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BRS Gastroenterology > Hepatobiliary System > Flashcards

Hepatobiliary System Flashcards

1
Q

Briefly outline the inflow and the outflow of the liver.

A 
Inflow:
Hepatic artery (25%)
Portal vein (75%)

Outflow:
Bile
3 x Hepatic veins

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2
Q

What parts of the liver does the middle hepatic vein separate?

A

Anterior segment of right hepatic lobe from the medial segment of the hepatic lobe.

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3
Q

How many hepatic segments are there?

A

8

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4
Q

List the micro-morphological and functional components of the liver.

A

Morphological - Lobules + Portal triads

Functional - Acinus, blood and bile flow

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5
Q

What shape is a hepatic lobule and describe the structure of 1 hepatic lobule?

A

Hexagon - Each corner consists of a portal triad which links with 3 adjacent lobules.

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6
Q

What does a portal triad consist of? What is the function of each constituent?

A

Branch of hepatic artery - Brings O2-rich blood into liver to support hepatocytes increased energy demands.

Branch of portal vein - Mixed venous blood from GIT (nutrients, bacteria and toxins) and spleen (waste products). Hepatocytes process nutrients, detoxify blood and excrete waste.

Bile Duct - Bile drains into bile canaliculi and then coalesce with cholangiocyte-lined bile-ducts around lobule perimeter.

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7
Q

What type of cell are bile-ducts lined by?

A

Cholangiocyte

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8
Q

What is the functional unit of the liver (in terms of micro-function) and what does it consist of?

A

Hepatic acinus

Consists of 2 adjacent 1/6th hepatic lobules sharing 2 portal triads. They extend into hepatic lobules as far as the central vein.

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9
Q

The diagram below shows the 3 zone model. At what point does blood drain out of the hepatic acinus?

A

Point B (central vein)

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10
Q

What zone receives the most oxygen and has the lowest toxin risk?

A

Zone 1: Highest oxygen concentration (also highest toxin risk)

Zone 3: Lowest toxin risk (also lowest oxygen concentration)

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11
Q

Do sinusoidal endothelial cells have a basement membrane?

A

No

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12
Q

Describe the structure of sinusoidal endothelium why it has this structure.

A

Fenestrated (discontinuous) endothelium allowing lipids and large molecule movement to and from hepatocytes.

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13
Q

What are Kuppfer cells and what are their functions?

A

Sinusoidal macrophage cells attached to endothelial cells.

Phagocytosis; they eliminate and detoxify substances arriving in liver from portal circulation.

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14
Q

What is another name for ito or perisinusoidal cells? List all the functions of these cells

A

Hepatic stellate cells

Store vitamin A in liver cytosolic droplets
Activated in response to liver damage
Deposit collagen in the ECM

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15
Q

What cell type makes up 80% of liver mass?

A

Hepatocyte

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16
Q

What does a cholangiocyte secrete into bile?

A

HCO3- and H20

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17
Q

Summarise the main hepatocyte functions

A

Metabolic and catabolic functions - make + use 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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18
Q

List 3 non-sugar molecules that can be used to produce glucose via gluconeogenesis.

A

Amino acids (from liver and renal cortex)
Lactate (from anaerobic glycolysis in RBCs and muscles)
Glycerol (lipolysis)

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19
Q

Outline the Cori Cycle

A

Lactate produced via anaerobic glycolysis in a muscle cell (myocyte) is transported to the liver and is converted to pyruvate via lactate dehydrogenase. Pyruvate then converted to glucose via gluconeogenesis.

Glucose via glycolysis to pyruvate → lactate and the cycle starts over again.

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20
Q

Where do amino acids undergo protein synthesis and what proteins are produced?

A

Liver

Plasma proteins, Clotting factors and Lipoproteins

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21
Q

Briefly explain what transamination is using alanine and alpha-keto glutarate as an example.

A

Keto-acids can be converted into multiple amino acids depending on the specific transaminase enzyme responsible for conversion. This will occur in the liver.

Alanine + alpha-keto glutarate → Glutamate + Pyruvate

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22
Q

What are the main non-essential amino acids that are formed from the deamination of alpha-ketoglutarate, pyruvate and oxaloacetate respectively?

