MCQs

• Hypoproliferative anaemias include all

except ___.
A. Iron Deficiency Anaemia
B. Anaemia due to chronic inflammation
C. Sickle Cell Anaemia
MCQ 1

D. Sideroblastic Anaemia
 • Transport of Iron across brush border
intestinal cell is facilitated by ___.
A.Ferroportin
B.Nramp 2
C.DMT 1
MCQ 2

D.Both B & C
 • The earliest sign of Iron deficiency anemia is
___.
A.Increase in TIBC
B.Decrease in serum Iron
C.Decrease in serum ferritin
MCQ 3

D.Increase in red cell protoporphyrin

 • Which of the following is false regarding the
stage of negative iron balance in IDA?
A.Bone marrow stainable iron decreases
B.TIBC decreases
C.RBC morphology normal
MCQ 4

D.Serum Iron Normal

 • A 28 year old female with fatiguability is
evaluated to have Hb – 6g/dL, MCV – 67fL,
MCH – 24pg, and elevated RDW. The most
likely diagnosis is ___.
A.Thalassemia
MCQ 5

B.Megaloblastic Anaemia
C.Iron Deficiency Anaemia
D.Hypothyroidism
 • The red blood cell indices of a 56 year old
male patient with a Hb of 9g/dL are as
follows: MCV = 112 fL and MCHC = 34
g/dL. Which of the following is the most
likely diagnosis?
MCQ 6

A.Folate deficiency
B.Sideroblastic anemia
C.Beta-thalassemia
D.Iron deficiency anaemia
 • 58-Co labeled cobalamin was administered to
a 65-yr-old female. 24-hr urinary excretion of
radiolabeled cobalamin was found to be less
than 10%. Which of the following conditions
is the most likely diagnosis?
MCQ 7

A.Perinicious Anemia
B.Chronic Pancreatitis
C.Both A & B
D.NORMAL individual
 • Monoglutamates of dietary folate are
absorbed from ___?
A.Upper small intestine
B.Mid-small intestine
C.Terminal illeum
MCQ 8

D.Ascending colon
 • A 30-yr-old female with a past medical history of
generalized seizures controlled with phenytoin
therapy. She had mild pallor on physical
examination. Lab values reveal Hb – 9.8g/dL,
MCV – 106 fL, Platelets – 1,80,000/cu.mm,
leukocytes – 7800/cu.mm. Which of the following
MCQ 9

supplementations could have prevented this

anemia?
A.Iron
B.Vitamin B12
C.Vitamin B6
D.Folic Acid
 • A patient with megaloblastic anemia was treated
with folate supplements. The patient’s signs of
anemia resolved but the patient continued to
complain of poor memory, numbness and tingling
in the extremities. You suspect that the patient was
originally misdiagnosed. Which of the following
MCQ 10

will correct the patient’s underlying condition?

A.Injection Hydroxycobalamin
B.Higher doses of Folic Acid
C.Chelation therapy
D.Thiamine supplementation
ANSWERS & EXPLANATION
 • Hypoproliferative anaemias include all
except ___.
A. Iron Deficiency Anaemia
B. Anaemia due to chronic inflammation
C. Sickle Cell Anaemia
MCQ 1

D. Sideroblastic Anaemia
MCQ 1
 • Transport of Iron across brush border
intestinal cell is facilitated by ___.
A.Ferroportin
B.Nramp 2
C.DMT 1
MCQ 2

D.Both B & C
MCQ 2
 • The earliest sign of Iron deficiency anemia is
___.
A.Increase in TIBC
B.Decrease in serum Iron
C.Decrease in serum ferritin
MCQ 3

D.Increase in red cell protoporphyrin

MCQ 3
 • Which of the following is false regarding the
stage of negative iron balance in IDA?
A.Bone marrow stainable iron decreases
B.TIBC decreases
C.RBC morphology normal
MCQ 4

D.Serum Iron Normal

MCQ 4
 • A 28 year old female with fatiguability is
evaluated to have Hb – 6g/dL, MCV – 67fL,
MCH – 24pg, and elevated RDW. The most
likely diagnosis is ___.
A.Thalassemia
MCQ 5

B.Megaloblastic Anaemia
C.Iron Deficiency Anaemia
D.Hypothyroidism
 Low MCV (N: 87-96 fL) and Low MCH (N:
27-33 pg) with an elevated RDW is
suggestive of Iron Deficiency Anemia.
• Microcytic Hypochromic anemia is seen in
both IDA and thalassemia.
MCQ 5

• However, RDW index is small (normal) in

thalassemia and elevated in IDA. Also,
serum iron levels and transferrin saturation is
normal in thalassemia.
• Hypothyroidism and megaloblastic anemia
show macrocytosis.
 • The red blood cell indices of a 56 year old
male patient with a Hb of 9g/dL are as
follows: MCV = 112 fL and MCHC = 34
g/dL. Which of the following is the most
likely diagnosis?
MCQ 6

A.Folate deficiency
B.Sideroblastic anemia
C.Beta-thalassemia
D.Iron deficiency anaemia
 • Folate deficiency presents with macrocytic
(Raised MCV, N: 80-100 fL) and
normochromic (Normal MCHC, N: 33-36
g/dL) anemia.
• Also characterized by increased MCH,
MCQ 6

RDW is elevated in two-thirds of all cases.

