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PHYSIO-BIOCHEMISTRY OF
ACID BASE BALANCE
Dr. Aniket Anil Shilwant
BAMS, MD (Ayurveda Physiology)
TABLE OF CONTENTS
• ACIDS
• BASES
• ACID BASE BUFFER
• BICARBONATE BUFFER
• PHOSPHATE BUFFER
• PROTEIN BUFFER
• RESPIRATORY MECHANISM
• RENAL MECHANISM
ACIDS – BASES
• An acid is the proton donor (the substance that liberates hydrogen ion).
• A base is the proton acceptor (the substance that accepts hydrogen ion).
• The normal H concentration in the extracellular fluid (ECF) is 38 to 42 nM/L.
• An increase in H+ ion concentration decreases the pH (acidosis) and a reduction
in H + concentration increases the pH (alkalosis).
• An increase in pH by onefold requires a tenfold decrease in H+ concentration.
BICARBONATE BUFFER SYSTEM
• It works at ECF level – Plasma
• It is Less powerful / effective as it is unable to cope with the pH difference to
that of Blood.
• Blood pH – 7.4
• Bicarb buffer pK – 6.1
• Chemical Equations –
HCl + NaHCO3 ----- H2CO3 + NaCl
Hydrochloric acid Sodium Bicarbonate Carbonic Acid (Weak) Sodium Chloride
NaOH + H2CO3 ----- NaHCO3 + H2O
Sodium Hydroxide Sodium Bicarbonate Carbonic Acid (Weak) Water
PHOSPHATE BUFFER SYSTEM
• It works at ICF and also at RBC level.
• It is More powerful / effective as it aptly matches the blood pH with least difference.
• Blood pH – 7.4
• Phosphate buffer pK – 6.8
• Chemical Equations –
HCl + Na2HPO4 ----- NaH2PO4 + NaCl
Hydrochloric acid Di-Sodium Hydrogen Phosphate Sodium Di-Hydrogen Phosphate Sodium Chloride
NaOH + NaH2PO4 ----- Na2HPO4 + H2O
Sodium Hydroxide Sodium Di-Hydrogen Phosphate Di-Sodium Hydrogen Phosphate Water
Note: At RBC level, due to excess concentration of Potassium, there is Potassium Di-
Hydrogen Phosphate and Di-Potassium Hydrogen Phosphate buffer.
PROTEIN BUFFER SYSTEM
• It works at both - ECF (Plasma) and RBC level
At ECF (Plasma) level
• At Plasma level weak acids that participate are –
 Carboxyl and Amino group of Glutamic acid
 Amino group of Lysine
 Imidazole group of Histidine
• Protein buffer systems in plasma are more powerful because of their high
concentration in plasma and because of their pK being very close to 7.4.
PROTEIN BUFFER SYSTEM
At RBC level
• Hemoglobin six times more powerful buffer due to its high concentration than
Plasma Proteins.
• Deoxygenated Hb is more powerful than Oxygenated Hb due to higher pK.
• Deoxygenated Hb easily binds the free H+ ions which are released when CO2 enters
capillaries. This attachment prevents fall in pH of blood.
RESPIRATORY SYSTEM
• Lungs maintain Acid-Base balance by removing CO2 produced during metabolic activities
in the body.
• CO2 combines with H2O to form Carbonic acid (H2CO3).
• Since carbonic acid is unstable, it splits into H+ and HCO3
CO2 + H2O → H2CO3 → H+ + HCO3-
• This entire reaction is reversed in lungs when CO2 diffuses from blood into the alveoli of
lungs.
H+ + HCO3– → H2CO3 → CO2 + H2O
• Where CO2 and H2O is blown off by ventilation.
RESPIRATORY SYSTEM
Sequence of Respiratory events to cope up with Metabolic Acidosis
1. Increase in metabolic activity
2. More CO2 is produced in tissues
3. Concentration of H+ ions also increases
4. State of Acidosis
5. Activation of Chemoreceptors
6. Hyperventilation – Pulmonary ventilation increases
7. Excess of CO2 is evaporated through breathing (Along with Insensible water loss)
RENAL MECHANISM
Kidneys play an important role in preventing Metabolic Acidosis by excretion of
H+ ions through 3 ways –
• Bicarbonate mechanism
• Phosphate mechanism
• Ammonia mechanism
H+ RELEASE VIA KIDNEYS – BICARBONATE MECHANISM
 For every H+ ion secreted into lumen of tubule, one bicarbonate ion is reabsorbed from the
tubule.
 In this way, kidneys conserve the HCO3.
 This reabsorption of filtered HCO3 is helpful in maintaining pH of the body fluids.
