2. FUNCTIONS
Blood is sometimes referred to as the river of life.
serves as a transportation system.
It carries vital materials to all the cells of the body and carries away the wastes that
cells produce.
Buffers in the blood help regulate the acid-base balance of body fluids.
the diverse functions of blood can be grouped into three categories: transportation,
protection, and regulation.
Helps regulate body temperature by absorbing heat produced and distributing it to
cooler regions and to the skin.
COMPOSITION
A single drop of blood contains more than 250 million blood cells.
Classified as a connective tissue because it contains cellular elements suspended in a
matrix.
The liquid matrix is called plasma, and the cellular elements are collectively called the
formed elements.
3. PLASMA
Is a straw-coloured liquid that makes up about 55% of blood.
Serves as the medium in which materials are transported by the blood.
Almost every substance that is transported by the blood is dissolved in the plasma.
These include nutrients, ions , dissolved, gases and every hormone.
In addition, it carries away cellular waste.
Most of the dissolved substances (solutes) in the blood are plasma proteins, which
make up 7% to 8% of plasma.
Plasma proteins help balance water flow between the blood and the cells.
Without the plasma proteins, water would be drawn out of the blood by the proteins in
cells.
As a result, fluid would accumulate in the tissues, causing swelling.
4. Types of plasma proteins fall into one of three general categories:
1) Albumins: {N range from 3.5-5.5g/dl. (35-55g/L)]
Make up more than half of the plasma proteins.
Most important in the blood's water-balancing ability.
Maintain intravascular colloid osmotic pressure, neutralize toxins, and transport therapeutic agents.
Synthesis occurs exclusively in the liver and depends on adequate nutrition and nitrogen intake.
Albumin molecules, which are highly soluble in water, carry many charged amino acid residues, resulting in a net charge
of -17 at a normal physiologic pH.
This creates a strong attraction of sodium ions and other cations around its core structure.
Water is also pulled into the vasculature as a result of the sodium attraction to albumin.
Endogenous albumin is produced exclusively by liver cells (hepatocytes) at a rate of 9 to 12 g/day.
Albumin also has antioxidant properties.
Glomerular loss of albumin in nephrotic syndrome has been thought to cause increased platelet aggregation and
thrombosis because of an increase in circulating levels of arachidonic acid available for metabolism to prostaglandins.
Prolonged hyperglycaemia or uncontrolled diabetes mellitus is thought to cause platelet aggregation through a similar
scenario.
Albumin has a heparin-like activity by enhancing antithrombin III activity. With this in mind, it is easy to surmise that
states of hypoalbuminemia, nephrotic syndrome, and uncontrolled diabetes can lead to coagulopathy.
5. 2)Globulins: [N value 2.5-3.5g (25-35g/L)]
Transport lipids, including fats and some cholesterol, as well as fat-soluble vitamins.
Other globulins are antibodies, which provide protection against many diseases.
3)Fibrinogen:
the clotting proteins.
It’s a glycol protein, during tissue & vascular injury fibrinogen converted enzymatically in to fibrin by
thrombin.
6. Formed Elements- platelets, white blood cells, and red blood cells
Platelets
Platelets, sometimes called thrombocytes (thromb, clot; cyte, cell), are essential to blood clotting.
Platelets are actually not true cells but merely circulating fragments of megakaryocytes.
The fragments are released into the blood at the rate of about 200 billion a day.
They then mature during the course of a week. Life span is about 5 to 10 days, has no nucleus.
Platelets contain several substances important in stopping the loss of blood through damaged blood
vessels
Platelet Production
Platelets are produced in the red bone marrow from megakaryocytes.
As megakaryocytes develop into giant cells, they undergo a process of fragmentation that results in
the release of over 1,000 platelets per megakaryocyte.
The dominant hormone controlling megakaryocyte development is thrombopoietin (often
abbreviated as TPO).
Platelet Function
Platelets are also the lightest., therefore they are pushed out from the center of flowing blood to the
wall of the blood vessel.
There they roll along the surface of the vessel wall, which is lined by cells called endothelium, a very
special surface, that prevents anything from sticking to it.
