(59a) Diseases of the Hepatobiliary system Flashcards Preview

12. CP - Diseases of the Hepatobiliary system and Pancreas > (59a) Diseases of the Hepatobiliary system > Flashcards

Flashcards in (59a) Diseases of the Hepatobiliary system Deck (142)
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1

Name 3 medical liver diseases

- jaundice
- hepatitis
- cirrhosis

2

What is the commonest sign of liver disease?

Jaundice

3

When is jaundice visible and where?

When bilirubin is higher than 40umol/l

First visible in the sclera of the eye

4

What are the 3 types of jaundice?

(classified according to where the abnormality is in the metabolism of bilirubin)

- pre-hepatic
- hepatic
- post-hepatic

5

What are the causes of pre-hepatic jaundice?

Too much bilirubin produced
- haemolytic anaemia

6

What is bilirubin?

The yellow breakdown product of normal heme catabolism, caused by the body's clearance of aged red blood cells which contain hemoglobin. Bilirubin is excreted in bile and urine, and elevated levels may indicate certain diseases

7

What are the causes of hepatic jaundice?

Too few functioning liver cells
- acute diffuse liver cell injury
- end stage chronic liver disease
- inborn errors

8

What are the causes of post-hepatic jaundice?

Bile duct obstruction
- stone or structure
- tumour of the bile duct or pancreas

9

Describe the pathway of bilirubin metabolism

- bilirubin is produced by red blood cell breakdown (unconjugated)
- metabolised in the liver (conjugated) and excreted in bile
- some bilirubin is re-absorbed from the gut (enterohepatic circulation)
- also bile salts

10

Where are erythrocytes broken down and unconjugated protein-bound bilirubin produced?

In the spleen

11

Where does conjugation of bilirubin occur? (becomes water-soluble)

In the liver

12

Where is urobilinogen produced?

In the intestines

13

Which protein carries unconjugated bilirubin?

Albumin

14

Describe the difference in solubility between unconjugated and conjugated bilirubin?

Unconjugated bilirubin = lipid-soluble

Conjugated bilirubin = water-soluble

15

What happens to conjugated bilirubin after the liver?

It is excreted in bile into the small intestine through the bile duct

16

What happens to conjugated bilirubin once it is in the small intestine?

Gets to ileum or first part of large intestine and is converted to urobilinogen (urobilinogen = lipid-soluble)

17

Most urobilinogen is oxidised to what?

Sterocobilin

18

Sterocobilin is responsible for what?

The brown colour of faeces

19

Describe the bilirubin in pre-hepatic jaundice

- unconjugated
- bound to albumin
- insoluble
- not excreted

20

What would the signs be in pre-hepatic jaundice?

Yellow eyes and skin only

21

Describe the bilirubin in hepatic jaundice

- mainly conjugated
- soluble

22

What would the signs be in hepatic jaundice?

Yellow eyes and dark urine

23

Describe the bilirubin in post-hepatic jaundice

- conjugated
- soluble
- excreted
- but can't get into gut

24

What would the signs be in post-hepatic jaundice?

Yellow eyes, pale stools and dark urine

25

The site of abnormality of bilirubin excretion can be deduced from what?

Clinical history of skin, urine and faeces colour

26

Why are liver enzymes measured in liver function tests?

Damage to cells in the liver causes enzymes to leak from the cells

27

Which enzymes leak from damaged hepatocytes? (measured in liver damage tests)

- ALT (alanine aminotransferase)
- AST (aspartate aminotransferase)

28

What leaks damaged bile ducts? (measured in liver damage tests)

Alkaline phosphate

29

What 3 things are measured in liver function tests?

- bilirubin
- albumin
- clotting factors

30

What would raised conjugated bilirubin without extrahepatic duct obstruction indicate?

Disease of hepatocytes or intrahepatic ducts

31

Why are clotting factors and albumin measured in LFTs?

They are manufactured by hepatocytes - so levels fall when insufficient liver synthetic function

32

When would albumin levels be low?

In chronic liver disease (has a long half life)

(could also be due to insufficient dietary intake, or nephrotic syndrome causing increased urinary excretion)

33

When would clotting factors be low?

