CPT2: Anaemia 3 Flashcards
What is megaloblastic anaemia?
What causes this?
What does this mean in terms of MCV and role of RBC?
- Anaemias characterised by large (megaloblastic/ macrocytic) immature & dysfunctional RBCs
- Caused by inhibition of - DNA synthesis and maturation of haematopoeitic cells in bone marrow due to lack of B12 and Folate which are the building blocks for these processes
- Characterised by a raised MCV:
- As RBC are bigger there is space for fewer RBC therefore less Hb therefore less O2 carrying capacity.
- They may also be too big to move from bone marrow to blood stream
Prevalance
- •Vitamin B12 deficiency (UK&US) - approx. 6% in people less than 60yrs.
- For people over 60 yrs - approx 20%.
- Adult pernicious anaemia (most common cause of B12 deficiency and megaloblastic anaemia) – affects women more (1.6:1)
- Most common in 40–70 age group
- Mean age of onset - 60yrs (white people) 50 yrs (black people), with a biomodal distribution due to an increased occurrence in young black females.
- Folate deficiency - serum folate below WHO clinical threshold [7 nanomol/L]) amongst adults and children is no more than 5%.
Where do we get our source of Vit B12 from?
What patients can be particularly affcted from Vit B12 deficency?
How is Vit B12 absorbed?
How would a gasterocetomy affect absorption?
- Dependent on dietary intake: meat, fish, eggs, milk (normally from animal products)
- Strict vegans (around 11% are deficient) - fortified cereals good source
- Vit B12 is absorbed from the ileum of the intestine, with assiatance from binding with intrinsic factor produced by the stomach.
- Patients with total/partial gastrectomy are at risk as part of all of the stomach is removed. This means Vit B12 may not be produced therefore there is poor absorption of Vit B12
Where do we get folate from?
When does folate defiency anaemia occur?
- Dependent on dietary intake: broccoli, brussels sprouts, asparagus, peas, chickpeas and brown rice, fortified breakfast cereals, some bread and oranges, bananas
- Deficiency occurs when there is – a decrease in intake or increase in demand (e.g. pregnancy, lactation)
What is the aetiology of:
- Vit B12 defiency anaemia?
- Folate defiency anaemia?
- Pernicious anaemia?
Vitamin B12 deficiency:
- Occurs due to inadequate intake or malabsorption
- Beware of drug causes e.g. Metformin à reduced B12
Folate deficiency anaemia:
- Occurs when demand for folate outweighs supply
- Adequate dietary intake is essential
- Main cause of folate malabsorption is gluten-induced enteropathy
- Beware of drugs interfering with folate – anti-epileptics
Pernicious anaemia:
- Reduced Vit B12 absorption due to lack of intrinsic factor
What are the alternative names for:
- Vit B12
- Folate?
- cobalamin
- Vit B9 or Folacin
What are cobalamin/ Vit B12 functions?
- Neurological function
- DNA synthesis (building block component) for RBC formation
Describe the absorption of Vit B12
Vit B12 enters the body through ingestion of supplementation. It binds to the glycoprotein, intrinisic factor, produced by the parietal cells of the stomach. This complex travels to the ileum where it binds to IF surface recptors which leads to absorbtion of Vit B12 by pinocytosis and it is stored in the liver
Causes of Vit B12 defiency anaemia
Most common cause of severe deficiency- Pernicious anaemia - IF production decreases therefore Vit B12 absorption decreases (malabsorption)
Less common causes:
- Drugs - colchicine, metformin, NO, PPIs, H2-RA’s.
- Gastric - total/partial gastrectomy, congenital IF deficiency/abnormality, Zollinger-Ellison syndrome.
- Inherited - intrinsic factor receptor deficiency (Imerslund Gräsback syndrome)
- Intestinal - malabsorption, ileal resection, Crohn’s disease, parasites (e.g. giardiasis, fish tapeworm).
- Nutritional - malnutrition, vegan diet. Cooking does not destroy Vit B12
What happens in pernicious anameia?
What can it increase risk of?
What can it be associated with?
Autoimmune origin
- Atrophy of gastric mucosa leads to reduction of parietal cells which means less IF secretion therefore reduced Vit B12 absorption
- People with Pernicious anaemia at slight increased risk of gastric cancer
- Associated with other autoimmune diseases (e.g. myxoedema, thyrotoxicosis, Addison’s disease)
What are symptoms of Megaloblastic anaemia in addition to normal anaemia symptoms?
- Onset is gradual and progressive:
- Bilateral periphary neuropathy - damage to nerves in periphery leading to numbness and weakness - usually hands and feet
- Increases suceptibility to infections
- Depression, confusion, memory loss, fatigue
What diagnostic investigations should be carried out to confirm megaloblastic anaemia?
IMPORTANT TABLE
- HCT - lower?
What are levels of folate and Vit B which could be used to confirm diagnosis of Megaloblastic anaemia?
Why do you need to be careful with this?
- Vit B12, Cobalamin levels- Below 200 nanograms/L (148 picomol/L) sensitive enough to diagnose 97%
- Beware! levels don’t always correlate with clinical symptoms
- Oral contraceptive use – lower cobalamin levels
- Reference values/units can differ between labs
- Folate levels - less than 7 nanomol/L (3 micrograms/L) used as a “guide”
What are non-megaloblastic causes of macrocytosis?
Non-megaloblastic causes of macrocytosis:
- Alcohol (affects ability to absorb Vit B12)
- Smoking
- Drugs – antimetabolites (e.g. Methotrexate, Azathioprine)
- Liver disease - chronic
- Haematological abnormalities
- Thyroid deficiency - severe
- Pregnancy
What are the goals of therapy?
- Treat underlying cause
- Check history - Hx of autoimmune disease, Diet, Meds
- Replacement therapy to replenish stores and improve symptoms
- Slow progression of neuropathy in Vit B12 deficiency
- Before treatment is started it is essential to identify if patient suffers from Vit B12 or folate deficiency or both
