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Phase 2: Gastrointestinal System > Lecture 7: Bilirubin lecture > Flashcards

Lecture 7: Bilirubin lecture Flashcards

1
Q

Where is bile generated?

A

In the liver

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2
Q

Where is bile stored?

A

In the gall bladder

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3
Q

What are the 5 components of bile?

A

Bicarbonate

Cholesterol

Phospholipids

Bile pigments

Bile salts

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4
Q

Which vessels collect bile secreted by hepatocytes?

A

Bile cannaliculi, which combine to form bile duct

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5
Q

Name the predominant bile pigment?

A

Bilirubin

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6
Q

How are bile pigments generated?

A

formed from the haem portion of haemoglobin (porphyrin ring) when odd or damanged erthyocytes are broken down in the spleen and liver.

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7
Q

What is the functional unit of the liver?

A

Hepatic lobule

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8
Q

What are the 3 parts of the portal triad?

A

Branches of the bile duct

Portal veins

Hepatic artery

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9
Q

Describe the flow of blood out of the liver?

A

Central vein drains the blood from each hepatic lobule.

The central veins converge creating hepatic veins.

Hepatic veins drain directly into the inferior vena cava

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10
Q

What are the 3 hepatic veins?

A

Right, left and intermediate

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11
Q

What is the enterohepatic circulation?

A

Recycled pathway from the liver to the intestine and back to the liver

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12
Q

How many days is an erthyrocyte lifespan?

A

120 days

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13
Q

Describe the steps of haem breakdown in the reticulo-endothelial system?

A

Step 1:

Haem converted to Biliverdin

Broken down by haem oxygenase

This is the point where the iron is removed

Step 2:

Biliverdin converted to unconjugated bilirubin

Broken down by biliverdin reductase

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14
Q

Key characteristics of bilirubin?

A

Hydrophobic

Cannot be transported without albumin bound

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15
Q

Describe what happens when the unconjugated bilirubin is bound with albumin and is transported out of the reticulo-endothelial system?

A

It is transported to the hepatocytes in the liver (the portal triad).

In the liver it is converted to conjugated bilirubin by UDP glucuronyl transferase (adding glucuronic acid)

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16
Q

Which vessel transports unconjugated bilirubin/albumin to the liver from the reticulo-endothelium system?

A

Portal vein

This carries the blood from the gastrointestinal tract, gallbladder, pancreas and spleen to the liver

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17
Q

Name these vessels?

A
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18
Q

Why does the unconjugated biliruibin be transformed into conjugated bilirubin?

A

Makes it hydrophilic so it can be transported out of the liver

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19
Q

Describe the route from conjugated bilirubin to the small bowel?

A

It is accumulated in bile

Bile is removed from the left and right bile ducts, which converge the become the common hepatic duct.

Bile can either be stored in the gallbladder (via cystic duct) or travels down the common bile duct.

The common bile duct converge with the pancreatic duct and becomes the hepatopancreatic ampulla.

This empties into the ilieum of the small bowel

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20
Q

What colour is bilirubin?

A

Yellow

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21
Q

What happens to conjugated bilirubin once it has entered the ileum of the small intestine?

A

Initially it is converted to unconjugated bilirubin by ß-glucoronidase

The intestinal microflora modifies the U-bilirubin into urobilinogens.The urobilinogens are not absorbed in the small intestine.

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22
Q

What happens to urobilinogens once it has entered the large intestines?

A

When they enter the large intestine, the intestinal microflora convert them into mesobilin, sterobilin and urobilin.

urobilin are absorbed into the blood stream and excreted by the kidneys i.e. in urine.

The mesobilin and sterobilin are insoluble and therefore are excreted in faeces.

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23
Q

What is the main two functions of bile salts?

A
  1. Act as surfactant aiding the absorption of fats and lipid-soluble vitamins e.g. vit K
  2. Excretion of bilirubin
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24
Q

Describe the structure of bile salts?

