By John Santangelo

Henderson-Hasselbach Equation

June 2010
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Blood pH is determined by a balance between
bicarbonate and CO2
Blood pH = 7.36 – 7.44
(slightly Alkaline)

Enzyme
 pH (potential of Hydrogen)

The logarithm of the reciprocal of

hydrogen-ion concentration in gram
atoms per liter; provides a measure on a
scale from 0 to 14 of the acidity or
alkalinity of a solution (where 7 is
neutral and greater than 7 is more basic
and less than 7 is more acidic);
 REGULATION OF ACID–BASE BALANCE
The body has the remarkable ability to
maintain plasma pH within the narrow
normal range of 7.36 to 7.44. It does so
by means of chemical buffering
mechanisms, by the kidneys, and by the
lungs. The pH is defined as hydrogen ion
concentration; the more hydrogen ions,
the more acidic the solution. The pH range
that is considered to be compatible with
life is (6.8–7.8)
 Formulae to describe the carbonic acid -
bicarbonate buffer system.
The two headed arrows indicate that the process
is reversible
H + HCO3 <---> H2CO3 <---> H2O + CO2
Carbonic Andydrase

Hydronium Ion (H+) + Bicarbonate (HCO3-) <--->

Carbonic Acid (H2CO3) <---> Water (H2O) +
Carbon Dioxide (CO2)
The Carbon Dioxide (CO2) and Water (H2O) are
blown off by the Lungs.
Hyperventilation will speed up the reaction and a
blockage in the airways will slow down the
reaction (Hypoventilation)
 Using the Hendersen-Hasselbach
equation,

pH = 6.10 + Log HCO3-

PCO2 X 0.030

In order to keep the pH of blood at 7.4,

and given pKa = 6.1 for bicarbonate, the
ratio of bicarbonate to 0.03 pCO2 should
remain constant. i.e. 20 to 1
 The Chief Mammalian Blood Buffer is a Mixture of
Bicarbonate and Carbon Dioxide.
All body fluids, inside or outside cells have buffers
which defend the body against pH changes.
The most important buffer in extracellular fluids,
including blood, is a mixture of carbon dioxide (CO2)
and bicarbonate anion (HCO3)
CO2 acts as an acid (it forms carbonic acid when it
dissolves in water), donating hydrogen ions when they
are needed.
HCO3 is a base, soaking up hydrogen ions when there
are too many of them.
There are also other buffers in blood, such as proteins
and phosphate, but they are less important.
 Abnormal acid-base balance

Acid-base imbalances can be defined as acidosis or

alkalosis.
Acidosis is a state of excess H+.
Acidemia results when the blood pH is less than 7.35.
Alkalosis is a state of excess HCO3-.
Alkalemia results when the blood pH is greater than 7.45.

When the acid-base disturbance results from a primary

change in HCO3-, it is a metabolic disorder; when the
primary disturbance alters blood pCO2, it is a respiratory
disorder.
Compensation for these disturbances can be respiratory or
metabolic (i.e. renal) in nature and is intended to minimize
further pH changes. The following table may help clarify
this for you.
Acid-base Plasma pH Primary Compensation
imbalance disturbance

Respiratory - low - increased pCO2 - increased renal

acidosis net acid excretion
with resulting
increase in serum
bicarbonate

Respiratory - high - decreased pCO2 - decreased renal

alkalosis net acid excretion
with resulting
decrease in serum
bicarbonate

Metabolic acidosis - low - decreased HCO3- - hyperventilation

with resulting low
pCO2

Metabolic alkalosis - high - increased HCO3- - hypoventilation

with resulting
increase in pCO2
 Understanding the cause of an acid-base
imbalance is the key to treating it.
The simplified approach to understanding the
relationship of acid and base starts with
carbonic acid (H2CO3).
Carbon dioxide is an acid when dissolved in
water.
Carbon dioxide is produced by metabolism.
As long as cells are functioning, there will be
CO2 produced.
The respiratory mechanism affects the pH
within minutes.
Metabolic changes can take days to affect
pH.
 Acid-base balance

• H+ importance and concentration in the body

• Chemistry of acid, base and buffers
• Sources of acids in the body
• Buffer mechanisms in the body
• The chemical buffers
H+ importance and concentration in
the body
• Hydrogen ions are very small and reactive.
• Normal concentration = 40nmole/L
(compare with concentration of 4 and
140mmole for K and Na).
• H+ concentration is therefore given within
the pH scale: pH = -log [H +]
• Normal range for pH of arterial blood is:
7.35-7.45
• Extreme ranges that may be tolerable with
life are: 6.9-7.8
 Chemistry of acid, base and buffers -I

• Acid - a substance that can donate [H+]

