8.3: Hepatobiliary system Flashcards

1
Q

What is the inflow of blood via the hepatic artery

A

25%

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2
Q

What is the inflow of blood to the liver via the portal vein

A

75%

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3
Q

What does the outflow of blood from the liver occur via

A

Bile
3x hepatic veins

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4
Q

What is the purpose of blood delivered to the liver by the portal vein

A

Contains all products of digestion absorbed from the GI tract
All useful and non-useful products are processed in the liver before being released back into the hepatic veins which join the IVC or stored in the liver for later use

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5
Q

What is the purpose of blood delivered to the liver by the hepatic artery

A

Delivers oxygenated blood from the general circulation

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6
Q

Morphological structure of liver

A

Lobules
Portal triads (tracts)

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7
Q

3 functions of morphology of liver

A

Acinus
Blood flow
Vile flow

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8
Q

Describe the Structure of the hepatic lobule

A

Hexagonal structural unit of liver tissue In
Each corner consists of a portal triad - links with 3 adjacent lobules

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9
Q

What is the centre of a liver lobule

A

Central vein

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10
Q

Function of central vein at liver lobule centre

A

Collects blood from hepatic sinusoids -> hepatic veins -> systemic venous system

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11
Q

What can be found within a liver lobule

A

Rows of hepatocytes
Each has sinusoid-facing side and bile canaliculi-facing side

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12
Q

Portal triad

A
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13
Q

3 uses of bile

A

Cholesterol homeostasis
Absorption of lipids and lipid soluble vitamins
Excretion of: xenobiotics, cholesterol metabolites, adrenocortical and steroid hormones, alkaline phosphatase

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14
Q

Two bile pigments

A

Bilirubin - yellow
Biliverden - green

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15
Q

4 lipid soluble vitamins

A

A
D
E
K

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16
Q

How much bile is produced per day

A

500mls

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17
Q

Two cells that secrete bile

A

Hepatocytes - 60%
Cholangiocytes - 40%

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18
Q

In Primary secretion of bile

A

Bile secretions reflect serum concentrations
Secretion of bile salts, lipids and organic ions

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19
Q

In Secondary modification of bile

A

Alternation of pH
H2O drawn into bile via osmosis via paracellular junctions
Luminal glucose and organ is acids reabsorbed
HCO3- Cl- actively secreted into bile by CFTR
IgA exocytosed

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20
Q

What is Hillary excretion of bile salts and toxins performed by

A

Biliary transporters

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21
Q

2 main transporters of bile salts

A

Basolateral membrane (importing)
Apical surface (exporting)

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22
Q

Which structure is the remenant of the umbilical vein of the foetus?

A

Ligamentum Teres

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23
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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24
Q

How many hepatic segments are there?

A

8

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25
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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26
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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27
Q

The centre of the lobule is the central vein.
Outline its drainage

A

Collects blood from hepatic sinusoids -> hepatic veins -> systemic venous system

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28
Q

Within a lobule there are rows of hepatocytes, what does each side of the row of hepatocytes face?

A

Each has a sinusoid-facing side -> picks up stuff from the inflow of blood

Bile canaliculi facing side → Makes bile by taking nutrients, processing it and shifting it across to the biliary canaliculi

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29
Q

What does a portal triad consist of ? What is 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 and spleen. Hepatocytes process nutrients, deoxify 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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30
Q

What type of cell are bile ducts lined by and what is the function of this cell type?

A

Cholangiocyte
Modification of hepatic canalicular bile as it is transported along the biliary tree

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31
Q

Through what vessels does blood flow through to get from the central vein to the right, left or middle hepatic veins?

A

Central → Intralobular → Interlobular → Right, Middle or Left Hepatic Veins

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32
Q

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

A

Hepatic acinus
Consist 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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33
Q

Do sinusoidal endothelial cells have a basement membrane?

A

No

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34
Q

Describe the structure of sinusoidal endothelial cells and how does this adapt the endothelium to its structure?

A

Discontinuous, fenestrated endothelium
Allows lipids and large molecule movement to and from hepatocytes

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35
Q

What is the difference between a bile canaliculus and a bile duct?

A

Bile canaliculi are thin tubes collecting bile secreted by hepatocytes and they empty into a series of progressively larger bile ductules and ducts that eventually become the common hepatic duct

36
Q

What are Kuppfer cells and what are their functions?

A

Sinusoidal macrophage cells attached to endothelial cells
Function - phagocytosis - detoxify substances arriving in liver from portal circulation

37
Q

Another name for perisinusoidal cells?

