Blood

1. Blood
By:
Maryam Bahrami
PhD Student of Anatomical Sciences ,shahid beheshti university
August, 2018

2. Blood is a fluid connective tissue that circulates through
the cardiovascular system.
Total blood volume in the average adult is about 5 to 6 L or 7%
to 8% of total body weight.
Blood consists of cells and their derivatives and a proteinrich
fluid called plasma.
The relative volume of cells and plasma in whole blood is
approximately 45% and 55%, respectively

3. oBlood cells and their derivatives include:
• erythrocytes, also called red blood cells (RBCs),
• leukocytes, also known as white blood cells (WBCs),
• thrombocytes, also termed platelets.
oPlasma is the liquid extracellular material that imparts
fluid properties to blood.

4. blood leaves the circulatory system
plasma proteins react with one another
produce a clot
which includes formed a yellowish liquid
called serum.

5. volume of packed erythrocytes in a sample of blood is
called the hematocrit.
A normal hematocrit reading is about 39% to 50% in men
and 35% to 45% in women.
Leukocytes and platelets constitute only 1% of the
blood volume.
leukocytes and platelets are contained in a narrow layer
at the upper part of the cell fraction called the buffy coat.

6. Composition of whole blood.

7. Blood’s many functions include:
delivery of nutrients and oxygen directly or indirectly to cells,
transport of wastes and carbon dioxide away from cells,
delivery of hormones and other regulatory substances to and
from cells and tissues,
maintenance of homeostasis by acting as a buffer,
participating in coagulation,
Thermoregulation,
transport of humoral agents and cells of the immune system
that protect the body from pathogenic agents, foreign proteins,
and transformed cells (i.e., cancer cells).
participates in heat distribution,
participates in osmotic balance.

8. Plasma is an aqueous solution, pH 7.4, containing substances of
low or high molecular weight.
Water
Proteins
Other solutes:
nutrients,
nitrogenous waste products,
hormones,
many inorganic ions

9. The major plasma proteins
 Appropriates approximately half of the total plasma proteins,
 is the smallest plasma protein,
 is made in the liver,
 serves in maintaining the osmotic pressure of the blood,
 acts as a carrier protein, it binds and transports hormones,
metabolites and drugs.
 Is the largest plasma protein,
 is made in the liver during clotting polymerizes as insoluble,
cross-linked fibers which block blood loss from small vessels.

10. Role in inflammation and destruction of microorganisms.
 immunoglobulins (γ-globulins)
are antibodies and secreted by plasma cells.
 Nonimmune globulins (α-globulin and β-globulin).
secreted by the liver,
maintain the osmotic pressure,
serve as carrier proteins for various substances.

12.  Erythrocytes are anucleate, biconcave discs
 are packed with the O2-carrying protein
hemoglobin,
 Under normal conditions, these corpuscles
never leave the circulatory system,
 They are 7.5 m in diameter, 2.6 m thick at the
rim, and 0.75 m thick in the center,
 concentration of them in blood is 3.9–5.5
million per microliter in women and 4.1–6
million per microliter in men,
 They are normally quite flexible,
 Lacking mitochondria, they rely on anaerobic
glycolysis for their energy needs.

13. the erythrocyte have soluble enzymes in cytosol:
 anhydrase carbonic enzyme
 Participating enzymes in the glycolytic pathway
 The enzymes involved in the pentose phosphate pathway

14. Erythrocyte membrane
consistsof about 40% lipid, 10% carbohydrate, and 50% protein,
contains two functionally significant groups of proteins:
Integral membrane proteins:
glycophorins
band 3 proteins.
Peripheral membrane proteins:
Spectrin,
actin,
band 4.1 protein,
adducin,
band 4.9 protein,
Tropomyosin,
Ankyrin
band 4.2 protein.

16. Erythrocytes contain hemoglobin, a protein specialized for the
transport of oxygen and carbon dioxide,
Hemoglobin consists of four polypeptide chains of globin complexed
to an iron-containing heme group,
the tetrameric O2-carrying protein that accounts for the cells'
uniform acidophilia,

20. LEUKOCYTES
According to the type of cytoplasmic granules and the shape of
their nuclei, leukocytes are divided into two groups:
they do contain azurophilic granules
The nucleus is round or indented.
Include:
lymphocytes
monocytes

21. They possess two types of granules:
specific granules
azurophilic granules
They have polymorphic nuclei with two or more lobes.
include :
neutrophils,
eosinophils,
basophils
Their Golgi complexes and rough ER are poorly developed.
They have few mitochondria.
They normally die by apoptosis in the connective tissue.

