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Pathophysiologic Basis of Acid-Base

Disorders Farrokh Habibzadeh


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Pathophysiologic
Basis of Acid-Base
Disorders

Farrokh Habibzadeh
Mahboobeh Yadollahie
Parham Habibzadeh

123
Pathophysiologic Basis of Acid-Base
Disorders
Farrokh Habibzadeh • Mahboobeh Yadollahie
Parham Habibzadeh

Pathophysiologic Basis
of Acid-Base Disorders
Farrokh Habibzadeh Mahboobeh Yadollahie
Petroleum Industry Health Organization Petroleum Industry Health Organization
Shiraz Shiraz
Iran Iran

Parham Habibzadeh
Persian BayanGene Research
and Training Center
Shiraz
Iran

ISBN 978-981-16-0525-3    ISBN 978-981-16-0526-0 (eBook)


https://doi.org/10.1007/978-981-16-0526-0

© The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Singapore
Pte Ltd. 2021
This work is subject to copyright. All rights are solely and exclusively licensed by the Publisher, whether
the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse of
illustrations, recitation, broadcasting, reproduction on microfilms or in any other physical way, and
transmission or information storage and retrieval, electronic adaptation, computer software, or by similar
or dissimilar methodology now known or hereafter developed.
The use of general descriptive names, registered names, trademarks, service marks, etc. in this publication
does not imply, even in the absence of a specific statement, that such names are exempt from the relevant
protective laws and regulations and therefore free for general use.
The publisher, the authors, and the editors are safe to assume that the advice and information in this book
are believed to be true and accurate at the date of publication. Neither the publisher nor the authors or the
editors give a warranty, expressed or implied, with respect to the material contained herein or for any
errors or omissions that may have been made. The publisher remains neutral with regard to jurisdictional
claims in published maps and institutional affiliations.

This Springer imprint is published by the registered company Springer Nature Singapore Pte Ltd.
The registered company address is: 152 Beach Road, #21-01/04 Gateway East, Singapore 189721,
Singapore
Preface

“In teaching the medical student, the primary requisite


is to keep him/her awake.”
Chevalier Jackson (1865–1958)

During our medical clerkship, we were feeling the lack of an appropriate text on
acid-base disorders. Later on, we found several books on the topic. Nevertheless, we
found none of them appropriate for medical students; the books were either too
detailed and lengthy to be used by a medical student who has a limited amount of
time, or too simple and concise to meet the needs of daily practice. This turned a
wheel in our mind to develop a proper text that we were long looking for—simple,
concise, and informative.
This book consists of nine chapters. It is assumed that the reader has only a very
basic knowledge of mathematics, chemistry, and medical terminology. We, there-
fore, decided to start from the scratch. The first four chapters deal with the basic
knowledge necessary for understanding the clinical concepts, which are explained
in Chapters 5–9. The material explored in each section is further clarified by several
examples throughout the text.
Although we have tried to prepare an error-free text, we are sure that an astute
reader may pick up many errors. The authors welcome all relevant critiques and
appreciate your correspondence.
We would like to thank all who have helped us in numerous ways in preparing
this book. Finally, we hope this book keeps all the medical students who read
it awake.

Shiraz, Iran Farrokh Habibzadeh, MD


Shiraz, Iran  Mahboobeh Yadollahie, MD
Shiraz, Iran  Parham Habibzadeh, MD
November 2020

v
Contents

1 Starting from Scratch��������������������������������������������������������������������������������   1


1.1 Calculation with Powers ��������������������������������������������������������������������   1
1.1.1 Multiplication and Division of Numbers
Having the Same Base, B��������������������������������������������������������   1
1.1.2 Powers Raised to Powers��������������������������������������������������������   4
1.2 Logarithm��������������������������������������������������������������������������������������������   6
1.3 Chemical Equilibrium������������������������������������������������������������������������   8
1.3.1 Equilibrium Constant�������������������������������������������������������������� 10
1.4 Things to Remember�������������������������������������������������������������������������� 11
References���������������������������������������������������������������������������������������������������� 12
2 ABC’s of Acid-Base Chemistry���������������������������������������������������������������� 13
2.1 Ionization of Water������������������������������������������������������������������������������ 13
2.2 pH, pOH, pK, pKw ������������������������������������������������������������������������������ 14
2.3 Acids and Bases���������������������������������������������������������������������������������� 19
2.4 Buffers������������������������������������������������������������������������������������������������ 24
2.4.1 Buffering Action �������������������������������������������������������������������� 25
2.4.2 Titration and Titration Curve�������������������������������������������������� 26
2.4.3 Amino Acids as Buffers���������������������������������������������������������� 28
2.5 Things to Remember�������������������������������������������������������������������������� 29
References���������������������������������������������������������������������������������������������������� 30
3 Gas Laws���������������������������������������������������������������������������������������������������� 31
3.1 Pressure and Partial Pressure of a Gas������������������������������������������������ 31
3.2 Dalton’s Law of Partial Pressure�������������������������������������������������������� 32
3.3 Composition of Alveolar Air�������������������������������������������������������������� 32
3.4 Gas-Liquid Equilibrium���������������������������������������������������������������������� 34
3.5 Henry’s Law���������������������������������������������������������������������������������������� 34
3.6 Things to Remember�������������������������������������������������������������������������� 36
References���������������������������������������������������������������������������������������������������� 37
4 What Happens in a Person������������������������������������������������������������������������ 39
4.1 Introduction���������������������������������������������������������������������������������������� 39
4.2 Pulmonary Ventilation, Perfusion, and Blood-Gas Exchange������������ 39
4.2.1 Ventilation ������������������������������������������������������������������������������ 39