A

Hepatic stellate cells

38
Q

3 Functions of perisinusoidal cells?

A

Store Vit A in liver cytosolic droplets
Activated in response to liver damage
Deposit collagen in the EMC

39
Q

What does a cholangiocyte secrete into bile?

A

HCO3- and H2O

40
Q

3 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

41
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)
42
Q

What is the name of the process where lactate from muscles is transported to liver and converted to glucose to then return to muscles to be metabolised back into lactate?

A

Cori cycle

43
Q

3 reactions of 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, releasing 6 ATP in the process

Glucose via glycolysis to pyruvate → lactate in muscle cells and the cycle starts over again

44
Q

Where do amino acids undergo protein synthesis and what are some examples of the proteins that are produced?

A

Liver
Plasma proteins, clotting factors and lipoproteins

45
Q

What is transamination

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

46
Q

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

A

Alpha-keto gluatarate - glutamate and proline (also arginine)
Pyruvate - alanine (also valine and leucine)
Oxaloacetate - aspartate (methionine and lysine)

47
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 goes from pyruvate to glucose through via gluconeogenesis. Glucose returned to muscle cell for glycolysis.
  2. Alanine also converted to glutamate. Glutamate to urea, gets deaminated and returned to blood.
48
Q

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

A

Beta-oxidation

49
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

50
Q

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

A

Glycogen

51
Q

What is the main functions 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

52
Q

What are the 2 major functions of cholesterol?

A

Maintaining membrane integrity
Steroidogenesis

53
Q

What do hepatocytes store?

A

Vit. A, D, E, K, B12
Store iron as ferritin
Copper

54
Q

What vitamin is responsible for blood clotting?

A

Vit. K

55
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.

56
Q

What is 97% of bile made up of?

A

97% water

57
Q

3 uses of bile

A

Cholesterol homeostasis

Absorption of lipids and lipid-soluble vitamins (ADEK)

Excretion of

Xenobiotics/drugs - chemical substance that is foreign to animal life

Cholesterol metabolites

Adrenocortical and other steroid hormones

Alkaline phosphatase

58
Q

Where can you find biliary transporters?

A

Apical surface of hepatocytes and cholangiocytes

59
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

Products of familial intrahepatic cholestasis gene (FIC1)

Products of multidrug resistance genes

MDR1 → excretion of xenobiotics and cytotoxins

MDR3 → phosphatidylcholine

60
Q

What are bile acids synthesised from

A

Cholesterol

61
Q

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

A

Glycine and Taurine

62
Q

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

A

Cholic acid
Chenodeoxycholic acid

63
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

64
Q

2 functions of bile salts?

A

Reduce surface tension of fats
Emulsify fat prior to its digestion and absorption

65
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

66
Q

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

A

It is closed
Bile diverted into gall bladder for storage

67
Q

What happens to the Sphincter of Oddi when you eat?

A

It relaxes, to release pancreatic juice and bile

68
Q

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

A

Cholecystokinin
Causes gall bladder to contract to release bile

69
Q

What is the function of enterohepatic circulation?

A

Allows for recycling of metabolised and non-metabolised compounds

70
Q

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

A

95%

71
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

72
Q

How much of 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

73
Q

What happens to bile salts absorbed from the colon?

A

Return back to the liver and are re-excreted in bile

74
Q

2 functions of the gallbladder

A

Stores bile (50ml) - concentrates and acidifies it
Contraction is controlled by CCK - binds to CCKA receptors and neuronal plexus of GB wall

75
Q

Is free bilirubin H2O soluble?

A

No, it’s insoluble

76
Q

Where does majority of BR come from?

A

Haemoglobin (75%) - erythrocyte breakdown

77
Q

Where does the rest of BR come from?

A

22% from catabolism of other haemoproteins
3% from ineffective Bone Marrow erythropoiesis

78
Q

What is free bilirubin bound to in the blood?

A

Albumin

79
Q

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

A

Low bilirubin
High Albumin

80
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 → bilirubin diglucuronide (direct bilirubin)

Secreted across concentration gradient into biliary canaliculi → GIT

81
Q

What happens to BR once it enters the large intestine?

A

85% secreted in faeces
15% enters enterohepatic circulation
1% enters systemic circulation and excreted by kidneys

82
Q

Which compound gives faeces its brown colour?

A

Stercobilin

83
Q

If BR cannot get into the guy, what condition does it 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

84
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 ballloon

Then pull the stones from the bile duct

85
Q

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

A

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

This is called Percutaneous Transhepatic Cholangiography