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BRS GASTROENTEROLOGY > Hepatobiliary System > Flashcards

Hepatobiliary System Flashcards

1
Q

Describe the surface anatomy of the liver.

A
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2
Q

Label this diagram.

A
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3
Q

What is the inflow of the liver?

A

hepatic artery (25%)
portal vein (75%)

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4
Q

the outflow of the liver?

A

BIle and 3x hepatic veins

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5
Q

Label these diagrams.

A
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6
Q

What is the Micro-morphology & micro-function of liver?

A

Morphological:
- Lobules
- Portal triads (tracts)

Functional:
- Acinus
- Blood flow
- Bile flow

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7
Q

What is the hepatic lobule?

A

Hexagonal structural unit of liver tissue

Each corner consists of a portal triad
- Links with 3x adjacent lobules

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8
Q

What is at the centre of a liver lobule?

A

Centre of liver lobule is a central vein
- Collects blood from hepatic sinusoids → hepatic veins → systemic venous system

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9
Q

What are the lobule rows made of?

A

Within lobule rows of hepatocytes

Each has sinusoid-facing side & bile canaliculi-facing side

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10
Q

Describe the parts of the portal triad.

A

Branch of hepatic artery:
- Brings O2-rich blood into liver to support hepatocytes ↑ energy demands

Branch of portal vein:
- Mixed venous blood from GIT (nutrients, bacteria & toxins) and spleen (waste products)
- Hepatocytes process nutrients, detoxify blood & excrete waste

Bile duct:
- Bile produced by hepatocytes drains into bile canaliculi
- Coalesce with cholangiocyte-lined bile ducts around lobule perimeter

cholangiocyte= cells that line bile ducts

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11
Q

Label this diagram.

A
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12
Q

What is a hepatic acinus?

A

= Functional unit of liver
- Hard to define anatomically cf hepatic lobule

Consists of two adjacent 1/6th hepatic lobules
- Share 2x portal triads
- Extend into hepatic lobules as far as central vein

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13
Q

What is the 3 zone model?

A

Micro function of hepatic acinus
- splits the hepatic acinus into 3 zones each with differences

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14
Q

What happens at point A?

A

blood into hepatic acinus (portal triad)

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15
Q

What happens at point B?

A

Blood drains out of hepatic acinus (central vein)

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16
Q

What happens to hepatocytes near outer hepatic lobule (zone 1)?

A

Hepatocytes receive early exposure to blood contents
good components= O2
bad= toxins

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17
Q

How is the acinus split?

A

zone 1, 2, 3

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18
Q

What is the O2 and toxin risk in zone 1?

A

O2 ↑,Toxin risk ↑

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19
Q

What is the O2 and toxin risk in zone 2?

A

O2 →,Toxin risk →

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20
Q

What is the O2 and toxin risk in zone 3?

A

O2 ↓,Toxin risk ↓

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21
Q

What are sinusoidal endothelial cells?

A

No basement membrane

Fenestrated (discontinuous endothelium)
- Allow lipids & large molecule movement to and from hepatocytes

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22
Q

What are Kupffer cells?

A

Sinusoidal macrophage cells

Attached to endothelial cells
Phagocytosis
Eliminate & detoxify substances arriving in liver from portal circulation

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23
Q

What are hepatic stellate cells?

A

Perisinusoidal (The plasma-filled extravascular space in the liver, between a hepatocyte and a liver sinusoid)

Exist in dormant state

Store vit A in liver cytosolic droplets

Activated (fibroblasts) in response to liver damage

Proliferate, chemotactic & deposit collagen in ECM

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24
Q

What are hepatocytes?

A

Cubical

Synthesis e.g. albumin, clotting factors & bile salts

Drug metabolism

Receive nutrients & building blocks from sinusoids

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25
Q

ow much of liver mass is hepatocytes?

A

80%

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26
Q

What are cholangiocytes?

A

Secrete HCO3- and water into bile

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27
Q

What are hepatocyte functions?

A

Metabolic & catabolic functions

Secretory & excretory functions

Detoxification & immunological functions

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28
Q

What are the metabolic and catabolic functions of hepatocytes?

A

synthesis & utilization of carbohydrates, lipids and proteins

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29
Q

What are the secretory and excretory functions of hepatocytes?

A

synthesis & secretion of proteins, bile and waste products

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30
Q

What are the detoxification and immunological functions of hepatocytes?

A

breakdown of ingested pathogens & processing of drugs

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31
Q

What is glycolysis?

