INTRODUCTION

• Acid-base balance refers to the mechanisms the body uses to keep its fluids close to
neutral pH (that is, neither basic nor acidic) so that the body can function normally.
• To achieve acid-base balance (homeostasis), there must be a balance between the
intake or production of hydrogen ions and net removal of hydrogen ions from the body.

• Acid- is defined as a substance that releases protons or H+ ions e.g. Hydrochloric acid
(HCl), Carbonic acid (H2CO3).
HCl--------> H+ +Cl-
H2CO3 ---> H+ + CO3-

• Base- is defined as a substance that accepts protons or hydrogen ions e.g. Bicarbonate
ion (HCO3-) and Hydrogen phosphate (HPO4)
HCO3- + H+ -------> H2CO3
HPO4-- + H+ --------> H2PO4-

• The pH is the negative logarithm of the concentration of hydrogen ions in the solution.
It is expressed as pH = −log [H+].
• The maintenance of a constant pH is important because, the activities of almost all
enzyme systems in the body are influenced by hydrogen ion concentration.
Therefore changes in hydrogen ion concentration alters virtually all cell and body
functions, the conformation of biological structural components and uptake and
release of oxygen.
 Acid-base balance in blood (Regulation of blood pH)
• Blood needs the right balance of acidic and basic compounds to function properly.
• The pH of blood is 7.35-7.45.
• Normal pH of arterial blood is 7.45 and that of interstitial fluid and venous blood is
7.35 because the extra amount of carbon dioxide (CO2) released from the tissues
to form carbonic acid (H2CO3) in these fluids.
• There are three primary systems that regulate the hydrogen ion concentration in
blood. These are

1.Buffer mechanism: First line of defense.

2.Respiratory mechanism: Second line of defense (Lungs).
3.Renal mechanism: Third line of defense (Kidneys).

• The first two lines of defense keep the hydrogen ion concentration from changing
too much until the more slowly responding third line of defense , the kidneys, can
eliminate the excess acid or base from the body.
• An increase in acidity causes the pH levels to fall. An increase in alkaline causes pH
levels to rise.
• When the levels of acid in the blood are too high it causes acidosis and when the
blood is too alkaline, it is called alkalosis.
• Respiratory acidosis and alkalosis are due to a problem with lungs.
• Metabolic acidosis and alkalosis are due to a problem with the kidneys.
 BUFFER
• A buffer is a solution that can maintain a nearly constant pH if it is diluted, or if
relatively small amounts of strong acids or bases are added. It consists of a mixture
of a weak acid and its conjugate base or vice versa.
• The buffer systems of the blood, tissue fluids and cells; immediately combine with
acid or base to prevent excessive change in hydrogen ion concentration.
• Buffer systems do not eliminate hydrogen ions from the body or add them to the
body but only keep them tied up until balance can be re-established.

• Blood buffers – Various buffer systems present in human body are given below
Buffers of extracellular fluid present in plasma
1.Bicarbonate buffer
2.Phosphate buffer
3.Protein buffer

Buffers of intracellular fluid present in RBC’s

1.Bicarbonate buffer
2.Phosphate buffer
3.Hemoglobin buffer
 Bicarbonate Buffer System (HCO3-/H2CO3)
• The bicarbonate buffer system is the most predominant extracellular buffer.
Mechanism of action of bicarbonate buffer.
When a strong acid, such as HCl is added to the bicarbonate buffer solution, the
increased hydrogen ions are buffered by HCO3-
HCl--------> H+ +Cl-
(strong acid)

HCO3- + H+ ----------> H2CO3

(weak acid)
• Thus, hydrogen ions from strong acid HCl react with HCO3- to form very weak acid
H2CO3.

