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Y4 - CCC & PC > Rarer Causes of Cirrhosis > Flashcards

Rarer Causes of Cirrhosis Flashcards

1
Q

What is primary biliary cirrhosis?

(also known as primary biliary cholangitis)

A
  • the immune system attacks the small bile ducts in the liver
  • there is obstruction to the outflow of bile, resulting in cholestasis
  • the back-pressure of bile obstruction eventually leads to fibrosis, cirrhosis + liver failure
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2
Q

What 3 factors build up in the blood in primary biliary cirrhosis?

A
  • bile acids
  • cholesterol
  • bilirubin
  • they are usually secreted through the bile ducts into the intestines
  • they build up in the blood when there is an obstruction to their outflow
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3
Q

What is the result of increased bile acids in the blood?

A

pruritis

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4
Q

What is the result of raised bilirubin in the blood?

A

jaundice

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5
Q

What is the result of raised cholesterol in the blood?

A
  • xanthelasma - cholesterol deposits in the skin
  • xanthomas - larger deposits of cholesterol in the skin / tendons
  • cholesterol deposits in blood vessels, increasing the risk of cardiovascular disease
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6
Q

What is the consequence of a lack of bile acids in the gut?

A
  • bile acids aid the gut in digesting fats
  • a lack of bile acids results in malabsorption of fats
  • steatorrhoea occurs as a result
  • steatorrhoea = greasy, fatty stools

the stools are also pale in colour due to a lack of bilirubin, which usually gives them a dark colour

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7
Q

What is the typical presentation of primary biliary cirrhosis?

A
  • pruritis
  • xanthelasma / xanthomas
  • steatorrhoea / pale stools
  • fatigue
  • GI disturbance / abdominal pain
  • jaundice
  • signs of cirrhosis / liver failure (e.g. ascites, spider naevi, splenomegaly)
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8
Q

What are the associations of primary biliary cirrhosis?

A
  • middle-aged women
  • rheumatoid conditions
  • other autoimmune diseases (e.g. thyroid / coeliac)

rheumatoid conditions = RA, Sjogren’s syndrome, systemic sclerosis)

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9
Q

How is primary biliary cirrhosis diagnosed?

A
  • LFTs
  • autoantibodies
  • ESR / IgM are both raised
  • liver biopsy (used for diagnosis and staging of disease)
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10
Q

What do LFTs show in primary biliary cirrhosis?

A
  • ALP is the first liver enzyme to be raised
  • other liver enzymes + bilirubin are raised in later disease

ALP is the first enzyme to be raised in most obstructive pathology

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11
Q

What autoantibodies are present in primary biliary cirrhosis?

A
  • anti-mitochondrial antibodies are most specific to PBC and form part of the diagnostic criteria
  • anti-nuclear antibodies are present in 35%

AMA M2 subtype are highly specific to PBC

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12
Q

What is involved in the treatment of primary biliary cirrhosis?

A
  • ursodeoxycholic acid
  • colestyramine
  • liver transplant (in end-stage liver disease)
  • immunosuppression with steroids considered in some patients
  • fat-soluble vitamin supplementation
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13
Q

What is ursodeoxycholic acid used for?

A

it reduces intestinal absorption of cholesterol

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14
Q

What is colestyramine used for?

A
  • it binds to bile acids to prevent their absorption in the gut
  • this reduces pruritis associated with raised bile acids
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15
Q

What is the disease progression like in primary biliary cirrhosis?

A
  • disease course / symptoms are highly variable
  • some individuals can live decades without symptoms
  • advanced cirrhosis and portal hypertension are the most significant end results
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16
Q

What are the other issues / complications associated with primary biliary cirrhosis?

A
  • distal renal tubular acidosis
  • hypothyroidism
  • osteoporosis
  • hepatocellular carcinoma
  • hyperpigmentation over pressure points
  • finger clubbing

RTA = kidneys fail to remove acids from the blood into the urine, resulting in acidosis

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17
Q

What imaging is required before a diagnosis of PBC can be made and why?

