on
Electrolyte and
Acid-Base Disturbances
Organisers
AK Agarwal, RK Singal
Editor
Praveen Aggarwal
Governing Body of Association of Physicians of India
Vice Presidents
BR Bansode, Mumbai (2009) Pritam Gupta, New Delhi (2010) Alaka Deshpande, Mumbai (2011)
Hon.Treasurer
Milind Y Nadkar, Mumbai (2009)
Members
Shyam Sundar, Varanasi (2009) Rohini Handa, New Delhi (2010) Narinder Pal Singh, New Delhi (2011)
Y Satyanarayan Raju, Hyderabad (2009) Amal Kumar Banerjee, Howrah (2010) Madhukar Rai, Varanasi (2011)
J Mukhopadhyay, Howrah (2009) R Sajithkumar, Kottayam (2010) Surendra Daga, Kolkata (2011)
NK Singh, Dhanbad (2009) Abhay N Rai, Gaya (2010) S Arulrhaj, Tuticorin (2011)
Zonal Members
North Zone Rajesh Upadhyay, New Delhi (2011) Mid South Zone G Narsimulu, Hyderabad (2011)
NorthWest Zone Gurpreet SWander, Ludhiana (2011) South Zone A Muruganathan, Tirupur (2011)
Central Zone Sanjiv Maheshwari, Ajmer (2011) Mid East Zone KamleshTewary, Muzaffarpur (2011)
West Zone Ashit Bhagwati, Mumbai (2011) East Zone Samar Kumar Banerjee, Kolkata (2011)
Ex Officio Member
Dean ICP
AK Das, Pondicherry
Invited Members
Hon.Editor,JAPI API House Chairman Editor-in-chief,APIText Book
Shashank R Joshi, Mumbai Siddharth N Shah, Mumbai YP Munjal, New Delhi
Co-opted Members
Jt.Secretary, Presidents Place Armed Forces, Medical Services Jt.Secretary (HQ)
JM Phadtare, Mumbai (2009) Lt.Gen.SR Mehta, New Delhi (2007-2008) Falguni Parikh, Mumbai
Convener
Praveen Aggarwal, All India Institute of Medical Sciences
New Delhi
Faculty
l Praveen Aggarwal, New Delhi
l Chhavi Sawhney, New Delhi
l Sanjeev Bhoi, New Delhi
A. K. Agarwal
Chairman, Scientific Committee
S. K. Bichile
President, Association of Physicians of India (API)
A. K. Das
Dean, Indian College of Physicians (ICP)
B. B. Thakur
Dean-Elect, ICP
Sandhya Kamath
Hony. General Secretary, API and ICP
Shashank R. Joshi
Hony. Editor, Journal of Association of Physicians of India (JAPI)
N. K. Soni
Organising Secretary, APICON - 2009
Principal Advisors
Y. P. Munjal B. K. Sahay Siddharth N. Shah
2. Acid-Base Disturbances 19
Praveen Aggarwal
The Body Water sweat, exudates, and transudates can also be considered
as specialized portions of the extracellular water, because
About a billion years ago, life began-in the sea. The sea when these are lost a severe loss of extracellular water
possessed unique properties for the maintenance of life. occurs.
For example, the water of the sea is a solvent for the
electrolytes and the oxygen that are necessary for life. The relation of the body water to the body weight are as
The sea is also a solvent for the carbon dioxide that follows:
accumulates during lifes processes. Since the carbon
Water Compartment Percentage Volume in
dioxide is volatile, it can be easily dissipated from the
of Body Liters
surface of the sea. In addition, the volume of the sea is
Weight (man, 70 kg)
so great that it can absorb large amounts of heat, or lose
large amounts of heat, with only relatively small changes Plasma water (plus) 4 2.8
in temperature. The volume of the sea is also so great Interstitial water 16 11.2
that significant changes in its composition occur only
over a period of hundreds of thousands of years. Finally, Total extracellular
its dielectric constant, its surface tension, and other water (plus) = 20 = 14
physical properties are all important in maintaining and Intracellular water 40 28
protecting life. Total average body
As a result, the water that surrounds the cells of water in a man = 60 = 42
vertebrates and of humans, namely, the extracellular Total average body
water, still has an electrolyte composition similar to what water in a 70 kg woman 50 35
the sea had in pre-recorded times, in spite of all the
countless changes in evolution that have occurred. Over These figures represent average values that we shall use
the years, the rivers of the world have eroded land and in calculating water and electrolyte requirements in this
washed elements into the sea. This has caused the book.