vii
viii Contents

4.2.2 Perfusion and Its Regional Distribution���������������������������������� 41


4.2.3 Regional Variation in the Matching of Ventilation
and Perfusion�������������������������������������������������������������������������� 42
4.3 Blood-Gas Interface and Gas Exchange �������������������������������������������� 43
4.4 Respiratory Quotient�������������������������������������������������������������������������� 45
4.5 Alveolar Air Composition������������������������������������������������������������������ 45
4.6 Carriage of O2 by the Blood���������������������������������������������������������������� 48
4.6.1 Oxyhemoglobin Dissociation Curve�������������������������������������� 50
4.7 Carriage of Carbon Dioxide���������������������������������������������������������������� 54
4.8 Control of Respiration������������������������������������������������������������������������ 55
4.9 Buffers������������������������������������������������������������������������������������������������ 57
4.9.1 Bone as a Buffer���������������������������������������������������������������������� 62
4.10 Renal Regulation of Extracellular Hydrogen Ion Concentration�������� 62
4.10.1 Bicarbonate Reabsorption������������������������������������������������������ 63
4.10.2 Addition of New Bicarbonate to the Plasma
and Renal Excretion of Acid �������������������������������������������������� 64
4.11 Things to Remember�������������������������������������������������������������������������� 67
References���������������������������������������������������������������������������������������������������� 70
5 Introduction to Acid-Base Chemistry and Arterial Blood Gases���������� 71
5.1 Terminology���������������������������������������������������������������������������������������� 71
5.2 Bedside Approach to a Patient with a Suspected
Acid-Base Disorder���������������������������������������������������������������������������� 72
5.3 Indications for Arterial Blood Gas Analysis �������������������������������������� 73
5.4 Obtaining the Sample�������������������������������������������������������������������������� 73
5.4.1 Allen’s Test ���������������������������������������������������������������������������� 74
5.4.2 Complications of Arterial Puncture and Cannulation ������������ 74
5.5 Analysis of the Sample ���������������������������������������������������������������������� 75
5.6 Venous Blood Gas Analysis���������������������������������������������������������������� 75
5.7 Anion Gap������������������������������������������������������������������������������������������ 75
5.8 Base Excess (BE)�������������������������������������������������������������������������������� 78
5.9 Normal Values������������������������������������������������������������������������������������ 78
5.10 Bicarbonate Space������������������������������������������������������������������������������ 79
5.11 Systemic Effects of Acidemia ������������������������������������������������������������ 80
5.12 Systemic Effects of Alkalemia������������������������������������������������������������ 80
5.13 Things to Remember�������������������������������������������������������������������������� 81
References���������������������������������������������������������������������������������������������������� 82
6 Respiratory Acidosis and Alkalosis���������������������������������������������������������� 83
6.1 Causes of Respiratory Acidosis and Alkalosis������������������������������������ 83
6.2 Mechanisms in Respiratory Acidosis�������������������������������������������������� 84
6.2.1 Acute Phase of Respiratory Acidosis�������������������������������������� 86
6.2.2 Chronic Phase of Respiratory Acidosis���������������������������������� 86
6.3 Clinical Manifestations of Respiratory Acidosis�������������������������������� 87
6.4 Diagnosis of Respiratory Acidosis������������������������������������������������������ 87
6.5 Treatment of Respiratory Acidosis ���������������������������������������������������� 89
Contents ix

