Introduction to hema

INTRODUCTION TO
HEMATOLGY
FACULTY: ABDUL QUDDUS
DESIGNATION: DEMONSTRATOR
DEPARTMENT: MEDICAL LAB TECHNOLGY

HEMATOLOGY
Hematology is the study of blood, blood-forming
organs and blood diseases. In the medical
field, hematology includes the treatment of blood
disorders and malignancies, including types of
hemophilia, leukemia, lymphoma and anemia
HEMA = BLOOD
TOLOGY = STUDY

The average human has 5 litres of blood(Average
Blood Volume is 4 to 6 liters).
 It is a transporting fluid
 It carries vital substances to all parts of the body
 Blood is the only fluid tissue.
 Blood is a complex connective tissue in which living
cells, the formed elements, are suspended in the
nonliving fluid called plasma.
Composition of Blood
Formed Elements : Erythrocytes, Leukocytes , Platelets &
Plasma.
Blood

Blood composition
55% Plasma (fluid matrix of water, salts, proteins, etc.)
45% Cellular elements:

 Red Blood Cells (RBCs): 5-6 million RBCs/ml of blood. Contain
hemoglobin which transport oxygen and CO2.
White Blood Cells (WBCs): 5,000-10,000 WBCs/ml of blood.
Play an essential role in immunity and defense. Include:


 Lymphocytes: T cells and B cells
Macrophages: (phagocytes)
Granulocytes: Neutrophils, basophils, and eosinophils.
 Platelets: Cellular fragments, 250,000- 400,000/ml of blood.
Important in blood clotting.

Physical Characteristics and Volume
Sticky and metallic tasting…
Color: Scarlet = O2 rich; Dull red = O2
poor
Heavier than H2O; 5X thicker
Normal pH = 7.35 - 7.45
Temp = 38ºC or 100.4ºF (higher than
normal)
8% body weight; 5 - 6 liters (for example a
person is 70kg then we can find blood
volume by using this formula 8×70÷100=
5.6liters

 Centrifuged blood
55% Plasma: Serum and fibrinogen
<1% Buffy Coat: White blood cells
(leukocytes)
45% Red blood cells (erythrocytes)
Hematocrit: RBC volume = ~45%

plasma (55%)
red blood cells
(5-6-million /ml)
white blood cells
(5000/ml)
platelets

Plasma
Straw-colored liquid.
Consists of H20 and dissolved
solutes.
Ions, metabolites, hormones,
antibodies.
Na+ is the major solute of the
plasma.
liquid part of blood
Plasma transports
soluble food molecules
waste products
hormones
antibodies

 90% of plasma is water:
 >100 other substances in plasma: salts (electrolytes),
nutrients, gases, hormones, plasma proteins, various
wastes and products of cell metabolism.
 Plasma proteins:
 Constitute 7-9% of plasma.
 Provide the colloid osmotic pressure needed to draw H20
from interstitial fluid to capillaries.




Maintain blood pressure.
Albumin:. Maintains osmotic pressure of
blood. Clotting proteins
Antibodies



Constitute 7-9% of plasma
Three types of plasma proteins: albumins, globulins, &
fibrinogen

 Albumin accounts for 60-80, plasma protein made by the
liver, Creates colloid osmotic pressure that draws H20 from
interstitial fluid into capillaries to maintain blood volume &
pressure
Globulins carry lipids
  globulin: Transport lipids and fat soluble vitamins.
  globulin: Transport lipids and fat soluble vitamins.
  globulin:Antibodies that function in immunity.

Gamma globulins are antibodies
Fibrinogen Constitutes 4% of plasma proteins. Important clotting
factor. Converted into fibrin during the clotting process.
Serum is fluid left
when
blood
clots

 Composition of plasma is kept
relatively constant:
 Liver replenishes blood proteins…
 Respiratory system and kidneys maintain pH
(acidosi
s
= too acid; alkalosis = too basic)
 Plasma helps maintain body heat.

for
ga
s
 Erythrocytesor RBCs
 Anucleate - they lack a nucleus
 Filled with hemoglobin which carries
oxygen
 Biconcave discs = greater surface
area exchange.
 5X106 cells/mm3 of
 Half-life ~ 120 days.
 Contain 280 million hemoglobin with 4 heme chains
(contain iron).