H+ RELEASE VIA KIDNEYS – BICARBONATE MECHANISM
INTERSTITIAL
FLUID
TUBULUAR CELL TUBULAR LUMEN
NaHCO3
Na+
H+ HCO3-
H2CO3
CO2 + H2O
H2O + CO2
H2CO3
HCO3- + H+
Na
Na+ + HCO3-
Na
HCO3-
NaHCO3
H+ RELEASE VIA KIDNEYS – PHOSPHATE MECHANISM
 The excess of H+ ions are secreted in renal tubules in the form of Sodium dihydrogen
phosphate.
 This excess H+ ions added to Urine in form of Sodium Dihydrogen Phosphate makes Urine
more acidic.
 This happens mainly in distal tubule and collecting duct because of the presence of large
quantity of sodium hydrogen phosphate in these segments.
H+ RELEASE VIA KIDNEYS – PHOSPHATE MECHANISM
INTERSTITIAL
FLUID
TUBULUAR CELL TUBULAR LUMEN
Na2HPO4
Na+
H+ NaHPO4
NaH2PO4
H2O + CO2
H2CO3
HCO3- + H+
Na
Na+ + NaHPO4
Na
HCO3-
NaHCO3
H+ RELEASE VIA KIDNEYS – AMMONIA MECHANISM
 On of the most important mechanism by which kidneys excrete H+ ions and make the urine
acidic.
 In the tubular epithelial cells, ammonia is formed when the amino acid glutamine is
converted into glutamic acid in the presence of the enzyme glutaminase.
 Ammonia (NH3) formed in tubular cells is secreted into tubular lumen in exchange for
sodium ion.
 Here, it combines with H+ ions to form Ammonium ions (NH4+).
H+ RELEASE VIA KIDNEYS – AMMONIA MECHANISM
 Thus, here the excess of H+ ions are secreted into renal tubules in the form of Ammonium
ions (NH4) resulting in acidification of urine.
 For each NH4 ion excreted, one HCO3- is added to interstitial fluid.
 This process takes place mostly in the proximal convoluted tubule because glutamine is
converted into ammonia in the cells of this segment.
 Thus, by excreting H+ and conserving HCO3, kidneys produce acidic urine and help to
maintain the acid-base balance of body fluids.
H+ RELEASE VIA KIDNEYS – AMMONIA MECHANISM
INTERSTITIAL
FLUID
TUBULUAR CELL TUBULAR LUMEN
Ammonia (NH3)
H2O + CO2
H2CO3
HCO3- + H+
Na Na+
Na
HCO3-
NaHCO3
Glutamine
Glutamic Acid
Ammonia (NH3)
H+
Ammonium ions NH4
Thank You!!!

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  • 1. PHYSIO-BIOCHEMISTRY OF ACID BASE BALANCE Dr. Aniket Anil Shilwant BAMS, MD (Ayurveda Physiology)
  • 2. TABLE OF CONTENTS • ACIDS • BASES • ACID BASE BUFFER • BICARBONATE BUFFER • PHOSPHATE BUFFER • PROTEIN BUFFER • RESPIRATORY MECHANISM • RENAL MECHANISM
  • 3. ACIDS – BASES • An acid is the proton donor (the substance that liberates hydrogen ion). • A base is the proton acceptor (the substance that accepts hydrogen ion). • The normal H concentration in the extracellular fluid (ECF) is 38 to 42 nM/L. • An increase in H+ ion concentration decreases the pH (acidosis) and a reduction in H + concentration increases the pH (alkalosis). • An increase in pH by onefold requires a tenfold decrease in H+ concentration.
  • 4. BICARBONATE BUFFER SYSTEM • It works at ECF level – Plasma • It is Less powerful / effective as it is unable to cope with the pH difference to that of Blood. • Blood pH – 7.4 • Bicarb buffer pK – 6.1 • Chemical Equations – HCl + NaHCO3 ----- H2CO3 + NaCl Hydrochloric acid Sodium Bicarbonate Carbonic Acid (Weak) Sodium Chloride NaOH + H2CO3 ----- NaHCO3 + H2O Sodium Hydroxide Sodium Bicarbonate Carbonic Acid (Weak) Water
  • 5. PHOSPHATE BUFFER SYSTEM • It works at ICF and also at RBC level. • It is More powerful / effective as it aptly matches the blood pH with least difference. • Blood pH – 7.4 • Phosphate buffer pK – 6.8 • Chemical Equations – HCl + Na2HPO4 ----- NaH2PO4 + NaCl Hydrochloric acid Di-Sodium Hydrogen Phosphate Sodium Di-Hydrogen Phosphate Sodium Chloride NaOH + NaH2PO4 ----- Na2HPO4 + H2O Sodium Hydroxide Sodium Di-Hydrogen Phosphate Di-Sodium Hydrogen Phosphate Water Note: At RBC level, due to excess concentration of Potassium, there is Potassium Di- Hydrogen Phosphate and Di-Potassium Hydrogen Phosphate buffer.