electrolytes of the sea to become more concentrated. In The total body water varies. It is related principally to
spite of this, there is still a remarkable similarity between the fat content of the body, and to sex. Fat has relatively
the proportional composition of electrolytes in seawater less water associated with it; therefore a fat person will
and in extracellular water. have relatively less water than a thin person. In addition,
The total amount of water in the body can be determined a woman has a lower content of body water than a man.
by introducing into the body a known quantity of a The water content of the body also decreases with age.
substance that diffuses evenly throughout the The average water content of a man is approximately
extracellular water and the cells, and then determining 60%. The average water content of a woman is
its concentration. Antipyrine, urea, thiourea, and more approximately 50%.
recently heavy water (deuterium oxide or tritium
oxide) have been used for this purpose. Body water is also composed of inaccessible bone water
and transcellular fluids.
The Extracellular Water Transcellular fluids include the fluid of organs such as
the kidneys, liver, pancreas, skin and the mucous
The body water is usually divided into two main
membranes of the gastrointestinal and respiratory, tracts;
compartments: the extracellular water (extracellular
and so on. It is difficult to measure the volume of the
fluid) and the intracellular water (intracellular fluid).
fluid in these compartments.
The extracellular water includes the plasma water and
the interstitial water (the fluid in the tissue spaces, lying Body water, including percentage of fat and of lean body
between the cells). Gastrointestinal secretions, urine, tissue, can now be measured using a bioelectrical
Organic acids 5 Na (at. wt. 23; valence 1) Cl (at. wt. 35.5; valence 1)
Na + Cl = 58.5
Total 153 200
*Adapted from Wilson, RF. Critial Care Manual: Applied Physiology Since the electrolyte concentration in blood and serum
and Principles of Therapy, ed 2. F.A. Davis, Philadephia, 1992, p are usually expressed in mEq/L, the following formulas
656. can be used to convert mg/dL into mEq/L, or vice versa:
It should be noted that the electrolyte concentration mg/dL x 10 x valence
of the plasma (or serum) is slightly different from the mEq/L =
electrolyte concentration in the interstitial portion of Atomic weight
the extracellular water. The major difference is that
mEq/L x 10 x atomic weight
the protein concentration of the plasma is greater that mg/dL =
that of the interstitial portion of the extracellular water. 10 x valence
Fig. 3: ECG showing prominent U waves after T waves and a premature ventricular ectopic (interposed between two QRS complexes).
Disturbances in acid-base balance are commonly maintaining the buffering capacity of the
encountered in the intensive care units and emergency extracellular fluid (ECF). Other minor buffers in
departments. These disorders may be life-threatening ECF include phosphates and proteins.
in themselves without regard to the underlying
2. The second physiological buffers are the
conditions causing them. Appropriate diagnosis and
intracellular proteins, of which, haemoglobin
management of these disorders in an acutely ill patient
is most important. It can buffer large amounts
require accurate and timely interpretation of specific
of H+ ions without disturbing the pH. In the
data. Physicians must be able to interpret the numbers
red cells, carbon dioxide combines with water
rapidly and accurately. In the present topic, a brief of
to form carbonic acid which dissociates to
physiological mechanisms by which acid-base balance
produce H + ions that are buffered by
is maintained in the body will be discussed. This will be
haemoglobin. Other buffers are intracellular
followed by various definitions used in acid-base
proteins and phosphates.