The reticulocyte count is decreased due to
destruction of fragile and abnormal
megaloblastic erythroid precursors.
• Other options listed are classified as
microcytic hypochromic anemia.
 • 58-Co labeled cobalamin was administered to
a 65-yr-old female. 24-hr urinary excretion of
radiolabeled cobalamin was found to be less
than 10%. Which of the following conditions
is the most likely diagnosis?
MCQ 7

A.Perinicious Anemia
B.Chronic Pancreatitis
C.Both A & B
D.NORMAL individual
 • Schilling test is abnormal in perinicious
anemia, chronic pancreatitis, bacterial
overgrowth and illeal disease.
• Schilling test is done to determine the cause
of cynocobalamin deficiency.
MCQ 7

• Schilling test is normalised by adding

intrinsic factor in perinicious anemia,
pancreatic enzymes in chronic pancreatitis
and a 5-day antibiotic course in bacterial
overgrowth.
 • Monoglutamates of dietary folate are
absorbed from ___?
A.Upper small intestine
B.Mid-small intestine
C.Terminal illeum
MCQ 8

D.Ascending colon
 • Dietary folates are rapidly absorbed from the
upper small intestine in the form of
monoglutamates.
• Vitamin B12 absorption takes place in the
terminal illeum.
MCQ 8
 • A 30-yr-old female with a past medical history of
generalized seizures controlled with phenytoin
therapy. She had mild pallor on physical
examination. Lab values reveal Hb – 9.8g/dL,
MCV – 106 fL, Platelets – 1,80,000/cu.mm,
leukocytes – 7800/cu.mm. Which of the following
MCQ 9

supplementations could have prevented this

anemia?
A.Iron
B.Vitamin B12
C.Vitamin B6
D.Folic Acid
 • This patient has mild megaloblastic anemia
(high MCV), probably due to chronic
phenytoin therapy.
• Some anti-epileptic drugs like phenytoin,
phenobarbital can cause megaloblastic
MCQ 9

anemia by impairing the absorption of folate

in the small intestine.
• Folic acid supplementation can prevent this
condition.
 • A patient with megaloblastic anemia was treated
with folate supplements. The patient’s signs of
anemia resolved but the patient continued to
complain of poor memory, numbness and tingling
in the extremities. You suspect that the patient was
originally misdiagnosed. Which of the following
MCQ 10

will correct the patient’s underlying condition?

A.Injection Hydroxycobalamin
B.Higher doses of Folic Acid
C.Chelation therapy
D.Thiamine supplementation
 • The patient’s underlying condition is Vitamin B12
deficiency.
• Administration of Folic Acid can partially reverse some
of the hematologic abnormalities associated with
vitamin B12 deficiency. However, the neurologic
manifestations of vitamin B12 deficiency are not
MCQ 10

treated by folic acid.

• Administration of folic acid to an individual with
vitamin B12 deficiency can potentially mask untreated
B12 deficiency or even worsen the neurologic
complications.
• Lead poisoning can cause neurologic symptoms but is
associated with microcytic anemia.
MEGALOBLASTIC ANAEMIA
Dr. Vivek Veeram Reddy
DEFINITION
• This results from a deficiency of vitamin
B12 or folic acid,
• or from disturbances in cobalamin or folic
acid metabolism.
 • Therapy with antifolate drugs (e.g., methotrexate)
• Independent of either cobalamin or folate deficiency
and refractory to cobalamin and folate therapy:
OTHER CAUSES

