Biochemistry of acidobasic regulations

1. Biochemistry of acidobasic regulations Alice Skoumalová, Bruno Sopko

2. Body water compartments:

3. Diagram showing chemical constituents of the three fluid compartmens: Derived values: AG(anion gap) (Na+ + K+) - (Cl- + HCO3-) 14-18 mmol/l SID(strong ion difference) (Na+ + K+) – Cl- 42 mmol/l

4. pH lemon 2,3 orange 3,7 sceletal muscle c. 6,9 prostatic c. 4,5 erythrocytes 7,3 trombocytes 7,0 osteoblasts 8,5 blood 7,36 – 7,44 gastric juice 1,2 – 3 pancreat. juice 7,5 – 8 bile 6,9 – 7,7 urine 4,8 - 8

5. Acids in the blood:

6. Buffer The Henderson-Hasselbalch equation Titration curve for acetic acid Equivalents of OH- added

7. Body buffers:

8. Plasma: • mixed buffer system Major physiological buffers:

9. The bicarbonate buffer system: in the body – an open system CO2 + H2O H2CO3 H+ +HCO3- erythrocytes (carbonic anhydrase) The Henderson-Hasselbalch equation for the bicarbonate buffer system: The pKa of carbonic acid – 3,8 But: carbonic acid is replenished from CO2 in body fluids and air (the concentration of dissolved CO2 is 400 times greater than that of carbonic acid) dissolved CO2 is in equilibrium with the CO2 in the alveoli (the availability of CO2 - breathing) the pKa combines the hydratation constant of CO2 with the chemical pKa - a modified version of the H.-H. equation: s - a conversion factor (0,23 in kPa 0,03 in Torr)

10. Phosphate buffer: • intracellular fluids (0,1M) • Protein buffer: • intracellular fluids (and also extracellular) • Hemoglobin buffer: • in erythrocytes • + Bohr effect

11. Buffers in an organism Co-operation of the body buffers:

12. Carbon dioxide transport: CO2 in the blood: 1. as HCO3-(ionization of H2CO3)75-85 % 2. as carbamino groups (CO2 reacts with amino groups of proteins)10-15 % 3. dissolved CO25-12 % Partial pressures air-inspiration air-expiration arterial blood venous blood pO2 (kPa) 21 15,3 12 – 13,3 4,6 - 6 pCO2 (kPa) 0,03 4,4 4,6 – 6 5,3 – 6,6 CO2 + H2O H2CO3 H+ +HCO3- erythrocytes (carbonate dehydratase)

13. O2 and CO2 transport: Bohr effect (the increase in acidity of hemoglobin as it binds O2, releases H+) Isohydric carriage of CO2(Hb‘s ability to take up H+ with no change in pH through Bohr effect) Chloride shift (the exchange of Cl- and HCO3- between the plasma and the erythrocyte)

14. Structure of a nephron: Urine pH 4,8 – 8 (most acids must be in some form other than H+) 60 mmol H+ / day Urine buffers: phoshate NH3 The physiological levels of the metab. acids: lactate – 0,6-2,4 mmol/l ketone bodies – 3-20 mg/l (0,2mmol/l)

15. The kidney in acid-base balance: Possibilities of H+ excretion: 1. Reaction with HCO3- (reabsorption of NaHCO3) 2. Reaction with HPO42- (titratable acidity of the urine) 3. Reaction with NH3

16. The liver in acid-base balance: In acidosis: induction of the glutamine synthesis and renal glutaminase (increased excretion of NH4+) In alkalosis: induction of the urea synthesis, excretion of HCO3-

17. The major indicators of acid-base imbalance (arterial blood): Measured: pH = 7,4 ± 0,04 [H+] = 40 nmol/l pCO2= 5,3 ± 0,5 kPa = 40 torr = 1,2 mmol/l Hb, pO2 Calculated:[HCO3-] = 24 ± 3 mmol/l BE (base excess) = 0 ± 2,5 mmol/l (the amount of acid that would have to be added to the blood to titrate it to pH 7,4 at a pCO2 of 5,3 kPa at 37 °C) NBB (buffer base) (the concentration of all bases in the blood at the standard conditions) plasma 42 ± 3 mmol/l blood 48 ± 3 mmol/l AG (anion gap) = 14-18 mmol/l AG = [Na+] + [K+] - [Cl-] - [HCO3-]

18. Classification of the acid-base disorders: Acidosis: a process leading to the accumulation of H+ in the body Alkalosis: a process leading to a decrease in H+ concentration in the body Two components of acid-base balance: respiratory, metabolic acute stage x compensated four main disorders x mixed acidemia x acidosis alkalemia x alkalosis

20. The maintenance of pH: Correction of the acid-base disorders: Buffer reactions Compensations - processes in which one system compensates the alteration of the other one Corrections

21. Diagram of Henderson-Hasselbalch equation showing compensations for acid-base disorders:

22. Metabolic acidosis (MAc): • 1. Increased production of H+: -lactasidosis (hypoxia, intensive muscular work, ethanol) • -ketoacidosis (starvation, diabetes) • -acid retention (renal failure) • 2. Exogenous intake of H+: - methanol, ethylene glycol intoxication, salicylate poisoning • 3. Loss of HCO3-: -diarrhoea, burns, renal tubular disorders, diuretics • 4. Relative dilution of HCO3-: -excessive infusion of isotonic solutions !

24. Metabolic alkalosis 1. Loss of H+: - vomiting, gastric lavage 2. Input of HCO3-: - bicarbonate overdosing 3. Loss of Cl- and K+: - diuretics

26. Respiratory acidosis Hypoventilation: - depression of the respiratory center (opiates, sedatives, narcotics, CO2) - failures -ventilation, diffusion, perfusion (respiratory diseases) -gass transport (anemia, circulatory failure, CO intoxication) -gass exchange between the blood and tissues (cyanide intoxication) -neuromuscular junction (pharmaceuticals, nikotine, botulin intoxication) -neural transmission (spinal cord injuries)

28. Respiratory alkalosis Hyperventilation: - mechanical ventilation - respiratory center stimulation: from CNS (hysteria, anxiety, infection), drugs (salicylates), from thermoregulation center (fever, physical effort)

30. Mixed acid-base disorders 1. Antagonistic – metabolic acidosis + metabolic alkalosis • acid-base indicators are often physiological (hypochloremia discovers MAlk) 2. Synergic – e.g. metabolic acidosis + respiratory acidosis Diagnosis: electrolytes, proteins, lactate, calculation from the iontogram, symptoms Study material: Liebrman and Marks, Mark‘s Basic Medical Biochemistry a Clinical Approach, 2009