leukocyt es

Neutrophil Eosinophil Basophil Monocyte Lymphocyte

LABORATORY TESTS

WBC count WBC differential counting

Relative count, Absolute count, Schillings method Neutro, Eosi, Baso, Mono, Lympho

Special stains Enzymatic determination

LEUKOPOIESIS
CFU-GM
CFU-G Myeloblast Promyelocyte Neutrophilic Myelocyte Neutrophilic Metamyelocyte Neutrohilic Band Neutrophil

LEUKOPOIESIS
CFU-GM
CFU-M Monoblast Promonocyte Monocyte Macrophage

LEUKOPOIESIS
CFU-Eo
Myeloblast Eosinophilic Myelocyte Eosinophilic Metamyelocyte Eosinophilic Band Eosinophil

LEUKOPOIESIS
CFU-Baso
Myeloblast Basophilic Myelocyte Basophil

LEUKOPOIESIS
Precursor T/NK cell
Pro-T cell Pre-T cell T cell Pro-NK cell NK cell

LEUKOPOIESIS
Precursor B cell
Pro-B cell Pre-B cell B cell Plasma Cell

LEUKOCYTIC DISORDERS
Non-neoplastic alterations Neoplastic Disorders Primarily Involving Leukocytes

PURPOSE OF THE STUDY

Help

in establishing diagnosis
e.g. Leukemia, acute appendicitis, IM

Help

in establishing prognosis
e.g. leukocytosis in Px w/ pneumonia or appendicitis is a GOOD prognosis e.g. monocytosis in Px w/ tuberculosis is a POOR prognosis

Helpful

in following the course of

disease

toxic effects of chemotherapy is recognized and monitored thru WBC examination

Non-Malignant Changes of White Blood Cells

Quantitative

(changes in numbers)

Qualitative

(morphologic alterations)

Quantitative changes of WBC

Includes:

the total WBC count and; the relative & absolute concentrations of the difft WBC

Definitions:
Leukopenia:

decrease in lymphocytes, segmenters or all cell types increase in one or more cell types

Leukocytosis:

Absolute Values
Relative

percentage of each WBC

differential count

Absolute

value

gives the actual number of each WBC/L

Calculation: Absolute count =Total WBC count x Percent
(as a decimal)

Definition

Examples:

relative neutrophilia, relative and absolute lymphocytopenia

Absolute WBC & Diffl count AGE 12 months TOTAL WBC 6.0 17.5 x 109/L 5.5 15.5 x 109/L 5.0 14.5 x 109/L 4.5 13.5 x 109/L 4.5 11.0 x 109/L NEUTRO 1.5 8.5 x 109/L 1.5 8.5 x 109/L 1.5 8.0 x 109/L 1.8 8.0 x 109/L 1.8 7.7 x 109/L EOSI 0.05 0.70 x 109/L 0.02 0.65 x 109/L 0 0.65 x 109/L 0 0.60 x 109/L 0 0.45 x 109/L BASO 0 0.20 x 109/L 0 0.20 x 109/L 0 0.20 x 109/L 0 0.20 x 109/L 0 0.20 x 109/L LYMPHO 4.0 10.5 x 109/L 2.0 8.0 x 109/L 1.5 7.0 x 109/L 1.5 6.5 x 109/L 1.0 4.8 x 109/L MONO 0.05 1.1 x 109/L 0 0.8 x 109/L 0 0.8 x 109/L 0 0.8 x 109/L 0 0.8 x 109/L

4 years

6 years

10 years

21 years

Qualitative Changes in WBC

Cytoplasm

altered primary granules ribosomal RNA in rows lysosomal alteration vacuolation; degranulation pyknotic: shrunken, dense, dehydrated hypersegmented: more than 5 segments

Nucleus

(megaloblastic anemia)

Quantitative alteration
Changes in number

Quantitative changes in WBC

GANULOCYTES

AGRANULOCYTES

Neutrophilia: Neutropenia: Eosinophilia: Eosinopenia: Basophilia: Basopenia:

Monocytosis: Monocytopenia: Lymphocytosis: Lymphocytopenia: Plasmacytosis:

NEUTROPHILI A
absolute

ct. of neutro above normal for age absolute count >7,000/mL

FACTORS

AFFECTING COUNT

rate of inflow of cells from BM proportion of MGP and CGP rate of outflow of cells from blood

NEUTROPHILIA

PHYSIOLOGIC

CAUSES

do NOT involve tissue damage NOT related to underlying tissue pathology

Hypoxia Severe exercise, stress (crying) After eating Injection of epinephrine Heat, cold Pain, fear, anger

NEUTROPHILIA

PATHOLOGIC

CAUSES

occurs as a result of disease or tissue damage

Tissue Destruction/Necrosis:

Myocardial Infarction, burns, surgical operations, crush

Infection:

Appendicitis, salphingitis, otitis media

Hemolysis:

acute and delayed HTR

NEUTROPHILIA

Toxins:

Metabolic (uremia, eclampsia, gout, diabetic acidosis) Drugs/Chemicals: (lead, mercury, potassium chlorate, turpentine, benzene)

Hemorrhage:

bleeding occurred in serous cavity

NEUTROPENIA
absolute

count < 1,800/mL agranulocytosis: decreased prod, increased destruction

CAUSES

Myeloid hypoplasia Ineffective granulocytopoiesis Decreased survival Combination Pseudoneutropenia

NEUTROPENIA

Myeloid

hypoplasia:

Kostmanns infantile genetic agranulocytopoiesis

rare, autosomal recessive w/c appears in early infancy BM shows (+) granulocytes but few maturing forms

Familial & Cyclic neutropenia

autosomal dominant condition due to periodic stem cell failure lasts for 21 days

NEUTROPENIA

Lymphocytic disorder

X linked agammaglobulinemia

Myelophthisic neutropenia

BM is damaged due to metastatic carcinoma or Gauchers dse

Drugs

Alkylating agents, ionizing radiation, chloramphenicol, benzene, sulfonamides, quinine, quinidine

NEUTROPENIA

Ineffective Granulocytopoiesis:

Chdiak Higashi syndrome Megaloblastic anemia Myeloproliferative disorder Exposure to drugs

Decreased survival:

Infections Splenic selective removal Feltys syndrome Drug - induced

NEUTROPENIA

Combination

of hypoplasia, ineffective production & decreased survival of neutrophils:

Psedoneutropenia:

Endotoxin Drug induced

anesthesia ether pentobarbital

IA
eosinophil

count exceed 0.35 x 109/L disorders

hypersensitive

release granules content that acts as anti-histamine

parasitic

infections

eosinophils release granule content w/c damages the target organism

EOSINOPHILIA

CAUSES

Allergic diseases:
bronchial

asthma, rhinitis, hay fever

mediated by IgE mast cells & basophils degranulation w/ the release of chemotactic factor

skin disorders:

atopic dermatitis eczema (red & itching; [+] scaly patches that may leak fluid) pemphigus (cxd by large blisters on the skin & mucous membranes) acute urticarial reactions (hives)

EOSINOPHILIA

parasitic infestations: trichinosis tapeworm infection visceral larva migrans creeping eruption Infectious diseases:

scarlet fever (cutaneous rash) Chorea (jerky spasmodic movements of limbs, trunk, & facial muscle)

EOSINOPHILIA

Loefflers syndrome

cxd by repeated, transient pulmonary exudates accompanied by cough sputum contains eosinophils

PIE syndrome

pulmonary infiltration w/ Eosinophilia chronic and relapsing fever, cough, dyspnea

EOSINOPHILIA

Tropical Pulmonary Eosinophilia

syndrome of paroxysmal cough and bronchospasm hyperimmune reaction [very high IgE]

Hypereosinophilic syndrome:

NO known cause heart, endocardial & myocardial fibrosis

EOSINOPHILIA

Splenectomy: Drugs:

Pilocarpine, physostigmine, digitalis, p-aminosalicylic acid, sulfonamides

A
count

is lower than 0.04 x 109/L margination or migration to inflammatory site

CAUSES

acute stress and acute inflammatory state epinephrine and adrenal corticoticoid secretion Cushings syndrome

caused by excessive production of ACTH by the pituitary gland

BASOPHILIA
count

in above 0.2 x 109/L hypersensitivity, leukemia

CAUSES

allergic reactions; hypothyroidism chronic myeloid leukemia, myeloid metaplasia polycythemia vera, chronic hemolytic anemia following splenectomy

BASOPENIA
decrease

count below 0.01 x 109/L diurnal [lowest in AM; highest in PM]

CAUSES

sustained Tx w/ adrenal corticosteroid acute infection acute stress hyperthyroidism

MONOCYTOSI S
increase

count above 1.0 x 109/L indicates recovery from marrow hypoplasia, dse, & acute infection if (+) in tuberculosis [poor prognosis]
CAUSES:

subacute bacterial endocarditis fungi, ricketsia, protozoan, virus infections

MONOCYTOPENI A
decrease

below 0.2 x 109/L follows administration of glucocorticoids

CAUSES:

administration of prednisone Hairy cell Leukemia

LYMPHOCYTOS IS
above

normal count for age

ADULT: 1.5-4.0 x 109/L CHILD: 1.5-8.8 x 109/L

viral

infections, antigen stimulation T cells (highest @ birth) B cells (remain stable for all stages of life)

LYMPHOCYTOSIS

CAUSES

Human T Lymphotropic Virus Type I

asstd w/ T-cell leukemia fever, lymphadenopathy, skin rash

Infectious Lymphocytosis

contagious disease among children asstd w/ coxsackie virus A, echovirus, adenovirus type 12 vomiting, fever, cutaneous rash, CNS involvement

Chronic Lymphocytosis

common among adults w/c waxes and wanes for mons - yrs

Infectious Mononucleosis

self-limited infectious dse w/c involves the RES 2O to EBV infection; (+) heterophil antibody fever, sore throat, lymphadenopathy (w/ ampicillin = rashes) associated w/ hemolytic anemia due antii antibody production

LYMPHOCYTOSIS

Cytomegalovirus Virus infection

fever, chills, profound malaise, myalgia, splenomegaly increased titer of Cold Aagglutinins, Rheumatoid Factor, and Anti-Nuclear Antibody

Pertussis [Whooping cough]

Bordetella pertussis inflammatory rxn of the entire RT

Toxoplasmosis

LYMPHOCYTOPENI A
below

normal count for age early stages of infection CAUSES

impaired lymphopoiesis or drainage of GIT lymphatics increased adenocorticortical hormones administration of chemotherapeutic drugs irradiation Hodgkins and Non-Hodgkins lymphoma terminal cases of carcinoma, AIDS

PLASMACYTOSIS
plasma

cells are seen in circulating blood

CAUSES

chronic infections, allergic states, neoplasms rubella, measles, chicken pox, mumps cutaneous exanthemas, mono, syphilis, SBE, sarcoidosis, collagen diseases

LEUKEMOID REACTION
excessive

WBC response with out-pouring of immature forms 50-100 x 109/mL leukocytosis w/ a shift-to-the-left

neutrophilic eosinophilic leukoerythroblastotic lymphocytic

Qualitative alteration
Morphologic alterations

Polymorphonuclear cells

Toxic granules

primary or azurophil granules have retained their basophilic staining reaction lack of maturation dark-blue to purple granules are PEROXIDASE (+)

Signs of toxicity:

presence of basophilic azure granules presence of cytoplasmic vacuoles presence of sharp or blunt spicules from nucleus is transient

found

in severe infections, cancer, hematoma, tissue undergoing necrosis

Dhle Inclusion Bodies

small oval inclusion in the peripheral cytoplasm stain pale blue w/ Wright stain remnants of free ribosomes/RER arranged in parallel rows accompany toxic granules

scarlet fever, other infectious diseases, burns, aplastic anemia, administration of toxic agents

May-Hegglin Anomaly

rare autosomal dominant condition Involving the nonmuscle myosin heavy chain 9 linked to chromosome 22q12-13 (+) pale blue inclusions like Dhle Bodies (randomly placed rods)