Some cases of acute myeloid leukemia, myelodysplasia

Therapy with drugs interfering with synthesis of DNA (e.g.,
cytosine arabinoside, hydroxyurea, 6-
mercaptopurine, azidothymidine [AZT])
Orotic aciduria (responds to uridine)
Thiamine-responsive
PATHOPHYSIOLOGY
• Folate is an important substrate of, and
vitamin B12 a co-factor for, the generation of
the essential amino acid methionine from
homocysteine.
• This reaction produces tetrahydrofolate,
which is converted to thymidine
monophosphate for incorporation into DNA.
• Deficiency of either vitamin B12 or folate
will therefore produce high plasma levels of
homocysteine and impaired DNA synthesis.
• The end result is cells with arrested nuclear
maturation but normal cytoplasmic
development: so-called nucleocytoplasmic
asynchrony.
• All proliferating cells will exhibit
megaloblastosis; hence changes are evident
in the buccal mucosa, tongue, small intestine,
cervix, vagina and uterus.
• Cells become arrested in development and die
within the marrow; this ineffective
erythropoiesis results in an expanded
hypercellular marrow.
• The megaloblastic changes are most evident
in the early nucleated red cell precursors, and
haemolysis within the marrow results in a
raised bilirubin and LDH, but without the
reticulocytosis characteristic of other forms
of haemolysis.
• The mature red cells are large and oval, and
sometimes contain nuclear remnants.
• Nuclear changes are seen in the immature
granulocyte precursors and a characteristic
appearance is that of ‘giant’ metamyelocytes with
a large ‘sausage-shaped’ nucleus.
• The mature neutrophils show hypersegmentation
of their nuclei, with cells having six or more
nuclear lobes.
• If severe, a pancytopenia may be present in the
peripheral blood.
VITAMIN B12
VITAMIN B12 - METABOLISM
• DIETARY INTAKE
• ABSORPTION
• TRANSPORT
• STORAGE
• UTILIZATION
 • The average daily diet contains 5–30 μg of
vitamin B12, mainly in meat, fish, eggs and
milk – well in excess of the 1 μg daily
DIETARY INTAKE

requirement.
 • In the stomach, gastric enzymes release
vitamin B12 from food and at gastric pH it
binds to a carrier protein termed R protein.
• The gastric parietal cells produce intrinsic
ABSORPTION

factor, a vitamin B12- binding protein which

optimally binds vitamin B12 at pH 8.
 • As gastric emptying occurs, pancreatic
secretion raises the pH and vitamin B12
released from the diet switches from the R
protein to intrinsic factor.
ABSORPTION
 • Bile also contains vitamin B12 which is
available for reabsorption in the intestine.
• The vitamin B12–intrinsic factor complex
ABSORPTION

binds to specific receptors in the terminal

ileum, and vitamin B12 is actively
transported by the enterocytes to plasma.
 • It binds to transcobalamin II, a transport
protein produced by the liver, which carries
it to the tissues for utilisation.
TRANSPORT
 • The liver stores enough vitamin B12 for 3
years and this, together with the
enterohepatic circulation, means that vitamin
B12 deficiency takes years to become
manifest, even if all dietary intake is stopped
STORAGE

or severe B12 malabsorption supervenes.

UTILIZATION
CAUSES OF VITAMIN B12
DEFICIENCY
• DIETARY DEFICIENCY
• GASTRIC PATHOLOGY
• PERNICIOUS ANEMIA
• SMALL BOWEL PATHOLOGY
 • This only occurs in strict vegans but the onset
of clinical features can occur at any age
DIETARY DEFICIENCY

between 10 and 80 years.

 • Hypochlorhydria in elderly patients
GASTRIC PATHOLOGY

• Total gastrectomy invariably results in

vitamin B12 deficiency within 5 years,
• Often combined with iron deficiency
• 10-20% patients with Partial gastrectomy
 • Organ-specific autoimmune disorder in which
the gastric mucosa is atrophic, with loss of
PERNICIOUS ANEMIA

parietal cells causing intrinsic factor

deficiency.
• Less than 1% of dietary vitamin B12 is absorbed.
• More common with other autoimmune disease
• Anti-intrinsic factor antibodies in the context
of B12 deficiency is diagnostic
• Antiparietal cell antibodies are present in over
90% of cases
• Schilling test
SMALL BOWEL PATHOLOGY
• Pancreatic exocrine insufficiency – chronic
pancreatitis
• Motility disorders or
hypogammaglobulinaemia can result in
bacterial overgrowth
• Fish tapeworm infestation
• Inflammatory disease of the terminal ileum,
such as Crohn’s disease
• Surgery on that part of the bowel.
FOLATE
FOLATE - METABOLISM
• DIETARY INTAKE
• ABSORPTION
• TRANSPORT
• STORAGE
• UTILIZATION
 • Folates are produced by plants and bacteria;
hence dietary leafy vegetables (spinach,
broccoli, lettuce), fruits (bananas, melons)
DIETARY INTAKE

and animal protein (liver, kidney) are a rich

source.
• An average Western diet contains more than
the minimum daily intake of 50 μg but excess
cooking destroys folates. Most dietary folate
is present as polyglutamates.
 • Polyglutamates are converted to
monoglutamate in the upper small bowel
and actively transported into plasma.
ABSORPTION
 • Plasma folate is loosely bound to plasma
TRANSPORT & STORAGE

