Normal Physiology
Pathophysiological Response to acidemia/alkalemia
Structured Approach
Simple Acid-Base disorders and compensatory responses
Anion Gap
Urinary Anion Gap/Urine Osmolar Gap
Delta-Delta or Delta Ratio
Osmolal Gap
Metabolic Acidosis
Metabolic Alkalosis
Respiratory Acidosis
Respiratory Alkalosis
Arterial-Alveolar Oxygen Tension Difference
References
References and Sources
versus
minimum attainable urine pH is 4.0 to 4.5:
cannot excrete HCL (requires urine pH of 1.0)
- The major titratable acid buffer is HPO42- (dependent on
diet, PTH)
- less important buffers are creatinine and uric acid.
- Ammonium production and excretion
Physiological Effects
of Metabolic Acidosis
Structured approach
1.
2.
3.
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5.
6.
7.
8.
History and Physical Exam: clues to what acid-base disorder might be present
Look at the pH (If normal consider mixed acid-base disorder)
Determine primary acid-base disorder and secondary (compensatory) response
Consider the metabolic component
• Metabolic acidosis: anion gap
• High
• Normal (urinary anion gap, Na<20mmpl/l: urinary osmol gap, both indirect
measures of ammonium)
• Metabolic alkalosis
• Chloride-responsive (Cl <25 mmol/l)
• Chloride-resistant (Cl> 40 mmol/l)
• Urinary K <20 or >30 mmol/l)
Evaluate mixed acid-base disorder
• Relate delta anion gap to the delta bicarbonate
Evaluate osmolal gap in unexplained high anion gap metabolic acidosis, coma, toxic
ingestions
Evaluate Respiratory component of acid base disorder
• Relate partial pressure of oxygen to ventilation (alveolar-arterial oxygen tension
difference)
Verification of diagnosis!
Anion Gap
There is NO GAP: sum of the positive and negative ion charges
in plasma are equal in vivo
[Na+] + [K+] + [Ca2+] + [Mg2+] + [H+] + unmeasured cations
=
[Cl−] + [HCO3−] + [CO32−] + [OH−] + albumin + phosphate + sulfate + lactate +
unmeasured anions (e.g., inorganic anions)
reference ranges of 3.0 to 12.0 mmol per liter up to 8.5 to 15.0 mmol/l
A= chloride or unmeasured anion
High Anion Gap
bicarbonate decreases relative to levels of sodium and chloride
G
O
L
D
Glycols (ethylene, propylene)
5-oxoproline (pyroglutamic acid)
L-Lactate,
D-Lactate
M
A
R
R
K
Methanol
Aspirin
Renal failure (GFR <20 ml/min)
Rhabdomyolysis
Ketoacidosis
High Anion Gap (Pitfalls)
• 50% patients with serum lactate between 3.0 and 5.0 mmol
per liter have an anion gap within the reference range
• Adjust for albumin (weak acid, up to 75% of the gap):
Decrease of 1 g/dl, add 2.3-2.5 mmol/l to the gap
Low or Negative Anion Gap
• high levels of cations:
- lithium toxicity
- monoclonal IgG gammopathy
- high levels of calcium or magnesium.
• pseudohyperchloremia in bromide or iodide intoxication.
Urinary Anion Gap
Normally, near zero or positive
Represents excretion of Ammonium NH4+
(as NH4Cl)
Negative in normal anion gap acidosis (Hyperchloremic acidosis should lead to increased
renal excretion of ammonium)
If positive: consider renal failure, distal renal tubular acidosis, hypoaldosternonism
Unreliable: polyuria, urinary pH >6.5, ammonium excreted with other anion (ketoacid,
salicylates, d-lactate, penicilline) or when UNa+< 20 mmol/l
Urinary Osmolal Gap
mmol/l
<40 mmol/l indicates impaired ammonium excretion, except in ketoacidosis
Delta-ratio
-If ratio between 1 and 2,
then pure elevated anion gap
acidosis
- If < 1, then there is a
simultaneous normal anion
gap acidosis
present.
- if > 2, then there is a
simultaneous metabolic
alkalosis present or
a compensated chronic
respiratory acidosis.
Delta-ratio
-if <0.4 pure normal anion gap
acidosis
- If < 1, then there is a
simultaneous normal anion gap
acidosis present
-If ratio between 1 and 2, then
pure elevated anion gap acidosis
- if > 2, then there is a
simultaneous metabolic
alkalosis present or a preexisting chronic respiratory
acidosis.
50% of excess acid is buffered intracellularly
and by bone, not by HCO3Excess anions remain in ECF
Increase in Anions > decrease in HCO3-
Lactic Acidosis: 1.6:1
Ketoacidosis 1:1 (loss of ketones with urine)
Mixed acid base disorders usually produce arterial blood gas results that could
potentially be explained by other mixed disorders. Oftentimes, the clinical picture will
help to distinguish.
Osmolal gap
Difference between measured serum osmolality and calculated
serum osmolality
Calculated Osmolality:
2 x [Na+] + (Glucose (mg/dl)/18) + (BUN (mg/dl)/2.8)
Normal: -10-10 mosmol/kg
Increased: toxic alcohols (lactate, ketones)
ethanol (mg/dl)/3.7
Note:
Acidic urine!
Alveolar-arterial Oxygen tension difference
For every decade a person has lived, A-a
difference increase by 2 mm Hg;
A-a O2 difference = [Age/4] + 4
Ventilation-Perfusion mismatch:
5-10 mmHg in young
15-20 mmHg in elderly
Stroomdiagram onderzoek Hypokaliemie