1. Acid-base balance and its disorders Figure is found on http://www.mfi.ku.dk/ppaulev/chapter17/Chapter%2017.htm Pavla Balínová

2. Definitions Acid (HA) is defined as a compound that can release a proton (H + ) Acidosis (acidaemia) is defined as a disorder with accumulation of acids in the extended ECV. The pH in the arterial blood is < 7.35 Base (B - ) can bind H + Alkalosis (alkalaemia) is defined as a condition with accumulation of bases in the extended ECV. The pH of the arterial blood is › 7.45 Buffer is a mixture of compounds which have the ability to absorb small amounts of H + or OH - with very little change of pH. pH = pK + log c s / c A

3. Proton concentration and pH Normally, the [H + ] of arterial blood of humans is maintained by the lungs, kidneys and liver within the range of 40  5 nM, corresponding to a pH of 7.35 - 7.45. pH = - log (40 x 10 -9 mol/L ) = 7.4 A pH of 6.8 - 6.9 is not sustainable for long, and the patient is dying in a state of coma. Figure is found on http://www.mfi.ku.dk/ppaulev/chapter17/Chapter%2017.htm

4. Production of acids ● CO 2 is a potential acid as H 2 CO 3, and because the lungs eliminate it, it is called a volatile acid. Production of CO 2 is up to 24 mol daily. ● Non-volatile acids: a) organic acids are continually produced as a by-product of metabolism: - anaerobic glycolysis in muscles and ery → l actic acid → lactate + H + - ketogenesis → acetoacetic acid → acetoacetate + H + → β-hydroxybutyric acid → β-hydroxybutyrate + H + - lipolysis → TAG → 3 FA + glycerol + 3 H + - urea synthesis in liver: CO 2 + 2 NH 4 → urea + H 2 O + 2 H + Under normal conditions, these acids are completely metabolized to CO 2 and H 2 O. They have no effect on proton balance. b) inorganic acids: excretion by kidneys H 2 SO 4 → HSO 4 - + H + H 3 PO 4 → HPO 4 2- + H + Note: H + are also released from acids in the diet e. g. citric acid, ascorbic acid

5. Consumption of acids (protons) gluconeogenesis: 2 lactate + 2 H + → Glc oxidation of neutral AA and Glu and Asp

6. The body maintains ECF physiologic pH by buffers Bicarbonate buffer HCO 3 - / CO 2 (53%) Hemoglobin (Hb) – in ery (35%) Plasma proteins (mainly albumin) (7%) Phosphate buffer HPO 4 2- / H 2 PO 4 - (3%) NH 3 /NH 4 + and HPO 4 2- /H 2 PO 4 - are the most important urinary buffer systems. About 30 mmol of NH 4 + is excreted in the daily urine, but the excretion is controlled during acid-base disorders.

7. HCO 3 - /CO 2 system is an effective open buffer system HCO 3 - and CO 2 are present in ratio of about 20 : 1. CO 2 is dissolved in the plasma and it is constantly exchanging with CO 2 in the gas phase of the alveoli of the lungs. Henderson-Hasselbach equation for HCO 3 - /CO 2 system: pH = pK + log [HCO 3 - ] / [H 2 CO 3 ] pH = pK + log [HCO 3 - ] / pCO 2 x α pH = 6.1 + log 24 / 40 x 0.03 (pCO 2 = 40 mmHg → factor α = 0.03) pH = 6.1 + log 20 pH = 6.1 + 1.3 = 7.4 Conversion: 1 kPa = 7.5 mmHg 1 mmHg = 133.22 Pa

8. CO 2 (pCO 2 ) elimination is controlled by lungs (respiratory system). It takes 1 – 3 min to respond to changes in pH and effect changes in the pH. ↑ ventilation → ↓ pCO 2 → alkalinization ↓ ventilation → ↑ pCO 2 → acidification HCO 3 - elimination is controlled by kidneys. It takes several hours to days for urinary system to compensate for changes in pH. Liver: CO 2 + 2 NH 4 → urea + 2 H + + H 2 O NH 4 + + Glu → Gln + H 2 O

9. Laboratory analysis of ABB state Determination of pH, HCO 3 -, pCO 2, pO 2 and BE Determination of concentration of cations (Na +, K +, Ca 2+, Mg 2+ ), concentration of anions (Cl -, lactate) and metabolites (urea, creatinine, ketone bodies) Normal values of: HCO 3 - = 22 – 26 mmol/L BE = from – 2.5 to + 2.5 mmol/L BE (base excess) is defined as the amount of acid that would be added to blood to titrate it to pH 7.4 at pCO 2 = 40 mmHg. positive value = base excess negative value = base deficit (BD)

10. Astrup determination is based on measurement of pH, pCO 2, pO 2 in blood It is measured by special electrodes in automatic apparatus. An arterial blood sample is used. Normal values of arterial blood: pH = 7.35 – 7.45 pCO 2 = 4.8 – 5.8 kPa = 36 – 43.5 mmHg pO 2 = 9.8 – 14.2 kPa = 73.5 – 106.5 mmHg These values are measured directly. Concentration of HCO 3 - and BE are calculated from measured values by software in automatic apparatus.

