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 AcidosisMetabolic AlkalosisRespiratory AcidosisRespiratory Alkalosis

Arterial-Alveolar Oxygen Tension Difference References

References and Sources

versus

- The major titratable acid buffer is HPO42- (dependent on diet, PTH)

- less important buffers are creatinine and uric acid.

- Ammonium production and excretion

minimum attainable urine pH is 4.0 to 4.5: cannot excrete HCL (requires urine pH of 1.0)

Physiological Effectsof Metabolic Acidosis

Structured approach

1. History and Physical Exam: clues to what acid-base disorder might be present2. Look at the pH (If normal consider mixed acid-base disorder)3. Determine primary acid-base disorder and secondary (compensatory) response4. 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)5. Evaluate mixed acid-base disorder

• Relate delta anion gap to the delta bicarbonate6. Evaluate osmolal gap in unexplained high anion gap metabolic acidosis, coma, toxic

ingestions7. Evaluate Respiratory component of acid base disorder

• Relate partial pressure of oxygen to ventilation (alveolar-arterial oxygen tension difference)

8. Verification of diagnosis!

Anion Gap

[Na+] + [K+] + [Ca2+] + [Mg2+] + [H+] + unmeasured cations=

[Cl−] + [HCO3−] + [CO32−] + [OH−] + albumin + phosphate + sulfate + lactate + unmeasured anions (e.g., inorganic anions)

There is NO GAP: sum of the positive and negative ion chargesin plasma are equal in vivo

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

G Glycols (ethylene, propylene)O 5-oxoproline (pyroglutamic acid)L L-Lactate, D D-Lactate

M MethanolA AspirinR Renal failure (GFR <20 ml/min)R RhabdomyolysisK Ketoacidosis

High Anion Gap

bicarbonate decreases relative to levels of sodium and chloride

High Anion Gap (Pitfalls)

• 50% patients with serum lactate between 3.0 and 5.0 mmolper 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

Represents excretion of Ammonium NH4+ (as NH4Cl)

Negative in normal anion gap acidosis (Hyperchloremic acidosis should lead to increasedrenal 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

Normally, near zero or positive

Delta-ratio

-If ratio between 1 and 2, then pure elevated anion gap acidosis

- If < 1, then there is a simultaneous normal anion gap acidosispresent.

- if > 2, then there is a simultaneous metabolic alkalosis present ora 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 pre-existing chronic respiratory acidosis.

50% of excess acid is buffered intracellularlyand by bone, not by HCO3-Excess anions remain in ECF

Increase in Anions > decrease in HCO3-

Lactic Acidosis: 1.6:1Ketoacidosis 1:1 (loss of ketones with urine)

Mixed acid base disorders usually produce arterial blood gas results that couldpotentially 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)

ethanol (mg/dl)/3.7

Normal: -10-10 mosmol/kg

Increased: toxic alcohols (lactate, ketones)

Note:Acidic urine!

Alveolar-arterial Oxygen tension difference

Ventilation-Perfusion mismatch:5-10 mmHg in young15-20 mmHg in elderly

For every decade a person has lived, A-a difference increase by 2 mm Hg;A-a O2 difference = [Age/4] + 4

Stroomdiagram onderzoek Hypokaliemie