Blood Cells and the

Hematopoietic
System
Elements of the Hematopoietic System

All the blood cells and their precursors

The bone marrow, where blood cells
have their origin
The lymphoid tissues where some blood
cells circulate as they develop and
mature
Composition and function of blood

 The only fluid tissue of the body

 Type of connective tissue

 Formed elements
 Blood cells: RBC’s, WBC’s, platelets, etc.
 Hematocrit: ~45% RBC’s of blood volume
 Plasma
 55% of the blood volume
Characteristics of Blood

Color dependent on the amount of

oxygenation

pH 7.35 – 7.45 (slightly alkaline)

~100.4o Fahrenheit (38o C, warmer than body

temperature)
Functions of Blood

 Deliver
 oxygen from the lungs and nutrients from the intestine to all cells
of the body
 Transport metabolic waste
 Transport hormones
 Regulate
 Distribute heat around body
 Maintain pH, serve as a bicarbonate reserve
 Maintain fluid volume
 Protect
 Excess blood loss
 Prevent infection
 Plasma
 Water (90% of volume) and dissolved solutes (hormones, ions, gases, etc.)
 Proteins
 Albumin (54 - 60% of plasma protein)
 Blood buffer
 Shuttles molecules
 Maintains osmotic pressure
 Globulins
 Comprise approximately 38% of plasma proteins Alpha globulins transport
bilirubin and steroids
 Beta globulins transport iron and copper.
 Gamma globulins constitute the antibodies of the immune system.
 Fibrinogen
 Makes up approximately 7% of the plasma proteins
 Is converted to fibrin in the clotting process
Plasma water is a transport medium
It transports inorganic substances such as Na+ and Cl-.
They carry out many body functions (e.g., membrane
excitability).
It transports organic substances such as plasma proteins.
They compose 6 to 8 percent of the plasma’s total weight.
They have numerous functions.
 Albumins establish an osmotic gradient between the
blood and interstitial fluid.
 Other proteins buffer pH changes.
 The globulins (alpha, beta, and gamma) have roles
ranging from blood clotting to transport.
 The gamma globulins function in immunity as
antibodies.
 Fibrinogen is a key factor in blood clotting.
Other substances carried in the plasma include nutrients,
waste products, dissolved gases, and hormones.
Formed elements

 Erythrocytes (Red-blood cells)

 Anucleated (no nucleus)
 Leukocytes (White-blood cells)
 Nucleated (lobed nucleus)
 Platelets
 Cell fragments

 About 99% of the cells are erythrocytes.

 The hematocrit is the percentage of total blood
occupied by erythrocytes. It averages 42% is
women and 45% in men.
Erythrocytes
 RBC’s
 Biconcave disks
Large surface area
 No nucleus
 The plasma membrane
is flexible. This allows it
to slide through a capillary.

 No organelles
No O2 consumption
 Lots of Hemoglobin
97% Hb

 Their concentration is about 5 billion per ml or 5

million per cubic mm.
Function of Erythrocytes

Protein: globin
Transport respiratory gases
2 a, 2 b bound to a
15 g/Hb can bind 1.35 ml/O2 heme
20.0 mlO2/100 ml blood Pigment: Heme

1 RBC = 250 million

hemoglobin
molecules

1 billion oxygen
molecules per RBC
Hemoglobin is a molecule
consisting of two parts
The globin is four, folded polypeptide chains.
The heme part is non-protein. Each of its four
iron atoms is bound to one of the polypeptides
and can combine with one molecule of
oxygen gas. This molecule is bright red when
combined with oxygen.
Hemoglobin can also combine with carbon
dioxide, hydrogen ions, carbon monoxide, and
nitric oxide.
Hemoglobin can buffer pH by binding with
hydrogen ions.
The erythrocyte contains glycolytic enzymes. Its
enzyme carbonic anhydrase converts carbon
dioxide into the bicarbonate ion. Carbon
dioxide is mainly transported as this ion in the
blood.
Oxygen transport
Hematopoiesis: Production of RBC’s
 Hematopoiesis (hemopoiesis) occurs in pluripotent stem cells in the
bone marrow
 All formed elements derived from the hematopoietic stem cell
(hemocytoblast)
 The proliferation, differentiation, and functional abilities of the
various blood cells are controlled by cytokines.
 Cytokines are hormone-like growth factors.
Regulation of Erythropoiesis
 Hormonal control: EPO
(erythropoietin)
 Can cause a 5 fold
increase in production
Takes ~8 days to
produce RBC from stem
cell
 Males: 5.4 million/ml
(mm3) produce 2
million/sec
 Females: 4.8 million/ml
(mm3)
Useful Hematopoietic Growth Factors

