11. Functions of the Liver II Flashcards
how is the LIVER’S BLOOD SUPPLY
DUAL BLOOD SUPPLY
- from HEPATIC PORTAL VEIN and HEPATIC ARTERIES
How much of the BLOOD SUPPLY comes from HEPATIC PORTAL VEIN
75%
HEPATIC PORTAL VEIN carries VENOUS BLOOD FROM..
SPLEEN and GI TRACT (intestines etc)
PARENCHYMAL CELLS (related to function) of liver
HEPATOCYTES (80%)
NON-PARENCHYMAL CELLS of Liver
KUPPFER, ENDOTHELIAL, SINUSOIDAL
(6.5%)
BIPOTENTIAL STEM CELLS - OVALOCYTES (from Hepatocytes and Cholangiocytes)
LIVER FUNCTIONS
SYNTHESIS
BREAKDOWN
STORAGE
IMMUNE SYSTEM
etc
BILE COLOUR
GREEN/YELLOWISH BROWN
where is BILE STORED and CONCENTRATED
in GALLBLADDER
BILE is DISCHARGED to the..
DUODENUM
GALLBLADDER BILE COMPOSITION
97% WATER
0.7% BILE SALTS
0.2% RUBIN
0.51% FATS (CHOLESTEROL, FATTY ACIDSM LECITHIN)
INORGANIC SALTS
how much of GALLBLADDER BILE is WATER
97%
how much of GALLBLADDER BILE is BILE SALTS
0.7%
how much of GALLBLADDER BILE is BILIRUBIN
0.2%
how much of GALLBLADDER BILE is FATS (CHOLESTEROL/FATTY ACIDS/LECITHIN)
0.51%
SYNTHESIS of BILE ACIDS is a major route of … METABOLISM
CHOLESTEROL METABOLISM
how much CHOLESTEROL does the BODY PRODUCE PER DAY
and how much of it is used for BILE ACID SYNTHESIS
800 MG/DAY CHOLESTEROL
- 400-600 MG used for BILE ACID SYNTHESIS
How much BILE ACIDS do we SECRETE into Intestines PER DAY
12-18 G
how much of BILE ACIDS is REABSORBED by TRANPORT in ILEUM and RECYCLED (ENTEROHEPATIC CIRCULATION)
95%
what is BILIRUBIN
YELLOW BREAKDOWN PRODUCT of HAEM METABOLISM (RBC breakdown)
what is the name of the PIGMENT from BILIRUBIN that gives FAECES its BROWN COLOUR
STERCOBILIN
if bile can’t flow into the duodenum ie jaundice it is filtered by KIDNEYS and BILIRUBIN gives URINE a DARK COLOUR by which PIGMENT:
UROBILIN
BILIRUBIN has what structure
TETRAPYROLE
/ PORPHYRINS in haem
- 4 RINGS
what is BILIRUBIN CONJUGATED WITH
GLUCORONIC ACID
(by GLUCORONIDATION)
what does BILE FORM to AID LIPID DIGESTION
MICELLES
- Increase SA to digest lipids
- MOVE LIPIDS near BRUSH BORDER for FAT ABSORPTION
FUNCTIONS of MICELLES
- AID LIPID DIGESTION and ABSORPTION (move near brush borders)
- ELIMINATE CHOLESTEROL
- DRIVES BILE FLOW
- EMULSIFY FAT SOLUBLE VITAMINS (D,E,A,K) to HELP ABSORPTION
- REDUCE BACTERIAL FLORA in SMALL INTESTINE and BILIARY TRACT
where can MICELLES REDUCE BACTERIAL FLORA
in SMALL INTESTINES and BILIARY TRACT
BILE ACIDS also have HORMONAL ACTIONS (METABOLIC) which function through 2 RECEPTORS:
- FARNESOID X RECEPTOR (NR1H4)
activates signalling molecules in liver and intestines - G-PROTEIN COUPLED BILE ACID RECEPTOR / TGR5
FARSENOID X RECEPTOR (NR1H4) ACTIVATES SIGNALLING MOLECULES in LIVER and INTESTINES involved in…
- TRIGLYCERIDE and GLUCOSE METABOLISM
- LIVER GROWTH
G-PROTEIN COUPLED BILE ACID RECEPTOR / TGR5 has what FUNCTIONS
METABOLIC, ENDOCRINE, NEUROLOGICAL functions
which bile acid RECEPTOR is involved in TRIGLYCERIDE and GLUCOSE METABOLISM
FARSENOID X RECEPTOR (NR1H4)
which bile acid RECEPTOR is used for METABOLIC, ENDOCRINE & NEUROLOGICAL FUNCTIONS
G-PROTEIN COUPLED BILE ACID RECEPTOR, TGR5
WHERE are PRIMARY BILE ACIDS SYNTHESISED
LIVER
WHERE are SECONDARY BILE ACIDS SYNTHESISED
COLON as a result of BACTERIAL ACTIONS
- PRIMARY bile acids are PARTIALLY HYDROXYLATED
PRIMARY BILE ACIDS:
- CHOLIC ACID
- CHENODEOXYCHOLIC ACID
PRIMARY BILE ACIDS FORMED VIA..
