• Wbc

• Rbc
• Platelet
• lipids
• Immune particles
• Hormones
• Water
• Salts
• Unknown substances
Blood as a Circulatory Fluid & the Dynamics of
Blood & Lymph Flow

• Introduction
• The circulatory system supplies inspired O2 as well as
substances absorbed from the gastrointestinal tract to the tissues,
returns CO2 to the lungs and other products of metabolism to the
kidneys, functions in the regulation of body temperature, and
distributes hormones and other agents that regulate cell function.
• The blood, the carrier of these substances, is pumped through
a closed system of blood vessels by the heart. The blood flow to
each tissue is regulated by local chemical and general neural
and humoral mechanisms that dilate or constrict its vessels.
• Blood is a specialized type of connective tissue, red in color,
syrupy fluid which has specific gravity 1.055 and the viscosity
2.5 times that of water.
• Blood is alkaline (PH=7.4) and appear scarlet
red when taken from arteries and purplish from
veins.
Introduction

• The difference in color is due to its O! content

.
• Blood consists of a protein-rich fluid known as
plasma, in which are suspended cellular
elements: white blood cells, red blood cells, and
platelets.
• The normal total circulating blood volume is
about 8% of the body weight (5600 mL in a 70-
kg man). About 55% of this volume is
plasma. Blood plays a role in maintaining the
cellular environment by serving as a
transport medium of the body.
• The various functions of blood result from
specialization within the cellular elements or the
plasma or the interaction between the two .
BLOOD AS A CIRCULATORY FLUID

• Blood consists of a protein-rich fluid known as

plasma, in which are suspended cellular
elements: white blood cells, red blood cells, and
platelets.
• The normal total circulating blood volume is
about 8% of the body weight (5600 mL in a 70-
kg man). About 55% of this volume is plasma.
BONE MARROW

• In the adult, red blood cells, many white blood

cells, and platelets are formed in the bone
marrow. In the fetus, blood cells are also formed
in the liver and spleen, and in adults such
extramedullary hematopoiesis may occur in
diseases in which the bone marrow becomes
destroyed or fibrosed.
• In children, blood cells are actively produced in the
marrow cavities of all the bones. By age 20, the
marrow in the cavities of the long bones, except for
the upper humerus and femur, has become inactive.
• Active cellular marrow is called red marrow;
inactive marrow that is infiltrated with fat is
called yellow marrow. The bone marrow is
actually one of the largest organs in the body,
approaching the size and weight of the liver. It is
also one of the most active.
BONE MARROW

• Normally, 75% of the cells in the marrow belong to the white

blood cell–producing myeloid series and only 25% are
maturing red cells, even though there are over 500 times as
many red cells in the circulation as there are white cells.
• This difference in the marrow reflects the fact that the average
life span of white cells is short, whereas that of red cells is long.
• Hematopoietic stem cells (HSCs) are bone marrow cells that
are capable of producing all types of blood cells. They
differentiate into one or another type of committed stem cells
(progenitor cells).
• These in turn form the various differentiated types of blood cells.
There are separate pools of progenitor cells for megakaryocytes,
lymphocytes, erythrocytes, eosinophils, and basophils;
neutrophils and monocytes arise from a common precursor.
• The bone marrow stem cells are also the source of
osteoclasts, Kupffer cells mast cells, dendritic cells, and
Langerhans cells. The HSCs are few in number but are capable
of completely replacing the bone marrow when injected into a
patient whose own bone marrow has been entirely destroyed.
WHITE BLOOD CELLS

• Normally, human blood contains 4000–11,000 white

blood cells per microliter (Table 31–1). Of these, the
granulocytes (polymorphonuclear leukocytes, PMNs) are
the most numerous.
• Young granulocytes have horseshoe-shaped nuclei that
become multilobed as the cells grow older (Figure 31–3).
Most of them contain neutrophilic granules (neutrophils),
but a few contain granules that stain with acidic dyes
(eosinophils), and some have basophilic granules
(basophils)
• The other two cell types found normally in peripheral
blood are lymphocytes, which have large round nuclei and
scanty cytoplasm, and monocytes, which have abundant
agranular cytoplasm and kidney-shaped nuclei (Figure 31–
3).
• Acting together, these cells provide the body with the
powerful defenses against tumors and viral, bacterial,
and parasitic infections .
FIGURE 31–3 Development of various formed
elements of the blood from bone marrow cells.
Cells below the horizontal line are found in
normal peripheral blood.
The principal sites of action of erythropoietin
(erythro) and the various colony-stimulating
factors (CSF) that stimulate the differentiation of
the components are indicated. G, granulocyte; M,
macrophage; IL, interleukin; thrombo,
thrombopoietin; erythro, erythropoietin; SCF,
stem cell factor.
PLATELETS

• Platelets are small, granulated bodies that

aggregate at sites of vascular injury.
• They lack nuclei and are 2–4 in
diameter). There are about 300,000/ of
circulating blood, and they normally have a
half-life of about 4 days. The
megakaryocytes, giant cells in the bone
marrow, form platelets by pinching off bits of
cytoplasm and extruding them into the
circulation.
• Between 60% and 75% of the platelets that
have been extruded from the bone marrow are in
the circulating blood, and the remainder are
mostly in the spleen. Splenectomy causes an
increase in the platelet count (thrombocytosis).
RED BLOOD CELLS

