Fluids, pH, ions and

electrolytes

Current Opinion In Critical Care 2010 16:323-331

MO presentation 21/02/2011
Mah Chou Liang
Jerry Tan

Fluids, pH, ions and

electrolytes
Lewis J. Kaplana and John A. Kellumb

Despite their ubiquitous use, well described

side effects, and ability to be titrated to a
physiologic endpoint, fluids are rarely
considered in a fashion similar to other
pharmacologic agents. Understanding their
physical and chemical properties allows the
clinician to understand, anticipate and
deliberately harness their expected impact on
acid-base balance. Expanded insights into the
pathogenesis of common acid-base disorders
may be gleaned from utilizing a
physicochemical approach that allows the
precise quantification of the ionic species that
impact pH.

Some physiology revisions

first.,

Body Composition

ECF: plasma, interstitial fluid, transcellular fluid (CSF, Joint Fluid, lymph, aqueous humor,
glandular secretions, GIT fluid, urine), water of dense connective tissue and water of bone

Body Composition
Extracellular fluid is made up of:
Interstitial fluid
Intravascular fluid
Water in dense connective tissue
Water in bone
Transcellular fluid (CSF, joint fluid,
aqueous humour, bile, bladder urine,
fluid in bowel, pleural and peritoneal
cavity)

Body Composition
Functional ECF consist of interstitial
fluid + intravascular fluid +
transcellular fluid.
Ratio of ICF : Function ECF (2:1) is
thus more relevant in the context of
acute fluid infusion compared to the
ICF : ECF ratio (55:45)

Body Composition
Water Content as a percentage of total body weight
Age (years)

Males (%)

Female (%)

Term

80%

1-3

65%

10-15

60

57

15-40

60

50

40-60

55

47

>60

50

45

Body Composition
Average young adult male:

Protein 18%
Mineral 7%
Fat 15%
Water 60% or 600ml water/kg body weight

Muscle water content 71-72ml/100g tissue

Fat Water content 10ml/100g
Total body water decrease with age due to
loss of muscle mass
Most occurs in the ICF volume, ECF remains
fairly constant

Regulation of
Compartments
Determined by osmotic and hydrostatic
forces acting across the membranes and
thus the division between intra and extra
cellular spaces.
Different compartments have different
concentrations of solutes determined by
active and passive transport mechanism
Sodium is the major cation in ECF and it is
associated with anions of equal charge for
electrical neutrality. Hence sodium and its
obligatory anions accounts for 86% of ECF
osmolality and 92% of ECF tonicty

Electrolyte composition
Electrolytes

ECF (plasma)

ICF

Sodium (mmol/l)

140

15

Potassium (mmol/l)

3.7

155

Chloride (mmol/l)

101

Bicarbonate (mmol/l)

27

10

Calcium (mmol/l)

1.1

<0.01

Magnesium (mmol/l)

0.5

0.5

Phosphate (mmol/l)

1.1

100

Osmolality
(mOsm/kg)

290

290

Sodium

99.5% of filtered sodium reabsorbed in kidney

Urine lost: 150mmol/day
10 mmol/day lost in faeces, sweat, skin
Daily requirement 1-2mmol/kg
Regulates total body water by providing 90%
of the osmotic solute in plasma and interstitial
fluid
Depolarisation in action potential secondary to
increased sodium conductance
Involved in co-transport mechanism e.g.
glucose

Potassium
Main intracellular cation (98%:2%)
Reabsorbed in the proximal
convoluted tubules
Daily requirement 1mmol/kg
Principle determinant of intracellular
tonicity
Regulates transmembrane potential
and hence excitability

Osmolality v.s. osmolarity

Pressure that must be applied to a solution to
prevent osmosis
Osmole: 1 osmole = molecular weight of substance
in grams divided by the number of freely moving
particles each molecule liberates in solution
Osmolarity number of osmoles per litre of solution
Osmolality number of osmole per kilogram of
solvent
Osmolarity is therefore affected by the volume of
solute in solution and the temperature (due to
expansion), osmolality is not
Calculated effect plasma osmolality
2[Na] + [glucose] + [urea]
2 x 140 + 5 + 5 = 290

