Hepatobiliary System Flashcards
Where is the liver?
Mostly in URQ just below the nipple and inside the rib cage
What is the morphological anatomy of the liver?
Sits under the diaphragm
Small gall bladder underneath right side
Falciform ligament down middle
Ligamentum teres under falciform
Two lobes; right and left, separated by the middle hepatic vein
What is the blood supply to the liver?
Inflow:
Hepatic artery 25% (oxygen rich blood to support active hepatocytes)
Portal vein 75% (mixed venous blood from GIT (nutrients,bacteria,toxins) and spleen (waste))
Outflow:
Bile
3 hepatic veins (these drain into the inferior vena cava)
What are the sections of the liver?
8segments
1: small and right next to IVC
2-8: start in top left (anatomical) and continue clockwise round
What is the micro morphology of the liver and the functions of the liver?
Morphological: lobules, portal triads
Functional: acinus, blood flow, bile flow
What is the structure of a hepatic lobule?
Hexagonal structural unit of liver tissue
Each corner consists of a portal triad (these link 3 adjacent lobules)
In the centre is a central vein: collects blood from hepatic sinusoids -> hepatic veins -> systemic venous system
Within the lobule are rows of hepatocytes: each had a sinusoid facing side and a bile cannuliculi facing side
What is the structure of a portal triad?
Branch of hepatic artery:
Brings oxygen rich blood into liver to support hepatocytes high energy demands
Branch of portal vein:
Mixed venous blood from GIT (nutrients, bacteria, toxins) and spleen (waste products)
Hepatocytes process nutrients, detoxify blood and excrete waste
Bile duct:
Bile produced by hepatocytes drains into bile cannuliculi
Coalesce with cholangiocyte lined bile ducts around lobule perimeter
What is a hepatic acinus?
Functional unit of liver
Consists of two adjacent sixths (triangles) of hepatic lobules
These share 2 portal triads
And extend into lobules as far as a central vein
What is the three zone model? (Hepatic acinus)
Acinus is split into three zones. 1 in the middle, 2 further out on either side, 3 furthest out and next to the central vein
Blood enters zone 1 through the portal triad
Drains out of zone 3 Via the central vein
Hepatocytes bear outer hepatic lobule (zone 1) recieve early exposure to blood contents (good Oxygen) (lots of bad too (toxins))
1: high o2, high toxin risk
2: middle o2, middle toxin risk
3: low o2, low toxin risk
What are all the liver cell types?
Sinusoidal endothelial cells
Kuppfer cells
Hepatic Stellate cells
Hepatocytes
Cholangiocyte
What at sinusoidal endothelial cells?
No basement membrane
Fenestrated
Allow lipids and large molecule movement to and from hepatocytes
What are kuppfer cells?
Sinusoidal macrophage cells
Attached to endothelial cells
Phagocytosis: eliminate and detoxify substances arriving in liver from portal circulation
What are hepatic stellate cells?
Aka ito cells or perisinusoidal
Exist in dormant state
Store vitamin A in liver cytosolic droplets
Activated in response to liver damage -> proliferate, chemo tactic and deposit collagen in ECM
What are hepatocytes?
80% of liver mass
Cubical
Synthesis (albumin, clotting factors, bile salts)
Drug metabolism
Recieve nutrients and building blocks from sinusoids
What are cholangiocytes?
Secrete HCO3- and H2O into bile
Found at the end of bile cannuliculi
What is the function of hepatocytes?
Metabolic and catabolic:
Synthesis and utilisation of carbohydrates, lipids and proteins
Secretory and excretory:
Synthesis and secretion of proteins, bile and waste products
Detoxification and immunological functions:
Breakdown of ingested pathogens and processing of drugs
What is the role of the liver in carbohydrate metabolism?
Glycolysis in muscle cells can produce pyruvate
This can either be used aerobicay in the TCA cycle and oxidative phosphorylation, or anaerobically in fermentation to make lactate
The liver can then make this lactate back into pyruvate in the cori cycle using lactate dehydrogenase
This pyruvate can then take part in gluconeogenesis to make glucose
What is the role of the liver in protein synthesis?
Amino acids travel to the liver (in the fed state from diet and in the fasted state from muscle breakdown)
In the liver amino acids are made into proteins which are then secreted
Eg. Plasma proteins, clotting factors, lipoproteins
What is the role of the liver in synthesis of non essential amino acids?
Amino acids form the diet such as alanine are carried to the liver
Here they can be combined with keto acids such as alpha keto glutamate
This reversibly makes pyrivate and glutamate (of another aa)
This is transamination
Dofferent keto acids can be converted into multiple amino acids depending on the transaminase enzyme
a-keto glutarate -> glutamate, proline, arginine
Pyruvate -> alanine, valine, leucine
Oxaloacetate -> aspartame, methionine, lysine
What is the problem solved by 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 liver (glucose-alanine cycle)
What is the glucose-alanine cycle?
Glutamate (from aa breakdown) and pyruvate (from glycolysis) can undergo deamination to form alanine
Alanine can then be used in the liver to combine with alpha keto glutarate to make pyruvate (which can be used to make glucose)
And glutamate
The pyruvate is used to make glucose which can be used in glycolysis in muscle
The glutamate can be turned into urea, then into the blood where it is excreted
What is the role of the liver in triglyceride metabolism?
