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
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
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
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
Myelodysplasia
Drugs that interfere with DNA synthesis
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
Drugs
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
What are the three main consequences of folate deficiency?
Megaloblastic anaemia
Neural tube defects
Increased risk of venous thromboembolism
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?
Very high homocysteine levels are associated independently with:
Atherosclerosis
Premature vascular disease
Mildly elevated homocysteine is associated with cardiovascular disease and probably with arterial and 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, bacterial overgrowth, parasitic infection
What is the relationship between Hb level and neurological symptoms in B12 deficiency?
Inverse relationship between Hb level and neurological symptoms
State some symptoms and signs of B12 deficiency.
Weak, tired, lethargic
Symmetrical parasthesia/numbness
Muscle weakness
Difficulty walking and loss of balance
Anaemia and jaundice giving ‘yellow tinge’
Neurology
Loss of vibration and joint position sense but also cutaneous sensation loss
Absent responses and up-going plantar responses in legs
Visual impairment
Memory impairment
Psychiatric disturbance
What is the test for B12 deficiency?
Serum cobalamin (B12) level PROBLEM: it measures total cobalamin levels (bound to transobalamin 1, 2 and 3) so you see a lot of healthy patients with low transcobalamin This means that the clinical circumstances must be taken into account when interpreting the results.
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 new test used to diagnose B12 deficiency.
Plasma homocysteine (high in B12 and folate deficiency)
What is pernicious anaemia and what does it result in?
A form of anaemia resulting from the deficiency of B12
It can be caused by autoimmune atrophic gastritic with the loss of intrinsic factor
This results in macrocytic/megaloblastic anaemia with or without neurological damage
Which antibodies are found in pernicious anaemia?
Anti-intrinsic factor antibodies (
Anti-gastric parietal cell antibodies
How are folate and B12 deficiency treated?
Oral folate or oral cyanobalamin for dietary deficiency or increased demand
Parenteral (IM/SC) hydroxycobalamin for malabsorption due to pernicious anaemia or bowel disease
