Hematology Physiology 1
Erythropoiesis
Brenda Beckett, PA-C
Terms to Understand
Hematopoiesis
Erythropoiesis
Pluripotent hematopoietic
stem cell (PHSC)
Committed stem cell
(progenitor cell)
Differentiation
Maturation
Self-renewal
Proliferation
Reticulocyte
Polychromasia
Normocyte
Erythropoietin
Adult hemoglobin
Fetal hemoglobin
Apotransferrin
Transferrin
Apoferritin
Terms, continued
Ferritin
Hemosiderin
Serum iron
Total iron binding capacity
-thalassemia
-thalassemia
Hemoglobinopathy
Anemia
Porphyria
A,B,O,Rh blood types
Red Blood Cell
Transports hemoglobin
 Carries oxygen from lungs to tissues
 Carries CO2 back to lungs
 Biconcave disc

– Able to change shape
– Has excess membrane
Red Blood Cell
Mature RBC has no nucleus
 5,200,000 (males), 4,700,000 (females)
per cubic milliliter
 Lifespan of 100-120 days
 Derived from pleuripotent hematopoietic
stem cells (PHSC)

PHSC
Retained in bone marrow
 Reproduction controlled by growth
inducers
 Differentiation controlled by
differentiation inducers

– Will become committed stem cell
(progenitor cell)
Erythropoiesis

Decreased O2 in tissues causes
increased production of erythropoietin
– Hormone
– Formed in kidney (80-90%) and liver
Occurs in fetal liver and spleen, then
shifts to fetal bone marrow
 Occurs in axial skeleton and proximal
end of long bones in adults

Reticulocytes
Final cell produced in marrow before
release
 Basophilic remnants of endoplasmic
reticulum remain, becomes mature RBC
(normocyte) within one day
 Normally ~1% of total RBCs

Reticulocyte Count
Can differentiate between anemias due
to decreased production and those of
increased destruction
 Will see polychromasia on Wright’s
stain, need to order separate test for
reticulocyte count

Hemoglobin Formation
Begins at proerythroblast stage,
continues until reticulocyte (before
leaving bone marrow)
 Heme molecule combines with globin
(long peptide chain) to form hemoglobin
chain.
 4 chains bind together to form
hemoglobin molecule.

Hemoglobin
Binds loosely and reversibly with O2
 Oxygen atom binds loosely with iron
atom in hemoglobin
 Bound as O2, released as dissolved O2

Iron Metabolism

Iron important part of hemoglobin,
myoglobin and other structures
– ~65% of total iron in hemoglobin
– 4% myoglobin
– 1% various heme compounds
– 0.1% in plasma combined with transferrin
– 15-30% stored in liver as ferritin
Iron Transportation & Storage





Absorbed in small intestine
Binds with apotransferrin (globulin) to form
transferrin – loosely bound
Excess deposited in liver and bone marrow
In liver, combines with apoferritin to form
ferritin.
Also stored as insoluble hemosiderin – iron
overload
Iron Usage
If plasma iron low, iron removed from
ferritin, transported as transferrin in
plasma
 Transferrin binds strongly with cell
membranes on erythroblasts in marrow
 Ingested, delivered to mitochondria
 Heme synthesized

Globin chains
4 globin chains combine with heme to
make hemoglobin molecule
 95-97% of adult hgb has 2 -chains and
2 -chains (22) aka Hgb A
 Fetal hgb (Hgb F) has 22. High O2
affinity, mostly changes to HgbA by birth
 Hgb A2 (22), 3-5% of adult

Abnormal Hemoglobins
Hemoglobinopathies: hemoglobin
chains are abnormal
 Thalassemias: hemoglobin chains
normal in structure but decreased or
absent. Named for which chain is
affected.

Genes are on chromosomes 11 & 16
Anemia

Qualitative or quantitative deficiency of
hemoglobin
– Significant blood loss
• Plasma replaced in 1-3 days
• RBCs replaced in 3-4 weeks
– Hemolysis
– Deficient RBC production
Vitamin B12/Folate
Important for final maturation of RBCs
 Essential to synthesize DNA
 Decrease in either leads to failure of
nuclear maturation and division
 RBCs also become larger, irregular
shape, flimsy membrane
 Carry O2 normally, have short lifespan

Vitamin B12/Folate Deficiency
Macrocytic or megaloblastic anemia
 Pernicious anemia: inability to absorb
Vitamin B12 from GI tract
 Gastric mucosa secretes Intrinsic Factor
(IF), combines with B12, available for
absorption
 B12 stored in liver and bone marrow

Iron deficiency
When iron stores are depleted, stored
iron is mobilized
 When iron stores drop, hemoglobin
synthesis is affected – iron deficient
erythropoiesis. (hypochromic)
 More severe, leads to decreased
erythropoiesis, smaller cells (microcytic)

Iron Deficiency Anemia
Low iron stores = low Ferritin
 Low circulating iron (transferrin) = low
Serum Iron
 Leads to increased Total Iron Binding
Capacity (TIBC)
Hypochromic, microcytic anemia

