Hepatobiliary System Flashcards
What supplies the inflow of blood to the liver?
What carries the outflow of blood from the liver?
What is the purpose of blood delivered to the liver by:
Portal vein?
Hepatic artery?
Inflow (blood supply)
- hepatic artery (25%)
- portal vein (75%)
Outflow
- bile
- 3x hepatic veins
Detail the morphological components of the liver and the functional elements
Morphological:
Lobules
Portal triads (tracts)
Functional:
Acinus
Blood flow
Bile flow
Micro morphology of the liver:
What is a hepatic lobule?
What does each corner of a hepatic lobule consist of?
What is in the centre of a liver lobule? What is its function?
There are rows of what within each lobule? What do they each have?
Hepatic lobule:
Hexagonal structural unit of liver tissue
Each corner consists of a portal triad
-links w 3x adjacent lobules
Centre of liver lobule is a central vein
-collects blood from hepatic sinusoids -> hepatic veins -> systemic venous system
Within lobules there are rows of hepatocytes
-each hepatocyte has sinusoid-facing side & bile canaliculi-facing side
Micro morphology:
What are the components of the portal triad?
What are the functions of these components?
What are the functions of hepatocytes?
Portal triad:
Branch of hepatic artery
-brings oxygen rich blood into liver to support hepatocytes during increased 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 duct:
Bile produced by hepatocytes drains into bile canaliculi
Coalesce with cholangiocyte-lined bile ducts around lobule perimeter
Micro-function
What is the hepatic acinus?
What does it consist of?
What does it share?
Where do the hepatic acinae extend into
Hepatic acinus:
Functional unit of liver
-hard to define anatomically cf hepatic lobule
Consists of two adjacent 1/6th hepatic lobules:
Share 2x portal triads
Extend into hepatic lobules as far as central vein
Micro function:
What is the three zone model?
What is the relationship between oxygen concentration and toxin risk in the three respective zones?
What does blood drain into hepatic acinus via?
What does blood drain out of the hepatic acinus via?
Point A: blood into hepatic acinus via portal triad (point A)
Point B: blood drains out of hepatic acinus via central vein (point B)
Hepatocytes near outer hepatic lobule (zone 1)
1) receive early exposure to blood contents:
- good components (O2)
- bad components (toxins)
Acinus split into 3x regions
Zone 1 - O2 inc, toxin risk inc
Zone 2 - O2 -> toxin risk ->
Zone 3 - O2 decreases, toxin risk decreases
Liver cell types:
Sinusoidal endothelial cells
Basement membrane?
What type of endothelium?
What is the function of sinusoidal endothelial cells?
Sinusoidal endothelial cells:
No basement membrane
Fenestrated (discontinuous endothelium)
Allow lipids & large molecule movement to and from hepatocytes
Liver cell types:
Kuppfer cells:
What type of sinusoidal cells are they?
What are they attached to?
What function do kuppfer cells carry out?
Kuppfer cells: Sinusoidal macrophage cells Attached to endothelial cells Phagocytosis: -eliminate & detoxify substances arriving in liver from portal circulation
Liver cell types:
Hepatic stellate cells
What state do they exist in?
What do they store in liver cytosolic droplets?
What activates hepatic stellate cells?
What are the functions of hepatic stellate cells?
Hepatic stellate cells:
(Ito;perisinusoidal)
- exist in dormant state
- store vit A in liver cytosolic droplets
- activated (fibroblasts) in response to liver damage
- proliferate, chemotactic & deposit collagen in ECM
Liver cell types:
Hepatocyte:
What percentage of liver mass?
What is the shape of hepatocytes?
What are the functions of hepatocytes?
Hepatocyte:
80% of liver mass
Cubical
Synthesis eg albumin, clotting factors & bile salts
Drug metabolism
Receive nutrients & building blocks from sinusoids
Liver cell types:
What is the function of cholangiocytes?
Cholangiocytes - secrete HCO3- & H2O into bile
Hepatocyte function:
What are the Metabolic & catabolic functions of hepatocytes?
What are the secretory and excretory functions of hepatocytes?
What are the detoxification and immunological functions of hepatocytes?
Metabolic & catabolic functions: synthesis & utilisation of carbohydrates, lipids and proteins
Secretory & excretory functions: synthesis & secretion of proteins, bile and waste products
Detoxification & immunological functions: breakdown of ingested pathogens & processing of drugs
Carbohydrate metabolism:
Define the following:
Glycolysis Glycogenesis Glycogenolysis Gluconeogenesis Lipolysis Lipogenesis
Glycolysis: anaerobic conversion of glucose -> lactate
(RBCs, renal medulla + skeletal muscle)
Aerobic oxidation of glucose (CNS, heart, skeletal muscle, most organs)
Glycogenesis: synthesis of glycogen from glucose (liver + muscles)
Glycogenolysis: breakdown of glycogen to glucose
Gluconeogenesis: production of glucose from non sugar molcecules:
Amino acids (glutamine) in liver and renal cortex
Lactate (anaerobic glycolysis in RBCs and muscles)
Glycerol (from lipolysis)
Lipolysis: breakdown of triacyglycerols-> glycerol & FFAs
Lipogenesis: synthesis of triacylglycerols (storage in fat depots)
Synthesis of non essential amino acids in the liver:
What is transamination and what does it depend on?
What are examples of transamination reactions including alpha keto glutarate, pyruvate and oxaloacetate?
Transamination:
Diff keto acids can be converted into multiple amino acids depending on the transaminase enzyme
Alpha keto glutarate -> glutamate, proline, arginine
Pyruvate -> alanine, valine, leucine
Oxaloacetate -> aspartate, methionine, lysine
Hepatocyte function - protein metabolism:
What is deamination?
