Makindo Medical Notes

Remember it is an acute phase reactant and can mirror the CRP and so does not always reflect iron stores.

Overview of Ferritin

• Ferritin is a protein complex that stores iron in a non-toxic, soluble form and releases it in a controlled manner.
• Needed for iron homeostasis. Found in nearly all cells of the body, especially liver, spleen, bone marrow, and skeletal muscles.
• Ferritin levels in the blood are a reflection of the body's iron stores.

Structure of Ferritin

• Composition:
  • Ferritin is composed of 24 subunits, forming a hollow, spherical shell.
  • These subunits are of two types: heavy (H) chains and light (L) chains, encoded by separate genes.
  • The H and L chains assemble in different ratios depending on the tissue type and iron storage needs.
• Iron Storage:
  • The hollow cavity of ferritin can store up to 4,500 iron atoms in the form of ferric hydroxide-phosphate complexes.
  • Iron is stored in a safe, bioavailable form, preventing toxicity from free iron, which can generate harmful free radicals through the Fenton reaction.

Functions of Ferritin

• Iron Storage and Release:
  • Ferritin stores excess iron and releases it when needed for processes such as erythropoiesis (red blood cell production), cellular respiration, and DNA synthesis.
  • Iron release is tightly regulated to maintain iron homeostasis and meet metabolic demands without causing toxicity.
• Protection Against Oxidative Stress:
  • By sequestering free iron, ferritin helps protect cells from oxidative damage caused by free radicals.

Regulation of Ferritin Levels

• Iron Levels:
  • Ferritin synthesis is upregulated in response to increased intracellular iron levels.
• Inflammation:
  • Ferritin levels can increase during inflammation or infection, acting as an acute-phase reactant.
• Hormonal Regulation:
  • Hepcidin, a hormone produced by the liver, plays a key role in regulating iron homeostasis and ferritin levels.

Clinical Significance

• Iron Deficiency:
  • Low ferritin levels are indicative of depleted iron stores and can be a marker for iron deficiency anaemia.
  • Symptoms may include fatigue, weakness, pallor, and shortness of breath.
• Iron Overload:
  • High ferritin levels can indicate iron overload conditions such as haemochromatosis, where excess iron is deposited in tissues, potentially causing damage to organs like the liver, heart, and pancreas.
  • Management includes phlebotomy or chelation therapy to reduce iron levels.
• Inflammation and Chronic Disease:
  • Elevated ferritin levels can be seen in chronic inflammatory conditions, infections, and malignancies, reflecting the body's response to inflammation rather than iron status.
• Ferritin Testing:
  • Serum ferritin is measured in clinical practice to assess iron stores and help diagnose conditions related to iron metabolism.
  • Interpreting ferritin levels requires consideration of the clinical context, as levels can be influenced by factors such as inflammation, liver disease, and malignancy.

Summary

Ferritin is a critical protein for iron storage and regulation, protecting the body from iron toxicity and oxidative stress. It serves as a key marker for assessing iron status and diagnosing related disorders. Understanding the structure, function, and clinical significance of ferritin is essential for managing conditions of iron deficiency, iron overload, and chronic inflammation.