Hepatobiliary System (37) Flashcards
What is the ligamentum teres?
remnants of umbilical vein
How can we divide the liver into left and right lobes using landmarks?
from left side of inferior vena cava- comes in the line of the gall
bladder
N.B. NOT separated by the falciform ligament
What vessels supply the liver?
inflow: hepatic artery (25%) and portal vein (75%)
outflow: bile duct and 3 hepatic veins
What is the hilar confluence/ hilum?
where the left and right hepatic ducts join to become common hepatic duct- then becomes common bile duct
What does the right hepatic vein divide in the liver?
divides the right lobe into anterior and posterior segments
How many functionally independent segments does the liver divide into?
8
What divides the left lobe into medial and lateral parts?
the falciform ligament
What does the middle hepatic vein divide?
liver into left and right lobes
What is a hepatic lobule?
- hexagonal structural unit of liver tissue
- portal triad in each corner: artery in, vein in, biliary duct out
- central vein at centre–> collects blood from hepatic sinusoids–> hepatic veins–> systemic venous system
- rows of hepatocytes: each row has sinusoid-facing side and bile canaliculi-facing side
What is the function of the hepatic arteries?
to bring oxygen-rich blood into the liver to support hepatocytes’ inc. energy demand
What is the function of the portal veins?
bring mixed venous blood from GI tract (and also from spleen), containing nutrients, bacteria and toxins
–> to be processed by hepatocytes
What is the function of the bile ducts?
starts off as biliary canaliculus- bile produced by hepatocytes drain here- coalesce with cholangiocyte-lined bile ducts on lobule edge
What is a hepatic acinus?
- a functional unit of the liver- hard to define anatomically
- each shares 2 portal triads (1/6 of each hepatic lobule)
- extend into hepatic lobules up to the central vein
What is the 3 zone model in the hepatic acinus?
- blood drains into hepatic acinus at point A (portal triad) and out at point B (central vein)
- zone 1 (within A) receives early exposure to blood contents- high oxygen, high toxin –> zone 3 (within B)- low oxygen, low toxin
- zone 2 ^ in between
What are the features of sinusoidal endothelial cells?
- no basement membrane
- fenestrations (discontinuous endothelium)- gaps, leaky
- allows lipids and large molecules from GI tract to get through to access hepatocytes
What are Kuppfer cells?
- specialised sinusoidal macrophage cells
- attached to endothelial cells
- -> undertake phagocytosis- eliminate and detoxify substances arriving from portal vein
What are hepatic stellate cells?
- exist between hepatocytes and sinusoids in ‘space of disse’
- lie dormant
- store vit A
- activated in response to liver damage–> act as fibroblasts–> scarring etc…
- proliferate, chemotactic and deposit collagen in ECM
What are hepatocytes?
- 80% of liver mass
- cubical shape
- synthesise albumin, clotting factors and bile salts
- metabolise drugs
- receive nutrients
What is the function of cholangiocytes?
secrete HCO3- and H20 into bile
What are the functions of hepatocytes?
- metabolic and catabolic functions: synthesis and use carbohydrates, lipids and proteins
- secretory and excretory functions: synthesise and secrete proteins, bile and waste products
- detoxification and immunological functions: processing drugs and breaking down ingested pathogens
What is glycolysis?
- anaerobic conversion of glucose–> lactate (in RBCs and muscle)
- or aerobic oxidation of glucose (CNS, heart, muscle)
What is glycogenesis?
synthesis of glycogen from glucose (liver and muscle)
What is glycogenolysis?
breakdown of glycogen to glucose
What is gluconeogenesis?
production of glucose from non-sugar molecules e.g. AAs, lactate and glycerol
What is lipolysis?
breakdown of triacylglycerols–> glycerol and FFAs
What is lipogenesis?
synthesis of triacylglycerols (for storage in fat depots)
What is the Cori cycle/ lactic acid cycle?
lactate produced by anaerobic glycolysis in muscles –> moves to liver–> converted to pyruvate by lactate dehydrogenase–> converted to glucose by gluconeogenesis–> returns to muscles–> cyclically metabolised back to lactate
What are ‘non-essential amino acids’?
amino acids that the liver CAN manufacture
How do you produce glutamate from alanine?
- alanine from diet
- transamination in liver using enzyme–> over to alpha-keto glutarate (a keto-acid)
- produces glutamate and pyruvate
What are some non-essential amino acids?
- glutamate
- proline
- alanine
- aspartate
What is the glucose-alanine cycle?
- pyruvate from glycolysis and glutamate from AA breakdown in muscle
- alanine transaminase converts these into alanine–> moved to liver along w/ alpha-keto glutarate
- reaction is reversed at liver–> pyruvate and glutamate produced
- pyruvate converted into glucose by gluconeogenesis–> transported back to muscle tissue for glycolysis
- glutamate converted into urea (deaminated)–> bloodstream
How do you produce energy from fat stores using hepatocytes?
- triglycerides broken down to fatty acids in adipose tissue cell
- -> moved to liver
- fatty acids converted to acetyl coA by beta oxidation
- -> acetyl coA goes into TCA cycle, producing energy
How is lipoprotein synthesised in hepatocytes?
- glucose goes into liver
- can be converted directly to glycerol OR to pyruvate then acetyl coA then to fatty acids and cholesterol
- glycerol and fatty acids combine–> triglycerides
- adding apoproteins, phospholipids and cholesterol –> MAKE LIPOPROTEINS?
