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
What does it mean if something is an "absolute neutropenia" as apposed to neutropenia?
refers to the actual number of cells, not a percentage
26
What are the causes of iron deficient anemia?
**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)
27
What does the blood panel look like in someone with iron deficient anemia?
anisocytosis, poikilocytosis, microcytosis, hypochromia MCV decreased (microcytosis) MCH decreased MCHC decreased (hypochromia) RBC decreased Reticulocyte count decreased as erythropoiesis decreases RDW increased
28
Histologically, when should iron deficient anemia be suspected?
hypochromic microcytic anemia with elevated RDW but no consistent shape changes in RBC
29
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 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
30
Which anemias have an elevated reticulocyte count?
sickle cell anemia G6PD def. Heriditary spherocytosis autoimmune hemolytic paroxysmal nocturnal hemoglobinuria
31
What is marked erythroid hyperplasia?
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
32
When do you see nucleated RBCs?
**Compensatory Erythropoiesis** - severe anemia - chronic hypoexmia **Hyposplenism, Asplenia** - sickle cell - traumatic splenectomy
33
When do you see magaloblastic hyperplasia?
folate or b12 deficiencies **bone marrow is hypercelluar** with giant metamyelocytes and band forms with **hypersegmented neutrophils and macrocytic ovalocytes (MCV high)**
34
What anemias have an elevated MCV (macrocytic)
megaloblastic anemia - B12 def. - Folate def. Alcoholic Liver Disease
35
Hypocellular bone marrow indicates what? What disease has this?
reduced hematopoiesis aplastic anemia (pancytopenia of all cell lines)
36
What anemias/diseases have low reticulocyte counts?
Marrow failure aplastic anemia myelofibrosis leukemia/metastasis renal failure anemia of chronic disease
37
Marrow replacement/invasion an occur by what?
tumor infection myelofibrosis myeloproliferative disorder
38
What is extramedullary hematopoeisis?
hematopoiesis occuring in organs outside of the bone marrow, frequently in the spleen, liver and LN normal during fetal development
39
In what anemias/diseases does extramedullary hematopoiesis function as a compensatory mechanism for abnormal hematopoiesis?
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
What anemias are microcytic (low MCV)
iron def. thalassemia anemia of chronic disease sideroblastic anemia
41
What are schistocytes indicative of?
microangiopathic hemolytic anemia (DIC, TTP/HUS) thrombocytopenia with anemia
42
What are "bite" cells and Heinz bodies associated with?
G6PD def. oxidative stress, cross binding and protein deposition
43
What are sickled RBCs associated with?
Sickle cell anemia deformed erythrocytes due to polymerized abnormal hgb S homozygous abnormal hb SS
44
What are spherical RBCs/Spherocytes associated with?
Spherocytosis
45
What is the normal WBC? What white cell makes up the most white cells? what lymphocyte makes up the most lymphocytes?
4.8-10.8 (x10^3/uL) neutrophils are the most T cells
46
What are causes of neutrophilia
acute bacterial infection medications (glucocorticoids, catecholamines) cigarette smoking various types of physical stress myeloproliferative neoplasms/leukemia
47
What is left shift? (he said this slide was important)
increased immature leukocytes, especially band forms
48
What is neutrophilia, especially neutrophilia with acute left shift, is associated with what?
**acute bacterial infections**
49
What is toxic granulation?
dark course granules within neutrophils, especially in inflammatory conditions
50
How do you tell the difference between band cells and metamyelocyte?
band cells have horseshoe nuclei metamyelocytes are juvenile granulocytes and look kidney-ish
51
what is a leukemoid reaction?
* 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
What should always be on top of the DDx list when the WBC is over 50,000?
leukemic or lymphoproliferative process
53
What is Chronic Myelogenous Leukemia?
* WBC count around **100,000** * insidious disease process, typically of **adults** * high WBC, progressive increase in blasts * starts in **chronic phase**, then a**ccelerated phase** has increase of **10-19% blasts**, then **blast phase** as over **20% blasts** in blood or bone marrow
54
What is acute myeloid leukemia?
* 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
What are some causes of inadequate granulopoiesis? **(leads to neutropenia)**
* 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
What can cause increased destruction/sequestration leading to neutropenia
* immunologically mediated injury to neutrophils (autoimmune, lupus) * splenomegaly (portal HTN, leads to mild neutropenia) * increased peripheral utilization (overwhelming bacterial or fungal infection)
57
What are some benign causes of absolute lymphocytosis?
EBV causing Mono CMV Pertussis Toxoplasmosis drug-induced RA hyperthyroidism
58
What are the findings in chronic lymphocytic leukemia? What are the findings in acute lymphoblastic leukemia?
older adults, \>5000 ALC, lymphadenopathy, hepatosplenomegaly children, numerous blasts on the peripheral smear or bone marrow test with cytometry
59
What are some additional causes of leukocytosis?
Eosinophilic leukocytosis-allergic conditions and parasites basophilic leukocytosis-rare, can be seen in leukemia monocytosis-atypical bacterial infections, autoimmune disease
60
Briefly describe platelet function in primary hemostasis
* 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
What is the physiologic range for platelets?
150,000-450,000/uL
62
What is thrombocytopenia
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
Increased platelet destruction can lead to thrombocytopenia. What can lead to increased platelet destruction?
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
What are some causes of decreased production of platelets that can also lead to thrombocytopenia?
bone marrow replacement due to tumor liver diseases reducing TPO production BONUS: Sequestration of platelets can lead to decrease. What causes that? Hypersplenism!
65
Anemia
dec. RBC volume or Hb
66
Polycythemia
inc. RBC or Hb
67
Thrombopenia
dec. platelets
68
Thrombocythemia
inc. platelets
69
Leukocytosis
inc. WBC
70
Leukopenia
dec. WBC
71
Lymphocytosis
inc. lymphocytes
72
Neutropenia
dec. lymphocytes
73
Eosinophilia
inc. eosinophils
74
Neutrophilia
inc. neutrophils
75
Pancytopenia
dec. of all cell lines
76
MCV calculation
Hct/RBC
77
MCH calculation
Hb\*10/RBC Average mass of hemoglobin in erythrocytes
78
MCHC calculation
Hb/Hct Concentration of hemoglobin in a given volume
79
RPI calculation
Retic % \* Hct/Normal Hct
80
RDW definition
Red cell distribution width (RDW) Measure of range in variation of red blood cell volume
81
Definitions Hg RBC Reticulocyte percentage Hct
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