Normal Red Cells

•No nucleus, enzyme

packets
•Biconcave discs –
Haem + Gl
•Center 1/3 pallor
•Pink cytoplasm (Hb
filled)
•Cell size 7- 8 µ - capill.
2µ
•100-120 days life span
 definition
• A reduction of more than 10% below the mean values for age,
sex, race and altitude for that population
– i.e. Values vary from population to population
– Each population needs to have its own normal values
• The following normal ranges can be used in general
– Values less than this values can be considered as abnormal(anemia)
• hemoglobin- g/dl
– Females:12 to 16, male:13.5 to 17.7
• HCT-%
– Females:36 to 48 male:40 to 52
• RBC count(in milion/microlitre)
– Females:4 to 5.4 male:4.5 to 6

• NB- the HCT, hgb and RBC count can falsely increase in
hemoconcentration and falsely decrease in hemodilution
 NORMAL VALUES FOR RBC PARAMETERS IN MEN & WOMEN

RBC parameters Adult men Adult women

Hemoglobin, g/dL 15.7 ± 1.7 13.8 ± 1.5

Hematocrit, % 46.0 ± 4.0 40.0 ± 4.0

RBC count, million/dL 5.2 ± 0.7 4.6 ± 0.5

Reticulocyte, % 1.6 ± 0.5 1.4 ± 0.5

MCV, fL 88.0 ± 8.0

MCH, pg/RBC 30.4 ± 2.8

MCHC, g/dL of RBC 34.4 ± 1.1

Red Cell Volume Distribution 13.1 ± 1.4

Width(RDW)
 Adaptation to anemia
• Main consequence of anemia is hypoxia
• Our body tries to adapt to the hypoxia by
1. In acute blood loss—blood redistribution to
important organs
2. In chronic anemia—bohr effect(2,3-BPG)
– More oxygen unloaded from the hgb
3. Hyperdynamic circulation
4. Stimulation of erythropoietin production
 Anemia classification/approach
• Can be approached ON 2 ways
• Both approaches can be combined to reach at the etiology
1. pathophysiologic classification
• Based on the underlying cause and RBC kinetics (reticulocyte
index)
– Hypoproliferative anemia
– Anemia of ineffective erythropoiesis
– Hemolytic anemia
– Anemia of blood loss
2. Morphologic classification
• Based on peripheral morphology and RBC indices(MCV,MCHC)
Hypoproliferative anemias: low reticulocyte index
• Early Iron deficiency anemia
• Anemia of chronic illness
• Anemia of chronic renal failure
• Hypothyroidism
• Hypopituitarism
• Aplastic anemia
• Bone marrow infiltration
– Leukemia, lymphoma, other tumors, infections of BM
• Ineffective erythropoiesis with
microcytic/macrocytic anemias
– Severe iron deficiency anemia
– Megaloblastic anemia
Hemolytic anemia: high reticulocyte index

• Intrinsic rbc pathology(usually hereditary)

– Membranopathies
– Hemoglobinopathies
– Enzyme deficiencies
• Extrinsic pathology(usually aquired)
– Immune hemolytic anemia
– Mechanical trauma
– Hyperspleenism
– Rbc infections
– Toxins
 Anemia of blood loss: high reticulocyte
index
• Acute blood loss
• NB- chronic blood loss causes
hypoproliferative anema (iron deficiency
anemia)
 MORPHOLOGIC CLASSIFICATION
1. Normocytic normochronmic: Normal
mcv:80 to 100
• Early form of iron deficiency
• 70% of anemia of chronic illness
• Anemia of chronic renal failure
• Bone marrow diseases
• Endocrine failure syndromes:
hypothyroidism, hypopituitarism
2. Microcytic hypochromic anemias: mcv<80fl
• Inherited
– Thalasemia, sideroblastic anemia
• Aquired
– Severe Iron deficiency anemia
– 30% of anemia of chronic illness
– Lead poisoning and aluminium toxicity
– myelodysplasia

