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Disorders of

WBC
Disorders of WBCs
Proliferative disorders
WBC
Leukopenias
WBC
REACTIVE
-common (not serious)
-in response to infection
NEOPLASTIC
-less frequent
-more important-Inncludes
LEaukemias, lymphomas.


The white blood cells
1. Neutrophils
2. Eosinophils
3. Basophils
4. Monocytes
5. Lymphocytes

Peripheral Blood Cells
A. Erythrocytes; B. Large Granular Lymphocyte; C. Neutrophil; D. Eosinophil;
E. Neutrophil; F. Monocyte; G. Platelets; H. Lymphocyte; I. Band Neutrophil; J. Basophil
BAND / STAB CELL immature PMN
EOSINOPHIL

NEUTROPHIL



LYMPHOCYTE

BASOPHIL


MONOCYTE


Granulopoiesis
Stages
Granulopoiesis stages
Disorders of WBCs
Proliferative disorders
WBC
Leukopenias
WBC
REACTIVE
-common
-in response to infection
NEOPLASTIC
-less frequent
-more important
Leucopenia
Decrease in circulating WBC.
Low WBC count
Decrease in neutrophils
Neutropenia or granulocytopenia
Decrease in lymphocytes
Lymphopenia


Case 1
The patient is a 10 month old male with a
history of recurrent upper respiratory
infections* and otitis media* since birth.
CBC:
WBC count= 3840/ul* (7,000-11,000 normal)
DLC:
25% monocytes; 4% eosinophils,
1% basophils; 70% lymphocytes,
1% neutrophils*.

Peripheral smear
WBC
Single band form (neutrophil)
Diagnosis:
Congenital neutropenia
consistent with Kostmanns
syndrome-(low PMN since birth)

Beside agranulocytosis, the bone
marrow and blood show a number of
other abnormalities (including
maturational arrest of neutrophil
precursors at the promyelocyte
stage, absolute monocytosis,
eosinophilia and thrombocytosis).

The gamma globulin level
(antibodies) in blood is low, further
increasing the risk for infection.
Case 2
15 year old male boy with high fever*- 10
days.
PE: scattered petechial hemorrhages*.
Bone marrow: normal*
CBC:
Low platelet count
Low WBC count (1850/mm3)*
DLC:
1% neutrophil*
98% lymphocyte
1% monocyte
Diagnosis: neutropenia due to
overwhelming bacterial infection* (probably
meningococcemia)
Neutropenia
Reduction in number of neutrophils in
peripheral blood (absolute count <1500/L)
Can be:
Mild (absolute count 1000-1500 cells)
Moderate (absolute count 500-1000 cells)
Severe (absolute count <500 cells)
Agranulocytosis = marked decrease in
granulocyte number predisposing to
development of infections.
Agranulocytosis when PMN drop 500 cells.
VERY LOW PMN.

Neutropenia
Pathogenesis
1. production
2. destruction
3. margination (increased adhesion
molecule synthesis)
Etiology: (imp causes)
Aplastic anemia
Autoimmune destruction -( SLE ), Feltys syndrome
(autoimmune neutropenia+RA+splenomegaly)
B12/folate deficiency - ineffective erythropoiesis and
granulopoeisis
Septic shock (inc. adhesion molecules)
Drugs: (Most common) - chloramphenicol,
alkylating agents (busulfan the worst ) , anti
cancer drugs (methotrexate),
phenylbutazone.propylthiouracil
Chemicals: benzene, insecticides


Neutropenia: clinical
findings
Counts <500 cells/uL impose a serious
risk of infection.
( Neutropenia + fever = infection)
Lesions of gingiva, floor of mouth,
buccal mucosa and pharynx
Systemic infections
Bacteria : gram negative
Bacterial colonies = botryomycosis
Fungi : candida
Viruses: Herpes simplex (type 1= oral,
type 2= genitalis)
Neutropenia / Agranulocytos :
Ulcerative Necrotizing Lesion

