Hematopoiesis and an introduction to peripheral blood Flashcards

1
Q

What are the two stem cell lineage that come from the hematopoietic stem cells? what are their major cells they give rise to

A

Myeloid cell

  • RBC
  • Platelets
  • Monocyte
  • neutrophil
  • eosinophil
  • basophil

Lymphoid cell

  • B lympohcytes
  • T lymphocytes
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2
Q

what are the Committed precursor cells in the Myeloid stem cell line?
and what are the factors needed for it to get to the functioning cell

A

BFU-E gives rise to RBC
-EPO

CFU-Mega gives rise to PLatelets
-TPO

Monoblasts to a monocyte
-GM-CSF, M-CSF

Myeloblasts to a neutrophil
-GM-CSF, M-CSF

Eosinophilic myleoblast to a eosinophil

  • GM-CSF
  • IL-5

Basophilic myleoblast to a basophil

  • IL-3
  • IL-4
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3
Q

what are the committed precursor cells in the lymphoid stem cell line?
what factors needed for it to get to the functioning cell

A

Pre-B-cell to B lymphocyte
-IL 1, 2, 4, 5, 6

Prothymocyte to a T lymphocyte
-IL-2, 4

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4
Q

where does Hematopoiesis occur throughout life?

A

as a fetus:

  • Yolk sac
  • Liver and spleen
  • Bone marrow

as a child:
-occurs in majority of bones

as an adult:
-more in the axillary region of skeleton

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5
Q

what produce some of the hematopoietic growth factors? and what are the 4 major growth factors?

A

Endothelial cells
Marrow fibroblasts
Stromal cells
and adipocytes

Colony stimuating factor (CSF)

Cytokines (Interleukins)

Erythropoietin (EPO)

Thrombopoietin (TPO)

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6
Q

what are the hematopoietic growth factors that distinguishes the Pluriopotent stem cell to differentiate either the Myleoid or Lymphoid cell line?

A

Myeloid:

  • Stem cell factor
  • IL-3
  • produced by fetal tissues and bone marrow

Lymphoid:

  • IL-1
  • IL-4
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7
Q

what does IL-6 have an important role in stimulating in the myleoid cell line?

A

Stimulates Megakaryocytes and neutrophil production

key factor in the leukemoid reaction (increase in WBC)

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8
Q

Production, and what does it stimulate: GM-CSF

A

Granulocyte macrophage colony stimulating hormone

produced by endothelial cells, T cells, fibroblasts, and monoblasts

Stimulates the production of all leukocytes and reticulocytes

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9
Q

Production and what does it stimulate: G-CSF

A

Granulocyte colony stimulating factor

Produced by endothelial cells, fibroblasts, and macrophages

stimulates an increase in neutrophils

treatment for neutropenia after chemotherapy or bone marrow transplant

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10
Q

what does M-CSF do?

A

Macrophage colony stimulating factor

stimulates an increase in monocytes and macrophages

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11
Q

where is EPO produced? where is TPO produced?

A

EPO produced in the kidney

TPO produced in the liver

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12
Q

Characteristics of a Reticulocyte, and when will this count be increased?

A

Reticulocytes will be increased in hemolytic anemias where the red blood cells are being destroyed and their count will be increased

they are enarged immature erythrocytes which show residular networks of ribosomal material (rough ER)

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13
Q

what are the 4 generations of a granulocyte and their characteristics?

A

Myeloblast

  • basophillic cytoplasm
  • no granules

Promeyelocyte

  • cytoplasm contains large black or purple granules
  • nucleoli may be present

Myelocyte

  • Eccentric round oval nucleus
  • primary azurophillic granules
  • fine secondary granules predominate

Metamyleocyte:

  • a juvenille granulocyte
  • indented nucleus is a major feature
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14
Q

where are plasma cells produced and what is a histological characteristic of them?

A

Plasma cells are produced from activated B-cells in spleen and lymph node with the help of T cells

they then travel back to the bone marrow

they have an eccentrically placed nucleus with perinuclear hoff

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15
Q

Histological Characteristics of Megakaryoblast and Megakaryocytes

A

Megakaryoblasts are large oval or kidney shaped nucleus
-and basophillic cytoplasm

Megakaryocyte:

  • large multilobed nucleus
  • endomitosis which is nuclear divisions that occur without cell division (polyploid nucleis)
  • plasma membrane invaginages and the platelets break off
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16
Q

what is the transition process for the monocytes/macrophages

A

in the Bone marrow:
-Monoblast

in the blood:
-monocyte

in the tissues
-macrophage
(then become, microgilia, kupffer cell, ALveolar macrophage, osteoclasts)

