Wbc Basics

8/12/2019 Wbc Basics

1/70

Disorders of

WBC


2/70

Disorders of WBCs

Proliferative disordersWBC

LeukopeniasWBC

REACTIVE-common (not serious)-in response to infection

NEOPLASTIC-less frequent

-more important-Inncludes


3/70

The white blood cells

1. Neutrophils

2. Eosinophils

3. Basophils

4. Monocytes

5. Lymphocytes


4/70

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


5/70

BAND / STAB CELL immature PMN

EOSINOPHIL

NEUTROPHIL

LYMPHOCYTE

BASOPHIL

MONOCYTE


6/70

Granulopoiesis

Stages


7/70

Granulopoiesis stages


8/70

Broadclassificationof WBCdisorders


9/70

Disorders of WBCs

Proliferative disordersWBC

LeukopeniasWBC

REACTIVE-common-in response to infection

NEOPLASTIC-less frequent

-more important


10/70

Leucopenia

Decrease in circulating WBC.

Low WBC count

Decrease in neutrophils

Neutropeniaor granulocytopenia

Decrease in lymphocytes

Lymphopenia


11/70

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*.


12/70

Peripheral smear

WBC

Single band form (neutrophil)


13/70

Diagnosis:

Congenital neutropenia

consistent with Kostmanns

syndrome-(low PMN since birth)


14/70

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.


15/70

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)


16/70

Neutropenia Reductionin number of neutrophils in

peripheral blood (absolute count


17/70

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


18/70

Neutropenia: clinical

findings Counts


19/70

Neutropenia / Agranulocytos :

Ulcerative Necrotizing Lesion


20/70

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


21/70

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


22/70

Reactiveproliferations of

WBCs


23/70

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


24/70

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


25/70

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.


26/70

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


27/70

Peripheral smear

WBC count

Increased neutrophils and its immature forms

h l l k


28/70

Neutrophilic leukocytosis


29/70

Band form

Toxic granulesMature neutrophil


30/70

Coarse purple cytoplasmic granules (toxic granulations)

Dohle bodies

Peripheral blood smear frompatient with bacterial sepsis

DOHLE BODY EXAM

CHARACTERISTIC

SEE THE BLUE


31/70

Cytoplasmic vacuolation


32/70


33/70

Bone marrow

Precursor

pool

Storage

poolMarginating

pool

Circulating

pool

Peripheral blood

Tissue

Pool

We always count?

circuLATING POOL


34/70

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.


35/70

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


36/70

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


37/70

Metamyelocyte

Neutrophilia : low power


38/70

Neutrophilia :medium power

MYELOCYTE


39/70

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


40/70

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:


41/70

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


42/70

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


43/70

LAP

positive neutrophils

LAP negative

neutrophils in CML

Exam picture

On LAP SCORE

Leukoerythroblastic


44/70

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


45/70

Metastatic cancer

to bone


46/70


47/70


48/70

Leukoerythroblastic

reaction

Lab findings:

PB findings: myeloblasts,

promyelocytes and other immature

forms plus nucleated RBCs

BM examination identifies the cause

of the reaction.

Eosinophilia


49/70

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 =


50/70

Eosinophilic leukocytosis =

Eosinophilia

Pathogenesis:

Release of Eosinophil chemotactic

factorfrom mast cells / basophilsin type I IgE mediated

hypersensitivity reactions.

****Growth factor: IL -5


51/70

Eosinophils

Eosinophilia Medium power


52/70

Eosinophils in Blood in

Allergy


53/70

Basophilia

Absolute basophil count

>110/L

Causes: Myeloproliferative disorders (MPD)

Excellent marker for polycythemia

rubra vera and CML.

>5% basophils suggests MPD


54/70

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


55/70

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


56/70


57/70

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


58/70

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.


59/70


60/70

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


61/70

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.


62/70

Typical lymphocytes

Atypical lymphocytesBallerina skirt appearance)

*****Infectious


63/70

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.


64/70

Qualitative white blood

cell disorders


65/70


66/70

Chediak-Higashi syndrome


67/70

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


68/70

Chediak-Higashi syndrome

4 Chronic granulomatous disease:


69/70

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)


70/70

Wbc Basics

Documents