Hepatobiliary System Flashcards
Describe the surface anatomy of the liver.
Label this diagram.
What is the inflow of the liver?
hepatic artery (25%)
portal vein (75%)
the outflow of the liver?
BIle and 3x hepatic veins
Label these diagrams.
What is the Micro-morphology & micro-function of liver?
Morphological:
- Lobules
- Portal triads (tracts)
Functional:
- Acinus
- Blood flow
- Bile flow
What is the hepatic lobule?
Hexagonal structural unit of liver tissue
Each corner consists of a portal triad
- Links with 3x adjacent lobules
What is at the centre of a liver lobule?
Centre of liver lobule is a central vein
- Collects blood from hepatic sinusoids → hepatic veins → systemic venous system
What are the lobule rows made of?
Within lobule rows of hepatocytes
Each has sinusoid-facing side & bile canaliculi-facing side
Describe the parts of the portal triad.
Branch of hepatic artery:
- Brings O2-rich blood into liver to support hepatocytes ↑ 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
cholangiocyte= cells that line bile ducts
Label this diagram.
What is a 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
What is the 3 zone model?
Micro function of hepatic acinus
- splits the hepatic acinus into 3 zones each with differences
What happens at point A?
blood into hepatic acinus (portal triad)
What happens at point B?
Blood drains out of hepatic acinus (central vein)
What happens to hepatocytes near outer hepatic lobule (zone 1)?
Hepatocytes receive early exposure to blood contents
good components= O2
bad= toxins
How is the acinus split?
zone 1, 2, 3
What is the O2 and toxin risk in zone 1?
O2 ↑,Toxin risk ↑
What is the O2 and toxin risk in zone 2?
O2 →,Toxin risk →
What is the O2 and toxin risk in zone 3?
O2 ↓,Toxin risk ↓
What are sinusoidal endothelial cells?
No basement membrane
Fenestrated (discontinuous endothelium)
- Allow lipids & large molecule movement to and from hepatocytes
What are Kupffer cells?
Sinusoidal macrophage cells
Attached to endothelial cells
Phagocytosis
Eliminate & detoxify substances arriving in liver from portal circulation
What are hepatic stellate cells?
Perisinusoidal (The plasma-filled extravascular space in the liver, between a hepatocyte and a liver sinusoid)
Exist in dormant state
Store vit A in liver cytosolic droplets
Activated (fibroblasts) in response to liver damage
Proliferate, chemotactic & deposit collagen in ECM
What are hepatocytes?
Cubical
Synthesis e.g. albumin, clotting factors & bile salts
Drug metabolism
Receive nutrients & building blocks from sinusoids
ow much of liver mass is hepatocytes?
80%
What are cholangiocytes?
Secrete HCO3- and water into bile
What are hepatocyte functions?
Metabolic & catabolic functions
Secretory & excretory functions
Detoxification & immunological functions
What are the metabolic and catabolic functions of hepatocytes?
synthesis & utilization of carbohydrates, lipids and proteins
What are the secretory and excretory functions of hepatocytes?
synthesis & secretion of proteins, bile and waste products
What are the detoxification and immunological functions of hepatocytes?
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 gluconeogenesis?
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 (storage in fat depots)
Describe carbohydrate metabolism in the liver.
Describe protein synthesis in the liver.
Describe the synthesis of “non-essential” AA.
(ketogenic and glucogenic AA- I think)
What is transamination (non-essential AA) and give examples?
Different keto-acids can be converted into multiple amino acids depending on the transaminase enzyme (vital for production of non- essential amino acids)
a-keto glutarate → e.g. glutamate, proline, arginine
Pyruvate →e.g.alanine, valine, leucine
Oxaloacetate →e.g.aspartate, methionine, lysine
What is the glucose-alanine cycle?
Deamination for gluconeogenesis
What is the purpose of the glucose-alanine cycle?
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)
Describe the glucose-alanine cycle?
What happens to the glutamate from the glucose-alanine cycle?
Describe triglyceride metabolism in the liver.
What is fat?
main energy store in body (100x glycogen).
Stored in adipose & liver.
When glycogen stores full, liver converts excess glucose & amino acids to fat for storage
What happens to acetyl CoA in lipoprotein synthesis?
What happens to glycerol in lipoprotein synthesis?
What happens to the lipoproteins formed in the liver?
What does the liver store?
- vitamins B12, A, D, E, K
- Iron
-Copper
fat soluble vitamins (A,D,E,K)
How long are the vitamins stored in the liver?
6-12 months
(except vitamin K where store is small)
Why is vitamin K essential?
essential for blood clotting
How is iron stored in the liver?
As ferritin
Why does iron need to be available?
For erythropoiesis
What are the 2 phases of liver detoxification?