• The opposite reaction takes place when a strong base, such as NaOH is added to
the bicarbonate buffer solution.
NaOH + H2CO3 ---------->NaHCO3 + H2O
(strong base) (weak base)
• In this case hydroxyl ion (OH-) from NaOH combines with H2CO3 to form weak base.
Thus strong base NaOH is replaced by a weak base NaHCO3.
• At a pH 7.4, the ratio of bicarbonate to carbonic acid (HCO3- / H2CO3) is 20:1. Thus
the bicarbonate concentration is much higher (20 times) than carbonic acid in
blood. This is referred to as alkali reserve and is responsible for the effective
buffering of H+ ions, generated in the body. Any alteration produced in the ratio
between HCO3- / H2CO3 leads to alkalosis or acidosis
 Respiratory mechanism in acid-base balance
• The second line of defence against acid-bases disturbances is by regulating the
concentration of carbonic acid (H2CO3) in the blood and other body fluids by the
lungs.
• The large volume of CO2 produced during cellular metabolic activity endanger the
acid-base equilibrium of the body. But in normal circumstances, all of this CO2 is
eliminated from the body in the expired air via lungs.

• The respiratory centre in the brain located in the medulla controls the rate of
respiration i.e. regulates the retention or removal of CO2, and thereby, carbonic
acid (H2CO3) by the lungs. Thus, lungs function by maintaining one component
carbonic acid (H2CO3) of the bicarbonate buffer as follows:

 An increase in (H+) or (H2CO3) stimulates the respiratory centre to increase the

rate of respiratory ventilation. Any decrease in blood pH causes hyperventilation
to blow off CO2. When the ventilation rate increases, more CO2 is released from
the blood and pH increases.
 Similarly, an increase in (OH-) or (HCO3-) depresses respiratory ventilation. A
decrease in ventilation rate will cause a decrease in release of CO2 from the blood.
The increased blood CO2 will result in the formation of more H2CO3. Thus there will
be decrease in Ph.
• Thus when the rate of ventilation is increased, excess acid (H2CO3) in the form of
CO2 is quickly removed. Similarly, when the rate of ventilation is decreased, acid
(H2CO3) in the form of CO2.
 Renal mechanism for pH regulation
• The renal mechanism tries to provide a permanent solution to the acid-base
disturbances. This is in contrast to the temporary buffering system and a short term
respiratory mechanism.
• Kidneys regulate the blood pH by maintaining the alkali reserve, besides excreting
or reabsorbing the acidic or basic substances, as the situation demands.
• Urine pH is normally acidic ̴6 because the H+ ions generated in the body in the
normal circumstances, are eliminated by acidified urine. However it might vary
between range 4.5-8 depending on the concentration of H+ ions.

