Hepatobiliary system Flashcards
What are the two primary lobes of the liver?
Right and left
Which folds connect the liver to the abdominal wall and diaphragm?
Pertioneal folds (ligaments)
What vessel delivers the majority of blood to the liver?
Hepatic portal veins
Which vessels deliver blood to the liver?
Hepatic portal veins
Hepatic artery
What % of blood flow arises from the hepatic artery into the liver?
25%
What is the hepatic artery?
Delivers oxygenated blood from the heart to the liver
What is the hepatic portal vein?
Delivers partially deoxygenated blood containing nutrients and toxins absorbed from the small intestine, pancreas, gall bladder and spleen to the liver
What is the main outflow of the liver?
There are 3 hepatic veins (right, middle and left), these drain into the inferior vena cava
The right and left hepatic duct converge to form which duct?
The common hepatic duct
Where do the right and left hepatic ducts converge?
The hilum
Which duct does the common hepatic duct converge with to form the common bile duct?
The cystic duct
What is the primary function for the common bile duct?
Carry bile to the duodenum of the small intestine. Bile produced by the liver is pushed back up the cystic duct y peristalsis to arrive in the gallbladder for storage.
What are the three main hepatic veins?
Right hepatic vein
Middle hepatic vein
Left hepatic vein
What is the middle hepatic vein, and its role in liver anatomy?
Obliquely runs from the inferior vena cava to the gallbladder fossa. Separates the anterior and medial segments of the right hepatic lobe.
What is the right hepatic vein and its anatomical divisions?
Divides anterior and posterior segments of the right hepatic lobe
What is the left hepatic vein and its anatomical divisions?
Left hepatic vein separates the medial and lateral segments of the left hepatic lobe
Where do the 3 hepatic veins drain into?
Inferior vena cava
Which ligament separates the lateral and medial segments?
Ligamentum teres
In which direction are segments II - VII numbered?
Clockwise fashion
What are the three main components of the liver?
Hepatocytes
Bile canaliculi
Hepatic sinusoids
What are the main hepatic cells?
Hepatocytes
What term is used to describe plates of hepatocytes?
Hepatic laminae
What are hepatic laminae?
Plates of hepatocytes.Hepatic laminae radiate outward from the portal vein in each hepatic lobule.
What is in the central of the hepatic lobule?
Central vein
What is the central vein in the hepatic lobule?
Collects blood from the hepatic sinusoids –> hepatic vein to the inferior venous cava
What are the two side faces of the lobule hepatocyte rows?
Sinusoid facing side, and bile canaliculi facing side
What is the function performed by bile canaliculi?
Adjacent hepatocytes, grooves in cell surface membrane provides bile canaliculus Accumulate bile produced by hepatocytes. Bilirubin processed & excreted into bile canaliculi.
What is a hepatic sinusoid?
Open porous blood space formed by sinusoidal capillaries from hepatic portal veins.Hepatocytes are densely packed around sinusoidal epithelium, proving accessibility to blood supply
What is a portal triad?
Arrangement around perimeter of hepatic lobules, consists of: Bile duct, hepatic artery branch, and a hepatic portal vein.
How many hepatic lobules are linked by a portal triad?
3 hepatic lobules
Describe the movement of bile through the ducts:
Bile flows into bile ductules Bile duct Right & left hepatic ducts Common hepatic duct + Cystic duct (from gallbladder) Common bile duct.
What is the role of the hepatic artery?
Delivers oxygenated blood into the live to support the metabolic demands of hepatocytes
Where does the portal vein arise from?
Mixed venous blood from the gastrointestinal tract (nutrients, bacteria & toxins), and spleen (metabolic waste substrates).
Hepatocytes process nutrients, detoxify & excrete waste.
What is the main outflow of the hepatic lobule?
Bile produced from hepatocytes drains into bile canaliculi, these ducts coalesce with cholangiocyte-lined bile ducts present around lobule perimeter
What is a hepatic acinus?