• Base - a substance that can receive [H+]
• Strong acid - completely dissolved in liquid.
• Weak acid - partially dissolved in liquid.
 Chemistry of acid, base and buffers -II

• Buffer - oppose big changes in the pH

of a liquid
• A buffer is usually composed of weak
acid (HA) and conjugated base (A-).
• The Hendeson-Hasselebach equation:
• pH=pK+log([A-]/[HA])
• Buffering is most effective for pH
values within +/- 1.5 pH units of the
pK.
 Sources of acids in the body
• Volatile acids - CO2,
• Non-volatile (Fixed) acids,
 Sources of acids in the body

- volatile acids
• End products of oxidation of glucose
and fats in aerobic metabolism
• Glucose, Fat +O2 -> ATP + CO2
• CO2+H2O <-> H2CO3 <-> H++HCO3-
• H2CO3 - carbonic acid is converted to
CO2 and expired by the lung - Volatile
acid.
 Sources of acids in the body

- Non-volatile (fixed) acids

• End products of metabolism of sulfur
containing amino-acid, phospholipids
or phospoproteins.
• Called Fixed acids because they can’t
be expired by the lungs and are
secreted by the kidney.
• Amount depends on diet.
 The main fixed acids
• Sulfuric acid - oxidation of sulfur
containing acids (e.g., cysteine)
• Phosphoric acid - oxidation of phospho-
lipids or phospo-proteins.
• HCl- Conversion of ingested ammonium
chloride to urea.
• Lactic acid - Anaerobic metabolism of
glucose
• Acetoacetic and Butyric acid - Diabetic
ketoacidosis
 The buffer systems of the body
• Chemical buffers
• Lung
• Kidney
 The chemical buffers

 The Bicarbonate buffer

 The Non-bicarbonate buffers:
– Hemoglobin
– Plasma proteins
– The phosphate buffer
H2PO4 <>H+ + HPO42-
 The importance of the bi-carbonate
buffer
• pK=6.1
• The total concentration of the buffer pair
(CO2, HCO3-) is quite high: 24+1.2=~
26mmol/L
• The Bi-carbonate buffer is part of an open
system:
• The lung holds the [CO2] constant by
adjusting alveolar ventilation
• The kidneys replace HCO3- that is lost
during the buffering process
 Normal Values
• pH = 7.35 – 7.45
• PCO2 = 38 – 42 mmHg (5.07 – 5.60 kPa)
• Actual [HCO3-] = 23 – 27 mmol/l
• Standard [HCO3-] = 23 – 27 mmol/l
• Buffer bases = 46 – 52 mEq/l
• Excess Base = - 2; +2 mEq/l
• Total CO2 = 24 – 28 mmol/l
• HCO3-/H2CO3 = 18 - 22
Causes of Acid Base disturbances

1. Respiratory Acidosis.
2. Respiratory Alkalosis.
3. Metabolic Acidosis.
4. Metabolic Alkalosis.
Causes of Acid Base disturbances
Respiratory Acidosis:
This is synonymous with CO2 retention and is
usually a sign of hypoventilation.
Causes:
1. Central Nervous System (CNS).
2. Lung & Airway disorders.
3. Chest wall abnormality.
4. Muscle disorders.
5. Neuro Muscular transmission.
6. Peripheral neuropathy.
Inhalation of CO2 is another cause of respiratory
acidosis but is only likely to occur under
situations of rebreathing,
e.g. under anaesthesia.
Respiratory Acidosis is associated with raised
alveolar CO2, raised re-breathing CO2 and high
PCO2 in the arterial blood.
Compensation for chronic respiratory acidosis is
loss of (H+)Cl- and retention of (Na+)HCO3- by
the kidneys.
Normal Blood pH is 7.36 to 7.42
i.e. slightly alkaline
Either mechanism (respiratory or metabolic)
can cause an acidosis or an alkalosis.
Hyperventilation will lead to respiratory
Alkalosis causing Tetany.
Tetany is a condition of prolonged and painful spasms of the voluntary
muscles, especially the fingers and toes (carpopedal spasm) as well as
the facial musculature.

An airway blockage will lead to respiratory

Acidosis (Hypoventilation).
 Respiratory Alkalosis
is associated with Hyperventilation

Causes:
1. Hysterical hyperventilation.
2. Some cases of CNS damage.
3. Deliberate hyperventilation during
anaesthesia.
4. Some cases of hypoxia.
 Respiratory Alkalosis is usually
acute so there is no time for Renal
Compensation, but if it prolonged,
there will Renal excretion of an
increased quantity of Base —
(NaHCO3)
Metabolic Acidosis
Due to increased Acids
Causes
a. Increased intake (alimentary or
parenteral).
b. Increased production of Acid.
c. And, Failure of excretion.
 Increased Intake
The Acid content of the blood can be raised by:
Ingestion or injection of NH4CL or diluteHCL.
The HCL directly increases the H+.
The NH4CL produces HCL by the NH3 being
split off and converted to Urea.
Adding NH4CL directly to blood would not
change the pH without the Liver intervening.
 Loss of intestinal contents by diarrhoea or small
bowel obstruction causes a loss of fluid of high pH,
i.e. containing an excess of Base (NaHco3.
The removal of Base allows the H+ to rise.

