WBC abnormalities (Exam III) Flashcards
Leukocytosis
increase in WBC
Leukopenia
decrease in WBC
Left shift / shift left
Increase in slightly immature neutrophils
- band neutrophils
- metamyelocytes
- **BM releasing sooner **(accelerated)
Terminology based on indention of nuclei
- myelocyte
- metamyelocyte (increase)
- band (increase)
- segmented
Leukemoid reaction
Exaggerated response to infections and inflammation
- Leukocytosis
- Shift Left
- Nonmalignant (Not leukemia)
Leukocytosis (WBC count)
WBC count: 20,000-50,000 ul
Leukocyte Alkaline Phosphatase Stain (LAP)
Leukemoid vs. leukemia
Stains neutrophilic granules containing LAP enzyme
- present in segmented neutrophils, bands, and metamyelocyte
Positive stain - blue intensified granules
Used to differentiate
- leukemoid rxn = High LAP score
- Chronic Myelogenous Leukemia (CML) = Low LAP
Low LAP score
CML
High LAP score
Leukemoid Reaction
LAP score
count and grade 100 mature neutrophils or band neutrophils based on their LAP staining intensity
LAP Score =
sum of 100 graded mature neutrophils and bands
Normal range of LAP
11-95.
Grade 0
Stain: 0
Granules: 0
Grade 1+
Stain: fine + diffuse
Granules: occasional
Grade 2+
stain: moderate
granules: moderate
grade 3+
stain: strong
granules: many
grade 4+
stain: brilliant
granules: nucleus obscured
Quantitive changes
Neutrophils
Increase: infections/inflammation
decrease: chemotherapy
Quantitative changes
Eosinophils
Increase: parastic infections
decrease: ACTH hormone
Quantitative Changes
Basophils
Increase: hypersensitivity
Decrease: steroid treatment
Quantitative changes
Monocytes
increase: chronic infections (TB)
decrease: autoimmune processes
Quantitative Changes
Lymphocytes
increase: viral infection
decrease: chemotherapy
Qualitative abnormalities
Toxic granulation
- primary granules persisting
Dohle Bodies
- RNA remnant of RER aggregated
Toxic vaculoziation
- Phagocytisis
Phagocytosis - Chemotaxis and Diapedisis
Marginating pool neutrophils roll along vessel endothelium
Cytokines are released from sites of inflammation
Neutrophils are attracted to these sites (follws trails to highest concentration) = chemotaxis
Neutrophil then squeezes between endothelial cells to enter tissue = diapedesis
chemotaxis
Neutrophils are attracted to inflammation sites (follows trail to highest concentration).
Diapedesis
Neutrophil squeezes between endothelial cells to enter tissue
Phagocytosis - Opsonization and recognition
Neutrophils cannot efficiently recognize most microorganisms
Requires opsonins
- promotes interaction of surface of microorganisms with receptors on neutrophil plasma membrane
Microorganisms coated in immunoglobin (antibodies) or complement = opsonization
Opsonin is recognized by the neutrophil
- receptors for Fc fragment of antobody or complement attach
Opsonization
Microorganism coated in immunoglobulin (antibodies) or complement.
