Acid – Base Balance
Where H+ come from and the importance of keeping pH relatively
constant
The metabolic sources of acids produced in the body in normal
metabolism and distinguish between fixed (eg. (e.g. H2SO4, H3PO4)
and volatile (H2CO3 / CO2) acids
How pH is controlled. Integration of ICF and ECF buffering systems,
respiratory systems and the kidney
The main buffer systems of ECF and how multiple buffer systems act in
parallel, using chemical equations
The Henderson-Hasselbalch equation, in its logarithmic or non-
logarithmic form
The successive stages of acidification of the urine (viz destruction of
bicarbonate ions, the acidification of phosphate and the production of
ammonia from glutamine)
An explanation that the rate of generation of H + into the lumen and
HCO3- into the plasma depends on ECF [H+]
How the generation of HCO3- into plasma reinforces ECF buffering
How tubule cells generate H+ and HCO3- and then secrete H+ into the
lumen and HCO3- (accompanied by Na+) into the plasma, indicating
the role of carbonic anhydrase
The regions of the kidney tubule which acidify the urine
Other buffer systems in the kidney explained ie. phosphate and
ammonia
The different roles of the respiratory system and kidneys in adjusting
the components of the bicarbonate buffer system and hence the
parallel buffer systems
Metabolic acidosis and alkalosis
Summary of acid-base balance and the compensatory mechanisms
It is very important for normal body functions that [H+]/pH of body fluids is kept
constant. This is because enzymes function at a particular pH within a narrow range
and as enzymes have such a huge number of functions in the body an abnormal pH can
disturb may body systems e.g. blood clotting, cardiac function, drug metabolism.
The normal [H+]/pH of body fluids is 7.35-7.45. Hence normal plasma [H +] is
0.00000004mol/L. This would be difficult to communicate etc. so we use pH which is
the inverse log of [H+]. –log10[H+].
Because it is inverse correlation, a low pH means there is a high concentration of
hydrogen ions, it is acidic.
So where is this acid coming from?
- We get acid from the metabolism of carbs and fats, which produces CO 2, this reacts in
the well known equation
CO2 + H2O <---> H2CO3 <---> H+ + HCO3-
,H2CO3 is carbonic acid, it is a volatile acid and so it is usually not really a problem,
because we can reduce the amount of carbonic acid by blowing off CO 2, which shifts
some of those protons to the left.
Another source of acid is the metabolism of proteins and this generates non-volatile
(fixed) acids.
So proteins that contain sulphur containing amino acids (cysteine, methionine) will
produce H2SO4 (sulphuric acid).
Lysine, arginine, histidine will produce HCl
These non-volatile acids need to be removed otherwise we will build up H +
Control of pH
We learnt about control of pH through experiments.
156ml of HCl were infused IV into a dog and the same amount of acid was added to
11.4L of water (equivalent to total body water of the dog), the pH changes in both
were compared.
It was found the pH of the dog’s arterial plasma decreased gradually from 7.44 to 7.14
(a state of severe acidosis, but one still comparable to survival). However the pH of the
distilled water dropped rapidly to a final level of 1.84, that would be fatal if it occurred
in vivo (in living thing).
So it is the presence of buffers which are controlling the pH in vivo.
Overview of pH control—
A disturbance in [H+]/pH is compensated for by ICF and ECF buffering systems, the
respiratory system and the kidney.
The first line of defence against pH changes consists of the intracellular and
extracellular buffer systems. All buffer systems participate according to their pK and
their quantity. Of particular importance is the bicarbonate buffer system which is the
major EC buffer.
The second mechanism is the respiratory system which regulates plasma PCO 2, by
controlling excretion or retention of metabolically produced CO 2, the acid component
of the bicarb buffer system.
The third mechanism is the kidney which plays a dual role, it regulates excretion or
retention of HCO3- (the basic component of the bicarb buffer system, obviously!)
and also regulates the regeneration of HCO3-
This is how the kidney helps regulate pH by dealing with H+ through bicarb.
(also involved in the excretion of fixed acids!)
Blood Buffering Systems
There are three blood buffering systems, which act together
, Bicarbonate buffer system
H+ + HCO3- <---> H2CO3 <---> CO2 + H2O
[H+] = K1 [CO2]
[HCO3-]
The phosphate system
H+ + HPO42- <---> H2PO4-
[H+] = K2 [H2PO4-]
[HPO42-]
The protein buffers (inc. Hb)
H+ + Pr- <---> HPr
H+ = K3 [HPr]
[Pr-]
The equilibrium reactions shown (with acid on top and anion on bottom) tell us that
by altering the concentrations of what is in the numerator/denominator will alter the
[H+] and hence pH.
K is the equilibrium constant of the reaction.
To measure the effectiveness of a buffer we look at the pK, when the pH is equal to the
pK is means the concentration of acid equals the concentration of the base.