However when there is an injury or cut, and the endothelial layer is broken, the tough fibers that
surround a blood vessel are exposed to the liquid flowing blood.
It is the platelets that react first to injury.
Figure. The tough fibers surrounding the vessel wall, like an
envelop, attract platelets like a magnet, stimulate the shape
change that is shown in the pictures, and platelets then clump
onto these fibers, providing the initial seal to prevent bleeding,
the leak of red blood cells and plasma through the vessel injury.
7. White Blood Cells and Defence against Disease: (Leukocyte) 5,000-10,000/ul
WBC’s perform certain mundane housekeeping duties—
such as removing wastes, toxins, and damaged or abnormal
cells—but they also serve as warriors in the body's fight
against disease.
Although leukocytes represent less than 1% of whole
blood.
Are the largest of the blood cells but also the fewest The
lifespan of white blood cells ranges from 5 to 20 days, after
which time they are destroyed in the lymphatic system
Because the number of WBCs increases when the body
responds to microbes, WBCs counts are often used as an
index of infection.
Produced in the red bone marrow.
WBCs are nucleated.
There are two groups of white blood cells. (See fig below)
FIGURE. White blood cells can squeeze between the cells that form the
wall of a capillary. They then enter the fluid surrounding body cells and,
attracted by chemicals released by microbes or damaged cells, gather at
the site of infection or injury.
8. Granulocytes
Have granules in their cytoplasm.
The granules are actually sacs containing chemicals that are used as weapons to destroy invading
pathogens, especially bacteria.
Account for almost 70 -75 percent of the WBCs
The life cycle of these cells is not that much and they have to be replaced every 12 hours.
The granulocytes are subdivided further in to three sub-categories which are:
1. Neutrophils
The most abundant of all white blood cells (40%-70%), multilobed nucleus has life span of 6-72hours.
Are the blood cell soldiers on the front lines and are the first ones to respond when a bacteria or fungus
tries to attack the body.
Arriving at the site of infection before the other types of white blood cells, neutrophils immediately
begin to engulf microbes by phagocytosis, thus curbing the spread of the infection. After engulfing a
dozen or so bacteria, a neutrophil dies.
But even in death it helps the body's defence by releasing chemicals that that attract more neutrophils to
the scene.
Dead neutrophils, along with bacteria and cellular debris, make up pus, the yellowish liquid we usually
associate with infection. These cells also referred to as PMN or polymorphonuclear leukocytes.
Elevated levels of this cell are a common indication of the presence of an infection in the body since
their production increase whenever an infection invades the body.
Neutrophil
9. Functions:
Chemotaxis
Neutrophils undergo a process called chemotaxis(is the movement of an organism in
response to a chemical stimulus) via amoeboid movement, which allows them to
migrate toward sites of infection or inflammation.
Cell surface receptors allow neutrophils to detect chemical gradients of molecules such
as IL-8, IFN-γ, C3a, C5a, and Leukotriene B4, which these cells use to direct the path
of their migration.
Anti-microbial function
Being highly motile, neutrophils quickly congregate at a focus of infection, attracted
by cytokines expressed by activated endothelium, mast cells, and macrophages.
Neutrophils express and release cytokines, which in turn amplify inflammatory
reactions by several other cell types.
Neutrophils have three methods for directly attacking micro-
organisms: phagocytosis (ingestion), degranulation (release of soluble anti-microbials),
and generation of neutrophil extracellular traps (NETs.
10. 2) Basophils
A type of granulocytes that are found in a very low quantity in the body, account for about 0.5-1% of the WBCs, they are equally
important for the immune system.
However, they are the largest type of granulocyte, life span 3-72hours.
Basophils arise and mature in bone marrow, bilobed nucleus.
Release histamine, a chemical that attracts other white blood cells to the site of infection and causes blood vessels to dilate (widen),
thereby increasing blood flow to the affected area.
They also play a role in some allergic reactions, such as acute and chronic allergic diseases, including anaphylaxis, asthma, atopic
dermatitis and hay fever.
Function
Basophils appear in many specific kinds of inflammatory reactions, particularly those that cause allergic symptoms.
Basophils contain anticoagulant heparin, which prevents blood from clotting too quickly.
