PERNICIOUS ANEMIA

BSMT 3D GROUP 1

PANIZA, ERIKA JOY

VILLANUEVA, ANDREW ARNOLD
YANDAN, CHARIS
 Case Report

A 29-year old young man presented with weakness of

lower limbs, unsteadiness and clumsiness while
walking with frequent falls for 3 months period.
Routine hematological investigation revealed :
 TEST RESULT NV Interpretation
Hemoglobin (gm%) 9.1 13.5–18.0 Decreased

MCV(fL) 121.6 80-100 Elevated,

Macrocytic
ESR(mm) 15 0-15 Normal
WBC(cml) 4,200 3.6-10.6 Normal
Differential Count Normal
Plt Count(lacs/cml) 2 2-5 Normal

FBS(mg/dL) 105 <140 Normal

T Bil(mg/dL) 2.4 0.1-1.2 Elevated
Direct Bil(mg/dL) 0.8 <0.3 Elevated
Liver enzymes Normal
Serum Vit. B12(pg/mL) 192 200-900 Decreased

Serum Folic Acid(πg/ml) 10.2 2-20 Normal

CPK 34 10-120 Normal
HIV Negative
VDRL Negative
Serum Anti-IF Positive
 Guide Questions

 1. What possible condition does the patient

have? Give possible causes.

The possible condition of the patient is Pernicious

anemia.
Possible causes include:
I. Inadequate Intake
This condition is possible for strict vegetarians
who do not eat meat, eggs, or dairy products.
 Guide Questions

II. Increased Need

Increased need for vitamin B12 occurs during
pregnancy, lactation, and growth.
III. Impaired Absorption

The absorption of vitamin B12 can be impaired by:

 Failure to Separate Vitamin B12 from Food
Proteins
A condition known as food-cobalamin
malabsorption is characterized by hypochlorhydria and
the resulting inability of the body to release vitamin B12
from food or intestinal transport proteins for subsequent
binding to intrinsic factor.
 Guide Questions

 Failure to Separate Vitamin B12 from

Haptocorrin
Lack of gastric acidity or lack of trypsin can
prevent vitamin B12 absorption because the vitamin
remains bound to haptocorrin in the intestine and
unavailable to intrinsic factor.
 Lack of Intrinsic Factor
Lack of intrinsic factor constitutes a significant
cause of impaired vitamin B12 absorption. It is most
commonly due to autoimmune disease, as in
pernicious anemia.
 Guide Questions

 Malabsorption
General malabsorption of vitamin B12 can be
caused by the same conditions interfering with folate
absorption.
 Inherited Errors of Vitamin B12 Absorption
and Transport
1. Imerslund-Gräsbeck syndrome
2. Transcobalamin deficiency
 Guide Questions

 Competition for Vitamin B12

Competition for available vitamin B12 in the
intestine may come from intestinal organisms.
1.Diphyllobothrium latum
2. Blind loops
 Etiology

 Autoimmune disease
 Formation of Anti-Intrinsic Factor Abs
 -failure to form IF-Vit. B12 complex

 Impaired absorption of B12

 Chronic: Lymphocyte mediated Immune Response

 Epidemiology

 Predominant with people of >40 years of age

 Often manifest in the 6th decade of life
 Usual with people of Blood Group A
 Congenital PA: autosomal recessive
 Epidemiology

 Defect that occurred is:

 defect in immunologic tolerance to some stomach,
thyroid, skin and pancreatic antigens, or
 defect in metabolic or enzyme system common with the
said tissues.
 Pathophysiology

 Intrinsic Factor(IF)
 GIF gene

 Parietal CellsHCl+IF

 IF-Vit. B12 protective complex

 Transcobalamin I, II, III

 Salivary gland

 Vit. B12 intermediate carrier

 Plasma carriers of B12

 Found in stomach, saliva, milk and sweat

Pathophysiology
 Pathophysiology

Parietal cell Abs vs Anti-IF Abs

PC Abs:
 IgG type
 occurs 84% of patients with PA
 not very useful for diagnosis since it is not specific for PA
 may be found in some healthy individuals or other types of
autoimmune diseases
Anti-IF Abs:
 IgG type
 expressed by 56% of patients with PA
 rare in normal people
 specific marker of PA
 Pathophysiology

