Liver Function

Biliruben Three fractions:

1) conjugated (direct), 2) unconjugated (indirect), & 3) delta

Three stages of liver injury due to excessive alcohol consumption

1. Alcoholic fatty liver: mild; recovery with removal of drug 2. Alcoholic hepatitis: evidence of liver damage 3. Alcoholic cirrhosis: most severe; poor prognosis

Portal triad contains

hepatic artery, portal vein, bile duct.

Benign:

hepatocellular adenoma, hemangiomas

Malignant:

hepatocellular carcinoma, hepatocarcinoma, hepatoma

Hepatitis lab findings

increased serum bilirubin, increased urine urobilinogen, positive urine bilirubin, increased AST

Hepatitis symptoms:

jaundice, dark urine, fatigue, nausea, vomiting, abdominal pain

Bilirubin—production

occurs in the Reticuloendothelial System and conjugation of bilirubin to glucuronide occurs in the liver.

Posthepatic:

problem occurs after liver

Prehepatic:

problem occurs before liver (increased bilirubin in the liver and increased serum unconjugated bilirubin)

Hepatic:

problem occurs in liver

Hepatitis B

Can cause both acute & chronic hepatitis Caused by infection with hepatitis B virus (HBV) via parenteral, perinatal, & sexual transmission Serologic markers of HBV infection: HBcAg, HBsAg, HBeAg

Synthetic

Carbohydrate synthesis Liver maintains stable glucose concentrations by storing it as glycogen & degrading glycogen when needed by body.

Hepatitis C

Caused by infection with hepatitis C virus (HCV) via parenteral transmission (primarily by blood transfusion)

Hepatitis E

Caused by infection with hepatitis E virus (HEV): a nonenveloped RNA virus that is only 27-34 nm in diameter Transmitted primarily by fecal-oral route Characterized by water-borne epidemics in developing countries

Cirrhosis

Condition in which scar tissue replaces healthy liver tissue Scar tissue blocks blood flow & prevents proper functioning. Commonly caused by chronic alcoholism & hepatitis C infection

Drug- and Alcohol-Related Disorders

Drug-induced liver disease accounts for 1/3 to 1/2 of all reported cases of acute liver failure in U.S. Most common mechanism of injury is adverse immune response to drug directed against liver. Ethanol (alcohol) is most significant cause of hepatic toxicity.

Two major cell types in liver

Hepatocytes: large cells radiating outward from central vein Kupffer cells: macrophages lining sinusoids; act as phagocytes, engulfing bacteria, debris, toxins

Hepatitis

Injury to liver characterized by inflammation in liver tissue

Tests Measuring Hepatic Synthetic Ability

Serum albumin—unconjugated bilirubin is bound to albumin when circulating in the blood stream Decreased level may be caused by decreased liver protein synthesis. Prothrombin time Commonly increased in liver disease

Hepatitis D

A unique subvirus satellite virus infection Requires HbsAg of HBV for replication; can only occur in patients who already have hepatitis B

Tumors

90-95% of hepatic malignancies are metastatic, not originating in liver cells (primary).

Reye Syndrome

A group of disorders caused by infectious, metabolic, toxic, or drug-induced disease found predominantly in children Often preceded by viral syndrome such as varicella, gastroenteritis, or upper respiratory tract infection (influenza) Associated with ingestion of aspirin during viral syndrome

Enzymes: Phosphatases

Alkaline phosphatase 5'-Nucleotidase Gamma-glutamyltransferase Lactate dehydrogenase

Bilirubin Analysis

All commonly used methods for measuring bilirubin stem from technique described by Malloy & Evelyn in 1937. Based on reaction of bilirubin with a diazotized sulfanilic acid solution with a 50% methanol solution as an accelerator Also quantified by bilirubinometry in neonatal population

Enzymes

Are released into circulation after an injury that results in cytolysis or necrosis Used to differentiate hepatocellular from obstructive liver disease

Enzymes: Aminotransferases

Aspartate aminotransferase (AST) Alanine aminotransferase (ALT)

Lipid synthesis

Liver breaks down fatty acids to form triglycerides, phospholipids, or cholesterol.

Excretory and Secretory

Liver is only organ with capacity to rid body of heme waste.

Detoxification and Drug Metabolism

Liver prevents toxic or harmful substances from reaching systemic circulation by binding or chemical modification.

Liver: Gross Anatomy

Liver weighs 1.2-1.5 kg in healthy adult Located beneath & is attached to diaphragm, protected by rib cage, held in place by ligamentous attachments Divided unequally into 2 lobes by falciform ligament Extremely vascular; receives blood from 2 sources: Hepatic artery (supplies 25%) Portal vein (supplies 75%) Bile canaliculi: small spaces between hepatocytes that form intrahepatic ducts where excretory products of cell can drain

Liver: Microscopic Anatomy

Lobules Microscopic units that divide liver Responsible for all metabolic & excretory functions 6-sided structures with centrally located vein & portal triads Portal triad contains hepatic artery, portal vein, bile duct.

Bile

Made up of bile acids or salts, bile pigments, cholesterol Body produces 3 L of bile per day & excretes 1 L.

Bilirubin Specimen Collection and Storage

May be performed on serum (preferred) or plasma Fasting sample is preferred; hemolyzed should be avoided. Is sensitive to light & should be protected

Hepatitis A

Most common form of viral hepatitis worldwide Caused by infection with the hepatitis A virus (HAV) via contaminated or improperly handled food (oral-fecal route)

Bilirubin Specimen testing Methods:

Most commonly used are Jendrassik-Grof (uses 2 reagents—sulfanilic acid and sodium nitrate in a diazo reaction) or Malloy Evelyn. Caffeine is used to accelerate indirect bilirubin reaction

Reye Syndrome Acute illness characterized by:

Noninflammatory encephalopathy Fatty degeneration of liver Clinical presentation of profuse vomiting Neurologic impairment

Tests Measuring Nitrogen Metabolism

Plasma ammonia level Increased level occurs with liver failure.

Liver: Largest internal organ; functionally complex

Plays critical role in: Metabolism Digestion Detoxification Elimination of substances from body Unique in resilience, ability to regenerate cells destroyed by short-term injury or disease

Bilirubin

Principal pigment in bile, derived from breakdown of red blood cells 200-300 mg produced per day Most is eliminated in feces, some in urine.

Serum Bile Acids

Rarely performed because methods are very complex Patterns of individual bile acids & their state of conjugation are examined.

Urobilinogen in Urine and Feces

Urobilinogen is a colorless end product of bilirubin metabolism that is oxidized by intestinal bacteria to brown pigment urobilin. This occurs in the small intestine. Increased levels in urine are found in hemolytic disease & defective liver cell function. Absence from urine & stool is seen with complete biliary obstruction. Most quantitative methods involve reaction of urobilinogen with p-dimethylaminobenzaldehyde (Ehrlich's reagent) to form a red color.

Hepatitis causes:

Viral, bacterial, & parasitic infections, radiation, drugs, chemicals, autoimmune diseases and toxins

Jaundice

Yellow discoloration of skin, eyes, & mucous membranes Results from retention of bilirubin or other substances