Acid-Base Balance

1
Acid-Base Balance

• James Howard

2
Acid-Base Balance

• H maintained at 35-45 nmol/L
• pH 7.35 7.45
• gt 120nmol or lt20nmol 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
• 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!

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In a Nutshell

• (CO2 H2O ? H2CO3 ? H HCO3- )
• CO2 H2O ? H HCO3-

Buffering
Controlled by lungs
Controlled by kidneys
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Respiratory Control

• ?pCO2 ? ?pH
• 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 ?pH
• Chemoreceptors input to medullar respiratory
  centre
• N.B Roles of peripheral chemoreceptors

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Gratuitous Schematic
Ventrolateral medulla
H HCO3-
CO2
CSF
CO2
HCO3-
H
Albumin
Blood
CO2
HCO3-
H
Albumin
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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, Ill go with
• We form ammonium (NH4) and bicarbonate
• We reabsorb them both
• We secrete what we dont want

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Renal Regulation

1. Glutamine ? NH4 HCO3-
2. Reabsorption of HCO3-
3. Reabsorption of NH4
4. Secretion of NH4

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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

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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) (4.6 - 6.0) (21 28) (10.5 13.5)
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Mr. X

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

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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
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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!