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Flashcards in RBC Disorders Deck (22):

What is G6PD deficiency?

--glucose 6-phoshate dehydrogenase deficiency.
--x-linked recessive
--reduced half life of G6PD, renders RBCs susceptible to oxidative stress


Why does G6PD deficiency cause RBCs to be more susceptible to oxidative stress?

--RBCs are normally exposed to oxidative stress, in particular hydrogen peroxide.
--Glutathione neutralizes hydrogen peroxide, but becomes oxidized in the process
--NADPH, a by product of G6PD, is needed to regenerate reduced glutathione.

Therefore, a decrease G6PD --> decrease NADPH --> decrease reduced glutathione --> oxidative stress/injury of RBCs --> intravascular hemolysis


Who gets G6PD?

There is an African variant and a Mediterranean variant

African: mildly-reduced half life--> mild intravascular hemolysis with oxidative stress

Mediterranean: greatly reduced half-life --> marked intravascular hemolysis with oxidative stress


What do we see on labs with G6PD?

Heinz bodies and bite cells on blood smear

Heinz bodies: oxidative stress causes precipitation of Hb
Bite cells: MOs in spleen remove Heinz bodies


What are causes of oxidative stress in G6PD?

(1) sulfa drugs
(2) antimalarials (e.g., primaquine)
(3) dapsone
(4) fava beans
(5) infections


How does G6PD present?

Back pain, hemoglobinuria days after exposure to oxidative stress. (and hemolytic anemia)


How is G6PD diagnosed?

Heinz preparation used to screen; enzyme studies used to confirm diagnosis


What is anemia?

a reduction in circulating RBC mass


How does anemia present?

with the signs and symptoms of hypoxia


What are the signs and symptoms of hypoxia?

(1) weakness, fatigue
(2) shortness of breath
(3) pale conjunctiva and skin
(4) headache and lightheadedness
(5) Angina, espcially with preexisting CAD


What measures are used as surrogates for RBC mass?

hemogloblin (Hb)
hematocrit (Hct)


How are anemias broadly classified?

By the MCV (mean corpuscular volume)


What is the root cause of microcytic anemias?

Microcytic anemias are due to decreased production of hemoglobin.

During RBD development, the cells from erythroid progenitor to the final, mature RBC get smaller with each division. These anemias can be thought of as having arisen due to an "extra" division in order to maintain Hb concentration in the face of decreased Hb production?


What are the components of hemoglobin?

Hb consists of heme and globin.
Heme is composed of an iron atom, and a protoporphyrin ring.

A decrease in any one of these components will lead to a microcytic anemia


List the main types of microcytic anemia

(1) iron deficiency anemia
(2) anemia of chronic disease
(3) sideroblastic anemia
(4) thalassemias
(5) lead poisoning


Describe the process of iron absorption to storage.

1. Iron is absorbed in the duodenum, via the DMT (divalent metal transporter)
2. Enterocytes transport iron from cell across basolateral MB to blood via ferroportin
3. iron is transported in the blood and delivered to storage sites via transferrin
4. iron is stored in bone marrow macrophages and hepatocytes bound to ferritin.


What are the laboratory measures of iron status?

1. serum iron --measures iron in the blood
2. total iron-binding capacity (TIBC) --measure of transferrin molecules in the blood
3. % saturation -- % of transferrin molecules that are bound by iron (normal is 33%)
4. serum ferritin -- reflects iron stores in macrophages and liver


What are the lab findings of iron deficiency anemia?

1. decreased serum ferritin
2. increased TIBC
3. decreased serum iron
4. decreased % saturation of transferrin
5. microcytic, hypochromic RBCs
6. increased RCDW (red cell distribution width)
7. increased free erythrocyte protoporphyrin (FEP)


What are the clinical features of iron deficiency anemia?

1. anemia
2. koilonychia (spoon-shaped nails)
3. pica (disorder where patients chew on things abnormally, such as ice or dirt)


What is the red cell distribution width?

This measure asks the question: what is the spectrum of the size of RBCs?

If all the RBCs are relatively the same size, the RDW will be low; if there is a wide spectrum of RBC size, the RDW will be high (increased)


Why do we see an increase in the RDW in iron deficiency anemia?

Initially in iron-deficiency anemia, the body tries to make less RBCs that are still normal -- a normocytic anemia. As the deficiency progresses, the body will produce smaller cells. We will therefore see a larger spectrum of cell size.


What is free erythrocyte protoporphyrin and why is it increased in iron deficiency anemia.

Protoporphryin is the organic ring structure that combines with iron to produce heme. When we have an iron deficiency, we are still producing protoporphyrin. However, not all of this will now be bound to iron--it will be "free". Therefore, in iron deficiency anemia, we will have in increase in the free, unbound protoporphyrin.