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CO 2 transport in blood: 1. Dissolved approx 7% 2. Combined with Hemoglobin 10–20% 3. As bicarbonate 83%. red cell. CO 2 + Hb carbamino-hemoglobin. CO 2. H. H. R—N. R—N. CO 2 +. H. COOH. Note: not the same combining site as O 2
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CO2 transport in blood: 1. Dissolved approx 7% 2. Combined with Hemoglobin 10–20% 3. As bicarbonate 83%
red cell CO2 + Hb carbamino-hemoglobin CO2 H H R—N R—N CO2 + H COOH • Note: • not the same combining site as O2 • reaction is in deoxygenated Hb • reaction is relatively slow quantitatively not as important as the next slide
carbonic anhydrase red cell carbonic acid CO2 CO2 + H2O H2CO3 HCO– + H+ plasma HHb H+ + Hb– H2O Cl– HCO3– ie Combination of CO2 + H2O produces a weak acid – buffered by Hb Effect of O2 on CO2 transport: Deoxygenated Hb is a better buffer than HbO2 deoxygenated Hb has a greater carrying capacity for CO2 (Haldane effect)
Tissue capillaries A PO2 = 40 mmHg Haldane Effect 55 % CO2 in blood (ml / 100 ml blood) 50 PO2 = 100 mmHg B Lung capillaries 45 PCO2 (mmHg) 35 40 45 50 Carrying capacity for CO2 is low when PO2 is high = Lungs ~easier unloading of CO2 Carrying capacity for CO2 is high when PO2 is low = Tissues ~easier loading of CO2
1. CO2 carrying capacity >> O2 carrying capacity 2. CO2 carrying capacity almost linearly with PCO2 in physiological range.
Buffers: HA H+ + A– Law of mass action: [H+] [A–] (2) = K [HA] now pH = negative log of [H+] rearranging (2) [A–] Henderson-Hasselbach equation pH = pK + log [HA] [H+] = 0.00004 mmol/L pH = 7.4 range 7.0 — 7.7
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 HC HC + H+ H N NH+ H N N H C C H C C R R • Deoxygenated Hb is a better buffer than HbO2
Phosphate: H2PO4 H+ + HPO42 pK 6.8 [A–] pH = pK + log [HA]
[HCO3–] [HCO3–] pH = pK1 + log pH = pK + log [H2CO3] [H2CO3] H2CO3 H+ + HCO3– but CO2 + H2O H2CO3 so [H2CO3] is proportional to [CO2] [HCO3–] = pK1 + log 0.03 x PCO2 CO2 at 37C dissolves at 0.03 mmol/L/mmHg pK1= 6.1
[HCO3–] regulated by kidneys cf • PCO2 regulated by lungs. • Isohydric principle: • all buffer systems are in equilibrium with one another: e.g. [A1–] [A2–] pH = pK1 + log = pK2 + log = etc [HA1] [HA2] kidneys pH = a constant + lungs
Respiratory disturbances • may cause changes in pH • e.g. ventilation PCO2 and pH • respiratory acidosis • HCO3– retention by kidney • tends to return pH to near normal Renal compensation takes days to occur
Hyperventilation PCO2 cerebral vaso-constriction lightheaded / dizziness + Alkalosis Ca2+ + albumin Ca—Alb and Ca2+ spontaneous firing nerves so pH Ca2+ pins and needles parasthesiae
Respiratory system may also compensate for other problems of acid base balance: • Metabolic acid eg lactic acid, ketones • or losses HCO3– • from severe vomiting of intestinal contents • severe diarrhoea • injection of H+ pH ventilation tends to return pH to near normal CO2
Summary • CO2 transport and acid base balance • CO2 in blood • dissolved • carbamino—Hb • bicarbonate • Haldane effect CO2 carried if PO2 is low • biological buffers • respiratory disturbances of acid-base balance • respiratory compensation for acid-base • disturbances