Leukocytic Disorders: Non-Neoplastic Alterations

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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 diff’t WBC

 Definitions:
 Leukopenia:
 decrease in lymphocytes, segmenters or all cell types
 Leukocytosis:
 increase in one or more cell types
Relative vs.
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 & Diff’l count

AGE TOTAL NEUTRO EOSI BASO LYMPHO MONO


WBC
12 months 6.0 – 17.5 1.5 – 8.5 0.05 – 0.70 0 – 0.20 4.0 – 10.5 0.05 – 1.1
x 109/L x 109/L x 109/L x 109/L x 109/L x 109/L

4 years 5.5 – 15.5 1.5 – 8.5 0.02 – 0.65 0 – 0.20 2.0 – 8.0 0 – 0.8
x 109/L x 109/L x 109/L x 109/L x 109/L x 109/L

6 years 5.0 – 14.5 1.5 – 8.0 0 – 0.65 0 – 0.20 1.5 – 7.0 0 – 0.8
x 109/L x 109/L x 109/L x 109/L x 109/L x 109/L

10 years 4.5 – 13.5 1.8 – 8.0 0 – 0.60 0 – 0.20 1.5 – 6.5 0 – 0.8
x 109/L x 109/L x 109/L x 109/L x 109/L x 109/L

21 years 4.5 – 11.0 1.8 – 7.7 0 – 0.45 0 – 0.20 1.0 – 4.8 0 – 0.8
x 109/L x 109/L x 109/L x 109/L x 109/L x 109/L
Qualitative Changes in
WBC
 Cytoplasm
 altered primary granules
 ribosomal RNA in rows
 lysosomal alteration
 vacuolation; degranulation
 Pseudopod formation

 Nucleus
 pyknotic: shrunken, dense, dehydrated
 hypersegmented: more than 5 segments
 (megaloblastic anemia)
Quantitative alteration
Changes in number
Quantitative changes in
WBC
 GRANULOCYTES  AGRANULOCYTES
 Neutrophilia:  Monocytosis:
 Neutropenia:  Monocytopenia:
 Eosinophilia:  Lymphocytosis:
 Lymphocytopenia:
 Eosinopenia:
 Plasmacytosis:
 Basophilia:
 Basopenia:
NEUTROPHILIA
 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
 Pseudoneutrophilia
 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
injuries

 Infection:
 Appendicitis, salphingitis, colitis, pancreatitis,otitis media

 Hemolysis:
 acute and delayed HTR
NEUTROPHILIA

 Toxins:
 Metabolic (uremia, eclampsia, gout, diabetic acidosis)
 Drugs/Chemicals:
 (lead, mercury, potassium chlorate, turpentine, benzene)
 Venoms: spiders,bees
 Hemorrhage:
 bleeding occurred in serous cavity
NEUTROPENIA
 absolute count < 1,800/mL
 Most common cause of leukopenia
 Extreme neutropenia-agranulocytosis: decreased
prod, increased destruction
 CAUSES
 Myeloid hypoplasia
 Ineffective granulocytopoiesis
 Decreased survival or increased destruction
 Pseudoneutropenia-after injection of
endotoxin,hypersensitivity
NEUTROPENIA

 Myeloid hypoplasia:
 Kostmann’s 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
Gaucher’s dse

 Drugs
 Alkylating agents, ionizing radiation, chloramphenicol,
benzene, sulfonamides, quinine, quinidine
NEUTROPENIA

 Ineffective Granulocytopoiesis:
 Chédiak – Higashi syndrome
 Megaloblastic anemia
 Myeloproliferative disorder
 Exposure to drugs

 Decreased survival:
 Infections
 Splenic selective removal
 Felty’s syndrome
 Drug - induced
NEUTROPENIA

 Combination of hypoplasia, ineffective


production & decreased survival of
neutrophils:

