Anemia and Iron

Anemia

Inability of the blood to supply tissue with adequate oxygen

Anemia causes

- ineffective hematopoiesis
- insuffisient erythropoiesis
- blood loss or hemolysis

Severity depends on

- Rate of onset
- Severity of blood loss
- Ability of body to adapt

Diagnosis

- patient history
- physical exam
- labs

Retic count categories

- Hypoproliferative
- Hyperproliferative

Anemia categories

- Normocytic, Normochromic
- Macrocytic, normochromic
- Microcytic, hypochromic

Response to anemia

- Right shift= Increase oxygenated blood flow
- Erythropoietin (EPO) production

EPO

- Glycoprotein/Hormone
- Growth Factor
- in kidneys due to tissue hypoxia
- Constant small amount for RBC level

EPO function

- primarily on CFU-E
- Releases marrow retics early= reduced marrow transit time
- Decreases apoptosis

EPO increases

reticulocyte count

Recombinant EPO

treatment for certain types of anemia, end stage renal disease, HIV associated anemia

Functional Iron

- 70%
- Hgb iron in the blood
- myoglobin in muscles

Stored iron

- 20%
- Ferritin and hemosiderin
- Macrophages and hepatocytes

Stored iron inclusion stains

- Wright stain: Pappenheimer bodies
- Prussian blue stain: Siderotic granules

Transported iron

- 10%
- transferrin in plasma

Factors that increase iron requirements

- menstruation
- pregnancy
- infancy/children

Heme iron molecules

- myoglobin
- hemoglobin

Heme iron

- Fe 2+ (Ferrous)
- red meat
- absorbed in intestines

Non-heme iron molecules

- Transferrin
- Ferritin
- Hemosiderin

Non-heme iron

- Fe 3+ (ferric)
- vegetables and grains
- needs to be reduced to be absorbed

Iron excretion

- not effective
- Exfoliated skin
- Hair
- Sloughed intestinal epithelial

Absorption is influenced by:

- Amount & type of iron from food
- State of the GI mucosa and pancreas
- iron stores
- Erythropoietic needs

Erythropoietic needs is

Inversely related to the amount of iron stores and the rate of erythropoiesis

Transporting Ferric iron (Fe 3+)

- reduced to ferrous by ferrireductase
- transported through luminal membrane of enterocyte
- stored as ferritin or oxidaized by ferroportin

Transporting Ferrous iron (Fe 2+)

- Absorbed by luminal enterocyte membrane heme transporter
- Iron is removed by HO-1
- stored as ferritin or oxidized by ferroportin

Iron Transport in blood

exported from enterocyte is ferrous (2+)
- converted to ferric (3+) to be carried by apotransferrin

Transferrin structure

2 iron + apotrasnferrin
(diferric)

Transferrin function

- transports iron from plasma to erythroblasts in bone marrow
- binds transferrin receptors (TfR) on the erythroblast membrane

Release of iron

- Transferrin binds to TfR on RBCs
- releases iron, and transferrin returns to circulation

Excess iron stored as

ferritin and hemosiderin
- Macrophages (RES) in liver, bone marrow, and spleen

Ferritin

- primary storage form
- Ferric iron + apoferritin = ferritin

Hemosiderin

Secondary storage form
- Partially degraded, slow release

Removed from storage by

transferrin

Iron state for oxygen binding

ferrous (2+)

Methemoglobin Reductase Pathway

ferric (3+) reduced to ferrous (2+)

Hepatocytes

- regulate iron levels by release hepcidin
- increase iron level= increase hepcidin

Hepcidin

binds to ferroportin and blocks iron from entering circulation