CONTENTS

Introduction Differentiation & proliferation of white blood cells Classification Concept of the pool Properties of white blood cells Mechanism, functions and life span of WBC Description of individual cells Applied aspects Disorders of white blood cells

INTRODUCTION

FACTORS HELPING PROLIFERATION

Interleukins GM-CSF M-CSF SC-F

CLASSIFICATION
A] Depending on the presence or absence of granules 1) Granulocyte with granules a) Neutrophil b) Eosinophil c) Basophil 2) Agranulocyte without granules a) Monocyte b) Lymphocyte
B] Depending on the stains, further the granulocytes are classified as 1) Basophilic granules which takes up the basic stain. 2) Eosinophilic granules which takes up the eosin (acidic) stain. 3) Amphophilic granules which takes both basic and acidic stain.

CONCEPT OF THE POOL

Marrow pool Blood pool Tissue pool

PROPERTIES
1) NORMAL COUNT
AGE
Adults Infants (full term at birth) Infants (1 yr) Children (4-7yr) Children (8-12 yr)

TLC
4,000-11,000 / l 10,000-15,000 / l 6,000-16,000 / l 5,000-13,500 / l 4,500-13,500 / l

DIFFERENTIAL COUNTS IN ADULTS

Polymorphs (Neutrophils) 40-75%

2,000-7,000 / l

Lymphocytes 50%)

(20- 1,500-4,000 / l
200-800 / l 40-400 / l

Monocytes (2-10%) Eosinophils (1-6%)

Basophils (<1%)

10-100 / l

PROPERTIES
Sex Diurnal variations Diapedesis Ameboid movement Chemotaxis phagocytosis

MYELOBLAST
Represants mitotic myeloid component, with transit time of approximately 18 hrs Comprises of 3% BM cells Size -15 to 20 m in diameter Cytoplasm blue Nucleus round or oval with 2 to 5 nucleoli

PROMYELOCYTE
Comprises of 2 to 4 % of BM cells Size 15 to 21 m in diameter Cytoplasm abundant Nucleus round to oval Cells are involved in primary granule formation Cells in mid stage of mitotic compartment with transit time of approximately 24 hrs

MYELOCYTE
Comprises 13 % of BM cells Size 10 to 15 m in diameter Cytoplasm moderate amount & contain various enzymes Nucleus oval to round

METAMYELOCYTE
Size 10 to 15 m in diameter Cytoplasm moderate Nucleus kidney shaped

BAND FORM
Characterized by condensation of nuclear chromatin & transformation of nuclear shape into sausage or band configuration Have uniform diameter through out their length

SEGMENTED NEUTROPHILS
Size 9 to 15 m in diameter Cytoplasm abundant , secondary granules present Nucleus 2 -5 lobes, coarse chromatin SIGNIFICANCE Enhances cell deformability & movement through vessel wall into site of inflammation

MATURE NEUTROPHIL

TYPES OF NEUTROPHILS

VARIOUS LOBES OF NEUTROPHILS

MOTILE NEUTROPHILS

ULTRASTRUCTURE OF NEUTROPHILS

SUBCELLULAR STRUCTURE
1) PRIMARY GRANULES 2) SECONDARY GRANULES 3) TERTIARY GRANULES

SUBCELLULAR STRUCTURE

CONTENTS

PRIMARY GRANULES (AZUROPHILS) Myeloperoxidase, Lysozyme, Defensins BPI(bacterial permeability increasing protein) Elastase Cathepsin G Proteinase 3 Cathepsin B Cathepsin D -D-glucoronidase -macrosidase phospholyphase A2 CD66C; CDB3 antiben

SECONDARY GRANULES (SPECIFIC) Lysopsyme Lactoferrin

TERTIARY GRANULES (GELATINASE)

SECRETORY VESICLES

Antimicrobial components

Neutral proteinases

Collagenase Complement Activator Phosphalypase A2

Acid hydrolases

Membrane

CD66a, CD66b CD15 antigen cytochrome b558 NBI antigen TNF receptor

Mac-1 (CD.11b) FMLP receptor cytocbrome b558 lanonine receptor

Alkaline phasphatase cytochrom b558 Mac-1 (CD11b) WPA receptors CD10, CD13, CD16. Plasma protein

Matrix

Apolactoferrin Histomine receptor vita B12binding protein Promyelocyte stage Myelocyte stage

