Anaemia _ IDA & Megaloblastic anaemia Lect 1.ppt

Anaemia _ IDA & Megaloblastic anaemia Lect 1.ppt

1. ANAEMIA ANAEMIA
Dr P. M. ROPLEKARDr P. M. ROPLEKAR

2. ERYTHROPOIESISERYTHROPOIESIS
SITES SITES

Intrauterine life : yolk sac, liver spleen Intrauterine life : yolk sac, liver spleen
bone marrowbone marrow

Newborn : all bone marrow cavities Newborn : all bone marrow cavities

Child : femur upper shaft, humerus, Child : femur upper shaft, humerus,
pelvis, spine pelvis, spine

Adult : vertebrae, ribs, femur, spineAdult : vertebrae, ribs, femur, spine

3. Bone marrow aspiration Bone marrow aspiration
SITES SITES

In children < 1 yr : Medial aspect of In children < 1 yr : Medial aspect of
proximal part of tibiaproximal part of tibia

In children > 1 yr : Iliac crestIn children > 1 yr : Iliac crest

In adult : Iliac crest, Body of sternumIn adult : Iliac crest, Body of sternum

4. AnaemiaAnaemia

Definition:Definition:
Anaemia is present when hemoglobin Anaemia is present when hemoglobin
level in the blood is below the lower level in the blood is below the lower
extreme of the normal range for the extreme of the normal range for the
age and sex of the individual.age and sex of the individual.
The lower limit of normality is reduced The lower limit of normality is reduced
during pregnancy.during pregnancy.

5. DefinitionDefinition : Anemia is reduction : Anemia is reduction
in oxygen carrying capacity of in oxygen carrying capacity of
blood due to decrease in blood due to decrease in
hemoglobin concentration or hemoglobin concentration or
hematocrit or RBC mass below hematocrit or RBC mass below
the lower limit of the normal for the lower limit of the normal for
the individuals age, sex and the individuals age, sex and
geographic location. geographic location.

6. Normal values for different age and sex:Normal values for different age and sex:
Birth Birth 1mth1mth 1 yr.1 yr.6 – 12yrs6 – 12yrsAdult Adult
malemale
Adult Adult
FemaleFemale
Hbgm %Hbgm % 14 - 2214 - 2212 - 1612 - 1611- 1411- 14 11- 1511- 15 15 - 1715 - 1713 - 1513 - 15
PCV%PCV% 45 - 7545 - 7540 - 5040 - 5030 - 3830 - 3834 - 4034 - 40 40 - 5040 - 5035 - 4535 - 45
RBC countRBC count
Mill/cumm.Mill/cumm.
5 – 7 5 – 7 3 – 5 3 – 5 4 – 5 4 – 5 4 – 5 4 – 5 4.5 - 5.54.5 - 5.54 – 4.54 – 4.5

7. WHO CUT OFF POINTS FOR THE WHO CUT OFF POINTS FOR THE
DIAGNOSIS OF ANEMIA DIAGNOSIS OF ANEMIA
Hb gm % Hb gm % MCHC %MCHC %
Adult male Adult male 13 13 3434
Adult femaleAdult female
Non pregnant Non pregnant
1212 3434
Adult femaleAdult female
Pregnant Pregnant
1111 3434
Child 6 yrs-14yrsChild 6 yrs-14yrs 1212 3434

8. Classification of anaemiaClassification of anaemia

1. Morphologic1. Morphologic

2. Patho-physiologic (functional)2. Patho-physiologic (functional)

9. Morphologic classificationMorphologic classification
It depends on size & Hb concentration:It depends on size & Hb concentration:

1) Normocytic Normochromic1) Normocytic Normochromic

2) Microcytic Hypochromic2) Microcytic Hypochromic

3) Macrocytic Normocytic3) Macrocytic Normocytic

10. Morphological classification of Morphological classification of
anemiaanemia
Types of anemiaTypes of anemia MCV [fl ]MCV [fl ] MCHC %MCHC %
Normocytic Normocytic
normochromicnormochromic
80 – 10080 – 100 Between 32 - 36Between 32 - 36
Macrocytic Macrocytic
normochromic normochromic
> 100> 100 32 - 3632 - 36
Macrocytic Macrocytic
hypochromic hypochromic
> 100> 100 < 32< 32
Microcytic Microcytic
normochromic normochromic
< 80< 80 Between 32 - 36Between 32 - 36
Microcytic Microcytic
hypochromichypochromic
< 80< 80 < 32< 32

