transferrin
Summary
Transferrin is a plasma glycoprotein synthesized by the liver that binds and transports iron in the blood. It reflects iron status and hepatic synthetic function, and is commonly assessed via transferrin saturation and total iron-binding capacity (TIBC) in iron disorder workups.
Detail
Transferrin binds ferric iron (Fe3+) and delivers it to cells via transferrin receptor-mediated endocytosis, particularly to erythroid precursors in the bone marrow for hemoglobin synthesis. Each transferrin molecule can bind two iron atoms. TIBC is an indirect measure of transferrin level, and transferrin saturation (serum iron/TIBC x100) indicates the percentage of transferrin binding sites occupied by iron.
Clinical significance: - Iron deficiency anemia: Low serum iron, low ferritin, HIGH transferrin/TIBC (increased hepatic synthesis to maximize iron capture), LOW transferrin saturation. - Anemia of chronic disease: Low serum iron, high ferritin (inflammation increases ferritin as acute phase reactant), LOW transferrin/TIBC (hepcidin-mediated suppression), variable saturation. - Hemochromatosis: HIGH serum iron, HIGH ferritin, LOW-normal or low transferrin/TIBC, HIGH transferrin saturation (>45%) - classic screening test. - Liver disease/malnutrition: Decreased transferrin synthesis (hepatic protein), can complicate interpretation. - Pregnancy/estrogen use: Increased transferrin synthesis. - Nephrotic syndrome: Transferrin lost in urine, contributing to microcytic anemia despite normal iron stores.
Transferrin receptor (CD71) expression is upregulated in iron-deficient states and used clinically (soluble transferrin receptor assay) to distinguish iron deficiency from anemia of chronic disease, especially when both coexist.
Atransferrinemia (rare genetic disorder) causes severe iron overload in tissues with paradoxical anemia due to impaired iron delivery to erythroid precursors, highlighting transferrin's essential transport role.
High-yield exam point: Understanding the inverse relationship between ferritin and transferrin/TIBC in different anemia types is frequently tested, as is calculating and interpreting transferrin saturation for hemochromatosis screening.
Sources
- First Aid for the USMLE Step 1
- Robbins Basic Pathology
- Harrison's Principles of Internal Medicine
- UpToDate: Iron deficiency and iron overload disorders
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