Acid-base Balance And Imbalance

Learning Objectives

❖ Describe what is meant by acids, bases and buffers. List

normal pH of the body fluids.
❖ Describe the processes involved in maintenance of normal
blood pH.
❖ Describe various types of acidosis and alkalosis.
❖ Describe what is meant by anion gap and its clinical
significance.
 Normal pH Of The Body Fluids

▪ The normal pH of arterial blood is 7.4

▪ pH of venous blood and interstitial fluids is about 7.35

▪ The pH of blood is maintained within a remarkable constant

level of 7.35 to 7.45.
Why maintenance of a pH is important
The activities of almost all enzyme systems in the body
are influenced by hydrogen ion concentration.

Changes in hydrogen ion concentration alter:

▪ all cell and body functions

▪ the conformation of biological structural components

▪ uptake and release of oxygen
Metabolic Sources Of Acids Which Alter Blood pH

Fixed acids or non-volatile acids:

• Phosphoric
• Sulphuric acids
• Pyruvic acid,
• Lactic acid
• Keto acids

Volatile acids breathe out through the lungs :

• Carbonic acid (H2CO3).
 Metabolic Sources Of Bases

▪ Citrate salts of fruit juices may produce bicarbonate salt.

▪ Deamination of amino acids produces ammonia

▪ Formation of bis-phosphate also contributes to

alkalinizing effect.
 Regulatory Mechanisms to maintain normal
Blood pH

▪ Buffer mechanism: First line of defense

▪ The respiratory mechanism: Second line of defense

▪ Renal mechanism: Third line of defense.

 WHAT IS BUFFER?

Buffer is a substance that can resist the change in pH

even after addition of strong acid or base. It is a mixture
of a weak acid and a salt of its conjugate base e.g.
NaHCO3/ H2CO3

If one molecule differs from another by only a proton,

the two are called as conjugate acid-base pair.

A buffer can reversibly bind hydrogen ions. The general
form of the buffering reaction is:

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.
Buffering capacity depends on the:
• Concentration of the buffer.
• Relationship between the pKa of the buffer and the
desired pH.

• A buffer has the maximum buffering capacity when

its pKa equals the pH.

• For the maximum blood buffering, the pKa of the

buffers should, therefore, be near 7.4.
 Blood Buffer

Buffer System Extracellular buffer Intracellular buffer

Bicarbonate NaHCO3/ H2CO3 KHCO3/H2CO3

Phosphate Na2HPO4/NaH2PO4 K2HPO4/KH2PO4

Protein Na Protein/H. Protein KHb/H.Hb

KHbO2/H.HbO2
 The Bicarbonate Buffer System
(HCO3– / H2CO3)

▪ The bicarbonate buffer system is the most important

extracellular buffer.
▪ It plays an important role in maintaining blood pH,
because of its high concentration.
▪ Two elements of the buffer system, HCO3– and H2CO3
are regulated by the kidneys, and by the lungs
respectively.
 Mechanism of Action of Bicarbonate Buffer

When a strong acid, such as HCI, is added to the

bicarbonate buffer solution, the increased hydrogen
ions are buffered by HCO3– to form very weak acid
H2CO3, which, in turn, forms CO2 and H2O.
When sodium hydroxide (NaOH), is added to bicarbonate

buffer, hydroxyl ion (OH–) from NaOH combines with

H2CO3 to form weak base HCO3– and H2O

▪ Any nonvolatile acid stronger than carbonic acid can be
buffered by bicarbonate (HCO3– ).
▪ Plasma bicarbonate is a measure of the base that remains
after all acids, stronger than carbonic have been
neutralized.