CYTOCHROME P450 Mediated OXIDATION of CHOLESTEROL
What is the RATE-LIMITING STEP in the SYNTHESIS of PRIMARY BILE ACIDS (cholesterol oxidation)
ADDITION of HYDROXYL GROUP of 7TH POSITION of the steroid nucleus
by ENZYME CHOLESTEROL 7 ALPHA-HYDROXYLASE
CHOLESTEREOL 7 ALPHA HYDROXYLASE ENZYME is DOWN-REGULATED by…
CHOLIC ACID
CHOLESTEREOL 7 ALPHA HYDROXYLASE ENZYME is UP-REGULATED by…
CHOLESTEROL
CHOLESTEREOL 7 ALPHA HYDROXYLASE ENZYME is INHIBITED by…
Actions of the ILEAL Hormone: FGF 15/19
what happens to PRIMARY BILE ACIDS to form SECONDARY BILE ACIDS
PARTIAL HYDROXYLATION
- GLYCINE and TAURINE GROUPS REMOVED
PRIMARY CHOLIC ACID becomes SECONDARY BILE ACID:
DEOXYCHOLIC ACID
PRIMARY CHENODEOXYCHOLIC ACID becomes SECONDARY BILE ACID:
LITHOCOLIC ACID
what happens in ENTERO-HEPATIC CIRCULATION
all BILE ACIDS and 95% of BILE is REABSORBED from TERMINAL ILEUM
and RECYCLED by the Liver
BILE ACIDS can BIND to some other PROTEINS such as..
NAPE-PLD
BILE ACIDS GENERATE BIOACTIVE…
LIPID AMIDES
eg. Cannabinoid Anandamide
BILE ACID ROLES in PYSIOLOGICAL PATHWAYS
- STRESS and PAIN RESPONSES
- APPETITE
- LIFESPAN
NAPE-BLD (binds bile acids) orchestrates a DIRECT CROSS-TALK Between..
LIPID AMIDE SIGNALS and BILE ACID PHYSIOLOGY
as SURFACTANTS or DETERGENTS, BILE ACIDS are potentially … to cells
TOXIC
what INHIBITS BILE ACID SYNTHESIS when LEVELS are too HIGH
ACTIVATION of FXR in the liver
- activation by bile acids during absorption in the intestine
-> INCREASES TRANSCRIPTION and SYNTHESIS of FGF19 (which inhibits bile synthesis)
Name of the SPHINCTER before the Ampulla that controls flow of BILE and PANCREATIC JUICE INTO DUODENUM
SPHINCTER OF ODDI (SOD)
how is BILE and PANCREATIC JUICE flow ALLOWED into the DUODENUM (via ampulla)
by GALLBLADDER CONTRACTION
and RELAXATION of the SPHINCTER OF ODDI
what STIMULATE GALLBLADDER CONTRACTION (which relaxes sphincter of oddi)
- ACID FROM STOMAC INTO DUODENUM
- CCK
- SECRETIN - Increases HCO3- / H2O (help relax SOD)
BILE from GALLBLADDER comes to/from COMMON BILE DUCT VIA..
(joins with common hepatic duct)
CYSTIC DUCT
CLINICAL problems that can be caused by BILE ACIDS
- HYPERLIPIDAEMIA
- CHOLESTASIS (excess blockage)
- GALLSTONES
- BILE ACID DIARRHOEA
- COLON CANCER (from deoxycholic acid conc.)
JAUNDICE (YELLOW SCLERA or SKIN) is from..
HYPERBILIRUBINAEMIA
- EXCESS BILIRUBIN in BLOOD
When does JAUNDICE become apparent
when SERUM BILIRUBIN is 2-3X Upper limit of NORMAL
how are blood LEVELS in PREHEPATIC JAUNDICE
RAISED BILIRUBIN ONLY
how are blood LEVELS in HEPATIC JAUNDICE
RAISED BILIRUBIN
RAISED AST
RAISED ALT
how are blood LEVELS in POST HEPATIC JAUNDICE (ie in bile duct)
RAISED BILIRUBIN
RAISED ALP (alkaline phosphatase)
RAISED GGT (gamma GT)
JAUNDICE INVESTIGATION
History and Examination
Urine Dip
prehepatic: Haemolysis
Hepatic: Ultrasound - not dilated ducts
Liver Screen
Post Hepatic: Ultrasound - Dilated ducts
CAUSES OF JAUNDICE
POST HEPATIC JAUNDICE
CONJUGATED HYPERBILIRUBINAEMIA
- bilirubin detectable in Urine
- blockage of floe of bile to duodenum
in bile LUMEN: STONES, TUMOUR
in WALL of LUMEN: STRICTURE, PSC
COMPRESSION on the LUMEN: PANCREATIC CANCER, HILAR LYMPHADENOPATHY