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The Circulatory System: Blood
(Chapter 18)
Lecture # 2
Blood (part -1)
Leukocytes
The leucocytes are the least
abundant formed elements (5,000 to
10,000 WBCs/m L).
They differ from erythrocytes in that
they
retain
their
organelles
throughout life.
The general function of the
leukocytes is protection against
infectious microorganisms and other
pathogens.
Neutrophils
- Granulocytes
Eosinophils
Basophils
Leukocytes (White
blood cells, WBCs)
Lymphocytes
- Agranulocytes
Monocytes
Granulocytes
They have specific granules, which contain enzymes
and other chemicals employed in defense against
pathogens.
The most abundant (60-70% of circulating leukocytes).
Nucleus with 3 to 5 lobules connected by slender
nuclear strands (polymorphonuclear leukocytes).
Neutrophils
Reddish to violet specific granules, which take up
histological stains at pH 7.
They are about 2% to 4% of the circulating leukocytes.
Nucleus with 2 lobules connected by a thin strand.
Coarse rosy to orange-colored specific granules, which
take up histological stains at acidic pH.
Eosinophils
They are the rarest of the WBCs (less than 0.5% to 1%
of the WBC count).
Nucleus largely hidden by the granules
Basophils
Abundant, very coarse, dark violet specific granules,
which take up histological stains at basic pH.
Granulocytes
Neutrophils
Functions:
1- Phagocytosis of bacteria.
2- They release antimicrobial chemicals.
The neutrophil count rises in response to
bacterial infection (neutrophilia).
Eosinophils
1-Phagocytosis
of
antigen-antibody.
complexes, allergens, and inflammatory
chemicals.
2- They release enzymes to destroy large
parasites.
They increase in parasitic infections and
allergies.
Basophils
1- They secrete histamine (vasodilator),
which speeds flow of blood to an injured
area
2- They secrete heparin (anticoagulant),
which promotes the mobility of other WBCs
in the area
Agranulocytes
They also contains granules but they are nonspecific
granules (lysosomes containing enzymes).
They are second to neutrophils in abundance (25% to 33%).
They are the smallest WBCs (5 to 17 mm in diameter).
Large and medium lymphocytes are usually seen in
connective tissues. Small lymphocytes are the most common
circulating lymphocytes.
Lymphocytes
Round, ovoid or slightly dimpled nucleus, which stains dark
violet and fills nearly the entire cell in small lymphocytes.
There are several classes of lymphocytes with different
immune functions, but they look alike through the light
microscope.
(B lymphocytes, T lymphocytes, and NK
lymphocytes)
They are the largest WBCs, often two or three times the
diameter of an RBC.
They are about 3% to 8% of WBC count.
The nucleus is large and clearly visible, often light violet. It is
typically ovoid, kidney-shaped, or horseshoe-shaped.
The cytoplasm contains fine granules.
Monocytes
Agranulocytes
Lymphocytes
Functions:
1-They destroy cells (cancer, foreign, and
cells infected by viruses).
2-They “present” antigens to activate other
immune cells.
3- They coordinate actions of other immune
cells.
4- They produce and secrete antibodies.
5- They provide immune memory.
Monocytes
They leave bloodstream and transform into
macrophages, which:
1-Phagocytize pathogens and debris.
2-“Present” antigens to activate other
immune cells - antigen presenting cells
(APCs).
The production of
WBCs is called
leukopoiesis.
The production of WBCs is called leukopoiesis.
Eosinophilic
CFUs
Myeloblasts
Eosinophilic
myeloblast
Basophilic
myeloblast
Basophilic
CFUs
Neutrophilic
CFUs
Neutrophilic
myeloblast
Monoblast
Monocytic
CFUs
Leukopoiesis begins in the
bone marrow with the
same pluripotent stem cells
as erythropoiesis.
Lymphoblast
Lymphocytic
CFUs
Immature
T-lymphocytes
migrate to the thymus
to complete their
development.
Eosinophilic
myeloblast
Eosinophilic
promyelocyte
Eosinophilic
myelocyte
Basophilic
CFU
Basophilic
myeloblast
Basophilic
promyelocyte
Basophilic
myelocyte
Neutrophilic
CFU
Neutrophilic
myeloblast
Neutrophilic
promyelocyte
Neutrophilic
myelocyte
Eosinophilic
CFU
Myeloblasts
Monoblast
Monocytic
CFU
Promonocyte
Lymphoblast
Lymphocytic
CFU
NK prolymphocyte, B prolymphocyte, T prolymphocyte
Mature lymphocytes and
macrophages secret several
types of Colony Stimulating
Factors in response to
infections and other immune
challenges.
Colony
Stimulating
Factors
Colony Stimulating Factors
determine
what
type
of
leukocytes will be produced in
response to infections and
other immune challenges.
Eosinophilic CFUs
Basophilic CFUs
Neutrophilic CFUs
Monocytic CFUs
They have receptors
for Colony
Stimulating Factors
Parasites, allergy
Lymphocytic CFUs
Bacterial infection
Colony
Stimulating
Factors
Eosinophilic
CFUs
Colony
Stimulating
Factors
Neutrophilic
CFUs
Erythropoiesis
Pluripotent
stem cell
Colony-forming
unit (CFU)
Erythroblast
Reticulocyte
Erythrocyte
Mature cells
Leukopoiesis
Pluripotent
stem cell
Colonyforming
unit (CFU)
Neutrophilic,
Eosinophilic,
Basophilic
Pluripotent
stem cell
Colonyforming
unit (CFU)
Lymphocytic
Monocytic
Myoblasts
Myelocytes
Mature
cells
Prolymphocytes
Promonocytes
Mature
cells
Promyelocytes
Lymphoblasts
Monoblasts
Platelets
Monocyte
Neutrophils
Lymphocyte
Erythrocytes
(a)
(b)
75 µm
Normal (a) and Leukemic (b) Blood
Leukocyte Life Cycle
The red bone marrow stores
and releases granulocytes and
monocytes.
