Liver

Question 1

Major Functions of Liver

Answer 1

• First site of processing
  
  • most absorbed nutrients
• Site of detoxification (phase 1-3)
  
  • Metabolism of toxic compounds, drugs
  • convert to excretable substances
• Synthesis and secertion of bile & bile products
• Synthesis of:
  
  • cholesterol
  • steroid hormones
  • proteins
  • amino acids
  • vitamins
  • Glycogen
• High metabolic level of:
  
  • carbohydrates
  • lipids
  • proteins
  • amino acids

Question 2

Zone 1, 2, 3

Answer 2

• Zone 1 cells (outer layer): Cytochrome p450 enzymes-oxidation and hydroxylation
  
  • most sensitive to toxic substances
  • closest to triad
  • greatest supply of nutrients and O2
  • most active in detoxification
• Zone 2 cells (middle): Conjugation w/water soluble molecules
  
  • respond to blood
  • in between portal and central vein
• Zone 3 cells (inner)
  
  • Excretion with bile
    • excretion in feces, and urine if molecules are small enough
    • not reabsorbed by intestines
  • most active in bile synthesis

Question 3

How does blood enter and leave the liver?

Answer 3

• Enter: 2 sources
  
  • Hepatic Artery
  • Hepatic Portal vein
• Leaves:
  
  • Hepatic Vein

Question 4

Bile Pathways

Answer 4

• Bile synthesized in the liver
• secreted into common hepatic duct
  
  • for storage in the gallbladder
• Gallbladder–>common bile duct–>lumen of intestine

Question 5

Causes of Abnormal Liver Function

Answer 5

• Hepatitis
• Fibrosis
• Cirrhosis
• Portal hypertension

Question 6

Hepatic Portal Vein

Answer 6

• Absorbed from GI Tract to liver
  
  • billirubin
  • nutrients
  • Drugs
  • Foreign Substances

Question 7

Hepatic Artery:

Answer 7

• Metabolites and drugs from peripheral tissues to liver
  
  • bilirubin
  • nutrients
  • metabolites of hormones and drugs

Question 8

Hepatic Vein

Answer 8

• Blood leaving the liver: Metabolites to peripheral tissues
  
  • glucose
  • plasma proteins
  • Albumin
  • clotting factors
  • angiotensinogen
  • Urea
  • Vitamin D
  • somatomedins
  • Metabolites for excretion

Question 9

Bile Duct

Answer 9

• liver produces bile and secretes into duodenum
  
  • bile salts
  • bilirubin
  • water, ions
  • phospholipids

Question 10

Jobs of liver

Answer 10

• Glucose and Fat metabolism
• Protein Synthesis
• Hormone synthesis
• Urea production
• detoxification
• Storage

Question 11

Lobules

Answer 11

• irregular hexagonal units of hepatocytes
• Centered around a central vein
  
  • drains into hepatic vein
• Periphery=Hepatic triad
  
  • hepatic portal vein
  • Hepatic artery
  • Bile ductule

Question 12

Significance of Kupfer Cells

Answer 12

• Macrophages
• line the walls of the sinusoids
• break down RBCs and split hemoglobin and breakdown heme into iron and bilirubin

Question 13

Stellate Cells

Answer 13

• found in space of disse
• storage unit for retinoids
• source of growth factors for hepatocytes
• Abnormal–produce large amounts of collagen=hepatic dysfunction

Question 14

Cholangiocytes

Answer 14

• classic columnar epithelial cells

Question 15

Tight Junctions

Answer 15

• leaky
• water and ions are drawn into canalicular lumen @ concentratin equal to plasma
  
  • glucose
  • calcium glutathione
  • amino acids urea

Question 16

Active Secretion

Answer 16

• mediated by ABC transporters
  
  • ATP binding cassettes
  • requires ATP
• MDR3
  
  • multidrug resistance protein 3
  • another class of ABC
  • flipps across the membrane

Question 17

Hepatocyte Bile Secretion Mechanism

Answer 17

• Hepatocyte brings in from sinusoidal blood
  
  • across sinusoidal membrane
• Transport within cell
• chemical modification or degradation
• export into bile across the apical (canalicular) membrane

Question 18

What are the main membrane transporters in hepatocytes?

Answer 18

• Hepatocytes:
  
  • NTCP
    
    • 2Na+ and bile acid symporter
  • OATP
    
    • bile acids
    • organic anions
    • xenobiotics
    • bilirubin
  • OCT-1
    
    • organic cations
• Hepatocyte to bile canaliculus
  
  • BSEP
    
    • bile acids
  • MRP2
    
    • organic anions
  • MDR1
    
    • organic cations
  • MDR3
    
    • phospholipids

Question 19

What are the main membrane transporters in cholangiocytes?

