A 33 year old female has Gram-negative bacteraemia and septic shock. The following are data from blood gas analysis.



Normal Adult Range

Barometric pressure

760 mmHg (100 kPa)





7.35 – 7.45


23 mmHg (3.1 kPa)

35 – 45 (4.6 – 5.9)


107 mmHg (14.3 kPa)


15 mmol/L

24 – 32

Standard Base Excess*

-8.6 mmol/L

-2.0 – +2.0


23.0 mmol/L

0.2 – 2.5


147 mmol/L

137 – 145


6.7 mmol/L

3.2 – 4.5


95 mmol/L

100 – 110

  • Describe the acid-base abnormalities.
  • What are the possible mechanisms for a raised lactate in sepsis?

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College Answer

6.4 a)

Lactic acidosis with anion gap elevation (37 mEq/L).

Metabolic alkalosis (Delta ratio >2).

Respiratory alkalosis (PCO2 lower than predicted for HCO3).

6.4 b)

Tissue hypoperfusion and hypoxia

Use of adrenaline (increased glycolytic flux)

Down regulation of pyruvate dehydrogenase by inflammatory mediators Underlying ischaemic tissue


This question is frequently repeated. A detailed discussion is carried out in the discussion of the answer for one such duplicate, Question 6.4 from the first paper of 2013. Otherwise, the causes of lactic acidosis in sepsis are discussed elsewhere.

Let us dissect these results systematically.

  1. The A-a gradient is high:
    PAO2 = (0.3 × 713) - (23 × 1.25) = 185
    Thus, A-a = ( 185 - 107) = 78mmHg.
    However, the college was only interested in the acid-base abnormalities
  2. There is acidaemia
  3. The PaCO2 is compensatory
  4. The SBE is -8.6, suggesting a severe metabolic acidosis
  5. The respiratory compensation is somewhat excessive- the expected PaCO2(15 × 1.5) + 8 = 30.5mmHg, 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 suggests that the high anion gap metabolic acidosis here is concurrent with a metabolic alkalosis

Thus, there is a triple disorder here:

  • Respiratory alkalosis
  • Metabolic alkalosis
  • Metabolic (high anion gap) acidosis

As for the question about sepsis: this is summarised  in the chapter on the causes of lactic acidosis in sepsis. Suffice to say, there are several contributing factors:

  • Shock state: inadequate tissue oxygenation, due to:
    • vasoplegia and low blood pressure
    • sepsis-associated cardiac dysfunction and decreased cardiac output
  • microvascular shunting
  • catecholamine excess influencing an increase in glycolysis
  • mitochondrial dysfunction (pyruvate dehydrogenase inhibition) due to endotoxins and cytokines

flowchart of lactic acidosis in sepsis

Microvascular stasis

Firstly, the slow circulation is to blame; this results in a delay in the delivery of oxygen to the tissues, as well as a delay in removing the metabolic byproducts, which has the tendency to concentrate the lactate. The evidence for this is strong; the term used to describe this is “microvascular stasis” where collecting post-capillary venules are so vasodilated that flow in them essentially halts. There is at least one excellent article which goes over the potential causes for this stasis, including the increased adhesion of blood cells to endothelia, decreased red cell deformability, microthrombi interfering with the flow, etc. etc.

Microvascular shunting

Another feature of sepsis is that in some tissues the circulatory beds are completely shut down, and there is microcirculatory shunting of oxygenated blood away from these tissues. The net result is decreased oxygen extraction from otherwise well oxygenated blood. This is the patient who has a raised lactate in spite of having a normal (or even elevated) ScVO2.

Catecholamine-related increase in glycolysis

Then, there is a catecholamine-driven increase in the rate of glycolysis, predominantly in the skeletal muscles, which leads to an excess of pyruvate. This is seen also in people receiving infusions of salbutamol or adrenaline – the mechanism is the same. Conversely, beta-blockade reverses this effect  and causes lactate to decrease.

Pyruvate dehydrogenase inhibition by cytokines and endotoxin

There is also a significant impairment of mitochondrial function, as a result of direct cytokine effects as well as bacterial endotoxin. The main dysfunction seems more to do with the disruption of mitochondrial enzyme complexes responsible for pyruvate metabolism, particularly pyruvate dehydrogenase.  The outcome of this is a switch to increased anaerobic metabolism, rather than pyruvate oxidation; and of course the amount of available pyruvate also increases.



Jones, Alan E., and Michael A. Puskarich. "Sepsis-induced tissue hypoperfusion." Critical care clinics 25.4 (2009): 769.

Crouser, Elliott D. "Mitochondrial dysfunction in septic shock and multiple organ dysfunction syndrome." Mitochondrion 4.5 (2004): 729-741.

Levy, Bruno. "Lactate and shock state: the metabolic view." Current opinion in critical care 12.4 (2006): 315-321.

Bateman, Ryon M., Michael D. Sharpe, and Christopher G. Ellis. "Bench-to-bedside review: microvascular dysfunction in sepsis-hemodynamics, oxygen transport, and nitric oxide." CRITICAL CARE-LONDON- 7.5 (2003): 359-373.

Jansen TC, van Bommel J, Schoonderbeek J, et al: Early lactate-guided therapy in ICU patients:
A multicenter, open-label, randomized, controlled trial
. Am J Respir Crit Care Med 2010 May 12

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