Neutropenia: Laboratory
findings
CBC: low neutrophil counts
BM examination:
Hypercellular
Increased destruction
Ineffective granulopoiesis
Hypocellular
Aplastic anemia
chemotherapeautic agents
Most common cause of neutropenia:
Decreased production due to drugs
Lymphopenia:
Decreased circulating lymphocytes
CAUSES :
1. Drugs: Corticosteroids (increased adhesion),
cyclophosphamide
2. Autoimmune destruction: SLE
3. Immunodeficiency syndrome: Di George
syndrome (T cell deficiency), AIDS, Severe
combined immunodeficiency.
4. Endocrine: Cushings syndrome
5. Increased adhesion of lymphatics in lymph
node prevent release of lymphocytes into the
blood.= corticoid steroids
6. Hypercortisol in cushings decrease the release
of lymphocytes from lymph node


Reactive
proliferations of
WBCs
Reactive proliferations
of WBCs
Leukocytosis: increase in number of
blood leukocytes.
1. Neutrophil =Neutrophilia
2. lymphocytes =Lymphocytosis
3. Eosinophils =Eosinophilia
4. Basophils =Basophilia
5. Monocytes =Monocytosis
BASOPHILIA means suffering from 1 of the
MYELOPROLIFERATIVE disorders.
(thrombocytopenia, Polycythemia RubraVera)
MOnocytes increase in chronic
infections..inflammation


A 55-year-old white man with chest pain and labored
breathing.
Overweight and smokes two packs of cigarettes a day.
EKG and serum cardiac marker profile : acute myocardial
infarction.
Complete blood count (CBC) :
Hemoglobin and Platelets : within normal limits
WBC count: increased (*15,500/mm3*)
Differential WBC count:
80% neutrophils *(increased)
11% band neutrophils, *
9% lymphocytes

NORMAL WBC is? 7,000-11,000
Band cells never more than 10, if the PMN are 100
if more immature PMN in blood implies? LEFT
SHIFT.

Case 3
Neutrophilic leukocytosis= Neutrophilia
Absolute count >7000 cell/uL
KEY FINDINGS:
Left shift: presence of immature neutrophil in
PB (>10% band neutrophil or any neutrophil
younger than a band).
Toxic granulation
Increase in azurophilic granules(large and prominent)
Cytoplasmic vacuolation
Phagolysosomes, indicating presence of
phagocytosis
Dohle bodies
Dull gray inclusions representing rough ER
A left shift is a colloquial term for the presence of
immature granulocytes in the peripheral blood.

Increase in PMN :
1. MI (tissue necrosis)
2. **MINOR Bacterial infections (wbc increased. (MC) (severe infections
margination thus less WBC
3. PMN more in number- then bacterial infection. if find band
cells/immature cells like metameylocytes, promeylocytes, meylocytes
(left shift) then it indicates severe BACTERIAL INFECTIONS.
4. If found only myeloblast (left shift) could be due to BM pathology
meyloproliferative dissorders, meylodisplastic syndromes or acute
leukemias
it should be noted that neutrophilia may be seen in
states of tissue necrosis, such as myocardial
infarction, due to the release of inflammatory
mediators from damaged tissue.
In addition, a mild neutrophilia may be seen in any
situation of acute stress, due to an epinephrine-
induced demargination of neutrophils within the
blood vessels. Glucocorticoid administration is also
a common cause of mild neutrophilia


Peripheral smear
WBC count
Increased neutrophils and its immature forms
Neutrophilic leukocytosis
Band form
Toxic granules
Mature neutrophil
Coarse purple cytoplasmic granules (toxic granulations)
Dohle bodies
Peripheral blood smear from
patient with bacterial sepsis
DOHLE BODY EXAM
CHARACTERISTIC
SEE THE BLUE
Cytoplasmic vacuolation

Neutrophilicleukocytosis:
Pathogenesis
Bone marrow
Precursor
pool
Storage
pool
Marginating
pool
Circulating
pool
Peripheral blood
Tissue
Pool
We always count?
circuLATING POOL
Neutrophilic leukocytosis:
pathogenesis
Increased release from marrow:
Endotoxemia, acute infection, hypoxia.
Decreased margination:
(decreased adhesion of leukocytes)
corticosteroids, epinephrine.
MI- release epienephrine which decreases adhesion
molecules
Decreased extravasation in tissues:
Corticosteroids
Increased marrow precursors:
Chronic infection or inflammation,
myeloproliferative disorders.
Neutrophilic leukocytosis:
causes
Infections: Acute bacterial
infections Ex: acute
appendicitis, abscess
Sterile inflammation with
necrosis: Myocardial infarction
Drugs: Decrease adhesion
molecule synthesis
(corticosteroids, lithium,
epinephrine)
A 37 year old female patient
With Fever of 1 week duration.
CBC:
Hb 13.9g/dl ; Hct 42.0%.
Platelet count: 210,000/mm3
WBC count : 56,000/mm3 (increased)
WBC differential:
63% segmented neutrophil ; 15 band cells*
6 Metamyelocyte*; 3 myelocyte*;1 blast*
8 lymphocyte ; 2 monocytes; 2 eosinophils
LAP ( Leukocyte alkaline phosphatase) score :
increased *
PB smear examination:
LEUKOMOID REACTION- resembles leukemia.
Exaggered response of WBC/lymphocytes to some
kind of infections.
Person with WHOOPING COUGH= increase of
lymphocytes in peripheral blood

