GI (+hepatobiliary) Flashcards
(20 cards)
what is haemochromatosis
autosomal recessive condition → problems with iron absorption + metabolism → iron accumulation in the body
excessive total body iron and deposition of iron in tissues
what is the genetic problem in haemochromatosis
- autosomal recessive inheritance
- mutation in both (recessive) copies of HFE gene on **chromosome 6 **
- HFE gene codes for human haemochromatosis protein - regulates iron metabolism in the body
iron levels slowly build up in the body over many years
what 2 parameters are used to monitor treatment in haemochromatosis
- serum ferritin (reflective of iron stores in body)
- transferrin saturation (amount of iron bound to this protein in the blood)
All patients diagnosed with haemochromatosis undergoing venesection should have monitoring of their transferrin saturation and serum ferritin until these are within range.
what marker is the first to rise in haemochromatosis
transferrin saturation
why is it important to measure serum ferritin during treatment of haemochromatosis
- ferritin = useful prognostic indicator of cirrhosis (ferritin is iron stores in body)
- it’s also used to monitor a complication of the treatment known as **iron avidity ** which is when pts are OVERTREATED → low/normal ferritin and high transferrin sat
Iron avidity = treated with iron supplementation/monitored till ferritin returns to normal
screening for iron overload?
tests for haemochromatosis
- general population = BLOOD TESTS transferrin saturation - considered the most useful marker (better than ferritin which can also be used but usually not abnormal in early stages of iron accumulation)
- family members - testing for the **HFE gene mutation **
haemochromatosis: 1st line management
Regular venesection (phlebotomy)- mainstay of treatment - initially every week (induction) → 2-4 times a year for the rest of your life (maintenance)
transferrin should be kept < 50% and serum ferritin < 50ug/l
Usually around 500ml of blood is removed - The removed blood includes red blood cells that contain iron, and your body will use up more iron to replace them, helping to reduce the amount of iron in your body.
50!!!!!!!!!!!!
serum ferritin and transferrin saturation are monitored
haemochromatosis: 2nd line management
Desferrioxamine (chelation therapy - used to help remove iron from blood and helps excrete it via urine/poo)
used in cases where regular phlebotomies are not possible because it’s difficult to remove blood regularly – for example, if you have very thin or fragile veins.
typical iron study profile in a pt w haemochromatosis
- transferrin saturation: men > 55%, women > 50% (raised if there is iron overload)
- raised serum ferritin (e.g. > 500 ug/l) and iron
- low TIBC (most of the transferrin is used up)
if serum ferritin and transferrin saturation are both high and there’s no other explanation for this, then **genetic testing is done to confirm the Dx **
if serum ferritin is high, then transferrin sat will help differentiate if it is due to iron overload or other stuff like inflam - so if iron overload transferrin sat will be high otherwise will be low/normal
other than core Ix for iron overload what other Ix are done for haemochromatosis
- LFTs
- to check the liver: Fibroscan (USS), MRI (helps quantify amount of iron in liver without need for biopsy)
- ECG/echo to check the heart (MRI can also be done for the heart to look for iron deposits)
- liver biopsy - only if cirrrhosis is suspected
- molecular genetic testing for the C282Y and H63D mutations (mutations other than HFE that can cause haemachormatosis)
haemochromatosis: typical age of presentation
over the age of 40 (usually between ages of 30-60)
* it takes time before enough iron builds up in the body for it to become symptomatic
in which gender does haemochromatosis present later and why
- haemochromatosis presents even later in females - because menstruation helps eliminate iron from the body
- Sx usually occur after the menopause (no menstruation to get rid of the iron anymore)
so it takes longer before the iron builds up enough for it to cause Sx
clinical features of haemochromatosis
iron deposition
* in joints: joint pain
* in skin: bronze discolouration
head stuff:
* hair loss
* tiredness
* cognitive problems - brain fog (memory), mood swings
sexual problems:
* ED - inability to get/maintain erections
* amenorrhoea (missed/irregular periods)
* loss of libido
* testicles becoming smaller
complications
high levels of iron depositing in certain parts of the body:
* liver - cirrhosis (scarring) → cancer (hepatocellular carcinoma): jaundice, abdominal swelling
* heart - cardiomyopathy (deposits) → HF, arrythmias: chest pain, SOB, oedema
* pancreas - T1DM (function of pancreas is affected): polyuria+polydipsia
* joints - chrondrocalcinosis (calcium deposits in joints due to iron overload) → arthritis
* brain (pituitary gland): amenorrhoea, hypogonadism, infertility
* hypothyroidism (if iron deposited in thyroid glands)
haemochromatosis: more common in which ethnic background
People with Celtic background - Irish, Scottish, Welsh
diet + lifestyle advice for pts with haemochromatosis
- avoid XS alcohol: increases iron levels + puts strain on liver
- avoid taking vit C and iron supplements
- be careful not to eat raw oysters and clams as these can contain a bacteria that can cause serious infections in people with high iron levels
bacteria = Vivrio Vulnificus which thrives in iron rich environments
causes of high iron levels other than haemochromatosis
- receiving regular blood transfusions: sickle cell, thalassemia
- renal dialysis (these pts often receive IV iron to combat anaemia)
- excessive intake: supplements, injections
- long-term liver conditions: cirrhosis
- alcohol misuse
- rare inherited conditions: atransferrinemia (problem w protein that transports iron), aceruloplasminemia (abnormal protein meaning iron accumulates in certain organs e.g. brain)
Alcohol misuse can lead to high iron levels primarily by disrupting the body’s iron regulation processes, particularly through affecting the hormone hepcidin. Hepcidin controls iron absorption and release, and alcohol consumption can suppress hepcidin production, leading to increased iron absorption and storage. Additionally, alcohol can damage the liver, which is a major site for iron storage and regulation, contributing to iron overload.
what is serum ferritin and why may it be unreliable
serum ferritin is a type of iron in the body, it is an acute phase reactant which means it can go up if there’s inflammatory conditions in the body making it unreliable for Dx of haemochromatosis
serum ferritin can be high for causes other than haemochromatosis
conditions where serum ferritin can be high
- Haemochromatosis
- Infections (it is an acute phase reactant)
- Chronic alcohol consumption
- Non-alcoholic fatty liver disease
- Hepatitis C
- Cancer
what was previously the gold standard Ix for diagnosing haemochromatosis
Liver biopsy using Perl’s stain - which helps identify the iron conc in the parenchymal cells of the liver
not used anymore due to availability of genetic testing
