Liver Fx

• • largest visceral and most versatile organ
  • reddish-brown
  • located in right upper quadrant
  • Hepatic artery (25%)
  • Portal vein (75%)


  Liver
• structural and functional unit of the liver

  pentagonal or hexagonal shape

  Lobule
• • Central vein / hepatic venule
  • portal triad
  • sinusoids - lined by Kupffer cells

  major structure of lobule
• • radiates from the central vein
  • regenerative property

  Hepatocytes
• phagocytic macrophages that ingest bacteria

  Kupffer cells
• • system of fluid circulating through liver separate from the blood
  • secretion of bile by hepatocytes

  Hepatobiliary System
• • chief metabolic organ
  • systemic and metabolic activities
  • detoxification and drug metabolism
  • circulatory, secretory, and excretory function

  Liver
• synthesis of albumin and globulin (except gamma globulins)

  deamination of glutamate

  Protein metabolism
• major player in glucose homeostasis

  converts galactose and fructose to glucose

  Carbohydrate Metabolism
• major site of chylomicron remnants

  conversion of cholesterol to bile acids

  synthesis of lipoproteins

  storage site of all fat soluble vitamins (ADEK)


  Fat metabolism
• transport, storage and metabolism of iron, copper and other minerals

  RES
• • ALT/SGPT - ALANINE AMINOTRANSFERASE/serum glutamic-pyruvic transaminase 
  • AST/SGOT - aspartate aminotransferase/serum glutamic-oxaloacetic transaminase
  • ALP - alkaline phosphatase
  • GGT - Gamma-glutamyl transpeptidase 
  • 5NT - 5 NUCLEOTIDASE


  Enzyme synthesis
• -scarring of the liver

  -proper function

  -liver function deteriorates

  -cannot be easily reversed

  -etiology

  Cirrhosis
• most important detoxification mechanismand takes place in liver microsomes via the cytochrome P-450 isoenzymes

  microsomal drug-metabolizing system
• • Primary bile acids: cholic and chenodeoxycholic acid
  • Secondary bile acids: deoxychotic and lithocholic acid


  Bile
• ~550 mL of bile enter the duodenum everday
• -hepatic and cholestatic disease

  -most clinically important: ethanol

  -other drugs like tranquilizers, antibiotic

  -acetaminophen: most common drug associated with serious hepatic injury and produces fatal hepatic failure

  Drug Related Disorders
• principal pigment in bile

  Bilirubin
• Hemoglobin - protoporphyrin ring + iron + globin (RES)
• 1. Protoporphyin ring

  2. Biliverdin - heme oxygenase

  3. Bilirubin 1 - Biliverdin reductase - UDPGT (uridine diphosphate-glucuronosyltransferase); transported to the liver by albumin

  4. Bilirubin 2 - secreted into bile - bacterial enzymes

  5. Mesobilirubin - mesobilirubinogen - urobilinogen - urine
• • non-polar
  • lipid soluble
  • unconjugated
  • free/unbound
  • hemobilirubin
  • prehepatic
  • Indirect
  • water insoluble
  • alcohol soluble
  • affinity to albumin
  • lipid membrane permeable
  • not excreted

  Bilirubin 1
• • polar
  • water soluble
  • conjugated
  • bilirubin diglucoronide
  • post hepatic
  • one minute
  • direct
  • alcohol soluble
  • not affinity to albumin
  • impermeable to lipid membrane
  • excreted in renal

  Bilirubin 2
• Icterus

  yellowish discoloration

  when exceeds 2-3 mg/dL

  well tolerated

  maybe prehepatic, hepatic, posthepatic

  Jaundice
• -ethanol metabolism via alcohol dehydrogenase

  -long term excessive consumption of alcohol

  Alcohol Liver Disease
• 0.2 to 1.2 mg/dL

  adult
• 1.0 to 1.2 mg/dL

  newborn
• • alcohol fatty liver: slight increase in AST, ALT, GGT
  • alcohol hepatitis: moderate increase in AST, ALT, GGT, ALP
  • alcoholic cirrhosis: most severe and irreversible

  3 stages of liver abnormalities
• • excessive erythrocyte destruction: hemolytic anemia, neonatal jaundice/HDFN/erythroblastosis fetalis, malaria
  • characterized by B1
  • bilirubin is not present in urine

  prehepatic jaundice
• -group of clinical manifestation

  -precise etiology is unknown

  -has strong epidemiologic association

  -patient develop neurologic abnormalities

  -absence of treatment leads to death

  Reye’s Syndrome
• prone to kernicterus

  usually treated with phototherapy with exchange transfusion

  Hepatic Jaundice
• -either primary or metastatic: begins in liver cells; tumors from other parts of the body

  -either benign or malignant: hepatocellular adenoma; hepatocellular carcinoma

  Tumors / Neoplasms
• • a circulating inhibitor (antibody) of bilirubin from mother's serum
  • causes transient unconjugated hyperbilirubinemia and jaundice in the first week of life

  Lucey-Driscoll syndrome
• • most common cause of hereditary jaundice
  • manifests during adolescence or early adulthood

  Gilbert Syndrome
• -serum is preferred as plasma protein may cause interferences

  -lipemia causes falsely

  -falsely decreased results

  -protected from direct light exposures: 30-50 degrees Celsius in carbon paper

  -within 2-3 hours if no preservation method

  -serum may be used for up 1 week if refrigerated


  Specimen Requirements
• hereditary hyperbilirunemia due to quantitative defect of UGT

  type 1- complete absence

  type 2- less severe deficiency

  rare

  Crigler-Najjar Syndrome
• -foam test

  -fouchet‘s test

  -ictotest/tablet test

  -dipsticks/multisticks

  Urine Biliburin
• ehrlich and its modifications (Terwen, Watson)

  Urine Urobilinogen
• • Serum: markedly increased B1
  • Urine bilirubin - normal (negative)
  • urobilinogen - increased
  • stool urobilin - darkly colored stool


  parameter results (1st four congenital disorder)
• B2, obstructive in albumin bound B2 (delta bilirubin)

  Pathognomonic sign: liver biopsy

  
  

  
  

  Dubin-Johnson Syndrome
• fecal Urobilinogen

  miscellaneous


  Other Bilirubin-Related Methods