A
  • RUQ USS or MRCP
  • needed to exclude extrahepatic biliary obstruction prior to diagnosis
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18
Q

What is haemochromatosis?

A

an iron storage disorder in which there is excessive total body iron and iron deposition in tissues

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19
Q

What are the majority of cases of haemochromatosis caused by?

A
  • a mutation in the human haemochromatosis protein gene (HFE)
  • this gene is important in regulating iron metabolism
  • this is located on chromosome 6
  • the mutation is autosomal recessive

there are other genes that can less commonly cause haemochromatosis

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20
Q

When does haemochromatosis typically present?

A
  • usually presents around the age of 40
  • this is because it takes time for the iron to build up and become symptomatic
  • it presents later in females (usually post-menopause)
  • menstruation regularly eliminates iron from the body via the bleeding

it usually starts with non-specific symptoms such as lethargy / arthralgia (particularly of the hands)

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21
Q

What are the symptoms of haemochromatosis?

A
  • bronze / slate-grey discolouration of the skin
  • joint pain
  • problems with memory / mood
  • erectile dysfunction / amenorrhoea
  • chronic tiredness
  • hair loss
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22
Q

How is haemochromatosis diagnosed?

A
  • blood tests for ferritin and transferrin saturation are performed
  • if BOTH ferritin + transferrin saturation are raised, genetic testing is performed to confirm the diagnosis

  • transferrin saturation >55% in men or >50% in women
  • ferritin > 500 ug/l
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23
Q

Why can haemochromatosis not be diagnosed through ferritin level alone?

A
  • ferritin is an acute phase reactant
  • it is raised in inflammation
  • transferrin saturation distinguishes between high ferritin due to iron overload (high) or due to inflammation (low / normal)
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24
Q

How did haemochromatosis used to be diagnosed?

A

liver biopsy with Perl’s stain

  • this establishes the iron concentration in the parenchymal cells

it used to be the gold-standard prior to the use of genetic testing

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25
Q

What other investigations may aid in the diagnosis of haemochromatosis?

A

CT abdomen:

  • shows non-specific increase in attenuation of the liver

MRI:

  • gives a more detailed picture of liver deposits of iron
  • can show iron deposits in the heart
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26
Q

What are the potential complications of haemochromatosis?

A
  • type 1 diabetes
  • cirrhosis / HCC
  • cardiomyopathy
  • hypothyroidism
  • arthritis (particularly of the hands)
  • endocrine / sexual problems such as hypogonadism, impotence, infertility & amenorrhoea

endocrine / sexual problems are due to iron deposits in the pituitary gland and gonads

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27
Q

Why does arthritis occur in haemochromatosis?

A
  • calcium deposits in the joints leads to chondrocalcinosis / pseudogout
  • this causes arthritis
chondrocalcinosis
28
Q

What is involved in the management of haemochromatosis?

A
  • venesection
  • monitoring serum ferritin
  • avoid alcohol
  • genetic counselling
  • monitoring / treating complications

venesection = a weekly protocol of removing blood to decrease total iron

  • this should keep transferrin saturation < 50% and ferritin < 50 ug/L
29
Q

What complications of haemochromatosis are irreversible / reversible?

A
30
Q

What is primary sclerosing cholangitis?

A
  • a condition in which the intrahepatic or extrahepatic ducts become strictured and fibrotic
  • this obstructs the flow of bile out of the liver and into the intestines (cholestasis)
  • chronic bile obstruction eventually results in hepatitis, fibrosis + cirrhosis

sclerosis = stiffening / hardening of the bile ducts

cholangitis = inflammation of the bile ducts

31
Q

What causes primary sclerosing cholangitis?

A
  • the cause is unknown
  • it is thought to be due to a variety of genetic, autoimmune and environmental factors
32
Q

What condition is primary sclerosing cholangitis associated with?

A

ulcerative colitis

  • around 80% cases are established alongside UC
  • only 4% of patients with UC have PSC

there are also a less common associations with Crohn’s and HIV

33
Q

What are the risk factors for primary sclerosing cholangitis?

