Serum ferritin
a. Definition: Ferritin is a soluble iron-binding storage protein
(1) Synthesized by BM MPs and hepatocytes
(2) Ferritin keeps iron in a nontoxic form.
(3) MPs are the primary storage site for ferritin in the BM.
(a) Refer to the shaded area in the small box in Figure 12-6 A.
(b) Most of the iron in MPs comes from phagocytosis of senescent RBCs in the spleen.
(4) Serum levels directly correlate with ferritin stores in the MPs. • 1 µg/L of serum ferritin correlates with 8 mg of storage iron.
(5) Synthesis of ferritin in MPs (and hepatocytes) increases in inflammation.
• Caused by the release of interleukin-6 (IL-6)
b. A decrease in serum ferritin is diagnostic of iron deficiency with or without anemia.
c. An increase in serum ferritin is present in ACD (Fig. 12-6 C) and iron overload disease
d. Hemosiderin is an insoluble product of ferritin degradation in lysosomes
(1) Decreased and increased levels of hemosiderin correlate with changes in the ferritin stores in the BM MPs.
(2) Hemosiderin is brown in hematoxylin and eosin–stained tissue and blue with the Prussian blue stain.
Serum iron
a. Definition: Refers to the iron that is bound to transferrin in the circulating blood
• Transferrin is synthesized by the liver and binds iron for transport in the bloodstream.
b. Serum iron is the shaded area of the column
• Note that the normal serum iron level is ~100 µg/dL.
c. Iron shown coming into the MPs is from the degradation of senescent MPs, not from transferrin.
• The amount of iron coming into the MP is equal to the amount of iron that is leaving the MP to bind with transferrin.
d. Decreased serum iron occurs in iron deficiency and ACD
e. Increased serum iron occurs in iron overload diseases
• Examples of iron overload diseases include the sideroblastic anemias (see later) and hemochromatosis .
Serum total iron-binding capacity (TIBC)
a. Definition: Correlates with the concentration of transferrin, the binding protein of iron
(1) Height of the column correlates with serum transferrin and TIBC.
(2) Note that the normal TIBC is ~300 µg/dL.
b. Relationship of transferrin synthesis with ferritin stores in MPs
(1) Inverse relationship between transferrin synthesis and ferritin stores in MPs
(2) Decreased ferritin stores leads to increased liver synthesis of transferrin • Increase in transferrin and TIBC is present in iron deficiency.
(3) Increased ferritin stores lead to decreased liver synthesis of transferrin.
• Decreases in transferrin and TIBC occur in ACD (Fig. 12-6 C) and iron overload disease . Primary function of transferrin is to deliver ferric iron (Fe3+) to erythroid precursors in
the BM.
• Iron on transferrin comes from the BM MPs and from the duodenum, the primary site for iron absorption.
Iron saturation (%)
a. Definition: Refers to the percentage of binding sites on transferrin that are occupied by iron
(1) Formula for calculating iron saturation is iron saturation (%) = serum iron/TIBC × 100.
(2) In Figure 12-6 A, the normal percentage of saturation is 100/300 × 100, or 33%.
b. Decreased iron saturation is present in iron deficiency and ACD (.
c. Increased iron saturation is present in iron overload diseases
Hb electrophoresis
1. Hb electrophoresis is used to detect hemoglobinopathies which include:
a. abnormalities in globin chain structure (e.g., sickle cell disease).
b. abnormalities in globin chain synthesis (e.g., thalassemia).
2. Types of normal Hb in adults that are detected by Hb electrophoresis include
a. HbA, which has 2α/2β globin chains (97% in adults).
b. HbA2, which has 2α/2δ globin chains (2% in adults).
c. HbF, which has 2α/2γ globin chains (1% in adults).
3. Examples of a few abnormal Hb detected by electrophoresis include: sickle Hb, Hb H, and Hb Bart.
Iron studies in normal people (A) and those with iron deficiency (B), anemia of chronic disease (C), and iron-overload diseases (D).
The column represents transferrin, the iron-binding protein. The small box represents bone marrow macrophage stores of ferritin. Note that iron comes into the macrophage and leaves the macrophage after attaching to transferrin via a ferroxidase reaction (not depicted). Every day an equal amount of iron goes into the macrophages and comes out of the macrophages. The iron coming into the macrophage derives from phagocytosis of senescent red blood cells and the degradation of heme into iron (binds to ferritin in the macrophage) + protoporphyrin, the latter converted to unconjugated bilirubin. Note that the amount of ferritin in the macrophages has a negative feedback on transferrin synthesis in the liver. If ferritin stores are decreased, the liver synthesizes more transferrin. If ferritin stores are increased, the liver synthesizes less transferrin. Refer to the text for discussion of the anemias. TIBC, Total iron-binding capacity