This document provides an overview of anemia. It begins by defining anemia and describing the classification, approach, investigations, and common causes of anemia including iron deficiency, anemia of chronic illness, and megaloblastic anemias. It discusses the pathophysiology, epidemiology, classification, symptoms, signs, and treatment approaches for different types of anemia. Specific details are provided on iron deficiency anemia stages, anemia of chronic illness diagnosis and treatment, vitamin B12 and folate deficiencies, and pernicious anemia.

1. Anemia
Outline
Introduction
Classification
Approach to anemic patient
Investigations
Fe deficincy anemia
Anemia of chronic illness
Megaloblastic anemias (folate,Vb12)
Aplastic anemia

2. Introduction
• Definition - A reduction of the Hemoglobin
concentration,or Hematocrite, to below normal levels.
• The likelihood and severity of anemia are
defined based on deviation of patients hgb or
hct from values expected for age & sex
matched normal.
Sex normal (hct) anemia
(hct/hgb)
male 47 (± 7) % < 39 (13g/dl)

3. Pathophysiology
• Erythropoiesis is the process of RBC
production in the erythroid bone marrow
under the influence of stromal
network,cytokins ,EPO (erythroid specific
growth factor or hormone)
• Erythropietin (EPO) is a glycoprotein
produced in the kidney in response to a
sense of hypoxia.
• Normal BM which is repleted by
Fe, Folate and cobalamine will increase

4. Epidemology
• Research done in gondar indicates
prevalence of anemia in rural population of
gondar to be 40.5% and was 4th leading
cause of hospitalization & death in 1982.
• 1987, in black lion it was the 3rd cause of
hematolgic admissions.
• Iron deficiency anemia is the commonest
type globally and especially in developing
country like ours,Ethiopia.

5. Çlassifiçation
1. Pathophysiologiç
 Hypoproliferative anemia
 Maturation disorder
 Anemia due to inçreased
destruçtion/blood loss
2. Morphologiç
 Noromoçytiç normoçhromiç
 Maçroçytiç
 Miçroçytiç hypoçhromiç

7. Approaçh to a patient
• Thorough history and P/E gives a çruçial
information to the cause and severity of
anemia.
• Sxs depend on the rapidity of anemia
devt,severity,age,presence of underlying
ds....
• Usually the body tries to çomensate mild
anemias and chronic anemias by different
mechanisms:

8. Çont’d
– Increased cardiac output when tissue
demand for oxygen increases, and
decrease in PVR to increase perfusion of
tissues.
– Redistribusion of blood flow from less
vital organs to vital organs.
– Increased bone marrow in response to
decrease in red cell mass.
** But this compensatory mechanisms fail if

9. Symptoms of anemia
• Non specific
• Fatigue
,dizziness,palpitation,sweating,angina,
exercise and cold
intolerance,tinnitus,verigo,
nausea,anorexia,bowel habit change .....
• Sxs of underlying disease; wt loss,fever,gi
bleeding bone pain etc
• Neurologic –irritability,difficulity
concentrating, tingling and

10. Signs
HEENT- pale conjuctiva,atrophied and beefy
tongue
angular stomatitis
LGS –lymphadenopathy
CVS –tachycardia,wide pulse pressure,ejeçtion
sys.
murmur,signs of CHF

11. Signs çont’d
GUS – bleeding..
Skin and muçous membrane
– pallor,peteçhea,içterus,spooning of finger
nails
MSS –bone tenderness
Neurologiç exam –sensory or motor
abnormalities
Fundusçopy- retinal hemmorage

12. Investigations
1 Complete blood count
A RBC count
• Hemoglobin
• Hct
• Reticulocyte count
B Red cell indicis
• Mcv (mean corpuscular volume) 80-100 fl
normal
< 80fl microcytic
> 100fl macrocytic

13. Invgn cont’d
• MCH( mean corpuscular hgb) 27 -36 pg
• MCHC (mean corpuscular hgb concentration) 32-
36%
The above two measures indicate defect in hgb
synthesis.
C -WBC count
D -Paletlate count
E –morphology
• size (anisocytosis)
• shape (poikilocytosis)
• hgb content

15. 2 Iron supply studies
– Serum iron level
– Total iron binding capacity
– Serrum ferritin
3 bone marrow exam ( aspiration,biopsy)
– M:E ratio
– Morphology
– Iron stain (prussian stain)
– Cellularity
4 work up for underlying causes
Eg tuberculosis,leishmaniasis,cancer, CRF,HIV
.......