Types of IFA:
 Blocking IFA-bind with IF and block its vitamin B12-binding site.
 Binding IFA-are usually found in conjunction with blocking
antibodies.
1st type-attaches to an antigenic site on IF that is distant from the actual
B12-binding site
2nd type-binds to both IF and its complexed B12.
 Pathophysiology

Lymphocyte-Mediated Immune response

 Pathologic CD4 T cells
 autoimmune responseH1/K1–adenosine triphosphatase in the
membrane of the parietal cell
 atrophic gastritisloss of the parietal cellsHCl and intrinsic
factorachlorhydria.
 Low gastric acidity(dxtic of PA)
 ↑Gastrin due to the achlorhydria-compensatory mechanism by G cells
 Pathophysiology

 Vitamin B12
 key role in the formation and maturation of RBCs
together with folate.
 ↓Vit. B12=↓RBCs and structurally abnormal

Deficiency:
↓O2 transport to organs=feeling tired, weak and
neuropathy or nerve damage
 Pathophysiology

 Folate, vitamin B12, and ironerythropoiesis.

 for proliferation during their differentiation.
 Deficiency :
 inhibits purine and thymidylate syntheses, impairs DNA synthesis,
and causes erythroblast apoptosis, resulting in anemia from
ineffective erythropoiesis.
 Megaloblastic vs Megaloblastoid

 Megaloblastoid
 resembling megaloblastic cells
 Abnormal erythrocyte maturation that is not caused by B2 or folate
deficiency
 Caused by malignancies in myeloid precursors
 More coarser clumping of nuclear chromatin
 MDS- with normal or increased folate and B12
 Megakryoblasts in PBS
 Neutrophil Hypolobulation(pseudo-Pelger-Huet cells)
 Guide Questions

 2. What other clinical signs and symptoms may a

patient exhibit with the diagnosis?

Classic triad:
Weakness
Sore tongue
Paresthesias
 Guide Questions

General symptoms
 Weight loss
 Low-grade fever
 Guide Questions

Cardiac symptoms
 Congestive heart failure
 Coronary insufficiency
 Guide Questions

Gastrointestinal symptoms
 Smooth, thick, red tongue
 Constipation or having several semisolid bowel
 Anorexia, nausea, vomiting, heartburn, pyrosis,
flatulence, and a sense of fullness
 Guide Questions

Neurologic symptoms
 Paresthesias, weakness, clumsiness, and an unsteady
gait
 Older patients: suggesting senile dementia or
Alzheimer disease; memory loss, irritability, and
personality changes
 Megaloblastic madness: delusions, hallucinations,
outbursts, and paranoid schizophrenic ideation
 Guide Questions

3. Give other laboratory findings that may be

present in this condition.

Bilirubin and Lactate Dehydrogenase Levels

Bilirubin
 Elevated Total and indirect bilirubin

Lactate Dehydrogenase Levels

 Significantly increased
 Serum gastrin levels

 Markedly elevated due to the gastric achlorhydria.

 Vitamin B-12

 Significantly decreased
 Due to:
 Hereditary intrinsic factor deficiency

 Malabsorption

 Bowel disease.
 Intrinsic factor

 Lack of intrinsic factor constitutes a significant cause

of impaired vitamin B12 absorption
 Due to:
 Autoimmune disease
 Loss of parietal cells
 Helicobacter pylori infection
 Total or Partial gastrectomy
 Hereditary intrinsic factor deficiency.
 Serum Folic Acid

 A serum folic acid assay is useful for ruling out folic

acid deficiency.
 Methylmalonic Acid and Homocysteine

 Important confirmatory tests

 Elevated
 Methylmalonic aciduria is a sign of cobalamin
deficiency
 Guide Questions

4. Correlate lab findings with patient signs and symptoms.

 General decay in your thinking skills: due to decreased oxygen in

the brain, resulting from less red blood cell production
 Symptoms of cognitive decline: due to myelin degeneration and loss
of nerve fibers in the dorsal and lateral columns of the spinal cord
and cerebral cortex.
 Older patients may present with symptoms suggesting senile
dementia or Alzheimer disease; memory loss, irritability, and
personality changes: Vitamin B12 is essential for maintaining brain
health.
 Vitamin B12 deficiency may lead to nerve damage. This can cause
tingling and numbness in your hands and feet, muscle weakness,
and loss of reflexes. You also may feel unsteady, lose your balance,
and have trouble walking. Vitamin B12 deficiency can cause
weakened bones and may lead to hip fractures.
 Complete Blood Count

