Acid Base Balance

INTRODUCTION
The hydrogen ion (H+) concentration in
blood is maintained within narrow limits.
Even small disturbances in the acid
base balance can severely affect
physiological and biochemical processes.
The body continuously produces
enormous amounts of H+ during metabolic
processes.

Hydrogen ion

A hydrogen ion (H+) is a proton which has

lost its accompanying electron.

In water it combines with the H2O

molecule to form a hydronium ion (H 3O+) ;
however , convention allows us to use the
symbol H+ when describing hydrogen ions
in an aqueous solution.
In physiological systems the hydrogen ion
concentration ([H+]) can be expressed in
absolute units , e.g. nmol/l , or in pH units
(pH= - log10[H+]).
The [H+] of blood (or plasma) in the
normal adult is around 35-45nmol/l (pH
7.35-7.45).
In severe acidaemia this concentration

[H+] higher than 160nmol/l (pH6.8) or

lower than 16nmol/l (pH7.8) are considered
incompatible with life but there have been
reports of patients having levels outside
these limits and surviving.

pH

Acids and Bases

An acid is any molecule able to donate a
H+ ; i.e.in aqueous solution it dissociates
into H+ and anions ; e.g. HClH+ +Cl-.
Any molecule capable of accepting a H+ is
termed a base ; i.e. in solution it combines
with H+ to form an undissociated molecule ;
e.g. H+ +OH-H2O.
The product formed by the acceptance of
a H+ depends on the nature of the base.

If the base is OH- then water is formed ; if

the base is an acid anion an undissociated
acid will be produced , e.g. H+ +
CH3CH2COO- (acetate)CH3CH2COOH(acetic
acid).

Buffers

A buffer is a chemical solution designed

to attenuate the change in [H+] when a
strong acid or alkali is added.
Its constituents are a mixture of a weak
acid and its conjugate base.

REGULATION OF BLOOD PH
To maintain the blood pH at 7.35 -7.45 ,
there are three primary systems that
regulate the hydrogen ion concentration in
the body fluids.
These are:-(A)Buffer mechanism:-First line
of defense.
(B)The respiratory mechanisms:-Second
line of defense.
(C)Renal mechanisms:-Third line of
defense.

The first two lines of define keep the

hydrogen ion concentration from changing
too much until the more slowly responding
third line of defense , the kidney , can
eliminate the excess acid or base from the
body.

(A)Role of buffer system

in acid base balance

The buffer systems of the blood , tissue

fluids and cells ; immediately combine with
acid or base to prevent excessive changes
in hydrogen ion concentration.

Buffer systems do not eliminate hydrogen

ions from the body or add them to body but
only keep them tied up until balance can
be re-established.
Various buffer systems present in human
body:(1)Bicarbonate Carbonic acid system:Mainly concerned with buffering in the ECF.
(2)Phosphate system:-An important
intracellular buffer (including erythrocytes)
and an important urinary buffer concerned
with the excretion of H+.
(3)Proteins:-Concerned mainly with

There are also two complex body buffer

systems which are important in special
circumstances:-(a)Cell buffering and ionic
shifts across cell membranes , and (b)Bone
buffering.

(1)Bicarbonate Carbonic
acid system

Present in ECF (plasma).

It consists of the protonated substance,
carbonic acid (H2CO3) which is a weak acid
and the unprotonated substance, HCO3,
which is a weak base. HCO3 is in the form
of salt, i.e. sodium bicarbonate (NaHCO3).

Prevents the fall of pH in a fluid to which

a strong acid like hydrochloric acid (HCl) is
added.
Normally, when HCl is mixed with a fluid,
pH of
that fluid decreases quickly because the
strong HCl
dissociates into H+ and Cl.
But, if bicarbonate buffer system
(NaHCO3) is
added to the fluid with HCl, the pH is not
altered much.
This is because the H+ dissociated from

HCl + NaHCO3 H2CO3 +

NaCl

CO2 in
+ pH
H2O
Also prevents the increase
in a fluid to
which a strong base like sodium hydroxide
(NaOH) is added.
Normally, when a base (NaOH) is added to a
fluid,
pH increases.
It is prevented by adding H2CO3, which
dissociates into H+ and HCO3.
The hydroxyl group (OH) of NaOH combines with
H+ and forms H2O.
And Na+ combines with HCO3 and forms

As sodium bicarbonate is a very weak

base, its
association with H+ is poor.
So the rise in pH of the fluid is very mild.

(2)Phosphate Buffer System

Consists of a weak acid, the dihydrogen

phosphate (H2PO4 protonated substance)
in the
form of sodium dihydrogen phosphate
(NaH2PO4) and the base, hydrogen
phosphate (HPO4 unprotonated substance)
in the form of disodium hydrogen
phosphate (Na HPO ).