 EPO (erythropoietin)
 Stimulates the formation of erythrocytes
 TPO (Thyroid Peroxidase)
 Protein that is an antigenic determinant, is the part of an antigen
that is recognized by the immune system, specifically by antibodies,
B cells, or T cells
 G-CSF (Granulocyte Colony Stimulating Factor)
 Growth factors are proteins made in the body and some of them
make the bone marrow produce blood cells. G-CSF makes the body
produce white blood cells to reduce the risk of infection after some
types of cancer treatment. It also makes some stem cells move from
the bone marrow into the blood.
 GM-CSF (Granulocyte-Macrophage Colony Stimulating Factor)
 Stimulates the formation of white blood cells (leukocytes)
Conditions Responding to Use of
Hematopoietic Growth Factors

Bone marrow failure Infectious diseases

caused by such as acquired
chemotherapy or immunodeficiency
aplastic anemia syndrome (AIDS)
Anemia of kidney Congenital and
failure myeloproliferative
disorders
Hematopoietic
neoplasms Some solid tumors
Hematopoietic Growth Factors

Increase peripheral stem cells for

transplantation
Accelerate cell proliferation after bone
marrow engraftment
Destruction of RBC’s

Useful life span of 100-120 days

Often trapped in the spleen
RBC’s engulfed by macrophages
Iron core recycled
Heme group degraded to bilirubin and taken
to liver
Secreted in bile and lost
Globin protein metabolized for its amino acids
Life cycle of a Red-blood cell
Erythrocyte disorders

Anemia: low oxygen carrying capacity of

blood
Insufficient number of cells
Hemmoragic: rapid blood loss
Hemolytic: rupture of RBC’s (infection,
etc.)
Aplastic: bone marrow destroyed
(leukemia), EPO levels elevated
Renal: Kidney disease
Nutritional: Dietary deficiency
Anemia disorders (cont.)

 Decreased hemoglobin content

Iron deficiency (creating microcytes)
Malnutrition, malabsorption, pregnancy (transferred to
fetus)
Pernicious: deficiency of B12 (intrinsic factor needed
for absorption of vitamin); B12 needed for DNA synthesis
 Abnormal hemoglobin
Thalassemias: faulty globin chains (a or b)
Sickle cell anemia: Change in the beta chain of HbS
Polycythemia: excess of RBC’s
Polycythemia (erythrocytosis) is an excess in
circulating erythrocytes

It produces an elevated hematocrit.

 Smoking (CO2 displaces O2), high
altitude (hypoxia)
Primary polycythemia is caused by
an tumor-like condition in the bone
marrow.
Secondary polycythemia is an
erythropoietin-induced adaptive
mechanism to improve the oxygen-
carrying capacity in the blood.
Other conditions can elevate the
hematocrit, such as dehydration.
Leukocytes (White-blood cells)

Less than 1% of blood (4000-11000 ml3)

Defense against disease (part of the immune

system)

Able to pass through capillary beds

(diapedesis), and move about tissues using
amoeboid motion
Classes of Leukocytes

Granulocytes- all phagocytic

 Cells have visual granules in
cytoplasm
Neutrophils
Basophils
Eosinophils
Agranulocytes
 Lack visual granules in
cytoplasm
Lymphocytes
Monocytes
Leukocytes are produced at varying rates
Their rates change depending on the changing defense needs of the
body.
They are produced from pluripotent stem cells in the bone marrow.
These cells can differentiate and proliferate into different cell lines,
producing the different kinds of white blood cells.
Granulocytes and monocytes are produced only in the bone marrow.
Lymphocytes are originally produced from precursor cells in the bone
marrow. Most new ones are produced from lymphocytes in lymphoid
tissue.
The total number of leukocytes ranges from 5 to 10 million cells per
milliliter of blood. An average count can also be expressed as 7000
per cubic mm. They are the least numerous cellular elements in the
blood.
Normally about two-thirds of the leukocytes in the blood are
granulocytes. However, the percentages of each WBC can change
depending on the defense needs of the body. Various hormones
signal these changes.
Granulocytes
 Neutrophils
 Most abundant: Constitute 50% to 60 % of white blood cells
 2X size of RBC
 Dye both red and blue
 Granules hold defensins: antibiotics
 Specialize in destroying bacteria