RED BLOOD CELLS SPECIALISATIONS
2) no nucleus
 extra space inside
3) contain haemoglobin
 the oxygen carrying
molecule
1) biconcave shape
increases the
surface area so
more oxygen can be
carried

 Are erythrocytes (RBCs) &
leukocytes (WBCs)
 RBCs are flattened
biconcave discs
 Shape provides increased
surface area for diffusion
 Lack nuclei & mitochondria
 Each RBC contains 280
million hemoglobins

HAEMOGLOBIN
blood cells
 gives red
their colour
 can carry up to 4
molecules of O2
and
 associates
dissociates with O2
 contains iron

 Red blood cells (RBCs)
 transport oxygen
 specialised to do this
 Also carry some CO2

Erythrocytesor
RBCs
While number of RBCs in the blood is
important….hemoglobin is the key.
The more hemoglobin molecules the RBCs
contain, the more oxygen they can carry.
1RBC - 250 million molecules of
hemoglobin, each binding 4
molecules of oxygen.

When there is a high concentration of oxygen e.g
in the alveoli haemoglobin combines with oxygen to
form oxyhaemoglobin. When the blood reaches the
tissue which have a low concentration of oxygen
the haemoglobin dissociates with the oxygen and
the oxygen is released into body tissues
FUNCTION OF HAEMOGLOBIN

 Anemia results from:
 Lower # RBCs
 Deficient
hemoglobin

 Hemorrhagic anemia: sudden hemorrhage
 Hemolytic anemia: lysis of RBCs from bact. infection
 Pernicious anemia: lack of B12
 Aplastic anemia: depression/destruction of
bone marrow by cancer, radiation, meds.

 Sickle Cell Anemia:
 Deficient hemoglobin - a point mutation
changes a single amino acid.

 Polycythemia - abnormal increase in
erythrocytes, caused by:
 Bone marrow cancer
 High altitudes
 Thickens and slows blood,
impairs circulation



Complete cells (nuclei, mitochondria and organelles)
Move in amoeboid fashion. Can squeeze (leave the blood vessels
through) capillary walls (diapedesis), respond to chemicals
 Almost invisible, so named after stains.
 Neutrophils are the most abundant WBC, accounts for 50 – 70% of
WBCs.
 Involved in immune function. Crucial for defense.
 Positive chemotaxis: they respond to chemical signals and move
toward damage or threats.
 Body increases amount in response to infection
 Leukocytosis: more than 11,000 cells/mm3 indicates infection
 Leukopenia: abnormally low, usually due to corticosteroids
and chemotherapy.

White blood cells
 the bodies “defence”
 part of the immune system
 much larger than RBCs
 far fewer
 have a nucleus
 4000-13000 per mm3
 2 types: phagocytes and
lymphocytes

 Have nucleus, mitochondria, & amoeboid
ability
 Can squeeze through capillary walls
(diapedesis)
 Granular leukocytes help detoxify
foreign substances & release heparin
 Include eosinophils, basophils, & neutrophils

 Agranular leukocytes are phagocytic
& produce antibodies
 Include lymphocytes & monocytes

 Granulocyte
s

Granules in their cytoplasm can be stained
Include neutrophils, eosinophils, and
basophils
 Agranulocyte
s

Lack visible cytoplasmic granules
Include lymphocytes and
monocytes

 Neutrophil
s

Multi-lobed nucleus with fine granules
Act as phagocytes at active sites of
infection
 Eosinophil
s

Large brick-red cytoplasmic granules
Found in response to allergies and parasitic
worms
 Basophil
s

Have histamine-containing
granules Initiate inflammation

 Lymphocyte
s

Nucleus fills most of the cell
Play an important role in the immune
response
 Monocyte
s


Largest of the white blood
cells Function as
macrophages
Important in fighting chronic
infection

Provide a specific immune responseto
infectious diseases.
There are 2 types: -
-T-cells & B-cells
They produce antibodies.