6.6 Mechanisms in Respiratory Alkalosis������������������������������������������������ 89


6.6.1 Acute Phase of Respiratory Alkalosis������������������������������������ 90
6.6.2 Chronic Phase of Respiratory Alkalosis �������������������������������� 90
6.7 Clinical Manifestations of Respiratory Alkalosis ������������������������������ 90
6.8 Diagnosis of Respiratory Alkalosis���������������������������������������������������� 91
6.9 Treatment of Respiratory Alkalosis���������������������������������������������������� 92
6.10 Things to Remember�������������������������������������������������������������������������� 93
References���������������������������������������������������������������������������������������������������� 94
7 Metabolic Acidosis and Alkalosis�������������������������������������������������������������� 95
7.1 Pathogenesis and Compensatory Mechanisms ���������������������������������� 95
7.1.1 Metabolic Acidosis����������������������������������������������������������������� 95
7.1.2 Metabolic Alkalosis���������������������������������������������������������������� 96
7.2 Causes of Metabolic Acidosis������������������������������������������������������������ 97
7.2.1 Over-Production of Fixed Acid���������������������������������������������� 97
7.2.2 Loss of Buffer Stores (Bicarbonate Wasting) ������������������������ 98
7.2.3 Decreased Normal Renal Acid Excretion ������������������������������ 98
7.3 Causes of Metabolic Alkalosis������������������������������������������������������������ 100
7.4 Systemic Manifestations of Metabolic Acidosis�������������������������������� 100
7.5 Systemic Manifestations of Metabolic Alkalosis�������������������������������� 102
7.6 Diagnosis of Metabolic Acidosis�������������������������������������������������������� 102
7.7 Treatment of Metabolic Acidosis�������������������������������������������������������� 103
7.7.1 Complications of Sodium Bicarbonate Therapy�������������������� 105
7.8 Diagnosis of Metabolic Alkalosis ������������������������������������������������������ 105
7.9 Treatment of Metabolic Alkalosis������������������������������������������������������ 108
7.9.1 Saline (Chloride) Responsive Alkalosis���������������������������������� 109
7.9.2 Saline (Chloride) Unresponsive Alkalosis������������������������������ 109
7.10 Things to Remember�������������������������������������������������������������������������� 113
References���������������������������������������������������������������������������������������������������� 114
8 Mixed Disorders ���������������������������������������������������������������������������������������� 117
8.1 Introduction and Diagnostic Procedures�������������������������������������������� 117
8.2 Clinical Approach to Mixed Acid-Base Disorders������������������������������ 117
8.3 Mixed Acid-Base Disorders���������������������������������������������������������������� 120
8.3.1 Mixed Metabolic and Respiratory Acidosis���������������������������� 120
8.3.2 Mixed Metabolic Acidosis and Respiratory Alkalosis������������ 123
8.3.3 Mixed Metabolic Acidosis������������������������������������������������������ 125
8.3.4 Mixed Metabolic Acidosis and Metabolic Alkalosis�������������� 129
8.3.5 Mixed Metabolic Alkalosis and Respiratory
Acidosis; Mixed Metabolic and Respiratory Alkalosis���������� 130
8.3.6 Mixed Acute and Chronic Respiratory Acidosis
or Alkalosis ���������������������������������������������������������������������������� 133
8.3.7 Triple Acid-Base Disorders���������������������������������������������������� 136
8.4 Things to Remember�������������������������������������������������������������������������� 138
References���������������������������������������������������������������������������������������������������� 139
x Contents

9 Arterial Blood Gas ������������������������������������������������������������������������������������ 141


9.1 Hypoxia and Its Causes����������������������������������������������������������������������
. . 141
9.1.1 Ventilation-Perfusion ( V / Q ) Mismatch�������������������������������� 141
9.1.2 Blood Shunt���������������������������������������������������������������������������� 141
9.1.3 Hypoventilation���������������������������������������������������������������������� 143
9.1.4 Thickening of Blood-Gas Interface���������������������������������������� 143
9.2 Oxyhemoglobin Dissociation Curve�������������������������������������������������� 143
9.3 Things to Remember�������������������������������������������������������������������������� 149
References���������������������������������������������������������������������������������������������������� 150
About the Author

Farrokh Habibzadeh is a general practitioner and author of more than 150 peer-­
reviewed articles and 6 book chapters. He has been involved in biomedical research,
scientific writing, and editorship craft since 30 years ago. He was the Editor of The
International Journal of Occupational and Environmental Medicine for 11 years.

Mahboobeh Yadollahie is a general practitioner and author of more than 50 peer-­


reviewed articles and 3 book chapters. She has been involved in biomedical research
and scientific writing since 15 years ago. She was the Deputy Editor of The
International Journal of Occupational and Environmental Medicine for 11 years.

Parham Habibzadeh graduated from Shiraz University of Medical Sciences with


first class honors. He is the author of more than 40 peer-reviewed articles and has
received many national and international awards including an Honorary Diploma
from the Iranian Academy of Medical Sciences. Currently, he is the Director of the
R&D Department, Persian BayanGene Research and Training Center.

xi
Starting from Scratch
1

It’s elementary, Watson


Sherlock Holmes

1.1 Calculation with Powers

When we say, A = 53 (read “five raised to the power of three”), we mean that 5 is to
be multiplied 3 times by itself. Thus:
A = 5´ 5´ 5
In general, if we have A = Bp, B is called the “base,” and p is named the “power,”
“exponent,” or “index.”