23. Leukocytes exit from the vesselare by two ways:
 chemotaxis
 Diapedesis
1. At sites of injury or infection, various substances termed
cytokines
2. released intercellular junctions in the endothelial cells
3. P-selectin appeare on their luminal surfaces from Weibel-
Palade bodies.
4. Neutrophils and other leukocytes interacte with P-selectin.
5. cells flowing through the venules slow down .
6. express integrins and other adhesion factors that produce firm
attachment to the endothelium.

25. Neutrophils
Neutrophils constitute 60–70% of circulating leukocytes. They
are 12–15 m in diameter, with nuclei having two to five
lobesIn females, the inactive X chromosome may appear as a
drumstick-like appendage on one of the lobes of the nucleus .
Neutrophils are inactive and spherical while circulating but
become actively amoeboid during diapedesis and upon
adhering to solid substrates such as collagen in the ECM.
They are usually the first leukocytes to arrive at sites of infection.
Neutrophils are short-lived cells with a half-life of 6–7 hours in
blood and a life span of 1–4 days in connective tissues before
dying by apoptosis.

26. Neutrophils contain three types of granules:
 Specific granules (secondary granules)
are the smallest granules .They are barely visible in the light microscope;
in electron micrographs, they are ellipsoidal .They contain various
enzymes as well as complement activators and other antimicrobial
peptides
 Azurophilic granules (primary granules)
are larger and less numerous than specific granules. The azurophilic
granules are the lysosomes of the neutrophil and contain
myeloperoxidase (MPO) . In addition to containing a variety of the
typical acid hydrolases, azurophilic granules also contain cationic
proteins called defensins, which function analogously to antibodies
and the antimicrobial peptide.

27.  Tertiary granules
They contain phosphatases ,metalloproteinases, such as gelatinases and
collagenases, which are thought to facilitate the migration of the
neutrophil through the connective tissue.

28. Diagram of events in the migration of a neutrophil from a
postcapillary venule into the connective tissue.

29. NEUTROPHIL FUNCTIONS
1. The binding of neutrophil chemotactic agents to the neutrophil's
plasmalemma facilitates the release of the contents of tertiary granules into
the extracellular matrix.
2. Gelatinase degrades the basal lamina, facilitating neutrophil migration.
Glycoproteins that become inserted in the cell membrane aid the process of
phagocytosis.
3. The contents of the specific granules are also released into the extracellular
matrix.
4. Microorganisms, phagocytosed by neutrophils, become enclosed in
phagosomes.
5. Bacteria are killed not only by the action of enzymes but also by the
formation of reactive oxygen compounds within the phagosomes of
neutrophils. These are superoxide (O2
-), formed by the action of NADPH
oxidase on O2 in a respiratory burst; hydrogen peroxide (H2O2), formed by the
action of superoxide dismutase on super-oxide; and hypochlorous acid
(HOCl), formed by the interaction of myeloperoxidase (MPO) and chloride
ions with hydrogen peroxide.

30. 6) Frequently, the contents of the azurophilic granules are released into the
extracellular matrix, causing tissue damage, but usually catalase and
glutathione peroxidase limit the tissue injury by degrading hydrogen
peroxide.
7) Once neutrophils perform their function of killing microorganisms, they also
die, resulting in the formation of pus, the accumulation of dead leukocytes,
bacteria, and extracellular fluid.
8) Not only do neutrophils destroy bacteria, they also synthesize leukotrienes
from arachidonic acids in their cell membranes. These newly formed
leukotrienes aid the initiation of the inflammatory process.

