Major components of blood
I. Fluid component - plasma.
A. Water - 90%
B. Plasma proteins - 7%
a. albumin
b. fibrinogen
c. alpha, beta, and gamma globulins - gamma
globulins are IgG antibodies (immunoglobulins)
C. Inorganic salts - 0.9%
D. Other organic molecules - 2.1% (vitamins, amino acids,
lipids, hormones, etc.)
Major components of blood
II. Cellular components - blood cells - two basic
types
A. Erythrocytes - red blood cells
1. no nucleus in mature erythrocyte
2. biconcave disk shape
3. mature cell is essentially a sac of hemoglobulin
4. 7-8  m in diameter
5. most common type of blood cell
3.6 - 6.1 billion erythrocytes per ml
of normal human blood.
6. reticulocytes - Young erythrocytes recently released
into blood that still contain ribosomal RNA that
precipitates and stains as a sort of reticulum.
http://medic.med.uth.tmc.edu/edprog/histolog/blood/b12.jpg
Erythrocyte
http://www.mc.vanderbilt.edu/histo/blood/platelets.jpg
Sickle cell anemia
http://www.unomaha.edu/~swick/blood.html
B. Leucocytes
4 - 11 million leukocytes per ml of
normal human blood.
1. White blood cells that can be sub-divided into a number of
major sub-types.
2. At the light level, these sub-types are distinguished by their 1)
nuclear and 2) cytoplasmic structure as characterized by specific
staining patterns.
3. Stains for this purpose were first developed by Dimitri
Romanovsky in 1891.
a. These initial stain mixtures were later modified by other
investigators,
b. Romanovsky type stains called Leishman's or Wright's
stains for example.
C. Romanovsky stain
1. Main components are methylene blue and eosin
2.Blood cells are classified by the type of stain that binds to
them or their components.
a. basophilia - affinity for methylene blue which is a basic stain.
b. azurophilia - affinity for azure dyes (purples) which result
from the oxidation of methylene blue in the mixture.
c. acidophilia or eosinophilia - affinity for eosin which is an acid
stain (yellowish-pink)
d. neutrophilia - affinity for complex dyes that are formed in the
mixture that have a salmon-pink to lilac color. The term
neutrophilia comes from the early misconception that these dyes
were neither acid nor base and thus neutral.
Note that the names of a number of leukocytes are based on their
type of staining.
D. Leucocyte classification systems
1. Two major types of classification are used for leukocytes.
a. One classification system is based on appearance of the
stained cell cytoplasm - whether or not visible “granules” are
present
granule - a stained, membrane bound vesicle in the
cytoplasm
•granulocytes - cells with specific granules that are quite
evident by virtue of the fact that they have affinity for
specific stains.
•agranulocytes - blood cells that don't have obvious
specifically stained cytoplasmic granules.
Leukocyte classification systems
b. The second classification system is based on the
morphology of the stained nucleus.
•mononuclear - nucleus is not composed of identifiable
lobes. Nucleus may be irregular.
•polymorphonuclear - nucleus is composed of two or more
distinct lobes.
Nuclear lobes are distinct structures that are connected by a
thin bridge of nucleoplasm surrounded by nuclear
membrane.
E. BASIC LEUKOCYTE CELL TYPES
1. Granulocytes
a. the
neutrophil (most common leukocyte)
•Compose 60-70% of the leukocytes
•Nucleus is polymorphonuclear - has 2-5 lobes linked
together by fine threads of chromatin - sometimes referred to
as “PMNs” (PolyMorphonuclear Neutrophils)
•Cytoplasm contains azurophilic and other specifically staining,
small membrane bound granules - these are often not particularly
evident.
•Granules are lysosomes that contain enzymes for digestion
of phagocytosed particles, e.g. bacteria.
•First line of defense against microorganisms phagocytose bacteria - sometimes called “microphages”
•Capable of amoeboid movement
NEUTROPHILS
http://www.som.tulane.edu/classware/pathology/Krause/Blood/BL10d.html
Band neutrophil
http://missinglink.ucsf.edu/lm/IDS_101_histo_resource/blood_cells.htm
Mature neutrophil
BASIC LEUKOCYTE CELL TYPES
Granulocytes
b. the
eosinophil
•Compose 1-4% of the leukocytes
•Nucleus is polymorphonuclear - usually bilobed. Sometimes called
“PMEs” (PolyMorphonuclear Eosinophils).
