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Biochemistry of acidobasic regulations Alice Skoumalová Body water compartments: 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+) – Cl42 mmol/l 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 Acids in the blood: The Henderson-Hasselbalch equation Buffer Titration curve for acetic acid Equivalents of OH- added Body buffers: Blood ISF HCO3- ICF HCO3-/H2CO3+ CO2 64% hemoglobin 29% proteins 6% proteins proteins HPO42-/H2PO4- 1% phosphates phosphates - HCO3- Plasma: mixed buffer system Major physiological buffers: Buffer pK concentration HCO3/CO2 6,1 24 mmol/l HPO42-/H2PO4- 6,8 1 mmol/l Proteins 4-12 5,6 – 7,0 histidine N-term. amino groups 7,6 – 8,4 15 mmol/l The bicarbonate buffer system: CO2 + H2O in the body – an open system 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) Phosphate buffer: intracellular fluids (0,1M) Protein buffer: intracellular fluids (and also extracellular) Hemoglobin buffer: in erythrocytes + Bohr effect Buffers in an organism Co-operation of the body buffers: Carbon dioxide transport: CO2 in the blood: 1. as HCO3- (ionization of H2CO3) CO2 + 75-85 % H2O H2CO3 H+ + HCO3- erythrocytes (carbonate dehydratase) 2. as carbamino groups (CO2 reacts with amino groups of proteins) 3. dissolved CO2 Partial pressures air-inspiration pO2 (kPa) 21 pCO2 (kPa) 0,03 10-15 % 5-12 % air-expiration 15,3 4,4 arterial blood 12 – 13,3 4,6 – 6 venous blood 4,6 - 6 5,3 – 6,6 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) 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) 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 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- The major indicators of acid-base imbalance (arterial blood): Measured: pH = 7,4 ± 0,04 pCO2 = 5,3 ± 0,5 kPa Hb, pO2 Calculated: [HCO3-] = 24 ± 3 mmol/l [H+] = 40 nmol/l = 40 torr = 1,2 mmol/l BE (base excess) = 0 ± 2,5 mmol/l NBB (buffer base) (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) (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-] 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 The maintenance of pH: Correction of the acid-base disorders: Buffer reactions Compensations Corrections processes in which one system compensates the alteration of the other one Diagram of Henderson-Hasselbalch equation showing compensations for acid-base disorders: 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 ! physiological acute compensation -lungs -hyperventilation [HCO3-] 24 mmol/l ↓ pCO2 5,3 kPa N ↓ [HCO3-]/[H2CO3+CO2] 20 : 1 < 20 : 1 ≤ 20 : 1 pH 7,34 – 7,44 < 7,34 ≤ 7,4 Metabolic alkalosis 1. Loss of H+: - vomiting, gastric lavage 2. Input of HCO3-: - bicarbonate overdosing 3. Loss of Cl- and K+: - diuretics physiological acute compensation -lungs -hypoventilation [HCO3-] 24 mmol/l pCO2 5,3 kPa N [HCO3-]/[H2CO3+CO2] 20 : 1 > 20 : 1 ≥ 20 : 1 pH 7,34 – 7,44 > 7,44 ≥ 7,4 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) physiological acute compensation -kidney - excretion of H2PO4- and NH4+ - resorption of HCO3- [HCO3-] 24 mmol/l N, pCO2 5,3 kPa [HCO3-]/[H2CO3+CO2] 20 : 1 < 20 : 1 ≤ 20 : 1 pH 7,34 – 7,44 < 7,34 ≤ 7,4 Respiratory alkalosis Hyperventilation: - mechanical ventilation - respiratory center stimulation: from CNS (hysteria, anxiety, infection), drugs (salicylates), from thermoregulation center (fever, physical effort) physiological acute compensation -kidney - excretion of HCO3- [HCO3-] 24 mmol/l N, ↓ ↓ pCO2 5,3 kPa ↓ [HCO3-]/[H2CO3+CO2] 20 : 1 > 20 : 1 ≥ 20 : 1 pH 7,34 – 7,44 > 7,44 ≥ 7,4 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