5.2-2 Microcytic anemia--chronic disease, sideroblastic

Question 1

What is rate limiting step in protoporphyrin synthesis?

-what can reduce function of this step?

Answer 1

1st step: S-CoA to ALA (via ALAS and B6 cofactor)

-B6 deficiency affects this step. Most commonly seen as side effect of isoniazid

Question 2

Pt who is an alcoholic. What anemia to be concerned about?

Answer 2

Sideroblastic anemia.

Alcohol is a mitochondrial poison–it inhibits mitochondrial reactions, including heme production from protoporphyrin and Fe.

Question 3

Pt with lead poisoning:

-what anemia to be concerned about?

Answer 3

Sideroblastic anemia.

• Lead inhibits 2 of the enzymes in heme synthesis:
  1. ALAD in protoporphyrin synthesis
  2. Ferrochelatase in heme synthesis (Fe + protoporphyrin)

Question 4

Anemia of chronic disease:

mech of anemia

Answer 4

Chronic inflammation induces liver to produce acute phase reactants, including hepcidin.

1. Hepcidin sequesters Fe by limiting Fe transfer from macrophages to erythroblasts in bone marrow.
2. Hepcidin suppresses EPO
   - goal is to hide Fe from bacteria during infection.

Question 5

Anemia of chronic disease:

-what causes it

Answer 5

chronic inflammation

-infection, autoimmune, cancer

Question 6

Sideroblastic anemia

-most common cause

Answer 6

-chronic alcoholism

Question 7

Anemia of chronic disease: lab findings

1. ferritin
2. TIBC
3. serum iron
4. % saturation
5. FEP

Answer 7

1. high
2. low (response to high ferritin)
3. low
4. low
5. high

Question 7

Sideroblastic anemia

-what do you see on blood smear? what is happening?

Answer 7

• ringed sideroblasts
• Fe accumulates in mitochondria surrounding nucleus of erythroblast b/c lack of protoporphyrin to make heme. Fe stains blue in Prussian blue stain.

Question 8

Hepcidin

Answer 8

• acute phase reactant release from liver in response to inflammation.
• causes anemia of chronic disease by:
  1. sequestering Fe in macrophages
  2. suppressing EPO

Question 9

Anemia of chronic disease:

-How to tx

Answer 9

1. Tx underlying cause (eg cancer, autoimmune)
2. Give EPO, esp for cancer pts

Question 10

Sideroblastic anemia

• size of RBCs
• mech

Answer 10

• microcytic anemia
• low protoporphyrin means low production of heme, therefore low Hb, therefore microcytic anemia.

Question 12

Sideroblastic anemia: lab findings and why?

1. ferritin
2. TIBC
3. serum Fe
4. % saturation

Answer 12

Bone marrow: because Fe overloads in mitochondria of erythroblasts, they eventually die and release their Fe, which is absorbed by macrophages and stored as ferritin. Some Fe also leaks into the blood.

1. high
2. low (liver response to high ferritin)
3. high
4. high (b/c of high serum Fe)

These are same lab findings as hemochromotosis (iron overload)

Question 13

Pt being treated for TB. What anemia to be concerned about?

Answer 13

Sideroblastic anemia.

-Isoniazid side effect is B6 deficiency. B6 is cofactor in rate limiting step of protoporphyrin synthesis (enzyme ALAS converts S-CoA –> ALA).

Question 14

biochemical steps in production of protoporphyrin, and enzymes.

Answer 14

inside erythocyte precursors:

1. Succinyl CoA –> ALA (enzyme: ALAS, B6 cofactor)
2. ALA –> porphobilinogen (enzyme: ALAD)
3. porphobilinogen –> protoporphyrin
4. protoporphyrin + Fe –> Heme (enzyme: Ferrochelatase)

Question 15

Sideroblastic anemia

-causes include (4)

Answer 15

1. congenital (usu at rate limiting enzyme ALAS)

acquired:

2. Alcohol–inhibits mitochondria function
3. Lead poisoning–inhibits ferrochelatase and ALAD enzymes
4. Isoniazid side effect (B6 deficiency in rate limiting step)

Question 16

Anemia of chronic disease:

-size of RBCs

Answer 16

Just like iron deficiency anemia:

1. early stage: normocytic anemia
2. later stage: microcytic anemia

Question 17

most common anemia in hospitalized patients

Answer 17

Anemia of chronic disease