Anemia Of Chronic Disease And Sideroblastic Anemia Flashcards
How do we characterize anemia of chronic disease?
Anemia associated with chronic inflammation or cancer. Most common type in hospitalized patients.
Explain How chronic inflammation leads to anemia?
Chronic inflammation results in acute phase reactants being released form the liver, one of these being hepcidin. The reason hepcidin is released is because the body doesn’t know that the chronic inflammation is from a disease; it thinks there is a microbe somewhere. So hepcidin is released to prevent iron from leaving the storage sites. Remember, bacteria needs iron to survive. So hepcidin not only keeps storage iron at bay and unavailable, but it suppresses EPO.
What are the lab values with anemia due to chronic inflammation?
High ferritin and low transferrin
Low serum and low saturation
High protoporphyrin
What are the two phases/stages of anemia due to chronic inflammation?
Normocytic anemia first and then the microcytic, hypochromic anemia
What is the problem in sideroblastic anemia, big picture?
Defective protoporhyrin synthesis
What are the first two steps in proptoporphyrin synthesis? What happens after these two steps?
- Convert succinyl coa to ALA by ALAS with vitamin b6.
- Convert ALA to porphobilinogen by ALAD
Additional reactions take porphobilinogen and make protoporphyrin
What is the final step in protoporphyrin synthesis and where does it occur?
Ferrochelatase attaches proto to iron to make heme.
Mitochondria
So, what is going on while protoporhyrin is being made?
Iron is being shuttled into the mitochondria to meet up with it
So with all this in mind, what is the mechanism of the problem?
Because we don’t have protoporphyrin being made to be attached to the iron to make heme so it can leave the mitochondria, the iron builds up in the mitochondria. All the mitochondria surrounded the nucleus are now stuffed full of iron, and they call these cells ringed sideroblasts.
What is the most common congenital cause of sideroblastic anemia?
Defect in ALAS and its so profound because it is the rate limiting step.
What are the three acquired causes of sideroblastic anemia and explain how each causes a problem?
Alcoholism because it is a mitochondrial poison
Lead poisoning because it inhibits ALAD and ferrochelatase
Vitamin B6 deficiency, remember this is a cofactor for ALAS
In what clinical setting would be most likely see a vitamin B6 deficiency?
Side effect of isoniazid treatment for TB
What are the 4 lab findings with sideroblastic anemia and what is the overall state of the disease?
Ferritin is jacked up, TIBC is down, serum is up and saturation is up. Iron overload because eventually those red blood cells will die because of free radicals and the iron will leak out. Bone marrow macros will eat up the iron from the dead RBCs and store them and iron will leak out of those.