Consists of 1/6th of hepatic lobule, comprises of two portal triads extending into the hepatic lobule towards the central vein
Where does the central vein reside in relation to the acinus?
Resides within the acinus apex.
How many zones comprise a hepatic acinus?
Three
Which hepatic acinus zone has the greatest oxygen concentration?
Zone 1
Which hepatic acinus zone has the lowest oxygen concentration, and lowest toxin risk?
Zone 3
Describe the structure of sinusoidal endothelium?
Absence of basement membrane
The endothelium is fenestrated (discontinuous), therefore increasing permeability to substrate, facilitating the movement of lipids and substrates to and from hepatocytes
Which cells are attached to the sinusoidal endothelium?
Kupffer cells
What are Kupffer cells?
Kupffer cells are attached to the sinusoidal endothelium exhibiting the capacity to undergo phagocytosis, agonistically functioning as sinusoidal macrophages Eliminating & detoxifying substances arriving in liver from portal circulation.
Hemosiderin store Available production of haemoglobin.
Which hepatic cells store vitamin A?
Stellate cells
What are hepatic stellate cells?
Hepatic stellate cells reside within the perisinusoidal space, the Space of Disse. Exist in quiescent state, providing available storage of Vitamin A in cytosolic droplets.
Stellate cells undergo activation in response to hepatic damage, expressing fibroblast activity Proliferate, chemotactic & deposit collagen in extra-cellular matrix.
What are hepatocytes?
Cubical cells responsible for the synthesis of albumin, clotting factors & bile salts. Site of drug metabolism; receives nutrients & substrates from sinusoids.
80% of liver mass
Where do cholangiocytes reside?
On the edge of the bile duct, secrete bicarbonate and water in bile
What do cholangiocytes secrete?
Bicarbonate & water into bile
What are the main functions of hepatocytes?
Metabolic & catabolic functions: Synthesis & utilisation of carbohydrates, lipids and proteins.
Secretory & excretory function: Synthesis and secretion of proteins, bile & waste prodcuts
Detoxification & immunological functions: Degradation of ingested pathogens, and processing of drugs
Carbohydrate metabolism
What is glycolysis?
Glycolysis: Anaerobic conversion of glucose Lactate (RBCs, renal medulla & skeletal muscle); aerobic oxidation of glucose Pyruvate (CNS, heart, skeletal muscle).
What is glycogenesis?
Synthesis of glycogen from glucose (Liver & muscle)
What is glycogenolysis?
Breakdown of glycogen to glucose
What is gluconeogenesi?
Gluconeogenesis: Production of glucose from non-sugar substrates: Amino acids (glutamine) in liver & renal cortex; lactate (from anaerobic glycolysis in RBCs & muscles); glycerol from lipolysis.
What is lipolysis?
Hydrolysis of triacylglycerols into glycerol and free fatty acids
What is lipoegenesis?
Synthesis of triacylglycerols (storage in adipose tissue)
Which cycle converts lactate into pyruvate?
The Cori cycle
What is the Cori cycle?
Refers to the metabolic pathway in which lactate produced through anaerobic glycolysis in the myocyte is transported to the liver under The action of lactate dehydrogenase to form pyruvate
Converted into glucose via gluconeogenesis
Where do amino acids undergo protein synthesis?
Within the liver
What proteins are formed within the liver?
Lipoproteins
Plasma proteins (albumin)
Clotting factors
Which enzyme are involved in the conversion of amino acids?
Transaminases
Alpha keto-glutarate can be converted into which 3 amino acids?
Glutamine
Proline
Arginine
Pyruvate can be converted into which 3 amino acids?
Alanine, valine and leucine
What amino acid is pyruvate transaminate into in the glucose-alanine cycle?
Alanine
What type of amino acid is alanine?
Glucogenic amino acid
How is pyruvate converted into alanine?
The amino group on glutamate is transferred to pyruvate by aminotransferase generating alpha-keto-glutarate, and converting pyruvate to alanine
How is nitrogen transported to the liver?