Acute liver disease and liver failure (short half life)

34

Why is poor clotting also seen in patients with obstructive jaundice?

Can't absorb fat-soluble vitamins (vitamin K)

35

What is the first histopathological feature in the liver of obstructive jaundice?

Bile in the liver parenchyma (jaundice in skin)

36

What are the further signs of obstructive jaundice with increasing time?

- portal tract expansion
- oedema
- ductular reaction (proliferation of ductules around the edge)
- bile salts and copper cannot get out (accumulate in hepatocytes, bile salts in skin = itchy)

Eventually, severe chronic liver disease and cirrhosis

37

What is used to first investigate a patient with jaundice?

Ultrasound scan (USS) to check for bile duct dilatation - if ducts are not dilated, then lover biopsy may be performed to investigate cause of jaundice

38

What is seen on obstructive jaundice, perivenular (zone 3) changes?

Bile pigment is visible in bile plugs which show that bile has been excreted by hepatocytes into intracellular canaliculi but accumulated because of low bile flow
- also get swelling and irregularity of hepatocytes, and increased activity of Kupffer cells phagocytosing dead hepatocytes

39

Were are the changes to the portal tract in obstructive jaundice?

Gets larger, initially due to swelling (oedema, tissue looks pale) then you get ductular reaction (increased number of small bile ducts around periphery of tracts) and some associated inflammatory cells including neutrophils

Over time, oedema reduces and fibrosis increases - characteristic appearance = biliary gestalt

40

Most non-obstructive cause of jaundice are due to what?

Acute hepatitis

41

What is acute hepatitis?

Inflammation in the liver, can only really be seen with liver biopsy (no classical pain and swelling etc) - symptoms usually mild/non-existant unless severe - recent onset and will resolve back to normal if cause does not persist

42

What is chronic hepatitis?

Present for over 6 months, results in ongoing liver cell injury and progressive structural liver damage of scarring and remodelling

43

The severity of acute hepatitis depends on what?

How many hepatocytes are damaged at once, and how good the liver regeneration is

44

What is at the most severe end of the spectrum in acute hepatitis?

- coagulopathy
- encephalopathy (confusion, coma)
- death

45

What are the causes of acute hepatitis?

- inflammatory injury (viral, drugs, autoimmune, unknown = seronegative)
- toxic/metabolic injury (alcohol, drugs eg. paracetamol)

46

Which viruses can causes severe inflammatory injury (acute hepatitis)?

Hepatitis A, B, E

47

What is DILI?

Drug-induced liver injury

48

How is the overall appearance of acute hepatitis on biopsy described?

Lobular disarray

49

What is seen on biopsy in acute hepatitis?

- apoptotic hepatocytes (acidophil body) = spotty necrosis
- inflammatory cells
- hepatocytes vary in size

Overall = lobular disarray

50

What is seen on biopsy in the more severe end of the spectrum of acute hepatitis?

Whole confluent areas of necrosis of hepatocytes = confluent panacinar necrosis

51

What is acute hepatitis with bridging necrosis?

Intermediate-severity acute hepatitis

Confluent necrosis of adjacent hepatocytes in a 'bridge' between a portal tract and hepatic vein

52

What are the 5 groups of causes of chronic hepatitis?

- immunological injury
- toxic/metabolic injury (fatty liver disease)
- genetic inborn errors
- biliary disease
- vascular disease

53

What is the most common group of causes of chronic hepatitis?

Toxic/metabolic injury

54

What can identify which of the 5 groups is the causes of chronic liver injury?

Liver biopsy

55

What are the immunological causes of chronic liver injury?

- virus
- autoimmune
- drugs

56

What are the toxic/metabolic causes of chronic hepatitis (fatty liver disease)?

- alcohol
- non-acoholic fatty liver disease (NAFLD)
- drugs

57

What are the genetic inborn errors causes of chronic liver injury?

- iron
- copper
- alpha1antitrypsin

58

What are the biliary disease causes of chronic hepatitis?

- autoimmune
- duct obstruction
- drugs

59

What are the vascular disease causes of chronic hepatitis?

- clotting disorders
- drugs

60

Describe the non-specific pathology of chronic liver disease?