11. Astrup apparatus Glass electrode – pH Membrane electrode – pCO 2 Clark´s oxygen electrode – pO 2

12. Anion gap (AG) AG represents the plasma anions which are not routinely measured (albumin, phosphates, sulphates, organic anions). AG is calculated as follows: AG = (Na + + K + ) – (HCO 3 - + Cl - ) The sum of the concentrations of Na + and K + is greater than the sum of concentrations of HCO 3 - and Cl -. Difference is called as a anion gap. Normal values of AG: 16 – 20 mmol/L AG is calculated in case of metabolic acidosis.

13. ABB disorders ACIDOSIS respiratory metabolic ALKALOSIS respiratory metabolic

14. Compensation of ABB disorders Metabolic disorder is compensated by respiration and conversely Correction of ABB disorders Metabolic disorder is corrected by metabolic processes

15. Respiratory acidosis (RAc) RAc is caused by hypoventilation (or breathing of CO 2 containing air). Hypoventilation is associated with an impaired ability to eliminate CO 2, whereby pCO 2 increases and the accumulated CO 2 reduces the arterial pH. Causes: airway obstruction, neuromuscular disorders, disorders of CNS, opiate poisoning Compensation: ↑ reabsorption of HCO 3 - is performed by kidneys (proximal tubule)

16. Respiratory alkalosis (RAl) The hyperventilation is disproportionately high compared to the CO 2 production, whereby the pCO 2 falls and the pH increases Causes: CNS injury, salicylate poisoning, fever, … Other typical cases are the anxious patient during an attack of asthma or the hysterical hyperventilation in neurotic patients. Compensation: ↑ renal excretion of HCO 3 - → plasma pH decreases toward normal pH

17. Metabolic acidosis (MAc) ● MAc is caused by accumulation of acids in ECF. ● negative BE Causes: hypoxia is a lack of O 2 in tissues → anaerobic glycolysis produces lactic acid → lactate acidosis overproduction of ketone bodies → ketoacidosis (DM, starvation) ingestion of methanol or ethylene glycol diarrhoea Compensation: 1 st step: buffering of excess of H + by HCO 3 - 2 nd step: respiratory compensation by hyperventilation 3 rd step: renal correction → ↑ excretion of H + in urine

18. Metabolic alkalosis (MAl) MAl is caused by a primary accumulation of bases in ECF. Both the [bicarbonate] and the [non-carbonic buffer base] are increased, so the BE is increased. Causes: ingestion of alkaline drugs (e. g. NaHCO 3 ) prolonged vomiting → loss of H + Compensation: 1 st step: buffering of excess of HCO 3 - 2 nd step: respiratory compensation by hypoventilation → ↑ pCO 2 in alveoli and arterial blood 3 rd step: renal correction: ↑ excretion of HCO 3 - in urine

19. Case report 1 A young man was injured in the chest from a car accident. Instrument ventilation was started. plasma measured values HCO 3 - 25 mmol/L Astrup pH 7.24 pCO 2 60 mmHg = 8 kPa pO 2 60 mmHg = 8 kPa Type of ABB disorder??

20. Solution of case report 1 Respiratory acidosis without compensation. Hypoventilation is a cause of ↑ pCO 2 in arterial blood.

21. Case report 2 A 45 year old man was admitted with a history of persistent vomiting. He had a long history of dyspepsia. Examination revealed dehydration and shallow respiration. plasma measured values K + 2.8 mmol/L HCO 3 - 45 mmol/L urea 34 mmol/L Astrup pH 7.56 pCO 2 54 mmHg = 7.2 kPa Type of ABB disorder??

22. Solution of case report 2 Metabolic alkalosis is a result of persistent vomiting loss of H + and dehydration. Small amount of urine (lower diuresis) is a cause of higher concentration of urea in blood. Respiratory compensation was started (hypoventilation) → ↑ pCO 2. Lower K + concentration indicates alkaleamia.

23. Case report 3 A 23 year old mechanic was admitted to hospital 12 hours after drinking antifreeze. He was given 400 mmol of HCO 3 - with a little effect. Dialysis was started but he went to shock and died 12 hours after admission. plasma admission dialysis 4 hours Na + 137 mmol/L 145 mmol/L K + 5.4 mmol/L 4.9 mmol/L Cl - 95 mmol/L 87 mmol/L HCO 3 - 4 mmol/L 5 mmol/L Glc 2.5 mmol/L Astrup pH 6.95 7.05 7.29 pCO 2 15 mmHg 16 mmHg 25 mmHg = 3.33 kPa Type of ABB disorder??

24. Solution of case report 3 Metabolic acidosis is due to antifreeze poisoning. Antifreeze contains ethylene glycol which is oxidized to oxalic acid in body. After 12 hours, the respiratory compensation was started → hyperventilation → ↓ pCO 2. Cause of his death is a renal failure due to oxalates in kidneys.

25. Case report 4 A young woman was admitted 8 hours after taking an overdose of aspirin. plasma measured values HCO 3 - 12 mmol/L Astrup pH 7.53 pCO 2 15 mmHg = 2 kPa Type of ABB disorder??

26. Solution of case report 4 Respiratory alkalosis is due to overdose of aspirin. pCO 2 is decreased because patient has a hyperventilation. Renal compensation was started → excretion of HCO 3 -.