Transcript blood - I am biomed

BLOOD
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• Cells of human body cannot move around to
obtain O2 and nutrients or eliminate CO2 &
wastes.
• These needs are met by 2 fluids:
1. Blood
2. Interstitial Fluid
• Blood forms 7% of the body weight.
• Blood in the vessel is always in motion
because of pumping action of the heart, this
continual flow maintains a fairly constant
environment for the body cells.
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Functions of Blood
1. Transportation
2. Regulation
3. Protection
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Transportation
Blood transports O2 from the lungs to the
cells of the body and CO2 from body cells to
lungs for exhalation.
Carries nutrients from GI trait to body cells &
hormones from endocine glands to other
body cells.
Transports heat & waste products to lungs,
kidney & skin for elimination from the body.
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Regulation
Circulating blood maintains homeostasis in all
body fluids.
Blood helps regulate pH through buffers.
Maintains body temperature.
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Protection
Blood can clot which can protect against its
excessive loss from the cardio vascular system
after an injury.
White blood cells protect against disease by
carrying on phagocytosis.
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Composition of Blood
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Composition of Blood
Composed of straw coloured transparent fluid
plasma, in which different types of cells are
suspended.
Blood Volume
Plasma
Cells
45%
55%
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Plasma
• Constituents of plasma are water (90 to 92%) and
dissolved substances including the following:• Plasma proteins (7% of plasma)
• Inorganic salts
• Nutrients, principally from digested foods
• Waste materials
• Hormones
• Gases
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Plasma Proteins
Retained within blood because they are too
large to escape through capillary pores into
tissues.
Responsible for creating osmotic pressure of
blood (25mmHg).
Plasma viscosity (thickness) is due to plasma
proteins mainly albumins and fibrinogen.
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Albumins
Formed in Liver.
Maintain normal plasma osmotic pressure.
Act as carrier molecules for lipids & steroid
hormones.
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Globulins
• Formed in liver & lymphoid tissue.
• As antibodies (Immunoglobulins), complex proteins
produced by lymphocytes that play an important part
in immunity, by binding to & neutralizing foreign
materials (antigens) such as micro organisms.
• Transportation of some hormones & mineral salts. E.g.
Thyroglobulin carries hormone thyroxine & transferrin
carries the mineral iron.
• Inhibition of some proteolytic enzymes E.g.
macroglobulin inhibits trypsin activity
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Clotting Factors
Substances essential for clotting of blood.
Senim is plasma from which clotting factors
have been removed
Synthesized
in liver
Essential for
blood coag
Fibrinogen
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Inorganic Mineral Salts
• They are involved in the following:A. Muscle contraction.
B. Transmission of nerve impulses.
C. Formation of secretions & maintenance of
acid-base balance
• pH is measure of the concentration of
hydrogen ion
• pH of blood is between 7.35 & 7.45.
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Nutrients
• Products of digestion pass into blood for
distribution to all body cells.
• These include amino acids (from proteins),
glucose (from carbohydrates), fatty acids &
glycerol (from triglycerides), vitamins & minerals.
• Together with mineral salts they are required by
all body cells to provide energy, heat, materials
for repair & replacement, for synthesis of other
blood components & secretions.
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• Urea, creatinine & uric acid
are waste products of
protein metabolism.
• Formed in liver and
conveyed in blood to
kidneys for excretion.
• Substances synthesized by
endocrine glands.
• Influence cellular activity.
Hormones
Endocrine cells
Blood
Target tissue
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Gases
O2 associated with hemoglobin inside RBC’s.
CO2 is dissolved in plasma.
N2 no known function.
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Cellular content of blood
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• All originate from pluripotent stem cells
(pluri=several). Pluripotent stem cells are cells
that have the capacity to develop into several
different types of cells.
• Stem cells in red bone marrow(which is highly
vascularized connective tissue located in the
microscopic spares between trabeculae of
spongy bone tissue) reproduce themselves
into proliferate & differentiate cells that give
rise to old cells.
• Process of blood cell formation called
haemopoiesis (poiesis= making).