A

anaerobic conversion of glucose → lactate
– (RBCs, renal medulla & skeletal muscle)
- Aerobic oxidation of glucose (CNS, heart, skeletal muscle, most organs)

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32
Q

What is glycogenesis?

A

synthesis of glycogen from glucose - (liver & muscle)

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33
Q

What is glycogenolysis?

A

breakdown of glycogen to glucose

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34
Q

What is gluconeogenesis?

A

production of glucose from non-sugar molecules:
- amino acids (glutamine) in liver & renal cortex
- Lactate (from anaerobic glycolysis in RBCs & muscles)
- Glycerol (from lipolysis)

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35
Q

What is lipolysis?

A

breakdown of triacylglycerols → glycerol & FFAs

36
Q

What is lipogenesis?

A

synthesis of triacylglycerols (storage in fat depots)

37
Q

Describe carbohydrate metabolism in the liver.

A
38
Q

Describe protein synthesis in the liver.

A
39
Q

Describe the synthesis of “non-essential” AA.

A

(ketogenic and glucogenic AA- I think)

40
Q

What is transamination (non-essential AA) and give examples?

A

Different keto-acids can be converted into multiple amino acids depending on the transaminase enzyme (vital for production of non- essential amino acids)

a-keto glutarate → e.g. glutamate, proline, arginine
Pyruvate →e.g.alanine, valine, leucine
Oxaloacetate →e.g.aspartate, methionine, lysine

41
Q

What is the glucose-alanine cycle?

A

Deamination for gluconeogenesis

42
Q

What is the purpose of the glucose-alanine cycle?

A

Problem: Muscle can potentially utilise amino acids to produce glucose for energy;

BUT

  1. To convert pyruvate to glucose requires energy
  2. To remove nitrogen as urea requires energy

Solution: – transfer problem to the liver (glucose-alanine cycle)

43
Q

Describe the glucose-alanine cycle?

A
44
Q

What happens to the glutamate from the glucose-alanine cycle?

A
45
Q

Describe triglyceride metabolism in the liver.

A
46
Q

What is fat?

A

main energy store in body (100x glycogen).

Stored in adipose & liver.

When glycogen stores full, liver converts excess glucose & amino acids to fat for storage

47
Q

What happens to acetyl CoA in lipoprotein synthesis?

A
48
Q

What happens to glycerol in lipoprotein synthesis?

A
49
Q

What happens to the lipoproteins formed in the liver?

A
50
Q

What does the liver store?

A
  • vitamins B12, A, D, E, K
  • Iron
    -Copper

fat soluble vitamins (A,D,E,K)

51
Q

How long are the vitamins stored in the liver?

A

6-12 months
(except vitamin K where store is small)

52
Q

Why is vitamin K essential?

A

essential for blood clotting

53
Q

How is iron stored in the liver?

A

As ferritin

54
Q

Why does iron need to be available?

A

For erythropoiesis

55
Q

What are the 2 phases of liver detoxification?

A

(xenobiotics= foreign to bodies)

P450 enzymes
- Phase 1 (modification)
– more hydrophilic

Phase 2 (conjugation)
– attach water soluble side chain to make less reactive

56
Q

What is the composition of bile?

A

mostly water
some bile salts
some bile pigments like bilirubin
more drug metabolites than urine
has some trace metals e.g., Fe, Zn, Cu

Alkaline phosphatase varies

57
Q

What are the uses of bile?

A

Cholesterol homeostasis

Absorption of lipids & lipid soluble vitamins (A, D, E, & K)

Excretion of:
- xenobiotics/drugs
- cholesterol metabolites
- adrenocortical & other steroid hormones
- Alkaline phosphatase

58
Q

How much bile is made each day?

A

500ml

59
Q

What is the colour of bile?

A

yellow/ green due to pigments such as bilirubin and biliverdin

60
Q

What secretes bile?

A

Hepatocytes 60% of total bile

Cholangiocytes 40% of total bile

61
Q

at type of bile secretion do hepatocytes do and describe it?

A

Primary secretion
- Bile secretions reflect serum concentrations
- Secretion of bile salts (acids), lipids & organic ions

62
Q

What type of bile secretion do cholangiocytes do?

A

Secondary modification
- Alteration of pH (alkaline electrolyte solution)
- H2O drawn into bile by osmosis via paracellular junctions
- Luminal glucose & organic acids reabsorbed
- HCO3- & Cl- actively secreted into bile by CFTR (Cystic Fibrosis Transmembrane Regulator)
- IgA exocytosed

63
Q

What performs biliary excretion of bile salts and toxins?