A
  • male gender
  • aged between 30 - 40
  • ulcerative colitis
  • family history
34
Q

How does primary sclerosing cholangitis typically present?

A
  • jaundice
  • pruritis
  • chronic RUQ pain
  • fatigue
  • hepatomegaly
35
Q

What will LFTs show in primary sclerosing cholangitis?

A
  • they show a “cholestatic picture”
  • ALP is raised the most
  • initially, only ALP is raised
  • there may be a rise in bilirubin and the transaminases as the disease progresses to hepatitis
36
Q

Why are autoantibodies measured in primary sclerosing cholangitis?

A
  • there are no autoantibodies that are highly sensitive or specific to PSC
  • they are NOT useful in diagnosis
  • they can indicate whether there is an autoimmune component to the disease that may respond to immunosuppression
37
Q

What autoantibodies are associated with PSC?

A
  • antineutrophil cytoplasmic antibody (p-ANCA) in 94%
  • antinuclear antibodies (ANA) in 77%
  • anticardiolipin antibodies (aCL) in 66%
38
Q

How is primary sclerosing cholangitis diagnosed?

A

magnetic resonance cholangiopancreatography (MRCP)

  • this involves an MRI scan of the liver, bile ducts and pancreas
  • it may show bile duct lesions / strictures

this is the gold-standard

39
Q

What are the associations / complications of PSC?

A
  • fat soluble vitamin deficiency
  • acute bacterial cholangitis
  • colorectal cancer
  • cholangiocarcinoma (10-20%)
  • cirrhosis / liver failure
  • biliary strictures
40
Q

What is involved in the management of PSC?

A
  • ERCP to dilate / stent strictures
  • colestyramine to prevent pruritis caused by raised bile acids
  • monitoring for complications
  • the only curative option is liver transplant
41
Q

What is involved in an ERCP procedure?

endoscopic retrograde cholangio-pancreatography

A
  • an endoscope is inserted to a point in the duodenum where the bile ducts empty into the GI tract
  • it passes through the sphincter of Oddi and into the ampulla of Vater
  • from the ampulla of Vater, the bile ducts can be entered
  • XRs / injecting contrast are used to identify any strictures
42
Q

How can ERCP be used in the management of PSC?

A
  • any identfied biliary strictures can be stented during the same procedure
  • this allows for improved flow through the ducts and symptomatic relief
43
Q

What is Wilson’s disease?

A

the excessive accumulation of copper in the body and its deposition in the tissues

44
Q

What causes Wilson’s disease?

A
  • it is an autosomal recessive inherited disorder
  • caused by a mutation in the ATP7B copper-binding protein
  • this is located on chromosome 13

ATP7B is also referred to as the “Wilson disease protein”

45
Q

When does the onset of symptoms typically begin in Wilson’s disease?

A
  • usually between 10 to 25 years
  • children tend to present with liver disease
  • young adults tend to present with neurological disease
46
Q

How do patients typically present in Wilson’s disease?

A
  • most patients will present with 1 or more of:
  1. hepatic problems (40%)
  2. neurological problems (50%)
  3. psychiatric problems (10%)
47
Q

Why do hepatic problems occur in Wilson’s disease?

A
  • copper deposition in the liver leads to chronic hepatitis
  • this eventually leads to cirrhosis
48
Q

Why do psychiatric / neurological problems occur in Wilson’s disease?

A

due to copper deposition in the central nervous system

49
Q

What are the typical neurological symptoms associated with Wilson’s disease?

A
  • they can be subtle (e.g. concentration / coordination difficulties)
  • dysarthria (speech difficulty)
  • dystonia (abnormal muscle tone)
  • parkinsonism
50
Q

Why does Parkinsonism occur in Wilson’s disease?

How can this be identified?