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DEVELOPMENT OF
BLOOD CELLS
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Erythrocytes (RBC’s)
 Biconcave discs, no nucleus, 8micron diameter.
 Main function is gas transport mainly of O2 but some carry CO2.
 Biconcavity increases surface area for gas exchange & slim structure
of the central portion allows fast entry & exit of gases.
 Cells are flexible so they can squeeze through capillaries & contain
no intracellular organelles leaving more space for haemoglobin,
large pigmented protein responsible for gas transport.
 Produced in red bone marrow, present in ends of long bones & in
flat and irregular bones.
 Lifespan in circulation = 120 days
 Development takes about 7 days called erythropoiesis.
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O2 Transport
 Haemoglobin large complex
protein containing globular
protein (Globin) & a
pigmented iron containing
complex called haem.
 Each haemoglobin molecule
contains 4 globin chains & 4
haem units, each with one
atom of iron.
 Each atom of iron can combine
with an oxygen molecule, this
means that a single
haemoglobin molecule can
carry up to 4 molecules of
oxygen.
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When all 4 O2 binding sites on a haemoglobin
molecule are full means it is saturated.
Hb binds reversibly to O2 to give
oxyhaemoglobin.
O2 of blood increases & gives bright red colour
due to high levels of oxyhaemoglobin as the
level of O2 falls it results in dark bluish colour
because it is not saturated.
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Association of O2 and Hb is loose so
oxyhaemoglobin releases O2 readily under
certain conditions.
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Low pH
Metabolically active tissues e.g. exercising
muscle, release acid waste products, so local
pH falls.
Oxyhaemoglobin readily breaks down to
provide additional O2 for tissue use.
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Low O2 levels
As O2 levels fall oxyhaemoglobin breaks down
to form O2 e.g. in body tissues which
constantly consume O2 keeping levels low.
At higher O2 levels as in lungs, the
oxyhaemoglobin formation is favoured.
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Temperature
• Actively metabolizing tissues which have
higher than normal O2 needs are warmer than
less active ones.
• This drives the equation to the left such that
O2 dissociation increases & ensures that active
tissues receive a higher O2 supply than less
active tissues.
• Lungs, alveoli exposed to inspired air,
temperature lower, oxyhaemoglobin formed.
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Control of Erythropoiesis
• Number of red cells fairly
constant i.e. Bone marrow
produces erythrocytes @ at
which they are destroyed.
• Due to homeostatic negative
feedback mechanism.
• Increase erythropoiesis due to
hypoxia i.e. Deficient O2 supply
to body cells.
• O2 carrying power of blood is
reduced by hemorrhage.
• O2 tension in air reduced at
high altitudes.
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Destruction of erythrocytes
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Destruction of erythrocytes
• Life span = 120 days
• Breakdown, or haemolysis carried out by phagocytic
reticuloendothelial cells.
• Main sites of haemolysis = spleen, bone marrow & liver
• Erythrocytes age results in changes in cell membrane which
is susceptible to haemolysis.
• Iron released by haemolysis retained in bone marrow to
form new haemoglobin molecules.
• Biliverdin formed from haem part of haemoglobin
• This is reduced to yellow pigment bilirubin, before being
bound to plasma globulin & transported to liver where it is
changed from a fat soluble to a water soluble form to be
excreted as a constituent of bile.
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ERYTHROCYTES NORMAL VALUES
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ABO SYSTEM
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BLOOD GROUPS
• 1) Depends on types of antigen on red blood cells
• 2) Individuals make antibodies to these antigen, but not to their
own type of antigen, since if they did the antigen and anti bodies
would react causing transfusion reaction which can be fatal.
• 3) Individuals that are transfused with blood of the same group that
is processing the same antigens on the surface of the cells, their
immune system will not recognize them as foreign and will not
reject them.
• 4) However, if individual is given different blood type (Different
type of antigen on red blood cells) , their immune system will
mount an attack upon them and destroy the transfused cells. This is
the basis of the TRANSFUSION REACTION: the two blood types , the
donor and recipient are incompatible .