▪ It represents the reserve of alkali available for the

neutralization of such strong acids and it has been
termed as the alkali reserve.
▪ At pH 7.4 the average normal ratio of the concentration
of HCO3– and H2CO3 in plasma is 25 mmol/L to 1.25
mmol/L = 20:1.
▪ Subsequently any changes in the concentration of either
bicarbonate (HCO3–) or carbonic acid (H2CO3) and
therefore in the ratio HCO3– : H2CO3 is accompanied by a
change in pH.
▪ The two elements of the buffer system, HCO3– and H2CO3
are regulated by:
1. Increasing or decreasing the rate of reabsorption

of HCO3 by the kidneys

2. By altering the rates of removal or retention of

H2CO3 by the lungs
The Phosphate Buffer System (HPO4– – /H2PO4–)

The phosphate buffer system is not important as a blood

buffer; it plays a major role in buffering renal tubular

fluid and intracellular fluids.

 Mechanism of Action of Phosphate Buffer
(HPO4– – /H2PO4–)

When a strong acid such as HCI is added to phosphate

buffer the H+ is accepted by the base HPO4– – and
converted to H2PO4– and strong acid HCI is replaced by
a weak acid NaH2PO4
When strong base, such as NaOH, is added to the phosphate
buffer the OH– is buffered by the H2PO4– to form HPO4– –
and water. Thus strong base NaOH is replaced by weak base
HPO4– –

At a plasma pH of 7.4 the ratio HPO4– – : H2PO4– is 4:1.

Organic phosphate in the form of 2,3 phosphoglycerate

(2, 3 BPG), present in erythrocytes accounts for about

16% of the non-carbonate buffer of erythrocyte fluid

 PROTEIN BUFFER
(Na Protein/H Protein)
▪ In the blood, plasma proteins especially albumin acts as
buffer.
▪ In acid solution the basic amino group (NH2) takes up
excess H+ ions forming (NH3+).

▪ Whereas in basic solutions the acidic COOH groups give

up hydrogen ion forming OH– of alkali to water.
▪ Other important buffer groups of proteins in the

physiological pH range are the imidazole groups of

histidine.

▪ Each albumin molecule contains 16 histidine residues.

 Hemoglobin Buffer
(KHb/H Hb and KHbO2/HHbO2)

▪ Haemoglobin is the major intracellular buffer of blood

which is present in erythrocytes.

▪ Each Hb molecule contains 38 molecules of histidine.

▪ The imidazole group of histidine has a pKa of

approximately 7.3, fairly close to 7.4.
▪ It buffers carbonic acid (H2CO3)
 Action of hemoglobin buffer

Hemoglobin works effectively in co-operation with the

bicarbonate system.
▪ The transport of an appreciable quantity of the CO2 released

from the tissues without change in pH is called isohydric

transport of CO2.

▪ Most of the CO2 is transported in the plasma as bicarbonate

(HCO3– ).

▪ Because HCO3 is much more soluble in blood plasma than is

CO2, this indirect route increases the blood’s capacity to carry

CO2 from the tissues to the lungs.

 Respiratory Mechanism

▪ Second line of defense against acid-base disturbances

▪ It functions by regulating the concentration of carbonic

acid (H2CO3) in blood and other body fluids by lungs.

▪ The respiratory center regulates the removal or retention

of CO2 and thereby H2CO3 from the extracellular fluid

by the lungs.
▪ Increase in (H+) or (H2CO3) stimulates the respiratory

center to increase the rate of respiratory ventilation and

excess acid (H2CO3) in the form of CO2 is quickly
removed
▪ Increase in (OH–) or (HCO3–) depresses respiratory

ventilation and release of CO2 from the blood

▪ The increased blood CO2 will result in the formation of

more H2CO3 acid to neutralize excess alkali (HCO3–)
 RENAL MECHANISM IN ACID-BASE BALANCE

• Renal mechanism is the third line of defense in acid base

balance.
• Long term acid-base control is exerted by renal
mechanisms.

• Kidney participates in the regulation of acid- base balance

by conservation of HCO3– (alkali reserve) and excretion of
acid.
▪ The pH of the initial glomerular filtrate is approximately
7.4 whereas the average urinary pH is approximately 6.0
due to excretion of non-volatile acids produced by
metabolic processes.

▪ The pH of the urine may vary from 4.5 to 8.0

corresponding to the case of acidosis or alkalosis.

