Haemochromatosis (Iron Overload) - iron physiology, causes and pathophysiology

Summary

This video provides an in-depth explanation of hemochromatosis, a condition characterized by iron overload in the body. It explores the different causes, including hereditary and secondary forms, and the mechanisms of iron absorption, storage, and regulation. The script highlights key processes such as the role of ferritin, transferrin, and hepsidin in iron metabolism. The consequences of excess iron include organ damage, leading to conditions like liver cirrhosis, diabetes, and arthritis. Diagnosis involves elevated ferritin levels, MRIs, and tissue biopsies, while treatment mainly focuses on phlebotomy or iron chelation to manage iron levels.

Takeaways

• 😀 Hemochromatosis is a condition characterized by iron overload in the body, affecting not just blood, but also tissues and organs.
• 😀 Iron exists in four main forms: ferritin/hemosiderin (storage), transferrin (transport), hemoglobin (oxygen transport), and other proteins/enzymes.
• 😀 Iron is absorbed in the duodenum of the small intestine through a transporter called DMT-1 and can be stored as ferritin or released into circulation via ferroportin.
• 😀 Transferrin is the protein responsible for carrying iron around the body, ensuring it reaches areas like the bone marrow for red blood cell production.
• 😀 The liver plays a crucial role in iron regulation, storing iron and producing hepcidin, which helps control iron absorption and metabolism.
• 😀 Hepcidin regulates iron by inhibiting ferroportin, especially when iron stores are high or during inflammation, leading to lower serum iron levels.
• 😀 Primary hereditary hemochromatosis is caused by mutations in the HFE gene, affecting iron regulation and causing excessive iron release into circulation.
• 😀 Secondary hemochromatosis can result from chronic liver disease, blood disorders like thalassemia, or repeated iron transfusions, leading to iron overload.
• 😀 Non-transferrin bound iron (NTBI) occurs when transferrin becomes saturated, allowing iron to deposit in organs like the liver, heart, joints, and pancreas, leading to tissue damage.
• 😀 Early signs of hemochromatosis include skin pigmentation (bronzing) and a triad of cirrhosis, diabetes, and skin pigmentation.
• 😀 Diagnosis of hemochromatosis includes elevated ferritin levels, MRI evidence of iron overload, and therapeutic phlebotomy, which helps reduce iron levels in the body.

Q & A

What is hemochromatosis and what causes it?

Hemochromatosis is a condition where there is an overload of iron in the body, leading to iron deposition in various organs and tissues. It can be caused by primary hereditary factors, such as mutations in the HFE gene, or secondary causes like chronic liver diseases or blood disorders such as thalassemia.

What are the main forms of iron in the body?

Iron in the body is found in four main forms: ferritin or hemosiderin (storage form), transferrin (transport form), hemoglobin (where most iron is found, carrying oxygen), and other proteins and enzymes involved in various functions.

How is iron absorbed in the body?

Iron is absorbed in the duodenum of the small intestine through a transporter called DMT-1. From there, it can be stored as ferritin or enter circulation via ferroportin, ultimately being bound to transferrin to be transported throughout the body.

What is the role of hepcidin in iron metabolism?

Hepcidin is a key regulator of iron metabolism. It lowers serum iron levels by inhibiting the transporter ferroportin, thus reducing the release of iron into circulation, particularly when iron stores are high or during inflammation.

How does hereditary hemochromatosis affect iron metabolism?

In hereditary hemochromatosis, mutations in the HFE gene (such as C282Y or H63D) reduce hepcidin production. With less hepcidin, ferroportin is not inhibited, leading to excessive iron release into circulation and subsequent iron overload in various organs.

What are some common causes of secondary hemochromatosis?

Secondary hemochromatosis can be caused by blood disorders like thalassemia or sickle cell anemia, where ineffective erythropoiesis leads to iron overload, or by transfusion overload, such as in patients receiving regular red blood cell transfusions.

What is the effect of non-transferrin bound iron (NTBI)?

When transferrin becomes saturated with iron, non-transferrin bound iron (NTBI) can form and is taken up by organs such as the liver, heart, and pancreas. This excess iron can cause reactive oxygen species (ROS), leading to tissue damage, inflammation, and fibrosis.

What organs and tissues are commonly affected by iron overload?

Iron overload commonly affects the liver (causing cirrhosis and increased risk of liver cancer), heart (leading to cardiomyopathy and arrhythmias), joints (causing arthritis), pituitary gland (leading to secondary hypothyroidism or hypogonadism), pancreas (causing diabetes), and gonads (resulting in testicular atrophy).

What are the key signs of hemochromatosis?

The key signs of hemochromatosis include a triad of cirrhosis, diabetes, and skin pigmentation (bronzing of the skin). These symptoms arise due to the accumulation of iron in tissues and organs.

How is hemochromatosis diagnosed?

Hemochromatosis is diagnosed through elevated serum ferritin levels, evidence of iron overload on MRI scans of the liver or heart, or tissue biopsy with iron staining. Additionally, therapeutic phlebotomy (removal of blood) can also normalize ferritin levels, confirming the diagnosis.