Download pdf - Megaloblastic aneamia

8/8/2019 Megaloblastic aneamia

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Blood


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Dr. Raghuveer ChoudharyAssistant Professor ofPhysiologyDr S.N.Medical College Jodhpur


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Anemia is decreased redAnemia is decreased redcell mass affecting tissuecell mass affecting tissue

oxygenationoxygenation

yy PracticalPractical -- Low Hb* or Low Hematocrit*Low Hb* or Low Hematocrit*


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y Anemia means a decrease in hemoglobin content,

y or RBCs count,

y or both of them below the normal range.

y Anemia leads to a decrease in blood ability totransport oxygen to tissue cells.


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Anaemia is labelledwhen Hb Conc is less

y 13 gm/dl in adult males

y

11.5 gm/dl in adultfemales

y 15 gm/dl in newborns

y 9.5 gm/dl at 3 month of

age

y 13 gm/dl in adult males

y

11.5 gm/dl in adultfemales

y 15 gm/dl in newborns

y 9.5 gm/dl at 3 month of

age

y Mild Aneamia- Hb 8-10Gm%

y Moderate Aneamia- 6-8Gm%

y Severe Aneamia Hb


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y Types & causes of anemia:

I-Bloodloss anemia:

A-Acute bloodloss anemia:

Due to severe hemorrhage.

Plasma volume is replaced rapidly by the fluidspresent in tissue spaces.

This leads to markeddilution ofthe blood.

RBCs are replaced within 2-3 weeks.

Sufficient iron gives normocytic cells butinsufficient iron will produce microcytic RBCs.


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y Types & causes of anemia:I-Bloodloss anemia:B-Chronic bloodloss anemia:

Due to repeatedloss ofsmall amounts ofbloodover a long period e.g.:-Gastrointestinal bleeding (peptic ulcer)-Excessive menstruation.-Hemorrhagic diseases.Due todepletion in iron stores the newlyformed

RBCS are microcytic.

y Types & causes of anemia:I-Bloodloss anemia:B-Chronic bloodloss anemia:

Due to repeatedloss ofsmall amounts ofbloodover a long period e.g.:-Gastrointestinal bleeding (peptic ulcer)-Excessive menstruation.-Hemorrhagic diseases.Due todepletion in iron stores the newlyformed

RBCS are microcytic.


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Types & causes of anemia:

II-Aplastic anemia:

It results from destructione ofbone marrow.

It may result from:1-Excessive exposure to x-rays or gamma rays.

2-Chemical toxins e.g. cancer therapy & prolonged exposureto insecticides or benzene.

3-Invasion ofbone marrow by cancer cells.

4-Following infection by hepatitis. Damaged bone marrow dont produce any RBCs, so in

aplastic anemia RBCS are normocytic. It is associated with decrease in WBCs & platelets.


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y Fanconi anemia congenital

y Direct stem celldestruction external radiation

y Drugs - chloramphenicol, gold, sulfonamides, felbamate

y Other Toxins - Solvents, degreasing agents, pesticides

y Viral infection - parvovirus B19, HIV, other

y Idiopathic


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III-Hemolytic anemia:It results from increased rate ofdestruction ofRBCs inside

the cardiovascular system.

Causes ofhemolytic anemia:

A-Hereditary:1-Membrane abnormalities.

2-Enzyme deficiency e.g. G-6-P Dehydrogenase.

3-Hemoglobin abnormalities.

B-Acquired:

1-Incompatible blood transfusion.

2-Parasitic infection e.g. malaria.

3-Toxic agents e.g. snake venom & insect poisons.

4-Thermal e.g. several burns.


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IV-Dyshemopoietic anemia: Which may be due to:

1-Iron deficiency anemia.

2-Maturation failure (megaloblastic) anemia:-a-Vitamin B

12 deficiency.

b-Folic aciddeficiency.

3-Anemia ofendocrine disorders.

4-Nutritional anemia.

5-Anemia ofrenalfailure.