▪ This ability to excrete variable amounts of acid or base

makes the kidney the final defence mechanism against
change in body pH.
 Renal conservation of HCO3 and excretion of
acid occur through four key mechanisms
1. Exchange of H+ for Na+ of tubular fluid.

2. Reabsorption of bicarbonate from tubular fluid.

3. Formation of ammonia and excretion of

ammonium ion (NH4+) in the urine.

4. Excretion of H+ as H2PO4– in urine

Exchange of H+ for Na+ of tubular fluid and reabsorption
of bicarbonate from tubular fluid.
Excretion of H+ as H2PO4 - in urine.
Formation of ammonia and excretion of ammonium
ions in the urine.
Disorders of Acid Base Balance

❑ Acidosis

❑ Alkalosis
 Acidosis And Alkalosis

Acid-base balance depends on the ratio HCO3–/ H2CO3

which is constant at 20:1 at physiological pH.
Any alteration produced in the ratio between carbonic
acid and bicarbonate results in an acid-base imbalance
and leads to acidosis or alkalosis.
Acidosis may be defined as an abnormal condition

caused by the accumulation of excess acid in the body or

by the loss of alkali from the body.

Alkalosis is an abnormal condition caused by the

accumulation of excess alkali in the body or by the loss

of acid from the body.

Acidosis and alkalosis are classified, in terms of their cause :
1. Metabolic acidosis: Dec. in bicarbonate (HCO3–) conc.

2. Respiratory acidosis: Inc. in H2CO3 concentration.

3. Metabolic alkalosis: Inc. in bicarbonate (HCO3–) conc.

4. Respiratory alkalosis: Dec. in H2CO3 concentration.

In all these four conditions, if the ratio HCO3–/ H2CO3

remains within normal limits, i.e. about 16:1 to 25:1,

corresponding to pH 7.3 to 7.5, the condition results in

compensated acidosis and alkalosis.

When the ratio actually changes and pH is outside of the

normal range the term uncompensated is used.

Metabolic Acidosis
A fall in blood pH due to a decrease in bicarbonate
levels of plasma is called metabolic acidosis.
Decrease in bicarbonate levels may be due to:

– Increased production of acids e. g., in uncontrolled

diabetes mellitus and starvation

– Excessive loss of bicarbonate e. g., in renal tubular

dysfunction and in severe diarrhoea.
Compensatory mechanisms for metabolic acidosis

Increasing rate of respiration to wash out CO2 (hence

H2CO3) faster. Consequently, the ratio HCO3–/ H2CO3
is elevated.
Increasing excretion of H+ ions as NH4+ ions.
Increasing elimination of acid H2PO4– in the urine.

All these compensatory mechanisms tend to reduce carbonic

acid and a compensated acidosis results.
 Respiratory Acidosis

▪ Acidosis results from an increase in concentration of

H2CO3

▪ An increase in concentration of H2CO3 is due to

decrease in alveolar ventilation, which leads to
retention of CO2
▪ Decreased alveolar ventilation may occur in:
-- Obstruction to respiration:
in pneumonia, emphysema, asthma, etc.
-- Depression of respiration:

administration of respiratory depressant toxic

drugs like morphine which depresses the
respiratory centre.
Compensatory mechanisms

Increase in renal reabsorption of bicarbonate.

Rise in urinary acid H2PO4– and ammonia.
 Metabolic Alkalosis
▪ A rise in blood pH due to rise in the bicarbonate levels of
plasma
▪ This is seen in the following conditions:

• Loss of gastric juice along with H+ ions in

prolonged and severe vomiting.

• Therapeutic administration of large dose of alkali

(in peptic ulcer) or chronic intake of excess
antacids.
 Compensatory mechanisms

▪ Increased excretion of alkali (HCO3–) by the kidney.

▪ Diminished formation of ammonia.

▪ Respiration is depressed to conserve CO2.

 Respiratory Alkalosis
A rise in blood pH due to lowered concentration of CO2
or H2CO3, due to hyperventilation.
This occurs in the following conditions:

Anxiety or hysteria

Fever

Hot baths
At high altitude
Working at high temperature, etc.
Compensatory mechanisms

Increased excretion of bicarbonate.