 Nuclei 3-6 lobes (polymorphonuclear)

 Primarily responsible for maintaining normal host defenses against invading

substances
 First cells to arrive at the site of infection
 Have their origins in the myeloblasts found in the bone marrow
 Move to the tissue for approximately 1 to 3 days
 Die in the tissue discharging phagocytic function or die of senescence
Granulocytes
 Eosinophils
 Bilobed nucleus
 Stain Red
 Granules hold digestive enzymes
 Defense against parasites (tapeworms, roundworms, etc) too large
to be phagocytized

 1% to 3% of the total number of white blood cells

 Increase in number during allergic reactions and parasitic infections
 The agents associated with allergic reactions
 In parasitic infections, the eosinophils use surface markers to attach
themselves to the parasite and then release hydrolytic enzymes.
Granulocytes
 Basophils
 Bilobed nucleus
 Stains blue with addition of dye

 0.3% to 0.5% of the total leukocytes

 Consist of heparin, an anticoagulant, histamine, a vasodilator, and
other mediators of inflammation
 Similar to mast cells
 Involved in allergic and hypersensitivity reactions
Agranulocytes
 Lymphocytes
 Second most numerous WBC
 Large, Spherical nucleus
 Most in tissues, few in bloodstream

 T-lymphocytes: act directly against virus infected cells and tumors

 B-lymphocytes: give rise to plasma cells, which produce antibodies
 Natural killer cells

 20% to 30% of the total blood leukocytes

 Function in the lymph nodes or spleen to defend against microorganisms
through the immune response
Agranulocytes
 Monocytes
 Largest WBC
 U shaped nucleus
 Macrophage function (swallow infected cells) and activate
lymphocytes

 3% to 8% of the total leukocyte count

 Cells survive for months to years in the tissues.
 Important role in chronic inflammation
 Involved in the immune response
 Activating lymphocytes
 Presenting antigen to T cells
Formation of Leukocytes

Controlled by hormones: cytokines (glycoproteins)

Formation of Leukocytes
Formation of Leukocytes
Leukocyte disorders

Leukopenia: lack of WBC’s (anti-cancer/ AIDS

drugs
Leukemia: impair normal bone marrow function
Acute: fast (from lymphoblasts)
Chronic: slow (from myelocytes)
Infectious mononucleosis: viral disease from the
Epstein-barr virus. No cure. Rarely fatal
Platelets (thrombocytes)
 Large cytoplasmic fragments (megakaryocytes)
 Function in blood clotting, regulated by thrombopoietin

 Circulating cell fragments of the large megakaryocytes

 Function to form the platelet plug to helps control bleeding
 8 to 9 days in circulation
Platelets (thrombocytes)
function in hemostasis.
They are cell fragments derived from megakaryocytes.
They average 250,000 per ml. Their range is also
reported as 150,000 - 350,000 per cubic mm.
They remain functional for about 10 days.
The hormone thrombopoietin increases the number of
megakaryocytes. Their overall production is not well
understood.
 Hemostasis

Control of bleeding

Vascular spasm
Constriction of
damaged vessel,
reducing blood
loss
Hemostasis
 Steps in Hemostasis
 The first steps to stop escaping blood from a vessel are:

 vascular spasm - This reduces blood flow through a damaged vessel.

