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Yr 4 - CCC > GI: Autoimmune Hepatitis, Wilson's & Haemachromatosis > Flashcards

GI: Autoimmune Hepatitis, Wilson's & Haemachromatosis Flashcards

1
Q

What is autoimmune hepatitis?

A

Autoimmune hepatitis is a rare cause of chronic hepatitis (inflammation in the liver).

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2
Q

What are the 2 types of autoimmune hepatitis?

What are the age distributions?

A

1) Type 1–> affects women in their late forties or fifties

2) Type 2 –> usually affects children or young people, more commonly girls

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3
Q

Who does type 1 autoimmune hepatitis usually affect?

A

Women in their late forties or fifities.

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4
Q

How does type 1 autoimmune hepatitis usually present?

A

Usually presents around or after menopause with fatigue and features of liver disease on examinatio

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5
Q

How does type 2 autoimmune hepatitis usually present?

A

iIt presents with acute hepatitis with high transaminases and jaundice.

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6
Q

Which type of autoimmune hepatitis usually presents more acutely?

A

Type 2

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7
Q

Describe typical LFT findings in autoimmune hepatitis

A

1) High transaminases (ALT and AST)

2) Minimal change in ALP levels (a “hepatitic” picture).

3) Raised immunoglobulin G (IgG) levels

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8
Q

What autoantibodies are seen in type 1 autoimmune hepatitis?

A

1) Anti-nuclear antibodies (ANA)
2) Anti-smooth muscle antibodies (anti-actin)
3) Anti-soluble liver antigen (anti-SLA/LP)

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9
Q

What autoantibodies are seen in type 2 autoimmune hepatitis?

A

1) Anti-liver kidney microsomes-1 (anti-LKM1)
2) Anti-liver cytosol antigen type 1 (anti-LC1)

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10
Q

Liver biopsy forms part of the diagnosis of autoimmune hepatitis.

What are 2 key histology findings?

A

1) Interface hepatitis

2) Plasma cell infiltration

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11
Q

Management of autoimmune hepatitis?

A

1) High dose steroids e.g. prednisolone

2) Other immunosuppressants are also used, particularly azathioprine.

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12
Q

What may be required in end-stage liver disease?

A

Transplant

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13
Q

What is haemochromatosis?

A

Haemochromatosis is an autosomal recessive genetic condition resulting in iron overload.

There is excessive total body iron and deposition of iron in tissues. It is an iron storage disorder.

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14
Q

Where is the human haemochromatosis protein (HFE) gene located?

A

Chromosome 6

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15
Q

The majority of cases of haemochromatosis related to what mutation?

A

C282Y mutations in the human haemochromatosis protein (HFE) gene

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16
Q

What gene is involved in haemochromatosis?

A

The human haemochromatosis protein (HFE) gene

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17
Q

Presentation of haemochromatosis?

A
  • Chronic tiredness
  • Joint pain
  • Pigmentation (bronze skin)
  • Testicular atrophy
  • Erectile dysfunction
  • Amenorrhoea (absence of periods in women)
  • Cognitive symptoms (memory and mood disturbance)
  • Hepatomegaly
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18
Q

At what age does haemochromatosis typically present?

A

Haemochromatosis usually presents after age 40 when the iron overload becomes symptomatic.

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19
Q

Why does haemochromatosis typically present later in women?

A

due to menstruation acting to eliminate iron from the body regularly.

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20
Q

Initial investigation in haemochromatosis?

A

Serum ferritin

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21
Q

What are some causes of a raised ferritin?

A

1) Haemochromatosis
2) Infections (it is an acute phase reactant)
3) Chronic alcohol consumption
4) Non-alcoholic fatty liver disease
5) Hepatitis C
6) Cancer

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22
Q

What test can help distinguish between high ferritin caused by iron overload and other causes?

A

Transferrin saturation

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23
Q

What is transferrin saturation?

A

A transferrin saturation test tells us how much iron in the blood is bound to transferrin

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24
Q

What is transferrin?

A

An iron transport protein.

The amount of transferrin in the blood indicates the amount of iron in the body i.e. high transferrin indicates low iron (as there is less iron bound to transferrin) .

