.

ACID BASE BALANCE

 The normal pH of blood is 7.35-7.45 i.e.Slightly alkaline.

 Maintenance of blood pH is an important homeostatic

Acid Base Balance mechanism of the body.

 Changes in blood pH will alter the intra-cellular pH, which in

Dr Bushra Fiza, Professor return influence the metabolism. Eg.-distortion in protein
structure, enzyme activity etc.
Dept. of Biochemistry, MGMCH

 It is estimated that the blood pH compatible to life is 6.8-7.8

ACIDS AND BASES

 An acid is a substance that gives off protons while base is a  Functions:

substance that accepts protons; thus an acid is a proton  Maintains pH homeostasis
donor and a base is a proton accepter.
 Maintenance of H+ concentration
 Acids are H+ donors.
 Bases are H+ acceptors, or give up OH- in solution.
 Acids and bases can be:  Potential Problems of Acid-Base balance
 Strong – dissociate completely in solution  Increased H+ concentration yields decreased pH
HCl, NaOH  Decreased H+ concentration yields increased pH
 Weak – dissociate only partially in solution
Lactic acid, ammonia

pH

The Body and pH

 Homeostasis of pH is tightly controlled
 PH is another term for H+ ion concentration.
 Extracellular fluid = 7.4
 The negative logarithim of H+ ion is taken for calculating the pH as
 Blood = 7.35 – 7.45
pH = log 1/[H+]
 < 6.8 or > 8.0 death occurs
pH = -log[H+]
 Acidosis (acidemia) below 7.35
 The normal blood pH = 7.4
 Alkalosis (alkalemia) above 7.45
 If H+ ion concentration increases is known as ACIDOSIS.
 If H+ ions decreases is known as ALKALOSIS.

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Small changes in pH can

produce major disturbances
 Most enzymes function only with narrow pH ranges
 Acid-base balance can also affect electrolytes (Na+, K+, Cl-)
 Can also affect hormones

7 8

Maintenance of acid-base balance

MAINTENANCE OF BLOOD
pH
Three systems perform this task :
 Body has developed three line of defence to regulate
the body’s acid-base balance and maintain the blood pH
(around 7.4).
• First line of defense– Buffer system
1.
1. Blood buffer
• Second line of defense– Respiratory 2. Respiratory mechanism
2. system 3. Renal mechanism

• Third line of defense– Renal system

3.

BUFFERS

 Buffer is a solution that resist change in pH where acid or base

is added
 The effectiveness depends on its pKa or pK.
 pK= pH at which the buffer is 50% ionised, means the acid
concentration is exactly equal to that of base conjugate
 The buffer is very efficient at a pH of ±1 around its pK.
eg: phosphate buffer pK=6.8
max. Buffer capacity=5.8-7.8
 A buffer solution is a mixture of weak acid and its Na or K salt
(base).

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BLOOD BUFFER SYSTEM Mechanisms of regulation of pH

 Buffer :Buffer is a solution that resist change

in pH where acid or base is added.
 The blood contain three buffer system:
 Buffers are 2 types.
1. Bicarbonate buffer
1. Mixture of weak acids with their salt with a
2. Phosphate buffer
strong base.
3. Protein buffer
2. Mixture of weak base with their salt with a
strong acids.

BICARBONATE BUFFER

⚫ Bicarbonate and carbonic acid pair (NaHCO3–

The buffers are present both in plasma ( sodium buffer ) and in H2CO3–) is the predominant buffer system in the
RBCs ( potassium buffers ) extracellular fluid.

The blood buffer consist of

Bicarbonate buffers
⚫ The concentration of the bicarbonate ion is not
phosphate buffers protein buffers directly measured, it is calculated from the
Henderson–Hasselbalch equation.
( including hemoglobin
and oxyhemoglobin )

HANDERSON–HASSELBALCH EQUATION
…Continues)

(Continued… (Continued…

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…Continues) …Continues)

The above equation is popularly known as the The Henderson–Hasselbalch equation for the bicarbonate
Henderson–Hasselbalch equation and is buffer pair is
applicable for any buffer pair.

Substitute the values discussed earlier in the above

equation (plasma pH = 7.4; pKa for H2CO3 = 6.1; HCO3– = 24
mmol/L; H2CO3 = 1.2 mmol/L).

(Continued… (Continued…

…Continues)

Thus the bicarbonate concentration is

much higher (20times than carbonic acid
in the blood). This is referred to as
alkali reserve and is responsible for the
effective buffering of H+ ions generated
in the body

HCl + NaHCO3 ↔ H2CO3 + NaCl

NaOH + H2CO3 ↔ NaHCO3 + H2O

Phosphate Buffer Protein Buffers

 Major intracellular buffer.
 The phosphate buffer system is effective at
wide range of pH because of more ionizable
groups, it has different pKa values.
 Has a major role in the elimination of H+ via
the kidney.
 Assists in the exchange of sodium for hydrogen.
 It participates in the following reaction
• HPO-24 + H+ --------------- H2PO – 4
 Essential within the erythrocytes
 Protein Buffer System
 Originates from amino acids
 ALBUMIN- primary protein due to high concentration in
plasma
 Buffer both hydrogen ions and carbon dioxide
 Hemoglobin Buffer System
 Binds CO2
 Binds and transports hydrogen and oxygen
 Participates in the chloride shift
 Maintains blood pH as hemoglobin changes from
oxyhemoglobin to deoxyhemoglobin

23 24

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RESPIRATORY ACID-BASE CONTROL