•Cytoplasm contains ovoid, eosinophilic (acidophilic) membranebound granules
•Granules are larger than those of neutrophils
•Granules are lysosomes that contain enzymes that can degrade
phagocytosed particles
•Recognize and phagocytose antigen-antibody complexes and
particles that are associated with these complexes that are formed
during an immune response.
•Capable of amoeboid movement
•May be involved in preventing blood clotting at times when it is best
that it not occur.
EOSINOPHIL
http://www.echt.chm.msu.edu/courseware/blockII/Pathology/InfectiousDisea
se_6.html
http://www.users.globalnet.co.uk/~aair/eosinophils.htm
Don’t confuse with a band
neutrophyll.
http://www.unomaha.edu/~swick/blood.html
http://pathhsw5m54.ucsf.edu/case17/image175.html
http://missinglink.ucsf.edu/lm/IDS_101_histo_resource/blood_cells.htm
http://www-medlib.med.utah.edu/
WebPath/HEMEHTML/HEME004.html
BASIC LEUKOCYTE CELL TYPES
Granulocytes
c. the
basophil
•Compose 0-1% of leukocytes.
•Have a large irregular lobed nucleus that is often Sshaped - polymorphonuclear. Sometimes called
“PMBs” (PolyMorphonuclear Basophils)
•Cytoplasm is filled with specifically staining granules
larger than those in other granulocytes.
•Granules are membrane bound and contain histamine
and heparin that are secreted by exocytosis.
•Histamine - causes dialation of blood vessels and in
effect makes them leaky. This allows serum proteins
such as antibodies to infiltrate into tissues. Heparine anticoagulant.
•Have limited capacity for amoeboid movement and
phagocytosis. Function in allergic reactions and
inflammatory response.
BASOPHIL
Probably an aberrant neutrophil
Basophil
Probably a Plasma
cell/
http://www.unomaha.edu/~swick/blood.html
http://www-medlib.med.utah.edu/WebPath/
HEMEHTML/HEME005baso.html
http://diaglab.vet.cornell.edu/clinpath/modules/heme1/baso.htm
http://pathhsw5m54.ucsf.edu/case17/image176.html
http://missinglink.ucsf.edu/lm/IDS_101_histo_resource/blood_cells.htm
BASIC LEUKOCYTE CELL TYPES
2. Agranulocytes
a. Lymphocytes
•Numbers in blood vary, usually 20-30% of circulating leukocytes. Second
most common leukocyte in normal blood.
•Have a spherical nucleus - mononuclear.
•Small lymphocytes have very little cytoplasm. Nucleus is
surrounded by a thin halo of blue cytoplasm in stained material (6-8
μm in diameter).
These cells are unactivated lymphocytes.
Two populations, one that can become T-lymphocytes and the other
B- lymphocytes.
When activated by encounter with foreign antigen presented by a
macrophage - become large lymphocytes that are capable of
mitosis.
BASIC LEUKOCYTE CELL TYPES
Agranulocytes
•Large lymphocytes (10-14 μm in diameter) have more cytoplasm relative to nuclear
size - mononuclear.
Small lymphocytes (either B- or T-lymphocytes) develop into large
lymphocytes after encounter with foreign antigen and activation in an
immune response.
These cells undergo repeated mitotic division to form clonal populations of
either B- or T- lymphocytes
If large B-lymphocytes, the clonal cells become either B-memory cells or
plasma cells (even larger in size) that actively produce antibodies that
function in humoral mediated immunity
If large T-lymphoctes, the clonal cells differentiate into a number of different
types of cells that function in cell mediated immune response.
B- and T- lymphocytes cannot be differentiated with the light microscope
using standard stains.