A

Ionically charged

Hydrophobic end

Hydrophilic end

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25
Describe how bile salts aid the absorption of fat?
The bile salts congregate around a fat droplet The hydrophobic side pointing towards the fat droplet The hydrophilic side points towards the water Thus increasing the surface area of the fat droplet for the action of triglyercide lipase
26
What does it mean by emulsification?
Breakdown of large lipid droplets into small uniform droplets
27
Describe the 3 stages of lipid metabolism with the aid of bile salts?
_Stage 1:_ Emulsify the fat globules in the intestines Bile salts surround the lipid droplets aiding the lipase activity. Fat droplets gets broken down into free fatty acids and bile salts _Stage 2:_ Bile salts form micelle the free fatty acids This allows it to be absorbed into the epithelial cell layer Stage 3: Absorbed free fatty acids form triglycerides and are packaged into chylomicrons for secretion in lacteals
28
What is the interdigestive period and what happens to the sphincter of oddi?
Period between meals Sphincter is contracted preventing the release of bile from the hepatopancreatic ampulla.
29
What happens in the gallbladder during the interdigestive period?
Pressure in the common bile duct increases. Hence, the bile moves through the cystic duct into the gallbladder. In the gallbladder, the epithelial cells reabsorbs water and electrolytes concentrating the bile
30
What stimulates the enteroendocrine cells to secrete cholecystokinin (CCK)?
Fatty acids and amino acids that enter the duodenum (occurs after a meal)
31
What does the cholecytokinin (CCK) do?
Stimulates the contraction of the smooth muscle of the gallbladder Relaxes the Sphincter of Oddi. Bile is released as a result
32
What stimulates the enteroendocrine cells to secrete secretin?
Acidic chyme in the duodenum stimulates the secretion of secretin
33
What does the secretin do?
Stimulates duct cells to release bicarbonate into the bile and stimulates bile production
34
Which cells in the liver secrete the bile salts and bile pigment?
Hepatocytes
35
Which cells in the liver secrete bicarbonate?
The epithelial cells lining the bile ducts
36
Describe the enterohepatic circulation for bile salts?
Bile salts present in the body are not enough to fully process the fats in a typical meal. The bile salts are absorbed by sodium coupled transporters in the ileum These absorbed bile salts are returned via the portal vein, back to the liver. Once back in the liver, they are once again secreted into the bile. A small amount of bile salts escape and are excreted in faeces
37
What percentage of bile salts are recycled in the enterohepatic circulation?
95% the rest (5%) are lost in faeces
38
Define the term hyperbilirubinaemia?
Too much bilirubin in the blood
39
In what way is bilirubin excreted?
Mostly in faeces A bit in the urine A bit reabsorbed as urobilinogen
40
Define jaudice?
Defined as elevated levels of bilirubin (hyperbilirubinaemia)
41
Where are the two clinical signs of jaudice?
Yellowing of the sclera Yellowing of the skin
42
What is the normal level of total bilirubin?
\< 21 µmol/L
43
At what level of total bilirubin will jaudice be visible in the sclera
\>30 µmol/L
44
At what level of total bilirubin will jaudice be visible in the skin
\> 100 µmol/L
45
What are the two components of total bilirubin?
Unconjugated bilirubin Conjugated bilirubin
46
What are the 3 groupings of jaudice?
1. Pre-hepatic jaudice 2. Hepatic jaudice 3. Post-hepatic jaudice
47
What are the possible causes of pre-hepatic jaudice?
Trophical disease e.g. malaria, yellow fever Sickle cell anemia or other genetics disorder
48
What is pre-hepatic jaudice associated with?
Associated with elevated haemolysis (breakdown of RBCs) The liver cannot cope with the high levels of unconjugated bilirubin
49
What are the levels of conjugated:unconjugated bilirubin for pre-hepatic jaudice?
very high levels of unconjugated high levels of conjugated
50
What are the two causes of neo-natal jaudice?
Physiological and haemolytic causes Physiological: too high a level of fetal haemoglobin Haemolytic; Incompatilibity between fetus and mother
51
What type of jaudice is neo-natal jaudice?
Pre-hepatic jaudice (i.e. too much erthryocyte breakdown)
52
Describe the physiological cause of neo-natal jaudice?
Common and usually harmless After birth, newborns but destroy fetal haemoglobin and replace with adult haemoglobin Undeveloped liver (with lack of glucuronyltransferase) is not able cope with the high haemolysis Last approx 14 days
53
What is the treatment of physiological neo natal jaudice?
Treat with phototherapy- blue light
54
How does phototherapy work?
Blue light changes unconjugated bilirubin to a water-soluble form This water-soluble form can be excreted
55
Describe the haemolytic cause of neo-natal jaudice?
rhesus incompability between mother and featus If maternal blood is rhesus -ve, the blood can be sensitised by a previous rhesus +ve fetus or by a blood transfusion which has rhesus +ve (very rare). Thus, when the mother has another baby who is rhesus +ve, the mother will have the antibodies and will start attacking the foetus blood
56
What is the treatment of haemolytic neo natal jaudice?
High dose of phototherapy and blood transfusion
57
What are the 3 points in the hepatic system that can go wrong to cause hepatic jaudice?
1. Impaired uptake of unconjugated bilirubin 2. Impaired conjugation of bilirubin 3. Impaired transport of conjugated bilirubin into the bile caniculi
58
Define Gilberts?
