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28 Cards in this Set
- Front
- Back
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What are all RBCs highly vulnerable to?
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Exogenous and Endogenous oxidants
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What allows RBCs to protect themselves against oxidative injury?
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-HMP shunt
-Glutathione metabolism |
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What is the most important enzyme in the HMP shunt for this purpose?
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Glucose-6-phosphate dehydrogenase (G6PD)
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What is G6PD required for?
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Reducing NADP to NADPH
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What is NADPH needed for?
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Conversion of oxidized GSH to reduced GSH
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What is GSH needed for?
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Catalyzing the breakdown of compounds like peroxide (an oxidant)
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What are the 2 variants of G6PD that cause the most clinically significant HAs?
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-G6PD A-
G6PD Mediterranean |
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What patients have a 10% prevalence of G6PD A-?
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American blacks
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Where is G6PD Mediterranean prevalent?
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Middle east
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Why are G6PD variants common in blacks and middle easterns?
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Because it is associated with protection from P. falciparum (malaria)
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How are G6PD variants different from the normal G6PD-B?
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They have reduced half lives - most markedly is the mediterranean variant.
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Why can't RBCs just make more of the G6PD enzymes when the variants with reduced half lives are degraded?
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Because RBCs do not make new protein
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So when does hemolysis and oxidant stress on RBCs incrase in G6PD associated HA?
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When enzyme levels fall as cells age.
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Is G6PD deficiency intrinsic or acquired?
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Intrinsic - hereditary
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What is the genetic inheritance pattern of G6PD deficiency?
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Recessive X-linked
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So what patients with G6PD variants are at highest risk for sympatomatic disease?
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Males
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What causes symptoms in G6PD deficiency?
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Exposure to oxidant stress
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What are 4 causes of oxidant stress?
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-Drugs (antimalarials, sulfonamides, nitrofurantoins)
-Foods (fava beans) -Infections (WBCs release ROS) |
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What type of hemolysis is seen in G6PD deficiency?
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Episodic - both intra AND extravascular!
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What gets oxidized when G6PD deficient RBCs are exposed? What happens as a result?
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Sulfhydryl groups - so globin chains denature and form membrane-bound precipitates.
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What are the precipitates in G6PD deficiency called? How are they visualized?
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Heinz bodies - seen with supravital staining
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What happens to cells with Heinz bodies?
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Macrophages attempt to pluck them out and create Bite cells
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So 3 abnormal morphologies seen in G6PD deficiency are:
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-Heinz bodies
-Bite cells -Spherocytes |
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What is the predominant type of hemolysis that occurs when G6PD deficient patients are exposed to oxidants? When does it begin?
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-Acute intravascular hemolysis
-Begins 2-3 days post exposure |
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Which patients have the worst degree of hemolysis?
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Mediterranean variants
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Why are the hemolytic episodes in G6PD deficiency self-limiting?
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Because only OLDER cells undergo hemolysis; it stops when only younger cells are left.
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What is the main feature of the recovery phase after a hemolytic episode?
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Reticulocytosis
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What results from the episodic nature of hemolytic episodes in G6PD deficiency?
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No features of chronic HA (no splenomegaly or gallstones)
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