Liver disease Flashcards
(78 cards)
1
Q
What are the functions of the normal liver?
A
- Glucose and fat metabolism
- Protein synthesis e.g. albumin and clotting factors
- Detoxification and excretion
- Defence against infection
2
Q
Describe key histological arrangements in the liver
A
- Arranged in acinar or lobular models (hepatocytes)
- Blood runs in sinusoids in close proximity to the hepatocytes to enable lots of metabolic activity
- Bile flows out and blood flows in through portal tracts forming a hexagonal structure around a central vein which drains into the hepatic vein
3
Q
How is acute and chronic liver injury defined in terms of time?
A
Acute: <6 months
Chronic: >6 months
4
Q
How does acute liver injury present histologically?
A
- Acute hepatocyte injury and death
- Cell death can occur by necrosis or apoptosis
- Usually characterised by inflammation
5
Q
How does acute liver injury more commonly present physiologically?
A
- Malaise
- Nausea
- Anorexia
- Jaundice
6
Q
How does chronic liver injury present histologically?
A
- Continued inflammation causes fibrosis so there is a lack of liver regeneration
- Stellate cells activate and cytokines cause fibrosis deposition
7
Q
How does chronic liver injury present more commonly physiologically?
A
- Ascites
- Oedema
- Hematemesis
- Malaise
- Anorexia
- Wasting
- Easy bruising
- Itching
- Hepatomegaly
- Abnormal LFTs
8
Q
How does acute liver injury less commonly present physiologically?
A
- Confusion (encephalopathy)
- Bleeding
- Liver pain
- Hypoglycaemia
9
Q
How does chronic liver injury present less commonly physiologically?
A
- Confusion
* Jaundice
10
Q
Why does oedema occur in chronic liver injury?
A
Due to low albumin
11
Q
Why does hematemesis occur in chronic liver injury?
A
Due to oesophageal or stomach varices
12
Q
Name the 3 key liver function tests
A
- Serum albumin
- Bilirubin
- Prothrombin time
13
Q
What is serum abumin a marker of?
A
Synthetic function
14
Q
In normal function, is bilirubin usually conjugated or unconjugated?
A
Unconjugated
15
Q
What is prothrombin time a marker of?
A
Synthetic function
16
Q
Why is prothrombin time a sensitive marker of acute and chronic liver disease?
A
Because it has a short half-life
17
Q
A deficiency of which vitamin will cause a prolonged prothrombin time?
A
Vitamin K deficiency
18
Q
Name the 2 important areas of liver biochemistry
A
- Aminotransferases
2. Alkaline phosphate
19
Q
What are the 2 aminotransferases?
A
- Aspartate aminotransferase (AST)
2. Alanine aminotransferase (ALT)
20
Q
Where is aspartate aminotransferase (AST) present?
A
Liver, heart, muscle, kidney and brain
21
Q
What can cause a rise in aminotransferase (AST)?
A
- Hepatic necrosis
- MI
- Muscle injury
- Congestive heart failure
22
Q
Where is alanine aminotransferase (ALT) present?
A
The liver
23
Q
What can cause a rise in alanine aminotransferase (ALT) ?
A
Liver disease
24
Q
Where is alkaline phosphate present?
A
- Liver
- Bone
- Intestine
- Placenta
25
When might alkaline phosphate be raised?
* Intrahepatic disease
* Extrahepatic cholestatic disease
* Hepatic infiltrations (e.g. metastases)
* Cirrhosis
26
What is jaundice?
Yellowing of the skin (+/- sclera) due to raised serum bilirubin
27
What is pruritus?
Itching
28
Why does skin go yellow in jaundice?
Raised serum bilirubin causes bile salt deposition in the skin
29
What are the 2 areas of classification of jaundice?
* Unconjugated – ‘pre-hepatic’
| * Conjugated – ‘cholestatic’
30
Give 2 causes of unconjugated jaundice
1. Gilbert's syndrome
| 2. Haemolysis
31
What can cholestatic jaundice be further divided into?
Hepatic and post-hepatic
32
What is Gilbert's syndrome?
Deficiency in UDP glucuronyl transferase
33
Give a cause of hepatic cholestatic jaundice
Liver disease e.g. hepatitis
34
Give a cause of post-hepatic cholestatic jaundice
Bile duct obstruction e.g. gallstones
35
In pre-hepatic jaundice what is urine like?
Normal
36
In pre-hepatic jaundice what are stools like?
Normal
37
In cholestatic jaundice what is urine like?
Dark
38
In cholestatic jaundice what are stools like?
