Lecture 10: Leukocyte Evaluation Flashcards
What is a cytokine?
Any number of substances secreted by certain cells of immune system and have an effect on other cells.
What is granulocytopenia?
Reduced # of neutrophils, eosinophils, basophils
What are the PMN leukocytes?
The granulocytes: neutrophils, basophils, eosinophils.
What are the mononuclear leukocytes?
Agranulocytes - lymphocytes and monocytes
What is the most common type of WBC generally?
Segmented neutrophils
Where do granulocytes come from?
Hematopoietic stem cell (HSC)
How do HSC’s replicate?
Self-renewal and differentiation.
What is the proliferation cycle of a myeloblast?
Myeloblast => promyelocyte => myelocyte.
What can myelocytes do?
Cell division
Differentiation
What happens in the differentiation stage for a metamyelocyte?
It becomes a metamyelocyte => band => PMN cells
What are the immature granulocytes?
Metamyelocytes and bands are immature granulocytes.
PMNs are MATURE granulocytes.
Capable of maturation and differentiation but are not capable of division
What can myeloblasts become?
Basophils
Neutrophils
Eosinophils
Monocytes
At what point do myeloblasts become unable to replicate?
Once they become metamyelocytes.
What is the difference between proliferation and differentiation?
Differentiation means no more splitting/replicating.
What is included in neutrophil count?
Mature or immature neutrophils
What is the difference between poly-A and poly-M?
Poly-A means automatic examination of PMNs neutrophils.
Poly-M means manual examination of PMNs neutrophils.
When do we prefer absolute values for WBC diffs?
Pathologic states.
What should you always keep in mind if the relative % of one leukocyte increases?
The other percentages will decrease.
What is a neutrophil?
WBC
Contains granules that digest microorganisms.
What do neutrophils typically protect from?
Bacterial and fungal infection
Where is the storage pool for neutrophils?
Bone marrow.
Cannot detect neutrophils if they are in the bone marrow.
What are extramedullary neutrophils?
Circulating neutrophils in the bloodstream. They circulate approx 24 hours prior to entering a tissue.
Also known as circulation pool. (1/2 of neutrophils)
OR
Marginal pool (1/2 neutrophils)
What are the 1/2 of neutrophils attached to endothelial walls called?
Marginal pool.
What are the 3 pools for neutrophils?
Storage pool in the bone marrow (in steady state)
Extramedullary neutrophils:
Circulation pool (50%)
Marginal pool (50%)
What is neutrophilia?
Elevated ANC, aka granulocytosis.
What are the two possible presentations for neutrophilia?
Neutrophilic shift
True neutrophilia
What is a neutrophilic shift?
Shift from marginal pool to circulating pool.
It is transient, lasting 20-30 mins with a 1-2 min onset.
What causes neutrophilic shifts?
Exercise
Seizure
Paroxysmal tachycardia
Epinephrine injection
Post-op state
What is true neutrophilia?
Release of neutrophils from storage pool.
ANC elevates 5-6x
What are the 3 etiologic classifications of true neutrophilia?
Suprious: false elevated
Primary: Inherited
Secondary: MC type, and MC cause is infection.
What do we call a early release of bands?
Left shift
What are some secondary causes of true neutrophilia?
Infection (MC)
Stress
Cigarette smoking (constant inflammation)
Glucocorticoids
Recombinant G-CSF or GM-CSF
What are some primary causes of true neutrophilia?
Myeloproliferative disorders
What are some spurious causes of true neutrophilia?
Platelet clumping
Mixed cryoglobulinemia
What are the 3 types of neutropenia?
Mild: ANC 1000-1800
Moderate: ANC 500-1000
Severe: ANC < 500
What PE finding in a wound can suggest neutropenia?
Lack of pus in a wound.
Increased risk of sepsis from open wound.
What are the 3 main pathophysiologic processes responsible for neutropenia?
Insufficient or injured bone marrow stem cells.
Shift in neutrophils from the circulating pool to the marginal pool or tissue pool
Increased destruction in the circulation.
What is pseudoneutropenia?
Fake neutropenia as a result of medications OR
CBC being taken in the morning. Neutrophils might be resting in the marrow in the morning.
What is the name of the medication SE we will see for causing neutropenia?
Agranulocytosis.
What disorder category would cause increased destruction of neutrophils?
Autoimmune disorders.
What is the most common demographic for neutropenia?
Elderly
Asians and African-Americans may have low NORMAL neutrophil counts.
What is the main complication we are worried about in neutropenia?
Bacterial infections.
Why can bacterial infections be so dangerous in neutropenia?
Initial presenting s/s may not occur.
