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HAEMATOLOGYBy
C. RONALD DARWIN.., M.Pharm, (PhD)
DEPARTMENT OF PHARMACOLOGY & PHYSIOLOGYK.K COLLEGE OF PHARMACY
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HAEMATOLOGYContents:-
Blood Composition
Function
Hematopoiesis Disorders
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COMPOSITION
Formed elements
Cells(45%)
ERYTHROCYTES (RBC)
LEUCOCYTES (WBC)
THROMBOCYTE (PLATLETS)
Plasma(55%)
Fluid
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COMPOSITION CONT..,
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COMPOSITION CONT..,
Centrifuged bloodPlasma55%
Hematocrit(WBC &RBC) 45%
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COMPOSITION CONT..,
Hematocrit Percentage of blood
occupied by cells
female normal range
38 - 46% (averageof 42%)
male normal range
40 - 54% (average
of 46%)
testosterone
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FUNCTION OF BLOOD
Transport of Food nutrients
Transport of Waste products of metabolism
Transport of Respiratory gases such as O2&Co2
Transport of Hormones secreted
Protect out body against foreign agents
Maintenance of pH of the body fluidMaintenance of osmotic pressure
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Plasma
Water 92%
Solutes 8%
plasma proteins
Ions, e.g., Na+, Cl-, Ca++
Nutrients, e.g., simple sugars, amino acids, lipids
Wastes, e.g., urea, ammonia, CO2
Miscellaneous: O2, hormones, vitamins,
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Plasma proteins
Albumin(60%)
Synthesized in liver
Helps control osmotic pressure
Helps control diffusion of water (recall edema)
Transport of Bilirubin and free fatty acid
Globulin (36%) Alpha, Beta globulins from liver
and Gamma globulins from lymphatic tissues
Includes antibodies (Abs)
Transport proteins (lipids, iron, copper, etc.)
Fibrinogen (4%) Produced in liver
Involved in clotting
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Substance Function in the body
(1) Plasma proteins,
eg. fibrinogen, antibodies
Body defence
(2) Lipids Energy reserve, heat insulation
(3) Glucose Energy release
(4) Amino acids Forms proteins
(5) Hormones Regulation body functions
(6) Mineral salts Regulate body activities
(7) Urea Metabolic waste
(8) Carbon dioxide Metabolic waste
Plasma proteins cont..,
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Serum
Plasma with clotting factors removed
Let blood sit, pour off supernatant
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FORMED ELEMENTS
RBCs (Erythrocytes)
WBCs (Leukocytes)
Granulocytes
Neutrophils Eosinophils
Basophils
Agranulocytes Monocytes
Lymphocytes
Platlets
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BLOOD SMEAR
Light microscope Stained
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Biconcave disc shape
surface area
efficiency for diffusion
of O2 & CO2
7-8 m diameter
ERYTHROCYTES
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ERYTHROCYTESSTRUCTURE
Plasma membrane
Cytoplasm
Hemoglobin
Binds O2 & CO2 No nucleus
Elastic
100-120 day life span
Originate in bone marrow
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ERYTHROCYTES
STRUCTURE cont..,
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HEMOGLOBIN O2 TRANSPORT
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Structure and function of Haemoglobin..,
Synthesis begins in proerythroblast 65% at erythroblast stage
35% at reticulocyte stage
Two parts Haem
Globin
Haem & globin produced at two different sites in
the cells Haem in mitochondria
Globin in polyribosomes
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Structure and function of Haemoglobin..,
Normal values of Hb
Male:-14-17gm%
Female:- 2-16gm%
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Oxyhemoglobin & Carboxyhemoglobin..,
Compounds of hemoglobin
Oxyhemoglobin
Hb combines with Oxygen
Methahemoglobin
Fe2+ is oxidized to Fe3+
CarboxyhemoglobinHb combines with Co2
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LEUKOCYTES (WBC)
Originate in bone marrow
Part of defense system
Attracted to sites of infection
Diapedesis
Ameboid movement
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DIAPEDESIS
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GRANULOCYTES
Neutrophils
Eosinophils
Basophils
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NEUTROPHILS
60% of WBCs
Lobed nucleus
Light staining granules
Digestive enzymes
Function
Phagocytize & destroy bacteria
First cells to respond to infection
Secrete antibacterial chemicals
Phagocytize & digest bacteria
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EOSINOPHILS
1-4% of WBCs
Lobed nucleus
Eosin-staining granules
Phagocytize allergen-Ab complexes
Secrete antihistamine
Attack parasites
