Liver Flashcards
1
Q
Major Functions of Liver
A
- 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
Q
Zone 1, 2, 3
A
- 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
- Excretion with bile
3
Q
How does blood enter and leave the liver?
A
- Enter: 2 sources
- Hepatic Artery
- Hepatic Portal vein
- Leaves:
- Hepatic Vein
4
Q
Bile Pathways
A
- Bile synthesized in the liver
- secreted into common hepatic duct
- for storage in the gallbladder
- Gallbladder–>common bile duct–>lumen of intestine
5
Q
Causes of Abnormal Liver Function
A
- Hepatitis
- Fibrosis
- Cirrhosis
- Portal hypertension
6
Q
Hepatic Portal Vein
A
- Absorbed from GI Tract to liver
- billirubin
- nutrients
- Drugs
- Foreign Substances
7
Q
Hepatic Artery:
A
- Metabolites and drugs from peripheral tissues to liver
- bilirubin
- nutrients
- metabolites of hormones and drugs
8
Q
Hepatic Vein
A
- Blood leaving the liver: Metabolites to peripheral tissues
- glucose
- plasma proteins
- Albumin
- clotting factors
- angiotensinogen
- Urea
- Vitamin D
- somatomedins
- Metabolites for excretion
9
Q
Bile Duct
A
- liver produces bile and secretes into duodenum
- bile salts
- bilirubin
- water, ions
- phospholipids
10
Q
Jobs of liver
A
- Glucose and Fat metabolism
- Protein Synthesis
- Hormone synthesis
- Urea production
- detoxification
- Storage
11
Q
Lobules
A
- 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
Q
Significance of Kupfer Cells
A
- Macrophages
- line the walls of the sinusoids
- break down RBCs and split hemoglobin and breakdown heme into iron and bilirubin
13
Q
Stellate Cells
A
- found in space of disse
- storage unit for retinoids
- source of growth factors for hepatocytes
- Abnormal–produce large amounts of collagen=hepatic dysfunction
14
Q
Cholangiocytes
A
- classic columnar epithelial cells
15
Q
Tight Junctions
A
- leaky
- water and ions are drawn into canalicular lumen @ concentratin equal to plasma
- glucose
- calcium glutathione
- amino acids urea
16
Q
Active Secretion
A
- mediated by ABC transporters
- ATP binding cassettes
- requires ATP
- MDR3
- multidrug resistance protein 3
- another class of ABC
- flipps across the membrane
17
Q
Hepatocyte Bile Secretion Mechanism
A
- 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
Q
What are the main membrane transporters in hepatocytes?
A
- Hepatocytes:
- NTCP
- 2Na+ and bile acid symporter
- OATP
- bile acids
- organic anions
- xenobiotics
- bilirubin
- OCT-1
- organic cations
- NTCP
- Hepatocyte to bile canaliculus
- BSEP
- bile acids
- MRP2
- organic anions
- MDR1
- organic cations
- MDR3
- phospholipids
- BSEP
19
Q
What are the main membrane transporters in cholangiocytes?
A
- Luminal:
- AQP
- water
- Cl- Channel (CFTR)
- HCO3-/CL- antiport
- GGT
- Glutathionine to AAs
- AQP
- Basolateral: (Facing ECF)
- NKCC1
- NBC
- Na/HCO3- symporter
- NHE1
- Na/H antiport
- K+ channel
- ABC5 and ABC8
- secrete cholesterol into canaliculus
20
Q
Components of bile
A
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
Q
Concentration of Bile in Gallbladder
A
- NaCl and H2O absorbed
- prolonged storage of bile/cholesterol can precipitate as gallstones
22
Q
Sphincter of Oddi
A
- usually closed
- Biled diverted to gallbladder for storage
23
Q
Meal stimulates CCK
A
- hepatic bile secretion
- gallbladder contraction
- pancreatic acinar secretion
- relaxation of sphincter of oddi
24
Q
Cholesterol
A
- Precursor for bile synthesis
- inefficient dietary uptake
- loss in the body can occur only through excretion
- bile output:
- 1/3 bile
- 2/3 cholesterol
- bile output:
- Loss of cholesterol compesenstated by synthesis to maintain daily balance
- hepatic and extrahepatic
25
Q
Hypercholesterolemia tx:
A
- interupt hepatic circulation of bile acids
26
Q
Primary Bile Acids
A
- Liver
- Cholic acid
- Chenodeoxycholic acid
27
Q
Secondary Bile Acids
A
- Intestinal bacteria form
- Deoxycholic acid
- Lithocholic acid
- Ursodeoxycholic acid
28
Q
Conjugatio of bile acids
A
- conjugated with glycine or taurine
- insures ionization
- Colon microflora deconjugate bile acids
- passive absorption in terminal ileum/colon
- Na+ coupled
29
Q
Where is bile produced?
A
Liver
30
Q
Where is bile secreted?
A
- Duodenum
- CCK mediated
31
Q
Where is bile absorbed after secretion into duodenum
A
- Majority absorbed into hepatic portal circulation from:
- terminal ileum
- asbt*, active trasnport
- apial Na+ dependent bile acid transporter
- asbt*, active trasnport
- Colon
- Passive, deconjugated
- terminal ileum
- Net effect:
- recycle bile acid pool between liver and intestines daily
- postprandial
32
Q
Cholestasis
A
- impaired production of bile or obstructed bile flow
- caused by defects in the:
- liver
- biliary tree
33
Q
Disorders of bile formation and secretion
A
- Cholestasis
- Primary biliary cirrhosis and cholangitis
- Congenital biliary atresia
- Obstructive jaundic
- Hereditary cholestasis syndrome
34
Q
Congenital BiliaryAtresia
A
- Pediatric condition
- defect in intrahepatic bile duct formation
35
Q
Obstructive jaundice
A
- Gallstone Blocks one of th extrahepatic bile ducts
36
Q
Hereditary Cholestasis syndrome
A
- mutaiton in specific transport protein
- can cause liver injury (cytotoxicity) due to accumulation of bile in hepatocytes
37
Q
Jaundice
A
- 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
- Hemolysis
38
Q
Bilirubin
A
- most important component of bile pigment
39
Q
What enzymes are measured to test liver injury
A
ALT, AST, GGT
