Vitamin B12 and Folic Acid Deficiency Flashcards
What is vitamin B12 and what types of food is it commonly found in?
Cobalamin (vitamin B12) is a bacterial product that is ingested and stored by animals.
It is found in meat, cheese, salmon, cod, milk, eggs
What is Vitamin B12 needed for?
DNA synthesis
Integrity of the nervous system (involved in myelination)
Broadly speaking, what can cause Vitamin B12 deficiency?
Dietary deficiency (vegans) Decreased absorption
What types of food have lots of folic acid?
Leafy green vegetables
Broadly speaking, what can cause folic acid deficiency?
Dietary deficiency
Increased demand for folate
Impaired absorption
Out of b12 and folic acid, which one do we have greater stores?
We have more B12 stores. You run out of folate much quicker than B12
What is folic acid required for?
DNA synthesis
Homocysteine metabolism
Describe the passage of vitamin B12 from entry into the GI tract tothe hepatic portal circulation.
It enters the stomach and binds to transcobalamin 1 (R protein –produced by the salivary glands)
The gastric parietal cells (at the bottom of the stomach) produce intrinsic factor
The B12 moves into the duodenum, bound to transcobalamin 1, and then pancreatic enzymes displace B12 from transcobalamin 1 The free B12 then binds to intrinsic factor
The B12-intrinsic factor complex continues all the way to the terminal ileum where it binds to specific receptors and is absorbed The B12 then goes into the portal circulation and binds to transcobalamin 2 making active B12
Describe the absorption of folic acid.
Folic acid enters the GI tract as polyglutamates
The acidic pH of the stomach hydrolyses the polyglutamates to monoglutamates
The folic acid is absorbed as pteroglutamates
It is then methylated in the luminal cells to form methyl tetrahydroflorate
Deoxythymidine (dTMP) is a major building block of DNA synthesis. How is it produced?
It is produced by the methylation of deoxyuridine (dUMP)
For the methylation to take place, you need the release of methyl groups from methyl-tetrahydrofolate by the action of B12 as a cofactor accompanied by the conversion of homocysteine to methionine.
In what reaction is B12 a co-factor?
The conversion of homocysteine to methionine
Enzyme = methionine synthetase
State some clinical features of B12 and folate deficiency.
Anaemia (macrocytic and megaloblastic) Jaundice (due to ineffective erythropoiesis) Angular Cheilosis Glossitis Sterility Weight loss and change of bowel habit
State some causes of macrocytic anaemia.
- Vitamin B12/Folate deficiency
- Liver disease and alcoholism
- Hypothyroidism
- Haematological disorders eg reticulocytosis
- Drugs that interfere with DNA synthesis
What is a reticulocyte?
A young red blood cell with no nucleus
Describe how the appearances of cells of the red cell lineage change as they mature.
Throughout development, nucleus gets smaller and smaller. Also, cytoplasm goes from blue to pink because the only protein left in the cytoplasm Is pretty much Hb
Given your previous answer, what two things do you look at when determining the maturity of a red blood cell?
Nucleus
Colour of the cytoplasm – how blue is it?
What is meant by ‘megaloblastic changes’?
These are changes seen in the red blood cell precursors in the bone marrow.
Megaloblastic change is when there is asynchronous maturation of the nucleus and cytoplasm.
Broadly speaking, what are megaloblastic changes the result of?
Defective DNA synthesis
In megaloblastic anaemia, you see changes in the red blood cells and the white blood cells. Describe these changes.
Red blood cells
Asynchrony between maturation of nucleus and cytoplasm (immature nucleus and mature cytoplasm)
Increase in size of red cell precursors at all stages of maturation
Increase in bone marrow activity because haemopoiesis is ineffective (dysplastic)
Phagocytosis of dysplastic red blood cells
White blood cells
Giant metamyelocytes (due to asynchronous maturation)
Hypersegmented neutrophils
Which groups are at particular risk of dietary folate deficiency?
Elderly, sick, eating disorders, alcoholics
What are the consequences of folate deficiency for DNA synthesis?
Folate deficiency means that you can’t methylate dUMP to dTMP, which affects DNA synthesis.
It also leads to the accumulation of homocysteine (it can’t be converted to methionine without folate)
State some physiological and pathological causes of increased folate demand.
Physiological (increased growth) Pregnancy Adolescence Premature babies Pathological (rapid cell turnover) Malignancy Erythroderma (whole body rash) Haemolytic anaemia
State some causes of malabsorption of folate.
Coeliac Disease
Surgery or inflammatory bowel disease (e.g. Crohn’s disease)
Drugs
What is coeliac disease caused by?
autoimmune reaction to gluten
State some tests to identify folate deficiency.
Full blood count
Blood film
-Serum folate – useful as a screening test
Shows diurnal variation
Affected by recent changes in diet
-Red cell folate – useful as confirmatory test
What are the three main consequences of folate deficiency?
Megaloblastic + macrocytic anaemia
Neural tube defects
increased chance of thrombotic events
What are the two types of neural tube defects?
Spinal cord = spina bifida
Brain = anencephaly
Homocysteine accumulates in folate deficiency. What are the consequences of this?
Main problem- CVD
Possibly also- Arterial/venous thrombosis
Which groups of people are at particular risk of vitamin B12 deficiency due to decreased intake?
Vegans
State some factors that can affect the absorption of B12.
Autoimmune – pernicious anaemia (lack of intrinsic factor)
Surgery – resection of parts of the GI tract
Inflammatory bowel conditions – Crohn’s, chronic pancreatitis,
Infections/infestations- bacterial overgrowth, parasitic infections
What are the two main consequences of B12 deficiency?
- Macrocytic and megaloblastic anaemia
- Neurological problems due to demyelination : eg
- Subacute combined degeneration of the spinal cord
- Neuropathy of central and peripheral nerves
- Optic atrophy (retinal ganglion cell death)
- dementia
What is subacute combined degeneration of the spinal cord and what are the symptoms?
Caused by demyelination of the posterior (dorsal) and lateral (pyramidal) tracts of the cervical and thoracic spinal cord
What is the role of B12 in DNA synthesis?
Both B12 and folate are needed for the production of dTMP (deoxythymidine), which is a crucial building block in DNA synthesis
What is the Schilling test for B12 absorption?
Give two capsules of B12 with different radioisotopes.
1 capsule will be B12 alone
1 capsule will be B12 + intrinsic factor
Collect urine for 24 hours after administration and measure the presence and relative proportion of each isotope.
What is pernicious anaemia and what does it result in?
Autoimmune condition associated with SEVERE LACK OF Intrinsic Factor and hence lack of B12 absorption
This causes gradual anaemia ie gradually more and more exhausted and tired. (peak age approx 60)
Which antibodies are found in pernicious anaemia?
Anti-intrinsic factor antibodies
Anti-gastric parietal cell antibodies
How are B12 and folate deficiency treated?
b12 injections
folate tablets
what drugs can cause low B12
metformin
Proton pump inhibitors
oral contraceptives
