Acid-Base Balance James Howard

Acid-Base Balance [H+] maintained at 35-45 nmol/L pH 7.35 – 7.45 > 120nmol or <20nmol incompatible with life Affecting Enzyme activity Hydrogen ion transporters (N.B K+) Osmolality K+ Cell H+

Acid Production Fixed (non-volatile) acids Mainly from oxidation of amino acids 60 mmol/day  4 mmol/L Respiratory (volatile) acids Carbonic acid (H2CO3) In a state of equilibrium with CO2

Balance Usually acid excretion = acid production, through Buffering – Practically instantaneous Respiratory control – Minutes Renal response – Days/weeks (The liver) Cliché

Buffering Dogs infused with 14mmol/L H+ Huge buffering capacity Rise of 36 nmol/L observed Huge buffering capacity Base excess – acid required to blood pH to 7.4 Bicarbonate mainly responsible in ECF HCO3- + H+  CO2 + H2O Catalysed by Carbonic anhydrase Amongst fastest enzymes in nature Also plasma proteins, phosphates, Hgb

But... Buffering relies on a steady supply of base Buffering system cannot handle changes in several variables pKa of the bicarbonate system is 6.1 Fortunately, the body is not a closed system!

(CO2 + H2O  H2CO3  H+ + HCO3- ) CO2 + H2O  H+ + HCO3- In a Nutshell (CO2 + H2O  H2CO3  H+ + HCO3- ) CO2 + H2O  H+ + HCO3- Buffering Controlled by lungs Controlled by kidneys

Respiratory Control ΔpCO2  ΔpH Rapid– good circulation + CO2 lipid soluble Typically pCO2 drives respiratory control via pH 1A physiology with CO2 absorber CSF has little buffering capacity BBB impermeable to protein, H+, HCO3- CO2 diffuses across BBB – proportional ΔpH Chemoreceptors input to medullar respiratory centre N.B Roles of peripheral chemoreceptors

Gratuitous Schematic H+ + HCO3- CO2 HCO3- Albumin CO2 H+ CO2 H+ HCO3- Ventrolateral medulla H+ + HCO3- CSF CO2 HCO3- Albumin CO2 H+ Blood CO2 H+ HCO3- Albumin

But... We can buffer changes in pH We can blow CO2 off to reduce H+ At the expense of HCO3- But what if ↑pCO2 – respiratory acidosis ↑ H+ - metabolic acidosis AND how do we (re)generate our HCO3-?

Renal Regulation So many different hypotheses, I’ll go with: We form ammonium (NH4+) and bicarbonate We reabsorb them both We secrete what we don’t want

Renal Regulation Glutamine  NH4+ + HCO3- Reabsorption of HCO3- Reabsorption of NH4+ Secretion of NH4+

The Liver Produces ~20% of daily CO2 ( HCO3- + H+) Protons can be consumed & bicarbonate formed Metabolism of organic anions (citrate, lactate, ketones etc.) Key in lactic acidosis etc. Bases can be eliminated in the urea cycle 2NH4+ + 2HCO3-  H2N-CO-NH2 + 3H2O + CO2 Inhibited by pH Produces plasma proteins, important for buffering

(CO2 + H2O  H2CO3  H+ + HCO3- ) CO2 + H2O  H+ + HCO3- In a Nutshell (CO2 + H2O  H2CO3  H+ + HCO3- ) CO2 + H2O  H+ + HCO3- Buffering Controlled by lungs Controlled by kidneys The Liver

Miss AM 20 y/o female Admitted with a crushed chest High [H+] & pCO2 Bicarbonate not increased ABG H+ PCO2 HCO3- PO2 Result 63 nmol/L 10.1 kPa 29 mmol/L 6.4 kPa (Reference) (35-45) (4.6 - 6.0) (21 – 28) (10.5 – 13.5)

Mr. X 28 y/o male 1/7 Hx of severe vomiting (non-bilous) Self-medicating chronic dyspepsia Severely dehydrated & shallow respiration

Uraemia, but normal creatinine Hypokalaemia, 3 causes Hypernatraemia ABG H+ PCO2 HCO3- PO2 Result 28 nmol/L 7.2 kPa 43 mmol/L 13 kPa (Reference) (35-45) (4.6 - 6.0) (21 – 28) (10.5 – 13.5) Serum Na+ K+ Cl- HCO3- Urea Creat. Result 146 mmol/L 2.8 mmol/L 83 mmol/L 41 mmol/L 31 mmol/L 126 μmol/L (Ref.) (135 - 145) (3.5 – 5.0) (95 - 105) (21 – 28) (2.5 – 8.0) (40 - 130) Urine showed: Na+, K+, pH 5 Diagnosis? Low [H+], high bicarb Raised pCO2 Uraemia, but normal creatinine Hypokalaemia, 3 causes Hypernatraemia Classical paradoxical acid urine H+ Cell K+

Summary 4 key players in acid-base balance, problems in any Ventilatory failure Renal failure Metabolic – lactic acidosis, diabetic ketoacidosis Look at the H+ to see if acidotic/alkalotic Look at bicarb/pCO2 to see if metabolic or acidotic Look at other electrolytes Hyperalosteronism, H+/K+, uraemia etc. The history is key!