95 Megaloblastic Anemia Flashcards
Causes of Megaloblastic anemia
B12 and Folate deficiency
Enzymes where cobalamin is a co factor
L methylmamonyl Co Enzyme A mutase
Methionine synthase
What is daily requirement for colabamin? How much are the body stores?
Daily requirements for cobalamin is 1-3 micrograms.
Body stores are at 1-3 mg sufficined to 3-4 years supply
How is cobalamin absorbed and where? Which the normal physiologic mechanism? What mediates this mechanism
Passive: buccal, duodenal, ileal; inefficient only 1% absorbed
Active: normal physiologic mechanism; ileum and efficient; mediated by intrinsic factor
Where is intrinsic factor produced?
Gastric parietal cell of the fundus and body of stomach
Two amin cobalamin transport protein
One HC or TC I
Transcobalamin: TC II
Food with the highest concentration of folate
Liver Yeast Spinach Greens Nut
Largest store of Folate in the body
Liver
Total body Folate store. Daily Folate requirement
Folate daily requirement 100 mcg
Body stores of Folate 10 mg, stores are only sufficient for 3-4 months
How much of Folate is absorbed from food and where is it absorbed rapidly? Dietary Folate is converted to what? What pH?
Only 50% of Folate from food is absorbed rapidly in the upper small intestines
All dietary Folate is converted to 5 methyl tetrahydrofolate (5-MTHF)
Most absorbed happens at pH 5.5
True or false. Pteroylglutamic acid at doses more than 400 mcg is largely absorbed unchanged and converted to natural Folates in liver
True.
How much of Folate is bound and unbound?
1/3 loosely bound to albumin
2/3 is unbound
3 types of Folate binding protein involved in Folate transport? Which is the major route of delivery to cells?
- Reduced Folate transporter (RFC): major route
- Folate receptor (FR2 and FR2)
- PCFT
Universal methyl donor
S adenosylmethionine (SAM)
Common feature of all Megaloblastic anemia
Defect in DNA synthesis
How does Folate or cobalamin affect DNA synthesis?
Either Folate or cobalamin deficiency leads failure to convert dUMP to dTMP.
Two reactions in the body that require cobalamin
Methylmamonyl CoA isomerization
Methylation of homocysteine to methionine
MTHF accumulates in the plasma and Folate concentrations fall because of failure in the formation of THF
THF starvation or methylfolate trap
Reason for psychiatric disturbance in Folate deficiency
Attributed to failure to synthesize SAM which is needed in methylation of biogenic amines
Most affected tissues with cobalamin and Folate deficiency
Epithelial surfaces of mouth, stomach, small intestines, Respiratory, urinary and female genital tracts
When Folic acid supplementation given to reduce neural tube defects
Conception to first 12 weeks of pregnancy
Protective dose of Folic acid to prevent neural tube defects in pregnancy
- 4 mg daily
Three enzymes defective in severe homocystinuria
Methionine synthase
MTHFR
Cystathionine synthase
What type of leukemia is prevented with Folic acid supplementation
Acute lymphoblastic leukemia (ALL)
What is the main feature of myeloblastic anemia on peripheral blood
Ovalocytes
MCV more than 100 fL
Hypersegmented neutrophils (more than 5 nuclear lobes)
What is the bone marrow picture of Megaloblastic anemia
Hypercellular with an accumulation of primitive cells due to selective death by apoptosis of more mature forms
Defined as severe lack of intrinsic favor due to gastric atrophy
Pernicious anemia
How much of ileal removal leads to cobalamin Malabsorption
Removal of 1.2 M of terminal ileum leads to Malabsorption of cobalamin