Example 6.023 = 6.02 ´ 6.02 ´ 6.02


74 = 7 ´ 7 ´ 7 ´ 7

1.1.1  ultiplication and Division of Numbers Having


M
the Same Base, B

If N = B6 and M = B2, then:

N ´ M = B6 ´ B 2
= ( B ´ B ´ B ´ B ´ B ´ B) ´ ( B ´ B)
= B´ B´ B´ B´ B´ B´ B´ B
= B8
= B6 + 2

© The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd. 2021 1
F. Habibzadeh et al., Pathophysiologic Basis of Acid-Base Disorders,
https://doi.org/10.1007/978-981-16-0526-0_1
2 1 Starting from Scratch

In general, if the numbers have the same base (here, B), powers must be
added. Thus:

B p ´ Bq = B p + q
Example
23 ´ 2 4 = 23 + 4 = 2 7
31 ´ 39 = 31+ 9 = 310
0.5 ´ 0.52 = 0.57 + 2 = 0.59
7

In a similar way, if N = B6 and M = B2, then:

N B6 B ´ B ´ B ´ B ´ B ´ B
= =
M B2 B´ B
= B´ B´ B´ B
= B4
= B6 - 2
In general, if the numbers have the same base, the power of the denominator
must be subtracted from that of the numerator, and we can write:

Bp
q
= B p-q
B
Example
B4
= B1 = B
B3
0.756
= 0.756 - 2 = 0.754
0.752
10.13 10.13
= 1
= 10.13-1 = 10.12
10 . 1 10 . 1

Example Now let us find the results of the following divisions:

34
A=
34

Solution: The numerator and denominator are equal and thus:

3´ 3´ 3´ 3
A= =1
3´ 3´ 3´ 3

but, according to our general rule, we have:

34
A= = 34 - 4 = 30
34
1.1 Calculation with Powers 3

Therefore, 30 = 1.

Bp
C=
Bp
Solution:
Bp
C= =1
Bp

because the numerator equals the denominator, but employing the general rule for
division, we have:

Bp
C= = B p - p = B0
Bp
Therefore, it can be stated that any non-zero number raised to the power of zero
equals one, that is:

B0 = 1
33
D=
35
Solution:
33 3´ 3´ 3
D= =
3 5
3´ 3´ 3´ 3´ 3
1
=
3´ 3
1
= 2
3

but, using our general rule, we have:

33
D= = 33- 5 = 3-2
35
Therefore:

1
3-2 =
32
1
F=
Bp

Solution: Using what we have learned earlier, and substituting B0 for 1, the above
division can be rewritten as:

1 B0
F= p
= p
B B
= B0 - p
= B- p
4 1 Starting from Scratch

Therefore:

1
= B- p
Example Bp

1
4
= 3-4
3
1
= 0.6 -3
0.63
1 1
-3
= éë3 + ( -3) ùû
0.8 ´ 0.8
3
0.8
1
=
0.80
1
= =1
1

1.1.2 Powers Raised to Powers


Example
(5 )
3
2
= 52 ´ 52 ´ 5 2
= ( 5 ´ 5) ´ ( 5 ´ 5) ´ ( 5 ´ 5)
= 5´ 5´ 5´ 5´ 5´ 5
= 56
= 52 ´ 3

In general, we have:

(B )
q
p
= B p´ q

Example If we have:

1
A = 125 3
raising both sides to the power of 3 gives:
3
æ 1
ö
A3 = ç 125 3 ÷
è ø
æ1 ö
ç ´3 ÷
= 125è 3 ø

= 1251
= 125
1.1 Calculation with Powers 5

Therefore, A is the number which multiplied 3 times by itself equals 125, that is
5. This expression is usually represented as “A is the 3rd-root of 125.” In a more
general form, if we have:
1

A=B p

A is the number which multiplied p times by itself equals B, and we say that “A
is the pth-root of B.”

Example Solve the equation:

64 = x 3

1
Solution: If we raise both sides to the power of (in other words, if we get the 3rd
root of both sides), then: 3

1 1

( )
64 3 = x 3 3

æ 1ö
ç 3´ ÷
= xè 3ø

= x1
=x

Therefore, x equals the 3rd-root of 64, which is 4 (because 43 = 64).


In practical works, the numbers are not like those we have used in our exam-
ples; calculation with them is usually not easy without a calculator; and the
answers are normally not exact; nonetheless, we can find the result with accept-
able precision.

Example Lowe’s formula for calculation of body surface area is:


2
S = 0.1 ´ wt 3

where S represents the body surface area in m2 and Wt is the body weight in kg.
Calculate the body surface area of a girl weighing 20 kg.
Solution: 2
S = 0.1 ´ 20 3
» 0.1 ´ 7.37
» 0.737 m 2

6 1 Starting from Scratch

1.2 Logarithm

In the previous section, we have dealt with problems in which the base was unknown.
Now, we want to solve problems with unknown powers, which are very important
in practice.

Definition If

A = Bp

then, by definition, p is called the logarithm of A to the base B, and it is writ-


ten as [1]:

p = log B A

Example If…

8 = 23 then 3 = log 2 8
2 = 10 0.301 then 0.301 = log10 2
1 1
= 3-2 then - 2 = log3
9 9
M = 0.6 9.1 then 9.1 = log 0.6 M

The most common types of logarithm which one commonly deals with in his or
her work are those to base 10. These are called common logarithms in which the
base is not usually written. Therefore, instead of writing log103, it is common to
write log 3.