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25
Q

How can transferrin saturation be used to distinguish between high ferritin caused by iron overload and other causes?

A

In high ferritin caused by iron overload –> transferrin is high

In other causes –> transferrin is normal

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26
Q

What is ferritin?

A

Ferritin is a protein that stores iron in your cells.

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27
Q

What are some reversible complications of haemochromatosis?

A

1) Cardiomyopathy
2) Skin pigmentation

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28
Q

When serum ferritin and transferrin saturation are both high, what is the next step?

A

Genetic testing for mutations in the HFE gene

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29
Q

What can be used to establish the iron concentration in the liver?

A

Liver biopsy with Perl’s stain

BUT genetic testing means that a liver biopsy is not usually necessary for establishing a diagnosis.

It may help stage the fibrosis and exclude other liver pathology.

30
Q

What imaging can give a detailed picture and quantify the iron concentration in the liver (avoiding a biopsy)?

A

MRI

31
Q

Complications of haemochromatosis?

A

1) 2ary diabetes (iron affects the functioning of the pancreas)

2) Liver cirrhosis

3) Endocrine and sexual problems (hypogonadism, erectile dysfunction, amenorrhea and reduced fertility)

4) Cardiomyopathy (iron deposits in the heart)

5) Hepatocellular carcinoma

6) Hypothyroidism (iron deposits in the thyroid)

7) Chondrocalcinosis (calcium pyrophosphate deposits in joints) causes arthritis

32
Q

Management of haemochromatosis?

A

1) Venesection (regularly removing blood to remove excess iron – initially weekly)

2) Monitoring serum ferritin

3) Monitoring and treating complications

33
Q

What is Wilson’s disease?

A

Wilson’s disease is an autosomal recessive genetic condition resulting in the excessive accumulation of copper in the body tissues, particularly in the liver.

34
Q

Inheritance of Wilson’s disease?

A

Autosomal recessive

35
Q

Inheritance of haemochromatosis?

A

Autosomal recessive

36
Q

What mutation causes Wilson’s?

A

It is caused by mutations in the Wilson disease protein gene on chromosome 13 (also called the ATP7B copper-binding protein).

This copper-transporting protein is important in helping remove excess copper from the body via the liver.

37
Q

How is copper excreted?

A

In the bile

38
Q

When does Wilson’s disease typically present?

A

Wilson’s disease typically presents in teenagers or young adults (rare for symptoms to start after age 40).

39
Q

How does Wilson’s typically present?

A

Liver problems usually arise first

Rarely it can present initially with neurological or psychiatric problems, although these typically occur with more advanced disease.

40
Q

How does Wilson’s affect the liver?

A

Copper deposition in the liver leads to chronic hepatitis, eventually leading to cirrhosis.

41
Q

Features of Wilson’s?

A
  • Liver: chronic hepatitis, cirrhosis
  • Neurological e.g. tremor, dysarthria, dystonia, Parkinsonism (tremor, bradykinesia and rigidity)
  • Psychiatric e.g. abnormal behaviour, depression, cognitive impairment and psychosis.
  • Kayser-Fleischer rings
  • Haemolytic anaemia
42
Q

What are Kayser-Fleischer rings?

A

Kayser-Fleischer rings in the cornea (deposition of copper in Descemet’s membrane) may be seen in Wilson’s disease.

These are green-brown circles surrounding the iris of the eye.

They can usually be seen by the naked eye but proper assessment is made using slit lamp examination.

43
Q

What is the initial screening test for suspected Wilson’s disease?

A

Serum caeruloplasmin

44
Q

What serum caeruloplasmin indicates Wilson’s?

A

A low serum caeruloplasmin is suggestive of Wilson’s

45
Q

What is caeruloplasmin?

A

Caeruloplasmin is the protein that carries copper in the blood.

46
Q

What can caeruloplasmin be falsely normal or elevated?

A

In cancer or inflammatory conditions.

47
Q

Investigations in Wilson’s?

A

1) Serum caeruloplasmin

2) A 24-hour urine copper assay

3) Liver biopsy

4) Scoring systems

48
Q

What will a 24-hour urine copper assay show in Wilson’s?

A

High urinary copper

49
Q

What is a characterstic MRI sign in Wilson’s?