Injury to liver cells, inflammation, formation of scar tissue and regeneration of hepatocytes

61

Specific pathology of chronic liver disease depends on what?

The cause of injury

62

What are the uses of liver biopsy in diagnosis of chronic liver disease?

- determine the causes of damage
- asses the stage of the stage (how much scarring, spectrum from normal to cirrhosis)

63

Describe how scarring progresses in chronic liver disease

Scarring gradually increases and starts to link vascular structures (bridging) - eventually transforming the liver into separate nodules = end stage = cirrhosis

64

What are the 4 general stages of scarring in chronic liver disease

1. normal
2. portal fibrosis
3. bridging fibrosis (from portal tract to hepatic veins)
4. cirrhosis

65

What are the hepatotrophic trophic viruses?

Ones that specifically infect the hepatocytes causing liver disease (hepatitis A, B etc)

D = delta, only seen in people with B
E = waterborne, zoonosis, pigs

66

What other viruses (not hepatotrophic) can cause hepatitis as part of systemic disease?

- EBV
- CMV
- HSV

67

Which hepatitis viruses are major causes of liver disease worldwide?

B and C

(hepatitis A does not cause chronic liver disease)

68

What is the treatment for hep B and C?

Hep B = IFN, lamivudine + new ones

Hep C = IFN, ribavirin + new ones

69

What is the prophylaxis for hep B and C?

Hep B = vaccine, Ig

Hep C = none

70

What is the spectrum of liver pathology due to alcohol?

- fatty change
- alcoholic steatohepatitis
- cirrhosis

71

Some patients with metabolic syndrome have a similar pathology of liver disease to that causes by alcohol. What is this called?

Non-alcoholic fatty liver disease (NAFLD)

72

The combination of which 2 risk factors in synergistic in causing liver disease?

Alcohol and obesity

73

A liver biopsy showing features of steatohepatits is likely to be due to what?

Alcoholic liver disease

74

Some patients with alcohol injury may just show fatty change; what is this?

A reversible stage of liver injury that may or may not progress to steatohepatitis?

75

How is steatohepatitis seen on liver biopsy?

- white blobs = steatosis
- ballooned hepatocyte with mallory body
- inflammatory cells
- pericellular fibrosis (around hepatocytes)
- fibrosis in portal tracts

76

What is Van Gieson stain?

The simplest method of differential staining of collagen and other connective tissue (used in liver biopsies)

77

Describe the pathology of NAFLD?

Same pathological spectrum as alcoholic liver disease (steatosis, steatohepatitis, cirrhosis, HCC)

78

NAFLD is associated with what?

Metabolic syndrome - obesity, type 2 diabetes, hyperlipidaemia, also some drugs

79

What is the commonest cause of liver disease?

Metabolic syndrome

80

What is the treatment for NAFLD?

Address the causes of metabolic syndrome

81

What is steatosis vs steatohepatitis?

Steatosis = fatty change

Steatohepatitis = fatty chnage plus hepatocyte injury - ballooning, Mallory Denk body, inflammation, sinusoidal fibrosis

82

Why is there injury to liver cell mitochondria in NAFLD?

Mitochondria injured by oxidative stress of too much energy transfer (too many calories)

83

What is there a risk of in any cause of cirrhosis?

Hepatocellular carcinoma

84

Drug-induced liver injury (DILI) is iatrogenic; what does this mean?

Induce inadvertently by a doctor/medical treatment/diagnostic procedures

Hepato-toxic drugs

85

DILI can be classified into which 2 categories?

- intrinsic (anyone taking drug is likely to get liver damage, predictable eg. paracetamol)

- idiosyncratic (depends on individual susceptibility, metabolic/immunoligcal) - rare and can be severe

86

What is the commonest symptom of DILI?

Jaundice

87

How is the type of acute liver injury decided?

Ratio of liver enzymes ALT: alk phos - classified at hepatitic, cholestatic, or mixed

Hepatic and mixed forms = risk of severe disease and liver failure

over 5 = hepatocellular
under 2 = cholestatic
2-5 = mixed

88

In the diagnosis of DILI, what other causes should be excluded?

- alcohol and NAFLD
- acute presentation of underlying chronic liver disease
- autoimmune
- biliary
- vascular

89

Which drugs should patients avoid?

