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Hepatology - Fundamentals Flashcards

1
Q

What are the three main functions of the liver?

A
  1. Metabolism
  2. Synthesis & storage
  3. Detoxification
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2
Q

What are the three most important metabolic processes of the liver?

A
  1. Gluconeogenesis
  2. Glycogenesis
  3. Fatty acid oxidation & storage
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3
Q

What are important detoxification processes performed by the liver?

A
  1. Removal of toxic byproducts & medications
  2. Removal of bacteria from the blood
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4
Q

True or false: the liver is the most important organ when it comes to clearing bacteria from the blood

A

False: the spleen is more important

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5
Q

What are products synthesized by the liver?

A
  1. Non-essential amino acids
  2. Clotting factors, albumin & immunological factors
  3. Cholesterol & lipoproteins
  4. Phospholipids
  5. Bile
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6
Q

Which nutrients are stored in the liver?

A
  1. Vitamins
  2. Minerals
  3. Sugar
  4. Fat-soluble vitamins
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7
Q

What is the function of lipoproteins?

A

Transport of lipids throughout the body

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8
Q

Why is the synthesis of phospholipids by the liver of vital importance?

A

These are needed in the cell membranes of all body cells

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9
Q

What are the functions of bile?

A
  1. Excretion of byproducts such as cholesterol & haem
  2. Digestion of fat & absorption of fat-soluble vitamins
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10
Q

In which form is cholesterol excreted in bile?

A

Bile salts

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11
Q

In which form is haem excreted in bile?

A

(Conjugated) bilirubin

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12
Q

Which vitamins are stored in the liver? What why are these vitamins explicitly stored in the liver?

A

A, D, E & K
All fat-soluble vitamins

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13
Q

How do nutrients enter the liver?

A

Via the portal vein

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14
Q

What is the primary immunological function of the liver?

A

Production of clotting factors, complement & other immunolgical proteins for systemic immunity

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15
Q

What is the secondary immunological function of the liver?

A

Local defence against gut-derived pathogens, bacterial products & food toxins

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16
Q

What is the blood supply of the liver? What are the characteristics of the blood in each of these vessels?

A
  1. Portal vein = nutrient-rich, oxygen-poor
  2. Hepatic artery = nutrient-poor, oxygen-rich
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17
Q

What is the drainage system from the liver?

A

Central veins drain on the hepatic vein, which drains on the v. cava inferior

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18
Q

What is a liver lobulus?

A

Anatomical subdivision, consisting of sheets of hepatocytes bordered by 3-6 portal triads, draining into one central vein

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19
Q

Which structures can be found in a portal triad?

A
  1. Portal vein
  2. Hepatic artery
  3. Bile duct
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20
Q

How does blood flow from the portal triad to the central vein?

A

Via sinusoids

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21
Q

Which cells can be found in the sinusoids of the liver? (2)

A
  1. Liver sinusoidal epithelial cells (LSECs)
  2. Kupffer cells
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22
Q

True or false: hepatocytes directly contact the full blood flowing through the sinusoids

A

False: LSECs keep larger particles in the sinusoids, but smaller particles & fluid are able to pass through and directly contact the hepatocytes

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23
Q

What are the three most important groups of immunological factors synthesized by the liver? (3)

A
  1. Complement proteins
  2. Soluble pattern recognition receptors (sPRRs)
  3. Acute phase proteins
24
Q

What are acute phase proteins? (definition)

A

Proteins that dramatically increase in concentration during the acute phase response during infections

25
Q

Which groups of proteins are seen as acute phase proteins? (4)

A
  1. Antimicrobial peptides (AMPs)
  2. Clotting factors (fibrinogen)
  3. Proteinase factors
  4. C-reactive protein (CRP)
  5. Haptoglobin
  6. Serum amyloid A (SAA)
26
Q

What kind of protein is CRP?

A

C-reactive protein = soluble PRR, produced during the acute phase response

27
Q

How is the acute phase response of the liver triggered?

A

IL-6 produced by macrophages at the site of infection

28
Q

Why is it especially crucial that liver immunity is finely balanced between tolerance & immunity?