11. Pathophysiological classification of anemia Pathophysiological classification of anemia
A. Impaired RBC production A. Impaired RBC production

a.a. Deficiency of nutrients essential for erythropoiesis Deficiency of nutrients essential for erythropoiesis
Iron deficiency Iron deficiency
Vitamin B 12 deficiency Vitamin B 12 deficiency
Folic acid deficiency Folic acid deficiency
Protein calorie malnutrition Protein calorie malnutrition
Less common – vitamin C, B 6, E,CULess common – vitamin C, B 6, E,CU

b. b. Depression of erythropoietic activity Depression of erythropoietic activity
Chronic diseases – Infection, collagen vascularChronic diseases – Infection, collagen vascular
diseases, disseminated malignancy,diseases, disseminated malignancy,
inflammatory diseases inflammatory diseases

c. c. Anemia of renal failure Anemia of renal failure

d.d. Aplastic anemia Aplastic anemia

e. e. Anemia due to replacement of normal bone marrowAnemia due to replacement of normal bone marrow
by leukemia, lymphoma, MPD, MDS, Multiple myeloma.by leukemia, lymphoma, MPD, MDS, Multiple myeloma.

12. B. Due to blood lossB. Due to blood loss

Acute Acute

Chronic Chronic
C. Due to red cell destruction / HemolyticC. Due to red cell destruction / Hemolytic
anemias anemias

Hereditary Hereditary

Acquired Acquired

13. Pathophysiologic (functional)Pathophysiologic (functional)
Depends on RBC Production Index & Depends on RBC Production Index &
Serum Iron studies :Serum Iron studies :
1) Proliferative defect1) Proliferative defect
2) Maturation defect2) Maturation defect
3) Survival defect3) Survival defect

14. Normocytic normochromicNormocytic normochromic

Survival defect Survival defect
1)1)HaemolysisHaemolysis
2)2)HemorrhageHemorrhage

Proliferation defectProliferation defect
1)1)Stem cell defectStem cell defect
2)2)Liver diseaseLiver disease
3)3)Renal diseaseRenal disease

15. Microcytic Hypochromic Microcytic Hypochromic

Iron deficiencyIron deficiency

ThalassemiaThalassemia

Chronic diseaseChronic disease

Lead intoxicationLead intoxication

Sideroblastic anaemiaSideroblastic anaemia

16. MACROCYTIC ANEMIASMACROCYTIC ANEMIAS
ETIOLOGY-ETIOLOGY-

1.Megaloblastic1.Megaloblastic

2.Nonmegaloblastic2.Nonmegaloblastic

**MEGALOBLASTIC-MEGALOBLASTIC-

1.Vit.B12 deficiency1.Vit.B12 deficiency

2.Folic acid deficiency2.Folic acid deficiency

3.Independent of b12/folic acid defi.-1.Erythroleukemia3.Independent of b12/folic acid defi.-1.Erythroleukemia
2.Orotic aciduria2.Orotic aciduria
3.Drugs -3.Drugs -
methotrexate,zidovudin,O.C.pillsmethotrexate,zidovudin,O.C.pills

*NONMEGALOBLASTIC-*NONMEGALOBLASTIC-

a. Macrocytosis common-hemolytic anemia, post hemorrhagic anemiaa. Macrocytosis common-hemolytic anemia, post hemorrhagic anemia

b. Macrocytosis occasional - alcoholism,liver disease, hypothyroidism,b. Macrocytosis occasional - alcoholism,liver disease, hypothyroidism,
aplastic anemia, sideroblastic anemia, MDS, cytotoxic drug therapy. aplastic anemia, sideroblastic anemia, MDS, cytotoxic drug therapy.


PATHOGENESISPATHOGENESIS- Defective DNA synthesis.- Defective DNA synthesis.

