H+ Homeostasis
H+ homeostasis
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Why is it so
important?
• Organ function
• Cellular function
• Enzyme and protein
function
Acid production
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Respiratory acid
• CO2 as carbonic acid
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Metabolic acids
•
•
•
•
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Organic acids
Lactate
Pyruvate
Keto-acids
Lungs
Kidneys
Traditional pH control
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Respiratory control of CO2
• Ventilation rate and depth
• Rapid and very sensitive
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Kidney control of H+ and HCO3- (maybe..)
• NH4+
• Phosphates
• Organic acids
• Slower and less efficient
Henderson equation:
[ H+ ] x [ HCO3- ] = k x [ CO2 ] x [ H2O ]
The trouble with Henderson..
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[H+] ≈ CO2/HCO3But if CO2 rises so will HCO3Danish polio epidemic
So how can you distinguish between
respiratory and metabolic problems?
• Standard bicarbonate (1957)
• BE or SBE (1958)
• Boston rules
History
terminology
bicarbonate at normal temp. and PCO2
An alternative explanation..
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All H+ comes from
the dissociation of
water
Anything that controls
or effects water
dissociation controls
pH
The Six Simultaneous Equations
used by Stewart
1. Water Dissociation Equilibrium
[H+] x [OH-] = K’w
2. Electrical Neutrality Equation
[SID] + [H+] = [HCO3-] + [A-] + [CO3-2] + [OH-]
3. Weak Acid Dissociation Equilibrium
[H+] x [A-] = KA x [HA]
4. Conservation of Mass for "A“
[ATot] = [HA] + [A-]
5. Bicarbonate Ion Formation Equilibrium
[H+] x [HCO3] = KC x pCO2
6. Carbonate Ion Formation Equilibrium
[H+] x [CO3-2] = K3 x [HCO3-]
3 factors independently control water
dissociation or [H+]
1.
2.
3.
CO2 (pCO2)
Strong ion difference (SID)
Total weak acid concentration (AH)
Neither pH nor HCO3- can be regulated directly.
Their concentrations are determined by other
independent variables.
The ratio of CO2/HCO3- describes pH but does
not determine it…Henderson is only 1/6th of
the story!
Strong Ion Difference (SID)
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SIDa is always positive
Should equal sum of
HCO3 and A- (SIDe)
SIG = unmeasured
anions and should be
zero
Unmeasured anions are
• Ketoacids,organic acids
• Exogenous acids
• Gelatins, citrate
Where does Anion gap fit in?
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Anion gap = (Na + K) – (Cl + HCO3)
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Clever AG = AG – [0.25 x albumin] – lactate
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Easier than SIG and well correlated
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Note that a low albumin will augment an
anion gap
If SID falls, pH falls.
SIG is a clever Anion gap
(corrects for albumin, phosphate, lactate, Mg and Ca)
Total concentration of weak acids (Atot)
3. Weak Acid Dissociation Equilibrium
[H+] x [A-] = KA x [HA]
4. Conservation of Mass for "A“
[ATot] = [HA] + [A-]
• Low albumin is alkalinizing…
• Less HA means less H+
• Low albumin may mask an acidosis
Stewart’s bottom line(s)..
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It is not the direct control of HCO3- and H+ that
determines pH.
It is the direct effect of CO2, SID and ATot that
regulates the dissociation of water.
• CO2 is controlled by ventilation (lungs)
• SID is controlled by strong ion handling esp.
Chloride/sodium (kidneys)
• ATot is chiefly determined by albumin and phosphate
concentration (kidneys and liver)
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It is the degree of water dissociation that
determines pH
Back to the traditional..
…..With some unification
Blood gas analysis
1.
Assess Oxygenation
•
•
2.
What is the pH
•
•
3.
pH>7.45 (H+ < 35) alkalosis
pH<7.35 (H+ > 45) acidosis
Is it a ventilation problem?
•
•
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Is the patient hypoxic
Is there a significant A-a Gradient
PaCO2:
PaCO2:
>6.0 kPa - respiratory acidosis
<4.7kPa - respiratory alkalosis
Both methods agree
4. Is there a metabolic problem?
What is the HCO3- or SBE? (..or SID)
