Hematopoiesis and Peripheral Blood Flashcards

1
Q

What is hematopoiesis?

A

the process by which blood cells are formed

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2
Q

What comes from hematopoietic stem cells?

A

red blood cells

granulocytes

monocytes

platelets

lymphocytes

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3
Q

What comes from myeloid precursors?

A

RBCs

platelets

monocytes

neutrophils

eosinophils

basophils

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4
Q

What comes from lymphoid precursors?

A

NK cells

B cells

T cells

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5
Q

Hematopoiesis locations by age

3-8wks gestation

6-30wks gestation

9-28wks gestation

28wks-onward

A

Yolk sac

Liver

Spleen

Bone Marrow

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6
Q

Hematopoiesis occurs in bone marrow throughout the skeleton until puberty when it moves where?

A

vertebra and pelvis, skull, sternum (axillary locations)

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7
Q

What are the components of the bone marrow?

A

hematopoietc cell compartment with vasculature and stem cells

marrow stromal compartment with fenestrated endothelia, adipocytes for energy and macrophages

hematopoietic growth factors produced by stromal compartment

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8
Q

How is hematopoiesis regulated?

A

by hematopoietic growth factors

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9
Q

What is the role of Stem Cell Factor (SCF)

A

produced by fetal tissue and bone marrow

weake stimulator of hematopoiesis

makes stem cells responsive to cytokines

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10
Q

What is the role of IL3?

A

influences the replication and growth potential of hematopoietic progenitors (myeloid lineage)

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11
Q

What is the role of IL6?

A

Stimulates megakaryotcutes and neutrophil production

key factor in leukemoid reaction

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12
Q

What is the role of IL2?

What is the effect of IL2 and IL6 together on the lymphoid lineage?

A

T cell growth factor (lymphoid lineage)

B cell growth factor

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13
Q

What is the role of GM-CSF?

A

stimulates the formation of all leukocytes and reticulocytes

comparable to G-CSF for increasing neutrophils during neutropenia, but G-CSF is used more often clinically

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14
Q

What is the role of G-CSF?

A

stimulates and increase in neutrophils

treatment for neutropenia after chemotherapy or bone marrow transplant

produced bny endothelial cells, fibroblasts, and macrophages

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15
Q

What is the role of M-CSF?

A

Stimulates an increase in monocytes and macrophages

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16
Q

What is the role of erythropoietin (EPO)

A

Produced in kidney

simulates formation of RBCs

EPO stimulators are used in treatment for anemia

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17
Q

What is the role of TPO?

A

TPO is produced in the liver

stimulates an increase in megakaryocytes and platelets

TPO receptor agonists are used therapeutically

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18
Q

What are reticulocytes?

What happens to the reticulocyte count in hemolytic anemias where RBCs are destroyed?

A

enlarged, immature erythrocytes which show a residual netowork of ribosomal material (RER)

increase

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19
Q

What is the evolution of the leukocyte?

A

myeloblast: basophilic cytoplasm, no granules
promyelocyte: large granules in cytoplasm, nucleoli maybe present
myelocyte: oval nucleus, azurophilic granules, 2’ granules
metamyelocyte: indented nucleus is major feature

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20
Q

What is the evolution of lymphocytes?

A

B and T lymphoblasts: no cytoplasmic granules

B and T cells: T cells mature in thymus, B cells in bone marrow

Plasma cells (from B cells): eccentrically plcaed nucleus with perinuclear hoff generated from activated B cells in spleen and LN with help of T cells and then travel back to bone marrow

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21
Q

What is the evolution of platelets?

A

megakaryoblasts: with large oval/kidney nucleus and basophilic cytoplasm

Megakaryocyte: large multilobed nucleus with endomitosis and invaginations of plasma membrane

Platelets: break off from megakaryocyte

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22
Q

What are the three compartments for monocytes/macrohages to live in?

A

Takes 24 hours to transport among the compartments

stem cell to monoblast in bone marrow

monocyte in blood

macrophage in tissues

(specialized in various tissues)

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23
Q

What is MCV?

What is MCH?

What is MCHC?

What is RPI?

A

average volume (or size) of RBC

average mass of Hb in RBC

concentration of Hb in a given volume

reticulocyte % based on RBC volume

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24
Q

What is anisocytosis?

What is poikilocytosis?

A

variation in size and increase in RDW

variation in shape (beta thalassemia)

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25
Q

What does it mean if something is an “absolute neutropenia” as apposed to neutropenia?

A

refers to the actual number of cells, not a percentage

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26
Q

What are the causes of iron deficient anemia?

A

dietary lack of iron or decreased absorption (poor diet, cow’s milk in infants)

impaired absorption (sprue, partial gastrectomy-acid increases solubility and uptake)

chronic blood or iron loss (tumor, ulcer, menometrorrhagia, extreme distance running)

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27
Q

What does the blood panel look like in someone with iron deficient anemia?

