1. Acid-Base Balance
James Howard

2. 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+

3. 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

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

5. 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

6. 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!

7. (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

8. 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

9. 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

10. 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-?

11. 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

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

13. 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

14. (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

15. 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)
( )
(21 – 28)
(10.5 – 13.5)

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

17. 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)
( )
(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.)
( )
(3.5 – 5.0)
( )
(21 – 28)
(2.5 – 8.0)
( )
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+

18. 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!