Liver Function and Metabolism Overview

Liver Function

• The liver performs essential synthetic and excretory functions, acting as a large metabolic factory
• It detoxifies substances and, like the kidneys, excretes metabolic waste products
• The primary blood supply to the liver is the portal vein

General Metabolic Functions

• When glucose levels are high in the portal vein, it's converted to glycogen and fatty acid carbon skeletons, transported to adipose tissue as VLDL
• During fasting, glucose levels are maintained by glycogenolysis (glycogen breakdown) or gluconeogenesis (glucose synthesis from substrates like glycerol, lactate, and amino acids)
• Fatty acids can be metabolized in the tricarboxylic acid cycle, converted to ketones, or incorporated into triglycerides

Synthetic Functions

• Hepatocytes synthesize various plasma proteins (e.g., albumin, globulin), excluding immunoglobulins and complement
• They synthesize most coagulation factors (e.g., fibrinogen, prothrombin (II), factors V, VII, IX, X, XI, XII, XIII), but vitamin K is crucial for the synthesis of factors II, VII, IX, and X
• The liver also synthesizes primary bile acids and lipoproteins like very-low-density lipoprotein (VLDL) and high-density lipoprotein (HDL)

Synthetic Functions (Further Detail)

• The liver has a large functional reserve, so deficiencies are only apparent with extensive liver disease
• Factors like protein loss through the kidneys, gut, skin, or across capillary membranes (in inflammation) can reduce plasma albumin
• Prothrombin levels (measured by prothrombin time) can decrease due to impaired hepatic synthesis (e.g., vitamin K malabsorption or hepatocellular damage). Parenteral vitamin K administration can correct this

Excretion and Detoxification

• Bilirubin and other substances are inactivated and excreted by the liver
  • Cholesterol is excreted in bile, possibly converted to bile acids
  • Amino acids are deaminated, and ammonia is converted to urea
  • Steroid hormones are conjugated with glucuronate and sulfate, becoming water-soluble and excreted in urine
• Many drugs are metabolized and inactivated by the liver's endoplasmic reticulum system, some excreted in bile
• The reticuloendothelial Kupffer cells remove toxic substances absorbed from the gastrointestinal tract.

Formation and Excretion of Bilirubin

• Red blood cell breakdown (primarily in the spleen) releases hemoglobin, which is split into globin and heme
• Heme is converted to bilirubin after iron removal
• Approximately 80% of bilirubin originates from heme breakdown
• Other sources include immature red blood cell breakdown in the bone marrow, as well as myoglobin and cytochromes
• Bilirubin is transported to the liver, bound to albumin, where it's conjugated, secreted into bile where potentially excreted out.