A

anisocytosis, poikilocytosis, microcytosis, hypochromia

MCV decreased (microcytosis)

MCH decreased

MCHC decreased (hypochromia)

RBC decreased

Reticulocyte count decreased as erythropoiesis decreases

RDW increased

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28
Q

Histologically, when should iron deficient anemia be suspected?

A

hypochromic microcytic anemia with elevated RDW but no consistent shape changes in RBC

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29
Q

The laboratory evaluation of enmial begins with what?

then, the anemia is catagorized how?

Then what is is done to confirm the diagnosis?

How are the microcytic anemias separated?

How is iron deficiency anemia separated from beta thal.?

A

a complete blood count and reticulocyte index

as microcytic, macrocytic, or normocytic based on MCV with or without reticulocytosis

peripheral smear

serum iron level, TIBC, and serum ferritin levels

erythrocyte size-distribution width may be particularly helpful in distinguishing iron deficiency from thalassemia

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30
Q

Which anemias have an elevated reticulocyte count?

A

sickle cell anemia

G6PD def.

Heriditary spherocytosis

autoimmune hemolytic

paroxysmal nocturnal hemoglobinuria

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31
Q

What is marked erythroid hyperplasia?

A

anemia caused by increased red cell loss or reduced red cell life span generating elevated reticulocyte counts in the peripheral blood and erythroid hyperplasia in the bone marrow

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32
Q

When do you see nucleated RBCs?

A

Compensatory Erythropoiesis

  • severe anemia
  • chronic hypoexmia

Hyposplenism, Asplenia

  • sickle cell
  • traumatic splenectomy
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33
Q

When do you see magaloblastic hyperplasia?

A

folate or b12 deficiencies

bone marrow is hypercelluar with giant metamyelocytes and band forms with hypersegmented neutrophils and macrocytic ovalocytes (MCV high)

34
Q

What anemias have an elevated MCV (macrocytic)

A

megaloblastic anemia

  • B12 def.
  • Folate def.

Alcoholic Liver Disease

35
Q

Hypocellular bone marrow indicates what?

What disease has this?

A

reduced hematopoiesis

aplastic anemia (pancytopenia of all cell lines)

36
Q

What anemias/diseases have low reticulocyte counts?

A

Marrow failure

aplastic anemia

myelofibrosis

leukemia/metastasis

renal failure

anemia of chronic disease

37
Q

Marrow replacement/invasion an occur by what?

A

tumor

infection

myelofibrosis

myeloproliferative disorder

38
Q

What is extramedullary hematopoeisis?

A

hematopoiesis occuring in organs outside of the bone marrow, frequently in the spleen, liver and LN

normal during fetal development

39
Q

In what anemias/diseases does extramedullary hematopoiesis function as a compensatory mechanism for abnormal hematopoiesis?

A

severe chronic anemia of thalassemia, sickle cell, B12, or folate def.

stem cell failure (toxic aplastic anemia)

infection (parvovirus)

malignant tranformation and replacement (lymphoma)

40
Q

What anemias are microcytic (low MCV)

A

iron def.

thalassemia

anemia of chronic disease

sideroblastic anemia

41
Q

What are schistocytes indicative of?

A

microangiopathic hemolytic anemia (DIC, TTP/HUS)

thrombocytopenia with anemia

42
Q

What are “bite” cells and Heinz bodies associated with?

A

G6PD def.

oxidative stress, cross binding and protein deposition

43
Q

What are sickled RBCs associated with?

A

Sickle cell anemia

deformed erythrocytes due to polymerized abnormal hgb S

homozygous abnormal hb SS

44
Q

What are spherical RBCs/Spherocytes associated with?

A

Spherocytosis

45
Q

What is the normal WBC?

What white cell makes up the most white cells?

what lymphocyte makes up the most lymphocytes?

A

4.8-10.8 (x10^3/uL)

neutrophils are the most

T cells

46
Q

What are causes of neutrophilia

A

acute bacterial infection

medications (glucocorticoids, catecholamines)

cigarette smoking

various types of physical stress

myeloproliferative neoplasms/leukemia

47
Q

What is left shift?

(he said this slide was important)

A

increased immature leukocytes, especially band forms

48
Q

What is neutrophilia, especially neutrophilia with acute left shift, is associated with what?

A

acute bacterial infections

49
Q

What is toxic granulation?

A

dark course granules within neutrophils, especially in inflammatory conditions

50
Q

How do you tell the difference between band cells and metamyelocyte?

A

band cells have horseshoe nuclei

metamyelocytes are juvenile granulocytes and look kidney-ish

51
Q

what is a leukemoid reaction?

A
  • WBC count is greater than 50,000/microL, with increased neutrophils without evidence of leukemia
  • due to infection, drugs, carcinoma (paraneoplastic IL-6)
  • bone marrow would show complete maturation without increased blasts
  • leukocyte Alkaline phosphatase is ELEVATED
52
Q

What should always be on top of the DDx list when the WBC is over 50,000?