Nitrogen is also transported to the liver in form of glutamine, synthesised from glutamate and ammonia in reaction catalysed by glutamine synthetase Ammonia released through action of glutaminase.
Which cells stored triglycerides?
Adipocytes
Which enzymes hydrolyse triglycerides into fatty acids in adipose tissue?
Hormone sensitive lipase
How are fatty acids shuttled into the liver?
Carnitine shuttle
What is the fate of fatty acids in the liver?
Undergo beta oxidation, into acetyl CoA, enters into the TCA cycle or substrate for ketogenesi
What is the main energy store within the liver?
Glycogen
What happens when glycogen hepatic storage reaches maximum capacity?
Results in glucose and amino acid conversion into triglycerides as storage within liver and adipose tissue.
2 molecules of acetyl-CoA form what compound?
Acetoacetate
How are lipids, triacylglyerols and cholesterol transported?
Lipoproteins
What are lipoproteins?
globular micelle like particles that consist of nonpolar core of triacylglycerols, and cholesteryl-esters surrounded by an amphiphilic coating of protein, phospholipid & cholesterol.
Which molecules transports triacylglycerols and cholesterol from small intestines to tissues?
Chylomicrons
Which lipoproteins transport endogenous triacylglycerols and cholesterol from the liver to tissues?
LDLs
IDLs
VLDls
What are HDLs?
High density lipoproteins, transport endogenous cholesterol from tissues to the liver
What is the lipoprotein synthesis pathway?
𝑮𝒍𝒖𝒄𝒐𝒔𝒆→𝑷𝒚𝒓𝒖𝒗𝒂𝒕𝒆 →𝑨𝒄𝒆𝒕𝒚𝒍−𝑪𝒐𝑨 →𝑭𝒂𝒕𝒕𝒚 𝒂𝒄𝒊𝒅𝒔 & 𝑪𝒉𝒐𝒍𝒆𝒔𝒕𝒆𝒓𝒐𝒍
𝑮𝒍𝒖𝒄𝒐𝒔𝒆 →𝑮𝒍𝒚𝒄𝒆𝒓𝒐𝒍
𝑮𝒍𝒖𝒄𝒐𝒔𝒆+𝟑 𝑭𝒂𝒕𝒕𝒚 𝒂𝒄𝒊𝒅𝒔 →𝑻𝒓𝒊𝒂𝒄𝒚𝒍𝒈𝒍𝒚𝒄𝒆𝒓𝒐𝒍+𝑨𝒑𝒐𝒑𝒓𝒐𝒕𝒆𝒊𝒏 𝒑𝒉𝒐𝒔𝒑𝒉𝒐𝒍𝒊𝒑𝒊𝒅𝒔+𝒄𝒉𝒐𝒍𝒆𝒔𝒕𝒆𝒓𝒐𝒍 →𝑪𝒉𝒚𝒍𝒐𝒎𝒊𝒄𝒓𝒐𝒏𝒔
What are the three main functions of cholesterol?
Stabilisation and membrane integrity through fluid dynamics within the phospholipid bilayer
Steroidgenesis (mineralcorticoids, cortisol, and aldosterone)
Vitamin K synthesis (essential for clotting factors)
Which clotting factors are reliant on vitamin K?
II, VII, IX, X
Which fat soluble vitamins are stored by hepatocytes?
A, D, E, K
Where is vitamin b12 stored?
Within hepatocytes
Where is copper stored?
Within hepatocytes
How long are the fat soluble vitamins stored for within hepatocytes?
6-12 months except Vitamin K
How is iron stored within the liver?
As ferritin and hemosiderin
What is haemochromatosis associated with?
Elevated iron levels
Which enzymes are involved in detoxification?
P450 enzymes
What is phase 1 of detoxification?
Modification, p450 enzymes are the predominant catalysts of phase 1 metabolism in liver. Phase 1 reactions are classified into: Oxidation, reduction & hydrolysis
What is the purpose of phase 1 detoxification?
