HAEMATOLOGY

By
C. RONALD DARWIN.., M.Pharm, (PhD)
DEPARTMENT OF PHARMACOLOGY & PHYSIOLOGY K.K COLLEGE OF PHARMACY CHENNAI-22
ronaldpharma@gmail.com

HAEMATOLOGY
Contents:Blood
Composition Function

Hematopoiesis
Disorders

COMPOSITION
Formed elements
Cells(45%) ERYTHROCYTES (RBC) LEUCOCYTES (WBC) THROMBOCYTE (PLATLETS)

Plasma(55%)
Fluid

COMPOSITION CONT..,

COMPOSITION CONT..,

Centrifuged blood Plasma55% Hematocrit(WBC &RBC) 45%

COMPOSITION CONT..,

Hematocrit
Percentage of blood occupied by cells female normal range 38 - 46% (average of 42%) male normal range 40 - 54% (average of 46%) testosterone

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 fluid Maintenance of osmotic pressure

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,

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

Plasma proteins cont..,

Substance
(1) Plasma proteins, eg. fibrinogen, antibodies
(2) Lipids (3) Glucose (4) Amino acids (5) Hormones (6) Mineral salts

Function in the body

Body defence
Energy reserve, heat insulation Energy release Forms proteins Regulation body functions Regulate body activities

(7) Urea
(8) Carbon dioxide

Metabolic waste
Metabolic waste

Serum
Plasma with clotting factors removed Let blood sit, pour off supernatant

FORMED ELEMENTS

RBCs (Erythrocytes) WBCs (Leukocytes)

Granulocytes
Neutrophils Eosinophils Basophils
Monocytes Lymphocytes

Agranulocytes

Platlets

BLOOD SMEAR

Light microscope Stained

ERYTHROCYTES
Biconcave disc shape
surface area efficiency for diffusion of O2 & CO2

7-8 m diameter

ERYTHROCYTES
STRUCTURE
Plasma membrane Cytoplasm Hemoglobin Binds O2 & CO2 No nucleus
Elastic 100-120 day life span Originate in bone marrow

ERYTHROCYTES STRUCTURE cont..,

HEMOGLOBIN O2 TRANSPORT

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

Structure and function of Haemoglobin..,

Normal values of Hb
Male:-14-17gm% Female:- 2-16gm%

Oxyhemoglobin & Carboxyhemoglobin..,

Compounds of hemoglobin
Oxyhemoglobin Hb combines with Oxygen Methahemoglobin Fe2+ is oxidized to Fe3+ Carboxyhemoglobin Hb combines with Co2

LEUKOCYTES (WBC)
Originate in bone marrow Part of defense system Attracted to sites of infection Diapedesis Ameboid movement

DIAPEDESIS

GRANULOCYTES
Neutrophils Eosinophils Basophils

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

EOSINOPHILS
1-4% of WBCs Lobed nucleus Eosin-staining granules Phagocytize allergen-Ab complexes Secrete antihistamine Attack parasites

BASOPHILS
0.5% of WBCs Lobed nucleus Large granules stained dark purple Granules Histamine creates inflammation in allergic reaction

MONOCYTES
Agranulocyte 4-8% of WBCs Horseshoe shaped nucleus Grey-blue stained cytoplasm Become wandering macrophages after diapedesis

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

LYMPHOCYTES cont..,
T lymphocytes can attack foreign cells directly

LYMPHOCYTES cont..,
B lymphocytes transform into plasma cells and secrete antibodies

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)

Summary of formed elements

Property RBC WBC Platelets

Site of formation

formed in bone marrow, life-span: 4 months biconcave discs, no nucleus, red colour

formed in bone marrow or thymus phagocytes: irregular, lobed nucleus & granular cytoplasm

formed in blood marrow

Shape

irregular shape, no nucleus, tiny pieces of cell fragments, no colour tiny cell fragments

Size

small in size

some large & some small

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

FORMATION OF BLOOD

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

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 divide and 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 & T lymphocytes in the lymphatic tissue after leaving the red marrow

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

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

Formation and Destruction of RBCs

Formation of Leukocytes

PROPERTIES OF BLOOD

HAEMOSTASIS

HAEMOSTASIS cont..,

SEM of a clot with Platelet, Fibrin mesh, RBCs

Haemostasis cont..,

Haemostasis cont..,

Dissolving the Clot and Anticoagulants

Haemostasis overview
BV Injury
Contact/ Tissue Factor

Neural

Blood Vessel Constriction

Platelet Aggregation Primary haemostatic plug Platelet Activation

Coagulation Cascade

Reduced Blood flow

Fibrin formation

Stable Haemostatic Plug

Blood Typing
(ABO blood grouping system)
ANTIGEN any 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.
ANTIBODY an immune or protective protein (usually associated with a particular type of cell) that is characterized by reacting with a a specific antigen.

