J1ii: Acid-Base balance

  • For acid-base balance, production = excretion
  • 150 moles of H+ produced every day

Volatile Acid

  • Oxidation of carbs/fats generates CO2
  • The acid is H2CO3 because by Bronsted-Lowry Theory, CO2 has no H+ to donate
  • 15,000 mmol CO2 produced per day
  • Most converted to H2CO3 → CO2 → eliminated by lungs
  • NB: Volatile = lung elimination

All other acids are:

Fixed Acids

  • An acid not excreted by lungs
  • Fixed acids produced ~ 1 mmol / kg / day
  • Due to incomplete metabolism of:
    • CARB → lactate → ~1500 mmol/day
    • PROTEIN → sulphate, phosphate → ~55 mmol/day
    • FATS → ketones → ~12 mol/day
  • These acids require excretion by kidneys
  • Lactic acid is exempt because the 1500 mol of lactic acid produced is oxidised in liver to regenerate HCO3–
  • NB: 30mmol HCO3– lost in faeces per day → this is equivalent to an acid-load because HCO3– is lost
  • Body → 3 lines of defence to acid-base ∆
    1. BUFFERING
    2. RESPIRATORY → alter PaCO2
    3. RENAL → alters HCO3– excretion

Acid Base Homeostasis maintains plasma [H+] = 35 – 45 mmol/L OR pH 7.35 – 7.45

  • Ultimately → correction of acid-base derangement is through correction of 1° disorder

Buffer Systems

  • A BUFFER is a substance with a capacity to bind/release H+ to minimise pH ∆
  • Buffer mixtures consist of weak acid & its conjugate base
  • Buffers are most effective at their pKa, where they are 50% ionised!
    • Target pH ECP = 7.4
    • Target pH ICP = 6.8
  • Buffering power determined by:
    1. pKa
    2. Concentration of buffer
  • Buffers classified as intracellular or extracellular

INTRACELLULAR

EXTRACELLULAR

Hb

HCO3–

Proteins

Hb

Phosphate

Plasma proteins

 

Phosphate

Extracellular Buffers

HCO3–

  • pKa 6.1
  • [ ] : highest, plasma [HCO3–] = 24mmol/L

CO2 + H2O ↔ (CA) H2CO3 ↔ H+ + HCO3–

  • HCO3– production occurs in RBC where CA is present (also present in renal tubule cells & alveolar cells)
  • Diffuses out & buffers ECF
  • Most powerful because although pKa v. different from target pH, such high [HCO3–] & also, ‘open-ended’
  • Open-ended because both elements (CO2 & HCO3–) can be regulated by other acid-base control mechanisms (lungs, renal)
  • NB: Can only buffer metabolic acids → cannot buffer H2CO3!

Hb

  • pKa 6.8
  • [ ] : 15g / dL
  • Actually intracellular but considered extracellular buffer because resent in ‘blood’, not tissue
    1. Each Hb has 3.8 histidine residues & pKa 6.8
    2. Hb present at high [ ]
    3. DeoxyHb pKa = 7.9

OxyHb pKa = 6.6

∴ A better buffer because closer to physiological pH

      • DeoxyHb dissociates greater OxyHb

    4. CO2 & H2CO3 can combine with terminal amine groups of Hb to form carbamino compounds (carrying 15% blood CO2)

Plasma proteins

  • pKa 6.8 (of imidazole of histidine residue)
  • [ ] : 7g / dL (half that of Hb)
  • Imidazole groups of histidine residues are the only buffer groups in proteins that are significant because pKa 6.8 close to physiological pH
  • Free amino & carboxyl terminals can also buffer H+, but amino pKa 9 & carboxyl pKa 2 → ∴ not important at physiological pH

Phosphate

    • pKa 6.8
    • [ ] : low in plasma, significant in urine

H2PO4– ⮂ H+ + HPO42-

  • [Phosphate] in plasma is v low
  • In urine important because should be no protein in urine & [phosphate] in urine is high & tubule fluid acidic → ∴closer to phosphate pKa

Intracellular Buffers

  • Hb – as above
  • Proteins
    • Imidazole groups of proteins buffer H+
    • Significant [ ] intracellularly of 6mmol/L
    • Cell pH 6.8 – 7.1 → ∴ closer to imidazole pKa 6.8
    • Very effective!
  • Phosphate
    • significant [ ] intracellularly 6 mmol/L
    • pKa 6.8 v. close to intracellular pH 6.8 – 7.1

Urinary Buffers

(See 14B12 answer)