• Carbonic anhydrase and renal regulation of pH :- Enzyme carbonic anhydrase (

inhibited by acetazolamide) is of central importance in the renal regulation of pH
which occurs by the following mechanisms-
1.Excretion of H+ ions
2.Reabsorption of bicarbonate
3.Excretion of titratable acid
4.Excretion of ammonium ions
 1.Excretion of H+ ions
• Kidney is the only route through which H+ can be eliminated from the body. H+
excretion occurs in the Proximal convoluted tubules (renal tubular cells) and is
coupled with the regeneration of HCO3-. The process occurs as follows:-
• In renal tubular cells, the carbonic anhydrase catalyses the formation of carbonic
acid (H2CO3) from CO2 and water. The carbonic acid thus formed dissociates to
yield H+ and HCO3-.
• The H+ ions are secreted into the tubular lumen exchange for Na+.
• The bicarbonate anion formed by the dissociation of H2CO3 in the tubular cell
diffuses into the blood as the accompanying ion to Na+. HCO3- is thus conserved
and increases the alkali reserve of the body.
 Reabsorption of bicarbonate from tubular fluid
• This mechanism is primarily responsible to conserve the blood HCO3- , with a
simultaneous excretion of H+ ions. The normal urine is almost free from HCO3-.
• Bicarbonate freely diffuses from the plasma into the tubular lumen. Here HCO3-
combines with H+ secreted by tubular cells , to form H2CO3.
• H2CO3 is then cleaved by carbonic anhydrase to form CO2 and H2O. As the CO2
concentration builds up in the lumen, it diffuses into the tubular cells along the
concentration gradient.
• In the tubular cell, CO2 again combines with H2O to form H2CO3 which then
dissociates into H+ and HCO3-. The H+ is secreted into the lumen in exchange for
Na+ . The HCO3- is reabsorbed into plasma along with Na+.
• The process of bicarbonate reabsorption is enhanced in states of acidosis and
decreased in alkalosis.
• The kidney reabsorbs all filtered bicarbonate at plasma bicarbonate concentration
below 25mEq/L. Only when bicarbonate levels become elevated above 25mEq/L ,
bicarbonate will be excreted into the urine.
 Excretion of titratable acid
• Titratable acid is a measure of acid excreted into urine by kidneys. It refers to the
number of millilitres of N/10 NaOH required to titrate 1L of urine to pH 7.4
.Titratable acidity reflects the H+ ions excreted into urine which resulted in fall of
pH from 7.4 (that of blood).
• As stated earlier, H+ ion is secreted into the tubular lumen in exchange for Na+ ion.
This Na+ is obtained from the base, disodium hydrogen phosphate (Na2HPO4). The
latter in turn combines with H+ to produce the acid, sodium dihydrogen phosphate
(NaH2PO4), which form the major quantity of titratable acid present in urine. As
the tubular fluid moves down the renal tubule more and more H+ ions are added,
resulting in acidification of urine.
 Excretion of ammonium ion
• Ammonia (the urinary buffer) is produced by deamination of glutamine in renal
tubular cell. Glutaminase present in tubular cells catalyzes this reaction.
• Ammonia is a gas and diffuses readily across the cell membrane into the tubular
lumen, where it buffers hydrogen ions to form ammonium ions (NH4+).
• The NH4+ ions formed in the tubular lumen cannot diffuse back into the tubular
cells and thus, is trapped in the tubular urine and excreted with anions, such as
phosphate, chloride or sulphate.
• NH4+ is a major urine acid. It is estimated that about half to two-thirds of body acid
load is eliminated in the form of NH4+ ions. For this reason, renal regulation via
NH4+ excretion is very effective to eliminate large quantities of acids produced in
the body. This mechanism becomes predominant particularly in acidosis.
The acid-base disorders are mainly classified as :
1.Acidosis– a decline in blood pH
(a)Metabolic acidosis – due to decrease in bicarbonate
(b)Respiratory acidosis -- due to an increase in carbonic acid

2.Alkalosis – a rise in blood pH

(a)Metabolic alkalosis – due to an increase in bicarbonate
(b)Respiratory alkalosis – due to a decrease in carbonic acid
 RESPIRATORY ACIDOSIS
• Respiratory acidosis is a condition that occurs when the lungs can’t remove enough
of the carbon dioxide (CO2) produced by the body. Excess CO2 causes the pH of
blood and other bodily fluids to decrease, making them too acidic (more carbon
dioxide more carbonic acid).
• Normally, the lungs take in oxygen and exhale CO2. Oxygen passes from the lungs
into the blood. CO2 passes from the blood into the lungs. However, sometimes the
lungs can’t remove enough CO2. This may be due to a decrease in respiratory rate
or decrease in air movement due to various conditions.

• Causes- Chest deformities or injuries, overdose of sedatives, obesity (if lungs

cannot fully inflate), asthma, chronic obstructive pulmonary disease (COPD), acute
pulmonary edema, lung disorders , emphysema, asthma, pneumonia), conditions
that affect the rate of breathing, muscle weakness that affects breathing or taking a
deep breath, obstructed airways (due to choking or other causes), cardiac arrest,
scoliosis.
Compensatory mechanism-1. Increase in renal reabsorption of bicarbonate.
2.The excretion of titratable acidity and NH4+ is elevated in urine.