17. INVESTIGATIONS-MACROCYTIC ANEMIASINVESTIGATIONS-MACROCYTIC ANEMIAS

MCV-increasedMCV-increased

RDW-increased in megaloblastic anemiaRDW-increased in megaloblastic anemia

Retic count – Normal - MBARetic count – Normal - MBA
Increased - Hemolytic anemiaIncreased - Hemolytic anemia
hemorrhagic anemiahemorrhagic anemia
Decreased-liver dis., alcoholDecreased-liver dis., alcohol
toxicity, hypothyroidismtoxicity, hypothyroidism

P.S.&BMA EXAM- P.S.&BMA EXAM-

18. Adaption to anaemiaAdaption to anaemia

Increase in oxygenated blood flowIncrease in oxygenated blood flow
1)1)Increase cardiac rateIncrease cardiac rate
2)2)Increase cardiac OutputIncrease cardiac Output
3)3)Increase in Circulation rateIncrease in Circulation rate
4)4)In blood flow to vital organsIn blood flow to vital organs
Increase in oxygen utilization by tissueIncrease in oxygen utilization by tissue
1)1)Increase in 2-3-DPG in erythrocytesIncrease in 2-3-DPG in erythrocytes
2)2)decrease in affinity of HB in tissue due to Bohr decrease in affinity of HB in tissue due to Bohr
effect effect

19. Iron deficiency Iron deficiency
anaemiaanaemia

20. 
Most common nutritional deficiency in Most common nutritional deficiency in
worldworld

Chlorosis = greenish tingeChlorosis = greenish tinge

DietDiet

Hook worm infestationHook worm infestation

21. Amount and distribution of Amount and distribution of
ironiron

Total body content of iron of adult varies from Total body content of iron of adult varies from
3-5 gms depending on sex & wt3-5 gms depending on sex & wt
haemoglobinhaemoglobin 2.32.3
Storage tissue iron Storage tissue iron
(ferritin & haemosiderin)(ferritin & haemosiderin)
1.01.0
Essential tissue iron (myoglobin)Essential tissue iron (myoglobin)0.50.5
Plasma ironPlasma iron 0.003-0.0040.003-0.004
TotalTotal 3.83.8

22. Iron absorption favored byIron absorption favored by
Dilatory factorsDilatory factors
1)1)Increase heam ironIncrease heam iron
2)2)Increase in animal foodsIncrease in animal foods
Luminal factorsLuminal factors
1)1)Acid pHAcid pH
2)2)Vitamine C, sugar amino acidsVitamine C, sugar amino acids
Ligands in meatLigands in meat
Systemic factorsSystemic factors
1)1)Pregnancy Pregnancy
2)2)HypoxiaHypoxia
3)3)Increase in erythropoiesisIncrease in erythropoiesis

23. Iron absorption reduced byIron absorption reduced by

Dilatory factors Dilatory factors
1)1)Decrease in heam ironDecrease in heam iron
2)2)Decrease in animal foodsDecrease in animal foods
LuminalLuminal
1)1)AlkaliesAlkalies
2)2)PhytatesPhytates
3)3)Tannates in teaTannates in tea

SystemicSystemic
1)1)Decrease in erythropoiesisDecrease in erythropoiesis
2)2)Inflammatory disordersInflammatory disorders

24. Causes of iron deficiency anemiaCauses of iron deficiency anemia
ExogenousExogenous
•Dietary Dietary
deficiency—deficiency—
poor quality poor quality
& &
absorbabilitabsorbabilit
y of dietary y of dietary
ironiron
EndogenousEndogenous
•Absorption defect-achlorhydria, Absorption defect-achlorhydria,
gastrectomy, duodenal bypass, gastrectomy, duodenal bypass,
celiac disease, sprueceliac disease, sprue
•Transport defectTransport defect
•Loss of blood/ironLoss of blood/iron
-- Hemorrhage (GI, menstrual, -- Hemorrhage (GI, menstrual,
urinary urinary
tract, etc)tract, etc)
-- Requirement>supply-- Requirement>supply
-infancy, pregnancy, lactation-infancy, pregnancy, lactation

25. Clinical featuresClinical features

Onset insidiousOnset insidious

Early stages no clinical manifestationEarly stages no clinical manifestation
WeaknessWeakness

LethargyLethargy
KoilonychiasKoilonychias

GlossitisGlossitis

Pharyngeal websPharyngeal webs
Muscle dysfunctionMuscle dysfunction

Impaired thermo genesisImpaired thermo genesis

GastritisGastritis

26. Pica syndromePica syndrome
ice phagophygiaice phagophygia
clay geophagiaclay geophagia
starch amylophagiastarch amylophagia
SymptomsSymptoms
IrritabilityIrritability
Loss of memoryLoss of memory
Difficulty in learningDifficulty in learning
Deficiency of immune systemDeficiency of immune system

