B12+ Folic acid deficiency Flashcards
What is the physiological function of Vitamine B12?
- DNA synthesis
* involved in thymine synthesis - Integrity of the nervous system
What is the physiological function of folic acid?
- DNA Synthesis
- needed for thymine generation
- Homocystine metabolism
Which cells are primarily affected by a Vit B12 and Folic acid deficiency?
Because of role in DNA synthesis–> all rapidly dividing cells are affected! (need more DNA synthesis)
- Bone marrow
- Epithelial surfaces of mouth and gut
- Gonads
- embryos
What are the clinical features or a B12 or Folic acid deficiency?
- Anemia: weak, tired, short of breath
- Jaundice
- Glossitis and angular cheilosis
- Weight loss, change of bowel habit
- Sterility –> expecially in male (spermatogenesis)
What is a megaloblastic anaemia?
- Type of anaemia only present in B12 or Folic acid deficiency
- change in the red cell precursors within the bone marrow
- leads to an asynchronous maturation of the nucleus and cytoplasm of erythrocytes (e.g. might see mature erythrocyte with nucleus)
- maturing erythrocytes seeing in circulaiton
Which changes to the blood film might occur in a megaloblastic anaemia?
- Anisocytosis (unequal size)
- large cell size
- hypersegmented neutrophils (>5 secments in nucleus) –> picture
- Giant metamyelocytes (precursor of ganulocytes)
What are possible causes for macrocytic anaemia?
- Vitamin B12/folate deficiency
- Liver disease or alcohol
- Hypothyroid
- Drugs e.g. azathioprine
-
Haematological disorders:
- Myelodysplasia,
- aplastic anemia
- Reticulocytosis e.g. chronic haemolytic anemia
What are possible causes for a megaloblastic anaemia?
Mainly: Vit B12 and Folic acid deficiency
Which test would you perform in someonw with a macrocytic anaemia?
- B12/Folate acid levels
- Thyroid test
- liver function test
What is the source of folate acid?
Diatary source in (uncooked) fresh, green leafy vegetables
When does the folic acid requirement increase?
- Physiologically
- pregnancy
- adolescence
- premature babies
- Pathologically
- malignancy–> more production of cells
- erythoderma (eczemas)
- haemolytic anaemias –> more production of cells
In which patients do you normally see a folic acid deficiency?
- Ignorance
- alcoholics, elderly–> don’t take care of themselves
- poor – >poor diet
How would you diagnose someone to have a folate deficiency?
FBC and Blood film
macrocytic, megaloblastic anaemia
Folate acid levels
How to you investigate the cause of a folate acid deficiency?
- EASY – history (diet/alcohol/illness)
- EXAMINATION – skin disease/ alcoholic liver disease
What are the consequences of folate deficiencies?
Macrocytic, megaloblastic anaemia but also
- neural tube defects in developing fetus
- increased risk of thrombosis in association with variant enzymes involved in homocysteine metabolism
Explain the relationship between homocysteine and folic acid
Folic acid is needed for homocystein metabolism
In folic acid deficiency:
- increase of homocystein leading to
- atherosclerosis, vascular disease, likely thrombosis
What are the possible consequences of vitamine B12 deficiency?
Countless neural symptoms –>
- Bilateral peripheral neuropathy
- Subacute comined degeneration of the cord
- Posterior and pyramidal tracts of the spinal cord
- Optic atrophy
- dementia
- Paraesthesiae
- Muscle weakness
- Difficult walking
- Visual impairment
- Psychiatric disturbance
How does someoe with a severe vitamine B12 deficiency present on examination?
Absent peripheral reflexes and upgoing plantar responses
but also
- glossitis
- tingeling fingers
- auto-immune dieseaes
- §Premature grey hair
- falling over when closing eyes, loss or proprioception
What are the possible cuases for a vit B12 deficiency?
- Poor absorbtion
- Low intake
- vegan diet
- Infectsions
- mainly parasites
What might be possible causes for a malabsorbtion of vitamine B12?
-
Reduction of Intrinsic factor
- post gastrectomy
- gastric atrophy
- antibodies to intrinsic factor or parietal cells –> autoimmune (common)
-
Diseases of small bowel (terminal ileum)
- Crohns
- Coeliac disease
- surgical resection
-
Infections
- H Pylori
- Giardia
- Fish tapeworm
- Bacterial overgrowth
-
Drugs
- metformin (diabetis)
- omenprazon (anti-acid)
- oral contraceptive pill
What is pernicious anaemia?
Anaemia due to Vit B12 deficiency, caused by autoimmune destruction of Intrinstic facotor
Normall in
- Peak age: 60 years
- Family history or auto-immune disease
How do you call the diese in patients with low IF due to autoimmune destruction of it?
Pernicious anaemia
–> also increased risk of Stomach Ca
Which investigations would you perform in someone with a B12 deficiency?
What is the cause of B12 deficiency?
- History (e.g. vegan diet) –> easy
- Antibodies to parietal cells and intrinsic factor (IF destruction?)
- Anitbodies for coeliac disease (malabsorbtion)
- Breath test for bacterial overgrowth
- Stool for H Pylori
- Test for Giardia
OLDEN DAYS - Shilling test (part I and part II)
What is the Shilling test?
When is it done?
Now: outrun , not performed anymore (radioactive)
It can investivate the absorbtion of Vit. B12, is done in Vit. B12 anaemia
- After high dose B12 injections–>
radioactive oral administration of B12 - excretion in urine is measured
- if urine radioactive –> absorbation possible
- if not–> malabsorbtion or no adherence to previous injections (no excretion of B12 due to still deficiency)
How do you treat someone with a vit B12 deficiency?
High dose IM injection of Vitamine B12
- 3x/week for 2 weeks
- Thereafter every 3 months
In neurological problems
- B12 injections alternate days until no further improvement – up to 3 weeks
- Thereafter every 2 months
What is the pyhsiolocial role of B12?
Als Methylcobalamin dient es der Methioninsynthase als Coenzym bei der Methylierung von Homocystein zu Methionin. Der Methylgruppendonor ist dabei N5-Methyltetrahydrofolat (N5-Methyl-THF). Und als Adenosylcobalamin dient Vitamin B12 bei der Umwandlung von Methylmalonyl-CoA zu Succinyl-CoA durch die Methylmalonyl-CoA-Mutase der Einschleusung von Propionyl-CoA (aus dem Abbau ungeradzahliger Fettsäuren und einiger Aminosäuren) in den Citratzyklus.
