How long do monocytes/macrophages take to develop, what is their morphology when mature, and what are their functions?
They mature in 7 days and are released after their last division in the bone marrow. They circulate in the blood for a few days, and then locate to the tissues. They are 10-18 microns across with grey cytoplasm and an indented nucleus. They function in inflammatory response, filtering of cells in the spleen, processing and presenting antigen, and clearance of apoptotic cells and debris.
How long do neutorphils take to develop, what is their morphology, and what is their function?
They mature in the marrow, including the storage pool, for 10-14 days (faster under stress). Spend 6 hours in blood stream, and then move to tissue (1-2 day life span). They are a major component of the innate immune system, non-specific defense against microbes and tissue injury.
How are eosinophils produced, what is their morphology, and what is their function?
Eosinophils are produced under the influence of IL-5, in 10-14 days, including storage pools. They are 12-14 microns across with large granules and bi-lobed nuclei. They locate to external surfaces (lungs, GI), and last weeks. They are very effective against parasites, and can have some phagocytic actions.
How are basophils produced, what is their morphology, and what functions do they have?
Basophils are produced in bone marrow and quickly locate to tissues, they are rarely seen in the blood. They are 12-14 microns across, with a bi-lobed nucleus and prominenet blue/purple granules. They contain receptors for IgE and function in hypersensitivity reactions (histamine release).
Where are neutrophils held in order to mount a quick response?
The mitotic pool contains dividing but immature cells. There are storage pools in the marrow where neutrophils continue to mature and marginating pools along the surface of blood vessels where neutrophils bind periodically. There are 20-30 neutrophils in storage pools for every 1 in circulation. There is also about 1 cell in a marginating pool for every cell that is in circulation.
What is the definition of neutropenia and what are the age and ethnicity related numbers?
Neutropenia is the decrease in absolute neutrophil count (including bands and segs) below accepted norms for age and other considerations. Newborn<1 week = < 3,000. Infant (1 week - 2 years) = < 1,100. Child, adolescent, adult = < 1,500. Ethinc/racial groups = < 900. High altitude = lower ANC.
What issues may neutropenia cause?
Neutropenia implies decreased delivery of neutrophils to tissues, which results in a disability to localize and resolve bacterial or fungal infections. ANC ranges: 1000-500 = minimal/mild; 500-250 moderate to severe; <250 = severe (sepsis, pneumonias) These numbers assume that the storage pools are also depleted, but that may not be true.
How do we evaluate a patient for neutropenia?
1. History - frequency/duration of infections, toxin or drug exposure, family history. 2. Physical exam - infection sites, teeth/gums (gingivitis, inflamed?) 3. Labs - CBC, bone marrow, blood chemistry, anti-neutrophil antibodies.
What are the general classifications of neutropenia?
Decreased bone marrow reserve and normal marrow reserve. Decreased marrow reserves result from primary disorders/diseases, complex phenotypes, secondary disorders (chemo, drugs) or are idiopathic. Normal marrow reserve neutropenia results from immune sources (benign neutrop of chilhood, autoimmune, alloimmune, drug induced) and non-immune (infection, hyperspleenism, excessive margination) Also catagorize by acute (<3 mo) or chronic (>3 mo)
What is the most common cause of neutropenia?
Infection Associated Neutropenia. Usually acute and resolves in days/months. Caused by increased utilization, complement mediated margination, marrow suppression, antibody production.
What are some secondary causes of neutropenia?
Immune response (antibody-tagged segs taken up by spleen), Toxic compounds, hypersensitivity, chemotherapy, aplastic anemia (disapperance of stem cells), Vit B12/folate def, hypersplenism.
What is the general management strategy for secodary neutropenias?
Withdraw unneccessary drugs and toxins, treat underlying disorder, replace specific deficiency, aggresively manage infections, supportive care including prophylactic antibiotics, G-CSF if needed (in the case of chemo).
What is the cause, effects, and categories of immune neutropenias?
Immune neutropenias are caused by antibodies to neutrophils, leading to increased turnover and decreased vascular comparment neutrophils. It is characterized by normal to increased production and normal to slightly decreased storage pools. Four categories: Alloimmune, autoimmune, chronic benign neutrop of childhood, and drug-induced.
Name three significant congenital causes of neutropenia
Kostmann's Syndrome - most severe, manifests in newborns/infants. Cyclic neutropenia - ANC levels cycle (21 +- 3 days) and bottom out at <200 for 3-5 days. Schwachman-Diamond syndrome - actual Schwachman-Diamond gene defect. All treatments include G-CSF.
What is the treatment strategy for neutropenia?
1. Define the type of neutropenia. 2. For undefined cases or severe congenital cases with ANC < 500 and infection or fever > 38.5 C culture and treat with anitbiotics. 3. For severe infections, aggresive attempts at IDing the infected site/organisms. 4. Start with broad spectrum antibio, procede to targeted when organism is known. 5. Consider prophylatic antibiotics. 6. Severe cases - G-CSF at 3-5ug/kg sc.
What are leukocytosis and "left shift"?
Leukocytosis is an increase in WBC beyond normal ranges. "Left Shift" refers to a change in the normal WBC differential characterized by an increase in neutrophils (segs and bands).
What is neutropilia?
Neutrophilia is an increase in ANC > 7500 cells/ug. Caused by increased production, enhanced release from storage pool, decreased egress from circulation, or reduced margination.
What is eosinophilia and what are its causes?
Eosinophilia is an absolute eosinophil count of >350/ul. Cause by allergic disorders, dematitis, parasitic/other infections, tumors, hereditary disorders, GI disorders.
What is monocytosis/monocytemia and what causes it?
Monocytosis is a monocyte count >500/ul. It is caused by hematologic disorders/lymphomas, collagen vascular disease, granulomatous disease, infection, malignant disease.
What are the causes of basophilia?
Hypersensitivity reactions, inflammation and infection, myeloproliferative diseases.