Circulating White Blood Cells
do not stay in bloodstream.
Granulocytes circulate for 4
to 8 hours. And then migrate
into the tissues, where they
live 4 or 5 days.
Monocytes travel in the blood for 10 to 20 hours,
then migrate into the tissues and transform in
macrophages, which can live as long as a few
years.
Macrophages Phagocytizing Bacteria
Immature lymphocytes are produced in
the bone marrow.
B lymphocytes mature the bone marrow.
T lymphocytes mature in the thymus.
After maturation, most of the lymphocytes move into lymph nodes, the
spleen and other lymphoid tissues
Lymphocytes can survive from a few weeks to decades. They leave
the blood stream for the tissues and eventually enter the lymphatic
system, which enter them back into the bloodstream.
The Circulatory System: Blood
(Chapter 18)
Lecture # 2
Blood (part -2)
Platelet Form and Function
Platelets are not cells but small fragments of marrow cells called
megacaryocytes.
They are the second most abundant formed elements, after
erythrocytes. Normal count from 130,000 to 400,000
Pseudopod
Lysosome
Open canalicular
system
Mitochondrion
Granule
They have a complex internal structure that includes lysosomes,
mitochondria, microtubules, microfilaments, granules filled with
platelet secretions and a system of channels called open canalicular
system. They have no nucleus.
When activated they emit pseudopods and can move.
Functions of Platelets
1- They secret vasoconstrictors that stimulate spasmodic constriction
of blood vessels and thus help reduce blood loss.
2- They stick together to form temporary platelet plugs to seal small
breaks.
3- They secrete procoagulants or clotting factors, which promote
clotting.
4- They initiate formation of clot-dissolving enzyme that dissolves
blood clots that are not useful.
5- They secret chemicals that attract neutrophils and monocytes to
sites of inflammation.
6- They internalize and destroy bacteria.
7- They secrete growth factors that stimulate mitosis to repair blood
vessels.
Colony
Stimulating
Factors
Platelet Production
Production of platelets is called thrombopoiesis
and takes place in the bone marrow.
Megakaryocytes are gigantic cells (150 mm),
visible to the naked eye, with a huge multilobular
nucleus and multiple sets of chromosomes.
Platelets
Bloodflow
Sinusoid of
bone marrow
Proplatelets
Duplication
of
DNA
several times without
cytoplasmic division
Endothelium
Megakaryocyte
Hemostasis
There are three hemostatic mechanisms: 1- Vascular spasm.
2- Platelet plug formation, and 3- Blood clotting (coagulation)
The most immediate protection against blood loss is the vascular
spasm.
a) Vascular spasm:
It is the prompt constriction of a
broken vessel.
Vascular spasm provides time for
other two clotting pathways.
It is produced by:
-Pain receptors (some directly
innervate
blood
vessels
to
constrict)
- Smooth muscle injury
- Platelets release serotonin
(vasoconstrictor)
b) Platelet plug formation
Platelets do not adhere to the
endothelium because it is smooth,
and is coated with prostacyclin, a
platelet repellant.
Broken vessel exposes collagen.
Upon contact with collagen, platelet
emit pseudopods
that stick to
damaged vessel and other platelets
Pseudopods contract and draw
walls of vessel together forming a
platelet plug.
Platelets degranulate releasing a
variety of substances that attract
more platelets, promote platelet
aggregation
and
produce
vasoconstriction.
Positive feedback
mechanism
STIMULUS
Feedback
cycle
initiated
Feedback cycle ends
after clot seals break.
Break or tear in
blood
vessel
wall.
Clotting occurs as platelets
adhere to site
and release chemicals.
Released chemicals
attract more platelets,
which release more
chemicals.
Clotting proceeds;
newly forming clot
grows.
Released chemicals
attract more platelets,
which release more
chemicals.
c) Coagulation (blood clotting)
It is the last but the most effective defense against bleeding.
The final goal of coagulation is to transform the fibrinogen (a
soluble protein) into fibrin, a sticky protein that adheres to the blood
vessels and form a net where blood cells are trapped.
The enzyme thrombin transforms the soluble fibrinogen into short
strands of fibrin. But before, prothrombin has to be activated to
active thrombin.
Factor XIII cross-links the fibrin strands to create a dense
aggregation called fibrin polymer, which is the structural
framework of the blood clot.
Prothrombin
Fibrinogen
Thrombin
Factor XIII
Fibrin
Fibrin
polymer
Extrinsic Mechanism
Intrinsic Mechanism
Damaged
tissue
Thromboplastin
(factor III)
The activation cascade
to factor X is shorter.
Platelets
Ca+2
Ca+2
Inactive
Factor X
The Two
Mechanisms
of Coagulation
Hageman factor
(factor XII)
The activation cascade
to factor X is longer.
Factor XIII
Active
Factor X
Prothrombin
activator
Prothrombin
Fibrinogen
Fibrin
Thrombin
Fibrin
polymer
Extrinsic Mechanism
It is initiated by release of
tissue
thromboplastin
(factor III) from damaged
tissue.
The activation cascade to
factor X is shorter.
Intrinsic Mechanism
It is initiated by platelets
releasing Hageman factor
(factor XII ).
The activation cascade to
factor X is longer.
Calcium is required
either pathway.
for
In most cases of bleeding,
both the extrinsic and
extrinsic mechanism work
simultaneously.