Morphologic and Distributive

Leukocyte Disorders

Leucocytes differentiation

Only Mature WBC cells should

present in peripheral Blood

Normal WBC count

The formation of Neutrophil,

Monocyte, Macrophage

Granules in Neutrophils:

Primary granules: promyelocyte stage

Secondary granules: myelocyte stage and predominate therafter

Life span of neutrophil

in Blood is 6-10 hours

Granulopoiesis

Neutrophil kinetics

Distribution of

Macrophages

Phagocytosis and bacterial

destruction 1. Bacteria enter the

neutrophil surrounded by

invaginated cell

membrane

2. Fusion with primary

lysosome to form

phagosome.

3. Enzymes including

lactoferrin attack the

organism

Undigested bacteria

remains excreted by

exocytosis

Abnormal WBC

Toxic granules

Peter heut anomaly

Basophilic inclusions Dohle bodies Hypersegmented

Bizzare giant granules Alders anomalies

Quantitative WBC Disorders

Introduction • Leukocytes function to protect the body against foreign

organisms or antigens.

• In doing so, they undergo visible changes that can be detected and evaluated macro- and microscopically.

• The changes fall into two categories:

1. Quantitative or macro changes

alterations in numbers of cells

Absolute

Relative

2. Qualitative or micro changes

alterations in cell morphology

Nucleus

Cytoplasm

Definitions

White Cell Numbers

Leukocytosis: increase in the numbers of circulating white cells

>12,000/uL

Leukopenia: decrease in the numbers of circulating white cells

< 4,000/uL

Left Shift – increased circulating numbers of immature neutrophils

Leukoerythroblastic Reaction – leukocytosis with a left shift accompanied by nucleated red cells: seen in malignancy.

Leukemoid Reaction – benign excessive leukocytosis accompanied by an exaggerated neutrophilia and a left shift in response to an infection; the WBC > 50 x 109/L

http://www.med-ed.virginia.edu/courses/path/innes/images/wcdjpeg/wcd%20leuko%20Eblastic%20x50.jpeg

Neutrophilia

>7.5 x 109/L

Other defining features:

1. Left shift

– Increased band forms

2. “toxic” cell

appearance

• Dohle bodies

• Vacuoles

• Intra-cellular

microbes

Causes of Neutrophilia

• Infections o (primarily bacterial)

• Drugs/Hormones o epinephrine

o corticosteroids

o lithium

o venoms/poisons/toxins

• Tissue necrosis o acute gout

o burns

o trauma

o infarcts

• Other o autoimmune disorders

o stress

o severe physical activity

o pregnancy

o smoking

o acute hemorrhage

o post-splenectomy

o myeloproliferative disorders

• Metabolic

o ketoacidosis

o uremia

o eclampsia

o thyrotoxicosis

Pathophysiology

Demargination of

marginated pool of cells

doubling of count

Release of BM-storage

pools

left shift

Increased cell production

sustained neutrophilia

• Stress

(pseudoneutrophilia)

Acute Inflammation

• Chronic Infection

Graphic accessed URL http://www.med-ed.virginia.edu/courses/path/innes/wcd/leukocytosis.cfm, 2010.

Eosinophilia

Absolute count >0.5 x 109/L

Causes:

parasites

Helminths

drug treatments

allergies

infections

neoplasms

Chronic myeloid leukemia

(CML)

autoimmune disorders

Basophilia

Absolute count >0.15 x 109/L

Causes:

CML

allergies

inflammatory

disorders

irradiation

viral infections

Monocytosis

Absolute count >0.8 x 109/L

Most commonly seen in

conditions with increased cell

damage -

Chronic infection [TB, syphilis,

protozoal infections, rickettsial

infections]

Recovery from agranulocytosis

Post-splenectomy

Strenuous exercise

Subacute bacterial endocarditis

Neutropenia

< 2.5 x 109/L • Definition: less than the normal

absolute count; greatly influenced by patient age and race.

– African and Middle Eastern populations

• Subclasses include mild, moderate and severe

Causes

• Reactions to Drugs – BM ablative therapy

• Infections – HIV/Hepatitis

– Typhoid/ miliary TB

– Malaria

• Immune Disorders – Systemic lupus erythromatous (SLE)

• Neoplasm

• BM Failure – Megaloblastic Anemia

– Aplastic Anemia

• Hypersplenism

• Idiopathic (of unknown cause).

Defects inside or outside the Bone Marrow

Decreased proliferation [failure of cells - aplasia]

Decreased maturation [insufficient number of

precursors undergoing abnormal maturation]

Decreased survival [increased destruction and/or

rapid removal of cells]

Distribution [total body pools are normal,

circulating numbers are reduced]

Neutropenia Pathophysiology

Lymphocytosis

Absolute count >5.5 x 109/L

Normally:

60-80% circulating

lymphs are T-cells

[2:1 CD4/CD8]

10-20% are B-lymphs

5-10% are natural

killer or NK cells

• Causes

– Infections

• Viral

– Infectious mononucleosis

• Bacterial

– Pertussis

– Thyrotoxicosis

– Recovery from acute infections

– Neoplasm

• Leukemias

• Lymphomas

Infectious Mononucleosis

• Acute, self-limiting, febrile infection of B-cells

• Circulating reactive lymphocytes are primary CD8 T-cells

• Typically occurs in those age 10-25 years

Fever

Sore throat

Lymphadenopathy

Lethargy

Positive serology – Heterophile antibodies

Graphic accessed URL http://www.md.huji.ac.il/mirror/webpath/HEME013.jpg, 2005.