They also contain the vasodilator histamine, which promotes blood flow to tissues. They can be found in unusually high numbers
at sites of ectoparasite infection, e.g., ticks.
When activated, basophils degranulate to release histamine, proteoglycans (e.g. heparin and chondroitin), and proteolytic
enzymes (e.g. elastase and lysophospholipase).
Each of these substances contributes to inflammation.
Recent evidence suggests that basophils are an important source of the cytokine, interleukin-4, perhaps more important than T
cells.
Interleukin-4 is considered one of the critical cytokines in the development of allergies and the production of IgE antibody by the
immune system.
Basophil function is inhibited by CD200. Herpesvirus-6, herpesvirus-7, and herpesvirus-8 produce a CD200 homolog which also
inhibits basophil function.
11. 3)Eosinophil
Less commonly, acidophiles, Eosinophils make up about 1-3% of the leukocytes found in our bodies, bilobed nucleus life
span 8-12 days.
These cells are tasked with the duty of fighting off parasites and infections that cause allergies.
Contain substances that are important in the body's defence against parasitic worms, such as tapeworms and hookworms.
They also lessen the severity of allergies by engulfing antibody-antigen complexes and inactivating inflammatory
chemicals.
Following activation, eosinophils effector functions include production of:
cationic granule proteins and their release by degranulation.
reactive oxygen species such as hypobromite, superoxide, and peroxide (hypobromous acid, which is preferentially
produced by eosinophil peroxidase)
lipid mediators like the eicosanoids from the leukotriene (e.g., LTC4, LTD4, LTE4) and prostaglandin (e.g., PGE2) families
enzymes, such as elastase.
growth factors such as TGF beta, VEGF, and PDGF.
cytokines such as IL-1, IL-2, IL-4, IL-5, IL-6, IL-8, IL-13, and TNF alpha
Basophil
13. Agranulocytes
In contrast to the granulocytes, the agranulocytes do not have any type of granules in their cytoplasm
Lack cytoplasmic granules or have very small granules.
They also do not have any membrane covering that is the characteristic feature of the granulocytes.
The agranulocytes are subdivided further into two subcategories which are:
1. Monocytes
A unique type of agranulocytes that have a very peculiar task to perform in our body’s immune system.
These cells have a much larger life span than the other WBCs and have the duty to patrol every inch of the body and
search for waste particles and other bacteria that have not yet been removed from the blood stream.
When the monocytes find such a particle they consume it and break it down in to small bits.
They display these bits on their surfaces to warn the T cells of their presence and help them in understanding their
chemical nature so that if more of these particles invade the body in future, the T cells can eliminate them with ease.
Macrophages are an enhanced form of Monocytes that have a similar type of function as them. The transformation of a
monocyte into a macrophage occurs when it leaves the blood stream and enters the tissues in the body.
Eosinophil
14. 2. Lymphocytes
Lymphocytes are the most abundant type of agranulocytes found in our bodies and account for about 25 percent of our white blood cells.
There is no single type of these cells and there are as many as three separate types of Lymphocytes which are named B cells, T cells and NK
cells.
1. The B cells
Are antibody producers and their main task is to generate antibodies whenever an infection invades the body.
These antibodies are produced for the sole purpose of destroying the foreign particle that has entered the blood stream. Their mode of
operation involves clinging to the cells of the bacteria and then launching a series of reactions that tear it apart and help the body in killing it.
2. The T cells are also divided in two types which are named CD4 and CD8 respectively.
The CD4 T cells perform the task of coordinating with the other cells in the destruction of the foreign bodies attacking the body.They can be
considered as the facilitators which provide the platform for the killing cells and antibodies to perform their task more effectively.
The CD8 T cells on the other hand are destroyers and can be considered as the soldiers which march in to battle and defeat the enemy cells.
3. The NK cells or Natural Killer cells.
Are a special type of lymphocytes which are tasked with the duty similar to that of the CD8 T cells, which is to annihilate their targets.The
difference between CD8 T cells and NK cells is that the latter do not need activation for killing the invaders.
Monocyte
15.