More hydrophilic xenobiotics
What is oxidation in terms of xenobiotic metabolism?
Addition of oxygen into xenobiotic
What is phase 2 of detoxification?
Conjugation
What happens during the conjugation (Phase II) phase of detoxication?
Activated xenobiotic metabolites are conjugated with a charged polar species
Products of conjugation reactions have increased molecular weight, tend to be less active
The addition of large anionic groups detoxifies reactive electrophiles, and produces more polar metabolites that cannot diffuse across membranes, thus are active transported
Where do right and left hepatic ducts converge?
At the hepatic hilum (portages hepatitis)
The right and left hepatic duct converge together to form what?
The common hepatic duct
Which duct converges with the common hepatic duct to form the common bile duct?
The cystic duct arising from the gall bladder
Where does the common bile duct converge with the main pancreatic duct?
Ampulla of Vater
Which spinchter regulates the entry of bile and pancreatic secretions into the duodenum?
The Sphincter of Oddi
What forms the majority of bile?
Water 97%
What colour is bilirubin?
Yellow-brownish pigment
What colour is biliverdin?
Green
Which cells secrete bile?
Cholangiocytes and hepatocytes
What components and molecules are essential for the emulsification of lipids?
Bile salts & phospholipids
Exhibit hydrophobic and hydrophilic properties
What is the function of the hydrophobic and hydrophilic regions of bile?
Interacts with large lipid molecules whereas the hydrophilic regions interacts with the watery chyme within the duodenum
How are bile salts reclaimed?
Reclaimed by enterohepatic circulation, bile in ileum absorbed and returned to liver in the hepatic portal blood system
What are the three main functions of bile?
Cholesterol homeostasis
Absorption of lipids & lipid soluble vitamins (A,D,E & K)
Excretion of: Xenobiotics, cholesterol metabolic, steroid hormones & alkaline phosphatases
What % bile secretion is attributed to hepatocytes?
60%
What function do cholangiocytes perform in secondary modification of bile?
Cholangiocytes lining the bile duct modify the canalicular bile, altering the pH (alkaline electrolyte solution), water is drawn into bile by osmosis via paracellular junctions. Canalicular bile enters the lumen of the canals of Hering, percolating towards the Cholangiocytes. These processes includes the active secretion of Cl- and HCO3- into the bile by CFTR proteins (Cystic fibrosis transmembrane regulatory).
Luminal glucose & organic acids reabsorbed
IgA exocytosis
Which protein transporter secretes bicarbonate ions into the bile?
CFTR proteins
What immunoglobulin is exocytosed by cholagiocytes?
IgA
What is the main biliary transporter?
Bile salt excretory pump (BSEP): Active transport of bile acid into bile
What is the function of MDR3?
Excretion of phosphatidylcholine
What is the function of MDR1?
Excretion of xenobiotics and cytotoxins into the bile
Which transporter located on the basolateral membrane transports bile salts & xenobiotics from the sinusoidal blood into the hepatocytes?
OATP transporters
What are OATP transporters?
OATP transporters present on the basolateral membrane transport bile salt & xenobiotics from the sinusoidal blood (portal) into the hepatocyte.
What are NTCP transporters?
Sodium dependent uptake transporters are expressed on the basolateral membrane
Uptake of bile salts from sinusoidal blood
Which is the main precursor of bile salts?
Cholesterol
Describe the pathway of cholic acid formation?
Cholesterol -> 7-alpha hydroxycholesterol -> cholic acid
What are the two primary bile salts?
Cholic acids
Chenodeoxycholic acid
What is the pathway of chenodeoxycholic acid formation?
Alternative pathway: Cholesterol 27-hydroxycholesterol (CYP27A-1) Chenodeoxycholic acid (CYP7B1).
Where are the primary bile salts synthesised?
Within hepatocytes & cholangiocytes
Where are the primary salts secreted into?
