How do blood gas parameters change?
The accumulation of methaemoglobin causes hemic hypoxia.
- Oxygen-transport capacity of blood (OTC) — ↓ (decreased). This is a key sign of methaemoglobin presence.
- $O_2$ content — decreased in both arterial ($CaO_2$) and venous ($C_v O_2$) blood. The arterial-venous oxygen difference ($C_{a-v} O_2$) also drops.
- Partial pressure of $O_2$ — in arterial blood ($P_a O_2$) and inspired air ($P_I O_2$) remains normal (N), but decreases in venous blood ($P_v O_2$).
- Saturation — with standard measurement, arterial saturation ($S_a O_2$) is determined as normal, while venous saturation ($S_v O_2$) is decreased.
- Acid-base balance — metabolic acidosis develops (pH ↓). Hyperventilation occurs as a compensatory mechanism, causing arterial partial pressure of $CO_2$ ($P_a CO_2$) to be normal or decreased.
What causes methaemoglobin formation?
Chemical agents known as methaemoglobin inducers provoke the conversion of hemoglobin into its inactive form.
- Nitrates and nitrites — enter the body via contaminated well or spring water, vegetables, as well as sausages and canned meats where sodium nitrite is used as a food additive. Nitrates are reduced to nitrites by microflora, which then oxidize the heme iron.
- Medicinal drugs — inorganic nitrites (vasodilators), local anesthetics, nonsteroidal anti-inflammatory drugs (NSAIDs), and sulfonamides, including dapsone.
- Toxic impurities — illicit or homemade preparations may contain manganese, phosphorus, iodine, acetic acid, benzocaine, and other substances causing acute poisonings with methaemoglobinaemia.
How do erythrocytes reduce methaemoglobin?
The process of methaemoglobin formation is reversible. When the provoking factor is removed, the heme iron returns to its active form ($Fe^{2+}$). In erythrocytes, enzyme systems are responsible for this:
- Methaemoglobin reductase — reduces methaemoglobin back into functional hemoglobin. The reaction requires the $NADH$ coenzyme, which is generated during anaerobic glycolysis with the participation of the enzyme glyceraldehyde-3-phosphate dehydrogenase.
- Antioxidant defense includes superoxide dismutase, catalase, and the glutathione system. The function of the glutathione system depends on $NADPH$ synthesized by the enzyme glucose-6-phosphate dehydrogenase (G6PD) in the pentose phosphate pathway. G6PD deficiency is most commonly associated with the development of drug-induced methaemoglobinaemia upon dapsone administration.
Clinical and diagnostic significance
- Toxic cyanosis — bluish discoloration of the lips and skin accompanied by shortness of breath. The presence of methaemoglobin is considered a diagnosis of exclusion in central cyanosis when other causes are not confirmed.
- Water-nitrate methaemoglobinaemia — an endemic disease of biogeochemical origin. The greatest threat exists for infants on formula feeding when formula is diluted with water containing an excess of nitrates. Severe hypoxia may lead to a fatal outcome.
- MRI diagnostics — methaemoglobin has a paramagnetic effect. This property is used in magnetic resonance imaging (MRI) to visualize the hemorrhagic component in chronic pancreatitis, where it produces a high-intensity signal.
Class and exam questions
Why might standard pulse oximetry show normal results in methaemoglobinaemia?
During standard measurement, arterial oxygen saturation ($S_a O_2$) is determined as normal, and arterial partial pressure of oxygen ($P_a O_2$) remains normal. At the same time, the oxygen-transport capacity of the blood is decreased.
Which population group is most vulnerable to nitrates in drinking water?
Infants who are formula-fed. Diluting milk formulas with water having a high nitrate content causes them to develop water-nitrate methaemoglobinaemia along with toxic cyanosis.
Which enzyme restores methaemoglobin to its normal state?
Methaemoglobin reductase. It reduces ferric iron ($Fe^{3+}$) to ferrous iron ($Fe^{2+}$) using the NADH coenzyme, which is produced in erythrocytes during glycolysis.
What else to study on this topic
- Hemic Hypoxia
- Erythrocyte metabolism and antioxidant defense
- Central cyanosis
- Toxicodynamics of nitrates and nitrites
Master the entire topic in the "Physiology" course
This is a summary. The course covers everything tested in classes and exams.
- Complete study guide on "Methaemoglobin" and 4,128 more pages of the subject
- Assignments and quizzes after every topic — just like in a colloquium
- AI tutor answers questions on the topic anytime
- 114 video lessons on the subject
Free video lessons: PhysiologyShort lessons with study notes — no registration required.
Prepared by WhiteCoat Pro faculty in accordance with the medical school curriculum. For educational purposes only.