16. Red Blood Cells
Red blood cells (RBCs), also called erythrocytes (erythro-, red; -cyt-, cell), pick up oxygen in the lungs and ferry it to all
the cells of the body.
RBCs also carry about 23% of the blood's total carbon dioxide, a metabolic waste product, they number 4-6
million/mm3 of blood and constitute approximately 45% of the total blood volume.
Red blood cells are quite small, and each is shaped like a biconcave disk—a flattened disk indented on each side.
This shape maximizes the surface area of the cell. Because of the greater surface area, oxygen can enter the red blood
cell more rapidly than if the disk did not have an indent.
A red blood cell is unusually flexible and thus able to squeeze through capillaries.
Matures in the red bone marrow, it loses its nucleus and most organelles.
Each RBCs is packed with approximately 280 million molecules of haemoglobin.
Transport of Oxygen
As can be seen in Figure(next page), each hemoglobin molecule is made up of four subunits.
Each subunit consists of a polypeptide chain and a heme group.
The heme group includes an iron ion that actually binds to the oxygen.
Therefore, each hemoglobin molecule can carry up to four molecules of oxygen.
The compound formed when hemoglobin binds with oxygen is called oxyhemoglobin.
Body cells use the oxygen to boost the amount of energy extracted from food molecules in cellular respiration.
As oxygen is used, carbon dioxide is produced.
17. Most of the carbon dioxide travels to the lungs dissolved in plasma, but some of it binds to
hemoglobin (at a site other than that where the iron atom binds oxygen).
As wonderfully adapted as it is for carrying oxygen, the hemoglobin molecule binds 200 times
more readily to carbon monoxide, a product of the incomplete combustion of any carbon-
containing fuel.
In other words, if concentrations of carbon monoxide and oxygen were identical in inhaled
air, for every 1 molecule of hemoglobin that binds to oxygen molecules, 200 molecules of
haemoglobin would bind to carbon monoxide molecules.
This is the reason carbon monoxide can be deadly.
When carbon monoxide binds to the oxygen-binding sites on hemoglobin, it blocks oxygen
from binding to it, preventing the blood from carrying life-giving oxygen to the cells.
Carbon monoxide is a particularly insidious poison because it is odorless and tasteless.
Its primary source is automobile exhaust, but it can also come from indoor sources, including
improperly vented heaters and leaky chimneys.
Thus, indoor carbon monoxide detectors can save lives.
Life cycle of red blood cells.
The creation of a red blood cell, which takes about 6 days, entails many changes in the cell's
activities and structure.
First, the very immature cell becomes a factory for hemoglobin molecules. And as noted
earlier, after the cell is packed with hemoglobin, its nucleus is pushed out.
18. Then a structural metamorphosis occurs, culminating in a mature red blood cell with a typical biconcave shape.
Once this change in shape takes place, the cell leaves the bone marrow and enters the bloodstream.
Red marrow produces roughly 2 million red blood cells a second, throughout the life of an individual, for a cumulative total of
more than half a ton in a lifetime.
A red blood cell lives for only about 120 days. During that time, it travels through approximately 100 km (62 mi) of blood vessels.
Its life span is probably limited by the lack of a nucleus that would otherwise maintain it and direct needed repairs.
Without a nucleus, for instance, protein synthesis needed to replace key enzymes cannot take place, so the cell becomes increasingly
rigid and fragile.
The liver and spleen are the "graveyards" where worn-out red blood cells are removed from circulation.
The old, inflexible red blood cells tend to become stuck in the tiny circulatory channels of these organs. Macrophages then engulf
and destroy the dying cells.
The demolished cells release their hemoglobin, which the liver degrades into its protein (globin) component and heme.
The protein is digested to amino acids, which can be used to make other proteins. The iron from the heme is salvaged and sent to
the red marrow for recycling.
The remaining part of the heme is degraded to a yellow pigment, called bilirubin, which is excreted by the liver in bile.
Bile is released into the small intestine, where it assists in the digestion of fats.
It is then carried along the digestive system to the large intestine with undigested food and becomes a component of feces.
The color of feces is partly due to bilirubin that has been broken down by intestinal bacteria.(See figure on next page)
19.
