1. The Blood: The general properties;
Functions
DR H.A ABDULRAHIM
2. Introduction
• Blood is a suspension of cells in fluid
• It is circulated around the body by the heart
• The fluid is known as plasma and a typical sample is
composed of 90% water, 8% protein, 1% inorganic
salts, 0.5% lipids, 0.1% glucose and other minor
components
• The proteins are numerous and diverse, including
albumin, blood coagulation factors, anti-proteases,
transport proteins and antibodies (immunoglobulins)
• Collectively, these proteins exert a water-binding
effect known as colloidal osmotic pressure which
helps regulate the distribution of fluid between the
plasma and the extracellular space, serving to keep
the fluid in the circulation
3. • Plasma components, including hormones,
lipids, salts, water molecules and small
proteins, are constantly exchanged with the
extracellular fluid of body tissues in
accordance with the blood’s transport
functions.
• As well as specialized proteins that functions
as catalytic enzyme
4. Developmental stages of blood cells
Developing stage Age Sites of production
Embryo 0-2 month Yolk sac
Fetus 2-7 month Spleen and Liver
5-9 month Spleen,Liver,Bone marrow
Infants 0-12 months Practically all Bone marrow
Adults Vertebrae, skull, sternum,
ribs,sacrum and pelvis,
proximal ends femurs and
humerus
5. Hierarchical organization of
haemopoiesis
Figure 2. Diagrammatic representation of the bone marrow pluripotent stem cell and the cell lines that arise from it.
Various progenitor cells can be identified by culture in semi-solid medium by the type of colony they form. Baso, basophil;
BFU, burst-forming unit; CFU, colony-forming unit; E, erythroid; Eo, eosinophil; GEMM, granulocyte, erythroid,monocyte
and megakaryocyte; GM, granulocyte, monocyte; Meg, megakaryocyte; NK, natural killer.
6. Cellular components of blood
• Basically, the cellular components of blood are grouped
into three categories:
the red blood cells (erythrocytes)
the white blood cells (leucocytes)
the platelets (megakaryocytes)
Red blood cells (Erythrocytes)
hemoglobin
Platelets (thrombocytes) are specialized cells which bind to
and coat damaged vessel walls, plug small defects in blood
vessel walls and help activate the blood-clotting cascade.
They are essential for haemostasis, the system
that controls bleeding
7. Cellular component of blood cont’d
LEUCOCYTES
• Five types of leucocytes are normally present in
human blood and are classified into two groups:
Granulocytes
• Neutrophils
• Eosinophils
• Basophils
Agranulocytes (Mononuclear leucocytes)
• Lymphocytes
• Monocytes/Macrophages
8. Blood composition
Suspension of cells in plasma (carrier fluid)
45% Cells
55% Plasma
Cells
Red cells (erythrocytes) 99%
5x106/mL
White cells (leukocytes)
7x103/mL < 1%
Platelets (thrombocytes)
3x105/mL
Figure 3. Seperation of blood components by centrifugation
9. Blood Plasma
• Straw colored clear liquid
• Contains 90% water
• 7-8% plasma proteins
synthesize in liver
confined to bloodstream
albumin
maintain blood osmotic pressure
immunoglobulins
antibodies bind to foreign
substances called antigens
form antigen-antibody complexes
fibrinogen
for clotting
• 2% other substances
Nutrients, electrolytes, gases, hormones, waste products
10. Functions of plasma proteins
1. Coagulation of blood –forming blood clots to prevent excess blood loss.
Fibrinogen to fibrin
2. Defense mechanism of blood – carrying cells and immunoglobulins that fight
infection
3. Transport mechanism –
transporting oxygen and nutrients to the lungs and tissues
α Albumin binds molecules and drugs , β globulin transport hormones, gases,
enzymes, etc.
bringing waste products to the kidneys and liver, which filter and clean the
blood
4. Maintenance of colloidal osmotic pressure in blood
5. Acid-base balance
6. Regulating body temperature
7. Provides viscosity to blood
8. Provides suspension stability of RBC
9. Reserve proteins
11. The red blood cells
• RBCs has a much simpler structure than most human
cells, being essentially composed of a membrane
surrounding a solution of hemoglobin (this protein forms
about 95% of the intracellular protein of the red cell).
• no intracellular organelles, such as mitochondria,
lysosomes, or Golgi apparatus in mature cells
• Human red blood cells (RBCs), are nonnucleated.