Any that have caused injury in the past

Antibiotics are the commonest cause

(any drug can cause liver injury and can cause diff injury in diff patients, time of onset is variable, usually improves on stopping drug)

90

What are the standard criteria for DILI?

1. onset of abnormal LFTs after intake of drug
2. improvement in LFTs after stopping drug
3. alternative causes excluded by detailed investigation, including liver biopsy
4. increase in LFTs by 100% in re-challenge

Drug induced if all of first 3 or 2 + positive re-challenge

91

What is the commonest cause of acute liver failure in the UK?

Paracetamol toxicity

92

How is paracetamol seen on liver biopsy?

Results in necrosis of a high proportion of hepatocytes in a predictable, zonal distribution, without any inflammation

Hepatocytes around the portal tracts are spared and able to regenerate the liver back to normal if toxicity is not too severe

93

What is the difference between safe and unsafe paracetamol metabolism?

2 safe metabolic pathways (metabolised by glucuronyl transferase or sulphotransferase)

Too much paracetamol = metabolised by cytochrome P450 pathway to a toxic metabolite (NAPBI)

94

What can be given to neutralise paracetamol overdose?

Glutathione

95

If glutathione is not given in the case of paracetamol overdose, what happens to the toxic metabolite?

It bind covalently to tissue membrane proteins and causes necrosis - irreversible cell death

96

How is paracetamol toxicity treated?

Treatment with IV N-actetyl cysteine - resorts glutathione

Avoids liver cell damage

97

What is cirrhosis?

A diffuse hepatic process characterised by fibrosis and the conversion of normal liver architecture into structurally abnormal nodules

End point of chronic liver disease

98

Why can the liver not perform properly when cirrhotic?

Liver cells still present, but portal vein blood bypasses the sinusoids so liver cells cannot perform their functions

99

Why do you get portal hypertension in cirrhosis?

As the pressure inside the liver increases

100

What are the causes of cirrhosis?

- alcohol
- non-alcoholic steatohepatitis (metabolic syndrome)
- chronic viral hepatitis (B and C)
- autoimmune liver disease (primary biliary cirrhosis, primary sclerosing cholangitis)
- metabolic (iron, copper, alpha 1 antitrypsin)

101

Describe the appearance of cirrhosis microscopically

- regenerative nodules of hepatocytes
- surrounded by sheets of fibrous tissue

102

In cirrhosis (the ned stage of all chronic liver disease), the liver is converted into what?

A mass of regenerating nodules wrapped by fibrous scar tissue

103

What are the complications of cirrhosis due to structural changes and fibrosis?

- portal hypertension
- increased blood flow, stiff liver
- pressure rises in portal vein
- oesophageal varices (bleeding can cause massive haemorrhage)

104

What are the complications of cirrhosis due to liver cell failure?

- fewer hepatocytes and blood bypasses sinusoids
- synthetic - oedema, bruising, muscle wasting
- detoxifying - drugs, hormones, encephalopathy
- ascites - low albumin, portal hypertension, hormone fluid retention (aldosterone)
- excretion: bile - jaundice, bile salts - itching

105

Why are patients with cirrhosis vulnerable to infections?

Liver is an important site of immune response (reticulo-endothelial cells)

106

Cirrhosis is a major risk factor for what?

Hepatocellular carcinoma

107

What is the role of liver biopsy in chronic liver disease?

- stage of disease
- cause of disease
- current activity
- response to treatment (if previous biopsies)

108

The benefits of definite diagnosis from liver biopsy is balanced against what?

The risks of haemorrhage and puncture of other organs

109

Name 3 metabolic disease in adults that can be diagnosed by specific changes on liver biopsy

- alpha 1 antitrypsin deficiency
- haemochromatosis
- Wilson disease

110

Describe the effect alpha 1 antitrypsin deficiency on the liver

- A1AT is made in the liver and excreted into the blood where it neutralises proteolytic enzymes (anti-protease)
- abnormal structure of A1AT means it cannot be excreted from hepatocytes
- accumulated A1AT forms globules of glycoprotein
- this damages liver cells and may cause fibrosis and cirrhosis

111

How are globules of glycoprotein due to accumulation of A1AT seen on biopsy?

