Vitamin B12 and Folic Acid Deficiency Flashcards by Georgia Leggett

What is vitamin B12 and what types of food is it commonly found in?

Cobalamin (vitamin B12) is a bacterial product that is ingested + stored by animals.
Found in meat, cheese, salmon, cod, milk, eggs

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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)

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What is Vitamin B12 needed for?

DNA synthesis

Integrity of the nervous system (involved in myelination)

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Broadly speaking, what can cause Vitamin B12 deficiency?

Dietary deficiency (vegans) 
Decreased absorption

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What types of food have lots of folic acid?

Leafy green vegetables

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What can cause folic acid deficiency?

Dietary deficiency
Increased demand for folate
Impaired absorption

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What is the dietary requirement of folic acid?

400-600 mcg

Run out of folate much quicker than B12

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What is folic acid required for?

DNA synthesis  
Homocysteine metabolism (potentially toxic)

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Where does B12 absorption occur? What happens when it is in excess?

Small intestine
Stored
When stores saturated, excreted in urine

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What are the 2 methods of B12 absorption?

In duodenum, slow + inefficient

2. B12 must combine with intrinsic factor (made by parietal cells of stomach). B12-IF binds to ileal receptors

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Deoxythymidine (dTMP) is a major building block of DNA synthesis. How is it produced?

Produced by methylation of deoxyuridine (dUMP)
For this to take place: need release of methyl groups from methyl-THF by the action of B12 as a cofactor accompanied by the conversion of homocysteine to methionine.

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In what reaction is B12 a co-factor?

Conversion of homocysteine to methionine

Enzyme = methionine synthetase

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State 6 clinical features of B12 and folate deficiency.

Anaemia (macrocytic + megaloblastic) 
Jaundice (due to ineffective erythropoiesis) 
Angular Cheilosis  
Glossitis  
Sterility (in males) 
Weight loss + change of bowel habit

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State 5 causes of macrocytic anaemia.

Vitamin B12/ Folate deficiency 
Liver disease / alcoholism 
Hypothyroidism 
Drugs that interfere with DNA synthesis e.g. Azathioprine
Haematological disorders: 
Myelodysplasia
Aplastic anaemia
Reticulocytosis e.g. chronic haemolytic anaemia

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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 (Megaloblastic)

Liver disease + alcoholism = ROUND macrocytes

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What is a reticulocyte?

A young red blood cell with no nucleus

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Describe how the appearances of cells of the red cell lineage change as they mature.

Become smaller + their cytoplasm becomes pinker

Nucleus starts off quite diffuse (open chromatin), becomes more + more compact until it is spit out

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What 2 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?

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What is meant by ‘megaloblastic changes’?

Morphological changes in red cell precursors in the BM
Asynchronous maturation of the nucleus + cytoplasm.
Results in immature, open nucleus with mature cytoplasm.

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Broadly speaking, what are megaloblastic changes the result of?

Defective DNA synthesis

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

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B12/Folate deficiency
Myelodysplasia
Drugs that interfere with DNA synthesis

Describe the changes to red and white blood cells in megaloblastic anaemia

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RBC’s:
Asynchrony between maturation of nucleus + cytoplasm
Large red cells
Anisocytosis
WBC’s:
Giant metamyelocytes (due to asynchronous maturation)
Hypersegmented neutrophils

What may cause decreased intake of folate?

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Ignorance, Poverty, Apathy

Elderly, Sick, Eating disorders, Alcoholics

What are the consequences of folate deficiency for DNA synthesis?

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Can’t methylate dUMP to dTMP, which affects DNA synthesis.

Also leads to the accumulation of homocysteine (can’t be converted to methionine)

State 3 physiological and 3 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 3 causes of malabsorption of folate.

Coeliac Disease Surgery or IBD (e.g. Crohn’s disease) Drugs (e.g. colestyramine, sulfasalazine + methotrexate)

State 3 tests to identify folate deficiency.

Full blood count Blood film Serum folate

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 Because B12 is required for folate to enter RBC's

What are the 3 main consequences of folate deficiency?

Megaloblastic anaemia Neural tube defects in developing foetus Increased risk of thrombosis in association with variant enzymes involved in homocysteine metabolism

What are the2 types of neural tube defects?

Spinal cord = spina bifida | Brain = anencephaly

What are the NICE guidelines for women to reduce risk of neural tube defects?

400 mcg folic acid preconception to 12 weeks gestation

Homocysteine accumulates in folate deficiency. What are the consequences of this?

Very high homocysteine levels are associated independently with: Atherosclerosis Premature vascular disease Mildly elevated homocysteine is associated with cardiovascular disease + probably with arterial + venous thrombosis.

How did the FDA in the USA attempt to reduce the incidence of NTDs due to folate deficiency?

Fortify grain with folate

Which groups of people are at particular risk of vitamin B12 deficiency due to decreased intake?

Vegans

State 3 factors that can affect the absorption of B12.

AI: pernicious anaemia (severe lack of intrinsic factor) Surgery: resection of parts of the GI tract Inflammatory bowel conditions: Crohn’s, chronic pancreatitis, bacterial overgrowth, parasitic infection

What are the 2 main consequences of B12 deficiency?

Macrocytic + megaloblastic anaemia Neurological problems due to demyelination Subacute combined degeneration of the spinal cord Bilateral peripheral neuropathy Optic atrophy Dementia

What may cause reduction in intrinsic factor leading to impaired B12 absorption?

Post-gastrectomy Gastric atrophy Antibodies to IF or parietal cells

State 5 symptoms and signs of B12 deficiency.

``` Symmetrical parasthesia Muscle weakness Difficulty walking + loss of balance Visual impairment Psychiatric disturbance ```

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

State 3 tests used to diagnose B12 deficiency.

Plasma homocysteine (high in B12 + folate deficiency) Serum methylmalonic acid levels Look for anti-IF antibodies

What is the Schilling test for B12 absorption?

Give 2 capsules of B12 with different radioisotopes. 1 capsule will be B12 alone 1 capsule will be B12 + IF Collect urine for 24 hours after administration + measure the presence + relative proportion of each isotope.

What is pernicious anaemia and what does it result in?

Autoimmune condition associated with severe lack of IF Males have decreased life expectancy Increased risk of stomach cancer

Which antibodies are found in pernicious anaemia?

Anti-IF antibodies (40-60% of adults with PA) | Anti-gastric parietal cell antibodies (80-90% of adults with PA)

How is B12 deficiency treated?

Injections of B12 3x/week for 2 weeks then every 3 months

Which cells are majorly affected in B12 and Folate deficiency?

``` Rapidly dividing cells: Bone marrow Epithelial surface of mouth + gut Gonads (spermatogenesis) Embryonic ```

How could B12 deficiency be indicated on examination?

Absent reflexes | Upgoing plantar responses

What 3 things are essential for B12 absorption?

Intact stomach Intrinsic factor Functioning small intestine

What 4 infections may cause B12 deficiency?

H Pylori Giardia Fish tapeworm Bacterial overgrowth

What 3 drugs are associated with low B12?

Metformin PPI's e.g. Omeprazole Oral contraceptive pill

What are the outcomes of the schilling test?

1. Normal = excretion of radioactive b12 in urine No B12 in urine = Pernicious anaemia/ small bowel disease 2. Pernicious anaemia: excretion of radioactive B12 (absorbed as given with IF) Small bowel disease: No B12 in urine

Vitamin B12 and Folic Acid Deficiency Flashcards

(50 cards)