 Also called thrombocytes.
 Derived from ruptured multinucleate cells (megakaryocytes)
 Smallest of formed elements.


Are fragments of megakaryocytes.
Lack nuclei.


Normal platelet count = 300,000/mm3
Survive 5-9 days
 Have amoeboid movement.
 Important in blood clotting:
 Constitute most of the mass of the clot.
 Release serotonin to reduce blood flow to area.
 Secrete growth factors
 Maintain the integrity of blood vessel wall.

PHAGOCYTES
 Monocytes and macrophages
 Provide a non-specific response to infection

HEMATOPOIESIS
 Is formation of blood cells from stem cells in
marrow (myeloidtissue) & lymphoid tissue
 Erythropoiesis is formation of RBCs
 Stimulated by erythropoietin (EPO) from
kidney
 Leukopoiesis is formation of WBCs
 Stimulated by variety of cytokines
 = autocrine regulators secreted by immune system

Formation of blood cells
2 types of hematopoiesis:
Erythropoiesis:
 Formation of RBCs.
Leukopoiesis:
 Formation of WBCs.
Occurs in myeloid tissue (bone marrow of long bones)
and lymphoid tissue.
Stem cells differentiate into blood cells.

 Active process.
 2.5 million RBCs are produced every
second.
 Regulated by erythropoietin.
 Erythropoietin binds to membrane
receptors, stimulating cell division.
 Old cells are destroyed in spleen and liver.
 Iron recycled back to myeloid tissue to be
reused in RBC synthesis.
 Need iron, vitamin B12 and folic acid for synthesis.

Cytokinesstimulate different types and stages of
WBCsproduction
Multi potent growth factor- 1 , interleukin-1 ,
and interleukin- 3:
 Stimulate development of different types of
WBC cells.
Granulocyte- colony stimulating
factor:
 Stimulates development of neutrophils.
Granulocyte- monocyte colony
stimulating factor:
 Simulates development of monocytes
and eosinophil's.

 2.5 million RBCs are
produced/sec
 Lifespan of 120 days
 Old RBCs removed
from blood by
phagocytic cells in
liver, spleen, & bone
marrow
 Iron recycled back into
hemoglobin production

Types of Blood Vessels
Arteries and Arterioles
Carry blood away from heart to body.
Have high pressure.
Have thick muscular walls, which make them elastic and
contractile.
 Vasoconstriction: Arteries contract:

 Reducing flow of blood into
capillaries. Increasing blood
pressure.
 Vasodilation: Arteries
relax:
 Increasing blood flow into
capillaries.
 Decreasing blood pressure.

Capillaries




Only blood vessels whose walls are thin enough to permit
gas exchange.
Blood flows through capillaries relatively slowly, allowing
sufficient time for diffusion or active transport of substances
across walls.
Only about 5 to 10% of capillaries have blood flowing through
them. Only a few organs (brain and heart) always carry full load
of blood.
Blood flow to different organs is controlled by pre capillary
sphincters of smooth muscle.

Veins and Venules
Collect blood from all tissues and organs and carry it back
towards heart.
Have low pressure and thin walls.
Veins have small valves that prevent backflow of blood towards
capillaries, especially when standing. If the valves cease to work
properly, may result in:

 Varicose veins: Distended veins in thighs and legs.
Hemorrhoids: Distended veins and inflammation of the
rectal and anal areas.

