Chapter 7: Granulocytes, Monocytes, and their benign disorders Flashcards Preview

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Flashcards in Chapter 7: Granulocytes, Monocytes, and their benign disorders Deck (56):

Are immature Leukocytes (phagocytes and lymphocytes) found in normal peripheral blood?

No only mature phagocytes and lymphocytes are found in peripheral blood


What sorts of granules are found in neutrophils?

Primary appear at the premyelocyte stage and contain MPO, acid phosphatase, and other acid hydrolases.
Secondary granules appear at the myelocyte stage and contain collagenase, lactoferrin, and lysozyme.


What is the average lifespan of a neutrophil in the peripheral blood?

6-10 hours.


What are myeloblasts?

Myeloblasts are the earliest recognizable precursors of neutrophils. (They make up 4% of normal bone marrow)


What is the lineage of the neutrophil?

myeloblast --> Promyelocyte --> Myelocytes --> Metamyelocytes --> Bands --> Neutrophils


What are the morphological characteristics of monocytes?

Oval indented nucleus, clumped chromatin, bluish cytoplasm, many vacuoles in the cytoplasm.


What is the lineage of the monocyte?

myeloblast --> promonocyte --> Monocyte --> Immature macrophage --> Mature macrophage.


To what cell type are basophils closely related?

Basophils are very closely related to mast cells.


What is more abundant in the bone marrow; myeloid cells or erythroid cells?

Myeloid cells are the most abundant in the bone marrow by a factor of 2:1 to 12:1. (Neutrophils and metamyelocytes are the most abundant specific types)


Are more granulocytes found in the bone marrow or the peripheral blood?

10-15 times more granulocytes are found in the bone marrow than in the peripheral blood.


What happens to granulocytes that are released from the bone marrow?

They spend about 6-10 days in the circulation. Then they marginate and move into the tissues where they spend 4-5 days carrying out their phagocytic function before they are destroyed or they senesce.


What growth factors stimulate granulocyte growth, maturation, functioning?

(1) IL-1
(2) IL-3
(3) IL-5 (eosinophils)
(4) IL-6
(5) IL-11
(6) GM-CSF
(7) G-CSF
(8) M-CSF


What is the result of the clinical application of G-CSF?

G-CSF will increase the numbers of Neutrophils.


What is the result of the clinical application of GM-CSF?

GM-CSF given intravenously has been shown to increase the numbers of neutrophils, eosinophils, and monocytes.


Why is G-CSF given after chemotherapy, radiotherapy, or bone marrow transplant?

G-CSF is given to accelerate hematopoietic recovery thus reducing the post-therapy neutropenic period.


Why is G-CSF given to treat acute myeloid leukemia?

G-CSF is used in AML post treatment speed up bone marrow recovery. Sometimes it is given with treatment to move cells into the cell cycle thus increasing sensitivity to antineoplastics.


Why is G-CSF used to treat Acute lymphoblastic leukemia?

G-CSF is used to reduce the severity of neutropenia after treatment of ALL.


How is G-CSF used to treat myelodysplasia?

G-CSF is used in conjunction with erythropoietin to improve bone marrow function without stimulating malignant transformation.


Why is G-CSF used to treat Severe Neutropenia?

G-CSF is found to be effective at stimulating replacement neutrophils in cases of severe neutropenia.


Why is G-CSF given to donors before peripheral blood stem cell transplants?

Because G-CSF will increase the number of multipotent progenitors in the circulation that can be harvested


Why is G-CSF given to treat lymphomas?

G-CSF is given to reduce infection, delay giving chemotherapy, and shorten hospitalization after chemotherapy.


How long do monocytes circulate in the blood?

20-40 hours


How long do mature macrophages live for?

months to years


What are the three basic functions of neutrophils and monocytes?

(1) Chemotaxis
(2) Phagocytosis
(3) Killing and digestion


What is neutrophil and monocyte chemotaxis?

Neutrophils and monocytes are attracted by chemicals, such as chemokines or complement, to bacteria or sites of inflammation.


On what cells do CXC chemokines act?



On what cells do CC chemokines act?

Monocytes, basophils, eosinophils, and natural killer cells.


What is the oxygen dependent intracellular killing/digestion pathway?

superoxide, hydrogen peroxide and other ROS react with MPO and halides to destroy ingested material/cells.


What is the non-oxidative microbicidal pathway?

microbicidal proteins such as cathepsin G, lysozyme, elastase, lactoferrin, and nitric oxide kill the ingested microbe.