A

“double panda sign”

50
Q

Management of Wilson’s?

A

Treatment is with copper chelation using either:

1) Penicillamine
2) Trientine

Other possible treatments:
- Zinc salts (inhibit copper absorption in the gastrointestinal tract)
- Liver transplantation

51
Q

What are the 2 options for copper chelation in Wilson’s?

A

1) Penicillamine
2) Trientine

52
Q

What is alpha-1 antitrypsin deficiency?

A

A genetic condition caused by low levels of alpha-1 antitrypsin.

53
Q

What are the 2 main organs affected by alpha-1 antitrypsin deficiency?

A

1) lungs
2) liver

54
Q

How does alpha-1 antitrypsin deficiency affect the lungs?

A

Can cause COPD and bronchiectasis (typically after 30 years old)

55
Q

How does alpha-1 antitrypsin deficiency affect the liver?

A

Dysfunction, fibrosis and cirrhosis of the liver (depending on the specific genotype)

56
Q

What gene is involved in alpha-1 antitrypsin?

What chromosome is it found on?

A

The SERPINA1 gene coding for alpha-1 antitrypsin is found on chromosome 14.

57
Q

How is a-1 antitrypsin deficiency inherited?

A

autosomal co-dominant pattern

58
Q

What is a co-dominant inheritance pattern?

A

Co-dominant refers to when both gene copies are expressed and contribute to the outcome (neither is dominant or recessive over the other).

The disease severity results from the combination of both copies of the gene.

59
Q

What is alpha 1 antitrypsin?

A

A protease inhibitor.

60
Q

What is a critical protease enzyme that is inhibited by alpha-1 antitrypsin?

A

Neutrophil elastase.

This enzyme is secreted by neutrophils and digests elastin (elastolysis). Elastin is a protein in connective tissue that helps keep the tissues flexible.

Alpha-1 antitrypsin (AAT) offers protection by inhibiting the action of neutrophil elastase.

61
Q

How does alpha-1 antitrypsin deficiency affect the lungs (pathophysiology)?

A

In the lungs, the lack of alpha 1 antitrypsin leads to excess protease enzymes attacking the connective tissues.

Destruction of elastic tissue in the lungs leads to bronchiectasis and emphysema.

62
Q

What dramatically accelerates lung damage in Alpha-1 antitrypsin deficiency?

A

Smoking

63
Q

Where is alpha-1 antitrypsin produced?

A

Liver

63
Q

Less commonly, what else can alpha 1 antitrypsin deficiency be associated with?

A

1) Panniculitis (tender skin nodules caused by inflammation of the subcutaneous fat)

2) Granulomatosis with polyangiitis (a small and medium vessel vasculitis)

64
Q

What is diagnosis of alpha-1 antitrypsin deficiency based on?

A

1) Low serum alpha-1 antitrypsin (the screening test)

2) Genetic testing

65
Q

How can lung damage in alpha-1 antitrypsin deficiency be assessed?

A

Chest x-ray
High-resolution CT thorax
Pulmonary function tests

66
Q

Pathophysiology of alpha-1 antitrypsin deficiency in the liver?

A

1) In specific genotypes of alpha-1 antitrypsin deficiency, an abnormal mutant version of the protein is made that gets trapped and builds up inside the liver cells (hepatocytes).

2) These mutant proteins are toxic to the hepatocytes, causing inflammation.

3) Over time this progresses to fibrosis, cirrhosis and potentially hepatocellular carcinoma.

67
Q

What can a liver biopsy show in alpha-1 antitrypsin deficiency?

A

Liver biopsy shows periodic acid-Schiff positive staining globules in hepatocytes, resistant to diastase treatment. These represent a buildup of the mutant proteins.

68
Q

Management of alpha-1 antitrypsin deficiency?

A

1) Stop smoking
2) Symptomatic management (e.g., standard treatment of COPD)
3) Organ transplant for end-stage liver or lung disease
4) Monitoring for complications (e.g., hepatocellular carcinoma)
5) Screening of family members

Giving an infusion of alpha-1 antitrypsin to boost the levels is possible, but there is doubt about the clinical benefit and cost.

69
Q
A

Yr 4 - CCC (54 decks)

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