Lymphopenia

Absolute lymphocyte count <0.6 x 109/L

• There are three types of abnormalities:

Decreased production

Increased destruction

Changes in distribution

Lymphopenia

– Decreased production

SCID = severe combined immunodeficiency

Protein-calorie malnutrition

Zinc deficiency

– Increased destruction

HIV infection

Radiation therapy

Neoplastic chemotherapy

SLE

– Redistribution

Glucocorticoid

therapy

Anesthesia

TB

Influenza

Burns

– Other

Hodgkin’s

Myasthenia gravis

Qualitative

WBC Disorders

Graphics accessed http://us.mms.com/us/mpire/tools/download/wallpapers/2.jpg, http://www.stephengates.com/Blog/uploaded_images/unsignedUser_662.unsignedChar_1170384615063-779906.png, &

http://3.bp.blogspot.com/_6B8tPuW7TwQ/Rtw2S9ud0zI/AAAAAAAACiw/tBI6crsT3nU/s400/mandm.jpg, 2009.

Think

Morphology

Changes

Altered Cell Morphology

• Nuclear Pelger-Huet

Hypersegmentation

• Cytoplasmic Alder-Reilly

Chediak-Higashi

May-Hegglin

Gaucher

Niemann-Pick

Mucopolysacchridoses

Toxic Granulation

Vacuolization

Dohle Bodies

Necrobiosis

Peripheral Blood, Wright’s, 100x.

Think

Neutrophilia

due to Severe

Bacterial

Infection

Definitions

• Pelger Huet – an

inherited condition

resulting in

hyposegmentation of

granulocyte nuclei with

increased density and

coarseness of the

chromatin.. Don’t confuse

this anomaly with a

neutrophilic left shift!

• May-Hegglin - a rare

syndrome characterized by

leukopenia, variable

thrombocytopenia,

GIANT PLATELETS,

and gray-blue cytoplasmic

inclusions in the

neutrophils and monocytes

[dohle-like bodies]

Pelger Huet vs band neutrophil

Definitions

• Alder-Reilly - an inherited trait characterized by the presence of abnormally large azurophilic and basophilic granules resembling neutrophilic toxic granulation.

• Chediak-Higashi - is a genetic disorder that has an equivalent syndrome in mink, cattle, mice, cats, & killer whales. Affected individuals display partial albinism, are very susceptible to common infectious agents, and have white cells demonstrating giant cytoplasmic granules.

Definitions • Gaucher & Niemann-Pick are

characterized by the lack of or defective activity of enzymes.

In Gaucher disease, there is a lack of beta-glucocerebrosidase and macrophages become laden with glucocerebrosides.

In Niemann-Pick, there is deficient activity of lysosomal hydrolase and sphingomyelinase resulting in the accumulation of cholesterol and sphingomyelin in mononuclear phagocytes.

• Mucopolysaccharidoses are

a group of genetically

determined deficiencies of

specific enzymes involved in

the degradation of

mucopolysaccharides.

Examples:

Hurlers

Hunter

Sanfilippo

Pelger-Huet & Hypersegmentation

Graphics accessed http://evolvels.elsevier.com/section/default.asp?id=1138_ccalvo7_0001, 2008.

May Hegglin

Graphic accessed http://evolvels.elsevier.com/section/default.asp?id=1138_ccalvo7_0001, 2008.

Alder Reilly

Graphic accessed http://evolvels.elsevier.com/section/default.asp?id=1138_ccalvo7_0001, 2008.

Chediak Higashi

Graphic accessed http://evolvels.elsevier.com/section/default.asp?id=1138_ccalvo7_0001, 2008.

Mucopolysacharidoses

Graphic accessed ttp://www.academic.marist.edu/~jzmz/topics/bloodsmears/bloodsmears27.html, 2005.

Toxic Granulation & Vacuolization

Graphics accessed http://evolvels.elsevier.com/section/default.asp?id=1138_ccalvo7_0001, http://www.mclno.org/webresources/kbase/cellatlas/images/Vacuolated%20Segmented%20Neutrophil.jpg, &

http://path.upmc.edu/cases/case53/images/micro2.jpg , 2008.

Dohle Bodies and Necrobiosis

Necrobiotic WBC displays nuclear degradation or

karyorrhexis. Indicates cell death in chemotherapy or a

poorly preserved specimen. (From Carr JH, Rodak BF:

Clinical Hematology Atlas, 2nd ed.

Philadelphia: Saunders, 2004.)

Graphics accessed http://evolvels.elsevier.com/section/default.asp?id=1138_ccalvo7_0001 & http://www.med-ed.virginia.edu/courses/path/innes/images/wcdjpeg/wcd%20dohle%20x100.jpeg, 2008.

Single or multiple blue cytoplasmic inclusions. They

represent remnants of rough endoplasmic reticulum

from earlier maturational stages. They are associated

with myeloid "left shifts" and are seen in conjunction

with toxic granulation.

Niemann Pick

Graphic accessed http://www.nlm.nih.gov/medlineplus/spanish/ency/images/ency/fullsize/1224.jpg, 2001.

Gaucher

Graphics accessed http://www.molmed.lu.se/images/gaucher-cell.jpg & http://arttoheartweb.com/images/Van_Gogh_Starry_Night.jpg, 2001.

Lymphocytosis

Bordatella pertussis

• Whooping Cough

– BUTT CELL

Graphic accessed http://pathmicro.med.sc.edu/ghaffar/pertussis-lympho.jpg, 1998.

Peripheral Blood, Wright’s, 100x.

Lymphocytosis

• Epstein-Barr Virus

– Infectious mononucleosis

• Reactive/atypical/variant

lymphocytes