PAS diastase stain - stain positive

112

How does alpha 1 antitrypsin affect the lungs?

Low levels of A1AT in the serum - failure to inactivate neutrophil enzymes - makes the patient susceptible to emphysema (particularly if they also smoke)

113

What is haemochromatosis?

Abnormality of HFE gene causing failure of iron absorption regulation leading to excess iron accumulating in various organs "bronzed diabetes"

114

Excess iron in liver causes...

Liver injury and eventually cirrhosis as well as high risk of hepatocellular carcinoma

115

Excess iron in pancreases causes...

Diabetes

116

Excess iron in skin causes..

Pigmentation

117

Excess iron in joints causes...

Arthritis

118

Excess iron in heart causes...

Cardiomyopathy

119

Patients with haemochromatosis have high serum levels of what?

Transferrin, and high transferrin saturation

120

How is haemochromatosis treated?

Venesection - deplete iron stores to normal

121

Which stain is used on liver biopsies for haemochromatosis?

Perl's stain: blue = iron

122

What is Wilson disease?

Inborn error of copper metabolism (rare)

123

In Wilson disease, where does copper accumulate?

- liver
- eyes
- brain

But low serum copper due to low caeruloplasmin (copper transport protein)

High urinary copper

124

What does copper accumulation in the liver cause?

Cirrhosis

125

What does copper deposition in the eyes cause?

Kayser-Fleischer rings (ring around the iris)

126

What does copper accumulation in the brain cause?

Ataxia etc.

127

How are live biopsies stained to see Wilson disease?

Rhodanine stain: copper = brown

Biopsy can also be sent to measure amount of copper in grams per dry weight liver tissue

128

What is the treatment for Wilson disease?

Chelate copper and enhance its excretion

129

Some patients with Wilson disease present in what way?

With acute liver failure and haemolysis - this is life-threatening and an indicate for super-urgent liver transplantation

130

What are the systemic effects of liver failure (physical signs of cirrhosis)?

- ascites
- muscle wasting
- bruising
- gynaecomastia
- spider naevi
- caput medusae

131

What is ascites?

Abdominal swelling due to fluid accumulating in the peritoneal cavity

132

What are spider naevi?

Small clusters of dilated capillary vessels in the skin due to hormone imbalance

133

What is kaput medusae?

Dilated veins radiating around the umbilicus in patients with severe portal hypertension, due to recanalisation of the embryonic vitelline vein to the umbilicus

134

What is portal hypertension?

High pressure in hepatic portal vein, bringing blood from GI tract to liver - due to increased stiffness of liver due to fibrosis and hyper dynamic circulation

135

What are the complications associated with portal hypertension?

- splenomegaly = low platelets
- oesophageal varices = risk of haemorrhage
- piles (perianal varices)
- part of cause of ascites

136

The main causes of portal hypertension can be divided into which 3 categories?

- pre-sinusoidal
- sinusoidal
- post-sinusoidal

137

What are the post-sinusoidal causes of portal hypertension?

Hepatic vein thrombosis = Budd Chiari syndrome

138

What are the sinusoidal causes of portal hypertension?

Cirrhosis (disease within liver parenchyma)

139

What are the pre-sinusoidal causes of portal hypertension?

- portal fibrosis in cirrhosis
- non-cirrhostic portal hypertension eg. sarcoid, schistosomiasis, portal vein thrombosis

140

Describe post-sinuoidal portal hypertension

Blood can't flow out of liver due to obstruction between intrahepatic branches of hepatic veins and right atrium

Budd Chiari syndrome is associated with pro-coagulant clotting syndrome

Causes ascites and hepatomegaly

Can be treated by stunting veins and anticoagulation

141

Describe sinusoidal portal hypertension

Liver insufficiency so patients have ascites (low albumin, disrupted metabolism of aldosterone) - so risk of developing liver failure if they have shunt procedure

142

Describe pre-sinusoidal portal hypertension

Liver cell function is well preserved and patient has problems from oesophageal varices and splenomegaly but not ascites - can beg treated by shunt procedure to decompress the portal vein into the hepatic vein