A

biliary transporters

64
Q

What are the 2 types of biliary transporters?

A

Basolateral membrane (importing)
apical surface (exporting)

65
Q

What are the basolateral membrane biliary transporters? (2)

A

Organic anion transporting peptide (OATPs) – bile salt uptake

Na+ taurocholate-cotransporting polypeptide (NTCP) - bile salt uptake

66
Q

What are the apical surface biliary transporters? (3)

A

Bile Salt Excretory Pump (BSEP) – active transport of BAs (bile acids) into bile

MDR related proteins (MRP2 & MRP3) – -vely charged metabolites
- multi drug resistant

Products of multidrug resistance genes
MDR1 → excretion of neutral & +ve xenobiotics & cytotoxins
* MDR3 → phosphatidylcholine.

67
Q

What are the key components of bile?

A

acids= salts (bile salts)

68
Q

What synthesises bile acids?

A

Bile acids synthesised from cholesterol

  • 2x primary bile acids synthesised in liver
  • 2x secondary bile acids produced from primary acids by gut bacteria
69
Q

What happens to bile acids in the liver?

A

Na+ & K+ salts of bile acids conjugated in liver to glycine & taurine

70
Q

What are the secondary bile acids formed from primary acids by gut bacteria?

A
71
Q

What is the role of bile salt?

A

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

Bile salts form Micelles…

  • Steroid nucleus planar- has 2x faces (Amphipathic)
  • 1x surface hydrophilic domains (hydroxyl & carboxyl) - faces OUT → dissolves in water
  • 2nd surface hydrophobic domains (nucleus & methyl) faces IN → dissolves in fat
  • FFAs & cholesterol INSIDE
72
Q

Diagram for bile salt function.

A
73
Q

How is bile flow and secretion regulated?

A

Between meals Sphincter of Oddi closed → bile diverted into gall bladder for storage

Eating → Sphincter of Oddi relaxes

Gastric contents (FFAs, AAs > CHOs) enter duodenum causing release of cholecystokinin (CCK)

CCK causes gallbladder to contract

74
Q

What are the functions of the gallbladder?

A
  1. Stores bile (50 mls) - concentrates bile - acidifies bile
  2. GB contraction triggered by CCK
    - Binds to CCKA receptors & neuronal plexus of GB wall (innervated by preganglionic parasympathetic fibres of vagus nerve)
75
Q

Describe the enterohepatic circulation.

A

95% bile salts reabsorbed from terminal ileum
- By Na+/bile salt co-transport Na+-K+ ATPase system

5% converted to 2ary bile acids in colon:
- Deoxycholic acid absorbed
- 99% Lithocolic acid excreted in stool

absorbed B.salts back to liver & re- excreted in bile

76
Q

Describe free BR?

A

free bilirubin

Free BR (indirect/unconjugated)
= H2O-INSOLUBLE, yellow pigment

77
Q

What is the source of bilirubin?

A

75% BR from Hb (erythrocytes) breakdown
22% from catabolism of other hemoproteins
3% from ineffective BM (bone marrow) erythropoiesis

78
Q

What is free BR bound to?

A

Free BR bound to albumin in blood

79
Q

What happens to BR bound to albumin?

A

Most dissociates in liver & enters hepatocytes

BR conjugated with 2x molecules of UDP-glucuronate → bilirubin diglucuronide (direct bilirubin)

Secreted ACROSS concentration gradient into biliary canaliculi → GIT

80
Q

How much bile is excreted a day?

A

200-250mg BR excreted into bile/day

81
Q

How is bile excreted?

A

85% excreted in faeces

BR → urobilinogen → stercobilinogen → stercobilin (brown compound)

82
Q

What happens to the rest of bilirubin that isn’t excreted?

A

15% enters enterohepatic circulation
- BR → deconjugated → lipophilic form
- Urobilinogen
- Stercobilinogen

1% enters systemic circulation & excreted by kidneys

83
Q

What are the cause of jaundice?

A

Post hepatic/ obstructive jaundice

84
Q

What is ERCP?

A

Endoscopic retrograde cholangiopancreatography

You may need ERCP to find the cause of unexplained abdominal pain or yellowing of the skin and eyes (jaundice)

85
Q

What is PTC?

A

Introduction Percutaneous transhepatic cholangiography (PTC)

is a procedure used to access the biliary tree for diagnostic purposes in obstructive jaundice, and to facilitate palliative stenting across biliary strictures

BRS GASTROENTEROLOGY (25 decks)

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