Ingestion of organic acids

Organic Acids would not usually produces changes
in the pH because the liver would metabolize them
but liver disease could allow organic acids, if
ingested, to gain access to the systemic circulation.
Infusion of stored blood will add acid to the body
because it contains citric acid.
 Excess Acid might accumulate in the blood from processes of
metabolism and cause a fall in blood pH.
There are two main mechanisms for this:

Hypoxia
Hypoxia from any cause, causes anaerobic glycolysis to increase.
This gives rise to Lactic Acid and not CO2.
The Lactic Acid lowers the pH

The causes of Hypoxia are:

1. Low oxygen in inspired air
2. Lung disorders
 3. Hypoventilation.
4. Low cardiac output (including shock states)
5. Blood defect: hypovolaemia, anaemia or CO
poisioning.
6. Tissue toxins, e.g. cyanide.
Circulatory occlusion to any large area will
cause accumulation of organic acids in the area
supplied. On restoration of the circulation these
acids will be distributed systemically. This is a
possible cause of acidosis if the general
circulation and temperature are not
maintained.
 Diabetes and Starvation
In both these states keto acids are produced and there
will be some attempt at renal excretion (Ketourea).
Failure of excretion of acid could lead to acidosis.
Normally, during metabolism some inorganic acids are
produced, i.e. H2SO4 and H3PO4. These cations have
to be excreted by the kidneys covered either by, Na+,
K+, (small amount) NH4+ (produced in the kidney)
Normally the amount involved is not great, but over a
long period if there is failure of excretion, accumulation
will occur with a fall in pH.
This is Renal Acidosis
 Any of these absolute or the relative
increases in acids can cause a fall in pH
and this would be a metabolic acidosis.

The final compensatory mechanism for

metabolic acidosis is induced respiratory
alkalosis produced by hyperventilation.
The low pH stimulates the respiratory
centre.
 Metabolic Alkalosis
This is due to ingestion or injection of excess
base. i.e NaHCO3 or NAOH or loss of gastric juice
containing HCL.
A common cause of alkalosis is excess loss of CL-
(i.e. HCL or NH4CL) from excessive and
improperly observed diuretic treatment.
Metabolic alkalosis is compensated by
respiratory depression which causes CO2
retention but might also cause hypoxia. The pH
is usually raised but might be high normal if
there is much CO2 retention.
 Diagnosis
Acid Base disturbances

Clinical picture
Anybody with, Pneumonia, Sweating, Bounding Pulse,
probably has CO2 retention.
Intestinal obstruction or severe diarrhoea probably has
acidosis due to loss of base. (NaHCO3)
A diabetic who is drowsy and hyperventilating with
urinary glucose and ketones probably has keto-acidosis.
Shock, with poor tissue perfusion may have lactic
acidosis.
 Treatment
Respiratory Acidosis is corrected by increased
ventilation.
Respiratory Alkalosis is corrected by reducing
ventilation or increasing the dead space.

Metabolic Acidosis
Treat the cause
Stop alimentary loss; correct hypoxia; reduce
renal load by diet; Give insulin; treat shock.
NaHCO3 is the most commonly used.
 Metabolic Alkalosis
Remove the cause.
1. relieve pyloric obstruction or modify diuretic
regime.
2. Ingestion or injection of sufficient NaCL for
the kidney to correct the alkalosis by excretion
of NaHCO3.
3. Direct correction of alkalosis with NH4CL (or
HCL) infusion or ingestion. This is only
indicated if the alkalosis is very severe or renal
or cardiac function are poor.
Blood gases are measured using Arterial Blood,
NOT Venous Blood.
A glass Syringe is usually used with a small
amount of Heparin as an anticoagulant.
Care should be taken not to include Air Bubbles
in the syringe as this would alter the values.
The blood and syringe should be transported on
to the laboratory, on ice, as soon as possible.
The Radial, Brachial or Femoral Arteries are
usually the preferred sites. The Radial artery
being the most common as it is easier to access
and less painful.
 Usually there is associated reduction of extracellular
volume so some Sodium has to be given in the form of
NaCL solution.
4. Control of respiratory failure if this is severe.