A

A lot of foreign compounds enter the body via the liver, which don’t need to trigger an immune response

29
Q

To which wanted (2) and unwanted (3) agents is the liver tolerant?

A

Wanted:
1. (Endo)toxins
2. Food antigens

Unwanted:
1. HBV & HCV viruses
2. Plasmodium sporozoites
3. Tumour metastases

30
Q

What is the most important endotoxin encounterd by the liver?

31
Q

To which agents does the liver have immunity?

A
  1. HAV
  2. Acute phase of HBV
  3. Many bacterial species
32
Q

What are the most important subsets of immune cells in the liver?

A
  1. Kupffer cells
  2. LSECs
  3. Dendritic cells
33
Q

What kind of cell type are Kupffer cells?

A

Tissue-resident macrophages

34
Q

How many % of body macrophages are Kupffer cells?

35
Q

What is the primary function of Kupffer cells?

A

Phagocytosis & degradation of particulate materials from blood

36
Q

Which particulate materials are cleared from the blood by Kupffer cells?

A
  1. Dying cells
  2. Aged erythrocytes
  3. Pathogens
37
Q

How do Kupffer cells phagocytose particulate matters?

A

They have a broad range of receptors to detect particulate matters in the blood

38
Q

Which phagocytic receptors can be found on Kupffer cells? (5)

A
  1. Scavenger receptors
  2. FcγR and FcαR
  3. Complement receptors
  4. TLR3, -4 & -9
  5. IgA-receptors
39
Q

What is the function of TLRs in Kupffer cells?

A

Help switch Kupffer cells from tolerogenic to pro-inflammatory in case of pathogen invasion

40
Q

What is the function of IgA-receptors on Kupffer cells?

A

Form a second line of defence in case of brech of the mucosal immune barrier

41
Q

True or false: Kupffer cells are professional APCs

42
Q

What is the role of Kupffer cells as APCs

A

Low MHCII expression = moderate T-cell stimulatory capacity -> mainly tolerogenic

43
Q

Which three tolerogenic mechanisms are employed by Kupffer cells?

A
  1. Production of IL-10 & prostaglandins -> suppresses T-cell activation
  2. Induction of Treg expansion
  3. Scavenging of pathogenic epitopes
44
Q

What is the primary function of LSECs?

A

Removal of waste products

45
Q

Why are LSECs especially suited to remove waste products from the blood?

A

The slow blood flow in sinusoids facilitates detection & capture of pathogens, proteins & toxins

46
Q

What is the main mechanism by which LSECs remove waste products from the blood?

A

Receptor-mediated endocytosis

47
Q

Which receptors do LSECs express to facilitate receptor-mediated endocytosis? (2)

A
  1. Scavenger receptors
  2. Carbohydrate receptors
48
Q

Which compounds are recognized by the scavenger receptors of LSECs? (3)

A
  1. Modified LDL
  2. Modified proteins
  3. Denatured collagen
49
Q

True or false: LSECs have a prominent role in liver immunity

A

False; they rarely stimulate the immune system

50
Q

Through which mechanisms do LSECs have some role in liver immunity? (2)

A
  1. Endocytosis
  2. Antigen presentation
51
Q

What are the tolerogenic mechanisms employed by LSECs?

A
  1. Production of anti-inflammatory factors
  2. Suppression of CD8+ activatoin
  3. Stimulation of Tregs through presentation on MHCII
52
Q

Which anti-inflammatory factors do LSECs produce? (2)

A
  1. TGF-β
  2. IL-10
53
Q

How do LSECs suppress CD8+ activation?

A
  1. Cross-presentation on MHCI -> non-productive activation
  2. Expression of PD-L1
54
Q

How do liver DCs differ from systemic DCs?

A

They have tolerogenic properties

55
Q

What is the specific tolerogenic property of liver-DCs?

A

IL-10 & IDO secretion upon TLR stimulation -> active induction of Tregs

56
Q

True or false: liver DCs can have pro-inflammatory effects

A

True; stimulation of specific PRRs may cause them to switch to a more pro-inflammatory phenotype

I&I WC2 (18 decks)

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