Pernicious anemia is a chronic disorder caused by Vitamin B12 deficiency due to failure of intrinsic factor secretion from gastric atrophy. It results in megaloblastic anemia and neurological manifestations. Diagnosis involves clinical features of macrocytic anemia, neurological symptoms, and low serum B12 levels. Treatment involves lifelong Vitamin B12 supplementation through injections.
2. INTRODUCTION
First described as a recognisable clinical entity by
Addison in 1855.
It is a chronic disorder of middle and old age, and the
basic pathological lesion is gastric atrophy which results
in Vitamin B12 deficiency.
With adequate treatment the prognosis is excellent.
3. PATHOGENESIS
Failure of secretion of Intrinsic factor (IF) by the stomach due
to permanent atrophy of the gastric mucosa membrane.
In the absence of IF, the Vit B12 of food is not absorbed,
resulting in Vit B12 deficiency.
The Diffuse mucosal atrophy, which is referred to as chronic
atrophic gastritis, is most marked in body of stomach.
The atrophic mucosa is heavily infiltrated by lymphocytes and
plasma cells.
4.
5. Histological examination reveals an almost complete
absence of chief and parietal cells, frequently with a
change to an intestinal type of epithelium.
The atrophy results in –
Loss of intrinsic factor
Decrease HCL secretion
Decrease pepsin
Decrease gastric secretion
7. • The current evidence suggests that the pathogenesis of
pernicious anaemia is uncertain and it is the end result of
complex interaction between genetic and auto immune
factors.
• AUTOIMMUNE FACTORS -
◦ The discovery that gastric parietal cell auto-antibodies were
frequently present in the seum and gastric juice, and it is presumed
that these auto-antibodies were responsible for the atrophy of gastric
mucosa.
8. • There are 2 Antibodies against the antegenic components of
gastric parietal cells in serum and gastric juice :-
PARIETAL CELL ANTIBODIES :
o 90% PA patients have serum IgG antibodies to surface
membrane and cytoplasmic antigens of gastric parietal cells.
o 35% in sera of patient relatives.
o 30-60% in patients of chronic atrophic gastritis without PA.
o Normal people, particularly females 70 years above.
9. INTRINSIC FACTOR ANTIBODIES :
oBlocking antibodies (Type I anti-IF antibody) -
React with Vit B12–combining site of IF and inhibit B12
binding.
Found in 50-70% patients.
oBinding antibodies (Type II anti-IF antibody) -
• Attach to site distant from Vit B12-combinig site and prevent
linkage of IF-Vit B12 complex to ileal receptor.
• Less frequently occurs and are usually present when titre of
blocking antibodies is high.
10. CLINICAL FEATURES
Anaemia
Glossitis (Red beefy tongue)
Nervous system manifestations :
◦ Axonal degeneration
◦ Peripheral neuropathy due to peripheral nerve lesion
◦ Demyelination of posterior and lateral columns of spinal cord
◦ Paraesthesia of feet (Bilateral, symmetrical, spreads gradually up the
legs to the thighs)
◦ Clumpsy fine movements of fingers
◦ Retrobulbar neuritis
◦ Mild mental disturbances
12. GI Manisfestations :
◦ Diarrohea
◦ Anorexia
◦ Dyspepsia
◦ Slight to moderate hepatomegaly
Congestive cardiac failure
Petechiae or small ecchymoses of skin
Mild pyrexia
Amenorrhea and infertility
13. BLOOD PICTURE
CBC –
◦ Hb 3 g/dl or even less
◦ MCV increased from 110-140 fl
◦ MCH increased from 33-38 pg
◦ MCHC normal
◦ Leucopenia from 3000-4000/ul
◦ Thrombocytopenia from 100000-150000/ul
14. PBF –
◦ RBC: show presence of macrocytic red cells along
with anisopoikilocytosis in form of Macro-ovalocytes,
microcytes and occassional fragmented cells. Some
cells show basophilic stippling. A small number of
Nrbc and Howell jolly bodies are often seen. In
severe anaemia, Nrbc may be typical megaloblasts.
◦ WBC: show moderate leucopenia. Hypersegmented
neutrophils are always present and few myelocytes
may appear.
15.
16. Bone marrow aspiration:
◦ Generally not necessary, but essential in doubtful
cases.
◦ It should be performed before the administration
of Vit B12, as this rapidly changes erthyropoiesis
from megaloblastic to normoblastic.
17. BIOCHEMICAL FINDINGS –
◦ S.bilirubin is from 14-17 umol/l
◦ S.haptoglobin reduced
◦ S.ferritin and S.iron increased but fall within 48hrs
of T/t
◦ Plasma LDH increased
◦ Serum folate is usually normal
◦ Red cell folate is almost always reduced
◦ Coombs is positive in 10% patients due to
complement coating of red cells.
18. DIAGNOSIS
Clinical picture
Macrocytic blood picture
Megaloblastic bone marrow
Low serum Vit B12
Positive serum IF antibody test
Radioactive Vit B12 assay test
Response to therapeutic trial of B12
19.
20. TREATMENT
Administration of Vit B12 :
◦ INITIAL DOSAGE : 1000 ug hydroxycobalamin
daily for 1 week
◦ MAINTENANCE DOSAGE : 1000 ug once every 3
months.
Symptomatic and supportive therapy.
Follow-up and early detection of gastric carcinoma and
carcinoids.