Liver Physiology and Lab Data Notes

Primary Functions of the Liver

  • Metabolism
    • Proteins
    • Carbohydrates
    • Fats
  • Digestion: Produces and secretes Bile
    • Important in fat digestion.
    • Bilirubin, a pigment from broken-down red blood cells, is excreted in bile.
  • Storage: Stores iron and vitamins.
  • Detoxification: Detoxifies drugs, poisons, and waste products.
  • Other Functions
    • Converts excess amino acids to fatty acids and urea.
    • Removes nutrients from the blood.
    • Phagocytizes bacteria and worn-out red blood cells.

Protein Metabolism

  • The liver produces various proteins, including:

    • Albumin

      • Functions as a transport medium for molecules in the bloodstream.
      • Draws water into the vascular system from tissue spaces, maintaining oncotic pressure.
      • Hypoalbuminemia (low albumin levels) in liver disease can cause edema (swelling), especially in the lower extremities, and ascites (fluid accumulation in the abdomen).

    • Fibrinogen (factor I), Prothrombin (factor II), Factors V, VII, IX, and X

      • Proteins essential for blood coagulation (clotting factors).
      • Deficiency can lead to uncontrollable hemorrhage.
      • Vitamin K is required by the liver to synthesize prothrombin (and factors VII and IX).

Liver Disease and Clotting Factors

  • Deficient production of clotting factors leads to hemorrhage.

  • Bile Obstruction and Clotting Factors

    • Obstruction causes Vitamin K deficiency, leading to deficient production of clotting factors and hemorrhage.

    • Vitamin K absorption depends on bile salts to help the body absorbs fat; bile obstruction impairs fat absorption and Vitamin K absorption.

    • Without Vitamin K, the liver cannot synthesize prothrombin.

    • Treatment involves administering Vitamin K in cases of bile obstruction.

  • Lab Tests

    • Clotting deficiencies related to liver disease can be detected by:
      • PT: Prothrombin Time (Pro Time)
      • PTT: Partial Thromboplastin Time

Carbohydrate Metabolism

  • The liver maintains a steady glucose level in the bloodstream to provide a source of energy for cells.
  • Major site for converting sugars into glucose
    1. Converts excess sugar to glycogen and stores it.
    2. When glucose is needed, it breaks down glycogen and releases it into the blood.
  • In severe liver disease
    • Hypoglycemia (glucose deficiency) can occur, affecting the brain and other organs.
    • Hyperglycemia (excess glucose) may result from the liver's inability to convert excess glucose to glycogen.

Fat Metabolism

  • Dietary fats are converted to lipoproteins for transport throughout the body for storage or use.
  • Stored fats are transported to the liver and converted into energy.
    • Fat is converted to glucose or other substances, like cholesterol.
    • The liver is the primary site for cholesterol synthesis.
  • In severe liver disease:
    • Low cholesterol levels may be observed.
    • Hypoglycemia can result from the failure of the liver to convert fat to glucose.
    • Fatty liver (accumulation of fat in liver cells) may occur, possibly due to the liver's inability to convert fat to lipoproteins. Other causes include viral hepatitis, alcoholic liver disease, obesity, diabetes, pregnancy, and toxic chemicals.

Bile

  • Bile, an excretory product, is continuously created by hepatocytes.
  • It collects in the bile canaliculi (tiny tubes) and is transported to the duodenum via the bile ducts.
  • Bile is stored in the gallbladder when not immediately needed for digestion.

Bile Functions

  • Primary functions of bile:
    1. Breaks down fats during digestion by emulsifying intestinal fat and aiding in fat absorption.
    2. Removal of waste products excreted by the liver.

Bile Components

  • Major components:
    • Water
    • Bile Salts
      • Essential for digestion and absorption of fats; they act as emulsifiers, suspending fat and allowing for body to absorb.
    • Bile Pigments
      • Major pigment is bilirubin (yellow color).
      • Formed mostly in the spleen during the breakdown of RBCs.
      • Carried to the liver, conjugated (transformed), and then excreted in bile.
      • Echogenic bile (caused by bile pigments) indicates stasis (slowed bile flow).
      • Cholestasis is the slowing or stalling of bile flow through the biliary system.
    • Other components:
      • Cholesterol, lecithin, and protein.

Bile Pathway

  • Bile drains from the liver into the right and left hepatic ducts, which converge to form the common hepatic duct.
  • The common hepatic duct meets the cystic duct of the gallbladder (GB), forming the common bile duct (CBD).
    • [Note: Bile is stored in the gallbladder. The cystic duct moves bile both ways: into the GB for storage and out of the gallbladder when released into the digestive tract.]
  • The CBD joins with the pancreatic duct at the ampulla of Vater (hepatopancreatic ampulla), which enters the duodenum.
  • The ampulla is controlled by the Sphincter of Oddi (hepatopancreatic sphincter).

