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HAEMATOLOGYBy

C. RONALD DARWIN.., M.Pharm, (PhD)

DEPARTMENT OF PHARMACOLOGY & PHYSIOLOGYK.K COLLEGE OF PHARMACY

[email protected]


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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%3Dactive


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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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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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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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