When blood pH falls
MECHANISMS
 More acid is formed
 HCO3-: H2CO3 decrease
When chemical buffers alone cannot revent  So respiratory centre is activated
changes in blood pH, the respiratory system is  Results in hyperventilation
the second line of defense against changes.  Increase CO2 expiration
 pCO2 is decreased
Eliminate or Retain CO₂  H2CO3 formation decreased
 HCO3-: H2CO3 increase
Change in pH are RAPID  pH increase
 RETURNS TO NORMAL
Occurring within minutes

When Blood pH increases

 Less acid is formed

 HCO3-: H2CO3 increase
 So respiratory centre is deactivated
 Results in hypoventilation
 Decrease CO2 expiration
 pCO2 is increased
 H2CO3 formation increased
 HCO3-: H2CO3 decreased
 pH decrease
 RETURNS TO NORMAL

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CHLORIDE SHIFT
RENAL ACID-BASE CONTROL
MECHANISMS
❑ The kidneys are the third line of defence
against
wide changes in body fluid pH.
❑ Normal urine has a pH around 6 ,this pH is
lower than that of extracellular fluid ( pH =7 )
.This is called acidification of urine.
❑ The pH of urine may vary from as low as 4.5
to as high as 9.8 , depending on the amount of
acid excreted.
Generation of bicarbonate by the erythrocytes

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REABSORPTION OF BICARBONATE
The major renal mechanisms for regulation of
pH are:
A. Excretion of H+

B. Reabsorption of bicarbonate
(recovery of bicarbonate )

C. Excretion of titrable acid (net acid excretion)

D. Excretion of NH+4

ADDITION OF NEW BICARBONATE

EXCRETION OF AMMONIUM IONS
TO THE PLASMA

CLINICAL CAUSES AND BIOCHEMICAL

ANION GAP
MECHANISMS OF ACID-BASE DISORDERS
● The difference between the sums of the
concentrations of the measured cations (Na+
and K+) and that of measured anions (C1– and
HCO3–) is known as the anion gap. Thus, the
anion gap represents unmeasured anions in
the plasma. It can be calculated as follows:
Anion gap (A–) = ([Na+] + [K+]) – ([Cl–] +
[HCO3–])
= (136 + 4)– (100 + 25)
A– = 15 mEq/L

(Continued…

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…Continues) Acid Base Imbalance

The anion gap in normal health is about
12–18 mEq/L. The alterations in the
anion gap are useful in the clinical
assessment of acid–base disorders.
 Acid–base imbalance is an abnormality of the
human body's normal balance of acids and
bases that causes the plasma pH to deviate
out of the normal range (7.35 to 7.45).

ACID-BASE DISORDERS

Metabolic acidosis
The primary abnormalities in metabolic acidosis are:

⚫ Increased production or decreased excretion of H+ ions

or both at once.
⚫ Loss of HCO3– from the body:

(Continued…

…Continues)

Causes of metabolic acidosis

⚫ Severe uncontrolled diabetes mellitus
⚫ Diabetic ketoacidosis (DKA).
⚫ Starvation ketosis, lactic acidosis and renal failure

Management: Metabolic acidosis can be effectively

managed by identifying and treating the underlying cause.
This includes treatment of diabetes, control of diarrhea,
correction of shock and so on.

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METABOLIC ALKALOSIS
…Continues)

The primary abnormality in metabolic alkalosis is an ⚫ Overdose of diuretic drugs

increase in plasma HCO3– concentration with a consequent
⚫ Mineralocorticoid excess (Cushing's syndrome, Conn's
reduction in H+ ion.
syndrome), alkalosis occurs due to increased H+ ion
excretion in the urine
⚫ Principles of management include correcting the
Causes underlying cause, adequate intravenous fluid
⚫ Sustained vomiting administration and replacement of K+ correcting
⚫ Bicarbonate administration for prolonged periods as hypokalemia.
a means of treating indigestion and overuse of
antacids for treatment of dyspepsia result in
metabolic alkalosis.

(Continued…

RESPIRATORY ACIDOSIS

The primary abnormality in respiratory acidosis is retention

of CO2 ( H2CO3) due to impaired alveolar ventilation
resulting in a rise in pCO2.
Causes
• Airway obstruction and pulmonary disease – chronic
obstructive airway disease (emphysema, bronchitis and
so on)

(Continued…

…Continues)

– severe asthma
– bronchopneumonia
– respiratory distress syndrome (RDS)
– flail chest
⚫ Depression of the respiratory centre by the
administration of overdose of anesthetics, sedatives and
narcotics.
⚫ Neuromuscular diseases like poliomyelitis, Guillian–Barre
syndrome, motor neuron disease and so on.

(Continued…

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RESPIRATORY ALKALOSIS
…Continues)

Management involves correction of causative factors. The
general principle of treating respiratory acidosis is to
improve alveolar ventilation and lower the pCO2.
The primary abnormality in respiratory alkalosis is a
decrease in H2CO3 concentration. A fall in pCO2,
reduces the ratio of carbonic acid to bicarbonate
resulting in acidosis.
Causes
• Hyperventilation resulting from hysteria and anxiety
states cause respiratory alkalosis.

(Continued…

…Continues)

⚫ Raised intracranial pressure and brain stem lesions

cause hyperventilation by stimulating the respiratory
centre. Ingestion of certain drugs (salicylates) also
stimulates the brain stem respiratory centre.
⚫ Hypoxia occuring in high altitudes, severe anemic
conditions and pulmonary disease

Principles of management include correcting the underlying

causes, alleviating anxiety. In acute cases, the patient is
subjected to re-breathing into a closed bag to allow CO2
levels to rise.

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