Flashcards in Anemia due to Chronic Disease, Sideroblastic anemia Deck (14)
What is the molecule that locks iron into its storage sites so it cannot be used, where does it come from?
Hepcidin locks iron out into its storage sites, so that it cannot be transferred to the erythrocytes. It is one of the mediators released by inflammation. Also HEPCIDIN suppresses EPO production.
When does Anemia of Chronic disease tend to present?
It presents commonly in hospitalized patients presenting with chronic inflammation or cancer.
What is the theory behind why the hepcidin is released if the overall effect is anemia in the end?
Bacteria requires iron to grow and in a state of chronic inflammation or cancer the body is thinking that it is being attacked by bacteria, ergo it reacts by sequestering its iron stores to "starve" the bacteria. Unfortunately this also prevents transport of iron into the bone marrow and suppresses bone marrow response to EPO resulting in anemia.
What are the lab values of ACD in terms of serum iron, TIBC, % sat, serum ferratin, FEP?
Serum ferratin will increase because more tissue iron will be stored, conversely serum iron will decrease and TIBC will decrease (ferratin and TIBC always does the opposite of one another) because there will be less iron in the blood. % sat will decrease as a result. FEP will increase.
What is the disease progression of ACD in terms of micro/macro/normocytic anemia?
It will initially begin as normocytic anemia, again the body will prefer to make less RBC's so long as they are well formed, and then progress into microcytic anemia when the iron deficiency is severe. This is similar to iron deficiency anemia.
How are cancer patients treated for ACD? For people with chronic inflammation?
They are treated with exogenous EPO and this is particularly helpful. For people with chronic inflammation, that issue is treated and therefore less hepcidin will be released once there is less inflammation.
What is "Sideroblastic anemia?"
Decreased propoporphorin synthesis, and since protoporphorin is needed in addition to iron to create heme, this will also lead to microcytic anemia.
What is the first step of production of protophorphorin? Why is this step important?
Succinyl CoA is converted to Amino Levoneic Acid, through the enzyme ALA Synthase (known as ALAS). ALAS is the rate limiting step, and vit B6 is a co-factor of this rate limiting step.
What is the enzyme that puts protophorphorin and iron together to make Heme? Where does this reaction occur?
Ferrochelatase. This reaction occurs in the mitochondria.
After Succinyl CoA turns into ALA, what is the next step?
ALA turns into Prophobillinogen through the enzyme ALAD.
What is the classic cell seen in sideroblastic anemia and why is it forming?
Fe and Protophorphorin have to meet in the mitochondria for the ferrochelatase to turn them into heme. However if there is a decreased synthesis of protophorphorin, iron will just sit in the mitochondria and just pile up. Since the mitochondria is arranged in a ring around the nucleus, we end up creating a "RINGED SIDEROBLAST" composed of mitochondria with iron trapped in it around the nucleus.
What is the most common cause of hereditary sideroblastic anemia?
Congenital deformity of the enzyme ALAS, which therefore prevents the rate limiting step of protophorphorin synthesis from occuring (succinyl CoA to ALA).
What are three causes of sideroblastic anemia that is acquired?
Alcoholism, because alcohol is a poison to the mitochondria and damages the production of protophorphorin. Lead posioning can denature ALAD (2nd step of protophorphorin synthesis) and Ferrochelatase (last step of heme production where iron and protoP are put together). Vitamin B6 deficiency because B6 is a cofactor of ALAS. Without it, ALAS wont function. Isoniazid leads to vitamin B6 deficiency and therefore sideroblastic anemia.