Topic 4: G6PD Deficiency Flashcards
what is G6PD deficiency?
Glucose-6-Phosphate Dehydrogenase (G6PD) Deficiency is a disorder of red blood cells (RBCs) that renders them susceptible to oxidative stress, causing hemolysis (breakdown of RBCs)
what is G6PD deficiency inheritance pattern?
x-linked recessive
what does glutathione do?
free radicals are produced in RBCs normally but if this is left unchecked, all RBC would undergo hemolysis
glutathione is an antioxidant
2GSH: reduced form
GS-SG oxidized state
GSH detoxifies H2O2 and turns it into water so we need lots of glutathione in our RBCs!!
what do we need to keep glutathione in its reduced state?
GSH detoxifies H2O2 and turns it into water so we need lots of reduced glutathione in our RBCs!!
we need NADPH to keep glutathione in reduced state
G6PD is the enzyme that keeps NADPH in its reduced state
what does G6PD do?
it keeps NADPH in its reduced state
NADPH is then whats used to keep glutathione in its reduced state GSH
the reduced form of glutathione is what detoxifies the ROS in RBC so they don’t hemolize
how do oxidizing agents effect RBCs?
usually G6PD-deficient red cells have enough of the enzyme to manage the free radical buildup that occurs as a part of normal cell metabolism
but when cells are exposed to oxidizing agents, they make more free radicals than usual that the G6PD deficient RBCs can’t keep up
a person with normal G6PD levels can generate adequate amounts of reduced glutathione to eliminate free radicals generated and avoid cellular damage
what are examples of oxidizing agents?
fava beans
certain drugs: sulfonamides, dapsone, cotrimoxazole, aspirin, primaquine, nitrofurantoin, chloramphenicol
what do free radicals do to RBCs?
Free radicals break disulfide bonds and cause the dissociation of hemoglobin into heme and globin
Globin in its denatured form then precipitates in the membrane of the RBC, forming an inclusion known as a Heinz body (looks like dots on the RBC)
what happens to RBCs that have oxidative damage once they get to the spleen?
As these RBCs pass through the spleen, macrophages recognize them as abnormal and engulf and remove the membrane containing the Heinz body, causing the formation of the characteristic “bite-cells”
where does RBC hemolysis occur in G6PD deficiency?
hemolysis that occurs in G6PD deficiency is both intravascular (within blood vessels) and extravascular (in the spleen)
what’s the problem with bite cells structure?
bite cells and spherocytes are more fragile and less deformable than normal, biconcave-disc-shaped red cells, so they have a tendency to get trapped in the splenic cords
in what population is G6PD deficiency more common?
Mediterranean descent: Greece, Spain, Italy, Turkey
what disorders give you malaria resistance?
- G6PD deficiency
- sickle cell disease/trait
- pyruvate kinase deficiency
- hemoglobin C
likely due to an inhospitable environment of RBCs
whats the clinical presentation of G6PD?
often clinically normal and not anemic if triggers like fava beans are avoided
if there is an exposure to oxidative agents, there can be signs and symptoms of a “hemolytic crisis”:
- hemoglobinuria (dark urine)
- jaundice
- extreme back or flank pain (from the kidneys getting clogged with hemoglobin)
what test shows you Heinz bodies?
supravital stains
what can you see in the blood smear of G6PD deficiency?
microspherocytes, bite cells, and RBC fragments may be seen
what size are the RBCs of G6PD deficiency?
normocytic anemia
how is the reticulocyte count effected in G6PD deficiency?
reticulocytosis = increased production of RBC precursors from the bone marrow
this is because G6PD deficiency is not a problem with RBC production
what are the Hb and hematocrit levels during an acute hemolytic episode vs. no episode?
during an acute hemolytic episode there’s low hemoglobin (Hb) and hematocrit (Hct)
if no hemolytic episodes occur, the Hb and Hct are usually normal
what CBC values are effected during an acute hemolytic episode?
indirect (unconjugated) hyperbilirubinemia
low levels of free haptoglobin
elevated levels of lactate dehydrogenase (LDH)
low Hb/Hct
why are LDH and free haptoglobin effected during an acute hemolytic episode?
after an RBC undergoes hemolysis, Hb and LDH are released into the bloodstream
haptoglobin then binds free Hb, resulting in low levels of free haptoglobin
the liver is overwhelmed by the amount of bilirubin produced by the breakdown of all these red cells, and it cannot conjugate bilirubin quickly enough so there is a buildup of unconjugated (indirect) bilirubin in the blood
what would G6PD enzyme levels be like after an acute hemolytic episode?
they’d be normal!
the RBCs undergoing hemolysis after exposure to the oxidizing agent are the ones with a reduced G6PD half-life (older RBCs) - these RBCs get wiped out
younger RBCs have a relatively longer half-life and would still be around
so if you’re going to do an enzymatic study you need to do it weeks after the hemolytic episode
how do you treat G6PD deficiency?
most practical treatment for this disease is trigger avoidance
if Hb/Hct are dangerously low, however, transfusion is appropriate
patients are hydrated to prevent the nephrotoxic effects of hemoglobinuria
