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101 Cards in this Set
- Front
- Back
What can myeloid stem cells differentiate into?
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Basophils
Eosinophils Neutrophils Monocytes Platelets Erythrocytes |
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What can myeloblasts differentiate into?
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Basophils
Eosinophils Neutrophils |
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What disease is associated with N. promyelocytes?
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Severe congenital neutropenia
There's an arrest in the bone marrow maturation |
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What are the properties of the neutrophil?
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Common
Nucleus is 2-5 segments Light pink granules Diameter: 12-15 uM |
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What are the properties of the monocyte?
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Commonly observed
Horse-shoe shaped nucleus Diameter: 16-20 uM |
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What are the properties of the eosinophil?
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Rare
Bi-lobed nucleus Vibrant pink-orange granules Diameter: 12-17 uM |
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What are the properties of the basophil?
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Very rare
Bi-lobed nucleus Large blue-purple granules Diameter: 9-10 uM |
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Where does neutrophil differentiation take place?
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Bone marrow: proliferiation, maturation
Circulation: final differentiation |
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How long does neutrophil maturation take?
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14 days
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How many of the neutrophils are in the proliferation phase?
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25%
6-7 days while proliferating |
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What are the proliferative neutrophils?
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Myeloblasts
Promyelocyte Myelocyte Mitotic |
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How many of the neutrophils are in the maturation phase?
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65%
Total of 6-7 days maturing |
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What are the maturing neutrophils?
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Metmyelocyte
Bands Neutrophils |
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What percentage of neutrophils are normally in the tissue? Circulation?
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Tissue: 2%
Circulating: 10% |
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What;s the NL for neutrophils?
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1.5-8.0 E 9 cells/L
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What's the definition of moderate neutropenia? Severe?
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Moderate: .5-1.0 E9 cells/L
Severe: 0-.5 E9 cells/L The lower the neutrophil levels, the more severe the risk of infection. |
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What are the normal levels of neutrophils for term infants? Infants? Kids?
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Term infant: 3,000
Infant: 1,100 Kids, adolescent, adults: >1,500 |
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What ethnic groups have lower absolute neutrophil counts?
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African-americans.
They don't have symptoms, though! |
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How do you calculate the absolute neutrophil count (ANC)?
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ANC = (% bands + % segmented neutrophils) * total WBC
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When should you have a clinical suspicion for neutropenia?
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Acute, severe bacterial infection
History of recurrent/rare infections Prolonged or recurrent fevers Recurrent mouth ulcers, chronic gingivitis, cellulitis, perirectal abscesses Findings associated with malignancy, immunodeficiency or syndrome |
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What is unique about the height and weight of patients with neutropenia?
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Short stature compared to weight
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Where are there often abnormal findings in a neutropenic patient?
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Oral cavity!
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What parts of the extremities are commonly compromised in patients with neutropenia?
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Forearms
Thumbs |
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What oral findings are characteristic of a patient with neutropenia?
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|
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What's usually the cause of neutropenia?
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Infection (virus, normally)
Drug-induced Immune-based |
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What patients are particularly vulnerable to neutropenia?
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Neonates
They can exhaust their bone marrow/reserve neutrophils easily->bacterial sepsis |
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What are the common mechanisms for drug-induced neutropenia?
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Toxic
Immunologic Hypersensitivity |
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What are some common drug classes that cause neutropenia?
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Anticonvulsants
Antipsychotics Antibiotics: chlorampehicol, bactram |
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What are the different types of immune-based acquired neutropenias?
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Alloimmune neutropenia of infancy
Autoimmune neutropenia of infancy |
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How does the alloimmune neutropenia of infancy occur?
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Passive transfer of maternal IgG against fetal neutrophils
Once the antibodies are cleared, the patient gets better This can happen with the first pregnancy - a way to differentiate from Rh disease |
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How does the autoimmune neutropenia of infancy occur?
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Appears around 1 year
ANC of 200-300 is classic Treatment isn't really indicated; the reserve is still there. |
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What are the different types of inherited neutropenias?