disorders, and detailed description of acid-base disorders
and their treatments. Finally, step-by-step approach to 3. Bone contains large amount of bicarbonate and
analyze acid-base disturbance will be discussed which can buffer parts of acute acid load. An acid load
will be followed by a case to illustrate various principles is associated with uptake of some of the excess
of acid-base interpretation. H+ ions by bone. This can occur in exchange for
surface Na+ and K+, and by dissolution of bone
mineral, resulting in the release of buffer
Normal Physiology of Acid-Base Balance compounds such as NaHCO 3 and KHCO 3
Acids are produced continuously during normal initially and then CaCO3 and CaHPO4 into
metabolism of body. About 20,000 mmol of carbonic extracellular fluid. The role of bone buffers may
acid and 80 mEq of non-volatile acids are produced daily. be even greater in the presence of a chronic acid
Despite this, the pH of extracellular fluid is maintained retention, such as seen in patients with chronic
between 7.36-7.44. The defense against fluctuations in renal failure.
pH is provided by three physiological buffer systems,
respiratory mechanics and renal mechanics. B. Pulmonary mechanisms
The principal volatile acid of metabolism is carbon
A. Physiological buffers dioxide which is equivalent to potential carbonic
acid. The normal concentration of carbon dioxide
The body buffers which are primarily weak acids,
in the body is maintained around 1.2 mmol/L by
are able to take up or release H+ so that changes in
the lungs. At this concentration, the pulmonary
the free H+ concentration are minimized. In the
excretion equals the metabolic production of carbon
body, three type of physiological buffers exist. These
dioxide.
are as follows:
1. The major physiological buffer is the bicarbonate- C. Renal mechanisms
carbonic acid system. Bicarbonate is converted
into water and carbon dioxide whenever H+ ions Kidneys reabsorb the filtered bicarbonate and also
are added. Carbon dioxide thus liberated is regenerate fresh bicarbonate. Bicarbonate is
excreted by the lungs. As the total buffering reabsorbed both in the proximal (75%) and distal
capacity of this system is about 15 mEq/L, at segments (25%) by secretion of protons into the
normal rate of production of non-volatile acids, tubular fluid. For each molecule of bicarbonate
the buffers will be depleted within a period of 15- filtered, one molecule is added to the blood by this
20 days. However, kidneys have the ability to mechanism (Figure 1).
regenerate bicarbonate and therefore help in New bicarbonate is regenerated by secretion of
l Total 11 mEq/L l Total 23 mEq/L However, full compensation of pH does not occur and
in acute metabolic acidosis, the minimum CO2 which
Potassium 4 Sulphates 1
can be achieved is 10 mmHg while in chronic acidosis,
Calcium 5 Phosphates 2 it is 15 mmHg.
Magnesium 2 Albumin 16
Lactic acid 1 Pathophysiology
Org. acids 3
Metabolic acidosis can be caused by three mechanisms:
Example: 1. Increased production of acids.
A patient has following ABG values: pH 7.20; pCO2 26; 2. Decreased excretion of acids by the kidneys
HCO3 10; Na+ 139; Cl- 110. His albumin is 2 g/dL. 3. Loss of alkali from the body
The anion gap = 139 (110 + 10) = 19 mmol/L Anion gap
Albumin correction: 2.5 x 2 = 5 mmol/L
An important tool employed in evaluating metabolic
Corrected Anion Gap: 19 + 5 = 24 mmol/L acidosis is anion gap. It is calculated as: (Na+) - (HCO3
Alterations in the concentration of unmeasured ions can + Cl) and is equal to 8-12 mmol/L. This is because of
lead to misestimation of the baseline AG. As an example, presence of unmeasured anions. Increased accumulation
both hypoalbuminaemia (reduced unmeasured anions) of these unmeasured anions leads to acidosis with raised
and hyperkalaemia (increased unmeasured cations) can anion gap. In some patients of acidosis, there is exchange
lower the AG. Thus a patient with one or both of these of bicarbonate with chloride leading to loss of
disorders may have a baseline AG of 2 rather than 8 bicarbonate and hyperchlorinaemia. This leads to a
meq/L. In this setting, an AG of 14 meq/L, which is normal anion gap with acidosis.
