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Yr 2 - GI & Metabolism > Structure and Function of Liver > Flashcards

Structure and Function of Liver Flashcards

1
Q

Describe the blood supply to the liver

A

75% is venous blood via the hepatic portal vein –> blood from SI, stomach, pancreas and spleen

25% is arterial blood via the hepatic artery –> oxygenated blood

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2
Q

Where do most substances absorbed by the GI tract pass before going to the rest of the body?

A

Liver

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3
Q

Describe the output of blood from the liver

A

Hepatic vein –> into the vena cava

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4
Q

Describe the internal structure of the liver

A

Lobules separated by connective tissue (hexagonal structure)

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5
Q

What is located at the corners of liver lobules?

A

Portal triad

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6
Q

What does the portal triad contain?

A

Bile duct, branch of hepatic artery, hepatic portal vein

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7
Q

Where does blood from the hepatic artery and hepatic portal vein flow together into?

A

Blood filled cavities called sinusoids –> these run into the hepatic vein

Allow blood to enter liver tissue

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8
Q

What forms part of the lining of sinusoids?

A

Kupffe cells

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9
Q

How are the plates of hepatocytes arranged?

A

Each cell has access to blood supply on one face and to bile canaliculi on the other

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10
Q

What runs along the face of the sinusoid facing side (of the plates of hepatocytes)?

A

A layer of endothelial cells

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11
Q

Describe this layer of endothelial cells of the sinusoid facing side

A

Forms an incomplete barrier between blood and hepatocytes –> pores and fenestra

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12
Q

What is purpose of these pores and fenestra?

A

Material can flow through

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13
Q

What runs between the hepatocytes and endothelial cells?

A

Space of Disse

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14
Q

What does the Space of Disse contain?

A

Stellate cells and collagen fibres

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15
Q

What are bile cannaliculi?

A

Tiny ducts into which bile is actively excreted

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16
Q

What are the 5 cell types that make up the liver?

A
  1. Hepatocytes
  2. Endothelial cells
  3. Kupffer cells
  4. Pit cels
  5. Hepatic stellate cells
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17
Q

What is the most common cell type?

A

60% are hepatocytes (parenchymal cells)

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18
Q

What is function of hepatocytes?

A

Carry out most metabolic functions

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19
Q

What is function of endothelial cells?

A
  • Lining cells of sinusoids

- Contain pores and fenestra so don’t form barrier for small molecules entering hepatocytes

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20
Q

What cells are associated with the immune system?

A

Kupffer cells and Pit cells

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21
Q

Where are Kupffer cells located?

A

Within sinusoidal lining

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22
Q

What is function of Kupffer cells?

A

Macrophages –> phagocytose bacteria, old erythrocytes, protect liver from gut derived bacteria

As there is very little lymphoid tissue present , Kupffer cells remove antigens without much antibody production, so preventing a more general systemic response to antigens

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23
Q

What is function of Pit cells?

A

Natural killer cells –> help protect liver from viruses / tumour cells

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24
Q

When stimulated, what do Kupffer cells produce?

A

Cytokines e.g. IL-6, IL-8 and TNF-a

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25
Q

What are hepatic stellate cells also called?

A

Ito cells or lipocytes

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26
Q

Where are hepatic stellate cells found?

A

In space of Disse

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27
Q

What is function of stellate cells?

A

Lipid-filled cells. Primary site of vitamin A storage. Also control turnover of connective tissue, synthesise collagen & regulate contractility of sinusoids

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28
Q

What reaches the liver via the hepatic portal vein / hepatic artery?

A

Almost everything absorbed from the GI tract – via the hepatic portal vein, and also has access to metabolites produced in other parts of the body via the hepatic artery.

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29
Q

What are the main functions of the liver?

A
  • Synthesis – proteins, nucleotides, cholesterol
  • Recycle compounds from other parts of the body
  • Control blood levels of substances e.g. glucose
  • Storage e.g. glycogen, vitamins
  • Carbohydrate, lipid & protein metabolism
  • Waste management
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30
Q

How is the liver involved in waste management?

A
  • Detoxification of xenobiotics

- Removal of internal waste e.g. degradation of bilirubin

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31
Q

How is liver involved in storage?

A

Glucose (as glycogen), vitamin A, D, K (fat soluble), B12, iron, copper

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32
Q

How is liver involved in maintaining blood glucose?

A

Gluconeogenesis, glycogen synthesis/breakdown)

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33
Q

How is liver involved in nitrogen metabolism?

A

Amino acid synthesis, breakdown, urea cycle

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34
Q

How is liver involved in lipid metabolism?

A

Cholesterol synthesis, lipid transport, bile formation

35
Q

How is liver involved in synthesis of blood components?

A

Albumin, clotting factors (red blood cell synthesis in the foetus), lipoproteins

36
Q

What are the constituents of bile?

A

Water, bicarbonate, bile salts, free cholesterol, phospholipids

37
Q

How are bile salts formed?

A

In the liver (hepatocytes) from cholesterol

38
Q

What is function of bile salts?

A

Emulsify fats

39
Q

What happens to 95% of bile salts?

A

Recirculated

40
Q

What is cholesterol breakdown inhibited by?

A

Bile salts –> if you can increase bile salt loss, more cholesterol can be metabolised

41
Q

What is cholestyramine (Questran)?

A

Drug used for high cholesterol

42
Q

How does cholestyramine work?

