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Gastrointestinal > Introduction to the Liver > Flashcards

Introduction to the Liver Flashcards

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1
Q

Describe distinguishable features of the liver

A
  • Largest gland (2nd largest organ)

- Numerous functions; impacts all body systems

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2
Q

What is the significance of the livers structure?

A

Major aspects of it’s structure influence it’s functions:

  • vascular system
  • billiary tree

3D arrangement of liver cells with vascular and biliary systems

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3
Q

Describe the structure of the liver

A

Divided into 2 lobes by the falciform ligament

- each lobe has own blood supply

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4
Q

What is the role of the gallbladder?

A

Stores bile (is green sac)

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5
Q

How does bile reach the duodenum?

A

The common bile duct delivers bile into the duodenum

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6
Q

Describe the venous blood supply of the liver

A

majority (75%) of liver blood supply is venous blood from the portal vein, carrying blood returning from GI full of digested products

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7
Q

Describe the arterial blood supply to the liver

A

25% from the hepatic artery

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8
Q

Describe the venous blood flow in the liver

A

Blood from the central veins in the liver lobules drain into the hepatic vein and then into vena cava

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9
Q

What are the 2 primary cells of the liver?

A 
Hepatocytes (60%)
Kupffer cells (30%)
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10
Q

What is the function of hepatocytes?

A

perform most metabolic functions

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11
Q

What is the role of the endothelial kupffer cells?

A

(type of macrophage)

carry out phagocytic activity by removing aged / damaged rbcs, bacteria, viruses and immune complexes

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12
Q

How does the liver deal with toxic substances?

A

Hepatocytes remove toxic substances, including alcohol from the blood
exits lobule through central vein (hepatic venule)

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13
Q

Describe the counter-current flow of blood and bile

A

Blood flows in the opposite direction to bile

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14
Q

What is the functional unit of the liver?

A

Hepatic lobules

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15
Q

What are hepatic lobules?

A

Hexagonal plates of hepatocytes around a central hepatic vein
At each 6 corners there’s a triad of portal vein, hepatic artery and bile duct branches

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16
Q

Describe the flow of bile through the billiary system

A 
Bile secreted by hepatocytes
↓
series of channels between cells (canaliculi)
↓
small ducts
↓
large ducts
↓
anastomose onto common bile duct
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17
Q

What is the benefit of the liver’s micro-structures?

A

Provides large SA for the exchange of molecules

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18
Q

How does the liver remove toxins?

A

Blood enters lobules through branches of the portal vein and hepatic artery, into smaller channels (sinusoid) lined with hepatocytes which pick up any bacteria from the intestine

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19
Q

What is bile?

A

Greenish-yellow liquid consisting of complex mix of water, electrolytes and organic molecules:

  • bile acids
  • cholesterol
  • bilirubin
  • phospholipids
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20
Q

What is the role of bile?

A

Essential for fat digestion & absorption via emulsification

Bile + pancreatic juice neutralises gastric juice as it enters the small intestine aids digestive enzymes

Elimination of waste products from blood in particular bilirubin & cholesterol

500mg of cholesterol converted to bile acids per day

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21
Q

What are the 2 stages of bile secretion?

A
  1. By hepatocytes:
    • Bile salts, cholesterol & other organic constituents
  2. By Epithelial cells lining bile ducts
    • Large quantity of watery Na+ & HCO₃⁻ solution
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22
Q

What causes the secretion of bile?

A

Release stimulated by secretin hormone in response to acid in the duodenum

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23
Q

Describe in detail the flow of bile

A
  1. Initially hepatocytes secrete bile into canaliculi
  2. Flows into bile ducts containing lots of bile salts,
    cholesterol and other organic constituents.
  3. Modified by water and bicarbonate-rich secretion from
    epithelial ductal cells
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24
Q

How does the gallbladder end up storing bile?