3. Macrocytic normochromic anemias: mcv>100

– Megaloblastic anemia: vit b deficiency, folate def., methotrexate, AZT
– Alcoholism
– Liver disease
– Hemolysis (reticulocytosis)
– Aplastic anemia
 Patient evaluation
• Anemia is not a disease but is a symptom/sign of a disease
• So you need to
– Diagnose anemia
– Determine the cause of anemia
History
SEARCH FOR CAUSES
• Nutritional history
• Blood loss(hemoptysis, AUB, blood donation, hemorrhoids, hematemess,PUD, blood
letting)
• Drugs being taken
• Alcohol use
• Family history
• Geography of the patient
• Pregnancy
• Menstrual history
• Any underlying disease
Symptoms of anemia per se
• Depends on severity of anemia, rapidity of its onset,etiology, and
demography of the patient (age, underlying disease)
• dyspnea, palpitation, light headedness, syncope, claudication,
angina, leg swelling
• Anorexia, nausea, diarrhea/constipation
• Urinary frequency,menstrual irregularity, loss of libido
• Headache, light headedness,tinnitus, vertigo
• Fatigue,muscle cramp, cold sensitivity,blurred vision
• Difficulty concentrating and irritability
• Low grade fever
• Impotense
• Physical exam
• Nutritional status
• Pulse rate,BP
• Facial abnormality—in chronic hemolysis
• Lymphadenopathy
• Bone tenderness
• Skin and mucus membranes:
– pallor, ictrus, tongue atrophy, angular chelities,
– petechea, finger nails, palmar creases
• Cardiovascular exam
• Hepatospleenomegally
• PR and pelvic examination
• Neurologic examination—position,vibration,reflex,gait
 Work up of anemia
1. CBC—wbc, hgb,platelate
2. RBC indices-MCV,MCH,MCHC,RDW
3. Peripheral film—
– size,shape,color,parasites,anisocytosis,poikilocytosis (bite cells, spherocytes,
eleptocytes,targert cells,sickle cells, fragmented rbcs) ,polychromasia,rbc
aggregation, rbc inclusion bodies
– Abnormality in wbc and platelates
4. Reticulocyte production index
• This is derived from the reported reticulocyte count which is actually
percentage of reticulocytes from all RBCs
• Corrected retic count
– i.e. corrected for the anemia
• Reticulocyte production index: correction for maturation time
• Done only if there are polychromatophilic macrocytes in peripheral film
Reticulocytes. Methylene blue stain demonstrates
residual RNA in newly made red cells
5. Hemoglobine electrophoresis for hemoglobinopathies
– Hemoglobinopathies are not common in our countries
6. Bone marrow examination
• Not important usually---but for hypoprolipherative anemia and to
see erythroid hyperplasia
• Cellularity—aplastic anemia etc
• Myeloid to erythroid ratio( erythroid hyperplasia)
• Morphology of rbcs, wbcs and platelates
• Iron stain—Fe defici vs anemia of inflamation, ringed sideroblasts,
normal sideroblasts
• Histologic exam for infections(TB,LD bodies,MAC,fungal infections)
• culture
 Erythroid hyperplasia
• .
 Iron deficiency anemia
• Develops when body iron store is inadequate for the needs of
normal erythropoiesis
• Most common cause of anemia in ethiopia and the world at
large
• A third of the world’s population is iron deficient
• Africa and parts of Asia bear 71% of the global mortality burden
• major role of iron
• carry O2 as part of hemoglobin
• O2 is also bound by myoglobin in muscle
• Useful in iron-containing enzymes, including the cytochrome system in
mitochondria
– for electron transport and energy metabolism
Distribution of iron in adults
 Iron metabolism
1-Absorption
• Iron is required by every cell
• Free iron is also toxic if excess—generates free radicals
• Total body iron is controlled precisely at the GI level
• Normally 1mg of iron is lost from the body by sloughing of epithelial
cells in the GI, skin etc
– In females 1.5mg/day is lost
– So 1mg of iron is absorbed daily irrespective of whatever excess iron is
ingested
– During pregnancy 2mg/day is lost….the whole pregnancy costs the mother
500mg; therefore iron replacement is needed
• Absorption can increase up to 5x if body store is depleted or
erythropoiesis increases
• Absorption can decrease severely if bone marrow is hypoplastic
• Absorption is through DMT1(divalent metal transport protein) at
the apical wall of the enterocytes and other proteins
• Heme iron is absorbed better than non heme iron
• Iron absorption is facilitated by
– HCL acid, ascorbic acid, and citrate
• Iron absorption is inhibited by
– Plant food(phytates)
– Antiacid
– Tea
– TTC
– phosphates
• Maximum iron absorption
– 20% of the iron present in a meat-containing diet
– 5–10% of the iron in a vegetarian diet
• Vegetarians are at an additional disadvantage
because certain foodstuffs that include
phytates and phosphates----- reduce iron
absorption by approximately 50%
• During the last two trimesters of pregnancy, daily iron
requirements increase to 5–6 mg
[DMT-1

