Untitled Flashcards Set

Hematopoiesis: Overall Blood Cell Maturation and
Function
• The total volume of blood in an average adult is about 5-6 L, or 7% to
8% of the body weight.
• Circulating blood is divided as follows:
• 45% cells (formed elements)
• Red blood cells
• White blood cells
• Platelets
• 55% plasma (liquid portion of whole blood)

Hematopoiesis: Overall Blood Cell Maturation and
Function
• Blood cell production, hematopoiesis, begins in embryonic
development, progresses to the fetal liver, and later occurs in
red bone marrow.
• Pluripotent stem cells give rise to the earliest myeloid and
lymphoid precursors.

Stem Cells
• Stem cells can repopulate bone marrow after injury or lethal
radiation the basis of bone marrow transplantation.
• Myeloid progenitors differentiate into colony-forming cells of the
erythroid and myeloid lineages to give rise to: erythrocytes,
platelets, neutrophils, monocytes and macrophages, eosinophils,
basophils, and mast cells (tissues).
• Lymphoid progenitors give rise to natural killer cells, T and B
lymphocytes
Erythrocytes
• Discuss:
• Function
• Formation – Hematopoiesis
• Maturation
• Destruction and Removal
• Hemoglobin – structure, function, variants and derivatives

Hematopoiesis: Overall Blood Cell Maturation and
Function
• The total volume of blood in an average adult is about 5-6 L, or 7% to
8% of the body weight.
• Circulating blood is divided as follows:
• 45% cells (formed elements)
• Red blood cells
• White blood cells
• Platelets
• 55% plasma (liquid portion of whole blood)

Hematopoiesis: Overall Blood Cell Maturation and
Function
• Blood cell production, hematopoiesis, begins in embryonic
development, progresses to the fetal liver, and later occurs in
red bone marrow.
• Pluripotent stem cells give rise to the earliest myeloid and
lymphoid precursors.
©2022, MLA/T Program, Anderson College
Reference: Turgeon, M.L. (Last Published). Linné & Ringsrud’s Clinical
Laboratory Science, Concepts, Procedures and Clinical Applications (Current
Ed.). Elsevier Health Sciences.

Stem Cells
• Stem cells can repopulate bone marrow after injury or lethal
radiation the basis of bone marrow transplantation.
• Myeloid progenitors differentiate into colony-forming cells of the
erythroid and myeloid lineages to give rise to: erythrocytes,
platelets, neutrophils, monocytes and macrophages, eosinophils,
basophils, and mast cells (tissues).
• Lymphoid progenitors give rise to natural killer cells, T and B lymphocytes.

Erythrocytes    • Discuss
• Function
• Formation – Hematopoiesis
• Maturation
• Destruction and Removal
• Hemoglobin – structure, function, variants and derivatives

Erythrocyte Function
• Carry O2 to tissues and removed CO2
HOW:
• Oxygen is transported in a chemical combination with
hemoglobin (Hb). The concentration of Hb in the blood is a
measure of its capacity to carry oxygen.
• To combine with and transport oxygen, the Hb molecule
must have a certain combination of heme (which contains
iron) and globin

RBC Stimulation
• RBC growth in the bone marrow is stimulated by the
hormone secreted by the kidney, Erythropoietin
• Hypoxia - a state in which oxygen is not available in
sufficient amounts at the tissue level to maintain adequate
homeostasis; this can result from inadequate oxygen
delivery to the tissues either due to low blood
supply releases ERYTHROPOIETIN

Erythrocytes - Maturation
• The red blood cell (RBC) begins as a nucleated cell within the bone
marrow. As the cell matures in the bone marrow, its diameter
decreases, and the nucleus becomes denser and smaller, and is finally
released from the cell (extruded) to become a biconcave disk.

Erythrocytes - Maturation
• RBC maturation exists in six stages of development.
• From the youngest to the mature cell are
(1) Rubriblast (pronormoblast)
(2) Prorubricyte (basophilic normoblast)
(3) Rubricyte (polychromatophilic normoblast)
(4) Metarubricyte (orthochromic normoblast)
(5) Reticulocyte (polychromatic erythrocyte)
(6) Mature erythrocyte

Erythrocyte - Maturation
Fig. 11.2. Maturation of red blood cells
series. (A) Rubriblast (pronormoblast); (B)
prorubricyte (basophilic normoblast); (C)
rubricyte (polychromatophilic normoblast);
(D) metarubricyte (orthochromic normoblast);
reticulocyte (diffusely basophilic erythrocyte);
(E) polychromatic erythrocyte; (F) mature
erythrocyte. (From Turgeon M: Clinical
hematology, ed 5, Philadelphia, 2011,

Notice how erythrocytes
begin as large nucleated
cells and as they
mature, they lose their
nucleus (become
anucleated) and get
smaller

Maturation - Reticulocytes
• Reticulocytes become fully mature in 1 or 2 days in the circulating
blood and all RNA disappears.
• Reticulocytes differ morphologically from mature RBCs because they
contain a fine basophilic reticulum or network of RNA, a cytoplasmic
remnant that decreases as the cell matures.