34. Neutrophil phagocytosis

35. Eosinophil
are about the same size as neutrophils, and their nuclei are typically
bilobed.Eosinophils are named for the large, eosinophilic,
refractile granules in their cytoplasm.
Eosinophils phagocytose antigen-antibody complexes .
modulate inflammatory responses in many ways.
They are an important source of the factors mediating allergic
reactions and asthma.
The cytoplasm of eosinophils contains two types of granules:
 Specific granules
 Azurophilic granules

36. Specific granules of eosinophils contain a crystalloid body that is
readily seen with the TEM, surrounded by a less electron-dense
matrix. They contain four major proteins: an arginine-rich protein
called major basic protein (MBP), which accounts for the intense
acidophilia of the granule; eosinophil cationic protein (ECP);
eosinophil peroxidase (EPO); and eosinophil-derived neurotoxin
(EDN).
Azurophilic granules are lysosomes. They contain a variety of the
usual lysosomal acid hydrolases and other hydrolytic enzymes that
function in destruction of parasites and hydrolysis of antigen–
antibody complexes internalized by the eosinophil.

42. Basophils
They are about the same size as neutrophils and the least numerous of
the WBCs, accounting for less than 0.5-1% of total leukocytes.
The nucleus is divided into two or more irregular lobes, but the large
specific granules overlying the nucleus usually obscure its shape.
By migrating into connective tissues, basophils may supplement the
functions of mast cells, with which they share a common progenitor
cell origin. Both basophils and mast cells have metachromatic
granules containing heparin and histamine, have IgE bound to surface
receptors, and secrete their granular components in response to
certain antigens

43. The basophil cytoplasm contains two types of granules:
specific granules
stain dark blue or metachromatically with the basic dye and are fewer
and more irregular in size and shape .The metachromasia is due to
the presence of heparin and other sulfated glycosaminoglycans
(GAGs) in the granules. They contain much histamine and various
mediators of inflammation, including platelet activating factor,
eosinophil chemotactic factor, and phospholipase A which
produces low molecular weight factors called leukotrienes.
Azurophilic granules
are the lysosomes of basophils and contain a variety of the usual
lysosomal acid hydrolases that are similar to those in other
leukocytes.

44. BASOPHIL FUNCTIONS
Basophils function as initiators of the inflammatory process.
1. Binding of antigens to the IgE molecules on the surface of a basophil
causes the cell to release the contents of its specific granules into the
extracellular space.
2. In addition, the enzyme phospholipase A generates arachidonic acid
residues from the plasma membrane which then are fed into the
cyclooxigenase or the lipoxigenase pathway to produce chemical
factors that mediate the inflammatory response.
3. The release of histamine causes vasodilation, smooth muscle
contraction (in the bronchial tree), and leakiness of blood vessels.
4. Leukotrienes have similar effects, but these actions are slower and
more persistent than those associated with histamine. In addition,
leukotrienes activate leukocytes, causing them to migrate to the site
of antigenic challenge.

49. Monocytes
They are the largest of the circulating blood cells and bone marrow–derived
agranulocytes with diameters varying from 12 to 20 m. The nucleus is
large, off-center, and may be oval, kidney-shaped, or distinctly U-shaped.
The cytoplasm of the monocyte is basophilic and contains very small
azurophilic granules (lysosomes).
In the electron microscope, nucleoli may be seen in the nucleus, and a small
quantity of rough ER, free polyribosomes, and many small mitochondria
are observed.
many microvilli and pinocytotic vesicles are found at the cell surface. The
periphery of the cell displays microtubules, microfilaments, pinocytotic
vesicles, and filopodia.
Circulating monocytes are precursor cells of the mononuclear phagocyte
system.

54. Lymphocytes
constitute a family of leukocytes with spherical nuclei.They constitute
20% to 25% of the total circulating leukocyte population.Most
lymphocytes in the blood are small with diameters of 6–8 m; medium
and large lymphocytes range in size from 9 to 18 m in diameter.
Lymphocytes vary in life span according to their specific functions.They
are the only type of leukocytes that, following diapedesis, can return
from the tissues back to the blood.
Lymphocytes are subdivided into three functional categories:
 B lymphocytes (B cells)
 T lymphocytes (T cells)
 Null cells.

