Sat27November0445PM 13

The liver is an important organ for drug biotransformation.

Which of the following types of liver cell has the most important role in phase I drug metabolism?

(Please select 1 option)

Ito cells

Centrilobular cells This is the correct answer

Mediolobular cells

Periportal cells Incorrect answer selected

Kupffer cells

Explanation

The centrilobular cells receive blood with relatively low oxygen content and are susceptible to reduced hepatic perfusion and ischaemia. These cells contain high concentrations of cytochrome P450 isoenzymes. It is therefore an important region for drug biotransformation.

Phase I metabolism has three reactions, hydrolysis, oxidation and reduction. These mainly involve a subset of mono-oxygenase enzymes called the cytochrome P450 system.

Phase II metabolism involves conjugation or acetylation. The molecules become water soluble and suitable for renal excretion.

The functional unit of the liver is the acinus. It consists of a mass of parenchymal cells between two centrilobular veins. The centre of the acinus is formed by the bile duct, hepatic artery and portal vein.

Hepatic acini (zones 1, 2 and 3) of Rappaport. The hepatic acinus represents a liver lobule that is divided into three regions based on their proximity to the distributing veins:

Zone I (periportal) - cells closest to the vessels (portal triad) and first to be affected by incoming blood. These cells receive blood with the highest oxygen content and have a high metabolic rate. Plasma proteins are manufactured in this zone.

Zone II (mediolobular) - cells which are second to respond to blood (in between portal triad and central vein).

Zone III (centrilobular) - cells near the central vein that see blood that has already been altered by cells in zones I and II.

The Kupffer cells are macrophages (15% of total liver cells); they comprise 80-90% of total macrophages in the body and are normally located in sinusoidal lumen anchored to the endothelium by a long cytoplasmic process.

The predominant location is periportal, but found in every region of liver. They remove particulate and other foreign materials from portal blood via phagocytosis.

Fat-storing (Ito, stellate) cells reside in space of Disse; they contain lipid droplets rich in vitamin A. They are responsible for the uptake, storage and release of retinoids, and synthesis and secretion of extracellular matrix proteins (collagenase).

Answer Statistics

1

1%

2

48%

3

3%

4

31%

5

19%

Times answered: 249