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The hepatobiliary system Flashcards

1
Q

How is the liver structured?

A

Divided into 2 primary lobes- large right lobe and much smaller left lobe
The right lobe has an inferior quadrate lobe and posterior lobe which are defined by internal features

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2
Q

What is the liver connected to?

A

connected to the abdominal wall and diaphragm by 5 peritoneal folds referred to as ligaments:
Falciform, coronary, 2x lateral and ligamentum teres hepatis
Falciform and ligamentum teres separate right and left lobes anteriorly
Lesser omentum tethers the liver to the lesser curvature of the stomach

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3
Q

At what structure does a major vein and artery enter the liver?

A

porta hepatis is where the hepatic artery and hepatic portal vein enter the liver along with the common hepatic duct- these run behind the lesser omentum

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4
Q

What provides the main inflow to the liver?

A

Hepatic artery- 25%
Hepatic portal vein: 75%
The hepatic artery delivers oxygenated blood from heart to liver
Hepatic portal vein delivers partially deoxygenated blood containing nutrients absorbed from intestine and actually supplies more oxygen than hepatic arteries, drugs and toxins also absorbed

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5
Q

How does the liver outflow invole?

A

Bile
3x hepatic veins
After processing bloodborne nutrients and toxins, liver releases nutrients needed by other cells back into the blood, drains into central vein and then through hepatic vein to inferior vena cava

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6
Q

What is significant about the middle hepatic vein?

A

Divides the left and right side of the liver

Goes into the IVC on left lateral side and goes to the gallbladder fossa

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7
Q

What’s the importance of hepatic portal circulation?

A

All blood from alimentary canal passes through liver

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8
Q

What is a hepatic lobe?

A

Hexagonal structural unit of liver tissue
Each corner is made up of portal triad (artery, vein and duct)- this links with 3 adjacent lobules
The centre of liver lobule is central vein- collects blood from hepatic sinusoids which goes to hepatic veins which goes to systemic venous system
Within lobules are rows of hepatocytes- each has sinusoid-facing side and bile canaliculi-facing side

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9
Q

What is the portal triad?

A

Has a:
- Branch of hepatic artery: brings O2 rich blood into liver to support hepatocytes with increased energy demands

  • Branch of portal Vein: mixed venous blood from GIT (nutrients, bacteria and toxins) and spleen (waste products)
  • Bile duct: bile produced by hepatocytes drains into bile canaliculi. it coleases with cholangiocyte-lined bile ducts around lobule perimeter
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10
Q

What is the hepatic acinus?

A

Functional unit of the liver

Consists of 2 adjacent 1/6th hepatic lobules- share 2x portal triads, extend into hepatic lobules as far as central vein

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11
Q

How is the hepatic acinus divided?

A

Has 3 zones:

Zone 1- oxygen high, toxin risk high
Zone 2- oxygen medium, toxin risk medium
Zone 3- oxygen low, toxin risk low

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12
Q

What are the names of different liver cells?

A 
Sinusoidal cell
Kupffer cells
Hepatic stellate cells
Hepatocyte
Cholangiocyte
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13
Q

What is a sinusoidal endothelial cell?

A

no basement membrane
Fenestrated (discontinuous epithelium)
allows lipids and large molecules movement to and from hepatocytes

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14
Q

What are kuppfer cells?

A

Sinusoidal macrophage cells
Attached to endothelial cells
Phagocytosis- eliminate and detoxify substances arriving in liver from portal circulation

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15
Q

What are hepatic stellate cells?

A

exist in dormant state
Store vitamin A in liver cytosolic droplets
Activated (fibroblasts) in response to liver damage
Proliferate, chemotactic and deposit collagen in ECM

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16
Q

What are hepatocytes?

A

80% of liver mass
Cubical
Synthesis e.g. albumin, clotting factors and bile salts
Drug metabolism
Receive nutrients and building blocks from sinusoids

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17
Q

What are cholangiocytes?

A

Secrete bicarbonate and water into bile

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18
Q

What are hepatocyte functions?

