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2.8 BRS Gastroenterology > Hepatobilliary System > Flashcards

Hepatobilliary System Flashcards

1
Q

Where is the liver?

A

Sits under the diaphragm on the right side

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2
Q

What are 4 sections of the liver?

A
  1. Right posterior
  2. Right anterior
  3. Left medial
  4. Left lateral
    Left and right split by middle hepatic vein
  • falciform ligament —> connects liver to ventral wall
    of abdomen
  • ligamentum teres
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3
Q

Which blood vessels supply the liver?

A

Inflow:
- Hepatic artery —> 25%
- Portal vein —> 75%

Outflow:
- 3 Hepatic veins —> join to inferior vena cava
- right, middle, left

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4
Q

How is the liver sectioned?

A

8 sections
- 1 —> posterior
- 2, 3, 4 —> left
- 5, 6, 7, 8 —> right

7 8 4 2
1
6 5 4 3

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5
Q

What is the micro-morphology of the liver? (2)

A
  1. Lobules —> hexagon of hepatocytes
  2. Portal triads —> at each corner of a lobule
    - each links with 3 lobules
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6
Q

What are the 6 key components of each hepatic lobule?

A
  1. Bile duct
  2. Portal vein
  3. Hepatic artery
  4. Hepatocytes
  5. Central vein
  6. Sinusoid
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6
Q

What are portal triads?

A
  1. Hepatic artery branch
  2. Portal vein branch
    • blood from GI tract and spleen —> hepatocytes
      process nutrients, detoxifies, excretes waste
  3. Bile duct
    • bile produced by hepatocytes —> drains into bile
      canaliculi —> join cholangiocyte-lined bile ducts
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7
Q

What are hepatic lobules?

A

Hexagonal structural unit of liver tissue
- central vein —> middle of lobule
- blood from hepatic sinusoids —>
hepatic veins —> systemic veins
- hepatocytes —> rows
- sinusoid-facing side, bile canaliculi-
facing side

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8
Q

What is the hepatic acinus?

A

Region of 2 adjacent lobules (1/6th of each) —> share 2 portal triads
- blood in via the 2 hepatic portal triads
- blood out via each central vein

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9
Q

What is the three zonal model?

A

3 sections of hepatic acini:
1. Near shared side - blood entering
—> high O2, high toxin
2. Middle of each - blood being processed
—> med O2, med toxin
3. Near each central vein - blood leaving
—> low O2, low toxin

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10
Q

What are the 5 cell types of the liver?

A
  1. Sinusoidal endothelial cells
  2. Kupffer cells
  3. Hepatic stellate cells
  4. Hepatocytes
  5. Cholangiocytes
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10
Q

What are sinusoidal endothelial cells?

A

Cells lining gap between hepatic lobules
- no basement membrane
- fenestrated —> discontinuous —> lipids and large
molecules can move to and from hepatocytes

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11
Q

What are kupffer cells?

A

Sinusoidal macrophages
- Attach to endothelial cells
- Phagocytosis —> eliminate and detoxify substances
from portal circulation

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12
Q

What are hepatic stellate cells?

A

Cells on hepatocyte side of sinusoidal endothelial cells
- dormant —> activated when liver damaged —>
proliferate, move (chemotaxis) and deposit ECM
- store vit A in cytosolic droplets
- in Space of disse —> space between sinusoid and
hepatocyte

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13
Q

What are cholangiocytes?

A

Cells lining end of bile ducts
- secrete HCO3- and H2O into bile

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14
Q

What are hepatocytes?

A

Main cells type of liver —> 80%
- cubical shape
- synthesis —> albumin, clotting factors, bile salts etc.
- receive nutrients/reactants from sinusoid
- drug metabolism

15
Q

What are the 3 categories of liver functions?

A
  1. Metabolic/catabolic - carbs, lipid, protein products
  2. Secretory/excretory - protein, bile, waste
  3. Detoxify/immunological - pathogens, drugs
16
Q

What is the function of the liver in carbohydrate metabolism?

A

Converts lactate (from anaerobic resp) to pyruvate via lactate dehydrogenase —> gluconeogenesis —> releases glucose for use in glycolysis

17
Q

What are the 6 metabolic functions of the liver?

A
  1. Carbohydrate metabolism
  2. Protein synthesis
  3. Non-essential amino acid synthesis
  4. Protein metabolism
  5. Triglyceride metabolism
  6. Lipoprotein synthesis
18
Q

What is the function of the liver in protein synthesis?

A

Converts amino acids (from diet or broken down muscle) into proteins
- plasma proteins
- clotting factors
- lipoproteins

19
Q

What is the function of the liver in non-essential amino acid synthesis?

A

Uses transamination reactions
eg. alanine + α-ketogluterate —> pyruvate + glutamate

  • α-ketogluterate —> glutamate, proline
  • pyruvate —> alanine
  • oxaloacetate —> aspartate
20
Q

What is the function of the liver in protein metabolism?

A

Amino acids sent to liver for gluconeogenesis requires too much energy for muscle

Glucose-alanine cycle:
1. muscle - pyruvate + glutamate —> alanine + α-
ketogluterate
2. alanine to liver
3. liver - alanine + α-ketogluterate —> pyruvate +
glutamate
4. liver - glutamate + 4 ATP —> urea —> excretion
- pyruvate + 6 ATP —> glucose —> glycolysis in
muscle

21
Q

What is the function of the liver in triglyceride metabolism?