Maturation - Reticulocytes in Circulation

There are two
populations of
erythrocytes in this
smear: mature RBCs
and reticulocytes.
i. Mature – Smaller,
staining darker red
ii. Reticulocytes –
Larger and staining
more purple
(polychromatic

Maturation - Mature Erythrocytes
• RBCs have a total life span of about 120 days.
• The bone marrow releases new cells into the circulatory system
every day.
• The concentration of RBCs and the measurement of the packed
volume of RBC (microhematocrit) are important laboratory
measurements for the detection of anemia or overproduction of RBC.

Erythrocytes – Destruction and Removal
• RBC formation and destructive process
• New red cells are formed in the bone marrow.
• Cells released into the circulating blood.
• As the cells wear out, the reticuloendothelial system breaks them down.
• Protein from them goes into a protein storage pool, which can be used again
in bone marrow to produce new cells.
• Iron from them is recycled into an iron storage pool to be reused in bone
marrow to produce new cells.
• Waste products are excreted in the form of bile in urine and feces.

Erythrocytes - Hemoglobin
• Hemoglobin (Hb) synthesis, structure, and function
• The heme (iron-containing) portion combines with globin (the protein portion) and forms an
activated form of Hb that is ready to transport oxygen.
• Each Hb molecule has four heme groups and a globin moiety, which is composed of four
polypeptide chains.
• Heme
• Because the heme molecule is a porphyrin, a group of diseases called the porphyrias
result from certain disorders of heme synthesis.
• Heme is excreted from the body as bilirubin.
• Iron from heme is normally removed and retained, stored, and reused in the production of new HB.

Erythrocytes – Hemoglobin Structure
Fig. 11.5. Hemoglobin
molecules. (A) The
heme moiety consists
of one protoporphyrin
ring (four pyrrole rings
that are joined to each
other) with a single
iron atom (Fe2+). A
complete hemoglobin
molecule consists of
four heme molecules.
(B) Normal adult
hemoglobin
(hemoglobin A)
consists of four heme
groups, and four
globin chains-two
alpha chains and two
beta chains.
Erythrocytes – Hemoglobin Function
Globin
• The globin portion of the Hb
molecule is a protein
substance that consists of
four chains of amino acids
(polypeptides).
• Each of the four globin
chains is attached to a heme
portion to form a single Hb
molecule

Erythrocytes – Hemoglobin Function
Hemoglobin function
• Iron is essential for the primary function of the Hb molecule: carrying oxygen
to the tissues. If iron is lacking, anemia results because Hb is not formed in
sufficient quantity.
• The molecule fully saturated with oxygen (four oxygen molecules per Hb
molecule) is called oxyhemoglobin.
• Oxyhemoglobin carries oxygen from the lungs to the tissues of the body. Hb
returning to the lungs with carbon dioxide from the tissues is known as
reduced hemoglobin

Erythrocytes – Hemoglobin Variants
Hemoglobin variants
• Hb variants differ in the content and sequence of amino acids in the globin
chains.
• Hemoglobin F: the major form found during intrauterine life and at birth
Abnormal hemoglobin variants
• Disorders where abnormal Hb plays an important role pathologically are
called hemoglobinopathies.
• Hemoglobin S: sickle cell anemia or disease (see next slide)
• Hemoglobin C

Inheritance of Hemoglobin S (Sickle Cell)
Fig. 11.9. Hemoglobin S
genetics. Sickle cell trait
and anemia. When two
persons with sickle cell
trait (genotype: A/S)
produce offspring, the
expected genotypic ratio
is 1:2:1, or a 25% chance
of offspring with a normal
hemoglobin (A/A), a 50%
chance of offspring with
sickle cell train (A/S), and
a 25% chance of
offspring with sickle cell
anemia (S/S). Hgb,
hemoglobin. (From Turgeon
M: Clinical hematology, ed 5,
Fig. 3.11, p. 62 Philadelphia,
2011, Lippincott Williams &
Wilk

