Hepatobilliary System Flashcards

(37 cards)

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
What does the liver specifically store? (3)
1. Fat-soluble vitamins - A, D, E, K - 6-12 months (except K) 2. Iron - as ferritin 3. Copper
23
How does the liver detoxify?
Uses P450 enzymes - Phase 1 = modification ---> make more hydrophilic - Phase 2 = conjugation ---> make less reactive via attaching water soluble side-chain
24
What are the 5 ducts of the hepatobiliary system?
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
What is the composition of bile?
97% water + bile salts inorganic salts pigments (yellow bilirubin, green biliverden) fatty acids etc.
26
What are the 3 functions of bile?
1. Cholesterol haemostasis 2. Absorption of lipids and lipid-soluble vits 3. Excretion - xenobiotics/drugs - cholesterol metabolites - steroid hormones (eg. adrenocortical) - alkaline phosphatase
27
How is bile produced?
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
What are the 5 biliary transporters?
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
What are bile salts?
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
How is bile secretion regulated?
1. Sphincter of Oddi ---> relaxes during eating 2. Gastric contents enter duodenum ---> CCK release 3. CCK ---> gall bladder contracts ---> bile leaves
31
What happens to bile after use? (2)
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
What is the function of the gall bladder?
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
What is bilirubin?
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
What are the 3 types of jaundice?
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