What are some disorders associated with defective chemotaxis?

Lazy leukocyte syndrome, corticosteroid therapy, acute/chronic myeloid leukemia, myelodysplasia, and myeloproliferative syndromes.


What causes disorders of phagocytosis?

Phagocytic disorders most commonly are the result of defective opsonization.


What are the disorders of leukocyte killing mechanisms?

(1) Chronic granulomatous disease
(2) MPO deficiency
(3) G6PD deficiency
(4) Chediak Higashi syndrome.


What is the Pelger-Heul anomaly?

A congenital condition characterized by bilobed or unsegmented neutrophils in the peripheral blood. Autosomal dominant


What is the May-Hegglin anomaly?

May-Hegglin anomaly is characterized by neutrophils that contain basophilic inclusions of RNA. There may be associated thrombocytopenia with giant platelets. Autosomal dominant.


What is Chediak-Higashi syndrome?

Chediak-Higashi syndrome is characterized by giant granules in neutrophils, eosinophils, monocytes, and lymphocytes, accompanied by neutropenia, thrombocytopenia, and hepatosplenomegaly. Autosomal recessive.


What causes hypersegmented neutrophils?

Megaloblastic anemia.


What causes Dohle bodies and toxic granules in neutrophils?



What pathological conditions can cause Pelger cells (bilobed or unsegmented neutrophils)?

Acute myeloid leukemia or myelodysplasia.


What conditions often accompany neutrophilia?

(1) Shift to the left (increased bands in peripheral blood)
(2)Toxic granules
(3) Dohle bodies
(4) elevated NAP score (0-400)(normal is 20-100)


What is the leukamoid reaction?

The leukamoid reaction is a reactive and excessive leukocytosis characterized by the presence of immature leukocytes in the peripheral blood.


With what conditions is a leukamoid reaction associated?

(1) severe or chronic infections
(2) severe hemolysis
(3) Metastatic cancer
(4) More pronounced in children.


What is hypereosinophilic syndrome?

A condition characterized by elevated eosinophils for over 6 months with associated tissue damage.


What is chronic eosionophilic leukemia?

Eosinophilic syndrome due to a clonal cytogenetic abnormality in the bone marrow.


What are the causes of basophilia?

All rare
(1) Chronic myeloid leukemia
(2) Polycythemia vera
(3) Myxoedema
(4) smallpox
(5) chickenpox
(6) ulcerative colitis.


What are some causes of Monocytosis?

(1) infection
(2) Connective tissue diseases (hypersensitivity)
(3) chronic neutropenia
(4) Malignancies
(5) treatment with growth factors.


What is the normal cutoff for neutropenia?

2.5x10^9/L except in blacks and middle easterners for which 1.5x10^9/L is normal.


What what level of neutrophils is the patient likely to have recurrent infections?



What is Kostman's syndrome?

Kostman's syndrome is an autosomal recessive condition that presents in the first year of life with serious infections due to neutropenia. (G-CSF therapy may be helpful)


What is a common cause of benign neutropenia?

Increased margination of neutrophils causes a decreased blood neutrophil count.


What are the clinical features of severe neutropenia?

(1) infections of the mouth and throat
(2) ulceration of the mouth, throat, and anus
(3) Septicemia
(4) pathogenic infection by usually tolerated organisms.


How is type of neutropenia diagnosed?

By examination of the bone marrow. (marrow aspiration of trephine biopsy).


How is neutropenia treated?

Neutropenia is treated by prophylactic used of antibiotics to prevent infection. Immunosuppresants may actually be effective if the neutropenia is caused by AI disease. G-CSF may be effective in some benign neutropenias.


What is Langerhans cell Histiocytosis?

LCH are a group of diseases that can be single organ or multi-system. The lesions found include Langerhans cells, eosinophils, lymphocytes, neutrophils, and macrophages. Additionally there are tennis racquet like birbeck bodies in the langerhans cells


What is hemophagocytic lymphohistiocytosis (hemophagocytic syndrome)?

It is a rare AR, or acquired disorder (EBV/Herpes/Tumors) that is characterized with fever, pancytopenia, hepatosplenomegaly, multi-organ dysfunction, lymphadenopathy, and macrophages that have ingested other leukocytes.


How is hemophagocytic syndrome treated?

treatment involve the underlying cause if it is known.


What is the Rosai-Dorfman syndrome?

Sinus histiocytosis with massive lymphadenopathy is a condition typified by chronic painless cervical lymphadenopathy with fever and weight loss. It usually subsides by itself.