Eythropoiesis and Erythrocytes

• Lifespan – 120 days. • Non nucleated. • Biconcave disc. • Production regulated by Epo. • Needs Fe, B12, folate and other elements for development.

RBC Life Cycle

• In the bone marrow, erythropoietin enhances the growth and of differentiation of burst forming units-erythroid (BFU-E) and colony forming units-erythroid (CFU-E) into reticulocytes.

• Reticulocyte spends three days maturing in the marrow, and then one day maturing in the peripheral blood.

• A mature Red Blood Cell circulates in the peripheral blood for 100 to 120 days. • Under steady state conditions, the rate of RBC production equals the rate of

RBC loss.

Hemoglobin • Hemoglobin is the protein molecule in RBC that carries O2 from the lungs to the body's tissues and returns carbon

CO2 from the tissues back to the lungs. • Hemoglobin maintains the shape of RBC also.

What Keep them Biconcave?

Anemia

Red cell disorders: 1- Anemias ↓ red cell mass 2- Polycythemia ↑ red cell mass • An (without) -aemia (blood). • Reduction of Hb concentration below the normal range for the age and

gender. • Leading to decreased O2 carrying capacity of blood and thus O2 availability to

tissues (hypoxia). May be due to: • Erythrocyte loss (bleeding). • Decreased Erythrocyte production.

o Low erythropoietin. o Decreased marrow response to erythropoietin.

• Increased Erythrocyte destruction (hemolysis).

Normal Ranges

Female Male Indices

11.5-15.5 13.5-17.5 Hemoglobin(g/dL)

36-48 40-52 Hematocrit (PCV) (%)

3.9-5.6 4.5-6.5 Red Cell Count (×10¹²)

80-95 Mean Cell Volume (MCV) (fL)

30-35 Mean Cell Hemoglobin (MCH) (pg)

Normal RBCs morphology

Normocytic normochromic RBCs

Measurements of Anemia

• Hemoglobin = grams of hemoglobin per 100 mL of whole blood (g/dL). • Hematocrit = percent of a sample of whole blood occupied by intact red blood cells. • RBC = millions of red blood cells per microL of whole blood. • MCV = mean corpuscular volume.

o If > 100 → Macrocytic anemia o If 80 – 100 → Normocytic anemia o If < 80 → Microcytic anemia

• MCH: mean corpuscular haemoglobin (normal range 26.7-32.5pg/cell): the average haemoglobin content of red blood cells. Cells with a reduced haemoglobin content are termed hypochromic and those with a normal level are termed normochromic. o RDW = Red blood cell distribution width. o = (Standard deviation of red cell volume ÷ mean cell volume) × 100. o Normal value is 11-15%. o If elevated, suggests large variability in sizes of RBCs.

What is Laboratory Definition Anemia?

Hemoglobin = grams of hemoglobin per 100 mL of whole blood (g/dL) The definition of anemia is primarily quantitative and is based on a reduction of hemoglobin, in grams per 100 mL, to at least two standard deviations below the mean, adjusted for age, sex, and altitude of residence Hgb: Women: <12.0 - Men: < 13.5. Hct: Women: < 36 - Men: <41

Clinical Features

General features of anemia • Weakness “related to anemia” • Headache “related to anemia” • Pallor “related to anemia” • Lethargy “related to anemia” • Dizziness “related to anemia” • Palpitation (tachycardia) “related to compensatory

mechanism” • Angina “related to compensatory mechanism” • Cardiac failure “related to compensatory mechanism”

Specific features Specific signs are associated with particular types of anemia: • Spoon nail with iron deficiency. • Leg ulcers with sickle cell anemia. • Jaundice with hemolytic anemia. • Bone deformities in thalassemia major.

History and Physical in Anemia

• Duration and onset of symptoms. • Change in stool habits: Stool Guaiacs in all. • Splenomegaly? • Jaundiced?

Classification of Anemias

Morphologic • Normocytic: MCV = 80-100fL. • Macrocytic: MCV > 100 fL. • Microcytic : MCV < 80 fL. Pathogenic (underlying mechanism) • Blood loss (bleeding). • Decreased RBC production. • Increased RBC destruction/pooling.

Normocytic Anemias Microcytic Hypochromic Anemia • Acute post-hemorrhagic

anemia • Hemolytic anemia

(except thalassemia and some other Hb disorders)

• Aplastic anemia • Pure red cell aplasia • Bone marrow infiltration

• Endocrin diseases • Renal failure • Liver disease • Chronic disease anemia • Protein malnutrition • Hypovitaminosis C

• Microcytes – when MCV < 80fl. • Retic count low or normal. • Anemia - Many weeks after Iron store depletion.