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THE ABO SYSTEM
 55% of the population has either A-type antigens (Blood
group A), or B-type antigens (Blood group B), or both (Blood
group AB) on their red cell surface.
 Remaining 45% have neither A nor B type antigens. (Blood
group O ) The corresponding antibodies are called anti-A and
anti-B.
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ABO SYSTEM
 Blood group A individuals cannot make anti-A, since otherwise a
reaction to their own cells would occur, however they make anti-B.
 Blood group B individuals, for the same reasons , make only anti A.
 Blood group – AB make neither anti-A nor anti-B, therefore they are
known as UNIVARSAL RECIPIENTS: Transfusion of either type A or
type B blood into these individuals is likely to be safe, since there
are no antibodies to react with them.
 Blood group O make both anti-A and anti-B but do not have neither
A nor B antigens on their red cell membranes, and their blood may
be safely transfused into A, B,AB or O types : group O is known as
the UNIVARSAL DONOR
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RHESUS SYSTEM
 The red blood cell membrane antigen important here is
the Rhesus (Rh) antigen, or Rhesus factor.
 About 85% of people have this antigen: they are
Rhesus +ve (Rh +) and do not therefore make antiRhesus antibodies
 Remaining 15 % have no Rhesus antigen : they are
Rhesus –ve (Rh –), therefore are capable of making antRhesus antibodies, but are stimulated to do so only in
certain circumstances, Ex. In pregnancy or as the result
of an incompatible blood transfusion.
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Leukocytes (white blood cells)
Function: Defending the body against
microbes and other foreign bodies.
They are the largest blood vessels.
They account for 1% of the blood volume.
They contain nuclei and some have granules in
their cytoplasm.
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Types of WBC’s
Granulocytes (polymorphenuclear leukocytes)
Basophils
Neutrophils
Eosinophils
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Types of WBC’s
Agranulocytes
Lymphocytes
Monocytes
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WBC’S
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WBC’S
Formation: Granulopoiesis
Follow a common line of development
through myeloblast to myelocyte before
differentiating into 3 types.
All granules have multilobed nuclei in their
cytoplasm.
Their names represent the dyes they take up
when stained in the laboratory,
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WBC’S
EOSINOPHILS
(RED ACID DYE-EOSIN)
BASOPHILS
(ALKALYINE
METHYLENE BLUE)
NEUTROPHILS
(BOTH DYES)
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NEUTROPHILS-DIAPEDESIS
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PHAGOCYTIC ACTION OF
NEUTROPHILS
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NEUTROPHILS
• Main Function: Protect against any foreign material
entering the body mainly microbes and to remove
waste materials e.g cell debris
• Attracted in large numbers to any area of infection by
chemical substances released by damaged cells
called CHEMOTAXINS.
• Are Highly mobile, and squeeze through the capillary
walls in the affected area by diapedesis.
• Thereafter they engulf and kill the microbes by
phagocytosis.
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NEUTROPHILS
• Their nuclei are characteristically complex with up to six lobes and
their granules are lysosomes containing enzymes to digest infected
material.
• Physiological Increase in circulating neutrophils:
• A) Strenuous exercise
• B) Later stages of normal pregnancy.
• C)Microbial Infection
• D)Extensive tissue damage e.g. inflammation,myocardial
infarction,burns.
• E)Metabolic Disorders e.g. diabetic ketoacidosis,acute gout.
• F) Leukaemia. G) Heavy Smoking. H) Use of oral contraceptives.
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EOSINOPHILS
 They leave capillaries and enter tissue fliuds.
 Although capable of phagocytosis, are less active in this than
neutrophils;their specialized role appears to be in elimination
of parasites,such as worms,which are too big to be
phagocytosed.
 They have certain toxic chemicals stored in their
granules,which they release when the eosinophils binds an
infecting organism.
 Found at sites of allergic inflammation such as asthmatic
airways and skin allergies.
 They are believed to release enzymes, such as histamine, that
combine the effects of histamine and other mediators of
inflammation in allergic reactions.