At what point are serious infections a real threat in regards to ANC?
ANC <500
Severe neutropenia.
What are some medications that are known to cause neutropenia?
Sulfonamides
PCN
Cephalosporins
Methimazole
Phenytoin
At what ANC level do we refer to heme/onc?
ANC <1000
What additional workup will heme/onc generally order for moderate-severe neutropenia?
Bone marrow biopsy
Serum antineutrophil antibodies
Rh factor and splenomegaly
What does + serum antineutrophils antibodies indicate?
Autoimmune neutropenia in the absence of bone marrow disorders.
What is the standard therapy for neutropenia?
Myeloid growth factors
Myeloblasts are the precursor to all granulocytes.
What are the two types of myeloid growth factors?
G-CSF (Granulocyte colony stimulating factor):
Filgrastim/neupogen
pegfilgrastim/neulasta
GM-CSF (Granulocyte-macrophage colony stimulating factor):
Sargramostim (Leukine)
When can we treat neutropenia OP vs IP?
ANC > 1000 (mild) = OP if no other complications.
ANC < 500 (Severe) = IP with IV ABX.
ANC 500-1000 (moderate) = case dependent.
What is the difference between filgrastim and sargramostim?
Filgrastim is just granulocytes. (G-CSF)
Sargramostim is granulocytes AND macrophages. (GM-CSF)
Sar Gra Mostim (GM)
How is autoimmune neutropenia (AIN) treated?
Pulse steroid + intermittent myeloid growth factor
How is myelosuppresive chemotherapy induced neutropenia treated?
Myeloid growth factor +/- prophylactic antimicrobials in intense therapy.
What is a granulocyte transfusion? What is the indication for it?
A donor receives growth factors so that they can have their leukocytes drawn and transfused into a recipient.
Indicated for bacterial infections WITHOUT a clinical response to ABX within 24-48 hrs.
What is a eosinophil and how do I recognize it?
Granules are stained by eosin. (red)
Bilobed nucleus.
Where are eosinophils typically found and what is their role?
Tissue dwellers.
Assist in fighting parasites, allergies, and asthma.
What are the MC target organs for eosinophils?
Skin
Airway
GI Tract
What 3 cytokines are responsible for eosinophil development and differentiation?
IL-5
IL-3
GM-CSF
How long do eosinophils circulate? How long do they live?
Circulate for 8-12 hours before entering a tissue.
Remain in tissue for 1-2 weeks.
Lifespan is 2-5 days normally, but increased to 2 weeks with cytokine aid.
What are the types of eosinophilia?
Mild: 500-1500
Moderate: 1500-5000
Severe: >5000
What are the causes of eosinophilia?
Primary clonal: genetic mutation or malignancy
Primary idiopathic: When all other causes have been ruled out. (HES)
Secondary: Reactive etiology
What is hypereosinophilic syndrome?
HES is a rare disease. Not testable. It is a rule out disease.
What is the general pathophysiology behind eosinophilia?
Dysregulation/overproduction of the cytokines (IL 3, IL 5, GM-CSF)
Results in either increased eosinophil production or longevity.
What is the main complication of eosinophilia?
Tissue damage, occurring most commonly at AEC > 1500.
How does organ damage occur because of eosinophilia?
Release of toxic granules
Production of lipid mediators that recruit inflammatory cells.
Release of cytokines involved in tissue remodeling and fibrosis.
What are the MC target organs for eosinophils?
Skin
Airway
GI Tract
What is a basophil?
Least-prominent WBC.
Dark-blue granules.
What do basophils contain?
Histamine
Heparin
What is the overall function of a basophil?
IgE antibody formation and activation.
What is the primary cause of basophilia?
CML
What are the secondary causes of basophilia?
Myeloproliferative disorders
Hypersensitivity/inflammation
Hypothyroidism
What are agranulocytes?
WBCs with ONE-lobed nucleus and NO granules.
What falls under agranulocytes?
Monocytes
Lymphocytes
What is a lymphocyte?
Small leukocyte with single round nucleus and receptor molecules on surface.
Can bind to antigens AND remove them.
Who has the greatest range of lymphocytes naturally?
Neonates < 28 days
What is the more common lymphocyte?
T-cells: 60-80%
Which mature lymphocyte CANNOT divide?
NK cells
Where do T-cells mature and differentiate?
Thymus
What is the function of a T-cell?
Destroy HUMAN cells that have been attacked by viruses or have become cancerous
What are the 3 types of T-cells?
Helper/CD4+ T-cell
Cytotoxic/CD8+ T-cell
Regulatory T-cell
What is the function of a helper/cd4+ t cell?