Ferroportin
2-iron transport
 3-cellular uptake and storage
• Steps of hemoglobin synthesis
Transferin
↓
trasferine receptors on developing erythroblasts
↓
Mitochondria of rbc
↓
Iron in cytoplasm
↓
Iron + protoporphyrine-----heme
↓
Heme + globuline→→hemoglobin
• Extra iron+ apoferittin →→ ferritin and hemosiderin which will be stored in the BM, LIVER AND
SPLEEN for feature use
• the cell having the greatest number of receptors (300,000 to 400,000/cell) is the developing
erythroblast
• a certain amount of the transferrin receptor protein is released into circulation
– can be measured as soluble transferrin receptor protein
 Degradation of rbcs and iron reutilization

• At the end of its life span the cell undergoes

phagocytosis--- 0.8–1% of red cells turn over each
day
• the iron on the macrophage is presented to
circulating transferrin
• It is this efficient and highly conserved recycling of
iron from senescent red cells that supports steady
state erythropoiesis
• blood loss or hemolysis places a demand on the
iron supply
• With extravascular hemolytic anemia, the rate of red cell
destruction is increased, but the iron recovered from the
red cells is efficiently reutilized for hemoglobin synthesis
• with intravascular hemolysis or blood loss anemia, the
rate of red cell production is limited by the amount of
iron that can be mobilized from stores
– Typically, the rate of mobilization under these circumstances
will not support red cell production more than 2.5 times
normal
– The result is a hypoproliferative marrow accompanied by
microcytic, hypochromic anemia
 CAUSES OF IDA
• Increased iron requirement
– Pregnancy and lactation
– adolescence
• Blood loss
– PUD, tumors,hookworm etc
– AUB,hematuria
– Hemoptysis,hemosiderosis
– Intravascular hemolysis
– Blood donation
– Dialysis
– NB--the appearance of iron deficiency in an adult male means gastrointestinal blood loss until
proven otherwise

• Inadequate intake
– Cereal rich meat poor diets
– Malabsorption
– Achlorhydria
– Gastric surgery
Characteristic features of IDA
• Pica
• Koilonychia
• Blue sclera
• Glossitis
• Peterson-kelly syndrome
 Specific Investigations to
diagnose IDA
1. Serum iron studies
• serum iron—50 -150microg/l
• TIBC: 300-360 microg/dl
• transferin saturation----25-50%

2. Serum ferritin level-:50-200

• the serum ferritin level correlates with total body iron stores
3. Bone marrow studies(prussian blue stain)
• Normally, when the marrow smear is stained for iron, 20–40% of developing
erythroblasts—called sideroblasts—will have visible ferritin granules in their
cytoplasm
• Red Cell Protoporphyrin Levels---increases in fe def
• Serum Levels of Transferrin Receptor Protein
– High in iron deficiency and low in anemia of chr illness
• Establish cause of IDA
1. PR examinatiion
2. Genitourinary examiantion
3. Occult blood test
4. Stool microscopy
5. Upper and lower GI endoscopy
6. Chest x-ray
7. bronchoscopy
DDX of microcytic hypochromic anemia
• Decreased iron store—IDA (low ferritin)
• Impaired iron use----anemia of chronic illness
(Normal/high ferritin and normal TIBC)
• Disorder of globine synthesis—thalasemia(small
RDW,many target cells, normal/high iron and
ferritin)
• Disorder of heme synthesis---sideroblastic anemia
• Needs BM staining to see ringed sideroblasts
 IDA treatment
• Identify cause of blood loss
• Iron replacement therapy:
– oral, between meals if pt tolerates
– A dose of 200–300 mg of elemental iron per day
should result in the absorption of iron up to 50
mg/d
– Side effects ---Abdominal pain, nausea, vomiting,
or constipation may lead to noncompliance
• Follow up
– Retic count-starts to increase on 3rd/4th day and pick on 10th day
– 3RD week—hgb(at least 2mg/dl increase)
– Donot stop replacement after correcting the hemoglobine;
continue to replenish the store for next 4-6months or until
FERRITIN>50MG/DL
• The ultimate proof of IDA is response to iron replacement
• absence of a response may be due to poor absorption,
noncompliance (which is common), or a confounding
diagnosis
• Indications for parenteral therapy?