Megaloblatic Anemia Flashcards
Vitamin B-12 is carried by which protein to through the GIT
Intrinsic Factor
Where in the GIT is vitamin B-12 (cobalamin) released
terminal ileum
Which protein transports B-12 to the liver
Transcobalamin
List three functions of B-12 in the body
1) development, myelination and function of the central nervous system
2) healthy red blood cell formation
3)DNA synthesis
What percentage of B-12 is absorbed passively without Intrinsic Factor?
1%
What is the function of R-Protein/Haptocorrin/
Transcobalamin I
This glycoprotein binds to B-12 forming haptocorrin-B12 complex that protects the B12 from stomach acid degradation
What is the main dietary source of B12
Food from Animals
List three (3) dietary sources of Folic Acid
Leafy vegetables, fruits, animal protein
What do we mean when we say Folate/folic acid is thermoliable?
when food is boiled excessively, it can destroy the folate present
List 2 foods that are now commonly fortified with folate
Rice and cereals
What is the daily requirement for folate?
400-600micrograms
What factors can increase the daily requirement of folate
- pregnancy
- haemolysis (haemolytic anemias like thallassemia and sickle cell)
- lactation
- growing children
What is the earliest time of onset of folate deficiency symptoms?
3 months
What is the main difference between Red Cell Folate and Serum Folate?
Red cell folate is acquired from RBC as shows how much folate the patient has taken up over the past few weeks, while Serum folate is taken from the serum and tells how much folate the patient has taken up over the past few hours.
What other test should be done if a patient with megaloblastic anemia has normal serum folate levels and why ?
A Red Cell Folate sample should be tested, as the serum folate might be normal as a result of a high folate meal taken a few hours prior to the test
Where is folate absorbed ?
proximal jejunum
What has to be done before polyfolate- the form that folate is consumed in can be used by the body?
It first has to be reduced to monofolateand then methylated
List 5 causes of B12- deficiency
1) Poor absorption (achlorhydria, impaired parietal cells - no IF )
2) Parasitic or Bacterial Infection (Tape worm)
3) Transcobalamin 2 mutation
4) Terminal Ileum Resection
5) decreased dietary intake
What is pernicious anemia
Anemia that results from poor absorption of B12 due to an autoimmune response that attacks the stomach’s parietal cells therefore decreasing the presence of intrinsic factor
What is megaloblastic anemia?
Anemia that results from a deficiency in B12 and B9
What is the morphology of the RBCs in Megaloblastic Anemia
1)abnormally large erythrocyte precursors (megaloblasts)
2)oval macrocytes
3)hypersegmented neutrophils (more than 5 lobes)
4) Tear-drop cells
5) fragments
List 4 causes of folate deficiency
1) decreased dietary intake
2) Increased demand
3) Malabsorption
4)impaired folate use
Where is folate stored ?
Folic acid is water-soluble. Leftover amounts of the vitamin leave the body through the urine. That means your body does not store folic acid. You need to get a regular supply of the vitamin through the foods you eat or through supplements.
List some signs of folate deficiency
1) Skin: yellow tinge, hyperpigmentation of palms and soles
2) premature greying
3)Glossitis (beefy red tongue)
4) Mild jaundice
What causes mild jaundice in B12/folate deficiency?
Ineffective erythropoeisis increases the breakdown of RBCs in bone marrow releasing bilirubin
Vitiligo is a condition that can be seen in what type of anemia
pernicious anemia
List 3 nvestigative finding in folate deficiency
1) low Hb
2) High MCV
3) low RDI (dietary folate equivalents)
What is hyporegenerative anemia?
Hyporegenerative anemia is characterized by low Hb and reticulocyte count
What chanes can be seen in the bone marrow in B12 and B9 deficiency?
- incresed bone marrow due to increased erythroid activity
-HYPERCELLULAR/ERYTHROID HYPERPLASIA
What is the main difference in a normal bone marrow and the bone marrow of a B12-B9 deficient patient
In normal bone marrow myeloid cells dominate, however here erythroid cells dominate in a hypercellular fashion
Why is Megaloblastic anemia not considered a haemolytic anemia eventhough there is increase RBC breakdown?
