December 3, 2022

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What is wrong with ‘bleeding blue’?

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Aimee Pinnington, Staffordshire University

Blood is red and there is no debating that, right? Wrong. Crabs, lobsters, spiders and octopuses all have blue blood. There are even tales of the blue people of Kentucky.

The term “blue blood” has been used since 1811 to describe royal families and the nobility. Having pale skin was once a sign of higher social standing, showing the royalty and nobility did not need to spend their time outside with the likes of the working class, such as farmers. They could, instead, take their leisure indoors away from the Sun’s rays. This gave them a paler complexion, which made the veins beneath the surface of the skin more visible, showing a blue tint.

But the blood in veins isn’t actually blue, it can just appear blue tinged because of the way light refracts when shining on the skin. This is because the blood in veins contains less oxygen than the blood in arteries. You could be forgiven for thinking this is the end of the story and that blue blood is just an old-fashioned misconception. But there are a handful of rare conditions that can indeed cause blood to turn blue. Methaemoglobinaemia is one of these diseases.

Under normal conditions, the protein haemoglobin found in red blood cells carries oxygen around your body and delivers it to tissues that need it. In human haemoglobin, there is a compound called heme that carries iron in the ferric (Fe3+) state. It is this iron that typically gives blood its red colour when bound to oxygen. But in a variant of haemoglobin called methaemoglobin, iron is carried in the ferrous (Fe2+) state,, which is unable to bind to oxygen.

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It is normal to have small amounts of methaemoglobin in the blood, but an excessive amount can be caused by a genetic defect, medicines or toxins. The lack of oxygen content leads to cyanosis. This is a condition where the blood has a bluish tinge rather than the typical bright red colour we associate with blood.

Blue people of Kentucky

The Fugate family, or the “blue people of Kentucky” are a good example of those affected by genetic variants leading to methaemoglobinaemia.

The tale of the blue people began when Martin Fugate, a French orphan, moved to Troublesome Creek in Kentucky. Years later, he married Elizabeth Smith, an American woman, and began a family. Both Martin and Elizabeth carried a rare recessive gene that causes high levels of methaemoglobin. It takes two people with the same recessive gene to produce a blue child. Four out of Martin and Elizabeth’s seven children had the recessive gene from both parents, causing them to have high levels of methaemoglobin in their blood. As a result, they had blue skin and lips.

As the family grew in number in such a remote location, intermarriage between cousins became increasingly common, limiting the genetic pool – this led to the recessive “blue blood” gene continuing to be passed through the generations.

The cyanosis seen in the Fugate family can also be caused by medicines. For example, the New England Journal of Medicine reported the case of a 25-year-old woman who developed methaemoglobinaemia after taking topical benzocaine for toothache. This “acquired” methaemoglobinaemia is a rare complication that usually resolves on its own.

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In animals such as crabs, the blue colour of blood is caused by a respiratory pigment containing copper as a key element instead of iron. If we look further into the animal kingdom, we can find examples of green blood in earthworms and skinks, purple blood in lamp shells, and even clear blood in ice fish, all due to the variation in haemoglobin and respiratory pigments. A small molecular change, with a rainbow of outcomes.


Aimee Pinnington, Senior Lecturer in Biomedical Science, Staffordshire University

This article is republished from The Conversation under a Creative Commons license. Read the original article.


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