B12 and folate def Flashcards
what is it B12 required for?
- DNA synthesis
- integrity of immune system
what is folic acid required for?
- DNA synthesis (dUMP –> dTMP needs methyl group from folate)
- homocystine metabolism
what cells are affected in B12 and folate def?
- all rapidly dividing cells affected
- i.e. bone marrow, epithelial surfaces of gut gonads, embryos
what are the clinical features of B12 and folate def?
- anaemia
- jaundice
- glossitis
- angular cheilosis (red swollen patches at corner of mouth)
- sterility (affects rapidly dividing sperm cell)
describe the red cells when there is a deficiency of B12 or folate
- LARGE red cells
- LARGE MCV
- macrocytic and megaloblastic anaemia
what does megaloblastic mean?
- morphological change in RBC precursors within bone marrow
what else can cause macrocytic anaemia?
- liver disease
- hypothyroidism
- drugs
- haematological disorders
describe normal RBC maturation
- erythoblast
- normoblast
- reticulocyte
- RBC
what is the colour change during RBC maturation?
- basophilic (blue)
- polychromatic
- RBC pink
what is megaloblastic anaemia?
asychronous maturation of nucleus and cytoplasm in erythoid series
in megaloblastic anaemia, what is the appearance of peripheral blood?
- anisocytosis
- large RBCs
- hypersegmented neutrophils
- giant metamyelocytes
if someone has macrocytosis, what are some tests you can do?
- blood test (folate, iron, B12)
- thyroid function test
- reticulocyte count and blood film
why do you do a thyroid function test?
- thyroid disease causes a macrocytosis and not a megaloblastic anaemia
what are the 2 possible clinical disorders that cause a hypersegmented neutrophil?
- B12/folate def
where is folate present?
- fresh leafy veg
- destroyed by overcooking/canning/processing
what are the causes of folate def?
- dec. intake
- inc. demand (physiological = pregnancy, adolescence, premature babies. Pathological = malignancy, HA)
what are the consequences of folate def?
- megaloblastic, macrocytic anaemia
- neural tube defects in developing foetuses
- inc, risk of thrombosis
consequences of B12 def?
- neurological problems (bilateral peripheral neuropathy)
- paraesthesia
- muscle weakness
- difficult walking
- visual impairment
- psychiatric disturbance
what would you see in an exam of someone with B12 def?
- absent reflexes and upgoing plantar responses
- combo of upper and lower motor neuron signs
what are the causes of B12 def?
- poor absorption
- reduced dietary intake (difficult for this as stores are large)
- infections
what are the 2 methods of absorption of B12?
- 1%: slow and inefficient absorption through duodenum
2. 99%: B12 combines with IF and this binds to Ileum receptors in ileum
what causes impaired B12 absorption?
- reduction in IF (post gastrectomy, gastric atrophy, Pernicious anaemia)
- diseases of small bowel (Chron’s, coeliac, surgical resection)
- infections/infestations (H. Pylori, giardia)
- drugs (metformin, the pill, PPIs)
what is pernicious anaemia?
AI condition ass/ w/ severe lack of intrinsic factor
what is there a presence of in PA?
- Intrinsic factor antibodies: occasionally found in other conditions
- parietal cell antibodies: 90% in adults with PA but also in 16% of NORMAL females over 60
so in patients with low B12, what should you measure?
- antibodies to parietal cells and IF
- antibodies for coeliac
- breath test ofr bacterial overgrowth
- stool test for H. pylori and test for giardia
- Shilling test
what is part 1 of Shilling test?
- give injections of B12 to saturate stores
- then pt drinks radiolabelled B12
- measure excretion of B12 in urine
- normally expect it to come out in urine as stores are full
- if none in urine, possibilities: not absorbing B12 (PA, small bowel disease), hasn’t corrected B12 def before test
what is part 2 of the Shilling’s test?
repeat test but with addition of IF and measure excretion of B12 in urine
what would be seen in these tests in someone with PA with autoantibodies to B12
P1: low, P2: normal
what is the treatment of B12 def?
- injections of B12 (3x a week for 2 weeks and thereafter every 3 month)
- if neurological involvement, B12 injections alternate days until no further improvement