Hemoglobin S
Fig. 11.11. Hemoglobin S amino acid sequence. Hemoglobin S differs
from hemoglobin A in one amino acid reside on the beta chain of the
hemoglobin molecule. On this chain, valine (Val) is substituted for
glutamic acid (Glu) at the sixth position of the chain. (From Turgeon M:
Clinical hematology, ed 5, Philadelphia, 2011, Lippincott Williams &

Erythrocytes – Hemoglobin Derivatives
Hemoglobin derivatives
• When sufficient quantities of Hb derivatives are present in circulating blood,
hypoxia (lack of oxygen) or cyanosis (bluish discoloration of skin and mucous
membranes) is seen.
• Oxyhemoglobin and reduced hemoglobin
• Carboxyhemoglobin
• Methemoglobin
• Hemiglobincyanide (cyanmethemoglobin)
• Sulfhemoglobin

Erythrocytes – Hemoglobin Values
Variations in hemoglobin concentrations
• The reference (or normal) values for Hb in peripheral blood vary with the age
and gender.
• Altitude: Normal Hb concentration is higher at high altitudes than at sea level.
• There may be a slight decrease in hemoglobin level after 50 years of age.
• When the Hb value is below normal, the patient is said to be anemic.
• In anemia, circulating erythrocytes may be deficient in number, in total Hb content per
unit of blood volume, or both.
• Increase in Hb can be seen in polycythemia and newborns

Basic RBC Diseases/Disorders
Anemias
• Iron Deficiency anemia – not enough dietary iron
• Pernicious anemia – autoimmune condition where body cannot
absorb vitamin B12
• Aplastic anemia – bone marrow stops making new blood cells
• Autoimmune hemolytic anemia (AHA) – immune system destroys
your RBCs faster than body can replace them
• Sickle cell anemia – genetic mutation leaving RBCs rigid and curved
and cannot carry enough O2 to tissues. Can also get stuck in blood
vessels

Basic RBC Diseases/Disorders
• Polycythemia vera
• Blood cancer
• Bone marrow makes too many RBCs – blood thickens, at risk for blood clots
• Treatment involves phlebotomy – remove excess blood
• Thalassemia
• Inherited blood disorder
• Genetic mutation which prevents normal production of hemoglobin
• O2 does not get to all parts of the body
• Organs do not function properly

Common Symptoms of RBC Disorders
• Shortness of breath
• Fatigue
• Muscle weakness
• Fast heart rate (tachycardia

RBC Terminology
• Erythrocytes – red blood cells
• Hemolysis – rupture of red blood cells

43
Leukocytes
White Blood Cells:
Main function is to
protect the body
from infection

Formed elements of the blood go through developmental stages
• As cells mature, they are able to move through the sinusoids of the marrow
because of decreased overall cell size, decreased nuclear cytoplasmic ratio,
and increased flexibility and mobility.
• Normal peripheral blood cells include lymphocytes, basophils, eosinophils,
segmented neutrophils, monocytes, and band neutrophils.
• Each cell type has a normal life span and function.
Normally, only mature cells are seen in the peripheral blood
circulation.
• Immature cells may appear in the peripheral blood in certain disease states,
called a shift to the left.

Leukocytes
Normal leukocyte morphology
• Leukocytes are larger and more complex in appearance than the RBCs.
• They consist of a nucleus surrounded by cytoplasm.
• Five types of white blood cells
• Neutrophils (segmented and band)
• Eosinophils
• Basophils
• Monocytes
• Lymphocytes

ig. 11.16. Normal
leukocytes.
(A) Polymorphonuclear
neutrophils;
(B) band neutrophils;
(C) lymphocytes;
(D) monocytes;
(E) eosinophils; and
(F) basophils. (From Carr JH,
Rodak BF

Identifying Leukocytes
Ways to identify the leukocytes under the microscope:
1. Nuclear chromatin pattern
2. Nuclear shape
3. Size and number of nucleoli, when present
4. Cytoplasmic inclusions
5. Nuclear/cytoplasmic (N/C) ratio

Granulocytes vs Non-granulocytes
Leukocytes are categorized as granulocytes and non-granulocytes
• Granulocytes are leukocytes that come from the myeloid series of cell
development.
• As mature cells, neutrophils, eosinophils, and basophils contain specific granulation in their
cytoplasm.
• Monocytes are classified as myeloid cells that contain non-specific granulation.
• Lymphocytes are cells derived from the lymphoid series of cell development.
• They are non-granulocytes that may contain nonspecific granulation

Granulocytes
49
Neutrophils
Eosinophils
Basophils

Granulocyte Development
Granulocytic leukocyte development
• Includes myeloblasts, promyelocytes, myelocytes, metamyelocytes, bands,
segmented neutrophils, eosinophils and basophils

