Veterinary Clinical Biochemistry and Laboratory Diagnosis-II

STORAGE AND CLEARANCE

Storage

• The liver is designed to store important substances such as glucose (in the form of glycogen).
• The liver also stores fat-soluble vitamins (vitamins A, D, E and K), folate, vitamin B 12 , and minerals such as copper and iron.
• However, excessive accumulation of certain substances can be harmful. Eg. patients with Wilson's disease cannot secrete copper into bile normally and usually have a low level of the copper-binding protein ceruloplasmin.
• Retained copper accumulates in the liver leading to cirrhosis and neuropsychiatric symptoms (in CNS).

Purification, Transformation and Clearance

• The liver removes toxins and ammonia from the blood and then breaks them down or transforms them into less harmful compounds.
• In addition, the liver metabolizes most hormones and ingested drugs to either more or less active products.
• Ammonia
  • The liver converts ammonia to urea, which is excreted into the urine by the kidneys.
  • In the presence of severe liver disease, ammonia accumulates in the blood because of both decreased blood clearance and decreased ability to form urea.
  • Elevated ammonia levels can be toxic, especially to the brain, and may play a role in the development of hepatic encephalopathy.
• Bilirubin
  • Bilirubin is an yellow pigment formed as a breakdown product of red blood cell hemoglobin.
  • The spleen, which destroys old red cells, releases "unconjugated" bilirubin into the blood, where it circulates in the blood bound to albumin.
  • The liver efficiently takes up bilirubin and chemically modifies it to "conjugated," or water-solube, bilirubin that can be excreted into bile.
  • Increased production or decreased clearance of bilirubin results in jaundice, an yellow pigmentation of the skin and eyes from bilirubin accumulation.
• Hormones
  • Since the liver plays important roles in hormonal modification and inactivation, chronic liver disease may cause hormonal imbalances.For eg. the masculinizing hormone testosterone and the feminizing hormone estrogen are metabolized and inactivated by the liver.
  • Men with cirrhosis, and who abuse alcohol, have increased circulating estrogens relative to testosterone derivatives, which may lead to body feminization.
• Drugs
  • Nearly all drugs are modified or degraded in the liver, particularly, oral drugs are absorbed by the gut and transported via the portal circulation to the liver.
  • In the liver, drugs on metabolism, are modified, activated or inactivated before they enter the systemic circulation, or they may be left unchanged.
  • Alcohol is primarily metabolized by the liver, and accumulation of its products can lead to cell injury and death.
  • In patients with liver disease, drug detoxification and excretion may be dangerously altered.
  • This results in drug concentrations that are too low or too high or the production of toxic drug metabolites.
• Toxins
  • The liver is generally responsible for detoxifying chemical agents and poisons, whether ingested or inhaled.
  • Pre-existing liver disease may inhibit or alter detoxification processes and thus increase the toxic effects of these agents.
  • Additionally, exposure to chemicals or toxins may directly affect the liver, ranging from mild dysfunction to severe and life-threatening damage.