ANEMIAS CAUSED BY DEFECTS OF DNA ▪ Inherited errors in

METABOLISM absorption or transport

– Imerslund-grasbeck
• Most but not all macrocytic anemias are
syndrome,
caused by impairment of DNA
transcobalamin
metabolism
deficiency
• There are macrocytic anemias that are ▪ Competition for the
not caused by DNA metabolism vitamin – D. latum, Blind
MEGALOBLASTIC ANEMIA loop syndrome (there is
a part of the intestine
• Macrocytic red cells is caused by that is cyanotic due to
impairment of DNA metabolism inflammation or
• Macrocytic RBC, Hyper segmented surgery)
neutrophils (5 and up) ▪ SYMPTOMS – Jaundice,
• Hallmark of the diseases affecting DNA Weakness, Glossitis,
metabolism (abnormality) Gastrointestinal
• Impaired DNA synthesis – very large disorder, Numbness,
bone marrow cells that develops Other CNS problems (3-
distinctive morphology 6 years development)
• Defective DNA synthesis causes o FOLATE DEFICIENCY
abnormal nuclear maturation; RNA (pteroylglutamic acid)
synthesis is normal, so the cytoplasm is ▪ Inadequate intake
not affected. The nucleus matures ▪ Increased need
slower than the cytoplasm. ▪ Impaired absorption
(asynchronism) ▪ Impaired use due to
• VITAMIN B12 DEFICIENCY drugs (antiepileptic
(COBALAMIN) and FOLATE DEFICIENCY drug, antineoplastic
• Megaloblastic erythropoiesis – slow drug/ chemotherapy)
maturation of cell (8 -12 um) ▪ Excessive loss with renal
• CAUSES: dialysis
o VB12 DEFICIENCY ▪ Body has a reserve for 3
▪ Inadequate intake months – if no intake
▪ Increased need – megaloblastic anemia
bleeding, pregnancy, may be developed
growth spurt, lactation ▪ Overcooking may
▪ Impaired absorption – diminish folic acid in
failure to split from food – heat labile
food, failure to split substance
from haptocorrin, lack ▪ SYMPTOMS: Poor diet,
of intrinsic factor pregnancy,
(pernicious anemia, chemotherapeutic anti-
achlorhydria) folic acid drugs
▪ General Malabsorption (Methotrexate)
 • OTHER CAUSES OF MEGALOBLASTOSIS: COBALAMIN METABIOLISM
o Myelodysplastic syndromes
• VB12 – liver, fish, poultry products, meat,
o Acute erythroid leukemia
and dairy products
o Congenital dyserythropoietic
o Formed by microorganisms and
anemia
fungi
o Reverse transcriptase inhibitors
o 5 ug per day
(HIV meds)
o Unlike iron, it can be excreted in
LABORATORY DIAGNOSIS OF MEGALOBLASTIC the urine or feces
ANEMIA o 1-5 mg is stored in liver
• Enters alimentary tract
• SCREENING TESTS
o R binders transports VB12 into
o CBC: slight macrocytosis is the
duodenum (saliva, food, peptic
earliest sign of megaloblastic
secretions)
anemia (oval macrocytes,
o Intrinsic Factor binds VB12 for
hypersegmented neutrophils
absorption in the ileum (parietal
with 6 or more lobes)
cells – produces HCl to maintain
o RETICULOCYTE COUNT: low
acidity)
absolute reticulocyte count
o Amnionless & Cubilin receptors
o WBC DIFFERENTIAL COUNT:
for VB12-IF complex (Epithelial
hypersegmentation of
cells of terminal Ileum)
neutrophils (right shift WBC
▪ If no IF – no binder for
histogram, hypo is left shift) is
VB12 and no absorption
pathognomonic for
will happen in the ileum
megaloblastic anemia
▪ If not absorbed or upon
o SERUM BILIRUBIN: elevated
absorption the VB12 will
total and indirect bilirubin
enter the storage. If not
o LACTATE DEHYDROGENASE:
stored it will go to liver
elevated values
or general circulation for
o SCHILLING’S TEST
other part of the body
▪ Test for cobalamin
▪ Impaired absorption TRANSPORT IN PLASMA
could indicate IF
o Methyl cobalamin is a transport
deficiency
form of cobalamin (VB12)
▪ Radioactive cobalamin
▪ Transcobalamin II +
is given orally
VB12
▪ 2 hrs after, a non-
▪ Haptocorrins
labelled “flushing” dose
(cobalophilin)
is given
▪ 24 hr urine is examined
for radioactive
cobalamin
SEQUENCE OF DEVELOPMENT OF
MEGALOBLASTIC ANEMIAS

• Decrease in vitamin levels

• Hypersegmentation of neutrophils in
peripheral blood
• Oval macrocytes in peripheral blood
• Megaloblastosis in bone marrow
• Anemia

TREATMENT

• Better nutrition
• Treatment for D. latum
• High dose orat VB12/ Folic acid
• Iron supplements

NON-MEGALOBLASTIC MACROCYTIC ANEMIA

• Alcoholism
• Liver disease
• Bone marrow disorder/ failure