Anemia and it's types with discription.

1. ANEMIA
-iron deficiency
-megaloblactic
-aplastic
-hemolityc

2. Normal ranges

3. Functions Of Hemoglobin
RBCs in arterial blood carry O2 from the lungs to the tissue
and take back CO2 in the venous blood.
 This main function is with the help of hemoglobin (Hb)
molecules, as the Hb molecule load and unload the O2.
 α1β1 and α2β2 globin stabilize the molecule

4. Classification by severity

5. Classification by size of
erythrocyte
MCV stands for mean
corpuscular volume.
An MCV blood test measures
the average size of red blood
cells.

6. Classification by chromia of
erythrocyte Mean corpuscular hemoglobin
concentration (MCHC) measures the
average hemoglobin concentration in a
given volume of red blood cells.

9. Classification of RBC by shape

10. Classification of RBC by shape

11. Classification of RBC by shape

12. Classification of Anemia On The
Basis Of Physiologic Abnormality
 Defective maturation of erythropoiesis.
 Hemolytic anemia is where the
increased breakdown of the RBCs
occurs.
 Defect due to an increase in RBC
precursors compared to the degree of
anemia.

13. Classification of Anemia On The
Basis Of Etiology
 Increased RBC destruction due to intra
or extra red blood cell defects.
 Increased blood loss, which may be
acute or chronic.
 Defective RBC formation due to a lack
of factors necessary for erythropoiesis.

14. Classification of Anemia On The
Basis Of Regeneration

15. Classification of Anemia On The
Basis Of Category
Normocytic
MCV 80-100 fl
MCH 26-34 pg
Hypochromic
Color index <0,8

16. Classification of Anemia On The
Basis Of Category
Normocytic
MCV 80-100 fl
MCH 26-34 pg
Normochromic
Color index 0,85-
1,05
Microcytic
MCV < 80 fl
MCH <26 pg
Hypochromic
Color index <0,8
Hyperchromic
Color index
>1,05
Macrocytic
MCV >100 fl
MCH > 34 pg

17. Classification of Anemia On The
Basis Of Category
Group of hemolytic anemias
Caused by erythrocyte factors
Hemoglobinopathy
Sickle cell=HbS. Reticulocytosis, Jolly bodies,
WBC ↑, PLT ↑, ESR ↑, non-conjugated
bilirubin ↑. Thrombosis, hepatosplenomegaly,
bone changes. Immunity to malaria. Less
commonly, abnormal HbC, HbD, HbE
Thalassemia. Hereditary.
Violation synthesis Hb
chains. Anisocytosis,
poikilocytosis. Fe ↑, non-
conjug. bilirubin ↑, HbA
appears
Erythrocyte
enzymo-pathies
Acanthocytic. Hereditary.
Violation of erythrocyte
membrane lipids. acanthocytes.
Reticulocytosis
Non-spherocytic hereditary
anemia. Defect of enzymes
pyruvate kinase, glu-6-phosphate
dehydrogenase. Anisocytosis,
splenomegaly, ↑ non-conjugated
bilirubin.
Erythropathies
Ovalocytic. Reticulocytosis. Heredi-
tary pathology of membrane prot.in
er. Jaundice, splenomegaly.
Microspherocytic (Minkowski-
Chauffard disease). Hereditary.
Reticulocytosis.
Poikilocytosis or
specific forms of
red blood cells
Normochromic
Color index 0,85-
1,05

18. Classification of Anemia On The
Basis Of Category
Group of hemolytic anemias
Caused by non-erythrocyte factors
Autoimmune hemolytic. Idiopathic,
autoimmune diseases.
Reticulocytosis. Anisocytosis, indirect
Coombs test+, IgM ↑
Isoimmune hemolytic. After
transfusion, in newborns. Hb-
emiya, Hb-uria,
hemosiderinuria, jaundice,
spleno-, hepatomegaly.
Caused by mechanical damage to
erythrocytes. DIC, burn, malaria,
trauma. PLT↓, Fibrinogen↓,
thrombin↓, jaundice,
hypersplenism
Normochromic
Color index 0,85-
1,05

19. What Are The Laboratory Criteria For
The Diagnosis Of Anemias?
 Hemoglobin when it is less than 12 to 13 G/dL.
 Hematocrit when it is less than 36 to 41%.
 Reticulocyte count was normal at 0.5 to 1.5%.
 MCV is a better choice for classifying the anemias and their
differentiation. This is useful for the screening of occult alcoholism.
 If MCV is high, then advise:
– Reticulocytes count., Vit.B12., Folate level.
 If MCV is low, advised:
– Serum Iron, Iron binding capacity (TIBC).
– If the above two tests are low, advise Ferritin and Bone marrow
examination.
– If normal, then advise electrophoresis.
 If MCV is normal, then advise:
– Serum Iron, Iron Binding Capacity. (TIBC)., Comb’s test., Peripheral blood
for RBC morphology.