 Pancytopenia
 Impaired cell production results in a low absolute
reticulocyte count
Laboratory Findings
 Hematocrit And Hemoglobin

 RBC precursors die during division in the bone

marrow -> Ineffective hematopoiesis
 Decreased
 Red Cell Indices

 Mean cell volume (MCV)

- Macrocytic
 Mean cell hemoglobin (MCH) - Elevated
 Mean cell hemoglobin concentration (MCHC)
- Hyperchromic
 The red cell distribution width is high.
 Peripheral Blood Smear

• The bone marrow is usually hypercellular with

megaloblastic changes but it can be hypocellular and
mimic aplastic anemia.
• Enlarged metarubricyte with a decreased nuclear-
cytoplasmic ratio with an immature nucleoplasm.
WBCs appears larger than normal
- Metamyelocytes
- Granulocytic precursors may also display
nuclear-cytoplasmic dissociation and enlargement.
 Myeloid-erythroid ratio (M:E ratio) - 1:1 or less
 Poikilocytes

 Variation in shape of the

RBC
 Ovalocytes

 Generally narrower and

more elongated than
megalocytes.
 Rod, cigar, or sausage
shape.
 They represent a
membrane defect in
which the membrane is
radically affected and
suffers a loss of integrity.
 Anisocytes

 Variation in size of the

RBCs
 Macrocytes

Megalocytes have an oval

or egg-like appearance
 Red Cell Inclusions

 Basophilic stippling
 Howell-Jolly bodies
 Cabot rings
 Basophilic stippling

 Appears as tiny, round,

solidstaining, dark-blue
granules.
 Granules are usually
evenly distributed
throughout the cell
 Coarse basophilic -
punctate stippling ->
arger than in the fine
form and are considered
to be more serious
 Cabot Rings

 Ring-shaped, figure-
eight, or loop-shaped
structures
 They may represent
remnants of
microtubules from the
mitotic spindle
 Represent nuclear
remnants or abnormal
histone biosynthesis
 Howell-Jolly Bodies

 Round, solidstaining, dark-

blue to purple inclusions, 1
to 2 mm in size.
 Nuclear remnants
predominantly composed
of DNA
 Seen in patients with an
abnormal erythropoiesis,
because the spleen cannot
keep up with pitting these
remnants from the cell
 Bilirubin

 Elevated Total and indirect bilirubin

 Lactate Dehydrogenase Levels

 Significantly increased
 Serum gastrin levels

 Markedly elevated due to the gastric achlorhydria.

 Vitamin B-12

 Significantly decreased
 Due to:
 Hereditary intrinsic factor deficiency

 Malabsorption

 Bowel disease.
 Intrinsic factor

 Lack of intrinsic factor constitutes a significant cause

of impaired vitamin B12 absorption
 Due to:
 Autoimmune disease
 Loss of parietal cells
 Helicobacter pylori infection
 Total or Partial gastrectomy
 Hereditary intrinsic factor deficiency.
 Serum Folic Acid

 A serum folic acid assay is useful for ruling out folic

acid deficiency.
 Methylmalonic Acid and Homocysteine

 Important confirmatory tests

 Elevated
 Methylmalonic aciduria is a sign of cobalamin
deficiency
 Treatment

*Treatment should be directed at the specific vitamin

deficiency
 Vitamin B12 is administered intramuscularly
 High-dose oral vitamin B12 treatment

 Lifelong vitamin replacement therapy.

 Folic acid can be administered orally.
 Iron
 References

 Rodak's Hematology Clinical Principles and

Applications by Keohone, E.M., et al ( 5th Edition
2016), pages 154-164, 290-292, 320-327
 Clinical Hematology Theory and Procedures by
Turgeon, Mary Louise (5th edition), pages 127-
136,181-189
 https://www.nhlbi.nih.gov/health-
topics/pernicious-anemia
 https://emedicine.medscape.com/article/204930-
clinical