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Primary disorders of myelopoiesis
Disorders of ribosomal function Disorders of granule sorting/trafficking Disorders of metabolism Neutropenia in disorders of immune fuction |
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What is the most common kind of congenital neutropenia?
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Severe congenital neutropenia
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What is the presentation of severe congenital neutropenia?
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Infant presents in the first year of life with recurrent/severe infections
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What's required for a diagnosis of severe congenital neutropenia?
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Three ANCs < 500
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What mutations are associated with severe congenital neutropenia?
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ELANE (autosomal dominant)
HAX1 (autosomal recessive) |
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What's the treatment for severe congenital neutropenia?
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G-CSF
Bone marrow transplant |
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What diseases are more common in patients with severe congenital neutropenia?
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AML
MDS |
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What is cyclic neutropenia?
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Cycles of neutropenia
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How long are the cycles in cyclic neutropenia?
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21 days
7-10 days of neutropenia |
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What's the presentationof cyclic neutropenia?
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Presents before 1
Recurrent fevers, malaise, apthous ulcers, bacterial infections |
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What bacteria are especially pathogenic to people with cyclic neutropenia?
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Clostridium septicum
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How do you diagnose cyclic neutropenia?
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You do CBCs 2-3 times/week for 6 weeks
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What gene is mutated in cyclic neutropenia?
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ELANE gene
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What's the treatment for cyclic neutropenia?
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G-CSF
Shortens the duration of the neutropenia NO RISK OF LEUKEMIA |
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What is the definition of neutrophilia?
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Abnormally high neutrophil counts
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What's the cause of neutrophilia?
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Acute shift from the marginating pool to the circulating pool
Chronic stimulation with excess cytokines increasing the proliferating pool |
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What are some things that can cause neutrophils to shift to the circulating pool from the marginating pool?
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Steroids
Exercise Epinephrine Hypoxia Seizures |
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What are somethings that can cause chronic proliferation of neutrophils?
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Infections
G-CSF Pregnancy Trisomy 21 Recovery from chemo Myeloproliferative disorders |
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What are the stages of neutrophil killing?
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1. Mobilization
2. Chemotaxis 3. Recognition/opsinization 4.Ingestion 5. Degranulation 6. Peroxidation 7. Killing and digestion 8. Net formation |
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What is myelokathexis?
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Apoptosis and retention of neutrophils in the bone marrow
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What gene is mutated in myelokathexis?
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CXCR4 chemokine receptor
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What are the clinical characteristics of myelokathexis?
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WHIM!
W: warts H: hypergammaglobulinemia I: infections M: myelokathexis |
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What's the treatmnet for myelokathexis?
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G-CSF
CXCR4 antagonist |
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What is the apperance of neutrophils in WHIM syndrome?
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Lots of segmentation of the neutrophils in the bone marrow.
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What are the steps of neutrophil migration into tissues?
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|
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What molecules are involved in neutrophil rolling?
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Selectins
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What molecules are involved in adhesion of the neutrophils to the endothelium?
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CD11/CD18
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What are the findings in leukocyte adhesion deficiency?
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Neutrophilia
Infections Absence of pus formation Impaired wound healing Delayed umbilical cord separation (LAD1) |
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What is the classic oral finding in LAD?
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Peridonitis
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What defect is present in LAD1? What process is inhibited?
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B2 integrin CD18
Adhesion |
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What's the treatment for LAD1?
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Bone marrow transplant
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What molecules are mutated in LAD1? What process is inhibited?
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Selectins
Rolling; can't be tethered to the tissue |
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What are the findings in LAD2?
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Neurologic defects
Craniofacial anamolies Rare erythrocyte phenotype |
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What's the treatment for LAD2?
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Very little we can do for them.
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What gene is mutated in LAD3? What process is inhibited?
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Kindlin
Integrin activation |
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What are the findings in LAD3?
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Neutrophil AND bleeding problems.
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What is Chediak higashi syndrome?
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Autosomal recessive disorder
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What are the findings in Chediak higashi syndrome?