 They promote tissue inflammation by releasing their array of
toxic chemicals.
v
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BASOPHILS
 They are closely associated with allergic reactions,contains
cytoplasmic granules packed with heparin ( an anticoagulant);
histamine (an inflammatory agent) and other substances that
produce inflammation.
 Stimulus that causes basophils to release the contents of their
granules is an allergen (an antigen that causes some kind of
allergy) of some type.
 Mast cells found in connective tissue are similar to basophils.
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AGRANULOCYTES
Large nucleus and no granules in their
cytoplasm.
Called Monocytes and Lymphocytes.
Make up 25% to 50% of all leukocytes.
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MONOCYTES
Large mononuclear cells that originate in red bone
marrow.
Some circulate in the blood and are actively motile
and phagocytic while others migrate into the tissues
where they develop into macrophages.
Monocytes arrive in large numbers and destroy more
microbes, upon arrival they enlarge and differentiate
into wandering macrophages, which clean up cellular
debris and microbes by phagocytosis after an
infection.
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MONOCYTES
Both type of cells produce interlukin 1,
which:
A) Acts on hypothalamus, causing the rise in
body temperature associated with microbial
infections.
B) Stimulates the production of some globulins
by the liver.
C) Enhances the production of T-lymphocytes.
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Monocyte-Macrophage System
 Sometimes called reticuloendothelial system and consists of
body’s complement of monocytes and macrophages.
 Some macrophages are mobile, whereas others are fixed i.e.they
reside in a particular tissue.
 Some Fixed Macrophages include:







1)Histiocytes in connective tissues.
2)Synovial cells in joints.
3) Osteoclasts in bone.
4)Mesangial cells in the glomerulus of nephrons in the kidney.
5) Microglia in the brain.
6) Kupffer cells in liver.
7)Langerhans cells in skin 8) Alveolar
macrophages in lungs.
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MACROPHAGES
 Actively phagocytic and if they encounter large amounts of
foreign or waste material, they tend to multiply at the site and
‘wall off’ the area, isolating the material, e.g. pockets of
tubercular infection in the lungs.
 They synthesise and release an array of biologically active
chemicals, called cytokines, including interlukin 1.
 They also have a central role linking the non-specific and specific
(immune) systems of body defence, and produce factors
important in inflammation and repair.
 Their numbers are increased in microbial infections, collagen
diseases and some non-infective bowel conditions.
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LYMPHOCYTES
 They are smaller than monocytes and have large nuclei.
 They circulate in blood and found in great numbers in
lymphatic tissue such as lymph nodes and the spleen.
 They develop from pluripotent stem cells in red bone
marrow and from precursors in lymphoid tissue, then
travel in the blood to lymphoid tissue elsewhere in the
body where they are activated, i.e. they become
immunocompetent which means they are able to
respond to antigens (foreign material).
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LYMPHOCYTES
Examples of antigens Include:
A) Cells regarded by lymphocytes as abnormal,
e.g. cells that have been invaded by viruses,
cancer cells,tissue transplant cells.
B) Pollen from flowers and plants.
C) Fungi. D) Bacteria.
 E) Some large molecule drug, e.g.
penicillin,asprin.
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LYMPHOCYTES
Although all lymphocytes originate from one
type of stem cell, when they are activated in
lymphatic tissue, two distinct types of
lymphocytes are produced.
Tlymphocytes
Blymphocytes
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T-Lymphocytes
 Processed by thymus gland, lies between heart and sternum.
 Hormone thymosin, produced by thymus, is responsible
for promoting the processing, which leads to the formation of
fully specialized (differentiated), mature, functional TLymphocytes.
 These T-Lymphocytes are programmed to recognize only one
type of antigen, and during its subsequent travels through the
body will react to no other antigen, however dangerous it
might be.
 T-Lymphocytes provide cell mediated immunity.
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CLONAL EXPANSION OF TLYMPHOCYTES
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CELL-MEDIATED IMMUNITY
 T-lymphocytes are released into circulation .
 When they encounter their antigen for the first time they
become sensitized to it.
