Pernicious Anemia

Pernicious Anemia: Failure of secretion of intrinsic factor (IF)

1. PERNICIOUS ANEMIA Presented by : Dr. Shubhi Saxena Under Guidance of : Dr. Narayani Joshi

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. 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

5. Normal Gastric atrophy PA

6. 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.

7. There are 2 Antibodies against the antegenic components of gastric parietal cells in serum and gastric juice :- PARIETAL CELL ANTIBODIES : 90% PA patients have serum IgG antibodies to surface membrane and cytoplasmic antigens of gastric parietal cells. 35% in sera of patient relatives. 30-60% in patients of chronic atrophic gastritis without PA. Normal people, particularly females 70 years above.

8. INTRINSIC FACTOR ANTIBODIES : Blocking antibodies (Type I anti-IF antibody) - React with Vit B12–combining site of IF and inhibit B12 binding. Found in 50-70% patients. Binding 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.

9. 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

10. Red beefy tongue

11. GI Manisfestations : Diarrohea Anorexia Dyspepsia Slight to moderate hepatomegaly Congestive cardiac failure Petechiae or small ecchymoses of skin Mild pyrexia Amenorrhea and infertility

12. 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/ u l Thrombocytopenia from 100000-150000/ u l

13. 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.

14. 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 .

15. BIOCHEMICAL FINDINGS – S.bilirubin is from 14-17 u mol /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.

16. 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

17. TREATMENT Administration of Vit B12 : INITIAL DOSAGE : 1000 u g hydroxycobalamin daily for 1 week MAINTENANCE DOSAGE : 1000 u g once every 3 months. Symptomatic and supportive therapy. Follow-up and early detection of gastric carcinoma and carcinoids .