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1. Morphological ApproachRed blood cell size

Microcytic (Cells Smaller than normal sizei.e. MCV< 80 fl)

Normocytic (Cells Normal sized i.e. MCV =80-00 fl)

Macrocytic (Cells bigger than normal sizei.e. > 100 fl)

Concentration of HbHyperchromic (Increased Hb

Concentration)Normochromic (Normal Hb Concentration)Hypochromic (Decreased Hb

Concentration- cells paler than normal)


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y Vitamin B12/Folic acid deficiency

y Second most common type of anemia.

y Multi System disease All organs with increased

cell division.y Macrocytic anemia, pancytopenia.

y Pernicious anaemia y autoimmune, Gastric atrophy, VitB12 def.


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y Malnutrition

y Intrinsic factor Ab - Pernicious anemia

y Gastrectomy, Ileal resection

y Inflammatory bowel diseasey Malabsorption syndromes - Sprue

y Blind loop syndrome


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y Decreased Vit B12 / Folatey Decreased DNA Synthesis

y Delayed maturation oferythroblasts (Nucleus)

y Increased cell size (macrocytes)

y Normal hb content (Normochromia)

y Decreased RBC number

y Decreased WBC number (pancytopenia)

y Anemia & Pancytopenia.

y Decreased Vit B12 / Folatey Decreased DNA Synthesis

y Delayed maturation oferythroblasts (Nucleus)

y Increased cell size (macrocytes)

y Normal hb content (Normochromia)

y Decreased RBC number

y Decreased WBC number (pancytopenia)

y Anemia & Pancytopenia.


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Vitamin B12 and Folic acid:

y Essentialfor DNA synthesis (Thymidine triphosphate)

y Abnormal anddiminished DNA

y Failure ofdivision and maturationy Macrocytic / Megaloblastic anemia


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y The presence ofmacro-ovalocytes

y having an MCV >115 fl,anisocytosis, poikilocytosis

andy hypersegmented

neutrophils suggests amegaloblastic disorder

y associated with a

nutritionaldeficiency, i.e.,vitamin B12 or

y folate deficiency.


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Smear

y Macro-ovalocytic

y Polychromasia

y Hypersegmented neutrophil

Other Labs

y Homocysteine Folate def.

y Methylmalonicacid B12 def.

y Intrinsic Factor Ab test very

specific for pernicious anemia butonly 50% sensitive

y Parietal cell AB test quitesensitive (90%) but not specific

y Schilling test

Smear

y Macro-ovalocytic

y Polychromasia

y Hypersegmented neutrophil

Other Labs

y Homocysteine Folate def.

y Methylmalonicacid B12 def.

y Intrinsic Factor Ab test very

specific for pernicious anemia butonly 50% sensitive

y Parietal cell AB test quitesensitive (90%) but not specific

y Schilling test


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The bone marrow is hypercellular,showing evidence ofabnormalproliferation and maturation ofmultiple

myeloid celllines.These abnormalities are most evident inthe erythroid precursors with large

megaloblastic erythroblasts present inincreased numbers throughout themarrow.


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Normal Hypercellular Hypocellular


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Similar morphologic abnormalities can be

seen in the other myeloid elements, e.g.,large or giant metamyelocytes andothergranulocytic precursors.This ineffective erythropoiesis is

accompanied by intramedullaryhemolysis causing an elevatedlactate dehydrogenase and indirect

bilirubin in the serum.However, the reticulocyte count is low dueto the abnormal maturation process.


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Methylmalonic Acid (MMA) and

Homocysteine Serum ConcentrationsCobalamin andfolate are cofactors in severalimportant metabolic pathways in the cell.

The hydroxylated form ofcobalamin plays animportant role in the metabolism ofhomocysteine and MMA. The conversion ofhomocysteine to methionine requires both

vitamin B12 andfolate as cofactors.


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However, the metabolism ofL-methylmalonyl CoA tosuccinyl CoA, an enzymatic

pathway involved in oxidativephosphorylation reactions withinthe cell, only requires

vitamin B12.


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Differentiating cobalamindeficiencyfrom folatedeficiency by measuring

serum MMA andhomocysteine levels.Both ofthese metabolites

are elevated in cobalamindeficiency,


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In folate deficiency patients, serumhomocysteine levels are markedly

increased, while serum MMAlevels are not elevated


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Parietal cells -

produce IFIF

B12

B12

B12+IFIF

Stomach

IF

Ileum -

IF receptorsB12

B12


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