A

Metabolic and catabolic functions: synthesis and utilisation of carbohydrates, lipids and proteins

Secretory and excretory functions: synthesis and secretion of proteins, bile and waste products

Detoxification and immunological functions: breakdown of ingested pathogens and processing of drugs

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19
Q

How do hepatocytes carry out carbohydrate metabolism?

A

Lactate is taken to the liver from muscle cells
Here it is converted to pyruvate by lactate dehydrogenase
Pyruvate is then converted to glucose through gluconeogenesis
This is the cori cycle

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20
Q

How do hepatocytes carry out protein synthesis?

A

Amino acids are taken to the liver from muscle cells where they are used to build important proteins (albumin, clotting factors and lipoproteins)

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21
Q

How are non-essential amino acids synthesised?

A

Through transamination different keto-acids can be converted into multiple amino acids depending on the transaminase enzyme (vital for production of non-essential amino acids)

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22
Q

What amino acids can a-keto glutarate be converted to?

A

glutamate, proline or arginine

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23
Q

What amino acids can pyruvate be converted to?

A

alanine, valine or leucine

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24
Q

What amino acids can oxaloacetate be converted to?

A

aspartate, methionine or lysine

25
How does the liver use amino acids to produce glucose?
Muscle can potentially utilize amino acids to produce glucose for energy However to convert pyruvate to glucose requires energy and to remove nitrogen requires energy So pyruvate is taken to the liver to be broken down through the glucose-alanine cycle (deamination)
26
How does the liver carry out triglyceride metabolism?
In adipose tissue cells triglycerides are converted to fatty acids They're then transported to the liver where they're converted to 2x acetyl CoA by B oxidation and then go on to the TCA cycle to form energy
27
What is the significance of fat?
Fat is the main energy store in the body (100x glycogen) Its stored in adipose and liver When glycogen stores are full liver converts excess glucose and amino acids to fat for storage
28
How does the liver synthesis lipoproteins?
Glucose is transported into the liver where it is stored as glycerol or converted to pyruvate where it the goes on to be converted to acetyl CoA which is converted to fatty acids or cholesterol
29
What can glycerol be converted to?
Tri-acyl glycerol, apoproteins phospholipids and cholesterol- these are lipoproteins
30
What happens to fatty acids produced in lipoprotein synthesis?
transported to adipose tissues by very low density lipoprotein (VLDL)
31
What happens to cholesterol produced in lipoprotein synthesis?
High density lipoproteins picks up excess cholesterol Low density lipoproteins transport cholesterol to tissues
32
What is the role of hepatocytes in storage?
Store fat soluble vitamins (A, D, E, K) Stores are sufficient for 6-12 months (except vit K where store is small) Vit K is essential for blood clotting- depleted in obstructive jaundice It stores iron as ferritin- this is available for erythropoiesis Hemochromatosis is excess iron causing liver disease
33
What is the role of hepatocytes in detoxification?
carries out xenobiotic detoxification- has 2 phases: Phase 1: modification- makes substance more hydrophilic Phase 2: conjugation- attach water soluble side chains to substance to make it less reactive
34
What colour is bilirubin?
Yellow
35
What colour is biliverdin?
green
36
What is bile used for?
Cholesterol haemostasis Absorption of lipids and lipid soluble vitamins (A,D,E and K) Excretion of: -xenobiotics/drugs -cholesterol metabolites -adrenocortical and other steroid hormones -alkaline phosphatase
37
Hiw much bile does the body produce a day?
500mls
38
What cells secrete bile?
Hepatocytes and cholangiocytes
39
What is the role of hepatocytes in bile secretion?
Secrete 60% of total bile Primary secretion Bile secretions reflect serum concentrations Secretion of bile salts (acids), lipids and organic ions
40
What role do cholangiocytes play in bile secretions?
