Hepatobiliary System Flashcards
What are the main parts of the liver (on the surface)?
- right lobe
- left lobe
- caudate lobe
- falciform ligaments
- quadrate lobe
- gall bladder
- ligamentum teres
Where is the liver in the GI system?
- anterior to gall bladder, duodenum, stomach , etc.
- superior to the large intestine
- in the right side of body
What is the hepatic portal system?
• connects capillaries of GI
tract with capillaries in liver
• nutrient-rich blood leaves GI tract + is first brought to liver for processing
before being sent to heart
What is the purpose of the hepatic portal vein?
- 75% of blood supply inflow
* carries in venous blood drained from spleen, GI tract + associated organs
What is the purpose of the 3 hepatic veins?
• drains de-oxygentaed blood from liver into inferior vena cava
What is the purpose of the hepatic artery?
- 25% of blood supply inflow
* carries in blood from aorta
How many functioning sections does the liver have?
8 : I-IV on left, V-VIII to right
What is a 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 → hepatic veins → systemic
venous system
• Within lobule are rows of hepatocytes, each has sinusoid-facing side & bile
canaliculi-facing side
What is a hepatic acinus?
- Functional unit of liver
- Hard to define anatomically
- Consists of two adjacent 1/6th hepatic lobules
- Share 2x portal triads
- Extend into hepatic lobules as far as central vein
What is a portal triad?
set of 3 vessels:
• branch of hepatic artery
• branch of hepatic vein
• branch of bile duct
• Branch of hepatic artery • Brings O2-rich blood into liver to support hepatocyte’s high energy demands • Branch of portal vein • Mixed venous blood from GIT (nutrients, bacteria & toxins) and spleen (waste products) • Hepatocytes process nutrients, detoxify blood & excrete waste • Bile produced by hepatocytes drains into bile canalicul • Coalesce with cholangiocyte-lined bile ducts around lobule perimeter
What is the function of the hepatic artery branch in the portal triad?
Brings O2-rich blood into
liver to support hepatocyte’s
high energy demands
What is the function of the hepatic vein branch in the portal triad?
Mixed venous blood from
GIT (nutrients, bacteria &
toxins) and spleen (waste
products) - Hepatocytes process nutrients, detoxify blood & excrete waste
What is the function of the bile duct branch in the portal triad?
Bile produced by hepatocytes drains into bile canaliculi - Coalesce with cholangiocyte-lined bile ducts around lobule perimeter
How is blood moved in + out of the hepatic lobules?
• blood moves into hepatic
acinus via portal triad
• blood drains out of hepatic acinus via central vein
What is the 3-zone model?
Acinus split into 3 regions:
• Zone 1 (centre oval, high O2 + high toxin risk)
• Zone 2 (surrounds zone 1, medium O2 + medium toxin risk)
• Zone 3 (surrounds zone 2, lower O2 + lower toxin risk)
What zone of the acinus receives the earliest exposure to blood contents?
Zone 1
What is a sinusoidal endothelial cell?
• No basement membrane
• Fenestrated endothelium
• Allow lipids & large molecule movement to +
from hepatocytes
What is a Kuppfer cell?
• Sinusoidal macrophages • Attached to endothelial cell • Phagocystosis • Eliminate & detoxify substances arriving in liver from portal circulation
What is a hepatocyte?
- 80% of liver mass
- Cubical
- Synthesis e.g. albumin, clotting factors & bile salts
- Drug metabolism
- Receive nutrients & building blocks from sinusoids
What is a hepatic stellate cell?
- Exist in dormant state
- Store vitamin A in liver cytosolic droplets
- Activated (fibroblasts) in response to liver damage
- Proliferate, chemotactic & deposit collagen in ECM
What is a cholangiocyte?
• Secrete HCO3- & H2O into bile
What are the functions of hepatocytes?
• Metabolic & catabolic functions: synthesis & utilisation of carbohydrates, lipids + proteins
• Secretory & excretory functions: synthesis
& secretion of proteins, bile + waste products
• Detoxification & immunological functions: breakdown of ingested
pathogens & processing of drugs
What is glycolysis?
- anaerobic conversion of glucose → lactate (RBCs, renal medulla & skeletal muscle)
- aerobic oxidation of glucose (CNS, heart, skeletal muscle, most organs)
What is glycogenesis?
synthesis of glycogen from glucose (liver & muscle)
What is glycogenolysis?
breakdown of glycogen to glucose
What is gluconeogensis?
production of glucose from non-sugar molecules
- amino acids (glutamine) in liver & renal cortex
- lactate (from anaerobic glycolysis in RBCs & muscles)
- glycerol (from lipolysis)
What is lipolysis?
breakdown of triacylglycerols → glycerol & FFAs
What is lipogenesis?
synthesis of triacylglycerols
What are the 4 lobes of the liver?
- right
- left
- caudate
- quadrate
What lobe of the liver is the biggest?
right
What separates the right and left lobes?
middle hepatic vein
How are the 8 functioning sections supplied with blood?
each functioning segment has its own blood supply, etc.
Why is it important to know that the 8 functioning sections are supplied by blood vessels separately?
when doing a sectorectomy (removing part of the liver), only one of the blood vessels need to be tied off, not the whole artery
How do hepatocytes help with carbohydrate metabolism?
- metabolises lactate from muscle cells to produce pyruvate
- pyruvate is converted into glucose by gluconeogenesis
- glucose is fed back into muscle cell for cell metabolism
How do hepatocytes help with protein synthesis?
AAs from muscle cells or diet converted into secreted proteins e.g. plasma proteins, clotting factors, lipoproteins, etc.
How do hepatocytes help with synthesis of non-essential AAs?
gg
What is the problem that muscle cells have with utilising AAs to produce glucose?