A

Glycogen stores full —> amino acids and glucose converted to fatty acids —> transported and stored in liver till energy needed —> β-oxidation —> TCA cycle or acetoacetate produced in liver

22
Q

What is the function of the liver in lipoprotein synthesis?

A

Glucose to pyruvate to acetyl CoA —> synthesise fatty acids (lipogenesis with malonyl CoA) and cholesterol (using HMG CoA reductase) —> lipoprotein production —> make VLDL, HDL or LDL

22
Q

What does the liver specifically store? (3)

A
  1. Fat-soluble vitamins - A, D, E, K
    - 6-12 months (except K)
  2. Iron - as ferritin
  3. Copper
23
Q

How does the liver detoxify?

A

Uses P450 enzymes
- Phase 1 = modification —> make more hydrophilic
- Phase 2 = conjugation —> make less reactive via
attaching water soluble side-chain

24
Q

What are the 5 ducts of the hepatobiliary system?

A
  1. Common hepatic duct —> above gallbladder
  2. Cystic duct —> from gallbladder
  3. Bile duct —> after cystic and common hepatic join
  4. Main pancreatic duct —> joins to bile duct at
    hepatopancreatic ampulla
  5. Accessory pancreatic duct
25
Q

What is the composition of bile?

A

97% water
+ bile salts
inorganic salts
pigments (yellow bilirubin, green biliverden)
fatty acids etc.

26
Q

What are the 3 functions of bile?

A
  1. Cholesterol haemostasis
  2. Absorption of lipids and lipid-soluble vits
  3. Excretion - xenobiotics/drugs
    - cholesterol metabolites
    - steroid hormones (eg. adrenocortical)
    - alkaline phosphatase
27
Q

How is bile produced?

A
  1. Primary secretion
    • hepatocytes 60% + cholangiocytes 40%
    • reflects serum concs (500mls produced/day)
    • secrete bile salts, lipids, organic ions
  2. Secondary modification
    • cholangiocytes main job
    • alter pH via HCO3- (+Cl- via CFTR)
    • H2O added via osmosis (paracellular junctions)
    • luminal glucose and organic acids reabsorbed
    • IgA exocytosed
28
Q

What are the 5 biliary transporters?

A

Basolateral membrane (import):
- portal blood —> hepatocyte
1. OATPs = Organic Anion Transporting Peptide
- uptake bile salts
2. NTCPs = Na+ Taurocholate-Cotransporting
Polypeptide
- uptake bile salts

Apical surface (export):
- hepatocyte —> bile duct
3. BSEP = Bile Salt Excretory Pump
- active transport bile
4. MDR1 - neutral/+ve xenobiotics and cytotoxins
MDR3 - phospatidylcholine
5. MRP2 - -ve metabolites
MRP3 - -ve metabolites

29
Q

What are bile salts?

A

Bile acids synthesised from cholesterol
—> reduce surface tension of fats
—> emulsifies fats
—> micelle formation - amphipathic (hydrophobic in)

  • primary —> synthesised in liver:
    - cholic acid
    - chenodeoxycholic acid
  • secondary —> gut bacteria alters primary:
    - deoxycholic acid
    - lithocolic acid
  • Na+ and K+ salts cojugated —> glycine and taurine
30
Q

How is bile secretion regulated?

A
  1. Sphincter of Oddi —> relaxes during eating
  2. Gastric contents enter duodenum —> CCK release
  3. CCK —> gall bladder contracts —> bile leaves
31
Q

What happens to bile after use? (2)

A
  1. 95% reabsorbed - from terminal ileum
    - to portal vein —> liver —> reuse
    - via Na+/bile salt co-t (Na+/K+
    ATPase involved)
  2. 5% to 2° acids —> deoxycholic acid absorbed
    —> lithocolic acid excreted in stool
    (99%)
31
Q

What is the function of the gall bladder?

A
  1. Stores bile - 50ml
    —> concentrates and acidifies
  2. Releases bile - CCK —> binds to CCKA receptors and
    neuronal plexus of wall (pre-
    ganglionic parasympathetic
    vagus nerve fibres)
32
Q

What is bilirubin?

A

Yellow pigment of bile

  • Sources - 200-250mg into bile/day
    1. 75% Hb breakdown
    2. 25% other haemoproteins
    3. 3% ineffective bone marrow erythropoiesis
  • Transport:
    1. Bound to albumin in blood ∵ free bilirubin H2O-
      insoluble
    2. Dissociates in liver —> enters hepatocytes
    3. Joins to 2 UDP-glucuronates —> bilirubin
      diglucoronide
    4. Secretes into biliary canaliculi
  • Post-use:
    1. 85% excreted in faeces
      • BR —> urobilogen —> stercobilinogen —>
        stercobilin (brown)
    2. 15% enterohepatic circulation
      • BR —> deconjugated —> lipophilic (urobilinogen
        or stercobilinogen)
    3. 1% systemic circulation
      • excreted by kidneys
33
Q

What are the 3 types of jaundice?

A
  1. Pre-hepatic - eg. haemolytic anaemia
  2. Intrahepatic —> liver not processing properly
    - uptake/conjugation/secretion dec
  3. Post-hepatic —> bile can’t leave
    - eg. gall stones, tumours

2.8 BRS Gastroenterology (13 decks)

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