Gelatinase acetyl transferase lysozyme

Formation

Band stage

and

segmented

Function

Fuse with phagocytic vesicles resulting in the delivery of their

Fuse with phagocytic vesicle sand largely release into the extra

POOL MARGINATION AND ITS IMPORTANCE

90% - Marrow pool

3% - Blood pool
7% - Tissue pool

FUNCTIONS OF NEUTROPHILS
Stimulus detection Transduction Chemotaxis Ingestion Degranulation Microbial killing

LIGAND
Formyl peptidase C3b (CRI) C3bi (CR3) C5a Fc portion of IgG LTB4 Platelet activating factor - adrenergic Prostaglandin E1 (PGE1) Adenosine (A2) Histamine

FUNCTIONS
1] STIMULATORY
Complete activation Phagocytosis Complete activation Complete activation Complete activation except chemotaxis Complete activation Complete activation

2] INHIBITORY
Elevate cyclic amp

3] ADHESIVE
C3bi Binds leukocyte and endothelial adhesion molecules Binds to activated platelets monocytes endothelial cells, and fibroblasts Binds matrix to extracellular

Thrombospondin

Laminin Fibronectin

STIMULUS RECEPTORS AND SIGNAL TRANSDUCTION

MOVEMENT, CHEMOTAXIS & INGESTION

OPSONIZATION

DEGRANULATION
Oxygen dependent microbial killing Oxygen independent microbial killing Nitric oxide mechanism

OXYGEN DEPENDENT MICROBIAL KILLING

OXYGEN INDEPENDENT MICROBIAL KILLING

Bacterial permiability increasing protein Lysozyme Lactoferrin Major basic protiens Defensin Elastase

PHAGOCYTOSIS

PHAGOCYTOSIS

APPLIED ASPECT OF NEUTROPHILS

LEUCOCYTOSIS
Neutrophil count above 7500/l Acute infections- localized or generaized Inflammatory conditions Intoxication Acute hemorrhage Acute hemolysis Disseminated malignancies Myeloproliferative disorders Miscellaneous

LEUCOCYTOSIS

NEUTROPENIA
Absolute count Below 2500/l 1] Infections 2] Overwhelming Bacterial Infections 3] Drugs and Chemicals 4] Hematological & other diseases 5] Cachaexia & Debilitating disease 6] Anaphylactoid shock 7] Congenital & Hereditary disorders

NEUTROPENIA

VERIATION IN MORPHOLOGY

1] Granules 2] Vacuoles 3] Dohle bodies 4] Nuclear abnormalities

DOHLE BODIES

TOXIC GRANULES

HYPERSEGMENTED NEUTROPHILS

EOSINOPHIL
In 1879 EHRLICH introduced the term EOSINOPHIL to discribe blood cells with many intracytoplasmic granules which has affinity for Acidic Die.

GROWTH FACTORS
Cytokine IL -3 GM-CSF IL 5 is KEY cytokine in terminal differentiation of eosinophils from committed precursor

MATURE EOSINOPHIL
SIZE 9 to 15 m Cytoplasm large Nucleus two lobes & Clumped chromatin

TYPES OF EOSINOPHILS

DISTRIBUTION OF EOSINOPHIL
Marrow pool - 5 to 6 days
Circulatory pool 8-12 hrs

Tissue pool die and removed

SUBCELLULAR STRUCTURE
1. PRIMARY GRANULES 2. SECONDARY GRANULES

3. TERTIARY GRANULES

GRANULE CONTENT

EOSINOPHILLIC MEDIATORS

1. 2. 3.

Granule derived proteins Membrane derived mediators Eosinophil derived cytokines

GRANULE DERIVED PROTEINS

MBP ECP EPO EDN Major basic protein Eosinophilic cationic protein Eosinophil peroxidase Eosinophil derived neurotoxin

Crystalloid granule of Eosinophil with stored

inflammatory cytokines & protiens

MEMBRANE DERIVED PROTEINS

Eosinophhils are rich source of sulidopeptide leucotriene LTC4

EOSINOPHIL DERIVED CYTOKINES

FUNCTIONS OF EOSINOPHILS
DEGRANULATION Parasitic infection Allergic conditions MBP & EPO-active against helminthus, bacteria & tumor cells EDN destroys myelinated nerve fiber

