L5 Megaloblastic anemia Flashcards
Production (source) of Vitamin B12?
Production (source) of Folate?
Vit B12: animal produced only
Folate: Vegetables, fruits, liver
The daily requirement of Vitamin B12?
The daily requirement of Folate?
Vit B12: 1-2 ug
Folate: 100-150 ug
Absorption site of Vitamin B12?
Absorption site of Folate?
Vit B12: Terminal ileum by IF-B12 complex
Folate: Duodenum and jejunum
Transport of Vitmain B12 and folate (difference?)
Folate: weakly bound to albumin
Vit B12:
- Transcobalamin (TC) is essential for cell uptake
- Haptoccrin (TC1): inactive form 70-90%
- Transcobalamin (TC2): an active form 10-30%
Measurement/ confirmation assay of Vitamin B12?
Serum active B12 (TC2 bound Vitamin B12)
Congenital TC2 deficiency cases? Serum VitB12?
Megaloblastic anemia;
Serum B12 is normal
(only active form is deficient)
Measurement/ confirmation assay of folate?
Serum folate
2 products of Vitamin B12 and their respective functions?
- Methyl B12
- cofactor for methionine synthase
- methylation in DNA synthesis - Deoxyadenosyl B12 (Ado B12)
- TCA cycle
- Hb synthesis
- transfer folate from intestinal lumen into cells
Elevated levels of MMA of homocysteine reflects?
B12 deficiency which causes Ado B12 deficiency
Function of Folate?
DNA synthesis (dUMP > dTMP)
Why willl B12 deficiency cause an elecation of folate?
False elevation of serum folate occurs due to reduced folate transfer from intestines to cells
5 causes for B12 deficiency?
- Diet - strict vegetarian
- Stomach
- pernicious anemia: autoimmune gastritis > impaired IF secretion
- CA stomach
- diagnosed by anti-IF Ab/ anti-parietal cell Ab - Pancreas - pancreatic insufficiency
- Small bowel:
- blind loops (bacterial overgrowth)
- fish tapeworm infection
- Crohn’s disease - Drugs
- N2O (inhibit methionine synthase) (Anaes)
- metformin
- H2 receptor antagonists
- PPI
3 causes for folate deficiency?
- Malabsorption
- poor dietary intake
- celiac disease - Excess utilization
- pregnancy
- hemolytic anemia
= CA - Drugs
- valporate
- MTX (methotrexate, for cancer)
Macrocytic anemia with nuclear-cytoplasmic maturation asynchrony =?
Megaoblastic anemia
In megaloblastic anemia, nuclear maturation is faster/delayed compared to cytoplasmic maturation. Why?
Delayed;
due to defective DNA synthesis
Why will patients with megaloblastic anemia have mild jaundice?
Excess breakdown of Hb (increase ineffective erythropoiesis > increase in intramedullary destruction)
Other than jaundice, what are the clinical features of megaloblastic anemia?
- Angular stomatitis, glossitis
- Neurological:
- memory loss
- peripheral neuropathy: resersible with VitB12
- Subacute combined cord degeneration: LL more affected, irreversible with B12 treatment - Subfertility
MCV increases
reticulocytes decreases
WBC and O
Megaloblastic anemia
Which of the following are true in megaloblastic anemia?
A. PB: Oval macrocytes
B. PB: hyposegmented neutrophils
C. Hypercellular BM
D. Nuclear maturation delayed compared to cytoplasmic
E. Serum Active B12 level
All except B
- Hypersegmented neutrophils
Regarding the treatment for megaloblastic anemia,
A. no transfusion needed
B. folate deficiency - give oral folic acid daily only
C. B12 deficiency - monitor serum Na after treatment
D. B12 deficiency - IV hydroxocobalamin 1000ug
Only A
B: must not be given alone unless ruled out B12 deficiency
C: Serum K! hypokalemia due to resumption of erythropoiesis
D: Intramuscular
What is non-megaloblastic macrocytic anemia?
Macrocytic anemia without impairment in DNA synthesis
Reasons for non-megaloblastic macrocytic anemia? (7)
- Alcohol (MC of raised MCV without anemia)
- Liver disease
- Hypothyroidism
- Aplastic anemia
- Myelodysplastic syndrome
- Cold Agglutination disease
- Others: smoking, hemolytic anemia (reticulocytes)
What should you fo when you fonud macrocytes without megalaloblastic features like Howell Jelly bodies, hypersegmented neutrophils etc?
- Check alcohol history, smoking etc
- Red cell agglutination may cause falsely elevated MCV
>
- LFT, TFT
If retic >2%, suspect?
Hemolytic anemia