BASIC LEUKOCYTE CELL TYPES
Agranulocytes
Lymphocytes
Small lymphocyte
Large lymphocyte
Similar in size to a
erythrocyte
Larger than a
erythrocyte
http://www.meddean.luc.edu/lumen/
MedEd/Histo/HistoImages/hl2B-55.jpg
http://missinglink.ucsf.edu/lm/IDS_101_histo_resource/blood_cells.htm
Lymphocytes - Clockface nuclei
BASIC LEUKOCYTE CELL TYPES
Agranulocytes (lack obvious stained granules)
b. Monocytes
2-6% of circulating leukocytes
Nucleus is usually kidney- or horseshoe-shaped (may be
oval) and may be positioned off center - mononuclear
Chromatin often fibrillar in appearance
Nucleus usually has 2-3 nucleoli
More cytoplasm than a lymphocyte
As is the case with other leukocytes, monocytes are circulating blood
cells that can cross the capillary endothelium and move into surrounding
tissues. When monocytes do this they differentiate into macrophages.
DIAPEDESIS = EXTRAVASATION = TRANSENDOTHELIAL MIGRATION
http://multimedia.mcb.harvard.edu/
BASIC LEUKOCYTE CELL TYPES
Agranulocytes
MONOCYTE
http://missinglink.ucsf.edu/lm/IDS_101_histo_resource/blood_cells.htm
http://www.unomaha.edu/~swick/blood.html
BASIC LEUKOCYTE CELL TYPES
Agranulocytes (lack obvious stained granules)
c. Megakaryocyte
Very large cells (40-100  m in diameter) found in red
bone marrow.
Irregular lobed nucleus -mononuclear.
Form platelets by fragmentation of pseudopodia.
Platelets are enucleate disk-like cell fragments
that are 2-5  m diameter often appear in clumps
in blood smears. Function in clotting.
BASIC LEUKOCYTE CELL TYPES
Agranulocytes
MEGAKARYOCYTE
http://www.deltagen.com/target/histologyatlas/atlas_files/hematopoietic/bone_marrow_40X.jpg
http://pro.corbis.com/images/42-18705415.jpg?size=67&uid=%7B42A68054-F702-4052-A48A-85113043EB0D%7D
III. Hematopoiesis
A. Blood cells have short life in circulatory system and so
they must be continually renewed.
1. erythrocytes and leukocytes are derived from stem cells
in the red bone marrow of mammals.
2. lymphocytes are derived from stem cells in the bone
marrow and also in the lymphatic organs.
B. Hematopoiesis involves a series of stem cell stages:
1. Hemocytoblast - multipotent stem cell that divides
to form stem cells for
erythrocytes or the various
types of leukocytes
http://www.som.tulane.edu/classware/pathology/Krause/Blood/EP.html
B. Hematopoiesis of erythrocytes
1. Proerythroblast - formed from division
of hemocytoblast - essentially the stem
cell for the erythrocyte cell line. Divides
by mitosis to form many
2. Basophilic erythroblasts - starts
synthesis of hemoglobin. Repeated
mitotic divisions to form many
3. Polychromatic erythroblasts - more
hemoglobin synthesis. Repeated mitotic
divisions to form many
http://www.som.tulane.edu/classware/pathology/Krause/Blood/EP.html
B. Hematopoiesis of erythrocytes
4. Normoblasts - synthesizes
abundance of hemoglobin. Divides 3
times. After last division the cells
extrude their nuclei and become
5. Reticulocytes - no further
division. Hemoglobin synthesis
completed. Organelles either
autophagocytosed or exocytosed.
Cells become
6. Mature erythrocytes
http://medic.med.uth.tmc.edu/edprog/histolog/blood/b12.jpg
http://www.som.tulane.edu/classware/pathology/Krause/Blood/EP.html
http://www.mc.vanderbilt.edu/histo/blood/platelets.jpg
B. Hematopoiesis of other blood cell types
1. Staged sequences of developmental cell types as
described in text.
Acute myelogenous (myeloblastic) leukemia (AML)
1. Characterized by the presence of (lots of) myeloblasts (undifferentiated
granulocyte precursors) in the bone marrow and blood.
2. These malignant cells do not differentiate normally.
3. The diagnosis of AML is made when over 30% of the marrow cells are
myeloblasts.
AML Presents clinically with:
1. Features of bone marrow failure, e.g., anemia, infections, bruising or bleeding.
2. Leukemic infiltration of organs (e.g. central nervous system, lymph nodes, skin)
may produce specific signs or symptoms.
Without treatment AML is rapidly fatal.
Cure rate in children, chemotherapy 40 - 50%, stem cell transplant from
brother/sister 55-60%.