Its ppt about B12 deficiencies

1. B12 and folic acid deficiency
anemia
M.Ananiashvili

2. Megaloblastic anemias
• Megaloblastic anemias result most often from
deficiencies of vitamin B12and folate. Ineffective
hematopoiesis affects all cell lines but particularly
RBCs. Diagnosis is usually based on a CBC and
peripheral smear, which may show a macrocytic
anemia with anisocytosis and poikilocytosis, large oval
RBCs (macro-ovalocytes), hypersegmented neutrophils,
and reticulocytopenia. Treatment is directed at the
underlying disorder.
• Megaloblasts are large nucleated RBC precursors with
noncondensed chromatin. Megaloblastosis precedes
macrocytic anemia.

3. Nonmegaloblastic macrocytosis
• Macrocytes are enlarged RBCs (ie, MCV > 100
fL/cell). Macrocytic RBCs occur in a variety of
clinical circumstances, many unrelated to the
megaloblastosis and the resultant anemia.
Macrocytosis may be due to megaloblasts or
other enlarged RBCs ( Nonmegaloblastic
Macrocytosis). Megaloblasts are large
nucleated RBC precursors with noncondensed
chromatin. Megaloblastosis precedes
macrocytic anemia.

4. Nonmegaloblastic macrocytosis
• Most macrocytic (ie, MCV >100 fL/cell) anemias are
megaloblastic. Nonmegaloblastic macrocytosis occurs in
various clinical states, not all of which are understood.
• Macrocytosis due to excess RBC membrane occurs in
patients with chronic liver disease when cholesterol
esterification is defective. Macrocytosis with an MCV of
about 100 to 105 fL/cell can occur with chronic alcohol use
in the absence of folate deficiency. Mild macrocytosis can
occur in aplastic anemia, especially as recovery occurs.
Macrocytosis is also common in myelodysplasia. Because
RBC membrane molding occurs in the spleen after cell
release from the marrow, RBCs may be slightly macrocytic
after splenectomy, although these changes are not
associated with anemia.

5. Nonmegaloblastic macrocytosis
• Nonmegaloblastic macrocytosis is suspected
in patients with macrocytic anemias when
testing excludes vitamin B12 and folate
deficiencies.
• The macro-ovalocytes on peripheral smear
and the increased RBC distribution width that
are typical of classic megaloblastic anemia
may be absent.

6. Nonmegaloblastic macrocytosis
• If nonmegaloblastic macrocytosis is unexplained
clinically (eg, by the presence of aplastic anemia,
chronic liver disease, or alcohol use) or if
myelodysplasia is suspected, bone marrow
examination and cytogenetic analysis are done to
exclude myelodysplasia.
• In nonmegaloblastic macrocytosis, the marrow is not
megaloblastic, but in myelodysplasia and advanced
liver disease there are megaloblastoid RBC precursors
with dense nuclear chromatin that differ from the
usual fine fibrillar pattern in megaloblastic anemias.

7. Etiology
• The most common cause of megaloblastic
states is deficiency or defective utilization of
vitamin B12 or folate

8. Pathophysiology
• Megaloblastic states result from defective DNA synthesis.
RNA synthesis continues, resulting in a large cell with a
large nucleus. All cell lines have dyspoiesis, in which
cytoplasmic maturity is greater than nuclear maturity; this
dyspoiesis produces megaloblasts in the marrow before
they appear in the peripheral blood. Dyspoiesis results in
intramedullary cell death, making erythropoiesis ineffective
and causing indirect hyperbilirubinemia and hyperuricemia.
Because dyspoiesis affects all cell lines, reticulocytopenia
and, during later stages, leukopenia and thrombocytopenia
develop. Large, oval RBCs (macro-ovalocytes) enter the
circulation. Hypersegmentation of polymorphonuclear
neutrophils is common

