Carbon Monoxide Poisoning

Types of Poisonous Gases

  1. Toxic Pulmonary Irritants: Irritate the mucosa.

  2. Simple Asphyxiants: Displace oxygen from the air.

  3. Chemical Asphyxiants: Inhibit mitochondrial cellular respiration by interfering with the electron transport chain.

    • Examples include cyanide and carbon monoxide.

    • Carbon Monoxide leads to carboxyhemoglobin.

    • Hydrogen sulfide leads to sulfhemoglobinemia (blood turns green).

  • Important Distinction: Carboxyhemoglobin (due to CO) vs. Carbaminohemoglobin (due to CO_2).

    • Carbaminohemoglobin is normal.

    • Carboxyhemoglobin is typically abnormal.

Complete vs. Incomplete Combustion

Complete Combustion

  • Requires abundant oxygen.

  • Converts carbon-containing substances to carbon dioxide (CO_2), which is not toxic (within limits).

  • CO_2 leads to carbaminohemoglobin, a normal physiological process.

Incomplete Combustion

  • Occurs when oxygen is limited.

  • Results in the formation of carbon monoxide (CO), a toxic gas.

  • CO leads to carboxyhemoglobin formation, which is typically abnormal.

Causes of Carbon Monoxide Poisoning

  • Fires: The most common cause of both cyanide and carbon monoxide poisoning.

  • Heaters and Fireplaces: Especially those with clogged vents.

  • Stoves and Mufflers: Obstructions can lead to CO buildup.

  • Barbecues: A classic scenario is a family experiencing headaches due to CO exposure during a barbecue.

    • Treatment: Administer oxygen immediately without waiting for lab results.

Classic (but outdated) Scenario

  • A teenager starts a car in a closed garage, intending to fall asleep.

  • Initially, complete combustion occurs, depleting oxygen.

  • As oxygen runs out, incomplete combustion begins, producing CO.

  • CO poisoning leads to a headache, but since CO doesn't affect PaO_2, the respiratory center is not stimulated, and the person quietly dies.

  • This scenario is less likely today due to catalytic converters in cars (since 1975).

Why Carbon Monoxide is Poisonous

  1. Carboxyhemoglobin Formation: Creates dysfunctional hemoglobin.

  2. Inhibition of Cellular Respiration: Interferes with the electron transport chain.

Electron Transport Chain Inhibition

  • Normal process: Glucose glycolysis to pyruvate, then to the TCA (Krebs) cycle, producing NADH and FADH2.

    • Complex I: NADH

    • Complex II: FADH2

  • Protons are pumped into the intermembrane space, creating a concentration gradient.

  • Protons flow back, converting ADP to ATP (energy).

  • Complex IV (cytochrome C oxidase) is inhibited by:

    • Carbon monoxide

    • Cyanide

    • Hydrogen sulfide

Effects on Oxygen Transport

  • Normally:

    • FiO_2 → Lungs ( PA O2) → Arterial Blood ( Pa O2) → Hemoglobin ( SaO_2 ) → Tissue (O2 in, CO2 out) → CO2 in Hb → venous blood (Pa O2)

    • Carbon dioxide is produced and binds to hemoglobin (carbaminohemoglobin).

  • In CO Poisoning:

    • Competitive Binding: CO binds to hemoglobin more strongly than oxygen.

    • Decreased Loading: Less oxygen binds to hemoglobin.

    • Decreased Unloading: Hemoglobin does not release oxygen to tissues.

    • Left Shift of Oxygen Dissociation Curve: Oxygen remains bound to hemoglobin, decreasing oxygen delivery to tissues. Tissue is "left behind."

Physiological Parameters in CO Poisoning

  • FiO_2: Normal

  • Pa O2: Normal

  • SaO_2: Decreased (due to competitive inhibition)

  • Hemoglobin concentration: Normal

  • Oxygen content: Decreased

Lack of Respiratory Stimulation

  • Hypoxemia (low Pa O2) normally stimulates the respiratory center to increase ventilation.

  • In CO poisoning, Pa O2 is normal, so hyperventilation does not occur.

  • This contributes to CO being a silent killer.

Carboxyhemoglobin Levels

  • Normal hemoglobin saturation calculation: Oxyhemoglobin / Total hemoglobin = 97%.

  • In CO poisoning, oxygen saturation may drop to 50%.

  • Normal carboxyhemoglobin level: 0-5% (due to normal heme degradation).

Pathophysiology of CO Poisoning

  • CO leads to:

    • Carboxyhemoglobin formation.

    • Decreased oxygen loading (decreased SaO_2).

    • Decreased oxygen unloading (left shift of the oxygen dissociation curve).

    • Tissue hypoxia.

    • Increased A-a gradient (only in chronic poisoning).

Consequences of Tissue Hypoxia

  • Mitochondria do not receive or utilize oxygen due to decreased unloading and inhibition of cytochrome oxidase (complex IV).

  • No ATP formation leads to anaerobic glycolysis, causing lactic acidosis (high anion gap metabolic acidosis).

  • Lack of concentration gradients between hemoglobin and tissue results in more oxygen remaining in venous blood, leading to cherry red skin (rare but specific).

Other Effects of CO Poisoning

  • Polycythemia: Can be caused by chronic CO poisoning due to increased EPO.

  • Rhabdomyolysis: Muscle destruction (especially skeletal) due to CO binding to myoglobin, reducing oxygen availability to muscles.

Normal Carboxyhemoglobin Production

  • Heme degradation: Hemoglobin is broken down into heme and globin.

  • Heme oxygenase converts heme into ferrous iron and carbon monoxide.

  • Further converted to biliverdin (green) and then bilirubin (yellow).