Lymphatic and Immune System
Defends against infection: bacteria, fungi, viruses, etc.
Destruction of cancer and foreign cells.
Synthesis of antibodies and other immune molecules.
Synthesis of white blood cells.
Components: Lymph, lymphatic vessels, bone marrow,
thymus, spleen, and lymph nodes.
Functions:




Homeostatic
Role:
 Returns fluid and proteins that have leaked from
blood capillaries into tissues.


Up to 4 liters of fluid every day.
Fluid returned near heart/venae
cavae.

RBC Antigens & Blood Typing
The most well known and medically important blood
types are in the ABO group. They were discovered in 1900
and 1901 at the University of Vienna by Karl Landsteiner in
the process of trying to learn why blood transfusions
sometimes cause death and at other times save a patient. In
1930, he belatedly received the Nobel Prize for this discovery.
All humans and many other primates can be typed for
the ABO blood group. There are four principal types: A, B,
AB, and O. There are two antigens and two antibodies that
are mostly responsible for the ABO types. The specific
combination of these four components determines an
individual's type in most cases.

ABO
Blood Type
Antigen
A
Antigen
B
Antibody
anti-A
Antibody
Anti-B
A yes no no yes
B no yes yes no
O no no yes yes
AB yes yes no no

People with type A blood will have the A antigen on the surface of their
red cells . As a result, anti-A antibodies will not be produced by them
because they would cause the destruction of their own blood. However,
if B type blood is injected into their systems, anti-B antibodies in their
plasma will recognize it as alien and burst or agglutinate the introduced
red cells in order to cleanse the blood of alien protein.

Individuals with type O blood do not produce ABO antigens.
Therefore, their blood normally will not be rejected when it is given to
others with different ABO types. As a result, type O people are
universal donors for transfusions, but they can receive only type O
blood themselves.
ABO antibodies.
other ABO type.
Those who have type AB blood do not make any
Their blood does not discriminate against any
Consequently, they are universal receivers for
transfusions, but their blood will be agglutinated when given to people
with every other type because they produce both kinds of antigens.
It is easy and inexpensive to determine an individual's ABO
type from a few drops of blood. A serum containing anti-A
antibodies is mixed with some of the blood. Another serum with
anti-B antibodies is mixed with the remaining sample. Whether or
not agglutination occurs in either sample indicates the ABO type. It
is a simple process of elimination of the possibilities. For instance, if
an individual's blood sample is agglutinated by the anti-A antibody,
but not the anti-B antibody, it means that the A antigen is present
but not the B antigen. Therefore, the blood type is A.

 ABOsystem:
 Major group of antigens of RBCs.
 Type A:
 Only A antigens present.
 Type B:
 Only B antigens present.
 Type AB:
 Both A and B antigens
present.
 Type O:
 Neither A or B antigens

 Each person inherits 2 genes that control
the production of ABO groups.
 Type A:


May have inherited A gene from each parent.
May have inherited A gene from 1 parent and O
gene from the other.

 Type
B
:


May have inherited B gene from each parent.
May have inherited B gene from 1 parent and O
gene from the other parent.
 Type
AB
:
 Inherited the A gene from one parent and the B
gene from the other parent.
 Type O:
 Inherited O gene from each
parent.

People with blood group 0 Rh - are called "universal donors" and
people with blood group AB Rh+ are called "universal receivers."
Rh+ blood can never be given to someone with Rh - blood, but the
other way around works. For example, 0 Rh+ blood can not be given
to someone with the blood type AB Rh -.

 People with Type A
blood make antibodies
to Type B RBCs, but not
to Type A




Type B blood has antibodies
to Type A RBCs but not to
Type B
Type AB blood doesn’t
have antibodies to A or B
Type O has antibodies to
both Type A & B
If different blood types are
mixed, antibodies will
cause mixture to
agglutinate

 If blood types do not match, the recipient’s
antibodies attach to donor’s RBCs and agglutinate.
 Type O


Universal donor.
Recipient’s antibodies cannot agglutinate the
donor’s RBCs.
 Type AB
Universal
recipient


Lack the anti-A and anti-B
antibodies. Cannot agglutinate
donor’s RBCs.