A 
Bile from hepatic ducts
↓
common bile duct
↓
duodenum
OR
diverted via cystic duct
↓
GALL BLADDER
↓
concentrated
& stored (30-50ml)
↓
Released by CCK in response to fat in the duodenum
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25
What is the role of the sphincter of Oddi?
controls entry of bile into duodenum
26
What is bilirubin?
Yellow pigment formed from breakdown of haemoglobin Useless & toxic but made in large quantities (~6g/day) → must be eliminated
27
What is the average lifespan of RBCs?
120 days
28
What happens to dead / damaged RBCs?
Digested by macrophages throughout body: - Spleen - Liver - Red bone marrow etc.
29
What is the fate of the Fe from breakdown of RBCs?
Fe is recycled and stored in liver
30
What happens to the globin chains after RBC breakdown
Globin chains are protein → catabolized into amino acids for protein synthesis
31
What is the fate of haeme groups after RBC breakdown?
Haeme (porphyrin) cannot be recycled → eliminated
32
Explain how haeme is eliminated
Haem → bilverdin → bilirubin → liver → incorporated into bile
33
Outline how bilirubin is eliminated
1. Haeme converted into free bilirubin, (intermediate product is biliverdin) 2. Released into plasma; carried around body to liver bound to albumin 3. Free bilirubin absorbed by hepatocytes → conjugated with glucoronic acid (to become soluble in bile) 4. Conjugated bilirubin secreted into bile → metabolised by bacteria intestinal lumen & eliminated into faeces / urine
34
What pigments cause the colour of urine and faeces?
Major metabolite in faeces is Stercobilin – brown colour | In urine – Yellow urobilin & urobilinogen
35
What is jaundice?
Excessive quantities of free or conjugated bilirubin accumulated in ECF causing a yellow discoloration of skin, sclera and mucous membranes
36
What is the normal bilirubin content in the plasma?
Normal plasma [bilirubin] <17µmol/L (1.0 mg/dl),
37
How much bilirubin is required to cause discolouration?
discolouration > 34-51µmol/L (2-3mg/dl)
38
What is the sclera?
opaque, white outer layer of the eye
39
What are the 3 types of jaundice that can occur?
Pre-hepatic (haemolytic) Hepatic Post-hepatic (obstructive)
40
Explain the cause of Pre-hepatic (haemolytic) jaundice
Excessive RBC breakdown | Excess conjugated bilirubin not excreted - remains in circulation
41
Give an example of pre-hepatic jaundice
e.g. Neonatal jaundice - baby in anaerobic environment in womb so lungs filled with fluid - switch to air when born →lots of RBCs broken down Treatment: Light therapy (UV) converts bilirubin→water soluble compound
42
Describe hepatic jaundice and its causes
Extensive (>80%) hepatocyte damage caused by: - cirrhosis - drugs - Hepatitis A, B, C, E - Gilbert's syndrome - excess (un)conjugated bilirubin
43
Give an example of hepatic jaundice
e.g. Gilbert's Syndrome - congenital disorder; patients have decreased enzyme to conjugate bilirubin with glucoronic acid - increases unconjugated bilirubin
44
What is post-hepatic (obstructive) Jaundice?
Excess conjugated bilirubin - enters circulation + urine (v. dark urine) Obstruction of passage into duodenum
45
What causes post-hepatic (obstructive) jaundice?
gallstones carcinoma pancreas/bile ducts
46
Which toxic substances does the liver metabolise?
``` Bilirubin Ammonia Hormones - e.g. inactivates all steroids: (androgens, oestrogen, cortisol, thyroxine, aldosterone) Drugs + exogenous toxins - e.g. aspirin, paracetamol, ethanol ```
47
What are the 2 phases the liver metabolises drugs and hormones in?
Phase 1 - oxidation/reduction Phase 2 - Conjugation *not all drugs require both phases
48
Explain what occurs in Phase 1 of metabolism
Primarily oxidation / reduction Occurs in SER Catalysed mainly by Cytochrome P450 family => polar compound formed
49
What happens in stage 2 of liver metabolism?
Conjugation to form a water soluble product | Glucoronyl is most prevalent
50
How are metabolised drugs / hormones excreted?
Elimination occurs via ATPase pumps
51
What is the chemical name of paracetamol?
acetaminophen
52
Why is overdose common with paracetamol?
Has a narrow therapeutic index so deliberate/accidental overdose is common
53
What is the maximum dose of paracetamol to be taken?
4 g/day or 1 g/dose | *not to be taken after alcohol consumption
54
How does the detoxification of paracetamol occur?
Metabolised by 3 pathways: 1. Glucoronidation 2. Sulfation (20-30%) 3. N-hydroxylation and dehydration - Intermediate = NAPQI (toxic) - detoxified by GSH conjugation
55
What is the effect of Paracetamol overdose?
Liver enzymes become saturated GSH stores are depleted => NAPQI builds up Causes liver necrosis and kidney damage
56
How is paracetamol overdose treated?
Via infusion of N-acetyl cysteine (GSH precursor) to conjugate NAPQI
57
What are the 2 effects (phases) of Paracetamol overdose?
- damage not immediate | - effective treatment but given too late
58
Where in the body is alcohol removed from?
Only in the liver
59
What happens to alcohol consumed?
Alcohol →acetaldehyde (via alcohol dehydrogenase) => produces NADH used by pyruvic acid→lactate => lactate build up = acidosis
60
How does alcohol consumption lead to hypoglycemia?
pyruvic acid is a substrate for gluconeogenesis => can develop hypoglycemia after drinking - reducing BGL
61
What is the fate of the NADH produced from alcohol metabolism?
NADH enters fat metabolism to generate FA and glycerol →FA burnt off as energy→acetyl coA (driven by NADH) →acetyl CoA→ketone bodies rather than entering tca
62
What happens if FA can't enter the tca?
build up as ketone bodies | form excess lipids and are deposited in adipose tissue
63
What is the fate of acetaldehyde production from alcohol metabolism?
Acetaldehyde is toxic - needs removal: | Acetaldehyde→Acetate→circulation via acetaldehyde dehydrogenase
64
Explain why alcohol flush reaction occurs so commonly among asians?
50% of asians have ALDH2 deficiency due to mutation of copy 1 gene → accumulation of acetaldehyde → alcohol flush reaction
65
What are the stages of alcohol induced liver damage?
Fatty liver → Liver fibrosis → cirrhosis
66
Describe a fatty liver caused by alcohol
Deposits of fat causes liver enlargement | Strict abstinence can lead to a full recovery
67
Describe liver fibrosis
Scar tissue forms on liver | Recovery is possible, but scar tissue remains
68
Describe liver cirrhosis
Growth of connective tissue destroys liver cells | Damage is irreversible
69
What are the effects of impaired detoxification?
Gynecomastia due to alcoholic cirrhosis
70
Name blood clotting factors synthesised in the liver
Fibrinogen Prothrombin nearly all other factors e.g. V, VI, IX, X, XII
71
What is the significance of vitamin K in coagulation factor synthesis?
Vitamin K is essential for prothrombin formation and Factors II, IX VII and X
72
What effect does liver damage have on clotting factors?
In severe liver disease, excessive bleeding may result due to a lack of coagulation factors
73
Outline the storage that occurs in the liver
Hepatocytes - depots for fat soluble vitamins: K, D, E A | Stores Vit. B12 , folate and Iron as ferritin
74
What is the consequence of liver dysfunction?
fat malabsorption→vit. deficiency
75
What is the effect of Vit. B12 deficiency?
pernicucus anemia
76
What is the requirement of folate?
Required during pregnancy

Gastrointestinal (18 decks)

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