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Zlotnik- Blood Physiology > Hematopoiesis, Stem cells, Bone Marrow transplant > Flashcards

Hematopoiesis, Stem cells, Bone Marrow transplant Flashcards

1
Q

3 classes of proteins

A

Intracellular Transmembrane Secretory

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2
Q

NCE Drugs

A

New Chemical Entities traditional drugs, usually are agonists or antagonists of a ligand(secreted protein)/receptor (transmembrane protein) interaction or enzyme modulators

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3
Q

Biological Drugs

A

Recombinant Proteins (Secreted proteins that fail in certain diseases). • Insulin (Diabetes) • Erythropoietin (Anemia) – Monoclonal Antibodies: These are highly specific antibodies that bind secreted or transmembrane proteins

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4
Q

“New Wave” drugs

A

New therapeutics that involve isolation of blood cells with specific functions, modification in vitro, and re-administration to the patient to modify his/her immune response

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5
Q

Blood consists of…

A

45% cells – The bulk of the cells consist of red blood cells (erythrocytes) – Platelets and leukocytes (neutrophils, monocytes, basophils, eosinophils, lymphocytes) make up the remainder 55% plasma typical volume ~ 5L

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6
Q

hematopoiesis

A

formation of blood cells in the bone marrow The bone marrow contains hematopoietic stem cells and their progeny, and supporting tissues (stroma) that produce cytokines that promote their development “Dry bone marrow” very few blood cells suggests that hematopoeisis is deficient. 0 to 3 months in utero: mesoderm of yolk sac; 3 to 7 months in utero: liver is the main blood-forming organ with spleen contributing; 7 months and beyond: Bone marrow; 70% in pelvis, vertebrae, sternum

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7
Q

hematocrit

A

volume % of RBCs in blood Normal 37.5-50% (higher in men, 48%, than women, 38%)

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8
Q

neutrophil

A

aka Polymorphonuclear cell first responders to microbial invasion pus 50-70% of wbcs 3000-6000 per microliter blood # increase for infections # decrease for poisoning, leukemia, genetic disease, vit B12 deficiency, autoimmunity, chemotherapy

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9
Q

eosinophil

A

immune responses to parasites 1-4% of wbcs 150-300 per microliter blood # increase for parasite infestation

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10
Q

basophils

A

0-1% of wbcs 0-100 per microliter blood -contain vasoactive amines which participate in allergic responses -May be involved in resistance to bites from venomous animals # increase for chronic myelogenous leukemia

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11
Q

lymphocytes

A

20-40% of wbcs 1500-4000 per microliter blood B lymphocytes- produce antibodies. CD4 T lymphocytes- ‘directors of the orchestra’ of the immune system through cytokine production CD8 T lymphocytes- aka cytotoxic T cells, especially good at killing virus-infected cells # increase for leukemias, infections # decrease for immunodeficiency

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12
Q

monocytes

A

2-8% of wbcs 300-600 per microliter blood - These are more serious ‘defenders’ that come into play if the neutrophils cannot do the job, or, to clear the field of dead neutrophils. -Big participants in INFLAMMATION -differentiate into tissue resident macrophages or dendritic cells # increase for infections and chronic inflammation # decrease for leukemias, stress, glucocorticoids, genetic diseases

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13
Q

platelets

A

200,000-500,000 per microliter blood key role in coagulation

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14
Q

mast cell

A

granulated cells that contain histamine and heparin, an anticoagulant. Both cells also release histamine upon binding to immunoglobulin E very similar to basophils

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15
Q

stroma

A

supporting tissue of hematopoietic stem cells fat cells, fibroblasts, macrophages, endothelial cells

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16
Q

Hematopoietic stem cells

A

Pluripotent stem cells: self renewing; destruction can lead to pancytopenia -destroyed by radiation, infections (e.g. hepatitis C), chemical poisons and drugs. -Main cytokines supporting them: Stem cell factor, flt-3ligand CXCL12 Committed stem cells: do not self renew, committed to a particular lineage. -Cytokines Promoting their differentiation: IL3, GM-CSF, G-CSF, M-CSF, IL-7. -Think of them as ‘adolescent’ cells