A
  • Binds bile acids and salts in the gut to prevent recirculation of bile (increases excretion)
  • Increases bile acid synthesis
  • Decreases blood cholesterol
43
Q

What is a natural method of decreasing cholesterol levels?

A

Increasing dietary fibre (bile salts tend to bind to dietary fibre so will be excreted)

44
Q

If too much cholesterol enters the bile than can be solubilised by bile salts, what happens?

A

Precipitation of cholesterol –> gallstones (can get stuck in common bile duct)

45
Q

What are xenobiotics?

A

A chemical substance found within an organism that is not naturally produced or expected to be present within the organism

Potentially toxic and of no nutritional value

46
Q

What are examples of xenobiotics?

A
  • Drugs (pharmacologic or recreational)

- Food additives or toxins present in food

47
Q

What is bilirubin?

A

From breakdown of erythrocytes

48
Q

What normal waste products of metabolism is the liver involved in the removal of?

A
  • Hormones e.g. insulin, growth hormone, oestrogen
  • Bilirubin – from breakdown of erythrocytes
  • Urea – removal of NH4+ ions - mainly from metabolism of protein, but also that produced by gut bacteria
49
Q

What are the 2 basic steps in the removal of a xenobiotic compound?

A

Phase 1 and phase 2 reactions

Xenobiotic compound –> primary metabolite –> secondary metabolite

50
Q

What are phase 1 reactions?

A

Oxidation, hydroxylation, hydrolysis, reduction

51
Q

What are phase 2 reactions?

A

Conjugation e.g. sulphation

52
Q

What is purpose of turning compound into metabolite?

A

Metabolites are usually pharmacologically inactive and more hydrophilic

More easily excreted in urine or bile

53
Q

What is phase 1 performed by?

A

Cytochrome P450 enzymes (CYP)

54
Q

What are CYP enzymes?

A

Large family of haem proteins –> mono-oxygenases found in smooth endoplasmic reticulum

55
Q

How is the individual variation in P450 enzymes important?

A

Important in therapeutics and how effective drug is for individual person

56
Q

How are P450 enzymes inducible?

A

Synthesis of them can be increased by certain compounds (drugs, alcohol)

57
Q

What are detoxification reactions important for?

A

Protection from ingested toxins

58
Q

Why can detoxification reactions be a problem?

A

When drugs are given orally –> first pass metabolism (drug can’t make it past liver)

59
Q

What is a prodrug?

A

A prodrug is an inactive (or less active) compound which is metabolised to produce the therapeutically active form in the body

60
Q

Why are prodrugs used?

A
  • To improve absorption of drug in gut

- To allow alternative route of administration (e.g. skin patch)

61
Q

What is Tamoxifen?

A

A prodrug used in treatment of hormone-sensitive breast cancer

62
Q

How is Tamoxifen activated?

A

It is activated by cytochrome P450 enzymes to produce endoxifen, 100 x more potent than tamoxifen

63
Q

How is paracetamol primarily metabolised?

A

Via phase 2 pathways

64
Q

What happens during a paracetamol overdose?

A

Depletion of glutathione allows free NAPQI to react with cell membranes

Hepatic necrosis –> liver failure (see pharmacology)

65
Q

How is the majority of alcohol metabolised?

A

Ethanol –> acetaldehyde –> acetate

66
Q

How is alcohol metabolised when alcohol levels are high?

A

Some is also metabolised by the cytochrome P450 enzymes

67
Q

What is effect of chronic alcohol use?

A

Induces synthesis of cytochrome P450 enzymes –> affects interaction between drugs and alcohol (drug may be broken down too quickly)

68
Q

How long do erythrocytes last before needing replacement?

A

About 120 days

69
Q

How are old RBCs taken up?

A

Phagocytosed by Kupffer cells in liver, spleen and bone marrow

70
Q

What happens to haemoglobin?

A
  • Globin protein degraded

- Haem broken down into bilirubin

71
Q

What does the breakdown of haem require?

A

NADPH and H+

72
Q

How is bilirubin transported to the liver?

A

Attached to albumin (as not very soluble)

73
Q

What happens once bilirubin reaches liver?

A

Is conjugated (mainly with glucuronic acid) and secreted into biliary canalicula (an active process)

74
Q

Where does bilirubin go after the liver?

A

Into the gut

75
Q

What happens to bilirubin in the gut?

A

Further metabolised by bacteria in the gut to urobilinogen

76
Q

What can urobilinogen then be converted into?

A
  • Urobilin

- Stercobilin

77
Q

How is urobilin excreted?

A

In urine

78
Q

How is stercobilin excreted?

A

In faeces

79
Q

What is result of problems with haem degradation (and liver function)?

A

Jaundice

80
Q

What is jaundice?

A

Bilirubin (insoluble) builds up and deposits in tissues (mainly seen in whites of eyes, sometimes skin)

81
Q

What is the removal of bilirubin pathway?

A

Haem –> bilirubin –> conjugated bilirubin –> bile secretion

82
Q

What is prehepatic jaundice?

A

Increase in rate of breakdown of RBCs (too much haem for liver to cope)

e.g. Haemolytic anaemia (sickle cell)

83
Q

What is intrahepatic jaundice?

A

Problems with liver itself conjugating bilirubin

Liver damage - infection, inflammation, cirrhosis

Inherited - Gilbert’s syndrome (individual doesn’t produce enough conjugating enzyme)

84
Q

What is extrahepatic jaundice?

A

Problems with bile secretion

Blockage –> gallstones, pancreatic carcinoma

Yr 2 - GI & Metabolism (51 decks)

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