APPLIED ASPECT

EOSINOPHILIA
1] Allergic disorders 2] Parasitic infections 3] Skin diseases 4] Loeflers syndrome 5] Pulmonary infections 6] Tropical eosinophilia 7] Hematopoietic diseases 8] Malignant diseases with metastasis 9] Irradiation

EOSINOPHILIA

BASOPHILS
BASOPHILS
MAST CELLS

DEVELOPMENT & MATURATION

Myelocyte Metamyelocyte Mature basophils Size -10 to 16 m Cytoplasm pink to colorless & water soluble granules Nucleus - bilobed

MATURE BASOPHIL

TYPES OF BASOPHILS

GRANULES OF BASOPHILS
PRIMARY GRANULES Water soluble, stain deep purple Peroxidase positive heparin, histamine, kallikrein, PAF, MBP, eosinophillic chemotactic factor, charcot laden crystals

GRANULES OF BASOPHILS

MAST CELLS
Not found in peripheral blood
Found in connective tissue, serous cavities, brain

Larger, oval nucleus, less water soluble

Contain histamine, heparin, hyaluronic acid, protease & myeloperoxidase

MAST CELLS

ACTIVETED MAST CELL

GRANULES OF MAST CELL

RELEASE OF HISTAMINE FROM MAST CELLS

MEDIATORS OF MAST CELLS

FUNCTIONS
Chemotaxis, phagocytosis and degranulation
Sluggish motility Granule contents

IgE receptors hypersensitivity response

Synthesis an eosinophilic chemotactic factor Inflammatory function

Immediate & delayed hypersensitivity reactions

APPLIED ASPECT

BASOPHIL
Basophil leukocytosis above 100/l 1] CML 2] Polycythemia Vera 3] Myelosclerosis 4] Ulcerative colitis 5] Splenectomy 6] Hodgkins disease 7] Urticaria pigmentosa

BASOPHILIA

GOOD MORNING

TYPES OF NEUTROPHILS

MONOCYTE

DEVELOPMENT
Monoblast Promonocyte Monocyte : Size 14 to 20 m Cytoplasm abundant Nucleus kidney shaped fine cromatin

MATURE MONOCYTES

DEVELOPMENT OF MONOCYTE INTO MACROPHAGE

DEVELOPMENT OF MONOCYTE INTO MACROPHAGE

MACROPHAGE
Size 15 to18 m
Cytoplasm coarse Nucleus egg shaped, sponge chromatin

CLASSIFICATION
Fixed macrophages
Unfixed (wandering) macrophages

DISTRIBUTION

FUNCTIONS
Second line of defense
Chemotaxis,phagocytosis & bactericidal activity Immunologic function

a) processes antigen information for lymphocytes

b) antibody dependent & independent cellular toxicity

FUNCTIONS
Removal of damaged & old cells,plasma
proteins & plasma lipids

Participation in iron metabolism

Synthesis & secretory function

MONONUCLEAR PHAGOCYTOSIS SYSTEM (MPS)

In 1924 German pathologist ASCHOFF together with LANDAU itroduced a term Reticuloendothelial System. But prasently known as Mononuclear Phagocyte system

MONONUCLEAR PHAGOCYTOSIS

Cells of MPS 1] Bone marrow i] Monoblast ii] Promonocyte iii] Monocyte 2] Blood
i] Monocyte

3] Tissue 1. Bone macrophage 2. Skin macrophage 3. Brain macrophage 4. Liver macrophage 5. Lung macrophage 6. Serosal macrophage 7. Reproductive tract macrophage

ANTIGEN OF MONONUCLEAR PHAGOCYTE

Major histocompatibility complex

1. Class I or HLA- A,B and C

2. Class II or HLA-D

RECEPTORS OF MPS
1] Fc receptors 2] Complement 3] Glycoprotein & Lipoprotein 4] Transferrin & Lactoferrin 5] Cytokine, Interleukin, Growth factor 6] Chemotactic peptide 7] Coagulation factor

PRODUCT OF MPS

1] Enzymes 2] Complement factors 3] Coagulation factors 4] Reactive oxygen species 5] Reactive nitrogen species 6] Bioactive lipids 7] ILS, TNF, Erythropoietin

FUNCTIONS OF MPS
1] Second line of defense 2] Helps in Lymphocyte mediated immunity i] APS ii] Secrete Cytokines iii] Proliferation of T & B Cells iv] Helps NK Cells

3] Act as scavengers 4] Kuffer cells remove bacteria of Portal venous blood 5] Secretes hematopoietic factor

IMMUNITY
IMMUNITY Is the ability to resist damage from foreign substance such as microorganism & harmful chemicals such as toxins released by microorganism.