20. How Will You Do The Routine Workup
Of The Patient With Anemias?
 The patient’s detailed clinical history for diagnosis, physical examination,
signs, and symptoms with the following lab workup.
 Hemoglobin and hematocrit.
 Red blood cell count.
 Blood indices.
 MCH has limited value in the differential diagnosis of anemias. This is
instrumental calibration.
 MCHC is also instrumental calibration, and changes occur very late in the
iron-deficiency anemia when anemia is very severe.
– This is better to evaluate hypochromasia than MCH.
 Red cell distribution width (RDW) helps to classify the anemia with
the help of MCV.
– RDW is more sensitive to the differentiation of the microcytic anemia than the
macrocytic RBCs cause.
– This has no value in patients without anemia.

21. How Will You Do The Routine Workup Of
The Patient With Anemias?
Serum iron (Normal = 50 to 150 µg/dL).
Serum total iron helps in the diagnosis of anemia.
It differentiates between hemochromatosis and hemosiderosis.
It should be measured along with TIBC for evaluation of iron deficiency.
This also helps to evaluate acute iron toxicity in children.
Total iron-binding capacity (TIBC = Normal = 250 to 450 µg/dL).
It helps in the differential diagnosis of anemias.
It should be done along with serum iron to evaluate the % saturation for the
diagnosis of iron deficiency anemia.
Transferrin: Serum Transferrin level is needed for the D/D of the anemia.
Percent transferrin saturation (normal % transferrin saturation = 20% to
50%).
Calculation of the % transferrin saturation = Serum iron ÷ TIBC x 100
= Transferrin normally 33% is saturated.
This is used for the D/D of the anemias.
This helps in the screening of hereditary spherocytosis.

22. How Will You Do The Routine Workup Of
The Patient With Anemias?
Ferritin: Serum ferritin (normal = 20 to 250 ng/dL).
 It correlates with the total body iron stores.
 It differentiates iron deficiency or excess.
 It correlates with total body iron stores.
 It will predict and monitor iron deficiency.
 It will give an idea about the effectiveness of iron-deficiency anemia
treatment.
 It differentiates iron deficiency from chronic diseases.
 It monitors the iron status in patients with chronic kidney diseases with or
without dialysis.
 It is used to study the population’s iron level and response to iron
supplements.
 It can detect iron overload and monitor iron accumulation.
 It can help to guide the response to iron depletion therapy.

23. How Will You Do The Routine Workup Of
The Patient With Anemias?
Peripheral blood smear.
 This will inform the abnormality of the RBC shape, size, and any inclusions.
 There is a dimorphic picture in a mixed deficiency of iron, vitamin B12, or folate;
there are microcytes and macrocytes. In this case, blood indices may be normal.
 Also, find the abnormal white cells and the assessment of the platelets.
 It can find blast cells like normoblast or granulocyte blast cells.
Reticulocyte count.
The normal range is 0.5 to 2.5%, and the absolute count is 25 to 125 x 109/L.
Reticulocytes are raised in anemia because of the raised level of erythropoietin.
After the acute hemorrhage:
Erythropoietin level rises in 6 hours.
Reticulocyte level increases in 2 to 3 days, and the peak level reaches 6 to 10 days.
Reticulocytes will be raised until the Hb becomes normal.
In the case of anemia, if there is no raised reticulocyte count, it means bone marrow
abnormality or lack of erythropoietin stimulus.

24. How Will You Do The Routine Workup Of
The Patient With Anemias?
 White blood cells count and platelets count. This will
rule out the pancytopenia from the anemia.
– In hemolysis or hemorrhage, the neutrophils and the platelets are
raised.
– In leukemias, the white cells are also raised.
 Bone marrow examination.
– Bone marrow may be aspirated or can take the biopsy.
– This will give the cellularity like myeloid: erythroid ratio, and the
presence of abnormal cells like cancer cells infiltrate.
– Can do Special stains like iron.