Through the common bile duct into the duodenum via the ampulla of Vater
Which ion salts are conjugated in the liver to glycine & taurine?
Sodium and potassium ion salts
What are the two main secondary bile salts?
Deoxycholic acid
Lithocholic acid
Where does primary bile salt biotransformation occur?
Occurs within the duodenum and jejunum by intestinal bacteria
What is the function of bile salts in terms of fats?
Reduces surface tension of fats - emulsification of lipids prior to digestion an absorption
What do bile salts form?
Bile salts form micelles *(steroid nucleus planar), exhibits amphiphatic characteristics Hydrophilic domains (carboxyl and hydroxyl groups) are externally exposed forming hydrogen bonds with water, and subsequently dissolving Hydrophobic domain *nucleus and metal components
What is encapsulated within the micelles?
FFAs and cholesterol, dissolve in lipids
what is the mechanism of fat globule lipid absorption?
Fat globules within the duodenum & jejunum are emulsified by bile salts & phospholipids Increases available surface area & binding sites for lipases (in conjunction with colipase) to hydrolyse the lipids into fatty acids & glycerol.
Which enzyme assists lipase in the hydrolysis of lipids?
Colipase
Which substrates stimulate CCK release?
Peptids and fatty acids
Which cells release CCK?
Enteroendocrine I mucous cells within the duodenal during the intestinal phase
When is CCK released during the gastric phases?
Intestinal phase formulating the enteric inhibitory phase
What effect does CCK have on the gall bladder?
Stimulates gall bladder contraction, facilitating the movement of bile through the common bile duct into the duodenum via the ampulla of Vater, this action is potentiated by the relaxation of the Sphincter of Oddi
Which sphincter relaxes in response to CCK stimulation?
Sphincter of Oddi
Which receptor is activated by CCK action?
CCKI receptor
What state is the Sphincter of Oddi in, pre-prandially?
Constricted- coxed state, bile is diverted upwards through the cystic duct into the gall bladder for storage
Where is 95% of bile salts absorbed?
Absorbed from the terminal ileum through the Na+/Bile salt co-transport Na+/K+ ATPase system
Which transporters causes enterocyte absorption of bile salts?
ABST
Which channels do bile salts enter through into portal venous circulation?
OST channels
Which transporters are used for bile salt uptake?
OATP-1 transporters on the basolateral membrane to resyntheise into bile
What is the fate of 5% of bile salts within the ileum?
Dehydroxylated undergoing modification into secondary bile salts within the colon
Which secondary bile salt is absorbed?
Deoxycholic acid
Which secondary bile salt is excreted into the stool?
Lithocholic acid is excreted in the stool
Where does the gallbladder reside?
Resides within the posterior aspect of the right lobe of the liver
What are the three main regions of the gall bladder?
Fundus
Neck
Cystic duct
What cell types form the gallbladder?
Simple columnar epithelium of the gallbladder mucosa is organised in rugae
There is no subbmucosa within the gall bladder wall
Which layer do the smooth muscle fibres reside within?
Muscular layer
Which receptors does CCK bind onto to cause gall bladder wall contraction?
CCKa receptors and neural plexus
What is the main role performed by the mucosa wall of the gallbladder?
Mucosa absorbs water and ions from the bile, concentrates and acidifies the bile 10 -fold
Where is 75% if bilirubin formed from?
Erythrocytes
How are erythrocytes converted into unconjugated bilirubin?
Removed from circulation within the spleen, under the activity of haem oxygenase, the haem group is cleaved oxidatively to form biliverdin - central methanyl bridge is reduced into bilirubin
What are the 3 main sources of bilirubin?
RBCs 75%
Catabolism of alternative haemoproteins (cytochromes) 22%
3% from ineffective bone marrow erythropoiesis>
How is bilirubin transported within the blood?
Albumin plasma protein
Which cells absorb bilirubin?
Hepatocyte
Which molecules does bilirubin conjugate with within hepatocytes?
