ZTF Gastro not covered

Question 1

What is haemochromatosis

Answer 1

iron storage disorder that results in excessive total body iron and deposition of iron in tissues

Question 2

what kind of inheritance pattern is haemochromatosis and which gene is involved

Answer 2

autosomal recessive
The human haemochromatosis protein (HFE) gene is located on chromosome 6.
this gene is important at regulating iron metabolism

Question 3

in which age range of person does haemochromatosis present

Answer 3

after the age of 40, but later in females due to menstruation acting to regularly eliminate iron from the body

Question 4

what are the symptoms of haemochromatosis

Answer 4

Chronic tiredness
Joint pain
Pigmentation (bronze / slate-grey discolouration)
Hair loss
Erectile dysfunction
Amenorrhoea
Cognitive symptoms (memory and mood disturbance)

Question 5

what is the main diagnostic for haemochromatosis

Answer 5

serum ferritin levels

transferrin saturation will be high as it is iron overload

Question 6

name some other reasons that ferritin may be high

Answer 6

inflammation

non alcoholic fatty liver disease

Question 7

name the main complications of haemochromatosis

Answer 7

Type 1 Diabetes (iron affects the functioning of the pancreas)

Liver Cirrhosis

Iron deposits in the pituitary and gonads lead to endocrine and sexual problems (hypogonadism, impotence, amenorrhea, infertility)

Cardiomyopathy (iron deposits in the heart)

Hepatocellular Carcinoma

Hypothyroidism (iron deposits in the thyroid)

Chrondocalcinosis / pseudogout (calcium deposits in joints) causing arthritis

Question 8

what is the management of haemochromatosis

Answer 8

Venesection (a weekly protocol of removing blood to decrease total iron)
Monitoring serum ferritin
Avoid alcohol
Genetic counselling
Monitoring and treatment of complications

Question 9

What is Wilsons disease

Answer 9

excessive accumulation of copper in the body and tissues

Question 10

what is the inheritance pattern in Wilsons disease and which chromosome does it affect

Answer 10

“Wilson disease protein” on chromosome 13

autosomal recessive

Question 11

What are the 3 main features of Wilsons

Answer 11

Hepatic problems (40%)
Neurological problems (50%)
Psychiatric problems (10%)

Question 12

what are the main hepatic problems in Wilsons

Answer 12

chronic hepatitis and eventually liver cirrhosis

Question 13

what are the main neurological problems in Wilsons

Answer 13

concentration and co-ordination difficulties
dysarthria (speech difficulty)
dystonia (abnormal muscle tone)
if deposits in basal ganglia then can get Parkinsonism

Question 14

what are the main psychiatric symptoms in Wilsons

Answer 14

mild depression to full psychosis

Question 15

what are the rings called in the cornea that are characteristic of Wilsons disease

Answer 15

Kayser-Fleischer rings

Question 16

name other features of Wilsons disease

Answer 16

Haemolytic anaemia
Renal tubular damage leading to renal tubular acidosis
Osteopenia (loss of bone mineral density)

Question 17

how is Wilsons diagnosed

Answer 17

The initial investigation of choice is serum caeruloplasmin. A low serum caeruloplasmin is suggestive of Wilson disease. This is the protein that carries copper in the blood.

liver biopsy for liver copper content is gold standard

Question 18

what is the management of Wilsons

Answer 18

Treatment is with copper chelation using:

Penicillamine
Trientene

Question 19

what is the pathophysiology of Alpha-1-antitrypsin deficiency

Answer 19

Elastase is an enzyme secreted by neutrophils.

This enzyme digests connective tissues. Alpha-1-antitrypsin (A1AT) is mainly produced in the liver, travels around the body and offers protection by inhibiting the neutrophil elastase enzyme.

A1AT is coded for on chromosome 14. In A1AT deficiency, there is an autosomal recessive defect in the gene for A1AT.

Question 20

what two main organs are affected by alpha-1-antitrypsin deficiency and what does this lead to

Answer 20

Liver cirrhosis after 50 years old

Bronchiectasis and emphysema in the lungs after 30 years old

Question 21

Alpha-1-antitrypsin deficiency in liver means that liver damage progresses to cirrhosis over time and this increases the risk of what cancer

Answer 21

HCC

Question 22

how is Alpha-1-antitrypsin deficiency diagnosed

Answer 22

Low serum-alpha 1-antitrypsin (screening test of choice)

Liver biopsy shows cirrhosis and acid-Schiff-positive staining globules (this stain highlights the mutant alpha-1-antitrypsin proteins) in hepatocytes

Genetic testing for the A1AT gene

High resolution CT thorax diagnoses bronchiectasis and emphysema

Question 23

what is the management of Alpha-1-antitrypsin deficiency

Answer 23

Stop smoking (smoking dramatically accelerates emphysema)
Symptomatic management
NICE recommend against the use of replacement alpha-1-antitrypsin, however the research and debate is ongoing regarding the possible benefits
Organ transplant for end-stage liver or lung disease
Monitoring for complications (e.g. hepatocellular carcinoma) - AFP

Question 24

what is primary binary cirrhosis (PBC)

Answer 24

the immune system attacks the small bile ducts within the liver.

