-associated ectopic PTH/PTH-related products
Systemic lupus erythematosus
Drugs
Thiazides, lithium, calcium and vitamin D supplements, vitamin A
Others
Idiopathic infantile hypercalcemia
Williams syndrome
Jansens metaphyseal dysplasia
Milk alkali syndrome
Addisons/Cushings disease
Phosphate depletion in preterm newborns

Clinical Features
The clinical features are often due to the underlying disease causing hyper-
calcemia.
The symptoms and signs depend on the severity and duration of hypercalcemia.

Clinical Features of Hypercalcemia

Gastrointestinal: nausea, vomiting, constipation, poor feeding

Cardiac: hypertension, arrhythmias, shortened QT interval
Neurological: hypotonia, poor activity, psychiatric disturbances, coma
Renal: polyuria, polydipsia, nephrocalcinosis, nephrolithiasis, distal renal tubular
acidosis, acute renal injury
Ocular: Band keratopathy, conjunctival and palpebral calcication
Others: Weakness, anorexia

Evaluation

Serum total and ionized calcium, phosphate

Calcium phosphate product
Serum alkaline phosphatase
Serum parathyroid hormone
Plasma 25 hydroxy vitamin D3
Urine calcium creatinine ratio
Serum creatinine
Thyroid function test
Ultrasound neck for parathyroids
2 Fluids, Electrolytes, and AcidBase Disorders 111

Approach to Hypercalcemia

High serum calcium

Phosphate, intact PTH

Phosphate normal/low,
Low phosphate, High phosphate,
PTH normal/low
high PTH high PTH

Primary Chronic kidney Urine Urine

hyperparathyroidism disease calcium low calcium high

Familial benign hypocalciuric William syndrome

hypercalcemia
Jansen dysplasia
Autoimmune hypocalciuric
hypercalcemia

Thiazide therapy

Treatment
The four main strategies in management of hypercalcemia are to decrease intes-
tinal calcium (Ca) absorption, increase urinary Ca excretion, decrease bone
resorption, and remove excess Ca with the help of dialysis.
Hydration with 3,000 ml/m2/day of isotonic saline if renal functions are normal.
Loop diuretics furosemide 1 mg/kg/dose q 6 h.
Hydrocortisone 1 mg/kg/dose every 6 h or equivalent dose of glucocorticoids in case
of vitamin D intoxication, granulomatous disease, or paraneoplastic syndrome.
Bisphosphonates:
Pamidronate: Mild hypercalcemia: 0.51 mg/kg/dose IV
Severe hypercalcemia: 1.52 mg/kg/dose IV
Dilute pamidronate initially in water but infuse in saline or 5 % dextrose. The
nal concentration should not exceed 12 mg/100 ml of diluent. It is given as
an infusion over 4 h initially and later over 24 h for three consecutive days.
Repeat infusion every 23 weeks or every 23 months according to the degree
and severity of hypercalcemia.
Calcitonin: Start at 4 IU/kg 1224 hourly intramuscular or subcutaneous and
may increase up to 8 IU/kg q 612 h. The effect, although rapid, is short lasting,
and prolonged use may lead to tachyphylaxis.
Dialysis (hemodialysis or peritoneal dialysis using low dialysate calcium concen-
trations) for hypercalcemia associated with renal failure or if above measures fail.
Surgical subtotal parathyroidectomy in cases of primary/tertiary hyperpara-
thyroidism.