Condition that results in a reduction in glycuronyl transferase activity (the enzyme that converts unconjugated bilirubin to conjugated bilirubin in the liver) Results in hepatic jaudice
59
What are the 3 major causes of hepatic jaudice?
Cirrhosis (e.g. alcohol-induced) Hepatotoxic drugs e.g. paracetamol overdose Viral hepatitis
60
What are the 3 vessels that are associated in getting obstructed resulting in post-hepatic jaudice?
Hepatic veins Cystic duct Common bile duct
61
Name these vessels
62
Cholestasis meaning
Reduction or stoppage of bile flow
63
What conditions are associated with post-hepatic jaudice?
Conditions associated with obstruction of the hepatic veins, cystic duct or common bile duct. e.g. Gallstones, pancreatitis and pancreatic tumours
64
Describe gallstones?
Small pebbles of cholesterol which move from the gall bladder into duct and obstruct the flow of bile (i.e. causing cholestasis). It arises if the capacity of bile salts and phospholipids to solubilise cholesterol is exceeded Can cause post-hepatic jaudice if bile flow is completely obstructed
65
Define pancreatitis?
Acute or chronic inflammation of the pancreas following infection or damage Swelling of the pancreas can block the flow resulting in post-hepatic jaudice
66
What are the symptoms associated with gallstones in area 1
Gallstones in the cystic duct Painful contractions No jaudice and bile can still move from the liver
67
How does gallstones move down the bile ducts?
As the gallbladder contracts it forces the stones to move further along the bile duct
68
What are the symptoms associated with gallstones in area 2
Gallstones in the common bile duct Staeorrhea Post-hepatic jaundice Pale stool Dark urine
69
What colour would the urine and stool be for post-hepatic jaudice?
Pale stool Dark urine
70
Define steaorrhea?
Fatty faeces as the fat cannot be broken down by bile salts
71
What are the symptoms associated with gallstones in area 3
Gallstones in the duodenal papilla, the opening of the pancreatic duct into the duodenum Acute pancreatitis Malnutrition- as both bile and exocrine pancreatic secretions cannot be excreted
72
Why are bile salts so important?
Required for efficient digestion and absorption of lipids Required for absorption of lipid soluble vitamins
73
Name some of the lipid soluble vitamins that bile salts aid in absorbing?
Vitamins A, D, E and K Vitamin K is important for coagulation
74
What coagulation factors is vitamin K a cofactor?
Coagulation factors 2, 7, 9 and 10
75
Why must vitamin K be administered to post-hepatic jaudice patients prior to surgery?
Patients who have post-hepatic jaudice are not able to absorb lipid-soluble vitamins (including Vitamin K). Therefore, must be given Vitamin K to prevent haemorrhage during surgery
76
Describe the pathway for urobilinogens to be excreted in the urine?
Urobilinogens in the small intestine are absorbed by the portal vein and taken to the liver. From the liver they go to the kidney and are excreted in urine in the urobilin form
77
How do we test for conjugated bilirubin?
Add diazo reagent to serum Conjugated bilirubin is converted into a blue product The wavelength can be measured. NOTE: unconjugated will not react
78
How do we measure to total bilirubin levels?
Add diazo and caffeine The caffeine will displace the unconjugated bilirubin from albumin. Once displaced, both the conjugated and unconjugated bilirubin can react to the diazo and become converted to a blue product. The wavelength is measured
79
Add diazo only is used to measure which bilirubin(s)?
Conjugated bilirubin only
80
Add diazo and caffeine to measure which bilirubin(s)?
Total bilirubin Both conjugated and unconjugated
81
What is the best way to measure bile pigments in urine?
MultiStix urinalysis Dip the stick in urine and see a colour change The percentage of colour change depends on the percentage of amylase present
82
Which bilirubin(s) does the MultiStix urinalysis measure?
Conjugated bilirubin only (because this is the soluble one)
83
Define hyperbilirubinuria and what does this tell you?
Detection of conjugated bilirubin in the urine Always pathological!!! No C-bilirubin should be present in the urine NOTE: urobilin are present normally but not C-bilirubin
84
What are the two key components of bile?
Bile salts Bile pigments
85
Where are bile pigments generated?
Generated in the reticulo-endothelial system from haem breakdown
86
Is it conjugated or unconjugated bilirubin that needs to be bound to albumin?
Unconjugated
87
What comes first the common hepatic duct or the common bile duct?
Common hepatic (comes from the liver) Common bile duct (the pathway for all of the bile)
88
What is the function of bile salts?
Emulsify lipids Incerase pancreatic lipase activity to ensure efficient digestion and absorption of fats and fat-soluble vitamins
89
What is the enzyme that converts haem to biliverdin?
Haem oxygenase
90
What is the enzyme that converts biliverdin into unconjugated bilirubin?
Biliverdin reductase
91
What is the enzyme that converts U-bilirubin into C-bilirubin in the liver?
UDP glucuronyl transferase
92
What is the enzyme that converts C-bilirubin in the small intestine to U-bilirubin?
ß-glucornoidase
93
Name the 3 urobilinogens?
Stercobilinogen Urobilinogen Mesobilinogen
94
Draw the flowchart of the bilirubin metabolism
95
Which enzyme acts on haem to remove Fe2+ ions?
Haem oxygenase
96
In physiological neonatal jaundice, which enzyme is in too little quantity to cope with the increased haemolysis of fatal haemoglobin?
UDP Glucoronyltransferase

Phase 2: Gastrointestinal System (30 decks)

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