9. Diagnosis
• CBC, RBC indices, reticulocyte count, and peripheral smear
• Sometimes bone marrow examination
• Megaloblastic anemia is suspected in anemic patients with
macrocytic indices. Diagnosis is usually based on peripheral smear.
When fully developed, the anemia is macrocytic, with MCV > 100
fL/cell. The smear shows macro-ovalocytosis, anisocytosis, and
poikilocytosis. The RBC distribution width (RDW) is high. Howell-
Jolly bodies (residual fragments of the nucleus) are common.
Reticulocytopenia is present. Hypersegmentation of the
granulocytes develops early; neutropenia develops later.
Thrombocytopenia is often present in severe cases, and platelets
may be bizarre in size and shape. If the diagnosis is questionable, a
bone marrow examination may be needed.

10. VITAMIN B 12 DEFICIENCY
• Dietary vitamin B12 deficiency usually results
from inadequate absorption, but deficiency
can develop in vegans who do not take
vitamin supplements. Deficiency causes
megaloblastic anemia, damage to the white
matter of the spinal cord and brain, and
peripheral neuropathy. Diagnosis is usually
made by measuring serum vitamin B12 levels

11. Schilling Test
• The Schilling test helps determine etiology.
Treatment consists of oral or parenteral vitamin
B12. Folate (folic acid) should not be used instead
of vitamin B12 because folate may alleviate the
anemia but allow neurologic deficits to progress.
• Schilling Test- The Schilling can determine
whether the body absorbs vitamin B12 normally.
It checks for certain types of anemia that are
caused by a low vitamin B12 level.

12. Etiology
Vitamin B12 deficiency can result from
• Inadequate intake-in vegans, Breastfed babies of vegan mothers
may develop vitamin B12deficiency by age 4 to 6 mo because in
these babies, liver stores are limited and their rapid growth rate
results in high demand.
• Inadequate absorption-is the most common cause of deficiency-
most commonly results from decreased acid secretion, Vitamin
B12 absorption may be inadequate if ileal absorptive sites are
destroyed by inflammatory bowel disease or are surgically
removed, may occur in blind loop syndrome (small intestinal
bacterial overgrowth (SIBO) or bacterial overgrowth syndrome ),
gastric or bariatric surgery
• Decreased utilization
• Use of certain drugs- antacids

13. Pernicious anemia
• Is often used synonymously with vitamin
B12 deficiency.
• It was first described by Addison and lately by Biermer
and was one of the most incurable diseases
• However, pernicious anemia specifically refers to
anemia resulting from vitamin B12deficiency caused
by an autoimmune metaplastic atrophic gastritis with
loss of intrinsic factor. Patients with classic pernicious
anemia, most commonly younger adults, are at
increased risk of stomach and other GI cancers.

14. AMAG
• Autoimmune metaplastic atrophic gastritis
(AMAG) is an inherited autoimmune disease
that attacks parietal cells, resulting in
hypochlorhydria and decreased production of
intrinsic factor. Consequences include atrophic
gastritis, B12 malabsorption, and, frequently,
pernicious anemia. Risk of gastric
adenocarcinoma increases 3-fold. Diagnosis is
by endoscopy. Treatment is with parenteral
vitamin B12.

15. Intrinsic factor
• In the gastric B12 by hydrochloric acid is released
from food. Then binds to R-proteins ( Rapid
binders). This proteins are in gastric , blood
plasma, breast milk and phagocytes.
• R+ B12 complex moves to duodenum where
under the influence of pancreatic enzymes B12 is
released and is bind to gastromucoprotein
(Intrinsic factor), which is produced by
the parietal cells of the stomach.
• 1mg of gastromucoprotein can bind 25 mg B12.

16. Intrinsic factor
• A new complex of B12 + intrinsic factor then is
absorbed by the epithelial cells (enterocytes) of
the ileum. Inside the cells, B12 dissociates once
again and in the blood binds to another protein,
transcobalamin II. Then it is carried to the liver
and the bone marrow. In the bone marrow B12 is
used for hemopoiesis and in the liver it is stored.
• In the humans B12 is 2-5 mg and without
exogenic intake, can preserve for about 5 years.