27. Overview of Lab diagnosis of Overview of Lab diagnosis of
AnemiasAnemias

Diagnosis of anaemia depends on Diagnosis of anaemia depends on
interpretation of various tests taken interpretation of various tests taken
togethertogether
Mis
c
test
Bioc
hem
tests
RBC
indice
s
C/F

Marro
w
examn
Perip
heral
smear
Hb

28. Peripheral smear examinationPeripheral smear examination

RBC morphology of greatest helpRBC morphology of greatest help

Degree of – Degree of –
--microcytosis (reduction of mean --microcytosis (reduction of mean
diameter of RBCs),diameter of RBCs),
--macrocytosis (increase of mean--macrocytosis (increase of mean
diameter of RBCs), diameter of RBCs),
--anisocytosis (variation in size of RBCs), --anisocytosis (variation in size of RBCs),
--poikilocytosis (variation in shape of RBCs)--poikilocytosis (variation in shape of RBCs)

Reticulocyte countReticulocyte count

29. Iron deficiency anemiaIron deficiency anemia

Peripheral blood Smear :-Peripheral blood Smear :-
Microcytic hypochromic RBCsMicrocytic hypochromic RBCs
AnisopoikilocytosisAnisopoikilocytosis

TLC :-TLC :-Mild to moderate leukopenia (in cases Mild to moderate leukopenia (in cases
of severe anemia) of severe anemia)
Leukocytosis (after blood loss)Leukocytosis (after blood loss)

Hemoglobin Hemoglobin ↓↓

Erythrocyte Sedimentation Rate Erythrocyte Sedimentation Rate ↑↑

Blood indices :-Blood indices :-
MCVMCV (60-80fl),
↓
(60-80fl),
↓
MCHMCH (15-26pg),
↓
(15-26pg),
↓
MCHCMCHC (20-30%),
↓
(20-30%),
↓
RDWRDW (>17.5)
↑
(>17.5)
↑

30. 
Reticulocyte count
↑
Reticulocyte count
↑
(in blood loss, after iron supplementation)(in blood loss, after iron supplementation)

Osmotic fragility
↓
Osmotic fragility
↓

Serum iron Serum iron
↓

↓

TIBCTIBC
↑

↑

Serum transferrin
↑
Serum transferrin
↑

Serum ferritin Serum ferritin
↓

↓
serum transferrin saturation (<16%)
↓
serum transferrin saturation (<16%)
↓

Micronormoblastic erythropoiesisMicronormoblastic erythropoiesis

Marrow iron stores Marrow iron stores ↓↓

31. Other testsOther tests

Osmotic fragilityOsmotic fragility

Routine stool examination (occult blood, ova, Routine stool examination (occult blood, ova,
parasites)parasites)

Routine urine examination (occult blood, RBCs)Routine urine examination (occult blood, RBCs)

Gastric juice analysisGastric juice analysis

Hb electrophoresisHb electrophoresis

32. INVESTIGATIONS INVESTIGATIONS
For typing of anemia & to find out etiology For typing of anemia & to find out etiology
Red cells Indices –Red cells Indices –
 MCV – MCV – PCV X10PCV X10
RBC count RBC count
Normal values -80-100 flNormal values -80-100 fl
 MCH – MCH – Hb gm% x10Hb gm% x10
RBC count RBC count
Normal values – 27-32 pgNormal values – 27-32 pg
 MCHC – MCHC – Hb gm%x100Hb gm%x100
PCV PCV
Normal values - 315-345 gm / ltr.Normal values - 315-345 gm / ltr.

33. Reticulocytes countReticulocytes count – –
1. Supravital stains- Brilliant cresyl blue / New methyleneblue 1. Supravital stains- Brilliant cresyl blue / New methyleneblue

Three drops of blood +Three drops of BCB/NMBThree drops of blood +Three drops of BCB/NMB
In test tube In test tube
Incubate for 15 mins at R.T.Incubate for 15 mins at R.T.

Air dried & wedge film is prepared.Air dried & wedge film is prepared.