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BASOPHILS
0.5% of WBCs
Lobed nucleus
Large granules stained dark purple
Granules Histaminecreates inflammation in allergic reaction
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MONOCYTES
Agranulocyte
4-8% of WBCs
Horseshoe shaped nucleus
Grey-blue stained cytoplasm
Become wandering macrophages after diapedesis
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LYMPHOCYTES
Agranulocyte
20-45% of WBCs
Spherical, dark-staining nucleus
Thin rim of blue staining cytoplasm
Each lymphocyte recognizes and acts against a
specific antigen
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LYMPHOCYTES cont..,
T lymphocytes can attack foreign cells directly
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LYMPHOCYTES cont..,
B lymphocytes transform into plasma cells and
secrete antibodies
PLATELETS
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PLATELETS
(THROMBOCYTES) Formed from megakaryocytes (large cell from red bone marrow)
Nucleus is absent, cell is round disc shaped
Count-1,30,000-3,60,000
Hormone: Thrombopioetin
The release serotonin (contracts blood vessel)
http://images.google.com/imgres?imgurl=http://www.purezenergy.com/bryan_brandenburg/blood_platelet.jpg&imgrefurl=http://bryanbrandenburg.blog.com/1317824/&h=800&w=800&sz=110&hl=en&start=1&um=1&tbnid=OC66dW1rjfxhzM:&tbnh=143&tbnw=143&prev=/images%3Fq%3Dpictures%2Bof%2Bblood%2Bplatelets%26svnum%3D10%26um%3D1%26hl%3Den%26safe%3Dactive8/3/2019 logy Darwin
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Property RBC WBC Platelets
Site of formation formed in bone marrow,
life-span:
4 months
formed in bone marrow or
thymus
formed in blood marrow
Shape biconcave discs,no nucleus,
red colour
phagocytes: irregular,lobed nucleus & granular
cytoplasm
irregular shape, nonucleus,
tiny pieces of cell
fragments,
no colour
Size small in size some large & some small tiny cell fragments
Number 5,000,000 /mm3 7,000 /mm3 250,000/mm3
Function contain hemoglobin to carry
oxygen from lungs to all
parts of body
Defense mechanism for blood clotting
Summary of formed elements
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FORMATIONOF
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HEMATOPOIESIS
Occurs in red marrow
Red marrow replaced by yellow in limbs between
8-18 yrs
Blood stem cells
Pleuripotential
Myeloid stem cell
Lymphoid stem cells
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Stages of Blood Cell Formation
Pluripotent stem cells
.1% of red marrow cells
Myeloid stem cell line of development continues:
progenitor cells(colony-forming units) no longer can divideand are specialized to form specific cell types
next generation is blast cells
develop within several divisions into mature cell types
Lymphoid stem cell line of development
pre-B cells & prothymocytes finish their develop into B & Tlymphocytes in the lymphatic tissue after leaving the redmarrow
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Hemopoietic Growth Factors
Regulate differentiation & proliferation
Erythropoietin (EPO)
produced by the kidneys increase RBC precursors
Thrombopoietin (TPO)
hormone from liver stimulates platelet formation
Cytokines are local hormones of bone marrow
produced by some marrow cells to stimulate proliferation in
other marrow cells
colony-stimulating factor (CSF) & interleukin stimulate
WBC production
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ERYTHROPOIESIS
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
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Formation and Destruction of RBCs
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Formation of Leukocytes
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PROPERTIESOF
BLOOD
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HAEMOSTASIS
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HAEMOSTASIS cont..,
SEM of a clot with Platelet, Fibrin mesh, RBCs
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Haemostasis cont..,
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Haemostasis cont..,
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Dissolving the Clot and Anticoagulants
H t i i
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Haemostasis overview
BV Injury
PlateletAggregation
Platelet
Activation
Blood VesselConstriction
Coagulation
Cascade
Stable Haemostatic Plug
Fibrinformation
Reduced
Blood flow
Contact/
Tissue
Factor
Primary haemostatic plug
Neural
Bl d T i
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Blood Typing(ABO blood grouping system)
ANTIGENany substance that, as a result of coming into contact with
appropriate tissues, induces a state of sensitivity and which reacts in a
demonstrable way with tissues of the sensitized subject.
