ZTF Gastro not covered Flashcards
Haemochromatosis, Wilsons Disease, alpha-1 anti trypsin, PBC, PSC
What is haemochromatosis
iron storage disorder that results in excessive total body iron and deposition of iron in tissues
what kind of inheritance pattern is haemochromatosis and which gene is involved
autosomal recessive
The human haemochromatosis protein (HFE) gene is located on chromosome 6.
this gene is important at regulating iron metabolism
in which age range of person does haemochromatosis present
after the age of 40, but later in females due to menstruation acting to regularly eliminate iron from the body
what are the symptoms of haemochromatosis
Chronic tiredness
Joint pain
Pigmentation (bronze / slate-grey discolouration)
Hair loss
Erectile dysfunction
Amenorrhoea
Cognitive symptoms (memory and mood disturbance)
what is the main diagnostic for haemochromatosis
serum ferritin levels
transferrin saturation will be high as it is iron overload
name some other reasons that ferritin may be high
inflammation
non alcoholic fatty liver disease
name the main complications of haemochromatosis
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
what is the management of haemochromatosis
Venesection (a weekly protocol of removing blood to decrease total iron)
Monitoring serum ferritin
Avoid alcohol
Genetic counselling
Monitoring and treatment of complications
What is Wilsons disease
excessive accumulation of copper in the body and tissues
what is the inheritance pattern in Wilsons disease and which chromosome does it affect
“Wilson disease protein” on chromosome 13
autosomal recessive
What are the 3 main features of Wilsons
Hepatic problems (40%) Neurological problems (50%) Psychiatric problems (10%)
what are the main hepatic problems in Wilsons
chronic hepatitis and eventually liver cirrhosis
what are the main neurological problems in Wilsons
concentration and co-ordination difficulties
dysarthria (speech difficulty)
dystonia (abnormal muscle tone)
if deposits in basal ganglia then can get Parkinsonism
what are the main psychiatric symptoms in Wilsons
mild depression to full psychosis
what are the rings called in the cornea that are characteristic of Wilsons disease
Kayser-Fleischer rings
name other features of Wilsons disease
Haemolytic anaemia
Renal tubular damage leading to renal tubular acidosis
Osteopenia (loss of bone mineral density)
how is Wilsons diagnosed
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
what is the management of Wilsons
Treatment is with copper chelation using:
Penicillamine
Trientene
what is the pathophysiology of Alpha-1-antitrypsin deficiency
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.
what two main organs are affected by alpha-1-antitrypsin deficiency and what does this lead to
Liver cirrhosis after 50 years old
Bronchiectasis and emphysema in the lungs after 30 years old
Alpha-1-antitrypsin deficiency in liver means that liver damage progresses to cirrhosis over time and this increases the risk of what cancer
HCC
how is Alpha-1-antitrypsin deficiency diagnosed
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
what is the management of Alpha-1-antitrypsin deficiency
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
what is primary binary cirrhosis (PBC)
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.
what does the build up of the following in the blood cause
bile acids
bilrubin
raised cholesterol
itching
jaundice
xanthelasma
what are the associations with PBC
Middle aged women Other autoimmune diseases (e.g. thyroid, coeliac) Rheumatoid conditions (e.g. systemic sclerosis, Sjogrens and rheumatoid arthritis)
how is PBC diagnosed
which LFT measurement is raised
which autoantibody
what other aspects of the blood
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
what is the treatment of PBC
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
what is primary sclerosing cholangitis (PSC)
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.
which GI condition is associated with PSC
ulcerative colitis, with around 70% of cases being alongside established ulcerative colitis
what are the risk factors of PSC
Male
Aged 30-40
Ulcerative Colitis
Family History
how does PSC present
Jaundice Chronic right upper quadrant pain Pruritus Fatigue Hepatomegaly
what kind of picture with LFTs show in PSC
cholestatic picture
ALP will be the most deranged
no antibodies are highly sensitive or specific to PSC but which ones may be raised in PSC, suggesting it might respond well to immunosuppression
Antineutrophil cytoplasmic antibody (p-ANCA) in up to 94% Antinuclear antibodies (ANA) in up to 77% Anticardiolipin antibodies (aCL) in up to 63%
what is the gold standard for diagnosis of PSC
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.
what are the main associations and complications of PSC
Acute bacterial cholangitis Cholangiocarcinoma develops in 10-20% of cases Colorectal cancer Cirrhosis and liver failure Biliary strictures Fat soluble vitamin deficiencies
name me the fat soluble vitamins
A
D
E
K
what is the management of PSC
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)