Reticulocytes are seen as pale blue RBCs containing bluish reticular or granular Reticulocytes are seen as pale blue RBCs containing bluish reticular or granular
material.material.
2.Reticulocytes can be counted by fluorescence microscopy.2.Reticulocytes can be counted by fluorescence microscopy.
RNA gives an orange – red fiuorescenceRNA gives an orange – red fiuorescence
DNA gives - yellow fiuorescenceDNA gives - yellow fiuorescence

37. IRON DEFICIENCY ANEMIAIRON DEFICIENCY ANEMIA

P.S.-microcytic hypochromic with moderate to markedP.S.-microcytic hypochromic with moderate to marked
anisocytosis, Pencil cells are the elliptical elongatedanisocytosis, Pencil cells are the elliptical elongated
tailed RBCs.tailed RBCs.

38. Bone marrow examinationBone marrow examination

Morphology of NormoblastsMorphology of Normoblasts

Morphology of myeloid precursorsMorphology of myeloid precursors

Marrow iron stores (Perl’s reaction)Marrow iron stores (Perl’s reaction)

40. 
B.M.A. - usually normocellular / moderately hypercellularB.M.A. - usually normocellular / moderately hypercellular

B.M. iron is usually increased in the absence of Fe deficiency.B.M. iron is usually increased in the absence of Fe deficiency.

41. Bone marrow aspirationBone marrow aspiration

Hypercellular-due to erythroid hyperplasia-predominantly Hypercellular-due to erythroid hyperplasia-predominantly
MICRONORMOBLASTIC.MICRONORMOBLASTIC.

42. B.M.A.IRON STORES-Decresed iron content.Normally 30-B.M.A.IRON STORES-Decresed iron content.Normally 30-
50% erythroblast are sideroblast.In IDA-<10% Are 50% erythroblast are sideroblast.In IDA-<10% Are
sideroblast,decreased iron content of macrophages.sideroblast,decreased iron content of macrophages.

43. MEGALOBLASTIC MEGALOBLASTIC
ANAEMIAANAEMIA

44. Causes of folate deficiencyCauses of folate deficiency
Inadequate diatory intakeInadequate diatory intake
1)1)InfancyInfancy
2)2)Institutional dietsInstitutional diets
3)3)Goat’s milkGoat’s milk
4)4)PovertyPoverty
5)5)Chronic debiliting disordersChronic debiliting disorders
MalabsorptionMalabsorption
1)1)Tropical sprueTropical sprue
2)2)Regional enteritisRegional enteritis
3)3)Intestinal bypassIntestinal bypass
4)4)Blind loop syndromeBlind loop syndrome
5)5)SteatorrheaSteatorrhea
6)6)Cong folate mal absorptionCong folate mal absorption

45. Causes of folate deficiencyCauses of folate deficiency
Drug inducedDrug induced
1)1) PhenytoinPhenytoin
2)2) PhenobarbitolPhenobarbitol
3)3) Oral pillsOral pills
4)4) Folate agonist (methotrexate)Folate agonist (methotrexate)
Inherited enzyme deficienciesInherited enzyme deficiencies
1)1) Dihydrofolate reductaseDihydrofolate reductase
2)2) NN
5 5
methyl tetrahydrofolate transferasemethyl tetrahydrofolate transferase
3)3) FormimotransferaseFormimotransferase
Increased requirementIncreased requirement
1)1) PregnancyPregnancy
2)2) LactationLactation
3)3) Chronic hemolysisChronic hemolysis
4)4) NeoplasmsNeoplasms
5)5) Chronic inflammationChronic inflammation
6)6) hyperthyroidismhyperthyroidism

46. Causes of cobalmin deficiencyCauses of cobalmin deficiency
Nutritional deficiencyNutritional deficiency
1)1)MalnutritionMalnutrition
2)2)Strict veg dietStrict veg diet
3)3)Breast feed infents of strict veg dietsBreast feed infents of strict veg diets
MalabsorptionMalabsorption

Impaired utilisationImpaired utilisation
1)1)Nitrous oxide deficiencyNitrous oxide deficiency
2)2)Transcobalmin II deficiencyTranscobalmin II deficiency
3)3)Inborn errors of metabolismInborn errors of metabolism
Increased demandIncreased demand
1)1)PregnancyPregnancy
2)2)Chronic haemolytic anaemiaChronic haemolytic anaemia
3)3)NeoplasmsNeoplasms
4)4)Myeloproliferative disordersMyeloproliferative disorders
5)5)hyperthyroidsmhyperthyroidsm

