Hepatobilliary system Flashcards

1
Q

How many liver segments are there and how many are there per lobe

A

8, 4 each

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2
Q

1?

A

Right lobe

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3
Q

2?

A

Diaphragm

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4
Q

3?

A

Left lobe

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5
Q

4?

A

Falciform ligament

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6
Q

5?

A

Ligamentum teres

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7
Q

6?

A

Gallbladder

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8
Q

Describe the blood inflow and outflow of the liver

A

Inflow:
75% Hepatic portal vein
25% Hepatic artery

Outflow:
Bile
3x hepatic veins

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9
Q

What is the purpose of blood delivered by the hepatic artery and the hepatic portal vein?

A

HPV:Deliver digested products to the liver

HA: Deliver oxygenated blood for resp/met

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10
Q

Describe the morphology of a liver lobule, incl what is in every corner and what’s in the center

A

Hexagonal structural unit of liver tissue

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

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

Within lobule rows of hepatocytes
Each has sinusoid-facing side & bile canaliculi-facing side

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11
Q

What are the 3 vessels contained within a portal triad and what are their functions?

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

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12
Q

What is a hepatic acinus and what is contained within it

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

Outline the microfunction of a hepatic acinus, including the blood supply and drainage and the zone by zone O2 conc and risk of toxicity.

A

Blood into hepatic acinus via Point A (portal triad)
Blood drains out of hepatic acinus via Point B (central vein)
Hepatocytes near outer hepatic lobule(zone 1) receive early exposure to blood contents:
Good components (O2)
Bad components (toxins)
Acinus split into 3x regions
Zone 1 – O2 ↑, Toxin risk ↑
Zone 2 – O2 →, Toxin risk →
Zone 3 – O2 ↓, Toxin risk ↓

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14
Q

What nerve innervates the gall bladder

A

The vagus nerve

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15
Q

Give 3 unusual characteristics of a hepatic sinusoid endothelial cell

A

No basement membrane

Fenestrated (discontinuous endothelium)

Allow lipids & large molecule movement to and from hepatocytes

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16
Q

What is the role of kupffer cells

A

Hepatic Sinusoidal macrophage cells

Attached to endothelial cells

-Phagocystosis
Eliminate & detoxify substances arriving in liver from portal circulation

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17
Q

What is the role of hepatic stellate cells

A

(Ito; perisinusoidal)
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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18
Q

What is the function and shape of a hepatocyte

A

80% of liver mass
Cubical
Synthesis e.g. albumin, clotting factors & bile salts
Drug metabolism
Receive nutrients & building blocks from sinusoids

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19
Q

What is the role of a hepatic cholangiocyte

A

Secrete HCO3- & H2O into bile

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20
Q

Give the 3 general functions of hepatocytes

A

Metabolic & catabolic functions:synthesis & utilization of carbohydrates, lipids and proteins.

Secretory& excretory functions:synthesis &secretion of proteins, bile and waste products.

Detoxification & immunological functions:breakdown of ingested pathogens & processing of drugs

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21
Q

Glycolysis def and where is occurs

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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22
Q

Glycogenesis def and where it occurs

A

synthesis of glycogen from glucose
- (liver & muscle)

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23
Q

Glycogenolysis def

A

Breakdown of glycogen into glucose

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24
Q

Gluconeogenesis def

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)

25
Q

Lipolysis def

A

Breakdown of triacylglycerols into FFAs and glycerol

26
Q

Lipogenesis def

A

Synthesis of triacylglycerols

27
Q

Outline the function of hepatocytes within carbohydrate met

A

Glucose from the liver is released, travels to muscle cell

Undergoes glycolysis, forming pyruvate then lactate

Lactate travels to hepatocyte and is recycled by lactate dehydrogenase into pyruvate

ATP is used to power gluconeogenesis to reproduce glucose and restart the cycle

28
Q

Outline the function of hepatocytes within protein synthesis

A

Amino acids (either from muscle cell in fasted state or diet in fed state) travel to hepatocyte

They are turned into secreted proteins

29
Q

Outline the function on hepatocytes within non-essential amino-acid synthesis

A

-All occurs in the liver

Dietary alanine is processed into a-ketoglutarate

Reversible reaction then forms glutamate and pyruvate via transamination

30
Q

Which amino acids can be formed from a-ketoglutarate?

A

Glutamate, proline, arginine

31
Q

Which amino acids can be formed from pyruvate?

A

Alanine, valine, leucine

32
Q

Which amino acids can be formed from oxaloacetate?

A

Aspartate, methionine, lysine

33
Q

What issue does the glucose alanine cycle solve?

