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Morphologic and Distributive Leukocyte Disorders. LabM 321 Introduction to Clinical Hematology Winter 2010 ©Cara Calvo, MS, MT(ASCP)SH – UW, 2009 - 2010. Graphic accessed http://www.med-ed.virginia.edu/courses/path/innes/images/wcdjpeg/wcd%20dohle%20x100.jpeg , 2001. Introduction.

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Morphologic and distributive leukocyte disorders l.jpg

Morphologic and Distributive Leukocyte Disorders

LabM 321 Introduction to Clinical Hematology

Winter 2010

©Cara Calvo, MS, MT(ASCP)SH – UW, 2009 - 2010.

Graphic accessed http://www.med-ed.virginia.edu/courses/path/innes/images/wcdjpeg/wcd%20dohle%20x100.jpeg, 2001.


Introduction l.jpg
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:

    • Quantitative or macro changes

      • alterations in numbers of cells

        • Absolute

        • Relative

  • Qualitative or micro changes

    • alterations in cell morphology

      • Nucleus

      • Cytoplasm

Graphic accessed http://home13.inet.tele.dk/gloerud/yellow_l.gif, 2008.



Definitions white cell numbers l.jpg
DefinitionsWhite 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

  • Leukocyte Alkaline Phosphatase – stain used to differentiate a leukemoid from a leukoerythroblastic reaction

Graphics accessed URL http://atlasgeneticsoncology.org/Anomalies/t0422q12q11ID1153.html & http://www.med-ed.virginia.edu/courses/path/innes/wcd/leukocytosis.cfm, , 2010.

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


Neutrophilia 7 5 x 10 9 l l.jpg
Neutrophilia>7.5 x 109/L

Other defining features:

  • Left shift

    • Increased band forms

  • “toxic” cell appearance

    • Dohle bodies

    • Vacuoles

    • Intra-cellular microbes

Graphisc accessed http://www.accessmedicine.com/loadBinary.aspx?name=licha&filename=licha_II.B.001.jpg, and http://www.wadsworth.org/chemheme/heme/microscope/pix/yeast_nw.jpg, 2007.


Causes of neutrophilia l.jpg

Infections

(primarily bacterial)

Drugs/Hormones

epinephrine

corticosteroids

lithium

venoms/poisons/toxins

Tissue necrosis

acute gout

burns

trauma

infarcts

Other

autoimmune disorders

stress

severe physical activity

pregnancy

smoking

acute hemorrhage

post-splenectomy

myeloproliferative disorders

Metabolic

ketoacidosis

uremia

eclampsia

thyrotoxicosis

Causes of Neutrophilia


Pathophysiology l.jpg

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.

Pathophysiology


Eosinophilia absolute count 0 5 x 10 9 l l.jpg
EosinophiliaAbsolute count >0.5 x 109/L

Causes:

  • parasites

    • Helminths

  • drug treatments

  • allergies

  • infections

  • neoplasms

    • CML

  • autoimmune disorders


Basophilia absolute count 0 15 x 10 9 l l.jpg
Basophilia Absolute count >0.15 x 109/L

Causes:

  • CML

  • allergies

  • inflammatory disorders

  • irradiation

  • viral infections

Graphic accessed URL http://healthsystem.virginia.edu/internet/hematology/HessImages/Mature-basophils-100x-website-arrow.jpg, 2006.


Monocytosis absolute count 0 8 x 10 9 l l.jpg
MonocytosisAbsolute 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 10 9 l l.jpg

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

SLE

Neoplasm

BM Failure

Megaloblastic Anemia

Aplastic Anemia

Hypersplenism

Idiopathic

Neutropenia< 2.5 x 109/L


Neutropenia pathophysiology l.jpg
Neutropenia Pathophysiology influenced by patient age and race.

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]


Lymphocytosis absolute count 5 5 x 10 9 l l.jpg

Normally: influenced by patient age and race.

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

LymphocytosisAbsolute count >5.5 x 109/L


Infectious mononucleosis l.jpg
Infectious Mononucleosis influenced by patient age and race.

