B12 and folate deficiencies

Question 1

what is the role of both B12 and folate *

Answer 1

DNA synthesis

Question 2

what is the effect of absence of B12 and folate *

Answer 2

severe anaemia - fatal

Question 3

what is just B12 used for *

Answer 3

integrity of the nervous system

Question 4

what is just folic acid used for *

Answer 4

homocystine metabolism

Question 5

how are folate and B12 involved in dna synthesis *

Answer 5

dUMP (deoxy urinodine monophosphate) is converted to dTMP (deoxy thymidine monophosphate) by the transfer of a CH3 group - dTMP goes on to become DNA

dUMP gets the CH3 group from 5,10 methylene THF-polyglutamate

THf-polyglutamte becomes DHF polyglutamate when it gives up teh CH3

DHF glutamate is converted back to DHF glutamate but needs diety folate to be converted to THF whhich requires B12 - so need both folate and B12

folate also is involved in the conversion of homocystiene which is toxic to methionine

Question 6

what is affected by B12 and phosphate *

Answer 6

all rapidly dividing cells:

bone marrow

epi cells of mouth and gut - produce lots of cells on daily basis)

gonads - spermatogeneis

embryos

Question 7

what are symptoms of B12 and folate deficiency *

Answer 7

anaemia - weak, tired, short of breath

jaundice - break red cells down = increased BR

problems with GI tract - glossitis (inflammed tongue) and angular cheilosis (cracks in thecorner of mouth)

sterility in males

Question 8

what are the 2 types of anaemia caused by B12 or folate acid deficiency *

Answer 8

(anaemia with a high MCV)

macrocytic

megaloblastic

Question 9

what is macrocytic anaemia *

Answer 9

average red cell is above the normal range

descriptive term

Question 10

causes of macrocytic anaemia *

Answer 10

vit B12/folate deficiency

liver disease/alcohol

hypothyroid

drugs eg azathroprine - immunosuppressant

haematological disorders - myelodysplasia, aplastic anaemia, reticulocytosis eg chronic haemolytic anaemia

Question 11

what is megaloblastic anaemia *

Answer 11

describes a morphalogical change in teh red cell precursers within the bone marrow

Question 12

what is the cause for megaloblastic anaemia *

Answer 12

b12 and folate deficiency

Question 13

describe normal red cell maturation *

Answer 13

erythroblast - earliest recognisable form visually - nucleus and lots of proteins = blue

normoblast - early/intermediate/late - this depends on colour, cytoplasm gets more pink

nucleus gets smaller and pyknotic

reticulocyte - maybe some nucleic acid

circulating red blood cell - no nucleus and lots of hb

Question 14

describe red cell maturation in megaloblastic anaemia *

Answer 14

asynchronus maturation of the nucleus and cutoplasm in the erythroid series

maturing red cells are seen in the bone marrow

Question 15

what is present in the periperal blood in megaloblastic anaemia *

Answer 15

anisocytosis

large red cells

hypersegmented neutrophils - DNA production is affected

giant metamyelocytes

red cells have mature (red) cytoplasm but nucleus = immaturity in nucleus development

Question 16

slide with asynchronus development of red cell *

Answer 16

Question 17

describe hypersegmented neutrophil *

Answer 17

can tell neutrophil because hypersegmented

have >5 lobules

associated with megaloblastic change - ie folate or B12 deficiency

Question 18

what tests would you do on someone with macrocytosis *

Answer 18

folate and B12

thyroid function test

liver function test

reticulocyte count - bigger than red cells

Question 19

what is the dietry source of folate *

Answer 19

fresh leafy veg - destroyed by overcooking/canning/processing

Question 20

2 causes of folate deficiency *

Answer 20

reduced intake

increased demand

Question 21

wy would folate intake be reduced *

Answer 21

ignorance

poverty

apathy

eg in elderly and alcoholics - not going to eat leafy veg

Question 22

why would folate demand be increased *

Answer 22

physiological - pregnancy, adolescence, premature babies (because rapidly reproducing cells)

pathological - malignancy, erythroderma (large percentage of body inflammed), haemolytic anaemias (red cell production has to increase)

Question 23

when would you see folate deficiency *

Answer 23

alcoholic admitted with head injury after fight

30yr old lady with infected whole body eczema

90yr old who only eats jam sandwich

Question 24

how would you diagnose folate deficiency *

Answer 24

Fbc and film - raised MCV/megaloblastic signs

folate levels in serum (recent folate intake) or in red cells (indicates body stores of folate)

Question 25

how would you assess te cause of decreased folate \*

Answer 25

history - diet/alcohol/illness examination - skin disease/alcoholic liver disease

Question 26

what are the consequences of folate deficiency \*

Answer 26

megaloblastic, macrocytic anaemia neural tube defects in developing foetus increased risk of thromosis - in association with variant enzymes involved in homocysteine metabolism - folate deficiency causes an increase in homocysteine

Question 27

describe neural tube defects from folate deficiency \*

Answer 27

spina bifida - anecepaly - born witout a brain all pregnant women take folic acid 0.4mg prior to conception for at least 12 weeks