Because the bone marrow function is not normal and in haemolytic anemias bone marrow function is normal
What does the term Red Cell Asynchrony mean
This condition is due to impaired DNA synthesis, which inhibits nuclear division. Cytoplasmic maturation, mainly dependent on RNA and protein synthesis, is less impaired. This leads to an asynchronous maturation between the nucleus and cytoplasm of erythroblasts, explaining the large size of the megaloblasts
List the neurological findings in B12 deficiency
- Numbing and tingling of hands and feet
- Dec sensation to light touch / pin prick
- optic atrophy
- decreased proprioception
- UMN signs
- Weakness
-Ataxia - Megaloblastic Madness
An increase in homocysteine can indicate a deficiency of which vitamin
B12
Which condition predisposes the patient to thrombosis and may first present as a DVT?
Hyperhomocysteinemia
Which test was used in the past to determine if B12 is being absorbed?
Shilling’s Test
Why does B12 deficincy cause hyperhomocysteinemia
This is because B12 is required as a cofactor in the conversion of homocysteine to methionine
How does B12 deficiency affect DNA synthesis
1) This is because B12 is required as a cofactor in the conversion of homocysteine to methionine
2) Methione is converted to S-adenosyyl Monophosphate and then to methyl THF
3) THF is polyglutamated in order for DNA synthesis to occur
4) that causes conversion of uracil monophosphate thymidine monophosphate and eventually triphosphaete for DNA synthesis
How does B12 deficiency affect DNA synthesis
Describe Step 1 in the Schilling Test
1) B12 is administered IM to saturate all B12 receptors
2) Radiolabelled B12 is administered orally and the excretion in urine is measured.
3) If the B12 excretion is >9% B12 absorption is normal and another aetiology must be causing deficiency
4) If the B12 excretion is <9% B12 absorption is impaired and you should proceed to step 2
Describe Step 2 in the Shilling’s Test
1) Give oral radio-labelled B12 bound to IF , if the excretion improves then the patient was IF deficient (pernicious anemia).
If not look for another causee
What is the disadvantage with the SHilling’s test
24 hr urine collection
What are three ways that folate deficiency can be corrected?
1)Oral replacement (2-5mg)
2)Alcoholics should be advised to stop drinking
3)Measure reticulocytes 7-10 days after starting folate replacement therapy
List 2 ways that B12 deficiency can be corrected
1) B12 IM
2) B12 supplements (in low b12 diet pts)
Why is B12 given IM in deficiency?
To bypass the GIT as Pernicious Anemia is the commonest cause of B12 deficiency
What dosage of B12 and in what increments , is administered to correct B12 deficiency?
1mg
-once per day for 1 week
-twice weekly for 1 week
-once weekly for 4 weeks
- once every 3 months for life
By what day do you expect a rise in reticulocyte count after B12 therapy has started
day 2-3
and peaks at 7-10
Why is blood transfusion contraindicated in Megaloblastic Anemia
Because the pts often decompensate during the transfusion and get tipped into heart failure
Which vitamin should be administered first, if you are not sure which vitamin is deficient in megaloblastic anemia?
B12
Why is there an increase in Methylmalonyl CoA in B12 deficiency
This is because B12 is required to convert methylmalonyl CoA to succinyl CoA
How does B12 deficiency cause Neurologic problems
The increase in Methylmalonyl CoA as a result of the absence of B12 has a negative effect on the myelination of nerves.
Succinyl CoA aids in nerve myelination, however in B12 deficiency, Methylmalonyl CoA is not converted to Succinyl CoA and the nerves are not adequately myelinated
What neurologic signs are observed in B12 deficiency
- Ataxia
- Pins and needles in glove and stocking distribution
- positive Rhomberg’s test
- impaired proprioception
Tetrahydrofolate is converted to methylcobalamin, then homocysteine then methionine.
How does B12 deficiency cause increased risk for thrombosis?
B12 is required to convert homocysteine to methionine.
Without B12 there is an increase in homocysteine. Homocysteine cause hypercoagulation which is a risk factor (virchow’s Triad) for DVT
High or Low
Serum B12 in B12 deficiency
low
High or Low
Serum folate in B12 deficiency
High or Normal
High or Low
RBC folate in B12 deficiency
Low or Normal
High or Low
Serum B12 in Folate Deficiency
Normal or borderline
High or Low
Serum or RBC folate in Folate deficiency
Low
