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
How much B12 is needed every day and how much is found in hepatic stores?
1.5-3 mcg/day required
Store: 2-5 mg (will last several years)
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
What is the dietary requirement of folic acid?
400-600 mcg
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:
Myelodysplasia (production of one or all types of blood cells by the bone marrow is disrupted)
Aplastic anaemia (failure of blood cell production resulting in pancytopenia)
Reticulocytosis (in response to haemolytic anaemia or bleeding)
Drugs that interfere with DNA synthesis
Prolonged nitrous oxide anaesthesia
How can you differentiate between the blood film of someone with B12/Folate deficiency and someone with liver disease or alcoholism causing macrocytosis?
B12/Folate deficiency = OVAL macrocytes
Liver disease and alcoholism = ROUND macrocytes
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.
They become smaller and their cytoplasm becomes pinker
Their nucleus starts off being quite diffuse (open chromatin) and it becomes more and more compact until it is spit out by the red cell
Given your previous answer, what two things do you look at when determining the maturity of a red blood cell?
Chromatin – how open is it?
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.
You get an immature, open nucleus with mature cytoplasm.