Secrete 40% of bile Secondary modification Alteration of pH (alkaline electrolyte solution) H2O drawn into bile by osmosis via paracellular junction Luminal glucose and organic acids reabsorbed HCO3- and Cl- actively secreted into bile by CFTR (cystic fibrosis transmembrane regulator- responsible for CF in lungs) IgA exocytosed
41
How is bile excreted?
Biliary excretion of bile salts and toxins is performed by biliary transporters on apical surface and basolateral membrane of hepatocytes and cholangiocytes
42
What are the main transporters of bile?
Bile salt excretory pump (BSEP)- active transport of BAs into bile MDR related proteins (MRP1 and MRP3) Products of the familial intrahepatic cholestasis gene (F1C1) Products of multidrug resistance genes - - MDR1 excretion of xenobiotics and cytotoxins - MDR3- phosphatidylcholine
43
What components make up bile salts?
Acids and salts Bile acids synthesised from cholesterol Na+ and K+ salts of bile acids conjugated in liver to glycine and taurine
44
What bile acids are synthesised in the liver?
2x primary bile acids synthesised in liver These are cholic acid: converted by gut bacteria to deoxycholic acid Chenodeoxycholic acid: converted by gut bacteria to lithocholic acid Deoxycholic acid and lithocholic acid are secondary bile salts
45
What is the function of bile salts?
Reduced surface area tension of fats | Emulsify fats prior to its digestion and absorption
46
What do bile salts form?
They form micelles They're steroid nuclear planar- has 2 faces (amphipathic- had hydrophilic and hydrophobic faces) Has a hydrophilic surface with hydrophilic domains (hydroxyl and carboxyl) which faces out- dissolves in water Has a hydrophobic surface with hydrophobic domains (nucleus and methyl) which faces in- dissolves in fat Have free fatty acids and cholesterol inside
47
How are micelles formed?
A fat globule is emulsified by bile salts to form triglycerides. These are broken down by lipase and colipase to fatty acids and monoglycerides These go on to form micelles
48
What regulates the flow of bile salts?
Between meals the sphincter of Oddi is closed- the bile is diverted into the gallbladder for storage During eating the sphincter of Oddi relaxes and opens Gastric contents enters the duodenum causing release of cholecystokinin (CCK) CCK causes gallbladder to contract
49
How does the enterohepatic circulation work?
95% of bile salts are reabsorbed from terminal ileum by the Na+/bile salt cotransport Na+-K+ATPase system 5% is converted to second degree bile acids in colon: - deoxycholic acid is absorbed - 99% of lithocholic acid is excreted in stool Absorbed bile salts are returned back to the liver and re-excreted in bile
50
What are the two functions of the gallbladder?
1. Stores bile (50ml)- concentrates and acidifies bile 2. Gallbladder contraction triggered by CCK- it binds to CCKa receptors and neuronal plexus of gallbladder wall (innervated by preganglionic parasympathetic fibres of vagus nerve)
51
What is bilurubin?
Free bilirubin is unconjugated | It's H2O- insoluble and has a yellow pigment
52
What are sources of bilirubin?
75% from Hb breakdown 22% from catabolism of other hemoproteins 3% from ineffective BM erythropoiesis
53
What is free bilirubin bound to?
Albumin in blood | Most dissociates in liver and enters hepatocytes
54
What is a second form of bilirubin?
BR conjugated with 2 molecules of UDP-glucuronate- bilirubin diglucuronide (direct bilirubin) Secreted across concentration gradient into biliary canaliculi-GIT
55
How much bilirubin is secreted a day?
200-250mg excreted into bile a day 85% is excreted into faeces: BR -> urobilinogen -> stercobilinogen -> stercobilin (brown component) 15% enters enterohepatic circulation: - BR -> deconjugated -> lipophilic form - Urobilinogen - stercobilinogen 1% enters systemic circulation and excreted by kidneys
56
What are causes of jaundice?
1. Prehapatic jaundice: produces more BR than usual- more indirect BR, a lot more Hb breakdown (before conjugation in liver) 2. Intrahepatic jaundice: liver not working properly: - not taking out much BR - decreased conjugation - decreased secretion - outflow obstruction in biliary tree 3. Post-hapatic jaundice - obstructive (everything outside the liver) when you can't get BR out can cause lots of pain- stones can get stuck in different places and cause different illnesses
57
What is a ERCP?
Put a wire into bile duct Balloon and pull gallstone out May need to be crushed
58
What is percutaneous transhepatic cholangiography (Ptc)?
Imaging used to see if theres a problem higher up in hepatic duct

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