Low MCV and Low Retics Differential diagnosis • Iron deficiency • Sideroblastic anemia • Thalassemia trait • Anemia of chronic disease

Laboratory evaluation • Iron, iron-binding capacity, and ferritin • Blood smear - Target cells, stippling, etc. • Hb electrophoresis for Thalassemia • Bone marrow iron stores, ring sideroblasts

High MCV and Low Retics Differential diagnosis • Megaloblastic anemia

o Vitamin B12 deficiency o Folate deficiency o Myelodysplastic syndrome o Drug-induced anemia

• Nonmegaloblastic anemia o Liver disease o Hypothyroidism o Reticulocytosis

Laboratory evaluation • Serum vitamin B12, RBC folate • Examination of peripheral smear for • hypersegmented neutrophils, giant platelets • Thyroid function tests, • Liver function tests • Bone marrow aspirate for evaluation for myelodysplastic

features

Non-megaloblastic Macrocytic Anemias Megaloblastic Macrocytic Anemias • Hemolytic anemias • Leukemias (esp: acute) • Myelodysplastic syndromes • Liver disease • Aplastic anemia • Diseases infiltrative to the bone marrow • Alcoholism • Hypothyroidism • Scurvy

• Vit B12 deficiency • Folic acid deficiency

Normal MCV and Low Retics Differential diagnosis

Primary bone marrow failure • Aplastic anemia • Constitutional red cell aplasia (Diamond- Blackfan) • Acquired red cell aplasia • Myelophthisis

Secondary bone marrow failure • Uremia • Endocrinology • Human immunodeficiency virus infection • Anemia of chronic disease

Laboratory evaluation • Iron, iron-binding capacity, and ferritin. • Blood smear for marrow disorders: ‘teardrop’. • Serum creatinine, thyroid function tests, liver function tests, cortisol levels if appropriate Erythropoietin level. • Bone marrow aspirate and biopsy.

Anemia with high Retics

• Acute blood loss, Splenic sequestration • Hemolysis

o Immune hemolytic anemia o Mechanical hemolysis Valve, Microangiopathic (DIC) o Hereditary hemolytic anemia o Acquired membrane defects: PNH o Infection-related hemolysis: Clostridia, malaria.

Laboratory evaluation • Blood smear –RBC Morphology • Urinary hemosiderin, • Direct and indirect Coombs test • Cold agglutinin titer • Appropriate further tests as indicated by • Hemoglobin electrophoresis, • G6PD, PK, Osmotic Fragility, sucrose lysis test, bacterial

cultures / smear for parasites.

Pathogenic Classification

(Causes of anemia)

• Decreased RBC production o Decreased Hb production o Defective DNA synthesis o Stem cell defects

– Pluripotent stem cell – Erythroid stem cell(progenitors)

o Other less defined reasons • Blood loss

o Anemia due to acute bleeding • Increased RBC destruction

Decreased Hb Production

• Iron deficiency anemia - Thalassemia • Sideroblastic anemia - Lead poisoning

Defective DNA

Synthesis

• Vit B12 deficiency • Folic acid deficiency

Other.

Pluripotent Stem Cell Defects

• Aplastic anemia • Leukemia or myelodysplastic

syndromes

Defective Erythroid Stem Cell

• Pure red cell aplasia • Anemia of chronic renal failure • Endocrin disease anemia • Congenital dyserythropoetic anemias

Decreased RBC Production Due

to Multipl or Undefined

Mechanisms

• Anemia of chronic diseases • Bone marrow infiltration • Anemia due to nutritional defects

Anemias Caused by Increased

RBC Destruction (Hemolytic Anemias)

Can be classified as; • Hemolysis due to intracorpuscular defects • Hemolysis due to extracorpuscular defects Or

• Hereditary hemolytic diseases • Acquired hemolytic diseases Or

• Intravascular hemolysis • Extravascular hemolysis etc.

Is the Patient Anemic?

• RBC count • HB level • Hct level • Volume status What is the Type

of Anemia?

• History and physical exam. • RBC,HB,Hct , • MCV, MCH,RDW • Red cell morphology ( peripheral smear)

o (Anisocytosis = variation in size) o (Poikilocytosis= variation in shape)

• Reticulocyte count o Incresed?

• Other Lab. investigations

Blood Smear

What is the Indication of Reticulocytosis (Poluchromasia) in Blood Smear? • The rise in bone marrow erythropoietic activity is signaled by (reticulocytosis) in the peripheral blood. • By contrast, anemias caused by decreased red cell production (a regenerative anemias) are associated with

(reticulocytopenia).

Lab. Investigation of Anemia

• WBC count and differential

• Platelet count and morphology

• ESR • Biochemistry, special

tests and others • Bone marrow exam.(only

when indicated)

Serum values of: • Iron • TIBC • Ferritin • Bilirubins • Proteins / electrophoresis • LDH • Vit B12 and /or Folic acid (None of these tests are routine screening tests)

• Red cell enzymes • Hb F, A2, Hb electrophoresis • Coombs tests • Liver, renal, endocrin functional

tests • Urinalysis

o Hemosiderin • Stool for Occult bleeding /

parasites etc. (tests should be chosen individually-do not order routinly)

Take a look at the case of the original presentation (last slide)