Leukocyte Evaluation and Disorders Flashcards
What cells are in the proliferation stage?
Myeloblasts
Promyelocyte
Myelocyte
What does the proliferation stage mean?
Cells can both self-renew and differentiate
What does the differentiation stage mean?
Cells are able to mature and differentiate but cannot divide
What cells are in the differentiation stage?
Metamyelocyte
Band
Polymorphonuclear (PMN) cells (mature granulocyte)
What is the function of a neutrophil?
Protect from bacterial and fungal infections
How long do the progenitor neutrophils spend in the marrow maturing?
7-10 days
Where are most neutrophils at steady state?
In the bone marrow storage pool
What are the extramedullary neutrophils and how many are there?
1/2 of neutrophils circulate in the blood for 24h to be used in the tissue for 1-2 days in the tissue. Called circulation pool. Other half are in endothelial walls and are known as the marginal pool.
What is neutrophilia?
Abs neutrophil count >7700
Can be neutrophilic shift (marginal move to circulation) or true neutrophilia (new neutrophils made)
What is neutrophilic shift?
Movement from marginal to circulating pool. Transient within 1-2 minutes lasting 20-30 minutes. Caused by acute physical/emotional stress (exercise, seizure, paroxysmal tachycardia, epinephrine injection, post-op state)
What is true neutrophilia?
The release of neutrophils from storage pool in the marrow. ANC may be 5-6 x normal. Can be false, inherited, acquired (MC is infectious).
What is neutropenia?
<1800 ANC
What is mild neutropenia?
1000-1800 ANC
What is moderate neutropenia?
500-1000 ANC
What is severe neutropenia?
<500 ANC
What are the causes of neutropenia?
- Injured bone marrow stem cells
- shift in neutrophils (circulating to marginal) aka pseudoneutropenia
- increased destruction in the circulation
When is pseudoneutropenia common?
Morning specimens and a side effect of various medications
Who is neutropenia most common in?
Elderly
African americans, asians have low neutrophils at bsl
What are complications of neutropenia?
Bacterial infections, note that sx can be absent due to decrease in neutrophils
How should we work up neutropenia?
Referral to hematology if persistently <1000
They will do a bone marrow biopsy, serum antineutrophil antibodies, rheumatoid factor and US for splenomegaly for Felty syndrome
What are the Myeloid growth factors?
Granulocyte colony-stimulating factor (G-CSF) Filgrastim or pegfilgrastim
Granulocyte-macrophage colony stimulating factor (GM-CSF) sargramostim
What is the guidelines for treating neutropenic fever?
Everyone gets ABx
>1000 can be outpatient
<500 must be inpatient
500-1000 call for help deciding
What are the treatments for neutropenic fever?
ABX but otherwise based on cause
Medication - Stop causative agents
Autoimmune - steroids and myeloid CSF
Chemo - myeloid CSF +/- if intense therapy
Can also give granulocyte transfusion
What is the function of eosinophils?
Primarily tissue dwellers that assist in fighting parasites, allergies and asthma. Most commonly in skin, airway and GI tract
What 3 cytokines stimulate eosinophil development?
IL-5
IL-3
GM-CSF (granulocyte-macrophage colony-stimulating factor)
What is the line span of an eosinophil?
Circulated for 8-12 hours before entering tissue for 2-5 days and up to 14 if exposed to cytokines
What is eosinophilia?
Eosinophil count >500
What is hypereosinophilic syndrome?
Idiopathic primary cause of eosinophilia (not genetic mutation or malignancy)
What is the pathophysiology of eosinophilia?
Dysregulation of the cytokines (IL 3, IL 5, GM-CSF) results in an increased eosinophil production and/or eosinophil longevity
What are the complications of eosinophilia?
Tissue damage
Mainly skin, airway, GI tract
Why? Release of toxic granule product damage epithelial tissue and nerves. Production of lipid mediations recruit inflammatory cells. Release cytokines that promote tissue remodeling and fibrosis
What are the functions of the basophil?
Contain heparin to prevent clotting and release histamine during contact with allergens. Thought to help with IgE formation and activation.
What is a common cause of primary basophilia?
CML
What is a common cause of secondary basophilia?
Myeloproliferative disorders, hypersensitivity or inflammatory reactions, hypothyroidism
How do T cells develop?
Mature and differentiate in the thymus and then exported to the blood and secondary lymph tissue
What is the function of T cells?
Destroy human cells that have been attacked by viruses or have become cancerous
What is the function of helper T cells/CD 4+?
stimulate antibody production and produce cytokines to activate other T cells
What is the function of cytotoxic T cells/CD 8+?
Attacks and destroys foreign cells
What is the function of regulatory T cells?
Turns off the immune response of other T cells to prevent autoimmune responses
How do the B cells develop?
Mature in the bone marrow
What are the functions of B cells?
- initiate T cell immune responses via antigens
- Express surface Ig receptors
- Become memory B cells to create long-lasting immunity
- Become plasma cells to produce hella antibodies during infection
What are the natural killer cells?
First responders that attack cancerous or virally infected cells. Does not require immune system activation, just does self vs not self
What is monoclonal lymphocytosis?
Expanded B-cell population in blood without sign of infection, autoimmune process, or lymphoproliferative disorder. Reflects a premalignant or malignant lymphoproliferative syndrome.
What is polyclonal lymphocytosis?
Underlying condition expected to normalize within 2 months after resolution of condition. Commonly caused by viral infections (mononucleosis)
What is the workup for lymphocytosis?
- Repeat CBC
- Peripheral blood smear
- Flow cytometry
What are the causes of lymphocytopenia?
Decreased production
Increased destruction
Lymphocyte become lodged in the spleen or lymph nodes
What are the adverse outcomes of lymphocytopenia?
Opportunistic infections
Increased risk of malignancy and autoimmune disorders
What are the acquired causes of lymphocytopenia?
Infectious disease - HIV
Iatrogenic (chemo)
Autoimmune
Nutritional deficiency (zinc, ETOH use)
What is the life cycle of a monocyte?
Remain in circulation for 1-3 days then enter tissues and differentiate into macrophages or dendritic cells. Half of monocytes are stored in the spleen.
What are the functions of monocytes?
- Phagocytosis
- Antigen presentation to T-cells
- Inflammatory cytokine production
What are the causes of moncytosis?
- bacterial infections (MC)
- AML CML Lymphomas
-Asplenia - Inflammatory/autoimmune conditions
- Treatment with corticosteroids or CSF
What is the management of leukopenia?
Broad spectrum ABx
Myeloid growth factors (G-CSF and GM-CSF)
Corticosteroids
Correction of nutritional deficiencies
Splenectomy
What patient education is required for leukopenia?
Avoid possible foodborne illness
Wash hands and care for indwelling catheters
Avoid rectal manipulation
What do we use for leukocyte analysis?
Peripheral smear
Flow cytometry immunophenotyping (detects antigens/markers and differentiates normal cells from malignant cells)