Forms of respiratory acidosis

There are two forms of respiratory acidosis: acute and chronic.

• Acute respiratory acidosis occurs quickly. It’s a medical emergency. Left untreated,
symptoms will get progressively worse. It can become life-threatening.

• Chronic respiratory acidosis develops over time. It doesn’t cause symptoms.

Instead, the body adapts to the increased acidity. For example, the kidneys produce
more bicarbonate to help maintain balance.

Chronic respiratory acidosis may not cause symptoms. Developing another

illness may cause chronic respiratory acidosis to worsen and become acute respiratory
acidosis.
Symptoms of respiratory acidosis
• Initial signs of acute respiratory acidosis include:
• headache
• anxiety
• blurred vision
• restlessness
• Confusion
Without treatment, other symptoms may occur. These include:
• sleepiness or fatigue
• lethargy
• delirium or confusion
• shortness of breath
• Coma
The chronic form of respiratory acidosis doesn’t typically cause any noticeable
symptoms. Signs are subtle and nonspecific and may include:
• memory loss
• sleep disturbances
• personality changes
 Diagnosis
Blood gas measurement- Blood gas is a series of tests used to measure oxygen and
CO2 in the blood. A healthcare provider will take a sample of blood from your artery.
High levels of CO2 can indicate acidosis.

Electrolytes- Electrolyte testing is a group of tests that measure levels of Na+ (sodium),
K+ (potassium), Cl- (chloride), and bicarbonate. One or more of the electrolytes will be
increased or decreased in people with acid-base disorders such as respiratory acidosis.

Lung function tests- Many people with this condition have reduced lung function.

Chest X-ray- X-rays can help doctors see injuries or other problems likely to cause
acidosis.

Other tests- Based on these tests, your doctor may also perform other tests to help
diagnose the underlying condition that’s causing the acidosis. (Another condition,
known as metabolic acidosis, may cause similar symptoms, and the doctor may order
tests to be sure the problem is solely respiratory. These tests measure the amount of
acid in your body, which may be caused by kidney failure, diabetes, or other
conditions, and include glucose, lactate, and ketones.) Other tests include drug testing,
a complete blood count (CBC), and a urinalysis (urine test).
Treatment-antibiotics (to treat infection)
• diuretics (to reduce excess fluid affecting the heart and lungs)
• bronchodilators (to expand the airways)
• corticosteroids (to reduce inflammation)
• mechanical ventilation (in severe cases)

Risk- Respiratory acidosis is serious and requires immediate medical attention.

Potential complications include respiratory failure, organ failure and shock.

Prevention- Maintain a healthy weight, take sedatives only under strict doctor
supervision and do not smoke.
 Respiratory alkalosis
• The primary abnormality in respiratory alkalosis in decrease in carbonic acid
(H2CO3) concentration.
• This may occur due to prolonged hyperventilation resulting in increased exhalation
of CO2 by the lungs.
 Renal mechanism tries to compensate by increasing the urinary excretion of HCO3-.

• Hyperventilation-is typically the underlying cause of respiratory alkalosis.

Hyperventilation is also known as overbreathing. Someone who is hyperventilating
breathes very deeply or rapidly.

• Causes of hyperventilation- hysteria, hypoxia, heart attack, chronic obstructive

pulmonary disease (COPD), action of certain drugs (salicylate) that stimulates
respiratory centre, fever, high altitude, working at high temperature.

• Compensatory mechanism- 1. Reduction in urinary ammonia formation

2.Increased excretion of bicarbonate.
Symptoms:-dizziness, bloating, feeling lightheaded, numbness or muscle spasms in the
hands and feet, discomfort in the chest area, confusion, dry mouth, tingling in the
arms, heart palpitations.

