Acid Base Balance

Acid = Proton donor Base = Proton acceptor

pH = Negative logarithm of H+ concentration
Neutral pH = 7
Acid = pH less than 7 Alkali = pH more than 7

Regulation of Plasma pH
Plasma pH is maintained in a narrow range.

Normal plasma pH is 7.4 ± 0.02 (7.38 – 7.42)

Intracellular pH may be less than this.

If plasma pH decreases below normal , it is called acidosis

If plasma pH increases above normal, it is called alkalosis

Change in pH is dangerous. The pH range that is compatible with life is 6.8 – 7.8

Plasma pH is regulated by 3 Mechanisms

1. Buffers
2. Respiratory regulation
3. Renal regulation

Buffers
Buffers are solutions that resist the change in pH when an acid or alkali is added.

A buffer is composed of a weak acid and its salt with a strong base [or a weak base and its salt with
a strong acid

Eg: Bicarbonate Buffer : NaHCO3 /H2CO3

Phosphate Buffer : Na2HPO4 / NaH2PO4

pH of a buffer obeys Henderson-Hasselbalch equation

Where pK is the acid dissociation constant of the buffer (pKa)

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Factors affecting pH of a Buffer
From Henderson-Hasselbalch equation it can be seen that pH of a buffer is affected by

(a) pK of buffer: The more the pK, more is the pH

(b) Ratio of [Salt] to [Acid]

The buffering capacity depends on the actual concentration of the salt and acid

A Buffer is most effective when the pH is equal to its pKa

This occurs when the ratio of [Salt] to [Acid] is 1

Effective range of a buffer is pK -1 to pK +1

Buffers act as the first line of defense against acid base disturbance

Important Buffers of body fluids

Plasma Intracellular RBC
Bicarbonate Phosphate Hemoglobin
Phosphate Protein Phosphate
Protein Bicarbonate Bicarbonate

Bicarbonate Buffer (NaHCO3 / H2CO3)

Bicarbonate /Carbonic acid buffer is the most important buffer in plasma

pKa of Bicarbonate buffer is 6.1

[HCO3 - ] = 24 ±2 mmol/L

[H2CO3 ] = 1.2 mmol/L (This is equal to a pa CO2 of 40 ±2 mmHg)

As per Henderson-Hasselbalch equation, a buffer is effective when pH = pK -1 to pK +1, and when

Ratio of [Salt] to [Acid] is 1

In case of bicarbonate buffer, pK is 6.1, which is different from plasma pH

Ratio of [Salt] to [Acid] is 20 (24 /1.2)

Even then, Bicarbonate buffer is effective because of 2 reasons

1. “Open at both ends” : Bicarbonate is regulated by renal mechanisms and Carbonic acid
(CO2) is regulated by respiratory mechanisms. Kidneys regulate the level of bicarbonate by
increasing or decreasing the excretion of H + by various mechanisms. Respiratory
mechanisms regulate pCO2 (and there by H2CO3) by increasing or decreasing the rate of
respiration.

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2. Metabolism usually produce acids. So, plasma is prone for an acid load. Plasma keeps an
excess of alkali to compensate for this (that is 20 times that of acid). This is called Alkali
reserve

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 Phosphate buffer (Na2HPO4 / NaH2PO4)

Most important intracellular buffer. Phosphate buffer has more than one pK values because of the
presence of more than one ionizable groups. So it can act as an effective buffer over a wide range of
pH. That is why it acts effectively as a buffer

Protein buffer

Proteins like Albumin , Hemoglobin etc act as good buffers.

Proteins act as buffers due to their ionizable side chains

Among the amino acids, the most effective one is imidazole group of Histidine. Its pK value (6.8) is
close to the plasma pH

Hemoglobin is 6 times more effective compared to plasma proteins because

(a) Concentration of Hb is 2 times that of plasma proteins

(b) Number of Histidine residues is 3 times that of plasma proteins

Buffers act as the first line of defense against an acid base disturbance

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 Respiratory regulation
It is the second line of defense

This is done by regulating the excretion of CO2 and thus adjusting the H2CO3 levels

Chemoreceptors that regulate the respiratory centre are sensitive to H+ concentration

When pH decreases the chemoreceptors sense this and stimulate the respiratory centre. This
increases the rate of respiration and increases the removal of CO2

When pH increases the opposite happens and rate of respiration decreases

Role of Hb in removal of CO2

CO2 enters RBCs from cells and combines with water to form carbonic acid. This splits to HCO3 - and
H+. Oxy Hb releases oxygen into cells and combines with H+. Bicarbonate diffuses into plasma in
exchange for chloride. This is called chloride shift.

Transport of CO2 as bicarbonate helps to transport CO2 without decreasing plasma pH. This is called
Isohydric transport of CO2. It has two advantages

a. Large amounts of CO2 can be transported without decreasing pH of plasma

b. Bicarbonate thus generated contributes to alkali reserve

The opposite changes happen when RBCs reach lungs (Explain)

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 Renal regulation
This is the final defense mechanism against an acid base disturbance

pH of glomerular filtrate is same as that of plasma (7.4)

Average pH of urine is around 6

This shows that there is net acidification of the tubular fluid

Depending on the acid base status, pH of urine can vary from 4.5 to 8

Acidification of tubular fluid by the kidney occurs by 4 different mechanisms

1. Excretion of H+ with generation of Bicarbonate (HCO3 - )

2. Reabsorption of filtered bicarbonate
3. Excretion of titratable acidity
4. Excretion of ammonium (NH4 +) ions

Excretion of H+ with generation of Bicarbonate (HCO3 - )

This occurs in PCT.

CO2 and H2O combine to form H2CO3 by Carbonic anhydrase in tubular cells

This splits to H+ and HCO3 –

H+ is secreted to tubular lumen in exchange for Na+

Na+ and HCO3 – are reabsorbed into plasma

This excretes H+ and generates HCO3 –

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Reabsorption of filtered bicarbonate

This also occurs in PCT

• Filtered NaHCO3 splits into Na+ and Bicarbonate

• Bicarbonate combines with the H+ secreted in exchange for Na+

• This forms carbonic acid which splits into water and CO2

• CO2 is reabsorbed

• In tubular cells, this forms bicarbonate which gets absorbed with Na+

• By this mechanism , the filtered bicarbonate is reabsorbed

• There is no net generation of bicarbonate or net excretion of H+

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Excretion of titratable acidity (Phosphate mechanism)
Titratable acidity is defined as the Number of ml of 0.1 N NaOH required to titrate 1 Litre of urine to
pH 7.4

Major titratable acid is sodium acid phosphate (NaH2PO4)

The process starts in PCT and continues till DCT

• H+ generated by carbonic anhydrase is secreted by in exchange for Na+

• By addition of this H+, basic phosphate (Na2HPO4) is converted to acid phosphate (NaH2PO4)

• Phosphate buffer is highly effective in urine

• The acid/basic phosphate pair is also known as “Urinary buffer”

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Excretion of ammonium ions

This occurs in DCT

Glutaminase Splits Glutamine to Glutamate and ammonia

• This ammonia diffuses into tubular fluid, and combines with H+ to form NH4+ ions

• This helps to excrete large quantities of H+ ions without much change in pH of urine

In summary, kidney excretes acids with the help of carbonic anhydrase and glutaminase.

Activity of both these enzymes increases during acidosis. This helps excretion of more acids during
acidosis

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