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PH-GI28

Liver cell injury and necrosis

How toxins, reactive drug metabolites such as paracetamol’s, low oxygen and immune attack injure liver cells; how swelling and fat give way to apoptosis or necrosis; and how the place and extent of necrosis decide recovery or liver failure.

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  • 5 steps · 9 questions
  • 3D anatomy, affected parts marked

By the end, you can

  • Relate the zones of the liver acinus and their blood supply to where each kind of injury strikes first.
  • Explain the four main routes of hepatocyte injury, including the paracetamol (acetaminophen) pathway through NAPQI and glutathione.
  • Distinguish reversible change (ballooning, fatty change) from death by apoptosis (acidophil bodies) and necrosis.
  • Describe the patterns of necrosis by place and extent, and explain how they lead to regeneration, scarring or acute liver failure.
  • Interpret the liver blood tests that show injury, recognise the classic appearances, and explain how the main treatments act on the mechanism.

What it is

Hepatocellular injury is damage to liver cells (hepatocytes) from toxins, drugs, low oxygen or immune attack. Mild injury causes reversible swelling (ballooning) or fat accumulation; severe or sustained injury kills hepatocytes by apoptosis (single cells) or necrosis (groups of cells). Where in the lobule cells die, and how many, decides whether the liver regenerates, scars or fails.

4 types to tell apart
Predictable (intrinsic) toxic injury
Dose-related injury that follows soon after exposure in anyone who takes enough, such as paracetamol overdose, carbon tetrachloride or death cap mushrooms; usually zonal necrosis.
Idiosyncratic drug injury
Rare, unpredictable injury appearing after weeks to months, often an immune reaction to drug-modified proteins; it can be hepatocellular, cholestatic or mixed.
Ischaemic (hypoxic) injury
Low blood flow or oxygen in shock, cardiac arrest or severe heart failure; centrilobular necrosis with little inflammation.
Immune-mediated injury
T cells kill hepatocytes that display viral or self antigens, as in viral and autoimmune hepatitis; scattered apoptosis and injury at the portal edges.

US spelling: fibres → fibers.

Normal function

Blood flows through three zones of the liver

The liver is built of plates of one cell thick. Blood enters at the , from branches of the portal vein and hepatic artery, runs along the between the plates and leaves by the . Seen by blood flow rather than by shape, the tissue forms an acinus with three zones: (periportal) receives blood first, richest in oxygen and nutrients; (centrilobular, round the central vein) receives it last, with the least oxygen; zone 2 lies between.

The zones also do different work. Zone 1 cells do most of the oxygen-hungry work, such as making glucose and urea. Zone 3 cells hold most of the cytochrome P450 enzymes, especially CYP2E1, which oxidise drugs and toxins, and have less glutathione, the small antioxidant molecule that neutralises reactive products. So oxygen is scarcest, and reactive molecules are made, in the same place.

Healthy hepatocytes rarely divide but can re-enter the cell cycle within hours of injury, so the liver can regrow after losing much of its mass, as long as its framework of reticulin fibres survives to guide the new cells. , macrophages in the sinusoids, clear debris. Hepatocytes contain the enzymes ALT (alanine aminotransferase) and AST (aspartate aminotransferase), which reach the blood when their membranes are damaged.

Point to it on the model