Case 4
Metamyelocyte
Neutrophilia : low power
Neutrophilia :medium power
MYELOCYTE
Benign reactive condition with
marked increase in WBC count
with shift to left.
The peripheral smear findings
resemble findings in chronic
myeloid leukemia.
Therefore, it is important to
differentiate this condition from
CML (low lap score).


Leukemoid reaction
Leukemoid reaction
Leukocyte count >30,000 (often >50,000 /
uL)
May involve any leukocyte (neutrophil,
lymphocyte, eosinophil)
Pathogenesis:
Exaggerated benign leukocyte response.
CAUSES
Infections:
Sepsis (neutrophils)
Perforated acute appendicitis (neutrophils)
Whooping cough (lymphocytes)
Infectious mononucleosis (lymphocytes)
Cutaneous larva migrans (eosinophils)
Severe hemorrhage
Leukemoid reaction:
Clinical findings
Frequently confused with leukemia
(esp. CML)
Factors favoring leukemoid reaction
include:
Fever resolution with treatment of
infection,
increased LAP score,*******
absence of splenomegaly or abnormal
chromosomes, *******
BM examination : reactive leukocytosis.

Leukemoid reaction : Lab findings
Leukocyte alkaline phosphatase
score (LAP) score:
LAP : present in specific granules
Marker of a mature neutrophil
Leukemoid reactions have an
increased LAP score
CML has a low score, since the cells
are neoplastic.
LAP
positive neutrophils
LAP negative
neutrophils in CML
Exam picture
On LAP SCORE
Leukoerythroblastic
reaction
Presence of immature WBCs and nucleated
RBCs in peripheral blood.
Pathogenesis:
Peripheralization of BM elements secondary to:
Metastasis, bone fracture, fibrosis
Causes:
Metastasis:
Breast cancer most common cause
Fibrosis
Myelofibrosis,CML, polycythemia vera
Fracture:
multiple comminuted fracture


Metastatic cancer
to bone
Peripheral smear
Nucleated RBC
Very immature
WBC precursor
Leukoerythroblastic reaction
Leukoerythroblastic reaction
Nucleated RBC
Immature
WBC precursors
Leukoerythroblastic
reaction
Lab findings:
PB findings: myeloblasts,
promyelocytes and other immature
forms plus nucleated RBCs
BM examination identifies the cause
of the reaction.
Eosinophilia
Absolute eosinophils count >700/L
CAUSES:
1. Type I hypersensitivity reactions :
Asthma, hay fever, drug reactions (penicillin)
2. Invasive helminthic infection:
Larval phase of Ascariasis
Strongyloidiasis, Ancylostomiasis, Trichinosis
Pinworms do not cause eosinophilia
(noninvasive)
3. Neoplasia: CML, Hodgkins disease;
4. Addisons disease,
5. Lofflers syndrome, Allergic aspergillosis

pinworm does not
cause eosinophilia i
Eosinophilic leukocytosis =
Eosinophilia
Pathogenesis:
Release of Eosinophil chemotactic
factor from mast cells / basophils
in type I IgE mediated
hypersensitivity reactions.
****Growth factor: IL -5

Eosinophils
Eosinophilia - Medium power
Eosinophils in Blood in
Allergy
Basophilia
Absolute basophil count
>110/L
Causes:
Myeloproliferative disorders (MPD)
Excellent marker for polycythemia
rubra vera and CML.
>5% basophils suggests MPD
Monocytosis
Absolute monocyte count
>800/L
Usually associated with :
Chronic infections:
TB, SBE, syphilis, brucellosis
Chronic inflammation:
SLE, RA, Ulcerative colitis and
Crohns disease
Marker of chronic inflammation

A 20-year-old male complains of sore throat,
fever, swollen lymph nodes on the back of
his neck, and malaise of ten days duration.