(xenobiotics= foreign to bodies)
P450 enzymes
- Phase 1 (modification)
– more hydrophilic
Phase 2 (conjugation)
– attach water soluble side chain to make less reactive
What is the composition of bile?
mostly water
some bile salts
some bile pigments like bilirubin
more drug metabolites than urine
has some trace metals e.g., Fe, Zn, Cu
Alkaline phosphatase varies
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 made each day?
500ml
What is the colour of bile?
yellow/ green due to pigments such as bilirubin and biliverdin
What secretes bile?
Hepatocytes 60% of total bile
Cholangiocytes 40% of total bile
at type of bile secretion do hepatocytes do and describe it?
Primary secretion
- Bile secretions reflect serum concentrations
- Secretion of bile salts (acids), lipids & organic ions
What type of bile secretion do cholangiocytes do?
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
What performs biliary excretion of bile salts and toxins?
biliary transporters
What are the 2 types of biliary transporters?
Basolateral membrane (importing)
apical surface (exporting)
What are the basolateral membrane biliary transporters? (2)
Organic anion transporting peptide (OATPs) – bile salt uptake
Na+ taurocholate-cotransporting polypeptide (NTCP) - bile salt uptake
What are the apical surface biliary transporters? (3)
Bile Salt Excretory Pump (BSEP) – active transport of BAs (bile acids) into bile
MDR related proteins (MRP2 & MRP3) – -vely charged metabolites
- multi drug resistant
Products of multidrug resistance genes
MDR1 → excretion of neutral & +ve xenobiotics & cytotoxins
* MDR3 → phosphatidylcholine.
What are the key components of bile?
acids= salts (bile salts)
What synthesises bile acids?
Bile acids synthesised from cholesterol
- 2x primary bile acids synthesised in liver
- 2x secondary bile acids produced from primary acids by gut bacteria
What happens to bile acids in the liver?
Na+ & K+ salts of bile acids conjugated in liver to glycine & taurine
What are the secondary bile acids formed from primary acids by gut bacteria?
What is the role of bile salt?
Reduce surface tension of fats
Emulsify fat prior to its digestion & absorption
Bile salts form Micelles…
- Steroid nucleus planar- has 2x faces (Amphipathic)
- 1x surface hydrophilic domains (hydroxyl & carboxyl) - faces OUT → dissolves in water
- 2nd surface hydrophobic domains (nucleus & methyl) faces IN → dissolves in fat
- FFAs & cholesterol INSIDE
Diagram for bile salt function.
How is bile flow and secretion regulated?
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 release of cholecystokinin (CCK)
CCK causes gallbladder to contract
What are the functions of the gallbladder?
- Stores bile (50 mls) - concentrates bile - acidifies bile
- GB contraction triggered by CCK
- Binds to CCKA receptors & neuronal plexus of GB wall (innervated by preganglionic parasympathetic fibres of vagus nerve)
Describe the enterohepatic circulation.
95% bile salts reabsorbed from terminal ileum
- By Na+/bile salt co-transport Na+-K+ ATPase system
5% converted to 2ary bile acids in colon:
- Deoxycholic acid absorbed
- 99% Lithocolic acid excreted in stool
absorbed B.salts back to liver & re- excreted in bile
Describe free BR?
free bilirubin
Free BR (indirect/unconjugated)
= H2O-INSOLUBLE, yellow pigment
What is the source of bilirubin?
75% BR from Hb (erythrocytes) breakdown
22% from catabolism of other hemoproteins
3% from ineffective BM (bone marrow) erythropoiesis
What is free BR bound to?
Free BR bound to albumin in blood
What happens to BR bound to albumin?
Most dissociates in liver & enters hepatocytes
BR conjugated with 2x molecules of UDP-glucuronate → bilirubin diglucuronide (direct bilirubin)
Secreted ACROSS concentration gradient into biliary canaliculi → GIT
How much bile is excreted a day?
200-250mg BR excreted into bile/day
How is bile excreted?
85% excreted in faeces
BR → urobilinogen → stercobilinogen → stercobilin (brown compound)
What happens to the rest of bilirubin that isn’t excreted?
15% enters enterohepatic circulation
- BR → deconjugated → lipophilic form
- Urobilinogen
- Stercobilinogen
1% enters systemic circulation & excreted by kidneys
What are the cause of jaundice?
Post hepatic/ obstructive jaundice
What is ERCP?
Endoscopic retrograde cholangiopancreatography
You may need ERCP to find the cause of unexplained abdominal pain or yellowing of the skin and eyes (jaundice)
What is PTC?
Introduction Percutaneous transhepatic cholangiography (PTC)
is a procedure used to access the biliary tree for diagnostic purposes in obstructive jaundice, and to facilitate palliative stenting across biliary strictures
