Vitamin B12 and Folic Acid Deficiency Flashcards Preview

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Flashcards in Vitamin B12 and Folic Acid Deficiency Deck (48)
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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
Weight loss and change of bowel habit


State some causes of macrocytic anaemia.

Vitamin B12/Folate deficiency
Liver disease and alcoholism
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.


Broadly speaking, what are megaloblastic changes the result of?

Defective DNA synthesis


Which of the causes of macrocytic anaemia also show megaloblastic changes in the bone marrow?

B12/Folate deficiency
Drugs that interfere with DNA synthesis
Prolonged nitrous oxide anaesthesia


In megaloblastic anaemia, you see changes in the red blood cellsand 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 (e.g. colestyramine, sulfasalazine and methotrexate)


What is coeliac disease caused by?

Sensitivity to gliadin (group of proteins found in wheat) leads to subtotal villous atrophy with crypt hyperplasia in the duodenum.


How can coeliac disease be diagnosed?

Anti-gliadin (transglutaminase) antibodies
Duodenal biopsy


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 would you expect the serum folate and red cell folate of a patient with B12 deficiency to be and why?

Serum folate = high
Red cell folate = LOW
This is because B12 is required for the folate to enter the red blood cells