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
