Transcript 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
K+
 Affecting
 Enzyme activity
 Hydrogen ion transporters (N.B K+)
 Osmolality
H+
Cell
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
2. Respiratory control – Minutes
3. Renal response – Days/weeks
4. (The liver)
1.
Cliché
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
But...
1.
Buffering relies on a steady supply of base

Buffering system cannot handle changes in several
variables
2. pKa of the bicarbonate system is 6.1
Fortunately, the body is not a closed system!
In a Nutshell
(CO2 + H2O  H2CO3  H+ + HCO3- )
Buffering
CO2 + H2O  H+ + HCO3-
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
Ventrolateral medulla
CSF
Blood
HCO3CO2
H+
H+
+
HCO3-
CO2
Albumin
CO2
HCO3-
H+
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+ + HCO32. Reabsorption of HCO33. Reabsorption of NH4+
4. Secretion of NH4+
1.
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
In a Nutshell
(CO2 + H2O  H2CO3  H+ + HCO3- )
Buffering
CO2 + H2O  H+ + HCO3-
Controlled by lungs
Controlled by kidneys
The Liver
Miss AM
 20 y/o female
 Admitted with a crushed chest
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)
 High [H+] & pCO2
 Bicarbonate not increased
Mr. X
 28 y/o male
 1/7 Hx of severe vomiting (non-bilous)
 Self-medicating chronic dyspepsia
 Severely dehydrated & shallow respiration
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?
H+
 Low [H+], high bicarb
 Raised pCO2
 Uraemia, but normal creatinine
 Hypokalaemia, 3 causes
 Hypernatraemia
 Classical paradoxical acid urine
K+
Cell
Summary
 4 key players in acid-base balance, problems in any
 Ventilatory failure
 Renal failure
 Metabolic – lactic acidosis, diabetic ketoacidosis
1. Look at the H+ to see if acidotic/alkalotic
2. Look at bicarb/pCO2 to see if metabolic or acidotic
3. Look at other electrolytes
 Hyperalosteronism, H+/K+, uraemia etc.
 The history is key!