55. FUNCTIONS OF B AND T CELLS
B cells are responsible for the humorally mediated immune system; that
is, they differentiate into plasma cells, which produce antibodies
against antigens.
T cells are responsible for the cellularly mediated immune system:
 cytotoxic T cells
 T helper cells
 T suppressor cells
They accomplish this by releasing signaling molecules known as cytokines.
Null cells are composed of two distinct populations:
 Circulating stem cells,
 Natural killer (NK) cells.

61. Platelets
Or thrombocytes are small, membrane-bounded, anucleate cytoplasmic
fragments derived from megakaryocytes.They are 2–4 m in diameter and
have a life span of about 10 days.
Normal platelet counts range from 200,000 to 400,000 per microliter of blood.

62. Structurally, platelets may be divided into four zones:
peripheral zone consists of the cell membrane covered by a thick
surface coat of glycocalyx. The glycocalyx consists of glycoproteins,
glycosaminoglycans, and … .
structural zone comprises microtubules, actin filaments, myosin, and
actin-binding proteins that form a network supporting the plasma
membrane. From 8 to 24 microtubules reside as bundle. They are
circumferentially arranged and are responsible for maintaining the
platelet’s disc shape.
membrane zone consists of two types of membrane channels:
 open canalicular system (OCS)
 dense tubular system (DTS)

63. organelle zone occupies the center of the platelet. It consists of
mitochondria, peroxisomes, glycogen particles, and at least three
types of granules:
delta granules (250–300 nm) contain ADP, ATP , serotonin, and histamine.
They are smaller, denser, and less numerous granules within the
cytoplasm.
Alpha granules (300–500 nm) that contain mainly fibrinogen,coagulation
factors, plasminogen, plasminogen activator inhibitor, and platelet-
derived growth factor. They are most numerous granules within the
cytoplasm.
lambda granules (175–250 nm) are similar to lysosomes found in other
cells and contain several hydrolytic enzymes.

69. The role of platelets in controlling hemorrhage can be summarized as
follows:
1. Normally the intact endothelium produces prostacyclins and NO, which
inhibit platelet aggregation. It also blocks coagulation by the presence of
thrombomodulin and heparin-like molecule on its luminal plasmalemma.
These two membrane-associated molecules inactivate specific coagulation
factors.
2. Injured endothelial cells cease the production and expression of the inhibitors
of coagulation and platelet aggregation and they release von Willebrand
factor and tissue thromboplastin. They also release endothelin, a powerful
vasoconstrictor that reduces the loss of blood.
3. Platelets avidly adhere to subendothelial collagen, especially in the presence
of von Willebrand factor, release the contents of their granules, and adhere to
one another. These three events are collectively called platelet activation.
4. The release of some of their granular contents, especially ADP and
thrombospondin, makes platelets "sticky," causing circulating platelets to
adhere to the collagen-bound platelets and to degranulate.

70. 5. Arachidonic acid, formed in the activated platelet plasmalemma, is converted
to thromboxane A2, a potent vasoconstrictor and platelet activator.
6. The aggregated platelets act as a plug, blocking hemorrhage. In addition, they
express platelet factor 3 on their plasmalemma, providing the necessary
phospholipid surface for the proper assembly of the coagulation factors
(especially of thrombin).
7. As part of the complex cascade of reactions involving the various coagulation
factors, tissue thromboplastin and platelet thromboplastin both act on
circulating prothrombin, converting it into thrombin. thrombin is an enzyme
that facilitates platelet aggregation. In the presence of calcium (Ca2+), it also
converts fibrinogen to fibrin.
8. The fibrin monomers thus produced polymerize and form a reticulum of clot,
entangling additional platelets, erythrocytes, and leukocytes into a stable,
gelatinous blood clot .The erythrocytes facilitate platelet activation, whereas
neutrophils and endothelial cells limit both platelet activation and thrombus
size.

71. 9. Approximately 1 hour after clot formation, actin and myosin monomers form
thin and thick filaments, which interact by utilizing ATP as their energy source.
As a result, the clot contracts to about half its previous size, pulling the cut
edges of the damaged vessel closer together and minimizing blood loss.
10. When the vessel is repaired, the endothelial cells release plasminogen
activators, which convert circulating plasminogen to plasmin, the enzyme
that initiates lysis of the thrombus. The hydrolytic enzymes of λ-granules
assist in this process.