14. Disorders of intermediary metabolism in general liver cell damage

Page created on February 12, 2019. Last updated on May 16, 2020 at 09:39


The term “intermediate metabolism” refers to intracellular metabolism of carbohydrates, proteins and lipids. The liver plays an important role in these processes.

The pancreatic beta-cells detects the increase in blood sugar levels after consuming a meal and starts to release insulin as a response. This promotes entry of glucose to insulin dependent muscle, fat and glycogen production in the liver, causing the excess glucose to disappear from the circulation.

A moderate decrease in blood sugar initiate processes in the opposite direction with the release of contrainsular adrenaline and glucagon, which promotes glucose release from the liver (glycogenolysis). Glucagon also stimulates gluconeogenesis in the liver and somewhat in the kidney.

The liver metabolises and eliminates substances like cortisol, cholesterol, oestrogen, glucagon and plasminogen activators. It also incorporates ammonia into urea.

Intermediate metabolism in liver damage

When the liver is damaged can either hypoglycaemia or hyperglycaemia occur. Hypoglycaemia occurs mostly in acute liver failure, end-stage liver failure and in alcohol intoxication. Hyperglycaemia occurs when there is portal hypertension. The portal hypertension causes glucose-rich blood to be shunted through other portocaval anastomoses and bypass the liver, so that the liver can’t regulate the blood sugar as efficiently. In liver damage is the liver’s ability to eliminate insulin-antagonist hormones like GH, cortisol and glucagon reduced as well, so their level in the blood will be high.

In liver damage will the normal protein synthesis of the liver be reduced, which reduces the plasma levels of proteins like albumin and coagulation factors. The plasma level of some enzymes however is elevated, like alkaline phosphatase (especially in cholestasis), gamma-glutamyltransferase (GGT), aspartate transaminase (AST/ASAT) and alanine transaminase (ALT/ALAT). The livers inability to eliminate proteins like plasminogen activator protein and vasodilatory peptides leads to enhanced fibrinolysis and low blood pressure, respectively.

Some proteins that shouldn’t normally be produced may be synthesised, like α-foetoprotein (AFP) and acute phase protein. The urea synthesis decreases, causing elevated levels of ammonia in the plasma. A damaged liver doesn’t utilize aromatic amino acids efficiently, causing these amino acids to reach high level in the plasma compared to branched chain amino acids. The shift in ratio between the two types of amino acids increases the levels of false neurotransmitters, compounds that mimic the function of neurotransmitters. This may influence the brain negatively.

The fat content of damaged livers is elevated from the normal 5% up to 50%, in which case we call it hepatic steatosis. This is because of low protein synthesis and production of abnormal apolipoproteins. Abnormal lipoproteins in the blood incorporate into the membrane of RBCs and increase their tendency to haemolyse. Due to the liver damage will the body’s ability to eliminate cholesterol be impaired, causing cholesterol levels in the serum to increase.

The liver’s ability to eliminate oestrogen and prolactin is insufficient. This may influence the balance between female and male sex hormones, potentially causing feminisation. Vitamin A and D deficiency is common in liver failure as the liver loses the ability to store them.


The following substances may be more abundant in the serum during liver damage:

  • α-foetoprotein (AFP)
  • Growth hormone
  • Glucagon
  • Cortisol
  • Cholesterol
  • Alkaline phosphatase
  • Gamma-glutamyltransferase (GGT)
  • Aspartate transaminase (AST/ASAT)
  • Alanine transaminase (ALT/ALAT)
  • Aromatic amino acids
  • Abnormal lipoproteins
  • Oestrogen
  • Prolactin
  • Plasminogen activator protein
  • Vasodilatory peptides
  • Ammonia

The following may be less abundant in the serum:

  • Albumin
  • Transporter proteins
  • Coagulation factors

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