A

Alpha-keto gluatarate - glutamate, arginine, proline (GAP)

Pyruvate - leucine, alanine, valine (LAV)

Oxaloacetate - methionine, aspartate, lysine (MAL)

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23
Q

Outline the glucose-alanine cycle.

A

Pyruvate is produced from anaerobic glycolysis in muscle cells and then transported to the liver where it is converted to alanine via an aminotransferase enzyme. Nitrogen is also transported to the liver in the form of glutamine made from glutamate and ammonia catalysed by glutamine synthetase.

  1. Alanine converted to glucose via gluconeogenesis. Glucose returned to muscle cell for glycolysis.
  2. Alanine also converted to glutamate. Glutamate to urea, gets deaminated and returned to blood.
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24
Q

How are fatty acids from triglyceride breakdown converted into acetyl CoA?

A

Beta-oxidation

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25
Q

How can Acetyl CoA be used as an alternative tissue energy source before running it through the TCA cycle?

A

2 Acetyl CoA can be converted into Acetoacetyl CoA via enzyme thiolase.
Add another Acetyl CoA to Acetoacetyl CoA to get HMG CoA.
HMG CoA can be cleaved to form a free Acetoacetate and another Acetyl CoA.

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26
Q

What is the main energy reserve stored in the liver and muscle?

A

Glycogen

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27
Q

What is the main function of LDLs, VLDLs and HDLs?

A

LDLs - Transport cholesterol to tissues

VLDLs - Transport fatty acids to tissues.

HDLs - Transport endogenous cholesterol from tissues to liver.

28
Q

What are the major functions of cholesterol?

A

Maintaining membrane integrity.

Steroidogenesis

29
Q

What do hepatocytes store?

A

Vitamine A, D, E, K and B12.
Store iron as ferritin (available for erythropoiesis)
Copper

30
Q

What vitamin is essential for blood clotting?

A

Vitamin K

31
Q

Outline how hepatocytes carry out detoxification.

A 
Phase 1 (modification) - P450 enzymes used. Reactions classified into oxidation, reduction and hydrolysis. More hydrophilic phase.   
Phase 2 (conjugation) - Attach water soluble side chain to make less reactive.
32
Q

What is the majority of bile made of?

A

97% Water

33
Q

What are the bile pigments?

A

Bilirubin and biliverdin

34
Q

List the uses of bile.

A

Cholesterol homeostasis

Absorption of lipids and lipid-soluble vitamins (ADEK)

Excretion of:
Adrenocortical and other steroid hormones
Xenobiotics/drugs - chemical substance that is foreign to animal life
Alkaline phosphatase
Cholesterol metabolites

35
Q

How much bile is produced daily? What percentage do hepatocytes and cholangiocytes secrete?

A

500 ml
Hepatocytes - 60%
Cholangiocytes - 40%

36
Q

What colour is biliverdin?

A

Green

37
Q

Outline the secondary modification of bile after primary secretion by hepatocytes.

A

Done by cholangiocytes:

  • Alteration of pH
  • H20 drawn into bile via osmosis
  • Luminal glucose and organic acids reabsorbed
  • HCO3- and Cl- actively secreted into bile by CFTR
  • IgA is exocytosed
38
Q

Where can you find biliary transporters?

A

Apical surface and basolateral membranes of hepatocytes and cholangiocytes.

39
Q

List the main biliary transporters and briefly their function.

A

Bile Salt Excretory Pump (BSEP) - active transport of BAs into bile
MDR related proteins (MRP1 and 3)
Products of familial intrahepatic cholestasis gene (FIC1)
Products of multidrug resistance genes

MDR1 → excretion of xenobiotics and cytotoxins
MDR3 → phosphatidylcholine

40
Q

What are bile acids synthesised from?

A

Cholesterol

41
Q

What 2 compounds are the Na+ and K+ salts of bile acids conjugated in the liver to?

A

Glycine and Taurine

42
Q

What are the 2 primary bile acids synthesised in the liver?

A

Cholic acid

Chenodeoxycholic acid

43
Q

What are the 2 secondary bile acids produced from the 2 primary acids by gut bacteria?

A

Cholic acid → Deoxycholic acid

Chenodeoxycholic acid → Lithocolic acid

44
Q

What are the 2 functions of bile salts?

A

Reduce surface tension of fats.