Question 28

describe how hhomocysteine is related to thrombosis \*

Answer 28

very high levels of homocysteine (inborn error of metabolism) = atherosclerosis, premature vascular disease - very high rate of thrombosis mildly elevated (when folate deficiency) = CVD definitely, arterial thrombosis probably, venous thrombosis possibly

Question 29

how has usa addressed folate defiency

Answer 29

fortify food with it

Question 30

what are the signs of B12 defiency \*

Answer 30

parasthesiae - pins and needles muscle weakness difficulty walking visual impairment psychiatric disturbance

Question 31

what are consequences of B12 deficiency \*

Answer 31

neurological problems - bilateral peripheral neuropathy, subacute combined degeneration of the cord (posterior and pyramidal tracts = paralysis), optic atrophy, dementia affects the central and peripheral nervous system can present in lots of ways

Question 32

what are classical clinical presentations of B12 deficiency \*

Answer 32

parathesiae low Hb, high MCV FH of autoimmune glossitis premature grey hair loss of proprioception

Question 33

what is romberg's sign and wat does it test for \*

Answer 33

for B12 defiency - loss of proprioception stand, put hands out and close eyes fall over because of loss of proprioception

Question 34

what would be seen in an examination for B12 deficiency \*

Answer 34

absent reflexes - periperal nerve loss upgoing plantar reflex - CNS damage

Question 35

what are the causes of B12 deficiency \*

Answer 35

poor absorption - most common reduced dietry intake - stores are large adn last for 3-4years, comes from diet, vegans at risk becasue on dairy infections/infestations - they consume the B12 eg abnormnal bacterial flora (stagnant loops), tropical sprue, fish tapeworms

Question 36

describe normal B12 absorption \*

Answer 36

occurs in SI - B12 stored - when stores are saturated B12 is excreted in the urine 2 methods: 1 - through the duodenum, slow and inefficient 2 - most this wayn - b12 combine wit intrinsic factor in SI, made by the parietal cells - B12-IF binds to ileal receptors and internalised

Question 37

what are the 3 things needed for most b12 absorption \*

Answer 37

intact stomac - parietal cells intrinsic factor functioning small intestine

Question 38

what can cause impaired B12 absorption \*

Answer 38

reduced IF diseases of the small bowel (terminal ileum) infection drugs

Question 39

how can IF be reduced \*

Answer 39

post gastrectomy gastric atrophy Ab to IF or parietal cells - autoimmune

Question 40

what is pernicious anaemia \*

Answer 40

autoimmune condition = severe lack of IF peak age - 60yrs have FH male have decreased life expectancy because of stomach cancer Have IF Ab (occaisionally found in other conditions) parietal cell Ab - less specific, increase with age anyway doesnt mean you have pernicious anaemia

Question 41

what are diseases of the small bowel that affect b12 absorption \*

Answer 41

crohns coeliac surgical resection

Question 42

what infections lead to B12 deficiency \*

Answer 42

h pylori giardia fish tapeworm bacterial overgrowth

Question 43

what drugs are associated with a low B12 \*

Answer 43

metformin - for PCOS and diabetes proton pump inhibitors eg omeprazole oral contraceptive pill

Question 44

what investigations do you do to determine cause of B12 deficiency \*

Answer 44

Ab to parietal cells and IF Ab to coeliac disease breath test - for bacterial overgrowth stool for H pylori test for giardia used to do shilling test - cant do now because needs radioactivity

Question 45

what is the implication for treatment if you have B12 deficiency because of IF Ab \*

Answer 45

cant give oral supplements - wont be able to absorb them

Question 46

describe the silling test \*

Answer 46

prior to test restore the B12 stores (saturate the transcobalamin - these are B12 carrier proteins) - 6IM injections over 2 weeks when diagnosed to avoid neurological problems drink radiolabled B12 measure excretion in urine if in urine - means it has been absorbed into blood then filtered by kidney if not in urine - not absorbed (pernicious anaemia, small bowel disease) - end up in stool, or hadnt corrected B12 before test - so not excreting it even though it is absorbed becasue it is just filling the stores if not in urine repeat with IF using diff radioactive isotope - then measure B12 in urine - if now normal, problem is missing IF ie pernicious anaemia. - IF dependant malabsorption is course of B12 def

Question 47

what is the treatment for B12 deficiency \*

Answer 47

injections of B12 - bypass the oral root 3 a week for 2 weeks then every 3 months - stores last this long if neurological involvement - b12 injections alternate days until no furter improvement up to 3 weeks -- then every 2 months - some neurological things are irreversible dont give IF to people with pernicious anaemia as ab will still attack it

Question 48

what test do you do if someone has low Hb and high MCV \*

Answer 48

folate, b12, thyroid function, liver function

Question 49

where does absorption of folate occur \*

Answer 49

duodenum and jejunum

Question 50

what is pancytopenia

Answer 50

low hb, leukocytes and platelets

Question 51

how do you manage folate deficiency \*

Answer 51

diet folate tablets daily