only mildly above the normal limit, represents a true It is important to calculate AG in all patients when acid-
elevation in the AG of as much as 12 meq/L. base interpretation is being done. An AG > 12 mmol/L
can indicate metabolic acidosis while an AG > 20 mmol/
Metabolic Acidosis L always indicates metabolic acidosis.
Metabolic acidosis is initiated by a reduction in plasma Diabetic ketoacidosis is typically associated with an
bicarbonate concentration. A pH < 7.2 may be life elevated AG. If renal function and volume status is
threatening because (i) the enzyme systems become well maintained, however, some or many of the excess
unreliable, (ii) electrolyte concentration is altered, (iii) ketone anions may be excreted in the urine as the
electrophysiological functions of the body become sodium and potassium salts. The net effect is that the
unreliable and this includes impaired cardiac rise in the AG may be much less than expected from
contractility and reduced threshold for ventricular the severity of metabolic acidosis. Furthermore, the loss
fibrillation, and (iv) the autonomic responses to drugs of these organic anions is equivalent to the loss of
are altered. bicarbonate, since metabolism of ketoacid anions
results in regeneration of bicarbonate. Thus a normal
Compensation in metabolic acidosis AG acidosis is typically seen during the treatment phase
of DKA due to the urinary loss of these bicarbonate
Because of increased H+ ion concentration in ECF, there precursors.
Osmolality of a solution is the number of osmoles of In normal individuals, approximately equal amounts of
solute per kilogram of solvent. Osmolarity of a solution H+ are buffered by ECF bicarbonate and ICF buffers.
is the number of osmoles of solute per litre of solution. Therefore, half of the administered bicarbonate will
The osmolar gap is the difference between the measured accept H+ from ICF and will be destroyed. Hence, the
osmolality and the calculated osmolarity. dose of bicarbonate required = Desired increase in
plasma bicarbonate x 40% of body weight (40% is double
Calculated osmolarity: 2 (Na+) + glucose/18 + BUN/ the ECF volume). This volume of 40% of body weight is
2.8 called bicarbonate space. In severe acidosis, bicarbonate
Normal osmolar gap is < 10 mOsm/L. It is elevated in space may be large due to intracellular shift of H+ and
several conditions including poisoning with ethanol, buffering of H+ by bone and cellular buffers. Therefore,
methanol, and ethylene glycol. frequent determinations of acid-base status are required.
Half of the calculated bicarbonate should be
Urinary anion gap administered first and acid-base estimation is repeated
after that before further bicarbonate is administered.
In normal circumstances, urine is free of HCO3. Spot
urine electrolytes are measured to calculate UAG. NH4 Example:
is the predominant unmeasured cation in urine. It is
accompanied by Cl-. A patient weighing 70 kg has following blood gas values:
pH = 7.1; pCO2 = 20 mmHg; HCO3 = 6 meq/L
UAG = Na+ + K+ - Cl-
Normal UAG = - 20 to positive The pH should be raised to 7.2. At the pH of 7.2, the H+
concentration will be 63 nmol/L. Therefore, using the
If non-renal source of non-anion gap metabolic acidosis modified Henderson-Hasselbach formula,
is present (e.g., diarrhea), there is dramatic increase in
NH4 excretion in urine and therefore UAG becomes more 63 = 24 x 20/HCO3 or HCO3 = 8 meq/L.