Example The concentration of hydrogen ion (represented as [H+]) in the most alka-
line body fluid, the pancreatic juice, is about 0.000 000 03 mol/L. Express this value
as a power of 10.

Solution: Mathematically, the problem is to solve the following equation:

0.00000003 = 10 x

Considering the definition of logarithm, we have


x = log 0.000 000 03
= -7.523
Thus:

0.000000003 = 10 -7.523
Using our definition for logarithms, the following useful rules can be
derived easily.
1.2 Logarithm 7

log ( A ´ B ) = log A + log B

Example
log 300 = log ( 3 ´ 100 )
= log 3 + log 100
= 0.477 + 2
= 2.477

Example Suppose: K = A´ B

calculate the −log K.

Solution:
log K = log ( A ´ B )
= log A + log B

and

- log K = - éë log ( A ´ B ) ùû
= - log A - log B

æ Aö
***** log ç ÷ = log A - log B
èBø

æ 3 ö
log 0.03 = log ç ÷
è 100 ø
= log 3 - log 100
= 0.477 - 2
Example = -1.523

Example Assume:

A´ B
K=
C
Then:

æ A´ B ö
log K = log ç ÷
è C ø
æ Bö
= log ç A ´ ÷
è Cø
æBö
= log A + log ç ÷
èC ø
= log A + log B - log C
8 1 Starting from Scratch

*****

log 1 = 0
æ1ö
log ç ÷ = - log A
è Aø
Example
1
log = - log éë H + ùû
éë H + ùû

where [H ] represents the concentration of hydrogen ion. As an example, the [H+] in
+

pancreatic juice is about 0.000 000 03 mol/L, thus

1
log = - log ( 0.000 000 03 )
0.000 000 03
= 7.523
§§§§§

1.3 Chemical Equilibrium

Chemical reactions can either be reversible or irreversible. In reversible chemical


reactions, an equilibrium state between the reactants and the product will be reached
under certain circumstances of concentrations and temperature. An example is the
dissociation of carbonic acid (H2CO3) to water (H2O) and carbon dioxide (CO2):

H 2 CO3 ® H 2 O + CO2 (1.1)


Under a condition where the produced carbon dioxide can be swept away, com-
plete conversion of carbonic acid to water and carbon dioxide is expected. On the
other hand, if the pressure of CO2 is high enough, it can react with water to form
carbonic acid, according to the following reaction:

H 2 O + CO2 ® H 2 CO3 (1.2)


This reaction is clearly the reverse of reaction (1.1). The fact that reactions (1.1)
and (1.2) are reversible is represented by the following formulation:

H 2 CO3  H 2 O + CO2 (1.3)


When pure H2CO3 is in a closed container, it dissociates according to reaction
(1.1). As CO2 accumulates, its pressure increases and reaction (1.2) begins to occur
at a higher rate which is accelerated as the pressure of CO2 increases. Eventually,
the rates of the decomposition reaction (1.1) and its reverse (1.2) reaction become
equal, the pressure of CO2 remains constant, and the system reaches an equilib-
rium state.
1.3 Chemical Equilibrium 9

It is important to bear in mind that the equilibrium state is dynamic, i.e., by say-
ing that the system of the reaction (1.3) reaches an equilibrium, it is not meant that
the reaction is stopped completely; it means that the rate of decomposition of H2CO3
to H2O and CO2 equals the rate of formation of H2CO3 from H2O and CO2. Therefore,
although no change occurs in the concentrations of reactants and products, the reac-
tion continues.
If any of the factors that determine the equilibrium state of a system are changed,
the system will respond in such a way to minimize the effect of the disturbance or the
stress exerted. This is known as Le Chatelier’s principle [2].
For example, by raising the pressure of CO2 in the reaction (1.3), the rate of gen-
eration of H2CO3 overcomes its rate of dissociation. Therefore, the net reaction
shifts to the left and more H2CO3 molecules are formed at the expense of the added
CO2. The externally applied stress (the increased pressure of CO2) is reduced. At
this point, the CO2 pressure decreases (though it never reaches that of the previous
equilibrium state), as it is used to form H2CO3; the decomposition of H2CO3 (from
left to right) accelerates as more H2CO3 is produced. Ultimately, a new equilibrium
state is reached where the rate of decomposition of H2CO3 equals the rate of its
formation. The new concentration of H2CO3 is, however, higher than that it was in
the previous equilibrium state.
On the other hand, if some H2CO3 is added to the system at equilibrium, the
concentration of H2CO3 is increased; the rate of dissociation overcomes the rate of
formation of H2CO3 and as a consequence, the externally increased H2CO3 concen-
tration is diminished. The net reaction directs to the right and eventually, a new
equilibrium state is reached.

Example Water ionizes according to the reversible reaction:

H 2 O  H + + OH -
What is the behavior of the system if…
(a) the concentration of H+ is increased?
(b) the concentration of H+ is decreased?

