A 33 year old female presented with high fever and abdominal pain. She has Gram negative bacteraemia and septic shock. The following is data from a blood gas analysis:

Test

Value

Normal Range

Barometric pressure

760 mm Hg

FiO2

0.3

pH

7.43

pO2

107 mm Hg

pCO2

23 mm Hg

HCO3 *

15 mmol/L

(24 – 26)

Standard base excess*

- 8.6 mmol/L

(-2.0 – 2.0)

Lactate*

23.0 mmol/L

(0.2 – 2.5)

Sodium*

147 mmol/L

(135 –145)

Potassium*

6.7 mmol/L

(3.2 – 4.5)

Chloride*

95 mmol/L

(100 –110)

24.1.   List the acid-base abnormalities.

24.2.   What are the causes of elevated plasma lactate in sepsis?

24.3.   Name three (3) drugs (each from a different class of drugs) which result in plasma hyperlactaemia.

24.4.   List two (2) inborn errors of metabolism associated with lactic acidosis.

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College Answer

24.1.   List the acid-base abnormalities.

•    High anion gap metabolic acidosis with raised lactate
•    Metabolic alkalosis ( Delta BE < Delta AG)
•    Respiratory alkalosis

24.2.   What are the causes of elevated plasma lactate in sepsis?

•    Circulatory failure due to hypotension and hypoxia
•    Microvascular shunting and mitochondrial failure (cytopathic hypoxia)
•    Use of adrenaline as an inotrope
•    Inhibition of pyruvate dehydrogenase (PDH) by endotoxin.

24.3.   Name three (3) drugs (each from a different class of drugs) which result in plasma hyperlactaemia.

•          Catecholamines
•         Metformin / Phenformin
•          Alcohols
•         Cyanide, nitroprusside
•          Salicylates
•         Lactate containing solutions – HRL, dialysates

24.4.   List two (2) inborn errors of metabolism associated with lactic acidosis.

•  Glucose 6 phosphatase deficiency
•  Fructose 1,6 diphosphatase deficiency
•  Pyruvate carboxylase deficiency
•  Deficiency of enzymes of oxidative phsophorylation

Discussion

The actual ABG itself and the attached patient history are identical to Question 22.2 from the second paper of 2011, and Question 18 from the first paper of 2007.

Generally, this question is frequently repeated, though the exact wording changes.
Question 6.4 from the first paper of 2013 contains a detailed discussion of the answer.

Let us dissect these results systematically.

  1. Yes, the A-a gradient is raised: 
    (0.3 x 713) - 28.8 = 185.1, thus the A-a difference is 195.5-107 = 78.1
  2. There is no acidaemia.
  3. The PaCO2 is compensatory
  4. The SBE is -8.6, suggesting a severe metabolic acidosis
  5. The respiratory compensation is excessive- the expected PaCO2(15 × 1.5) + 8 = 30.3mmHg, and thus there is also a respiratory alkalosis.
  6. The anion gap is raised:
     (147) - (95  + 15) = 37, or 43.7 when calculated with potassium
    The delta ratio, assuming a normal anion gap is 12 and a normal bicarbonate is 24, would therefore be (37 - 12) / (24 - 15) = 2.77
    This delta ratio suggests that there is a high anion gap metabolic acidosis coexisting with a metabolic alkalosis.
     

24.1. List the acid-base abnormalities.

  • Respiratory alkalosis
  • High anion gap metabolic acidosis
  • Metabolic alkalosis

24.2. What are the causes of elevated plasma lactate in sepsis?

Copying directly from Question 22.2:

  • Tissue hypoperfusion and hypoxia
  • Use of adrenaline (increased glycolytic flux)
  • Down regulation of pyruvate dehydrogenase by inflammatory mediators
  • Underlying ischaemic tissue
  • Microvascular shunting
  • Sepsis-associated cardiomyopathy

It is interesting to note that though these two questions are identical, the answers are not.

24.3. Name three (3) drugs (each from a different class of drugs) which result in plasma hyperlactaemia.

  • Metformin
  • Isoniazid
  • Iron
  • Toxic alcohols
  • Isoniazid
  • Cyanide
  • Salicylates
  • Catecholamines

24.4. List two (2) inborn errors of metabolism associated with lactic acidosis.

These are discussed in (slightly) greated detail in the chapter on the inherited defects of lactate metabolism. The full list is extensive; the college asks for only two.

The sleep-deprived candidate is likely to remember only glucose-6-phosphatase deficiency. "Deficiency of enzymes of oxidative phsophorylation" is a good all-encompassing statement which is general but still accurate.

References

References

Christopher, Rita, and Bindu P. Sankaran. "An insight into the biochemistry of inborn errors of metabolism for a clinical neurologist." Annals of Indian Academy of Neurology 11.2 (2008): 68.

 

DiMauro S, Schon EA. Mitochondrial respiratory-chain diseases. N Engl J Med 2003;348(26):2656–68.

 

D C Gore, F Jahoor, J M Hibbert, and E J DeMaria Lactic acidosis during sepsis is related to increased pyruvate production, not deficits in tissue oxygen availability. Ann Surg. 1996 July; 224(1): 97–102.