• However, the red cell is not metabolically inert.
• ATP is synthesized from glycolysis and is important in
processes that help the red blood cell maintain its
biconcave shape and also in the regulation of the
transport of ions (eg, by the Na+-K+ ATPase and the anion
exchange proteins; and of water in and out of the cell.
12. Figure 4. Comparison of the DNA and RNA content and marrow and peripheral
blood distribution, of the erythroblast (normoblast), reticulocyte and mature red
blood cell (RBC).
13. The red blood cells cont’d
• The biconcave shape increases the surface-to-volume ratio of the
red blood cell, thus facilitating gas exchange.
• About Two Million Red Blood Cells Enter the Circulation per Second
• The life span of the normal red blood cell is 120 days;
• this means that slightly less than 1% of the population of red cells
(200 billion cells, or 2 million per second) is replaced daily.
• The new red cells that appear in the circulation still contain
ribosomes and elements of the endoplasmic reticulum.
• The RNA of the ribosomes can be detected by suitable stains (such
as cresyl blue), and cells containing it are termed reticulocytes
(normally, about 1% of the total red blood cell count)
• The number of reticulocytes is markedly increased in haemolytic
anaemia, as the bone marrow attempts to compensate for rapid
breakdown of red blood cells by increasing the amount of new,
young red cells in the circulation
14. The red blood cells cont’d
Erythropoietin Regulates Production of Red Blood Cells
• Production of RBCs occurs mainly in the bone marrow by erythropoiesis
• Human erythropoietin is a glycoprotein of 166 amino acids (molecular mass about
34 kDa).
• Its amount in plasma can be measured by radioimmunoassay.
• It is the major regulator of human erythropoiesis.
• Erythropoietin is synthesized mainly by the kidney and is released in response to
hypoxia into the bloodstream, in which it travels to the bone marrow.
• Erythropoietin interacts with committed progenitor cells , known as the burst-
forming unit-erythroid (BFU-E), causing it to proliferate and differentiate.
• In addition, it interacts with a later progenitor of the red blood cell, called the
colony-forming unit-erythroid (CFU-E), also causing it to proliferate and further
differentiate.
• For these effects, erythropoietin requires the cooperation of other growth factors
eg,interleukin 1 (IL-1) which act on the stromal cells; interleukin-3 &6 (IL-3,IL-6)act
on the multipotential progenitor cells
15. Figure 5. Greatly simplified scheme of differentiation of stem cells to red blood cells.
Various interleukins (ILs), such as IL-3, IL-4, IL-9, and IL-11, are involved at different steps of
the overall process. Erythroid precursors include the pronormoblast, basophilic,
polychromatophilic, and orthochromatophilic normoblasts,and the reticulocyte. Epo acts
on basophilic normoblasts but not on later erythroid cells. (CFU-GEMM, colony-forming
unit whose cells give rise to granulocytes, erythrocytes, macrophages, and
megakaryocytes; BFU-E, burst-forming unit-erythroid; GM-CSF, granulocyte-macrophage
colony-stimulating factor; Epo,erythropoietin; RBC, red blood cell.)
16. The red blood cells cont’d
• The Red Blood Cell Has a Glucose Transporter in Its Membrane
• The circulatory glucose enter the red cells by facilitated diffusion
• The specific protein involved in this process is called the glucose
transporter 1(GLUT 1)or glucose permease.
• The process of entry of glucose into red blood cells is of major
importance because it is the major fuel supply for these cells.
• The red cell contains cytoskeletal components that play an
important role in determining its shape.
17. Functions of RBCs
1. Transport oxygen from lungs to the tissues (oxyhemoglobin).
2. Transport carbon-dioxide from tissues to lungs
(carboxyhemoglobin)
3. Hemoglobin acts as a buffer and regulates the hydrogen ion
concentration (acid base balance)
4. Carry the blood group antigens and rhesus (Rh) factor
18. Monocytes/Macrophages
• Monocytes spend only a short time in the marrow and,
• after circulating for 20-40 hours, leave the blood to enter the
tissues where they mature and carry out their principal
functions.
• Their extravascular lifespan after their transformation to
macrophages may be as long as several months or even years.
• They may assume specific functions in different tissues (e.g. skin,
gut, liver) (Figure 5).