Solution: If the concentration of H+ is increased, the Le Chatelier’s principle pre-


dicts that the reaction proceeds in a direction to minimize the effect of this change,
that is, a reaction which removes H+ from the solution. The rate of formation of H2O
will be more than that of its dissociation; the reaction will thus shift to the left. On
the contrary, by decreasing the concentration of H+, the reaction will shift to the
right to reach a new equilibrium state.

Example Carbonic acid ionizes according to the reversible reaction:

H 2 CO3  HCO3- + H +
10 1 Starting from Scratch

Predict the behavior of the system if…


(a) the concentration of H+ is increased.
(b) the concentration of H+ is decreased.

Solution: As before, if you add some H+ to the system, reconsidering the Le


Chatelier’s principle, the reaction proceeds in a way that removes the excess H+
from the solution, that is, the formation of H2CO3 from H+ and HCO3- . In the new
equilibrium state, the concentration of H2CO3 will be increased relative to that in the
initial state. According to the same discussion, reducing the concentration of H+ will
result in decreased H2CO3 concentration at the new equilibrium state.

1.3.1 Equilibrium Constant

Experiments reveal that, for a reaction of the form:


a A+ bB  gC +d D
at equilibrium, the equilibrium constant (K) can be defined as:

[C ] [ D ]
g d

K=
[ A] [ B ]
a b

where brackets ([]) represent the concentrations. This equilibrium constant only
depends on the temperature of the reaction mixture.

Example For the ionization of water, we have:

H 2 O  H + + OH -
The equilibrium constant can then be written as:

éH + ù éOH - ùû
K = ë ûë
[H 2 O]
For ionization of carbonic acid:

H 2 CO3  HCO3- + H +
the equilibrium constant is:

éHCO3- ùû éëH + ùû
K=ë
[H 2 O]
Now, the basic concepts of mathematics and chemistry necessary for our follow-
ing discussions have been reviewed, and we are ready to start understanding the
“Acid–Base Chemistry.”
1.4 Things to Remember 11

1.4 Things to Remember

In general, for any A, B, C, p, and q we have

Powers

B p ´ Bq = B p + q
Bp
= B p-q
Bq
B0 = 1, if B ¹ 0

(B )
q
p
= B p´ q
1
B- p =
Bp
1
p
(
B p = B p th - rooot of B )
Logarithm

if B ¹ 0, then ¼
A = BC Û C = log B A
log B ( A ´ C ) = log B A + log B C
A
log B = log B A - loog B C
C
log B 1 = 0
1
log B = - log B A
A
log B A p = p ´ log B A

§§§§§

Chemical Equilibrium

 e Chatelier’s Principle
L
If any of the factors that determine the equilibrium state of a system are changed,
the system will respond in such a way to minimize the effect of the disturbance or
the stress exerted. This is known as Le Chatelier’s principle.
12 1 Starting from Scratch

Equilibrium Constant

For a reaction of the form:


a A+ b B  g C +d D
at equilibrium, the equilibrium constant (K) is defined as:

[C ] [ D ]
g d

K=
[ A] [ B ]
a b

References
1. Murray FJ. Logarithm. Encyclopædia Britannica; 2019. https://www.britannica.com/science/
logarithm. Accessed 18 Nov 2020.
2. Russell JM. Simple models for teaching equilibrium and Le Châtelier’s principle. J Chem
Educ. 1988;65(10):871–2. https://doi.org/10.1021/ed065p871.
ABC’s of Acid-Base Chemistry
2

2.1 Ionization of Water

Although water has only a very slight tendency to ionize, its products have intense
biological effects [1]. Experiments indicate that water ionizes according to the
reversible reaction:

H 2 O  H + + OH - (2.1)
Using the general concepts of chemical equilibrium discussed in the previous
­chapter, for this reaction we can write:

éH + ù éOH - ùû
K = ë ûë
[H 2 O] (2.2)
where K is the equilibrium constant, and [H+], [OH−], and [H2O] are concentrations
of H+, OH −, and water, respectively. However, since the ionization is, at best, very
small, the concentration of water in any aqueous solution is essentially constant and
is equal to the number of grams of H2O in 1 L, divided by the gram molecular
weight, or 1000/18 = 55.5 mol/L; thus, it can be included in K and Eq. (2.2) can be
written as:

K w = K ´ [ H 2 O ] = ëéH + ùû éëOH - ùû (2.3)


Kw is called the ion product of water. It varies with temperature (Table 2.1). The ion
product of water is 1 × 10−14 only at 25 °C; at other temperatures, the constant has
different values.