The first parts to be affected are the intralobar ducts, also known as the Canals of Hering.

This causes obstruction of the outflow of bile, which is called cholestasis.

The back-pressure of the bile obstruction and the overall disease process ultimately leads to fibrosis, cirrhosis and liver failure.

Question 25

what does the build up of the following in the blood cause bile acids bilrubin raised cholesterol

Answer 25

itching jaundice xanthelasma

Question 26

what are the associations with PBC

Answer 26

``` Middle aged women Other autoimmune diseases (e.g. thyroid, coeliac) Rheumatoid conditions (e.g. systemic sclerosis, Sjogrens and rheumatoid arthritis) ```

Question 27

how is PBC diagnosed which LFT measurement is raised which autoantibody what other aspects of the blood

Answer 27

Liver Function Tests Alkaline phososphatase is first liver enzyme to be raised (as with most obstructive pathology) Other liver enzymes and bilirubin are raised in later disease Autoantibodies Anti-mitochondrial antibodies is the most specific to PBC and forms part of the diagnostic criteria Anti-nuclear antibodies are present in about 35% of patients Other blood tests: ESR raised IgM raised Liver biopsy is used in diagnosing and staging the disease

Question 28

what is the treatment of PBC

Answer 28

Ursodeoxycholic acid reduces the intestinal absorption of cholesterol Colestyramine is a bile acid sequestrate in that it binds to bile acids to prevent absorption in the gut and can help with pruritus due to raised bile acids Liver transplant in end stage liver disease Immunosuppression (e.g. with steroids) is considered in some patients

Question 29

what is primary sclerosing cholangitis (PSC)

Answer 29

a condition where the intrahepatic or extrahepatic ducts become strictured and fibrotic. This causes an obstruction to the flow of bile out of the liver and into the intestines. Sclerosis refers to the stiffening and hardening of the bile ducts, and cholangitis is inflammation of the bile ducts. Chronic bile obstruction eventually leads to liver inflammation (hepatitis), fibrosis and cirrhosis.

Question 30

which GI condition is associated with PSC

Answer 30

ulcerative colitis, with around 70% of cases being alongside established ulcerative colitis

Question 31

what are the risk factors of PSC

Answer 31

Male Aged 30-40 Ulcerative Colitis Family History

Question 32

how does PSC present

Answer 32

``` Jaundice Chronic right upper quadrant pain Pruritus Fatigue Hepatomegaly ```

Question 33

what kind of picture with LFTs show in PSC

Answer 33

cholestatic picture | ALP will be the most deranged

Question 34

no antibodies are highly sensitive or specific to PSC but which ones may be raised in PSC, suggesting it might respond well to immunosuppression

Answer 34

``` Antineutrophil cytoplasmic antibody (p-ANCA) in up to 94% Antinuclear antibodies (ANA) in up to 77% Anticardiolipin antibodies (aCL) in up to 63% ```

Question 35

what is the gold standard for diagnosis of PSC

Answer 35

MRCP, which is short for magnetic resonance cholangiopancreatography. This involves an MRI scan of the liver, bile ducts and pancreas. In primary sclerosis cholangitis it may show bile duct lesions or strictures.

Question 36

what are the main associations and complications of PSC

Answer 36

``` Acute bacterial cholangitis Cholangiocarcinoma develops in 10-20% of cases Colorectal cancer Cirrhosis and liver failure Biliary strictures Fat soluble vitamin deficiencies ```

Question 37

name me the fat soluble vitamins

Answer 37

A D E K

Question 38

what is the management of PSC

Answer 38

Liver transplant can be curative but is associated with its own problems (around 80% survival at 5 years). ERCP can be used to dilate and stent any strictures Ursodeoxycholic acid is used and may slow disease progression Colestyramine is a bile acid sequestrate in that it binds to bile acids to prevent absorption in the gut and can help with pruritus due to raised bile acids Monitoring for complications (such as cholangiocarcinoma, cirrhosis and oesophageal varices)