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The Blood

Chapter 11

The three types of cellular elements in


the blood are: erythrocytes, leukocytes,
and platelets.
The plasma is the liquid part of the

blood.
The plasma is 90% water.
The hematocrit is the percentage of
total blood occupied by formed
elements.
~42% in women & ~45% in men.
About 99% of
the
hematocrit
erythrocytes.
About 1% of cells
leukocytes

is

Packed
are cell
volume, or
hematocrit

Plasma = 55%
of whole blood
Buffy coat <1%
Platelets &
White blood
cells

Red blood
cells = 45%
of whole
blood

Plasma is a transport medium.


It transports inorganic substances such as Na + & Cl-.
Plasma proteins compose 6 to 8 percent of the plasmas total weight

& have numerous functions.


Albumins establish an osmotic gradient between the blood and
interstitial fluid.
Other proteins buffer pH changes.
The globulins (alpha & beta,) 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.

Erythrocytes transport oxygen.

Erythrocytes are also called red blood cells (RBCs).


They transport O2, to a lesser extent, CO2 and H+
Their concentration is about 5 x 109 per ml
Also read as 5 x 106 / mm3.
Its flat, biconcave, disc shape
It has a large surface area
2 m
& is thin.
RBCs lack a nucleus, organelles,
& ribosomes.
It is mainly a bag of hemoglobin.
Has a lifespan of ~120 days
The plasma membrane of the
erythrocyte is flexible allowing
it
to slide through a capillary.

8 m

Hemoglobin is a molecule consisting of


two parts.
The globin is four, folded
The heme part is inorganic.
Each of its four iron atoms
one

molecule of O 2 gas.

Hemoglobin can also combine


NO

Hemoglobin can buffer

polypeptide chains.

binding with hydrogen ions.

can combine with


with CO 2, H+, CO,
pH by

The erythrocyte contains glycolytic enzymes.


Its contains carbonic anhydrase: converts CO 2 HC03-.

The bone marrow produces erythrocytes


in children and adults.
An erythrocyte in the circulation cannot reproduce, as
it lacks a nucleus.
Erythropoiesis (erythrocyte production) is the
production of new red cells, replacing the worn-out
cells in the circulation.
Pluripotent stem cells in the red marrow differentiate
into the different types of blood cells.
Regulatory factors act on hemopoietic (bloodproducing) red marrow to govern the type and number
of cells produced and discharged into the circulation.

Erythropoiesis is controlled by erythropoietin

The average life span of an erythrocyte is 120 days.


The final demise of old erythrocytes is in the spleen.
The number of erythrocytes normally remains steady.
Cell production equals cell death.
However, a low level of oxygen delivery to the tissues stimulates an increased
rate of erythrocyte production.
If O2 delivery to the tissues is decreased, the kidneys detect this and increase
the output of erythropoietin.
Erythropoietin induces new RBC production
Erythropoietin can be produced synthetically
Reticulocytes are released from the bone marrow into the when circulation
erythropoiesis is rapid.
Reticulocytes are immature erythrocytes.

Erythropoietin (EPO) Mechanism


Imb
al

anc
e

Start

Normal blood oxygen levels


Imb
ala
nce

Increases
O2-carrying
ability of
blood

Enhanced
erythropoiesis
increases RBC
count

Stimulus:, decreased
availability of O2 to tissue,
or increased tissue
demands for O2

Reduces
O2 levels in
blood
Erythropoietin
stimulates red
bone marrow

Kidney (and
liver to a
smaller extent)
releases
erythropoietin

Anemia is a reduction below the normal


capacity in the blood to carry oxygen.

Types of anemia.
Nutritional anemia is caused by a dietary deficiency of a factor needed
for erythropoiesis (iron).
Pernicious anemia is due to the inability to absorb sufficient vitamin B 12
from the digestive tract.
This deficiency is due to the lack of the intrinsic factor
Aplastic anemia is due to the failure of the bone marrow to make
adequate numbers of RBCs.
Renal anemia is due to kidney disease.
Hemorrhagic anemia is due to the loss of significant amounts of blood.
Hemolytic anemia is due to the rupture of many RBCs.
Sickle cell cells are fragile

Polycythemia is an excess in circulating erythrocytes.

Primary polycythemia is caused by an tumorlike

70%
70%

45%
30%
(=

Plasma

Hematocrit

condition in the bone marrow.


Secondary polycythemia is an erythropoietin-induced
adaptive mechanism to improve the oxygen-carrying
capacity in the blood.
Dehydration plasma decrease relative to
hematocrit.

Erythrocytes

Normal

Anemia

Polycythemia Dehydration

Leukocytes are the mobile units of


the bodys immune system.
Leukocytes are also called white blood cells (WBCs)
They function mainly as defense & housekeeping
agents
They defend against the invasion of pathogens.
They identify cancer cells.
They remove the bodys litter by phagocytosis.
They can leave the circulation and go to the sites
of invasion and tissue damage.

