Acid–Base Buffers — Body Buffer Systems

Buffer

• Weakly ionised acid or base in equilibrium with its full ionised salt
• A buffer can “resist” change in pH by absorbing or releasing H+ ions
• Works best when pKa is closest to the target pH (7.4)
• Isohydric Principle
  • All buffer systems which participate in defence of acid-base changes are in equilibrium with each other. There is after all only one value for [H⁺] at any moment. This is known as the Isohydric Principle.

Effectiveness:

• buffer pKa (most effective if pKa = pH of carrying solution)
• pH of carrying solution
• amount of buffer present
• open (physiological) vs closed (chemical) system

Buffer Systems by site

Buffer Systems

Protein (Intracellular)

• pKa of imidazole group is 6.0
• pKa of the histadine residues themselves = 6.8
• Protein buffer ability is proportional to Histadine residue content.

Haemoglobin (Blood)

• Protein buffering system
• Important intracellular buffer in RBC
  • Exists as weak acid – HHb and potassium salt KHb.
  • Hb a pK_a of 8.2 in deoxy form and 6.6 in oxyHb
  • Buffering capacity due to imidazole residues on 38 histidine residues on Hb molecule
    • pKa of residues 6.8 à close to physiological pH

• Also important in extracellular buffering (following bicarbonate buffer system)
  • Due to fast equilibration of HCO₃^– (Hamburger Shift)
  • Band3 Transporter (HCO₃^–/Cl^– antiporter)
  • Allows carbonic anhydrase reaction to take place by limiting build-up of HCO₃^– (la chatelier principle)

• Formed in erythrocytes as a tetramer of 4 subunits
• Hb ~ 6 times the number of histadine (38) residues compared with albumin. (3-6x buffering capacity)
• Hb is in much greater concentrations than any other protein (15 g/dL vs 7 g/dL)
• For each mmol OxyHb, 0.7mmol H⁺ is buffered and 0.7mmol of CO₂ can enter circulation without a change in pH
• Available at high concentrations in RBC
• Isohydric exchange
  • the buffer system (HHbO₂-HbO₂-) is converted to another more effective buffer (HHb-Hb-) exactly at the site where an increased buffering capacity is required
  • Deoxyhaemoblobin is a much more effective buffer
  • oxygen unloading increases the amount of deoxyhaemoglobin and this better buffer is produced at exactly the place where additional H⁺ are being produced because of bicarbonate production for CO₂ transport in the red cells.

Bicarb (Plasma, Interstitium, Urine (minimal))

• Catalysed by carbonic anhydrase (slow where CA is absent (plasma))
• Open at both ends
• Bicarb regulation at kidneys
• CO₂ regulation at lungs

Ammonia (Urine)

Equlibrium between ammonia and ammonium

Steps:

• Glutamine enters PCT cells
  • 20% from filtrate
  • 80% from peritubular capillaries
• Ammonia (NH3) produced from glutamine in PCT by glutaminase secreted into lumen
• Reabsorbed in TAL of LoH
• Diffuses into peritubular cells of CD down conc Grad
• H+ secreted into lumen of CD
• Combines with ammonia to form ammonium
• Ammonium positive charge prevents reabsorption
• Thus “excess hydrogen can be secreted with ammonium”

Phosphate (Urine, Bone)

Effect in urine is limited due to:

• Minimal urinary pH is 4.5 → equation B is >99% ionised → of little use.
• Requires filtered PO4 → Normally low levels.
• Depends on Diet and PTH.
• Where H is secreted in distal tubules, there is minimal PO4 excretion

CaCO3 (Bone)

• Important in chronic metabolic acidosis
• Release of calcium carbonate from bone is the most important buffering mechanism involved in chronic metabolic acidosis.

Please Note: This answer is viewed from the Traditional approach to Acid-Base theory. Alternative (physicochemical approaches) deemphasise bicarb due to its equilibrium with water and relatively low concentration compared with the strong ions.

Gladwin / Sakurai / JC 2020

Answer by Gladwin, JC, Sakurai