IMMUNITY
1] INNATE IMMUNITY A] NONSPECIFIC IMMUNITY B] SPECIFIC IMMUNITY (ADAPTIVE ) 2] AQUIRED IMMUNITY A] ACTIVE i] NATURAL ii] ARTIFICIAL

B] PASSIVE
i] NATURAL ii] ARTIFICIAL

NON SPECIFIC IMMUNITY Non specific when it indicates adegree of resistance to all infections

mediated by neutrophils & monocytes

SPECIFIC IMMUNITY Specific when it show resistance

to particular pathogens
Mediated by lymphocytes Two specific features are - specificity & memory

SPECIFICITY - is the ability of the immune system to recognize a particular substance MEMORY- is the ability of the immune system to remember previous encounters with a particular

substances & as a result respond to it more rapidly

COMPONENTS OF IMMUNE SYSTEM

1] CELLULAR COMPONENT - Lymphocytes - Monocytes - Dendritic cells - Langerhans cell 2] CHEMICALS Immunoglobulines - Cytokines

COMPONRNT OF SPECIFIC IMMUNITY

1] HUMORAL IMMUNITY
2] CELL MEDIATED IMMUNITY

LYMPHOID ORGAN
1] Primary lymphoid organ
a) Lymphoid
Bone marrow Thymus

b) Non lymphoid cellular elements

Epithelial cells Macrophages Interdigitating dendritic cells Myeloid cells Lymphoid cells

Secondary lymphoid organs

Lymph node Spleen
Gut associated lymphoid

tissue
Lymph nodules of the intestine which are also termed as

Peyers patches
waldeyers ring of lymphoid tissue in the tonsils.

LYMPOCYTE PRODUCTION & DEVELOPMENT

STAGES OF DEVELOPMENT
1] Lymphoblast
2] Prolymhocyte 3] Mature Lymphocyte

MATURE LYMHOCYTE
Size 8 to 16 m
Cytoplasm Pale blue Nucleus Round or oval

MATURE LYMHOCYTE

MATURATION OF T-CELL & BCELL

CLUSTER OF DIFFERENTIATION (CD)

These are surface marker molecules Are cell membrane proteins or receptors that allow the identification of multiple cell lines at different surface of maturation

SIGNIFICANCE
Their presence and identification on malignant cells frequently help to provide necessary information to confirm malignancy of the clone & to determine from what tissue or cell line the malignant clone is derived

LIFE SPAN & CIRCULATION

1] Life span : i] Long lived 4yrs ii] Short lived 3 to 4 days
2] Circulation : i] Recirculation of mature differentiated lymphocytes ii] Immature lymphocytes

FATE OF LYMPHOCYTES

1] Lymphocytic stem cells

2] Migrates to peripheral lymphatic system 3] Building blocks for future generation of lymphocytes 4] In Thymus lymphocytes are replaced every 3 to 4 days

CLSSIFICATIONS OF LYMPOCYTES
1] T Lymphocyte A] CD8+ T-Cells (30%) i] Cytotoxic T- Cells ii] Suppressor T-Cells B] CD4+ T-Cells (60%) 2] B Lymphocyte 3] NK Cells (Non B Non T Cells) 4] Memory Cells (Can be of T or B Cells)

ACTIVATION OF LYMHOCYTES

1] Lymphocytes must be able to recognize the ANTIGEN

2] After recognition the lymphocyte must increase in number to effectively destroy the ANTIGEN

CHARACTERISTICS OF AN ANTIGEN
IMMUNOGENICITY : Is the ability to provoke an immune response by stimulating the production of specific antibodies. REACTIVITY : Is the ability of the antigen to react specifically with the antibodies

ANTIGEN DETERMINANT

ANTIGEN RECEPTORS

MAJOR HISTOCOMPATIBILITY COMPLEX MOLECULES CLASS-I & CLASS-II

CYTOKINES

Cytokines are small protein hormones that stimulate or inhibit many normal cell functions such as cell growth & differentiation Types of cytokines i] Monokine ii] Lymphokine