16. Iron deficiency anemia
• Commonest cause of anemia.
• Causes both hypoproliferative disorder (mild to
moderate ) and ineffective erythropoiesis or
maturation disorder ( severe deficiency).
• Marrow only synthesizes hgb when there is
adequate Fe available.
• The only natural source of Fe is diet (1-1.4mg/d)
absorbed in the duodenum and jejnum circulation
bound to transferrin ( transport protein) enters to
BM &
in mitocondria,Fe is realeased and transf.returns
back some part is used for heme synthesis and
the rest is stored as ferritin (storage form)
When the RBC dies the Fe recycles back.

17. Causes of Fe def. anemia
1- Increased demand
– Pregnancy
– Infancy
– Blood loss
2- Increased loss
Blood loss ( mensus,hookworm ,gi loss)
3- Decreased intake and malabsorption
iron in vegetables ( w/ch contain phytates,phosphate
decrease abs.)
but Fe in liver, meat is absorbed well.

18. stages of iron deficiency
anemia
1st negative iron balance
**Demands exceed absorption,early phase
– Ferritin starts to fall
– BM stainability decreases
– Serum iron (SI) normal
– TIBC – normal
– Transferrin saturation –normal
2nd Fe deficient erythropoiesis
- iron store is depleted

20. Stages cont’d
– Serum iron level begin to fall
– TIBC increases
– Transferrin saturation falls (<20%)
– Morphology may remain normal
3rd Fe deficiency anemia
– Microcytic hypochromic
– Fall in hgb and hct
– TS falls (<10-15%)
– Poikiloanisocytosis
– Ineffective erythropoisis

21. • Sxs of Fe deficiency are similar to the
general sign & symptoms of anemia but
:pica
Cheilosis , Koilonychia may be specific for Fe def. A
• Treatment
- Severe anemia with heart failure
(uncompensated ) should be rxed with blood
transfusion.
- Compensated anemia- Fe replacment
- Oral or parentral preparations
- Hgb will normalize by 6-8 wks
- But to replace store, Rx should continue for 4-
6month.

22. Anemia of chronic illness
• Includes
– infection ( TB,HIV)
– Inflammation (RA,Crhon’s ds)
– Maliganancy
– Cronic renal failure, liver disease
• Impotant DDx of fe def anemia b/se effects are due to
inadequate delivery of Fe to BM despite nl or
increases iron stores.
• Mzm of damage
 Hepsidine – decrease Fe absorption and release from
storage forms
 IL-1 directly decreases EPO production
 TNF & IFN gamma –suppress the response of Bm to EPO

23. Diagnosis
• Usually anemia is mild to moderate
• Serum iron- low
• TS – low 15-20%
• Ferritin –normal or increased
• Marrow –hypocellular
• Other comorbid conditions evidenced from
HX,P/E and lab findings.

24. Treatment
• Treatment of underlying factors
• EPO supplementation for CRF
• Transfusion.
• Avoid iron supplementation.

25. Megaloblastic anemias
• This are disorders caused by imapaired
DNA synthesis which helps for cells to
mature
• Only cell division is affected so cytoplasmic
maturation will not be affected so
eventhough the marrow production is
normal or increased but the cells get
dystroyed easily (ineffective
erythropoisis).

26. Causes of MBA.
1. Vit. B12 deficiency
2. Folic acid deficiency
26

27. Folate and Cobalamin Daily
Requirements
Diet
Vitamin B12
(Cobalamin) Folate
Source Animal products Widespread
Body stores 5 mg( liver) 5 mg(liver)
Daily requirement 2-5 µg 50-200 µg
Absorption site ileum duodenum and proxymal
jejinum

28. Causes of Folic acid deficiency
1. Inadequate intake
- diet ; chronic alcoholism, total parenteral nutrition
2. Malabsorption
- small bowel disease (sprue, celiac disease,)
- alcoholism
3. Increased requirements:
- pregnancy and lactation
- infancy
- chronic hemolysis
- malignancy
- hemodialysis
4. Defective utilisation
Drugs:folate antagonists(methotrexate, trimethoprim, triamteren), purine analogs (azathioprine),
primidine analogs (zidovudine), RNA reductase inhibitor (hydroxyurea), miscellaneous (phenytoin, N2)
28

29. Cobalamin (Vitamin B12)
deficiency
Function –cofactor for 2 enzymes Methionine Synthase and
methylmalonyl coA mutase which are involved in many
reactions,esp DNA metablism.
Causes
1 nutritional- vegeterians
2 malabsorption (commonest)
A -gastic causes
– Achlorhydria
– Pernicious anemia (commonest)
– Congenital lack or abnormality of IF
– Total or partial gasrectomy

30. Enteric Processing and absorption
of Cobalamin
Stomach Food-Cbl
H+ Peptic
digestion
Cbl + R-binder
R-Cbl
Duodenum
Pancreatic
enzymes Cbl-TC complex
IF + Cb R-Cbl
OH -
Cbl-IF
Distal ileum
IF receptor Cbl + TC
Cbl-IF