20. Production of RBC
A negative feedback mechanism regulates RBCs production according to the needs of the
body, especially the need for oxygen (Figure). Most of the time, RBCs production matches
RBCs destruction.
However, there are circumstances—blood loss, for instance—that trigger a homeostatic
mechanism that speeds up the RBC production.
This mechanism is initiated by a decrease in the oxygen supply to the body's cells.
Certain cells in the kidney sense the reduced oxygen, and they respond by producing the
hormone erythropoietin.
Erythropoietin then travels to the red marrow, where it steps up both the division rate of
stem cells and the maturation rate of immature RBCs.
When maximally stimulated by erythropoietin, the red marrow can increase red blood cell
production tenfold—to 20 million cells per second!
The resulting increase in red blood cell numbers is soon adequate to meet the oxygen needs
of body cells.
The increased oxygen-carrying capacity of the blood then inhibits erythropoietin
production.
21.
22. Blood Types
Human blood is classified into different blood types, depending on the presence or absence of
certain molecules— mostly proteins—on the surface of a person's red blood cells.
Each of your body cells is labeled as "self" (that is, as belonging to your body) by proteins on its
surface.
If a cell that lacks these self markers enters the body, the body's defense system recognizes that
the foreign cell is "nonself" and does not belong.
The foreign cell will have different proteins on its surface. To the body's defense system, these
proteins are antigens, identifying the cell as foreign and marking it for destruction.
As was mentioned earlier, one way the body attacks the foreign cell is by producing proteins
called antibodies that specifically target the antigen on the foreign cell's surface.
Let's consider the role of antigens and antibodies in blood types and transfusions.
ABO Blood Types
When asked about your blood type, you are probably used to responding by indicating one of
the types in the ABO series: A, B, AB, or O.
Red blood cells with only the antigen A on their surface are type A.
When only the B antigen is on the red blood cell surface, the blood is type B.
Blood with both A and B antigens on the red blood cell surface is designated type AB.
When neither A nor B antigens are present, the blood is type O.
23. Normally, a person's plasma contains antibodies against those antigens that are not on his or her own red blood cells.
Thus, individuals with type A blood have antibodies against the B antigen (anti-B antibodies), and those with type B blood have
antibodies against A (anti-A antibodies).
Because individuals with type AB blood have both antigens on their red blood cells, they have neither antibody.
Those with type O blood have neither antigen, so they have both anti-A and anti-B antibodies in their plasma.
In a typical test for blood type, technicians mix a drop of a person's blood with a solution containing anti-A antibodies and mix
another drop of the blood with a solution containing anti-B antibodies.
If clumping(agglutination) occurs in one of the mixtures, it means the antigen corresponding to the antibody in that mixture is
present (See Figure)
24. What blood type will agglutinate to each serum when mixed separately with sera containing anti-A, anti-B, and anti-Rh
antibodies?
AB+
Similarly, when a person is given a blood transfusion with donor blood containing foreign antigens, the antibodies in the recipient's
blood will cause the donor's cells to clump, or agglutinate. This clumping of the donor's cells is damaging and perhaps even fatal.
The clumped cells can get stuck in small blood vessels and block blood flow to body cells. Or they may break open, releasing their
cargo of hemoglobin. The hemoglobin then clogs the filtering system in the kidneys, causing death.
It is important to be sure that the blood types of a donor and recipient are compatible, which means that the recipient's blood does
not contain antibodies to antigens on the red blood cells of the donor.
The plasma of the donor's blood may contain antibodies against antigens on the recipient's red blood cells, but these will be diluted
as they enter the recipient's circulation. Therefore, the donor's antibodies are not a major problem.
The questions to ask in this case are (1) what, if any, antigens are on the donor's cells and (2) what, if any, antibodies are in the
recipient's blood. For example, if a person with blood type A is given a transfusion of blood type B or of type AB, the naturally
occurring anti-B antibodies in the recipient's blood will cause the donor's red blood cells to clump because they have the B antigen.
The transfusion relationships among blood types in the ABO series are shown in Table.(next page)
26. Rh factor
The A and B antigens are not the only important antigens found on the surface of red blood cells.
The presence or absence of an Rh factor is also an important component of blood type.