• One particularly important lineage is that of dendritic
cells(specialised macrophages) which are involved in antigen
presentation to T cells
• granulocytes macrophage GM-CSF and M-CSF are involved in their
production and activation
19. Monocytes migration to tissues Functions of
monocytes/macrophages/neutrophils
• Chemotaxis (cell mobilization and
migration): The phagocyte is attracted to
bacteria or the site of inflammation by
chemotactic substances released from
damaged tissues or by complement
components
• Phagocytosis: The foreign material (e.g.
bacteria, fungi) or dead or damaged cells
of the host are phagocytosed
• Recognition of a foreign particle is aided
by opsonization with immunoglobulin or
complement because both neutrophils
and monocytes have Fc and C3b
receptors.
• Opsonization of normal body cells (e.g.
red cells or platelets) also makes them
liable to destruction by macrophages of
the reticuloendothelial system
Figure 5. The reticuloendothelial system: distribution of macrophages
20. Figure 6. Phagocytosis and bacterial destruction. On entering the neutrophil, the bacterium is
surrounded by an invaginated surface membrane and fuses with a primary lysosome to form a
phagosome.Enzymes from the lysosome attack the bacterium. Secondary granules also fuse with the
phagosomes, and new enzymes from these granules including lactoferrin attack the organism. Various
types of activated oxygen, generated by glucose metabolism, also help to kill bacteria. Undigested
residual bacterial products are excreted by exocytosis
Functions of monocytes/macrophages/neutrophils
21. • Killing and digestion : This occurs by
oxygen-dependent and oxygen-
independent pathways.
• In the oxygen-dependent reactions,
superoxide (02-)'hydrogen peroXide
(H202) and other activated oxygen
(02) species, are generated from 02
and reduced nicotinamide adenine
dinucleotide phosphate (NADPH).
• In neutrophils, H202 reacts with
myeloperoxidase and intracellular
halide(hypochlorous HClO) to kill
bacteria; activated oxygen may also
be involved.
• The non-oxidative microbicidal
mechanisms involve microbicidal
proteins.
• These may act alone (e.g. cathepsin G)
or in conjunction with H202 (e.g
lysozyme, elastase).
• They may also act with a fall in pH
within phagocytic vacuoles into which
lysosomal enzymes are released.
• An additional factor lactoferrin-an iron-
binding protein present in neutrophil
granules-is bacteriostatic by depriving
bacteria of iron and generating free
radicals (Figure 6).
• Finally, nitric oxide (NO) generated
through nitric oxide synthase (NOS)
from L-arginine is another mechanism
by which phagocytes kill microbes.
Functions of monocytes/macrophages/neutrophils cont’d
22. Functions of neutrophils
1. First line of defence against invading micro-organisms.
2. Powerful and effective killer machinery – contains enzymes
like protease, elastase, metalloproteinase, NADPH oxidase;
antibody like substances called defensins.
Defensins – antimicrobial peptides active against bacteria and
fungi.
3. Secrete Platelet Aggregation Factor (PAF) – accelerates the
aggregation of platelet during injury to the blood vessels
23. S/No Constituents Major Functions Source
1 Water Solvent for carrying substances absorbed round
the body
Plasma
2 Electrolytes : sodium; potassium;
calcium; magnesium; chloride;
bicarbonate
Osmotic pressure balance; pH buffering ;
regulation of membrane permeability; signaling
transduction
Plasma
3 Plasma proteins: Albumin;
Fibrinogen
Globulin
Lipoproteins
Osmotic pressure balance; pH buffering
Blood clotting
Immune defense
Solubilized &transport of long chain fatty acids
Plasma
4 Molecules Transporting in blood:
Nutrients
Waste products
Synthetic products
Glucose; Fatty acids ;Amino acids;
CO2; Urea; Uric acid
Hormones ; Enzymes; Growth factors
Plasma
5 Leucocytes Body defense/immunity; cytokines; interleukins Formed element (Buffy coat)
6 Red blood cells: Transport oxygen , CO2 Formed elements (Sediment)
7 Platelets Control bleeding Formed elements
8 The Lymph Drainage of excess tissue fluid/immune system Sterling force interactions
24. Lymphocytes
• Lymphocytes are the immunologically competent cells that assist the phagocytes in
defence of the body against infection and other foreign invasion
• Two unique features characteristic of the immune system are the ability to generate
antigenic specificity and the phenomenon of immunological memory.