31. Causes cont’d
B intestinal causes
– Ileal disease (crhon’s ds,tropical sprue)
– Bacterial overgrowth ,diphlobotrium latum--
competes for VB12.
– Past ileal resection
C Rare causes
– Transcobalamin deficency
– drugs

32. Pernicious Anemia
• Most common cause of vitamin B12 deficiency
• Occurs in all ages and ethnic backgrounds
• Results from immunologic destruction of
parietal cells in stomach( antrum) which
produces IF,like in atrophic gastritis.
• ~90 % patients show parietal cell antibody.
• Schilling test helps to identify underlying
cause of Vb12 deficincy.
• 24 hr urine cobalamine excreted is
measured,normally > 8% should be
excreted,but if not,it may indicate Vb12
malabsorption.

33. Radiolabled cobalamin (orally) +
unlabled cobalamin IM to saturate
body needs.(1)

34. C/f of VB12 & folate
Hematologic, Gi, neurologic ( only for VB 12 deficiency)
Hematologic
Anemia (macrocytic)
May –leucopenia and thrombocytopenia
Pts have symptoms of anemia, stms bleeding.
GI
b/se GI epithelial cells are rapidly proliferating cells.
Pts may experiance symptoms of malabsorption like diarrihea.
Sore ,beefy tongue
Neurologic ( demylination and axonal degeneration)
Sxs – Spinal cord or PNS
arestesia or numbness,weakness,sphincter disturbance,reflexes depressed
or increased ,position and vibration sense loss.

35. MEGALOBLASTIC ANEMIAS
Diagnosis(1)
1. Blood cell count:
• macrocytic anemia ( MCV>100fl )
• thrombocytopenia
• leucopenia (granulocytopenia)
• low reticulocyte count
2. Blood smear:
• macroovalocytosis , anisocytosis, poikilocytosis
• hypersegmentation of granulocytes
35

37. MEGALOBLASTIC ANEMIAS
Diagnosis(2)
3. Laboratory features
• indirect hyperbilirubinemia
• elevation of lactate dehrogenase (LDH)
• serum iron concentration- normal or increased
4. Bone marrow smear
• hypercellular
• increased erythroid /myeloid ratio
• erythroid cell changes (megaloblasts, RBC precursor a abnormally large with nuclear-
cytoplasmic asynchrony)
• myeloid cell changes (giant bands and metamyelocytes , hypertsegmentation)
• megakariocytes are decreased and show abnormal morphology
5 serum levels of folate and cobalamine should be measured.
37

38. Treatment of VB12 def.
Anemia
• Almost always malabsorption,so Rx should be
parentral.
• 1000µg IM weekly for 8wks followed by
1000µg once every month for life.
• emperical treatment with folate may correct the
anemia but if pt has neurologic
manifestations,may even worse the condition.
• Neurologic complications may fail to respond to Rx

39. RX of FOLIC ACID DEFICIENCY
ANEMIA
1. Oral administration of folic acid 1 to 5 mg per day, for 3
months, and maintance therapy if it’s necessary.
2. Reticulocytosis after 5-7 days
3. Correction of anemia is over after 1-2 months
therapy
39

40. Aplastic Anemia
• Inherited, but can be acquired from chemical
exposure or radiation
• Other causes- viral (
EBV,HIV,Heptitis,parvovirus B19 ),
pregnancy
• Failure of bone marrow to produce adequate
amounts of RBCs, leukocytes, & platelets
• Pancytopenia
• Usually seen in young individual, median age 25
years

41. Aplastic Anemia, cont.
• BM suppression, destruction or aplasia resulting in
failure of BM to produce adequate no of stem cells
• Biopsy
– BM cellularity < 25%
• If severe (ANC < 500/ul) & platelet < 20,000/ul
and retic count < 60000/ul

42. Clinical manifestations
• Fatigue • Epistaxis
• Dyspnea • Purpura
• Petechiae
• Multipel infections (late)
• Ecchymosis
•  temperature (late) • Pallor
• Headache • Palpitations
• Weakness • Tachycardia
• Anorexia • Tachypnea
• Gingivitis • Melena

43. Diagnostic Tests
• degeneration with Prepheral blood smear -
pancytopenia
• BM biopsy- fatty few or no stem cells.
Treatment
• Stem cell transplantation
• Bm transplant
• Blood transfusion
• Without treatment – rapid deterioration & death.

46. • There are also other many causes of
anemia including hemolytic anemias
(intravascular &extra-avascular),blood
loss,mylofibrosis, myelophythias
(infiltrative ds by tumor,infection), MDS.
• Presentation of almost all forms of anemia
are similar.
• Transfusion is indicated for patients with
decompensated anemia.

47. thank
you!