wbc basics
TRANSCRIPT
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Disorders of
WBC
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Disorders of WBCs
Proliferative disordersWBC
LeukopeniasWBC
REACTIVE-common (not serious)-in response to infection
NEOPLASTIC-less frequent
-more important-Inncludes
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The white blood cells
1. Neutrophils
2. Eosinophils
3. Basophils
4. Monocytes
5. Lymphocytes
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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
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BAND / STAB CELL immature PMN
EOSINOPHIL
NEUTROPHIL
LYMPHOCYTE
BASOPHIL
MONOCYTE
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Granulopoiesis
Stages
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Granulopoiesis stages
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Broadclassificationof WBCdisorders
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Disorders of WBCs
Proliferative disordersWBC
LeukopeniasWBC
REACTIVE-common-in response to infection
NEOPLASTIC-less frequent
-more important
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Leucopenia
Decrease in circulating WBC.
Low WBC count
Decrease in neutrophils
Neutropeniaor granulocytopenia
Decrease in lymphocytes
Lymphopenia
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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*.
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Peripheral smear
WBC
Single band form (neutrophil)
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Diagnosis:
Congenital neutropenia
consistent with Kostmanns
syndrome-(low PMN since birth)
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Beside agranulocytosis, the bone
marrow and blood show a number of
other abnormalities (including
maturational arrest of neutrophilprecursors at the promyelocyte
stage, absolute monocytosis,
eosinophilia and thrombocytosis).
The gamma globulin level
(antibodies) in blood is low, further
increasing the risk for infection.
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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 tooverwhelming bacterial infection*(probably
meningococcemia)
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Neutropenia Reductionin number of neutrophils in
peripheral blood (absolute count
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Neutropenia Pathogenesis
1. production2. destruction
3. margination (increased adhesionmolecule synthesis)
Etiology: (imp causes) Aplastic anemia
Autoimmune destruction -( SLE ), Feltys syndrome(autoimmune neutropenia+RA+splenomegaly)
B12/folate deficiency - ineffective erythropoiesis andgranulopoeisis
Septic shock (inc. adhesion molecules) Drugs: (Most common) - chloramphenicol,alkylating agents (busulfan the worst ) , anticancer drugs (methotrexate),phenylbutazone.propylthiouracil
Chemicals:benzene, insecticides
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Neutropenia: clinical
findings Counts
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Neutropenia / Agranulocytos :
Ulcerative Necrotizing Lesion
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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
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Lymphopenia:
Decreased circulating lymphocytes
CAUSES :
1. Drugs:Corticosteroids (increased adhesion),cyclophosphamide
2. Autoimmune destruction:SLE
3. Immunodeficiency syndrome:Di Georgesyndrome (T cell deficiency), AIDS, Severecombined immunodeficiency.
4. Endocrine:Cushings syndrome5. Increased adhesion of lymphatics in lymph
node prevent release of lymphocytes into theblood.= corticoid steroids
6. Hypercortisol in cushings decrease the releaseof lymphocytes from lymph node
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Reactiveproliferations of
WBCs
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Reactive proliferations
of WBCs Leukocytosis:increase in number ofblood leukocytes.
1. Neutrophil =Neutrophilia
2. lymphocytes =Lymphocytosis3. Eosinophils =Eosinophilia
4. Basophils =Basophilia
5. Monocytes =Monocytosis
BASOPHILIA means suffering from 1 of theMYELOPROLIFERATIVE disorders.(thrombocytopenia, Polycythemia RubraVera)
MOnocytes increase in chronicinfections..inflammation
C 3
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A 55-year-old white man with chest pain and laboredbreathing.
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
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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.
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Increase in PMN :1. MI (tissue necrosis)
2. **MINOR Bacterial infections (wbc increased. (MC) (severe infectionsmargination thus less WBC
3. PMN more in number- then bacterial infection. if find bandcells/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 acuteleukemias
it should be noted that neutrophilia may be seen instates of tissue necrosis, such as myocardialinfarction, due to the release of inflammatory
mediators from damaged tissue. In addition, a mild neutrophilia may be seen in anysituation of acute stress, due to an epinephrine-induced demargination of neutrophils within theblood vessels. Glucocorticoid administration is alsoa common cause of mild neutrophilia
Peripheral smear
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Peripheral smear
WBC count
Increased neutrophils and its immature forms
h l l k
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Neutrophilic leukocytosis
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Band form
Toxic granulesMature neutrophil
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Coarse purple cytoplasmic granules (toxic granulations)
Dohle bodies
Peripheral blood smear frompatient with bacterial sepsis
DOHLE BODY EXAM
CHARACTERISTIC
SEE THE BLUE
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Cytoplasmic vacuolation
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Bone marrow
Precursor
pool
Storage
poolMarginating
pool
Circulating
pool
Peripheral blood
Tissue
Pool
We always count?
circuLATING POOL
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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.
