How does too much Paracetamol cause Liver toxicity?


Paracetamol toxicity is the leading cause of acute liver failure in the Western world, including Australia, and New Zealand. So how exactly does it cause liver damage?

Let’s take a look at what happens when you take a normal dose of paracetamol. The drug is rapidly absorbed from the stomach and small intestine into the blood stream (Farrell 2018). It’s transported from the blood into liver cells. Liver cells contain enzymes that pick up each paracetamol molecule and stick a sugar group or a sulphate group onto the side of the molecule. Paracetamol molecules with these added sugar or sulphate groups are no longer active as a pain killer, and are non-toxic and very water soluble allowing them to be passed back into the blood stream, transported to the kidneys & eliminated in the urine (See diagram).

When a somewhat larger paracetamol dose is taken, the above two enzymes become overwhelmed. This forces the excess paracetamol molecules to overflow from the normal pathways. Paracetamol that overflows is converted in liver cells to a new and highly toxic & reactive molecule called ‘NAPQI’. But before NAPQI can do any damage another back up set of enzymes comes to the rescue taking every NAPQI and sticking a funny molecule called ‘glutathione’ onto it. This renders NAPQI harmless & water soluble, allowing elimination via the kidneys and urine. Emergency room Doctors actually give a compound called NAC to paracetamol overdose patients to help liver cells make glutathione to detoxify NAPQI.

If a very large paracetamol dose is taken, or a relatively high dose over a prolonged period, liver cells end up running out of ‘glutathione’ molecules to detox NAPQI which means that this backstop detox pathway no longer works. This leaves a lot of highly toxic NAPQI inside liver cells to do damage and here’s where problems occur.

When NAPQI is allowed to roam free inside liver cells it binds to liver cell proteins and stops many from working. In particular NAPQI binds to proteins in mitochondria – the energy producing organelles within your liver cells – that produce ‘most’ of the cell’s energy. When mitochondria stop working properly, they produce large amounts of free radicals which further damage cell proteins. Eventually the cell loses its ability to produce energy, and this leads to cell DNA breakdown, and finally the whole cell ‘explodes’ leaking toxic contents into the tissue spaces around it and into the blood stream. When this happens to ‘many cells’ at the same time doctors can measure increased levels of liver enzymes in your blood.

Thus, it is the excess NAPQI that leads to hepatocellular damage & death, and eventually to hepatic failure.

Similar enzymatic reactions occur in organs other than the liver also, such as the kidney, and can contribute to some degree of organ dysfunction in other areas of the body.

If you have ongoing chronic musculoskeletal pain, physical therapy such muscle elongation therapy can often help, so why not call us at the clinic to discuss your issues.

Article: Article Written + Submitted by: Andreas Klein Nutritionist + Remedial Therapist from Beautiful Health + Wellness | P: 0418 166 269

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