- converting pyruvate to glucose requires energy
* removing nitrogen as urea requires energy
What is the solution to the muscle cells’ problem w utilising AAs?
let liver deal with it in the glucose - alanine cycle
How do hepatocytes help with deamination + protein metabolism?
g
How do hepatocytes help with triglyceride metabolism?
g
How do hepatocytes help with lipoprotein synthesis?
g
How do hepatocytes help with storage?
• Stores fat soluble vitamins (A,D,E,K) sufficient for 6-12 months (except Vitamin K where store is
small)
• stores iron as ferritin so it is available for erythropoiesis
How do hepatocytes help with detoxification (xenobiotics)?
P450 enzymes
• Phase 1 (modification) = more hydrophilic
• Phase 2 (conjugation) = attach water soluble side chain to make less reactive
What is bile?
g
What are the uses of bile?
- Cholesterol homeostasis
- Absorption of lipids & lipid soluble vitamins (A, D, E, & K)
- Excretion of xenobiotics/drugs, cholesterol metabolites, adrenocortical & other steroid hormones, alkaline phosphatase
How much bile is produced everyday?
500 ml
What colour is bile?
- yellow = pigment bilirubin
* green = pigment biliverdin
What two cells secrete bile? In what proportions?
- hepatocytes = 60% of bile
* cholangiocytes = 40%
What happens in primary secretion?
- Bile secretions reflect serum concentrations
* Secretion of bile salts (acids), lipids & organic ions
What happens in secondary modification?
• 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
How is biliary excretion of bile salts + toxins carried out?
performed by biliary transporters on apical surface of hapatocytes + cholangiocytes
What are the main transporters of bile salts + toxins?
- 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
What are bile salts synthesised from?
cholesterol
How does the liver modify bile salts?
Na+ and K+ salts of bile acids are conjugated in liver to glycine + taurine
How does gut bacteria affect bile acids?
converts primary bile acids from the liver to secondary bile acids
What is the function of bile salts?
- Reduce surface tension of fats
* Emulsify fat prior to its digestion & absorption
What are the two primary bile acids?
- cholic acid
* chenodeoxycholic acid
What does cholic acid get converted into?
deoxycholic acid
What does chenodeoxycholic acid get converted into?
lithocolic acid
What do bile salts form?
micelles
What are the features of micelles?
- Steroid nucleus planar - has 2 faces (amphipathic)
- 1 surface hydrophilic domains (hydroxyl & carboxyl) faces out, dissolves in water
- 2nd surface hydrophobic domains (nucleus & methyl) faces in, dissolves in fat
- Free fatty acids & cholesterol INSIDE
How is bile flow + secretion regulated between meals?
sphincter of oddi closed + bile diverted into gall bladder for storage
How is bile flow + secretion regulated when eating?
sphincter of oddi relaxes
How is increase in bile mediated?
- gastric contents enter duodenum causing release of cholecystikinin (CKK)
- CCK causes gall bladder to contract = increase in bile
What is the enterohepatic circulation?
g
What happens to 95% of bile salts in the enterohepatic circulation?
absorbed by the terminal ileum by the Na+/bile salt co-transport Na+ / K+ ATPase system
What happens to 5% of bile salts in the enterohepatic circulation?
converted to secondary bile acids in colon:
• deocycholic acid is absorbed
• 99& of lithocolic acid excreted in stool
What happens to absorbed bile salts?
absorbed bile salts go back to the liver + re-excreted in bile
What are the functions of the gall bladder?
stores + concentrates + acidifies bile
How is gall bladder contraction triggered by CKK?
binds to CCKA receptors & neuronal plexus of GB wall (innervated by preganglionic parasympathetic fibres of vagus nerve)
What is bilirubin?
water insoluble yellow pigment
What happens to bilirubin in the liver?
- dissociates in the liver + enters hepatocytes
* bilirubin combined w/ 2 molecules of UDP-glucuronate = bilirubin diglucuronide (direct bilirubin)
What are the 3 sources of bilirubin?
- 75% from Hb (erythrocytes) breakdown
- 22% from catabolism of other haemoproteins
- 3% from ineffective bone marrow erythropoiesis
How much bilirubin is excreted into bile everyday?
200-250mg
How is bilirubin processed?
- 85% excreted in faeces
- 15% enters enterohepatic circulation
- 1% enters systemic circulation & excreted by kidneys
How is bilirubin excreted in faeces?
bilirubin → urobilinogen → stercobilinogen → stercobilin (brown compound)
How is bilirubin processed in enterohepatic circulation?
- Bilirubin → deconjugated → lipophilic form
- Urobilinogen
- Stercobilinogen
What is jaundice?
- medical condition w/ yellowing of the skin or eyes, arising from excess of pigment bilirubin
- typically caused by obstruction of bile duct, by liver disease, or by excessive breakdown of RBCs
What are normal levels of bilirubin?
• normal = < 17 µmol/L and • not normal = > 34-51 µmol/L
What are the two types of high bilirubin?
- unconjugated (indirect)
* conjugated (direct)
How do you confirm conjugated bilirubin?
by finding bilirubin in the urine
What are causes of jaundice?
- acute inflammation of the liver
- inflammation of bile duct
- obstruction of bile duct
- haemolytic anaemia
- gilbert’s syndrome
- cholestasis
- Crigler-Najjar syndrome
- Dubin-Johnson syndrome
- Pseudojaundice
What is ERCP?
- endoscopic retrograde cholangiopancreatography
- combines use of endoscopy + fluoroscopy to diagnose + treat certain problems of the biliary or pancreatic ductal systems
What is percutaneous transhepatic cholangiogrpahy? (PTC)
Radiological technique used to visualise the anatomy of the biliary tract