What is the function of VLDL (very low density lipoproteins)?
to transport fatty acids to adipose tissues to be stored as triglycerides
What is the function of HDL (high density lipoproteins)?
empty (bc high protein content, not fat)–> pick up excess cholesterol
What is the function of LDLs?
once VLDLs have got rid of fatty acids, LDLs transport cholesterol to tissues
What does the liver store?
- lipid soluble vitamins (B, A, D, E, K) … N.B. vit K essential in blood clotting
- iron and copper (excess Cu causes Wilson’s disease)
What are the 2 phases of detoxification by P450 enzymes in the liver?
- phase 1 (modification): make more hydrophilic
- phase 2 (conjugation): attach water soluble side chain to make less reactive
Where does the common bile duct travel to and what does it join with?
- dives into pancreas
- picks up main pancreatic duct
What are the uses of bile?
- cholesterol homeostasis
- helps w/ absorption of lipids and lipid soluble vitamins (A,D,E and K)
- excretes xenobiotics/drugs, cholesterol metabolites, adrenocortical+ other steroid hormones, alkaline phosphatase
What is the composition of bile?
97% water
- 7% bile salts/acids
- 2% bile pigments (bilirubin- yellow, bilivirden- green)
How much bile is produced each day?
500mL
What is the role of hepatocytes in bile production?
- produce 60% of total bile
- primary secretion: bile salts, lipid and organic ions
What is the role of cholangiocytes in bile production?
- produce 40% of total bile
- secondary modification: alteration of pH, addition of water, addition of bicarbonate and chloride by CFTR
What are the main biliary transporters?
- bile salt excretory pump (BSEP)
- MDR related proteins
- MDR1- excretion of xenobiotics and cytotoxins
- MDR3- phopatidylcholine
ETC..
What are bile salts?
- made of bile acids that are conjugated with glycine or taurine
- produced in liver, directly from cholesterol
- 1y bile acids synthesised in liver–> go into bowel via biliary tube–> converted to 2y bile acids by gut bacteria
What are the 2 primary bile acids synthesised in the liver and what are their 2y counterparts?
cholic acid and chenodeoxycholic acid
–> deoxycholic acid and lithocolic acid
What is the function of bile salts?
- to reduce surface tension of fats
- emulsify fat globules prior to its digestion and absorption
What property of bile salts allows them to coat fat globules and form micelles?
amphipathic- 1 side= hydrophilic, other side= hydrophobic
How is bile flow and secretion regulated?
- when not eating, Sphincter of Oddi remains closed–> bile diverted into gall bladder for storage
- when eating, Sphincter of Oddi relaxes–> bile and pancreatic juice flows out
- gall bladder stimulated to contract by CCK (cholecystokinin)–> inc. bile after fatty meal
N.B. gastric contents (FFAs, AAs) enter duodenum, causing release of CCK
How does the enterohepatic circulation work?
following entry into the small intestine, 95% of bile salts are absorbed back by the enterocyte from the terminal ileum by Na+/bile salt co-transport system–> transport ed back to the liver by portal vein–> then re-excreted into bile
N.B. approx. 5% of bile salts excreted in faeces
What are the functions of the gall bladder?
- stores bile (50ml)–> concentrates and acidifies it
2. its contraction is triggered by CCK binding to CCKa receptors and neuronal plexus on gallbladder wall
What is bilirubin?
- toxic
- water insoluble
- yellow pigment
- free BR= indirect/unconjugated
- 75% comes from Hb breakdown
- 22% from catabolism of other haemoproteins
- 3% from ineffective bone marrow erythropoiesis
How does bilirubin exist in the body and how does it end up in the GIT?
- insoluble, free BR bound to albumin in blood
- when at liver, BR released from albumin and gets conjugated w/ 2 molecules of UDP-glucuronic acid–> becomes bilirubin diglucuronide (direct BR)
- soluble, direct BR actively transported by cMOAT (transporter) into biliary canaliculi across conc. gradient (then to GIT)
What is responsible for the brown colour in faeces and how is it made?
stercobilin (brown compound)
- 85% of bilirubin–> urobilinogen (bc of anaerobic bacteria)
- -> stercobilinogen (^both colourless and odourless)
- -> oxidised to stercobilin
What is a typical signpost of obstructive jaundice?
white/pale faeces
What is the fate of bilirubin (%)?
85% excreted in faeces
15% enters enterohepatic circulation
1% enters systemic circulation–> excreted by kidneys
What causes pre-hepatic jaundice?
too much bilirubin produced
e.g. in sickle cell, abnormal RBCs–> broken down more–> Hb broken down–> more indirect bilirubin
What causes intrahepatic jaundice?
liver not functioning properly
- -> dec. uptake of bilirubin
- -> dec. conjugation
- -> dec. secretion
What causes post-hepatic jaundice?
‘obstructive jaundice’
e.g. gall stones, tumours etc…
bile cannot get out, so faeces pale
What is cholecystitis?
gall stones stuck in cystic duct–> gall bladder gets infected
What is cholangitis?
gall stone gets stuck in common bile duct
–> bile gets infected
What 2 surgeries are used to treat post-hepatic/obstructive jaundice?
- ERCP
- PTC