negative ( < 20 and may even become -50). If patient Presuming bicarbonate space of 70%, the amount of
has renal tubular acidosis (RTA), UAG is positive bicarbonate required to increase pH to 7.2 will be:
6. Intracellular acidosis may occur because of Under normal conditions, kidneys excrete excessive
intracellular diffusion of liberated carbon dioxide. bicarbonate rapidly so that alkalosis will not be sustained
Intracellular acidosis may hamper the functions of unless bicarbonate reabsorption in the kidneys is
metabolic enzymes. enhanced or alkali is generated at a great rate. The
maintenance of alkalosis is due to three factors:
Other options 1. Stimulation of bicarbonate reabsorption due to
Carbicarb: It consists of equimolar concentrations of volume depletion when renal conservation of
sodium bicarbonate and sodium carbonate. Because sodium takes precedence over correction of
carbonate is a stronger base, it is used in preference to alkalosis. Since a large fraction of plasma sodium is
bicarbonate for buffering hydrogen ions, generating bound with bicarbonate, complete absorption of
bicarbonate rather than carbon dioxide in the process filtered sodium requires reabsorption of bicarbonate
(CO3 + H+ = HCO3). In addition, the carbonate ion as well. Alkalosis is sustained till volume depletion
can react with carbonic acid, thereby consuming carbon exists. On administering sodium chloride, tubular
dioxide (CO3 + H2CO3 = 2HCO3). Thus, Carbicarb avidity for sodium decreases. Also, chloride is
limits but does not eliminate the generation of carbon available as an alternative to bicarbonate.
dioxide. However, the risks of hypervolemia and 2. Another mechanism which can maintain alkalosis
hypertonicity are similar to bicarbonate, and neither is hypermineralocorticoidism which stimulates
agent prevents progressive reduction in myocardial-cell increased renal H+ secretion as ammonium and
pH in animals with ventricular fibrillation. titrable acidity. The patients are not volume-depleted
Respiratory Alkalosis with Metabolic Acidosis Step 4: Calculate compensatory response. The formulas
1. Septic shock are listed in table 9. In acute metabolic acidosis for
2. Salicylate overdose example, Winters Formula can be used to calculate
whether the respiratory compensation is appropriate.
3. Renal failure with sepsis In metabolic acidosis, pCO2 should be equal to 1.5 times
Respiratory Acidosis with Metabolic Alkalosis bicarbonate levels plus 8 2. If the patients pCO2 is
1. COAD with diuretic use higher, the patient has a superimposed respiratory
acidosis. If the pCO2 is below this range, the patient has
Metabolic Acidosis with Metabolic Alkalosis a superimposed respiratory alkalosis.
1. Diarrhea and vomiting
2. Metabolic acidosis with excessive bicarbonate Step 5: Calculate anion gap. Presence of high anion gap
therapy indicates high anion-gap metabolic acidosis.
Lastly, one case scnario will be discussed to give step-by-step approach to acid-base interpretation.
Practice Case
l 60 year male presents to the ED with rapid breathing l Step 1: Is there an acidemia or alkalemia?
and less responsive than usual. No other history is Acidemia
available
ABG: pH 7.31 Chem: Na+ 123
ABG: pH 7.31 Chem: Na+ 123
PCO2 10 K+ 5.0
+
PCO2 10 K 5.0
HCO3 5 Cl 99
HCO3 5 Cl 99
HCO3 5
HCO3 5
Chairman Dean
SK Bichile, Mumbai (2009) AK Das, Pondicherry (2010)
Elected Members
S Chugh, Delhi (2009) Subhash Chandra, New Delhi (2009)
MP Shrivastava, New Delhi (2009) BN Jha, Muzaffarpur (2009)
HM Lal, Hyderabad (2009) S Chandrasekharan, Chennai (2010)
Vinay Goel, New Delhi (2010) RK Goyal, Ajmer (2010)
Rajat Kumar, New Delhi (2010) MP Singh, Ranchi (2010)
Ex-Officio Members
President Elect Hon.Editor, JAPI
AK Agarwal Shashank R.Joshi
New Delhi (2009) Mumbai (2009)