hematology exam 1 - hemoglobin structure and fxn, iron metabolism, iron lab tests

hemoglobin molecule

6composed of 4 heme grps and 2 pairs of dissimilar polypeptide chains

4 polypeptide chains: (two al6pha and two beta)

4 iron (ferrous state, Fe2+66) molecules (heme group)

what is the most functional iron a constituent of

hemoglobin and myglobin (heme proteins that carry oxygen)

25% is in a storage form

where is most non-heme iron stored

in ferritin or hemosiderin in hepatocytes or macrophages

how are body iron levels regulated

absorption → humans cannot actively excrete iron

how is iron absorbed and transported

by enterocytes in the duodenum and jejunum and carried to basolateral membrane where it passes to plasma via ferroportin

hephaestin converting ferrous to ferric iron

transferrin: carrier protein, binds to iron and transports it in the plasma

• transferrin receptors: located on all cells (except mature RBCs)

  • provide cells with transferrin bound iron w/in the cell

• in hemopoietic centers (mainly bone marrow), enters immature erythroid cells AFTER transferrin has attached to transferrin receptors on the cell membrane

hepcidin

antimicrobial peptide

• regulates basolateral iron transport

• when hepcidin is elevated in chronic inflammation and infection, can interfere with absorption = iron deficiency anemia

ferritin and hemosiderin

storage forms of iron

ferritin: water soluble complex

hemosiderin: insoluble complex

• made up of ferritin aggregates found in liver and bone marrow

• degradation product of ferritin produced by digestion of protein + release of iron

normally most stored iron is in ferritin form, but when iron stores are abundant, proportion of hemosiderin increases

where is iron stored

liver, bone marrow and spleen

when iron is needed from iron stores, returned to transferrin to be used by cells that need iron for metabolism

laboratory tests for iron

serum ferritin

serum iron

serum transferrin

transferrin saturation

bone marrow or liver biopsy

serum transferrin receptor analysis

erythrocyte protoporphyrin assay

serum ferritin

analyte: serum ferritin

adult reference range: 12-300 mcg/L

indicates: iron stores

serum iron

analyte: serum iron

adult reference range: 10-30 mmol/L

indicates: tissue iron supply

serum transferrin (TIBC)

analyte: serum transferrin (TIBC)

adult reference range: 47-70 mmol/L

indicates: tissue iron supply

transferrin saturation

analyte: transferrin saturation

adult reference range: 16-60%

indicates: tissue iron supply

bone marrow or liver biopsy

analyte: bone marrow or liver biopsy

adult reference range: normal stores seen in tissue

indicates: direct observation of functional iron

relationship b/w hemolysis and clinical events

• decrease in RBC, HgB, Hct = symptoms of anemia, pallor, fatigue, tachycardia

• increase of bilirubin = jaundice

  • releases massive amounts of hemoglobin into the bloodstream, which is broken down into heme.

  • The heme is rapidly converted into excess unconjugated (indirect) bilirubin, temporarily exceeding the liver's capacity to process and clear it

• hemoglobinemia = blood-tinged plasma

  • excess free Hb in plasma

• hemoglobinuria = blood-tinged urine

  • excess fre Hb in urine

• hyperplasia: increase in RBC precursors = M:E of 1:2

  • normally 3:1 or 4:1

• peripheral blood smear shows polychromasia = a laboratory finding where red blood cells appear larger and have a bluish-gray tint under a microscope

  • rapidly releasing reticulocytes (immature RBCs) into bloodstream to compensate for loss of RBCs

• spherocytosis may appear (if Abs present) = when RBCs go through spleen the Abs are sheared off and spherocytes form

extravascular hemolysis

90% of hemolysis

occurs in spleen, liver, lymph nodes, bone marrow, and RES

RBC destroyed and contents phagocytized by macrophages

leads to release of Heme and globin groups

globin AA are recycled into AA pool and the heme components go diff pathways

iron is transported by transferrin (protein carrier) to bone marrow for erythropoiesis

intravascular hemolysis

10% is intravascular and it occurs when RBCs are destroyed directly in the blood vessel

Hb released into plasma

• can be observed in the red-tinged plasma after blood is centrifuged

hemoglobinuria (blood in urine)

ex of potential causes: transfusion incompatibility, complement mediated hemolysis

how to distinguish extravascular from intravascular hemolysis in lab

hemoglobin released from ruptured RBCs binds haptoglobin (transport protein) in plasma

Hgb - Haptoglobin complex is too large to be filtered by kidneys

• not excreted, but transported to liver to be destroyed

• Undetectable Haptoglobin = Intravascular: Because cells break directly in the blood, a massive flood of hemoglobin is released. Haptoglobin quickly binds to this hemoglobin and is rapidly cleared by the liver, leaving almost zero haptoglobin remaining.

• Low or Normal Haptoglobin = Extravascular: Because the destruction happens in the spleen or liver, the hemoglobin is safely processed inside macrophages. It leaks into the blood at much lower levels. Therefore, haptoglobin is moderately decreased but rarely fully consumed.

idek results to differentiate b/w extravascular and intravascular hemolysis

Useful Lab tests:

1. Plasma Haptoglobin is low during hemolysis (no place for transporting HB)

• intravascular

2. Hemoglobin conc., Hematocrit, and RBC count decreased

• extra and intra

3. Reticulocyte count elevated

• extra and intra

4. Plasma LDH enzyme elevated (RBC enzyme)

• lactate dehydrogenase enzyme, normally present in high lvls inside RBC

5. Hemoglobinemia (hemoglobin in plasma elevated)

6. Hemoglobinuria (hemoglobin in urine).