A

For conversion of amino acids into glucose

-Removal of nitrogen as urea
-Conversion of pyruvate into glucose

34
Q

Outline the glucose alanine cycle?

A

Glutamate/pyruvate is converted to alanine in muscle cell

Alanine travels to the liver, is deaminated to produce urea as well as converted into pyruvate

The pyruvate is converted into glucose in the liver and then transported to muscle to be respired

35
Q

Outline hepatocytes role within fat metabolism

A

Triglycerides are converted to fatty acids

They are transported to the liver

B-oxidation converts them into acetyl CoA which enters the TCA cycle(Conversion to acetoacetate and then release as tissue energy source)

36
Q

How are lipoproteins synthesised within hepatocytes?

A

Hepatic glucose is converted into pyruvate and glycerol, then acetyl CoA, then into cholesterol via HMG CoA-reductase

The glycerol is converted into tri-acyl glycerol, apoproteins, phospholipids and cholesterol, which combine to form lipoproteins

37
Q

What occurs to lipoproteins after synthesis?

A

HDL-Picks up excess cholesterol

LDL-Transport cholesterol to tissues
VLDL-Transport fatty acids to tissues(incl. muscle)

38
Q

What do hepatocytes store?

A

Storage of fat soluble vitamins (A,D,E,K)
Stores sufficient 6-12 month (except Vit K where store is small)
Vit K essential blood clotting

Storage of iron as ferritin
Available for erythropoeisis

Vitamin B12
Copper(Excess Cu is Wilsons’)

39
Q

How do hepatocytes detoxify blood?

A

P450 enzymes
Phase 1 (modification)
– more hydrophilic

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

40
Q

Outline the gross composition of bile

A
41
Q

Give the 3 major functions 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

42
Q

What causes biles’ colour?

A

Yellow-Bilirubin
Green-Biliverdin

43
Q

How much bile is produced per day and by what?

A

500mls/day
60% from hepatocytes
40% from cholangiocytes

44
Q

Outline the primary/secondary secretion stages of bile and what happens in each of them

A

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

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

45
Q

What are the proteins which are responsible for the biliary excretion of bile salts & toxins

A

Biliary transporters

46
Q

What are the main importers(basolateral) in the bile tube?

A

Organic anion transporting peptide (OATPs) – bile salt uptake
Na+ taurocholate-cotransporting polypeptide (NTCP) - bile salt uptake

47
Q

What are the main exporters(apical) in the bile tube?

A

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

MDR related proteins (MRP2 & MRP3)
-vely charged metabolites

Products of multidrug resistance genes
MDR1 → excretion of neutral & +ve xenobiotics & cytotoxins
MDR3 → phospatidylcholine

48
Q

What is the key component of bile and what is it synthesised from?

A

Bile salts(acids)

-Synthed from cholesterol

49
Q

What are Na+ and K+ conjugated into in the liver?

A

Glycine and taurine

50
Q

What are the 2 primary bile acids, where are they synthesised and what do they turn into and how?

A

Cholic acid –> Deoxycholic acid

Chenodeoxycholic acid –> Lithocolic acid

> Both are converted by gut bacteria

51
Q

What are the 2 surfaces of micelles and give their properties

A

1x surface hydrophilic domains (hydroxyl & carboxyl) - faces OUT → dissolves in water

2nd surface hydrophobic domains (nucleus & methyl) faces IN → dissolves in fat

52
Q

Outline the overall function of bile salts and enzymes in the digestion of lipids

A
  1. Emulsification
    Bile salts and phospholipids form micelles around triglycerides
  2. Enzyme action
    Lipase and Colipase break down the triglycerides into glycerol and FFAs
53
Q

What is the sphincter of Oddi and when does it open/close?

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 gall bladder to contract

54
Q

What happens to bile salts after their role in absorption?

A

95% bile salts reabsorbed from terminal ileum

By Na+/bile salt co-transport Na+-K+ ATPase system

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

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

55
Q

Give 2 functions of the gall bladder in relation to bile

A

Stores ~50ml of bile
-Concentrates and acidifies bile

56
Q

How does the gall bladder contract?

A

CCK(Cholecystokinin) binds to CCKA receptors & neuronal plexus of GB wall (innervated by preganglionic parasympathetic fibres of vagus nerve)

57
Q

Give the sources of bilirubin

A

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

58
Q

How much bilirubin is excreted into bile daily and what is the percentage breakdown of where it ends up

A

200-250mg BR excreted into bile/day

85% excreted in faeces
BR→urobilinogen→stercobilinogen→stercobilin(brown)

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

1% enters systemic circulation & excreted by kidneys

59
Q

Outline some of the causes of jaundice

A