Acid Base

Maintenance of Blood pH
• The body has developed three lines of defense
to regulate the body's acid-base balance and
maintain the blood pH (around 7.4).
I. Blood buffers
ll. Respiratory mechanism
lll. Renal mechanism
 Blood buffer
• A buffer is a solution of a weak acid and its salt
with a strong base. It resists the change in pH
by the addition of acid or alkali.
• Buffering capacity is dependent on the absolute
concentration of salt and acid, buffer cannot
remove H+ ions from the body.
• lt temporarily acts as a shock absorbant to
reduce the free H+ ions. The H+ ions have to be
ultimately eliminated by the renal mechanism
• The blood contains 3 buffer systems.
1. Bicarbonate buffer
2. Phosphate buffer
3. Protein buffer
 Bicarbonate buffer system
• Sodium bicarbonate and carbonic acid
(NaHCO3 - H₂CO3) is the most predominant
buffer system of the extracellular fluid,
particularly the plasma.
• Carbonic acid dissociates into hydrogen and
bicarbonate ions.
• At blood pH 7.4, the ratio of bicarbonate to carbonic
acid is 20 : 1.
• The bicarbonate concentration is much higher (20
times) than carbonic acid in the blood is referred to as
alkali reserve and is responsible for the effective
buffering of H+ ions, generated in the body.
• In normal circumstances, the concentration of
bicarbonate and carbonic acid determines the pH of
blood. Further, the bicarbonate buffer system serves as
an index to understand the disturbances in the acid-
base balance of the body.
 Phosphate buffer system
• Sodium dihydrogen phosphate and disodium
hydrogen phosphate (NaH₂PO₄ - Na₂HPO₄) constitute
phosphate buffer.
• lt is mostly an intracellular buffer and is of less
importance in plasma due to its low concentration.
• With a pK of 6.8 (close to blood pH 7.4), the
phosphate buffer would have been more effective,
had it been present in high concentration.
• The ratio of base to acid for phosphate buffer is 4
compared to 20 for bicarbonate buffer.
 Protein buffer system
• The plasma proteins and hemoglobin together constitute
the protein buffer system of the blood.
• The buffering capacity of proteins is dependent on the pK
of ionizable groups of amino acids. The imidazole group of
histidine (pK = 6.7) is the most effective contributor of
protein buffers.
• The plasma proteins account for about 2% of the total
buffering capacity of the plasma.
• Hemoglobin of RBC is also an important buffer. lt mainly
buffers the fixed acids, besides being involved in the
transport of gases (O₂ and CO₂).
Respiratory mechanism for pH regulation