Leukocytes (WBCs)
Leukocytes the only blood components that are
complete cells:
Includes:
Granulocytes
Neutrophils, Esinophils & Basophils
Agranulocytes
Lymphocytes
T & B cells as well as NK cells
Monocytes
Can leave capillaries via diapedesis and move
through tissue spaces
Make up 1% of the total blood volume
(5-10 X 103 cells per mm3)

Granulocytes
Granulocytes neutrophils, eosinophils, and basophils
Contain cytoplasmic granules that stain specifically
(acidic, basic, or both) with Wrights stain
Are larger and usually shorter-lived than RBCs
Have lobed nuclei
Are all phagocytic cells
Normally about two-thirds of the leukocytes in the
blood are granulocytes.
Their rates change depending on the changing
defense needs of the body.

Neutrophils
Neutrophils have two types of

granules that:
Take up both acidic and basic
dyes
Give the cytoplasm a lilac
color
Contain peroxidases,
hydrolytic enzymes, and
defensins (antibiotic-like
proteins)
Neutrophils are our bodys
bacteria slayers

Eosinophils

Eosinophils account for 14%

of

WBCs
Have red-staining, bilobed
nuclei
connected via a broad band of
nuclear material
Have red to crimson
(acidophilic)
large, coarse, lysosome-like
granules
Lead the bodys counterattack
against parasitic worms &
protozoans
Can induce allergeric response via
release of leukotrienes in response
to to bound IgE

Basophils
Account for 0.5% of WBCs and:
Have U- or S-shaped nuclei

with two or three


conspicuous constrictions
Are functionally similar to mast cellspromote
inflammation
Have large, purplish-black (basophilic) granules
that contain histamine
Histamine inflammatory chemical that acts
as a vasodilator and attracts other WBCs
(antihistamines counter this effect)

Agranulocytes
Agranulocytes lymphocytes and

monocytes:
Lack visible cytoplasmic granules
Have spherical (lymphocytes) or kidneyshaped (monocytes) nuclei

Lymphocytes
Account for 25% or more of

WBCs and:
Have large, dark-purple,
circular nuclei with a thin
rim of blue cytoplasm
Most are found mostly enmeshed in lymphoid
tissue (some circulate in the blood)
There are two types of lymphocytes: T cells and
B cells
T cells direct cell to cell killing and cytokine
production
B cells give rise to plasma cells, which produce
antibodies

Monocytes
Monocytes account for 48%

of

leukocytes
They are the largest
leukocytes
They have abundant
paleblue cytoplasms
They have purple-staining, U- or kidney-shaped
nuclei
They leave the circulation, enter tissue, and
differentiate into macrophages
Macrophages:
Are highly mobile and actively phagocytic
Activate lymphocytes to mount an immune
response

The leukocytes
production.
The bone marrow

can greatly alter


relative percentage
of WBC produced.

Platelets (thrombocytes) function


in hemostasis.

They are cell fragments derived from megakaryocytes.


They average 2.5 x 108 per ml. Their range is also
reported as 1.5 3.5 x 105 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.

In bone
marrow
Undifferentiated
pluripotent
stem cell
Myeloid stem cell

Megakaryocytes

Erythrocyte
precursors

Granulocyte
precursors

Lymphoid stem cell


Monocyte
precursors
Lymphocytes in
lymphoid tissues

Platelets

In
circulation

Erythrocytes Granulocytes

Monocytes

Lymphocytes

Hemostasis prevents blood loss from


damaged blood vessels.
The first two steps to stop escaping blood from a vessel are:
1) vascular spasm - This reduces blood flow through a
damaged vessel.
2) platelet plugging - An aggregation of platelets forms a
plug.
Platelets aggregate on contact with exposed collagen in the
damaged wall of a vessel.

The platelet plug seals a break in a vessel.

ADP stimulates platelets to become sticky.


Other substances from the endothelium of a blood vessel
inhibit platelet aggregation, keeping it open.

Platelets
ADP
Vessel
lumen

Inhibits platelet
aggregation
Prostacyclin
& nitric acid

Vessel
wall

Prostacyclin
& nitric acid

Normal
endothelium
Aggregating
platelet plug

Normal
endothelium

Exposed collagen
at site of
vessel injury

Collagen

The third step to block escaping blood from


an injured blood vessel is 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 crosslinkage from factor XIII.

The clotting cascade is a series of steps


involving twelve clotting factors.
Platelet
factor 3
(PF3)
Other steps
in cascade

Prothrombin

Secretes

Platelet
aggregation

Enhances

Activates

Thrombin
Stimulates
conversion

Fibrinogen
(soluble)

Fibrin:
loose
mesh

Activates
Factor
XIII

Fibrin:
tight
mesh

Pathway
for clot
formation
in vessels

Pathway
for clot
formation
in tissues
Amplification occurs in the clotting

process.
One molecule can activate one
hundred molecules in the next step

Exposed
collagen
activates
both the
clotting
cascade as
well as
platelet
aggregation

Vessel damage
Exposed collagen

Platelet
aggregation
PF3

Activation
of
factorXII
Activation of
factors
Activation
of thrombin
Formation of
fibrin mesh

Seal damaged
vessel

Hageman
factor

Clotting
cascade

Plasmin eventually breaks down the clot


making it a temporary structure
Fast

Activation of
factor XII
(Hageman factor)

Fast
(Cascade of
reactions)

(Cascade of
reactions)
Clot
formation

Plasmin
activation

Dissolution
of clot
Slow

Other facts on blood clotting include:


Clot retraction occurs after the clot is formed.
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.
Macrophages 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

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