Tonicity
Tonicity is a measure of only those particles which are
capable of exerting an osmotic force across the cell
membrane, i.e. the effective osmolality of a solution
Most solutes e.g. sodium, chloride do not cross
membrane easily and effective at exerting an osmotic
force
Other solutes e.g. rea can cross the membrane easily
and are ineffective at exerting an osmotic force
Osmoreceptors in hypothalamus respond to
extracellular tonicity rather than to osmolality but the
latter is easy to measure
Thus tonicity can be estimated as osmolality minus
the concentration of urea and glucose as these two
are the only 2 present at any significant concentration

Chemical properties of
crystalloid fluids
3 general components: sugar, water,
electrolytes
Sugar

Generally provided as dextrose

Decrease gluconeogenic stress
Reduce lean body mass catabolism
Appropriate only for maintenance, not for
resuscitation
Large quantity leads to osmotic diuresis as Km for glucose
transport overwhelmed leading to confusion of
significance of increase urine output during resuscitation

Chemical properties of
crystalloid fluids
Remember that approximately 75% of an
administered normotonic crystalloid
infusion extravasates into the
extracellular space
E.g. 1000ml of crystalloid expands the
intravascular volume by 250ml

All crystalloid fluids are prepared in a

water base and hence 1000ml of any
crystalloid provides 1000ml of water
regardless of added electrolyte contect.
Dilutional hyponatremia

Common crystalloid
resuscitation fluids
Fluids

Na

Cl

Ca

Mg

Lacta
te

pH

mOsm

Plasma

140

100

7.4

285295

0.9% NS

154

154

5.5

308

Lactated
Ringers

130

109

2.7

28

6.5

273

Chemical properties of
colloids
Defined as preparations of homogenous noncrystalline substance that are dispersed
throughout another substance that is usually water
based
Large macromolecules or smaller particles but do
not precipitate and are not separable from their
suspending solution by filtration or centrifugation
Colloid preparations contribute very little free
water to the patients system and should always
be utilized with maintence solution to avoid
inadvertently creating a hyperoncotic state leading
to acute kidney injury or acute renal failure

Starches
Synthetic colloid preparations
dervied from amylopectin extracted
from either maize or sorghum

Starches
Amylopectin is a D-glucose polymer that is
synthetically modified with hydroxyethyl substitutions
at C2 as well as C6 with rather few substituion at C3
Hydroxylation slows the rate of hydrolysis by plasma
nonspecific alpha-amylases
Characterized by average molecular weight and
average molecular size
Further classification by molecular weight into high
(>450 kDa), medium (~200 kDa) and low (70-130
kDa)
Characterized by C2/C6 substitution ratio
Ratios expressed as number 0-1
Greater the degree of substitution, longer the plasma
persistence and plasma half life

Starches
Colloid

MW/DS

Concentration

Diluent

Voluven

HES 130/0.4

6%

NSS

Hextend

HES 670/0.7

6%

Balanced
solution

Hespan

HES 670/0.7

6%

NSS

DS: degree of substituion

HES: hydroxyethyl starch
MW: molecular weight in kDA
NSS: 0.9% normal saline solution
All are FDA approved colloids
Balanced solution: physiologically balanced medium of glucose,
sodium, chloride, calcium, potassium and lactate.

Starches
Sides effects of starches:
Anaphylactoid reactions <0.1%
Pruritus 1-10%
Rise in serum amylase which can confound
diagnosis of pancreatitis 1-10%, dose dependent
Dilutional effects with decreased level of
coagulation factors and other plasma proteins
and decrease in hematocrit 1-10%, dose
dependent

Ceiling dose of voluven 20ml/kg

Gelatins
Preparations created from hydrolysis of
bovine collagen and further modified by
either succinylation (Gelofusine) or urealinkage (Hemaccel)
Diluents are different between Hemaccel and
Gelofusine as only Hemaccel being prepared
with calcium and potassium
Risk of
Allergic reactions following rapid infusion 1:10,000
May interfere with platelet function and
coagulation

Dextrans

Homogeneous preparations of D-glucose polymer principally joined by

a alpha 1,6 bonds creating linear macromolecules that are
characterized by their concentration into 2 commerically available
preparations
Dextran 40 (molecular weight avg 40 kDa)
Dextran 70 (molecular weight avg 70 kDa)

Not in use due to allergic reaction and bleeding

Generally used by microsurgeons to decrease vascular thrombosis

Reduces erythrocyte aggregation and platelet adhesiveness
Reduce vWB factor
Inhibits alpha 2 antiplasmin, it serves as a plasminogen activator and possesses
thrombolytic features