  • 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 10 9 l l.jpg
Lymphopenia influenced by patient age and race.Absolute lymphocyte count <0.6 x 109/L

  • There are three types of abnormalities:

  • Decreased production

  • Increased destruction

  • Changes in distribution


Lym pho pen ia l.jpg

Decreased production influenced by patient age and race.

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

Lymphopenia


Qualitative wbc disorders l.jpg
Qualitative influenced by patient age and race.WBC Disorders

Think Morphology Changes

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.


Altered cell morphology l.jpg
Altered Cell Morphology influenced by patient age and race.

  • Nuclear

    • Pelger-Huet

    • Hypersegmentation

  • Cytoplasmic

    • Alder-Reilly

    • Chediak-Higashi

    • May-Hegglin

    • Gaucher

    • Niemann-Pick

    • Mucopolysacchridoses

    • Toxic Granulation

    • Vacuolization

    • Dohle Bodies

    • Necrobiosis

Think Neutrophilia due to Severe Bacterial Infection

Peripheral Blood, Wright’s, 100x.


Definitions l.jpg

Pelger Huet influenced by patient age and race.– 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]

Definitions


Definitions20 l.jpg

Alder-Reilly influenced by patient age and race. - an inherited trait characterized by the presence of abnormally large azurophilic and basophilic granulesresembling 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 demonstratinggiant cytoplasmic granules.

Definitions


Definitions21 l.jpg

Gaucher influenced by patient age and race. & Niemann-Pickare characterized by the lack of or defective activity of enzymes.

In Gaucher disease, there is a lack ofbeta-glucocerebrosidaseand macrophages become laden with glucocerebrosides.

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

Mucopolysaccharidosesare a group of genetically determineddeficiencies of specific enzymesinvolved in the degradation of mucopolysaccharides.Examples:

Hurlers

Hunter

Sanfilippo

Definitions


Pelger huet hypersegmentation l.jpg
Pelger-Huet & Hypersegmentation influenced by patient age and race.

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


May hegglin l.jpg
May Hegglin influenced by patient age and race.

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


Alder reilly l.jpg

Graphic accessed influenced by patient age and race.http://evolvels.elsevier.com/section/default.asp?id=1138_ccalvo7_0001, 2008.

Alder Reilly


Chediak higashi l.jpg
Chediak Higashi influenced by patient age and race.

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


Mucopolysacharidoses l.jpg
Mucopolysacharidoses influenced by patient age and race.

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


Toxic granulation vacuolization l.jpg
Toxic Granulation & Vacuolization influenced by patient age and race.

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 l.jpg

Graphics accessed influenced by patient age and race.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.

Dohle Bodies and Necrobiosis

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.

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.)


Niemann pick l.jpg
Niemann Pick influenced by patient age and race.

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


Gaucher l.jpg
Gaucher influenced by patient age and race.

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


Lymphocytosis l.jpg
Lymphocytosis influenced by patient age and race.

Peripheral Blood, Wright’s, 100x.

Bordatella pertussis

  • Whooping Cough

    • BUTT CELL

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


Lymphocytosis32 l.jpg
Lymphocytosis influenced by patient age and race.

  • Epstein-Barr Virus

    • Infectious mononucleosis

      • Reactive/atypical/variant lymphocytes

Graphic accessed http://www.wadsworth.org/chemheme/heme/microscope/imono.htm, 1998.


Check point hematography case studies l.jpg
Check Point influenced by patient age and race.Hematography Case Studies

  • Case 1

  • Case 10

  • Case 14

  • Case 25


References l.jpg
References influenced by patient age and race.

  • Rodak BF, Fritsma GA, and Doig K. (2007). Hematology Clinical Principles and Applications. St. Louis, Missouri. Saunders Elsevier. Chapter 28

  • Anderson SC and Poulsen KB. (2003). Atlas of Hematology. Philadelphia, Pennsylvania. Lippincott Williams Wilkins.

  • University of Virginia Pathology Hematology

    • Benign Disorders http://www.med-ed.virginia.edu/courses/path/innes/wcd/benign.cfm Qualitative Disorders http://www.med-ed.virginia.edu/courses/path/innes/wcd/qualitative.cfm


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