Tuesday, 12 February 2008

Why are patients with liver cirrhosis jaundiced?

Firstly: what is jaundice?

Jaundice is the clinical manifestation of an elevated serum bilirubin; it's basically a yellow discolouration of the skin and (particularly) the sclera. Bilirubin is most easily conceived as the breakdown product of the 'haem' part of the haemoglobin molecules. (Why would your body be breaking down haemoglobin molecules - don't you need them? Of course you do, but unfortunately red blood cells have a finite lifespan of about 120 days. At around this period, they start to lose their ability to squash into capillaries, which are often smaller than themselves. To prevent their getting stuck, the spleen removes old red blood cells from the circulation. The iron-porphorin ring is recycled, but the haem part is simply degraded and excreted.)

As you are no doubt aware, an elevated bilirubin is helpfully subdivided into two categories, depending on whether the bilirubin has been water-solublised ('conjugated' to another protein) or not. The liver is responsible for such conjugation. Thereafter, it is excreted, via the bile, into the gut.

So why is the bilirubin raised in cirrhosis?

In cirrhosis, the architecture of the liver is massively distorted (and there is copious fibrosis and regenerative nodules). Since the supply of blood to the hepatocytes (liver cells) consequently leaves much to be desired, and since the hepatocytes themselves may still destroyed or dysfunctional, the liver's ability to conjugate bilirubin is decreased. This leads to an elevated unconjugated bilirubin.

The same two factors (disrupted architecture and hepatocyte loss/dysfunction) prevent the hepatocytes from excreting into the bile any conjugated bilirubin it may have managed to create. As a result, what conjugated bilirubin there is backs up (like a blocked pipe) and eventually spills into the blood stream. This causes an elevated conjugated bilirubin.

This, in cirrhosis, one often gets a 'half and half' picture, with a raised serum bilirubin measurement - half of which is conjugated, and half of which is unconjugated.

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