Hepatic Enzymes

  • Enzymes are proteins that catalyze (speed up) chemical reactions and metabolism.
  • Large quantities of enzymes are present in hepatocytes.
  • With liver disease, damaged cells leak enzymes into the bloodstream.
  • LAB VALUES (Enzymes): Elevated enzymes in blood indicate hepatocellular disease:
    • Aspartate aminotransferase (AST) SGOT - is more sensitive than ALT
    • Alanine aminotransferase (ALT) SGPT - is more specific for liver disease than AST
    • Alkaline phosphatase (ALP)

Hepatic versus Obstructive Disease

  • Classification of Liver Disease:
    • Hepatocellular disease
      • Liver cells (hepatocytes) are the primary problem.
      • Treated medically with supportive measures and drugs.
    • Obstructive disorders
      • Bile excretion is blocked.
      • Treated surgically.

Detoxification

  • The liver is a center for detoxification of waste products from the body and foreign chemicals (drugs, poisons).
  • Transforms harmful substances into harmless substances excreted by the kidneys.

Bilirubin Detoxification

  • Bilirubin, a breakdown product of hemoglobin, is detoxified in the liver.

    • Red blood cells survive an average of 120 days and are broken down by reticuloendothelial cells (REC), primarily in the spleen.

    • Spleen:

      • Hemoglobin released from the red cells is converted to bilirubin by the REC’s and then released into the bloodstream.

    • Bilirubin molecules attach to albumin in the blood and are transported to the liver.

    • Liver:

      • Conjugates (transforms) the bilirubin and then releases it into bile ducts.

Ammonium Detoxification

  • Ammonium (NH4), a toxic product of nitrogen metabolism, is converted to nontoxic urea in the liver.
  • Urea is eliminated from the body by the kidneys.
  • LAB VALUES: BUN (blood urea nitrogen) indicates the level of urea.
  • In severe liver disease:
    • Falloff of urea production causes BUN
    • NH4 levels in the blood may rise to toxic levels, causing brain dysfunction. Failure of ammonium detoxification is a serious consequence of liver failure.

Liver Function Tests

  • Aspartate aminotransferase (AST) SGOT
  • Alanine aminotransferase (ALT) SGPT
  • Lactic acid dehydrogenase (LDH)
  • Alkaline phosphatase (alk phos) (ALP)
  • Bilirubin (indirect, direct, total)
  • Prothrombin time (PT)
  • Albumin and globulins

AST/SGOT and ALT/SGPT (Transaminases)

  • Metabolic enzymes
    • AST (SGOT) (Aspartate aminotransferase, also known as serum glutamic oxaloacetic transaminase)
      • More sensitive than ALT
      • Present in other organs
    • ALT (SGPT) (Alanine aminotransferase, also known as serum glutamic pyruvic transaminase)
      • More specific for liver disease than AST
    • Increased AST/SGOT with hepatocellular disease (might be unrelated to liver)
    • Increased ALT/SGPT with hepatocellular disease (more specific for liver disease)

ALP and LDH

  • LDH (Lactic dehydrogenase)
    • Metabolic enzyme
    • Found in tissue of several systems. LDH (mild increase) in liver disease
  • ALP (Alkaline phosphatase)
    • Metabolic enzyme
    • produced by bone and liver
    • ALP increased for biliary obstruction, hepatic carcinoma
    • ALP (mild increase) with hepatocellular disease

Bilirubin Tests

  • LAB VALUES: Direct (conjugated), Indirect (unconjugated), and total Bilirubin Tests
  • Biliary obstruction: increased Direct bilirubin
    • Example: stone in CBD
    • the hepatocytes pick up bilirubin and conjugate it however, they cannot dispose it.
  • Hemolytic anemias, transfusion reactions: increased Indirect bilirubin
    • With the abrupt breakdown of large numbers of red blood cells, the liver may receive more bilirubin from the reticuloendothelial system than it can detoxify
  • Liver (hepatocellular) Disease: increased Direct bilirubin
    • Example: Cirrhosis or Hepatitis
    • Excretion of bilirubin is the step most readily affected when the hepatocytes are damaged; therefore the diseased hepatocytes continue to take in and conjugate bilirubin but are unable to excrete it.

Prothrombin Time (PT)

  • Prothrombin: one of the clotting factors produced by the liver.
    • Vitamin K is needed to produce prothrombin.
  • PT (Prothrombin Time): Measures the time it takes for blood to clot.
  • PT increased with liver disease (Hepatocytes unable to form prothrombin) or with warfarin (coumadin) treatment.

Albumin, Cholesterol, and AFP

  • Liver is principal site for cholesterol synthesis.

  • Major component of bile

  • low levels of cholesterol in severe liver disease

  • low level of serum Albumin indicates hepatocellular damage (look for limb edema)

  • High Levels AFP: Hepatocellular Carcinoma (Hepatoma) or Liver metastasis

  • AFP (Alpha fetoprotein)