 If the antigen has come from outside the body, it needs to be
‘presented’ to the T-lymphocytes on the surface of an antigen
presenting cell
 There are different types of antigen presenting cell, including
macrophages
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CELL MEDIATED IMMUNITY
 Macrophages are part of the non-specific defenses, b’coz they engulf and
digest antigens indiscriminately, but they also participate in immune
responses.
 To do this, after digesting the antigen they transport the most antigenic
fragment to their own cell membrane and display it on their surface.
 On their movement around the body, still displaying the antigen fragment,
they eventually come into contact with the T-lymphocyte that has been
processed to target that particular antigen.
 If the antigen is an abnormal body cell, such as a cancer cell, it too will be
displaying foreign (non-self) material on its cell membrane that will
stimulate the T-lymphocyte. Whichever way the antigen is presented to the
T-Lymphocytes, it stimulates the division and proliferation (clonal
expansion) of the T-lymphocyte.
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Types of T-Lymphocytes
Memory T-Cells
• These provide cell-mediated immunity by responding rapidly
to another encounter with the same antigen.
Cytotoxic T-Cells
• These directly inactivate any cells carrying antigens.
• They attach themselves to target cell and release powerful
toxins, which are effective because the two cells are so close
together.
• The main role of cytotoxic T-lymphocytes is in destruction of
abnormal body cells, e.g. infected cells and cancer cells.
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Types of T-Lymphocytes
Helper T-Cells
 Their central role in immunity is emphasized in situations where they are
destroyed, as by the human immunodeficiency virus (HIV).
 When helper T-Lymphocytes fall significantly, the whole immune system is
compromised.
 They are the commonest of the T-Lymphocytes; their main functions
include:
 A) Production of special chemicals called cytokines,e.g. interleukins and
interferons, which support promote cytotoxic T-Lymphocytes and
macrophages.
 B) Co-operating with B-Lymphocytes to produce antibodies; although BLymphocytes are responsible for antibody manufacture, they require to be
stimulated by a helper T-Lymphocyte first.
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B-Lymphocytes
• Processed in bone marrow.
• Their role is in production of antibodies
(immunoglobulins), which are proteins designed to
bind to, and cause the destruction of, an antigen
• Each B-lymphocyte targets one specific antigen: the
antibody released reacts with one type of antigen
and no other.
• B-lymphocytes provide antibody-mediated immunity.
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CLONAL EXPANSION OF
B-LYMPHOCYTES
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Antibody-Mediated (Humoral)
Immunity
• B-Lymphocytes are fixed in lymphoid tissue
( e.g. the spleen and lymph nodes).
 They recognize and bind antigen particles without having
to be presented with them by an antigen presenting cell.
 Once its antigen has been detected and bound, and with
the help of a helper T-Lymphocyte, the B-Lymphocyte
enlarges and begins to divide (clonal expansion).
 It produces two functionally distinct types of cell,plasma
cells and memory B-Cells.
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Plasma Cells
 Secrete antibodies into the blood.
 Antibodies carried throughout the tissues, while the B-Lymphocytes
themselves remain fixed in lymphoid tissue.
 Plasma cells live no longer than a day and produce only one type of
antibody, which targets specific antigen that originally bound to BLymphocyte.
Antibodies:
 A) Bind to antigens, labelling them as targets for other defence cells
such as cytotoxic T-Lymphocytes and macrophages.
 B) Bind to bacterial toxins, neutralising them.
 C) Activate complement.
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Memory B-Cells
These cells remain in body long after the
initial episode has been dealt with, and rapidly
respond to another encounter with the same
antigen by stimulating the production of
antibody – secreting plasma cells.
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INTERDEPENDANCE OF T AND B
LYMPHOCYTE
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LEUKOCYTE-COUNT
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PLATELETS
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PLATELETS (THROMBOCYTES)
Very small non-nucleated discs, 2 to 4µm in
diameter, derived from the cytoplasm of
megakaryocytes in red bone marrow.
They contain a variety of substances that
promote blood clotting, which causes
haemostasis (cessation of blood).
Normal blood platelet count is between
200*109/l and 350*109/l (200000 to
350000/mm3).
