Acid- base Balance

Murugavel . K
Assistant professor
Dept. of. Biochemistry
 Acid- base Balance
• Acids and bases in the body must be in balance.
• For optimal functioning of cells
• Metabolic processes within our bodies function within a very
narrow pH range.
• Two types of acids are produced from tissue metabolism. They
include both volatile and non-volatile acid.
• Volatile acid: Carbon dioxide
• Non-Volatile acid: Sulphuric acid, Phosphoric Acid , Ketoacid ,Lactic
acid, Pyruvic acid, Citric acid and other organic acids.
• Volatile acid is eliminated by lungs and the non volatile acids are
buffered and excreted by kidney
 Source for Acid

• Due to constant metabolic and respiratory activity

H+ is produced
• Carbohydrate – Pyruvate & lactate & CO2
• Proteins ----- Aminoacids & CO2
• Lipids -------- Ketoacids & CO2
• Sulfur containing Aminoacids -----sulfuric acid
• Nucleic acid ----- phosphoric acid
• The body produces more acids than bases
 pH
• pH = - log [H+]
• Maintenance of Intracellular and extracellular
pH is critical for normal cellular function.
• Maintenance of arterial blood pH is extremely
important for the body Homeostasis , since even
small changes in the blood pH can lead to severe
metabolic consequences.
• The pH scale ranges from 0 - 14. Neutral pH is 7.
More than 7 is Alkaline & Less than 7 is acidic.
pH
pH
• Physiological

• Referenc
e Range

• Pathologic
al
 pH
Normal pH of the blood is 7.35 – 7.45

At this pH all the known intermediates of metabolism are

completely ionized
Effectively traps all these metabolites in their respective
cellular spaces as any ionized compound cannot pass through
the non - polar membranes of the cells.
Glucose and urea are not ionized at this pH 7.4 and can move
across membranes
Intracellular pH is maintained at about the pH of neutrality
(6.8 at 37˚C) because this is the pH at which metabolite
intermediates are all charged and trapped inside the cell
 What we should ideally do is to study the
Intercellular pH.

 This is not possible practically and therefore

blood pH is monitored.
 Almost all the clinical manifestations in acid
base disorders reflect intracellular changes
The most important pH for the body is the intracellular pH

In assessment of acid-base disorders, the clinician is always looking from the outside in

we use the extracellular results to make inferences about the intracellular conditions
Regulation of blood pH
( Acid-base homeostasis )
Organs involved in the regulation of
Acid- base Balance

RBC : Haemoglobin – main buffer for CO2

LUNGS : Excretion of CO2 by alveolar ventilation

KIDNEY : Re-absorption of filtered bicarbonate ;

excretion of the fixed acids
 pH changes are handled by

• BUFFER SYSTEM : Buffer are the FIRST LINE OF DEFENCE against

acid load.
• RESPIRATORY SYSTEM : Respiratory system acts as a SECOND
LINE OF DEFENCE in the regulation of Blood PH.
• RENAL SYSTEM : It acts as a THIRD LINE OF DEFENCE in
the regulation of blood PH. Kidney regulate the acid base
balance by altering the amount of ammonia excretion.
 BUFFER SYSTEM

• Buffer is mixture of weak acid and its conjugate base. Buffer resists the
change in the pH on addition of acid or base.
• They play an important role in transport of acids produced in the body
from other site of production to the site of excretion that is, Kidneys and
lungs and their by maintains the blood PH.
• The buffering capacity of buffer is 1 PH unit on either side of its pKa value.
The buffer is more effective when the PH of a fluid and pKa of acid are
equal i.e PH = Pka. The blood buffer maintain the PH of blood. The following
are blood buffer.

1.Bicarbonate buffer.
2.Phosphate buffer.
3.Protein buffer.
4.Hemoglobin buffer
 BUFFER SYSTEM
Bicarbonate buffer:
• It is major buffer in plasma. It is composed of acid component
(H2CO3) and base component (HCO3-).
• The base component is regulated by kidney and the acid
component is regulated by lungs.
• The measured pK of this buffer is 6.3
• (HCO3-) / (H2CO3) = 24 mEq/L / 1. 2 mEq/L = 20/1
• Maintain a 20:1 ratio : HCO3- : H2CO3 under normal conditions
• The ratio of 20 ( a high alkali reserve ) ensures high buffering
efficacy against acids. When H+ ion is added, it is buffered by
bicarbonate component of the bicarbonate buffer system to
(Acid) H+ + HCO-
-----> H CO
produce weak carbonic acid and when base is added , It is buffered
3 2 3

by(Base)
the OH+
H+ ions
2+ H CO produced
3 -----> byHCO
3 dissociation
-
+H o 2
of weak carbonic acid.
 BUFFER SYSTEM
Phosphate Buffer:
• It is the major intracellular buffer in the cell and urine .
• It is composed of acid component HPO4 / H2Po4 base
component.
• pK =6.8 at physiological pH
• It is an effective buffer system, because its pKa value is
nearest to physiological PH. The buffering efficiencies
of the phosphate buffer in plasma are dependent on
renal function.
H+ + HPO42- ↔ H2PO4-