Side effects

Fluid overload
Renal failure esp in dehydrated patients
Bleeding risks
Anaphylactoid reactions

Dosing
Shock: 20ml/kg in first 24 hours and 10ml/kg daily up to 5 days
Prophylaxis of thromboembolic disorders: 10ml/kg

Albumin
Biologically active protein with molecular weight of 60 kDa
5% or 25% formulation
Uses:
Large volume paracentesis (<5L)
Acute hepatic failure in pretransplant setting
In combination with antimicobials for management of spontaneous
bacterial peritonitis
Hepatorenal syndrome

SAFE trial
6997patients assigned to 4% albumin or saline
726 deaths in albumin group, 729 deaths in saline
No significant difference between groups in the mean number of
days spent in ICU/hospital/mechanical ventilation or RRT
Conclusion: similar outcomes at 28days between albumin and
saline
A Comparison of albumin and saline for fluid resuscitation in ICU
NEJM 2004;350:2247-56

Ionic composition of fluids and

their clinical effects
Water
Requirement: 1.5 2.0l of water /day
Excess intake as well as metabolic water
(1l) eliminated as urine and principally
managed by altering the ADH activity

Sodium and potassium

70kg man need between 70-140mmol/l
Na+ and 70 mmol/l K+ per day

Sodium Potassium Chloride

balance
Dilutional hyponatremia
Most common inpatient disorder of sodium
balance
Patient usually received salt far in excess of their
minimum requirement and complicated by high
ADH level that support water retenion
Thus a falling soidum indicates free water excess
rather than a true total body sodium deficit
Frequently normal or nearly normal plasma
chloride and high urinary Na+
Fluid restriction, judicious diuretics
Avoid raising more rapidly than 0.5-1mmol/l per
hour to prevent CPM

Sodium Potassium Chloride

balance
Salt depletion hyponatremia
Chronic diuretic therapy coupled with
salt restricted diet
Acoompany cerebral salt wasting
Urinary salt loss
Both sodium and chloride are reduced
with low urine Na+ concentration
Salt administration either IV or oral

Sodium Potassium Chloride

balance
Estimating anticipate change in serum sodium
when correcting hyponatremia
Change in Na for 1 liter of fluid =
[(infusate Na + infusate K) serum Na] divided by
(total body water + 1)
e.g. for a 70kg man with sodium of 120mmol/l, 1 liter
of 0.9% NS without K+ would raise the sodium by
0.8mmol/l
But if 40mmol/l K+ added, the change would be
1.7mmol/l, as both are exchangable cations and K+
will increase the plasma Na+ by exchanging with
intracelluar Na.
This is to avoid overly rapid correction of serum Na+

Sodium Potassium Chloride

balance
Hypernatremia
Rules to correct symptomatic hypernatremia
Correct no more rapidly than 1-2mmol/l /hour
Provide 50% of water deficit in first 12-24hours and rest over
next 24hours
Measure electrolyte q2H during correction to adjust the rate of
correction to avoid cerebral edema
Asymptomatic chronic hypernatremia should be corrected not
exceeding 0.5mmol/l per hour and not more than 10mmol/l
over 24 hours

Intravenous free water, commonly D5% used but may be

supplemented by GI luminal free water
Similar formula (see before) can be use to calculate the
change in sodium
E.g. administration of 1l of D5% to 70kg man with serum
Na+ of 160mmol/l would result in a decrease of
3.7mmol/l of sodium assuming no loss of water

Sodium Potassium Chloride

balance
Hypokalemia
As K+ is principally an intracelluar cation,
the deficit does not demostrate linearity
with the amount needed to restore a
normal concentration
A total body body deficit exist when serum
K+ is less than 3.0mmol/l and patient
generally require 200mmol/l K+ to replace
intracellular and extracelluar K+ to normal,
especially in ongoing renal/GI losses

Sodium Potassium Chloride

balance
Hyperchloremia and hyperchloremic
metabolic acidosis
Consider infusion of 10l of 0.9% NS to a 70kg
male
Total body sodium = (42 x 140) + (10 x 154) =
5880
Total body chloride= (42 x 100) + (10 x 154) =
5740
Thus serum Na increase from 140 5880/52 =
143 and serum Cl increase from 100 5740/52
= 110 mmol/l

Traditional
HendersonHasselblach
Describes the derivation of pH as a
measure of acidity
Derived from the acid dissociation
constant:

The Stewarts physiochemical

approach
Complex metabolic disorders are difficult
to define and treat during the traditional
method
This concept was challenged by Peter
Stewart in late 1970 that treats body
fluids as physicochemical systems,
governed by:
Electrochemical neutrality
Conservation of mass
Law of mass action equilibrium constraints
on dissociation reactions must be satisfied

Physical chemistry of aqueous

solution
Biological solutions are both water based
and primarily alkaline in nature.
Using Stewarts physiochemical approach,
the concentration of H+ in any aqueous
solution depends upon the degree of
dissociation of water into H+ and OH- and
is determined by 3 variables. The 3
independent variables that determine pH
in human plasma:
pCO2; the volatile component
Strong ion difference (SID)
Sum of total weak acid concentration

Physical chemistry of aqueous

solution
Strong ions
Strong ions are those that exist completely
dissociated from their ionic partners at
physiological pH e.g. Na+, K+, Ca++, Mg++, Cland lactate
SID is the sum of all strong cations sum of all
strong anions
Plasma SID ranges 40-42mEq/l in health but lower
in critical illness.
Since SID is positive, it must be balanced with
negative charges to maintain electrical neutrality
and these come from both CO2 and weak acids (A-)
Total weak acid derives principally from albumins
exposed histidine residue and PO4--.

Physical chemistry of aqueous

solution
SIDa or the apparent SID is based on easily
measured strong ions.
Another method for calculating SID, the SIDe or
effective SID is based upon the concentration of
bicarbonate and the charge contribution from
inorganic phosphates and albumin in plasma.
SIDa and SIDe should be eqal and any
difference is termed the strong ion gap (SIG)
which is similar to anion gap.
However unlike anion gap, SIG is not affect by
ariations in albumin or lactate concentration
and therefore may provide a more precise
mechanism underlying a metabolic acidosis.

Physical chemistry of aqueous

solution

Physical chemistry of aqueous

solution
Albumin and weak acids, [Atot]
Second determinant of blood pH is the
total weak acid concentration and these
are mainly proteins (predominantly
albumin) and phosphates

PCO2
Manipulation of pCO2 by adjusting alveolar
ventilation causes rapid [H+] changes in
aqueous solutions due to the reversible
dissociation of carbonic acid.

Physical chemistry of aqueous

solution
An important principle of this theory is
that dependent variable only change in
response to changes in one or more of
the independent variables.
As SID increases (more positive), there
is less dissociation of water and [H+]
reduces, pH increases.
As SID falls, [H+] increases and pH falls

Physical chemistry of aqueous

solution
Stewarts model clarifies the role of
kidneys, liver and gut in acid base
control
Renal control of plasma electrolytes,
particulary chloride allows
manipulation of SID
Liver and gut function influence
[Atot]

How do fluids influence

plasma pH
Metabolic acidosis is produced by a decrease
in the SID which may be brought by

generation of organic anions (lactate, ketones)

loss of cations (diarrhea)
mishandling of ions (renal tubular acidosis)
addition of exogenous anions (iatrogenic,
poisoning)

Metabolic alkalosis occur as results of

inappropriately large SID
Loss of anions in excess of cations (vomiting,
diuretics)
Adminstration of strong cations in excess of
strong anions (large volume transfusion of blood)

How do fluids influence

plasma pH
Hyperchloremic metabolic acidosis
Result of chloride handling or related to movement of
chloride from one compartment to another
Shown that 0.9% saline causes metabolic acidosis not
by diluting bicarbonate ions but rather its chloride
content.
Chloride ion decreases the SID, and increase water
dissociation and thus increase [H+] and produces a
decrease in pH
Although 0.9% saline contains equal amount of both
Na+ and Cl-, plasma do not and thus administrating
large amount of salt would result in large increase in
chloride concentration than sodium. (Na+ 140 -> 143;
Cl 100-110)

Consequence of
hyperchloremia
Evidence to suggest that crystalloid fluids
are proinflammtory and serve as potent
immune activation triggers.
Crystalloid may serve as potent triggers of
macrophage stimulation and activation of
MAP kinase, P38 and NF-KB pathway when
compared to starch based colloids or
albumin
Incorrect interpretation of acidosis due to
hypoperfusion instead of hyperchloremic
metabolic acidosis may result in
unnecessary fluid prescription.

Other references
Acid-base balance: Stewarts
physicochemical approach
Current Anaesthesia & Critical care
(2005) 16,133-135