Neutrophil Maturation
Neutrophils normally mature in the bone marrow in stages, from the youngest to
the most mature: myeloblast, promyelocyte, myelocyte, metamyelocyte, band, and
segmented neutrophils.
• Cells of the neutrophil series are generally round with smooth margins or edges. As the
cells mature, they become smaller.
• Most immature cells have cytoplasm that stains dark blue and becomes light pink as the
cells mature. As the cells mature from the myeloblast to the promyelocyte stage,
nonspecific granules that stain blue to reddish purple appear in the cytoplasm.
• Eventually, these nonspecific granules are replaced by specific neutrophilic granules.
• Nuclear changes also occur as the cells mature.
• Nucleoli may be apparent in the early forms but gradually disappear as the chromatin
thickens and the cell matures

Neutrophils
Segmented Neutrophils
• The most numerous of the granulocytes, neutrophils make up about 59%
of the leukocytes in peripheral blood, with a range of 35% to 71%.
• The usually lobular nucleus forms a relatively small part of the cell.
• The nuclear chromatin is coarse and clumped and stains deep purple. The
nuclear membrane is distinct, and no nucleoli are visible.
• The abundant cytoplasm is colorless or faintly pink and contains a large
number of very small, often indiscrete, lilac-specific neutrophilic granules
distributed irregularly throughout it

Neutrophils
Band neutrophils
• The band neutrophil is a younger form of the mature neutrophil.
• Band neutrophils resemble segmented cells except for the shape of the nucleus. An
increase in their numbers is significant.
Neutrophil counts
• Generally, an increased WBC count (leukocytosis) results from an increase in the absolute
number of neutrophils present in the blood, called neutrophilia
• Neutropenia is a decrease in the absolute neutrophil count

Neutrophils
Characteristics of Neutrophils
• The neutrophilic granules contain several digestive enzymes that are able to
destroy many types of bacteria.
• The cells are capable of random locomotion and can be directed to an area of
infection by the process of chemotaxis (chemical messaging).
• Once in the tissues, the neutrophils destroy bacteria by engulfing them and
releasing digestive enzymes into the phagocytic vacuole thus formed.
• Referred to as Phagocytes

Eosinophils
Characteristics of Eosinophils
• Eosinophils exist in the peripheral blood for less than 8 hours after release
from the marrow and have a short survival time in the tissues.
• The function of eosinophils is not completely understood.
• They do leave the peripheral blood when adrenocorticosteroid hormones
increase and proliferate in response to immunologic stimuli.
• Eosinophils are capable of locomotion and phagocytosis and respond to
foreign proteins.
• They are active in allergic reactions and parasitic infections, especially those
involving parasitic invasion of the tissues

Eosinophils
Eosinophil Morphology
• Slightly larger than neutrophils, usually with a bilobed nucleus.
• Cytoplasm is usually colorless, but crowded with spherical acidophilic
granules, which stain red-orange.
Eosinophil counts
• Eosinophilia, an increase in the number of eosinophils above normal, is
associated with a wide variety of conditions, but especially with allergic
reactions and drug reactions.
• Decreased number of eosinophils, is seen with hyperadrenalism.

Basophils
Characteristics of Basophils
• Basophils occur in very low numbers in normal peripheral blood.
• The granules contain histamine, heparin or a heparinlike substance, and
peroxidase.
• The rapid release of mediators from immunoglobulin E (IgE)–primed
basophils and mast cells activated by exposure to parasite-associated
antigens is thought to contribute significantly to the local inflammation
associated with IgE-dependent immune responses to parasites.
• If the same events are triggered by antigens from pollen, food, drugs, or
insect venom, the result is a disorder of immediate hypersensitivity

Basophils
Basophil Morphology
• About the same size as neutrophils, basophils’ nuclei usually occupy a greater portion of
the cell.
• Irregularly shaped nucleus
• Cytoplasm is usually colorless; it contains a number of deeply stained, coarse, round, or
angular basophilic granules.
• Note that tissue basophils, also called mast cells, are similar but not identical to
basophilic granulocytes.
Basophil counts
• Basophilia, an increase in the number of basophils, occurs in chronic myelogenous
leukemia and other conditions

Agranulocytes
60
Monocytes
Lymphocytes

Monocytes
Monocyte function and morphology
• Monocytes remain in the peripheral blood for hours to days after leaving the
bone marrow.
• Can move from blood into tissue, then called macrophages
• They are motile, phagocytic cells, but they do not die after they engage in
phagocytotic activity.
• Function in the defense against microorganisms.
• The largest of the normal leukocytes
• Nucleus is large and usually indented.
• Gray-blue cytoplasm with extremely fine and abundant azurophilic granules