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17
Q

Lab Values definitions:

  • Hemoglobin (Hg)
  • Hematocrit (Hct)
  • Red blood count
  • Reticulocyte percentage
  • Red cell distribution width (RDW)
A

Hemoglobin (Hg): concentration of hemoglobin per unit volume

Hematocrit (Hct): volume percantage of red blood cells in blood

RBC: number of red blood cells per unit volume of blood

Reciulocyte percentage: % or RBC that are reticulocytes

Red cell distribution width (RDW): measure of range in variation of red blood cell volume

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18
Q

Lab value definitions and calculations:

  • Mean corpuscular volume
  • Mean corpuscular hemoglobin
  • mean corpuscular hemoglobin concentration
  • reticulocyte production index
A

Mean corpuscular volume (MCV)

  • average volume of a red blood cell
  • Hct/RBC = MCV

Mean corpuscular hemoglobin (MCH)

  • average mass of hemoglobin in erythrocytes
  • Hb x10/RBC = MCH

mean corpuscular hemoglobin concentration (MCHC)

  • concentration of hemoglobin in a given volume
  • Hb/Hct = MCHC

reticulocyte production index (RBI)

  • corrected reticulocyte percentage based on RBC volume
  • Retic% x Hct/Normal Hct = RPI
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19
Q

Anisocytosis?

Poikilocytosis?

A

Ansiocytosis: variation in size
-increased in the RDW (red cell distribution width)

Poikilocytosis: variation in shape

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20
Q

penia?
cytosis?
phillia?
cythemia?

Pancytopenia?

A

these endings of words mean:

penia = decreased

cytosis: increased
phillia: increased
cythemia: increase of blood

Pancytopenia: decrease of all cell lines (RBC, platelets, WBC)

21
Q

What are signs and symptoms of iron deficiency anemia?

A
Fatigue
weakness
headaches
dizziness or lightheadednes
pale or yelowish skin
irregular heartbeats
shortness of breath
chest pain
cold hands and feet
22
Q

what are the three main ways that causes an iron deficiency anemia?

A

Dietary lack of iron or decreased absorption:

  • poor diet
  • cows milk fed to infants

Imapired absorption

  • sprue
  • partial gastrectomy

Chronic blood or iron loss:

  • tumor
  • ulcer
  • menometrorrhagia
  • extreme distance running
23
Q

in an iron deficiency anemia, how does the RDW, RBC, and MCV behave?

A

Ansiocytosis, microcytosis and hypochromia

elevated RDW

decreased Mean cell volume

RBC decreases

Reticulocyte count decreases

24
Q

what is the comprehensive list for the main causes of Anemia?

A
Iron deficiency anemia
anemia of chronic disease
sideroblastic anemia
megaloblastic anemia (B12 or folate deficiency)
Hemoglobinopathies (sickle cell, B-thalassemia)
G6PD deficiency
Autoimmune hemolytic anemia
COngenital (fanconi, vlackfan-diamond)
Myelodysplastic neoplasm 
metastasis to bone, tumor
25
Q

what are key labroatory evaluations for anemia?

A

begins with a complete CBC and reticulocyte index

categorize the blood cells as: based on MCV

  • microcytic
  • macrocytic
  • or normocytic

know the reticulocyte count

then to seperate the microcytic anemias utilize the iron level, total iron binding capacity (TIBC), serum ferritin level

26
Q

common anemia diseases showing an MCV less than 80 fL/cell (microcytic)

A
  • Iron dificiency
  • Thalassemia (increased RBC and reticulocyte as well)
  • Anemia of chronic disease
  • sideroblastic anemia
27
Q

common anemia diseases showing Normocytic MCV (80-100 fl/cell) but low reticulocyte count

A
  • Marrow failure
  • Aplastic anemia
  • Myelofibrosis
  • leukemia/metasis
  • renal failure
  • anemia of chronic disease
28
Q

common anemia disease showing Normocytic MCV (80-100 fl/cell) but high reticulocyte count

A
  • Sickle cell anemia
  • G6PD deficiency
  • hereditary spherocytosis
  • autoimmune hemolytic anemia
  • paroxysmal nocturnal hemoglobinuria
29
Q

common anemia disease showing Macrocytic MCV greater than 100 fl/cell

A
  • Megablastic anemia

- alcohol liver disease

30
Q

when do we see Nucleated red blood cells?

A

Compensatory erythropoiesis

  • severe anemia
  • chronic hypoxemia

Hyposplenism, asplenia

  • sickle cell anemia
  • traumatic splenectomy
31
Q

what do we see in the bone marrow during aplastic anemia and marrow failure?