Answer 19

• Luminal:
  
  • AQP
    
    • water
  • Cl- Channel (CFTR)
  • HCO3-/CL- antiport
  • GGT
    
    • Glutathionine to AAs
• Basolateral: (Facing ECF)
  
  • NKCC1
  • NBC
    
    • Na/HCO3- symporter
  • NHE1
    
    • Na/H antiport
  • K+ channel
  • ABC5 and ABC8
    
    • secrete cholesterol into canaliculus

Question 20

Components of bile

Answer 20

micellar solution w/major composition of: BA/PC/choleseterol in 10:3:1 ratio

• Bile acids-65%
• Phospholipids-20%
  
  • Mainly lecithins, ex: PC
• Proteins-5%
• Cholesterol-4%
• Bile pigments-0.3%
  
  • ex: Bilirubin
• Electrolytes-5-6%

Question 21

Concentration of Bile in Gallbladder

Answer 21

• NaCl and H2O absorbed
• prolonged storage of bile/cholesterol can precipitate as gallstones

Question 22

Sphincter of Oddi

Answer 22

• usually closed
• Biled diverted to gallbladder for storage

Question 23

Meal stimulates CCK

Answer 23

• hepatic bile secretion
• gallbladder contraction
• pancreatic acinar secretion
• relaxation of sphincter of oddi

Question 24

Cholesterol

Answer 24

• Precursor for bile synthesis
• inefficient dietary uptake
• loss in the body can occur only through excretion
  
  • bile output:
    
    • 1/3 bile
    • 2/3 cholesterol
• Loss of cholesterol compesenstated by synthesis to maintain daily balance
  
  • hepatic and extrahepatic

Question 25

Hypercholesterolemia tx:

Answer 25

* interupt hepatic circulation of bile acids

Question 26

Primary Bile Acids

Answer 26

* Liver * Cholic acid * Chenodeoxycholic acid

Question 27

Secondary Bile Acids

Answer 27

* Intestinal bacteria form * Deoxycholic acid * Lithocholic acid * Ursodeoxycholic acid

Question 28

Conjugatio of bile acids

Answer 28

* conjugated with glycine or taurine * insures ionization * Colon microflora deconjugate bile acids * passive absorption in terminal ileum/colon * Na+ coupled

Question 29

Where is bile produced?

Answer 29

Liver

Question 30

Where is bile secreted?

Answer 30

* Duodenum * CCK mediated

Question 31

Where is bile absorbed after secretion into duodenum

Answer 31

* Majority absorbed into hepatic portal circulation from: * terminal ileum * asbt\*, active trasnport * apial Na+ dependent bile acid transporter * Colon * Passive, deconjugated * Net effect: * recycle bile acid pool between liver and intestines daily * postprandial

Question 32

Cholestasis

Answer 32

* impaired production of bile or obstructed bile flow * caused by defects in the: * liver * biliary tree

Question 33

Disorders of bile formation and secretion

Answer 33

* Cholestasis * Primary biliary cirrhosis and cholangitis * Congenital biliary atresia * Obstructive jaundic * Hereditary cholestasis syndrome

Question 34

Congenital BiliaryAtresia

Answer 34

* Pediatric condition * defect in intrahepatic bile duct formation

Question 35

Obstructive jaundice

Answer 35

* Gallstone Blocks one of th extrahepatic bile ducts

Question 36

Hereditary Cholestasis syndrome

Answer 36

* mutaiton in specific transport protein * can cause liver injury (cytotoxicity) due to accumulation of bile in hepatocytes

Question 37

Jaundice

Answer 37

* aka hyperbilirubinemia * bilirubin not metabolized by liver * Yellow skin and conjunctiva (whites of eyes) * Infants: * mild jaundice is common in newborns * Liver enzyme UDP-glucurony transferase synthesized slowly * 50% of full term * 80% of premature * appears 2nd to 3rd day postpartum * Tx: White light Phototherapy: * changes transbilirubin to cisbilirubin (water soluble) * Adults: * Hemolysis * sickle cell anemia * malaria * Hepatic Malfunction * hepatitis * cirrhosis * Bile duct obstructed * pancreatic cancer * gallstones

Question 38

Bilirubin

Answer 38

* most important component of bile pigment

Question 39

What enzymes are measured to test liver injury

Answer 39

ALT, AST, GGT