Rbc disorders-4

RBC Disorders

Dr.CSBR.Prasad, M.D.,

Normal gastric epithelium

Atrophic gastritis

Hyperplastic gastropathy

Perietal cell hyperplasia

Megaloblastic anemia


• Group of disorder characterized by impaired DNA synthesis & distinctive morphological changes in blood & BM

• Erythroid precursor & erythrocytes – abnormally large

• Defect in cell maturation & division

• Deficiency of vit. B12 & folic acid


• Vit B12 & Folic acid are coenzyme in the DNA synthetic pathway

• ↓ DNA synthesis – defective nuclear maturation

• Synthesis of RNA & proteins are unaffected – cytoplasmic maturation is normal

• Asynchronism bet. Cytoplasmic & nuclear maturation


• PBS – Anisopoikilocytosis

– Macrocytes, ovalocytes

– No central pallor

– Retic count – low

– Occasional nucleated RBC

• MCV - ↑ 100 fl , MCHC – N

• Neutrophils- Hypersegmented macropolys – larger in size

– hypersegmented ( 5-6 or more lobes)

Elliptical macrocytes

Hypersegmented macropoly


Bone Marrow • Hypercellular with megaloblastic

erythropoiesis • M:E ratio- 1:1 • Granulocytic precursor –

– N/C asynchrony – Giant metamyelocyte & band forms – Hypersegmented neutrophils

• Megakaryocytes – – large with multilobated nuclei

Megaloblastic anemia (BM aspirate) A,C-Megaloblasts. B-Intermediate Normoblast,

D-Giant metamyelocyte

D


• Mechanisms of anemia

– Ineffective erythropoiesis

– Hemolytic destruction of RBC

• Leukopenia

• Thrombocytopenia

Vit B12 deficiency

Megaloblastic anemia – Vit B12 deficiency

• Organometallic compound – cobalamin

• Animal products – rich in Vit B12

• Plants & vegetables- poor source

• 2-3µg/day

FIGURE 14-18 Schematic illustration of vitamin B12 absorption. IF, intrinsic factor; R-binders, cobalophilins


• Decreased intake – Inadequate diet – Veganism

• Impaired absorption – Intrinsic factor deficiency

• Pernicious anemia • Gastrectomy

– Malabsorption syndrome – Diffuse intestinal disease – Ileal resection, ileitis – Competative parasite uptake – fish tape worm – Bacterial overgrowth in blind loop – Zollinger – Ellison syndrome – Imerslund syndrome – Drug induced Vit B12 malabsorption – Chronic disease of the pancreas

• Increased requirement – Pregnancy , hyperthyroidism & disseminated cancers

Parasites causing Megaloblastic anemia

• Diphillobothrium latum (Fish tape worm)

• Fluke…..

Cases have been reported

from Puduchery1

Ref: 1 vvvvvv


1. Methyl cobalamin is essential cofactor for enzyme methionine synthase.

Methionine is required for synthesis of folate polyglutamate

2. Cobalamine is involved in isomerization of Methyl malonyl CoA to succinyl Co A

Relationship of N5-methyl FH4, methionine synthase, and thymidylate synthetase


• Vit B12 deficiency - ↑ methyl malonate excretion in urine as methylmalonic acid

• ↑ methyl malonate leads to formation of abnormal fatty acids that may incorporated into neuronal lipids – myelin breakdown – neurological complication

Pernicious Anemia

What is pernicious?

Pernicious Anemia

• Autoimmune disorder

• Destruction of gastric mucosa

• Chronic atrophic gastritis – loss of parietal cells & inflammatory cell infiltrate

Pernicious Anemia

3 types of Auto antibody

• Type I – – 75% cases

– Blocks binding of Vit B12 to IF

– Present in gastric juice & plasma

• Type II autoantibody – Prevent binding of Vit B12 + IF complex to ileal receptor

• Type III autoantibody – 85- 90% cases

– Ab against α & β subunits of gastric proton pump

– Seen in 50% cases of idiopathic chronic gastritis without PA

FIGURE 14-18 Schematic illustration of vitamin B12 absorption. IF, intrinsic factor; R-binders, cobalophilins

Pernicious Anemia

• Morphology

• BM & blood

• GIT – Atrophic glossitis – shiny, glazed & beefy tongue

– Diffuse chronic gastritis – atrophy of fundic glands

– Intestinalization of gastric mucosa

– Some cells show megaloblastic change

– Higher incidence of gastric cancer

Pernicious Anemia - CNS

• 75 % of fulminant PA

• Spinal cord – – Degeneration of myelin in dorsal & lateral tract

– Degenerative changes in the ganglia of posterior roots & in peripheral nerve

• Spastic paraperesis, sensory ataxia, severe paresthesias in lower limb

• Subacute combined degeneration

Pernicious Anemia – C/F

1. Moderate to severe megaloblastic anemia 2. Leukopenia with hypersegmented

granulocytes 3. Mild to moderate thrombocytopenia 4. Mild jaundice due to ineffective

erythropoiesis 5. Neurological changes – postero lateral spinal

tract 6. Achlorohydria even after histamine

stimulation (Histamine fast achlorhydria)

Beefy red tongue

Vitiligo

Pernicious Anemia

7. Schilling test – urinary excretion of radiolabelled cyanocobalamin

8. ↓Serum B12 level

9. ↑Homocysteine & methyl malonic acid in serum

10. intra venous vit B12 –

Reticulocytosis (after 5days of Tx)

11. Serum Ab to IF

Folate deficiency

Folate

• Folic acid or Tetrahydrofolate (FH4) derivatives act as biological Middle man in transfer of one carbon units (formyl / Methyl) groups to various compounds

• Accepts 1 carbon unit from serine / Formiminoglutamic acid (FIGLU)

Role of folate derivatives in the transfer of one-carbon fragments for synthesis of biologic macromolecules

Folate - Functions

1. Synthesis of purines

2. Synthesis of Methionine from homocysteine

3. Synthesis of deoxythymidine monophosphate (dTMP)

Role of folate derivatives in the transfer of one-carbon fragments for synthesis of biologic macromolecules

Relationship of N5-methyl FH4, methionine synthase, and thymidylate synthetase

Folate deficiency - Etiology

• Daily requirement : 50 – 200 mg • Green veg – rich source • Fruits & animal protein – lesser amount 1. ↓ intake – alcoholism, infancy 2. Impaired absorption

Malabsorption state Intrinsic intestinal disease Anticonvulsant, OCP

3. ↑ loss - hemolysis 4. ↑ requirement –

pregnancy, infancy, cancer

Folate deficiency

5. Impaired use

– Folic acid antagonists – Mercaptopurines, methotrexate, flurouracil

Folate deficiency

Diagnosis

– ↓ Folate levels in serum or red cells

– ↑ Excretion of FIGLU after an administrated dose of histidine

END

Dr.CSBR.Prasad, M.D.,

Associate Professor of Pathology,

Sri Devaraj Urs Medical College,

Kolar-563101,

Karnataka,

INDIA.

[email protected]

Documents

Rbc disorders-4