47. Causes of cobalmine Causes of cobalmine
deficiencydeficiency
MalabsorptionMalabsorption
A) Decreased availability of intrinsic factorA) Decreased availability of intrinsic factor
1)1)Pernicious anaemiaPernicious anaemia
2)2)Cong intrinsic factor deficiencyCong intrinsic factor deficiency
3)3)Abnormal intrinsic factor moleculeAbnormal intrinsic factor molecule
4)4)GastrectomyGastrectomy
B) Failure of intestional absorption other causesB) Failure of intestional absorption other causes
1)1)Ileal ressectionIleal ressection
2)2)Crohn diseaseCrohn disease
3)3)Celiac diseaseCeliac disease
4)4)Bacterial overgrowth syndromeBacterial overgrowth syndrome
5)5)Pancreatic malabsorptionPancreatic malabsorption
6)6)drugsdrugs

48. Assimilation of cobalmineAssimilation of cobalmine
cobalmine+food complexcobalmine+food complex
stomach stomach
R-binder protein+cobalmine R-binder protein+cobalmine
pancreatic protease in duodenum, IF pancreatic protease in duodenum, IF
IF+cobalmine R binder proteinIF+cobalmine R binder protein
iliumilium
cobalmine+receptor on mucosal cellscobalmine+receptor on mucosal cells
mucosal cells mucosal cells
Transcobalmine II+cobalminTranscobalmine II+cobalmin
plasmaplasma
TissueTissue

49. CLINICAL FEATURESCLINICAL FEATURES
LethargyLethargy

WeaknessWeakness
Yellow waxy pallorYellow waxy pallor
Dyspeptic symptomsDyspeptic symptoms

Glossitis with beefy red OR smooth pale tongue.Glossitis with beefy red OR smooth pale tongue.
Loss of weightLoss of weight

Loss of appetiteLoss of appetite
Atrophy pf gastric parietal cellsAtrophy pf gastric parietal cells
diarrheadiarrhea

50. NeurologicalNeurological

TinglingTingling

NumbnessNumbness
Weakness of extremitiesWeakness of extremities
Loss of proprioceptive sensation-abnormal gaitLoss of proprioceptive sensation-abnormal gait

MentalMental
Loss of memoryLoss of memory
DepressionDepression
IrritabilityIrritability

51. Lab diagnosis of Megaloblastic Lab diagnosis of Megaloblastic
anemiaanemia

Hemoglobin Hemoglobin ,
↓
,
↓

Periphrial Smear –Periphrial Smear –
Macrocytic hypochromic anemia, Macrocytic hypochromic anemia,
Macrovalocytes, Macrovalocytes,
Howell-Jolly bodies. Howell-Jolly bodies.
Macro ++/+++, Macro ++/+++,
anisocytosis +, anisocytosis +,
poikilocytosis +,poikilocytosis +,
polychromasia+/-,polychromasia+/-,
megaloblast, megaloblast,

Blood indices Blood indices
MCVMCV (>94 fl)
↑
(>94 fl)
↑
, ,
MCHMCH (>32pg),
↑
(>32pg),
↑
MCHCMCHC (>32),
↑
(>32),
↑
RDWRDW ,
↑
,
↑

Reticulocyte count- N/ ,
↓
Reticulocyte count- N/ ,
↓

RBC (>> Hb)
↓ ↓
RBC (>> Hb)
↓ ↓

52. 
WBC series :WBC series :
moderate leukopenia, moderate leukopenia,
marked neutropenia, marked neutropenia,
hypersegmented neutrophils hypersegmented neutrophils

mild thrombocytopeniamild thrombocytopenia

BONE MARROW –BONE MARROW –
↓↓M:E ratio.M:E ratio.
Hypercellular marrow with megaloblastic erythropoiesis, Hypercellular marrow with megaloblastic erythropoiesis,

↑

↑
reticulum cells, reticulum cells,
giant stab form of metamyelocytes, giant stab form of metamyelocytes,
macropolycytes, macropolycytes,

53. Biochemical parametersBiochemical parameters

Biochem- S.bilirubin ( total, indirect),
↑ ↑
Biochem- S.bilirubin ( total, indirect),
↑ ↑