A

hypocellular bone marrow with less than 30 percent of cells

pancytopenia of all cell lines

32
Q

what diseases do we see where their is marrow replacement and invasion?

A

Tumor (metastic carcinoma, lymphoma, myeloma)

Infection (Tb granulomas, fungal)

Myelofibrosis (idiopathic chronic, toxin/radiation)

Myleoproliferative disorder

one tell sign is leukoerythroblastosis: nucleated and teardropped RBCs and immature WBC

33
Q

where do we see extramedullary hematopoiesis and what diseases is it compensating for?

A

seen in organs outside the bone marrow, frequently the spleen, liver, and lymph nodes
-this all happens in normal fetal development

EMH compensates for abnormal hematopoiesis:

  • severe chronic anemia or thalassemia or sickle cell
  • stem cell failure (aplastic anemia)
  • infection (parovirus)
  • Severe chronic anemia (B12 or folate deficiency)
  • Malignant transformation and replacement (lymphoma, metasisis)
34
Q

High yield Morphologic RBC findings: Schistocytes

A

Microangiopathic hemolytic anemia

  • Disseminated intravascular coagulation
  • Hemolytic uremic syndrome
  • Thrombotic thrombocytopenia purpura

Thrombocytopenia with anemia

35
Q

High yield Morphologic RBC findings: Bite cells and Heinz bodies

A

G6PD deficiency

oxidative stress (infection, drugs, certain foods) cross binding and protein deposition

36
Q

High yield Morphologic RBC findings: Spherocytes

A

sign of Hereditary spherocytosis

37
Q

what are normal percentages of WBC types

A

40% neutrophils

20-40% lymphocytes

2-6% monocytes

1-6 eosinophils

1-2 basophils

38
Q

What are some main causes of Neutrophilla

A

Acute bacterial infection

Medications (glucocorticoids, catecholamines)

Cigarette smoking

Various types f physical stress

Myeloproliferative neoplasms/leukemia

39
Q

what is the left shift?

A

Increased immature leukocytes due to persistent infection and need to produce more and more neutrophils

40
Q

what is the leukemoid reaction

A

WBC over 50000 without the evidence of leukemia

due to infection, drugs, or carcinoma (paraneoplastic IL-6)

there is an elevated alkaline phosphatase which is unlike in leukemia

41
Q

What is Chronic Myelogenous Leukemia (CML)

A

Median WBC around 100,000

Insidious disease process typically disease of adults

as the disease processes get more and more blasts in blood marrow

  • 10-19 = accelerated phase
  • greater 20% blast phase
42
Q

What is acute Myeloid leukemia?

A

occurs at all ages but peaks at age 60

accumuation of immature myeloid blasts in the bone marrow

can present with anemia, thrombocytopenia, and neutropenia and neutropenia due to bone marrow crowding

43
Q

what are the two main categories of neutropenia?

A

Inadequate granulopoiesis:
-suppression of granulocytic precursors (drugsm toxins)

  • suppression of hematopoietic stem cells (aplastic anemia, marrow replacement invasion)
  • ineffective hematopoiesis (megablastoic anemia)

Increased destruction/sequestration:
-immunolgically mediated injury (lupus, autoimmune)

  • Splenomegaly (such as portal hypertension)
  • Increased peripheral utilization (overwhelming bacteria infections)
44
Q

what presents with atypical looking T-lymphocytes on a smear?

A

Mononucleosis from epstein barr virus

45
Q

what are the 2 different types of leukemia?

A

Chronic lymphocytic leukemia

  • older aduts
  • lymphadenopathy
  • hepatosplenomegaly’

Acute lymphoblastic leukemia

  • children
  • numerous blasts on the peripheral smear or bone marrow
  • can be analyzed on a flow cytometry
46
Q

Some weird causes of Leukocytosis

A

Allergic conditions, parasites
-Eosinophilic leukocytosis

Basophilic leukocytosis
-seen in leukemia

Monocytosis
-bacterial infection or autoimmune disease

47
Q

what is Thrombocytopenia? and relative risks

A

Mucocutaneous bleeding due to low levels of platelets

lower than 100k means high risk for surgery

less than 50k means surgical bleeding

less than 20k is severe and could lead to spontaneous hemorrhage, intracranial

48
Q

what are some causes of Thrombocytopenia?

A

Increased platelet destruction:

  • ITP (idiopathic throbocytopenia purpura)
  • Autoimmune destricution (SLE, HIV)
  • Drug induced, Heparin induced thrombocytopenia
  • DIC disseminated intravascular coagulation
  • HiV associated thrombocytopenias

Decreased production of platelets

  • bone marrow replacement:
  • liver disease and decrease in TPO

Sequestration: hypersplenism