Hepatobiliary System Flashcards
What are the upper and lower limits of the liver
Nipple and subcostal margin
What are the inflows and outflows of the liver
Inflow - Hepatic artery (25%), portal vein (75%)
Outflow - Bile, 3x hepatic veins
What is the purpose of blood delivered to liver by:
portal vein?
hepatic artery?
- From digestive system
- Supply oxygen and nutrients
Where is the 1st segment of the liver
Behind portal vein in front of vena cava
What is the micro-function of the liver
Acinus
Blood flow
Bile flow
What is the micro-morphology of the hepatic lobule
Hexagonal structural unit of liver tissue
Each corner consists of a portal triad - links with 3x adjacent lobules
Centre of liver lobule is a central vein - collects blood from hepatic sinusoids
Within lobule there are rows of hepatocytes - sinusoid facing side and bile canliculi facing side
What is the micro-morphology of portal triad
Branch of hepatic artery - O2 rich blood to support hepatocytes
Branch of portal vein - mixed venous blood from GIT (nutrients, abcteria nad toxins) and spleen (waste products), Bile duct - bile produced by liver drain into bile canliculi, coalesce with colangiocyte-lined bile ducts are lobule perimeter
What is the hepatic acinus
FUnctional unit of the liver
Consists of two adjacent 1/6th hepatic lobules
- Share 2 portal triads
- Extend into hepatic lobules as far as central vein
What is the three zone model of hepatic acinus
Blood into hepatic acinus via point A
Blood drains out of hepatic acinus via point B
Hepatocytes near outer hepatic lobule receive early exposure to blood contents - o2 but also toxins
What are the sinusoidal endothelial cells
No basement membrane
Fenestrated (discontinuous endothelium)
Allow lipid and large molecule movement to and from hepatocytes
What are kuppfer cells
Sinusoidal macrophage cells
Attatched to endothelial cells
Phgocytosis (eliminate substances arriving from portal circulation)
What are hepatic stellate cells
Exist in dormant state
Store VIt A in liver cytosolic droplets
Activated (fibroblasts) in response to liver damage
Proliferate, chemotactic and deposit collagen in ECM
Collagen cause damage cirrhosis
What are hepatocyte cells
Synthesis e.g. albymin, clotting factors and bile salts
Drug metabolism
Receive nutrients and building blocks from sinusoids
80% of liver mass
Cubical
What are cholangiocyte
Secrete HCO3 and H2O
What are the hepatocyte functions
Metabolic and catabolic functions: synthesis carbs, lipids and proteins
Secretory and excretory functions: syntehsis of proteins, bile and waste products
Detoxification and immunological functions: breakdown of ingested pathogens and processing of drugs
Where does anaerobic conversion of glucose happen
RBCs, renal medulla and skeletal muscle
Where does aerobic oxidation of glucose
CNS, heart, skeletal muscle, most organs
What is the cori cycle
Lactate to pyruvate using lactate dehydrogenase
Diagram of hepatocyte function - protein synthesis
Synthesis of non-essnetial amino acids
Different keto-acids being converted into multiple amino acids
alpha-keto glutarate - glutamate, proline, arginine
Pyruvate - alanine, valine, leucine
Oxaloacetate - aspartate, methionine, lysine
How do you resolve the issue that muscle can potentially utilise amino acids to produce glucose for energy
Convert pyruvate to glucose requires energy
Removing nitrogen as urea requires energy
Solution: transfer problem to the liver (glucose-alanine cycle)
What can alanine be converted to in the liver
Glutamate 0 can be converted to urea or combined with alpha ketogutarate to use in kreb cycle
Alpha ketoglutarate
Pyruvate
Diagram of triglyceride metabolism in liver
What can acetyl CoA produce in the liver
Fatty acids
Cholesterol
How do you make lipoproteins in teh liver
Glycerol, tri-acyl glycerol, apoproteins, phospholipids, cholesterol, fatty acids
What is one of the major roles for cholesterol in the cells
Maintain cell membrane, make hormones
How are the liporoteins in the liver used
What deos the liver store
Fat soluble vitamins (A,D,E,K) - sufficient for 6 months except for vit K essential for blood clotting
Storage of iron as ferritin (available for erythropoeisis)
How does the liver detoxify
Phase 1 (modification_ - P450 enzymes - makes molecules more hydrophilic
Phase 2 (conjugation) - attach water soluble side chain to make less reactive
What is the composition of bile
What are the uses of bile
Cholesterol homeostasis
Absorption of lipids and lipid soluble vitamins (A,D,E and K)
Excretion of
- drugs
- xenobiotics
- cholesterol metabolites
- adrenocortical and otehr steroid hormones
- alkaline phosphatase
What is the primary secretion of bile
Hepatocytes (60%)
- Bile secretions reflect serum concentrations
Secretion of bile salts, lipids and organic ions
What is the secondary modifaction of bile
Cholangiocytes (40%)
- Alteration of pH
- H20 drawn into bile by osmosis via paracellular junctions
- Luminal glucose and organic acids reabsorbed
- HCO3 and Cl actively secreted into bile by CFTR (cystic fibrosis transmembrane regulator)
- IgA exocytosed
What are the facts about production of bile
500mls produced each day
Bile is yellow/green due to pigments such as billirubin and biliverdin
What are the main transporters of biliary system
Bile Salt Excretory Pump
MDR related proteins (MRP1 nad MRP3)
Products of familial intrahepatic cholestasis gene (FIC1)
Products of mulitdrug resistance genes (MDR1(xenobiotics and cytotoxins) and MDR3(phospatidylcholine))
How does bile salts perform its function
Form micelles
Hydrophilic domain - faces out, dissolves in water
Hydrophobic domain - nucleus and methyl - faces in and dissolves fat
What enzymes convert triglyceride to fatty acids
Lipase and colipase
How does the regulation of bile flow happen
Between meals Sphincter of Oddi is closed - bile diverted into gall bladder
Eating - sphincter of oddi relaxes
Gastric contents enter duodenum causing release of cholecystokinin (CCK)
CCK causes gall bladder to contract
What happens during bile salts after entering the GIT
95% reabsorbed by terminal ileum by Na+/bile salt cotransport Na+K+ ATPase system
5% coverted to secondary bile acids in colon - deoxycholic acid is absorbed wheras 99% lithocolic acid excreted
absobred B salts back to liver
What are the fucntions of gallbladder
Stores bile - concentrates bile/ acidifies bile
GB contraction triggered by CCK, CCKa receptors and neuronal plexus of GB wall (innervated by parasympathetic fibres of vagus nerve)
Where is bilirubin derived from
75% from Hb breakdown
22 from catabolism of otehr haemoproteins
3% from ineffective BM erythropoiesis
Free BR - H20 insoluble, yellow pigment
How is bilirubin excreted
85% excreted in faeces - (BR-urobilinogen-stercobilinogen-stercobilin (brown compound))
15% enters enterohepatic circulation - deconjugated into lipophilic form of stercobilinogen, urobilinogen
1% enters systemic circulation and excreted by kidneys
What are some causes of jaudice
Hemolysis
Decrease uptake, conjugation and secretion of bilirubin
Extrahepatic outflow
What is a endoscopic retrograde cholangiopancreatography
It is used to diagnose biliary and pancreatic duct systems using endoscopy and fluoroscopy
What is a percutaneous transhepatic cholangiography
Radiology to visualise anatomy of the biliary tract
