Circulatory System

1. Within the circulatory system the liver has a unique anatomic location in that it effectively filters all blood coming from the intestinal tract by way of the portal vein before it is pumped to the general circulation. The liver often sees drugs at their highest concentrations, since it is the first organ perfused by blood containing the drug after absorption from the intestinal tract. Approximately 10-15% of total blood volume can be presented to the liver at any given time. The entire absorbed dose must process through the liver before reaching the systemic circulation. The drug may still be subject to repeat extraction and metabolism by the liver even after it reaches the systemic circulation. This anatomic location within the circulatory system makes the liver prone to chemical-induced toxicity.

Once transported to the liver, enzymes break down parent drug into less biologically active forms that are less toxic to the body in a process known as biotransformation. This process also makes drugs more suitable for excretion by the kidneys. During the biotransformation process toxic reactive chemicals or intermediate chemicals may be formed in the liver, which have
These immune cells have the ability to mediate an inflammatory response by releasing cytotoxic mediators including: proinflammatory mediators such as chemokines and cytokines, and reactive oxygen species. Neutrophils can also be recruited to the site of inflammation by way of vasculature. Neutrophils can be chemotactically stimulated and attach to hepatocytes, where they can induce necrosis by releasing reactive oxygen species within the cells. The liver injury is further aggravated by both neutrophils and kupffer cells because they have the ability to affect healthy liver