A
  • due to deposition of copper in the basal ganglia
  • characterised by a triad of rigidity, bradykinesia & tremor
  • these symptoms are symmetrical (opposed to asymmetrical in Parkinson’s disease)
51
Q

What are the psychiatric symptoms associated with Parkinson’s disease?

A
  • can range from mild depression to full psychosis
  • Wilson’s disease is often missed and treatment is delayed
52
Q

What sign is present in the eyes in Wilson’s disease?

A
  • Kayser-Fleischer rings in the cornea
  • they are brown circles surrounding the iris

due to deposition of copper in Descemet’s corneal membrane

53
Q

How are Kayser-Fleischer rings identified?

A
  • they are usually visible to the naked eye
  • proper assessment is made using a slit lamp examination
54
Q

What are the other features associated with Wilson’s disease?

A
  • haemolytic anaemia (destruction of RBCs)
  • renal tubular damage leading to renal tubular acidosis
  • osteopenia (loss of bone mineral density)
  • blue nails
55
Q

What is the initial investigation for Wilson disease?

A

serum caeruloplasmin

  • a LOW serum caeruloplasmin is suggestive of Wilson disease
  • this can be falsely normal / elevated in cancer / inflammatory conditions
  • it is NOT specific to Wilson disease

caeruloplasmin is the protein that carries copper in the blood

56
Q

How is serum copper different in Wilson disease?

A
  • there is REDUCED total serum copper
  • this is because 95% of plasma copper is carried by ceruloplasmin
  • there is also reduced caeruloplasmin
  • there is an increase in free serum copper (not bound by caeruloplasmin)
57
Q

What is the gold-standard test for diagnosing Wilson disease?

A
  • liver biopsy for liver copper content
  • genetic analysis of the ATP7B gene can also be performed
58
Q

Other than biopsy, how else can Wilson disease be diagnosed?

A

24-hour urinary copper excretion

  • this will be elevated
  • this involves collecting all the urine for 24 hours so is rarely performed due to inconvenience
59
Q

What is involved in the treatment of Wilson disease?

A

treatment is with copper chelation

  • penicillamine is the first-line medication
  • trientene hydrochloride can also be used
60
Q

What is alpha-1-antitrypsin deficiency and why does it occur?

A
  • alpha-1-antitrypsin (A1AT) is an enzyme produced in the liver that inhibits neutrophil elastase
  • elastase breaks down connective tissues
  • in A1AT deficiency, there is an autosomal recessive defect in the gene for A1AT
  • this is located on chromosome 14
61
Q

What organs are affected by A1AT deficiency?

A

liver:

  • cirrhosis and HCC in adults after 50 years
  • cholestasis in children

lungs:

  • bronchiectasis and emphysema (i.e. COPD) after 30 years
  • typical presentation is in young patients who are non-smokers
62
Q

Why does liver disease occur in A1AT deficiency?

A
  • an abnormal “mutant” version of A1AT is produced
  • this mutant protein becomes trapped within the liver
  • it builds up to cause liver damage that progresses to cirrhosis and HCC
63
Q

Why does A1AT deficiency cause disease within the lungs?

A
  • the lack of a normal, functioning A1AT leads to an excess of protease enzymes
  • these attack the connective tissue in the lungs
64
Q

How is A1AT deficiency diagnosed?

A
  • there is low serum A1AT
  • genetic testing for the A1AT gene can be performed
  • liver biopsy
  • high-resolution CT thorax to diagnose bronchiectasis / emphysema
65
Q

What is seen on liver biopsy in A1AT deficiency?

A
  • periodic acid-Schiff-positive staining globules in hepatocytes
  • this stain highlights the mutant A1AT proteins

also known as PAS staining

66
Q

What is involved in the management of A1AT deficiency?

A
  • stop smoking (this accelerates emphysema)
  • manage symptoms (e.g. bronchodilators)
  • monitor for complications
  • organ transplant for end-stage liver / lung disease
  • IV alpha-1-antitrypsin protein concentrates are NOT currently recommended by NICE as there is ongoing debate about the possible benefits

Y4 - CCC & PC (34 decks)

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