© The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd. 2021 13
F. Habibzadeh et al., Pathophysiologic Basis of Acid-Base Disorders,
https://doi.org/10.1007/978-981-16-0526-0_2
14 2 ABC’s of Acid-Base Chemistry

Table 2.1 Ion product of Temperature (°C) Kw × 1014 pKw


water, Kw and pKw at a 0 0.114 14.943
number of temperatures
10 0.292 14.535
25 1.008 13.997
40 2.919 13.535

2.2 pH, pOH, pK, pKw

In the human body, the concentration of hydrogen ion ([H+]) has a wide range. It is
about 0.13 mol/L in the most acidic gastric juice, to about 0.000 000 03 mol/L in the
most alkaline pancreatic juice. Working with these numbers is very difficult.
However, they can be expressed as powers of 10 as follows:

0.13 = 10 -0.886
0.000 000 03 = 10 -7.523
Søren Peter Lauritz Sørensen, a Danish chemist, proposed the use of the pH (puis-
sance d’Hydrogen) scale to get rid of difficulties with expressing the concentration
of hydrogen ion ([H+]), which in normal biological settings usually involves nega-
tive exponents. The term pH is defined as the negative logarithm to the base 10
(common logarithm) of the hydrogen ion concentration ([H+]) in solution [1, 2]. The
definition can be written mathematically as:

pH = - log éëH + ùû (2.4)



Similarly, the concentration of hydroxyl ion ([OH ]) can be expressed on a pOH
scale by the following definition:

pOH = - log éëOH - ùû (2.5)

Example The concentrations of hydrogen ion and hydroxyl ion in the blood of a
patient with a body temperature of 40 °C, are 4.02 × 10−8 and 7.26 × 10−7 mol/L,
respectively. Calculate the corresponding pH and pOH.

Solution:

éëH + ùû = 4.02 ´ 10 -8 mol / L


By definition:
pH, pOH, pK, pKw
2.2  15

pH = - log éëH + ùû

(
then pH = - log 4.02 ´ 10 -8 )
(
= - log 4.02 + log 10 -8 )
= - ( 0.604 - 8 )
= 7.396
and

éëOH - ùû = 7.26 ´ 10 -7 mol/L


Thus:

pOH = - log éëOH - ùû


(
then pOH = - log 7.26 ´ 10 -7 )
(
= - log 7.26 + log 10 -7 )
= - ( 0.861 - 7 )
= 6.139
Now let’s define pK and pKw in the same way as follows:
pK = - log K (2.6)
and

pK w = - log K w (2.7)
For convention, in all of the previously defined terms (i.e., pH, pOH, pK, and pKw),
the symbol p denotes “negative logarithm of…”
Considering Eq. (2.3), we have:

K w = éëH + ùû éëOH - ùû
where Kw is the ion product of water. Taking logarithm from both sides gives:

(
log K w = log éëH + ùû éëOH - ùû )
= log éëH + ùû + log éëOH - ùû
Multiplying both sides by −1 yields:

(
- log K w = - log éëH + ùû + - log éëOH - ùû )
16 2 ABC’s of Acid-Base Chemistry

employing Eqs. (2.4), (2.5), and (2.7), then:

pK w = pH + pOH (2.8)
The ion product of water (Kw) is 1 × 10−14 only at 25 °C, and consequently pKw is 14
only at 25 °C; at other temperatures, it has other values [1]. Table 2.1 shows the
values of Kw, and their corresponding pKw at various temperatures.

Example Use the results of the previous example to confirm the Eq. (2.8).

Solution: In the previous example, our calculations showed that, pH = 7.396, and
pOH = 6.139 at the body temperature of 40 °C. Then:
pH + pOH = 7.396 + 6.139
= 13.535
which is the same as the value of pKw at 40 °C (Table 2.1).

Example The pOH of a blood sample stored at 10 °C is measured at 7.520. What


are the pH, and the hydrogen ion concentration in this sample?

Solution: Calling Table 2.1, the pKw at 10 °C is 14.535. Using Eq. (2.8), we have:

pK w = pH + pOH
then pH = pK w - pOH
= 14.535 - 7.520
= 7.015
By definition:

pH = - log éëH + ùû
Therefore:

log éëH + ùû = - pH
but, from the definition of logarithm:

éëH + ùû = 10 - pH
and

éëH + ùû = 10 -7.015
= 9.661 ´ 10 -8 mol / L
» 97 nmol / L

Example At 37 °C, the extreme limits of hydrogen ion concentrations of arterial


blood are 1.26 × 10−7 and 1.6 × 10−8 mol/L. What are the corresponding pH limits?
pH, pOH, pK, pKw
2.2  17

Solution: By definition:

pH = - log éëH + ùû
Then:

(
pH min = - log 1.26 ´ 10 -7 )
(
= - log1.26 + log10 -7 )
= 6.90 ( Minimum )
and

(
pH max = - log 1.68 ´ 10 -8 )
(
= - log1.68 + log10 -8 )
= 7.78 ( Maximum )

Example The normal arterial blood pH is 7.4. Calculate the effect of…

(a) an increase of 2 × 10−8 mol/L in [H+],


(b) a decrement of 2 × 10−8 mol/L (the same quantity) in [H+].