FUNCTIONS OF CYTOKINES
1] Local Action
i) Assist WBC emigration, chemotaxis, phagocytosis, ii) Hematopoietic Growth Factor iii) Stimulate & activate B or T lymphocytes

iv) Generate prostaglandins

2] Systemic Actions
i) Act as powerful Pyrogen

ii)TNF- produces fall of BP & shock

iii) Produces anorexia / loss of body weight cachexia

LYMPHOCYTE PROLIFERATIPON

B - LYMPOCYTES
ANTIBODY MEDIATED IMMUNITY
OR

HUMORAL IMMUNITY

PROLIFERATION OF B - CELL

ACTIVATION, PROLIFERATION & DIFFERENTIATION OF B-CELL INTO PLASMA CELLS

PLASMA CELLS

DIFFERENTIATION OF PLASMA CELLS INTO ANTIBODY

STRUCTURE OF ANTIBODY

ANTIBODY

PRODUCTION OF ANTIBODY

ACTIONS OF ANTIBODY

T - LYMPHOCYTE OR CELL MEDIATED IMMUNITY

ACTIVATION, PROLIFERATION AND DIFFERENTIATION OF T- CELL

TYPES OF T - CELLS
1] HELPER T CELL 2] MEMORY CELL 3] CYTOTOXIC T - CELL

ACTIVITY OF CYTOTOXIC CELLS

WHITE BLOOD CELLS

Neutrophil Eosinophil Basophil Monocyte Lymphocyte

LABORATORY INVESTIGATIONS
TOTAL BOOD COUNT Total RBC count /mm3 of blood Hb % g/dl of blood The hematocrite or PCV Red cell indices (MCV,MCHC,MCH) Total white cell count Differential count

ROMANOWSKY STAIN
Leishmans stain Wrights stain Giesma stain Jenners stin FOR TOTAL WBC COUNT Turks fluid Glacial acetic acid - Gentian violet - Distilled water Neubaur chamber used for counting WBC

No. of WBC per cumm of whole blood =

No. of cells counted x 20 4 x 0.1

= No. of cells counted x 50

Where 20 = dilution Area counted = 4 x 1 sqmm. Depth of the field = 0.1 mm

DIFFERENTIAL COUNT
Leishmans stain Eosin Acedic dye, stains positively charged particles. Exa RBC & granules of eosinophil Methylene blue Bsic dye, stains negatively charged particles. Exa cytoplasm, nuclei of WBC & granules of basophil

NITROBLUE TETRAZOLIUM REDUCTION TEST

Normal PMN contain enzyme that convert colorless NBT to dark blue granules within cell. When dark blue granules are not seen the PMN show defect in chemotactic & phagocytic activity.

NEUTROPHIL & ITS GRANULES

EOSINOPHIL & ITS GRANULES

BASOPHIL & ITS GRANULES

MONOCYTE

LYMPHOCYTE

MONOCYTES
Monocytosis above 800/l 1] Bacterial infections 2] Protozoal or Rickettesial infections 3] Convalescence from acute infections 4] Malignancies 5] Granulomatous diseases 6] Collagen vascular disease

APLIED ASPECT OF LYMHOCYTES

IMMUNODIFICIENCY SYNDROME 1] Primary Brutons disease Di Georges syndrome 2] Secondary Hypersensitivity - AIDS - Graft Rejection

BRUTONS DISEASE
B Lymphocyte maturation does not occur Poor Ig formation Result in Agammaglobulinemia

Di GEORGES SYNDROME
Development of Thymus does not occur, remains rudimentary Affects the T-Lymphocyte population

HYPERSENSITIVITY REACTIONS
HYPERSENSITIVITY IS DEFINED AS AN EXAGGERATED ADAPTIVE IMMUNE RESPONSE TO AN ANTIGEN, RESULTING IN TISSUE DAMAGE

TYPES OF HYPERSENSITIVITY REACTIONS

1] Type I hypersensitivity or Immediate hypersensitivity
reaction. 2] Type II hypersensitivity or Cytotoxic hypersensitivity reactions 3] Type III hypersensitivity or Immune complex

hypersensitivity reaction
4] Type IV or Delayed hypersensitivity reaction

TYPE I HYPERSENSITIVITY REACTION

TYPE II HYPERSENSITIVITY REACTION

TYPE III HYPERSENSITIVITY REACTION

TYPE IV HYPERSENSITIVITY REACTION

TRANSPLANT REJECTION
MECHANISM OF ACTION MHC class 1 antigen molecule of the transplanted tissue are recognized as foreign material by the Lymphocytes of recipient Proliferation of cytotoxic Tcells- Rejection of transplanted material