• Respiratory system provides a rapid

mechanism for the maintenance of acid-base
balance.
• It is achieved by regulating the concentration
of carbonic acid (H2CO3) in the blood i.e. the
denominator in the bicarbonate buffer system.
• The large volumes of CO₂ produced by the
cellular metabolic activity endanger the
acidbase equilibrium of the body.
• In normal circumstances, all of this CO₂ is
eliminated from the body in the expired air via
the lungs.
• The rate of respiration is controlled by a
respiratory centre, located in the medulla of
the brain.
• This centre is highly sensitive to changes in the
pH of blood.
• Any decrease in blood pH causes
hyperventilation to blow off CO₂, thereby
reducing the H₂CO₃ concentration.
Simultaneously, the H⁺ ions are eliminated as H₂0.
• Respiratory control of blood pH is rapid but only
a short term regulatory process, since
hyperventilation cannot proceed for long.
 Hemoglobin as a buffer
• Hemoglobin of erythrocytes is important in the
respiratory regulation of pH.
• At the tissue level, hemoglobin binds to H⁺ ions
and helps to transport CO₂ as HCO₃⁻ with a
minimum change in pH (referred as isohydric
transport).
• ln the lungs, as hemoglobin combines with 0₂, H⁺
ions are removed which combine with HCO₃⁻ to
form H₂CO₃, which dissociates to release CO₂ to be
exhaled.
Generation of bicarbonate by the
erythrocyte
 Generation of HCO₃⁻ by RBC
• Due to lack of aerobic metabolic pathways, RBC produce very
little CO₂.
• The plasma CO₂ diffuses into the RBC along the concentration
gradient where it combines with water to form H₂CO₃,
catalysed by carbonic anhydrase (also called carbonate
dehydratase).
• In the RBC, H₂CO₃ dissociates to produce H⁺ and HCO₃⁻ . The
H⁺ ions are trapped and buffered by hemoglobin. As the
concentration of HCO₃⁻ increases in the RBC, it diffuses into
plasma along with the concentration gradient, in exchange for
Cl⁻ ions, to maintain electrical neutrality. This phenomenon,
referred to as chloride shift, helps to generate HCO₃⁻.
Renal mechanism for pH regulation
• The role of kidneys in the maintenance of acid-base
balance of the body (blood pH) is highly significant.
• The renal mechanism tries to provide a permanent
solution to the acid-base disturbances.
• The kidneys regulate the blood pH by maintaining
the alkali reserve, besides excreting or reabsorbing
the acidic or basic substances, as the situation
demands.
• The pH of urine is normally acidic (6.0). It indicates that
the kidneys have contributed to the acidification of
urine, when it is formed from the blood plasma (pH
7.4).
• In other words, the H+ ions generated in the body in
the normal circumstances, are eliminated by acidified
urine. Hence the pH of urine is normally acidic (6.0),
while that of blood is alkaline (7.4).
• Urine pH, however, is variable and may range between
4.5-9.5, depending on the concentration of H+ ions.
Carbonic anhydrase and renal regulation of
pH
• The 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
Excretion of H+ ions
Reabsorption of bicarbonate
Excretion of titratable acid
Excretion of ammonium ions
Acid Base Disorders
• The body has developed an efficient system
for the maintenance of acid-base equilibrium
with a result that the pH of blood is almost
constant.
• The blood pH (H+ ion concentration) is
dependent on the relative concentration
(ratio) of bicarbonate (HCO₃⁻) and carbonic
acid (H₂CO₃)
• The acid-base disorders are mainly classified as
1. Acidosis-a decline in blood pH
(a) Metabolic acidosis-due to a 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.
• The four acid-base disorders are primarily due to
alterations in either bicarbonate or carbonic acid.
• lt may be observed that the metabolic acid-base balance
disorders are caused by a direct alteration in bicarbonate
concentration while the respiratory disturbances are due
to a change in carbonic acid level (i.e. CO₂).
• This type of classification is more theoretical. ln the actual
clinical situations, mixed type of disorders are common.
• The terms acidemia and alkalemia, respectively, refer to an
increase or a decrease in H⁺ ion concentration in blood.
They are, however, not commonly used
 Causes of Acid-Base Disorders
• Metabolic acidosis could occur due to
diabetes mellitus (ketoacidosis), lactic
acidosis, renal failure etc.
• Respiratory acidosis is common in severe
asthma and cardiac arrest.
• Vomiting and hypokalemia may result in
metabolic alkalosis while hyperventilation and
severe anemia may lead to respiratory
alkalosis
• To counter the acid-base disturbances, the
body gears up its homeostatic mechanism and
makes every attempt to restore the pH to
normal level (7.4).
• It is referred to as compensation which may
be partial or full. Sometimes the acidbase
disorders may remain uncompensated.
• For the acute metabolic disorders (due to
changes in HCO₃⁻, respiratory compensation
sets in and regulates the H₂CO₃ (i.e. CO₂) by
hyper or hypoventilation.
• As regards acute respiratory disorders (due to
changes in H₂CO₃), the renal compensation
occurs to maintain the HCO₃⁻ level, by
increasing or decreasing its excretion.
 Anion gap
• For a better understanding of acid-base
disorders, adequate knowledge of anion gap is
