Hepatobiliary system Flashcards
Describe the blood supply to the liver?
Hepatic artery 25%
Portal vein 75%
Describe the outflow from the liver?
Bile through bile duct
3 Hepatic vein to inferior vena cava to heart
What is the purpose of the blood delivered to the liver by the portal vein?
?
What is the purpose of the blood delivered to the liver by the portal vein?
? check rexording
What is the structural unit of the liver?
Hepatic lobule In a hexagonal shape
What links 3 adjacent lobules?
Portal triad
What is in the centre of the liver lobule?
Central vein which collects blood from the hepatic sinusoids –> hepatic veins –> systemic venous system
What is within the lobule?
Rows of hepatocytes
Each with a sinuosoid-facing side
And a bile canaliculi facing side
What is found within the portal triad?
Branch of hepatic artery
Branch of portal vein
Bile duct
What does the bile duct do which is brought to lobules by portal triad?
Bile produced by hepatocytes drains into bile canaliculi
Coalesce with cholangiocyte-lined bile ducts around lobule perimeter
What does the branch of portal vein bring?
Mixed venous blood from GIT (nutrients, bacteria & toxins) and spleen (waste products)
Hepatocytes process nutrients, detoxify blood & excrete waste
What does the bile duct do which is brought to lobules by portal triad?
Bile produced by hepatocytes drains into bile canaliculi
Coalesce with cholangiocyte-lined bile ducts around lobule perimeter
What is the functional unit of the liver?
Hepatic Acinus :
Consists of two adjacent 1/6th hepatic lobules
Share 2x portal triads
Extend into hepatic lobules as far as central vein
What three regions can the acinus be split into?
Zone 1
Zone 2
Zone 3
- Hepatocytes near outer hepatic lobule - Zone 1 : Receives most oxygen but most toxin risk. So it is where liver damage takes place first
What are the characteristics of Sinusoidal endothelial cells?
- No basement membrane
- Fenestrated
- Allow lipids & large molecule movement to and from hepatocytes
What are the characteristics of Kuppfer cells?
‘Sinusoidal macrophage cells’
- Attached to endothelial cells
- Phagocystosis
- Eliminate & detoxify substances arriving in liver from portal circulation
What are the characteristics of Hepatocytes, what roles are they involved in?
- 80% of liver mass
- Cubical
- Synthesis e.g. albumin, clotting factors & bile salts
- Drug metabolism
- Receive nutrients & building blocks from sinusoids
- could test for the albumin molecules to check liver function
What is the cholangiocytes?
Cells which Secrete HCO3- & H2O into bile
- gall bladder epithelial cells
What is the Cori cycle?
Metabolic pathway in which lactate produced by anaerobic respiration in muscles is taken into the liver, converted by lactate dehydrogenase into pyruvate.
Gluconeogenesis then takes place = glucose
How does the synthesis of non-essential amino acids take place?
Different keto-acids can be converted into multiple amino acids depending on the transaminase enzyme (vital for production of non-essential amino acids)
a-keto glutarate → e.g. glutamate, proline, arginine
Pyruvate → e.g. alanine, valine, leucine
Oxaloacetate → e.g. aspartate, methionine, lysine
Why is the glucose-alanine cycle carried out in the liver?
Muscles could use amino acids to produce energy but
Pyruvate to glucose conversion takes energy
Removal of nitrogen as urea takes energy
Transferring the problem to the kidney is saving energy
Describe the glucose-alanine cycle
Muscle cell : Glutamate ? plus pyruvate –> Alanine
Liver cell : Alanine into liver. ?
Describe triglyceride metabolism occurring in the liver?
Fatty acids go into the liver, Beta oxidation turns it into acetyl CoA
Series of reaction then gives Acetoacetate = tissue energy source
Describe lipoprotein synthesis occurring in the liver?
Glucose in the liver can turn into either:
- -> Glycerol
- -> Pyruvate –> Acetyl CoA
Acetyl CoA can then turn into either fatty acids or cholesterol.
If the glycerol + cholesterol combine lipoproteins are created
What is stored in the liver?
Storage
fat soluble vitamins (A,D,E,K).
Stores sufficient 6-12 month (except Vit K where store is small)
Vit K essential blood clotting
Storage of iron as ferritin.
Available for erythropoeisis
Describe the two phases of detoxification occuring in the liver?
P450 enzymes
Phase 1 (modification)
– more hydrophilic
Phase 2 (conjugation)
– attach water soluble side chain
to make less reactive
What two organs does the bile connect to?
Pancreas
Liver
What are the uses of Bile?