ACQUIRED IMMUNO DEFICIENCY SYNDROME

AIDS is a viral disease & was first recognized in 1981 with description of pneumocystis carini by the Centers for Disease Control in Atlanta

STUCTURE OF HIV

AIDS

STRUCURE OF HIV

PATHOGENESIS OF HIV

ROLE OF CD4 LYMPHOCYTES IN THE IMMUNE RESPONSE

MECHANISM OF T-CELL IMMUNODIFICIENCY IN HIV INFECTION

ROLE OF CD4+ CELLS

Loss of immature precursors of CD4+ T cells either by direct infection of thymic progenitor cells or by infection of accessory cells that secrete cytokines essential for CD4+ T cells maturation. Fusion of infected and uninfected cells with formation of syncytia (giant cells) Apoptosis by uninfected CD4+ T cells by binding of soluble gp 120 to the CD4 molecules followed by activation through the T cell receptors by antigens such cross linking of CD4 molecule and T cell activation leads to aberrant signaling and activation of death pathway.

 CD8+ cytotoxic T lymphocytes may kill uninfected CD4+ T cell that are coated with gp120 released from infected cells. Qualitative defect in T-cells leading to imbalance between TH1 and TH2 responses resulting in profound deficiency in cellmediated immunity. Selective loss of the memory subset of CD4+ helper T cells early in the course of disease because memory T-cell express higher levels of the HIV-1 co-receptors CCRS.

DISORDERS OF WHITE BLOOD CELLS

CLASSIFICATIONS
1] QUNTITATIVE DISORDERS 2] QUALITATIVE DISORDERS 3] MYLOPROLIFERATIV DISORDERS I] MYELOFIBROSIS II] MYELOID METAPLASIA III] LEUKEMIA

4] LYMPHOMA
5] MULTIPLE MYELOMA

QUANTITATIVE DISORDES OF GRANULOCYTE

1] Neutropenia
2] Agranulocytosis

3] Cyclic neutropenia
4] Chediak Higeshi syndrome

5] Lazy leukocyte syndrome

NEUTROPENIA
Decrease in number of Neutrophil below 1500/mm3 Cause : i) Decreased production or increased destruction Ii) Infancy congenital or genetic abnormality Iii) Adult malignancies or metabolic diseases iv) Drugs anticancer, antibiotic,tranquilizers, ect V) Infections viral , bacterial

CLINICAL FEATURES
SITE : middel ear, oral cavity,perirectal area ORALMANIFESTATIONS: oral ulcerations without surrounding inflammation, large irregular,deep lesions, exstreamly painful, foul smelling necrotic tissue,advanced periodontal diseases, pericoronitis,pulpal infections leading to bacteremia & septicemia - Bri Dent J 1986;160:43

TREATMENT
Detection of underlying cause Discontinuation of drugs Sensitivity test & Antibiotic 0.2% Chlorhexidin mouth wash Solution 5% Dyclonine + 5% Diphen hydramine mixed with magnesium hydrocloride

ORAL MANIFESTATIONS

AGRANULOCYTOSIS
Condition in which the cells of the granulocyte series, particularly neutrophils are absent CAUSE Decreased production or increased dustruction, drugs, congenital agranulocytosis caused by Kostamann sydrome (decreased level of cytokine & G-CSF)

CLINICAL & ORAL MANIFESTATIONS & TREATMENT

Bacterial infections with signs & symptoms of sore throat,swelling,fever,chills,bone pain, pneumonia ORAL Necrotizing deep punched out ulcerations of buccal mucosa,tongue & palate Treatment Discontinuation of drug, mouth wash,administration of G-CSF - Text Rose & Kaye 2nd Edition

CYCLIC NEUTROPENIA
DEFINITION: Cyclic neutropenia characterized by ossillation of every 14 to 36 days in number of neutrophilic granulocyte in blood & bone marrow. - J periodontal 1996;67:425

CYCLIC NEUTROPENIA
CAUSE: Periodic failure of stem cells in the bone marrow due to abnormality in regulation of bone marrow precursor cells.

