Module 6 Path 2
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- Define Leukocytosis.
- Total WBC count >12,000/microL
- To determine the clinical significance of an elevated WBC, it is important to...?
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...examine the absolute cell counts:
absolute cell count = total WBC x %cell
EX: total WBC is 20,000/microL and differential is 80%segPMNs and 20%lymphs
Absolute PMN = 20,000 x 0.8 = 16,000
Absolute lymphocyte = 20,000 x .20 = 4,000 - Define Neutrophilia.
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Absolute PMN count > 8,000
NORMAL ANC = 2,000-8,000 - Where do neutrophils normally exist?
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Four functional sites:
1. stem cell pool
2. mitotic pool
3. maturation/storage pool
4. marginated/circulating pool
Marginated/circulating is in peripheral blood and all others are in BM - Neutrophilia can result from...?
- Shift of cells btwn pools or an increase in production of cells.
- Types of neutrophilia?
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1. immediate rxn
2. acute rxn
3. pathologic neutrophilia
4. leukemoid rxn
5. leukoerythroblastosis - Immediate rxn neutrophilia
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Results due to a shift from the marginated to the circulating pool.
Equal numbers of cells in the marginated and circulating, so a shift can result in almost doubling the total WBC
Cells will predom be segmented PMNs - Causes of immediate rxn neutrophilia?
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extreme exercise
acute stress
epinephrine
Occurs w/in minutes of exposure - Acute rxn neutrophilia
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Due to shift:
maturation/storage --> marginated/circulating
Cells: segs w/ some bands and few metamyelocytes - Causes of acute rxn neutrophilia?
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steroids
endotoxins
Occurs w/in few hours of exposure - Pathologic neutrophilia
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Caused by pathologic state that induces a sustained PMN response
Increase in:
-- stem cell pool
-- mitotic pool
-- maturation/storage pool
-- marginated/circulating pool - Causes of pathologic neutrophilia?
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1. infections
-- espec bacterial
-- also fungal, early viral
2. metabolic disturbances
-- uremia
-- gout
-- diabetic ketoacidosis
3. exposure to certain drugs/chemicals
-- lead
-- steroids
-- benzene
4. Tissue necrosis, post-surgical stress, hemorrhage, hemolysis - What is toxic granulation?
-
increase in number and predominance of primary granules in PMNs
-- most often seen in bacterial infections and can be important clue, espec if WBC not increased
DOHLE BODIES - consist of ribosomes and appear as irregularly shaped areas of cytoplasm of PMNs
-- usually seen w/ toxic granulation - Leukemoid Reaction
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Term used when WBC elevated and immature cells circulating:
-- metamyelocytes
-- myelocytes
Still a predominance of segs and bands, and toxic granulation w/ Dohle bodies may be seen
Form of pathologic neutrophilia and occurs in response to pathologic state, frequently BACTERIAL infection
"Leukemoid" used b/c looks like leukemia, partic CML - Leukoerythroblastosis
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Smear w/ circulating immature PMNs as well as nucleated RBCs
Total WBC may be high, low, or normal depending on cause - Causes of leukoerythroblastosis?
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1. severe BM stress
-- hemorrhage
-- hemolysis
-- severe infection
2. Marrow replacement by tumor or granuloma -- MYELOPHTHISIS
3. True hematopoietic neoplasm such as myeloprolif d/o's
-- myelofibrosis w/ myeloid metaplasia - Define eosiniphilia
- Absolute count eosinophils > 450
- Causes of eosiniphilia?
-
allergic rxns
skin d/o's
parasitic infections
various neoplasms
GI d/o's
idiopathic hypereosinophilic syndrome
part of various hematopoietic neoplasms - Define basophilia.
- Absolute count basophils > 200
- Causes of basophilia?
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May be rarely seen in allergic responses
Most cases is part of myeloprolif d/p, particularly CML - Define monocytosis.
- Absolute count monocytes > 1000
- Causes of monocytosis?
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chronic infectious disease
TB
CT d/o's
various neoplasms
Part of hematopoietic neoplasms, especially CML - Define lymphocytosis.
- Absolute count lymphocytes > 4000
- Causes of lymphocytosis?
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1. Reactive (atypical) lymphocytes w/ LARGE transformed cells:
-- mono
-- hepatitis
-- toxoplasmosis
-- CMV
-- various other viral diseases
2. Reactive lymphocytosis w/ SMALL NON-transformed lymphocytes:
-- pertussis
-- infectious lymphocytosis - Define neutropenia.
- Absolute PMN count < 1500
- Causes of neutropenia?
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1. decreased production
-- aplastic anemia
-- leukemia
-- drug inhibition
2. ineffective production
-- megaloblastic anemia
-- myelodysplastic states
3. decreased survival
-- bacterial infections
-- splenic sequestration
4. combined - What are some morphologic d/o's of WBCs?
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1. Pelger-Huet anomaly
2. Hypersegmentation
3. Intracellular organisms - Pelger-Huet anomaly
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PMNs are HYPOsegmented w/ two lobes to the nucleus connected w/ either a thin thread of chromatin of w/ a thicker segment, appearing as a band
Congenital:
-- autosomal dominant
-- PMNs w/ normal fxn
Acquired:
-- "pseudo-Pelger-Huet"
-- non-lobated PMNs and/or hypogranular cytoplasm
-- NON-normal fxn
-- pts prone to increased infection - Hypersegmentation
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10% of cells w/ 5 of 5+ lobes
Most common cause: Megaloblastic anemia
Rarely: inherited d/o - Intracellular organisms
- In severe infections, may be seen in PMNs in the periph blood smear
- What are some qualitative WBC d/o's?
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1. chronic granulomatous disease
2. Chediak-Higashi Syndrome
3. Other miscellaneous d/o's that may result in ineffective phagocytosis, adhesion, or bacterial killing - Chronic Granulomatous Disease
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Pts have repeated infections w/ bacteria that are CATALASE (+)
Group of d/o's that have common defects in genes encoding different components of NADPH oxidase
-- x-linked inherited OR
-- autosomal recessive
WBC are able to phagocytose, but not able to destroy
-- orgs remain intracellular
-- granulomatous inflamm develops
Manifest of disease vary among patients from mild to very severe - Chediak-Higashi Syndrome
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Rare autosomal recessive d/o
-- lysosomes of various cell types are abnormal
-- Pancytopenia w/ abnormal appearing lysosomes in lymphocytes and neutrophils
-- WBC do not fxn normally and pts have severe infections early in life
-- also involvement of melanosomes w/ partial albinism
**Usually fatal w/in first two years of life
BM transplant is only possible treatment