Lymphocytes
Lymphocyte maturation and function
• Lymph nodes are located all along the lymphatic vessels, and lymph (fluid within
the system) circulates through the nodes as it progresses through the system.
• Many lymphocytes circulate between the blood, the organs, and the lymphatic
tissues.
• Functionally, there are two types of lymphocytes, T cells, or T lymphocytes, and B
cells, or B lymphocytes.
• T cells arise in the thymus from precursors that seed the thymus during embryonic
development. These CD34+ progenitor cells develop in the thymic cortex.
• B lymphocytes are derived from hematopoietic stem cells in the bone marrow by a complex
series of differentiation events

Lymphocytes
• B-lymphocyte differentiation is complex and culminates in
the generation of mature, end-stage, nonmotile cells called
plasma cells or into memory B cells, long-lived cells that
circulate in the blood.
• Lymphocytes act to direct the intra-cellular immune
response system of the body

Lymphocytes
• Comprise about 34% of leukocytes in normal adults
• Two sizes, large and small; most are small
• Described based on size and cytoplasmic granularity
• After antigenic stimulation, small lymphocytes can undergo
transformation, and are then called reactive, atypical, variant, or
reticular lymphocytes.
• Lymphocytosis, an increase in the number of lymphocytes, is
associated with viral infections

Lymphocytes – Plasma Cells
• In addition to the five types of mature WBCs that normally appear in
the peripheral blood, the plasma cell is rarely seen.
• Plasma cells are derived from B cells and are large with a round or oval
nucleus that is usually in an eccentric position.
• The chromatin consists of deeply stained, heavy masses that may be arranged
in a radial pattern.
• The cytoplasm is strongly basophilic.
• There may be a pale, clear zone in the cytoplasm to one side of the nucleus,
referred to as a hof.
• They function in the synthesis of immunoglobulins

Basic WBC Diseases/Disorders
• Lymphoma
• blood cancer that occurs in the lymphatic
system.
• WBCs change and grow out of control
• Leukemia
• blood cancer where malignant
(cancerous) cells multiply inside the bone
marrow
• can be either acute (fast) or chronic
(slow)

Common Symptoms of WBC Disorders
• Chronic Infections – WBCs are the cells of the immune system
• Fatigue
• Unexplained weight loss
• Feeling unwell

WBC Terminology
• Leukocytes – white blood cells
• Leukocytosis – have a high white blood cell count
• Leukopenia – have a low white blood cells count
• Pancytopenia – decrease in all cell lines (RBC, WBC, Plts)
• Neutropenia – decrease of neutrophils
• Neutrophilia – increase of neutrophils
• Lymphocytosis – increase in lymphocytes
• Monocytosis – increase in monocytes
• Monocytopenia – decrease in monocytes
• Eosinophilia – increase of eosinophils
• Basophilia – increase of basophils

WBC Terminology Question
Q: Why is there no term discussing the decrease of eosinophils or
basophils?
A: Because those cells are typically found in low numbers already

Thrombocytes (Platelets)
Produced in the bone marrow, platelets are an essential part of the
blood-clotting mechanism.
• They act as plugs around the opening of a wound and release factors necessary for blood
clot formation.
• Platelets do not have a nucleus and are not actually cells; they are portions of cytoplasm
pinched off from megakaryocytes and released into the bloodstream.
• Mature platelets are small, colorless bodies 1.5 to 4 micrometers in diameter.
• Platelets are generally round or ovoid, although they may have projections called
pseudopods.
• Platelets have a colorless to pale-blue background substance containing centrally
located, purplish red granules

Basic Platelet Diseases/Disorders
• Von Willebrand disease
• Most common inherited bleeding disorder
• Deficiency of protein that helps blood clot (von Willebrand factor – VWF)
• Hemophilia
• Best-known clotting disorder
• Almost always in males
• Excessive and prolonged bleeding
• Due to inhibition or deficiency of clotting factors in plasma
• Primary thrombocythemia
• Bone marrow produces too many platelets
• Leads to increased blood clotting

Common Symptoms of PLT Disorders
Not enough platelets = can cause serious blood loss
Too many platelets = clots can form and cause stroke or heart attack
Non-functioning platelets = can’t clot properly
• Cuts or sores that are slow to heal
• Blood not clotting after an injury
• Bruises
• Nosebleeds or bleeding from the gums

Platelet Terms
• Thrombocytes - platelets
• Thrombocytopenia – have a low platelet count
• Thrombocytosis – where the body produces too many platelets