26. Summary of lab findings
in various anemias:

27. Summary of lab findings
in various anemias:

28. Summary of lab findings
in various anemias:

31. Non-specific signs

32. Specific signs

35. Megaloblastic Anemia
 A subclass of macrocytic anemia
(under morphologic classification)
Or
 A subclass of anemias due to defective
DNA synthesis
(pathogenetic classification)

36. Megaloblastic Anemia
 Main causes of “Megaloblastic Anemia”
– Vit.B12 deficiency
– Folic acid deficiency
– Others
30-50 % of all macrocytic anemias are
caused by folic acid and/or Vit.B12
deficiency.

37. Vit B12
 Metabolic active cobalamins in the body
are;
– Methyl cobalamin and adenosyl cobalamin
 Hydroxocobalamin can be reversed to the
above cobalamins.
 Pharmacy:
– Most stable cobalamin: cyanocobalamin

38. Vit B12
 Natural forms
– Produced by microorganisms
(bacteria/fungi)
– Plants do not produce or contain Vit B12
(except contamination)
– Colonic bacterial production occurs but
their location is distal to the site of
absorbtion

39. Vit.B12
 Food sources rich in Vit.B12
– Liver
– Kidney
– Muscle
– Egg
– Milk ,Cheese and other diary products
– Seafood

40. Folic Acid
Pteroyl glutamic acid and similar compounds are
termed as folic acid .
Polyglutamate is the natural form.
Dihydro or tetrahydro folate are metabolic active forms.

41. Folic acid
Sources :
 Produced by plants and some
microorganisms
 Folate rich foods;
– vegetables (Green leaf),
– Liver and kidney (parenchymal organs)
– Molds.

42. Folate absorbtion
 Mainly jejunum.
 In the form of monoglutamate .
 Methyltetrahydrofolate monoglutamate is
the form it is found in serum .

43. Folate levels:
Normal ranges
 Serum: 6 – 21 g/L (RBC volume)
 Red cell: 160 – 640 g/L (RBC volume)
Folate deficiency
 Serum folate : <4g /L
 Red cell folate: <140g /L

44. Functions of folic acid:
Transfer of methyl or formyl groups to other
compounds.
eg-During the production of thymidylate for the synthesis of
DNA (methylation of deoxyuridylate)
Source of the 1-carbon moieties;
1-serine
Serine + THF glycine + N-methylene THF
2-Formiminoglutamic acid
Formiminoglutamate+FH4 glutamate+N-formimino THF

45. Causes of VitB12 deficiency
I-Decreased intake
( complete vegetarianism)
II-Impaired absorbtion
 Gastric causes
( Pernicious anemia, gastrectomy , caustic injury, Zollinger-Ellison )
 Intestinal causes
( Ileal resection or disease,eg:sprue,blind loop syndr,Diph.Latum, )
 Pancreatic disease-(insufficiency)
 Familial selective Vit B12 absorbtion defect (Imerslund –
Grasbeck)
 Drugs
( PAS, colchicin, neomycine, omeprazol,potasyum chloride,ethanol )
III-Other causes

46. Causes of Folate deficiency
A) Decreased intake
1-Dietary causes
Senility,
Alcoholism
Hyperalimentation
Hemodialysis
Prematurity
Synthetic diet feeding
Goat’s milk feeding
2- Malabsorbtion
Nontropical sprue
Tropical sprue
Intestinal resection
Other intestinal diseases

47. Causes of Folate Deficiency
B) Increased demands
Pregnancy
Chronic hemolytic diseases
Myeloproliferative diseases
Dermatitis(expholiat.)
Hyperthyroidism
C) Drugs
Oral contraseptive drugs
Some anticonvulsant drugs
Triamterene
Cholestyramine

48. Drugs Possible cause of cobalamin or
folate deficiency
Prolonged proton pump
inhibition
Omeprazole or equivalent result in
a gastric pH of 30, this may affect
cobalamin release from food and
cause low cobalamin levels
Metformin Metformin may cause
malabsorption and low cobalamin
levels
Oestrogen contraceptive
pill
May be associated with mild
reduction in cobalamin levels

49. Clinical features of megaloblastic
anemia
Anemia Atrophic glossitis Neurologic changes
Folic acid deficiency
Vit B12 Deficiency

50. Tissues or organs other than
bone marrow are also affected
 Skin,GIS, female genital system mucosal
epithelium
 Congenital abn.(neural tube defects)
 Neurologic changes(Vit.B12 deficiency)
– Peripheral neuropathy
– Subacute combined degeneration of spinal cord
– Cerebral -Mental changes
 Hyperhomocysteinemia