 Pseudoneutropenia:
 Endotoxin
 Drug induced
 anesthesia
 ether
 pentobarbital
EOSINOPHILIA
 eosinophil count exceed 0.35 x 109/L
 Inherited, malignant or reactive
 hypersensitivity disorders
 release granules content that acts as anti-histamine
 parasitic infections
 eosinophils release granule content w/c damages
the target organism(MBP)
 abnormal morphology of eosinophils is seen
 Not characteristic of any protozoan infections
EOSINOPHILIA

 CAUSES
 Allergic diseases:
 bronchial asthma, rhinitis, hay fever
 mediated by IgE
 mast cells & basophils degranulation w/ the release of chemotactic factor

 skin disorders: (dermatoses)


 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: tse parasites provoke


higher degree of eosinophilia
 Trichinosis, strongyloidiasis,filariasis,hookworm
infxn, schistosomiasis, and fasciolopsiasis
 Moderate- Taenia,Paragonimus,trichuris,ascaris

 Infectious diseases:
 scarlet fever (cutaneous rash)
 Chorea (jerky spasmodic movements of limbs, trunk, & facial muscle)
EOSINOPHILIA

 Loeffler’s 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
EOSINOPENIA
 count is lower than 0.04 x 109/L
 Rare and stress related
 margination or migration to inflammatory site
 CAUSES
 acute stress and acute inflammatory state
caused by virus or bacteria
 epinephrine and adrenal corticotropic
secretion
 Cushing’s syndrome
 caused by excessive production of ACTH by the pituitary gland
BASOPHILIA
 count in above 0.075 x 109/L
 in general: hypersensitivity, leukemia
 Not generally affected by factors such as time, age,
physical activities
 CAUSES
 allergic reactions; hypothyroidism
 chronic myeloid leukemia, myeloid metaplasia
 polycythemia vera, chronic hemolytic anemia
 following splenectomy, ulcerative colitis
 Chicken pox & small pox infections
BASOPENIA
 decrease count below 0.01 x 109/L
 diurnal [lowest in AM; highest in PM]
 Hormonal ( corticotropin,progesterone)
 Hard to assess
 CAUSES
 sustained Tx w/ adrenal corticosteroid
 acute infection
 acute stress
 Hyperthyroidism and thyrotoxicosis
MONOCYTOSIS
 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
 RA
MONOCYTOPENIA
 decrease below 0.2 x 109/L
 follows administration of glucocorticoids

 CAUSES:
 administration of prednisone
 Hairy cell Leukemia
LYMPHOCYTOSIS
 above normal count for age
 ADULT: 1.5-4.0 x 109/L… more than 5.5
 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
 asst’d w/ T-cell leukemia
 Cxd by-fever, lymphadenopathy, skin rash

 Infectious Lymphocytosis
 contagious disease among children
 asst’d w/ coxsackie virus A, echovirus, adenovirus type 12
 vomiting, fever, cutaneous rash, CNS involvement
 Chronic Lymphocytosis
 adults, suspicion for neoplastic dse= chronic lymphocyte
leukemia

 Infectious Mononucleosis
 self-limited infectious dse w/c involves the RES
 2O to EBV infection; (+) heterophil antibody
 fever, sore throat, lymphadenopathy , prolonged malaise
 associated w/ hemolytic anemia due anti–i antibody
production
LYMPHOCYTOSIS

 Cytomegalovirus Virus infection


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

 Pertussis [Whooping cough]


 Bordetella pertussis
 inflammatory rxn of the entire RT (-paroxysms)

 Toxoplasmosis
LYMPHOCYTOPENIA
 below normal count for age 3x109 in adults
and 2.0 in children
 early stages of infection
 CAUSES
 impaired lymphopoiesis or drainage of GIT
lymphatics
 increased adenocorticortical hormones
 administration of chemotherapeutic drugs
 irradiation
 Hodgkin’s and Non-Hodgkin’s lymphoma
 terminal cases of carcinoma, AIDS
PLASMACYTOSIS
 plasma cells are seen in circulating blood
 An increase beyond 4%

 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
 monocytic
 Lymphocytic
 leukoerythroblastosis

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