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Neutrophilic leukocytosis:
causes
Infections:Acute bacterial
infections Ex: acute
appendicitis, abscess Sterile inflammation with
necrosis:Myocardial infarction
Drugs: Decrease adhesionmolecule synthesis
(corticosteroids, lithium,
epinephrine)
C 4
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A 37 year old female patient With Feverof 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 somekind of infections.
Person with WHOOPING COUGH= increase oflymphocytesin peripheral blood
Case 4
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Metamyelocyte
Neutrophilia : low power
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Neutrophilia :medium power
MYELOCYTE
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Benign reactive condition withmarked increasein WBC countwith shift to left.
The peripheral smear findings
resemblefindings in chronicmyeloid leukemia.
Therefore, it is important todifferentiate this condition fromCML (low lap score).
Leukemoid reaction
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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:
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Leukemoid reaction:
Clinical findings
Frequently confused with leukemia(esp. CML)
Factors favoringleukemoid reaction
include:
Fever resolution with treatment ofinfection,
increased LAP score,*******
absence of splenomegaly or abnormal
chromosomes, *******
BM examination : reactive leukocytosis.
Leukemoid reaction : Lab findings
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Leukemoid reaction : Lab findings
Leukocyte alkaline phosphatase
score (LAP) score: LAP : present in specific granules
Marker of a mature neutrophil
Leukemoid reactions have anincreased LAP score
CML has a low score, since the cellsare neoplastic.
LAP ti
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LAP
positive neutrophils
LAP negative
neutrophils in CML
Exam picture
On LAP SCORE
Leukoerythroblastic
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Leukoerythroblastic
reaction Presence of immature WBCsand nucleated
RBCsin 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
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Metastatic cancer
to bone
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Leukoerythroblastic
reaction
Lab findings:
PB findings: myeloblasts,
promyelocytes and other immature
forms plus nucleated RBCs
BM examination identifies the cause
of the reaction.
Eosinophilia
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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 causeeosinophilia
(noninvasive)
3. Neoplasia:CML, Hodgkins disease;
4. Addisons disease,
5. Lofflers syndrome, Allergic aspergillosis
Eosinophilic le koc tosis =
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Eosinophilic leukocytosis =
Eosinophilia
Pathogenesis:
Release of Eosinophil chemotactic
factorfrom mast cells / basophilsin type I IgE mediated
hypersensitivity reactions.
****Growth factor: IL -5
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Eosinophils
Eosinophilia Medium power
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Eosinophils in Blood in
Allergy
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Basophilia
Absolute basophil count
>110/L
Causes: Myeloproliferative disorders (MPD)
Excellent marker for polycythemia
rubra vera and CML.
>5% basophils suggests MPD
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Monocytosis
Absolute monocyte count>800/L
Usually associated with : Chronic infections:
TB, SBE, syphilis, brucellosis
Chronic inflammation: SLE, RA, Ulcerative colitis andCrohns disease
Marker of chronic inflammation
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A 20-year-old male complains of sore throat,fever, swollen lymph nodes on the back ofhis neck, and malaise of ten days duration.
On examination: Fever, Enlargement of cervical lymph
nodes; exudative tonsillitis; slightlyenlarged spleen and liver.
Labs: CBC and peripheral smear : marked
leukocytosis (83,000) with lymphocytosisand atypical lymphocytes.
Case 5
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Lymphocytosis Absolute lymphocyte count >4000/L in
adults or >8000/L in children.
Atypical lymphocytes: Antigen stimulated lymphocytes, with
prominent nucleoli and bluish discoloration ofcytoplasm
Pathogenesis: Increased production (antigen driven) : viral
infections
Increased releasefrom lymph nodes:whooping cough
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Case 6 A 2-year-old female with paroxysmsof
multiple coughs in a single expiration,followed by a high-pitched inspiratorywhistle or whoop.
Her immunization schedule isincomplete.
On examination:fever. Childapprehensive and becomes cyanotic
during cough paroxysm; CBC: marked leukocytosis with
lymphocytosis.
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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
I f ti
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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 againstinvaded B cells and form atypical lymphocytes(Downey cells).
Atypical lymphocytes found in the peripheralblood and T cell areas of lymphnodes.
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Typical lymphocytes
Atypical lymphocytesBallerina skirt appearance)
*****Infectious
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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), includesadoloscents 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.
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Qualitative white blood
cell disorders
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Chediak-Higashi syndrome
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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
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Chediak-Higashi syndrome
4 Chronic granulomatous disease:
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4. Chronic granulomatous disease:
Absence of NADPH oxidase
Abnormal NBT Can kill Strep but not Staph
5. Acquired chemotactic problems:
Seen in new born, leukemicneutrophils and in diabetics
6. Adhesion defects:
Present at birth with failure toseparate the umbilical cord
Normal nitroblue tetrazolium test (NBT) Abnormal nitroblue tetrazolium test (NBT)
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