 platelet plugging - An aggregation of platelets forms a plug. Platelets
aggregate on contact with exposed collagen in the damaged wall of a vessel.
 clot formation - This reinforces the platelet plug and converts the blood to a
gel in the area of the vessel damage.
 The ultimate step in clot formation is the conversion of fibrinogen (large
and soluble plasma protein) into fibrin (thread-like protein). This
conversion is catalyzed by thrombin.
 Fibrin threads trap RBCs, forming a clot. This clot is a meshwork
strengthened by cross-linkage from factor XII.
 Thrombin is formed from the precursor prothrombin by the activation of
factor X. This conversion involves the clotting cascade.
 The functions of thrombin are fibrin formation, activating factor XII, acting
through positive feedback to facilitate its own formation, and enhancing
plate aggregation.
The clotting cascade is a series of steps
involving twelve clotting factors. They lead to
the final conversion of fibrinogen into fibrin.
The clotting factors serve as proteolytic
enzymes in a series of reactions, the
clotting sequence. One factor in the
sequence is activated which in term
activates another factor and so on. This
sequence is called the clotting cascade.
The last two steps in the cascade are:
 prothrombin is converted to
thrombin
 fibrinogen is converted to fibrin
intrinsic pathway - This uses the
sequence of factors in the cascade.
extrinsic pathway - This requires only four
steps and requires contact with tissue
factors external to the blood. Damage
exposed blood to tissue factor (TF)
activating Factor VII then Factor X
Other facts on blood clotting include:
Clot retraction occurs after the clot is formed.
Amplification occurs in the clotting process. One molecule can
activate one hundred molecules in the next step and so forth.
The clot is not a permanent solution for injury to a vessel.
Fibroblasts form scar tissue for vessel repair.
The clot is slowly dissolved by the enzyme plasmin. It is made in
the liver from plasminogen.
Phagocytic white blood cells remove the products of clot
dissolution.
tPA prevents inappropriate clot formation.
Inappropriate clotting can produce a thromboembolism.
Causes of this include roughened surfaces on a vessel.
Hemophilia is a condition responsible for excessive bleeding. It is
due to a deficiency of factor VIII in the cascade. A vitamin K
deficiency can cause a bleeding tendency.
 Bleeding disorders
 Von Willebrands Disease: Von Willebrands
factor stimulates platelet adhesion to initiate
clotting cascade
 Thrombocytopenia: deficiency in the
number of platelets
 Impaired liver function: unable to synthesize
pro-coagulants. Often due to a Vitamin K
problem
 Hemophilia: hereditary bleeding disorder
Factors VIII (type A), IX (type B)
Sex linked (males get it more often)
Exercise can cause bleeding in joints
The Complete Blood Count (CBC)

A complete blood count provides

information regarding the number of
blood cells and their structural and
functional characteristics.
The white cell differential count is the
determination of the relative proportions
(percentages) of individual white cell
types.
Diagnostic Tests

A complete blood count (CBC) is a commonly

performed screening test that determines the
number of red blood cells (hematocrit: HCT, and
sometimes the hemoglobin Hbg), white blood
cells (WBC), and platelets (Plt) per unit of blood.
CBC w/
automated
differential
 Obtaining Blood Specimens

Skin puncture (capillary

blood)
Venipuncture
Infuse
Arterial puncture
Never infuse
Bone marrow aspiration
 Diagnostic Tests

 Blood count
 Erythrocyte
sedimentation rate
 Bone marrow
aspiration and biopsy
Transfusions
A loss of blood greater than 30% (~2-3 liters)
can cause severe shock; possibly fatal

 Whole blood transfusions

 Packed red cells (most of plasma removed), with
heparin as the anticoagulant
Types of Blood Antigens

Glycoproteins (antigens) located on the surface

of RBC’s
There are at least 30 different types of
antigens

ABO
Rh
M, N, Duffy, Kell, Lewis, etc.
ABO antibodies

Antigens promote agglutination (clumping), and

are termed agglutinogens
In the plasma, there are preformed antibodies
called agglutinins, which are unreactive to a
persons own red blood cells
Blood types (ABO)
 Rh (rhesus) blood groups

 8 different types
 85% of Americans are Rh+

 Male Rh+ X Female Rh- = 50% Rh+ Child

 Female and Baby may have opposite Rh factors
(Female must be Rh-)
First baby builds titer level in blood
Second baby problematic- hemolysis of blood
Erythroblastosis fetalis
Universal Donor and Recipients

Donor: Type O
Recipients: Type AB

Autologous transfusions: pre-donate blood for

elective surgery, to avoid transfusion problems
and/or disease transmission