Fat is the main energy store in the body. It is stored in adipose and liver. When glycogenstores are full, the liver converts excess glucose and amino acids into fat for storage
In adipose, triglycerides are broken down into fatty acids
In the liver the fatty acids undergo beta oxidation to form acetyl CoA
This then entered the TCA cycle
Or 2 acetyl CoA can be used to make acetoacetate, this can be used as an energy source in tissues
What is the role of the liver in lipoprotein synthesis?
Glucose in the liver can be made into glycerol. Or pyruvate, which can be used to make Acetyl CoA, which can make cholesterol and fatty acids
The glycerol can be used to make tri acyl glyceride
This can be combined with apoproteins and phospholipids and cholesterol to make lipoproteins
What are lipoproteins?
VLDL - transports fatty acids to tissues
LDL- bad cholesterol - transports cholesterol to tissues
HDL - empty, picks up excess cholesterol
The role of cholesterol: making steroid hormones, cell membrane integrity
What is the storage function of the liver?
Storage of:
Fat soluble vitamins - A,D,E,K
Storage lasts around 6-12 months (except vitamin K which is essential for blood clotting)
Storage of iron as ferritin
Available for erythropoiesis
What is the role of the liver in detoxification?
Detoxification of xenobiotics
P450 enzymes
Phase 1- modification - more hydrophilic
Phase 2 - conjugation - attach a water soluble side chain to make less reactive
What is the morphological anatomy of the biliary system?
Right and left hepatic ducts of liver
Gall bladder (bile stored)
Bile duct and sphincter
Ampulla and sphincter
What is the composition of bile?
97% water
- 7% bile salts
- 7% inorganic salts
- 2% bile pigments (bilirubin/bilivirden)
- 15% fatty acids
- 1% lecithin
Fat, cholesterol, alkaline phosphatase, drug metabolites, trace metals
What are the uses of bile?
Cholesterol homeostasis
Absorption of lipids and lipid soluble vitamins (A,D,E,K)
Excretion of: xenobiotics, cholesterol metabolites, adrenocortical and other steroid hormones, alkaline phosphatase
What is the production of bile like?
500 mls per day
Yellow/green due to bilirubin/biliverdin
Hepatocytes: 60% of total bile
Primary secretion - bile secretions reflect serum concentrations, secretion of bile salts, lipids and inorganic ions
Cholangiocytes: 40% of total bile
Secondary modification - alteration of pH. H2O drawn in by osmosis via para cellular junctions. Luminal glucose and organic acids reabsorbed. HCO3- (bicarbonate) and Cl- actively secreted into bile by CFTR (cystic fibrosis transmembrane regulator). IgA exocytosed
What are biliary transporters?
Biliary excretions of bile salts and toxins performed by biliary transporters on apical surface and basolateral membranes of hepatocytes and cholangiocytes
Look at pp for examples but let’s be honest I’m never gonna remember them
What are bile salts?
Synthesised from cholesterol
Sodium and potassium of bile salts conjugated in the liver to glycine and taurine
2 primary bile acids synthesised in liver: cholic acid and chenodroxycholicacid
2 secondary bile acids produced from primary acids by gut bacteria: deoxycholic acid and lithocolic acid
(Cholic -> deoxycholic. Chenodeoxycholic -> lithocolic)
What is the function of bile salts?
Reduce surface renationalise of fats
Emulsify fat prior to digestion and absorption
Bile salts for Micelles:
Steroid nucleus planar- amphipathic (two faces)
1 is hydrophilic, faces outwards and dissolves in water
1 is hydrophobic , faces in and dissolves in fat
FFS and cholesterol inside
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 enter duodenum causing release of cholecystokinin (CCK)
CCK causes gall bladder to contract
What is interohepatic circulation?
95% of bile salts reabsorbed from terminal ileum
By Na+/bile salt cotransporter sodium potassium ATPase system
5% converted into secondary bile acids in colon: - deoxycholic acid absorbed. - 99% lithocolic acid excreted in stool
Absorbed bile salts back to liver (via portal vein) and re excreted in bile
What are the functions of the gall bladder?
- Store 50 mls of bile. Concentrates and acidifies bile
- Gall bladder contraction triggered by CCK
Binds to CCKa receptors and neuronal plexus of GB wall
What is bilirubin?
Free BR is H2O insoluble, yellow pigment
75% from haemoglobin breakdown
22% from catabolism of other haemoproteins
3% from immefective BM erythropoiesis
Free BR is bound to albumin in blood, most dissociates in the liver and enters hepatocytes
BR conjugated with 2 molecules of UDP-glucuronate -> bilirubin diglucuronide
This is secreted across concentration gradient into biliary canaliculi -> GIT
What happens to bilirubin?
200-250 mg excreted into bile/day
85% excreted in faeces:
BR -> urobilinogen -> stercobilinogen -> stercobilin (brown compound)
15% enters enterohepatic circulation
BR -> deconjugated -> lipophilic form
1% enters systemic circulation and is excreted by kidneys