Blood Typing ..,

Blood Typing ..,

Blood Typing ..,

Blood Typing ..,

Blood type being tested RBC agglutinogens (Contains antigens) Serum Reaction (Contains antibodies) Anti-A AB B A O A and B B A None + + Anti-B + +

Production of antibodies to antigens..,

The "A and "B" antigens are also produced by some other plants and microorganisms. Thus, individuals who do not recognize one or more of these antigens as "self" will produce antibodies against the plant or microbial antigens. These antibodies will also react with human antigens of the same kind whether introduced via a blood transfusion or a tissue graft.

Possible Blood group Genotypes

Parent A B O

A
B O

AA
AB AO

AB
BB BO

AO
BO OO

Blood Transfusions
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. Universal Donor 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 can receive any blood type. Rh + Can receive + or Rh - Can only receive -

Universal Recipient

The Rhesus (Rh) System

Well, it gets more complicated here, because there's another antigen 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 will therefore 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

Rh antigens are transmembrane proteins with loops exposed at the surface of red blood cells. They appear to be used for the transport of carbon dioxide and/or ammonia across the plasma membrane. They are named for the rhesus monkey in which they were first discovered. 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.

The Rhesus (Rh) System cont..,

Scientists sometimes study Rhesus monkeys to learn more about the human anatomy because there are certain similarities between the two species. While studying Rhesus monkeys, a certain blood protein 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 referred to 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 not contain the protein, your blood is said to be Rh negative (Rh-).

The Rhesus (Rh) System

Person with Rh- blood can develop Rh 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.

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 AB foetus is resistant to sensitisation to the Rh antigen.

Her anti-A and anti-B antibodies destroy any foetal cells that enter her blood before they can elicit anti-Rh antibodies in her. This phenomenon has led to an effective preventive measure to avoid Rh sensitisation. Shortly after each birth of an Rh+ baby, the mother is given an injection of anti-Rh antibodies (or Rhogam).
These passively acquired antibodies destroy any foetal cells that got into her circulation before they can elicit an active immune response in her.

During Pregnancy..,

DISORDERS OF BLOOD

DISORDERS OF BLOOD..,

Erythrocyte disorder
Polycythaemia (increase)
Polycythemia vera Secondary polycythemia Blood doping

Anemia (decrease)

ERYTHROCYTE DISORDERS
Polycythemia Abnormal excess of erythrocytes Increases viscosity, decreases flow rate of blood Anemia blood has abnormally low oxygen-carrying capacity It is a symptom rather than a disease itself Blood oxygen levels cannot support normal metabolism Signs/symptoms include fatigue, paleness, shortness of breath, and chills

ERYTHROCYTE DISORDERS cont.., (Anemia)

Anemia: Insufficient Erythrocytes Hemorrhagic anemia result of acute or chronic loss of blood Hemolytic anemia prematurely ruptured erythrocytes Aplastic anemia destruction 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.., (Anemia)

Pernicious anemia results from: Deficiency of vitamin B12 Lack of intrinsic factor needed for absorption of B12 Treatment is intramuscular injection of B12 Thalassemias absent or faulty globin chain in hemoglobin Erythrocytes are thin, delicate, and deficient in hemoglobin Sickle-cell anemia results from a defective gene Codes for an abnormal hemoglobin called hemoglobin S (HbS) This defect causes RBCs to become sickle-shaped in low oxygen situations

Leukocytes Disorders:
Leukemias Leukemia refers to cancerous conditions involving white blood cells Leukemias are named according to the abnormal white blood cells involved Myelocytic leukemia involves myeloblasts Lymphocytic leukemia involves lymphocytes Acute leukemia involves blast-type cells and primarily affects children Chronic leukemia is more prevalent in older peopleImmature white blood 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 marrow transplants

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.

The Problems with Clotting Cascade

Hemophilia A: Deficiency of Factor VIII accounts for 85% cases.
Almost exclusively in males. Females are usually carriers caused by a gene mutation on the X chromosome. Occurs in about 1/10,000 male births

Other Hemophilias account for another 15%

Hemophilia B (Factor IX) Hemophilia C (Factor XI) Hemophilia D (Factor XII)

Thank you!