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Immunodeficiency
Partial oculo-cutaneous albinism Bleeding diathesis Progressive neurologic deterioration Oddly colored hair |
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What process are people with Chediak Higashi syndrome unable to perform?
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Granule trafficking in neutrophils
You see giant neutrophils! |
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What gene is mutated in Chediak higashi syndrome?
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CHS1/LYST gene
Responsible for lysosomal trafficking |
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What are people with chediak higshi syndrome vulnerable to?
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Hemophagocytic lymphohistiocytosis: can't turn off phagocytois
Hepatomegaly, splenomegaly |
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What's the treatment for Chediak higashi syndrome?
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Antibiotics
G-CSF Bone marrow treatment (cures hematologic, immunodeficiency problems, doesn't affect albinism/neurologic features) |
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What are the different types of neutrophil granules?
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Primary: neutral proteases, myeloperoxidase
Secondary: lactoferrin Tertiary: gelatinase Secretory: alkaline phosphatase |
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What are the findings in myeloperoxidase deficiency?
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Largely asymptomatic
Only see disease in people with diabetes |
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What is the action of myeloperoxidase?
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Forms bleach from H2O2 and chloride
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What organism is particularly targeted by the formation of HOCl in the body?
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Candida
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How does acquired MPO deficiency happen?
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You get a disruption of the bone marrow that causes an induced mutation
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What is the treatment for MPO?
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Very little for the disease itself
Aggressively manage the fungal diseases Control the glucose tightly if there's DM |
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What occurs in chronic granulomatous disease?
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Mutation in NADPH oxidase-->no superoxide
Can't destroy catalase-positive microbes |
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What kinds of infections are people with CGD vulnerable to?
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S. aureus
Aspergillus |
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Where do you get infections in CGD?
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Lungs
Skin Lymph nodes LIVER |
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What's commonly mutated in NADPH in CGD?
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gp91phox: 65%; X-linked
p47phox: 25%; autosomal recessive |
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How do you go about diagnosing CG?
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Rhodamine dye test: dye is taken up by phagocytes-->oxidized; fluoresence
Nitroblue tetrazolium test: changing the color of a dye when superoxide is produced |
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What's the treatment for CGD?
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Antimicrobial prophylaxis: bactram
Immune modulation: interferon gamma Aggressive treatment of infections Bone marrow transplant is the only cure |
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What process needs to be intact for net formation to occur? What disease states cannot perform this?
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Hydrogen peroxide production
CGD MPO |
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What are the stages of monocyte differentiation?
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Proliferation
Maturation SHorter tissue phase They then differentiate into macrophages |
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What's the usual monocyte count?
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300/uL
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How long does it take monocytes to arrive at the scene?
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12 hours
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What are causes of a low monocyte count?
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Stress
Endotoxemia Glucocorticoids |
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What are causes if high monocyte counts?
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Bone marrow disease
Infection Inflammatory disease |
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What are the stages of eosinophil naturation?
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Proliferation (9 days)
Maturation Intravascular |
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What is the precursor to eosinophils?
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Myeocytes
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What are some causes of eosinopenia?
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Infection
Corticosteroids Prostaglandins Epinephrine No additional risks from having this |
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What is eosinophilia? What are causes?
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>500/ uL
Causes: Neoplasms Allergies Asthma Collagen vascular diseases |
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What are the characteristics of idiopathic hypereosinophilic syndrome?
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>1500 cells/uL for 6 months
Happens in people who are 20-50 Lots of organ dysfunction |
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What is the cause of pathology in idiopathic hypereosinophilic syndrome?
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Large scale eosinophil degranulation and release of major basic protein into the tissues
You can also get an eosinophilic leukemia |
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How long do basophils live in the tissues?
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A long time!
Up to days |
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What are causes of low basophil counts?
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Hypersensitivity
Glucocorticoids |
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What's the role of the basophil?
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Unknown.
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What causes a high basophil count?
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Allergies
Infections Endocrinopathies Myeloproliferative disorders Systemic mastocytosis |