CLINICAL FEATURES
Fever,anorexia,malaise,pharingitis, lymph node enlargement Oral ulcerations on lip, tongue,buccal mucosa with erythmatous halo Gingivitis,bone lose,marked gingival recession,tooth mobility - Textbook Neville 2nd Edition

RADIOGRAPHIC FEATURES & TREATMENT

Mild to sever alveolar bone loss around teeth Antibiotic therapy, Corticosteroid therapy,Nutritionalsupplement, Administration of cytokine & G-CSF

CYCLIC NEUTROPENIA

CHEDIAK HIGASHI SYNDROME

Autosomal recessive disorder Occulocutaneous albinism,progressive neurologic abnormalities & large blue gray granules in the cytoplasm of granulocytes & platelets Decreased chemotactic & bacterial ability

CLINICAL MANIFESTATIONS & TREATMENT

Hypopigmentation Recurrent bacterial infections Gingival & periodontal desease TREATMENT: Antibiotic ,Treatment of neutrophils,Hematopoitic stem cell transplantation

LAZY LEUKOCYTE SYNDROME

First described by MILLAR,OSKI & HORNICS in 1971 Loss of chemotactic function of neutrophils Cells are unable to migrate from the marrow to the peripheral

CLINICAL FEATURES
Gingivitis,stomatitis,otitis media & bronchitis Total WBC count is in the normal range but absolute neutrophil count low.

DIFFERENTIAL DIAGNOSIS
Traumatic ulcer Recurrent Apthous ulcer Herpengina

LEUKEMIAS
DEFINITION: A group of disorders characterized by malignant transformation of blood forming cells. -Burkitts 10th edition

Leukemia results from the proliferation of a clone of abnormal hematopoietic cells with impaired differentiation,reguletion, and programmed cell death (apoptosis). -O00 2000;89:137-9

CLASSIFICATION
1] Depending on the cell type a] Myeloid b] Lymphoid 2] Depending on the basis of natural history of disease a] Acute b] Chronic MAIN TYPES 1] Acute myeloid leukemia 2] Acute lymphoid leukemia 3] Chronic myeloid leukemia 4] Chronic lymphoid leukemia

ETIOLOGY
1] Genetic factors
2] Environmental factors

3] Infections

PATHOGENESIS
Malignant transformation of a singal clone belonging to myeloid or lymphoid series followed by proliferation of transformed clone Defect lies in the DNA

INCIDENCE
ALL Commonly in children AML More frequent in adult CML 3rd to 5th decade of life CLL 4TH to 6th decade of life (males)
Except with CML the incidence of leukemia is higher in males than in females J oral disease 1997;3:31-38

GENERAL CLINICAL FEATURES OF LEUKEMIA

Due to bone marrow failure - Fever - Anemia - Thrombocytopenia - Infections

Due to organ infiltration - Pain & tenderness of bone - Lymphadenopathy - Splenomegaly - Hepatomegaly - Bleeding tendencies - Gum hypertrophy - Gingival & periodontal diseases - Leukemic infiltration of kidney - Meningeal involvement - Cloromas

ACUTE LEUKEMIAS
Characterized by predominance of undifferentiated leukocyte precursor or leukemic blasts.

ACUTE MYELOGENOUS LEUKEMIA

AML is a clonal proliferation of immature myeloid cells It presents with marrow failure &cytopenia Symptoms fever,fatigue,pallor &local infections Oral findings mucosal bleeding,petechiae & gingival enlargement Diagnosis Presence of at least 30% myeoblasts in BM

ACUTE MYELOCYTE LEUKEMIA

1] M1- Acute myeloblastic without differentiation 2] M2- Acute myeloblastic with differentiation 3] M3- Hypergranular promyelocytic 4] M4- Acute myelomonocytic 5] M5- Monocytic 6] M6- Erytroleukemia -JADA 1988;117(7):835-37

ACUTE LYMPHOID LEUKEMIA

ALL is the clonal proliferation of lymphoid cells that have undergone maturational arrest in early differentiation. ALL accounts -10% to 15% adult acute leukemia - 75% childhood acute leukemia High incidence of central nervous system (CNS) disease -OOO 2000;89:137-9

