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.
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
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.
24.1. List the acid-base abnormalities.
24.2. What are the causes of elevated plasma lactate in sepsis?
Copying directly from Question 22.2:
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.
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.
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.