ANTIBODYan immune or protective protein (usually associated with aparticular type of cell) that is characterized by reacting with a a specific antigen.
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Blood Typing ..,
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Blood Typing ..,
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Blood Typing ..,
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Blood Typing ..,
Blood type being
tested
RBC agglutinogens
(Contains antigens)
Serum Reaction
(Contains antibodies)
Anti-A Anti-BAB A and B + +B B +A A + O None
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Production of antibodies to antigens..,
The "A and "B" antigens are also producedby some other plants and microorganisms.Thus, individuals who do not recognize one or
more of these antigens as "self" will produceantibodies against the plant or microbialantigens.
These antibodies will also react with human
antigens of the same kind whether introducedvia a blood transfusion or a tissue graft.
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Parent A B OA AA AB AOB AB BB BOO AO BO OO
Possible Blood group Genotypes
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A blood transfusion is a procedure in which blood is given to a patient through an
intravenous (IV) line in one of the blood vessels. Blood transfusions are done to replace
blood lost during surgery or a serious injury. A transfusion also may be done if a persons
body can't make blood properly because of an illness.
Who can give you blood?
People with TYPE O blood are called
Universal Donors, because they can give
blood to any blood type.
People with TYPE AB blood are called
Universal Recipients, because they canreceive any blood type.
Rh + Can receive + or -Rh - Can only receive -
Universal Donor
Universal Recipient
Blood Transfusions
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Well, it gets more complicated here, because there's anotherantigen to be considered - the Rh antigen.
Some of us have it, some of us don't.
If it is present, the blood is RhD positive, if not it's RhD negative.
So, for example, some people in group A will have it, and willtherefore be classed as A+ (or A positive).
While the ones that don't, are A- (or A negative).
And so it goes for groups B, AB and O.
The Rhesus (Rh) System
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The Rhesus (Rh) System
Rh antigens are transmembrane proteins with loops exposed at thesurface of red blood cells.
They appear to be used for the transport of carbon dioxide and/or ammoniaacross the plasma membrane.
They are named for the rhesus monkey in which they were firstdiscovered.
RBCs that are "Rh positive" express the antigen designated D.
85% of the population is RhD positive, the other 15% of the population is
running around with RhD negative blood.
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Scientists sometimes study Rhesus monkeys tolearn more about the human anatomy because thereare certain similarities between the two species.While studying Rhesus monkeys, a certain bloodprotein was discovered. This protein is also present
in the blood of some people. Other people,however, do not have the protein.
The presence of the protein, or lack of it, is referredto as the Rh (for Rhesus) factor.
If your blood does contain the protein, your blood is
said to be Rh positive (Rh+). If your blood does notcontain the protein, your blood is said to be Rhnegative (Rh-).
The Rhesus (Rh) System cont..,
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The Rhesus (Rh) System
Person with Rh- blood can developRh antibodies in the blood plasma if
he or she receives blood from a person with Rh+ blood, whose Rh
antigens can trigger the production of Rh antibodies.
Person with Rh+ blood can receive blood from a person with Rh- blood
without any problems.
