20
RAHUL THAKUR ROLL NO.1167 MEGALOBLASTIC ANAEMIA

Megaloblastic anaemia

Embed Size (px)

Citation preview

Page 1: Megaloblastic anaemia

RAHUL THAKURROLL NO.1167

MEGALOBLASTIC ANAEMIA

Page 2: Megaloblastic anaemia

Definition: Macrocytic Anemia

MCV>100fLImpaired DNA formation due to lack of

vitamin B12 or folate in ultimately active form.

Therefore, maturation of nucleus is delayed relative to that of cytoplasm.

Page 3: Megaloblastic anaemia

Vitamin B12: Cobalamin

SOURCE:Meat and dairy products onlyMinimum daily requirement 6-9 mcg/dTotal body store 2-5 mg.

Helps to synthesize thiamine, thus deficiency leads to problems with DNA replication.

Page 4: Megaloblastic anaemia

B12: Cobalamin absorption

Initially bound to protein in diet, liberated by acid and pepsin, then binds to R factors in saliva and gastric acids

Freed from R factors by pancreatic proteases then binds to Intrinsic Factor secreted by gastric parietal cells

Absorbed together (Cbl + IF) in ileum

Released from IF in ileal cell then exocytosed bound to trans-Cbl II

Cbl bound to transcobalamin II binds to cell surface receptors and is endocytosed

Page 5: Megaloblastic anaemia

Functions of Cobalamin

Page 6: Megaloblastic anaemia

Causes of B12 Deficiency: Pernicious Anemia

Autoantibody to Intrinsic Factor detectable in <70% cases.

Blocks attachment of Cbl to IF Blocks attachment of Cbl-IF complex to

ileal receptorsChronic atrophic gastritis

Autoantibody against parietal cells

Page 7: Megaloblastic anaemia

Other Causes of B12 Deficiency:

Gastrectomy Ileal resection Ileal disease (TB, lymphoma, amyloid, Crohn’s) Enteropathies (protein losing, chronic diarrhea, celiac sprue) Bacterial overgrowth HIV infection Chronic alcoholism Strict vegetarian diet Inherited:o Methylmalonic aciduriao Homocystinuriao Congenital intrinsic factor deficiency Decreased absorption from medication:

Neomycin Metformin (biguanides) up to 10-25% PPI Nitric oxide (inhibits methionine synthase)

Page 8: Megaloblastic anaemia

B12 Deficiency SymptomsAtrophic glossitis

(shiny tongue)Shuffling broad gaitAnemia and related

symptomsVaginal atrophyMalabsorptionJaundicePersonality changesHyperhomocysteinemiaNeurologic symptoms

(next slide)

Page 9: Megaloblastic anaemia

B12 Symptoms: Neurologic

Memory lossNumbnessWeaknessSymmetric neuropathy

legs>armsSevere weakness,

spasticity, clonus, paraplegia

Subacute combined degeneration of the dorsal (posterior) and lateral spinal columns

Due to a defect in myelination

Page 10: Megaloblastic anaemia

Subacute Combined Degeneration

Degeneration and demyelination of the dorsal (posterior) and lateral spinal columns

Page 11: Megaloblastic anaemia

B12 Lab findings

Macroovalocytic anemia with elevated serum bilirubin. Increased red cell

breakdown due to ineffective hematopoiesis

Reticulocytes, WBC & platelets normal to low

Hypersegmented neurophils

Page 12: Megaloblastic anaemia

Bone Marrow

Hypercellular marrow Megaloblastic

erythroid hyperplasia Giant metamyelocytes

Due to slowing of DNA synthesis and delayed nuclear maturation

Methionine deficiency may play a central role

Page 13: Megaloblastic anaemia

Folate

SOURCE:Animal products (liver), yeast and leafy vegetables

Normal requirement 400mcg/dayBody stores: 5-10mg

Page 14: Megaloblastic anaemia

Folate Metabolism

Binds to folate receptor, becomes polyglutamated intracellularly

Site of absorption is duodenum and jejunum.

Page 15: Megaloblastic anaemia

Causes of Folate Deficiency

Malnutrition: Destroyed by heat during cooking

Alcoholism (decreased in 2-4 days): impairs enterohepatic cycle and inhibits absorption

Increased requirement in hemolytic anemia, pregnancy, exfoliative skin disease

IBD, celiac sprueDrugs

Trimethoprim, Methotrexate, Primethamine (inhib DHFR)

Phenytoin: blocks FA absorption, increases utilization

Page 16: Megaloblastic anaemia

Folate deficiency symptoms

Similar symptoms as B12 except for neurologic symptoms

Page 17: Megaloblastic anaemia

Shilling Test

PART 1: Oral labeled B12 and IM

unlabeled B12[ to saturate tissue stores] are given at the same time

24h urinary excretion is detected to assess absorption:>5% normal<5% impaired

PART 2: Repeat with oral IF if now normal

=PA[due to intrinsic factor deficiency]if impaired = malabsorption

Part 1 test result

Part 2 test result

Diagnosis

Normal -Normal or vitamin B12 deficiency

Low NormalPernicious anemia

Low Low Malabsorption

Page 18: Megaloblastic anaemia

Diffferential diagnosis

Aplastic anaemiaPure red cell aplasiaTransient erythroblastopenia of childhoodCongenital dyserythropoietic anemiaChronic liver diseaseHypothyroidismMyelodysplastic syndrome

Page 19: Megaloblastic anaemia

Treatment

folate deficiency is treated with folate supplements:5 mg tablets are available.a dose of 1-5 mg/day for 3-4 weeks.

Vit.B12 is given parenterally at a dose of 1mg-followup shows decrease in MCV,reticulocytosis and improvement in platelet and neutrophil counts.

Lower doses are used in infants[250mcg].

Page 20: Megaloblastic anaemia

THANKYOU