PMNs, Eosinophils, Basophils Monocytes Giant platelets

Alder-Reilly Anomaly

With large, darkly staining metachromatic granules composed of mucopolysaccharides like toxic granulation but unrelated to infection found in ALL WBC Incomplete degradation of MPS There may be a structural abnormality in the myeloperoxidase gene

Pelger-Hut Anomaly

hereditary, autosomal dominant condition HYPOLOBULATION

failure of segmentation of granulocytic nuclei

cells are functionally normal Mutation of the lamin B receptor (integral protein in the inner nuclear membrane) Chromosome band 1q41-43

Pseudo-Pelger-Hut Anomaly

Acquired form of nuclear hyposegmentation Seen in myeloproliferative neoplasms Fewer PMNs are affected (50%) Usually accompanied by other morphologic indications of malignancy (e.g. blast forms)

bilobed neutrophils with more condensed chromatin.

Hereditary Neutrophil Hypersegmentation

Benign Autosomal Dominant condition

Hypersegmented PMN w/o clinical S/S There is no macrocytic anemia Myelokathexis Neutropenia with hypersegmented PMN Bone marrow hyperplasia of myeloid cells Pyknotic Increased apoptosis

Chdiak Higashi Syndrome

rare autosomal recessive disorder With enlarged lysosomal vesicles All cells are affected including the melanosomes of melanocytes in the skin, dense granules of platelets, and leukocyte granules Associated with a mutation in the LYST gene that encodes for a type of vesicle trafficking regulatory protein

frequent pyogenic infections, lymphoma-like phase, death ensues at early age

Functional abnormality
Lazy

Leukocyte

the actin filaments in the neutrophil is defective

chemotaxic response defective defective mobility

Chediak-Higashi

PMNs are sluggish

 Chronic

granulomatous disease:

Inability of phagocytes to produce superoxide and reactive oxygen species Mutations in any of 4 genes for NADPH oxidase Nitroblue tetrazolium reduction test Normal PMN reduce the yellow water-soluble nitroblue tetrazolium to a dark blue insoluble formazan

 Jobs

syndrome

a familial disorder clinical laboratory observations are limited to the monocytes & lymphocytes both cells may contain fine vacuolation

observed in 2 primary diseases:

muscular dystrophy [directional motility impairment] xeroderma (ichthyosis) [patient has boils and abscesses]

also found in Infections, toxic effect of ethanol, Jordan's anomaly

Monocytes and Macrophages

Lipid

Storage Disorders

Gauchers Disease:

deficiency of -glucocerebrosidase leading to an accumulation of its substrate, the fatty substance glucocerebroside

Gaucher cell

Niemann Pick Disease: is an autosomal recessive disorder affecting lipid metabolism (the breakdown and use of fats and cholesterol in the body), in a way which causes harmful amounts of lipids to accumulate in the spleen, liver, lungs, bone marrow, and brain deficiency of the enzyme sphingomyelinase Defective NPC1 and NPC2 genes that regulate intracellular processing and transport of LDLderived cholesterol large cells filled with lipid droplets

Foamy Histiocyte in Nieman-Pick Disease

Tay-Sachs disease:

deficiency of the enzyme hexosaminidase A occurs when harmful quantities of a fatty acid derivative called a ganglioside accumulate in the nerve cells of the brain

Sea-blue histiocytosis:

accumulation of phosphosphingolipids in cytoplasm

Neimann Pick

vacuolization due to infection

Lymphocytes
Nuclear

Clefting

Cytoplasmic

Increased cytoplasm Vacuolization Azurophilic granulation

Atypical

Lymphocyte/Reactive lymphocyte
Larger than normal size

 Trk's

cell or irritation leukocyte :

a nongranular, mononuclear cell displays morphologic cxs of both an atypical lymphocyte and a plasma cell

observed

during severe anemia, chronic infections, and leukemoid reactions

 Leukemoid

Reaction

An excessive leukocytic response in the peripheral blood

Due to elevation of cytokines or granulocyte colonystimulating factor by tumor

Neutrophilic Eosinophilic Eryhthroblastosis Leukoerythroblastosis Lymphocytic

leukemoid reactions