OH- + H2PO4- ↔ H2O + H2PO42-

 BUFFER SYSTEM
Protien buffer:
• Plasma proteins are minor buffer in the plasma.
• They can act as acid donors and acid acceptors.
• Histidine is the most effective amino acid that helps
protein to work as buffers.
• The Imidazole ring of histidine has buffering action.
• Imidazole group of Histidine has a pK of 7.3
• The plasma protein albumin has 16 histidine residues,
which help it to act as an effective buffer in plasma.
 BUFFER SYSTEM
Hemoglobin Buffer:
• It is the major buffer in RBC and plays important role in
acid base balance.
• It is composed of reduced Haemoglobin (HHb) and
oxidized Haemoglobin (Hb) .Deoxygenated haemoglobin
has more affinity for H+ ions. Oxygenated haemoglobin
releases H+ions and this occurs in lungs. Formation of
carbamino haemoglobin also acts as a buffer.
• [CO2+Hb > Carbaminohaemoglobin]

H+ + Hb ----> HHb

HHb ----> H+ + Hb.

 BUFFER SYSTEM

Ammonia Buffer:
It is the major buffer system in urine for removal of
H+ ions through kidneys. Kidney regulate acid base
balance by altering the ammonia excretion.

•Henderson-Hasselbalch equation is an equation that describes the relationship of

pH to the concentration of acid and base in a buffer system
•[ pH= pK + log Base/Acid ]
•Significance: It is useful in determining the acid-base status of individual during
disorders of acid-base balance
 RESPIRATORY SYSTEM

• Respiratory system acts as a SECOND LINE OF DEFENCE in the

regulation of Blood PH. The lungs are able to effect changes
very quickly, within 1-2 minutes.
• Regulation of acid base balance by lungs occurs by altering the
rate of respiration (Hypo or Hyperventilation) and hence the
rate of removal of CO2 in response to acidosis and alkalosis.
• The CO2 formed as a result of tissue metabolism diffuses from
the cells into the extracellular fluid and reaches the lungs
through the blood.
• The hemoglobin serves to transport the CO2 formed in the
tissues and generate bicarbonate by the action of the enzyme
CARBONIC ANHYDRASE [ CA ]
 RESPIRATORY SYSTEM
CO2 is transported in the blood in three forms
1. Most as bicarbonate ion (HCO3)
2. Dissolved CO2 – as HCO3
3. CO2 attached to hemoglobin – amino end (Carbaminohemoglobin)

The reverse occurs in the lungs during oxygenation and elimination of CO2 .
When the blood reaches the lungs , the bicarbonate re-enter the erythrocyte by
the reversal of chloride shift.
 RENAL SYSTEM

• It acts as a THIRD LINE OF DEFENCE in the regulation of blood

PH. Kidney require several hours or days to respond.
• Kidney regulate the acid base balance by altering the amount
of ammonia excretion. The role of kidney in acid base
regulation are …

A. Re-absorption of bicarbonate in the glomerular filtrate by

proximal renal tubule
B. Excretion of hydrogen ions as titrable acid and ammonium
ions
 Renal handling of HCO3

1. Reabsorption of filtered HCO3

2. Reclamation – reclaim the HCO3
used for buffering
3. New Bicarb synthesis
 RENAL SYSTEM
Reclamation of HCO3

a ) Re-absorption of bicarbonate : In the tubular cells CO2 combines with H2O to form carbonic
acid in the presence of Carbonic anhydrase. Carbonic acid dissociate to give H+ and HCO 3. H+
ions enter the lumen in exchange for sodium. In the lumen H+ combine with HCO 3 to form
H2CO3 and thus H2CO3 dissociate to form CO2+H2O and CO2enters the tubular cell and the cycle
repeats.
 RENAL SYSTEM

b) Excretion of Hydrogen Ion as titrable acid

The H+ ions formed in the tubular cell enters into the lumen. In thelumen, H+ ions combines with
sodium hydrogen phosphate to form sodium dihydrogen phosphate . This is called titrable acidity.
Excretion of H+ ions as ammonium ion (NH4+):
In the renal tubular lumen, H+ ions combines with ammonia to for ammonia ions. The ammonia is
produced in distal renal-tubular cells from glutamine by the action of glutaminase. The
ammonium ions combine with chloride ions to form ammonium chloride. Ammonia excretion is
the main mechanism for the regulation of acid base balance by the kidneys.
 Excretion of other Acids

• Strong acids such as sulfuric , hydrochloric and phosphoric

are fully ionized at the pH of urine and excreted after the
H+ derived from these acids reacts with buffer base.
• Excretion of these is often accompanied by removal of ions
such as Na+, K+/NH4+
• Some acids such as Acetoacetic acid and βhydroxybutyric
acid are present in both ionized form and un-dissociated
form