May be pale
39
In pre-hepatic jaundice, is there itching?
No
40
In cholestatic jaundice, is there itching?
Maybe
41
In pre-hepatic jaundice what are liver tests like?
Normal
42
In cholestatic jaundice what are liver tests like?
Abnormal
43
What might dark urine, pale stool and itching sugget?
Cholestatic not pre-hepatic
44
What key symptoms may also be present in jaundice?
* Biliary pain
* Rigors
* Abdomen swelling
* Weight loss
45
What key points of past medical history should be asked about in jaundice?
* Biliary disease/intervention
* Malignancy
* Heart failure
* Blood produces
* Autoimmune disease
46
What tests should you do investigate jaundice?
• Liver enzymes
• Biliary obstruction
• Further imaging
• CT
- Magnetic resonance cholangiopancreatography (MRCP)
- Endoscopic retrograde cholangiopancreatography (ERCP)
47
Where do most gallstones form?
In the gallbladder
48
What are the 2 types of gallstone?
Cholesterol and bile pigment
49
What percentage of gallsones are cholesterol stones?
70%
50
What percentage of gallsones are bile pigment stones?
30%
51
What is the most common symptom of gallstones?
Most are asymptomatic
52
What are the 3 classifications of gallstones?
* Gallbladder stones
* Intrahepatic stones
* Extrahepatic stones
53
What are the risk factors for gallstones?
* Female
* Fat
* Fertile
* Smoking
54
What are the main causes of gallstones?
* Obesity and rapid weight loss
* Diet high in animal fat and low in fibre
* Diabetes mellitus
* Contraceptive pill
* Liver cirrhosis
55
Are cholesterol gallstones usually small or large?
Large
56
Are cholesterol gallstones usually solitary or more numerous?
Solitary
57
How do cholesterol gallstones form?
There is cholesterol crystalisation in bile
58
Give 4 reasons for cholesterol gallstones to form
1. Relative deficiency in bile salts and phospholipids
2. Relative excess of cholesterol in bile
3. Reduced gallbladder motility and stasis
4. Crystalline promoting factors in bile e.g. mucus and calcium
59
What are bile pigment stones mostly formed of?
Calcium (Ca2+)
60
Describe the key features of bile pigment stones
* Friable (easily crumbled)
* Irregular
* Mostly calcium
61
What is the main cause of bile pigment stones?
Haemolysis
62
What are the main types of bile pigment stones?
Black and brown
63
Describe the composition of black bile pigment stones
Made of calcium bilirubinate and a network of mucin glycoproteins that interlace with salts e.g. calcium bicarbonate
64
Describe the composition of brown bile pigment stones
Calcium salts
65
In which patients are black bile pigment stones usually seen?
Patients with haemolytic anaemias
66
In what conditions are brown bile pigment stones usually found?
In bile stasis and/or biliary infection
67
How would you manage gallbladder stones?
* Laparoscopic cholecystectomy
| * Bile acid dissolution therapy
68
How would you manage bile duct stones?
```
• ERCP with sphincterotomy and:
- Removal (balloon or basket)
- Crushing (mechanical or laser)
- Stent placement
• Surgery for large stones
```
69
What proportion of bile acid dissolution therapy procedures are successful?
<1/3
70
What are the 4 drug mechanisms involved in causing liver damage?
* Disruption of intracellular Ca2+ homeostasis
* Disruption of bile canalicular transport mechanisms
* Induction of apoptosis
* Inhibition of mitochondrial function, which prevents fatty acid metabolism and accumulation of lactate and reactive oxygen species
71
What are the 3 types of drug-induced liver injury?
1. Hepatocellular
2. Cholestatic
3. Mixed
72
What is the usual onset for a drug-induced liver injury?
1-12 weeks
73
What are the main causes of drug-induced liver injuries?
* Antibiotics
* CNS drugs
* Immunosuppressants
* Analgesics
* GI drugs
* Dietary supplements
* Multiple drugs
74
Give 4 antibiotics which cause DILI
* Augmentin
* Flucloxacillin
* TB drugs
* Erythromycin
75
Give 2 CNS drugs which cause DILI
* Chlorpromazine
| * Carbamazepine
76
Give 1 analgesic which causes DILI
Diclofenac
77
What type of GI drugs may cause a DILI?
PPIs
78
Name 6 types of drug which do not cause DILI
* Low-dose aspirin
* NSAIDs except diclofenac
* Beta blockers
* Ace inhibitors
* Thiazides
* Calcium channel blockers