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17
Q

pancytopenia

A

decrease in all blood cell lineages

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18
Q

cytokines

A

Small secreted proteins produced by many cell types that control inflammation, immune responses, and other important processes through their ability to induce differentiation and/or proliferation of certain cells

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19
Q

SCF

A

-produced by fibroblasts and endothelial cells - Ligand of c-kit (recepotor on HSC) -supports pluripotent hematopoietic stem cells - no SCF -> death by anemia

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20
Q

Interleukin 3

A

Supports stem cells and committed precursors

21
Q

GM-CSF

A

Granulocyte-Monocyte Colony Stimulating Factor: Source: T cells, stromal cells; Supports growth of neutrophils and monocytes

22
Q

G-CSF

A

Granulocyte Colony Stimulating Factor: Source: T cells, stromal cells; Supports differentiation and growth of neutrophils

23
Q

M-CSF

A

Monocyte Colony Stimulating Factor: Source: T cells, stromal cells; Supports differentiation and growth of monocytes

24
Q

EPO

A

Erythropoietin- Supports growth and terminal differentiation of RBC

25
Q

iron

A

required for heme synthesis

26
Q

folate

A

Vit B-12, required for DNA synthesis

27
Q

Thrombopoietin

A

required for megakaryocyte (platelet) development.

28
Q

CXCR4

A

A chemokine receptor that along with its ligand (CXCL12) plays a key role in maintaining the HSC in the bone marrow it is down-regulated during maturation until cell is released from stroma

29
Q

bone marrow aspiration

A

Pelvis is the preferred site for bone marrow aspiration, sternum can also be used for obese pts

30
Q

CD34+

A

a cell surface glycoprotein and functions as a cell-cell adhesion factor. It may also mediate the attachment of stem cells to bone marrow extracellular matrix or directly to stromal cells on HSCs

31
Q

Ckit+

A

cell surface marker that identifies HSCs

32
Q

Lin-

A

lack lineage markers on HSCs

33
Q

pancytopenia

A

decreased numbers of white blood cells, red blood cells, platelets

34
Q

leukopenia

A

decreased white blood cells

35
Q

neutropenia

A

aka granulocytopenia, decreased neutrophils

36
Q

monocytopenia

A

decreased monocytes

37
Q

Eosinopenia

A

decreased eosinophils

38
Q

Basocytopenia

A

(basopenia): decreased basophils.

39
Q

Lymphopenia

A

decreased lymphocytes

40
Q

Thrombocytopenia

A

decreased platelets

41
Q

Erythropenia

A

decreased red blood cells

42
Q

CYTOSIS

A

white blood cells above the normal values

43
Q

plasma

A

all plasma proteins 7g/dL -albumin (4g/dL) -globulin -transferrin -ceruloplasmin

44
Q

CFU-GEMM

A

-colony forming unit that generates myeloid cells -multipotential progenitor cells -give rise to granulocytes (neutrophils), erythrocytes (RBC), monocytes- macrophages, megakaryocytes- platelets, eosinophils, basophils NOT lymphocytes (CFU-L)

45
Q

CFU-L

A

-aka lymphoblast -give rise to lymphocytes

46
Q

reticulocyte

A

-RBC precursors that leave the BM, stay in blood for 1 day before maturing into RBC -contain cytoplasmic RNA which stain with supravital dyes giving a reticular pattern -nucleus is delete during last erythroblast stage (dead weight) before becoming a reticulocyte

47
Q

Absolute Reticulocyte Count

A

retic% x RBC count

48
Q

Reticulocyte Index

A

determines rate of RBC production retic%x(patient’s hematocrit/normal hematocrit)

49
Q

Hematopoesis- image

A

Zlotnik- Blood Physiology (5 decks)

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