1. CO 2 transport in blood: 1. Dissolved approx 7% 2. Combined with Hemoglobin10–20% 3. As bicarbonate83%

2. CO 2 red cell CO 2 + Hb carbamino-hemoglobin CO 2 + R—N H H H COOH Note: not the same combining site as O 2 reaction is  in deoxygenated Hb reaction is relatively slow  quantitatively not as important as the next slide

3. CO 2 red cell CO 2 + H 2 O H 2 CO 3 HCO – + H + HHb H + + Hb – plasma H2OH2O Cl – carbonic acid carbonic anhydrase HCO 3 – ie Combination of CO 2 + H 2 O produces a weak acid – buffered by Hb Effect of O 2 on CO 2 transport: Deoxygenated Hb is a better buffer than HbO 2  deoxygenated Hb has a greater carrying capacity for CO 2 (Haldane effect)

4. Haldane Effect % CO 2 in blood (ml / 100 ml blood) 35404550 55 45 B Lung capillaries PO 2 = 100 mmHg PCO 2 (mmHg) A PO 2 = 40 mmHg Tissue capillaries Carrying capacity for CO 2 is low when PO 2 is high = Lungs ~easier unloading of CO 2 Carrying capacity for CO 2 is high when PO 2 is low = Tissues ~easier loading of CO 2

5. 1. CO 2 carrying capacity >> O 2 carrying capacity 2. CO 2 carrying capacity  almost linearly with  PCO 2 in physiological range.

6. Buffers: HA H + + A – Law of mass action: [H + ] [A – ] [HA] = K (2) now pH = negative log of [H + ] rearranging (2) pH = pK + log [A – ] [HA] Henderson- Hasselbach equation [H + ] = 0.00004 mmol/L pH = 7.4 range 7.0 — 7.7

7. R Buffers (biological): Proteins: 1. RCOOH RCOO  + H + ~large conc RNH3 + RNH2 + H + Collectively Protein Protein  + H + 2. pK 7.4 Hb (histidine) - 36 per molecule NH + HCHC H N H C C R N HCHC H N H C C + H + Deoxygenated Hb is a better buffer than HbO 2

8. Phosphate: H 2 PO 4  H + + HPO 4 2  pH = pK + log [A – ] [HA] pK 6.8

9. H 2 CO 3 H + + HCO 3 – pH = pK 1 + log [HCO 3 – ] [H 2 CO 3 ] but CO 2 + H 2 O H 2 CO 3 so [H 2 CO 3 ] is proportional to [CO 2 ] pH = pK + log [HCO 3 – ] [H 2 CO 3 ] = pK 1 + log [HCO 3 – ] 0.03 x PCO 2 CO 2 at 37  C dissolves at 0.03 mmol/L/mmHg pK 1 = 6.1

11. [HCO 3 – ] regulated by kidneys cf PCO 2 regulated by lungs. Isohydric principle: all buffer systems are in equilibrium with one another: e.g. pH = pK 1 + log [A 1 – ] [HA 1 ] = pK 2 + log [A 2 – ] [HA 2 ] = etc pH = a constant + kidneys lungs

12. Respiratory disturbances may cause changes in pH e.g.  ventilation   PCO 2 and pH  respiratory acidosis HCO 3 – retention by kidney tends to return pH to near normal Renal compensation takes days to occur

13. Hyperventilation  PCO 2  cerebral vaso-constriction lightheaded / dizziness + Alkalosis Ca 2+ + albumin Ca—Alb and  Ca 2+  spontaneous firing nerves so  pH   Ca 2+ pins and needles parasthesiae

14. Respiratory system may also compensate for other problems of acid base balance: Metabolic acid eg lactic acid, ketones or losses HCO 3 – from severe vomiting of intestinal contents severe diarrhoea injection of H +  pH  ventilation  CO 2 tends to return pH to near normal

15. Summary CO 2 transport and acid base balance CO 2 in blood dissolved carbamino—Hb bicarbonate Haldane effect  CO 2 carried if PO 2 is low biological buffers respiratory disturbances of acid-base balance respiratory compensation for acid-base disturbances