Centrilobular region

APAP, although a safe drug in therapeutic doses, can lead to severe and potentially lethal liver and kidney injury in cases of overdose. Liver injury involves a characteristic centrilobular hepatic necrosis. The centrilobular region is rich in metabolic enzymes, such as the CYP family of isozymes. CYP2E1 is the predominant P450 isozyme in catalyzing the oxidation of APAP to a reactive intermediate, N-acetyl-p-benzoquinonimine (NAPQI), which possesses an electrophilic carbon that will covalently bind to cellular proteins [35], as shown in Scheme 3.2. 

More recent immunohistochemical studies using antiparacetamol antibodies have shown that covalent binding of a paracetamol metabolite occurs in the damaged centrilobular regions of human liver after overdoses. 

This enzyme is a cytoplasmic enzyme located mainly in the centrilobular region of the liver it catalyzes the oxidation of ethanol to acetaldehyde with nicotinamide adenine dinucleotide as coenzyme. The enzyme is present in relatively low levels in plasma, and it has been used as a marker of hepatotoxicity by some investigators (Moser, Papenberg, and von Wartburg 1968 Khayrollah et al. 1982 Zimatkin, Pronko, and Grinevich 1997). 

Figures 1-4. (Figure 1) Normal liver. Saline-treated control mouse. H E stain. C = central vein. (Figure 2) Normal liver. Saline-treated control mouse. Anti 3-Cys-A immunostain for acetaminophen adduct is negative. C = central vein. (Figure 3) Mouse liver 3 hours after 400 mg/kg acetaminophen. H E stain. Hepatocytes in centrilobular region (within arrows) are swollen and vacuolated. Many are anuclear. Most are necrotic. The periportal region appears normal. C = central vein, P = portal vein. (Figure 4) Same liver as Figure 3. Anti 3-Cys-A immunostain for acetaminophen adduct is strongly positive in centrilobular hepatocytes (dark cells), and negative in periportal hepatocytes. C = central vein, P = portal vein.

Thin-section CT delineates the changes of the thorax in kaolinosis more than chest radiography. Small nodules distributed mainly in centrilobular regions. The appearance of large opacity resembles that of complicated coal workers pneumoconiosis or complicated silicosis (Fig. 12.10c). Peripheral emphysema typically occurs with such masses. Unlike with silicosis, hilar and mediastinal lymph node enlargement more than 1 cm in diameter is not usually seen. 

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