Solution:

pH = - log éëH + ùû

Then:

éëH + ùû = 10 - pH
= 10 -7.4
= 4 ´ 10 -8 mol / L
= 40 nmol / L

An increase of 2 × 10−8 mol/L in [H+] makes [H+] equal to 6 × 10−8


(= 4 × 10−8 + 2 × 10−8) mol/L. Therefore, the corresponding pH is:

pH = - log éëH + ùû
(
= - log 6 ´ 10 -8 )
(
= - log 6 + log10 -8 )
= 7.22
18 2 ABC’s of Acid-Base Chemistry

On the other hand, a decrease of 2 × 10−8 mol/L in [H+] makes [H+] equal to 2 × 10−8
(= 4 × 10−8 − 2 × 10−8) mol/L, and the corresponding pH is:

pH = - log éëH + ùû
(
= - log 2 ´ 10 -8 )
(
= - log 2 + log10 -8 )
= 7.70

Example Solve the previous example, if the original pH is 7.0 (instead of 7.4).

Solution: The solution is the same as before. It can easily be calculated that an
increase of 2 × 10−8 mol/L in hydrogen ion concentration decreases the pH from 7.0
to 6.92. On the contrary, a decrease of 2 × 10−8 mol/L in hydrogen ion concentration
increases the pH from 7.0 to 7.1.
As the two previous examples show, an equal change in the hydrogen ion con-
centration causes different changes in the pH scale, which depend on the original
pH. It is also clear that the increase or decrease of hydrogen ions concentration
causes unequal changes in pH (with the same original pH). Thereby, the pH scale is
not linear, which means that equal intervals on the pH scale do not correspond to
equal intervals on the hydrogen ion concentration scale.

Example The same volumes of two blood samples, having pH values of 7.2 and
7.6, respectively, are intermixed. What is the resultant pH in the final mixture?

Solution: The concentration of hydrogen ion in the first blood sample is:

éëH + ùû = 10 - pH1
1
= 10 -7.2
= 6.31 ´ 10 -8 mol/L

and in the second sample, it can be calculated to be:

éëH + ùû = 10 - pH2
2
= 10 -7.6
= 2.51 ´ 10 -8 mol/L

The volumes of the samples are the same, thus the hydrogen ion concentration of
the resultant mixture will be:
2.3 Acids and Bases 19

éH + ù + éH + ù
éëH + ùû = ë û1 ë û 2
final 2
6.31 ´ 10 -8 + 2.51 ´ 10 -8
=
2
= 4.41 ´ 10 -8 mol / L

Then:

pH final = - log éëH + ùû


final

(
= - log 4.41 ´ 10 -8 )
= 7.36

Note that the mean value of pH1 and pH2 is:

pH1 + pH 2
pH mean =
2
7.2 + 7.6
=
2
= 7.4

which is different from the actual calculated value of 7.36. So it is not correct to
take arithmetical means of pH values; instead, the individual pH values should be
converted to their corresponding hydrogen ion concentration; the resultant hydro-
gen ion concentration must then be calculated; and finally, this value must be recon-
verted to its corresponding pH.

2.3 Acids and Bases

Acids and bases influence many biological activities, and equilibria involving them
are perhaps one of the major classes of equilibria.
Historically, acids were recognized by their sour taste (from Latin acidus mean-
ing sour; acetum, vinegar); alkalis (from Arabic al kali meaning ashes of a plant)
were considered those substances that could neutralize the effects of acids. The
chemical properties of acids are the results of their reversible dissociation into ions,
one of which is H+.
In 1923, Lowry and Brønsted proposed their general concept of acids and bases
[3]. According to the Lowry-Brønsted definition, an acid is a substance that has a
tendency to donate a proton (H+), whereas a base has the tendency to accept a pro-
ton. Carbonic acid (H2CO3) ionizes according to this reversible reaction:
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FOOTNOTES:
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[4] Pronounced “shees.”
[5] This story is not imagination, but truth.
[6] A kind of floury Scotch roll.
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smaller seaweed with pleasant pungent flavour, that is eaten as a relish along with it.
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side, or gets leaking badly, or has a heavy list, or from a thousand and one other
causes gets dangerous, her crew are frequently only too ready to leave her. There are
some notable cases, and only just within the last week or two the Bahama, a fine large
steel sailing vessel on her first voyage, was deserted in the Atlantic, and was sighted
afterwards in an apparently seaworthy condition. But there is to be an inquiry into her
case, so I will say nothing more about her, except that she is not yet charted, and is
knocking about without lights, without foghorn, without anything—in fact, a
tremendous danger to navigation. Over and over again a crew has left a ship when
another crew from the relieving vessel has stayed behind and brought the otherwise
derelict safely into port. Many of these derelicts, I should tell you, are waterlogged
timber ships; and it may interest you to learn, while I think of it, that one of the
United States vessels engaged in sinking derelicts is the old Kearsarge, who fought
and sunk the Alabama in the English Channel.”—Pall-Mall Gazette.

Typographical error corrected by the


etext transcriber:
“your a thrifty lad."=> “you’re a
thrifty lad.” {pg 218}
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