Phagosome (ingestion and killing)
Pseudopods extend around microbe forming a vacuole
Phagolysosome (ingestion and killing)
lysosomes with cytoplasmic granules fuse with phagosome
In phagolysosome, granules degranulate…
realeasing lytic elements and leads to drop of pH
- non oxygen dependent mechanism
- Able to cleave bacterial cell wall
Phagocytosis finale - Respiratory burst
NADPH converts oxygen into lethal metabolites including:
- H2O2 - hydrogen peroxide
1. causes major microorgnaism injury
2. accelerates the destructiion process
Oxygen dependent mechanism
Any remnant are removed through exocytosis
Diseases of improper phagocytosis
Disease can occur due to
Ingestion by cell has normal enzyme activity, BUT…
- Thing ingestied is resistant to being killed
- Cell is overzealous in amount it has ingested
Actual deficiency of lysosomal enzymes
Symptoms of improper phagocytosis
Accumulation of unmetabolized material in lysosomes
Undigested metabolic products accumulate in cells
Metabolic enzyme deficiency -> Undigested metabolic product
Chronic Granulomatous Disease
Most cases - X linked
- primarily males
Problem: Deficiency in Cytochrome B
- Needed for Respiratory Burst
- H2O2 of respirary burst needs to kill catalase positive organisms
1. Staphylococcus aureus, Mycobacteria, Serrita
2. Fungus: Asperigillus
Granulomas accumulate
Average life span: 10 years
Prone to recurrent infections
Chediak Higashi Syndrome
Rare, Fatal, autosomal recessive disorder
Problem: Defective fusion protein
- lysosomes will not secrete and release enzymes properly
- creates giant azurophilic granules in cytoplasm
Found in granulocytes, lymphocytes, and monocytes
Susceptible to recurrent infections (S. auereus)
Additional clinical features: Neutropenia, albinism, photophobia, thrombocytopenia, PLT dense granule deficiency
Gauchers Disease
Most common lipid storage disease
Autosomal Recessive
Problem: deficiency of betaglucocerebrosidase
- Glucocerebroside (a glycolipid waste product) accumulates. Gaucher cell
Additional clinical features: Neutropenia, anemia, thrombocytopenia, hepatomegaly
Classified into 3 types
- Type II: infantile form is the most severe
Niemann-Pick Disease
2nd most common lipid (lysosomal) storage disease
Autosomal Recessive
Problem: Deficiency og sphingomyelinase
- Sphingomyelin and Cholesterlol accumuates in cytoplasm of macrophages
- foamy Histiocytes = Niemann Pick cells
Additional Clinical Features
- Mental retardation, delayed structural development - lipids accumulate in nervous tissue
Hepatosplenomegaly
Tay Sachs - aka Gangliosidosis
Autosomal Recessive
Problem: Deficiency in hexosaminidase A
- lipids and gangliosides accumulate - leads to nercous and eye tissue damage
Life expectancy less than 4 years
No abnormal morphological characteristics
Alder-Reilly Anomaly - aka “Alders Anomaly”
Autosomal Recessive
Problem: Deficiency in alpha-L-iduronidase
- Mucopolusaccharides accumulate
- creayes large granules in neutrophils, lymphocytes, monocytes, eosinophils, basophils
1. can give a clearing (halo) around the granule
2. can be misinterpreted as toxic granulatpion
Additional clinical features: Dwarfism, skeletal problem (humped back), frontal bossing
Average life expectancy: 6-10 years
Formerly called Gargolyism
Lymphocyte Review
WBC differential: 20-44%
1.Resting small lymphocyte
- small (8-12 um), scanty cytoplasm, with round nucleus
Reactive lymphocyte
- Large (9-30 um), abundant cytoplasm, round to irregular nucleaus, and possible nucleoli
- Can be confused with malignant conditions
Viral infections (Causes of reactive lymphocytosis)
Chickenpox, cytomegalovirus, EBV (infectiousmononucleosis)
Bacterial infection (causes of reactive lymphocytosis)
Brucellosis
Perussis (whooping cough)
Tuberculosis
Drug reactions (reactive lymphocytosis)
Due to medications for infections
Miscellaneous (causes of reactive lymphocytosis)
Allergic reactions, auto immune disease, malnutrition
Infectious mononucleosis - NOTHING to do with monocytes
**Vast majority are caused by Epstein Barr Virus (EBV) **
**EBV infects B lymphocytes
**T lymphocytes (CD8) react becoming reactive lymphocytes. **
Virus is transmitted through bodily fluids, espeially saliva
- increased prevalence in young adults (17-25 years old)
1. correlates to prime dating and social interaction years
-Usually self-limiting, general symtpoms: sore throat, and flu like symptoms
1. lymph nodes become enlarged (possible hypersplenism)
Lab findings infectious mononucleosis
Usually diagnosed on symptoms only
Screening test - Monospot test
- detects heterophile antibodies produced against EBV
heterophile antibodies
antibodies that crossreact either with other antigens that did not stimulate its formation or proteins across species lines
Test against Sheep or horse RBCs
Infectious Mononucleosis
Peripheral smear
- Increased reactive lymphocytes
- T lymphocytes working against the infection
- Cytoplasm tends to stain darker and morph arounf RBC - “ballerina skirt”
Infectious Mononucleosis
Additional sereoly tests detects antibodies to:
- Viral capsid antigen (IgM and IgG)
- EBV nuclear antigen
- EBV early antigen complex
Using this combination, we can judge the time frame of a current infection or historical infection.