Cholesterol homeostasis
Absorption of lipids and lipid soluble vitamins e.g. ADEK
Excretion of: xenobiotics/drugs
cholesterol metabolites
adrenocortical & other steroid hormones
Alkaline phosphatase
Describe the composition of bile
Water - 97% Bile salts - 0.7% Inorganic salts - 0.7& Bile pigments - 0.2% Fatty acids - 0.15% Trace metals : Fe, Zn, Mn, Pb, Cu
Describe secondary secretion of bile by cholangiocytes?
Secrete 40% of total bile
Alteration of pH (alkaline electrolyte solution)
H2O drawn into bile by osmosis via paracellular junctions
Luminal glucose & organic acids reabsorbed
HCO3- & Cl- actively secreted into bile by CFTR (Cystic Fibrosis Transmembrane Regulator)
IgA exocytosed
What do Biliary transporters do?
Biliary excretion of bile salts and toxins on the apical and basolateral membranes of hepatocytes and cholangiocytes
+
Main transporters include:
Bile Salt Excretory Pump (BSEP) – active transport of BAs into bile
MDR related proteins (MRP1 & MRP3)
Products of the familial intrahepatic cholestasis gene (FIC1)
Products of multidrug resistance genes
MDR1 → excretion of xenobiotics & cytotoxins
MDR3 → phospatidylcholine.
Which two primary bile acids are synthesised in the liver?
Cholic acid
Chenodeoxycholic acid
Which two secondary bile acids are produced when gut bacteria convert cholic acid and chenodeoxycholic acid?
Deoxycholic acid
Lithocolic acid
What does it mean by Bile salts are ‘Amphipathic’ ?
Steroid nucleus planar- has 2x faces
How does emulsification lead to micelles by bile salts?
Fat globule is emulsified - broken down into bile salts and phospholipids
Emulsification drops are created with these breakdown products
Lipase and Colipase enzymes create these droplets into fatty acids and or monoglycerides
These then form micelles:
Bile salts surrounding the inner micelle made of phospholipids, fatty acids, monoglycerides
describe the structure of bile salts?
Form Micelles
1x surface hydrophilic domains (hydroxyl & carboxyl) - faces OUT → dissolves in water
2nd surface hydrophobic domains (nucleus & methyl) faces IN → dissolves in fat
FFAs & cholesterol INSIDE
1x surface hydrophilic domains (hydroxyl & carboxyl) - faces OUT → dissolves in water
2nd surface hydrophobic domains (nucleus & methyl) faces IN → dissolves in fat
FFAs & cholesterol INSIDE
How does emulsification lead to micelles by bile salts?
Emulsified droplets can be turned into fatty acids by Lapse and Colipase.
The indivitual fatty acid - Monoglyceride can be trapped between bile salts = micelle
Micelles are absorbed by the gut
Describe Enterohepatic circulation
95% bile salts reabsorbed from terminal ileum
By Na+/bile salt co-transport Na+-K+ ATPase system
5% converted to secondary bile acids in colon:
Deoxycholic acid absorbed
99% Lithocolic acid excreted in stool
absorbed B.salts back to liver & re-excreted in bile
What causes the the release of cholecystokinin (CCK)
What does it do?
Gastric contents (FFAs, AAs > CHOs) enter duodenum causing release of cholecystokinin (CCK)
CCK causes gall bladder to contract
Describe the functions of the gall bladder?
Stores 50ml of Bile, concentrated and acidifies it
Gallbladder contracts by CCK
Binds to CCKA receptors & neuronal plexus of GB wall (innervated by preganglionic parasympathetic fibres of vagus nerve)
Describe the functions of the gall bladder?
Stores 50ml of Bile, concentrated and acidifies it
Gallbladder contracts by CCK
Binds to CCKA receptors & neuronal plexus of GB wall (innervated by preganglionic parasympathetic fibres of vagus nerve)
What two forms can bilirubin exist as?
- biliverdin = green bile
Free BR - water insoluble, yellow pigment
75% BR from Hb (erythrocytes) breakdown
22% from catabolism of other haemoproteins
3% from ineffective BM erythropoies
What is conjugated/direct bilirubin?
Bilirubin diglucuronide
How is 85% of bilirubin excreted in stool?
Bilirubin –> Urobilinogen –> stercobilinogen –> stercobilin ( brown compound )
How is 15% of Bilirubin excreted trough the enterohepatic circulation?
BR–> deconjugaed –> lipohilic form : urobilinogen, stercobilinogen
How is 1% of Bilirubin excreted?
enters systemic circulation & excreted by kidneys
What is ERCP?
Endoscopic Retrograde Cholangiopancreatography
What is PTC?
Percutaneous Transhepatic Cholangiography (PTC): remove blockages