A

leukemic or lymphoproliferative process

53
Q

What is Chronic Myelogenous Leukemia?

A
  • WBC count around 100,000
  • insidious disease process, typically of adults
  • high WBC, progressive increase in blasts
  • starts in chronic phase, then accelerated phase has increase of 10-19% blasts, then blast phase as over 20% blasts in blood or bone marrow
54
Q

What is acute myeloid leukemia?

A
  • occurs at all ages, peaks over 60
  • accumulation of immature myeloid blasts (>20%) in the bone marrow
  • can present with anemia, thrombocytopenia, and neutropenia due to bone marrow crowding
55
Q

What are some causes of inadequate granulopoiesis?

(leads to neutropenia)

A
  • suppression of granulocytic precursors (drugs/toxins)
  • suppression of hematopoietic stem cells (aplastic anemia, marrow replacement/invasion)
  • ineffective hematopoiesis (neutropenia seen with B12/folate deficient anemias)
56
Q

What can cause increased destruction/sequestration leading to neutropenia

A
  • immunologically mediated injury to neutrophils (autoimmune, lupus)
  • splenomegaly (portal HTN, leads to mild neutropenia)
  • increased peripheral utilization (overwhelming bacterial or fungal infection)
57
Q

What are some benign causes of absolute lymphocytosis?

A

EBV causing Mono

CMV

Pertussis

Toxoplasmosis

drug-induced

RA

hyperthyroidism

58
Q

What are the findings in chronic lymphocytic leukemia?

What are the findings in acute lymphoblastic leukemia?

A

older adults, >5000 ALC, lymphadenopathy, hepatosplenomegaly

children, numerous blasts on the peripheral smear or bone marrow

test with cytometry

59
Q

What are some additional causes of leukocytosis?

A

Eosinophilic leukocytosis-allergic conditions and parasites

basophilic leukocytosis-rare, can be seen in leukemia

monocytosis-atypical bacterial infections, autoimmune disease

60
Q

Briefly describe platelet function in primary hemostasis

A
  • platelets from a primary plug that initially seals vascular defects and allows coagulation factors to bind
  • platelets bind via Gp1b von Willebrand factor on exposed collagen
  • platelets change shape and release ADP and thromboxane A2
  • ADP and TxA2 cause more platelet activation and allow GpIIb-IIIa receptor affinity to fibrinogen to increase causing aggregation of platelets via fibrinogen
61
Q

What is the physiologic range for platelets?

A

150,000-450,000/uL

62
Q

What is thrombocytopenia

A

mucocutaneous bleeding occurs with low platelets

Plts <100K are high risk for surgery and should be avoided

Plts <50k will cause surgical bleeding

Plts <20k will cause severe bleeding, spontaneous hemorrhage and IC bleeds

63
Q

Increased platelet destruction can lead to thrombocytopenia. What can lead to increased platelet destruction?

A

idiopathic thrombocytopenic purpura

idiopathic or secondary autoimmune destruction {(SLE, HIV)

Drug induced, Heparin induced

disseminated intravascular coagulation

thrombotic thrombocytopenic purpura/hemolytic uremic syndrome

hiv associated thrombocytopenia

64
Q

What are some causes of decreased production of platelets that can also lead to thrombocytopenia?

A

bone marrow replacement due to tumor

liver diseases reducing TPO production

BONUS:

Sequestration of platelets can lead to decrease. What causes that? Hypersplenism!

65
Q

Anemia

A

dec. RBC volume or Hb

66
Q

Polycythemia

A

inc. RBC or Hb

67
Q

Thrombopenia

A

dec. platelets

68
Q

Thrombocythemia

A

inc. platelets

69
Q

Leukocytosis

A

inc. WBC

70
Q

Leukopenia

A

dec. WBC

71
Q

Lymphocytosis

A

inc. lymphocytes

72
Q

Neutropenia

A

dec. lymphocytes

73
Q

Eosinophilia

A

inc. eosinophils

74
Q

Neutrophilia

A

inc. neutrophils

75
Q

Pancytopenia

A

dec. of all cell lines

76
Q

MCV calculation

A

Hct/RBC

77
Q

MCH calculation

A

Hb*10/RBC

Average mass of hemoglobin in erythrocytes

78
Q

MCHC calculation

A

Hb/Hct

Concentration of hemoglobin in a given volume

79
Q

RPI calculation

A

Retic % * Hct/Normal Hct

80
Q

RDW definition

A

Red cell distribution width (RDW)

Measure of range in variation of red blood cell volume

81
Q

Definitions

Hg

RBC

Reticulocyte percentage

Hct

A

Hemoglobin (Hg)

Concentration of hemoglobin per unit volume

Red blood cell count (RBC)

Number of red blood cells per unit volume of blood

Reticulocyte percentage

% of RBCs that are reticulocytes

Hematocrit (Hct)

Volume percentage of red blood cells in blood