Emulsify fat prior to its digestion and absorption.

45
Q

What compound does a bile salt form and describe briefly the structure of this compound?

A

Micelles - Steroid nucleus planar with 2 faces (Amphipathic)

1st surface is hydrophilic due to hydroxyl and carboxyl groups - faces out → dissolves in water
2nd surface is hydrophobic due to nucleus and methyl - faces in → dissolves in fat

Composed of FFAs and cholesterol

46
Q

What happens to the Sphincter of Oddi and therefore bile, between meals?

A

It is closed → bile diverted into gall bladder for storage.

47
Q

What happens to the Sphincter of Oddi when you eat?

A

It relaxes, to release pancreatic juice and bile.

48
Q

When gastric contents (FFAs, AAs > CHOs) enter the duodenum, what chemical is released by the duodenum and what does it do?

A

CCK

Causes gall bladder to contract to release bile

49
Q

What is the function of the enterohepatic circulation?

A

Allows for recycling of metabolised and non-metabolised compounds.

50
Q

What % of bile salts is reabsorbed from the terminal ileum?

A

95%

51
Q

What is the name of the system used to reabsorb bile in the terminal ileum?

A

Na+/Bile salt co-transport Na+-K+ ATPase system

52
Q

How much of the primary bile salts are converted into secondary bile salts in the colon?

A

5%:
All deoxycholic acid is absorbed.
99% lithocolic acid is excreted in stool.

53
Q

What happens to these absorbed bile salts?

A

They go back to the liver and are re-excreted in bile.

54
Q

What are the 2 functions of the gallbladder?

A 
Stores bile (50ml):
Concentrates and acidifies bile

Gallbladder contraction controlled by CCK:
CCK binds to CCKA receptors and neuronal plexus of GB wall (innervated by preganglionic parasympathetic fibres of vagus nerve)

55
Q

Is free bilirubin H20 soluble, and what colour is it?

A

No, H20-Insoluble

Yellow pigment

56
Q

Where does the majority of BR come from?

A

Haemoglobin (75%) - erythrocyte breakdown

57
Q

Where does the rest of the BR come from?

A

22% from catabolism of other haemoproteins.

3% from ineffective bone marrow erythropoiesis

58
Q

What is free bilirubin bound to in the blood?

A

Albumin

59
Q

What should the concentration results of Bilirubin and Albumin of a sample from a patient with a functioning liver be?

A

Low Bilirubin - would be good as it removes bile

High Albumin

60
Q

Describe the conversion of indirect bilirubin into direct bilirubin and then how is this taken up into the GIT?

A

Most of the bilirubin dissociates with the albumin in the blood and enters the hepatocytes.
BR is conjugated with 2 molecules of UDP-glucuronate catalysed by glucuronyl transferase → bilirubin diglucuronide (direct/conjugated bilirubin).
Secreted across concentration gradient into biliary canaliculi → GIT.

61
Q

What happens to BR once it enters the large intestine?

A

85% secreted in faeces:
BR → Urobilinogen → stercobilinogen → stercobilin

15% enters enterohepatic circulation:
BR → deconjugated → lipophilic form
Urobilinogen and stercobilinogen ~15% comes back into enterohepatic circulation.

1% enters sytemic circulation and excreted by kidneys

62
Q

Which compound gives faeces its brown colour?

A

Stercobilin

63
Q

If BR cannot get into the gut, what condition does this cause?

A

Obstructive Jaundice:
BR cannot be converted into stercobilin and so the faeces becomes very pale.
This causes the bile to leave via the kidneys so this causes dark urine.

64
Q

How would you clear a blockage that prevents blood getting out distally from the pancreatic side of the biliary system?

A

Endoscopic Retrograde Cholangiopancreatography (ERCP)

Put camera into duodenum and access ampulla via Sphincter of Oddi. Run deflated balloon past the stones in the bile duct and then inflate the balloon. Then pull the stones from the bile duct

65
Q

How would you clear the blockages of ducts in the liver?

A

Percutaneous Transhepatic Cholangiography:
Run needle into skin with local anesthetic, into the liver and into the bile duct and to wherever the blockage might be.
Then remove the blockage through the Sphincter of Oddi so they can enter the duodenum.

BRS Gastroenterology (11 decks)

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