Reduction of urinary ammonia formation
Causes of acidosis and alkalosis.
Arterial Blood Gas Analysis In Acid-base Imbalance
▪ Arterial blood gas (ABG) analysis is a common
investigation in emergency departments and intensive
care units for monitoring patients with acute respiratory
failure.

▪ An arterial blood gas result can help in the assessment

of a patient’s gas exchange, ventilatory control, and

acid base balance.

The ABG analysis becomes necessary in view of the

following advantages:
–– Aids in establishing diagnosis.
–– Guides treatment plan.
–– Aids in ventilator management.

–– Improvement in acid/base management.

–– Acid/base status may alter electrolyte levels

critical to a patient’s status.

Anion Gap
The concentration of anions and cations in plasma must be

equal to maintain electrical neutrality. Therefore, there is

no real anion gap in the plasma. Anion gap is not a

physiological reality.
The concept of anion gap originally was developed when it

was found that if the sum of the Cl– and HCO3_ values was

subtracted from the Na+ and K+ values the difference or

‘gap’ averaged 16 mmol/L in healthy individuals.

Anion gap = ([Na+] + [K+]) – ([Cl–] + [HCO3– ])
= (142 + 4) – (103 + 27)
= 146 – 130
= 16 mEq/L
The most important unmeasured cations include Ca,

Mg, and the major unmeasured anions are albumin,

phosphate, sulphate and other organic anions.

The anion gap ranges between 8 –16 mEq/L.

Acid base disorders are often associated with alterations

in the anion gap.

In metabolic acidosis the anion gap can increase or

remain normal depending on the cause of acidosis.

Metabolic Acidosis Associated with Increased Anion Gap

▪ In metabolic acidosis, the plasma HCO3– is reduced. To

keep electroneutrality, the concentration of anions (either Cl–
or an unmeasured anion) must increase.
▪ If the decrease in plasma HCO3– is not accompanied by
increased Cl–, the anion gap value will increase and referred
to as increased anion gap acidosis or normochloremic
acidosis.
Metabolic Acidosis Associated with Normal Anion Gap

If the decrease in plasma HCO3– is accompanied by

increased Cl–, the anion gap is remained normal, this
referred to as Hyperchloremic metabolic acidosis or
normal anion gap acidosis.
Clinical Significance of Anion Gap

The anion gap is a biochemical tool which sometimes

helps in assessing acid-base problems. It is used for the

diagnosis of different causes of metabolic acidosis.

A 38-year-old man reported in the emergency ward of a

hospital emergency with complaints of persistent

vomiting for one week. He had generalized muscular

cramps. On examination, he appeared dehydrated and

had shallow respiration. Blood sample was analyzed

with the following results:

• pH = 7.8 (normal 7.35- 7.45)
• Bicarbonates = 35 mEq/L (normal 22- 30 mEq/L)
• pCO2 = 50 mm Hg (normal 30- 45 mm Hg)
• Na+= 145 mEq/L (normal 136- 145 mEq/L)
• K+ = 2.9 mEq/L. (normal 3.5 -5 mEq/L)
Questions
1. Identify the nature of acid-base disorder.

2. What could be the cause of this acid-base disorder?

3. What is the cause of shallow respiration?

4. Give reason for development of muscle cramps.
A 50-year-old male was admitted with a history of chronic

obstructive airways disease for many years. On

examination, he was found cyanosed, and breathless.

Blood sample was analyzed with the following results:

• Blood pH = below normal

• pCO2 = markedly elevated

• (HCO3–) = markedly elevated.

Questions

1. Identify the nature of acid-base disorder.

2. What could be the cause of elevated pCO2?

3. What could be the cause of elevated (HCO3–)?

A person presents himself with untreated diabetes
mellitus. He is treated for acidosis.
1. What is the type of acidosis?
2. What is the normal bicarbonate/carbonic acid ratio? What will
happen to the ratio in this patient?
3. How will compensation occur?
4. What is the role of kidney in correcting acidosis?
THANK YOU