2 molecules of UDP-Glucuronic acid under the action of glucronyl-transferase –> Bilirubin diglucuronide (Direct BR)
What is the name of conjugated bilirubin?
Bilirubin diglucuronide (Direct BR)
Which transporter actively transported direct BR into the biliary canaliculi?
cMOAT transporter
Which bilirubin is water insoluble?
Unconjugated bilirubin
What % of bilirubin is excreted into faeces?
85%
What is the fate of bilirubin in the faeces?
Bacterial enzymes in the large intestine hydrolyse the glucuronic acid groups in a multistep process Urobilinogen (colourless & odourless) Stercobilinogen Stercobilin (Brown pigment)
Which compound is responsible for the brown pigment in faecal matter?
Stercobilin
Why does obstructive jaundice result in white stools?
No bile into large bowel therefore no bilirubin to be converted into stercobilin (White stools)
What % of bilirubin enter into enterohepatic circulation?
14% enters enterohepatic circulation: BR Deconjugated into lipophilic form (Urobilinogen & Stercobilinogen).
What molecules arising from bilirubin is excreted by the kidneys?
Urobilin
What are the 3 types of jaundice?
Prehepatic
Intrahepatic
Post-hepatic
What is jaundice?
Characterised by elevated unconjugated serum bilirubin levels -> Yellowish pigmentation
What are the main causes of prehepatic jaundice?
Bilirubin production is exaggerated due to erythrocyte abnormalities and degradation within the spleen, this potentiates the haem oxygenase activity in cleaving the haem groups to resultantly form unconjugated bilirubin. Conditions which are associated with this include: Sickle cell anaemia & hereditary spherocytosis
What are the main causes of intrahepatic jaundice?
Intrahepatic jaundice is affiliated with dysfunctional hepatocytes. This includes:
Dysfunctional transporter proteins to intake indirect serum bilirubin from albumin
Decreased conjugation ability (Glucuronyl transferase inactivation)
Decreased outflow of conjugated bilirubin from hepatocytes (cMOAT inactivation or obstruction within biliary tree (canaliculi).
What are the main causes of post-hepatic jaundice?
Interruption to the drainage of bile containing conjugated bilirubin in the biliary system. Associated causations include gallstones in the common bile duct, and pancreatic cancer in the head of the pancreas.
What are gall stones?
Gall stones are crystalline masses formed abnormally within the gal bladder of bile ducts from bilirubin, cholesterol and calcium salts
What is cholecystitis?
Inflammation of the gall bladder
What is cholelithiasis?
The formation of gall stones resulting in obstruction within the bile ducts. Gallstone obstruction within the cystic duct causes Mirizzi’s syndrome.
What is Mirizzi’s syndrome?
Gallstone obstruction within the cystic duct
What are the common obstruction sites for gal stones?
Cystic duct
Common bile duct
Hepatopancreatic duct
Main pancreatic duct
What is cholangitis?
Bacterial infection associated with the common bile duct
What does ERCP mean?
Endoscopic retrograde cholangiopancreatography
What is ERCP?
A procedure used to diagnose diseases of the gallbladder, biliary system, pancreas & liver. The procedure identifies upstream through the main pancreatic duct, common bile duct towards the biliary system in comparison to entrance through the Ampulla of Vater within the duodenum.
Wires can be inserted into the common bile duct to assist with the removal of obstructive bile stones within the common bile ducts, this can be identified using contrast dyes (cholangiogram) (Obstruction = black).
What is spincterotomy?
Small incision of the sphincter of Oddi within the Ampulla of Vater, can help remove small gallstones
How can a stent placement relieve gall stones?
Stent is a drainage tube that misplaced in the bile duct or the pancreatic duct to hold the duct open allowing it to drain
What is the main limitation of gallstone removal using ERCP?
ERCP remove gall stones from bile duct not gallbladder itself.
What does PTC mean?
Percutaneous Transhepatic Cholangiography