↑↑Urine urobilinogen,Urine urobilinogen,

↑↑LDH, LDH,

↑↑SGPT,SGPT,


↓

↓
serum/RBC Bserum/RBC B
1212, ,

↓↓serum/RBC folate,serum/RBC folate,

schilling testschilling test
1)1)Intrinsic factor(IF) in gastric juiceIntrinsic factor(IF) in gastric juice
2)2)Anti IF antibodiesAnti IF antibodies

Serum methylmalonic acidSerum methylmalonic acid

Serum homocysteineSerum homocysteine

Deoxyuridine(dU) suppression testDeoxyuridine(dU) suppression test

54. SPECIAL INVESTIGATIONSSPECIAL INVESTIGATIONS
- MACROCYTIC ANEMIAS- MACROCYTIC ANEMIAS

1.Sr.vit.b12 assay1.Sr.vit.b12 assay

2.Sr.& red cell folate assay2.Sr.& red cell folate assay

3.Tests of malabsorption-3.Tests of malabsorption-
Schilling testSchilling test

4.Detection of sr.parietal cell 4.Detection of sr.parietal cell
& Intrinsic factor antibodies & Intrinsic factor antibodies

5.Jejunal biopsy5.Jejunal biopsy

6.Liver function tests etc.6.Liver function tests etc.
- 160 – 760 ng / l- 160 – 760 ng / l
-Sr Folate – 3-20 mcg/l-Sr Folate – 3-20 mcg/l
-Sr Red Cell Folate –160-640-Sr Red Cell Folate –160-640
mcg/l mcg/l

55. SCHILLING TEST- for vit. B 12 absorbtionSCHILLING TEST- for vit. B 12 absorbtion
0.5-2.0 mcg of radioactive Cobalamin orally0.5-2.0 mcg of radioactive Cobalamin orally
Flushing dose of nonlabelled cobalamin ParenterallyFlushing dose of nonlabelled cobalamin Parenterally
Normally-Excrete 7% of 1 mcg dose of injected B12 in 24 hrs.Normally-Excrete 7% of 1 mcg dose of injected B12 in 24 hrs.
Patient with lack of INTRINSIC FACTOR excrete lessPatient with lack of INTRINSIC FACTOR excrete less
If excretion less, IF given along with B12If excretion less, IF given along with B12
If excretion N- low values in 1If excretion N- low values in 1
stst
due to IF deficiency due to IF deficiency
If excretion still low - malabsorptionIf excretion still low - malabsorption

59. MEGALOBLASTIC ANEMIA-P.S.MEGALOBLASTIC ANEMIA-P.S.

60. In pernicious anemia – cabot ringIn pernicious anemia – cabot ring

61. ANEMIA OF LIVER DISEASE-P.S.ANEMIA OF LIVER DISEASE-P.S.

Usually macrocytic,target cells.Usually macrocytic,target cells.

Can be NCNC –due to bld loss.Can be NCNC –due to bld loss.

acanthocytes-[spurr cells]-hemolytic anemia.acanthocytes-[spurr cells]-hemolytic anemia.

62. B.M.A.B.M.A.

64. NORMOCYTIC NORMOCYTIC
NORMOCHROMIC NORMOCHROMIC
ANAEMIAANAEMIA

65. Normocytic Normochromic anemia Normocytic Normochromic anemia
1.1.Etiology Etiology

Disorders causing depression of erythropoiesis Disorders causing depression of erythropoiesis
-Infection, Renal failure, Diss.malignancy, liver Infection, Renal failure, Diss.malignancy, liver
disease, CVD, Chr. inflammatory diseasedisease, CVD, Chr. inflammatory disease

BM Infiltration – Leukemia,lymphoma, MM, Ca, BM Infiltration – Leukemia,lymphoma, MM, Ca,
MyelofibrosisMyelofibrosis

Aplastic anemiaAplastic anemia

Endocrine disorders – Myxoedema, Endocrine disorders – Myxoedema,
hypopituitarism. hypopituitarism.

Bloos loss with adequate iron stores Bloos loss with adequate iron stores

66. PATHOGENESISPATHOGENESIS

1.1.Supressed erythropoisis due to inhibitarySupressed erythropoisis due to inhibitary
effects of INTERLEUKIN 1 released byeffects of INTERLEUKIN 1 released by
macrophages.macrophages.

2.2.Decreasd delivary of iron from RE cells toDecreasd delivary of iron from RE cells to
erythroblasts.erythroblasts.

3.3.Impairment of erythropoietin production.Impairment of erythropoietin production.

