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CHAPTER 52 spider and scorpion bites occasionally are followed by hemolytic ane-
The spiders usually responsible are
11–16
mia and hemoglobinuria.
ERYTHROCYTE DISORDERS Loxosceles laeta and Loxosceles recluse. In such cases, sphingomyelinase
D is one of the causative toxins. The venom preferentially hydrolyzes
17
AS A RESULT OF CHEMICAL band 3 of the red cell membrane protein. Band 3 has dual functions
of ion exchange and anchoring of the cell membrane to the underlying
cellular skeleton. It appears disruption of the structural role is respon-
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AND PHYSICAL AGENTS sible for cell lysis.
One of the most intriguing mechanisms of membrane damage
is that induced by a class of pore-forming cytotoxins, usually from
Bacillus cereus. Toxins using similar mechanisms of hemolysis are
19
Paul C. Herrmann found in marine organisms including jelly fish (Chironex fleckeri), sea
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cucumbers (Cucumaria echinata), and sea anemones (Stichodactyla
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helianthus). X-ray crystallography reveals these toxins to be composed
of proteins that associate to span the erythrocyte membrane forming an
21
SUMMARY ion permeable pore. Aged cells appear preferentially damaged.
Additional discussion of hemolysis associated with microorganism-
produced toxins, including Clostridium-induced spherocytosis and
Erythrocyte disorders from physical or chemical agents occur via such processes massive hemolysis, is found in Chap. 53.
as red cell volume expansion within hypotonic solutions, erythrocyte mem-
brane damage from biotoxins, damage to the spectrin skeleton from insults
such as heat, and eryptosis associated with oxidizing agents such as oxygen, DAMAGE TO SKELETAL OR STRUCTURAL
arsine gas, and chlorates. Erythrocyte damage also can be induced by other PROTEINS
agents that lack well defined mechanisms of action (see Table 52–1). These Gross hemoglobinemia was observed in 11 of 40 patients with second-
processes include erythrocyte damage caused by lead, copper, and radiation, and third-degree burns involving 15 to 65 percent of body surface area.
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as well as neocytolysis, a phenomenon once thought unique to microgravity, Within the first 24 hours following a burn, hemolytic anemia results
but subsequently observed in individuals demonstrating altitude induced from the direct effect of heat on circulating erythrocytes. Blood heated
polycythemia upon transition to normoxic conditions. to temperatures above 49°C demonstrates morphologically similar
damage (Fig. 52–1A), consistent with increased osmotic and mechani-
cal fragility. 24,25
In addition to acute damage, heat decreases erythrocyte resilience.
MECHANISTICALLY DESCRIBED A normal erythrocyte in liquid behaves physically as a drop of fluid
ERYTHROCYTE DAMAGE because the flexible membrane allows the surface of the cell to rotate
around the intracellular contents. These fluid-like properties couple
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Chemical and physical agents causing erythrocyte disorders within the collisional energy between the erythrocyte membrane and the viscous
context of enzyme deficiency, unstable hemoglobins, cell fragmentation or hemoglobin solution within the cell, allowing dissipation of collisional
immune dysfunction are discussed in Chaps. 46 to 51 and 54. The present energy through the entire cell and ultimately protecting the cell mem-
chapter deals with drugs, toxins, and other physical agents that can cause brane. When heated, the spectrin comprising the erythrocyte skeleton
red cell disorders, which are not discussed elsewhere within this text. melts, and upon cooling becomes rigid. This rigidity prevents collisional
energy dissipation, making such cells particularly susceptible to mem-
ERYTHROCYTE VOLUME EXPANSION AND brane damage. The ensuing damage to the erythrocyte membrane
27
HYPOTONIC LYSIS structure results in splenic sequestration and cell removal. 28
When large amounts of distilled water gain access to the systemic cir-
culation, either by intravenous injection or when used as an irrigating OXIDANT DAMAGE
solution during surgery, hemolysis will occur. Severe hemolysis may Although oxygen is a powerful oxidizing agent, quantum mechanical
1
also result from water inhalation in near-drowning. Occasionally properties of the oxygen molecule prevent spontaneous oxidation of
2
self-induced hypotonic lysis secondary to water intoxication from poly- biologic membranes. When bound to hemoglobin, oxygen has sig-
29
dipsia in the setting of psychiatric illness or hazing rituals occurs. In all nificantly different quantum mechanical properties and occasionally, an
3
cases, hemolysis follows expansion of the erythrocyte volume, transi- exceptionally reactive superoxide molecule escapes. It is estimated that
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tion to a spherical shape and ultimately cell rupture. 4 2 to 3 percent of total hemoglobin would be oxidized daily in the absence
of enzyme systems to protect against escaped superoxide. 31,32 Although
DAMAGE TO THE RED BLOOD CELL MEMBRANE the hemolysis that occurs when these systems are overwhelmed is
Bee and wasp stings, as well as contact with caterpillar bristle from dealt with in Chap. 47, a few additional examples are briefly described
7–9
5,6
below. Hemolysis following oxidation is thought to occur via eryptosis
Lonomia obliqua, are associated with severe hemolysis. In addition,
10
(Chap. 33). In addition to oxidative stress, osmotic shock and certain
toxic ions, including gold and aluminum, may act through eryptosis. 33,34
Abbreviations and Acronyms: AsH , arsenic hydride (arsine gas); EDTA, ethylen- Oxygen Gas and Ozone
3
ediaminetetraacetic acid; G6PD, glucose-6-phosphate dehydrogenase; NADPH, Hemolytic anemia can occur when ambient oxygen (O ) concentration
2
reduced nicotinamide adenine dinucleotide phosphate. is increased markedly. Hyperbaric oxygenation has been associated
35
with acute hemolysis. Ozone (O ), which has been widely used in
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