Vitamin B12 and folic acid deficiency

Question 1

what are the roles of vit B12 and folate

Answer 1

Required for DNA synthesis

Absence leads to severe anaemia which can be fatal

Question 2

B12 required for

Answer 2

1. DNA synthesis

2. Integrity of the nervous system

Question 3

folic acid required for

Answer 3

DNA Synthesis

Homocystine metabolism

Question 4

what are the clinical features of B12/folate deficiency

Answer 4

Anemia: weak, tired, short of breath
Jaundice
Glossitis and angular cheilosis
Weight loss, change of bowel habit
Sterility

Question 5

what cells does B12 and folate deficiency effect?

Answer 5

ALL RAPIDLY DIVIDING CELLS ARE AFFECTED
Bone marrow
Epithelial surfaces of mouth and gut
Gonads
embryos

Question 6

what does deficiency of B12 or folate lead to?

Answer 6

ANEMIA

This is macrocytic and megaloblastic

Question 7

what is macrocytic mean?

Answer 7

Average red cell size is above the normal range

Question 8

what can cause macrocytic anemia?

Answer 8

Vitamin B12/folate deficiency
Liver disease or alcohol
Hypothyroid
Drugs e.g. azathioprine
Haematological disorders:
-Myelodysplasia, 
-aplastic anemia
-Reticulocytosis e.g. chronic haemolytic anemia

Question 9

what does megaloblastic mean?

Answer 9

Describes a morphological change in the red cell precursors within the bone marrow

Question 10

what is the order for normal red cell maturation?

Answer 10

Erythroblast
Normoblast: early/intermediate/late
Reticulocyte
Circulating red blood cell

Question 11

what is megaloblastic anemia?

Answer 11

Defined by asynchronous maturation of the nucleus and cytoplasm in the erythroid series.

Maturing red cells seen in the bone marrow

Question 12

what are the features in peripheral blood in megaloblastic anaemia?

Answer 12

Anisocytosis
Large red cells
Hypersegmented neutrophils
Giant metamyelocytes

Question 13

what would define hypersegmented neutrophil?

Answer 13

neutrophil with 5 or more segments/lobes

Question 14

where do you get dietary folate from?

Answer 14

Fresh leafy vegetables

Destroyed by overcooking/canning/processing

Question 15

folate: decreased intake reasons:

Answer 15

IGNORANCE
POVERTY
APATHY

Question 16

what are some common reasons for increased demands of folate?

Answer 16

PHYSIOLOGICAL
Pregnancy
Adolescence
Premature babies

PATHOLOGICAL
Malignancy
Erythoderma
Haemolytic anaemias

Question 17

Laboratory diagnosis of folate deficiency

-what would you use?

Answer 17

FBC and film

Folate levels in the blood

Question 18

assessing cause of decreased folate:

Answer 18

EASY – history (diet/alcohol/illness)

EXAMINATION – skin disease/ alcoholic liver disease

Question 19

consequences of folate deficiency:

Answer 19

Megaloblastic, macrocytic anemia

Neural tube defects in developing fetus

Increased risk of thrombosis in association with variant enzymes involved in homocysteine metabolism

Question 20

what can neural tube defects lead to

Answer 20

Spina bifida
Anencephaly

ALL PREGNANT WOMEN TAKE FOLIC ACID 0.4MG PRIOR TO CONCEPTION AND FOR FIRST 12 WEEKS

Question 21

what are high homocysteine levels associated with?

Answer 21

Very high homocysteine levels are associated with
atherosclerosis
premature vascular disease

Mildly elevated levels of homocysteine are associated with:
cardiovascular disease DEFINITELY
arterial thrombosis PROBABLY
venous thrombosis POSSIBLY

Question 22

what are the consequences of B12 deficiency

Answer 22

Neurological problems
Bilateral peripheral neuropathy
Subacute comined degeneration of the cord
Posterior and pyramidal tracts of the spinal cord
Optic atrophy
dementia

Question 23

example of symptoms in B12 deficiency history

Answer 23

Paraesthesiae
Muscle weakness
Difficult walking
Visual impairment
Psychiatric disturbance

Question 24

what do you find upon examination of B12 deficient patient

Answer 24

Absent reflexes and upgoing plantar responses

Question 25

B12 Deficiency cause

Answer 25

``` POOR ABSORPTION Reduced dietary intake Stores are large and last for 3-4 years Animal produce Vegans are at risk ``` Infections/infestations Abnormal bacterial flora (stagnant loops) Tropical sprue Fish tapeworm

Question 26

what is normal B12 absorption?

Answer 26

Occurs in small intestine – B12 is then stored – when stores are saturated excess B12 is excreted in the urine 2 methods of absorption Method 1 - Slow and inefficient (1%) - duodenum Method 2..most absorption this way. B12 must combine with intrinsic factor Intrinsic factor is made in the stomach (parietal cells) B12-IF binds to ileal receptors

Question 27

3 key things for B12 absorption to occur

Answer 27

THREE THINGS ARE ESSENTIAL Intact Stomach Intrinsic factor Functioning small intestine

Question 28

what can cause reduction in intrinsic factor?

Answer 28

a) post gastrectomy b) gastric atrophy c) antibodies to intrinsic factor or parietal cells

Question 29

what is pernicious anemia?

Answer 29

Autoimmune condition associated with SEVERE LACK OF IF Peak age: 60 years Family history Males have a decreased life expectancy- increased risk of cancer in stomach

Question 30

what conditions may lead to impaired B12 absorption

Answer 30

Diseases of small bowel (terminal ileum) a) Crohns b) Coeliac disease c) surgical resection

Question 31

infections that might cause B12 deficiency

Answer 31

H Pylori Giardia Fish tapeworm Bacterial overgrowth

Question 32

Drugs associated with low B12

Answer 32

Metformin Proton pump inhibitors e.g. omeprazole Oral contraceptive pill

Question 33

what is the procedure you'd carry out in patients with low B12

Answer 33

What is the cause of B12 deficiency? Antibodies to parietal cells and intrinsic factor Anitbodies for coeliac disease Breath test for bacterial overgrowth Stool for H Pylori Test for Giardia OLDEN DAYS - Shilling test (part I and part II)

Question 34

what do you do in shilling test part 1

Answer 34

Prior to test, replenish stores a) drink radiolabelled B12 b) measure excretion in the urine

Question 35

what if you dont measure B12 in urine part 1 schilling

Answer 35

1. Not absorbing B 12 - pernicious anaemia - small bowel disease 2. Hadn’t corrected B 12 deficiency before the test

Question 36

schilling test part 2

Answer 36

Repeat test with addition of intrinsic factor | Measure excretion of B12 in the urine

Question 37

classic case but normal B12

Answer 37

Measure methylmalonyl acid Measure homocysteine Look for anti-intrinsic factor antibodies Treat as B12 deficiency until you get all of the results back

Question 38

treatment for B12 deficiency

Answer 38

Injections of B12…. 1000ug (i.m) 3x/week for 2 weeks Thereafter every 3 months IF NEUROLOGICAL INVOLVMENT B12 injections alternate days until no further improvement – up to 3 weeks Thereafter every 2 months