Phosphate buffer system is useful in the

intracellular fluid (ICF), in red blood cells or
other cells, as the concentration of
phosphate is more in ICF than in ECF.
When a strong acid like hydrochloric acid
is mixed with a fluid containing phosphate
buffer, sodium dihydrogen phosphate
(NaH2PO4 weak acid) is formed.
This permits only a mild change in the pH
of the fluid.

HCl + Na2HPO4
(strong acid)

NaH2PO4 + NaCl
(weak acid)

If a strong base such as sodium hydroxide

(NaOH)
is added to the fluid containing phosphate
buffer, a weak base called disodium
hydrogen phosphate (Na2HPO4) is formed.
This prevents the changes in pH.
NaOH + NaH2PO4 NaHPO4 + H2O
(strong base) (weak base)

(3)Proteins
Are present in the blood ; both in the
plasma and erythrocytes.
Elements of proteins , which form the
weak acids in plasma are:-(i)C-terminal
carboxyl group , N-terminal amino group
and side-chain carboxyl group of glutamic
acid.
(ii)Side chain amino group of lysine.
(iii)Imidazole group of histidine.

(4)Haemoglobin buffer
The major non-bicarbonate
system buffering

system of blood is haemoglobin which

plays an additional crucial role in the
transport of CO2 from the tissues to the
lungs.
At the tissue level over 90% of the CO2

Here , under the influence of the enzyme

carbonic anhydrase (ca) CO2 is converted
to H+ and HCO-3.

At this stage the red cell contains

increased amounts of H+ , HCO-3 , and CO2.
These analytes enter into the following
reaction:-

(I)Hydrogen ion

Haemoglobin has a high concentration of

histidine residues and the imidazole group
of this amino acid acts as a buffer with a pK

Deoxgenation of haemoglobin causes this

group to act as a base and it accepts H+.
Oxygenatedhaemoglobin , on the other
hand , is weakly acidic and releases H+
from this group , i.e.:

(II)Bicarbonate ion
When the cellular concentration of HCO 3
exceeds that of the plasma this ion diffuses
out of the cell in exchange for plasma Cl-.
This process is known as the chloride

(III)Carbon dioxide
Some of the CO2 which diffuses into the
red cell reacts nonenymatically with amino
group of protein to form carbamino
groups , a reaction which tends to offset
the haemoglobin binding of H+ describe
above.

When the red cell reaches the lung ,

where O2 is absorbed and CO2 is lost to
the alveoli , the above three reaction
reverse , i.e.:(1)Oxygenation of haemoglobin releases
H+ from the histidine residues , under the
influence of carbonic anhydrase these ions
react with HCO-3 to form CO2 which in turn
diffuses out of the Cell ad into the lung
alveoli.
(2)As the intracellular concentration of
-

(3)Carbamino compounds release CO2.

Cell buffering and ionic

exchange
In acidaemia and alkalaemia the cells of
the body act as a buffer by absorbing , or
releasing , hydrogen ions in exchange for
the other ions.
Three reactions have been described:(1)H+ and K+ exchange.
(II)H+ and Na+ exchange.
(III)Cl- and HCO3- exchange.

Bone buffering

(B)Respiratory
Lungs playmechanism
an important role in the
maintenance of acid base balance by
removing CO2 which is produce during
various metabolic activities in the body.
This CO2 combines with water to form
carbonic acid.
Since carbonic acid is unstable , it splits
into H+ and HCO-3.

Entire reaction is reversed in lungs when

CO2 diffuses from blood into the alveoli of
lungs.
And CO2 is blown off by ventilation.
When metabolic activities increase , more
amount of CO2 is produced in the tissues
and the concentration of H+ increases.
Increased H+ concentration increases the
pulmonary ventilation (hyperventilation) by
acting through the chemoreceptors.
Due to hyperventilation , the excess of
CO2 is removed from he body.

(C)Renal mechanism
The kidneys also play an important role in
maintaining acid-base homeostasis by
regulating the pH of the bloodplasma.
The kidneys have two very important
roles in maintaining the acid-base balance:
to reabsorb bicarbonate from urine, and to
excrete hydrogen ions into urine.
The kidneys are slower to compensate
than thelungs, butrenalphysiologyhas
several powerful mechanisms to control pH
by the excretion of excess acid or base.

The major homeostatic control point for

maintaining a stable balance is renal
excretion.
Bicarbonate (HCO3-) does not have a
transporter, so itsreabsorptioninvolves a
series of reactions in the tubulelumenand
tubularepithelium.
In response to acidosis, tubular cells
reabsorb more bicarbonate from the
tubular fluid, collecting duct cells secrete
more hydrogen and generate more
bicarbonate, and ammoniagenesis leads to

In response to alkalosis, the kidneys may

excrete more bicarbonate by decreasing
hydrogen ion secretion from the tubular
epithelialcells, and lowering rates of
glutamine metabolism and ammonium
excretion.