• In postnatal life, the bone marrow and thymus are the primary lymphoid organs in
which lymphocytes develop.
• The secondary lymphoid organs in which specific immune responses are generated
are the lymph nodes, spleen and lymphoid tissues of the alimentary and respiratory
tracts.
B and T lymphocytes
• The immune response depends upon two types of lymphocytes, B and T cells which
are derived from the haemopoietic stem cell.
• B cells mature in the bone marrow and circulate in the peripheral blood until they
undergo recognition of antigen.
• The B cells receptor is membrane-bound immunoglobulin and after activation this is
secreted as free soluble immunoglobulin.
25. • At this point they mature into
memory B cells or plasma cells.
• The plasma cells home to the bone
marrow and have a characteristic
chromatin rich eccentric round
nucleus and strongly basophilic
cytoplasm.
• T cells develop from cells that have
migrated to the thymus where they
differentiate into mature T cells
during passage from the cortex to the
medulla.
• During this process, self-reactive T
cells are deleted (negative selection)
whereas T cells with some specificity
for host human leucocyte antigen
(HLA) molecules are selected
(positive selection).
• The mature helper cells express CD4
and cytotoxic cells express CD8
Figure 7. The thymus
26. • Lymphocyte circulation
• Lymphocytes in the peripheral blood
migrate through post-c capillary venules
into the substance of the lymph nodes
or into the spleen or bone marrow.
• T cells home to the perifollicular zones
of the cortical areas of lymph nodes
(paracortical areas) and to the
periarteriolar sheaths surrounding the
central arterioles of the spleen.
• B cells selectively accumulate in follicles
of the lymph nodes and spleen.
Lymphocytes return to the peripheral
blood via the efferent lymphatic stream
and the thoracic duct. CD4 helper cells
predominate in normal peripheral blood
and germinal centres, but in the marrow
and gut the major T-cell subpopulation
is CD8 positive.
Figure 8.The primary and secondary lymphoid organs
27. Immunoglobulins
• These are a group of proteins produced
by plasma cells and B lymphocytes that
bind to antigen. They are divided into five
subclasses or isotypes: immunoglobulin G
(IgG), IgA, IgM, IgD and IgE.
• IgG, the most common, contributes
approximately 80% of normal serum
immunoglobulin
• IgM is usually produced first in response
to antigen
• IgA is the main immunoglobulin in
secretions, particularly of the
gastrointestinal tract.
• IgD and IgE (involved in delayed
hypersensitivity reactions) are minor
fractions.
• Some important biochemical and
biological properties
Complement system
• This consists of a series of plasma proteins
consisting an amplification enzyme system
which is capable of lysis of bacteria (or of
blood cells) or can 'opsonize'
• (coat) bacteria or cells so that they are
phagocytosed.
• The complement sequence consists of
nine major components-C1, C2, etc.-which
are activated in turn (denoted thus C1-)
and form a cascade, resembling the
coagulation sequence .
• The most abundant and pivotal protein is
C3, which is present in plasma at a level of
approximately 1.2 g/L.
• The early (opsonizing) stages leading to
coating of the cells with C3b .
28. Functions of Eosinophils
Secrete lethal substances at the time of exposure to foreign
proteins/parasites
1. Eosinophill peroxidase – detroy worms, bacteria and tumor cells.
2. Major basic protein – damage parasites
3. Eosinophil cationic protein (ECP)- destroys helminths
4. Eosinophil derived neurotoxin – destroys nerve fibres (myelinated nerve
fibres)
5. Modulates allergic responses
29. Functions of Basophils
Basophill granules release some important substances like –
1. Histamine – Acute hypersensitivity reaction- vascular changes, increase
capillary permeability
2. Heparin – prevents intravascular blood clotting
3. Hyaluronic acid – necessary for deposition of ground substances in
basement membrane
4. Proteases – exaggerate inflammation
• Basophill have IgE receptor – hypersensitivity reaction
31. Functions of Platelets
1.Blood clotting
2.Clot retraction
3.Defence mechanism
4.Homeostasis
5.Repair and rupture of blood vessel
32. Assignments
1. Emunerate the developmental stages of blood
cells
2. Discuss the general properties of erythrocytes
3. Concisely, describe the physicochemical roles
of each component of blood cells
4. Enumerates the various chemical released by
leucocytes and their biological significance