On examination:
Fever, Enlargement of cervical lymph
nodes; exudative tonsillitis; slightly
enlarged spleen and liver.
Labs:
CBC and peripheral smear : marked
leukocytosis (83,000) with lymphocytosis
and atypical lymphocytes.
Case 5
Peripheral smear
Atypical lymphocytes
Lymphocytosis
Absolute lymphocyte count >4000/L in
adults or >8000/L in children.
Atypical lymphocytes:
Antigen stimulated lymphocytes, with
prominent nucleoli and bluish discoloration of
cytoplasm
Pathogenesis:
Increased production (antigen driven) : viral
infections
Increased release from lymph nodes:
whooping cough
Case 6
A 2-year-old female with paroxysms of
multiple coughs in a single expiration,
followed by a high-pitched inspiratory
whistle or whoop.
Her immunization schedule is
incomplete.
On examination: fever. Child
apprehensive and becomes cyanotic
during cough paroxysm;
CBC: marked leukocytosis with
lymphocytosis.

Lymphocytosis in Pertussis
Lymphocytosis : Causes
Infections:
Viral : infectious mononucleosis, CMV,
mumps, measles, etc.
Bacterial: whooping cough, tuberculosis,
brucellosis
Parasitic: toxoplasmosis
Drugs: e.g. phenytoin
Autoimmune disease: SLE
Endocrine: Graves disease
Malignancy: ALL and CLL
Infectious
mononucleosis
An example of virus disease causing
lymphocytosis.
Caused by Epstein Barr virus (EBV).
Sequence of events:
EBV invades B lymphocytes via CD 21 receptors
Cytotoxic (CD8) T lymphocytes respond against
invaded B cells and form atypical lymphocytes
(Downey cells).
Atypical lymphocytes found in the peripheral
blood and T cell areas of lymphnodes.
Typical lymphocytes
Atypical lymphocytes
Ballerina skirt appearance)
*****Infectious
mononucleosis*****
Antibody production: heterophil antibodies
(antibodies against other species e.g. RBC
of sheep) , used as the monospot test.
Clinical :
Age group: (kissing disease), includes
adoloscents and young adults.
Symptoms: classic triad: fever, sore throat and
lymphadenopathy (posterior auricular) and fourth
is hepatosplenomegaly.
Complications: hepatic dysfunction, splenic
rupture and rash if treated with ampicillin.
Heterophil antibody
and rash with
Ampicillin
Qualitative white blood
cell disorders

Clues suggesting qualitative
disorders:
Infection by unusual pathogen (e.g.
coagulase negative Staphylococcus)
Recurrent infections and growth failure
in children
Lack of inflammatory response
Qualitative white blood cell disorders
1. Acquired MPO deficiency
2. Chediak Higashi syndrome
3. Chronic granulomatous disease
4. Acquired chemotactic problems
5. Adhesion defects
Qualitative white blood cell
disorders
1.Acquired MPO deficiency
Seen in new born, pregnancy and CML
MPO stain : negative
NBT normal
2.Chediak Higashi syndrome
Defect in polymerization of microtubules
Abnormal chemotaxis, phagolysosome
formation, and bacterial killing
Giant lysosomes in cytoplasm


Chediak-Higashi syndrome
A history of recurrent bacterial infections and giant
granules seen in peripheral blood leukocytes is
characteristic.
Microtubules fail to form properly, and the
neutrophils do not respond to chemotactic stimuli.
Giant lysosomal granules fail to function.
Soft tissue abscesses with Staphylococcus aureus
are common.
Other cells affected by this disorder include
platelets (bleeding), melanocytes (albinism),
Schwann cells (neuropathy), NK and cytotoxic T
cells (aggressive lymphoproliferative disorder).
Chediak-Higashi syndrome
4. Chronic granulomatous disease:
Absence of NADPH oxidase
Abnormal NBT
Can kill Strep but not Staph
5. Acquired chemotactic problems:
Seen in new born, leukemic
neutrophils and in diabetics
6. Adhesion defects:
Present at birth with failure to
separate the umbilical cord


Normal nitroblue tetrazolium test (NBT) Abnormal nitroblue tetrazolium test (NBT)

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