Post on 06-Feb-2018
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