ACUTE LYMPHOID LEUKEMIA

CLASSIFICATION 1] L1 - Childhood ALL 2] L2 Adult ALL 3] L3 Burkitts type ALL -JADA 1988;117(7):835-37

CHRONIC LEUKEMIAS
Characterized by presence of large number of well differentiated cells in the bone marrow, peripheral blood & tissues

CRONIC MYELOID LEUKEMIA

CML is disorder of the BM,speen & other blood forming organs in which the marrow elements,especially granulocytes & sometimes megacariocytes &erythroid precursors,proliferate inappropriately - Textbook Rose & Kaye 2nd edition

CLINICAL FEATURES
Fatigue, swetting,indigetion,abdominal pain Chronic phase Large number of granulocytes are present in the bone marrow &peripheral blood but cells retain their normal function,it tekes 5-8yrs Blastic phase Characterized by further malignant transformation to immature cells,takes 2-4yrs after detection of leukemia

CHRONIC LYMPHOID LEUKEMIA

CLL result from slow accumulation of clonal B lymphocytes in 95% cases, which are responsible for Ig synthesis & antibody response

ACCYMOSIS AND HEMATOMA FORMATION IN ACUTE LEUKEMIAS

GINGIVAL INFILTRATION WITH LEUKEMIC CELLS

ULCERATIONS

TREATMENT
CHEMOTHERAPY
1] Induction 2] Consolidation 3] Maintenance chemotherapy

BONE MARROW APLASIA

1] Packed red cells 2] Hematopoietic stem cell transplantation 3] Stem cell grafts - Syngeneic - Allogenic - Autologous

ORAL & DENTAL CONSIDERATIONS

For gingival bleeding
- Removal of local irritants - Direct pressure - Absorbable gelatin - Topical thrombin - Microfibrillar collagen - Trenexamic acid or - aminocaproic acid Oral rinses Chlorhexidin, kaolin, pectin & diphenhydramin - OOO 2000;89:137-9

LYMPHOMAS
DEFINITION Lymphomas are a group of malignant solid tumors involving cells of lymphoreticular or immune system such as B- lymphocyte,T-lymphocytes and monocytes.

CLASSIFICATION
1] HODGKINS LYMPHOMA
2] NON-HODGKINS LYMPHOMA

HODGKINS LYMPHOMA
Primarily arises within lymph node Age young adult Sex male than females Diagnostic feature presence of REED STERNBERG (RS) cell Etiology : Infections,Genetic

CLASSIFICATION
RYA CLASSIFICATION 1] Lymphocyte predominate 2] Nodular sclerosis 3] Mixed cellular 4] Lymphocyte depletion

CLINICAL FEATUREs
Superficial lymph node enlargement, lymphadenopathy is painless Cervical & mediastinal lymph node involvement Low grade fever,night sweat & weight loss,malaise, futigue,weekness

ANNE ROBER CLASSIFICATION

Stage I : Involvement of singal lymph node region Stage II : Involvement of two or more lymph node on the same side Stage III : Involvement of lymph node on both side Stage IV : Disseminated involvement of one or more lymphoid organ

REED STERNBERG CELLS

NON HODGKINS LYMPHOMA

Arises from B or T lymphocytes Seen in above 40yrs of age group Painless persistant enlargement of lymph nods seen in Waldeyers ring, GIT,speen, skin bone marrow. Treatment : Radiotherapy Chemotherapy

BURKITTS LYMPHOMA
Associated with EPSTEIN BARR virus in 90% of cases Rapid growing extranodal jaw tumors Treatment : Chemotherapy

MULTIPLE MYELOMA
Malignant neoplasm of plasma cells characterized by production of M-proteins, bone lesions, kidney disease, hyperviscosity hypercalcemia

CLINICAL FEATURES
1] Skeletal pain 2] Pathologic fracture of the bone 3] Proliferation of plasma cells that produces M-protein 4] Deposition of amorphous protein under the skin or mucosa 5] Renal failure, amyloidosis, hypercalcemia 6] Infections

ORAL MANIFESTATION
1] Pain, swelling, numbness of jaws,

epulis formation
2] Mobility of teeth

3] Skull lesions

RADIOGRAPHIC FEATURES
Multiple radiolucent lesions
of varying size

And punched out radiolucent

lesions

RADIOGRAPHIC FEATURES

TREATMENT

CONCLUSION