Disorders of Granulocyte/Monocyte Number Flashcards
Identify the basic morphologic features of neutrophils and explain their production, distribution, and turnover
The polymorphonuclear leukocyte (PMN), neutrophil or granulocyte is produced in the marrow (GM-CSF, G-CSF), remains there for a few days in a storage pool (metamyelocytes, bands, and segmented neutrophils (segs) which no longer have the capacity to divide) held in reserve to fight infections, is subsequently released into peripheral blood where it may marginate between the post-capillary venules and the laminar blood flow (non-stressed conditions, 10-14 days to move from pluripotent stem cells to mature neutrophils; stressed, be shortened to 5 days). After 6 hrs, the neutrophil moves into the tissues where it turns over in 1-2 days. The neutrophil is a major component of the innate immune system migrating quickly to the site of infection where it ingests and kills microbes. It is the prototypic first responder but is also important in stimulating wound healing and tissue repair.
Identify the basic morphologic features of eosinophils and explain their production, distribution, and turnover
Produced in the bone marrow under the influence of IL-5, its maturation and kinetics are like neutrophils. The eosinophil, however, is slightly larger, has prominent eosinophilic (red/orange) granules and bilobed nucleus. After transversing the peripheral blood, eosinophils move to mucosal surfaces (GI tract, tracheobronchial tree, etc.) where they survive for weeks. These cells play a role in allergic reactions, parasitic infections and response to tumors. They can play the role of a phagocyte and be immunostimulatory or immunoinhibitory.
Identify the basic morphologic features of basophils and explain their production, distribution, and turnover
After production in the marrow, basophils spend most of their life in tissues. Similar in size to eosinophils, they have prominent basophilic (blue-purple) primary granules and receptors for IgE. These cells appear to play a major role in hypersensitivity (allergic) reactions
Identify the basic morphologic features of monocytes and macrophages and explain their production, distribution, and turnover
Derived from myeloid/monocyte precursor under stimulation of GM-CSF and M-CSF, these cells have a shorter development time in the bone marrow (7 days), move to the peripheral blood for 3-5 days. Some then emigrate to tissues where they develop into tissue based macrophages lasting for days-months. Major functions of these cells is to a) migrate from blood to sites of infection and provide effector cells to remove microbes, dead and dying inflammatory cells, and debris; b) filter out microbes from blood stream (spleen); c) process and present antigens to the adaptive immune system; and, d) remove apoptotic cells
Neutropenia:
a decrease in the absolute neutrophil count (bands and segs) below accepted norms. This may vary with age (<250/μl a very severe risk)
Clinical consequences of neutropenia:
- Once defined, the workup should include: thorough history (duration or periodicity of the low counts) and associated symptoms or signs; numbers, sites, and agents involved in infections; exposure to drugs and toxins; and family history of recurrent infections, immune disorders or hematologic abnormalities.
- complete PEx should be performed with special attention paid to infected sites; teeth and gums, lymph nodes, liver, spleen and other findings (nails, skin, dysmorphic features, etc.).
- Initial labs: initial CBC with a white blood cell differential and review of leukocyte morphology.
- For chronic neutropenia: counts 2x/week for 6 weeks will define the extent and persistence of the neutropenia. Blood chemistries, neutrophil ABs and a bone marrow aspirate and biopsy may be essential to defining the specific cause
- Patients with severe neutropenia and production defects are predisposed to bacterial or fungal infections. (S. aureus and gram-neg bacteria are the most common pathogens)
Diagram the major causes and differentiate the major acquired or congenital/genetic disorders of neutropenia
Causes: neutropenias can be classified as those with a decreased bone marrow production (Kostmann Syndrome, Shwachman-Diamond Syndrome, cyclic neutropenia and idiopathic neutropenia) or those with a normal or near normal reserve but increased turnover (infection, drugs, antibody-associated neutropenia or hypersplenism). Infection or drug related neutropenia can be related to an increase in turnover or decreased production or both.
Discuss major treatment strategies including growth factors for treating neutropenia
- Effective management begins with dx of the specific type of neutropenia.
- For chemotherapy induced neutropenia, severe congenital syndromes, or undiagnosed cases with ANC 38.5°C, appropriate cultures (including blood) and prompt institution of antibiotics capable of covering a broad spectrum of pathogens is required. Aggressive attempts should be made to identify the infected site and involved organisms.
- With identification of organisms, a change to specific antibiotics is warranted. In addition, G-CSF given at a dose of 3-5 μg/kg will help to normalize production, increase numbers of neutrophils in all compartments and delivery to all tissues, and prevent infection. Depending on the neutropenia syndrome, chronic administration of G-CSF on a daily or every other day basis may be required to prevent recurrent infections. Some antibody mediated syndromes may respond to intravenous gamma-globulin (IVIG).
Define leukocytosis and provide reasons for a high white blood cell count.
Leukocytosis: an increase in total number of WBCs beyond normal values.
Reasons for a high WBC in leukocytosis: infection, inflammation, non-specific physiologic stress, or malignancy (leukemia).
Describe the term “left shift” and what it indicates
changes in the white cell differential with an increase in segs and bands and possibly some immature myeloid precursors usually only found in marrow (metamyelocytes or myelocytes)
Eosinophilia:
absolute count >350/ul is abnormal. The etiologies fall into three main categories: allergies/allergic disorders (asthma, atopic dermatitis, hay fever, hives, etc.), parasitic infections, and drug reactions (allergic).
Basophilia:
Increase in peripheral basophils is seen primarily in drug or food hypersensitivity or urticaria. It may also be seen in infection or inflammation (rheumatoid arthritis, ulcerative colitis, influenza, chickenpox, smallpox, tuberculosis) as well as myeloproliferative diseases (CML, myeloid metaplasia).
Monocytosis:
absolute monocyte count of >1,000/μl in newborns and >500/μl in children and adults. Monocytosis may be found in hematologic (pre) malignancies (AML, pre-leukemia states, lymphoma, Hodgkin’s disease), collagen vascular diseases (SLE, RA), granulomatous diseases (sarcoid, ulcerative colitis, Crohn’s disease), infections (subacute bacterial endocarditis, syphilis, tuberculosis, protozoal rickettsial, and Pertussis infections), and carcinoma.