Treatment- treating panic and anxiety related causes to raise carbon dioxide level in
blood.
Breathe into a paper bag
• Fill the paper bag with carbon dioxide by exhaling into it.
• Breathe the exhaled air from the bag back into the lungs.
• Repeat this several times.
Doing this several times can give the body the carbon dioxide it needs and bring levels
back up to where they should be.

• Prevention- Prevention is a matter of addressing the cause of hyperventilation. The

most common causes are psychological: stress, panic, and anxiety. You can adjust
to and learn to control these causes.
• Working with a therapist may help. So can breathing exercises, meditation, and
regular exercise. Medication may be needed in some cases
 Metabolic acidosis
• A fall in blood pH due to decrease in bicarbonate levels of plasma is called
metabolic acidosis.
• Decreased in bicarbonate levels may be due to:-
-Increased production of acids. In uncontrolled diabetes mellitus and starvation,
there is an excessive production of acetoacetic acid and β-hydroxybutyric acid. These
acids are buffered by utilizing base component (i.e. HCO3-) of the bicarbonate buffer.
Consequently, the concentration of bicarbonate ions falls giving rise to bicarbonate
deficit and results in metabolic acidosis (ketoacidosis).
-Excessive loss of bicarbonate occurs in urine in renal tubular dysfunction and from
GI tract in severe diarrhea.

Compensatory mechanism
1.Increasing rate of respiration to wash out CO2 (hence H2CO3) faster. Consequently,
the ratio HCO3-:H2CO3 is elevated.
2.Increasing excretion of H+ ions as NH4+ ions.
3.Increasing elimination of acid (H2PO4-) in the urine.
All these compensatory mechanisms tend to reduce carbonic acid to keep the pH in
the normal range
• Symptoms-rapid and shallow breathing, confusion, fatigue, headache, sleepiness,
lack of appetite, increased heart rate, breath that smells fruity which is a sign of
diabetic acidosis (ketoacidosis)

• Diagnosis- Blood gad measurement, urine analysis, basic metabolic panel checks
your kidney functioning and your pH balance.
 Metabolic alkalosis
• A rise in blood pH due to rise in the bicarbonate levels of plasma is called metabolic
alkalosis. This is seen in the following conditions:-
1.Loss of gastric juice along with H+ ions in prolonged and severe vomiting.
2.Therapeutic administration of large dose of alkali ( as in peptic ulcer) or chronic
intake of excess antacids.

Compensatory mechanism:- 1.Increased excretion alkali (HCO3-) by the kidney.

2. Diminished formation of ammonia.
3.Respiration is depressed to conserve CO2.

• Symptoms:- nausea, difficulty in breathing, dizziness, confusion, hand tremors,

coma.

• Diagnosis:-urinalysis, urine pH level test, basic metabolic panel, arterial blood gas
analysis.
 Anion Gap
• The total concentration of cations and anions (expressed as mEq/l) is equal in the
body fluids. This is required to maintain electrical neutrality. The commonly
measured electrolytes in the plasma are Na+, K+, Cl- and HCO3-. Na+ and K+ together
constitute about 95% of the plasma cations. Cl- and HCO3- are the major anions
contributing to about 80% of the plasma anions. The remaining 20% of plasma
anions (it normally measured in the laboratory) include proteins, phosphate,
sulphate, urate.

• Anion gap is defined as the difference between the total concentration of

measured cations (Na+ and K+) and that of measured anion (Cl- and HCO3-). The
anion gap (A-) in fact represents the unmeasured anions in the plasma which may
be calculated as follows by substituting the normal concentration of electrolytes.
Na+ + K+ = Cl- + HCO3- + A-
136 + 4 = 100 + 25 + A-
A- = 15 mEq/l
The anion gap in a healthy individual is around 15 mEq/l (range 8-18 mEq/l).
• Clinical significance:- Anion gap is a biochemical tool which sometimes helps in
assessing acid-base problems. In metabolic acidosis, the anion gap can increase.