17. B12
B12 takes place in hemopoiesis with
methylcobalamin. and when there is B12
deficiency it can cause megaloblastic anemia,
leucopenia, thrombocytopenia
and by Desoxyadenosyncobalamin it takes part
in myelination.

18. Symptoms and Signs
• GI symptoms ( including weight loss and poorly
localized abdominal pain, may occur. Glossitis, usually
described as burning of the tongue, is uncommon).
• Neurologic symptoms (decreased position and
vibratory sensation in the extremities, with mild to
moderate weakness and hyporeflexi)
• Some patients are also irritable and mildly depressed
• Paranoia (megaloblastic madness), delirium,
confusion, and, at times, postural hypotension may
occur in advanced cases

19. Diagnosis
• CBC and vitamin B12 and folate levels( A vitamin
B12 level < 200 pg/mL indicates vitamin B12 deficiency. The
folate level is measured because vitamin B12 deficiency
must be differentiated from folate deficiency as a cause of
megaloblastic anemia;
• Pheripherial blood: MCV >96mkm3; Fi>1; poykilocytosis,
anysocytosis, The RBC distribution width (RDW) is high.
Howell-Jolly bodies (residual fragments of the nucleus) are
common. Reticulocytopenia is present. Hypersegmentation
of the granulocytes develops early; neutropenia develops
later. Thrombocytopenia is often present in severe cases.
• Bone marrow-

20. Treatment
• Supplemental vitamin B12
• Vitamin B12 1000 to 2000 mcg po can be given once/day to patients who
do not have severe deficiency or neurologic symptoms
• For more severe deficiency, vitamin B12 1 mg IM is usually given 1 to 4
times/wk for several weeks until hematologic abnormalities are corrected;
then it is given once/mo.
• Although hematologic abnormalities are usually corrected within 6 wk
(reticulocyte count should improve within 1 wk), resolution of neurologic
symptoms may take much longer. Neurologic symptoms that persist for
months or years become irreversible. In most elderly people with vitamin
B12 deficiency and dementia, cognition does not improve after treatment.
• Vitamin B12 treatment must be continued for life unless the
pathophysiologic mechanism for the deficiency is corrected.
• Infants of vegan mothers should receive supplemental vitamin B12 from
birth.

21. Folic acid deficiency
• Folate B9 (is one of the B vitamins) deficiency
is common. It may result from inadequate
intake, malabsorption, or use of various drugs.
Deficiency causes megaloblastic anemia
(indistinguishable from that due to vitamin
B12deficiency). Maternal deficiency increases
the risk of neural tube birth defects

22. Etiology
The most common causes of folate deficiency are:
• Inadequate intake (usually in patients with
undernutrition or alcoholism)
• Increased demand (eg, due to pregnancy or lactation)
• impaired absorbtion (eg, in celiac disease, sprue, due
to certain drugs)
• Deficiency can also result from inadequate
bioavailability and increased excretion
• Increased excretion
• Renal dialysis

23. Symptoms and Signs
• Symptoms are due to anemeia and identical to
B12 anemia, but without neurological lesions.
• Lab/ Tests, bone marrow also like B12
• differentiation must be done with serum
folate levels.

24. Treatment
• Supplemental oral folate
• Folate 400 to 1000 mcg po once/day replenishes tissues and is
usually successful
• The normal requirement is 400 mcg/day
• CAUTION: In patients with megaloblastic anemia, vitamin
B12deficiency must be ruled out before treating with folate. If
vitamin B12 deficiency is present, folate supplementation can
alleviate the anemia but does not reverse, and may even worsen,
neurologic deficits .) For pregnant women, the recommended daily
allowance (RDA) is 600 mcg/day.
• For women who have had a fetus or infant with a neural tube
defect, the recommended dose is 4000 mcg/day, started 1 mo
before conception (if possible) and continued until 3 mo after
conceptio