The name Rh comes from the beginning of the name of the rhesus monkey, in which an Rh antigen was first discovered.
People who have the Rh antigens on their red blood cells are considered Rh-positive (Rh+).
When Rh antigens are missing from the red blood cell surface, the individual is considered Rh-negative (Rh-).
An Rh-negative person will not form anti-Rh antibodies unless he or she has been exposed to the Rh antigen.
For this reason, an Rh-negative individual should be given only Rh-negative blood in a transfusion.
If he or she is mistakenly given Rh-positive blood, it will stimulate the production of anti-Rh antibodies.
A transfusion reaction will not occur after the first such transfusion, because it takes time for the body to start making
anti-Rh antibodies.
After a second transfusion of Rh-positive blood, however, the antibodies in the recipient's plasma will react with the
antigens on the red blood cells of the donated blood. This reaction may lead to the death of the patient.
The Rh factor can also have medical importance for pregnancies in which the mother is Rh-negative and the fetus is Rh-
positive, a situation that may occur if the father is Rh-positive (Figure on next page).
Ordinarily, the maternal and fetal blood supplies do not mix during pregnancy.
However, as a result of blood vessel damage, some mixing may occur during a miscarriage or delivery.
27. If the baby's red blood cells, which bear Rh antigens, accidentally pass into the mother's bloodstream,
she will produce anti-Rh antibodies.
There are usually no ill effects associated with the first introduction of the Rh antigen.
However, if antibodies are present in the maternal blood from a previous pregnancy with an Rh-positive
child or from a transfusion of Rh-positive blood, the anti-Rh antibodies may pass into the blood of the
fetus during a subsequent pregnancy.
This transfer can occur because anti-Rh antibodies, unlike red blood cells, can cross the placenta.
These anti-Rh antibodies may destroy the fetus's red blood cells.
As a result, the child may be stillborn or very anemic at birth. This condition is called hemolytic disease
of the newborn.
The incidence of hemolytic disease of the newborn has decreased in recent years .
The Rh-positive cells are killed by injecting RhoGAM, a serum containing antibodies against the Rh
antigens, at about the seventh month of pregnancy and shortly after delivery if the baby is Rh-positive.
Rh antigens are thus prevented from being "set" in the memory of the mother's immune system.
The injected antibodies disappear after a few months. Therefore, no antibodies linger to affect the fetus
in a subsequent pregnancy.
28. Blood Clotting
When a blood vessel is cut, several responses are triggered to stop the bleeding.
To understand the process of clotting, imagine how you might respond if the garden hose you are using springs a leak.
Your initial response might be to squeeze the hose in hopes of stopping the water flow. Likewise, the body's immediate
response to blood vessel injury is for the vessel to constrict (squeeze shut).
The next response is to plug the hole (Figure next). Your thumb might do the job on your garden hose; in an injured
blood vessel, platelets form a plug that seals the leak.
The platelet plug is formed when platelets cling to cables of collagen, a protein fiber on the torn blood vessel surface.
When the platelets attach to collagen, they swell, form many cellular extensions, and stick together.
Platelets also produce a chemical that attracts other platelets to the wound and makes them stick together even more.
Aspirin prevents the formation of this chemical and, therefore, inhibits clot formation.
For this reason, a daily dose of aspirin is sometimes prescribed to prevent the formation of blood clots that could block
blood vessels nourishing heart tissue and thus cause the death of heart cells (a heart attack). It is also why aspirin can
cause excessive bleeding.
The next stage in stopping blood loss through a damaged blood vessel is the formation of the clot itself. There are >30
steps in the process of clot formation, but here described only the key events.
Clot formation begins when clotting factors are released from injured tissue and from platelets
At the site of the wound, the clotting factors convert an inactive blood protein to prothrombin activator, which then
converts prothrombin—a plasma protein produced by the liver—to an active form, thrombin.
Thrombin then causes a remarkable change in another plasma protein produced by the liver, fibrinogen.
29. The altered fibrinogen forms long strands of fibrin, a protein that makes a web that traps blood cells and forms a clot.
The clot is a barrier that prevents additional blood loss through the wound in the vessel.