Download Chapter 8 WBC

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
Life span of neutrophil
in Blood is 6-10 hours
Granules in Neutrophils:
Primary granules: promyelocyte stage
Secondary granules: myelocyte stage and predominate therafter
Granulopoiesis
Neutrophil kinetics
Distribution of
Macrophages
Phagocytosis and bacterial
destruction1. 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
Dohle bodies
Hypersegmented
Bizzare giant granules
Basophilic inclusions
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.
2.
Quantitative or macro changes
 alterations in numbers of cells
 Absolute
 Relative
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
o
o
o
acute gout
burns
trauma
infarcts
• Other
o
o
o
o
o
o
o
o
autoimmune disorders
stress
severe physical activity
pregnancy
smoking
acute hemorrhage
post-splenectomy
myeloproliferative disorders
• Metabolic
o
o
o
o
ketoacidosis
uremia
eclampsia
thyrotoxicosis
Graphic accessed URL http://www.med-ed.virginia.edu/courses/path/innes/wcd/leukocytosis.cfm, 2010.
Pathophysiology
 Demargination of
marginated pool of cells
• Stress
(pseudoneutrophilia)
 doubling of count
 Release of BM-storage
pools
Acute Inflammation
left shift
 Increased cell production
sustained neutrophilia
• Chronic Infection
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
•
Causes
• Reactions to Drugs
– BM ablative therapy
•
Infections
– HIV/Hepatitis
– Typhoid/ miliary TB
– Malaria
Subclasses include mild, moderate
and severe
•
Immune Disorders
– Systemic lupus erythromatous (SLE)
•
•
Neoplasm
BM Failure
– Megaloblastic Anemia
– Aplastic Anemia
•
•
Hypersplenism
Idiopathic (of unknown cause).
Neutropenia Pathophysiology
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 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
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
• Nuclear
 Pelger-Huet
 Hypersegmentation
• Cytoplasmic










Peripheral Blood, Wright’s, 100x.
Alder-Reilly
Chediak-Higashi
May-Hegglin
Gaucher
Niemann-Pick
Mucopolysacchridoses
Toxic Granulation
Think
Neutrophilia
Vacuolization
due to Severe
Dohle Bodies
Bacterial
Necrobiosis
Infection
Definitions
Pelger Huet vs band neutrophil
• 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]
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 • Mucopolysaccharidoses are
characterized by the lack of or
a group of genetically
defective activity of enzymes.
determined deficiencies of
 In Gaucher disease, there is a
specific enzymes involved in
lack of beta-glucocerebrosidase
the degradation of
and macrophages become laden
mucopolysaccharides.
with glucocerebrosides.
Examples:
 In Niemann-Pick, there is
Hurlers
deficient activity of lysosomal
hydrolase and
Hunter
sphingomyelinase resulting in
Sanfilippo
the accumulation of cholesterol
and sphingomyelin in
mononuclear phagocytes.
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.
Graphic accessed http://evolvels.elsevier.com/section/default.asp?id=1138_ccalvo7_0001, 2008.
Alder Reilly
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.
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.
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
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
Peripheral Blood, Wright’s, 100x.
Bordatella pertussis
• Whooping Cough
– BUTT CELL
Graphic accessed http://pathmicro.med.sc.edu/ghaffar/pertussis-lympho.jpg, 1998.
Lymphocytosis
• Epstein-Barr Virus
– Infectious mononucleosis
• Reactive/atypical/variant
lymphocytes