Liver Degenerative Disease
The liver has three main detoxification pathways:
- Filtering the blood to remove large toxins.
- Enzymatically breaking down unwanted chemicals. This usually occurs in two steps, with Phase I modifying the chemicals to make them an easier target for the Phase II enzyme systems.
- Synthesizing and secreting bile for excretion of fat-soluble toxins and cholesterol.
Filtering the blood is an essential detoxifying function of the liver. As noted earlier, total blood supply passes through the liver several times a day and at any given time, about a pint of blood is in the liver being detoxified. Blood detoxification is critical because blood is loaded with bacteria, endotoxins, antigen-antibody complexes, and other toxic substances from the intestines. A healthy liver clears almost 100% of bacteria and toxins from blood before the blood enters general circulation.
The second essential detoxifying role of the liver involves a two-step enzymatic process for the neutralization of unwanted chemical compounds, such as drugs, pesticides, and enterotoxins from the intestines. Even normal body compounds such as hormones are eliminated in this way. Phase I enzymes directly neutralize some of these chemicals, but many others are converted to intermediate forms then processed by Phase II enzymes. These intermediate forms are often much more chemically active and thus, more toxic than the original substances. Therefore, if the Phase II detoxification system is not working properly, the intermediates linger and cause damage.
Phase I detoxification involves a group of 50-100 enzymes named the cytochrome P450 system. These enzymes play a central role in the detoxification of both exogenous (beginning outside the body, such as drugs and pesticides) and endogenous (coming from inside the body, such as hormones) compounds, as well as in the synthesis of steroid hormones and bile acids.
A side effect of this metabolic activity is the production of free radicals (ie, highly reactive molecules that will bind to cellular components and cause damage). The most important antioxidant for neutralizing these free radicals is glutathione, which is needed for Phase I and Phase II detoxification. When exposure to high levels of toxin produces so many free radicals from Phase I detoxification that glutathione is depleted, Phase II processes dependent on glutathione cease. This causes an imbalance between Phase I and Phase II activity, causing severe toxic reactions as a result of the build-up of toxic intermediate forms.
Phase II detoxification involves conjugation (ie, a protective compound becomes bound to a toxin). Besides glutathione conjugation, the other pathways are amino acid conjugation, methylation, sulfation, sulfoxidation, acetylation, and glucuronidation. These enzyme systems need nutrients and metabolic energy to function. As noted earlier, if liver cells do not function properly, Phase II detoxification slows down and increases the load of toxic intermediates.
The third essential detoxifying role of the liver is synthesis and secretion of bile. The liver manufactures approximately a quart of bile daily. Bile serves as a carrier to effectively eliminate toxic substances from the body. In addition, bile emulsifies fats and fat-soluble vitamins in the intestine, improving their absorption. When excretion of bile is inhibited (cholestasis), toxins stay in the liver longer, subjecting the liver to damage.