SBE -2=metabolic acidosis
SBE +2=metabolic acidosis
5. Is it both?
6. Investigate Metabolic acidosis
(hunt the kipper)
Gem 3000
Measured variables
 Ph
 pCO2
 P02
 Na
 K
 Ca total
 Glucose
 Lactate
 Hct
Derived variables
 Ca ionised
 HCO3 BE/SBE
 O2 %Sats
 Hb
Respiratory Acidosis
Any cause of hypoventilation (high CO2)
• CNS depression
• Neuromuscular disease
• Acute or chronic lung disease
• Cardiac arrest
• Ventilator malfunction
Respiratory Alkalosis
Any cause of hyperventilation (low CO2)
• Hypoxia
• Acute lung conditions
• Anxiety
• Fever
• Pregnancy
• Hepatic failure
• Some central CNS lesions
Metabolic Acidosis (low SID)
Increased anion gap or SIG (unmeasured anions)
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Endogenous acids
• Renal failure..organic acids
• Ketoacidosis/starvation
• Lactic acidosis
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Exogenous acids
• Salicylate/Tricyclic/methanol overdose
• Citrate
• gelatins
Metabolic Acidosis
Decreased or normal anion gap or SIG
•
•
•
•
•
Diarrhoea (loss Na>Cl)
Carbonic anhydrase inhibitors
Ureteral diversion
Chloride administration
Renal tubular acidosis ?Cl retention
Metabolic Alkalosis (increased SID or
low albumin)
Loss of acid or gaining alkali or
loss Chloride gaining Na
• Vomiting
• Diarrhoea
• Diuretics (and hypokalaemia generally)
• Cushings/steroids/mineralocorticoids
• Ingestion/administration of alkali or is it Na?
Reminder of normal values
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pH = 7.35 – 7.45 [H+ = 35 -45nmol/l]
pO2 = 10 -13 kPa on air
pCO2 = 4.6 – 6.0 kPa
HCO3 = 25 – 35 mmols/l
Base excess ± 2.0
Lactate < 1.0 mmols/l
Chloride = 100
Albumin 35
Anion gap 10-12 but less if albumin low
SIG = 0
Bed 1
Middle aged man admitted with cough
sputum and haemoptysis. Life-long
smoker
pO2
4 on air
H+
65
pH
7.19
PaCO2 9.7
HCO3
28
Bed 2
Middle aged man admitted with cough
sputum and haemoptysis. Life-long
smoker
pO2
6 on air SpO2 92%
H+
46
pH
7.32
PaCO2 10.0
HCO3
39
Bed 9
50 yr-old man admitted with exacerbation
of long-standing bronchial asthma.
Respiratory rate of 18
pO2
5.1 on 60% oxygen
H+
41
pH
7.39
PaCO2 5.8
HCO3
26
or corrected Anion
Gap (AGc)
Bed 3
Young female admitted with overdose of unknown
tablets and smelling of alcohol
pO2
12 kPa on air
H+
58
pH
7.24
PaCO2
2.5
HCO3
8
I need to know…
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SBE
Lactate
Corrected Anion gap or Strong ion gap
(chloride)
SBE -12
Lactate 4
Corrected Anion gap high (>12)
Bed 4
Elderly male admitted from nursing home with
one week history of fever and vomiting
pO2
12 kPa on 4L/min by mask
H+
32
pH
7.49
PaCO2
6.3
HCO3
35
SBE
+8
Lactate
3
Bed 5
Middle aged man post cardiac arrest. Breathing
spontaneously on endotracheal tube
pO2
35 on 15l via resus bag (with reservoir)
H+
126
pH
6.9
PaCO2
8.9
HCO3
13
SBE
-20
Lactate 12
Cl
111
Bed 6
Elderly lady with congestive cardiac failure
pO2
9 on 40% oxygen
H+
23
pH
7.64
PaCO2 3.5
HCO3
29
SBE
+2
Bed 7
Young diabetic male admitted with chest infection,
vomiting and drowsiness
pO2
12 on air
H+
49
pH
7.31
PaCO2
1.6
HCO3
6.0
SBE
-18
Lactate 6
Cl
111
Bed 8
54 yr-old lady post MI. Acutely unwell, cold,
clammy, hypotensive and oliguric
pO2
10 on 60% oxygen
H+
102
pH
6.99
PaCO2
7.8
HCO3
14
SBE
-17
Lactate 6
Cl
101
Bed 10
40 year old woman with pancreatitis and sepsis has
been resuscitated aggressively with IV fluids on
the ward for 24 hours
pH
7.30
Na
138
pO2
8.21 FiO2 0.7
K 3.5
pCO2 3.5
Ca2+ 1.15
HCO3- 14.6
Cl- 116
Anion gap =10.9
albumin 15
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Apparently “normal anion gap” acidosis,
points to chloride…but
Albumin is very low
SIG is high…because SIDe (A- + HCO3-)
is low
Lactate was 4
Still underesuscitated.