• The red blood cells (erythrocytes) carry hemoglobin

in the circulation.
• They are biconcave disks that are manufactured
in the bone marrow. In mammals, they lose their
nuclei before entering the circulation. In humans,
they survive in the circulation for an average of
120 days.
• The average normal red blood cell count is 5.4
million/ in men and 4.8 million/ in women.
• The number of red cells is also conveniently
expressed as the hematocrit, or the percentage of the
blood, by volume, that is occupied by erythrocytes.
• Each human red blood cell is about 7.5 in
diameter and 2 thick, and each contains
approximately 29 pg of hemoglobin (Table 31- 2).
• There are thus about 3 × 1013 red blood cells and about 900 g of
hemoglobin in the circulating blood of an adult man (Figure 31–5).
The feedback control of erythropoiesis by erythropoietin
hormone released by renal tissue in presence of low O2 content
in blood .
HEMOGLOBIN

• The red, oxygen-carrying pigment in the red

blood cells of vertebrates is hemoglobin, a
protein with a molecular weight of 64,450.
• Hemoglobin is a globular
molecule made up of four
subunits (Figure 31–6).
• Each subunit contains a heme moiety
conjugated to a polypeptide.
• Heme is an iron containing porphyrin
derivative. The polypeptides are referred to
collectively as the globin portion of the
hemoglobin molecule.

Figure (31-6) Diagrammatic representation of a molecule of

hemoglobin A, showing the four subunits.
 HEMOGLOBIN

• There are two pairs of polypeptides in each hemoglobin

molecule. In normal adult human hemoglobin (hemoglobin A),

• 2 2. Not all the

hemoglobin in the blood of normal adults is hemoglobin A.
About 2.5% of the hemoglobin is hemoglobin A2
2 2).
• 10 individual amino acid residues that

hemoglobin A derivatives closely associated with hemoglobin

A that represent glycated hemoglobins.

• HbA1a , HbA1b , HbA1c one of these, hemoglobin A1c

(HbA1c), has a glucose attached to the terminal valine in each

blood of patients with poorly controlled diabetes mellitus and

is measured clinically as a marker of the progression of that
disease and/or the effectiveness of treatment.
REACTIONS OF HEMOGLOBIN

• O2 binds to the Fe2+ in the heme moiety of hemoglobin to form

oxyhemoglobin.
• The affinity of hemoglobin for O2 is affected by pH,
temperature, and the concentration in the red cells of 2,3-
bisphosphoglycerate (2,3-BPG).
• 2,3-
concentration of 2,3-BPG lower the affinity of hemoglobin for
O2 causing more O2 to be liberated and H+ compete with O2 for
binding to deoxygenated hemoglobin, decreasing the affinity of
hemoglobin for O2 by shifting the positions of the four peptide
chains (quaternary structure).
• When blood is exposed to various drugs and other oxidizing
agents in vitro or in vivo, the ferrous iron (Fe2+) that is normally
present in hemoglobin is converted to ferric iron (Fe3+), forming
methemoglobin.
REACTIONS OF HEMOGLOBIN

• Methemoglobin is dark-colored, and when it is present in large quantities in

the circulation, it causes a dusky discoloration of the skin resembling
cyanosis.
• Some oxidation of hemoglobin to methemoglobin occurs normally, but
an enzyme system in the red cells, the dihydronicotinamide adenine
dinucleotide (NADH)-methemoglobin reductase system, converts
methemoglobin back to hemoglobin.
• Carbon monoxide reacts with hemoglobin to form carbon
monoxyhemoglobin (carboxyhemoglobin).
• The affinity of hemoglobin for O2 is much lower than its affinity for carbon
monoxide, which consequently displaces O2 on hemoglobin, reducing the
oxygen-carrying capacity of blood .
SYNTHESIS OF HEMOGLOBIN

• The average normal hemoglobin

content of blood is 16 g/dL in men
and 14 g/dL in women, all of it in
red cells.
• In the body of a 70-kg man, there are about 900
g of hemoglobin, and 0.3 g of hemoglobin is
destroyed and 0.3 g synthesized every hour
(Figure 31–5).
• The heme portion of the hemoglobin molecule is
synthesized from glycine and succinyl-CoA

• (Clinical Box 31–2)

Sickle cell disease
CATABOLISM OF HEMOGLOBIN

• When old red blood cells are destroyed by tissue macrophages, the globin
portion of the hemoglobin molecule is split off, and the heme is converted
to biliverdin.
• In humans, most of the biliverdin is converted to bilirubin and excreted
in the bile.
• The iron from the heme is reused for hemoglobin synthesis.
• Exposure of the skin to white light converts bilirubin to lumirubin, which
has a shorter half-life than bilirubin.
• Phototherapy (exposure to light) is of value in treating infants with jaundice
due to hemolysis. Iron is essential for hemoglobin synthesis; if blood is lost
from the body and the iron deficiency is not corrected, iron deficiency
anemia results

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