Where H+ come from and the importance of keeping pH relatively
constant
The metabolic sources of acids produced in the body in normal
metabolism and distinguish between fixed (eg. (e.g. H2SO4, H3PO4)
and volatile (H2CO3 / CO2) acids
How pH is controlled. Integration of ICF and ECF buffering systems,
respiratory systems and the kidney
The main buffer systems of ECF and how multiple buffer systems act in
parallel, using chemical equations
The Henderson-Hasselbalch equation, in its logarithmic or non-
logarithmic form
The successive stages of acidification of the urine (viz destruction of
bicarbonate ions, the acidification of phosphate and the production of
ammonia from glutamine)
An explanation that the rate of generation of H + into the lumen and
HCO3- into the plasma depends on ECF [H+]
How the generation of HCO3- into plasma reinforces ECF buffering
How tubule cells generate H+ and HCO3- and then secrete H+ into the
lumen and HCO3- (accompanied by Na+) into the plasma, indicating
the role of carbonic anhydrase
The regions of the kidney tubule which acidify the urine
Other buffer systems in the kidney explained ie. phosphate and
ammonia
The different roles of the respiratory system and kidneys in adjusting
the components of the bicarbonate buffer system and hence the
parallel buffer systems
Metabolic acidosis and alkalosis
Summary of acid-base balance and the compensatory mechanisms
It is very important for normal body functions that [H+]/pH of body fluids is kept
constant. This is because enzymes function at a particular pH within a narrow range
and as enzymes have such a huge number of functions in the body an abnormal pH can
disturb may body systems e.g. blood clotting, cardiac function, drug metabolism.
The normal [H+]/pH of body fluids is 7.35-7.45. Hence normal plasma [H +] is
0.00000004mol/L. This would be difficult to communicate etc. so we use pH which is
the inverse log of [H+]. –log10[H+].
Because it is inverse correlation, a low pH means there is a high concentration of
hydrogen ions, it is acidic.
So where is this acid coming from?
- We get acid from the metabolism of carbs and fats, which produces CO 2, this reacts in
the well known equation
CO2 + H2O <---> H2CO3 <---> H+ + HCO3-
,H2CO3 is carbonic acid, it is a volatile acid and so it is usually not really a problem,
because we can reduce the amount of carbonic acid by blowing off CO 2, which shifts
some of those protons to the left.
Another source of acid is the metabolism of proteins and this generates non-volatile
(fixed) acids.
So proteins that contain sulphur containing amino acids (cysteine, methionine) will
produce H2SO4 (sulphuric acid).
Lysine, arginine, histidine will produce HCl
These non-volatile acids need to be removed otherwise we will build up H +
Control of pH
We learnt about control of pH through experiments.
156ml of HCl were infused IV into a dog and the same amount of acid was added to
11.4L of water (equivalent to total body water of the dog), the pH changes in both
were compared.
It was found the pH of the dog’s arterial plasma decreased gradually from 7.44 to 7.14
(a state of severe acidosis, but one still comparable to survival). However the pH of the
distilled water dropped rapidly to a final level of 1.84, that would be fatal if it occurred
in vivo (in living thing).
So it is the presence of buffers which are controlling the pH in vivo.
Overview of pH control—
A disturbance in [H+]/pH is compensated for by ICF and ECF buffering systems, the
respiratory system and the kidney.
The first line of defence against pH changes consists of the intracellular and
extracellular buffer systems. All buffer systems participate according to their pK and
their quantity. Of particular importance is the bicarbonate buffer system which is the
major EC buffer.
The second mechanism is the respiratory system which regulates plasma PCO 2, by
controlling excretion or retention of metabolically produced CO 2, the acid component
of the bicarb buffer system.
The third mechanism is the kidney which plays a dual role, it regulates excretion or
retention of HCO3- (the basic component of the bicarb buffer system, obviously!)
and also regulates the regeneration of HCO3-
This is how the kidney helps regulate pH by dealing with H+ through bicarb.
(also involved in the excretion of fixed acids!)
Blood Buffering Systems
There are three blood buffering systems, which act together
, Bicarbonate buffer system
H+ + HCO3- <---> H2CO3 <---> CO2 + H2O
[H+] = K1 [CO2]
[HCO3-]
The phosphate system
H+ + HPO42- <---> H2PO4-
[H+] = K2 [H2PO4-]
[HPO42-]
The protein buffers (inc. Hb)
H+ + Pr- <---> HPr
H+ = K3 [HPr]
[Pr-]
The equilibrium reactions shown (with acid on top and anion on bottom) tell us that
by altering the concentrations of what is in the numerator/denominator will alter the
[H+] and hence pH.
K is the equilibrium constant of the reaction.
To measure the effectiveness of a buffer we look at the pK, when the pH is equal to the
pK is means the concentration of acid equals the concentration of the base.