Anemia of Chronic Disease
Most likely due to inflammation
 Iron stores aren’t released
 Decreased erythropoiesis
 Upregulation of WBC production causes
decreased erythropoiesis
 Normocytic or microcytic

Hemolytic anemias
RBCs are fragile, shorter lifespan
 Rupture as pass through capillaries and
spleen
 Hereditary or acquired (immune
mediated)
 Increased destruction leads to
increased bilirubin (jaundice)

Hemolytic anemias

Hereditary spherocytosis (and others)
– Cells are spherical, can’t withstand
compression – easily ruptured

Sickle cell anemia
– Abnormal Hgb S (on  chain)
– Exposed to low O2, forms crystals,
elongates cell – “sickle”
– Sickle trait – protective against malaria
Thalassemias
Autosomal recessive, Mediterranean
 Reduced synthesis of one globin chain,
leads to microcytic anemia
  or  chain affected
 Can coexist with hemoglobinopathies
 Carrier state can be protective against
malaria

G6PD Deficiency
Hereditary
 Low levels of G6PD (enzyme)
 Certain triggers lead to hemolysis,
anemia, jaundice
 Foods, medications, infection
 Protective against malaria

Polycythemia
Increased number of RBCs – primary or
secondary
 High altitude – physiologic polycythemia
 Cardiac failure, smoking, tumors
 Polycythemia vera: blast cells continue
to produce RBCs even though there are
too many in circulation. Viscous blood.
Treatment: phlebotomy

Porphyria
Inherited or acquired
 Disorder of enzymes in heme pathway
 7 different types
 Different combos of elevated porphyrins
(heme precursors) in tissues

– Excreted in urine and stool

Sx: photosensitivity, abd pain, port wine
urine, muscle weakness, behavior
changes
RBC/Hemoglobin destruction
Changes to plasma membranes as cell
ages
 Recognized by phagocytes
 Phagocytosis in spleen
 Heme broken down into iron & biliverdin

– Biliverdin converted to bilirubin
– Iron bound to transferrin
Effects of anemia
Lack of oxygen in tissues
 Symptoms can be vague

– Weakness, fatigue, malaise
– Dyspnea
– Pallor

Increased cardiac output: plapitations,
heart failure
Blood Groups ABO
A&B antigens: “agglutinogens” on RBC
 Anti-A &/or Anti-B develop in absence of
antigens
 Will agglutinate RBCs, lyse, leads to
renal failure, death

Rh Typing
Other antigens can be present on RBCs
 Antibodies develop if exposed to
antigen
 D (Rh), d, C, c, E, e
 Erythroblastosis fetalis

WBC

The overall concentration of white blood
cells of all types in the blood, expressed
as thousands of cells per cubic
millimeter (mm3) of blood. The terms
used to describe a decreased and an
increased WBC are leukopenia and
leukocytosis, respectively.
RBC

The concentration of erythrocytes in the
blood, most commonly expressed as
millions of cells per cubic millimeter
(mm3). The terms describing a
decreased and an increased RBC are
erythrocytopenia and erythrocytosis,
respectively, or, more commonly,
anemia and polycythemia.
HGB/HCT

The overall concentration of hemoglobin
in the blood, expressed as grams of
hemoglobin per 100 milliliters of blood.

The hematocrit, the percentage of the
blood volume consisting of red cells,
expressed as a percent (%).
MCV

mean corpuscular volume, the average
volume of individual erythrocytes in a
blood sample, expressed as femtoliters
(fl) per cell. One femtoliter is the
equivalent of 10-15 liters. The terms
used to describe an erythrocyte with a
normal, decreased, or increased cell
volume are normocyte, microcyte, and
macrocyte, respectively.
MCHC

mean cell hemoglobin concentration, the
average concentration of hemoglobin within
erythrocytes, expressed as grams of
hemoglobin per dL of cells. Because the
intracellular hemoglobin concentration
determines the density of color (suffix chromia) of erythrocytes on a stained blood
smear, the morphological descriptions
associated with a normal, increased or
decreased MCHC are normochromia,
hyperchromia and hypochromia, respectively.
MCH

mean cell hemoglobin, the average
quantity of hemoglobin in individual
erythrocytes, expressed as picograms
(pg) per cell. One picogram is the
equivalent of 10-12 grams.
RDW

red cell distribution width, expressed as the
coefficient of variation around the mean cell
volume (MCV). The larger the value for
RDW, the greater the variability in size within
the erythrocyte population. The morphological
correlate of an increased RDW is variation in
the diameters of individual erythrocytes seen
on the peripheral smear, or anisocytosis.
PLT/MPV


the concentration of platelets in the peripheral
blood, expressed as thousands of platelets
per cubic millimeter (mm3) of blood.
mean platelet volume, the average volume of
individual platelets, expressed as cubic
microns per platelet or as femtoliters per
platelet.
RETIC

the reticulocyte percentage, or the
percentage of immature erythrocytes in a
peripheral blood sample. These immature
cells usually constitute from 0.5 to 1.5% of the
circulating red blood cell population. An
absolute reticulocyte count, expressed as
millions of cells per cubic millimeter (mm3),
can be obtained by multiplying the RBC by
the reticulocyte percentage.