Erythrocyte disorders can be caused by a wide variety of toxic agents. Whereas some erythrocyte toxins damage red blood cells through well-defined mechanisms, others have mechanisms that are incompletely defined or for which there is complexity involving multiple simultaneous pathways. The well-defined mechanisms include neocytolysis, damage from oxidation, damage to structural proteins, damage to erythrocyte membranes, and direct damage to metabolic pathways. Incompletely defined mechanisms are responsible for toxicity from nanoparticles and metals with broad biological activity spectra such as lead. A table of other toxins not specifically described in the text is included.
Acronyms and Abbreviations
AsH3, arsenic hydride (arsine gas); EDTA, ethylenediaminetetraacetic acid; G-6-PD, glucose-6-phosphate dehydrogenase; NADPH, reduced nicotinamide adenine dinucleotide phosphate.
ERYTHROCYTE TOXINS ACTING THROUGH WELL-DEFINED MECHANISMS
Certain toxins cause erythrocyte damage through clearly defined mechanisms, in some cases affecting the processes or functions of single subcellular systems. Other mechanisms causing erythrocyte damage within the context of enzyme deficiency, unstable hemoglobins, or immune dysfunction are discussed in Chaps. 48, 50, and 56. The present chapter deals with cell destruction from toxic agents that are not discussed elsewhere within this textbook.
The earth’s oxidizing atmosphere, although necessary for metabolic processes, also provides a potential ubiquitous source of oxidizing toxins. Oxidative damage affects a number of the erythrocyte structural and functional elements that tend to lead to red cell destruction through the final common pathway of eryptosis.1
Astronauts experience significant anemia after space flight in the presence of normal or elevated ambient oxygen concentration.2 Neocytolysis describes this phenomenon of rapid hemolysis observed after transition from acclimated hypoxic or hypobaric environments to normoxic atmospheric conditions. Observations of altered erythropoietin levels and research with radiolabeled erythrocytes from astronauts suggest there is selective hemolysis of young erythrocytes less than 12 days old.3 In addition to space flight, neocytolysis has been invoked to explain the anemia resulting when high-altitude dwellers relocate to sea level and has also been demonstrated within the first neonatal week of life.4,5 Although long a mechanistic mystery, neocytolysis has recently been convincingly demonstrated to be induced by intrinsically generated toxic agents within the cell. Reticulocytes generated within hypoxic or hypobaric environments contain expanded mitochondria and low levels of catalase. In the presence of suddenly increased oxygen levels, oxidant radicals are rapidly generated by the expanded mitochondria at levels, which overwhelm the decreased catalase enzyme activity, resulting in cell lysis.5
Oxygen is a powerful oxidizing agent. Fortunately, quantum mechanical properties of the oxygen molecule prevent spontaneous oxidation of biological membranes under normal atmospheric conditions.6 However, when bound to hemoglobin, oxygen has significantly different quantum mechanical properties and occasionally, an exceptionally reactive superoxide molecule escapes.7 It ...