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 ∆
- BUFFERING
- RESPIRATORY → alter PaCO2
- 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:
- pKa
- 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
- Each Hb has 3.8 histidine residues & pKa 6.8
- Hb present at high [ ]
- 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)