proteins such as albumin and there is an

Enterohepatic circulation.
• Total body stores of folate are small and
deficiency can occur in a matter of weeks.
UTILIZATION
CAUSES OF FOLATE
DEFICIENCY
Diet
• Poor intake of vegetables
Malabsorption
• e.g. Coeliac disease
Increased demand
• Cell proliferation, e.g. haemolysis
• Pregnancy
Drugs
• Certain anticonvulsants (e.g. phenytoin)
• Contraceptive pill
• Certain cytotoxic drugs (e.g. methotrexate)
• The edentulous elderly or psychiatric patient is
particularly susceptible to dietary deficiency and this
is exacerbated in the presence of gut disease or
malignancy.

• Pregnancy-induced folate deficiency is the most

common cause of megaloblastosis worldwide and is
more likely in the context of twin pregnancies,
multiparity and hyperemesis gravidarum.
 CLINICAL FEATURES OF
MEGALOBLASTIC ANAEMIA
 • Malaise (90%)
• Breathlessness (50%)
• Paraesthesiae (80%)
• Sore mouth (20%)
SYMPTOMS

• Weight loss
• Altered skin pigmentation
• Impotence
• Poor memory
• Depression
• Personality change
• Hallucinations
• Visual disturbance
 • Smooth tongue
• Angular cheilosis
• Vitiligo
• Skin pigmentation
SIGNS

• Heart failure
• Pyrexia
NEUROLOGICAL
MANIFESTATIONS OF VITAMIN
B12 DEFICIENCY
 • The main pathological finding is focal
demyelination affecting the spinal cord,
PATHOPHYSIOLOGY

peripheral nerves, optic nerves and cerebrum.

• The most common manifestations are
sensory, with peripheral paraesthesiae and
ataxia of gait.
 Peripheral nerves
• Glove and stocking paraesthesiae
• Loss of ankle reflexes

Spinal cord
FINDINGS

• Subacute combined degeneration of the cord

Posterior columns – diminished vibration
sensation and proprioception
Corticospinal tracts – upper motor neuron signs

Cerebrum
• Dementia
• Optic atrophy

Autonomic neuropathy
INVESTIGATIONS
MEGALOBLASTIC ANEMIA
 Serum Cobalamin Levels - decreased
VITAMIN B12 DEFICIENCY

Special Investigations
• Serum Methylmalonate & Homocysteine -
raised
• Serum Gastrin - raised
• Gastric Endoscopy
• Anti bodies against intrinsic factor and
parietal cells - elevated
• Intestinal Endoscopy (Colonoscopy)
 Diagnostic findings
• Serum folate levels may be low but are difficult to
FOLATE DEFICIENCY

interpret
• Low red cell folate levels indicate prolonged folate
deficiency and are probably the most relevant
measure
Corroborative findings
• Macrocytic dysplastic blood picture
• Megaloblastic marrow
MANAGEMENT
 • If severe angina or heart failure is present,
MEGALOBLASTIC ANEMIA

transfusion can be done.

• The volume load imposed by transfusion may
result in decompensation and severe cardiac
failure.
• In such circumstances, exchange transfusion
or slow administration of 1 U of red cells
with diuretic cover may be given cautiously.
 • Hydroxycobalamin 1000 μg IM for 6 doses
VITAMIN B12 DEFICIENCY

2 or 3 days apart, followed by maintenance

therapy of 1000 μg every 3 months for life.
• Reticulocyte count will peak by the 5th–10th
day.
• The haemoglobin will rise by 0.1g/mL every
week.
• A sensory neuropathy may take 6–12 months
to correct; long-standing neurological damage
may not improve.
 • The response of the marrow is associated
with a rapid depletion of iron stores.
DIMORPHIC ANEMIA

• If an initial response is not maintained and

the blood film is dimorphic (i.e. shows a
mixture of microcytic and macrocytic cells),
the patient may need additional iron therapy.
 • Oral folic acid 5 mg daily for 3 weeks will
treat acute deficiency
FOLATE DEFICIENCY

• 5 mg once weekly is adequate maintenance

therapy.
• Supraphysiological supplementation (400
μg/day) can reduce the risk of coronary and
cerebrovascular disease by lowering plasma
homocysteine levels.
 • Prophylactic folic acid in pregnancy prevents
FOLATE PROPHYLAXIS

megaloblastosis in women at risk, and

reduces the risk of fetal neural tube defects.
• Prophylactic supplementation is also given in
chronic haematological disease associated
with reduced red cell lifespan.
THANK YOU