 Another group of antigens found on RBCs.
 Rh positive:
 Have these antigens.
 Rh negative:
 Do not have these antigens.
 Significant when Rh negative mother give birth
to Rh positive baby.

 At birth, mother may become exposed to Rh
positive blood of fetus.
Mother at subsequent pregnancies may
produce antibodies against the Rh factor.

 If blood types don't
match,
recipient’s
antibodie
s agglutinate donor’s RBCs
 Type O is “universal
donor” because lacks A &
B antigens
antibodies
won’t
donor’s Type
O
 Recipient’
s
agglutinat
e RBCs
 Type AB is
“universal
recipient” because doesn’t
make anti-A or anti-B
antibodies
 Won’t agglutinate donor’s
RBCs
 Insert fig. 13.6

 Is cessation of bleeding
 Promoted by reactions initiated by vessel injury
 Breakage of endothelial lining exposes collagen
proteins causing:



Vasoconstrictio
n. Platelet plug.
Web of fibrin.

 Platelets don't stick to intact endothelium because of
presence of prostacyclin (PGI2--a prostaglandin)
& NO
 Keep clots from forming & are vasodilators

 Damage to
endothelium
exposed
collagen
allows platelets to bind to
increases bond by binding to both
 von Willebrand
factor collagen &
platelets
 Platelets stick to collagen & release ADP, serotonin, &
thromboxane A2
 = platelet release reaction

 Serotonin & thromboxane A2
stimulate vasoconstriction, reducing
blood flow to wound
thromboxane A2 cause other platelets to
sticky & attach & undergo platelet
release
 ADP &
becom
e
reactio
n
 This continues until platelet plug is
formed

 Platelets normally repelled away from
endothelial lining by prostacyclin
(prostaglandin).
 Do not want to clot normal vessels.

 Exposes sub endothelial tissue to
blood.
 Platelet release reaction:

 Endothelial cells secrete von Willebrand factor to
cause platelets to adhere to collagen.
Platelet secretory granules release ADP
,
serotonin and thromboxane A2.

 Serotonin and thromboxane A2 stimulate
make other
platelets
vasoconstriction.
 ADP and thromboxane
A2 “sticky”.
of plasma
clotting
 Platelets adhere to
collagen.
 Produce platelet plug.
 Strengthened by
activation
factors.

forms a
more
 Platelet plug strengthened by
fibrin.
 Clot reaction:
 Contraction of the platelet
mass compact plug.
 Conversion of fibrinogen to fibrin occurs.
 Fluid squeezed from the clot is called
serum (plasma without fibrin).

Intrinsic
Pathwa
y
Initiated by exposure of blood to a negatively
charged surface (collagen).
This activates Factor XII (protease), which
activates other clotting factors.
Ca++ and phospholipids convert prothrombin
to thrombin.
Thrombin converts fibrinogen to fibrin.
Produces meshwork of insoluble fibrin polymers.






 Thromboplastin is not a part of the blood,
so called extrinsic pathway.
 Damaged tissue release a thromboplastin.
 Thromboplastininitiates a short cut to
formation of fibrin.

 Activated factor XII converts an inactive
molecule into the active form (kallikrein).
 Kallikrein converts plasminogen to plasmin.
 Plasmin is an enzyme that digests the fibrin.
 Clot dissolution occurs.

 When damage is repaired, activated factor
XII causes activation of kallikrein
 Kallikrein converts plasminogen to
plasmin
 Plasmin digests fibrin, dissolving clot

 Clotting can be prevented by Ca+2 chelators
(e.g. sodium citrate or EDTA)
 or heparin which activates antithrombin
III (blocks thrombin)
 Coumarin blocks clotting by
inhibiting activation
of Vit K
 Vit K works indirectly by reducing Ca+2 availability

Introduction to hema

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