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During Pregnancy..,
Most anti-A or anti-B antibodies are of the IgM class (large molecules)and these do not cross the placenta.
In fact, an Rh/type O mother carrying an Rh+/type A, B, or ABfoetus is resistant to sensitisation to the Rh antigen.
Her anti-A and anti-B antibodies destroy any foetal cells that enter herblood before they can elicit anti-Rh antibodies in her.
This phenomenon has led to an effective preventive measure to avoidRh sensitisation.
Shortly after each birth of an Rh+ baby, the mother is given an injectionof anti-Rh antibodies (or Rhogam).
These passively acquired antibodies destroy any foetal cells that gotinto her circulation before they can elicit an active immune response inher.
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During Pregnancy..,
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DISORDERSOFBLOOD
DISORDERS OF BLOOD
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DISORDERS OF BLOOD..,
Erythrocyte disorder
Polycythaemia (increase)
Polycythemia vera
Secondary polycythemia Blood doping
Anemia (decrease)
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ERYTHROCYTE DISORDERS
Polycythemia
Abnormal excess of erythrocytes
Increases viscosity, decreases flow rate of blood
Anemiablood has abnormally low oxygen-carryingcapacity
It is a symptom rather than a disease itself
Blood oxygen levels cannot support normal metabolism
Signs/symptoms include fatigue, paleness, shortness ofbreath, and chills
ERYTHROCYTE DISORDERS cont
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ERYTHROCYTE DISORDERS cont..,(Anemia)
Anemia: Insufficient Erythrocytes
Hemorrhagic anemiaresult of acute or chronic loss of blood
Hemolytic anemiaprematurely ruptured erythrocytes Aplastic anemiadestruction or inhibition of red bone
marrowIron-deficiency anemia results from:
A secondary result of hemorrhagic anemia
Inadequate intake of iron-containing foods
Impaired iron absorption
ERYTHROCYTE DISORDERS cont
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ERYTHROCYTE DISORDERS cont..,(Anemia)
Pernicious anemia results from:
Deficiency of vitamin B12
Lack of intrinsic factor needed for absorption of B12
Treatment is intramuscular injection of B12
Thalassemiasabsent or faulty globin chain in hemoglobin
Erythrocytes are thin, delicate, and deficient inhemoglobin
Sickle-cell anemiaresults from a defective gene
Codes for an abnormal hemoglobin called hemoglobinS(HbS)
This defect causes RBCs to become sickle-shaped in lowoxygen situations
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Leukocytes Disorders:
Leukemias
Leukemia refers to cancerous conditions involving white bloodcells
Leukemias are named according to the abnormal white blood cellsinvolved
Myelocytic leukemiainvolves myeloblastsLymphocytic leukemiainvolves lymphocytes
Acute leukemia involves blast-type cells and primarily affects children
Chronic leukemia is more prevalent in older peopleImmature whiteblood cells are found in the bloodstream in all leukemias
Bone marrow becomes totally occupied with cancerous leukocytes
Severe anemia ensues due to excess production of WBCs The white blood cells produced, though numerous, are not functional
Death is caused by internal hemorrhage and overwhelming infections
Treatments include irradiation, antileukemic drugs, and bone marrowtransplants
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Platelets and Abnormal Clotting
Thrombocytopenia: Abnormally low levels of
platelets. Usually below 50,000/ul of blood. In
many cases, specific antibodies are produced
against platelets destroying them Thrombus: Abnormal clot that develops in a blood
vessel.
Embolus: Free thrombic clots carried in the blood
that usually get caught in arterioles in the brain,kidney, and lungs.
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The Problems with Clotting Cascade
Hemophilia A: Deficiency of FactorVIII accounts for 85% cases.
Almost exclusively in males. Females areusually carriers
caused by a gene mutation on the Xchromosome. Occurs in about 1/10,000male births
Other Hemophilias account for another15%
Hemophilia B (Factor IX)
Hemophilia C (Factor XI)
Hemophilia D (Factor XII)
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Thank you!
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