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1
Question:

A 66-year-old man with poorly controlled type 2 diabetes is admitted to the hospital due to a 2-day history of fever and confusion.  Blood pressure is 110/50 mm Hg.  Pulse oximetry shows an oxygen saturation of 97% on room air.  Examination reveals warm extremities with full peripheral pulses, an infected neuropathic foot ulcer with surrounding cellulitis, and normal lung sounds.  A central venous catheter terminating in the superior vena cava is placed.  Blood aspirated from the catheter appears red.  Blood gas analysis of this venous sample reveals an oxygen saturation of 87% (normal: 65%-70%), and lactate is moderately elevated.  Which of the following is the most likely cause of this patient's abnormal blood gas findings?

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Explanation:

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Abnormal oxygen metabolism in sepsis

↓ Global
O2 delivery

  • Hypovolemia: ↓ ECBV (capillary leak)
  • Hypoxemia: ↓ PaO2 (ARDS)

↓ Microcirculatory
O2 extraction

  • Vasodilation: rapid shunting of blood through organs
  • Edema: ↓ O2 diffusion (↑ interstitial distance)
  • Microthrombosis: capillary obstruction

↓ Mitochondrial
O2 use

  • ROS ⇄ mitochondrial damage & ↓ ETC function
  • Result: ↓ oxidative phosphorylation & ↓ ATP production

ARDS = acute respiratory distress syndrome; ATP = adenosine triphosphate; ECBV = effective circulatory blood volume; ETC = electron transport chain; PaO2 = arterial partial pressure of oxygen; ROS = reactive oxygen species.

This patient has sepsis due to an infected diabetic foot ulcer with surrounding cellulitis.  Sepsis is a florid host inflammatory response to infection that can lead to multiple organ system dysfunction.

Septic organ dysfunction is driven mainly by poor tissue oxygen use.  This cellular dysoxia is caused by 3 major mechanisms:

  • Bacterial components (eg, endotoxin) and acute phase cytokines (eg, IL-1-beta) trigger production of free radicals that damage mitochondria and interfere with the electron transport chain.  Immediate postmortem analysis of patients with sepsis reveals surprisingly minimal tissue necrosis but, often, extensive mitochondrial damage.  This mitochondrial dysfunction leads to decreased oxidative phosphorylation with loss of ATP production.  A compensatory bioenergetic shift toward glycolysis often results in lactic acidosis.
  • Widespread microcirculatory failure with vasodilation causes blood to shunt rapidly through organs, decreasing the opportunity for oxygen extraction.
  • Increased capillary permeability causes tissue edema (third spacing), which increases the diffusion distance for oxygen to reach mitochondria of target cells.

Because oxygen use decreases, the transorgan arteriovenous oxygen gradient is small; therefore, oxygen saturation of central venous blood (ScvO2) (superior vena cava) – returning from the periphery – increases.  Central venous catheters are often placed therapeutically to deliver medications; they can be used diagnostically to differentiate septic (↑ ScvO2) from cardiogenic (↓ ScvO2) shock.

(Choice A)  Cardiac output (oxygen delivery) is typically increased in sepsis due to systemic vasodilation (warm extremities, wide pulse pressure).  Decreased cardiac output is the hallmark of severe heart failure (cold extremities, narrow pulse pressure), and ScvO2 decreases with heart failure because peripheral oxygen consumption outstrips its delivery.

(Choice C)  Sepsis is associated with microvascular (rather than macrovascular) thrombosis due to endothelial injury and focal or disseminated intravascular coagulation, further impairing oxygenation.  Widespread large-vessel thrombosis and infarction are seen in conditions such as catastrophic antiphospholipid-antibody syndrome.

(Choice D)  Sepsis can induce capillary permeability in the lung, leading to pulmonary edema with resultant arterial hypoxemia (acute respiratory distress syndrome).  However, this patient's pulmonary function and oxygenation are intact, as evidenced by normal lung examination (no crackles) and arterial oxygen saturation.

(Choice E)  Hemoglobin oxygen unloading to peripheral tissues is facilitated by sepsis-induced (lactic) acidosis and fever, which lead to rightward shifting of the oxyhemoglobin dissociation curve (ie, weaker oxygen-hemoglobin binding).

Educational objective:
Sepsis is a host inflammatory response to infection that can lead to multiple organ dysfunction due to defective mitochondrial oxidative respiration, resulting in a widespread dissociation between oxygen delivery and extraction.  This manifests as elevated central venous oxygen saturation.