essential.
• The total concentration of cations and anions
(expressed as mEq/l) is equal in the body
fluids 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 (not
normally measured in the laboratory) include
proteins, phosphate, sulfate, urate and organic
acids.
• Anion gap is defined as the difference between the
total concentration of measured cations (Na⁺ and
K⁺) and that of measured anion (Cl⁻ and HCO⁻).
• The anion gap (A⁻) in fact represents the
unmeasured anions in the plasma.
• The anion gap in a healthy individual is around 15
mEq/l (range 8-18 mEq/l).
• Acid-base disorders are often associated with
alterations in the anion gap
 Metabolic acidosis
• The primary defect in metabolic acidosis is a reduction
in bicarbonate concentration which leads to a fall in
blood pH.
• The bicarbonate concentration may be decreased due
to its utilization in buffering H+ ions, loss in urine or
gastrointestinal tract or failure to be regenerated.
• The most important cause of metabolic acidosis is due
to an excessive production of organic acids which
combine with NaHCO₃⁻ and deplete the alkali reserve.
• Metabolic acidosis is commonly seen in severe
uncontrolled diabetes mellitus which is associated
with excessive production of acetoacetic acid and
p-hydroxybutyric acid (both are organic acids).
• Anion gap and metabolic acidosis : Increased
production and accumulation of organic acids
causes an elevation in the anion gap, is seen in
metabolic acidosis associated with diabetes
(ketoacidosis).
• Compensation of metabolic acidosis : The
acute metabolic acidosis is usually
compensated hy hyperventilation of lungs.
• This leads to an increased elimination of CO₂
from the body, hence H₂CO₃↑, but respiratory
compensation is only short-lived.
• Renal compensation sets in within 3-4 days
and the H+ ions are excreted as NH₄⁺ ions.
 Respiratory acidosis
• The primary defect in respiratory acidosis is due to a retention
of CO₂ (H₂CO₃↑).
• There are several causes for respiratory acidosis which include
depression of the respiratory centre (overdose of drugs),
pulmonary disorders (bronchopneumonia) and breathing air
with high content of CO₂.
• The renal mechanism comes for the rescue to compensate
respiratory acidosis. More HCO3⁻ is generated and retained by
the kidneys which adds up to the alkali reserve of the body.
• The excretion of titratable acidity and NH₄⁺ is elevated in
urine.
 Metabolic alkalosis
• The primary abnormality in metabolic alkalosis
is an increase in HCO3⁻ concentration.
• This may occur due to excessive vomiting
(resulting in loss of H⁺) or an excessive intake
of sodium bicarbonate for therapeutic
purposes (e.g. control ol gastric acidity).
Cushing's syndrome (hypersecretion of
aldosterone) causes increased retention of Na⁺
and loss of K⁺ from the body.
• Metabolic alkalosis is commonly associated with low K⁺
concentration (hypokalemia). In severe K+ deficiency, H⁺
ions are retained inside the cells to replace missing K⁺
ions.
• In the renal tubular cells, H⁺ ions are exchanged
(instead of K⁺) with the reabsorbed Na⁺. Paradoxically,
the patient excretes acid urine despite alkalosis. The
respiratory mechanism initiates the compensation by
hypoventilation to retain CO₂ (hence H₂CO₃↑).
• It is slowly taken over by renal mechanism which
excretes more HCO3⁻ and retains H⁺.
 Respiratory alkalosis
• The primary abnormality in respiratory alkalosis is a
decrease in H₂CO₃ concentration.
• This may occur due to prolonged hyperventilation
resulting in increased exhalation of CO₂ by the lungs.
• Hyperventilation is observed in conditions such as
hysteria, hypoxia, raised intracranial pressure,
excessive artificial ventilation and the action of certain
drugs (salicylate) that stimulate respiratory centre.
• The renal mechanism tries to compensate by
increasing the urinary excretion of HCO₃⁻
 Mixed acid-base disorders
• Sometimes, the patient may have two or more
acid-base disturbances occurring simultaneously.
• In such instances, both HCO₃⁻ and H₂CO₃ are
altered. In general, if the biochemical data (of
blood gas analysis) cannot be explained by a
specific acid-base disorder, it is assumed that a
mixed disturbance is occurring.
• Many a times, compensatory mechanisms may
lead to mixed acid-base disorders.
Acid-base disorders and plasma potassium

• Plasma potassium concentration (normal 3.5-

5.0 mEq/l) is very important as it affects the
contractility of the heart.
• Hyperkalemia (high plasma K⁺) or
hypokalemia (low plasma K⁺) can be Iife-
threatening.
• Potassium and diabetic ketoacidosis : The
hormone insulin increases K⁺ uptake by cells
(particularly from skeletal muscle). The patient of
severe uncontrolled diabetes (i.e. with metabolic
acidosis) is usually with hypokalemia.
• When such a patient is given insulin, it stimulates
K+ entry into cells. The result is that plasma K+
level is further depleted. Hypokalemia affects
heart functioning, and is life threatening.
• Potassium and alkalosis : Low plasma
concentration of K⁺ (hypokalemia) leads to an
increased excretion of hydrogen ions, and thus
may cause metabolic alkalosis. Conversely,
metabolic alkalosis is associated with
increased renal excretion of K⁺.