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Flashcards in Liver Deck (39)
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1

Major Functions of Liver

  • 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

 

2

Zone 1, 2, 3

  • 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

3

How does blood enter and leave the liver?

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

4

Bile Pathways

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

5

Causes of Abnormal Liver Function

  • Hepatitis
  • Fibrosis
  • Cirrhosis
  • Portal hypertension

6

Hepatic Portal Vein

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

7

Hepatic Artery:

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

8

Hepatic Vein

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

9

Bile Duct

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

10

Jobs of liver

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

11

Lobules

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

12

Significance of Kupfer Cells

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

13

Stellate Cells

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

14

Cholangiocytes

  • classic columnar epithelial cells

15

Tight Junctions

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

16

Active Secretion

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

17

Hepatocyte Bile Secretion Mechanism

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

18

What are the main membrane transporters in hepatocytes?

  • 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

19

What are the main membrane transporters in cholangiocytes?

  • 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

20

Components of bile

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%

21

Concentration of Bile in Gallbladder

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

22

Sphincter of Oddi

  • usually closed
  • Biled diverted to gallbladder for storage

23

Meal stimulates CCK

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

24

Cholesterol

  • 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

25

Hypercholesterolemia tx:

  • interupt hepatic circulation of bile acids

26

Primary Bile Acids

  • Liver
  • Cholic acid
  • Chenodeoxycholic acid

27

Secondary Bile Acids

  • Intestinal bacteria form
  • Deoxycholic acid
  • Lithocholic acid
  • Ursodeoxycholic acid

28

Conjugatio of bile acids

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

29

Where is bile produced?

Liver

30

Where is bile secreted?

  • Duodenum
    • CCK mediated