What are the problems with using amino acids to produce glucose for energy?
Glucose-alanine cycle - deamination
Problem: muscle can potentially utilise amino acids to produce glucose for energy
BUT:
- To convert pyruvate to glucose requires energy
- To remove nitrogen as urea requires energy
Solution - transfer problem to the liver (glucose-alanine cycle)
Hepatocyte function - triglyceride metabolism
What is fat?
Where is fat stored?
When are glucose and amino acids converted to fat?
Fat:
Main energy store in body (100x glycogen)
Stored in adipose and liver
When glycogen stores full, liver converts excess glucose & amino acids to fat for storage
Hepatocyte function - storage:
What does the liver store? For how long?m
What is vitamin K essential for?
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 erythropoiesis
Hepatocyte function - detoxification
What are the two stages of detoxification?
What enzymes are involved?
Detoxification (xenobiotics):
P450 enzymes
-phase 1 (modification) -> more hydrophilic
Phase 2 (conjugation) - attach water soluble side chain to make less reactive
Biliary system:
What are the uses of bile?
Cholesterol homeostasis
Absorption of lipids and lipid soluble vitamins (A, D, E & K)
Excretion of: Xenobiotics/drugs Cholesterol metabolites Adrenocortical & other steroid hormones Alkaline phosphatase
Biliary system - production of bile
How much bile is produced each day?
Why is bile yellow/green?
Where is bile secreted from?
500 mls bile produced each day
Bile is yellow/green due to pigments like bilirubin & biliverdin
Hepatocytes - secrete 60% of total bile
Cholangiocytes - secrete 40% of total bile
Biliary system:
Primary secretion
Secondary modification
Primary secretion:
Bile secretions reflect serum concs
Secretion of bile salts (acids), lipids and organic ions
Secondary modification:
Alteration of pH (alkaline electrolyte solution)
H2O drawn into bile by osmosis via pracellular junctions
Luminal glucose & organic acids reabsorbed
HCO3- & Cl- actively secreted into bile by CFTR (cystic fibrosis transmembrane regulator)
IgA exocytosed
Biliary system - bile flow - (biliary transporters)
Biliary excretion of bile salts and toxins is performed by what and where?
What are the main transporters?
Biliary excretion of bile salts & toxins performed by biliary transporters on apical surface + basolateral
membranes of hepatocytes & cholangiocytes
Main transporters:
Bile salt excretory pump (BSEP) - active transport of BAs into bile
MDR related proteins
Products of the familial intrahepatic cholestasis gene (FIC1)
Products of multi drug resistance genes:
MDR1 -> excretion of xenobiotics and cytotoxins
MDR3 -> phospatidylcholine
Bile salts:
What are bile acids synthesised from?
The Na+ and K+ salts of bile acids are conjugated in the liver to?
2x primary bile acids are synthesised in?
2x secondary bile acids are produced from ______ _______ by ____ _______
Gut bacteria converts:
Cholic acid to?
Chenodeoxycholic acid to?
Bile salts are a key component of bile
Bile salts synthesised from cholesterol
Na+ and k+ salts of bile acids conjugated in liver -> glycine & taurine
2x primary bile acids synthesised in liver
2x secondary bile acids produced from primary acids by gut bacteria
Gut bacteria:
Cholic acid -> deoxycholic acid
Chenodeoxycholic acid -> lithocolic acid
Bile salts (function):
Reduce surface tension of fats
Emulsify fat prior to its digestion & absorption
Bile salts from micelles
Steroid nucleus planar - 2 faces (amphipathic)
1x surface hydrophilic domains (hydroxyl and carboxylase) - faces OUT -> dissolves in water
2nd surface hydrophobic domains (nucleus and methyl) faces IN -> dissolves in fat
FFAs and cholesterol INSIDE
Regulation of bile flow and secretion
Between meals sphincter of oddi closed -> bile diverted into gall bladder for storage
Eating -> sphincter of oddi relaxes
Gastric contents (FFAs, AAs > CHOs) enter duodenum causing re,ease of cholecystokinin (CCK)
CCK causes gall bladder to contract
Biliary system - enterohepatic circulation:
What percentage of bile salts are reabsorbed from terminal ileum?
By what system?
What happens to 5% of bile salts?
95% of 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 bile salts back to liver and re excreted in bile
Biliary system - functions of gallbladder:
- Stores bile (50 mls)
- concentrates bile
- acidifies bile - GB contraction triggered by CCK
- binds to CCKA receptors and neuronal plexus of GB wall (innervated by preganglionic parasympathetic fibres of vagus nerve)
Bilirubin (BR)
What are the properties of free BR?
What are the sources of BR?
What is free BR bound to in blood? What happens at the liver?
WhT is BR conjugated w ?
Free BR (indirect/unconjugated) = H2O soluble, yellow pigment
Source:
75% BR from Hb (erythrocytes) breakdown
22% from catabolism of other haemoproteins
3% from ineffective BM erythropoiesis
Free BR bound to albumin in blood
Most dissociated in liver and enters hepatocytes
BR conjugated w 2x molecules of UDP-glucuronate -> bilirubin diglucuronide (direct bilirubin)
Secreted ACROSS conc grad into biliary canaliculi -> GIT
Bilirubin (BR)
200-250 mg BR excreted into bile/day
85% excreted in faeces
BR -> urobiliogen -> stercobilinogen -> stercobilin (Brown compound)
15% enters enterohepatic circulation:
BR -> deconjugated -> lipophilic form
Urobilinogen
Stercobilinogen
1% enters systemic circulation & excreted by kidneys