4.4.Blood loss due to Portal Hypertension.Blood loss due to Portal Hypertension.

5.5.Supressed erythropoiesis due toSupressed erythropoiesis due to
involvement of BM by other cells.involvement of BM by other cells.

67. 
MCV, MCH, MCHC - NormalMCV, MCH, MCHC - Normal

ESR – N – Bld loss ESR – N – Bld loss
↑ ↑ Infections, Collagen vascularInfections, Collagen vascular
diseases, Carcinoma, Leukemia diseases, Carcinoma, Leukemia

Retic – N – Renal failure, Liver disease,Retic – N – Renal failure, Liver disease,
Disseminated Malignancy Disseminated Malignancy
↓ ↓ Myxoedema, Hypopituitarism Myxoedema, Hypopituitarism
↑ ↑ Chronic haemorrhage, acute blood lossChronic haemorrhage, acute blood loss

PS Ex – PS Ex –
Normocytic normochromic with mild aniso poikilocytosisNormocytic normochromic with mild aniso poikilocytosis
Normocytic normochromic with markedNormocytic normochromic with marked
anisopoikilocytosisanisopoikilocytosis

WBC – N / ↓ / ↑ WBC – N / ↓ / ↑

Platelate - N / ↓ / ↑ Platelate - N / ↓ / ↑
Investigations -Investigations - Normocytic Normochromic anemia Normocytic Normochromic anemia

68. 4 B.M.A. and BX 4 B.M.A. and BX
Normo cellular – Infections, Collagen vascularNormo cellular – Infections, Collagen vascular
diseases, Renal Failure, Liver disease,diseases, Renal Failure, Liver disease,
Acute blood loss.Acute blood loss.
Hypocellular – Aplastic anemia,Myelofibrosis, RenalHypocellular – Aplastic anemia,Myelofibrosis, Renal
failure, Hypothyroidismfailure, Hypothyroidism
Hypercellular – moderate -infectionHypercellular – moderate -infection
Severe – BM Infiltration by leukemia,Severe – BM Infiltration by leukemia,
lymphomalymphoma

69. Anemia of chronic diseasesAnemia of chronic diseases

Usually Normocytic NormochromicUsually Normocytic Normochromic

Microcytic hypochromic-secondary Fe deficiency.Microcytic hypochromic-secondary Fe deficiency.

Aplastic anemia-due to drugs.Aplastic anemia-due to drugs.

70. Anemia of chronic renal failureAnemia of chronic renal failure

-In uncomplicated case-P. S – normocytic-In uncomplicated case-P. S – normocytic
normochromic.normochromic.

With development of microangiopathic With development of microangiopathic
hemolytic anemia – Burr cells, spherocytes,hemolytic anemia – Burr cells, spherocytes,
helmet cells,echinocyteshelmet cells,echinocytes

Bone marrow _ usually N/moderatelyBone marrow _ usually N/moderately
hypercellular.hypercellular.

With severe uremia _ hypocellur B.M.With severe uremia _ hypocellur B.M.

72. Aplastic anemiaAplastic anemia

Aplastic anemia-is said to be Aplastic anemia-is said to be
present -present -

Granulocytes - <500 cells/LGranulocytes - <500 cells/L

Platelets - <20,000/LPlatelets - <20,000/L

Retic count - <1%Retic count - <1%

BM - <30% cellularBM - <30% cellular

BMA - dry or blood tap .BMA - dry or blood tap .
marrow hypocellular withmarrow hypocellular with
increase in fat cells.increase in fat cells.

74. Special investigationsSpecial investigations

1. Renal function tests1. Renal function tests

2. Liver function tests2. Liver function tests

3. Barium meal, endoscopy (G.I. bleeding)3. Barium meal, endoscopy (G.I. bleeding)

4. Test for Abs to DNA (SLE)4. Test for Abs to DNA (SLE)

5. Tests for thyroid function (myxoedema)5. Tests for thyroid function (myxoedema)

6. Blood culture (bacterial endocarditis)6. Blood culture (bacterial endocarditis)

7. Fecal occult blood (G.I.bleeding)7. Fecal occult blood (G.I.bleeding)

8. Skeletal X - ray (secondary carcinoma, multiple8. Skeletal X - ray (secondary carcinoma, multiple
myeloma, lymphoma)myeloma, lymphoma)

75. Thank youThank you