  • 6. PROTEIN BUFFER SYSTEM • It works at both - ECF (Plasma) and RBC level At ECF (Plasma) level • At Plasma level weak acids that participate are –  Carboxyl and Amino group of Glutamic acid  Amino group of Lysine  Imidazole group of Histidine • Protein buffer systems in plasma are more powerful because of their high concentration in plasma and because of their pK being very close to 7.4.
  • 7. PROTEIN BUFFER SYSTEM At RBC level • Hemoglobin six times more powerful buffer due to its high concentration than Plasma Proteins. • Deoxygenated Hb is more powerful than Oxygenated Hb due to higher pK. • Deoxygenated Hb easily binds the free H+ ions which are released when CO2 enters capillaries. This attachment prevents fall in pH of blood.
  • 8. RESPIRATORY SYSTEM • Lungs maintain Acid-Base balance by removing CO2 produced during metabolic activities in the body. • CO2 combines with H2O to form Carbonic acid (H2CO3). • Since carbonic acid is unstable, it splits into H+ and HCO3 CO2 + H2O → H2CO3 → H+ + HCO3- • This entire reaction is reversed in lungs when CO2 diffuses from blood into the alveoli of lungs. H+ + HCO3– → H2CO3 → CO2 + H2O • Where CO2 and H2O is blown off by ventilation.
  • 9. RESPIRATORY SYSTEM Sequence of Respiratory events to cope up with Metabolic Acidosis 1. Increase in metabolic activity 2. More CO2 is produced in tissues 3. Concentration of H+ ions also increases 4. State of Acidosis 5. Activation of Chemoreceptors 6. Hyperventilation – Pulmonary ventilation increases 7. Excess of CO2 is evaporated through breathing (Along with Insensible water loss)
  • 10. RENAL MECHANISM Kidneys play an important role in preventing Metabolic Acidosis by excretion of H+ ions through 3 ways – • Bicarbonate mechanism • Phosphate mechanism • Ammonia mechanism
  • 11. H+ RELEASE VIA KIDNEYS – BICARBONATE MECHANISM  For every H+ ion secreted into lumen of tubule, one bicarbonate ion is reabsorbed from the tubule.  In this way, kidneys conserve the HCO3.  This reabsorption of filtered HCO3 is helpful in maintaining pH of the body fluids.
  • 12. H+ RELEASE VIA KIDNEYS – BICARBONATE MECHANISM INTERSTITIAL FLUID TUBULUAR CELL TUBULAR LUMEN NaHCO3 Na+ H+ HCO3- H2CO3 CO2 + H2O H2O + CO2 H2CO3 HCO3- + H+ Na Na+ + HCO3- Na HCO3- NaHCO3
  • 13. H+ RELEASE VIA KIDNEYS – PHOSPHATE MECHANISM  The excess of H+ ions are secreted in renal tubules in the form of Sodium dihydrogen phosphate.  This excess H+ ions added to Urine in form of Sodium Dihydrogen Phosphate makes Urine more acidic.  This happens mainly in distal tubule and collecting duct because of the presence of large quantity of sodium hydrogen phosphate in these segments.
  • 14. H+ RELEASE VIA KIDNEYS – PHOSPHATE MECHANISM INTERSTITIAL FLUID TUBULUAR CELL TUBULAR LUMEN Na2HPO4 Na+ H+ NaHPO4 NaH2PO4 H2O + CO2 H2CO3 HCO3- + H+ Na Na+ + NaHPO4 Na HCO3- NaHCO3
  • 15. H+ RELEASE VIA KIDNEYS – AMMONIA MECHANISM  On of the most important mechanism by which kidneys excrete H+ ions and make the urine acidic.  In the tubular epithelial cells, ammonia is formed when the amino acid glutamine is converted into glutamic acid in the presence of the enzyme glutaminase.  Ammonia (NH3) formed in tubular cells is secreted into tubular lumen in exchange for sodium ion.  Here, it combines with H+ ions to form Ammonium ions (NH4+).
  • 16. H+ RELEASE VIA KIDNEYS – AMMONIA MECHANISM  Thus, here the excess of H+ ions are secreted into renal tubules in the form of Ammonium ions (NH4) resulting in acidification of urine.  For each NH4 ion excreted, one HCO3- is added to interstitial fluid.  This process takes place mostly in the proximal convoluted tubule because glutamine is converted into ammonia in the cells of this segment.  Thus, by excreting H+ and conserving HCO3, kidneys produce acidic urine and help to maintain the acid-base balance of body fluids.
  • 17. H+ RELEASE VIA KIDNEYS – AMMONIA MECHANISM INTERSTITIAL FLUID TUBULUAR CELL TUBULAR LUMEN Ammonia (NH3) H2O + CO2 H2CO3 HCO3- + H+ Na Na+ Na HCO3- NaHCO3 Glutamine Glutamic Acid Ammonia (NH3) H+ Ammonium ions NH4