Recognize foreign antigens
Stimulate antibody production
Produce cytokines to activate other T cells.
What is the function of a cytotoxic/CD8+ T-cell?
Attack and destroy foreign cells.
What is the function of a regulatory T cell?
Dampen/turn off immune response of other T cells.
Lack of regulatory T cells leads to autoimmune diseases.
Where do B-cells mature?
Bone marrow
What is the function of a B-cell?
Present antigens to initiate T-cell response.
Express surface Ig receptors to specific antigens.
Become memory B-cells to provide long-lasting immunity.
Become plasma cells.
What is the function of a plasma cell?
Produces large numbers of immunoglobulins (Ig) until infection is gone.
What are the functions of NK cells?
Cytotoxic granule release to attack cancerous or VIRALLY infected cells. (no immune system activation required)
Maintain control of immune response. (Can differentiate between foreign and self)
What are the two kinds of lymphocytosis?
Monoclonal lymphocytosis: benign or lymphoproliferative disorder.
Polyclonal lymphocytosis: Infectious, transient, reactive, benign.
What is monoclonal lymphocytosis?
Expanded clonal B-cell population in blood.
No sign of any infection, autoimmune, or lymphoproliferative process.
What does a monoclonal lymphocytosis suggest?
Premalignant or malignant lymphoproliferative syndrome.
What is the MC premalignant etiology of a monoclonal lymphocytosis?
Monoclonal B cell lymphocytosis.
What are the malignant etiologies of a monoclonal lymphocytosis?
CLL
NHL w/ circulating disease
Hairy cell leukemia (HCL)
Large granular lymphocytic leukemia (LGL)
Why is polyclonal lymphocytosis not always a big concern?
Symptom of an underlying condition caused it, expected to normalize in 2 months if underlying cause is resolved.
What is the MC infectious etiology of polyclonal lymphocytosis?
Mono
Other causes:
Pertussis
Cat-scratch
Toxoplasmosis
What are the 4 etiology types for polyclonal lymphocytosis?
Infectious
Transient
Reactive
Benign persistent
How do we workup lymphocytosis?
CBC
Smear
Flow cytometry (if high suspicion it is bacterial)
What is flow cytometry used for in lymphocytosis?
Detects surface antigens specific to B or T cells.
Can detect clonal lymphocyte proliferation.
No use in viral infection.
What are the 3 pathophysiologies behind lymphocytopenia?
Decreased production
Increased destruction
Splenic or lymph sequestration
Note:
Just like RBCs.
What are the main complications we are worried about in lymphocytopenia?
Opportunistic infections
Malignancy and autoimmune disorder risk.
What are the two types of lymphocytopenia?
Inherited
Acquired
What are the types of acquired lymphocytopenia?
Infectious disease (HIV MC)
Iatrogenic (Radio/chemo)
Autoimmune
Nutritional def (ZINC, alcoholic)
What is a monocyte?
Large phagocyte with oval nucleus and clear, grayish cytoplasm.
Where do monocytes differentiate?
Within tissues, into macrophages or dendritic cells.
Where are most monocytes stored?
Spleen (50%)
What are the functions of monocytes?
Phagocytosis
Antigen presentation
Inflammatory cytokine production
How is monocytosis described as in terms of duration?
Transient if no hematopoietic suppression.
What are the etiologies of monocytosis?
(bacterial infections MC)
Acute/chronic leukemia/lymphomas
Aspenia
Inflammatory/autoimmune
Corticosteroids
CSF (increasing granulocytes only)
What are the primary treatment options for leukopenia?
Broad spectrum ABX
G-CSF-GM-CSF
Corticosteroids
Nutritional deficiency correction
Splenectomy if chronic.
What kind of PE exam should you never do on someone immunocompromised?
Rectal exams, because skin breaks and inflammatory responses will ensue.
What is a possible source of error for a peripheral blood smear?
Mechanical trauma to cells.
When do we commonly seen hypersegmentation of neutrophils?
Megaloblastic anemias
Myeloproliferative disorders
Chemo
When do we commonly see granulation of leukocytes?
Bacterial infections
When do we commonly see Dohle bodies?
Infection in general.
It is an irregular blue stain in the cytoplasm.
When do we commonly see smudge or basket cells?
Fragile lymphocytes in CLL.
When do we commonly see platelet satellitosis?
Artifact of EDTA anticoagulation.
EDTA is an AC used in tubes for CBC.
What tissue type does flow cytometry assess?
Blood
Bone Marrow
Lymph Node
What is the main function of flow cytometry?
Differentiating between normal and malignant cells.
It can detect antigens/markers via lasers.