51. Clinical findings(1)
 Anemia:
Symptoms of anemia + palor+slight
icterus
 Glossitis :
Sore tongue, poor taste sensation, pain
Papill. atrophy-beefy tongue

53. Clinical findings(2)
 Neurologic changes-Vit B12 deficiency
(may occur without anemia)
Paresthesias
Loss of position sense, ataxia
Decreased deep tendon reflexes
Muscle weakness
Loss of vibration sense ( post column )
Spasticity, reflex changes, Babinsky
(lateral column )
Romberg
Mental changes:Memory loss, confusion, dementia,
hallutination etc

54. Clinical findings(3)
 Other signs:
Vitiligo
Hyperpigmentation
Premature graying of hair
Weight loss
Fever
Diarhea
Constipation
Meteorismus
Splenomegaly

55. Peripheral blood
CBC:
Anemia 
Leukopenia 
Thrombocytopenia

56. RBC Indexes:
 MCV
 MCH
 RDW

57. Peripheral smear(1) :
RBC’s
 Macroovalocytosis ,
 Anisocytosis, poikilocytosis ,
 Bazophilic stippling ,
 Howell-Jolly bodies and Cabot ring,
 Nucleated red cells

58. Peripheral smear(2) :
Neutrophyls
 Neutrophyl hypersegmentation
(an early sign of megaloblastic hematopoiesis)

59. Bone marrow
Hypercellular with erythroid hyperplasia.
Erythroid series
 Giant erythroblasts called megaloblasts
 Increased numbers of early erythroblasts
 Nuclear cytoplasmic asynchronism
 Increased mytosis

60. Biochemical findings
 LDH ( LDH -1> LDH - 2)
 Bilirubin(indirect)
 Ferritin and serum iron
 Haptoglobin

61. Special Lab tests
1- VitB12deficiency
 Serum Vit B12
 Methylmalonic acid
excretion***
 Formiminoglutamate
(FIGlu) excr.(50% cases )
 Radioactive VitB12
absorbtipon test
 Deoxyuridine supression
test
 Hyperhomocysteinemia
2-Folate deficiency
 Serum folate
(misleads in case of recent folate intake)
 RBC folate
(Misleads in cases of Vit B12 deficiency)
 Formiminoglutamate (FIGlu)
excretion
 Deoxyuridine supression test
 Hyperhomocysteinemia

62. Treatment
 Treat underlying disease
 Replacement treatment
1- Vit B12 deficiency
cobalamine replacement
For 2 weeks: 1000 g / day İM
Followed by:
1000 g / week until Hb returns to normal
1000 g /mo:life long if necessary(eg:pern.anemia)
Do not administer folic acid alone to patients with B12 deficiency.

63. Cobalamine replacement
 Neurologic response is unpredictable
 BM: Megaloblastic changes are lost in 1 - 3
days.
 Reticulocytosis : max:5 – 8 days
 Hypesegmentation: lost in 1-2 weeks.
 Hb:Normalises in 5 – 6 weeks.
 MCV :Normalises in 10 weeks.
 Hypokalemia.

64. Treatment
2- Folate deficiency
 Treat underlying condition
 Folic acid replacement:
Dose :
 Start with 1 mg / day ( 2 - 3 weeks )
 Continue with 0.25 - 0.50 mg / day
 Pregnants: 1 mg / day

65. Pernicious Anemia
( Addison - Biermer )
Deficiency of intrinsic factor and
 Megaloblastic anemia
 Athrophic glossitis
 Neurologic changes

66. Types of PA:
 Adult: Med: 60 years
 Juvenile : 10 - 20 years
 Congenital : < 2 years

67. P.A.
Pathogenesis:
Adult type
Atrophic gastritis:
•Gastric (body)Corpus involved
•All gastric secretions are decresed
•Chief cells and parietal cells are lost and
•intestinal metaplasia may occur.
Congenital type
Selective IF deficiency ( Autosomal res )

68. Pathogenesis of Gastritis in P.A.
Heredity:
 P.A can be found in the relatives of the patients.
 Related to certain HLA antigens ;
HLA-B7, DW2, DW5, DR2
Autoimmunity:
 Anti –parietal cell antibodies : 85 %
 Anti-IF antibodies : 55 - 70 %
 Anti-thyroid antibodies
 Other autoimmune diseases and cellular immunity

69. P.A.
Treatment
 Life long
 Cobalamine replacement.
Complication
 Gastric Ca: 2 times normal population