I have always believed that knowledge is power. Once we understand something, it can give us a form of acceptance, and in turn, give us closure. The more we understand, the more everything makes sense. Some of the following information has been taken from an article written by Prof Christopher F. Rose and Prof Rajiv Jalan entitled “Heretical thoughts into hepatic encephalopathy“. This appeared back in March 2022: https://www.journal-of-hepatology.eu/article/S0168-8278(22)00183-0/fulltextMany lines of investigation have confirmed that hepatic encephalopathy is irreversible in many patients and suggests the need for further studies focussing on mechanisms of neuronal injury and death to guide future drug development for these patients. The clinical evidence behind using lactulose for all severities of hepatic encephalopathy, which is currently considered the standard of care is poor and placebo-controlled trials for hepatic encephalopathy should be considered ethically sound. This expert opinion identifies current challenges in hepatic encephalopathy and highlights areas which require further debate and investigation to help advance the field both scientifically and clinically.
Ammonia production occurs in all tissues of the body during the metabolism of a variety of compounds. Food is broken down by friendly bacteria in the gut, the production of ammonia being a byproduct. Ammonia is also produced by the metabolism of amino acids and other compounds which contain nitrogen. Ammonia is produced from leftover amino acids, and it must be removed from the body. The liver produces several chemicals (enzymes) that change ammonia into a form called urea, which the body can remove in the urine. If this process is disturbed, ammonia levels begin to rise. A metabolic mechanism exists by which nitrogen is moved from peripheral tissues to the liver for its ultimate disposal as urea, while at the same time maintaining low levels of circulating ammonia.Due to the buildup of scar tissues of a cirrhotic liver, the liver struggles to process the ammonia. This can then enter the bloodstream and be carried up to the brain. In the brain, there are billions of neurons, that are constantly firing and talking to each other. These neurons, need to be kept functioning properly to work. This is one of the many jobs carried out by a special type of Glial cell called Astrocytes. Astrocytes are believed to be involved with intelligence. In this lovely lecture, “Astrocytes and Intelligence” - Dr Isabel Christie (FameLab 2013 UK Final). Explains in easy-to-understand language what Astrocytes are and talks of their function. What I like about this video is that while Isabel is talking about the role of the astrocytes, she experiences an attack of brain fog.
One of the primary roles of astrocytes is to protect neurons against excitotoxicity by taking up excess ammonia and glutamate and converting it into glutamine via the enzyme GS. Changes in GS expression may reflect changes in astroglial function, which can affect neuronal functions. Hyperammonemia is an important factor responsible for hepatic encephalopathy (HE) and causes astroglial swelling. Hyperammonemia can be experimentally induced and an adaptive astroglial response to high levels of ammonia and glutamate seems to occur in long-term studies.I have included this next video, “How Alzheimer's Changes the Brain” because of the superb graphics. And this leads to the important subject of “Alzheimer's Type ii Astrocytes” in Hepatic Encephalopathy.