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PLATELETS (THROMBOCYTES)
The kidneys release a substance called
thrombopoietin, which stimulates platelet
synthesis, other cytokines may also be involved.
Lifespan of platelets is between 8 and 11 days and
those not used in haemostasis are destroyed by
macrophages, mainly in spleen.
About a third of platelets are stored within the
spleen rather than in the circulation; this is an
emergency store that can be released as required
to control excessive bleeding.
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HAEMOSTASIS
 When a blood vessel is damaged, loss of blood is stopped and healing
occurs in a series of overlapping processes, in which platelets play a vital
part.
1)
VASOCONSTRICTION
2) PLATELET PLUG
FORMATION
3) COAGULATION
(BLOOD CLOTTING)
4)FIBRINOLYSIS
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STAGES OF CLOTTING
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BLOOD CLOTTING FACTORS
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1-VASOCONSTRICTION
When platelets come in contact with a damage
blood vessel, their surface become sticky and
they adhere to the damaged wall.
They then release serotonin (5hydroxyptamine), which constricts (narrows)
the vessel, reducing blood flow through it.
Other chemicals that cause vasoconstriction,
e.g. thromboxanes , are released by the
damaged vessel itself
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2-PLATELET PLUG FORMATION
The adherent platelets clump to each other and
release other substances, including adenosine
diphosphate (ADP), which attract more platelets to
the site.
 Passing platelets stick to those already at the
damaged vessel and they too release their chemicals.
This is a positive feedback system by which many
platelets rapidly arrive at the site of vascular damage
and quickly form a temporary seal – the platelet plug.
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3-COAGULATION
(BLOOD CLOTTING)
Complex process that involves a positive feedback
system.
Blood clotting results in formation of insoluble
thread-like mesh of fibrin which traps blood cells and
is much stronger than the rapidly formed platelet
plug.
In the final stages of this process Prothrombin
activator acts on plasma protein Prothrombin
converting it to thrombin.
Thrombin then acts on another plasma protein
fibrinogen and converts
it to fibrin.
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EXTRINSIC/INTRINSIC PATHWAYS
Prothrombin activator can be formed by two
processes which often occur together: the
extrinsic and intrinsic pathways.
The extrinsic pathway occurs rapidly(within
seconds) when there is tissue damage outside
the circulation .
Damaged tissue releases a complex of
chemicals called thromboplastin or tissue
factor, which initiate coagulation.
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EXTRINSIC/INTRINSIC PATHWAYS
The intrinsic pathway is slower (3-6 min) and is
confined to the circulation.
It is triggered by damage to the blood vessel
lining (endothelium) and the effects of
platelets adhering to it.
After a time the clot shrinks, squeezing out
serum, a clear sticky fluid that consists of
plasma from which clotting factors have been
removed.
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CLOTTING OF BLOOD
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4-FIBRINOLYSIS
 After the clot has formed the process of removing it and healing the
damage blood vessel begins.
 The breakdown of the clot, of fibrinolysis, is the first stage.
 An inactive substance called plasminogen is present in the clot and
is converted to the enzyme plasmin by activators released from the
damaged endothelial cells.
 Plasmin initiates the breakdown of fibrin to soluble products that
are treated as waste material and removed by phagocytosis.
 As the clot is removed, healing process restores the integrity of the
blood vessel wall.
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CONTROL OF COAGULATION
 The process of blood clotting relies heavily on several
processes that are self-perpetuating-that is, once started ,
positive feedback mechanism promotes their
continuation.
 For e.g. thrombin is a powerful stimulator of its own
production.
 The body therefore possess several mechanisms to control
and limit the coagulation cascade: otherwise once started
the clotting process would spread throughout the
circulatory system, far beyond requirements.
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CONTROL OF COAGULATION
 The main controls are :
 1) The perfect smoothness of normal blood vessel
lining ; platelets do not adhere to this surface
 2) The binding of thrombin to a special thrombin
receptor on the cells lining blood vessels; once bound,
thrombin is inactivated
 The presence of natural anticoagulants, e.g. heparin, in
the blood, which inactivate clotting factors
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